Antibiotics

Arch Pediatr, 2005 Jan, 12(1), 34 - 41

Laugel V, Escande B, Entz-Werle N, Mazingue F, Ferster A, Bertrand Y, Missud F, Lutz P.
Asparaginase is frequently used in the treatment of lymphoblastic malignancies in children and is a major cause of drug-induced acute pancreatitis . Severe cases of iatrogenic pancreatitis are uncommon but potentially lethal, and represent a diagnostic and therapeutic challenge . Patients and method . - We have retrospectively collected pediatric cases of severe acute pancreatitis induced by asparaginase, having occurred since January 1996 in participating centers from France and Belgium . Results . - Eleven patients, between four and 15 years old, have been included . Pancreatitis has been observed in all treatment phases, after 6 to 21 doses of asparaginase, 2 to 16 days after the last injection . Circulatory collapse (5/11), insulin-dependent diabetes (6/11) and pancreatic pseudokysts (7/11) were the major complications . Non-surgical treatment mainly included digestive rest, broad-spectrum antibiotic therapy and prolonged use of morphine . Asparaginase has been eventually reintroduced in three cases, and has caused a recurrence of pancreatitis in two of them . Conclusion . - Intensive supportive management should enable a favourable outcome in most cases of acute pancreatitis induced by asparaginase in children . There is no way to predict the occurrence of this adverse event . Re-use of asparaginase should probably be ruled out.

Arch Pediatr, 2005 Jan, 12(1), 10 - 15

Assathiany R, Kemeny J, Sznajder M, Hummel M, Van Egroo LD, Chevallier B; l'Arepege.
Objectives . - To assess the presence and impact of health education messages in pediatricians' waiting rooms . Methods.- In September 2001, 81 pediatricians completed a questionnaire about the furnishings and equipment in their waiting rooms . They also distributed a questionnaire about waiting room health education messages to parents, to be completed at home . Results . - The analysis considered 1830 questionnaires . Health education messages were posted in 91% of the waiting rooms and most frequently concerned children's accidents, vaccines, hygiene and nutrition . The best topics that the parents remembered involved child neglect, antibiotic therapy, AIDS and other sexually transmitted diseases, and nutrition . Although memorization of the messages was not influenced by duration of the wait, it was higher among parents who had previously visited the pediatrician . These messages led 14% of the parents to discuss them spontaneously with their pediatrician . Conclusion . - Health education messages are posted in nearly all the waiting rooms studied; parents remember them in a variable and rather inexplicable order . Posting these messages demonstrates the pediatricians' willingness to be involved - beyond the simple consultation - in the health education of children and families . Identifying the real impact of these messages would require further study.

J Int Med Res, 2005 Jan-Feb, 33(1), 1 - 20
Cell wall-deficient bacteria as a cause of infections: a review of the clinical significance; Onwuamaegbu ME et al.; Cell wall-deficient bacteria (CWDB) are pleomorphic bacterial forms . These atypical organisms may occur naturally or they can be induced in the laboratory . Their presence has been known about for over a century, but a definite link to clinical disease outcomes has not been demonstrated . A number of case reports and laboratory studies suggest some disease associations, however . Considerable controversy surrounds the true relevance of CWDB to disease; there is a widespread belief that they may represent a response by the walled organism to adverse extracellular conditions like antibiotic pressure . This review looks at studies published between 1934 and 2003, which were identified by Dialog DataStar using the key words 'cell wall deficient bacteria and clinical significance and infections' and by further scanning the reference list at the end of the papers retrieved . We conclude that the evidence for the clinical significance of CWDB in disease is not compelling.

Z Gastroenterol, 2005 Jan, 43(1), 35 - 46
{Gastrointestinal bleeding in portal hypertensive patients.}; Biecker E et al.; There are three major goals in the prophylaxis and treatment of upper gastrointestinal bleeding in portal hypertensive patients: prophylaxis of the first bleeding episode, therapy of active bleeding and prophylaxis of recurrent bleeding . Several therapeutic options are available: non-selective beta-blockers are the treatment of choice in the primary prophylaxis of the first bleeding episode in patients with large esophageal varices . Alternatively, endoscopic band ligation therapy is an option . Acute bleeding varices should be treated by ligation pharmacological and antibiotic therapy . Prophylaxis of recurrent bleeding is patient-dependent: shunt surgery is an option in young patients in a good medical condition (Child-Pugh class A) . In patients with refractory ascites and a bilirubin below 3 mg/dl, TIPS is a good option together with recurrent bleeding . At the moment, there are no trials showing that endoscopic ligation therapy is superior to prevent pharmacological therapy . Nevertheless, the first-line treatment in most patients in Germany is endoscopic band ligation . Bleeding from ectopic varices and bleeding from hypertensive gastropathy should be treated individually either by endoscopy, TIPS or drug therapy.

Curr Opin Ophthalmol, 2005 Feb, 16(1), 65 - 70
Endophthalmitis: incidence and prevention; Soriano ES et al.; PURPOSE OF REVIEW: To present current peer-reviewed articles related to the incidence and prevention of postoperative endophthalmitis . RECENT FINDINGS: Recent literature indicates that the incidence of postoperative endophthalmitis may be on the rise . Although the preoperative use of antibiotics as prophylaxis is still controversial, it is becoming more common . SUMMARY: The reports of endophthalmitis analyzed from peer-reviewed ophthalmic journals suggest that the incidence of endophthalmitis has increased, ranging from 0.1 to 0.18% in different countries . This may be related to factors associated with the incision . Although some resistance has been detected, fourth-generation fluoroquinolones seem to be a proper antibiotic for endophthalmitis prophylaxis because of their spectrum, mode of action, and penetration.

Protist, 2004 Dec, 155(4), 381 - 93
The bacterial paromomycin resistance gene, aphH, as a dominant selectable marker in Volvox carteri; Jakobiak T et al.; The aminoglycoside antibiotic paromomycin that is highly toxic to the green alga Volvox carteri is efficiently inactivated by aminoglycoside 3'-phosphotransferase from Streptomyces rimosus . Therefore, we made constructs in which the bacterial aphH gene encoding this enzyme was combined with Volvox cis-regulatory elements in an attempt to develop a new dominant selectable marker--paromomycin resistance (PmR)--for use in Volvox nuclear transformation . The construct that provided the most efficient transformation was one in which aphH was placed between a chimeric promoter that was generated by fusing the Volvox hsp70 and rbcS3 promoters and the 3' UTR of the Volvox rbcS3 gene . When this plasmid was used in combination with a high-impact biolistic device, the frequency of stable PmR transformants ranged about 15 per 106 target cells . Due to rapid and sharp selection, PmR transformants were readily isolated after six days, which is half the time required for previously used markers . Co-transformation of an unselected marker ranged about 30% . The chimeric aphH gene was stably integrated into the Volvox genome, frequently as tandem multiple copies, and was expressed at a level that made selection of PmR transformants simple and unambiguous . This makes the engineered bacterial aphH gene an efficient dominant selection marker for the transformation and co-transformation of a broad range of V . carteri strains without the recurring need for using auxotrophic recipient strains.

Mund Kiefer Gesichtschir . 2005 Jan 13; {Epub ahead of print}
{Castleman's disease Seltene Differenzialdiagnose einer submandibularen Schwellung.}; Holzle F et al.; CASE REPORT: A 25-year-old patient with fever, dysphagia, and reduced general condition was referred to our department by his dentist after 1 week of antibiotic therapy . He presented with a painful palpable mass in the right lower jaw that had developed 2 weeks before . The orthopantomogram showed a caries and periapical lesion at the right lower wisdom tooth . During extraction of the tooth and putative intra- and extraoral abscess incision, no pus could be drained and the mass persisted . CT scans then revealed lobulated soft tissue masses on both sides of the neck with the main focus on the right side . In an additional operation with excision of the mass, Castleman's disease of the hyaline vascular type was diagnosed.HISTOPATHOLOGIC FINDINGS: Staging could not detect further pathological findings and the patient's postoperative general condition improved continuously . The histological features of the hayline vascular type of Castleman's disease were characterized by multiple germinal centers surrounded by circumferentially arranged layers of small lymphocytes interconnected by a prominent vascular stroma with occasional plasma cells ("onion skin").CONCLUSION: Castleman's disease is a rare and yet poorly understood disease, characterized by inhomogeneous growth of lymphoid tissue . Mostly benign it remains a diagnostic challenge before histological investigation . In unclear submandibular swellings and neck lumps assumed to be an abscess, this rare differential diagnosis must be considered . Facing recurrence and potential for malignancy, follow-up of the patients over several years is necessary.

Health Aff (Millwood), 2005 Jan-Feb, 24(1), 102 - 13
Making policy when the evidence is in dispute; Atkins D et al.; Policymakers often struggle with medical issues that are the subject of fierce scientific debate . On closer examination, many of these debates are manifestations of conflicting perspectives and values as much as disagreements over the evidence . We summarize common factors underlying recent debates and outline a series of questions that can help disentangle questions of evidence from those of values . These questions focus on identifying the most important outcomes, evaluating the quality of evidence, and assessing the trade-offs involved . We then use four recent policy debates-involving prostate-specific antigen (PSA) screening, high-dose chemotherapy for breast cancer, antibiotic therapy for otitis media, and newborn hearing screening-to illustrate how this approach can help clarify areas of agreement and disagreement of the opposing sides.

Breast J, 2005 Jan-Feb, 11(1), 57 - 9
A Rare Case of Primary Actinomycosis of the Breast Caused by Actinomyces viscosus: Diagnosis by Fine-needle Aspiration Cytology under Ultrasound Guidance; Capobianco G et al.; We report the case of a 27-year-old woman with primary actinomycosis of the breast . Diagnosis was established by culture examination of specimen recovered by fine-needle aspiration cytology (FNAC) under ultrasound guidance . To our knowledge, this is the first description in the literature of a case of primary actinomycosis of the breast caused by Actinomyces viscosus . Twenty-nine previous cases of primary actinomycosis of the breast have been published, but these were caused by the more common species Actinomyces israelii . Targeted antibiotic therapy did not ameliorate the condition, thus drainage and excision of the mass were carried out . No other medical therapy was administered . Six years after surgery, no recurrence has been observed on both ultrasonographic and mammographic examinations.

ILAR J, 2005, 46(1), 8 - 14
Administrative issues related to infectious disease research in the age of bioterrorism; Jaax J; The recent unprecedented growth in infectious disease research funding and infrastructure has resulted in part from an outgrowth of concern about newly emerging and re-emerging diseases and the progressive development of antibiotic-resistant pathogens . However, the most compelling impetus is the suspected and demonstrated capability and will of unknown individuals, groups, or states to use biological agents and/or toxins as weapons . Although the actual number of known victims and fatalities from bioterrorism in the United States has been miniscule compared with many other daily hazards, biological agents have the potential to cause human mass casualties, severely damage segments of our economy or agricultural infrastructure, poison or compromise our food or water supply, and, perhaps most damaging, disrupt our society physically and psychologically . The significant institutional commitment necessary to participate in infectious disease research is described, with a focus on programs that involve research with pathogens thought to have potential for use by bioterrorists . Administrative considerations are described, and include obtaining necessary research funding to offset high operating costs; complying with "select agent" regulations, security screening of employees; building or renovating a biocontainment facility; finding skilled professional and technical manpower; providing adequate physical security in a threat environment; conducting targeted training; overcoming potential internal and external dissent; developing and/or providing sufficient occupational health and safety programs; achieving and maintaining compliance standards in a fluid regulatory environment; mitigating potentially hazardous working conditions; understanding personal and institutional liability; and reassuring and dealing with a concerned, skeptical, or even hostile public.

Aliment Pharmacol Ther, 2005 Jan 1, 21(1), 91 - 6
Rifabutin- and furazolidone-based Helicobacter pylori eradication therapies after failure of standard first- and second-line eradication attempts in dyspepsia patients; Qasim A et al.; Summary Background : Optimal management approach is not well defined for subjects who fail initial first- and second-line Helicobacter pylori eradication attempts and are dealt on a case-by-case basis by the specialists . Aim: To evaluate the efficacy and safety of standard and 'rescue' eradication therapies at primary and secondary care levels . Methods : H . pylori infected dyspepsia patients referred to our C13 urea breath testing laboratory between January 1999 to February 2002 were included . Eradication failure at secondary care level was treated using strategies including antibiotic sensitivity testing and the use of rifabutin- and furazolidone-based therapies . Results : 3280 patients received standard first-line eradication therapy, which was successful in 2530 (77%) patients . Second-line therapy (bismuth-based 'quadruple') or triple therapy (altering constituent antibiotics) was successful in 56% of 270 treated patients . Subsequent eradication attempts using rifabutin-based (n = 34) and furazolidone-based (n = 10) regimens were successful in 38% and 60% patients respectively . H . pylori eradication rates were significantly different for guidelines compliant (94.8%) and non-compliant (82%) groups (P = 0.0001) . H . pylori eradication rates for non-ulcer dyspepsia (40%) and peptic ulcer disease (36%) were not significantly different . Conclusions : Available H . pylori eradication therapies remain very effective and compliance to guidelines achieves high success rates . Furazolidone-based 'rescue' regimen achieved high eradication rates after failure of the standard first-line, second-line and rifabutin-based therapies.

Int J STD AIDS, 2004 Dec, 15(12), 831 - 2
Treatment of Chlamydia trachomatis in North Thames region 2003; Sethi G et al.; Following on from the survey of techniques used for testing chlamydia, a multi-centre re-audit of the treatment of C . trachomatis in genitourinary clinic attendees in the North Thames region from February to March 2003 was performed . This showed an improvement since our previous audit with a significant increase in the number of centres following national guidelines in antibiotic prescribing and offering test of cure in clinically indicated cases.

Nat Struct Mol Biol . 2005 Jan 09; {Epub ahead of print}
Surface charge and hydrophobicity determine ErbB2 binding to the Hsp90 chaperone complex; Xu W et al.; The molecular chaperone Hsp90 modulates the function of specific cell signaling proteins . Although targeting Hsp90 with the antibiotic inhibitor geldanamycin (GA) may be a promising approach for cancer treatment, little is known about the determinants of Hsp90 interaction with its client proteins . Here we identify a loop within the N lobe of the kinase domain of ErbB2 that determines Hsp90 binding . The amino acid sequence of the loop determines the electrostatic and hydrophobic character of the protein's surface, which in turn govern interaction with Hsp90 . A point mutation within the loop that alters ErbB2 surface properties disrupts Hsp90 association and confers GA resistance . Notably, the immature ErbB2 point mutant remains sensitive to GA, suggesting that mature and nascent client kinases may use distinct motifs to interact with the Hsp90 chaperone complex.

Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi, 2004 Sep, 18(3), 287 - 8
{Clinical analysis of 77 liver failure patients with nosocomially infected septicemia.}; He WP et al.; BACKGROUND: To study the clinical characteristics and preventive measures of liver failure with nosocomial septicemia . METHODS: Retrospective analysis of nosocomial septicemia seen between 2001 and 2002 was carried out in our hospital . RESULTS: Incidence of nosocomial septicemia was 0.61%, mortality was 14.29%, the main pathogen was Escherichia coli, the drug resistance occurred in most pathogens to the commonly used antibiotics . CONCLUSION: In order to reduce nosocomial septicemia, antibiotics should be used rationally, should be paid attention to bacterial culture and antibiotic sensitivity, and preventive measures should be taken.

Bone Marrow Transplant . 2005 Jan 10; {Epub ahead of print}
A prospective study of real-time panfungal PCR for the early diagnosis of invasive fungal infection in haemato-oncology patients; Jordanides NE et al.; Summary:A blinded prospective study was performed to determine whether screening of whole blood using a real-time, panfungal polymerase chain reaction (PCR) technique could predict the development of invasive fungal infection (IFI) in immunocompromised haemato-oncology patients . In all, 78 patients (125 treatment episodes) were screened twice weekly by real-time panfungal PCR using LightCyclertrade mark technology . IFI was documented in 19 treatment episodes (five proven, three probable and 11 possible), and in 12, PCR was sequentially positive . PCR positivity occurred in: 4/5 proven; 2/3 probable; 6/11 possible; and 29/106 with no IFI . In 8/12 with IFI and sequentially positive PCR results, PCR positivity occurred before (median 19.5 days) and in 4/12 (median 10.5 days) after the initiation of empirical antifungal therapy . Based on sequential positive results for proven/probable IFI sensitivity, specificity, positive predictive value and negative predictive value were 75, 70, 15 and 98%, respectively . Real-time panfungal PCR is a sensitive tool for the early diagnosis of IFI in immunocompromised haemato-oncology patients . It may be most useful as a screening method in high-risk patients, either to direct early pre-emptive antifungal therapy or to determine when empirical antifungal therapy can be withheld in patients with antibiotic--resistant neutropenic fever . However, these strategies require further assessment in comparative clinical trials.Bone Marrow Transplantation advance online publication, 10 January 2005; doi:10.1038/sj.bmt.1704768.

Yi Chuan, 2003 Jul, 25(4), 466 - 70
{Using of selective marker gene in transgenic plants and its removal.}; Hou AJ et al.; Selective marker gene is usually used to select transformed cells or tissue during gene transfer.However,the use of selective marker gene,especially antibiotic-resistant gene,is harmful to environment,plant development and affects multi-transformation.A new strategy that offers a approach for the elimination of those disadvantages caused by the selectable marker gene is developed.We summarized correlative marker genes used in transgenic plants and some methods of its removal.

Yi Chuan, 2003 Jan, 25(1), 119 - 22
{The new safe strategy on the marker genes in transgenic plant.}; Zhao Y et al.; The presence in transgenic plants of antibiotic and herbicide resistant selective marker genes might be an unpredictable hazard to the ecosystem as well as to human health.There are two applicable strategies can be used to resolve this problem.One is to remove the resistant marker genes before the transgenic plants are released to field.The other is to develop and use safe marker genes to produce transgenic plants.The present paper reviewed three technique systems employed to remove resistant marker genes in transgenic plants and several safe marker genes used in plant transformation.

Arch Biochem Biophys, 2005 Feb 15, 434(2), 232 - 40
Amplification of C1027-induced DNA cleavage and apoptosis by a quinacrine-netropsin hybrid molecule in tumor cell lines; Iwamoto T et al.; We examined the effect of a newly synthesized DNA-binding ligand, quinacrine-netropsin hybrid molecule (QN), on cytotoxicity, apoptosis, and DNA strand breaks induced by an enediyne antitumor antibiotic, C1027 . QN significantly enhanced C1027-induced cellular DNA strand breaks, caspase-3 activation, and DNA ladder formation, characteristic of apoptosis, in human HL-60 cells . Flow cytometry revealed that C1027-induced intracellular H(2)O(2) generation was enhanced by QN, suggesting that QN enhances C1027-induced cytotoxic effect through H(2)O(2)-mediated apoptosis . QN also significantly enhanced C1027-induced apoptosis in BJAB cells, and the inhibition of apoptosis was observed in BJAB cells transfected with Bcl-2 gene . The experiment using (32)P-labeled DNA fragments showed that the addition of QN enhanced C1027-induced double-stranded DNA cleavage at the 5'-AGG-3'/3'-TCC-5' sequence (cutting sites are underlined) . These results suggest that QN enhances C1027-induced antitumor effect via DNA cleavage and apoptosis . The present study shows a novel approach to the potentially effective anticancer therapy.

Curr Protein Pept Sci, 2005 Jan, 6(1), 103 - 14
Membrane Interactions of Host-defense Peptides Studied in Model Systems; Jelinek R et al.; Host-defense, antibiotic peptides are believed to generate their cytolytic effects by interacting with the membranes of bacterial cells . Direct analyses of peptide interactions with real cellular membranes are difficult, however, due to the high complexity of physiological membranes . This review summarizes experimental work aiming to understand peptide-membrane interactions and their relationships with the peptides' biological actions using specific model systems . Varied model assemblies have been constructed that generally aim to mimic the fundamental lipid bilayer organization of the membrane . The model systems we will describe include multilamellar and unilamellar vesicles, planar lipid bilayers, lipid monolayers and micelles, and colorimetric biomimetic membranes . The different artificial models have facilitated examination of specific biological or chemical parameters affecting peptide action, for example the effect of membrane lipid composition on peptide affinities and membrane penetration, the relationship between membrane fluidity and peptide interactions, the conformations of active peptides, and other factors . We evaluate the strengths and limitations of the various approaches, and point to future directions in the field.

Neurosurg Focus . 2004 Dec 15;17(6):E2.
Diagnosis and management of adult pyogenic osteomyelitis of the cervical spine; Acosta FL Jr et al.; Establishing the diagnosis of cervical osteomyelitis in a timely fashion is critical to prevent catastrophic neurological injury . In the modern imaging era, magnetic resonance imaging in particular has facilitated the diagnosis of cervical osteomyelitis, even before the onset of neurological signs or symptoms . Nevertheless, despite advancements in diagnosis, disagreement remains regarding appropriate surgical treatment . The role of instrumentation and type of graft material after cervical decompression remain controversial . The authors describe the epidemiological features, pathogenesis, and diagnostic evaluation, and the surgical and nonsurgical interventions that can be used to treat osteomyelitis of the cervical spine . They also review the current debate about the role of instrumentation in preventing spinal deformity after surgical decompression for cervical osteomyelitis . Based on this review, the authors conclude that nonsurgical therapy is appropriate if neurological signs or symptoms, instability, deformity, or spinal cord compression are absent . Surgical decompression, debridement, stabilization, and deformity correction are the goals once the decision to perform surgery has been made . The roles of autogenous graft, instrumentation, and allograft have not been clearly delineated with Class I data, but the authors believe that spinal stability and decompression override creating an environment that can be completely sterilized by antibiotic drugs.

Neurosurg Focus . 2004 Dec 15;17(6):E11.
Cervical osteomyelitis: a brief review; Barnes B et al.; OBJECT: The authors conducted a literature-based review of the etiology, diagnosis, and treatment of cervical vertebral osteomyelitis (CVO) . METHODS: A Medline (PubMed) search using the key words "cervical vertebral osteomyelitis" yielded 256 articles . These were further screened for relevance, yielding 15 articles . Each publication was reviewed, and several others not identified in the PubMed search were screened and included in the review according to relevance . Each article was identified as involving either the epidemiology/etiology, diagnosis, or treatment of CVO . Separate categories were created for case reports and general reviews . CONCLUSIONS: Cervical vertebral osteomyelitis has a spectrum of origins, which include spontaneous, postoperative, traumatic, and hematogenously spread causes . The majority of patients have medical risk factors and comorbidities that include diabetes, trauma, drug abuse, and infectious processes in extraspinal areas . The diagnosis of CVO can be accomplished in most cases by using plain x-ray films and computerized tomography scans . Nevertheless, preferential use of magnetic resonance imaging in cases in which there is a neurological deficit is helpful in identifying epidural compressive processes . Treatment for CVO can be successfully initiated with intravenous antibiotic therapy . Nevertheless, in cases in which there is a neurological deficit, spinal deformity and/or progressive lysis, or intractable pain, the earliest feasible surgical intervention with debridement and fusion is warranted.

Am J Otolaryngol, 2005 Jan-Feb, 26(1), 35 - 8
Subacute infratemporal fossa cellulitis with subsequent abscess formation in an immunocompromised patient; Akst LM et al.; Abstract Objectives To present a case of subacute infratemporal fossa cellulitis with subsequent abscess formation to show important anatomic relationships as they effect presentation and treatment of infections in this area . Study design Case report and brief literature review . Methods The case of an immunocompromised patient who developed subacute infratemporal fossa cellulitis with subsequent abscess formation is presented . A literature review discusses etiology, diagnosis, and treatment of these infections . Results Careful history and physical examination revealed unilateral facial pain, swelling, and trismus to be caused by an infratemporal fossa abscess . Intraoral drainage and intravenous antibiotic therapy led to resolution of the infection . Conclusion Infratemporal fossa abscesses are potentially dangerous complications of odontogenic infections . Although clinical diagnosis may be difficult, knowledge of relevant anatomy and pathways of spread allow more effective diagnosis and treatment of these infections.

Am J Otolaryngol, 2005 Jan-Feb, 26(1), 1 - 6
A comprehensive study on lesions of the pinna; Prasad KC et al.; Abstract Purpose Pinna contributes enormously to the facial aesthesis . Lesions affecting the pinna can lead to overt disfigurement and change the entire appeal of the face . Gross deformity can occur because of a delay in diagnosis and mismanagement . The aim of our study was to determine the clinical presentation, relevant investigations, appropriate treatment, timing of surgical intervention, and complications encountered . Factors that predispose and aggravate the condition and their appropriate management are also discussed . The point to be emphasized is that a good clinical history and examination alone is sufficient to diagnose the conditions without the aid of any special investigation . Materials and Methods Our clinical study comprised of 307 cases of men and women patients presenting with swelling of the pinna, who attended the Ear, Nose, and Throat Department, Kasturba Medical College, Mangalore, India, during the period of February 1992 to June 2002 . Wide bore needle aspiration was done for the majority of cases of seroma and hematoma . Patients who had recurrence were managed by window procedure . Incision and drainage with or without curettage of diseased cartilage was performed for perichondritis . Other lesions like keloid, hemangioma, dermoid cyst, sebaceous cyst, and malignancy were managed by complete excision . A firm pressure dressing was applied in all cases after surgery . Majority of the cases were done under local anesthesia . Results Prompt surgical intervention under good antibiotic cover gave excellent results with minimal complications . Conclusions Surgical intervention at the earliest followed by a firm pressure dressing under antibiotic cover decreases the morbidity . Diabetes mellitus plays a significant role in few of the conditions and has to be simultaneously controlled.

J Oral Maxillofac Surg, 2005 Jan, 63(1), 36 - 41
Ultrasound-guided drainage of submasseteric space abscesses; Al-Belasy FA; Purpose The oral approach for incision and drainage (I&D) in patients presenting with submasseteric space (SMS) abscesses and marked trismus is more difficult and requires a general anesthetic, necessitating an anesthetist experienced in fiberoptic-guided nasal intubation . In such patients, ultrasound-guided drainage (USGD) has been attempted to obviate this need . The purpose of this trial was to report our experience with the surgical management of 11 SMS abscesses, with special reference to their USGD . Materials and methods Seven men and 4 women ranging in age from 18 to 41 years (average age, 25 years) participated in this trial . They were initially examined with US, and their abscesses were subsequently drained under US guidance using a 16-gauge intravenous catheter . An antibiotic regimen was prescribed, and arrangements were made to see the patients daily for 5 days . USGD was repeated after 24 hours, and 24 hours later the infection course was monitored in each patient . Patients with nonresolving infection had their abscesses formally incised and drained extraorally . The source of infection was removed as soon as the acute phase of infection passed and the interincisal opening (IIO) allowed . The catheter or corrugated drain was removed when the discharge ceased or became minimal . Patients were then instructed to continue a 3-day course of an antibiotic and to return after 1 week and then after 1 month . Results Resolution of infection was successfully achieved by USGD with no need for I&D in 8 of the 11 patients (73%) . In those patients, the average total amount of pus removed was 8.5 mL, and the average IIO was 17.4 mm immediately after an average initial aspirate of 4.5 mL of pus . I&D was required in the remaining 3 patients (27%) . In those patients the average total amount of pus removed was 17.5 mL, and the average IIO was 7.7 mm immediately after an average initial aspirate of 9.3 mL of pus . Conclusions Resolution of infection with USGD is more probable if there was an immediate improvement of the IIO to about 1.5 cm or more after an initial aspiration of 5 mL of pus.

J Bone Joint Surg Am, 2005 Jan, 87-A(1), 8 - 12
The effect of surgical delay on acute infection following 554 open fractures in children; Skaggs DL et al.; BACKGROUND: Traditional recommendations hold that open fractures in both children and adults require urgent surgical debridement for a number of reasons, including the preservation of soft-tissue viability and vascular status as well as the prevention of infection . Following the widespread use of early administration of antibiotics, a number of single-institution studies challenged the belief that urgent surgical debridement decreases the risk of acute infection . METHODS: We performed a retrospective, multicenter study of open fractures that had been treated at six tertiary pediatric medical centers between 1989 and 2000 . The standard protocol at each medical center was for all children to be given intravenous antibiotics upon arrival in the emergency department . The medical records of all children with open fractures were reviewed to identify the location of the fracture, the interval between the injury and the time of surgery, the Gustilo and Anderson classification, and the occurrence of acute infection . RESULTS: The analysis included 554 open fractures in 536 consecutive patients who were eighteen years of age or younger . The overall infection rate was 3% (sixteen of 554) . The infection rate was 3% (twelve of 344) for fractures that had been treated within six hours after the injury, compared with 2% (four of 210) for those that had been treated at least seven hours after the injury; this difference was not significant (p = 0.43) . When the fractures were separated according to the Gustilo and Anderson classification system, there were no significant differences in the infection rate between those that had been treated within six hours after the injury and those that had been treated at least seven hours after the injury . Specifically, these infection rates were 2% (three of 173) and 2% (two of 129), respectively, for type-I fractures, 3% (three of 110) and 0% (zero of forty-four), respectively, for type-II fractures, and 10% (six of sixty-one) and 2% (two of thirty-seven), respectively, for type-III fractures (p > 0.05 for all three comparisons) . CONCLUSIONS: In the present retrospective, multicenter study of children with Gustilo and Anderson type-I, II, and III open fractures, the rates of acute infection were similar regardless of whether surgery was performed within six hours after the injury or at least seven hours after the injury . The findings of the present study suggest that, in children who receive early antibiotic therapy following an open fracture, surgical debridement within six hours after the injury offers little benefit over debridement within twenty-four hours after the injury with regard to the prevention of acute infection . LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions to Authors for a complete description of levels of evidence.

J Biol Chem . 2005 Jan 4; {Epub ahead of print}
Cyclin D1 and c-Myc internal ribosome entry site (IRES)-dependent translation is regulated by AKT activity and enhanced by rapamycin through a p38 MAPK and ERK-dependent pathway; Shi Y et al.; The macrolide antibiotic rapamycin inhibits the mammalian target of rapamycin protein (mTOR) kinase resulting in the global inhibition of cap-dependent protein synthesis, a blockade in ribosome component biosynthesis and G(1) cell cycle arrest . G(1) arrest may occur by inhibiting the protein synthesis of critical factors required for cell cycle progression . Hypersensitivity to mTOR inhibitors has been demonstrated in cells having elevated levels of AKT kinase activity, whereas cells containing quiescent AKT activity are relatively resistant . Our previous data suggest that low AKT activity induces resistance by allowing continued cap-independent protein synthesis of cyclin D1 and c-myc proteins . In support of this notion, the current study demonstrates that the human cyclin D1 mRNA 5' untranslated region contains an internal ribosome entry site (IRES) and that both this IRES and the c-myc IRES are negatively regulated by AKT activity . Furthermore, we show that cyclin D1 and c-myc IRES function is enhanced following exposure to rapamycin and requires both p38 MAPK and RAF/MEK/ERK signaling, as specific inhibitors of these pathways reduce IRES-mediated translation and protein levels under conditions of quiescent AKT activity . Thus, continued IRES-mediated translation initiation may permit cell cycle progression upon mTOR inactivation in cells whose AKT kinase activity is relatively low.

Orthopedics, 2004 Dec, 27(12), 1289 - 91
Addition of hand-blended generic tobramycin in bone cement: effect on mechanical strength; DeLuise M et al.; This study compared the mechanical strength of commercially prepared antibiotic bone cement (Simplex With Tobramycin; Stryker, Mahwah, NJ), cement with generic tobramycin (Pharma-Tek, Huntington, NY) blended in by the orthopedic nursing staff, and standard nonantibiotic bone cement . The results showed an approximate 36% decrease in the strength of the cement with hand-mixed generic tobramycin, while the commercial antibiotic cement remained unchanged relative to the nonantibiotic control . These results indicate the mechanical properties of bone cement can be severely compromised by hand-mixing antibiotics into bone cement at the time of surgery.

Pediatr Pulmonol, 2005 Feb, 39(2), 156 - 61
Prevalence of thrombophilia and catheter-related thrombosis in cystic fibrosis; Barker M et al.; Venous thrombosis in children and young adults is frequently associated with predisposing conditions and with an indwelling catheter or totally implantable venous access device (TIVAD) . These systems are commonly used for the delivery of antibiotic therapy in patients with cystic fibrosis (CF) . We reviewed our CF center's history of catheter-related events over 13 years and prospectively investigated the presence of risk factors for thrombosis in 66 children and adults with CF (age, 3-38 years; 32 females) . Five thrombotic events had occurred in 4 patients, 2 of whom carried the factor V Leiden mutation . Five asymptomatic patients were diagnosed with heterozygous mutations of the factor V or prothrombin gene . Functional activity of protein C was decreased in 13 subjects, with a correlation to impaired liver function . Protein S activity was abnormal in 20 patients and was related to CF genotype . Anti-phospholipid antibodies (APA) were present in 6 asymptomatic patients . A reinvestigation after 3 years confirmed protein S deficiency in 12 of 14 patients, while most abnormalities for protein C or APA were inconsistent . In conclusion, a thrombophilic state was detected in 53% of patients, and 2 out of 4 subjects with TIVAD-related thrombosis carried a genetic defect . It may thus be helpful to include a hemostatic evaluation in the clinical decision process for or against TIVAD insertion in eligible CF patients . Pediatr Pulmonol . 2005;39:156-161 . (c) 2005 Wiley-Liss, Inc.

Neurocirugia (Astur), 2004 Dec, 15(6), 543 - 51; discussion 551-2
{Spinal epidural empyema . Analysis of 14 cases}; Gelabert-Gonzalez M et al.; OBJECTIVE: The goal of this study was to review our series of spinal epidural empyema diagnosed in the last 20 years and review the literature regarding the pathogenesis, diagnosis and treatment of these lesions . PATIENTS AND METHODS: This is a retrospective study over 14 patients diagnosed of spinal epidural empyema . We review the epidemiological data, clinical symptoms, laboratory and imaging data, the treatment regimen and the results . RESULTS: Fourteen patients, 7 males and 7 females, with an age range from 8 to 76 years (mean 48.9) were identified . The first symptom was localized back/ neck pain in 12 patients and the mean duration of symptoms was 9.3 days . Erythrocyte sedimentation rate (ESR) was elevated in all patients; peripheral leukocyte count was elevated in 13 cases (92.9%) . Site of spinal epidural empyemas was distributed along the axis but in 11 cases the location was thoracic . Thirteen patients had surgery for debridement and spinal decompression and one patient was treated successfully with antibiotics alone . CONCLUSIONS: Patients with localized back pain and fever who are at risk for developing such empyemas with elevation of white blood cells and increased ESR, should have an immediate magnetic resonance imaging sean . Urgent surgical drainage and antibiotic use are the treatment of choice in order to prevent irreversible neurological deficits . Nonsurgical treatment should be reserved for poor surgical candidates and patients without neurological deficits.

Acta Med Port, 2003 Nov-Dec, 16(6), 389 - 394 Epub 2003 Dec 1.
{Monitoring serum levels of gentamicin in neonates.}; Rocha MJ et al.; Newborn infants in intensive care units demonstrated a higher incidence of gestational age below 31 week . Obstetrical and neonatal diseases procedures required for the management of critically ill neonates are associated with an increased risk of infections . Gentamicin is an aminoglycoside antibiotic often used to treat gramnegative bacillary infections and suspected sepsis in neonates . The risk of toxicity or poor efficacy is further increased due to the recognised wide intra and interpatient variability of the newborn . The present work involved 49 infants of 31.3 +/- 4.1 (mean +/- SD) weeks of gestational age, weighing 1.7 +/- 0.8 kg and were treated with standard doses of gentamicin (3.8 +/- 0.9 mg/kg/day) . Routine clinical care data were retrospectively collected from the medical records in the neonatal intensivecare unit at Coimbra University Hospital . Data analysis demonstrated that potentially toxic serum levels were observed in 49% of newborn infants (trough > 2 mg/L) . Additionally, the obtained results also showed that 7.5% of peak concentrations were found to be higher than 10 mg/L . Potentially sub-therapeutic concentrations were observed in 15% of the patients (peak > 6 mg/L).

J Bacteriol, 2005 Jan, 187(2), 687 - 96
Biochemical Activities of the absA Two-Component System of Streptomyces coelicolor; Sheeler NL et al.; The AbsA1 sensor kinase and its cognate response regulator AbsA2 are important regulators of antibiotic synthesis in Streptomyces coelicolor . While certain point mutations in absA1 reduce or eliminate the synthesis of several antibiotics, null mutations in these genes bring about enhanced antibiotic synthesis . We show here that AbsA1, which is unusual in sequence and structure, is both an AbsA2 kinase and an AbsA2 approximately P phosphatase . The half-life of AbsA2 approximately P in solution is 68.6 min, consistent with a role in maintaining a relatively stable state of transcriptional repression or activation . We find that mutations in the absA locus that enhance antibiotic synthesis impair AbsA2 kinase activity and that mutations that repress antibiotic synthesis impair AbsA2 approximately P phosphatase activity . These results support a model in which the phosphorylation state of AbsA2 is determined by the balance of the kinase and phosphatase activities of AbsA1 and where AbsA2 approximately P represses antibiotic biosynthetic genes either directly or indirectly.

Farm Hosp, 2004, 28(6), 410 - 418
{A study of antibiotc use at a county hospital . Years 1998-2002.}; Aparici Bolufer J et al.; Introduction: Adequate antibiotic use clearly influences the development of bacterial resistance, adverse events and healthcare costs . Studies of drug usage allow us to detect deviations in antibiotic use . Material and methods: Antibiotic use during the period 1998-2002 was analyzed using data provided by management software applications . The prescription of restricted-use antibiotics during years 2001 and 2002 was analyzed by selecting patients according to the information available in the unit-dose drug distribution area database at the pharmacy department . Results: Antibiotic use increased from 78 to 100 DDD during the period of time studied . The use of new quinolones has displaced macrolides . Two thirds of piperacillin -tazobactam prescriptions are for surgical patients . Conclusions: 1.Changes in the pattern of antibiotic use have been detected . 2.The relative weight of restricted-use antibiotics has increased . 3.This study allows a prioritization of intervention areas.

Biochemistry, 2005 Jan 11, 44(1), 268 - 277
Fungal Metabolite Sulfamisterin Suppresses Sphingolipid Synthesis through Inhibition of Serine Palmitoyltransferase; Yamaji-Hasegawa A et al.; Sphingolipids and their metabolites are known to modulate various cellular events including proliferation, differentiation, and apoptosis . Serine palmitoyltransferase (SPT) is the enzyme that catalyzes the first step of the biosynthesis of all sphingolipids . Here, we report that a newly identified antibiotic, sulfamisterin, derived from the fungus Pycnidiella sp., is a specific inhibitor of SPT . The chemical structure of sulfamisterin resembles both that of sphingosine as well as a potent inhibitor of SPT, ISP-1 (myriocin) . Sulfamisterin inhibited SPT activity with IC(50) = 3 nM in a cell-free lysate prepared from Chinese hamster ovary (CHO) fibroblasts . Sulfamisterin markedly inhibited the biosynthesis of sphingolipids in living CHO cells and in yeast Saccharomyces cerevisiae as monitored by radioactive precursors . Unlike the cell-free experiments, 10 muM sulfamisterin was required for complete inhibition of sphingolipid biosynthesis in intact cells . We also synthesized a series of structural analogues of sulfamisterin and examined their activities both in cell-free and in living cell systems.

Antibiot Khimioter, 2004, 49(6), 15 - 9
{Pharmacokinetic substantiation of ceftriaxone prophylaxis of hereditary syphilis}; Frontal ataxia in childhood; Department of Paediatric Neurology, University Medical Centre St . Radboud, Nijmegen, The Netherlands . c.erasmus@cukz.umcn.nl

Frontal ataxia may be the result of a unilateral frontal lesion . In this report three cases are presented with ataxia due to right frontal lesions . One case concerns a boy presenting with an unsteady gait and titubation of the trunk, mimicking developmental disequilibrium and with complex partial seizures . It proved to be caused by a small right-sided cavernoma in the middle frontal gyrus . After surgical intervention the symptoms and the seizures disappeared . Two subsequent cases concern teenage patients presenting with headache after an ENT infection and on physical examination mild dysmetric function of the upper limbs and slight disequilibrium, due to right-sided frontal lobe abscesses . After neurosurgical and antibiotic therapy the symptoms were relieved . The frontal origin of ataxia should be considered in children presenting with a "cerebellar syndrome" . Frontal gait disorders consist of a clinical pattern of different gait disorders . The syndrome has been mentioned in the literature under different names . Our patients show signs compatible with the term frontal disequilibrium, a clinical pattern of frontal gait disorder . This assumes walking problems characterized by loss of control of motor planning, leading to imbalance . Remarkably, frontal ataxia may mimic developmental delay as demonstrated in the first case and may be the leading mild symptom in extensive frontal lobe damage as demonstrated by the two other cases . We suppose that frontal ataxia is the result of a disturbance in the cerebellar-frontal circuitries and an impairment of executive and planning functions of the basal ganglia-frontal lobe circuitry.

Pediatr Pulmonol . 2004 Dec 30;39(2):156-161 {Epub ahead of print}
Prevalence of thrombophilia and catheter-related thrombosis in cystic fibrosis; Barker M et al.; Venous thrombosis in children and young adults is frequently associated with predisposing conditions and with an indwelling catheter or totally implantable venous access device (TIVAD) . These systems are commonly used for the delivery of antibiotic therapy in patients with cystic fibrosis (CF) . We reviewed our CF center's history of catheter-related events over 13 years and prospectively investigated the presence of risk factors for thrombosis in 66 children and adults with CF (age, 3-38 years; 32 females) . Five thrombotic events had occurred in 4 patients, 2 of whom carried the factor V Leiden mutation . Five asymptomatic patients were diagnosed with heterozygous mutations of the factor V or prothrombin gene . Functional activity of protein C was decreased in 13 subjects, with a correlation to impaired liver function . Protein S activity was abnormal in 20 patients and was related to CF genotype . Anti-phospholipid antibodies (APA) were present in 6 asymptomatic patients . A reinvestigation after 3 years confirmed protein S deficiency in 12 of 14 patients, while most abnormalities for protein C or APA were inconsistent . In conclusion, a thrombophilic state was detected in 53% of patients, and 2 out of 4 subjects with TIVAD-related thrombosis carried a genetic defect . It may thus be helpful to include a hemostatic evaluation in the clinical decision process for or against TIVAD insertion in eligible CF patients . Pediatr Pulmonol . 2005;39:156-161 . (c) 2005 Wiley-Liss, Inc.

Eur Radiol . 2004 Dec 31; {Epub ahead of print}
Cerebral infections; Karampekios S et al.; Despite the development of many effective antibiotic therapies and the general improvement in hygiene and health care systems all over the world, the incidence of central nervous system (CNS) infection has increased significantly in the past 15 years . This can be attributed primarily to the acquired immunodeficiency syndrome (AIDS) epidemic and its devastating effect on the immune system and secondarily to various immunosuppressive agents that are being used in aggressive cancer treatment and in organ transplantations . The brain particularly is protected from infection by the calvarium, meninges and blood brain barrier . However, different types of pathogens, including bacteria, viruses, fungi and parasites, can reach the brain hematogenously or, less likely, by direct extension from an adjacent infected focus . The early detection and specific diagnosis of infection are of great importance, since brain infections are potentially treatable diseases . Imaging studies play a crucial role in the diagnostic process, along with the history (exposure to infectious agents), host factors (open head trauma, CSF leak, sinusitis, otitis, immune status), physical examination and laboratory analysis of CSF.

Curr Opin Urol, 2004 Nov, 14(6), 375 - 80
Current role of penile implants for erectile dysfunction; Moncada I et al.; PURPOSE OF REVIEW: The purpose of this review is to appraise new developments and publications in the field of penile prosthetic surgery . Urologists dealing with erectile dysfunction need to recognize the value of penile prosthetic surgery as a very efficacious treatment for this common condition . This type of surgery is needed in a considerable proportion of patients with erectile dysfunction so this review is timely and relevant . RECENT FINDINGS: The main themes in the literature covered include risk factors for infection of penile prostheses, its prevention with the use of hydrophilic and antibiotic-coated prostheses, particularly in re-operations, and its management with the new rescue procedures . Surgical tips for prosthetic surgery are also reviewed as well as clinical outcomes and factors influencing them . SUMMARY: Of all the invasive treatments currently available, placement of a penile prosthesis is one of the most successful, giving high levels of satisfaction . With the aid of new technical advances, the risk of infection--the most feared complication--can be minimized so prosthetic surgery may play a major role in the treatment of erectile dysfunction.

Pediatr Hematol Oncol, 2004 Oct-Nov, 21(7), 585 - 92
Intracranial hemorrhage due to vitamin K deficiency after the newborn period; Demiroren K et al.; This study presents clinical and laboratory findings and outcome of infants with intracranial hemorrhage (ICH) due to vitamin K deficiency after the newborn period, and evaluates vitamin K prophylaxis . The hospital records of 19 infants with a diagnosis of ICH due to vitamin K deficiency after the newborn period, seen in our clinic in less than 4 years, were retrospectively evaluated . The mean age at onset of the symptoms was 49 +/- 18 days . The most frequent presenting complaints were convulsion (58%), vomiting (47%), and irritability (47%) . The most frequent examination findings were coma (74%), fontanel bulging (68%), and absence of pupil reaction (42%) . The localizations of the ICHs were as follows: parenchymal (47%), subarachnoid (47%), subdural (42%), and intraventricular (26%) . Four patients had used antibiotics and 1 patient had suffered diarrhea before the onset of the symptoms . One patient had a mild hepatic dysfunction that resolved spontaneously in a few weeks and its cause was not found . Mortality was observed in 6 (32%) patients . Ten patients were followed up for a mean period of 26.9 +/- 22.6 months . The follow-up findings were developmental delay (40%), microcephaly (30%), epilepsy (30%), blindness (20%), strabismus (20%), spastic tetraparesis (10%), spastic hemiparesis (10%), growth retardation (10%), and hydrocephaly (10%) . Three (30%) patients remained neurologically normal . Vitamin K deficiency leads to death and neurological defects . Vitamin K prophylaxis at birth is therefore a priority . In this series, hepatic dysfunction had been detected in only 1 patient . The authors speculate that additional vitamin K to breast-fed infants with liver problem, antibiotic use, diarrhea, etc., should be considered.

Am J Physiol Renal Physiol . 2004 Dec 29; {Epub ahead of print}
Acute Renal Failure in Zebrafish - A Novel System to Study a Complex Disease; Hentschel DM et al.; Acute renal failure (ARF) is characterized by a very high mortality essentially unchanged over the past 40 years . Simple vertebrate models are needed to improve our understanding of ARF and facilitate the development of novel therapies for this clinical syndrome . Here we demonstrate that gentamicin, a commonly used nephrotoxic antibiotic, causes larval zebrafish to develop ARF characterized by histological and functional changes that mirror aminoglycoside toxicity in higher vertebrates and inability of zebrafish to maintain fluid homeostasis . We developed a novel method to quantitate renal function in larval zebrafish, and demonstrate a decline in glomerular filtration rate after gentamicin exposure . The anti-neoplastic drug cisplatin, whose use in humans is limited by kidney toxicity, also causes typical histological changes and a decline in renal function in larval zebrafish . A specific inhibitor of Omi/HtrA2, a serine protease implicated in cisplatin-induced apoptosis, prevented renal failure and increased survival . This protective effect was confirmed in a mouse model of cisplatin-induced nephrotoxicity . Therefore zebrafish provides a unique model system, amenable to genetic manipulation and drug screening, to explore the pathophysiology of ARF and establish novel therapies with potential use in mammals.

J R Army Med Corps, 2004 Sep, 150(3), 182 - 6
Hospitalisation due to Lyme disease: case series in British Forces Germany; Baker BC et al.; Lyme disease is a tick-transmitted infection with disabling sequelae and important occupational health implications for a military workforce . It is likely that some military patients with typical clinical signs remain undiagnosed and untreated . Prompt treatment with an antibiotic is essential, besides targeted education on preventing infection through avoiding exposure to tick bites . We describe four British Forces Germany personnel (two serving military personnel, one adult civilian, one child) who during 2002--2003 required hospital inpatient treatment for Lyme disease . The epidemiology, pathogenesis, clinical features, diagnosis and treatment of the disease are discussed.

Electrophoresis, 2005 Jan, 26(1), 196 - 201
Direct determination of gentamicin components by capillary electrophoresis with potential gradient detection; Yuan L et al.; A simple and fast method was developed to determine non-UV active compounds directly without derivatization . The usefulness of the method was demonstrated by detecting the major components in aminoglycoside antibiotic mixtures using capillary zone electrophoresis with potential gradient detection . Under optimized separation conditions (0.2 mM cetyltrimethylammonium bromide (CTAB), 1 mM ammonium citrate, pH 3.5), gentamicin was separated into three major peaks (C1, C1a, and C2+C2a) within 15 min . This method showed better sensitivity than other capillary electrophoresis (CE) methods for determining underivatized gentamicin . The linear range was from 10 to 500 ppm . Because of its good repeatability and simplicity, this new method could be a good alternative for the current assays given by US Pharmacopoeia and European Pharmacopoeia.

Indian Pediatr, 2004 Dec, 41(12), 1205 - 10
Prevalence and Risk Factors of Asthma and Wheeze in School-going children in Lucknow, North India; Awasthi S et al.; OBJECTIVE: To assess the prevalence of asthma and wheeze and factors associated with it in children aged 6-7 and 13-14 years . METHOD: School based, prospective survey using self/parental reporting of occurence of asthma or wheeze on pre-designed questionnaire . RESULTS: Out of 112 schools, 17 and 15 schools were randomly selected for recruitment of subjects in age group 6-7 and 13-14 years, respectively . Prevalence of asthma and wheeze reported were 2.3 PERCNT and 6.2 PERCNT, respectively, in age group 6-7 years and 3.3 PERCNT and 7.8 PERCNT, respectively, in age group 13-14 years . On the basis of adjusted odds ratio, risk factors for wheeze or asthma were tertiary education of mother, antibiotic use in the first year of life, eating pasta or fast-food or meat once or more per week and exercise once or more/week while the protective factors were intake of vegetables once or more and fruits thrice or more per week . In univariate analysis, breastfeeding was also found to be protective . CONCLUSION: Promotion of rational use of antibiotic in first year of life, avoidance of fast food and promotion of breastfeeding and intake of fruits and vegetables may reduce the risk of asthma/wheeze and should be encouraged.

J Vasc Surg, 2004 Dec, 40(6), 1234 - 7
Combined endovascular stent grafting and endoscopic injection of fibrin sealant for aortoenteric fistula complicating esophagectomy; Mok VW et al.; A 67-year-old man with previous total gastrectomy and roux-en-Y esophagojejunostomy had hematemesis 4 weeks after esophagectomy performed because of carcinoma of the esophagus . Investigation showed an aortojejunal fistula with a thoracic aortic pseudoaneurysm . Endovascular stent grafting of the pseudoaneurysm, followed by endoscopic injection of fibrin sealant for the fistula, was performed, and the infection was controlled with broad-spectrum antibiotic agents together with drainage and daily irrigation of the pseudoaneurysm sac . The fistula subsequently healed . The patient remained well 14 months after the procedure; follow-up computed tomograms at 12 months did not show any pseudoaneurysm, and there was no evidence of reopening of the fistula.

Plast Reconstr Surg, 2005 Jan, 115(1), 142 - 7
The use of anterolateral thigh perforator flaps in chronic osteomyelitis of the lower extremity; Hong JP et al.; From April of 2000 to May of 2003, 28 consecutive patients with chronic osteomyelitis of the lower extremity underwent surgical debridement and reconstruction with anterolateral thigh perforator flaps (six cases were combined with vastus lateralis muscle flaps) . All wounds were open for a minimum period of 6 weeks (average, 24.7 months; range, 6 weeks to 52 months) . The average patient age was 42.8 years (range, 18 to 71 years), there were 21 male and seven female patients, and the average follow-up period was 18.2 months (range, 5 to 41 months) . The cause of injury was an open fracture in 10 cases, secondary wound complications after reduction in eight cases, and diabetic foot in 10 cases . The surface defects ranged from 50 to 153 cm . The wounds were debrided an average of 2.5 times and then reconstructed with flap and treated with antibiotics for 6 weeks . Antibiotic beads were used in six cases and secondary bone graft procedures were performed in seven cases 3 months after the flap coverage . All 28 flaps were successful without any signs of recurrences or persistent osteomyelitis, but partial wound dehiscence was observed during early rehabilitation in two cases suspected of delayed healing caused by diabetes . These wounds healed spontaneously . All patients achieved acceptable gait function after rehabilitation . No debulking procedure was necessary in any case . Although the muscle flap is known to provide superior vascular supply, the type of flap used for coverage seems to be less critical in the final outcome, provided that total debridement and obliteration of dead spaces are achieved . A well-vascularized anterolateral thigh perforator flap was successfully used to combat infection and bring stability to wounds with chronic osteomyelitis.

Autoimmunity, 2004 Sep, 37(5), 387 - 92
Molecular Mimicry toBorrelia burgdorferi: Pathway to Autoimmunity?
Bolz DD, Weis JJ.
Lyme borreliosis is due to infection with the tick-borne spirochete Borrelia burgdorferi, and is associated with persistent infection unless treated with antibiotics . The persistent nature of infection by B . burgdorferi can lead to development of chronic disease, as found in patients infected before recognition of the effectiveness of antibiotic therapy . Much speculation has surrounded the possibility that autoimmune mechanisms are involved in chronic symptoms . In most cases, involvement of autoimmunity in Lyme disease has not received experimental support . The exception is in a small group of patients with chronic arthritis whose abnormal joint symptoms persist after apparent elimination of the bacteria . In this review, the evidence supporting autoimmune mechanisms in Lyme disease will be discussed.

Med Mal Infect, 2004 Nov, 34(11), 538 - 45
{Acute exacerbation of chronic bronchitis: patients, antibiotherapy, and guidelines}; Gaillat J et al.; OBJECTIVE: The aim of this study was to compare antibiotic prescriptions made by general practitioners to French recommendations for the management of Acute Exacerbation of Chronic Bronchitis (AECB) referring to the patient's socio-demographic data, history of Chronic Bronchitis (CB), current episode management, and quality of life . METHODS: This cross-sectional study was made on 101 general practitioners . RESULTS: Four hundred eighteen patients were included: mean age: 66 +/- 12 years; male patients 71%; mean history of CB: 13 years; cardiac comorbidity: 45%; depression: 34%; obstructive ventilatory syndrome: 64%; respiratory functional test performed: 44%; FEV1 <35%: 10% . An antibiotic was prescribed in 95% of cases . 94% of treated patients were classified as type 1 or 2, according to Anthonisen's criteria: 85% of these presented with purulent expectoration . The classification used in French recommendations was applied in 364/418 patients, 79 had simple CB, 231 had moderate obstructive CB, 43 had severe obstructive CB . The antibiotic (AB) prescriptions concerned mostly group 2 . Group 2 AB were over-prescribed in 70% of patients suffering from obstructive CB or simple CB . But group 2 AB were under-prescribed in 25% of patients suffering from severe obstructive CB . CONCLUSION: Group 1 AB prescriptions were compliant with Anthonisen's criteria in most cases but the choice of AB did not follow French recommendations, with an over-prescription of group 2 AB and a bad assessment of simple CB.

J Ethnopharmacol, 2005 Jan 15, 96(3), 597 - 601 Epub 2004 Nov 30.
Interesting biological activities from plants traditionally used by Native Australians; Pennacchio M et al.; Four plants routinely used for medicinal purposes by Native Australians were screened for various biological activities . Methanol extracts of Eremophila maculata, Acacia auriculoformis and Acacia bivenosa exhibited antibiotic effects, while Eremophila alternifolia yielded an extract that induced significant changes to the heart activity of spontaneously hypertensive rats . We report on these biological activities.

Am J Surg, 2004 Dec, 188(6), 628 - 32
Could medical intervention work for aortic aneurysms?
Baxter BT.
BACKGROUND: Aortic aneurysms represent a serious and common condition . Current therapies are based on mechanical treatment . With increased knowledge of the biochemical mechanisms responsible for aneurysm expansion, it may be possible to prevent the growth of small aneurysms . METHODS: A series of experiments performed in the investigator's laboratory during the past decade is outlined to show the evolution of our concepts of the processes underlying aneurysm formation and progression . RESULTS: Our understanding of aortic aneurysms has changed dramatically . Once thought to represent a simple degenerative process, aneurysm tissue is highly active metabolically with ongoing synthesis and degradation of matrix proteins . Several members of a family of matrix-degrading enzymes play an important role in this process . These enzymes can be inhibited by the antibiotic doxycycline . CONCLUSIONS: With a better understanding of aneurysm pathology, it may be possible in the future to inhibit the growth of small aortic aneurysms before they reach a size at which the risk of rupture is significant.

Mol Phylogenet Evol, 2005 Feb, 34(2), 371 - 81 Epub 2004 Dec 15.
Reconstructing evolutionary relationships from functional data: a consistent classification of organisms based on translation inhibition response; Briones C et al.; The last two decades have witnessed an unsurpassed effort aimed at reconstructing the history of life from the genetic information contained in extant organisms . The availability of many sequenced genomes has allowed the reconstruction of phylogenies from gene families and its comparison with traditional single-gene trees . However, the appearance of major discrepancies between both approaches questions whether horizontal gene transfer (HGT) has played a prominent role in shaping the topology of the Tree of Life . Recent attempts at solving this controversy and reaching a consensus tree combine molecular data with additional phylogenetic markers . Translation is a universal cellular function that involves a meaningful, highly conserved set of genes: both rRNA and r-protein operons have an undisputed phylogenetic value and rarely undergo HGT . Ribosomal function reflects the concerted expression of that genetic network and consequently yields information about the evolutionary paths followed by the organisms . Here we report on tree reconstruction using a measure of the performance of the ribosome: antibiotic sensitivity of protein synthesis . A large database has been used where 33 ribosomal systems belonging to the three major cellular lineages were probed against 38 protein synthesis inhibitors . Different definitions of distance between pairs of organisms have been explored, and the classical algorithm of bootstrap evaluation has been adapted to quantify the reliability of the reconstructions obtained . Our analysis returns a consistent phylogeny, where archaea are systematically affiliated to eukarya, in agreement with recent reconstructions which used information-processing systems . The integration of the information derived from relevant functional markers into current phylogenetic reconstructions might facilitate achieving a consensus Tree of Life.

Eur J Gastroenterol Hepatol, 2004 Nov, 16(12), 1309 - 14
Recurrence of Helicobacter pylori infection 1 year after successful treatment: prospective cohort study in the Republic of Yemen; Gunaid AA et al.; OBJECTIVES: To investigate the prevalence of Helicobacter pylori infection in dyspeptic patients in the Republic of Yemen and the recurrence rate 1 year after apparently successful eradication . METHODS: A total of 275 patients with chronic dyspepsia seen in one clinic were enrolled . Gastric biopsies were obtained at endoscopy and H . pylori infection was diagnosed using the rapid urease test . Patients with H . pylori infection were given either clarithromycin or metronidazole-based triple therapy . Six weeks later H . pylori status was assessed using the C-urea breath test (C-UBT) . Those who were negative for H . pylori had a further C-UBT after 1 year to establish the recurrence rate . RESULTS: The prevalence of H . pylori infection at entry to the study was 82.2% {95% confidence interval (CI) 78-87%} . The overall eradication rate 6 weeks after treatment was 49.1% (95% CI 42.6-55.6%) by intention-to-treat analysis, and 60% (95% CI 53-67%) by per-protocol analysis . Recurrence rate of H . pylori infection at 1 year was 34% (95% CI 14-45%) and the only predictor of recurrence was an excess delta C-UBT value less than 3.5 per million but equal to or greater than 2.5 per million at 6 weeks after treatment (odds ratio 2.28; 95% CI 1.17-4.44; P = 0.028) . CONCLUSION: The prevalence of H . pylori infection in dyspeptic patients in Yemen is very high, the eradication rate with standard triple therapy was unsatisfactory probably because of widespread bacterial resistance due to unrestricted antibiotic use . The recurrence rate of infection at 1 year was high, as a result of recrudescence of incompletely eradicated organisms rather than reinfection.

Drug News Perspect, 1998 Nov, 11(9), 523 - 79
Glutamate in CNS disorders as a target for drug development: an update; Parsons CG et al.; The authors provide an extensive review of new data related to the role of glutamate in CNS disorders, describing new aspects in glutamate and glutamatergic receptors-NMDA receptors, NR2B-selective antagonists, non-NMDA ionotropic glutamate receptors, N-acetylaspartylglutamate, and glutamate and glycine transporters . New findings in animal models and in human diseases-stroke, traumatic brain injury, Alzheimer's, Parkinson's and Huntington's diseases, tardive dyskinesia, ALS, olivopontcerebellar degeneration, AIDS, allergic encephalomyelitis, epilepsy, anxiety, depression, schizophrenia, liver disease, aminoglycoside antibiotic-induced hearing loss, hemiplegia, chronic pain and drug tolerance and abuse-are presented . Finally, the authors cite the progress achieved in the development of agents that interact with the glutamatergic system: NMDA channel blockers, competitive NMDA receptor antagonists, NR2B-selective antagonists, glutamate release inhibitors, glycineB antagonists, AMPA and kainate receptor antagonists, AMPA receptor-positive modulators and agents that act by modifying endogenous kynurenic acid metabolism . (c) 1998 Prous Science . All rights reserved.

Minn Med, 2004 Nov, 87(11), 42 - 4
Advanced medical care for soldiers injured in Iraq and Afghanistan; Polly DW Jr et al.; War inevitably advances medical knowledge, particularly in the area of orthopedic surgery . This article presents an overview of the types of injuries emerging from the current conflicts in Iraq and Afghanistan, the majority of which are extremity injuries, and the care soldiers are receiving on the battlefield, while being evacuated, and at Walter Reed Army Medical Center . It highlights the Army's use of new therapeutic approaches such as use of methyl methacrylate antibiotic beads, vacuum-assisted closure devices, and new prosthetic technologies.

J Math Biol . 2004 Dec 20; {Epub ahead of print}
Modeling the impact of periodic bottlenecks, unidirectional mutation, and observational error in experimental evolution; Joyce P et al.; Antibiotic resistant bacteria are a constant threat in the battle against infectious diseases . One strategy for reducing their effect is to temporarily discontinue the use of certain antibiotics in the hope that in the absence of the antibiotic the resistant strains will be replaced by the sensitive strains . An experiment where this strategy is employed in vitro {5} produces data which showed a slow accumulation of sensitive mutants . Here we propose a mathematical model and statistical analysis to explain this data.The stochastic model elucidates the trend and error structure of the data . It provides a guide for developing future sampling strategies, and provides a framework for long term predictions of the effects of discontinuing specific antibiotics on the dynamics of resistant bacterial populations.

Rev Gastroenterol Peru, 2004 Oct-Dec, 24(4), 314 - 22
{Percutaneous endoscopic gastrostomy: prospective experience at a national private center}; Yriberry Urena S et al.; Percutaneous endoscopic gastrostomy tube feeding is a safe and effective method of providing long-term enteral nutrition in patients who are unable to swallow and offers important advantages over nasogastric tub feeding . The indications of this procedure have been received and over 7 years of practice on 103 patients and 128 procedures have been experienced with Ponsky pull techniques . All patients were given vitamin K and a prophylactic antibiotic (chephalotine) prior to testing . 1.56% of major deadly complications have been reports both for reflux and aspiration at 48 and 72 hours post treatment . The most common minor complication was wound infection in 8.9% of patients . There was no further mortality during testing or while undergoing treatment in the following 30 days . All patients were suffering from post heart attack dementia and stroke (CVA) at a rate of 23.3% and 21.4%, respectively . Percutaneous endoscopic gastrostomy has become the method of choice to sustain long-term enteral nutrition.

Med Mal Infect, 2004 Jun, 34(6), 246 - 56
{Treatment and prophylaxis of opportunistic infections in the course of HIV disease: a state of the art in 2004 . Part 2: Viral, fungal and bacterial infections}; Lacombe K et al.; Remarkable progress has been made in antiretroviral therapeutics, as well as in the prophylaxis and treatment of opportunistic infections, since the beginning of the AIDS epidemic . The patient's life expectancy and quality of life have consequently improved, thanks to better management of opportunistic diseases . The introduction of protease inhibitors-containing regimen (i.e . highly active antiretroviral therapy or HAART), since 1996, has drastically reduced the incidence of opportunistic infections by restoring immunity . The large panel of antiretroviral drugs responsible for frequent sustained viral and immune responses has thus allowed a new definition of guidelines for the prophylaxis and treatment of opportunistic infections . A better use of prophylactic drugs should help to reduce the risk of drug-related toxicity and pharmaceutical interactions . It should also decrease the cost of HIV management and eventually increase compliance to treatment and quality of life.

Can Respir J, 2004 Nov-Dec, 11(8), 559 - 64
Rates and patterns of chronic obstructive pulmonary disease exacerbations; de Melo MN et al.; BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are believed to be a common occurrence in patients with COPD and are known to be associated with considerable morbidity . OBJECTIVE: To describe the frequency of treated COPD exacerbations in a large population-based cohort . SUBJECTS AND METHODS: A cohort of newly treated patients with COPD was formed from the administrative databases of Saskatchewan Health . The outcome was the occurrence of all moderate or severe exacerbations from 1990 to 1999 . Exacerbations were defined in three ways: dispensing of a prescription for a systemic antibiotic; dispensing of both a prescription for an antibiotic and a prescription for an oral corticosteroid on the same day; and requiring a hospitalization with a primary discharge diagnosis of COPD . RESULTS: There were 5645 patients who entered the COPD cohort between 1990 and 1997, of whom 4453 experienced at least one exacerbation requiring treatment during follow-up . The overall rate of acute exacerbations was 1.12/person-year . It was constant across all age groups, and was similar in both men and women (1.13/person-year versus 1.11/person-year, respectively) . The rate of exacerbations was highest in the first trimester of therapy for the disease (1.39/person-year) and stabilized thereafter at 1.04 exacerbations/person-year . CONCLUSIONS: The results indicate that in a population-based cohort of patients with COPD, the average rate of exacerbations was 1.12/person-year . Men and women had similar rates of exacerbations.

RNA, 2005 Jan, 11(1), 1 - 6
Binding of manganese(II) to a tertiary stabilized hammerhead ribozyme as studied by electron paramagnetic resonance spectroscopy; Kisseleva N et al.; Electron paramagnetic resonance (EPR) spectroscopy is used to study the binding of MnII ions to a tertiary stabilized hammer-head ribozyme (tsHHRz) and to compare it with the binding to the minimal hammerhead ribozyme (mHHRz) . Continuous wave EPR measurements show that the tsHHRz possesses a single high-affinity MnII binding site with a KD of < or =10 nM at an NaCl concentration of 0.1 M . This dissociation constant is at least two orders of magnitude smaller than the KD determined previously for the single high-affinity MnII site in the mHHRz . In addition, whereas the high-affinity MnII is displaced from the mHHRz upon binding of the aminoglycoside antibiotic neomycin B, it is not from the tsHHRz . Despite these pronounced differences in binding, a comparison between the electron spin echo envelope modulation and hyperfine sublevel correlation spectra of the minimal and tertiary stabilized HHRz demonstrates that the structure of both binding sites is very similar . This suggests that the MnII is located in both ribozymes between the bases A9 and G10.1 of the sheared G . A tandem base pair, as shown previously and in detail for the mHHRz . Thus, the much stronger MnII binding in the tsHHRz is attributed to the interaction between the two external loops, which locks in the RNA fold, trapping the MnII in the tightly bound conformation, whereas the absence of long-range loop-loop interactions in the mHHRz leads to more dynamical and open conformations, decreasing MnII binding.

Vet Res, 2005 January-February, 36(1), 101 - 116
High milk neutrophil chemiluminescence limits the severity of bovine coliform mastitis; Mehrzad J et al.; Polymorphonuclear neutrophil (PMN) function changes during mastitis . To investigate the contribution of milk PMN to the severity of Escherichia coli (E . coli) mastitis, chemiluminescence (CL) of blood and milk PMN and their efficiency to destroy coliform bacteria in the mammary gland were examined following the induction of E . coli mastitis in early lactating cows . To better assess and define the degree of mastitis severity, cows were classified as moderate and severe responders according to milk production loss in the non-infected quarters at post-infection hour (PIH) 48 . There was an inverse relationship between pre-infection milk PMN CL and colony-forming units at PIH 6 . In moderate cows, the pre-infection blood and milk PMN CL was ~ 2-fold higher than that of severe cows . The probability of severe response increased with decreasing pre-infection PMN CL . At the beginning of the infection blood and milk PMN CL was consistently higher, and milk PMN CL increased faster after infection in moderate cows . At PIH > 48 milk PMN CL in severe cows exceeded that of moderate cows . The somatic cell count (SCC) in moderate cows increased faster than colony-forming units, whereas in severe cows the results were reversed . The kinetics of CL activity for blood and milk PMN before and during the early phase of infection confirmed an impairment in PMN CL activity for severe responding cows . High pre-infection blood and milk PMN CL and the immediate increase of milk PMN CL and SCC after infection limited bacterial growth thereby facilitating the recovery of E . coli mastitis in moderate cows . Our study strengthens the idea that pre-existing milk PMN (a static part of the udder's immune defense) functions as a "cellular antibiotic" before and during infection, and low milk PMN CL is a risk factor for bovine coliform mastitis.

Int Braz J Urol, 2004 Sep-Oct, 30(5), 403 - 5
Vesical metastasis of gastric adenocarcinoma; Antunes AA et al.; Metastatic vesical tumors are rare, and constitute approximately 1% of all neoplasias affecting this organ . The authors report the case of a 63-year old woman with vesical metastasis of gastric adenocarcinoma . Patient presented signs of cachexia and complained of left lumbar pain and dysuria unresponsive to antibiotic therapy for approximately 5 months . She reported a previous partial gastrectomy due to ulcerative undifferentiated gastric adenocarcinoma 1 year and 9 months before . Cystoscopy revealed an extensive vegetative lesion in bladder, occupying its entire mucosal surface . The biopsy revealed metastatic signet-ring cell adenocarcinoma.

J Neurol Sci, 2005 Jan 15, 228(1), 41 - 8 Epub 2004 Nov 05.
Referral and previous care of children with meningitis in Nigeria: implications for the presentation and outcome of meningitis in developing countries; Akpede GO et al.; There is a paucity of data on the referral of children with meningitis in developing countries, and on the relationship of presentation and outcome to previous care . Referral and previous care were investigated in 281 post-neonatal children treated in two tertiary centres . Data were obtained through the review of referral notes from orthodox health facilities, interview of parents/guardians and review of admission notes . Forty-four (16%) children were facility-referred and 81 (29%) self-referred from orthodox facilities while 156 (55%) were self-referred without previous care in these facilities . The facility-referrals (n=44) included 19 (43%) with meningitis on treatment, 13 (30%) with suspected meningitis and 12 (27%) with unsuspected meningitis . Twenty-two (50%) were referred because of deterioration, partial response or non-response to treatment, 5 (11%) on request by the parents, 9 (21%) on the suspicion of meningitis or other neurological disorder and 7 (16%) for mixed reasons . No reason was given in 1 case of meningitis on treatment . Among the 19 children referred with meningitis on treatment, only 1 was referred within 24 h of diagnosis, a confirmatory lumbar puncture was done only in 7, and only 10 of 18 (no data in 1 case) were on reasonably appropriate antibiotic regimens . Previous care in orthodox facilities was significantly associated with delayed presentation (>3 days of illness, p<0.001), partial treatment (p<0.001), lack of typical signs (p<0.05), severe illness (p<0.01), and adverse outcome (death or recovery with neurological sequelae, p<0.05) . Limited recognition of the possibility of meningitis in acutely ill children and an inadequate referral practice may account for these effects . A clear delineation of referral needs might reduce the magnitude of these problems.

No Shinkei Geka, 2004 Dec, 32(12), 1263 - 8
{Four cases of the infectious cerebral aneurysms}; Oshita J et al.; The authors evaluated various clinical courses of ruptured infectious cerebral aneurysms associated with infective endocarditis in 4 patients . The first case: A 60-year-old male, who had a large hematoma resulting from rupture of a distal anterior cerebral artery aneurysm at the left frontal lobe co-existing with cerebral infarction at the right temporo-occipital lobe, with complications of renal and liver embolisms and pyogenic spondylitis, was treated with antibiotic therapy . However, he died of rupture of another newly formed aneurysm 29 days after onset . The second case: A 71-year-old female presented cerebral infarction in the right occipital lobe at onset . Two days later, abrupt occurrence of a large hematoma at the left parietal lobe led to deterioration of her consciousness . She underwent emergent evacuation of a large hematoma containing the infectious cerebral aneurysm proven histologically afterwards . The third patient: A 49-year-old female was suffered from a large hematoma and subdural hematoma accompanied distal posterior cerebral artery aneurysm at the right occipital lobe . She was operated by removal of the hematoma and the aneurysm proven as a bacterial infectious aneurysm . The fourth patient: A 71-year-old female had hemiplegia caused by a brain abscess and cerebral hemorrhage in the right temporal lobe and a distal middle cerebral artery aneurysm adjacent to the same region . Trapping of the aneurysm was undertaken and clinical course was uneventful . Attention needs to be paid to the various cerebrovascular condition arising from the bacterial embolus of infective endocarditis.

Ann Ital Chir, 2004 May-Jun, 75(3), 353 - 6
{Bleeding gastric lymphoma: report of two cases}; Benfatto G et al.; We report two cases of bleeding gastric lymphoma . The stomach is the most common site of primary extranodal Non-Hodgkins Lymphomas . The best treatment for primary gastric lymphoma has not yet been defined . For many years the treatment of choice has been the gastric resection . Helicobacter pylori (H . pylori) has been associated with many gastric pathologies, including gastric lymphoma . Eradication of H . pylori is now considered essential for the treatment of this pathology, and usually consists of antibiotic therapy, combined with acid suppression by a proton pump inhibitor . This simple treatment in patients with low grade histology and tumor confined to the stomach can often obviate the need for surgical intervention . Surgery is a necessary treatment, independently of the grading and the staging of lymphoma, in the bleeding complication as the cases we showed.

Cornea, 2005 Jan, 24(1), 66 - 71
Comparison of corneal surface effects of gatifloxacin and moxifloxacin using intensive and prolonged dosing protocols; Herrygers LA et al.; PURPOSE: To compare the effects of the commercial formulations of moxifloxacin and gatifloxacin on rabbit corneal epithelium using two dosing protocols: high-frequency dosing for bacterial keratitis and cataract surgery prophylaxis . METHODS: Forty eyes of 20 New Zealand white rabbits were randomized to receive topical gatifloxacin, topical moxifloxacin, or no drops as controls . Eighteen eyes received 1 drop of antibiotic every 5 minutes for 15 minutes followed by 1 drop every 15 minutes for 4 hours . Twelve eyes received topical gatifloxacin or topical moxifloxacin 4 times a day for 10 days . Rabbits were euthanized, eyes enucleated, and the corneas separated, washed, and fixed; scanning electron microscopy was performed . Photomicrographs of three separate areas from the corneal apex were taken at x1200 and x3000 for each cornea . Two masked, experienced examiners then graded the corneal epithelial damage . RESULTS: In the high-frequency dosing group, mean corneal damage score for eyes treated with gatifloxacin was 1.593, that for moxifloxacin was 1.407, and control was 1.000 . No statistically significant difference was found between gatifloxacin and moxifloxacin (P = 0.41), gatifloxacin and control (P = 0.14), or moxifloxacin and control (P = 0.23) . In the cataract surgery prophylaxis group, mean corneal damage scores for eyes treated with gatifloxacin was 1.167, that for moxifloxacin was 1.368, and control was 1.000 . No statistically significant difference was found between gatifloxacin and moxifloxacin (P = 0.23), gatifloxacin and control (P = 0.08), or moxifloxacin and control (P = 0.23) . CONCLUSION: Despite differences in formulations, with short-term dosing neither gatifloxacin nor moxifloxacin appears to be toxic to the corneal epithelium in this rabbit model.

Plant Mol Biol, 2004 Sep, 56(2), 203 - 16
Stable transformation of the cotton plastid genome and maternal inheritance of transgenes; Kumar S et al.; Chloroplast genetic engineering overcomes concerns of gene containment, low levels of transgene expression, gene silencing, positional and pleiotropic effects or presence of vector sequences in transformed genomes . Several therapeutic proteins and agronomic traits have been highly expressed via the tobacco chloroplast genome but extending this concept to important crops has been a major challenge; lack of 100 homologous species-specific chloroplast transformation vectors containing suitable selectable markers, ability to regulate transgene expression in developing plastids and inadequate tissue culture systems via somatic embryogenesis are major challenges . We employed a 'Double Gene/Single Selection (DGSS)' plastid transformation vector that harbors two selectable marker genes (aph A-6 and npt II) to detoxify the same antibiotic by two enzymes, irrespective of the type of tissues or plastids; by combining this with an efficient regeneration system via somatic embryogenesis, cotton plastid transformation was achieved for the first time . The DGSS transformation vector is at least 8-fold (1 event/2.4 bombarded plates) more efficient than 'Single Gene/Single Selection (SGSS)' vector (aph A-6; 1 event per 20 bombarded plates) . Chloroplast transgenic lines were fertile, flowered and set seeds similar to untransformed plants . Transgenes stably integrated into the cotton chloroplast genome were maternally inherited and were not transmitted via pollen when out-crossed with untransformed female plants . Cotton is one of the most important genetically modified crops (120 billion US dollars US annual economy) . Successful transformation of the chloroplast genome should address concerns about transgene escape, insects developing resistance, inadequate insect control and promote public acceptance of genetically modified cotton.

Ann N Y Acad Sci, 2004 Nov, 1026, 118 - 24
Comparative study of three surgical treatments for two forms of the clinical presentation of bovine pododermatitis; Silva LA et al.; In this study, 1013 animals showing signs of clinical pododermatitis were examined and divided into five unevenly numbered groups . Affected animals in Groups I and II showed only signs of vegetative interdigital pododermatitis . The lesions were surgically removed and either protected with bandages (in Group I) or cauterized with incandescent iron (Group II) . The animals in Groups III, IV, and V, showed signs of necrotic pododermatitis . These were treated with different protocols after the necrotic tissue was surgically removed: in Group III, the lesion was cauterized; in Group IV, the wound was protected with bandages; and in Group V, both the second and the third phalanges were amputated . There was a statistically significant relapse difference between Group III and Group V, as well as a difference among Group IV and Group V animals, and there were fewer relapses among the latter . The treatment used in Groups II and III proved to be efficient and inexpensive . Amputation of the phalanges was the treatment that resulted in fewer relapses among all protocols, despite its mutilating effect . The association of a local and parenteral treatment with an antibiotic agent, as well as the use of foot baths, contributed greatly to a fast recovery.

East Mediterr Health J, 2002 Jul-Sep, 8(4-5), 550 - 5
General practitioner prescribing patterns in Babol city, Islamic Republic of Iran; Moghadamnia AA et al.; To determine patterns of prescribing in Iranian primary care, we analysed 4000 randomly selected prescriptions from 52 general practitioners (GPs) in Babol city during 1999-2000 . The mean number of drugs prescribed per encounter was 4.4 +/- 1.7, with 98% prescribed by generic name . The most commonly prescribed items were non-steroidal anti-inflammatory drugs (62.9% of encounters) and antibiotics (61.9%), followed by central nervous system drugs, gastrointestinal tract drugs, corticosteroids, vitamins and cardiovascular system drugs respectively . Injections were prescribed in 58.0% of encounters . Female and male doctors had significantly different antibiotic prescribing patterns . Our study confirms the tendency of GPs to overprescribe.

Org Biomol Chem, 2005 Jan 7, 3(1), 39 - 47 Epub 2004 Nov 15.
Conformational analysis of oleandomycin and its 8-methylene-9-oxime derivative by NMR and molecular modelling; Novak P et al.; Conformations of the 14-membered macrolide antibiotic oleandomycin and its 8-methylene-9-oxime derivative were determined in various solvents . The experimental NMR data-coupling constants and NOE contacts-were compared with the results of molecular modelling-molecular mechanics calculations and molecular dynamics simulations . The conformational changes, on the right-hand side of the 14-membered ring, affected mostly the (3)J(H2,H3) values and NOE crosspeaks H3 or H4 to H11 . Oleandomycin was found to be present predominantly in the C3-C5 folded-in conformations in DMSO-d(6) solution, whereas in buffered D(2)O, acetone-d(6) and CDCl(3), there was a mixture of folded-in and folded-out conformational families . The predominant conformation of the 8-methylene-oleandomycin-9-oxime derivative in solution was a folded-out one although different amounts of folded-in conformation were also present depending on the solvent . Oleandrose and desosamine sugar moieties adopted the usual and expected chair conformation . The conformation around the glycosidic bonds, governing the relative orientation of sugars vs . the lactone ring, showed a certain flexibility within two conformationally close families . We believe that by combining the experimental NMR data and the molecular modelling techniques, as reported in this paper, we have made significant progress in understanding the conformational behaviour and properties of macrolides . Our belief is based on our own current studies on oleandomycins as well as on the previously reported results and best practices concerning other macrolides . A rational for macrolide conformational studies and advances in methodology has been suggested accordingly.

Vestn Otorinolaringol, 2004, (5), 17 - 20
{Effects of extrastimulation on morphofunctional state of cochlear stria vascularis}
{Postradiation dental extractions}
Chaux-Bodard AG, Gourmet R, Montbarbon X, Bodard S, Breton P.

Centre Leon Berard, 28, rue Laennec, 69373 Lyon 08 . anneetsteph.bod@freesbee.fr

INTRODUCTION: Healing may fail after postradiation dental extractions, with a risk of followed osteoradionecrosis, and its dramatic prognosis . We propose a protocol for postradiation extractions . MATERIAL AND METHODS: From January 2000 to December 2001, 107 patients underwent 287 dental extractions after radiation therapy: 80.5% in mandibular jaw, average radiation dose 61.6 Gy, average time between radiation and extraction 6 years . Extractions were performed under general anesthesia, diazanalgesia or local anesthesia, and extraction wounds were sutured after insertion of a collagenic sealant impregnated with gentamicin . General antibiotic prophylaxy was given . RESULTS: Healing failed in only two cases . The first case involved early-stage osteoradionecrosis and the second a tumoral localization . The rate of post-extraction osteoradionecrosis was thus 0.35% . DISCUSSION: A strict protocol associating non-traumatic surgery and an alveolar sealant can considerably decrease the risk of osteoradionecrosis after dental extraction in radiated bone.

Int J STD AIDS, 2004 Dec, 15(12), 815 - 21
Chlamydial infection in women along the US-Mexico border; Baldwin SB et al.; Few studies have reported on sexually transmitted infections at the US-Mexico border, so the prevalence of Chlamydia trachomatis in this population remains uncertain . This binational project investigated the prevalence of, and risk factors for, C . trachomatis among women along the Arizona, US-Sonora, Mexico border . Women who self-referred for routine gynaecological care were invited to complete an interviewer-administered questionnaire and to undergo a Pap smear, C . trachomatis test, and HPV test . In 2270 women, C . trachomatis prevalence overall was 8.2% as measured by hybrid capture and 2.6% by enzyme immunoassay . Infection was associated with young age, a history of new sexual partner(s) in the previous three months, HPV infection, and proximity of clinic to the international border . Antibiotic use in the previous 30 days was associated with decreased odds of infection . Women in Arizona-Sonora border communities are at increased risk for C . trachomatis infection compared to women attending clinics in non-border locations.

Phys Rev E Stat Nonlin Soft Matter Phys . 2004 Oct;70(4 Pt 1):041912 . Epub 2004 Oct 29.
Interaction of a polar molecule with an ion channel; Levadny V et al.; The binding of a polar macromolecule to a large ion channel is studied theoretically, paying special attention to the influence of external conditions (applied voltage and ion strength of solution) . The molecule behavior in bound state is considered as random thermal fluctuations within a limited fraction of its phase space . The mean duration of molecule binding (residence time tau r) is represented as the mean first passage time to reach the boundary of that restricted domain . By invoking the adiabatic approximation we reduce the problem to one dimension with the angle between macromolecule dipole and channel axes being the key variable of the problem . The model accounts for experimental measurements of tau r for the antibiotic Ampicillin within the bacterial porin OmpF of Escherichia coli . By assuming that the electrical interaction between Ampicillin dipole and OmpF ionizable groups affects the fluctuations, we find that the biased residence time-voltage dependence observed in experiments is the result of the strong transversal electric field in OmpF constriction with a tilt approximately 30 degrees aside the cis side.

Herz, 2004 Dec, 29(8), 802 - 805
Effectiveness of Intrapericardial Administration of Streptokinase in Purulent Pericarditis; Zbyszek Tomkowski W et al.; BACKGROUND AND PURPOSE: : Purulent pericarditis is very rare . However, among patients suffering from this disease the mortality rate is very high . The aim of this study was to evaluate the effectiveness and side effects of intrapericardial streptokinase administration in patients with confirmed purulent pericarditis . PATIENTS AND METHODS: : Three patients, one 50-year-old man and two women aged 64 and 40 years, who were admitted to the intensive care unit (ICU) due to purulent pericarditis, entered the study . In all three cases a subxiphoid pericardiotomy followed by insertion of a drainage line into the pericardial space was performed . Antibiotic therapy was started immediately on admission to the hospital . Despite continued antibiotic therapy in all three patients, daily drainage from the pericardium-during several days after surgery-staggered between 50-200 ml/day . Due to considerable purulent pericardial drainage loculations and/or fibrin deposits confirmed by echocardiography, streptokinase (500,000 IU dissolved in 50 ml of normal saline) was administered into the pericardial space over 10 min, using the previously inserted drainage catheter . This regimen was repeated after 12 and 24 h . The total dose of streptokinase was 1,500,000 IU . RESULTS: : The clinical effect of intrapericardial streptokinase administration was excellent . Several days after intrapericardial administration of streptokinase, drainage of purulent pericardial fluid stopped . No complications associated with intrapericardial streptokinase administration were observed . In the follow-up echocardiography (in two patients repeated 6 and 9 months after delivery of streptokinase), pericardial fluid and echocardiographic signs of pericardial constriction were not observed . CONCLUSION: : Intrapericardial administration of streptokinase in purulent pericarditis is effective and safe.

Mund Kiefer Gesichtschir . 2004 Dec 14; {Epub ahead of print}
{Incorporation of multiple foreign bodies due to borderline personality disorder Literaturubersicht und Fallbeschreibung.}; Hermes D et al.; BACKGROUND: Autoaggressive behaviour is one of the pathognomonic characteristics in patients with borderline personality disorder . Clinical symptoms of such behaviour can be the self-induced incorporation of foreign bodies . In the head and neck area, this form of autoaggressivity causes primary or secondary infectious complications with different clinical manifestations . Below follows a description of diagnosis, therapy and follow-up of such a case, comparing our own findings with the corresponding literature.CASE REPORT: A 24-year-old woman with manifest borderline personality disorder was referred to the Department of Maxillofacial Surgery after developing a swelling in the infra-auricular region . After antibiotic therapy failed to reduce inflammatory symptoms, local revision was performed including excision of two metallic foreign bodies . Comprehensive radiological evaluation identified multiple foreign bodies in the head and neck region and lower arms . A total of 76 metallic foreign bodies was removed surgically . During early surgical follow-up and subsequent psychiatric treatment, the patient incorporated new foreign bodies.DISCUSSION: The case reported represents a pattern of foreign body incorporation which is unusual based on review of the literature but characteristic for patients with borderline personality disorder . Diagnostics and therapy require an individual concept which only can be implemented in close co-operation with psychiatrists . Secondary clinical benefit derived from surgical diagnostics and therapy as well as the possibility of autoaggressive relapse have to be taken into consideration.

J Clin Gastroenterol, 2005 Jan, 39(1), 64 - 7
Hepatitis in a United States tertiary referral center; Galan MV et al.; BACKGROUND/GOALS: There are limited data regarding the frequency and proportionality of drug-induced hepatotoxicity in the United States . We sought to determine the scope of nonfulminant drug-induced hepatitis as seen in a community-based hepatology referral service . STUDY: From a population of 4,039 outpatients referred for evaluation of acute (n = 96) and chronic (n = 3,943) liver disease over a 10-year period, we reviewed the records of those patients diagnosed with acute bona fide drug-induced hepatitis . RESULTS: Thirty-two patients presented with self-limited acute drug-induced hepatitis, representing 0.8% of all hepatology patients and 33% of those patients presenting with acute liver injury . Antibiotics (amoxicillin/clavulanic acid, minocycline, nitrofurantoin, an investigational ketolide antibiotic, trimethoprim-sulfamethoxazole, and trovafloxacin) were the class of drugs most frequently implicated (14 of 32; 44%), while amiodarone was the single agent most commonly associated with liver injury (7 of 32; 22%) . The mean age of affected patients was 52.2 years, and we found a male predominance (18 of 32; 56%) . The mean time to biochemical resolution after discontinuation of the offending agent was 14.1 weeks . CONCLUSIONS: Drug-induced hepatitis is an uncommon entity in clinical hepatology but does represent a significant proportion of acute self-limited liver disease in the United States . Antibiotics and amiodarone were the most common drug culprits in our population . Time to resolution following the discontinuation of the offending agent may be protracted . Prospective studies are needed to further assess the burden of drug-induced liver injury.

Zhi Wu Sheng Li Yu Fen Zi Sheng Wu Xue Xue Bao, 2004 Apr, 30(2), 121 - 6
{Excision of selectable marker gene from transgenic plant}; Lu HJ et al.; Currently used plant transformation systems require selectable marker genes encoding antibiotic or herbicide resistance, along with the gene of interest, to select transformed cells from a large population of mostly untransformed cells . The continued presence of these selectable markers, especially in food crop, is of increasing public concern . The generation of selectable marker-free transgenic plant is one of the new projects in plant biotechnology research . Two techniques, segregation excision and recombination excision, for removal of selectable marker genes are described in this article . The advances in producing selectable marker-free transgenic plants are reviewed too.

Ann Pharmacother . 2004 Dec 14; {Epub ahead of print}
Verapamil Toxicity Resulting from a Probable Interaction with Telithromycin (February); Reed M et al.; OBJECTIVE: To report a case of hypotension and bradyarrhythmia caused by verapamil toxicity in a patient prescribed telithromycin . CASE SUMMARY: A 76-year-old white woman receiving verapamil 180 mg/day for hypertension experienced a sudden onset of shortness of breath and weakness and was found to be profoundly hypotensive and bradycardic, with a systolic blood pressure of 50-60 mm Hg and a heart rate of 30 beats/min . She had been taking telithromycin 800 mg/day for 2 days previously for acute sinusitis . The patient was treated with crystalloids, vasopressors, and transvenous pacing . Approximately 72 hours after admission, her blood pressure and heart rate rapidly returned to normal, and she was discharged several days later . DISCUSSION: Telithromycin is a known substrate of the CYP3A4 system, and several pharmacokinetic interactions can occur by displacement of other drugs from this system . Verapamil is metabolized through several cytochrome P450 isoenzyme systems . Although there are no previous reports of an interaction between these drugs, other possible causes for the patient's symptoms were excluded and the diagnosis of a probable interaction between verapamil and telithromycin leading to verapamil toxicity was made . CONCLUSIONS: Telithromycin is a ketolide antibiotic approved for treatment of respiratory tract infections and acute sinusitis . The potential for clinically significant drug interactions should be considered before using this agent, especially in patients taking other drugs that are metabolized through the CYP3A system . Caution should be exercised when considering the use of this antibiotic in patients receiving verapamil.

J Heart Valve Dis, 2004 Nov, 13(6), 997 - 1004
Impact of echocardiography in the short- and long-term prognosis of patients with infective endocarditis and negative blood cultures; Zamorano J et al.; BACKGROUND AND AIM OF THE STUDY: Higher morbidity and mortality have been attributed to patients suffering endocarditis but with negative blood cultures . The study aim was to determine whether, in the present era of routine echocardiography, patients with negative-culture endocarditis had a worse short- and long-term outcome, and whether outcomes in patients with true negative and aborted positive blood cultures were different . METHODS: When endocarditis was clinically suspected, an early (<24 h) echocardiographic examination was performed in all patients, regardless of blood culture results . In total, 151 patients diagnosed with infective endocarditis (IE) comprised the study group . Among these patients, 40 (26%) had negative blood cultures, and 28 of this subgroup (70%) had received previous antibiotic therapy . Short- and long-term features and prognosis were compared between both groups . The combined main end-point was death or need for surgical repair . RESULTS: Similar anatomic and clinical characteristics were present among those patients with positive and negative cultures . In addition, mortality and need for surgery with regard to short- and long-term follow up of both groups was similar . There were no significant differences between patients with true- or aborted-negative cultures in terms of short- and long-term prognosis . CONCLUSION: No differences in short- and long-term prognosis were seen among patients with IE and positive versus negative blood cultures . The prognosis was also similar between those with true negative culture versus aborted negative cultures . Early echocardiography in patients with clinically suspected IE may have changed the outcome in patients with negative cultures.

Infection, 2004 Dec, 32(6), 350 - 5
Concentrations of macrophage inflammatory proteins MIP-1alpha and MIP-1beta and interleukin 8 (il-8) in lyme borreliosis; Grygorczuk S et al.; BACKGROUND: Components of the spirochete Borrelia burgdorferi sensu lato ( B . burgdorferi s.l.) do not have chemotactic activity . However, B . burgdorferi s.l . causes a chemotactic response, probably by stimulating synthesis of cytokines of the chemokine family by host cells . Our aim was to confirm that the synthesis of chemokines is increased in Lyme borreliosis and that they may account for leukocyte migration, thus being involved in inflammatory response . MATERIALS AND METHODS: We measured concentrations of chemokines: interleukin 8 (Il-8) and macrophage inflammatory protein 1alpha and 1beta (MIP-1alpha, -1beta) in serum of 20 patients with erythema migrans (early localized infection, group I), of 19 patients with Lyme arthritis (chronic infection, group II), and in serum and cerebrospinal fluid (CSF) of 20 patients with neuroborreliosis (early disseminated infection, group III), before and after 2 weeks of antibiotic therapy (examinations 1 and 2), as well as in the sera of 12 healthy blood donors and CSF of ten patients in whom Lyme borreliosis and meningitis were excluded (control group) . Interleukin 1beta (Il-1beta) level in serum and CSF and pleocytosis of CSF were assessed simultaneously . RESULTS: The mean concentrations of all studied chemokines in serum were significantly elevated in all study groups in examination 1 and decreased in examination 2 . The concentration of Il-8 in serum was higher in group I and the concentration of MIP-1alpha in group III was higher in comparison with group II . Serum concentrations of all chemokines in group I and III correlated with the concentration of Il-1beta, while in group II this correlation appeared only for Il-8 in examination 2 . Concentrations of all chemokines in CSF were significantly increased, but as for MIP-1alpha and 1beta they remained lower than in serum . The concentration of Il-8 in CSF was variable and reached values several fold higher than in the serum in some patients . There was no correlation between chemokine concentrations and CSF pleocytosis . CONCLUSION: The synthesis of chemokines (Il-8, MIP-1alpha and 1beta) is increased in Lyme borreliosis and, at least in the early stages of the disease, is related to the synthesis of Il-1beta . Chemokine concentrations depend on the clinical form of Lyme borreliosis, with a tendency for higher values in early infection (erythema migrans and neuroborreliosis) . Of the chemokines studied, Il-8 created a chemotactic gradient towards the inflammation site, and thus might be responsible for leukocyte migration.

Protein Expr Purif, 2005 Jan, 39(1), 8 - 17
Tetracycline-regulated highly inducible expression of the human prion protein in murine 3T3 cells; Stuke AW et al.; To provide an in vitro system that allows inducible or conditional overexpression of human prion protein (PrP), we have established a tetracycline (Tc)-regulated system in murine 3T3 L1 fibroblast cells . A replacement-type gene targeting vector cassette was constructed to express the human fatal familial insomnia (FFI) prion protein gene (PRNP) under control of a Tc-responsive element . Following stable integration of the vector into 3T3 Tet-Off cells, we have isolated and characterised six 3T3 L1 pTet-Off FFI clones . These clones were analysed by PCR and their expression level was determined by Western blot using species specific monoclonal antibodies (anti-mouse and human 3B5, 4F2, 12F10, 11C6, 8G8, and 14D3; anti-mouse l3) . Addition of the antibiotic Tc to the culture medium turned off expression of human PrP . This supression was repeatedly reversible . However, no significant transcriptional leakiness of repressed P(min)CMV promoter was observed . In the absence of Tc, expression of human PrP was induced 10- to 20-fold as estimated from densitometric analyses . PrP was analysed by Proteinase K (PK) digestions and found to be PK sensitive . Subcellular fractionation revealed that PrP was located mainly in the cytoplasmic membrane fraction . Furthermore, we partially purified PrP by PrP-specific copper-binding . After immobilised metal affinity chromatography, majority of PrP showed a molecular weight consistent with non-glycosylated PrP . These clones offer a new tool to facilitate the investigation of PrP interaction with potential cellular ligands and PrP ex vivo propagation.

Biochemistry, 2004 Dec 21, 43(50), 15936 - 45
Carboxymethylproline synthase from Pectobacterium carotorova: a multifaceted member of the crotonase superfamily; Gerratana B et al.; The simplest carbapenem antibiotic, (5R)-carbapen-2-em-3-carboxylic acid, is biosynthesized from primary metabolites in Pectobacterium carotorova by the action of three enzymes, carboxymethylproline synthase (hereafter named CarB), carbapenam synthetase, and carbapenem synthase . CarB, a member of the crotonase superfamily, catalyzes the formation of (2S,5S)-5-carboxymethylproline from malonyl-CoA and l-pyrroline-5-carboxylate . In this study we show that, in addition, CarB catalyzes the independent decarboxylation of malonyl-CoA and methylmalonyl-CoA and the hydrolysis of CoA esters such as acetyl-CoA and propionyl-CoA . The steady-state rate constants for these reactions are reported . We have identified the intermediates in the CarB reactions with l-pyrroline-5-carboxylate and malonyl-CoA or methylmalonyl-CoA as the CoA esters of (2S,5S)-5-carboxymethylproline and (2S,5S)-6-methyl-5-carboxymethylproline, respectively . The data provided indicate that these intermediates partition between completing turnover and dissociating from the enzyme . On the basis of the steady-state rate constants measured for the CarB-catalyzed hydrolysis of synthetic (2S,5S)-5-carboxymethylprolyl-CoA and for the CarB reaction with malonyl-CoA and l-pyrroline-5-carboxylate, we have calculated the rate constants for each step of these reactions . The results identify CarB as a particularly interesting member of the crotonase superfamily that combines in one net reaction three activities of this superfamily, decarboxylation, C-C bond formation, and CoA ester hydrolysis.

Curr Opin Pulm Med, 2005 Jan, 11(1), 14 - 20
The hygiene hypothesis and asthma; Ramsey CD et al.; PURPOSE OF REVIEW: Reduced exposure to childhood infections may explain the increased prevalence of allergic diseases in industrialized countries (the hygiene hypothesis) . This review will examine recent epidemiologic studies of the hygiene hypothesis and asthma . RECENT FINDINGS: Recent studies have confirmed previous findings of an inverse association between increased exposure to other children during childhood and either allergen sensitization or hay fever . However, there is conflicting evidence regarding the relation between exposure to other children and asthma . Although it has been hypothesized that vaccinations may influence the development of asthma, recent findings do not support this association . Serologic evidence of exposure to certain gastrointestinal pathogens (eg, hepatitis A virus) has been inversely associated with either allergen sensitization or asthma in some, but not all, recent studies . Although heavy infestation with certain parasites (eg, helminths) is protective against allergen sensitization, there is conflicting evidence regarding the relation between parasitic infection and asthma . The results of recent studies suggest that the relation between endotoxin exposure and asthma is complex and likely influenced by factors related to the exposure itself, the host, and other covariates . Although it has been postulated that antibiotic use in early life is a risk factor for asthma, this hypothesis is not supported by recent findings . SUMMARY: For every exposure studied with regard to the hygiene hypothesis, there are inconsistent findings in relation to asthma . The hygiene hypothesis is not likely to be the sole explanation for the ongoing asthma epidemic in industrialized nations.

J Vasc Interv Radiol, 2004 Dec, 15(12), 1415 - 21
Risk of intrauterine infectious complications after uterine artery embolization; Rajan DK et al.; PURPOSE: To identify risk factors for the development of intrauterine infection following uterine artery embolization . MATERIALS AND METHODS: A retrospective review of uterine artery embolizations (UAE) performed for the treatment of symptomatic fibroids from January 2000 to July 2003 was conducted . With logistic regression and the Fisher exact test, multiple variables were analyzed as predictors for intrauterine infectious complications requiring medical and/or surgical therapy, including the use of preprocedural antibiotics, embolic agent used, quantity of embolic material, location of fibroids (submucosal, nonsubmucosal), and size and location of the dominant fibroid . RESULTS: A total of 414 UAE procedures were performed in 410 patients with a technical success rate of 99% . Average age of the patient cohort was 42.8 years (SD, 5.8 years) . One hundred forty-eight patients (36.1%) had submucosal fibroids or fibroids projecting submucosally, 262 patients (63.9%) had nonsubmucosal fibroids . Intrauterine infectious complications requiring intravenous antibiotic therapy and/or surgery occurred in five patients (1.2%) . A total of five infectious complications requiring therapy occurred in the submucosal group (3.4%) and none in the nonsubmucosal group . Patients within the submucosal group were more likely to develop intrauterine infectious complications than patients with nonsubmucosal fibroids based on univariate analysis (P = .006) but with logistic regression, the association was not significant (P = .079) . No significant difference with embolic agent, quantity of embolic particles, use of preprocedure antibiotics, or size of or location of the dominant fibroid was found . CONCLUSION: No specific risk factor for intrauterine infection following UAE was identified in this study . Infection after UAE is rare and appears to be a sporadic occurrence . Nevertheless, close surveillance is warranted in all women following UAE given the potential morbidity of this complication.

J Matern Fetal Neonatal Med, 2004, 16 Suppl 2, 13 - 6
Early diagnosis of bacterial infection in the neonate; Volante E et al.; The diagnosis of neonatal bacterial infection remains one of the greatest and most tantalizing challenges to neonatologists . At birth it must be based on the history of pregnancy and take into account a number of now well-defined risk factors . In addition, if promptly started, antibiotic therapy can reduce its sequelae and improve the prognosis . However, the number of tests that obstetricians can rely on for the diagnosis of infection is quite limited . Tests of maternal inflammation indicators have a low specificity, culture tests are not immune from the risk of contamination, and the measurement of interleukins in the amniotic fluid and maternal blood serum is not yet routine . Observation of clinical signs therefore remains crucial to neonatologists, at the same time that new and more sophisticated laboratory tests enable them to establish a diagnosis of infection at an increasingly earlier stage . In recent years, several infection markers have been investigated, such as procalcitonin and especially C-reactive protein (CRP) . Currently, the measurement of plasma concentrations of interleukins (IL), IL-6 and IL-8 in particular, appears to be one of the most sensitive and specific infection indicators in newborns . Cytokine levels are increased even before infants develop any clinical symptoms and routine laboratory tests turn positive . However, owing to their short half-life, their sensitivity decreases after 12-24 h from the onset of inflammation, increasing the risk of false negatives . Ideally, they should then be used in combination with other inflammation indicators, such as CRP . The measurement of cytokines and other new inflammatory markers might be helpful in the early diagnosis of both early-onset infection (assay in umbilical cord blood) and late-onset infection (serial assays performed during the stay in the neonatal intensive care unit) . In spite of their time-consuming techniques, culture tests remain of the utmost importance to plan a targeted treatment; blood culture, in particular, is crucial to the diagnosis of sepsis.

J Mol Biol, 2005 Jan 28, 345(4), 745 - 58
Atomic force microscopy study of the structural effects induced by echinomycin binding to DNA; Tseng YD et al.; Atomic force microscopy (AFM) has been used to examine the conformational effects of echinomycin, a DNA bis-intercalating antibiotic, on linear and circular DNA . Four different 398 bp DNA fragments were synthesized, comprising a combination of normal and/or modified bases including 2,6-diaminopurine and inosine (which are the corresponding analogues of adenine and guanosine in which the 2-amino group that is crucial for echinomycin binding has been added or removed, respectively) . Analysis of AFM images provided contour lengths, which were used as a direct measure of bis-intercalation . About 66 echinomycin molecules are able to bind to each fragment, corresponding to a site size of six base-pairs . The presence of base-modified nucleotides affects DNA conformation, as determined by the helical rise per base-pair . At the same time, the values obtained for the dissociation constant correlate with the types of preferred binding site available among the different DNA fragments; echinomycin binds to TpD sites much more tightly than to CpG sites . The structural perturbations induced when echinomycin binds to closed circular duplex pBR322 DNA were also investigated and a method for quantification of the structural changes is presented . In the presence of increasing echinomycin concentration, the plasmid can be seen to proceed through a series of transitions in which its supercoiling decreases, relaxes, and then increases.

J Int Med Res, 2004 Nov-Dec, 32(6), 590 - 607
Comparative clinical study of cefcapene pivoxil and cefteram pivoxil in chronic respiratory tract infections by a double-blind method; Saito A et al.; In a double-blind study, the efficacy and safety of the novel cephem antibiotic cefcapene pivoxil (CFPN-PI; 450 mg/day) was compared with cefteram pivoxil (CFTM-PI; 600 mg/day) in 171 patients with chronic respiratory tract infections . There was no significant difference between the clinical efficacy of the two drugs (80.2% for CFPN-PI versus 78.9% for CFTM-PI) . There was no significant difference in the rate of elimination of the causative bacteria (60.5% for CFPN-PI versus 65.9% for CFTM-PI) . Side-effects were observed in 6.0% of patients treated with CFPN-PI compared with 6.4% of patients treated with CFTM-PI . There were no significant differences in incidence of abnormal laboratory findings following treatment with the two drugs (13.9% for each), and none of the side-effects was severe . We conclude that CFPN-PI (450 mg/day) was as effective and as well tolerated as CFTM-PI (600 mg/day) in the treatment of chronic respiratory tract infections.

Pharmazie, 2004 Nov, 59(11), 864 - 8
{Tyrothricin powder in the treatment of cutaneous lesions}; Bayerl C et al.; BACKGROUND AND OBJECTIVES: The efficacy and tolerance of an antiseptic wound powder based on the antibiotic tyrothricin was investigated in a prospective, randomized multicenter trial in patients with posttraumatic and surgical cutaneous lesions . PATIENTS AND METHODS: In 5 centers, 131 male and female patients from 18-85 years were included with posttraumatic or surgical cutaneous lesions with infection or in danger of infection (area > or = 200 mm2) . In a double-blind study, tyrothricin (n = 62; 0.1 g tyrothricin per 100 g of vehicle) or placebo powder (n = 69) was applied to the wound twice daily for 9 days . The primary aim was to evaluate the average daily reduction of the radius from the lesion area between the start and end of the randomized treatment (alpha = 0.025; one-sided) . Secondly, a wound index (range 0-15) was calculated from the assessments of rubor, crusting, exudation, pain and functional impairment . RESULTS: The treatment groups were comparable at baseline . During randomized treatment, the radius of the lesions was reduced at an average of 0.55 +/- 0.31 mm/day (mean +/- SD) for tyrothricin and 0.47 +/- 0.30 mm/day for placebo (p = 0.016; one-sided; intention-to-treat data set) . The wound index decreased at an average of 4.2 +/- 1.7 and 3.3 +/- 1.9 points for tyrothricin and placebo, respectively (p = 0.0048; one-sided) . 4 adverse events occurred in each group . A causal relationship with the investigational drug could not be excluded in 3 of the placebo group . CONCLUSION: The results confirm the tendency to an acceleration of wound healing by tyrothricin powder (Tyrosur Powder) in case of infection or danger of infection . A superior efficacy compared to placebo was demonstrated . Due to its good tolerability and the absence of a systemic effects tyrothricin powder is appropriate for the treatment of superficial skin lesions.

Vet Hum Toxicol, 2004 Dec, 46(6), 315 - 8
Acute sheep poisoning from a copper sulfate footbath; Ortolani EL et al.; An outbreak of footrot occurred in a flock of Corriedale sheep; 27 animals were treated with antibiotic and footbathed in a 5% copper sulfate solution . Being deprived of water for > 17 h, many sheep drank the footbath solution . After 6 h 16 sheep became ill with acute copper poisoning, 10 animals died within 10 h; 6 were severely ill and were sent to Veterinary Hospital, and 4 had mild signs and recovered without treatment . The sick sheep had anorexia, dullness, grinding teeth, moaning, rumen atony, dehydration, dark blue-green diarrheic feces and congested membranes . They were treated with 3.4 mg tetrathiomolybdate/kg body weight and lactated Ringer's solution iv, oral molybdate, sulfate, kaolin and pectin, and drenched with antacids . Two of the 6 sheep died during hospitalization . The ingestion of copper solution caused an intense gastrointestinal injury that resulted in ulcers, petechial and echymotic hemorrhages in the mucosa, mild hemolysis detected by microscopic hemoglobinuria and a lowered packed cell volume, severe hepatic injury that raised the AST and gammaGT blood values, and moderate kidney lesions with increasing serum blood urea and nitrogen creatinine levels.

J Natl Med Assoc, 2004 Nov, 96(11), 1499 - 502
Kawasaki disease in a postpartum patient; Fason JT et al.; Kawasaki disease, also known as mucocutaneous lymph node syndrome, is a multisystem disease . It usually affects children below the age of five, but it occasionally affects adults . There are less than 50 English-reported adult cases in the literature, and only five reported cases of Kawasaki disease and pregnancy, as of 2003 . The cases associated with pregnancy involved patients who had a history of Kawasaki disease during childhood and addressed how the complications of the illness (i.e, . coronary artery aneurysms) were managed during pregnancy and delivery . There are no reported cases of Kawasaki disease in postpartum patients . This article presents a case of Kawasaki disease in a 21-year-old, four-week postpartum patient who initially responded to intravenous (IV) antibiotic therapy . This paper will review the diagnosis and treatment of Kawasaki disease as well as the multiple outside variables that impact the management of adult postpartum patients with Kawasaki disease.

J Vet Diagn Invest, 2004 Nov, 16(6), 567 - 71
Granulomatous pneumonia caused by Pythium insidiosum in a central American jaguar, Panthera onca; Camus AC et al.; A 7-month-old, male jaguar presented with dyspnea and leukocytosis unresponsive to antibiotic therapy . Radiographs revealed unilateral pulmonary consolidation . An exploratory thoracotomy was performed, and the left lung, which contained a large multilobular mass with extensive fibrosis and numerous caseonecrotic foci, was removed . Microscopically, eosinophilic granulomatous inflammation surrounded broad (4.4-8.3 microm) rarely septate hyphae . A diagnosis of Pythium insidiosum infection was confirmed by immunohistochemistry, immunoblot serology, culture, and polymerase chain reaction . Dyspnea recurred despite treatment, and the animal succumbed 3 weeks after surgery . Necropsy findings indicated that death resulted from occlusion of the right main stem bronchus by a fungal granuloma . The oomycete P . insidiosum typically causes granulomatous disease of the skin or gastrointestinal tract in animals and arteritis, keratitis, or cellulitis in humans . Infection is uncommon in felines, and pulmonary involvement is rare . This report details the first case of P . insidiosum infection in an exotic felid and provides the first description of primary pulmonary pythiosis in any species.

Vet Dermatol, 2004 Dec, 15(6), 341 - 8
A retrospective study comparing the histopathological features and response to treatment in two canine nasal dermatoses, DLE and MCP; Wiemelt SP et al.; Canine discoid lupus erythematosus (DLE) and mucocutaneous pyoderma (MCP) have overlapping clinical and histopathological changes, often making diagnosis difficult . Histopathological features of 27 nasal planum biopsies were scored to determine whether DLE and MCP were histopathologically distinguishable . Long-term follow-up, enabling assessment of clinical diagnoses, was available on 15 cases; 11/15 cases were immunomodulatory responsive (ImR) and 4/15 were antibiotic responsive (AbR) . Clinical diagnosis, determined by response to treatment for 15/27 cases, was not predictable based on scoring of histopathological features . Distinct histopathological patterns were observed: 2/11 ImR cases had a lymphocyte-rich interface dermatitis . All other cases had the same histopathological changes: a band-like diffuse superficial plasmacytic to lymphoplasmacytic dermatitis +/- focal basal cell damage, but different clinical diagnoses (4/4 AbR, 9/11 ImR) . German shepherd dogs/crosses were over-represented (44.4% of the cases) and tended to have more multifocal lesions (41.7% vs . 26.7% of all other breeds) . Longer duration of disease was associated with a preponderance of plasmacytic infiltrate (P = 0.026).

J Chromatogr A, 2004 Nov 19, 1057(1-2), 229 - 35
Direct high-performance liquid chromatographic separation of unusual secondary amino acids and a comparison of the performances of Chirobiotic T and TAG columns; Peter A et al.; Two macrocyclic glycopeptide antibiotic-type chiral stationary phases (CSPs) based on native teicoplanin and teicoplanin aglycone, Chirobiotic T and TAG, respectively, were evaluated with regard to the high-performance liquid chromatographic separation of the enantiomers of 10 secondary alpha-amino acids (imino acids) . The chromatographic results are given as the retention, separation and resolution factors, together with the enantioselective free energy difference corresponding to the separation of the enantiomers . By application of these two CSPs, excellent resolutions were achieved for the investigated compounds by using reversed-phase mobile mode systems . The separation conditions were optimized by variation of the mobile phase composition . The difference in enantioselective free energy between the aglycone CSP and the teicoplanin CSP for these particular amino acids ranged between 0.70 and -1.83 kJ mol(-1) . It was established that better enantioseparations of the secondary alpha-amino acids were attained in most cases on the aglycone CSP.

J Chromatogr A, 2004 Nov 19, 1057(1-2), 125 - 31
Enhancement of evaporative light scattering detection in high-performance liquid chromatographic determination of neomycin based on highly volatile mobile phase, high-molecular-mass ion-pairing reagents and controlled peak shape; Megoulas NC et al.; In the frame of the development of a novel HPLC-ELSD (evaporative light scattering detection) method for the determination of the aminoglycoside antibiotic neomycin sulfate, the influence of mobile phase composition and peak broadening on ELSD response was evaluated . ELSD response was enhanced by: (a) increase of mobile phase volatility (solvents examined: water, acetonitrile, methanol and acetone), (b) increase of molecular mass of ion-pairing species {acidic reagents tested: formic, acetic, trifluoroacetic, trichloroacetic and heptafluorobutyric acid (HFBA)}, and (c) decrease of peak width and asymmetry obtained by controlling the concentration of the ion-pairing acidic reagent (HFBA) . Utilizing a Waters ODS-2 C18 Spherisorb column, evaporation temperature of 45 degrees C and nitrogen pressure of 3.5 bar, the optimized mobile phase was water-acetone (50:50), containing 11.6 mM HFBA, in an isocratic mode at a rate of 1.0 ml/min . Neomycin was eluted at 4.9 min, with asymmetry factor 1.3 . Logarithmic calibration curve was obtained from 2 to 50 microg/ml (r > 0.9997) . Limit of detection (LOD) was 0.6 microg/ml and R.S.D . = 1.7% (n = 3, 3.3 microg/ml) . In raw materials, the simultaneous determination of sulfate (LOD = 3 microg/ml, R.S.D . = 1.7%, r> 0.9998) and of minor impurities was feasible . The developed method was also applied for the determination of neomycin in pharmaceutical formulations (powder, aerosol and cream) without any interference from excipients (recovery from spiked samples ranged from 99 to 102%) and a %R.S.D . of <2.1 (n = 3) . The HPLC-ELSD method was also found applicable in the determination of neomycin in animal feeds (LOQ=0.2%) without any interference from the feed matrices.

Oncol Rep, 2005 Jan, 13(1), 157 - 60
Increased systemic efficacy of aphidicolin encapsulated in liposomes; Michaelis M et al.; Aphidicolin, a tetracyclic diterpene antibiotic produced by Cephalosporium aphidicola, is under investigation as anti-cancer drug . Because of its poor solubility in water, it cannot be administered directly in vivo . Systemic application of aphidicolin glycinate or aphidicolin gamma-cyclodextrin complexes resulted in tumour growth inhibition but not in cures . To improve the pharmacokinetics, a liposomal preparation of aphidicolin was developed and tested in neuroblastoma-bearing (UKF-NB-3) mice . The loading capacity of these liposomes was limited . Therefore, 4.5 mg aphidicolin/kg body weight was the maximum aphidicolin dose that could be applied as liposomal preparation in this approach . Comparison of effects on tumour growth exhibited by aphidicolin liposomes (4.5 mg aphidicolin/kg) given for 15 consecutive days to those of gamma-cyclodextrin inclusion complexes (15 mg aphidicolin/kg) revealed comparable tumour growth inhibition, although aphidicolin concentrations were approximately 3-fold lower . This shows that liposomal encapsulation is a promising strategy for the improvement of systemic anti-cancer activity of aphidicolin.

Curr Opin Struct Biol, 2004 Dec, 14(6), 748 - 56
Structural aspects of non-ribosomal peptide biosynthesis; Challis GL et al.; Small peptides have powerful biological activities ranging from antibiotic to immune suppression . These peptides are synthesized by non-ribosomal peptide synthetases (NRPS) . Structural understanding of NRPS took a huge leap forward in 2002; this information has led to several detailed biochemical studies and further structural studies . NRPS are complex molecular machines composed of multiple modules and each module contains several autonomously folded catalytic domains . Structural studies have largely focused on individual domains, isolated from the context of the multienzyme . Biochemical studies have looked at individual domains, isolated whole modules and intact NRPS, and the combined data begin to allow us to visualize the process of peptide assembly by NRPS.

Diagn Microbiol Infect Dis, 2004 Dec, 50(4), 231 - 5
Susceptibility of Helicobacter pylori isolates to the antiadhesion activity of a high-molecular-weight constituent of cranberry; Shmuely H et al.; The sensitivity of a large number of antibiotic-resistant and nonresistant Helicobacter pylori isolates to the antiadhesion effect of a high-molecular-mass, nondialysable constituent of cranberry juice was tested . Confluent monolayers of gastric cell line in microtiter plate wells were exposed to bacterial suspensions prepared from 83 H . pylori isolates from antibiotic-treated and untreated patients in the presence and absence of the cranberry constituent . Urease assay was used to calculate the percentage of adhesion inhibition . In two thirds of the isolates, adhesion to the gastric cells was inhibited by 0.2 mg/mL of the nondialysable material . There was no relationship between the antiadhesion effect of the cranberry material and metronidazole resistance in isolates from either treated or untreated patients (N=35) . Only 13 isolates (16%) were resistant to both the nondialysable material and metronidazole, and 30 (36%) were resistant to the nondialysable material alone . There was no cross-resistance to the nondialysable material and metronidazole . These data suggest that a combination of antibiotics and a cranberry preparation may improve H . pylori eradication.

J Pediatr Adolesc Gynecol, 2004 Oct, 17(5), 351 - 2
Tubo-ovarian abscess mimicking ovarian tumor in a sexually inactive girl; Dogan E et al.; Tubo-ovarian abscess is a serious complication of pelvic inflammatory disease rarely seen in sexually inactive girls . Early diagnosis and treatment are essential to prevent further sequela including infertility, ectopic pregnancy, and chronic pelvic pain . We present a case of 19-year-old sexually inactive girl who presented with abdominal pain and pelvic mass resembling ovarian tumor . Unilateral tubo-ovarian abscess with extensive bowel adhesions was determined at laparotomy . Drainage of the abscess and postoperative antibiotic therapy cured the patient.

BMC Pregnancy Childbirth . 2004 Dec 06;4(1):23.
Successful obstetrical management of 110-day intertwin delivery interval without cerclage: counseling and conservative management approach to extreme asynchronous twin birth; Ghulmiyyah LM et al.; BACKGROUND: This report describes a patient counseling approach and non-surgical management of a dichorionic-diamniotic twin pregnancy where delivery of the second twin followed the delivery of the first by 110 days . CASE PRESENTATION: An early transvaginal sonogram at 19 1/2 weeks suggested cervical dilation with protruding amniotic membranes . Tocolytic and antibiotic therapy was initiated; no cerclage was placed . Spontaneous rupture of membranes and cord prolapse occurred 48 h later, resulting in delivery of a stillborn female infant . Conservative management was offered after counseling for possible risks associated with maternal sepsis, need for extended hospitalization, potential for hysterectomy and death . The cervix appeared closed after delivery and the umbilical cord was ligated, with subsequent spontaneous cord retraction in utero . Reassuring fetal status was observed for twin B without evidence of contractions or chorioamnionitis . A viable male infant (2894 g) was delivered vaginally at 35 1/2 weeks . CONCLUSIONS: This report outlines a counseling approach useful for patients with premature delivery of one twin, and presents application of conservative obstetrical management principles for the aftercoming twin even when delivery interval is extreme.

Schweiz Arch Tierheilkd, 2004 Nov, 146(11), 499 - 505
{Pharmacovigilance for veterinary drugs}; Muntener CR et al.; Pharmacovigilance is a system concerned with the acquisition, evaluation and classification of informations about suspected adverse drug reactions (SADR) . Such a system was developed in Switzerland under the supervision of Swissmedic after the introduction of the federal law on therapeutic products on January 1st 2002 . By sending declarations about SADRs, veterinary practitioners play a central role in this scheme . The reports are processed according to international standards (ABON) and provide useful hints to enhance the safety of drug usage by both patients and owners . The system acquired 58 reports in its first complete year of operation (2003) . Analysis of these reveals that trends observed in foreign countries are also applicable to Switzerland: most of the reports concerned the use of antiparasitic or antibiotic drugs in small animals . The first year also revealed a high percentage of declarations coming from the pharmaceutical companies and the authors would therefore like to encourage practitioners to take a more active part in this scheme.

Surg Endosc . 2004 Dec 2; {Epub ahead of print}
Obesity surgery: Evidence-based guidelines of the European Association for Endoscopic Surgery (EAES); Sauerland S et al.; BACKGROUND . The increasing prevalence of morbid obesity together with the development of laparoscopic approaches has led to a steep rise in the number of bariatric operations . These guidelines intend to define the comparative effectivness and surrounding circumstances of the various types of obesity surgery.METHODS . A consensus panel representing the fields of general/endoscopic surgery, nutrition and epidemiology convened to agree on specific questions in obesity surgery . Databases were systematically searched for clinical trial results in order to produce evidence-based recommendations . Following two days of discussion by the experts and a plenary discussion, the final statements were issued.RECOMMENDATIONS . After the patient's multidisciplinary evaluation, obesity surgery should be considered in adults with a documented BMI greater than or equal to 35 and related comorbidity, or a BMI of at least 40 . In addition to standard laboratory testing, chest radiography, electrocardiography, spirometry, and abdominal ultrasonography, the preoperative evaluation of obesity surgery patients also includes upper gastrointestinal endoscopy or radiologic evaluation with a barium meal . Psychiatric consultation and polysomnography can safely be restricted to patients with clinical symptoms on preoperative screening . Adjustable gastric banding (GB), vertical banded gastroplasty (VBG), Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD) are all effective in the treatment of morbid obesity, but differ in degree of weight loss and range of complications . The choice of procedure therefore should be tailored to the individual situation . There is evidence that a laparoscopic approach is advantageous for LAGB, VBG, and GB (and probably also for BPD) . Antibiotic and antithromboembolic prophylaxis should be used routinely . Patients should be seen 3 to 8 times during the first postoperative year, 1 to 4 times during the second year and once or twice a year thereafter . Outcome assessment after surgery should include weight loss and maintainance, nutritional status, comorbidities and quality-of-life.

Med Oral Patol Oral Cir Bucal, 2004, 9 Suppl, 133 - 8; 126-33
Maxillofacial cellulitis; de-Vicente-Rodriguez JC; Of all infections associated to oral pathology, the most relevant ones are those that are related to dental pathology . Cellulitis is an infection of the cellular adipose tissue located in the aponeurotic spaces . It can be classified on the basis of location, severity and evolution . The aponeurotic compartments that allow odontogenic infections to spread have been categorised as: superficial compartment, floor of the mouth, masticator compartment, parapharyngeal space, parotid space and paratonsillar space . The present work describes the anatomical structures that comprise these spaces . The clinical forms of facial cellulitis are divided into acute and chronic . Potential complications consist of orbital infections, necrotising fascitis, thrombosis of the cavernous sinus, cerebral abscess and mediastinitis . Diagnosis is made on the basis of anamnesis, physical examination and complementary procedures (analytical tests and imaging studies) . Treatment includes: treatment of causes (depending on the underlying cause in each case), incision and drainage, antibiotic therapy (chosen empirically) and complementary medical care . Odontogenic infections are primarily treated with surgery and coadjuvant antibiotic therapy.

Heredity . 2004 Dec 01; {Epub ahead of print}
Wolbachia and nuclear-nuclear interactions contribute to reproductive incompatibility in the spider mite Panonychus mori (Acari: Tetranychidae); Gotoh T et al.; Maternally transmitted bacteria of the genus Wolbachia are obligate, intracellular symbionts that are responsible for cytoplasmic incompatibility in a wide range of arthropods such as insects and mites . Spider mites often show uni- and bidirectional incompatibilities among populations with and without Wolbachia . Therefore, we surveyed the presence of Wolbachia by PCR and then conducted crossing experiments among 25 populations of Panonychus mori to determine how Wolbachia are related to the incompatibility in this species . Five out of the 25 populations were infected with Wolbachia . These five populations were treated with an antibiotic (rifampicin) to eliminate Wolbachia . We carried out round-robin crosses among 20 Wolbachia-uninfected populations, five infected populations and five rifampicin-treated populations (30 x 30=900 crosses in total) . Incompatibility among P . mori populations was caused by Wolbachia infection, nuclear-cytoplasmic interactions or nuclear-nuclear interactions . Wolbachia-mediated incompatibility was observed in crosses between uninfected females and infected males or between females and males harboring different Wolbachia strains . Nuclear-cytoplasmic interactions may be responsible for the unidirectional incompatibility in crosses between the two northern populations and one of the southern populations . Bidirectional incompatibility caused by nuclear-nuclear interactions was observed in 99 combinations of interpopulation crosses (99/300=0.33) . Although no geographical trends were detected in the distribution of bidirectionally compatible populations, the results reveal a genetic divergence among P . mori populations.Heredity advance online publication, 1 December 2004; doi:10.1038/sj.hdy.6800605.

J Bacteriol, 2004 Dec, 186(24), 8533 - 6
Interaction between the TolC and AcrA proteins of a multidrug efflux system of Escherichia coli; Husain F et al.; This paper provides the biochemical evidence for physical interactions between the outer membrane component, TolC, and the membrane fusion protein component, AcrA, of the major antibiotic efflux pump of Escherichia coli . Cross-linking between TolC and AcrA was independent of the presence of any externally added substrate of the efflux pump or of the pump protein, AcrB . The biochemical demonstration of a TolC-AcrA interaction is consistent with genetic studies in which extragenic suppressors of a mutant TolC strain were found in the acrA gene.

Biol Chem, 2004 Nov, 385(11), 1029 - 34
Secretory leukoprotease inhibitor and pulmonary surfactant serve as principal defenses against influenza A virus infection in the airway and chemical agents up-regulating their levels may have therapeutic potential; Kido H et al.; Influenza A virus (IAV) is one of the most common infectious pathogens in humans . Entry of this virus into cells is primarily determined by host cellular trypsin-type processing proteases, which proteolytically activate viral membrane fusion glycoprotein precursors . Human IAV and murine parainfluenza virus type 1 Sendai virus are exclusively pneumotropic, and the infectious organ tropism of these viruses is determined by the susceptibility of the viral envelope glycoprotein to cleavage by proteases in the airway . Proteases in the upper respiratory tract are suppressed by secretory leukoprotease inhibitor, and those in the lower respiratory tract are suppressed by pulmonary surfactant, which by adsorption inhibits the interaction between the proteases and viral membrane proteins . Although the protease activities are predominant over the activities of inhibitory compounds under normal airway conditions, intranasal administration of inhibitors was able to significantly suppress multi-cycles of viral replication in the airway . In addition, we identified chemical agents that could act as defensive factors by up-regulating the levels of the natural inhibitors and immunoglobulin A (IgA) in airway fluids . One of these compounds, ambroxol, is a mucolytic and anti-oxidant agent that stimulates the release of secretory leukoprotease inhibitor and pulmonary surfactant in the early phase, and IgA in the late phase of infection at an optimal dose, i.e . a dose sufficient to inhibit virus proliferation and increase the survival rate of animals after treatment with a lethal dose of IAV . Another agent, clarithromycin, is a macrolide antibiotic that increases IgA levels through augmentation of interleukin-12 levels and mucosal immunization in the airway . In addition to the sialidase inhibitors, which prevent the release of IAV from infected cells, inhibitors of the processing proteases and chemical agents that augment mucosal immunity and/or levels of the relevant defensive compounds may also ultimately prove to be useful as new anti-influenza agents.

Appl Environ Microbiol, 2004 Dec, 70(12), 7511 - 9
Construction and characterization of a highly efficient Francisella shuttle plasmid; Maier TM et al.; Francisella tularensis is a facultative intracellular pathogen that infects a wide variety of mammals and causes tularemia in humans . It is recognized as a potential agent of bioterrorism due to its low infectious dose and multiple routes of transmission . To date, genetic manipulation in Francisella spp . has been limited due to the inefficiency of DNA transformation, the relative lack of useful selective markers, and the lack of stably replicating plasmids . Therefore, the goal of this study was to develop an enhanced shuttle plasmid that could be utilized for a variety of genetic procedures in both Francisella and Escherichia coli . A hybrid plasmid, pFNLTP1, was isolated that was transformed by electroporation at frequencies of >1 x 10(7) CFU mug of DNA(-1) in F . tularensis LVS, Francisella novicida U112, and E . coli DH5alpha . Furthermore, this plasmid was stably maintained in F . tularensis LVS after passage in the absence of antibiotic selection in vitro and after 3 days of growth in J774A.1 macrophages . Importantly, F . tularensis LVS derivatives carrying pFNLTP1 were unaltered in their growth characteristics in laboratory medium and macrophages compared to wild-type LVS . We also constructed derivatives of pFNLTP1 containing expanded multiple cloning sites or temperature-sensitive mutations that failed to allow plasmid replication in F . tularensis LVS at the nonpermissive temperature . In addition, the utility of pFNLTP1 as a vehicle for gene expression, as well as complementation, was demonstrated . In summary, we describe construction of a Francisella shuttle plasmid that is transformed at high efficiency, is stably maintained, and does not alter the growth of Francisella in macrophages . This new tool should significantly enhance genetic manipulation and characterization of F . tularensis and other Francisella biotypes.

Front Biosci, 2005 Jan 1, 10, 275 - 87 Print 2005 Jan 1.
Polyoxometalates: introduction to a class of inorganic compounds and their biomedical applications; Hasenknopf B; An increasing number of potential applications for polyoxometalates in human medicine have been reported in the literature . These inorganic complexes are composed of early transition metals (mainly molybdenum, tungsten and vanadium) and oxygen . The present review gives an introduction into the chemistry of these compounds, and an overview of the principal studies of their biological and biochemical effects and their therapeutic potential . The reported antitumoral and antibiotic properties of molybdates and tungstates in vitro and in vivo are compiled and discussed, as are their influences on the blood glucose level in diabetic animals . Aspects of antiviral activities and cell penetration are treated.

An Pediatr (Barc), 2004 Dec, 61(6), 551 - 3
{Chronic multifocal osteomyelitis.}; Salinas Sanz JA et al.; The cases of three female Guinean children are described . Bloods tests were nonspecific, showing a moderately high globular sedimentation rate . The patients received combined therapy with systemic antibiotic therapy (including local gentamicin administration in two of the three patients) and surgery . One patient returned to Guinea and was lost to follow-up . The second patient showed severe sequelae and the third patient had a favorable outcome . In recent years, the prevalence of chronic osteomyelitis in Africa has increased . Most patients have multiple bone involvement and multiple etiology . Blood cultures are negative in 40 % of patients and severe radiologic abnormalities, most commonly fractures, are frequent . A successful therapeutic regimen must be based on antibiotic and surgical treatment.

Ann Saudi Med, 2004 Sep-Oct, 24(5), 350 - 3
Glucose tolerance in pregnant women with vaginal candidiasis; Kelekci S et al.; BACKGROUND: The use of traditional historic risk factors to identify gestational diabetes mellitus (GDM) will miss half of women with gestational diabetes mellitus . Our aim was to evaluate whether impaired glucose tolerance is a risk factor for vaginal candidiasis in pregnant women . PATIENTS AND METHODS: In a cross-sectional study, we compared the prevalence of impaired glucose tolerance in 64 pregnant women with vaginal candidiasis (positive microscopy) and 59 Candida-negative control subjects . Subjects underwent standardized 75-gram oral glucose tolerance testing between the 24th and 28th weeks of their pregnancies . Patients were included only if they had no known diabetes mellitus or historic risk factors for gestational diabetes mellitus, and had not been receiving antibiotic or steroid therapy . We compared glucose levels at fasting, 30 minutes, 60 minutes and 120 minutes, and perinatal and neonatal outcomes in the two groups . RESULTS: There were no statistical differences between cases and controls in demographic characteristics . Glucose concentrations were higher in pregnant women with vaginal candidiasis than in control subjects at fasting (89 vs . 84 mg/dL, P=0.021), 30 minutes (139 vs . 126 mg/dL, P=0.050), and 60 minutes (124 vs . 106 mg/dL, P= 0.018) after intake of 75 gram of glucose . The two groups did not differ in glucose level at 120 minutes after glucose administration . Gestational diabetes prevalence was 3.1% and 3.4% in the study and control group, respectively (P=0.274) . CONCLUSION: The tolerance to glucose in pregnant women with vaginal candidiasis seems discretely impaired.

Pediatr Pulmonol . 2004 Nov 30; {Epub ahead of print}
Randomized, Double-Blind, Placebo-Controlled, Dose-Escalating Study of Aerosolized Interferon Gamma-1b in Patients With Mild to Moderate Cystic Fibrosis Lung Disease; Moss RB et al.; Interferon gamma-1b (IFN-gamma1b) is a pleiotropic cytokine with immunomodulatory activities that could decrease bacterial burden, inflammation, and obstruction in patients with CF . Patients with CF (>/=12 years old, FEV(1) >/=40% predicted) were randomly assigned to sequential dose cohorts inhaling 500 mug IFN-gamma1b, 1,000 mug IFN-gamma1b, or placebo by Respirgard II((R)) nebulizer thrice weekly for 12 weeks . Sputum bacterial density and spirometry were measured . Safety, antibiotic use, hospitalization, and sputum neutrophils, elastase, DNA, IL-8, and myeloperoxidase were also evaluated . Sixty-six patients (mean age, 24 years, with mean baseline FEV(1) of 74 +/- 20 (SD) percent predicted) were studied . One patient had bronchospasm after the first dose of IFN-gamma1b; the overall withdrawal rate was 15% (5 in the placebo group, 2 in the 500-mug IFN-gamma1b group, and 3 in the 1,000 mug IFN-gamma1b group) . The 500-mug IFN-gamma1b dose was well-tolerated, but the 1,000-mug dose cohort, who had a higher baseline bacterial density than placebo patients (mean difference, 1.2 log(10) CFU/g sputum, 95% confidence interval (CI), 0.1,2.8, P = 0.04), had 24% more hospitalizations for exacerbation than placebo patients (95% CI, 2,45%, P = 0.05) . There was a 0.12-l difference between the 500-mug IFN-gamma1b and placebo groups with respect to the 12-week change in FEV(1) (active group minus placebo group, 95% CI, -0.03,0.26, P = 0.11), as compared to a 0.01-l difference between the 1,000-mug IFN-gamma1b and placebo groups (95% CI, -0.16,0.17, P = 0.96) . No effects of IFN-gamma1b were seen in sputum bacterial density or inflammatory biomarkers at 12 weeks . Aerosolized IFN-gamma1b did not improve pulmonary function, reduce sputum bacterial density, or affect inflammatory sputum markers in patients with mild-moderate lung disease . (c) 2004 Wiley-Liss, Inc.

World J Surg, 2004 Oct, 28(10), 1046 - 51; discussion 1051-2 Epub 2004 Oct.
Patterns and clinical outcomes associated with routine intravenous sodium and fluid administration after colorectal resection; Tambyraja AL et al.; Excess intravenous water and sodium may be associated with postoperative complications and an adverse outcome . However, the effect of the magnitude of the surgery on such a relation has not been studied . This study assesses current practice in intravenous fluid and sodium administration after colonic and rectal resection and its relation to the postoperative outcome . A series of 100 consecutive patients undergoing elective colonic (n = 44) or rectal resection (n = 56) were included in a retrospective case-cohort study . The volumes of water and sodium from intravenous fluid and antibiotic administration on the day of surgery and the next 5 days were recorded together with the clinical outcome . The mean +/- SEM fluid and sodium administration on the day of operation was greater after rectal than colonic resection (4.6 +/- 0.2 vs . 3.6 +/- 0.2 liters and 507 +/- 34 vs . 389 +/- 22 mmol, respectively (p < 0.05) . The mean +/- SEM rate of daily fluid and sodium administration for the 5 subsequent days was greater following rectal than colonic resection (2.1 +/- 0.1 vs . 1.8 +/- 0.1 L/day and 155 +/- 8.7 vs . 128 +/- 8.0 mmol/day; p < 0.05) . For all resections, there were no differences in fluid and sodium administration on the day of surgery in patients with or without postoperative complications . During the subsequent 5 days, patients with complications after colonic resection had a higher postoperative mean rate of intravenous sodium administration than those who did not (149 +/- 12 vs . 115 +/- 10 mmol; p < 0.05) . A similar pattern was not observed following rectal resection . Current postoperative intravenous fluid prescription delivers approximately 2 liters of fluid and 140 mmol of sodium per day . Complications after colonic, but not rectal, resection are associated with more early postoperative daily intravenous sodium administration . Because colonic resection poses less of a physiologic insult than rectal resection, the overall outcome in the former group may be more sensitive to the interplay between fluid and sodium overload and patient co-morbidity.

Mol Cell Biol, 2004 Dec, 24(24), 10792 - 801
Functional genetic screen for genes involved in senescence: role of Tid1, a homologue of the Drosophila tumor suppressor l(2)tid, in senescence and cell survival; Tarunina M et al.; We performed a genetic suppressor element screen to identify genes whose inhibition bypasses cellular senescence . A normalized library of fragmented cDNAs was used to select for elements that promote immortalization of rat embryo fibroblasts . Fragments isolated by the screen include those with homology to genes that function in intracellular signaling, cellular adhesion and contact, protein degradation, and apoptosis . They include mouse Tid1, a homologue of the Drosophila tumor suppressor gene l(2)tid, recently implicated in modulation of apoptosis as well as gamma interferon and NF-kappaB signaling . We show that GSE-Tid1 enhances immortalization by human papillomavirus E7 and simian virus 40 T antigen and cooperates with activated ras for transformation . Expression of Tid1 is upregulated upon cellular senescence in rat and mouse embryo fibroblasts and premature senescence of REF52 cells triggered by activated ras . In accordance with this, spontaneous immortalization of rat embryo fibroblasts is suppressed upon ectopic expression of Tid1 . Modulation of endogenous Tid1 activity by GSE-Tid1 or Tid1-specific RNA interference alleviates the suppression of tumor necrosis factor alpha-induced NF-kappaB activity by Tid1 . We also show that NF-kappaB sequence-specific binding is strongly downregulated upon senescence in rat embryo fibroblasts . We therefore propose that Tid1 contributes to senescence by acting as a repressor of NF-kappaB signaling.

Peptides, 2004 Dec, 25(12), 2069 - 78
Structural and functional characterization of N-terminally blocked peptides isolated from the venom of the social wasp Polybia paulista; Ribeiro SP et al.; Two novel peptides were isolated from the crude venom of the social wasp Polybia paulista, by using RP-HPLC under a gradient of MeCN from 5 to 60% (v/v) and named Polybine-I and -II . Further purification of these peptides under normal phase chromatography, rendered pure enough preparations to be sequenced by Edman degradation chemistry . However, both peptides did not interact with phenylisothiocyanate reagent, suggesting the existence of a chemically blocked N-terminus . Therefore, the sequences of both peptides were assigned by ESI-MS/MS under CID conditions, as follows: Polybine-I Ac-SADLVKKIWDNPAL-NH2 (Mr 1610 Da) and Polybine-II Ac-SVDMVMKGLKIWPL-NH2 (Mr 1657 Da) . During the tandem mass spectrometry experiments, a loss of 43 a.m.u . was observed from the N-terminal residue of each peptide, suggesting the acetylation of the N-terminus . Subsequently, the peptides with and without acetylation were synthesized on solid phase and submitted to functional characterizations; the biological activities investigated were: hemolysis, chemotaxis of polymorphonucleated leukocytes (PMNL), mast cell degranulation and antibiosis . The results revealed that the acetylated peptides exhibited more pronounced chemotaxis of PMNL cells and mast cell degranulation than the respective non-acetylated congeners; no hemolytic and antibiotic activities were observed, irrespective to the blockage or not of the alpha-amino groups of the N-terminal residues of each peptide . Therefore, the N-terminal acetylation may be related to the increase of the inflammatory activity of both peptides.

Neurobiol Dis, 2004 Dec, 17(3), 359 - 66
Clinical potential of minocycline for neurodegenerative disorders; Blum D et al.; Minocycline, an antibiotic of the tetracycline family, has been shown to display neurorestorative or neuroprotective properties in various models of neurodegenerative diseases . In particular, it has been shown to delay motor alterations, inflammation and apoptosis in models of Huntington's disease, amyotrophic lateral sclerosis and Parkinson's disease . Despite controversies about its efficacy, the relative safety and tolerability of minocycline have led to the launching of various clinical trials . The present review summarizes the available data supporting the clinical testing of minocycline for these neurodegenerative disorders . In addition, we extend our discussion to the potential applications of minocycline for combining this treatment with cellular and molecular therapy.

Surgeon, 2003 Aug, 1(4), 207 - 14
Dentistry and the medically compromised patient; Seymour RA; Certain medical conditions and their accompanying drug treatment do have an impact upon oral structures and the delivery of dental care . Recent evidence suggests that oral health could be a significant risk factor for coronary artery disease . Many medical conditions can affect dental care are often over-stated and lack an evidence base . Examples include the need for antibiotic cover in patients at risk from infective endocarditis and the necessity to provide supplementary corticosteroids for those patients on longterm steroid therapy . By contrast, certain systematic drug treatments can have a profound affect on the oral tissue . The most obvious is drug-induced gingival overgrowth . Drugs frequently implicated in this unwanted effect include phenytoin, ciclosporin and the calcium channel blockers . Several risk factors for drug-induced overgrowth have been identified and include age, sex, peridontal variables and a range of drug pharmacokinetic variables . The relationship between oral health and coronary artery disease opens up a potentially new vista for the delivery of oral care . Although the association is convincing, casualty has not been established . If casualty for this relationship can be confirmed then the delivery of dental care and the promotion of oral health will receive a significant impetus.

J Coll Physicians Surg Pak, 2003 Dec, 13(12), 704 - 7
Comparative efficacy of amoxicillin, cefuroxime and clarithromycin in the treatment of community -acquired pneumonia in children; Aurangzeb B et al.; OBJECTIVE: To compare the clinical response to amoxicillin, cefuroxime and clarithromycin in the treatment of community-acquired pneumonia in children and to see the cost effectiveness of each treatment . DESIGN: Randomized clinical control trial . PLACE AND DURATION OF STUDY: Department of Pediatrics, Khyber teaching hospital, Peshawar, from October 2001 to February 2002 . SUBJECTS AND METHODS: Patients between 3 to 72 months of age, admitted in the hospital with community acquired pneumonia, were randomly divided into three groups,1,2,3 . They were started on amoxicillin, cefuroxime and clarithromycin respectively . The patients were assessed daily . If there was no clinical improvement at 48 hours the antibiotic was changed . ANOVA statistical test was applied to see the clinical response to the treatment in the three groups . Cost effectiveness of the treatment was compared . RESULTS: There was no statistical difference in the clinical response at 48 hours of initiating treatment and at discharge (p > 0.01 each) . The mean hospital stay in group 1 and 2 was 3.3 days and group 3 was 3.2 days respectively (p > 0.01) . Ninety-seven percent patients in group 1 and 3, and 95% patients in group 2 showed clinical improvement . The cost of treatment of community acquired pneumonia for 8 days was Rs 496/-, 730/-, 1018/- for amoxicillin, clarithromycin and cefuroxime respectively . CONCLUSION: Amoxicillin was found the most cost effective followed by clarithromycin and cefuroxime respectively in the treatment of non-severe and severe community-acquired pneumonia.

Di Yi Jun Yi Da Xue Xue Bao, 2004 Nov, 24(11), 1333 - 4
{Cyst puncture aspiration in 40 cases of abdominal echinococcosis.}; Peng SZ et al.; OBJECTIVE: To evaluate the efficacy of cyst puncture aspiration in treating abdominal echinococcosis . METHOD: A retrospective analysis was performed in 40 cases of abdominal echinococcosis with formation of isolated single cyst in close adhesion with the abdominal wall, for which cyst puncture aspiration was carried out under ultrasound guidance . RESULTS: No death occurred in these patients and only 15 developed mild fever . The days for antibiotic use, jaundice resolution, bile secretion, time of extubation and hospital stay were 2.88+/-0.65, 3.50+/-0.71, 4.25+/-0.96, 5.38+/-0.98 and 9.35+/-1.08 days, respectively . Ultrasound examination in the follow-up showed no relapse in these patients, with the time of the residue adhesive cyst closure and calcification of 4.50+/-1.13 and 13.90+/-2.38 months, respectively . CONCLUSION: Cyst puncture aspiration under ultrasound guidance produces good therapeutic effects on abdominal echinococcosis with isolated single cyst closely adhering to the abdominal wall.

Trends Mol Med, 2004 Dec, 10(12), 580 - 3
Inflammation and apoptosis: linked therapeutic targets in spinal cord injury; Beattie MS; The secondary cascade of cell death that follows central nervous system (CNS) injury or ischemia has long been considered a target for neuroprotective agents aimed at sparing tissue and function . Recently, several laboratories have shown remarkable protection and recovery of function in rodent models of spinal cord injury using treatments that target components of the CNS inflammatory response . The use of minocycline, an antibiotic that reduces microglial activation, antibody blockade of the CD95 (FAS) ligand and the blockade of glycosphingolipid-induced iNOS (inducible nitric oxide synthase) have recently been shown to reduce neuronal and glial apoptosis with concomitant improvement in neurological function, and appear to enhance the efficacy of cell transplantation strategies.

Eur J Pharm Biopharm, 2005 Jan, 59(1), 63 - 71
Applying pattern recognition methods and structure property correlations to determine drug carrier potential of nicotinic acid and analogize to dihydropyridine; Bartzatt R; Multivariate methods are utilized to compare nicotinic acid and dihydropyridine as a drug carrier . Nicotinic acid and dihydropyridine form ester groups on 10 beta-lactam antibiotics with an oxymethyl group forming a linkage between the antibiotic and the drug carrier (nicotinic acid or dihydropyridine) . Calculated molecular properties are analyzed by self-organizing tree algorithm (SOTA), bivariate regression, cluster analysis, factor analysis, discriminant analysis, hierarchical classification, and principal coordinates analysis . Ten important pharmacological properties for each of the nicotinic acid and dihydropyridine antibiotic derivatives are numerically similar and highly correlated . Calculated molecular properties include molar refractivity, molar volume, parachor, index of refraction, partition coefficient (log P), polarizability, and polar surface area . Dermal permeability coefficients (Kp) for nicotinic acid derivatives are similar to values for dihydropyridine derivatives . Dermal permeabliity coefficients analyzed by hierarchical classification and SOTA analysis were shown to be closely interrelated and highly correlated . Ten properties of the nicotinic acid and dihydropyridine were compared by Passing-Bablok regression analysis and shown to be highly correlated (r=0.9879) . Box plot analysis of 10 properties, inclusive of both groups of derivatives, showed narrow ranges in values . Cluster analysis of derivative properties showed the nicotinic acid derivatives to be highly similar to the dihydropyridine derivatives of the same antibiotics . Cluster analysis was performed by single linkage, complete linkage, and centroid linkage . Factor analysis showed the nicotinic acid derivatives to be interrelated and similar to the dihydropyridine derivatives . Discriminant analysis performed on all derivatives formed a single highly cohesive and non-differentiated cluster, demonstrating strong similarity among nicotinic acid and dihydropyridine derivatives . Principal coordinates analysis (determines similarity) of Kp values showed high similarity between the nicotinic acid and dihydropyridine antibiotic derivatives.

J Microbiol Methods, 2005 Jan, 60(1), 31 - 40
Effect of natamycin on the enumeration, genetic structure and composition of bacterial community isolated from soils and soybean rhizosphere; Mohamed MA et al.; Natamycin is commonly used to control fungal growth on agar media used for bacterial enumeration or strain isolation . However, there is no conclusive report on the possible effect of this antibiotic on bacterial growth or on the diversity of the recovered soil bacteria . Therefore, the possible effects of natamycin on the numbers of bacteria isolated at 12 degrees C from three different soils and soybean rhizosphere soil were investigated using natamycin concentrations ranging from 0 to 200 mg l(-1) . Our results demonstrate that natamycin concentrations, which inhibit the growth of fungi on the media, have a small but significant inhibitory effect on the number of bacterial colony forming units . A natamycin concentration of 50-200 mg l(-1) is required for an efficient control of fungal growth on media in our experimental conditions depending on the soil type . Bacterial community structure was assessed on culturable cells (cells washed from enumeration plates: plate-wash approach) obtained at 12 degrees C from soybean rhizosphere soil by performing Ribosomal Intergenic Spacer Analysis (RISA) fingerprinting . We demonstrate that all natamycin concentrations used alter the structure of the recovered, culturable bacterial community, compared to control without natamycin . Using ARDRA (amplification of the 16S rDNA gene and restriction analysis) genotyping of individual isolates, some differences were observed between the bacterial isolates obtained in the presence or absence of natamycin . Bacterial isolates recovered in the presence of natamycin are more tolerant (maximal growth rate and lag phase) to this compound than those isolated without natamycin, indicating a possible selection of resistant strains . Therefore, high concentration of natamycin cannot be used for isolation of bacterial strains with the aim of studying biodiversity and could bias a selection of strains for practical applications.

Lancet Infect Dis, 2004 Dec, 4(12), 777 - 84
A mechanic with a bad valve: blood-culture-negative endocarditis; Albrich WC et al.; A 33-year-old man with a known bicuspid aortic valve presented with fever, chills, progressive fatigue, anorexia, and night sweats . Echocardiography confirmed aortic-valve endocarditis, but blood cultures remained negative . Bartonella henselae endocarditis was ultimately confirmed by serology as well as by immunohistochemistry and PCR testing of the excised valve . The patient recovered with appropriate antibiotic therapy . B henselae is a common cause of culture-negative endocarditis . It predominantly affects men with underlying valvular disease, and has a predilection for aortic valves . Diagnosis is usually made serologically and with either tissue culture, immunohistochemistry, or PCR . Treatment of this destructive endocarditis consists of a combination of long-term antibiotic therapy and surgical valve repair . This case is used to discuss the approach towards the treatment of patients with endocarditis that is blood-culture negative.

Crit Care, 2004 Dec, 8(6), 485 - 91 Epub 2004 Dec.
Clinical review: immunomodulatory effects of dopamine in general inflammation; Beck GCh et al.; Large quantitaties of inflammatory mediators are released during the course of endotoxaemia . These mediators in turn can stimulate the sympathetic nervous system (SNS) to release catecholamines, which ultimately regulate inflammation-associated impairment in tissue perfusion, myocardial impairment and vasodilatation . Treatment of sepsis is based on surgical and/or antibiotic therapy, appropriate fluid management and application of vasoactive catecholamines . With respect to the latter, discussions on the vasopressor of choice are still ongoing . Over the past decade dopamine has been considered the 'first line' vasopressor and is frequently used to improve organ perfusion and blood pressure . However, there is a growing body of evidence that dopamine has deleterious side effects; therefore, its clinical relevance seems to be more and more questionable . Nevertheless, it has not been convincingly demonstrated that other catecholamines are superior to dopamine in this respect . Apart from its haemodynamic action, dopamine can modulate immune responses by influencing the cytokine network . This leads to inhibition of expression of adhesion molecules, inhibition of cytokine and chemokine production, inhibition of neutrophil chemotaxis and disturbed T-cell proliferation . In the present review we summarize our knowledge of the immunomodulatory effects of dopamine, with an emphasis on the mechanisms by which these effects are mediated.

Compr Ther, 2004 Summer, 30(2), 93 - 100
Tubo-ovarian abscess: diagnosis, medical and surgical management; Krivak TC et al.; Tubo-ovarian abscess (TOA), a serious manifestation of pelvic inflammatory disease, has been treated with aggressive surgical therapy . With improvements in antibiotic therapy, laparoscopic surgery and interventional radiological techniques have lessened the need for radical surgical treatment in stable patients.

J Gastroenterol, 2004 Sep, 39(9), 838 - 43
Results of triple eradication therapy in Japanese children: a retrospective multicenter study; Kato S et al.; BACKGROUND: Large-scale clinical trials in children are lacking concerning Helicobacter pylori eradication therapies . The purpose of this study was to assess the efficacy of proton pump inhibitor (PPI)-based triple therapies in Japanese children . METHODS: This was a retrospective analysis of the first- and second-line PPI-based triple therapies from pediatric gastrointestinal units between 1996 and 2003 . Data collected included doses and duration of regimens, drug compliance, success or failure of eradication, ulcer healing, and symptom response of those with dyspepsia and no ulcers . The results of antibiotic susceptibility tests were also reported in cases where these were performed . RESULTS: A total of 149 pediatric patients (mean age, 12.6 years) were studied, including 123 patients who received first-line therapy: 115 received a PPI plus amoxicillin and clarithromycin (PAC) and 8 received a PPI plus amoxicillin and metronidazole (PAM) . Overall eradication rates of the first-line PAC and PAM therapies were 77.4% and 87.5%, respectively ( P = 0.68) . All 14 patients with failed PAC therapy received the second-line PAM regimen, resulting in an eradication rate of 100% . Mild side effects were reported only in PAC regimens (13.8%) . Primary resistance to amoxicillin, clarithromycin, and metronidazole was detected in 0%, 34.7%, and 12.5% of the strains, respectively . The PAC regimen showed a high eradication rate for clarithromycin-susceptible strains (91.7%), but was relatively ineffective for resistant strains (40.0%) ( P < 0.01) . Eradication of H . pylori was associated with ulcer healing and symptomatic improvement among those with gastritis only (both; P < 0.001) . Among 17 patients with iron-deficiency anemia, post-treatment hemoglobin levels were higher than the pretreatment levels ( P < 0.001) . CONCLUSIONS: The PAC regimen is effective in children . Clarithromycin resistance is associated with eradication failure . Metronidazole is a good substitute for clarithromycin as the second-line option for children.

Laryngoscope, 2004 Dec, 114(12), 2200 - 4
Treatment of olfactory dysfunction, II: studies with minocycline; Kern RC et al.; OBJECTIVES/HYPOTHESIS: The treatment of anosmia has changed minimally since the early 1970s, despite dramatic advances in the understanding of the molecular biology of olfaction . Recent studies from the authors' laboratory have suggested that most common causes of clinical olfactory dysfunction, including rhinosinusitis, appear to be associated with increased apoptotic death of olfactory sensory neurons . This appears to result in a decline in the number of functioning mature olfactory sensory neurons, despite the capacity of the olfactory epithelium for regeneration . The current study evaluated the ability of the antibiotic minocycline to inhibit olfactory sensory neuron apoptosis . This drug is known to inhibit apoptosis separate from its anti-infective properties . Olfactory sensory neuron apoptosis was triggered by surgical deafferentation ("bulbectomy"), the standard experimental model . Earlier studies have indicated that bulbectomy and sinusitis invoke similar proteolytic enzyme cascades in olfactory sensory neurons . STUDY DESIGN: Histological analysis of animal olfactory tissue . METHODS: Mice underwent unilateral olfactory bulbectomy to induce apoptotic olfactory sensory neuron death, with and without 45 mg/kg intraperitoneal minocycline given 12 hours before surgery and every 12 hours until death . Mice were killed at 2 and 4 days after bulbectomy and assessed for activation of capsase-3 and olfactory sensory neuron survival by immunohistochemical analysis . RESULTS: Minocycline resulted in partial suppression of cell death at 2 days after surgery when compared with untreated animals . CONCLUSION: Minocycline inhibits olfactory sensory neuron death in the face of a potent pro-apoptotic stimulus . This drug is well tolerated and is currently undergoing human trials for the management of a variety of neurological disorders associated with apoptosis . The current results suggest that minocycline may be efficacious in the management of peripheral olfactory loss as well.

Asian J Surg, 2004 Oct, 27(4), 306 - 12
Inguinal hernia repair by surgical trainees at a malaysian teaching hospital; Chan KY et al.; OBJECTIVE: To assess the outcome of inguinal hernia repaired by surgical trainees at Universiti Kebangsaan Malaysia Hospital . METHODS: Retrospective review of 103 patients who underwent surgery between November 2001 and October 2002 . RESULTS: The mean age of patients was 50 years and the male-to-female ratio was 20:1 . Most hernias (60%) were right-sided inguinal hernias . Admissions consisted of 60% elective, 31% day-case and 9% emergency . General anaesthesia was administered in 66% of cases, spinal anaesthesia in 33% and local anaesthesia in 1% . Ten inguinal hernia repairs were performed by first-year trainees, 61 by third-year trainees and 19 by fourth-year trainees . First-year trainees did more darning (60%) and fewer mesh (40%) repairs . Third-year trainees still used darning (57%) but also performed more mesh repairs (43%) . Fourth-year trainees performed 68% darning (mainly to teach the first-year trainees) and 32% mesh repairs . Senior surgeons assisted in 13 difficult cases where mesh repair was preferred (92%) to darning repairs (8%) . Prophylactic antibiotic was more frequently used in patients undergoing mesh repair (p < 0.001) . The mean operative time was the same for both types of repair . There were no significant differences in complications between the two types of repair . One hernia recurred after darning repair but none after mesh repair . CONCLUSIONS: Mesh repair of inguinal hernia is effective . Trainees easily acquire this skill and it becomes their preferred method of repair.

Gene, 2004 Dec 8, 343, 107 - 15
Analysis and manipulation of amphotericin biosynthetic genes by means of modified phage KC515 transduction techniques; Carmody M et al.; Amphotericin B is a medically important antifungal antibiotic that is produced by Streptomyces nodosus . Genetic manipulation of this organism has led to production of the first amphotericin analogues by engineered biosynthesis . Here, these studies were extended by sequencing the chromosomal regions flanking the amphotericin polyketide synthase genes, and by refining the phage KC515 transduction method for disruption and replacement of S . nodosus genes . A hybrid vector was constructed from KC515 DNA and the Escherichia coli plasmid pACYC177 . This vector replicated as a plasmid in E . coli and the purified DNA yielded phage plaques on Streptomyces lividans after polyethylene glycol (PEG)-mediated transfection of protoplasts . The left flank of the amphotericin gene cluster was found to include amphRI, RII, RIII and RIV genes that are similar to regulatory genes in other polyene biosynthetic gene clusters . One of these regulatory genes, amphRI, was found to have a homologue, amphRVI, located in the right flank at a distance of 127 kbp along the chromosome . However, disruption of amphRVI using the hybrid vector had no effect on the yield of amphotericin obtained from cultures grown on production medium . The hybrid vector was also used for precise deletion of the DNA coding for two modules of the AmphC polyketide synthase protein . Analysis by UV spectrophotometry revealed that the deletion mutant produced a novel pentaene, with reduced antifungal activity but apparently greater water-solubility than amphotericin B . This shows the potential for use of the new vector in engineering of this and other biosynthetic pathways in Streptomyces.

Tex Heart Inst J, 2004, 31(3), 306 - 8
Composite graft endocarditis: repair with a mechanical prosthesis; Apaydin AZ et al.; We report the case of a 64-year-old man who developed a mediastinal pseudoaneurysm due to severe endocarditis, 2 years after aortic root replacement with a prosthetic composite graft containing a mechanical valve . After a short period of stabilization and antibiotic therapy, the patient underwent surgery . The coronary buttons and the sewing ring of the composite graft were found to be detached from the graft and the annulus, respectively . Re-replacement with a prosthetic composite graft (Dacron graft with a mechanical valve) by the Cabrol procedure was performed . Although the homograft is considered by many surgeons to be the best graft for aortic root replacement, the synthetic composite graft can also be used to treat composite graft endocarditis successfully . The technical aspects of homograft versus synthetic aortic root replacement in patients with endocarditis are discussed briefly.

Clin Liver Dis, 1997 May, 1(1), 129 - 55
Pathophysiology, complications, and treatment of ascites; Gines P et al.; In the past few years, there have been important advances in the field of pathogenesis and management of ascites and spontaneous bacterial peritonitis in cirrhosis . A new pathogenic theory of ascites and renal dysfunction in cirrhosis has been presented, and previously ill-defined conditions, such as refractory ascites and hepatorenal syndrome, have been defined precisely . The reintroduction of therapeutic paracentesis has modified markedly the way in which patients hospitalized for ascites are treated . The use of potent and safe antibiotics has improved the resolution rate and survival of patients with spontaneous bacterial peritonitis, and the use of oral antibiotics will simplify the management of this condition in the near future . Finally, prophylactic antibiotic regimens represent a major step forward in the prevention of spontaneous bacterial peritonitis in subsets of cirrhotic patients with a great risk of developing this complication.

Am J Geriatr Pharmacother, 2004 Sep, 2(3), 181 - 9
Clinical efficacy, tolerability, and cost savings associated with the use of open-label metronidazole plus ceftriaxone once daily compared with ticarcillin/clavulanate every 6 hours as empiric treatment for diabetic lower-extremity infections in older males; Clay PG et al.; BACKGROUND: Patients with diabetes mellitus, particularly those with poor glucose control, commonly experience various medical complications related to the disease (eg, renal impairment, decreased peripheral vascular circulation, suppressed immune function) . Infections of the lower extremities can range from superficial cellulitis to ulcerative, deep soft-tissue infections to osteomyelitis that necessitates some degree of amputation . OBJECTIVE: This study compared the efficacy, tolerability, and cost differences associated with the use of metronidazole plus ceftriaxone (MTZ/CTX) given once daily with those of ticarcillin/clavulanate potassium (T/C) given every 6 hours in hospitalized older males with diabetic lower-extremity infections . METHODS: This prospective, open-label study was conducted at a Veterans Affairs Medical Center . Male patients with diabetes and a lower-extremity infection were randomized to receive MTZ/CTX 1 g once daily or T/C 3.1 g every 6 hours . Treatment success was determined at 96 hours or on discontinuation of antibiotic . Success was measured in terms of body temperature <38.3 degrees C (100.6 degrees F), normalization of the finger-stick blood sugar concentration, improvement in wound staging, or a white blood cell count <10,000 cells/mm3 . Medication acquisition costs per treatment arm were calculated and compared . RESULTS: Seventy patients were enrolled in the study (36 MTZ/CTX, 34 T/C) . The study population had a mean (SD) age of 63.8 (10.8) years, a duration of diabetes of 12.4 (9.1) years, 0.5 (0.7) diabetes-related comorbidities, and an initial creatinine clearance of 67.1 (26.0) mL/min . There were no significant differences between groups at randomization . At 96 hours, treatment success was achieved in 31 (86%) patients in the MTZ/CTX group, compared with 28 (82%) patients in the T/C group (P=NS) . Twenty-six patients were considered successfully treated on the final day of therapy in both the MTZ/CTX group (72%) and the T/C group (76%) (P=NS) . There were no significant differences in primary or secondary measures of success between the 2 groups . No single or multiple baseline factors predicted treatment success or failure . No patient experienced adverse events considered related to study medication . MTZ/CTX was associated with savings of $61.06 per hospital admission, or $2198.05 for all patients who received this combination . CONCLUSION: In this population of older males, once-daily MTZ/CTX was as well tolerated and effective as T/C in the treatment of diabetic lower-extremity infections and was associated with reduced institutional costs.

Pain, 2004 Dec, 112(3), 315 - 23
In vivo recruitment by painful stimuli of AMPA receptor subunits to the plasma membrane of spinal cord neurons; Galan A et al.; The persistent increase in pain sensitivity observed after injury, known as hyperalgesia, depends on synaptic plasticity in the pain pathway, particularly in the spinal cord . Several potential mechanisms have been proposed, including post-synaptic exocytosis of the AMPA subclass of glutamate receptors (AMPA-R), which is known to play a critical role in synaptic plasticity in the hippocampus . AMPA-R trafficking has been described in spinal neurons in culture but it is unknown if it can also occur in spinal neurons in vivo, or if it can be induced by natural painful stimulation . Here we have induced referred mechanical hyperalgesia in vivo by intracolonic instillation of capsaicin in mice and have observed a recruitment of GluR1 AMPA-R subunits to neuronal plasma membranes in the lumbar spinal cord . Intracolonic capsaicin induced a rapid (10 min) increase in GluR1, but not GluR2/3 in the synaptosomal membrane fraction which lasted at least 3 h and a decrease in GluR1 subunit in the cytosolic fraction . Capsaicin treatment also provoked CaMKII activation and pre-treatment with a specific CaMKII inhibitor prevented the GluR1 trafficking . Brefeldin-A, an antibiotic that inhibits exocytosis of proteins, not only prevented GluR1 trafficking to the membrane but also inhibited referred hyperalgesia in capsaicin-treated mice . Our results show that delivery of GluR1 AMPA receptor subunits to the cell membrane through a CaMKII activity-dependent exocytotic regulated pathway contributes to the development of hyperalgesia after a painful stimulus . We conclude that AMPA-R trafficking contributes to the synaptic strengthening induced in the pain pathway by natural stimulation.

Transplant Proc, 2004 Oct, 36(8), 2328 - 30
Acute renal failure after cadaveric related liver transplantation; Chuang FR et al.; Acute renal failure (ARF) is a frequent medical complication after liver transplantation (LT) . We analyzed cadaveric related liver transplant recipients who had developed ARF early in the postoperative course . Between January 1982 and August 2003, a total of 67 patients underwent cadaveric related LT . Their mean age was 28.64 years at LT . The 67 recipients had the following indications: biliary atresia (n = 17), Wilson's disease (n = 15), hepatitis B-related liver cirrhosis (n = 14), hepatitis C-related liver cirrhosis (n = 4), primary biliary cirrhosis (n = 4), hepatitis B-related liver cirrhosis with hepatoma (n = 3), hepatitis C-related liver cirrhosis with hepatoma (n = 2), Budd-Chiari syndrome (n = 2), neonatal hepatitis (n = 1), choledochus cyst (n = 1), autoimmune cirrhosis (n = 1), neuroendocrine tumor (n = 1), and hemangioendothelioma (n = 1) . Forty-nine patients received cyclosporine (CsA), azathioprine, and steroids and 18, a combination with tacrolimus (FK506) . Eight (11.94%) patients developed ARF at a mean time of 17.25 days after LT . The mean peak serum creatinine was 2.24 mg% . Four of these patients had a diagnosis of hepatitis B-related liver cirrhosis; two, hepatitis C-related liver cirrhosis; one, primary biliary cirrhosis; and one, hepatitis B-related liver cirrhosis with hepatoma . The ARF etiology was multifactorial for the majority of patients . Eight ARF patients had a history of liver cirrhosis, which may be a risk factor for intraoperative ARF . ARF treatment included fluid replacement, decreased or altered immunosuppressive agents, avoiding exposure to nephrotoxic drugs, and adjusting antibiotic dosages . The majority of patients returned to normal renal function at 1 to 3 weeks after the diagnosis of ARF . No patient required dialysis and/or experienced a mortality . We conclude that the incidence of ARF is relatively low and with good outcomes . ARF etiology was multifactorial for the majority of patients, but eight patients had a history of liver cirrhosis, which may be a risk factor for intraoperative ARF . We suggest that in the early postoperative period of LT cases diagnosis and treatment of ARF are important.

Ann Thorac Surg, 2004 Dec, 78(6), 1898 - 902
Medium-term follow-up after deployment of ultraflex expandable metallic stents to manage endobronchial pathology; Madden BP et al.; BACKGROUND: Between March 1997 and March 2004 we deployed 80 Ultraflex metallic expandable stents (Boston Scientific, Waterson, MA) in 69 patients under direct vision using rigid bronchoscopy . We report our medium- to long-term experience in patients for whom these stents were deployed . METHODS: To date 15 patients have been followed for more than 1 year (median 41 months, range 12 to 83 months) after stent deployment . Indications for stenting in these patients were neoplasia (5), stricture (5), airway malacia (1), iatrogenic tracheal tear (1), and compression from an aortic aneurysm (1), a right interrupted aortic arch (1), and a right brachiocephalic artery aneurysm with tracheomalacia (1) . Ten tracheal stents (9 covered, 1 uncovered) and 10 bronchial stents (8 uncovered, 2 covered) were inserted, and 5 patients received two stents . RESULTS: Five of these patients experienced no long-term problems . Complications included troublesome halitosis (5), which was difficult to treat despite various antibiotic regimes; granulation tissue formation above and below the stent that was successfully treated with low-power Nd:YAG laser therapy (7); and metal fatigue (1) . We did not encounter stent migration . CONCLUSIONS: We conclude that Ultraflex expandable metallic stents have an important role in the management of selected patients with diverse endobronchial pathologies and are well tolerated in the long-term . Although associated granulation tissue can be successfully treated with Nd:YAG laser, halitosis can be a difficult problem to address.

Dtsch Med Wochenschr, 2004 Nov 26, 129(48), 2590 - 3
{Monitoring of plasma disappearance rate of indocyanine green in a patient with necrotizing fasciitis and septic shock}; Kortgen A et al.; HISTORY AND ADMISSION FINDINGS: A 45-year old man with diabetes mellitus and arterial hypertension was transferred with fever of unknown origin, suspected diabetic angiopathy and sepsis . On admission the patient presented all signs of septic shock . Livid coloured injuries on his right hand and petechial bleeding in distal extremities were observed . INVESTIGATIONS: A different origin of sepsis was not found in transesophageal ultrasound cardiography and computed tomography of cranium, chest and abdomen . DIAGNOSIS, TREATMENT AND COURSE: Immediately after admission early goal-directed therapy was initiated . Apart from calculated antibiotic therapy intensive insulin therapy and hydrocortisone substitution was begun . The patient presented a multiple organ dysfunction syndrome . Plasma disappearance rate of indocyanine green (PDR (ICG)) on admission was 20,4 %/min (normal range > 18 %/min) and fell to 6,8 %/min within 12 hours, while central venous oxygen saturation remained normal . Despite therapy according to current guidelines for severe sepsis, the patient deteriorated . Surgical debridement was performed suspecting necrotizing fasciitis and application of recombinant human activated protein C (rhAPC) started . PDR (ICG) rapidly raised to normal values; the patient recovered and was discharged after 9 days . CONCLUSIONS: Monitoring of PDR (ICG) allows for improved bedside evaluation of liver perfusion of the critically ill and is not only able to predict prognosis but may help in decision making for supportive therapies.

Arch Orthop Trauma Surg . 2004 Nov 19; {Epub ahead of print}
Clear cell chondrosarcoma of the proximal femur with intrapelvic extension; Simsek A et al.; Clear cell chondrosarcoma is a rare tumor that can be easily confused with benign tumors . The aim of this report is to present a case that is rare, initially diagnosed as aneurysmal bone cyst and then chondroblastoma, and has an interesting extension pattern . A 41-year-old male patient was treated for an apparently benign cystic lesion of the right proximal femur by intralesional excision and bone grafting . The pathological diagnosis was aneurysmal bone cyst . Two years later, the patient presented with a pathological fracture at the same site and a total hip arthroplasty was performed . The pathological specimen was diagnosed as chondroblastoma . Three years later, clinical and radiological examination of the patient revealed a large mass located on the intrapelvic side of the acetabulum . There was no evidence of distant metastases . Both tumors were resected with a wide margin on the femoral side and a marginal margin on the intrapelvic side . The extremity was reconstructed with a resection-type total hip prosthesis . Again, the pathological diagnosis was chondroblastoma . The patient developed a deep infection that was treated by antibiotic therapy and surgical debridement . One year later, there was recurrence of the femoral and intrapelvic masses and right hemipelvectomy was performed; the specimen was reported as clear cell chondrosarcoma . Since then, the patient has been leading an active life, and there is no evidence of local recurrence or distant metastasis . Clinically and pathologically, clear cell chondrosarcoma may be confused with benign bone tumors . This caused a delay in the final diagnosis of this patient and he received inadequate surgical treatment, leading to a hemipelvectomy . We also found that the intrapelvic mass seemed to have developed independently on the intrapelvic side of the acetabulum . We were unable to find an exact explanation for this finding and postulated that tumor cells might have been seeded into the inner wall of the acetabulum during acetabular preparation of the total hip prosthesis.

FEMS Microbiol Lett, 2004 Dec 1, 241(1), 95 - 101
Porphyromonas gingivalis induces its uptake by human macrophages and promotes foam cell formation in vitro; Giacona MB et al.; Porphyromonas gingivalis is an etiologic agent of periodontal disease in humans, which has been linked to an increased risk for atherosclerosis-related events . In this study, we examined the effect of P . gingivalis infection on human macrophages with respect to foam cell formation, the hallmark of early atherogenesis, and the potential of P . gingivalis to induce its uptake by these cells . Human monocyte-derived macrophages were incubated with low density lipoprotein and infected with P . gingivalis FDC381 or its fimbriae deficient mutant, DPG3 . Consistent with a role for fimbriae in this process, strain 381 significantly increased foam cell formation as compared to DPG3 . Recovery of viable P . gingivalis in antibiotic protection experiments was significantly higher for strain 381 than for DPG3 . By transmission electron microscopy, the wild-type strain was shown to adhere to and enter THP-1 cells . These results suggest that properties of P . gingivalis which render it capable of adhering to/invading other cell types may also be operative in macrophages and play an important role in its atherogenic potential.

Chem Biol, 2004 Nov, 11(11), 1561 - 72
Production of 8'-halogenated and 8'-unsubstituted novobiocin derivatives in genetically engineered streptomyces coelicolor strains; Eustaquio AS et al.; In the present study, we produced a hybrid antibiotic, carrying a chlorine atom instead of a methyl group at position 8 of the aminocoumarin moiety of novobiocin . This compound was not accessible by conventional gene inactivation/gene expression experiments due to difficulties in the genetic manipulation of the novobiocin producer Streptomyces spheroides . However, the desired compound was obtained after modification of the novobiocin biosynthetic gene cluster by using lambda-Red-mediated recombination in Escherichia coli, followed by integration of the resulting modified cosmid into the phiC31 attachment site of Streptomyces coelicolor and coexpression of the halogenase Clo-hal of clorobiocin biosynthesis . The halogenase BhaA, responsible for chlorination of tyrosyl moieties of the glycopeptide antibiotic balhimycin, was unable to functionally replace the halogenase Clo-hal, suggesting that the two enzymes have different substrate specificities.

Chem Biol, 2004 Nov, 11(11), 1513 - 21
Rifampicin inhibits alpha-synuclein fibrillation and disaggregates fibrils; Li J et al.; The aggregation of alpha-synuclein in dopaminergic neurons of the substantia nigra is a critical step in the pathogenesis of Parkinson's disease . We show that the antibiotic rifampicin inhibited alpha-synuclein fibrillation and disaggregated existing fibrils in a concentration-dependent manner . Size-exclusion chromatography data indicated that rifampicin stabilized alpha-synuclein as both a monomer and soluble oligomers comprised of partially folded alpha-synuclein . Experiments using aged samples of rifampicin indicated that the most active species in inhibiting fibrillation and disaggregating fibrils is an oxidation product of rifampicin, which was confirmed in experiments under anaerobic conditions . These results indicate that rifampicin-mediated inhibition of alpha-synuclein fibrillation and disaggregation of fibrils involves preferential stabilization of monomeric and soluble oligomeric forms, and that rifampicin potentially may have therapeutic application for Parkinson's disease.

Lancet, 2004 Nov 20, 364(9448), 1865 - 71
Co-trimoxazole as prophylaxis against opportunistic infections in HIV-infected Zambian children (CHAP): a double-blind randomised placebo-controlled trial; Chintu C et al.; BACKGROUND: No trials of co-trimoxazole (trimethoprim-sulfamethoxazole) prophylaxis for HIV-infected adults or children have been done in areas with high levels of bacterial resistance to this antibiotic . We aimed to assess the efficacy of daily co-trimoxazole in such an area . METHODS: We did a double-blind randomised placebo-controlled trial in children aged 1-14 years with clinical features of HIV infection in Zambia . Primary outcomes were mortality and adverse events possibly related to treatment . Analysis was by intention to treat . FINDINGS: In October, 2003, the data and safety monitoring committee recommended early stopping of the trial . 541 children had been randomly assigned; seven were subsequently identified as HIV negative and excluded . After median follow-up of 19 months, 74 (28%) children in the co-trimoxazole group and 112 (42%) in the placebo group had died (hazard ratio {HR} 0.57 {95% CI 0.43-0.77}, p=0.0002) . This benefit applied in children followed up beyond 12 months (n=320, HR 0.48 {0.27-0.84}, test for heterogeneity p=0.60) and across all ages (test for heterogeneity p=0.82) and baseline CD4 counts (test for heterogeneity p=0.36) . 16 (6%) children in the co-trimoxazole group had grade 3 or 4 adverse events compared with 18 (7%) in the placebo group . These events included rash (one placebo), and a neutrophil count on one occasion less than 0.5x10(9)/L (16 {6%} co-trimoxazole vs seven {3%} placebo, p=0.06) . Pneumocystis carinii was identified by immunofluorescence in only one (placebo) of 73 nasopharyngeal aspirates from children with pneumonia . INTERPRETATION: Our results suggest that children of all ages with clinical features of HIV infection should receive co-trimoxazole prophylaxis in resource-poor settings, irrespective of local resistance to this drug.

Mol Microbiol, 2004 Dec, 54(5), 1295 - 306
Mutations in ribosomal protein L3 and 23S ribosomal RNA at the peptidyl transferase centre are associated with reduced susceptibility to tiamulin in Brachyspira spp . isolates; Pringle M et al.; The pleuromutilin antibiotic tiamulin binds to the ribosomal peptidyl transferase centre . Three groups of Brachyspira spp . isolates with reduced tiamulin susceptibility were analysed to define resistance mechanisms to the drug . Mutations were identified in genes encoding ribosomal protein L3 and 23S rRNA at positions proximal to the peptidyl transferase centre . In two groups of laboratory-selected mutants, mutations were found at nucleotide positions 2032, 2055, 2447, 2499, 2504 and 2572 of 23S rRNA (Escherichia coli numbering) and at amino acid positions 148 and 149 of ribosomal protein L3 (Brachyspira pilosicoli numbering) . In a third group of clinical B . hyodysenteriae isolates, only a single mutation at amino acid 148 of ribosomal protein L3 was detected . Chemical footprinting experiments show a reduced binding of tiamulin to ribosomal subunits from mutants with decreased susceptibility to the drug . This reduction in drug binding is likely the resistance mechanism for these strains . Hence, the identified mutations located near the tiamulin binding site are predicted to be responsible for the resistance phenotype . The positions of the mutated residues relative to the bound drug advocate a model where the mutations affect tiamulin binding indirectly through perturbation of nucleotide U2504.

J Chromatogr A, 2004 Oct 29, 1054(1-2), 365 - 71
Quantitative determination of chloramphenicol in milk powders by isotope dilution liquid chromatography coupled to tandem mass spectrometry; Guy PA et al.; A method is described for the determination of residues of the illegal antibiotic chloramphenicol (CAP) in milk powders . The analyte is quantified by liquid chromatography coupled to electrospray ionisation tandem mass spectrometry (LC-ESI-MS-MS) operating in negative ion multiple reaction monitoring mode (MRM) after a liquid-liquid extraction followed by a clean-up step on solid phase extraction (SPE) cartridge . Because of the presence of two chlorine atoms in the CAP molecule, four specific transition reactions of CAP were monitored by MS-MS in selecting m/z 321 --> 257, 321 --> 152 (35Cl2) and m/z 323 --> 257, 323 --> 152 (37Cl35Cl) . Two calibration curves were constructed by plotting the area ratio of m/z 321 --> 152 versus 326 --> 157 and m/z 321 --> 257 versus 326 --> 262 against their corresponding amount ratio . Indeed, even if m/z 321 --> 152 was found to give a higher MS-MS response (calibration curve used by default), an interfering chemical substance was sometimes observed for some milk extracts and not for the transition m/z 321 --> 257 . The quantitation method was validated according to the European Union (EU) criteria for the analysis of veterinary drug residues at 0.1, 0.2 and 0.5 microg/kg concentration levels using d5-CAP as internal standard . The decision limit (CCalpha) and detection capability (CCbeta) of CAP in milk were calculated for m/z 321 --> 152 at 0.02 microg/kg and 0.03 microg/kg, respectively, and for m/z 321 --> 257 at 0.02 microg/kg and 0.04 microg/kg, respectively . At the lowest fortification level (i.e . 0.1 microg/kg), repeatability and within-laboratory reproducibility were calculated for m/z 321 --> 257 both at 0.02 microg/kg and for m/z 321 --> 152 at 0.03 and 0.05 microg/kg, respectively . Moreover, the measurement of uncertainty of the analytical method was calculated at the same spiking levels and falls within the precision values of the within-laboratory reproducibility . This method can be applied to several types of milk powders (e.g . full cream, skim) and can serve as a monitoring tool to avoid that unacceptable levels of residues of CAP enter the food chain.

J Drugs Dermatol, 2004 Sep-Oct, 3(5 Suppl), S12 - 22
Advances in the topical treatment of acne and rosacea; Ceilley RI; Acne and rosacea are common skin diseases which may present similarly and both involve inflammation . Both can result in significant cosmetic impairment and lead to quality of life decrements if not optimally treated . The conventional approach for both diseases involves the use of topical therapy to treat inflammatory lesions in combination, when needed, with a systemic or topical antibiotic . An important issue in the management of both diseases at present is the need to reduce antibiotic usage due to the increasing problem of bacterial resistance . One of the emerging treatment paradigms that is becoming increasingly useful as an antibiotic-sparing strategy is the use of procedural therapies in combination with medical management . Such procedural modalities include lasers, intense pulsed light (IPL), and photodynamic therapies (PDT) . Topical regimens are used pre-treatment and following physical modalities for maintenance of remission.

Clin Orthop, 2004 Oct, (427), 72 - 8
The current status of material used for depot delivery of drugs; Nelson CL; The ideal local antibiotic delivery system has not been created . Antibiotic-laden bone cement has become the gold standard in the treatment of infected orthopaedic implants and there are confirmatory laboratory and clinical data that support the use of these materials . Heat-stable antibiotics elute from antibiotic-laden bone cement and do not have a notable influence on the compressive strengths of bone cement if the antibiotics are used in appropriate amounts . If the proper antibiotic is chosen, placed in the appropriately porous materials in sufficient amounts, and implanted in bone, antibiotic levels in the surrounding bone are many times greater than can be achieved by safe systemic antibiotic doses . Although the materials that have been manufactured commercially have been used for over 30 years in Europe, until recently, they have not been available in the United States . Currently, there are five antibiotic-laden bone cement composites that have been approved by the FDA and that are available for clinical use . Studies are being done to search for biodegradable implants preferable to antibiotic-laden bone cement; however, these studies and the materials are still in early stages and development . Currently, there are no FDA-approved biodegradable materials available for use to treat infected orthopaedic implants . As new materials become available and their elution characteristics are recorded, it is important for surgeons to understand how the data were collected so they can have a clear understanding of the elution characteristics of the material used and how the material acts in different environments . Even with extensive historic, clinical, and research data that prove the effectiveness of antibiotic-laden cement, the ideal drug delivery system is neither agreed on nor available.

Clin Orthop, 2004 Oct, (427), 25 - 7
The effect of glycine filler on the elution rate of gentamicin from acrylic bone cement: a pilot study; McLaren AC et al.; Elution of antibiotics from acrylic bone cement (polymethylmethacrylate {PMMA}) is dependent on the access of fluid to the depths of the cement that contains the antibiotic . Commercially prepared antibiotic beads that are porous have higher elution rates than hand-mixed, nonporous antibiotic PMMA mixtures . To increase the elution of gentamicin from hand-mixed PMMA, glycine was added as a filler to produce porosity . Elution of gentamicin from the antibiotic PMMA-glycine mixture increased with increasing amounts of glycine . With 3.6 g gentamicin powder and 14 g of crystalline glycine per batch of Palacos PMMA, the elution of gentamicin from the PMMA at 2 days was, similar to the previously documented elution of gentamicin from commercially prepared porous Septopal PMMA beads . With further investigation it may be possible to identify a specific filler and a volume of filler that can be hand mixed in antibiotic PMMA to produce the elution behavior that is needed for specific clinical requirements.

Pediatr Cardiol . 2004 Nov 11; {Epub ahead of print}
The Pediatric Cardiology Pharmacopoeia: 2004 Update; Barnes S et al.; Seven years ago, Pediatric Cardiology published the first version of a review article outlining the various medications used in the field of heart diseases in children . This article is an update and expansion to what we have previously presented . Therapeutic intervention, both surgical and through cardiac catheterization, has enabled cure and palliation of an increasingly expanding spectrum of diseases at earlier ages and with more complex lesions . Refinement of these procedures includes more advanced tools as well as the support of an expanding armament of pharmacopoeia used to stabilize and support patients before, during, and after such procedures . In addition to updating previously published data regarding inotropes, antiarrhythmics, vasodilators, diuretics, sedatives, and analgesics as well as a variety of miscellaneous medications, this article describes the use of pulmonary medications frequently needed in patients with congestive heart failure, pulmonary edema, and chronic lung disease . We also describe the difficult management of withdrawal as a result of use of sedatives and analgesics . The most recent recommendation for subacute bacterial endocarditis prophylactic antibiotic regimens is also described.

J Gastroenterol, 2004 Oct, 39(10), 927 - 30
Efficacy of metronidazole for the treatment of clarithromycin-resistant Helicobacter pylori infection in a Japanese population; Shimoyama T et al.; BACKGROUND: Eradication of Helicobacter pylori has become a common treatment for several diseases . There is an increase in antibiotic-resistant strains, which causes the failure of eradication . The aim of this study was to investigate the usefulness of metronidazole for the treatment of H . pylori infection in patients who failed eradication therapy . METHODS: Seventy H . pylori-positive patients who had failed eradication treatment with first-line triple therapy, which consisted of a proton pump inhibitor, amoxicillin, and clarithromycin, were enrolled into the study . Before the second-line therapy, patients underwent endoscopy to obtain H . pylori strains to test susceptibility to antibiotics . Lansoprazole (30 mg b.d.), amoxicillin (750 mg b.d.), and metronidazole (250 mg b.d.) were administered for 1 week, and the result was tested by 13C-UBT . RESULTS: H . pylori was isolated from 62 patients, and 52 of them (83.9%) were clarithromycin resistant . There was no amoxicillin- or metronidazole-resistant strain . No major adverse effects were seen, and all the patients completed the 1-week regimen . The eradication rates of lansoprazole-amoxicillin-metronidazole were 96.2% (51/53; 95% CI, 87.0%-99.5%) using both intention-to-treat analysis and per protocol analysis . CONCLUSIONS: Lansoprazole-amoxicillin-metronidazole triple therapy is an effective and promising second-line H . pylori eradication therapy in a north Japanese population, which has a low frequency of metronidazole resistance.

Br J Ophthalmol, 2004 Dec, 88(12), 1487 - 92
A randomised trial of povidone-iodine to reduce visual impairment from corneal ulcers in rural Nepal; Katz J et al.; AIM: To assess whether povidone-iodine provided any benefit over and above a standard regimen of antibiotic therapy for the treatment of corneal ulcers . METHODS: All patients diagnosed with corneal ulcers presenting for care at a primary eye care clinic in rural Nepal were randomised to a standard protocol of antibiotic therapy versus standard therapy plus 2.5% povidone-iodine every 2 hours for 2 weeks . The main outcomes were corrected visual acuity and presence, size, and position of corneal scarring in the affected eye at 2-4 months following treatment initiation . RESULTS: 358 patients were randomised and 81% were examined at follow up . The two groups were comparable before treatment . At follow up, 3.9% in the standard therapy and 6.9% in the povidone-iodine group had corrected visual acuity worse than 20/400 (relative risk (RR) 1.77, 95% confidence interval (CI) 0.62 to 5.03) . 9.4% in the standard therapy and 13.1% in the povidone-iodine group had corrected visual acuity worse than 20/60 (RR 1.39, 95% CI 0.71 to 2.77), and 17.0% and 18.8% had scars in the visual axis in each of these groups, respectively (RR 1.11, 95% CI 0.67 to 1.82) . CONCLUSIONS: A small proportion of patients with corneal ulceration treated in this setting had poor visual outcomes . The addition of povidone-iodine to standard antibiotic therapy did not improve visual outcomes, although this design was unable to assess whether povidone-iodine on its own would have resulted in comparable visual outcomes to that of standard therapy.

J Biol Chem . 2004 Nov 17; {Epub ahead of print}
Aclacinomycin-10-hydroxylase is a novel substrate-assisted hydroxylase requiring S-adenosyl-L-methionine as cofactor; Jansson A et al.; Aclacinomycin 10-hydroxylase is a methyltransferase homologue that catalyses a S-adenosyl-L-methionine (AdoMet) dependent hydroxylation of the C-10 carbon atom of 15-demethoxy-beta-rhodomycin, a step in the biosynthesis of the polyketide antibiotic beta-rhodomycin . S-adenosyl-L-homocysteine is an inhibitor of the enzyme, whereas the AdoMet analogue sinefungin can act as cofactor indicating that a positive charge is required for catalysis . 18O2 experiments show that the hydroxyl group is derived from molecular oxygen . The reaction further requires thiol reagents such as glutathione or dithiothreitol . Incubation of the enzyme with substrate in the absence of reductant leads to the accumulation of an intermediate with a molecular mass consistent with a perhydroxy compound . This intermediate is turned into product upon addition of glutathione . The crystal structure of an abortive enzyme-AdoMet-product ternary complex reveals large conformational changes consisting of a domain rotation leading to active site closure upon binding of the anthracycline ligand . The data suggest a mechanism where decarboxylation of the substrate results in the formation of a carbanion intermediate, which is stabilized by resonance through the aromatic ring system of the anthracycline substrate . The delocalisation of the electrons is facilitated by the positive charge of the cofactor AdoMet . Activation of oxygen and formation of a hydroxyperoxide intermediate occurs in a manner similar to that observed in flavoenzymes . RdmB is the first example of a AdoMet dependent hydroxylation reaction, a novel function for this cofactor . The enzyme lacks methyltransferase activity due to the positioning of the AdoMet methyl group unfavorable for a SN2 type methyl transfer to the substrate.

J Neurol Neurosurg Psychiatry, 2004 Dec, 75(12), 1727 - 30
Neurosyphilis in the modern era; Timmermans M et al.; OBJECTIVE: To review the nature of the presentation of neurosyphilis, the value of diagnostic tests, and the classification of the disease . METHODS: A retrospective review was carried out of the records of patients who had been identified as possible cases of neurosyphilis by a positive FTA-abs test in the CSF . The review extended over 10 years at a single hospital which served a population of mixed ancestry in a defined catchment area in the Western Cape province of South Africa . Patients were placed in predefined diagnostic categories, and clinical, radiological, and laboratory features were assessed . RESULTS: 161 patients met diagnostic criteria for neurosyphilis: 82 presented with combinations of delirium and dementia and other neuropsychiatric conditions, and the remainder had typical presentations such as stroke (24), spinal cord disease (15), and seizures (14) . The average age of presentation ranged from 35.9 to 42.6 years in the different categories of neurosyphilis . Of those followed up, 77% had residual deficits from their initial illness . Cerebrospinal fluid (CSF) VDRL was positive in 73% of cases . CONCLUSIONS: The diagnosis of neurosyphilis can be made with reasonable certainty if there is an appropriate neuropsychiatric syndrome associated with a positive CSF VDRL . If the VDRL is negative, a positive FTA-abs in an appropriate clinical setting, associated with raised CSF cell count, protein, or IgG index, is a useful method of identifying neurosyphilis . Tabes dorsalis has become uncommon, but this is likely to be the only manifestation of neurosyphilis that has been altered during the antibiotic era.

Am J Otolaryngol, 2004 Nov-Dec, 25(6), 442 - 6
Rapid evolution of acute mastoiditis: three case reports of otogenic meningitis in adults; Felisati G et al.; Otogenic meningitis is the most common intracranial complication of neglected otitis media . In the western world, such complications seldom occur in children and young adults and are extremely rare in adults and elderly people . The current use of antibiotics and of more sophisticated surgery has greatly diminished the incidence of otogenic meningitis in comparison with the past . This has resulted in physicians having less experience concerning diagnosis and treatment of this complication . The authors reported 3 consecutive cases of otogenic meningitis in adults, which occurred in the space of 3 months after a 6-year absence of such pathology at their institution . In all 3 cases, conventional antibiotic therapy proved ineffective; the course of the disease worsened rapidly in contrast with the lack of symptoms during the period before treatment . Emergency surgical treatment was mandatory.

J Fr Ophtalmol, 2004 Oct, 27(8), 924 - 6
{Eales disease and tuberculin hypersensitivity}; Amazouzi A et al.; The authors report the case of a 25-year-old woman who presented unilateral Eales disease associated with biologically confirmed pulmonary tuberculosis . The patient, from a family with a history of tuberculosis, showed a painless and abrupt decrease in visual acuity of the right eye with venous and arterial vasculitis . Fluorescein angiography confirmed the existence of peripheral ischemia and vascular abnormalities . The biological exam showed a positive PPD and the BK was isolated . Antibiotic and corticosteroid drugs were used in the treatment . The clinical, immunopathological and therapeutic aspects of this disease are discussed.

Clin Orthop, 2004 Oct, 1(427), 72 - 78
The Current Status of Material Used for Depot Delivery of Drugs; Nelson CL; The ideal local antibiotic delivery system has not been created . Antibiotic-laden bone cement has become the gold standard in the treatment of infected orthopaedic implants and there are confirmatory laboratory and clinical data that support the use of these materials . Heat-stable antibiotics elute from antibiotic-laden bone cement and do not have a notable influence on the compressive strengths of bone cement if the antibiotics are used in appropriate amounts . If the proper antibiotic is chosen, placed in the appropriately porous materials in sufficient amounts, and implanted in bone, antibiotic levels in the surrounding bone are many times greater than can be achieved by safe systemic antibiotic doses . Although the materials that have been manufactured commercially have been used for over 30 years in Europe, until recently, they have not been available in the United States . Currently, there are five antibiotic-laden bone cement composites that have been approved by the FDA and that are available for clinical use . Studies are being done to search for biodegradable implants preferable to antibiotic-laden bone cement; however, these studies and the materials are still in early stages and development . Currently, there are no FDA-approved biodegradable materials available for use to treat infected orthopaedic implants . As new materials become available and their elution characteristics are recorded, it is important for surgeons to understand how the data were collected so they can have a clear understanding of the elution characteristics of the material used and how the material acts in different environments . Even with extensive historic, clinical, and research data that prove the effectiveness of antibiotic-laden cement, the ideal drug delivery system is neither agreed on nor available.

Clin Orthop, 2004 Oct, 1(427), 25 - 27
The Effect of Glycine Filler on the Elution Rate of Gentamicin from Acrylic Bone Cement: A Pilot Study; McLaren AC et al.; Elution of antibiotics from acrylic bone cement (polymethylmethacrylate {PMMA}) is dependent on the access of fluid to the depths of the cement that contains the antibiotic . Commercially prepared antibiotic beads that are porous have higher elution rates than hand-mixed, nonporous antibiotic PMMA mixtures . To increase the elution of gentamicin from hand-mixed PMMA, glycine was added as a filler to produce porosity . Elution of gentamicin from the antibiotic PMMA-glycine mixture increased with increasing amounts of glycine . With 3.6 g gentamicin powder and 14 g of crystalline glycine per batch of Palacos PMMA, the elution of gentamicin from the PMMA at 2 days was, similar to the previously documented elution of gentamicin from commercially prepared porous Septopal PMMA beads . With further investigation it may be possible to identify a specific filler and a volume of filler that can be hand mixed in antibiotic PMMA to produce the elution behavior that is needed for specific clinical requirements.

Clin Infect Dis, 2004 Nov 15, 39(10), e100 - 5 Epub 2004 Oct 26.
Syphilitic hepatitis in HIV-infected patients: a report of 7 cases and review of the literature; Mullick CJ et al.; BACKGROUND: A recent resurgence of primary and secondary syphilis has been observed in certain population groups, particularly among persons infected with human immunodeficiency virus (HIV) . Liver involvement is an infrequently recognized complication of early syphilis, with no previous reports among HIV-infected patients . METHODS: We describe 7 cases of syphilitic hepatitis in HIV-positive individuals and review the literature . RESULTS: At our institutions, all patients presented with a rash consistent with secondary syphilis . Each case was characterized by a conspicuous increase in serum alkaline phosphatase level (mean level +/- standard deviation, 905 +/- 523.6 IU/L) and milder elevations in serum transaminase levels . The mean CD4+ absolute T cell count was 317 cells/mm3, and the median rapid plasma reagin (RPR) titer was 1 : 128 . There was a significant correlation between higher CD4+ cell counts and the RPR titers (R=0.93; P=.002) . Symptomatic resolution and biochemical improvement, particularly a significant decrease in serum alkaline phosphatase levels (P=.02), occurred following antibiotic therapy . CONCLUSIONS: Hepatic dysfunction is not uncommon in HIV-infected persons and is attributable to multiple causes . In the appropriate clinical setting, syphilitic hepatitis is an easily diagnosed and reversible etiology of liver dysfunction . The recognition of this entity will prevent unnecessary evaluation of abnormal liver enzyme levels in HIV-positive patients.

Arch Otolaryngol Head Neck Surg, 2004 Nov, 130(11), 1303 - 7
Randomized, controlled, multisite study of intracapsular tonsillectomy using low-temperature plasma excision; Chan KH et al.; OBJECTIVE: To determine the efficacy of intracapsular tonsillectomy using low-temperature plasma excision for improving the quality of the postoperative experience and for treating obstructive symptoms through 12 months postoperatively . DESIGN: Prospective, randomized, controlled, single-blind study . SETTING: Multiple private or institutional otolaryngology clinics . PATIENTS: Fifty-five children (aged 3-12 years) with obstructive tonsillar hypertrophy . INTERVENTION: Patients were randomly assigned and blinded to undergo either intracapsular tonsillectomy using low-temperature plasma excision (n = 27) or total tonsillectomy using conventional electrosurgery (n = 28) . MAIN OUTCOME MEASURES: Operative data, 14-day recovery variables, and obstructive symptoms were prospectively collected through 12 months . RESULTS: During the first 14 days, significantly fewer children in the intracapsular group reported nausea (P = .01) or lost weight (P = .003) . The intracapsular group had a significantly faster resolution of pain (P = .01), had an earlier return to a normal diet (P = .004), ceased taking pain medication sooner (P = .002), and returned to normal activity sooner (P = .04) . Postoperatively, the intracapsular group had more residual tonsil tissue than the total tonsillectomy group (P = .002 for the 3- and 12-month visits) . However, the incidence of recurring obstructive symptoms, pharyngitis, and antibiotic use was similar in both treatment groups during the 12 months . CONCLUSIONS: Postoperative morbidity normally associated with traditional (total) tonsillectomy was significantly reduced after intracapsular tonsillectomy using low-temperature plasma excision . The residual tonsillar tissue associated with this technique was of no clinical consequence.

Arch Facial Plast Surg, 2004 Nov-Dec, 6(6), 384 - 8
Subcutaneous superficial musculoaponeurotic system grafting of the aging melolabial furrow; Lamperti TA et al.; OBJECTIVE: To describe a technique of subcutaneous superficial musculoaponeurotic system grafting during rhytidectomy to treat the aging melolabial furrow . DESIGN: Two hundred seventeen patients received bilateral superficial musculoaponeurotic system grafts from December 1, 1996, through June 30, 2003 (a 78-month period) . The patients' charts were reviewed for demographic data, follow-up dates, and complications . Selected preoperative and postoperative photographs were viewed . RESULTS: In the 217 patients, 434 grafts were performed, with a mean follow-up of 23.2 months . Follow-up postoperative photographs showed effective long-term effacement of the melolabial furrow . There was a 0.9% complication rate involving 4 cases of unilateral graft infection that resolved with oral antibiotic therapy . CONCLUSIONS: Subcutaneous superficial musculoaponeurotic system grafting of the melolabial furrow is a safe, effective technique of treating the prominent melolabial furrow . It adds very little time to the rhytidectomy procedure, is well tolerated by patients, and shows durable results.

J Clin Pharmacol, 2004 Dec, 44(12), 1405 - 11
Metabolism by N-acetyltransferase 1 in vitro and in healthy volunteers: a prototype for targeted inhibition; Cantilena LR et al.; Inhibition of drug metabolism is generally avoided but can be useful in limited circumstances, such as reducing the formation of toxic metabolites . Acetylation is a major pathway for drug elimination that can also convert substrates into toxic species, including carcinogens . Sulfamethoxazole, a widely used antibiotic, is metabolized via arylamine N-acetyltransferase 1 . p-Aminosalicylate, used for antitubercular treatment, is also metabolized by N-acetyltransferase 1 and could potentially inhibit sulfamethoxazole metabolism . Human hepatocytes from 4 donors were incubated in vitro with sulfamethoxazole and paminosalicylate at clinically achievable concentrations . p-Aminosalicylate competitively reduced the acetylation of sulfamethoxazole in vitro by 61% to 83% at 200 microM . Four healthy volunteers were studied following doses of 500 mg sulfamethoxazole either alone or during administration of paminosalicylate (4 g ter in die) . Plasma concentrations of paminosalicylate exceeded 100 microM . With each subject as his or her own control, p-aminosalicylate reduced by 5-fold the ratio of plasma concentrations of acetylsulfamethoxazole relative to parent drug (P < .001) . Metabolic drug-drug interaction studies in vitro successfully predicted inhibition of acetylation via N-acetyltransferase 1 in vivo . Although no specific toxic species was investigated in this work, the potential was demonstrated for improving the therapeutic index of drugs that have toxic metabolites.

Eur J Radiol, 2004 Dec, 52(3), 257 - 63
Superficial inflammatory and primary neoplastic lymphadenopathy: diagnostic accuracy of power-doppler sonography; Magarelli N et al.; OBJECTIVE: To evaluate the sensitivity, specificity and diagnostic accuracy of a cut-off of the resistive index of 0.5 for the differentiation between inflammatory and neoplastic primary lymphadenopathies . SUBJECTS AND METHODS: We measured the resistive index of superficial enlarged lymph nodes in a total of 50 patients (29 males and 21 females; age range 12-72 years, mean age 41.6 year) using an ATL 5000 HDI . A resistive index greater than or equal to 0.5 indicated an inflammatory lymph node and a resistive index <0.5 was consistent with neoplastic primary lymphadenopathies . The gold standard was either surgical biopsy or lymph-node reduction seen with ultrasound examination after antibiotic therapy . RESULTS: The sensitivity of the resistive index for distinguishing inflammatory from neoplastic lymphadenopathy was 84.6%, the specificity 100% and the diagnostic accuracy 95.7% (P < 0.001, statistically significant) . CONCLUSION: The results of this study indicate that power-Doppler using a resistive index cut-off of 0.5 was a valid technique for distinguishing between inflammatory and primary neoplastic lymph nodes in patients with superficial lymphadenopathies.

Curr Med Chem, 2004 Oct, 11(19), 2585 - 637
Recent advances in 4'-thionucleosides as potential antiviral and antitumor agents; Gunaga P et al.; The classical 4'-oxonucleoside analogs exhibit interesting biological activities such as antibiotic, antiviral and antitumor, which are believed to be the result of inhibition of the viral or cellular DNA or RNA polymerase after being converted to their corresponding 5'-triphosphates . However, the activity of 4'-oxonucleosides were limited by their susceptibility to degradation by nucleoside phosphorylases or acid hydrolysis . This aspect called for the chemical modification of the carbohydrate portion . This compulsion led to two kinds of strategies; (1) replacement of the 4'-oxygen by the methylene group - carbocyclic nucleosides; (2) replacement of the 4' oxygen by sulphur-4'-thionucleosides . This group has also conferred the resistance to the nucleoside cleavage . Although, there were some pioneering work on 4'-thionucleosides in 1960s and 1970s, the interest in this group of compounds was rekindled by the antiviral activities of 2'-deoxy-4'-thionucleosides reported independently by Secrist et al . and Walker et al . Subsequent contributions by the other authors, enhanced its standing as an important class of antiviral agents . Following is a reasonably exhaustive account of this class of compounds reported after 1990.

Mol Cell Biochem, 2004 Sep, 264(1-2), 183 - 91
Expression of matrix metalloproteinase activity in idiopathic dilated cardiomyopathy: a marker of cardiac dilatation; Reddy HK et al.; BACKGROUND: Idiopathic dilated cardiomyopathy (DCM), ventricular systolic dysfunction and chamber dilatation are accompanied by architectural remodeling, wall thinning and cardiac myocyte slippage . Recent work has demonstrated an association between collagen degradation and an increased expression of matrix metalloproteinases (MMPs) . Accordingly, we have sought to correlate (a) collagen degradation with MMP elevations and, (b) assay the neutralizing potential of a known inhibitor of MMP, tetracycline on MMPs in DCM . METHODS: Assessment of LV volume and shape by 2-D echocardiography was performed . Light microscopic assessment of histopathology in picrosirius red stained biopsy samples of 11 DCM patients and six post-transplant patients was performed . Zymographic estimation of MMP activity and influence of tetracycline on MMP activity was assessed . RESULTS: Small amount of interstitial collagen was noted in the control group, whereas in the DCM hearts, chamber dilatation was associated with areas of scanty myocyte necrosis, islands of excess collagen, and focal areas of absent or scanty collagen with intact myocytes . In cardiomyopathic tissue, collagenase activity was markedly elevated at 63% compared with 8% in post-transplant tissue . Tetracycline at a concentration of 285+/-10 microM (IC50) inhibited collagenase activity by 50% in cardiomyopathic tissue . CONCLUSIONS: Areas of focal interstitial collagen accumulation were accompanied by collagen fiber lysis and increased collagenase activity in dilated cardiomyopathy . This enhanced collagenolytic activity found in endomyocardial biopsy tissue was inhibited by tetracycline . The non-antibiotic property of tetracycline may be of potential value in the prevention of ventricular dilatation in idiopathic dilated cardiomyopathy.

Mayo Clin Proc, 2004 Nov, 79(11), 1372 - 9
Eight-month prospective study of 14 patients with hospital-acquired severe acute respiratory syndrome; Chiang CH et al.; OBJECTIVE: To define the clinical characteristics and clinical course of hospital-acquired severe acute respiratory syndrome (SARS) . PATIENTS AND METHODS: This 8-month prospective study of 14 patients with hospital-acquired SARS in Taipei, Taiwan, was conducted from April through December 2003 . RESULTS: The most common presenting symptoms in our 14 patients with hospital-acquired SARS were fever, dyspnea, dizziness, malaise, diarrhea, dry cough, muscle pain, and chills . Lymphopenia and elevated serum levels of lactate dehydrogenase (LDH) and C-reactive protein (CRP) were the most common Initial laboratory findings . Initial chest radiographs revealed various pattern abnormalities and normal results . Five of the 14 patients required mechanical ventilation . The need for mechanical ventilation was associated with bilateral lung involvement on the initial chest radiograph and higher peak levels of LDH and CRP . Clinical severity of disease varied from mild to severe . At 8 months after disease onset, patients with mild or moderate SARS had normal findings or only focal fibrosis on chest high-resolution computed tomography . However, bilateral fibrotic changes remained in the 4 patients who had recovered from severe SARS, 1 of whom had mild restrictive ventilatory impairment . One patient with severe SARS died; she was elderly and had other comorbidities . Five additional patients had reduced diffusing capacity . CONCLUSION: The clinical picture of our patients presenting with hospital-acquired SARS revealed atypical pneumonia associated with lymphopenia, elevated serum levels of LDH, rapid clinical deterioration, and lack of response to empirical antibiotic therapy . Substantially elevated levels of LDH and CRP correlated with severe illness requiring mechanical ventilatory support . In those receiving mechanical ventilation, pulmonary function was only mildly reduced at 6 to 8 months after acute illness, consistent with the natural history of acute respiratory distress syndrome due to other causes.

Gut, 2004 Dec, 53(12), 1801 - 5
Human lymphocyte stimulation with pouchitis flora is greater than with flora from a healthy pouch but is suppressed by metronidazole; Bell AJ et al.; BACKGROUND/AIMS: The gut flora may play an important role in the pathogenesis of inflammatory bowel disease . An ileal reservoir or pouch can be created to replace the excised rectum after proctocolectomy . In patients with ulcerative colitis this is subject to inflammation and termed pouchitis . Using bacteria from patients the authors sought evidence for the presence rather than the identity of a pathogenic species in pouchitis, and for its absence in healthy pouches by the differential effect on lymphocyte proliferation . METHODS: An ex vivo cell culture assay was used in which peripheral blood mononuclear cells or lamina propria mononuclear cells were cultured with sterile sonicates of gut flora from patients with or without pouchitis in the presence of antigen presenting cells . RESULTS: Sonicated pouchitis flora produced a consistent and intense proliferation of the mononuclear cells but that produced by sonicates from healthy pouches was minimal (p = 0.012 or 0.018, peripheral blood or lamina propria mononuclear cells) . Preparation of the sonicates with the antibiotic metronidazole abolished their stimulatory ability (p = 0.005, peripheral blood mononuclear cells) . In separate assays neither direct addition of metronidazole nor of its hydroxy metabolite affected the mononuclear cells' proliferation with alternative stimuli . CONCLUSIONS: These results strongly support a bacterial aetiology for pouchitis.

J Anim Sci, 2004 Nov, 82(11), 3308 - 13
Influence of ceftiofur sodium biobullet administration on tenderness and tissue damage in beef round muscle; Morgan JB et al.; The effect of a biobullet (BB) containing freeze-dried ceftiofur sodium antibiotic on the presence of injection lesions, tissue damage, and histological properties, as well as Warner-Bratzler shear force (WBSF), of the biceps femoris was investigated . Steer calves (n = 25) were individually identified and assigned randomly to a product administration treatment date (7, 14, 21, 28, or 35 d before slaughter) . At each pre-slaughter ceftiofur BB administration time, identified steers (n = 5) were humanely placed into a standard commercial restraining chute, where a BB implant was administered from a distance of 6.09 m . Following a standard finishing period (120 d), steers were transported to a commercial beef processing and humanely slaughtered . Following a 36-h postmortem chilling (1 degree C) period, carcasses were graded and fabricated according to industry-accepted procedures . Paired muscle samples were individually identified, collected, and aged for 14 d postmortem . Muscles were dissected into 1.27-cm strips, followed by observation and palpation for the presence of injection site lesions . Preslaughter administration times of 7 and 14 d resulted in the presence of injection lesions (80 and 20%, respectively) . In addition to the control samples, no muscle damage was observed in cattle treated with BB implants 21, 28, or 35 d before slaughter . Warner-Bratzler shear force measurements taken near lesions of BB steaks and in areas 5.08 cm from lesions of control steaks tended to be higher (P < 0.10) than for other BB and control sample locations . Concentrations of insoluble and soluble collagen were higher (P < 0.05) at the site of the lesion center in lesion-afflicted vs . with control steaks . Histological determinations of the relative proportions of muscle, connective tissue, and fat were altered (P < 0.05) in BB lesion-afflicted steak cores; however, these differences were negated outside the core location of BB-treated and control steaks . It seems that using the ceftiofur BB implant system within 14 d of slaughter does create injection site lesions and increase WBSF; however, when the BB implant system, containing 100 mg of freeze-dried ceftiofur sodium, was used according to the recommended procedure (> or = 30 d preslaughter), tissue damage, alterations in histological and collagen properties, and increased meat toughness were not observed.

Curr Urol Rep, 2004 Dec, 5(6), 460 - 6
Penile prosthesis coating and the reduction of postoperative infection; Abouassaly R et al.; Despite the recent development of effective oral agents for the treatment of erectile dysfunction, penile prosthesis implantation remains an effective and acceptable treatment for the significant number of men who fail to respond to nonsurgical therapy . The most serious complication that can affect the use of most prosthetic devices is infection . In penile prostheses, this can be devastating and frequently results in removal of the device despite aggressive antibiotic therapy . In recent years, new strategies have been developed in an attempt to minimize this risk . This review focuses on one such method, namely the use of an antibiotic coating on the device . It reviews recent published data regarding the effectiveness of such devices at decreasing infection rates.

Chem Res Toxicol, 2004 Nov, 17(11), 1406 - 13
5'-(2-phosphoryl-1,4-dioxobutane) as a product of 5'-oxidation of deoxyribose in DNA: elimination as trans-1,4-dioxo-2-butene and approaches to analysis; Chen B et al.; Oxidation of deoxyribose in DNA leads to the formation of a spectrum of electrophilic products unique to each position in the sugar . For example, chemical reactions following abstraction of the C5'-hydrogen atom partition to form either a nucleoside 5'-aldehyde residue attached to the 5'-end of the DNA strand or a 5'-formyl phosphate residue attached to the 3'-end of the DNA strand that is accompanied by a four-carbon fragment on the 5'-end . We now present two approaches that both identify the latter fragment as 5'-(2-phosphoryl-1,4-dioxobutane) and provide a means to quantify the formation of this residue by different oxidizing agents . The first approach involves oxidation of DNA followed by reaction with O-benzylhydroxylamine to form stable dioxime derivatives of the putative 5'-(2-phosphoryl-1,4-dioxobutane) residues . The beta-elimination product of this dioxime proved to be the expected trans-1,4-dioxo-2-butene, as judged by gas chromatographic and mass spectrometric (GC/MS) comparison to authentic dioximes of cis- and trans-1,4-dioxo-2-butene, which revealed a unique pattern of three signals for each isomer, and by X-ray crystallography . Using a benzylhydroxylamine dioxime derivative of {2H4}-labeled cis-1,4-dioxo-2-butene as an internal standard, the dose-response for the formation of 5'-(2-phosphoryl-1,4-dioxobutane) was determined to be linear for gamma-radiation, with approximately 6 lesions per 10(6) nt per Gy, and nonlinear for Fe2+-EDTA . A comparison of 5'-(2-phosphoryl-1,4-dioxobutane) formation to total deoxyribose oxidation suggests that gamma-radiation produces approximately 0.04 lesions per deoxyribose oxidation event . As a positive control for 5'-oxidation of deoxyribose, the enediyne calicheamicin was observed to produce 5'-(2-phosphoryl-1,4-dioxobutane) at the rate of approximately 9 lesions per 10(6) nt per microM . A second approach to identifying and quantifying the sugar residue involved derivatization with hydrazine and beta-elimination to form pyridazine followed by quantification of the pyridazine by GC/MS . Using this approach, it was observed that the enediyne, neocarzinostatin, produced a linear dose-response for pyridazine formation, as expected given the ability of this oxidant to cause 1'-, 4'-, and 5'-oxidation of deoxyribose in DNA . The antitumor antibiotic, bleomycin, on the other hand, produced pyridazine at a 10-fold lower rate, which is consistent with 4'-chemistry as the predominant mode of deoxyribose oxidation by this agent . These results provide novel insights into the chemistry of deoxyribose oxidation in DNA and two approaches to quantifying the 5'-(2-phosphoryl-1,4-dioxobutane) precursor of trans-1,4-dioxo-2-butene, an electrophile known to react with nucleobases to form novel DNA adducts.

J Neurosurg, 2004 Nov, 101(5), 757 - 61
Prophylactic administration of ceftriaxone for the prevention of meningitis after traumatic pneumocephalus: results of a clinical trial; Eftekhar B et al.; OBJECT: The purpose of this study was to compare the efficacy of the prophylactic use of ceftriaxone for the prevention of meningitis in patients with acute traumatic pneumocephalus . METHODS: In this prospective, single-institution, randomized clinical trial, 109 patients with mild head injury and traumatic pneumocephalus were randomly assigned to receive or not receive an antibiotic medication (ceftriaxone, 1 g given twice a day) until occurrence of meningitis or at least 5 days after trauma . The patients were followed up for 1 month posttrauma . The 109 patients were divided into two groups: 53 were assigned to the prophylactic antibiotics therapy group and 56 to the control group . The overall rate of meningitis was 20.1% and the rates of meningitis in the two groups were not significantly different . The results were the same when adjusted for the patient's Glasgow Coma Scale score, sex, and age, as well as for an intradural location of air, air volume, presence of cerebrospinal fluid (CSF) rhinorrhea or CSF otorrhea, radiological sign of a skull base fracture, or intracranial hemorrhage . CONCLUSIONS: The results of this study do not substantiate the efficacy of ceftriaxone used in the prevention of meningitis in patients with traumatic pneumocephalus after mild head injury or in any specific subgroup of these patients . Cerebrospinal fluid rhinorrhea and intracranial hemorrhage may be considered primary risk factors for the development of meningitis in patients with posttraumatic pneumocephalus and, in the absence of these symptoms, intradural location of air and air volume greater than 10 ml may be considered secondary risk factors . Further studies in this area are warranted.

MMW Fortschr Med, 2004 Jul 22, 146(29-30), 38 - 41
{Pain and neuroborreliosis}; Berthele A et al.; Pain is one of the presenting symptoms in acute neuroborreliosis . Classically, acute neuroborreliosis--also known in Europe as Bannwarth's syndrome--is a combination of radicular pain, cranial neuritis and peripheral radiculitis and inflammatory changes of the CSF . The prognosis following antibiotic therapy is favorable . At least in its early stages, however, the diagnosis neuroborreliosis might be missed or mistaken . Thus, targeted assessment of typical signs is needed to expedite examination of the CSF which then permits definitive diagnosis.

Laryngorhinootologie, 2004 Nov, 83(11), 750 - 3
{The interesting case -- case no . 65}; Durisin M et al.; Bilateral Osteomyelitis following frontal sinusitis is a rare complication in the antibiotic era . The main risk of a progredient course is mainly the formation of external subperiostal, epidural, subdural abscesses or brain abscesses with potentially life-threatening complications . This is a report on a patient who presented in our department with progredient cephalgia and swelling in the area around the glabella and frontal sinus . Macroscopical examination revealed septum deviation to the right side and nasal polyposis of the right nasal passage . A computed tomography of the paranasal sinuses showed subtotal soft tissue obstruction of all sinuses with the exception of the sphenoidal sinus . Bilateral osteolysis of the ventral osseous borders of the frontal sinus with accompanying osteosclerosis was also observed . The therapy consisted of radical frontal sinus surgery via Unterberger approach . This case demonstrates a rare case of bilateral frontal osteomyelitis together with the necessary diagnostic and therapeutic measures . The management consisted of the removal of all osteomyelitic bone and antibiotic therapy . Differential diagnostic procedures must be carried out in order to exclude orbital and intracranial complications . Regular follow-up examinations and a CT scan of the paranasal sinuses are part of the standard therapy.

Ann Pharmacother, 2004 Dec, 38(12), 2035 - 40 Epub 2004 Nov 09.
Intraperitoneal cefazolin and ceftazidime effects on human peritoneal mesothelial cell release of cancer antigen-125; Manley HJ et al.; BACKGROUND: Intraperitoneal (IP) cefazolin and ceftazidime are recommended as empiric treatment for peritoneal dialysis (PD)-associated peritonitis . Human peritoneal mesothelial cells (HPMCs) may be affected by high IP cefazolin and ceftazidime concentrations . Peritoneal dialysate cancer antigen-125 (CA-125) appearance rate can be used to measure HPMC damage . OBJECTIVE: To determine whether IP cefazolin and ceftazidime increase peritoneal CA-125 appearance rate . METHODS: The study consisted of 2 phases . In phase I, no antibiotic was administered, and in phase II, patients received IP cefazolin and ceftazidime (15 mg/kg rounded to nearest 100 mg) . Phase II occurred immediately after phase I . Each phase used a 4-hour dwell time with 2 L of dextrose 2.5% dialysate . Dialysate samples were collected at 0, 0.5, 1, 2, and 4 hours during each phase . Samples were assayed for CA-125, and CA-125 appearance rate was calculated . RESULTS: Thirteen patients were recruited (7 men; aged 44.0 +/-16.0 y) . The mean +/- SD (range) CA-125 dialysate concentration after phases I and II were 6.6 +/- 3.7 U/mL (2.3-15.0) and 6.4 +/-3.8 U/mL (1.6-13.8), respectively (p = 0.46) . The CA-125 appearance rate after phases I and II were 51.9 +/- 31.3 U/min/1.73 m(2) (13.8-113.0) and 50.5 +/- 32.9 U/min/1.73 m(2) (11.0-104.0), respectively (p = 0.57) . The slopes of the regression lines of CA-125 appearance rate were not significantly different between phases I and II . CONCLUSIONS: These findings demonstrate that concurrently administered IP cefazolin and ceftazidime have no effect on HPMC release of CA-125 in non-infected PD patients.

Chem Biol Interact, 2004 Nov 20, 150(2), 137 - 47
An evaluation of the P450 inhibition and induction potential of daptomycin in primary human hepatocytes; Oleson FB et al.; Two in vitro studies assessed the potential of daptomycin (Cubicin), a newly marketed antibiotic, to affect the cytochrome P450 (CYP450) isoforms in primary cultured human hepatocytes . Both induction and inhibition of isoforms 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 were evaluated . The highest concentrations of daptomycin used in both the induction and inhibition assays were approximately eight-fold higher than the peak total drug concentration (50-60 microg/mL), or the peak free drug concentration (estimated 5-6 microg/mL), in plasma at the clinical dose regimen of 4 mg/kg qd . Results in primary human hepatocytes indicate that daptomycin, at concentrations up to 400 microg total drug/mL, demonstrated no biologically significant induction of any of the CYP450 isoform activities in comparison with the negative control or known inducers . At daptomycin concentrations up to 40 microg free drug/mL, no biologically significant inhibition of the activities of these CYP450 isoforms was observed as compared with known inhibitors . The human hepatocyte results demonstrate that daptomycin has no effects on hepatic CYP450-mediated drug metabolism and, therefore, suggest that daptomycin is unlikely to show potential for pharmacokinetic interactions with concomitantly administered drugs that are metabolized by CYP450 isoforms.

Am Surg, 2004 Oct, 70(10), 841 - 4
Necrotizing soft tissue infections: improved outcomes with modern care; Tillou A et al.; The outcome of necrotizing soft tissue infections (NSTI) remains unchanged despite advances in care . Reasons cited are changing patterns of causative factors, delays in diagnosis, and inadequate antibiotic coverage and surgical treatment . To document outcomes of NSTI after aggressive management and to identify risk factors of mortality and prolonged hospital stay, we reviewed all our patients with NSTI admitted from January 2000 to January 2002 . Causative factors, comorbid conditions, site of NSTI, physiologic parameters, symptoms, diagnostic tests, therapeutic interventions, and outcomes were analyzed . Patients were treated aggressively with antibiotics, admission to ICU, and frequent surgical debridements . Of 46 patients identified, 28 (61%) were admitted in ICU, and eight (17%) died . The patients who died had higher admission white blood cell counts (46 +/- 22 vs 22 +/- 10 x 10(3)/mm3, P = 0.01), higher admission pain score (8 +/- 1 vs 5 +/- 3, P = 0.02), longer intervals from admission to antibiotic administration (16 +/- 20 vs 6 +/- 12 hours, P = 0.02), and fewer surgical debridements (2.6 +/- 1.1 vs 3.6 +/- 1.7, P = 0.04) . No independent risk factors of mortality or ICU admission were identified . We concluded that severe local pain and a significantly elevated white blood cell count on admission should alert the physician to the presence of severe infection and prompt the initiation of expeditious aggressive treatment.

Clin Orthop, 2004 Nov, (428), 190 - 7
Extended medial gastrocnemius rotational flap for treatment of chronic knee extensor mechanism deficiency in patients with and without total knee arthroplasty; Busfield BT et al.; Nine patients with chronic extensor mechanism disruption were treated with an extended medial gastrocnemius rotational flap reconstruction of the extensor mechanism . Seven patients previously had total knee arthroplasty and two patients had chronic infection of nonreplaced, native knees . Four patients previously had failed Achilles' tendon allograft reconstruction after total knee arthroplasty and two were complicated by infection . Infected arthroplasty patients had a staged procedure with placement of an antibiotic spacer after debridement and extended medial gastrocnemius rotational flap, followed by total knee arthroplasty replant 8 weeks later . The four infected arthroplasty patients had medical comorbidities that included a patient with HIV and hemophilia, and two with diabetes mellitus . Another patient with rheumatoid arthritis was severely malnourished as a result of dumping syndrome . Of the four patients treated by this two-stage procedure, one died in the early postoperative period from chronic medical issues after the second stage and another patient elected to have above-knee amputation after the first stage because of severe reflex sympathetic dystrophy . The final group of seven patients was studied at a mean followup of 21 months (range, 7-31 months), the average extensor lag was 13.5 degrees (range, 0-50 degrees ), and the average range of motion was 2 degrees to 93 degrees . The two patients with nonreplaced, native knees had extensor lags of 30 degrees and 10 degrees . All patients were able to regain sufficient extensor mechanism strength to return to independent ambulation, and all infections resolved after treatment . Two patients were able to ascend stairs foot over foot without support . In addition to the patient who had amputation, the other complication involved a wound breakdown that required a free flap at 13 months in a patient who had a failed Achilles' tendon allograft reconstruction after takedown of a knee fusion . Medial gastrocnemius flap reconstruction can provide successful salvage of a failed extensor mechanism allograft or an alternative to allograft reconstruction in patients with poor soft tissue coverage, previous infection, or a compromised immune system.

Clin Orthop, 2004 Nov, (428), 35 - 9
Mid-term to long-term followup of two-stage reimplantation for infected total knee arthroplasty; Haleem AA et al.; Between January 1989 and December 1994, 94 patients (96 knees) had a two-stage reimplantation for treatment of an infected total knee arthroplasty . All patients were treated with an interval antibiotic-loaded static cement spacer and had antibiotic-loaded bone cement for prosthesis fixation at the time of reimplantation . The purpose of this study was to assess the long-term risk of reinfection and the mechanical durability of these reimplantation arthroplasties . Patients were followed up for a median of 7.2 years (range, 2.5-13.2 years) . At final followup, 15 knees (16%) had required reoperation . Nine knees (9%) had component removal for reinfection and six knees (6%) were revised for aseptic loosening . The median time to reoperation for reinfection was 1 year (range, 0.1-9.8 years) . The risk of recurrent infection was not correlated with the type of organism, patient demographics, or method of prosthesis fixation at reimplantation . The survivorship free of implant removal for any reason was 90% (confidence intervals, 83.9-96.4%) at 5 years and 77.3% (confidence intervals, 65.5-89.6%) at 10 years . The survivorship free of implant removal for reinfection was 93.5% (confidence intervals, 88.5-98.7%) at 5 years and 85% (confidence intervals, 73.8-96.3%) at 10 years . Survival free of revision for mechanical failure (aseptic loosening or radiographic loosening) was 96.2% (confidence intervals, 92-100%) at 5 years and 91% (confidence intervals, 80.8-98.3%) at 10 years . These results suggest that the high likelihood of early success after two-stage reimplantation of an infected TKA is well maintained throughout long-term followup, with a modest rate of late recurrent infection or mechanical implant failure.

J Pharm Biomed Anal, 2004 Nov 19, 36(4), 871 - 6
A high-performance liquid chromatographic method for determination of praziquantel in plasma; Hanpitakpong W et al.; A simple, sensitive, selective and reproducible method based on a reversed-phase chromatography was developed for the determination of praziquantel in human plasma . Praziquantel was separated from the internal standard (diazepam) on a Luna C18 column (250 mm x 4.6mm, 5 microm particle size), with retention times of 4.8 and 6.2 min, respectively . Ultraviolet detection was set at 21 7 nm . The mobile phase consisted of acetonitrile and distilled water (70:30, v/v), running through the column at a flow rate of 1.0 ml/min . The chromatographic analysis was operated at 25 degrees C . Sample preparation (1 ml plasma) was done by a single step liquid-liquid extraction with the mixture of methyl-tert-butylether and dichloromethane at the ratio of 2:1 (v/v) . Calibration curves in plasma at the concentrations 0, 50, 100, 200, 400, 800 and 1600 ng/ml were all linear with correlation coefficients better than 0.999 . The precision of the method based on within-day repeatability and reproducibility (day-to-day variation) was below 15% (relative standard deviation: R.S.D.) . Good accuracy was observed for both the intra-day or inter-day assays, as indicated by the minimal deviation of mean values found with measured samples from that of the theoretical values (below +/-15%) . Limit of quantification (LOQ) was accepted as 5 ng using 1 ml samples . The mean recovery for praziquantel and the internal standard were greater than 90% for both praziquantel and internal standard . The method was free from interference from the commonly used antibiotic and antiparasitic drugs . The method appears to be robust and has been applied to a pharmacokinetic study of praziquantel in three healthy Thai volunteers following a single oral dose of 40 mg/kg body weight praziquantel.

J Pharm Biomed Anal, 2004 Nov 19, 36(4), 851 - 8
DNA-modified carbon paste electrode applied to the study of interaction between Rifampicin (RIF) and DNA in solution and at the electrode surface; Girousi ST et al.; Rifampicin (RIF) is an antibiotic widely used against tuberculosis and a DNA intercalator . The interaction of RIF with double-stranded (ds) and single-stranded (ss) calf thymus DNA was studied in solution as well as at the electrode surface by means of transfer voltammetry using differential pulse as stripping mode with carbon paste electrode (CPE) at 0.2M acetate buffer at pH 5.0 and at 0.2M phosphate buffer pH 7.4 . Differentiations in the above-mentioned interaction at different pH values are presented and compared in order to optimize the detection of Rifampicin (RIF).

J Pharm Biomed Anal, 2004 Nov 19, 36(4), 751 - 7
Development of a liquid chromatographic method for ear drops containing neomycin sulphate, polymyxin B sulphate and dexamethasone sodium phosphate; Pendela M et al.; Two liquid chromatographic methods were developed to analyse ear drops containing neomycin sulphate, polymyxin B sulphate and dexamethasone sodium phosphate . This formulation will be described in the Belgian National Formulary . Since neomycin, an aminoglycoside antibiotic, has no UV chromophore and pre or post column derivatization is complicated, pulsed electrochemical detection on a gold electrode was chosen to determine neomycin . Polymyxin B sulphate and dexamethasone sodium phosphate do have a UV chromophore . So, a single LC method with UV detection was developed for the determination of polymyxin B sulphate and dexamethasone sodium phosphate . The sample pretreatment is simply done by diluting the formulation with water . For each method, the influence of the different chromatographic parameters on the separation, the interference of other active compounds and excipients, the repeatability and the linearity were investigated . Finally, the content of the actives in the formulation was studied at 0, 2, 4, 6, and 8 weeks.

J Mol Biol, 2004 Nov 26, 344(3), 653 - 63
Analysis of the context dependent sequence requirements of active site residues in the metallo-beta-lactamase IMP-1; Materon IC et al.; The metallo-beta-lactamase IMP-1 catalyzes the hydrolysis of a broad range of beta-lactam antibiotics to provide bacterial resistance to these compounds . In this study, 29 amino acid residue positions in and near the active-site pocket of the IMP-1 enzyme were randomized individually by site-directed mutagenesis of the corresponding codons in the bla(IMP-1) gene . The 29 random libraries were used to identify positions that are critical for the catalytic and substrate-specific properties of the IMP-1 enzyme . Mutants from each of the random libraries were selected for the ability to confer to Escherichia coli resistance to ampicillin, cefotaxime, imipenem or cephaloridine . The DNA sequence of several functional mutants was determined for each of the substrates . Comparison of the sequences of mutants obtained from the different antibiotic selections indicates the sequence requirements for each position in the context of each substrate . The zinc-chelating residues in the active site were found to be essential for hydrolysis of all antibiotics tested . Several positions, however, displayed context-dependent sequence requirements, in that they were essential for one substrate(s) but not others . The most striking examples included Lys69, Asp84, Lys224, Pro225, Gly232, Asn233, Asp236 and Ser262 . In addition, comparison of the results for all 29 positions indicates that hydrolysis of imipenem, cephaloridine and ampicillin has stringent sequence requirements, while the requirements for hydrolysis of cefotaxime are more relaxed . This suggests that more information is required to specify active-site pockets that carry out imipenem, cephaloridine or ampicillin hydrolysis than one that catalyzes cefotaxime hydrolysis.

Clin Otolaryngol, 2004 Dec, 29(6), 598 - 601
The use of perioperative Sofradex eardrops in preventing tympanostomy tube blockage: a prospective double-blinded randomized-controlled trial; Arya AK et al.; Around 11-12% of tympanostomy tubes are reported to become blocked by middle ear secretions or blood immediately following surgery, and so no longer function . Many otologists routinely instil an antibiotic and steroid-containing solution at the time of surgery in the belief that this may reduce this complication . The aim of the study was to investigate the efficacy of instilling the antibiotic and steroid-containing solution Sofradex at the time of grommet insertion in preventing grommet blockage . Double-blind randomized-controlled trial, comparing rates of grommet blockage in ears treated with Sofradex drops against control (no drops) in patients undergoing bilateral grommet insertion . Sixty-one pairs of results were obtained . There was a significant difference between the rates of grommet blockage in the two groups . Grommets with Sofradex drops instilled perioperatively were nine times less likely to be blocked than controls {1.6%versus 13.1%, odds ratio (Sofradex/control) = 9.06, 95% confidence interval (CI): 1.04-78.82, P = 0.05} . There was no association between grommet blockage and perioperative bleeding or the nature and presence of middle ear secretions . Sofradex eardrops are effective in reducing the rate of grommet blockage when instilled perioperatively.

Ann Acad Med Singapore, 2004 Sep, 33(5), 656 - 9
Acute isolated sphenoid sinusitis; Tan HK et al.; INTRODUCTION: Acute isolated sphenoid sinusitis is seen in fewer than 3% of all cases of sinusitis . It is frequently misdiagnosed because of its vague symptoms and the paucity of clinical findings . We report 2 cases of isolated acute isolated sphenoid sinusitis with unusual presentations . CLINICAL PICTURE: Both patients presented with acute headache, eye pain and fever, and were provisionally diagnosed as meningitis . In 1 case, the symptoms were on the contralateral side of the sphenoid infection . Intracranial complications were also present . TREATMENT: Treatment included intravenous antibiotics and endoscopic sphenoidotomy . OUTCOME: Both patients recovered with no residual neurological disability . CONCLUSION: Acute sphenoiditis usually presents with subtle symptoms and elusive physical findings and hence a high index of suspicion is necessary . Complications may arise due to the close proximity of important structures to the sphenoid sinus . Uncomplicated cases can resolve with optimal antibiotic therapy if diagnosed and treated early . Persistence or progression of disease with development of intracranial complications are indications for immediate surgical drainage.

Int J Tuberc Lung Dis, 2004 Oct, 8(10), 1173 - 9
Pentaglobin in steroid-resistant severe acute respiratory syndrome; Ho JC et al.; SETTING: The treatment of severe acute respiratory syndrome (SARS) is at best controversial, although there is considerable anecdotal experience to show the benefits of corticosteroid therapy for selected patients . Some patients deteriorate relentlessly despite treatment with antibiotic, corticosteroid and mechanical ventilation . OBJECTIVE: To attempt to determine the clinical efficacy of pentaglobin, an IgM-enriched immunoglobulin preparation, on 12 severe SARS patients who continued to deteriorate despite corticosteroid and ribavirin therapy . DESIGN: Retrospective analysis of daily quantitative and radiographic data on the cohort in a regional teaching hospital . RESULTS AND CONCLUSION: There was significant improvement in radiographic scores, when compared with day 1, on days 5, 6 and 7 (P < 0.05) after commencement of pentaglobin treatment . Similarly, there was significant improvement in oxygen requirement, when compared with day 1, on days 6 and 7 (P < 0.05) after commencement of pentaglobin treatment . There were no reported adverse events attributable to pentaglobin administration . Ten patients made an uneventful recovery after treatment . One elderly man died from cardiorespiratory arrest despite clinical and radiological improvement, and another patient is making good progress . Pentaglobin is safe and probably effective in the treatment of steroid-resistant SARS . A double-blind placebo-controlled study should therefore be considered.

Med Pr, 2004, 55(2), 189 - 92
{Should ticks be regarded as a tularemia vector in habitants of North-Eastern Poland?}; Pancewicz SA et al.; BACKGROUND: A growing incidence of tick borne encephalitis and Lyme borreliosis in north-eastern Poland as well as an increasing number of Ixodes ricinus ticks in wooded areas and meadows have prompted the authors to evaluate the presence of antibodies against Francisella tularensis in serum of forest workers . MATERIALS AND METHODS: Sera of 820 persons, including 765 healthy forest workers (group I) and 55 patients with lymphadenopathy (group II) admitted to the Department of Infectious and Neuroinfectious Diseases, Medical Academy, Bialystok, were diagnosed for antibodies against F . tularensis . Agglutination test at 37 degrees C, with suspensed F . tularensis (Biomed, Krakow, Poland) were used . Simultaneously all sera were tested for the presence of antibodies against B . burgdorferi, using ELISA test, Borrelia IgM and Borrelia IgG recombinant (Biomedica, Austria) . RESULTS: Of the 765 forest workers (group I), 20 (2.06%), persons showed positive (1:20) result of agglutination test, including 8 persons with antibodies against B . burgdorferi in IgG, of these 1 in IgM and IgG . Twenty persons with positive agglutination test had no signs of present or past tularemia in physical examination . Nine persons with prior diagnosis of arthritic form of Lyme boreliosis had undergone repeated antibiotic therapy (two 30-days therapy courses with cefotaksym or doxycycline) . In group II, sera of 55 patients were negative in the agglutination test with F . tularensis . CONCLUSIONS: The results of our study show that in North-Eastern Poland, Ixodes ricinus is not essential in Francisella tularensis transmission in this region.

Ophthalmology, 2004 Nov, 111(11), 2015 - 22
Post-traumatic endophthalmitis; Essex RW et al.; OBJECTIVE: To establish risk factors for the occurrence of post-traumatic endophthalmitis, to observe the efficacy of prophylaxis, and to describe the clinical features of post-traumatic endophthalmitis . DESIGN: Partially prospective consecutive case-control study . PARTICIPANTS: A total of 250 consecutive patients admitted to a single ophthalmic hospital with open globe injuries during a 3-year period were included . METHODS: Patients with post-traumatic endophthalmitis were identified prospectively and added to an endophthalmitis database . All open globe injuries during the same time period were identified through a retrospective search of inpatient admissions, and their charts were reviewed . Information collected from all patient files included patient age; gender; injury setting (indoor/outdoor); wound contamination; nature of injury (site on eye, lens involvement, retained intraocular foreign body); mechanism of injury (penetration/perforation/rupture/ruptured surgical wound); prophylactic antibiotic administration, including route and timing; timing of primary repair; lensectomy at the time of primary repair; and depot corticosteroid at the time of primary repair . Any association between these parameters and the subsequent development of endophthalmitis was investigated . Any association between endophthalmitis and final visual acuity (VA) and also enucleation was evaluated . MAIN OUTCOME MEASURE: Development of endophthalmitis . RESULTS: The frequency of endophthalmitis after open globe injury was 6.8% . The following factors were associated with the subsequent development of endophthalmitis by univariate analysis: dirty wound (14.3% vs . 4.1%, P = 0.01), retained intraocular foreign body (13.0% vs . 4.4%, P = 0.02), lens capsule breach (12.8% vs . 3.2%, P = 0.01), delayed primary repair (> or =12 hours) (11.3% vs . 2.9%, P = 0.02), and rural address (10.1% vs . 4.3%, P = 0.07) . Risk factors identified after multivariate analysis were dirty injury (odds ratio {OR}, 5.3; 95% confidence interval {CI)}, 1.5-18.7), breach of lens capsule (OR, 4.4; 95% CI, 1.2-15.6), and delay in primary repair (per hour: OR, 1.013; 95% CI, 1.002-1.024) . None of the following factors was found to be associated with post-traumatic endophthalmitis: patient age, gender, injury setting, site of injury on eye, mechanism of injury, antibiotic administration, lensectomy at the time of primary repair, and depot corticosteroid at the time of primary repair . Final VA tended to be worse in eyes with endophthalmitis (P = 0.08) . Endophthalmitis did not significantly influence the frequency of enucleation/evisceration (5.9% vs . 4.3%, P = 0.55) . CONCLUSIONS: Delay in primary repair, ruptured lens capsule, and dirty wound were each independently associated with the development of post-traumatic endophthalmitis . Patients with > or =2 of these 3 risk factors had a particularly high frequency of infection.

Am J Manag Care, 2004 Oct, 10(10), 681 - 6
Improving care for nursing home-acquired pneumonia in a managed care environment; Hutt E et al.; OBJECTIVE: To characterize care of nursing home residents who became ill with nursing home-acquired pneumonia (NHAP) in a group-model, nonprofit HMO, and to pilot-test a strategy to implement evidence-based NHAP care guidelines . STUDY DESIGN: Medical record review and intervention pilot test . METHODS: Nursing home medical records of 78 patients who developed NHAP in 6 homes where the HMO contracts for Medicare services were reviewed for demographics, functional status, comorbidity, NHAP severity, care processes, and guideline compliance . The intervention, combining organizational change (facilitating immunization and providing appropriate emergency antibiotics) and education (quarterly in-services for nursing and aide staff), was pilot-tested for 7 months in 1 facility . Measures of baseline and intervention guideline adherence at that facility were compared with Fisher's exact test . RESULTS: Among the patients with NHAP, 83% had a response from their physician in less than 8 hours, 82% were treated with an antibiotic that met spectrum recommendations, and 74% were able to swallow were treated with oral antibiotics . However, few patients had documentation of influenza and pneumococcal vaccination; less than half the direct care staff had been vaccinated; and nursing assessments were incomplete for 23% . At the pilot-test facility, improvement was seen in influenza vaccination (14% to 52%, P = .01) and use of the most appropriate antibiotics (47% to 85%; P = .03) . The guideline adherence score improved from 52% to 63% (P = .04) . CONCLUSION: Use of a multidisciplinary, multifaceted intervention resulted in improvement in quality of care for nursing home residents who become ill with pneumonia.

Environ Pollut, 2005 Feb, 133(3), 389 - 401
Aquatic microcosm assessment of the effects of tylosin on Lemna gibba and Myriophyllum spicatum; Brain RA et al.; Tylosin is a macrolide antibiotic commonly used for therapeutic treatment and prophylaxis in livestock . As part of a larger ecotoxicological study, the potential phytotoxic effects of tylosin on the rooted macrophyte Myriophyllum spicatum and the floating macrophyte Lemna gibba were assessed under semi-field conditions using 15 12 000-L microcosms . Concentrations of 0, 10, 30, 300 microg/L (n = 3), and 600, 1000, and 3000 microg/L (n = 1) were evaluated as part of separate ANOVA and regression analyses over an exposure period of 35 days . Fate of tylosin was monitored over time in the highest three treatments, where dissipation followed pseudo-first order kinetics with associated half-lives ranging from 9 to 10 days . For both M . spicatum and L . gibba, tylosin was found to cause no biologically significant changes to any endpoint assessed compared to controls at a Type I error rate of 0.1 . However, subsequent power analyses revealed that there was generally insufficient power to declare that there were no significant differences at a Type II error rate of 0.2 . Conclusions concerning biologically significant impacts were therefore further assessed based on other statistical criteria including comparisons of percent differences between replicated treatments and controls, minimum significant and minimum detectable differences, and coefficients of variation . Based on these criteria, at an ecological effect size of >20% change, tylosin was concluded to elicit no biologically or ecologically significant toxicity to M . spicatum or L . gibba . A hazard quotient assessment indicated that tylosin poses little risk to either species of macrophyte, with an HQ value calculated to be nearly three orders of magnitude below 1 (0.002).

Immunopharmacol Immunotoxicol, 2004 Aug, 26(3), 469 - 80
Immune tolerance to drugs . (II).: Long-term tolerability of nimesulide in patients with NSAID hypersensitivity; Nettis E et al.; Nimesulide is well-tolerated as an alternative to nonsteroidal antiinflammatory drugs (NSAIDs) in patients with a previous adverse reaction to other classes of NSAIDs . However, there is little information in the literature about its long-term tolerability . The study was carried out on 625 patients who had experienced adverse reactions to one or more NSAIDs . All patients received and tolerated peroral challenges with nimesulide . On the first day, patients were given an equivalent number of placebo doses to the planned number of nimesulide doses . In a successive session, the test was administered by means of increasing doses of nimesulide at 30 min intervals until the common daily therapeutic dose of 100 mg was reached (10 mg-20 mg-30 mg-40 mg) . A questionnaire was distributed to all subjects . In particular, they were asked to clarify any reactive symptoms they had developed after ingestion of the drug . It was found that only 2.1% (4/192) of subjects who were given this drug experienced urticaria during treatment . We have identified three significant risk factors: a history of chronic urticaria, a history of antibiotic hypersensitivity and a history of hypersensitivity to more than one class of NSAIDs . In patients with the above risk factors, a prior tolerance test with a selective COX2 antagonist should be administered.

Pol Merkuriusz Lek, 2004 Apr, 16(94), 358 - 61
{Application of the fusafungine in perioperative period in patients after tonsillectomy}; Jurkiewicz D et al.; The only treatment method in chronic palatine tonsillitis is the removal of tonsils (tonsillectomy) . The study aimed at a clinical evaluation of postoperative fusafungine use in patients who underwent tonsillectomy . The study included 200 patients who underwent tonsillectomy for chronic palatine pyotonsillitis in the Otolaryngology Clinic of the Military Institute for the Health Services in Warsaw between 2000 and 2002 . The patients were divided into two groups, each group including 100 patients: group I--patients who underwent tonsillectomy, including 67 females and 33 males, aged 16 to 52 (mean age 34.8), in whom fusafungine was used; group II--patients who underwent tonsillectomy, including 58 females and 42 males, aged 17 to 56 (mean age 36.1), who did not receive fusafungine . The subjects were observed during the first 14 days following the operation . The treatment was administered from the first day after the operation, by spraying 4 doses into the throat, 4 times a day, at 8.00 hrs, 12.00 hrs, 16.00 hrs and 20.00 hrs . The two groups were then compared in terms of: symptoms of sore throat, body temperature, swallowing difficulties, the course of healing, appearance of the pharyngeal mucosa, quality of life and general affection . Post-tonsillectomy fusafungine use was found to improve the patients' quality of life, appeases the sore throat and swallowing difficulties, decreases the need for general antibiotic therapy; the above results are statistically significant . Fusafungine was not found to influence body temperature, the appearance of the pharyngeal mucosa or the healing process.

Pol Merkuriusz Lek, 2004 Apr, 16(94), 328 - 31
{The organic disorders in the course of Lyme disease}; Rudnik I et al.; In the last decade the number of patients with Lyme disease has been continuously growing worldwide including Poland . Psychiatric examinations with the help of psychometric tests were performed in the group of 77 patients with arthritis, in 20 with neuroborreliosis and 26 with erythema migrans . First evaluations started before antibiotic therapy, second 5-6 months after the treatment, third one year since the first assessment . Mental state examinations and psychometric testing revealed in majority of the patients, mainly in those suffered from neuroborreliosis and erythrema migrans evidence of various psychiatric symptomatology . The range of psychiatric presentations included: mild cognitive deficits, organic mood disorders, mild dementias, depressive and anxiety episodes with non organic etiology.

Mikrobiol Z, 2004 Jul-Aug, 66(4), 28 - 33
{Some properties of mutant of Streptomyces globisporus 1912 supersensitive to ultraviolet radiation}
{Severe chlamydia pneumoniae pneumonia requiring mechanical ventilation and steroid therapy in an elderly patient}
Kikawada M, Watanabe D, Nakai T, Esaki S, Kiuchi A, Umahara T, Iwamoto T, Takasaki M.

Department of Geriatric Medicine, Tokyo Medical UniversityA 75-year-old man first developed dyspnea and low-grade fever in late March . A chest X-ray film showed infiltration in the right lower lung field and blood gas analysis revealed severe hypoxemia . Accordingly, he was diagnosed as having pneumonia and was admitted to our hospital on March 11, 2003 . Mechanical ventilation for progressive respiratory failure was started immediately after admission, and he was treated with antibiotics . Chlamydia pneumoniae pneumonia was diagnosed due to an increase of the Chlamydia pneumoniae antibody titer . He had prolonged respiratory failure despite antibiotic therapy . Therefore, steroid therapy was started on day 15 for respiratory failure . At 21 days after admission, the infiltration was found to be decreased on chest X-ray films and improvement of hypoxemia allowed extubation . In conclusion, when severe community-acquired pneumonia occurs in elderly patients, we should remember the possibility of atypical pneumonia such as that due to Chlamydia pneumoniae infection.

Chembiochem, 2004 Nov 5, 5(11), 1567 - 70
Function of lanGT3, a glycosyltransferase gene involved in landomycin A biosynthesis; Luzhetskyy A et al.; The glycosyltransferase gene lanGT3, involved in the biosynthesis of the angucyclic antibiotic landomycin A, has been characterised by targeted gene deletion . A lanGT3 mutant was shown to produce landomycin E, which consists of a trisaccharide side chain attached to the polyketide moiety . Expression of lanGT3 in the mutant restored landomycin A production . Our results indicate that LanGT3 is responsible for the transfer of the fourth sugar during landomycin A biosynthesis.

J Drug Target, 2004 Jun, 12(5), 297 - 307
Norfloxacin-poly(L-lysine citramide imide) conjugates and structure-dependence of the drug release; Gac-Breton S et al.; Norfloxacin (Nflx), an antibiotic which is active against some intracellular bacteria, was coupled to a polymeric carrier, namely poly(L-lysine citramide) via a lysine or an ethylcarbamate spacer to obtain a macromolecular prodrug . The carrier, which derived from the two metabolites citric acid and L-lysine, is known to be biocompatible and slowly degradable under slight acidic conditions . Conjugates were characterised by UV, 1H and 13C NMR and SEC . The presence of Norfloxacin and the lysine type spacer caused chain aggregation, due to a probable physical cure . The release of Norfloxacin from these prodrugs and from a prodrug where Norfloxacin is bound to the carrier backbone without spacer arm was investigated comparatively in vitro . Conjugation via a carbamate-type linkage appeared as a method to achieve the release of Norfloxacin from a PLCA-type conjugate at neutral.

J Obstet Gynaecol, 1999, 19(5), 509 - 10
Topical antiseptic agent after large loop excision of the transformation zone: results of a randomised controlled trial; J Gornall D W G Beynon N J Shepherd I E Boyd R; One hundred patients undergoing large loop excision of the transformation zone (LLETZ) were randomised to receive postoperative local treatment with sultrin (sulphathiazole 3.42%, sulphacetamide 2.86%, sulphabenzamide 3.7%) pessaries: one pessary twice daily for 5 days, or no treatment . Outcome measures included duration and severity of vaginal bleeding, discharge, pelvic pain, need for oral antibiotic therapy and unplanned hospital admission . There was no significant difference in the severity of symptoms in the treatment and control groups for bleeding, discharge or pain, averaged over the study period . Postoperative morbidity following LLETZ was frequent but mild . Use of prophylactic antiseptic agents is not recommended.

Pacing Clin Electrophysiol, 2004 Oct, 27(10), 1449 - 50
Gatifloxacin induced torsades de pointes; Fteha A et al.; The authors present an unusual case of torsades de pointes in an elderly woman treated with intravenous gatifloxacin antibiotic therapy.

Trop Doct, 2004 Oct, 34(4), 203 - 5
Bacterial meningitis in a high HIV prevalence setting in sub-Saharan Africa--challenges to a better outcome; Scarborough M et al.; Bacterial meningitis remains an important cause of mortality and morbidity worldwide . Approaches to reducing the incidence include the deployment of effective anti-retroviral therapy in areas where HIV co-infection is common, vaccination, and prophylactic antibiotic therapy . Health education, improved diagnostic speed and capacity, and ensuring appropriate antibiotic therapy may improve outcome amongst patients presenting with bacterial meningitis.

Pol Merkuriusz Lek, 2004 Jun, 16(96), 513 - 5
{The presence of Chlamydia pneumoniae in carotid artery}; Janczak D et al.; There is growing experimental evidence that Chlamydia pneumoniae is a risk factor and contribute to the development of atherosclerosis of carotid artery . This process might cause stenosis of carotid artery and TIA or stroke . AIM: Aim of this study was to evaluate the frequency of Ch . pneumoniae infection in carotid artery stenosis patients and in control group-healthy artery from multiorgan donors . MATERIAL AND METHODS: From each of 84 patients undergoing carotid endarterectomy the samples were analyzed by nested PCR for Ch . pneumoniae DNA . Furthermore we determined DNA Ch . pneumoniae in carotid artery from 20 multiorgan donors . RESULTS: In control group-healthy artery the PCR for Ch . pneumoniae was negative in all samples . Ch . pneumoniae was detected in 57 patients (67.85%) with symptomatic carotid artery stenosis, however in 27 patients (32.15%) the PCR test was negative . CONCLUSIONS: We did not observe infection of Ch . pneumoniae in healthy carotid artery-control group . We noted great frequency of infection in patients with stenosis of carotid artery . Patients with stenosis of carotid artery can be candidates to antibiotic therapy, which can slow down the progression of artery stenosis.

Jpn J Thorac Cardiovasc Surg, 2004 Sep, 52(9), 429 - 31
Mitral valve repair in a child with infectious endocarditis followed by meningitis; Suzuki Y et al.; A one-year-old boy without congenital cardiac anomaly suffered from meningitis and subsequent acute infective endocarditis that resulted in mitral regurgitation . During antibiotic therapy and management of congestive heart failure, he suddenly developed an acute subdural hematoma, and an aneurysm of the cerebral artery was detected by brain computed tomography . Clipping of the aneurysm was performed by neurosurgery, and 9 days after clipping, we performed mitral valve repair . Kay-Reed annuloplasty was performed and annulus size was reduced from 20 to 16 mm, and edge to edge repair of anterior and posterior leaflets near the commissure to reconstruct ruptured anterior leaflet chordae . This method is easy and useful to control mitral regurgitation when mitral chordae are detached from near commissure especially in child case.

Int J Urol, 2004 Nov, 11(11), 1028 - 30
Intravesical mass consisting of mucosa-associated lymphoid tissue; Suzuki T et al.; We report on a patient with an intravesical mass consisting of hyperplastic follicles in mucosa-associated lymphoid tissue . Computed tomography and ultrasonography revealed two intravesical masses measuring 3.5 cm and 1.5 cm along the long axis . Imaging diagnosis was invasive tumors of the bladder . However, the pathological diagnosis on transurethral bladder tumor biopsy was a lesion in lamina propria consisting of hyperplastic follicles and lymphatic infiltrate between them with no cell atypia . Light microscopically, the lesion was considered to be reactive follicular hyperplasia . Antibiotic therapy resulted in an almost complete disappearance of the tumors . Such large follicular hyperplasia in the lamina propria of the bladder is rare.

Am J Obstet Gynecol, 2004 Oct, 191(4), 1497 - 502
Contemporary management of preterm premature rupture of membranes (PPROM): a survey of maternal-fetal medicine providers; Ramsey PS et al.; OBJECTIVE: This study was undertaken to characterize variations in the management for women with preterm premature rupture of membranes (PPROM) among maternal-fetal medicine (MFM) specialists in the context of current recommendations for clinical practice and evidenced-based practice . STUDY DESIGN: We performed a Web-based survey of 1375 MFM providers . Participants were queried on practice characteristics and management issues including use of tocolytics, antibiotics, steroids, and timing of delivery . RESULTS: A total of 508 providers (37%), representing all 50 states and 13 countries, responded to the survey . Only 30% reported a formal departmental protocol for managing women with PPROM . Consistent use of steroids (99.4%) and antibiotics (99.6%) were reported . Administration of steroids was confined to < or =32 weeks by 37%, and < or =34 weeks by 51% of practitioners . Repeated dosing of steroids was uncommon (16%) . The antibiotics use and rationale for use varied among respondents . Tocolytics were used by 73% of respondents with magnesium sulfate the main agent used (98%) . Use of tocolytics was generally used for 48 hours or less to attain steroid benefit (88%) . Amniocentesis was used by 66% of practitioners in the acute evaluation of PPROM . Fetal lung maturity testing was reported by 78% with variability noted with respect to the test used . Outpatient management of women with PPROM after viability was noted by 43% of respondents . Gestational age at which expectant management is abandoned in women with PPROM varied significantly between respondents: > or =34 weeks by 56%, > pr =35 weeks by 26%, > or =36 weeks by 12%, and > or =37 weeks by 4.0% . CONCLUSION: Although many management practices for women with PPROM are consistent with currently available evidence and practice recommendations, substantial variations still exist among MFM providers.

J Obstet Gynaecol Can, 2004 Oct, 26(10), 899 - 911, 913-28
Uterine fibroid embolization (UFE); Lefebvre GG et al.; OBJECTIVE: To help direct the organized and effective implementation of uterine fibroid embolization into clinical practice in Canada . OPTIONS: This document is restricted to the management of uterine fibroid embolization as performed by the radiologists utilizing a trans-femoral artery approach with arteriography followed by vessel embolization . OUTCOMES: Uterine fibroid embolization has been evaluated in terms of patient satisfaction, risks of complications, risks in subsequent pregnancy and rate of hysterectomy within a few months of the procedure . As the procedure is relatively new, data on long-term outcomes are not available . EVIDENCE: Published opinions of experts, supplemented by evidence from clinical trials where appropriate . VALUES: The quality of the evidence is rated using the criteria described by the Canadian Task Force on the Periodic Health Examination . BENEFITS, HARMS, AND COSTS: For women presenting with symptomatic uterine fibroids who are candidates for UFE, there is often a benefit to avoiding an abdominal surgery . The risks of the UFE procedure, possible complications, and short- and long-term prognosis must be measured on an individual basis against the well-studied surgical alternatives . Patient preference is an important component of this evaluation . The non-material costs of ongoing symptoms from the fibroids are difficult to measure and use comparatively against the cost of hospitalization and treatment . In evaluating costs of UFE, the calculations should take into consideration the cost of managing occasional complications including subsequent hysterectomy . The cost of myomectomy or hysterectomy will vary largely depending on technique used and length of hospital stay . RECOMMENDATIONS: 1 . Women considering treatment of fibroids should be counselled that while the early results of uterine artery embolization are encouraging, no long-term data exist . (II-2-B) 2 . UFE should only be considered for women with symptomatic or problematic fibroids who might otherwise be advised to have surgical treatment . (III-A) 3 . UFE as a treatment for fibroids in patients wishing to preserve their fertility should be undertaken with full disclosure to the patient about the limitations of such a procedure and the lack of existing data regarding future fertility and pregnancy outcomes . (III-C) 4 . UFE is contraindicated in women who have evidence of current genitourinary infection and/or malignancy . (II-2-B) 5 . Women who choose UFE as an alternative to hysterectomy should be counselled regarding the risk of major complications f UFE where hysterectomy may be urgently required and potentially lifesaving . In view of this small but important risk, UFE is relatively contraindicated in women who are unwilling to have a hysterectomy under any circumstances . (III-C) 6 . Genitourinary infection is the predominant cause of serious morbidity and mortality . Further research on the utility of prophylactic antibiotic therapy and the value of pretreatment screening for infection is needed . (II-2-B) 7 . A gynaecologist who is familiar with UFE should evaluate all patients considered for UFE before the procedure is booked and a consensus on the suitability of the procedure achieved between the gynaecologist and radiologist . (III-C) 8 . Only radiologists with specialized embolization experience and techniques should perform UFE . (III-C) 9 . The particular responsibilities of both gynaecologist and radiologist should be established prior to treatment and be set out in a relevant hospital protocol . A particular physician must be responsible for the patient at all times . (III-C) 10 . A Canadian national registry of numbers, indications, outcomes, complications, and successful pregnancies associated with UFE should be created and jointly administered and funded by the SOGC, CAR, and CIRA . (III-C).

J Am Chem Soc, 2004 Nov 3, 126(43), 14267 - 72
Importance of structural tightening, as opposed to partially bound States, in the determination of chemical shift changes at noncovalently bonded interfaces; Williams DH et al.; Two models (A and B) have been proposed to account for decreased downfield chemical shifts of a proton bound by noncovalent interactions at a ligand/antibiotic interface as the number of ligand/antibiotic interactions is decreased . In model A, the proton involved in the noncovalent bond suffers a smaller downfield shift because the bond is, with a relatively large probability, broken, and not because it is longer . In model B, the proton involved in the noncovalent bond suffers a smaller downfield shift because the bond is longer, and not because it is, with a relatively large probability, broken . We show that model A cannot account for the chemical shift changes . Model B accounts for the process of positively cooperative binding, in which noncovalent bonds are reduced in length and thereby increase the stability of the organized state.

Ann Dermatol Venereol, 2004 Aug-Sep, 131(8-9), 795 - 8
{Superficial granulomatous pyoderma.}; Mitcov Milea M et al.; INTRODUCTION: Superficial granulomatous pyoderma is a rare variant of pyoderma gangrenosum, which is often diagnosed at a late stage because of misleading clinical-histopathological features . We report a new case of this rare disease . CASE REPORT: A 67 year-old man presented with inflammatory lesions that had become ulcerated over the past 4 months despite prolonged antibiotic therapy . The histopathological aspect was initially suggestive of palisading granuloma annulare and subsequently a necrotizing granuloma compatible with a mycobacteriosis . The various supplementary examinations eliminated the possibility of an infectious or systemic disease . The lesions became painful and ulcerated . A second biopsy showed a neutrophilic dermatosis with dermal necrosis and a granuloma leading to the diagnosis of superficial granulomatous pyoderma . The lesions healed after 3 months of systemic corticosteroids at the dose of 1 mg/kg/day . DISCUSSION: The clinical features of superficial granulomatous pyoderma are similar to those of classical pyoderma gangrenosum . However, its histological profile is more superficial and is associated with dermal granulomas . The latter are unusual in neutrophilic dermatosis and would suggest an infectious disease . This explains the frequent diagnostic errors, with inappropriate anti-infectious treatments and notably unnecessary surgical exeresis.

Vet Microbiol, 2004 Nov 15, 103(3-4), 195 - 9
Oxytetracycline as a predisposing condition for chalkbrood in honeybee; Flores JM et al.; Antibiotics, particularly oxytetracycline, have been discussed as a possible predisposing condition in the appearance of chalkbrood in the honeybee (Apis mellifera L.) . Nevertheless, the scientific data to support this belief have been insufficient . We have developed a method to study the effects of this antibiotic as a predisposing factor under different circumstances . We conclude that oxytetracycline does not increase the risk of chalkbrood in susceptible worker brood in the short or mid-term.

Nephrology (Carlton), 2004 Oct, 9(5), 262 - 4
Simultaneous multiple tendon ruptures complicating a seizure in a haemodialysis patient; Palmer S et al.; Non-traumatic rupture of large tendons is identified as a contributor to morbidity in patients who receive haemodialysis . The injury is likely to become more common as the duration of survival on dialysis extends . A number of predisposing factors leading to tendon injury have been identified in the literature, including secondary hyperparathyroidism, beta(2)-microglobulin associated amyloidosis, corticosteroid treatment and fluoroquinolone antibiotic use . This is a case report of a 31-year-old male who presented with simultaneous large tendon ruptures following epileptiform seizures . These occurred after 10 years of treatment for end-stage renal failure, including haemodialysis, with progressive secondary hyperparathyroidism . A review of the literature confirms progressive hyperparathyroidism as an important risk factor for large tendon rupture in patients on haemodialysis.

Biochemistry, 2004 Nov 2, 43(43), 13621 - 7
Effects of the C4'-oxidized abasic site on replication in Escherichia coli . An unusually large deletion is induced by a small lesion; Kroeger KM et al.; The C4'-oxidized abasic site (C4-AP) is produced in DNA as a result of oxidative stress by a variety of agents . For instance, the lesion accounts for approximately 40% of the DNA damage produced by the antitumor antibiotic bleomycin . The effect of C4-AP on DNA replication in Escherichia coli was determined using the restriction endonuclease and postlabeling (REAP) method . Three-nucleotide deletion products are the sole products observed following replication of plasmids containing C4-AP under SOS conditions in wild-type cells . Full-length products are formed in varying amounts depending upon the local sequence in wild-type cells under non-SOS-induced conditions . The "A-rule" is followed for the formation of substitution products . C4-AP is the first example of a DNA lesion that produces significant levels of three-nucleotide deletions in a variety of sequence contexts . Experiments carried out in cells lacking specific polymerases reveal that formation of three-nucleotide deletion products results from a coordinated effort involving pol II and pol IV . This is the first example in which these SOS inducible polymerases are shown to work in concert during lesion bypass . Three-nucleotide deletions are not observed during the replication of other abasic lesions, and are rarely produced by bulky adducts . The effect of C4-AP on DNA replication suggests a significant role for this lesion in the cytotoxicity of bleomycin . Formation of the C4-AP lesion may also be responsible for the formation of mutant proteins containing single-amino acid deletions that exhibit altered phenotypes.

Refuat Hapeh Vehashinayim, 2004 Jul, 21(3), 60 - 4, 95
{Pre-septal orbital cellulitis from odentogenic origin--combined surgical and endodontic approach: a case report}; Blanc O et al.; Orbital abscesses are common infectious diseases . The etiology of orbital abscesses may vary from common sinusitis in most of the cases, to cocaine sniffing . As a result of the proximity to the brain, orbital abscesses may complicate to life threatening situations . The infectious process spreads to the orbit in several ways: hematogenous, via anatomic spaces in the maxillofacial region, direct invasion . The treatment philosophy combines surgical and Antibiotic therapy to resolve the acute phase of the disease, followed by elimination of the source . The purpose of this paper is to report a case of pre septal orbital cellulitis, that was treated surgically combined with endodontic therapy . To describe the different subtypes of orbital abscesses, differential diagnosis, imaging and treatment options.

Cornea, 2004 Nov, 23(8), 797 - 803
Electron microscopic study of anterior lens capsule allotransplants in chronic corneal ulcers; Kozak I et al.; PURPOSE: This study provides ultrastructural morphology and quantitative analysis of allotransplants of anterior lens capsule in the treatment of recurrent corneal ulcers . METHODS: Mechanical ulcers of uniform size were created with a 6-mm corneal trephine in 9 eyes at one-third corneal depth in 6 white New Zealand male rabbits . Following initial epithelial regrowth, an identical injury was created in the same area of each cornea a second time . In 6 eyes (treated group), an anterior lens capsule from a healthy donor rabbit was sutured into the ulcer bed, followed by antibiotic/steroid drops 3 times daily for 1 week . The remaining 3 control eyes were allowed to heal without surgical intervention using the same antibiotic/steroid drops only . Slit-lamp examination, histopathology, and electron microscopic findings with hemidesmosome counts and size were recorded over a 3-month follow-up period . RESULTS: The control injured group had discontinuous epithelial basement membrane with significant reduction in hemidesmosome count compared with noninjured controls (P<0.0001) . The treated subgroup 7 days after surgery showed linear basement membrane with identifiable lamina lucida and densa and newly-formed hemidesmosomes, which were significantly more numerous than in the injured but nontreated group (P<0.0001) . Numerous hemidesmosomes and firm adhesion of epithelium to underlying stroma were seen in this group with lens capsule allografts 3 months after surgery . The number and size of hemidesmosomes did not significantly differ between groups 7 days and 3 months after surgery . CONCLUSIONS: On the ultrastructural level, anterior lens capsule allotransplants in mechanically induced corneal ulcer heal with continuously formed epithelial basement membrane and numerous hemidesmosomes . This enables significant reformation of hemidesmosomes that are identical in size to hemidesmosomes in healthy corneas and helps forming a stronger apposition for epithelial cells to underlying structures in eyes where epithelial basement membrane has been destroyed from chronic ulceration.

Biophys Chem, 2004 Nov 1, 111(3), 259 - 65
Interaction of echinomycin with guanine: electrochemistry and spectroscopy studies; Li N et al.; The interaction of antitumor antibiotic, echinomycin (Echi) with guanine (Gua) was thoroughly investigated by adsorptive transfer stripping cyclic voltammetry, ultraviolet and visible adsorption spectra (UV/Vis) and Fourier-transform infrared spectroscopy (FTIR) . Electrochemistry provided a simple tool for verifying the occurrence of interaction between Echi and Gua . Echi could be accumulated from the solution and give well-defined electrochemical signals in 0.1 M phosphate buffer solution (pH 7.0) only when Gua was present on the surface of the electrochemically pretreated glass carbon electrode (GCE), suggesting a strong binding of Echi to Gua . All the acquired spectral data showed that a new adduct between Echi and Gua was formed, and two pairs of adjacent intermolecular hydrogen bonds between the Ala backbone atoms in Echi and Gua (Ala-NH to Gua-N3 and Gua-NH(2) to Ala-CO) played a dominating role in the interaction . Electrochemistry coupled with spectroscopy techniques could provide a relatively easy way to obtain useful insights into the molecular mechanism of drug-DNA interactions, which should be important in the development of new anticancer drugs with specific base recognition.

J Exp Ther Oncol, 2004 Jul, 4(2), 137 - 43
Berberine sensitizes human glioma cells, but not normal glial cells, to ionizing radiation in vitro; Yount G et al.; The identification of nontoxic agents that can enhance the efficacy of postoperative radiotherapy for patients with glioblastoma multiforme (GBM) remains a challenge in oncology . We evaluated human GBM cell lines for their responsiveness to berberine, an alkaloid compound used commonly in Asia as an antibiotic . In experiments measuring clonogenic survival, treatment with a nontoxic dose of berberine rendered GBM cells more sensitive than vehicle-treated control cells to x-rays . Such radiosensitization was not observed in parallel experiments with primary human glial cultures . These data suggest that berberine could be integrated with postoperative radiotherapy to selectively promote residual GBM tumor cell death

Lin Chuang Er Bi Yan Hou Ke Za Zhi, 2004 Jul, 18(7), 406 - 7
{Adjuvant treatment of anisodamine to acute serous otitis media}; Jiang Z et al.; OBJECTIVE: To evaluate the adjuvant treatment of anisodamine to acute serous otitis media . METHOD: Sixty-one acute otitis media patients were divided randomly into two groups . Group A with 30 patients were treated with 1% ephedrine nosedrop, antibiotic and antihistamine . Group B with 30 patients were treated with 1% ephedrine nose drops, antibiotic, antihistamine and anisodamine . They took anisodamine 10 mg twice a day . Then the treating efficiency of group A was compared with that of group B in 5 days and 10 days respectively . RESULT: The symptoms including hearing loss, tinnitus, hydrotympanum and eustachian tube function of group B recover more guickly than that of group A . CONCLUSION: Anisodamine adjuvant treatment of acute serous otitis media by improving the function of eustachian tube and microcirculation.

Yan Ke Xue Bao, 2004 Sep, 20(3), 144 - 8
The clinical analysis of endogenous endophthalmitis; Liang L et al.; PURPOSE: To study the clinical characteristics, therapeutic efficacy and investigate prognostic factors of endogenous endophthalmitis . METHODS: Twenty-eight cases (28 eyes) of endogenous endophthalmitis were surveyed retrospectively . The clinical characteristics, primary infection foci, predisposing systemic disease, complications, pathogens examination, therapeutic options and efficacy were analysed . RESULTS: The endogenous endophthalmitis occurred more frequently in the right eye than in the left one . The respiratory tract was the most common primary foci . The positive rate of pathogens culture was higher in vitreous sample than that in other tissues . Cataract and retinal detachment were the common complications . The visual improvement and infection control were achieved in 13 eyes (46.43%) . These 13 patients received treatment (3.77 +/- 2.49) days after onset of endophthalmitis being much earlier than that of others {(10.13 +/- 4.98) days, P = 0.002} . The prognosis was relevant to the type of the disease . The anterior segment inflammation type (anterior type) had better prognosis than posterior segment inflammation type (posterior type) and that of inflammation in both parts (mix type) (P < 0.05) . There were no significant relation between the prognosis and the age, predisposing systemic disease, vitreous antibiotic injection and vitrectomy (P > 0.05) . CONCLUSIONS: Endogenous endophthalmitis is a vital ocular emergency . Early diagnosis and effective treatment combination with systemic and local antibiotics are of significant value . The anterior type is prone to have better outcome than the others.

Ostomy Wound Manage, 2004 Sep, 50(9A Suppl), 11S - 15S
Silver dressings in clinical practice; Driver VR; Silver is among several topical antiseptics that are once again gaining popularity due, in part, to the rise of antibiotic-resistant genotypes . Because of differences in wounds and the variety of products--including various silver vehicles--available to treat them, all of the dressing characteristics appropriate for the specific wound being managed must be considered . This article addresses why silver is (and is not) a good choice for particular wounds and offers suggestions about what silver products best serve individual situations.

Proc Natl Acad Sci U S A, 2004 Nov 2, 101(44), 15676 - 81 Epub 2004 Oct 21.
Correction of ATM gene function by aminoglycoside-induced read-through of premature termination codons; Lai CH et al.; Approximately 14% of genetic mutations in patients with ataxia-telangiectsia (A-T) are single-nucleotide changes that result in primary premature termination codons (PTCs), either UAA, UAG, or UGA . The purpose of this study was to explore a potential therapeutic approach for this subset of patients by using aminoglycosides to induce PTC read-through, thereby restoring levels of full-length ATM (A-T mutated) protein . In experiments using a modified in vitro cDNA coupled transcription/translation protein truncation test, 13 A-T cell lines carrying PTC mutations in different contexts exhibited read-through expression of ATM fragments, with three of four aminoglycosides tested . In ex vivo experiments with lymphoblastoid cell lines, we used radiosensitivity, radioresistant DNA synthesis, and irradiation-induced autophosphorylation of ATM Ser-1981 to show that the aminoglycoside-induced full-length ATM protein was functional and corrected, to various extents, the phenotype of A-T cells . These results encourage further testing of other compounds in this class, as well as follow up animal studies . Because some A-T patients with 5-20% of normal levels of ATM protein show slower neurological progression, A-T may prove to be a good model for aminoglycoside-induced read-through therapy.

J Biol Chem, 2004 Dec 31, 279(53), 55792 - 800 Epub 2004 Oct 21.
A homolog of Albino3/OxaI is essential for thylakoid biogenesis in the cyanobacterium Synechocystis sp . PCC6803; Spence E et al.; YidC/OxaI play essential roles in the insertion of a wide range of membrane proteins in Eschericha coli and mitochondria, respectively . In contrast, the chloroplast thylakoid homolog Albino3 (Alb3) facilitates the insertion of only a specialized subset of proteins, and the vast majority insert into thylakoids by a pathway that is so far unique to chloroplasts . In this study, we have analyzed the role of Alb3 in the cyanobacterium Synechocystis sp . PCC6803, which contains internal thylakoids that are similar in some respects to those of chloroplasts . The single alb3 gene (slr1471) was disrupted by the introduction of an antibiotic cassette, and photoautotrophic growth resulted in the generation of a merodiploid species (but not full segregation), indicating an essential role for Alb3 in maintaining the photosynthetic apparatus . Thylakoid organization is lost under these conditions, and the levels of photosynthetic pigments fall to approximately 40% of wild-type levels . Photosynthetic electron transport and oxygen evolution are reduced by a similar extent . Growth on glucose relieves the selective pressure to maintain photosynthetic competence, and under these conditions, the cells become completely bleached, again indicating that Alb3 is essential for thylakoid biogenesis . Full segregation could not be achieved under any growth regime, strongly suggesting that the slr1471 open reading frame is essential for cell viability.

Zhonghua Nan Ke Xue, 2004 Sep, 10(9), 676 - 7
{Xinxibao for the treatment of chronic bacterial prostatitis}; Liao D et al.; OBJECTIVE: To study the effect of Xinxibao as a supplementary drug in the treatment of chronic bacterial prostatitis (CBP) . METHODS: Eighty-one cases of CBP were divided into two groups: Group A (n = 38), treated with Xinxibao combined with sensitive antibiotic, and Group B (n = 43), treated with sensitive antibiotic only . Contrast studies were made on the therapeutic effects in the two groups, and the results were analyzed . RESULTS: The effectivity rate was significantly higher in Group A than in Group B . CONCLUSION: Xinxibao can effectively relieve the symptoms of CBP.

Ophthalmic Surg Lasers Imaging, 2004 Sep-Oct, 35(5), 423 - 5
Transpalpebral migration of solid silicone explant in a phthisical globe; Shah NJ et al.; A rare case of transpalpebral migration of a solid silicone explant associated with polymicrobial infection in a pthisical eye is described . The condition resolved completely after surgical removal, wound repair, and antibiotic therapy.

Org Lett, 2004 Oct 28, 6(22), 4101 - 4
MPC1001 and its analogues: new antitumor agents from the fungus Cladorrhinum species; Onodera H et al.; {structure: see text} Eight new compounds, MPC1001 and MPC1001B-H, were isolated from the fungus Cladorrhinum sp . KY4922 . Multiple NMR experiments and CD data revealed MPC1001 to be an O-methyl derivative of emestrin, a 15-membered antifungal antibiotic containing a unique epidithiodioxopiperazine skeleton . Other compounds were elucidated to be structurally related novel analogues . MPC1001 and the analogues exerted potent antiproliferative activities against a human tumor cell line.

Biomedica, 2004 Jun, 24 Supp 1, 27 - 33
{Memories of an antituberculous sanatorium}; Maldonado H et al.; A summary of the existence of the Hospital San Carlos in Bogota as an antituberculous sanatorium is presented . Its origins, architectonic aspects of its building, the criteria with which it was equipped with state of the art scientific equipment and elements and the excellent facilities for attention of inpatients during their prolonged hospital stay are presented . The life of a sanatorium in the pre-antibiotic era, the changes in its routine brought upon by the introduction of effective anti-TB drugs as well as the evolution of treatments which eventually led to the disappearance of sanatoriums, with all its traumatic effects on the hospitals which had been specifically built for this purpose, are described . The contributions made by the hospital to the different medical and surgical aspects of TB management and to the introduction of effective short course ambulatory treatment regimens are also referred . Mention is also given to the rescue of this memory, an important part of the Health Sciences Museum which will shortly open in Bogota.

Ann Pharmacother, 2004 Dec, 38(12), 2041 - 4 Epub 2004 Oct 19.
Stability of cefepime in icodextrin peritoneal dialysis solution; Elwell RJ et al.; BACKGROUND: Icodextrin is a glucose polymer used as an alternative osmotic agent in peritoneal dialysis (PD) solutions . Cefepime may be a suitable antibiotic for the treatment of PD-related peritonitis . The stability of cefepime in icodextrin PD solution has not been examined . OBJECTIVE: To determine the chemical stability of cefepime in icodextrin PD solution over a 7-day period . METHODS: Samples were prepared by adding cefepime HCl 1000 mg to commercially available 2.0-L bags of icodextrin 7.5% PD solution . Nine bags were prepared and stored in the following conditions: 3 under refrigeration (4 degrees C), 3 at room temperature (20 degrees C), and 3 at body temperature (37 degrees C) . Study samples were drawn from each bag immediately after preparation and at predetermined intervals over the subsequent 7 days . Solutions were visually inspected for precipitation, cloudiness, or discoloration at each sampling interval . Total concentration of cefepime in dialysate fluid was determined by liquid chromatography-tandem mass spectrometry . RESULTS: Under refrigeration, a mean +/- SD of 95.7 +/-4.2% of the initial cefepime concentration remained at 168 hours (7 days) . At room temperature, 92.0 +/- 17.9% remained at 48 hours . At body temperature, 92.2 +/- 4.7% remained at 4 hours . Beyond these respective time points, <90% of the initial cefepime concentrations remained . CONCLUSIONS: Pre-mixed cefepime-icodextrin PD solutions stored at room temperature were stable for up to 48 hours . However, it is recommended that these be kept refrigerated whenever possible . When refrigerated, cefepime-icodextrin solutions were found to be stable for up to 7 days . Solutions stored at body temperature were stable up to 4 hours, permitting the practice of pre-warming solutions prior to administration.

Ann Surg, 2004 Nov, 240(5), 910 - 5
Prevention of postsurgery-induced abdominal adhesions by electrospun bioabsorbable nanofibrous poly(lactide-co-glycolide)-based membranes; Zong X et al.; OBJECTIVES: The objective of this study was to evaluate the efficacy of nonwoven bioabsorbable nanofibrous membranes of poly(lactideco-glycolide) for prevention of postsurgery-induced abdominal adhesions . SUMMARY BACKGROUND DATA: Recent reports indicated that current materials used for adhesion prevention have only limited success . Studies on other bioabsorbable materials using a new fabrication technique demonstrated the promising potential of generating an improved and inexpensive product that is suitable for a variety of surgical applications . METHODS: All rats underwent a midline celiotomy . The cecum was identified and scored using an abrasive pad until serosal bleeding was noted on the anterior surface . A 1 x 1 cm of abdominal wall muscle was excised directly over the cecal wound . The celiotomy was then closed in 2 layers immediately (control) after a barrier was laid in between the cecum and the abdominal wall . All rats underwent a second celiotomy after 28 days to evaluate the extent of abdominal adhesions qualitatively and quantitatively . RESULTS: Cecal adhesions were reduced from 78% in the control group to 50% in the group using biodegradable poly(lactide-co-glycolide) (PLGA) nonwoven nanofibrous membranes (n = 10, P = 0.2) and to 22% in the group using membranes containing PLGA and poly(ethylene glycol)/poly(D,L-lactide) (PEG-PLA) blends (n = 9, P = 0.03) . Electrospinning method also enabled us to load an antibiotic drug Cefoxitin sodium (Mefoxin; Merck Inc., West Point, PA) with high efficacy . The electrospun PLGA/PEG-PLA membranes impregnated with 5 wt% cefoxitin sodium, which amounts to approximately 10% of the systemic daily dose typically taken after surgery in humans, completely prevented cecal adhesions (0%) in rats . CONCLUSIONS: Electrospun nonwoven bioabsorbable nanofibrous membranes of poly(lactide-co-glycolide) were effective to reduce adhesions at the site of injury using an objective rat model . The membrane acted as a physical barrier but with drug-delivery capability . The combined advantages of composition adjustment, drug-loading capability, and easy placement handling (relatively hydrophobic) make these membranes potentially successful candidates for further clinical evaluations.

J Biol Chem . 2004 Oct 18; {Epub ahead of print}
Interaction of thiostrepton and elongation factor-G with the ribosomal protein L11-binding domain; Bowen WS et al.; Ribosomal protein L11 and the L11-binding region of ribosomal RNA constitute an important domain involved in active functions of the ribosome during translation . We studied the effects of L11 knockout and truncation mutations on the structure of the rRNA in this region and on its interactions with a translation elongation factor and the antibiotic thiostrepton . The results indicated that the structure of the L11-binding rRNA becomes conformationally flexible when ribosomes lack the entire L11 protein, but not when the C-terminal domain is present on ribosomes . Probing wild type and mutant ribosomes in the presence of the antibiotic thiostrepton and elongation factor-G rigorously localized the binding cleft of thiostrepton and suggested a role for the rRNA in the L11-binding domain in modulating factor binding . Our results also provide evidence that the structure of the rRNA stabilized by the C-terminal domain of L11 is necessary to stabilize EF-G binding in the post-translocation state, and thiostrepton may modulate this structure in a manner that interferes with the ribosome-EF-G interaction . The implications for recent models of thiostrepton activity and factor interactions are discussed.

Int J Med Inform, 2004 Nov, 73(11-12), 743 - 50
Can data from an electronic medical record identify which patients with pneumonia have Pneumocystis carinii Infection?
Diero L, Stiffler T, Einterz RM, Tierney WM.
BACKGROUND: Pneumocystis carinii is the leading opportunistic pulmonary infection in HIV-infected patients . Invasive diagnostic procedures might be avoided if available electronic data can accurately identify patients with Pneumocystis pneumonia (PCP) . METHODS: We extracted data from electronic hospital records, emergency department records, and a pathology database for 299 HIV-infected patients with pneumonia who underwent bronchoscopy . We identified independent indicators of confirmed PCP using logistic regression analysis on a random half of the patients and validated the predictive power of the resulting model on the other half . RESULTS: Bronchoscopy confirmed pneumocystis carinii in 111 patients (37%) . Five of the seven significant independent predictors of PCP came from patients' electronic medical records: infiltrate on chest radiograph, male gender, lower red cell distribution width, lower serum creatinine, and a prior positive HIV test . The other two (duration of illness and presence of dyspnea) came from the emergency department record . A simple index found 43% of patients at low risk (18% with pneumocystis), 37% at moderate risk (36% with pneumocystis), and 20% at high risk (74% with pneumocystis) . CONCLUSIONS: Data from electronic medical records can help quantify the risk of PCP among HIV-infected patients . However, the model failed to identify 18% of patients with PCP in the low risk group, and empiric therapy would erroneously treat 26% of patients classified as high risk . Bronchoscopy is needed to accurately diagnose PCP among HIV-infected patients with pneumonia . However, if bronchoscopy is not available, the model can help with initial decisions about antibiotic therapy.

Perit Dial Int, 2004 Sep-Oct, 24(5), 440 - 6
Cefazolin plus ceftazidime versus imipenem/cilastatin monotherapy for treatment of CAPD peritonitis--a randomized controlled trial; Leung CB et al.; BACKGROUND: Peritonitis is a serious complication of peritoneal dialysis (PD) . We studied the efficacy of imipenem/cilastatin monotherapy in the treatment of PD-related peritonitis . METHODS: We performed an open-label, randomized control study comparing imipenem/cilastatin monotherapy (treatment group) versus cefazolin plus ceftazidime (control group) in the treatment of PD peritonitis . The result was further compared to a historic group treated with cefazolin plus netilmycin . Outcome measures were primary response rate at day 10 and complete cure rate . RESULTS: We enrolled 51 patients in the treatment group, 51 in the control group, and identified 96 in the historic group . The primary response rate to the assigned antibiotics was 49.0%, 51.0%, and 49.0% for the treatment, control, and historic groups, respectively (p = 0.97) . The primary response rate allowing for change in antibiotic was 82.4%, 90.2%, and 82.3%, respectively, for the three groups (p = 0.41) . The complete cure rate was 72.5%, 80.4%, and 82.3%, respectively (p = 0.60) . Tenckhoff catheter removal was needed in 6 cases in the treatment group, 6 cases in the control group, and 13 cases in the historic group (p = 0.90) . CONCLUSIONS: We concluded that monotherapy of imipenem/cilastatin has similar efficacy compared to the two standard regimens of cefazolin plus ceftazidime or netilmycin in the treatment of PD peritonitis.

Clin Microbiol Rev, 2004 Oct, 17(4), 794 - 803, table of contents
Trichomoniasis; Schwebke JR et al.; Trichomoniasis is perhaps the most common curable sexually transmitted disease worldwide, yet few resources are devoted to its control . It is associated with potentially serious complications such as preterm birth and human immunodeficiency virus acquisition and transmission . The immunology of a related organism, Tritrichomonas foetus, which causes disease in cattle, has been investigated to some extent, but more work is needed for the human strain, Trichomonas vaginalis . In addition, although trichomoniasis is easily treated with oral metronidazole, there is concern that the number of strains resistant to this antibiotic are increasing, and currently no alternative is licensed in the United States . As more is appreciated concerning the important public health implications of this common infection, more work will need to be done in understanding the diagnosis, treatment, and immunology of this organism.

Clin Microbiol Rev, 2004 Oct, 17(4), 783 - 93, table of contents
Treatment of infections caused by metronidazole-resistant Trichomonas vaginalis; Cudmore SL et al.; Infections with the sexually transmitted protozoan Trichomonas vaginalis are usually treated with metronidazole, a 5-nitroimidazole drug derived from the antibiotic azomycin . Metronidazole treatment is generally efficient in eliminating T . vaginalis infection and has a low risk of serious side effects . However, studies have shown that at least 5% of clinical cases of trichomoniasis are caused by parasites resistant to the drug . The lack of approved alternative therapies for T . vaginalis treatment means that higher and sometimes toxic doses of metronidazole are the only option for patients with resistant disease . Clearly, studies of the treatment and prevention of refractory trichomoniasis are essential . This review describes the mechanisms of metronidazole resistance in T . vaginalis and provides a summary of trichomonicidal and vaccine candidate drugs.

Lancet, 2004 Oct 16, 364(9443), 1428 - 34
Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda; Mermin J et al.; BACKGROUND: Prophylaxis with co-trimoxazole (trimethoprim-sulphamethoxazole) is recommended for people with HIV infection or AIDS but is rarely used in Africa . We assessed the effect of such prophylaxis on morbidity, mortality, CD4-cell count, and viral load among people with HIV infection living in rural Uganda, an area with high rates of bacterial resistance to co-trimoxazole . METHODS: Between April, 2001, and March, 2003, we enrolled, and followed up with weekly home visits, 509 individuals with HIV-1 infection and their 1522 HIV-negative household members . After 5 months of follow-up, HIV-positive participants were offered daily co-trimoxazole prophylaxis (800 mg trimethoprim, 160 mg sulphamethoxazole) and followed up for a further 1.5 years . We assessed rates of malaria, diarrhoea, hospital admission, and death . FINDINGS: Co-trimoxazole was well tolerated with rare (<2% per person-year) adverse reactions . Even though rates of resistance in diarrhoeal pathogens were high (76%), co-trimoxazole prophylaxis was associated with a 46% reduction in mortality (hazard ratio 0.54 {95% CI 0.35-0.84}, p=0.006) and lower rates of malaria (multivariate incidence rate ratio 0.28 {0.19-0.40}, p<0.0001), diarrhoea (0.65 {0.53-0.81}, p<0.0001), and hospital admission (0.69 {0.48-0.98}, p=0.04) . The annual rate of decline in CD4-cell count was less during prophylaxis than before (77 vs 203 cells per microL, p<0.0001), and the annual rate of increase in viral load was lower (0.08 vs 0.90 log(10) copies per mL, p=0.01) . INTERPRETATION: Daily co-trimoxazole prophylaxis was associated with reduced morbidity and mortality and had beneficial effects on CD4-cell count and viral load . Co-trimoxazole prophylaxis is a readily available, effective intervention for people with HIV infection in Africa.

Am J Health Syst Pharm, 2004 Sep 15, 61(18), 1895 - 905; quiz 1906-7
Management of pressure ulcers; Cannon BC et al.; PURPOSE: Wound healing, the epidemiology and staging of pressure ulcers, and pressure ulcer prevention and treatment are discussed . SUMMARY: The principal event leading to the formation of pressure ulcers appears to be a consistent interruption in blood supply to the skin . Several known risk factors exist and can be attributed to patient-specific variables and wound-specific conditions . Initial management should include removal of the source of pressure, a comprehensive assessment of the patient, and proper staging of the ulcer . Preparation of the wound for treatment is essential and can have a significant impact on healing . While the patient's nutritional status is thought to affect wound healing, only an increased protein content in the diet has been demonstrated to have a benefit . Specialized wound dressings are available for pressure ulcers of all stages and drainage characteristics . With wide variation in cost and in application regimens, a direct cost-effectiveness comparison of commercially available dressing products is difficult . Many of the growth factors commonly present in healing wounds have been synthesized and evaluated as treatments . Although topical platelet-derived growth factor has demonstrated benefit in some studies, its use remains controversial . To date, no topical growth factors carry FDA-approved labeling for use in the treatment of pressure ulcers . Human skin equivalents mark the latest advancement in therapy . Certain species of bacteria have been associated with poorly healing ulcers and may warrant intervention with either local or systemic antibiotic therapy . CONCLUSION: No pharmacologic intervention has been conclusively shown to be effective for pressure ulcers . The cornerstones of therapy remain elimination of the source of pressure or friction and appropriate wound care . usa.

J Pediatr Surg, 2004 Oct, 39(10), e11 - 3
Camel bite: an unusual type of head injury in an infant; Suess O et al.; Small children are predisposed for animal bite wounds in the craniofacial region, because the likelihood of sustaining trunk and extremity injuries increases with height . The clinical picture of animal bite wounds is highly variable . Depending on the dental anatomy of the biting animal, such wounds may range from sharp stitch wounds to extensive lacerations with or without tissue loss . The ears and nose are injured most often because of their exposed location . Nevertheless, depressed skull fractures with injury to the dura and to the brain parenchyma are extremely rare . This case presentation describes the rare case of a craniocerebral camel bite wound (Lackmann stage IV B) in a 3-year-old girl that required immediate neurosurgical management . The neurosurgical management, choice of antibiotic, postoperative treatment, and clinical course are discussed, and background information on camel bite injuries is given.

Int Clin Psychopharmacol, 2004 Nov, 19(6), 337 - 42
Neuroprotection in Huntington's disease: a 2-year study on minocycline; Bonelli RM et al.; Huntington's disease (HD), a relentlessly progressive neurodegenerative disorder, is characterized by a clinical triad of psychiatric, cognitive and motor disturbances . The antibiotic minocycline, a caspase inhibitor exhibiting antiapoptotic properties, has been shown to prolong survival in the transgenic mouse model of HD . We administrated minocycline to 14 patients with genetically confirmed HD . The patients were psychiatrically, neurologically and neuropsychologically evaluated at baseline, and after 6 and 24 months of treatment, using the Unified HD Rating Scale and a neuropsychological test battery . After 12 months, three patients were lost to follow-up so that 11 patients were analysed at the endpoint . Minocycline was well tolerated . Unlike the expected natural course of HD, patients exhibited stabilization in general motor and neuropsychological function at endpoint, after improving in the first 6 months . Moreover, we found a significant amelioration of psychiatric symptoms that was not apparent after the first 6 months . In detail, the Mini-Mental State Examination, the Total Motor Score, the Total Functional Capacity Scale and the Independence Scale, as the most prominent scales in HD, were stabilized after 3 years of treatment . Our results confirm previous animal studies and indicate a neuroprotective effect of this agent in HD . A long-term, double-blind, placebo-controlled trial appears highly warranted for definitively establishing the value of minocycline in HD.

Chir Main, 2004 Aug, 23(4), 167 - 77
{Antibioprophylaxy in hand surgery: toward a professional consensus}; Dumontier C et al.; Antibioprophylaxy in surgery follows, in France, the guidelines published by the French Society of Anesthesia {Societe francaise d'Anesthesie et reanimation (SFAR)} . However these guidelines were mostly made for prosthetic and traumatologic surgery of the lower limb and guidelines for upper limb and hand surgery have been made by extrapolation . The French Society for Surgery of the hand has made multiples studies including: a survey to precise the infection rate for hand surgery which has been estimated to be around 0.1% . A search in the international literature, according to the classification criteria proposed by the "Agence Nationale D'accreditation et d'Evaluation Sanitaire (ANAES)" to better define correct antibioprophylaxy that should be used in hand surgery . Results of those surveys have been presented by national experts at the French Society Meeting of 2003 . The attendance was given the opportunity to answer questions from the experts . A jury was present and its conclusion are reported here . Except for total wrist prosthesis and for surgical procedures that last more than 2 hours, there are very few indications for an antibioprophylaxy in hand surgery . In cases where an antibioprophylaxy is needed, the jury recommends that the guidelines proposed by the SFAR, regarding the choice of antibiotics, should be followed.

J Arthroplasty, 2004 Oct, 19(7), 874 - 9
Patient satisfaction and functional status after aseptic versus septic revision total knee arthroplasty using the PROSTALAC articulating spacer; Meek RM et al.; This study compared the functional results of an articulating antibiotic spacer for 2-stage revision knee arthroplasty for infection, to the functional results of aseptic revision . One hundred twenty-five patients who underwent revision of total knee arthroplasty for infection and aseptic loosening were identified . All of the patients with infection were treated with the PROSTALAC system (DePuy) . At a minimum 2-year follow-up, WOMAC, Oxford-12, SF-12, patient satisfaction data, Harris Hip Score knee scores, and range of motion were assessed . The 2 cohorts (4 deaths in total, leaving 54 septic, 57 aseptic) were equivalent for age, gender, and comorbidity scores . At a mean of 41 months, none of the outcomes were significantly worse for the septic group, which had 2 recurrences of infection (4%) . The satisfactory functional results of the PROSTALAC system may be related to the design features.

Rev Gastroenterol Peru, 2004 Jul-Sep, 24(3), 238 - 62
{Primary gastric lymphoma}; Barreda B F et al.; INTRODUCTION: Primary Gastric Lymphoma is an uncommon malignancy among gastric malignancies . Histology of the Primary Gastric Lymphoma is varied and the extranodal marginal zone B-cells lymphoma is specially significant on account of its potential remission with antibiotic therapy . OBJECTIVES: Observe the clinical characteristics of patients with Primary Gastric Lymphoma, assess the most relevant endoscopic findings, identify the factors that influence survival and evaluate the effects of therapy . MATERIALS AND METHODS: The study is an observational, analytical, cross evaluation including 169 patients with histological diagnosis of Gastric Lymphoma, treated at the National Institute for Neoplastic Diseases, Lima, Peru, from January 1995 to December 2000 . Staging was based on the Ann Arbor system, modified by Musshoff and histology, on the REAL-WHO classification . The statistical analysis included the student-t and the chi-square tests . Survival data were entered using the Kaplan Meier curves and prognosis factors, using the Cox regression test . RESULTS: The sample represents patients from the Peruvian Coast, with a mean age of 55 years old and slight predominance of female patients (54.4%) . Signs and symptoms are unspecific . Clinical stage I-II corresponds to 75% of the patients . The endoscopic pattern of multiple ulcerated lesions is characteristic of the Gastric Lymphoma . A total of 71% of the patients with extranodal marginal zone B-cells lymphoma showed total remission of the disease with antibiotic therapy (5/7) . The histological type of the Gastric Lymphoma in the 169 patients was as follows: Large, diffuse, B-cells Lymphoma, 137 patients, extranodal marginal zone B-cells lymphoma, 16 patients, peripheral T-cell Lymphoma, 6 patients, anaplastic large T-cell Lymphoma, 3 patients, undetermined Lymphoma, 3 patients, mantle cell Lymphoma, 2 patients, adult T-cell Lymphoma, 1 patient and follicular Lymphoma, 1 patient . Global survival after 36 months was of 61.34%, survival according to the histological type was of 92.31% for extranodal marginal zone B-cells Lymphomas, 62.21% for large, diffuse B-cells Lymphomas and 29.63% for T-cell Lymphomas . Survival after 36 months in patients in clinical stage I-II treated with chemotherapy, was of 82.16%, with surgery, 71.89% and with surgery and chemotherapy, 70.39, with similar results in all three groups (p: 0.6530) . The groups classified according to the international index, showed a clear difference between them (p:0.0000) . The univariate analysis revealed that Zubrod (p:0.0000) DHL (p:0.0073) disease remission (p:0.0000) stage (p:0.0000) treatment (p:0.0000) and location (p:0.0000) had statistical significance . Multivariate analysis showed that in the Cox regression model, remission (OR:13,342, p:0.0000) and location (OR:2.375, p:0.041) fall within the equation of such function . CONCLUSIONS: The multiple ulcerated lesions are characteristic of the Gastric Lymphoma . Remission of the disease in the extranodal marginal zone B-cells Lymphoma is evidenced with the use of antibiotic therapy (5/7) . Chemotherapy in patients with EC I-II achieves survival results similar to those treated with surgery and with a combination of both . Validity of the international index is confirmed and the multivariate analysis proved that remission and location of the disease have statistical significance.

Curr Opin Nephrol Hypertens, 2004 Nov, 13(6), 623 - 9
Vascular access for hemodialysis: 2004 and beyond; D'Cunha PT et al.; PURPOSE OF REVIEW: Developments in vascular access are accruing rapidly . The last systematic Kidney Disease Outcomes Quality Initiative guidelines review took place in 2000 . The purpose of this review is to update several major areas in which clear progress has been made . A major 'Fistula First Initiative' in the USA is an attempt to increase markedly the fraction of patients receiving an autologous arteriovenous fistula as opposed to a graft . Preoperative mapping to evaluate veins and artery may permit construction of arteriovenous fistula in up to 70% of all patients, thereby reducing access thrombosis, infection, and perhaps increasing survival of patients . RECENT FINDINGS: Although a number of different synthetic materials have been tried, none seems to have any definite advantage over plain expanded polytetrafluoroethylene for constructing synthetic bridge grafts . Two developments may influence practice: use of composite self-sealing grafts that can be used within hours may eliminate the need for temporary catheters; and use of nitinol surgical clips may reduce endothelial trauma and improve patency . Large-bore catheters can deliver blood flows of over 400 ml/min initially, but they are prone to progressive occlusion . Optimal means of using a fibrinolytic to preserve flow must be evaluated . Surveillance techniques are undergoing rapid re-evaluation . Finally, a variety of antibiotic lock techniques are being evaluated for their ability to prevent catheter-related infections . SUMMARY: Greater efforts must be made to establish pre-end-stage renal disease programs to educate and prepare patients for hemodialysis and improve arteriovenous fistula placement rates, and to encourage clinicians to re-examine their current clinical practices and dedicate themselves to improving vascular access outcomes.

J Dairy Sci, 2004 Nov, 87(11), 3736 - 45
Growth performance and health of dairy calves bedded with different types of materials; Panivivat R et al.; Granite fines, sand, rice hulls, long wheat straw, and wood shavings were compared as bedding for 60 female dairy calves . Growth, health, stress indices, and behavior of newly born calves, along with physical characteristics and bacterial counts of bedding, were evaluated for 42 d during August to October, 2002 . Overall average daily gain and dry matter intake of calves did not differ due to bedding type, although during wk 2 calves housed on rice hulls had the greatest dry matter intake and those housed on wood shavings had the lowest . During wk 2, calves housed on granite fines and sand were treated more often for scours, and calves housed on long wheat straw received the fewest antibiotic treatments (week by bedding material interaction) . Granite fines formed a harder surface than other bedding, and calves housed on granite fines scored the dirtiest . When bedding materials were evaluated, sand was scored to be the dirtiest, while pens bedded with rice hulls, long wheat straw, and wood shavings scored cleaner . Long wheat straw had the warmest surface temperature, and rice hulls and wood shavings were warmer than granite fines and sand . Serum cortisol, alpha(1)-acid glycoprotein, immunoglobulin G concentrations, and the neutrophil:lymphocyte ratio were not affected by bedding type . On d 0, coliform counts were greatest in rice hulls . After use, coliform counts were greatest in long wheat straw (week by bedding material interaction) . On d 42, the concentration of ammonia at 10 cm above the bedding was lowest for long wheat straw . Growth performance of calves bedded for 42 d with 5 bedding types did not differ; however, the number of antibiotic treatments given for scours was greatest on granite fines and sand; coliform counts in the bedding were highest in rice hulls before use and in long wheat straw after 42 d of use.

Expert Rev Anti Infect Ther, 2004 Jun, 2(3), 357 - 66
Fluconazole for the treatment of candidiasis: 15 years experience; Cha R et al.; Candidia spp . are responsible for contributing to the increasing global prevalence of fungal infections . Fluconazole (Diflucan((R)), Pfizer) is a triazole that has established an exceptional therapeutic record for candida infections including oropharyngeal and esophageal candidiasis, vulvovaginal candidiasis, candidemia and disseminated candidiasis . It is both an oral and parenteral fungistatic agent that inhibits ergosterol synthesis in yeasts . Extensive clinical studies have demonstrated fluconazole's remarkable efficacy, favorable pharmacokinetics and reassuring safety profile, all of which have contributed to its widespread use . Fluconazole became the first antifungal with worldwide sales exceeding billions of dollars, therefore providing an incentive for the pharmaceutical industry to develop new antifungals . This review will examine the contributions and limitations of fluconazole in the treatment of superficial and invasive candidiasis syndromes.

Expert Rev Anti Infect Ther, 2003 Oct, 1(3), 505 - 16
Management of respiratory infections in the elderly; Lieberman D et al.; Respiratory infections are common at all ages but are particularly sinister among the elderly because of the fragility and chronic comorbidity associated with this age group . The three types of respiratory infection in the elderly are community-acquired pneumonia, acute exacerbation of chronic obstructive pulmonary disease and nonpneumonic respiratory tract infection . The etiology of these three types of infection includes classic bacteria, atypical pathogens and respiratory viruses . The relative frequency of each of the etiological groups as the causative agent of the infection varies significantly among these types of infection, but in all three types a significant proportion of infections involves more than one pathogen . The causative agent of respiratory infection in the elderly cannot be determined on the basis of clinical manifestation or the results of routine imaging procedures or laboratory tests . Thus, initial antibiotic therapy in these patients should be empiric, based on accepted guidelines . In recent years, the antipneumococcal fluoroquinolones have gained in stature as one of the best options to treat these infections . Pneumococcal and influenza vaccinations can reduce morbidity and mortality from respiratory infections in the elderly, so it is important that all elderly individuals are vaccinated through a structured program in the framework of primary care . The economic impact of respiratory infections in the elderly is primarily associated with the requirement for hospitalization in many of the cases . Any action that can reduce hospitalization rates has important economic ramifications . In light of the difficulty in reaching an early etiologic diagnosis in respiratory infections, it is essential to invest in the development of a compact diagnostic kit for the early stages of the disease, which could change reality in this important area of medicine.

Acta Orthop Belg, 2004 Aug, 70(4), 355 - 60
The management of musculoskeletal infection in HIV carriers; Bahebeck J et al.; Over a three-year period, the authors prospectively implemented a protocol for management of musculoskeletal sepsis (MSS) in HIV carriers in Yaounde, Cameroon . The diagnosis of MSS was based on conventional criteria . HIV carriage was screened by an ELISA test and confirmed with the Western Blot technique . The immune status was based on CD4 lymphocyte count by flow cytometry; patients were classified as non-immunodepressed (NID), mildly immunodepressed (MID), or severely immunodepressed (SID) based on their CD4 lymphocyte count, as the latter was respectively over 500, between 200 and 500 or less than 200 per ml . Infection was treated by surgical debridement followed by a long-course targeted antibiotic therapy . All SID patients and some MID patients with AIDS-related symptoms also had standard antiretroviral (ARV) therapy . Thirty-one of 294 patients seen with musculoskeletal sepsis during the study period and tested for HIV were found to be HIV carriers . Their mean age was 33 years; the male/female ratio was 1.58 . The following clinical pictures were observed: chronic osteomyelitis (COM) in 32.3% of the cases, septic arthritis (SA) in 38.7%, soft tissue infection (STI) in 25.8%; the last case was a severe leg complication of Buruli Ulcer (BU) . Among these 31 patients, 38.7% were classified as SID (5 COM, 4 SA, 2 STI and the BU patient), 25.8% as MID (2 COM, 4 SA, 2 STI) and 35.5% as NID (3 COM, 6 SA, 2 STI) . The organisms involved were not specific . Fifteen patients were managed conventionally, while the other 16 had the usual treatment associated with ARV therapy . The immediate outcome of MSS was good in 29 patients, after a mean hospital stay of five weeks; in two cases of septic arthritis of the knee, a second debridement was needed, due to persistent drainage, and the sinuses all closed . Three months after discharge, one patient with COM of the humerus developed a low-flow fistula which was closed after a revision sequestrectomy . After one year, none of the patients complained of any symptom suggesting reactivation of their MSS . There is no evidence that HIV carriage is in itself a high risk factor for musculoskeletal sepsis; the incidence of HIV carriage was indeed virtually similar in the 294 patients with MSS and in the general population, i.e . around 10% . However, in order to improve the outcome following musculoskeletal infections in patients with HIV, their management should take into account their immune status, based on a CD4 lymphocyte count . NID patients should be treated as any other patients with MSS, while SID should have additional standard ARV treatment . For those who are MID, the indication for antiretroviral therapy should depend on the presence of one or more AIDS-related signs.

Mol Genet Genomics, 2004 Nov, 272(4), 397 - 410 Epub 2004 Nov.
Arabidopsis thaliana expresses multiple Golgi-localised nucleotide-sugar transporters related to GONST1; Handford MG et al.; Transport of nucleotide-sugars across the Golgi membrane is required for the lumenal synthesis of a variety of essential cell surface components, and is mediated by nucleotide sugar transporters (NSTs) which are members of the large drug/metabolite superfamily of transporters . Despite the importance of these proteins in plants, so far only two have been described, GONST1 and AtUTr1 from Arabidopsis thaliana . In this work, our aim was to identify further Golgi nucleotide-sugar transporters from Arabidopsis . On the basis of their sequence similarity to GONST1, we found four additional proteins, which we named GONST2, 3, 4 and 5 . These putative NSTs were grouped into three clades: GONST2 with GONST1; GONST3 with GONST4; and GONST5 with six further uncharacterized proteins . Transient expression in tobacco cells of a member of each clade, fused to the Green Fluorescent Protein (GFP), suggested that all these putative NSTs are localised in the Golgi . To obtain evidence for nucleotide sugar transport activity, we expressed these proteins, together with the previously characterised GONST1, in a GDP-mannose transport-defective yeast mutant (vrg4-2) . We tested the transformants for rescue of two phenotypes associated with this mutation: sensitivity to hygromycin B and reduced glycosylation of extracellular chitinase . GONST1 and GONST2 complemented both phenotypes, indicating that GONST2, like the previously characterized GONST1, is a GDP-mannose transporter . GONST3, 4 and 5 also rescued the antibiotic sensitivity, but not the chitinase glycosylation defect, suggesting that they can also transport GDP-mannose across the yeast Golgi membrane but with a lower efficiency . RT-PCR and analysis of Affymetrix data revealed partially overlapping patterns of expression of GONST1-5 in a variety of organs . Because of the differences in ability to rescue the vrg4 - 2 phenotype, and the different expression patterns in plant organs, we speculate that GONST1 and GONST2 are both GDP-mannose transporters, whereas GONST3, GONST4 and GONST5 may transport other nucleotide-sugars in planta.

J Foot Ankle Surg, 2004 Sep-Oct, 43(5), 327 - 31
Madura foot: atypical finding and case presentation; Foltz KD et al.; Mycetomas are chronic, subcutaneous infections characterized by a clinical triad of chronic induration, draining sinuses, and discharge of granules . The granules are composed of colonies of either actinomycotic bacteria or eumycotic fungi . The infection develops after traumatic inoculation with contaminated soil and progresses to adjacent tissues or bone . The foot, hand, and lower-leg regions are the most commonly affected areas . Treatment can be difficult and includes surgical debridement with prolonged antibiotic or antifungal treatment . Mycetomas are primarily found in tropical and subtropical areas of the world and are relatively rare in the United States . A case of indigenously obtained actinomycoses that was successfully treated with surgical resection and long-term antibiotic therapy is presented . This case is unique because of the rarity of contracting this type of infection in the United States . Mycetomas have been reported in southern states, but there are no reported cases of obtaining this pathogen in Michigan . This case stresses the need for clinical suspicion of this rare dermatosis, especially considering the increase in immigration to the United States.

J Perinat Neonatal Nurs, 2004 Jul-Sep, 18(3), 259 - 74
Viral infection and antiviral therapy in the neonatal intensive care unit; Barford G et al.; Viral diseases are leading causes of mortality and morbidity among infants requiring care in the neonatal intensive care unit (NICU), with ongoing discoveries of new viral pathology likely to add to the burdens posed . Many viral diseases in NICU infants are undiagnosed or appreciated only late in the course because of subtle or asymptomatic presentation, confusion with bacterial disease, and failure to consider viral disease . We present an overview of viral disease in NICU infants, with emphasis on pharmacologic agents currently employed for prophylaxis and treatment of such diseases . Advances in molecular biology and popular demand to develop antiviral agents for viral diseases (eg, human immunodeficiency virus) offer great promise for the future.

Mol Biotechnol, 2004 Oct, 28(2), 87 - 95
Construction and characterization of a minimized version of the HIV-1 pNL4-3 plasmid and its application for pseudotyping HIV-1 vectors; Abad ML et al.; The pUC-based pNL4-3 plasmid is the most widely used vector for in vitro manipulations of the HIV-1 proviral sequences . We have developed a minimal plasmid (pCHUS) based on pNL4-3, which may be useful to facilitate the design of HIV-based constructions . The strategy that has allowed us to construct pCHUS includes the following steps: (1) pNL4-3 digestion by using restriction sites contained within the long terminal repeats (LTRs), (2) recircularization of the fragment containing the pUC18 sequence, (3) amplification of the LTR region restored in the previous step, (4) double digestion of the products obtained in steps 2 and 3, (5) ligation of the fragment containing ColE1+Amp(R) with the LTR fragment, (6) linearization of the intermediate plasmid obtained, and (7) insertion of the fragment containing the proviral genome into the linearized vector . The pCHUS plasmid includes essential information for its replication and antibiotic selection in bacteria, but it lacks all the unnecessary sequences . Our results suggest that pCHUS may be more advantageous than pNL4-3 for in vitro manipulation of the HIV-1 proviral genome . In addition, we describe a potential application of this new vector for pseudotyping HIV-1 particles, using a single plasmid transfection, as a more helpful alternative to the traditionally used cotransfection method.

Nucleic Acids Res, 2004 Oct 11, 32(18), 5398 - 408 Print 2004.
Biochemical evidence of translational infidelity and decreased peptidyltransferase activity by a sarcin/ricin domain mutation of yeast 25S rRNA; Panopoulos P et al.; A C-->U mutation (rdn5) in the conserved sarcin/ricin domain of yeast 25S rRNA has been shown to cause translational suppression and paromomycin resistance . It also separates the killing from the misreading effect of this antibiotic . We confirm these findings and provide in vitro evidence that rdn5 causes a 3-fold increase in translational errors and resistance to paromomycin . The role of this 25S rRNA domain in ribosome's decoding function was further demonstrated when 60S subunits from rdn5 cells were combined with 40S subunits from cells carrying an error-prone mutation in the eukaryotic accuracy center ribosomal protein S23, an homologue of Escherichia coli S12 . These hybrids exhibited an error frequency similar to that of rdn5 alone, despite the error-prone mutation in S23 . This was accompanied by extreme resistance to paromomycin, unlike the effects of the individual mutations . Furthermore, rdn5 lowers peptidyltransferase activity measured as a second-order rate constant (kcat/K(s)) corresponding to the rate of peptide bond formation . This mutation was also found to affect translocation . Elongation factor 2 (EF2)-dependent translocation of Ac-Phe-tRNA from the A- to P-site was achieved at an EF2 concentration 3.5 times lower than in wild type . In conclusion, the sarcin/ricin domain of 25S rRNA influences decoding, peptide bond formation and translocation.

Clin Ther, 2004 Aug, 26(8), 1274 - 85
Comparison of topical tobramycin-dexamethasone with dexamethasone-neomycin-polymyxin and neomycin-polymyxin-gramicidin for control of inflammation after cataract surgery: results of a multicenter, prospective, three-arm, randomized, double-masked, controlled, parallel-group study; Notivol R et al.; BACKGROUND: Intraocular inflammation is typically treated with a combination of anti-inflammatory and anti-infective drugs . Tobramycin-dexamethasone (TD) has not been associated with any serious adverse events, indicating good tolerability . OBJECTIVE: The aims of this study were the following: (1) to demonstrate noninferiority of TD compared with dexamethasone-neomycin-polymyxin (DNP) in terms of anti-inflammatory efficacy, (2) to compare the anti-inflammatory efficacy of TD and DNP with that of a "placebo" control (antibiotic without anti-inflammatory agent), and (3) to provide additional safety data on TD . METHODS: This prospective, double-masked, parallel-group study was conducted at 22 ophthalmology clinics across Europe and Brazil . Patients aged > 18 years undergoing cataract surgery were randomly assigned, in a 2:2:1 ratio, to receive tobramycin 3 mg/mL plus dexamethasone 1 mg/mL, dexamethasone 1 mg/mL plus neomycin sulfate 3500 IU/mL plus polymyxin B sulfate 6000 IU/mL, or neomycin sulfate 3500 IU/mL plus polymyxin B sulfate 7500 IU/mL plus gramicidin 20 microg/mL . All treatments were given as 1 drop instilled in the operated eye q.i.d . for 21 days . The primary efficacy end point, intraocular inflammation (determined using the sum of scores on anterior chamber cells and aqueous flare), was assessed at days 3, 8, 14, and 21 after surgery . RESULTS: A total of 271 patients were enrolled (158 women, 113 men; age range 42-90 years) (TD, 104 patients; DNP, 110 patients; and neomycin-polymyxin-gramicidin {NPG}, 57 patients) . Intraocular inflammation was similar in the TD and DNP groups at all time points . At days 8, 14, and 21, inflammation scores were significantly lower with TD than with NPG (all, P < 0.05) . At day 8, the inflammation score was significantly lower with DNP than with NPG (P < 0.05) . A greater number of patients receiving NPG experienced treatment-related ocular allergic reactions compared with patients receiving TD (P < 0.05) . One patient receiving TD (1.0%) and 5 given NPG (9.0%) were withdrawn due to ocular allergic reactions . None of the patients experienced an increase in intraocular pressure > or =10 mm Hg from baseline . CONCLUSIONS: In this study of patients undergoing cataract surgery combination therapy with TD was noninferior to DNP and was well tolerated.

Am J Surg, 2004 Oct, 188(4A Suppl), 52S - 56S
Gynecologic use of robotically assisted laparoscopy: Sacrocolpopexy for the treatment of high-grade vaginal vault prolapse; Elliott DS et al.; Transabdominal sacrocolpopexy is an excellent treatment option for patients with high-grade vaginal vault prolapse, with long-term success rates ranging from 93% to 99% . However, it is associated with increased morbidity compared with vaginal repairs . In this article, we describe a novel minimally invasive technique of vaginal vault prolapse repair and present our initial experience . The surgical technique involves placement of 4 laparoscopic ports, 3 for the surgical robot and 1 for the assistant . A prolene mesh is then attached to the sacral promontory and to the vaginal apex using nonabsorbable expanded polytetrafluoroethylene sutures . At the end of the case, the mesh material is covered by the peritoneum . A total of 20 patients underwent a robot-assisted laparoscopic sacrocolpopexy at our institution in the past 18 months for severe symptomatic vaginal vault prolapse; 8 of the 20 (40%) underwent a concomitant anti-incontinence procedure . Mean follow-up was 5.1 (range, 1-12) months and mean age was 66 (range, 47-82) years . The mean total operative time was 3.2 (range, 2.25-4.75) hours . Of these patients, 1 was converted to an open procedure secondary to unfavorable anatomy . All but 1 patient, who left on postoperative day 2, were discharged from the hospital after an overnight stay . Complications were limited to mild port-site infections in 2 patients, which resolved with oral antibiotic therapy . Recurrent grade 3 rectocele developed in 1 patient, but there was no evidence of cystocele or enterocele . Significant incontinence (>1 pad/day) was present in 2 patients . All 18 patients reported being satisfied with the outcome of their surgery and all 10 would recommend it to a friend . This novel technique for vaginal vault prolapse repair combines the advantages of open sacrocolpopexy with the decreased morbidity and improved cosmesis of laparoscopic surgery . It is associated with decreased hospital stay, low complication and conversion rates, and high rates of patient satisfaction . Although our early experience is encouraging, long-term data are needed to confirm these findings and establish longevity of the repair.

Arch Pediatr, 2004 Oct, 11(10), 1209 - 11
{Sudden sight impairment revealing a cat-scratch disease: report of three cases}; Besson-Leaud L et al.; Cat-scratch disease is a frequent but innocuous cause of chronic lymphadenopathy in children . Numerous atypical forms have been described . We report three cases of acute sight impairment revealing a cat-scratch disease . BACKGROUND: A 13 year-old boy and two girls aged 10 and 13 suffered from a sudden bilateral sight impairment with papillary edema, with fever in two cases . Neurological examinations, X-rays and lumbar puncture results were found normal . However, all patients were tested positive to Bartonella Henselae . Antibiotic and anti-inflammatory treatments were efficient in two cases . CONCLUSION: Cat-scratch disease can be characterized by an isolated and acute sight impairment with a stellate neuroretinitis . The potency of antibiotic treatments is debatable.

Cell Immunol, 2004 Jun, 229(2), 93 - 105
Polymyxin B enhances ISS-mediated immune responses across multiple species; Marshall JD et al.; The immunostimulatory effects of bacterial DNA on mammalian cells have been localized to unmethylated CpG motifs, and synthetic CpG-containing oligodeoxynucleotides that mimic these effects are known as immunostimulatory sequences (ISS) . We have found that the polycationic antibiotic, polymyxin B (PMXB), associates with ISS and serum albumin in vitro and forms microparticles that greatly increase the activity of ISS on plasmacytoid dendritic cells (PDCs) . Specifically, ISS/PMXB greatly enhanced IFN-alpha production from PDCs and other activities downstream of IFN-alpha, including IFN-gamma secretion, NK lytic activity, and the expression of genes dependent upon IFN-alpha/IFN-gamma . This amplification was specific for the IFN-alpha pathway since other ISS activities, including B cell proliferation, B cell IL-6 secretion, and PDC maturation, were not affected by PMXB . Both the polycationic peptide and lipophilic fatty acid side chain domains of PMXB, as well as the presence of a third party stabilizing agent such as albumin or Tween 85, were required for particle formation and enhanced ISS activity . The ISS-enhancing activity of PMXB was observed across multiple species (human, primate, and mouse) and in vivo (primate, mouse) . These data illustrate the usefulness of formulating ISS with a cationic lipopeptide such as PMXB, which focuses and greatly amplifies the ISS-induced pathway of IFN-alpha-mediated responses.

Joint Bone Spine, 2004 Sep, 71(5), 433 - 7
Sciatica, disk herniation, and neuroborreliosis . A report of four cases; Dupeyron A et al.; We report four cases of sciatica in patients with same-level disk herniation confirmed by computed tomography and a final diagnosis of acute radiculitis caused by Borrelia burgdorferi, with a favorable response to ceftriaxone therapy . The neurological manifestations of Lyme disease are protean, and a potential contribution of concomitant disk disease to sciatica can lead to diagnostic wanderings . Disk lesions and infectious conditions that can cause sciatica are discussed . Whether a favorable response to antibiotic therapy should be taken as proof of B . burgdorferi radiculitis deserves discussion . In practice, in a patient with clinical manifestations suggesting disk-related nerve root pain and residing or having traveled to an endemic area, B . burgdorferi infection should be looked for, as both etiologies can coexist.

Neurobiol Dis, 2004 Nov, 17(2), 310 - 8
Neuronal co-expression of EGFP and beta-galactosidase in mice causes neuropathology and premature death; Krestel HE et al.; Dose-dependent co-expression of enhanced green fluorescent protein (EGFP) and beta-galactosidase (beta-gal) in the cytoplasm of forebrain neurons of two independent mouse lines resulted in growth retardation, weakness, and premature lethality . In primary motor cortex and striatum, apoptosis, glial fibrillary acidic protein proliferation, and cell loss were found . In addition, we observed aggregations of EGFP and beta-gal that colocalized with ubiquitin . GFP is unlikely to be toxic per se, as a third mouse line that expressed twice as much GFP in the cytoplasm of forebrain neurons as the two affected lines was normal . Cytoplasmic aggregations of EGFP and beta-gal occurred in affected and phenotypically normal mice suggesting a storage function rather than being detrimental . We successfully prolonged survival of affected mice with granulocyte colony-stimulating factor (GCSF) and the antibiotic minocycline . These compounds could protect neurons from EGFP and beta-gal-induced dysfunction, as demise of mice started after treatment was discontinued.

J Heart Valve Dis, 2004 Sep, 13(5), 831 - 40
Prototype anionic detergent technique used to decellularize allograft valve conduits evaluated in the right ventricular outflow tract in sheep; Hilbert SL et al.; BACKGROUND AND AIM OF THE STUDY: Biodegradable polymeric materials or extracellular matrix scaffolds are used in tissue-engineered heart valve designs, with the expectation of replicating the anatomic, histological and biomechanical characteristics of semi-lunar valves . The study aim was to evaluate the extent of in-vivo recellularization and the explant pathology findings of a prototype anionic, non-denaturing detergent and endonuclease technique used to decellularize allograft (homograft) valve conduits implanted in the right ventricular outflow tract (RVOT) of sheep, and to identify possible risks associated with tissue-engineered heart valve conduits based on decellularized allograft semilunar valve scaffolds . METHODS: Valve conduits were decellularized using a solution of N-lauroylsarcosinate and endonucleases, rinsed in lactated Ringers solution, and stored in an antibiotic solution at 4 degrees C until implanted . Explanted valves and unimplanted controls were examined macroscopically, radiographically (for calcification) and histologically using immunohistochemistry (IHC), routine and special histological stains, transmission electron microscopy (TEM) and polarized light microscopy (evaluation of collagen crimp) . RESULTS: Cells and cellular remnants were uniformly absent in the decellularized cusps, but occasional focal sites of arterial wall smooth muscle cells and to a greater extent subvalvular cardiac myocytes were variably retained . The trilaminar histological structure of the cusp was preserved . Valve conduit-related pathology consisted of intracuspal hematoma formation, collagen fraying, thinning of the conduit wall, and inflammatory cells associated with cardiac myocyte remnants . Cuspal calcification was not seen, but elastic fibers in the conduit wall and retained subvalvular cardiac myocyte remnants were liable to calcification . Fibrous sheath formation was present on the luminal surface of the conduit and extended over the cuspal surfaces to a variable extent . Myofibroblast-like cells repopulated the conduit wall and the basal region of the cusp . Re-endothelialization was variably present on the cuspal surfaces . CONCLUSION: Explant pathology findings showed that in-vivo recellularization occurred, but was focally limited to regions of the arterial wall and cusp base . Safety concerns related to detergent and endonuclease use were identified . Methods to eliminate the potential for structural deterioration and enhance the rate and extent of recellularization of valve conduit tissue are required . Pathology findings showed implantation of valve conduits in the RVOT of juvenile sheep for 20 weeks to be a reliable animal model for the initial in-vivo assessment of decellularized valves . A 20-week period may be insufficient however to evaluate the long-term safety and effectiveness of a tissue-engineered valve conduit, as these depend on effective and phenotypically appropriate recellularization accompanied by sustained cell viability and function.

Environ Mol Mutagen, 2004, 44(4), 277 - 82
Analysis of streptonigrin-induced incomplete chromosome elements and interstitial fragments in Chinese hamster cells using a telomeric PNA probe; Bolzan AD et al.; We investigated the induction of incomplete chromosome elements (ICEs; i.e., elements with a telomeric signal at only one terminal end) and interstitial fragments induced by the antibiotic streptonigrin (SN) in a Chinese hamster embryo (CHE) cell line using FISH with a telomeric peptide nucleic acid probe . CHE cells were treated with 0-250 ng/ml SN and chromosomal aberrations were analyzed in the first mitosis after treatment using the telomeric probe . Exposure of CHE cells to SN resulted in a linear concentration-related increase in all of the aberration types analyzed (P < 0.05) except ring chromosomes . Depending on the SN concentration employed, 33-68% of the metaphases contained one or more pairs of ICEs (an incomplete chromosome accompanied by a terminal fragment or two incomplete chromosomes accompanied by a compound fragment) . Pooled data from all SN concentrations revealed that 77.8% of the acentric fragments were terminal fragments, 18.8% interstitial fragments, and 3.4% compound fragments . Furthermore, it was estimated that about 80% of excess acentric fragments induced by SN originated from incomplete exchanges or terminal deletions and 20% from complete exchanges (interstitial deletions) . These results show that incomplete chromosomes and terminal fragments are the most frequent asymmetrical chromosomal aberrations induced by SN and indicate that true incompleteness is a very common event following exposure to SN.

Vet Clin North Am Food Anim Pract, 2004 Nov, 20(3), 547 - 68
The importance of the nonlactating period in the epidemiology of intramammary infection and strategies for prevention; Bradley AJ et al.; The dry period is a high risk period for the acquisition of new environmental IMIs, with over 60% of new IMIs occurring at this time . It also offers an ideal opportunity to improve udder health, through the judicious use of antibiotics to treat high SCC cows.The prophylactic use of antibiotics in food producing animals is increasingly being called into question; DCT is the primary example of such antibiotic use in the dairy cow . A holistic approach to management of the dry cow is a vital part of mastitis control, and should encompass environmental and nutritional management as well as the blanket use of therapeutic and prophylactic medicinal products . In high SCC cows, it is important to select cows appropriate for treatment (as opposed to culling), and there is a good clinical justification for the use of antibiotics to treat existing IMIs . In low SCC cows, teat sealants provide a viable alternative to antibiotic DCT, and careful consideration should be given to their use.

Wien Klin Wochenschr, 2004 Aug 31, 116(15-16), 542 - 51
{Is it possible to reduce CMV-infections after heart transplantation with a three-month antiviral prophylaxis? 7 years experience with ganciclovir}; Antretter H et al.; BACKGROUND: In the early phase after heart transplantation (HTX) patients are at high risk for infection because of intensified immunosuppression . This retrospective study evaluates the efficacy of a three-month antiviral cytomegalovirus (CMV) prophylaxis . Patients and methods: 133 patients received a three-month combined intravenous and oral CMV prophylaxis with Ganciclovir (Cymevene after HTX between 1997 and April 2003 (group II) . They were compared to a historical group consisting of 40 patients, who had undergone HTX between 1995 and 1996 (group I; CMV-prophylaxis: hyperimmune globuline (Cytotect) for the first post-operative month in combination with orally administered aciclovir (Zovirax) for 6 months) . Demographic data of organ recipients and donors in both groups were comparable, except for underlying cardiac diseases (p = 0.016) . All patients had identical postoperative immunosuppressive regimes . RESULTS: Group II had a significantly lower mortality rate (GI: 37.5%, GII: 9.8%; p < 0.001); one year survival (p = 0.001) and overall survival (p = 0.001) were significantly better than in group I . Patients of group II had fewer rejection episodes > or = grade II ISHLT requiring treatment (p < 0.001) . Group II presented significantly fewer positive CMV blood samples (p = 0.005) and CMV infections (26% versus 47,5% in GI; p = 0.008), and a later onset of infections after HTX than group I (group I with a mean interval of 5.8 weeks after HTX, group II: 24.8 weeks after HTX; p < 0.001) . CONCLUSION: Incidence of CMV infection was significantly lowered under ganciclovir prophylaxis, infections occurred at a later time point after HTX, when patients were immunologically more competent . The proportion of higher grade rejection episodes was markedly reduced and survival was improved.

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