Antibiotics

Schweiz Med Wochenschr, 2000 Jan 29, 130(4), 122 - 7
{The hospitalized patient with fever and mental status changes}; Guillet EM et al.; The case is discussed of a 74-year-old patient hospitalised with acute colitis, who newly developed headache, fever, and mental status changes on the 14th day after admission . The course of the disease was characterised by rapid progression with loss of consciousness and the development of extensive brain oedema, despite broad-spectrum antibiotic therapy . The patient died on the 17th of hospitalisation.

Can J Microbiol, 2000 Apr, 46(4), 333 - 8
Shuttle vectors for genetic manipulations in Ustilago maydis; Kojic M et al.; Shuttle vectors with new or improved features were constructed to enable facile genetic manipulations in the plant pathogen Ustilago maydis . Sets of plasmids selectable in media containing geneticin, carboxin, nourseothricin, or hygromycin, able to replicate autonomously, to transform U . maydis by integration, and to express foreign genes under control of the homologous glyceraldehyde-3-phosphate dehydrogenase promoter, were built upon a common pUC19 vector backbone . This permits a large number of choices for a cloning site, blue/white screening for recombinant plasmids, rapid transfer of a cloned DNA fragment between plasmids, and choice of several dominant drug-resistance markers for selection in U . maydis.

Cancer Lett, 2000 May 29, 153(1-2), 51 - 6
Preferential cytotoxicity of caffeic acid phenethyl ester analogues on oral cancer cells; Lee YJ et al.; As part of our previous search for new compounds with improved biological activities including antibiotic, antiviral, anti-inflammatory, and tumor growth inhibition activities, we synthesized some caffeic acid phenethyl ester (CAPE)-like compounds from commercially available caffeic acid . Nine chemicals were tested by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on the growth of buccal mucosal fibroblast (BF), oral submucosus fibroblast (OSF), neck metastasis of Gingiva carcinoma (GNM), and tongue squamous cell carcinoma (TSCCa) cells . CAPE and its ethyl analogue show significant cytotoxicity on OSF, GNM, and TSCCa cells, but not on BF cells . The results suggest that CAPE-like compounds may be potential chemotherapy agents against oral cancer.

Exp Toxicol Pathol, 2000 Mar, 52(1), 37 - 42
Hypovolemia in rats increases mortality rates following endotoxin administration; Zurovsky Y et al.; The aim of the present study was to examine whether acute or chronic hypovolemia increase the mortality rates of rats following endotoxin injection . Another aim of this study was to examine whether this increase in sensitivity can be explained by increased leakage of endotoxin from the digestive tract to the blood stream . Chronic hypovolemia was caused by water deprivation for 8 days . Acute hypovolemia was caused by injection of sucrose (300mg/100g) or by hemorrhage of a volume of up to 2.1 ml/100g . The hypovolemia was examined by measuring the plasma volume using Evans Blue (EB) . Endotoxin at various doses was injected to the hypovolemic rats and the lethality of the various treatments was examined . Acute and chronic hypovolemia caused a significant increase inthe mortality rates of rats injected IP with a dose of 1-1.5 mg/100g endotoxin . Endotoxin administration (6mg/100g) by drinking to hypovolemic rats did not cause death at all . In contradistinction, injection of galactoseamine to rats that underwent similar treatments caused 100% mortality . Endotoxin tolerance reduced the mortality rates following galactoseamine injection to the control level of administration of endotoxin without hypovolemia (p < 0.001) . Injection of the antibiotic polymixin B following the galactoseamine injection also decreased mortality rates to 40% (p < 0.05) . Examination of plasma endotoxin concentration exhibited a significant increase following administration of endotoxin by drinking to hypovolemic rats (p < 0.001) compared to rats that received the same amount of endotoxin but without hypovolemia . These results indicate that one possible explanation for the increased mortality rate of the hypovolemic rats after endotoxin injection is due to leakage of endotoxin from the digestive tract.

Int J Tuberc Lung Dis, 2000 Apr, 4(4), 350 - 5
Referral times of Vietnamese refugees with tuberculosis in camps in Hong Kong; Taylor WR et al.; SETTING: Two closed camps in Hong Kong for Vietnamese refugees . OBJECTIVE: To determine the referral times by clinicians (doctor's delay) of cases of tuberculosis (TB) from refugee camp clinics to the hospital/chest clinic . DESIGN: Retrospective case-note study of 97 Vietnamese patients receiving treatment for tuberculosis . RESULTS: The sites of TB were pulmonary (n = 61), glandular (n = 15), pleural effusion (n = 15), and other (n = 6) . The median referral time was 18 days (range 0-417) . Median consultations numbered three (range 1-16) . Fifty-three (54.6%) patients were prescribed antibiotics . Thirty-nine (40%) patients were referred within 10 days; of these, 18 were referred the same day . These 39 patients were less likely to have received antibiotics (9/39 {23.1%} vs 44/58 {75.9%}, relative risk {RR} 0.3 95% confidence interval {CI} 0.17-0.55), but were equally likely to have been physically examined (RR 0.66, 95%CI 0.39-1.1) . Sixteen (16.5%) patients were referred after 90 days . They attended the clinic more often (median attendances 6.5 vs 3, P = 0.0002), and were prescribed more antibiotic courses (mean antibiotic prescriptions 1.6 vs 0.7, P = 0.03) . CONCLUSION: Referral times by these clinicians varied widely, with long delays for approximately 60% of patients . Guidelines pertinent to primary care clinicians are needed to heighten their awareness of tuberculosis to prevent referral delays and subsequent TB treatment.

Rev Clin Esp, 2000 Feb, 200(2), 60 - 3
{Migratory erythema (Lyme borreliosis) . Clinicoepidemiologic features of 50 patients}; Oteo Revuelta JA et al.; BACKGROUND AND OBJECTIVE: Erythema migrans (EM) is the earliest and most common manifestation of the infection caused by B . burgdorferi (Lyme borreliosis) . The objective of the present work was to report the clinicoepidemiological features in a series of patients . PATIENTS AND METHODS: Retrospective collection of clinicoepidemiological features of the first fifty patients diagnosed of EM at La Rioja Hospital (March 1989-September 1998) . RESULTS: In our series, no differences were observed regarding sex or living in a rural or urban area . Mean age was 41 years (range 9 to 78) . In 70% of patients the antecedent of a tick bite was obtained and the incubation period was 6.48 days (1 to 15 days) . The mean size of the lesions was 14.3 cm (5 to 40) and in 16% of patients satellite cutaneous lesions were observed . The areas where EM appeared were lower limbs and the perineal region (60%), chest (24%), head and neck (10%) and upper limbs (6%) . Forty-eight percent of patients reported extra-cutaneous manifestations . All cases occurred during the spring, summer and autumn months, with a peak in June . The most common referred antecedent was walking in forest areas . All patients responded to antibiotic therapy . CONCLUSIONS: EM is common in the studied environment and presents with a marked polymorphism.

Eur J Nucl Med, 2000 Mar, 27(3), 314 - 8
Indium-111 labelled platelet scintigraphy can predict the immunological origin of fever in patients on dialysis carrying a non-functioning renal allograft; Fuster D et al.; The purpose of this study was to evaluate the usefulness of labelled platelet scintigraphy in the differential diagnosis of a prolonged febrile syndrome (PFS) in patients on dialysis carrying a non-functioning renal allograft . We prospectively performed an indium-111 mercaptopyridine-labelled platelet scan on 91 patients (54 men, 37 women; mean age 39.6+/-12 years) . The mean duration of PFS was 35 days (range 7-122) . Forty-six of the 91 patients underwent steroid therapy (2-10 mg/day) . Platelet labelling was carried out following Thakur's method . Platelet scans were performed 48 h after reinjection of labelled platelets . The platelet uptake index (PUI) was calculated by dividing the cpm/pixel in the allograft ROI by cpm/pixel in a mirror background ROI . The final diagnosis of PFS was established depending on the outcome after treatment . In 61/91 patients the fever had an immunological origin because it disappeared after graft embolisation or transplantectomy . In 30/91 patients the PFS disappeared after antibiotic therapy (non-immunological origin) . The PUI in patients with immunological PFS was 1.80+/-0.7, while in patients with non-immunological PFS it was 1.12+/-0.1 (P<0.05) . When a PUI of > or =1.5 was considered as the threshold to establish PFS of immunological origin, the sensitivity of platelet scan was 76%, the specificity 100%, and the negative and positive predictive values 69% and 100%, respectively . In patients classified with immunological PFS who underwent steroid therapy, the PUI was significantly lower than in patients without steroids (P<0.05) . These results suggest that 111In-labelled platelet scintigraphy can accurately predict an immunological PFS in patients on dialysis carrying a non-functioning renal allograft . Therapy with steroids could reduce the sensitivity of 111In-labelled platelet scintigraphy in detecting immunological PFS.

Med Clin (Barc), 2000 Mar 4, 114(8), 299 - 301
{Emergency valvular replacement in infective endocarditis: hospital and long term clinical course . Analysis of 45 patients}; Alegret JM et al.; BACKGROUND: To define the evolution of patients with infective endocarditis who require urgent valve replacement in our environment . PATIENTS AND METHODS: We followed 45 consecutive cases of infective endocarditis that require valve replacement during their hospitalization . 32 patients had native valve infective endocarditis, 7 early prosthesis valve endocarditis and 6 late prosthesis valve endocarditis . Patients were followed for a long-term period, clinical and echocardiographycally . RESULTS: In 39 cases valve replacement was performed before ending antibiotic therapy . The main indications for surgery were refractory heart failure (24 patients) and shock (11 patients) . The mortality rate was 24%: 19% in native valve infective endocarditis, 43% in early prosthetic valve endocarditis and 33% in late prosthesis valve endocarditis . The first cause of death was septic shock (46%) . We followed 31 over 34 survivors for a mean time 65 (DS 49) months . We found two relapses and six deaths (1 sudden death, 2 endocarditis) and 72% of patients presented class I NYHA . We detected 17% prosthetic leaks (34% in the prosthetic valve endocarditis group) . CONCLUSIONS: The need of urgent valve replacement in the context of infective endocarditis is associated with a high mortality rate, and should be considered a serious condition . Long term prognosis is, however, acceptable, although 17% of patients had prosthesis leak, specially those with prosthetic valve endocarditis.

Indian J Pediatr, 1998 Sep-Oct, 65(5), 717 - 21
Prevalence of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community acquired pneumonia; Chaudhry R et al.; A prospective one year study was performed on 62 children admitted at the All India Institute of Medical Sciences with community acquired pneumonia (CAP) for the prevalence of Mycoplasma pneumoniae and Chlamydia pneumoniae . Diagnosis of infection with M . pneumoniae was based on serological tests viz microparticle agglutination test for detection of IgM antibodies and indirect immunofluorescence test for antigen detection from throat swabs (sensitivity 85.7%, specificity 93.3%) . The indirect solid-phase enzyme immunoassay for detection of IgG antibodies was used to determine the prevalence of C . pneumoniae (sensitivity 88.8%, specificity 75.8%) . Seventeen patients (27.4%) were found to have serological evidence of M . pneumoniae infection whereas only 4 (6.4%) patients were seropositive for C . pneumoniae . Results of this study indicate that M . Pneumoniae plays a significant role in CAP in infants and young children . Thus specialized laboratory testing for these agents should be more widely used thereby affecting empiric antibiotic regimens.

Am J Nephrol, 2000 Mar-Apr, 20(2), 138 - 41
Subcutaneous nodules attributed to nocardiosis in a renal transplant recipient on tacrolimus therapy; Wong KM et al.; We report a renal transplant patient who suffered from disseminated nocardiosis after empirical tacrolimus rescue therapy for chronic allograft rejection . The nocardiosis presented initially as only mildly tender subcutaneous calf nodules without any other signs of inflammation nor constitutional upset, which later spread to the lung and brain causing bronchopneumonia and brain abscesses . The risk factors for nocardial infection in our patient include the use of potent immunosuppressive agents such as tacrolimus, poorly controlled diabetes mellitus and kidney dysfunction . She responded well to combination antibiotic therapy comprising parenteral meropenem, cefotaxime and oral minocycline . We conclude that in transplant recipients, especially those receiving newer and more potent immunosuppressive agents like tacrolimus, nocardial infection can present as apparently 'cold' subcutaneous nodules without any systemic upset . An associated brain lesion should be excluded even in patients without neurological symptoms .

Transfusion, 2000 Apr, 40(4), 414 - 9
Functional characteristics of neutrophils collected and stored after administration of G-CSF; Leavey PJ et al.; BACKGROUND: Granulocyte transfusion may be used in neutropenic patients with severe bacterial or fungal infections that are unresponsive to antibiotic therapy . However, the inability to store granulocyte concentrates limits their clinical usefulness . STUDY DESIGN AND METHODS: Neutrophil chemotaxis and NADPH oxidase activity and the integrity of the neutrophil NADPH oxidase system were examined after apheresis collection and during storage to 48 hours . Neutrophils were mobilized in vivo by G-CSF, collected by apheresis techniques, and stored in apheresis bags in the presence and absence of additional G-CSF . For all experiments, cells were further purified by standard techniques of dextran sedimentation and hypotonic RBC lysis . RESULTS: Neutrophil chemotaxis was preserved to 24 hours of storage but was not affected by the G-CSF added to storage units . The NADPH oxidase system was also preserved as a functioning complex, and both cytosolic proteins and membrane-associated proteins were normal to 48 hours . However, there were divergent responses by intact cells to activating stimuli and reduced oxidase activity in the cell-free system . G-CSF did not appear to significantly affect NADPH oxidase activity or NADPH oxidase system integrity during storage . CONCLUSION: Neutrophils collected after the administration of G-CSF retained functional and biochemical characteristics for at least 24 hours of storage, which suggests additional effects of G-CSF mobilization beyond enhancing PMN yields and the possibility of storage of these components after collection.

Nucleosides Nucleotides Nucleic Acids, 2000 Jan-Feb, 19(1-2), 283 - 95
Synthesis of biomimetic analogs of neomycin B: potential inhibitors of the HIV RNA Rev response element; Nishizono N et al.; The aminoglycosidic antibiotic, neomycin B, is an inhibitor of the binding of Rev to RRE . This paper reports on the synthesis of analogs of neomycin B as potential anti-HIV compounds designed to function as inhibitors of Rev/RRE binding.

Drug Metab Dispos, 2000 May, 28(5), 529 - 37
Rabbit pregnane X receptor is activated by rifampicin; Savas U et al.; Reverse transcriptase-polymerase chain reaction was used to amplify a partial cDNA from rabbit lung mRNA that shared 77% protein sequence identity with the mouse pregnane X receptor (PXR) . Rapid amplification of cDNA ends from a rabbit kidney lambdaZAP expression library resulted in the isolation of overlapping cDNAs spanning the complete coding sequence . The deduced amino acid sequence of 411 residues exhibited 79% overall amino acid identity with human PXR and 77% identity with mouse PXR . Based on this protein sequence relationship and a similar degree of conservation exhibited by the mouse and human PXR orthologs, the cDNA appears to encode the rabbit PXR ortholog . 5'-rapid amplification of cDNA ends performed on an adaptor-ligated cDNA library from rabbit liver revealed the presence of an alternate mRNA, which differed at the 5'-terminus . RNase protection assays indicated that the alternate mRNA was expressed at >50-fold lower levels in rabbit kidney and liver . Rifampicin treatment of CV-1 cells cotransfected with a rabbit PXR expression plasmid and a luciferase reporter construct containing two copies of the DR3 enhancer from CYP3A23 produced a 6-fold induction of luciferase activity . In contrast, rat PXR was not responsive to this antibiotic under the same conditions . Pregnenolone 16alpha-carbonitrile was an efficacious activator of rat PXR, but failed to significantly activate rabbit PXR at equivalent concentrations . These results indicate that the ligand activation profile of rabbit PXR is distinct from rat PXR and more closely resembles that of human PXR . The rabbit PXR activation profile is consistent with the cytochrome P450 (P450) 3A6 induction profile in rabbits.

Antimicrob Agents Chemother, 2000 May, 44(5), 1214 - 22
Identification of the novobiocin biosynthetic gene cluster of Streptomyces spheroides NCIB 11891; Steffensky M et al.; The novobiocin biosynthetic gene cluster from Streptomyces spheroides NCIB 11891 was cloned by using homologous deoxynucleoside diphosphate (dNDP)-glucose 4,6-dehydratase gene fragments as probes . Double-stranded sequencing of 25.6 kb revealed the presence of 23 putative open reading frames (ORFs), including the gene for novobiocin resistance, gyrB(r), and at least 11 further ORFs to which a possible role in novobiocin biosynthesis could be assigned . An insertional inactivation experiment with a dNDP-glucose 4, 6-dehydratase fragment resulted in abolishment of novobiocin production, since biosynthesis of the deoxysugar moiety of novobiocin was blocked . Heterologous expression of a key enzyme of novobiocin biosynthesis, i.e., novobiocic acid synthetase, in Streptomyces lividans TK24 further confirmed the involvement of the analyzed genes in the biosynthesis of the antibiotic.

Anesteziol Reanimatol, 2000 Jan-Feb, (1), 36 - 8
{Characteristics of the strategy of intensive care of unconscious children}; Mel'nikova EV et al.; Three major groups can be distinguished among children hospitalized in resuscitation and intensive care wards in a state of unconsciousness: patients with bacterial meningitis and meningoencephalitis, viral meningoencephalitis, and noninfectious involvement of the NCS . Common strategy of treatment of these patients is characterized by some specific features: etiotropic antibiotic therapy in group 1 patients, antiviral drugs in group 2, and mainly symptomatic measures in group 3 . Immunotherapy used in each of these groups is substitute in group 1, immunomodulating and immunostimulating in group 2 and even more so in group 3 . Better results in group 1 are due to highly effective etiotropic antibiotics and drugs.

Arch Pediatr Adolesc Med, 2000 Apr, 154(4), 370 - 4
Are signs and symptoms associated with persistent corneal abrasions in children?
Rittichier KK, Roback MG, Bassett KE.
BACKGROUND: Corneal abrasions are common eye injuries in children . Most are treated with antibiotic drops or ointment, patching of the affected eye, and follow-up within 24 hours to confirm resolution by fluorescein examination . OBJECTIVE: To determine if signs and symptoms at follow-up were associated with the presence of a persistent corneal abrasion or abnormal visual acuity . DESIGN: Retrospective case series . SETTING: A children's hospital . PATIENTS: Children who were aged 4 years or older with the diagnosis of corneal abrasion between May 1992 and December 1996 and who had a follow-up examination . RESULTS: Seventy-seven patients (57% male) were enrolled (median age, 7 years) . The respective sensitivities, specificities, positive predictive values, and negative predictive values of selective signs and symptoms for persistent abrasions were as follows: for pain, 53%, 93%, 80%, and 80%; for photophobia, 57%, 100%, 100%, and 80%; for redness, 100%, 46%, 44%, and 100%; for pain and redness, 40%, 96%, 80%, and 80%; and for at least 1 sign or symptom, 95%, 48%, 47%, and 95% . Twenty-six patients had persistent corneal abrasions at follow-up . Six of these 26 patients were symptom free at follow-up, and 15 patients had only redness as a persistent sign . Five patients had abnormal visual acuity, one of whom was asymptomatic . All 3 patients with complications were symptomatic . CONCLUSIONS: Signs and symptoms are inconsistently associated with persistent corneal abrasions . Asymptomatic patients may have persistent corneal abrasions, suggesting the need for selective follow-ups.

Crit Care Clin, 2000 Apr, 16(2), 233 - 49
Pharmacologic issues in the management of septic shock; Jindal N et al.; Despite our increased understanding of the biochemistry and physiology of sepsis, the treatment of septic shock remains a challenge . Initial management of septic shock entails urgent and emergent stabilization of the patient followed by broad-spectrum, empiric antibiotic therapy . After volume resuscitation, vasopressors or inotropic therapy or both may be necessary to restore perfusion . Adjunctive therapies and monitoring strategies may be helpful in preventing complications in the intensive care setting . Additional research and clinical trials are needed to identify supportive interventions that may affect the outcome of the septic patient.

Antibiot Khimioter, 2000, 45(3), 7 - 8
{The augmentin (amoxicillin/clavulanate) prophylaxis of postoperative infectious complications in patients with acute surgical diseases of the abdominal cavity organs}; Grinberg AA et al.; Augmentin was used prophylactically in 25 patients with an account of the infectious complication risk according to 4 regimens: ultrashort-term (1.2 g intravenously with initial narcosis), short-term (1.2 g intravenously with initial narcosis followed by intravenous administration in a dose of 600 mg in 8 and 16 hours), middle-term (1.2 g intravenously with initial narcosis followed by intravenous administration in a dose of 600 mg every 8 hours for 2 days) and long-term (1.2 g intravenously with initial narcosis followed by intravenous administration in a dose of 600 mg every 8 hours for 3 days) . One complication episode as wound suppuration was recorded . The routine approach to the use of antibiotics in emergency abdominal surgery, when antibiotics are administered every day for several days after the operation, should be revised.

Minerva Stomatol, 1999 Nov, 48(11), 559 - 62
{Evaluation of the efficacy of flurbiprofen in subjects undergoing extraction of impacted 3d molar}; Roggia S et al.; INTRODUCTION: In this open controlled study the authors evaluated the anti-inflammatory, antalgic and antipyretic efficacy of flurbiprofen in 200 mg capsules as a complementary treatment to antibiotic therapy following minor oral surgery . METHODS: A total of 100 patients of both sexes, aged between 13 and 65, were monitored after extraction of impacted 3rd molar . Patients were treated with flurbiprofen SR 200 mg/day for five days and were controlled on the 2nd and 5th day after surgery . The following parameters were evaluated: painful symptoms, objective examination of mucosa and fever . RESULTS: The results showed the clear efficacy of flurbiprofen SR in reducing all the parameters examined.

Eur J Obstet Gynecol Reprod Biol, 2000 May, 90(1), 67 - 71
Outcome of premature infants delivered after prolonged premature rupture of membranes before 25 weeks of gestation; Xiao ZH et al.; OBJECTIVE: To identify factors influencing the outcome of premature infants delivered after prolonged premature rupture of membranes before 25 weeks' gestation . DESIGN AND POPULATION: All premature infants with gestational age <34 weeks, either inborn or outborn, with history of rupture of membranes before 25 weeks' gestation, admitted to our NICU between January 1992 and July 1997, were eligible for this retrospective study . Collected information included birth weight, gestational age at rupture of membranes and at delivery, duration between rupture of membranes and delivery (latency period), severity of oligohydramnios, pre- and post-natal managements, and follow-up of survivors . RESULTS: A total of 28 neonates fulfilled the inclusion criteria . Despite new strategies of ventilation and optimal management, the overall mortality rate was 43% (12/28) . Nonsurvivors were significantly less mature at rupture of membranes, and had severe oligohydramnios (anamnios) . We also noted less antenatal corticosteroids and antibiotic therapy in this group . Nine of eleven infants (82%) following rupture of membranes before 22 weeks' gestation died shortly after birth . The two remaining infants developed severe bronchopulmonary dysplasia . Nine deaths occurred in thirteen cases (69%) of anamnios . The major death causes were refractory respiratory failure and neurologic complications . Half of all survivors (8/16) developed bronchopulmonary dysplasia . CONCLUSION: The outcome of premature infants following prolonged premature rupture of membranes before 25 weeks' gestation is influenced by gestational age at rupture, severity of oligohydramnios, and antenatal antibiotics and corticosteroids . Neonates with rupture of membranes before 22 weeks have a very low chance of survival at the present time.

Scand J Gastroenterol, 2000 Mar, 35(3), 260 - 3
Efficacy of different Helicobacter pylori eradication regimens in patients affected by insulin-dependent diabetes mellitus; Gasbarrini A et al.; BACKGROUND: Patients with insulin-dependent diabetes mellitus (IDDM) are often affected by chronic infections; antibiotic absorption, however, may be influenced by the disease . H . pylori eradication appears to be reduced in IDDM patients . The aim of the study was to evaluate the efficacy of the most common H . pylori eradication regimens in a population of IDDM-infected patients . METHODS: One hundred and seventy-two IDDM patients were evaluated . H . pylori infection was assessed through the 13C-urea breath test . Infected patients were randomly assigned to three different standard 7-day eradication regimens: 1) amoxicillin, clarithromycin, pantoprazole; 2) tinidazole, clarithromycin, ranitidine bismuth citrate; or 3) tinidazole, clarithromycin, pantoprazole . Patients in whom eradication was not successful in the first cycle were subsequently submitted to a 7-day therapy with tinidazole, tetracycline, bismuth, and pantoprazole . RESULTS: Thirty-seven per cent of IDDM patients were infected . None of the triple therapies used provided an eradication higher than 62% . Conversely, the quadruple regimen was successful in 88% of the patients . Ten per cent of the subjects undergoing the triple therapies showed minor side effects, without significant differences among groups, whereas side effects occurred in 25% of the patients treated with the quadruple therapy (P < 0.05) . CONCLUSIONS: IDDM patients show a low H . pylori eradication rate with a standard triple therapy regardless of the regimen utilized, the dosage and/or the duration of the therapy used appearing not to be sufficient to eradicate the infection efficiently . The use of a quadruple regimen leads to the cure of a large percentage of the infected patients in whom the eradication was unsuccessful in the first therapy, although it is accompanied by a greater incidence of minor side effects.

Anticancer Drug Des, 1999 Oct, 14(5), 433 - 42
A DNA binding indolocarbazole disaccharide derivative remains highly cytotoxic without inhibiting topoisomerase I; Qu X et al.; NB-506 is a glucosylated indolocarbazole related to the antibiotic rebeccamycin and is currently under clinical trials as an anticancer drug . This compound is a DNA intercalating agent and a potent topoisomerase I poison . The glucose residue attached to the planar indolocarbazole chromophore plays a significant role in the interaction of the drug with nucleic acids and contributes positively to the stabilization of topoisomerase I-DNA covalent complexes . To investigate further the influence of the carbohydrate moiety, we studied the DNA binding and topoisomerase I inhibition properties of an analogue of NB-506 bearing a disaccharide side chain . Fluorescence and footprinting studies indicate that the replacement of the glucose chain of NB-506 with a maltose residue does not hinder the capacity of the drug to bind to DNA and to recognize GC-rich sequences . The addition of the second sugar residue does not reinforce the interaction with DNA but abolishes the capacity of the drug to inhibit topoisomerase I . Unexpectedly, the disaccharide analogue of NB-506 has totally lost its capacity to stimulate DNA cleavage by topoisomerase I . In addition, like NB-506, the new analogue is not an inhibitor of topoisomerase II . However, despite the absence of topoisomerase poisoning activity, the cytotoxic activity is fully maintained . The maltosyl-indolocarbazole drug proved to be as potent as NB-506 at inhibiting the growth of various human and murine tumour cell lines . The study raises the question as to whether topoisomerase I poisoning is important for the antitumour activity of rebeccamycin analogues.

Acad Radiol, 2000 Apr, 7(4), 228 - 31
Is the stat Gram stain helpful during percutaneous image-guided fluid drainage?
Ketai L, Washington T, Allen T, Rael J.
RATIONALE AND OBJECTIVES: The purpose of this study was to use logistic regression to analyze both Gram stain results and other clinical information to create a decision rule capable of predicting which abdominal or pelvic fluid collections would later prove to be infected and therefore require catheter drainage . MATERIALS AND METHODS: The authors retrospectively collected Gram stain results and clinical data (postoperative status and antibiotic use) regarding 124 abdominal or pelvic fluid drainage procedures performed between 1991 and 1996 . They then analyzed these data by using logistic regression to create an equation that predicted the presence of fluid infection . Finally, they validated this equation by applying it to 39 abdominal or pelvic fluid drainage procedures performed in 1997 . RESULTS: The resulting equation predicted that a fluid collection was likely to be infected if any of the following were present: Gram stain positive for bacteria, Gram stain showing moderate or many white blood cells, and purulent fluid at visual inspection . For the initial data set, the sensitivity of the decision rule was 91%, the specificity was 54%, and the overall accuracy was 77% . For the 1997 data set, the sensitivity of the decision rule was 88%, the specificity was 50%, and the accuracy was 77% . CONCLUSION: When combined with clinical information, Gram stain results are sensitive but nonspecific in the detection of abdominal or pelvic fluid infection . Use of the decision rule could prevent unnecessary catheter placement in a minority of patients with abdominal or pelvic fluid collections.

Quintessence Int, 1999 Nov, 30(11), 785 - 90
Early-onset periodontitis in a patient with Ehlers-Danlos syndrome type III; Reichert S et al.; This case history describes the course of disease in a 17-year-old boy with Ehlers-Danlos syndrome type III and early-onset periodontitis . Flow cytometric tests showed a reduced cell count in the specific immune system . Immunoglobulin concentrations in saliva and serum were within normal limits . Infection with T-lymphotropic viruses was excluded . The phagocytic capacity of the peripheral blood polymorphonuclear leukocytes was unimpaired . The anaerobic infection present in the early-onset periodontitis was treated with systemic antibiotic therapy and closed curettage . Following 14 days of this treatment, signs of acute inflammation subsided, and 18 months after therapy ended, a slight gain in clinical attachment was found, and bone growth was visible via radiology . However, a continuing lack of adequate oral hygiene represents a risk to the success of therapy in the long term.

Am J Ophthalmol, 2000 Apr, 129(4), 531 - 3
Bilateral orbital hemorrhage in a newborn; Ezzadin EM et al.; PURPOSE: To report a case of severe bilateral proptosis resulting from orbital hemorrhage in a newborn and to discuss the differential diagnoses and management . METHOD: Case report of a 13-day-old male infant with bilateral proptosis since birth . The proptosis was monitored with clinical examinations and computed tomography as well as magnetic resonance imaging (MRI) scans, and it was managed with antibiotic ointment and patching . The MRI scans demonstrated bilateral subperiosteal orbital hemorrhage . RESULTS: Proptosis decreased, and there was successful, complete recovery without untoward sequelae in 14 days; follow-up indicated no late complications at age 1 year . CONCLUSION: Spontaneous orbital hemorrhage, unilateral or bilateral, is uncommon in an otherwise healthy newborn without apparent history of birth trauma . Magnetic resonance imaging scans are helpful in making the diagnosis of subperiosteal hemorrhage, and conservative management is advised.

Cancer Lett, 2000 Apr 3, 151(1), 25 - 9
Cells in cryptophycin-induced cell-cycle arrest are susceptible to apoptosis; Kessel D et al.; Exposure of murine leukemia L1210 cells to the antitumor antibiotic cryptophycin 52 (C52) led to cell-cycle arrest at the prometaphase/metaphase interface within 18 h, but apoptotic nuclei did not appear until 36 h later . To determine whether accumulation of cells in early metaphase might have delayed the apoptotic process, cells were treated with C52 for 18 h and a photodynamic process was used to initiate the release of mitochondrial cytochrome c . Apoptosis was observed within 60 min, indicating that the slow apoptotic response was not caused by an impaired ability of genomic DNA to undergo endonucleosomal cleavage during cell-cycle arrest induced by cryptophycin 52.

J Am Board Fam Pract, 2000 Mar-Apr, 13(2), 101 - 6
How family physicians distinguish acute sinusitis from upper respiratory tract infections: a retrospective analysis; Little DR et al.; BACKGROUND: The purpose of our study was to examine how physicians diagnose sinusitis in practice . We addressed three specific questions: (1) what clinical factors do physicians look for in evaluating and caring for patients with suspected sinusitis, (2) to what extent do physicians use transillumination and radiograph evaluations in diagnosing sinusitis, and (3) how does the diagnosis of sinusitis influence the decision to prescribe antibiotic therapy? METHODS: We conducted a retrospective review using charts from 25 local family physicians who volunteered to participate in the study . After selecting a random sample of charts of adult patients treated for sinusitis and for upper respiratory tract infection (URI) by each physician, we reviewed the charts to determine the nature of the information collected to differentiate between sinusitis and URI . RESULTS: Rhinorrhea, sinus tenderness, visualization of purulent secretions, and a history of sinusitis were significant predictors of the diagnosis of sinusitis . Antibiotics were prescribed for 98.4% of patients with sinusitis and 13.1% of patients with URI . CONCLUSIONS: This sample of physicians based the diagnosis of sinusitis on three prominent clinical findings, which were also significant factors in diagnosing sinusitis in previous studies . The history of sinusitis might influence patient and physician expectations for the diagnosis.

Laryngoscope, 2000 Apr, 110(4), 603 - 7
Calciphylaxis: is there a role for parathyroidectomy?
Kriskovich MD, Holman JM, Haller JR.
OBJECTIVE: Calciphylaxis, a rare disorder typically affecting renal failure patients, results in vascular calcification with subsequent skin necrosis, gangrene, and often death from sepsis . Parathyroid hormone is thought to act as a tissue sensitizer leading to these soft tissue changes . As such, parathyroidectomy is often advocated to control this complicated condition . A discussion of calciphylaxis does not exist in the otolaryngology literature, and head and neck surgeons performing parathyroidectomy should be aware of this phenomenon . This study evaluates the success of parathyroidectomy in reversing the ill effects of calciphylaxis in both our patient population and the literature . STUDY DESIGN: Retrospective study and review of the literature . METHODS: Five patients with calciphylaxis treated at our institution were evaluated for mortality, surgical and perioperative complications, wound healing, and predictors of patient outcomes . RESULTS: Two patients died from sepsis and infectious complications of their calciphylaxis shortly after surgery . Of the three survivors, two later died (15 and 18 mo after surgery) from causes not directly related to calciphylaxis . The other long-term survivor required partial amputation of a leg for osteomyelitis . There was one operative complication-- wound infection requiring antibiotic therapy, drainage, and packing . Postoperative hypocalcemia required treatment in two patients . Immediate perioperative survival was more likely in patients with leukocyte counts less than 20,000 cells/mL CONCLUSIONS: Calciphylaxis is a serious disease and patients often succumb to sepsis and infectious complications . Patients with extremely high leukocyte counts from coexistent infections may have a worse prognosis . Although a conclusive effective therapy does not exist, parathyroidectomy can be safely performed and may benefit some patients with what is often an otherwise fatal disease . The literature to date generally confirms our findings . Key Words: Calciphylaxis, parathyroid hormone, parathyroidectomy, skin necrosis, chronic renal failure.

J Bacteriol, 2000 May, 182(9), 2445 - 52
Efficient targeted mutagenesis in Borrelia burgdorferi; Bono JL et al.; Genetic studies in Borrelia burgdorferi have been hindered by the lack of a nonborrelial selectable marker . Currently, the only selectable marker is gyrB(r), a mutated form of the chromosomal gyrB gene that encodes the B subunit of DNA gyrase and confers resistance to the antibiotic coumermycin A(1) . The utility of the coumermycin-resistant gyrB(r) gene for targeted gene disruption is limited by a high frequency of recombination with the endogenous gyrB gene . A kanamycin resistance gene (kan) was introduced into B . burgdorferi, and its use as a selectable marker was explored in an effort to improve the genetic manipulation of this pathogen . B . burgdorferi transformants with the kan gene expressed from its native promoter were susceptible to kanamycin . In striking contrast, transformants with the kan gene expressed from either the B . burgdorferi flaB or flgB promoter were resistant to high levels of kanamycin . The kanamycin resistance marker allows efficient direct selection of mutants in B . burgdorferi and hence is a significant improvement in the ability to construct isogenic mutant strains in this pathogen.

J Clin Pharmacol, 2000 Apr, 40(4), 360 - 9
Acetaminophen controlled-release sprinkles versus acetaminophen immediate-release elixir in febrile children; Wilson JT et al.; Current acetaminophen (APAP) formulations approved for antipyretic use in children require up to five doses/day, which compromise compliance and risk breakthrough fever over 4 hours after dosing . A total of 112 evaluable febrile children received oral APAP-equivalent doses of either one dose of APAP controlled release (CR) as sprinkles on applesauce or one dose q 4 hours x 2 of APAP immediate-release (IR) elixir in an 8-hour, double-blind, double-dummy, randomized, multicenter study . Prior or concurrent antibiotic use did not significantly affect either the magnitude or the pattern of temperature reduction during the 8-hour observation period . Significantly greater aural temperature reductions were found with APAP-CR than with APAP-IR at 4 and 5 hours . However, the 8-hour AUCs of temperature reduction were not significantly different between treatments . Pharmacokinetic/pharmacodynamic modeling of APAP was performed in 8 patients with values in both treatments similar to previous results, except for expected differences in AUC0-infinity . Similar 8-hour temperature reduction for APAP-CR (one dose) and APAP-IR (two doses) demonstrates the efficacy of APAP-CR as an antipyretic in children 2 to 11 years of age . A decrease in the number of APAP daily doses and the prolonged antipyretic effect of APAP-CR may assist those who care for febrile children at home.

Plant Physiol, 2000 Apr, 122(4), 1003 - 13
Activation tagging in Arabidopsis; Weigel D et al.; Activation tagging using T-DNA vectors that contain multimerized transcriptional enhancers from the cauliflower mosaic virus (CaMV) 35S gene has been applied to Arabidopsis plants . New activation-tagging vectors that confer resistance to the antibiotic kanamycin or the herbicide glufosinate have been used to generate several tens of thousands of transformed plants . From these, over 30 dominant mutants with various phenotypes have been isolated . Analysis of a subset of mutants has shown that overexpressed genes are almost always found immediately adjacent to the inserted CaMV 35S enhancers, at distances ranging from 380 bp to 3.6 kb . In at least one case, the CaMV 35S enhancers led primarily to an enhancement of the endogenous expression pattern rather than to constitutive ectopic expression, suggesting that the CaMV 35S enhancers used here act differently than the complete CaMV 35S promoter . This has important implications for the spectrum of genes that will be discovered by this method.

Clin Exp Obstet Gynecol, 2000, 27(1), 24 - 6
Postpartum ovarian vein thrombosis; Hippach M et al.; OBJECTIVE: Ovarian vein thrombosis (OVT) is known as a rare but serious postpartum complication . The condition is often clinically not distinguishable from endometritis, appendicitis or pyelonephritis . OVT may cause sepsis, septic pulmonary thromboembolism, and thrombosis of the inferior vena cava and the renal veins, and is potentially fatal . The objective of this study was to report the clinical findings and outcome of two patients with diagnosed ovarian vein thrombosis after delivery managed at this institution . METHOD: Two patients fit the study criteria of documented ovarian vein thrombosis after delivery . An imaging diagnosis (CT) of ovarian vein thrombosis was required for final study inclusion . RESULTS: We present two patients with ovarian vein thrombosis . The symptoms of one patient disappeared two days after beginning heparin and antibiotic therapy . The control-CT 93 days after the diagnosis of POVT showed unsuspected ovarian veins . The other patient suffered from POVT 13 days after spontaneous delivery . Because of lethal embolisms she died during the operation for embolectomy . CONCLUSION: On the basis of our series and other recent series, OVT may likely be more common than previously thought and may become clinically apparent only when complicated by infection, expansion of the thrombus or pulmonary embolism . POVT is a potentially fatal condition most commonly seen as a complication of pelvic surgery or inflammatory disease.

Can J Gastroenterol, 2000 Mar, 14(3), 188 - 98
From bench to bedside to bug: an update of clinically relevant advances in the care of persons with Helicobacter pylori- associated diseases; Chiba N et al.; In-depth meetings of the XIth International Workshop on Gastroduodenal Pathology and Helicobacter pylori led to the presentation and discussion of extensive new data on H . pylori and its diseases . The mode of transmission of H . pylori remains unclear, and it remains unknown why only a small proportion of infected individuals develop duodenal or gastric ulcer disease and even fewer develop gastric cancer . The role of H . pylori eradication in persons with uninvestigated dyspepsia remains controversial . New clinical trials of H . pylori treatment show symptom relief and improvement in the quality of life of persons with functional dyspepsia, especially in those with ulcer-like or reflux-like dyspepsia . Clearly the move is toward symptom-based management of persons with dyspepsia, with fewer endoscopies being needed in the otherwise healthy young dyspeptic patients . It remains controversial whether eradicating H . pylori in duodenal ulcer or functional dyspepsia increases the risk of subsequent development of gastroesophageal reflux disease . The one-week proton pump inhibitor-based triple regimens remain the gold standard of H . pylori therapy, but some of the ranitidine bismuth citrate plus two antibiotic regimens also achieve an 80% H . pylori eradication rate on an intention-to-treat basis . While the urea breath test remains the noninvasive test of choice, interesting new data are available on the use of stool antigen testing to diagnose H . pylori infection . The number of H pylori-associated gastroduodenal diseases grows to include possible liver, vascular, immune and skin conditions.

Neurotoxicol Teratol, 2000 Mar-Apr, 22(2), 213 - 20
Exacerbation of iminodipropionitrile-induced behavioral toxicity, oxidative stress, and vestibular hair cell degeneration by gentamicin in rats; Al Deeb S et al.; This study describes the effect of gentamicin, an aminoglycoside antibiotic on iminodipropionitrile (IDPN)-induced abnormal neurobehavioral syndrome in female Sprague-Dawley rats . The animals were exposed to IDPN in the dose of 100 mg/kg/day intraperitoneally for 7 days . Gentamicin (GM) was administered intraperitoneally daily 1 h before IDPN in the doses of 10, 40, and 80 mg/kg body weight in three different groups of rats . One more group of animals received gentamicin alone (80 mg/kg) and served as the gentamicin-alone group . The intensity of IDPN induced characteristic excitation with choreiform, and the circling movement (ECC) syndrome was examined using an observational test battery including dyskinetic head movements, circling, tail hanging, air righting reflex, and contact inhibition of the righting reflex on days 6, 8, 10, 12, 19, 26, and 33 . The animals for histopathological observation were sacrificed on day 10, whereas the remaining animals that were used for long-term behavioral studies were sacrificed on day 35 for biochemical observations . The blood and brain samples were collected for the analysis of blood urea nitrogen (BUN), serum creatinine, cerebral malondialdehyde (MDA), conjugated dienes, and lipid hydroperoxides, whereas temporal bones were collected for inner ear histopathology . Our results showed that gentamicin significantly and dose dependently exacerbated the incidence and the severity of the IDPN-induced behavioral syndrome . The histopathology of the inner ear demonstrated more severe loss of sensory hair cells in the crista ampullaris of the rats treated with IDPN plus gentamicin compared to the IDPN-alone treated animals . Concomitant treatment with gentamicin also potentiated IDPN-induced increase in free radical indices, suggesting a possible role of oxidative stress in gentamicin-induced aggravation of IDPN toxicity . Further studies are warranted to determine the role of aminoglycosides in nitrile toxicity and drug-induced movement disorders.

Oncol Res, 1999, 11(7), 319 - 29
Establishment of a quantitative mouse dorsal air sac model and its application to evaluate a new angiogenesis inhibitor; Funahashi Y et al.; We have developed an improved mouse dorsal air sac model for quantifying in vivo tumor-induced angiogenesis . In our improved model, tumor angiogenesis is determined by measuring the blood volume in an area of skin held in contact with a tumor cell-containing chamber, using 51Cr-labeled red blood cells (RBC) . The blood volume induced by murine B16-BL6 melanoma cells increased linearly with the cell number in the range from 2 x 10(5) to 5 x 10(6) . Ten of 11 human tumor cell lines examined induced a significant increment in blood volume . For three representative human tumor cell lines (A549, WiDr . and HT1080 cells) that showed different angiogenic potencies, the levels of vascular endothelial growth factor (VEGF) produced by the tumor cells cultured under conditions of hypoxia and high cell density were correlated with the degree of in vivo angiogenesis . Using the improved model, it was confirmed that TNP-470, a well-known inhibitor, and borrelidin, an antibiotic from Streptomyces rochei, significantly inhibited the WiDr cell-induced angiogenesis . Borrelidin also inhibited spontaneous lung metastasis of B16-BL6 melanoma at the same dose that inhibited angiogenesis . Our results suggest that the improved mouse dorsal air sac model can be used for simple and quantitative measurement of tumor-induced angiogenesis and its inhibition.

J Chromatogr A, 2000 Mar 24, 873(2), 149 - 62
Novel simulated moving-bed method for reduced solvent consumption; Jensen TB et al.; Simulated moving-bed (SMB) chromatography is attractive for reducing sorbent and solvent consumption relative to fixed-bed systems . In this contribution, we describe a novel and versatile method for further reducing solvent consumption in the case of reversed-phase chromatography . The method is based on the variation of the distribution coefficients of solutes to be separated upon varying the composition of a multi-component mobile phase . If the solvent strength of the desorbent is set higher than the solvent strength of the feed, the components will have smaller distribution coefficients in the extraction section of the SMB and hence will be more easily eluted . This will result in a lower desorbent flow and possibly also in a shorter desorbent zone, and, ultimately, in more concentrated products . The so-called "Triangle-method" by Storti et al . {AIChE J., 39 (1993) 471} to obtain the region of complete separation, is extended for this novel SMB method . Theoretical evaluation of the proposed methodology supports the anticipated solvent reduction relative to fixed-bed RP-HPLC for the cases of the purification of the polyketide antibiotic nystatin and the separation of bovine insulin from porcine insulin.

In Vivo, 1999 Nov-Dec, 13(6), 503 - 6
Inhibitory action of roxithromycin on tumour necrosis factor-alpha production from mast cells in vitro; Shimane T et al.; This study was designed to evaluate the effects of roxithromycin (RXM), a newly synthesized macrolide antibiotic, on cytokine production from mast cells . Mast cells, induced by long-term culture of spleen cells from BALB/c mice, were stimulated with 2.5 micrograms/ml concanavalin A in the presence or absence of various concentrations of RXM . The culture supernatants were obtained 24 h after stimulation . RXM caused a reduction in TNF-alpha levels in culture supernatants in a dose dependent manner and was first detected at a concentration of as little as 0.5 microgram/ml . Metabolized RXM (RU 39001, RU 44981, and RU45179) also suppressed TNF-alpha production in a dose dependent fashion with a minimum concentration of 0.5 microgram/ml . However, metabolized RXM, RU 28111, scarcely affected TNF-alpha production from cultured mast cells . These results strongly suggest that RXM inhibits mast cell function, especially inflammatory cytokine production and may result in favorable modification in inflammatory diseases.

J Mol Biol, 2000 Apr 21, 298(1), 95 - 110
Aminoglycoside binding in the major groove of duplex RNA: the thermodynamic and electrostatic forces that govern recognition; Jin E et al.; We use a combination of spectroscopic, calorimetric, viscometric and computer modeling techniques to characterize the binding of the aminoglycoside antibiotic, tobramycin, to the polymeric RNA duplex, poly(rI).poly(rC), which exhibits the characteristic A-type conformation that is conserved among natural and synthetic double-helical RNA sequences . Our results reveal the following significant features: (i) CD-detected binding of tobramycin to poly(rI).poly(rC) reveals an apparent site size of four base-pairs per bound drug molecule; (ii) tobramycin binding enhances the thermal stability of the host poly(rI).poly(rC) duplex, the extent of which decreases upon increasing in Na(+) concentration and/or pH conditions; (iii) the enthalpy of tobramycin- poly(rI).poly(rC) complexation increases with increasing pH conditions, an observation consistent with binding-induced protonation of one or more drug amino groups; (iv) the affinity of tobramycin for poly(rI).poly(rC) is sensitive to both pH and Na(+) concentration, with increases in pH and/or Na(+) concentration resulting in a concomitant reduction in binding affinity . The salt dependence of the tobramycin binding affinity reveals that the drug binds to the host RNA duplex as trication . (v) The thermodynamic driving force for tobramycin- poly(rI).poly(rC) complexation depends on pH conditions . Specifically, at pH< or =6.0, tobramycin binding is entropy driven, but is enthalpy driven at pH > 6.0 . (vi) Viscometric data reveal non-intercalative binding properties when tobramycin complexes with poly(rI).poly(rC), consistent with a major groove-directed mode of binding . These data also are consistent with a binding-induced reduction in the apparent molecular length of the host RNA duplex . (vii) Computer modeling studies reveal a tobramycin-poly(rI) . poly(rC) complex in which the drug fits snugly at the base of the RNA major groove and is stabilized, at least in part, by an array of hydrogen bonding interactions with both base and backbone atoms of the host RNA . These studies also demonstrate an inability of tobramycin to form a stable low-energy complex with the minor groove of the poly(rI).poly(rC) duplex . In the aggregate, our results suggest that tobramycin-RNA recognition is dictated and controlled by a broad range of factors that include electrostatic interactions, hydrogen bonding interactions, drug protonation reactions, and binding-induced alterations in the structure of the host RNA . These modulatory effects on tobramycin-RNA complexation are discussed in terms of their potential importance for the selective recognition of specific RNA structural motifs, such as asymmetric internal loops or hairpin loop-stem junctions, by aminoglycoside antibiotics and their derivatives .

Eur J Med Res . 2000 Mar 27;5(3):125.
Extrinsic allergic alveolitis in domestic environments (Domestic allergic alveolitis) caused by mouldy tapestry
Schwarz H, Wettengel R, Kramer B.
Extrinsic allergic alveolitis often occures as bird fancier's lung or is caused by occupational treatment with antigenic materials . In housing environments antigens of allergic alveolitis are also found, especially mould fungi . lf a source of antigens is absent in the anamnesis and the clinical picture as well as the clinical findings are ambiguous, the diagnosis of extrinsic allergic alveolits is delayed or unobtained . The following example shows that in spite of a detailed allergic anamnesis the source of antigens may remain occult and only an inspection of the dwelling rooms leads to an elucidation . - A sixty-one year old non-smoking women was twice admitted to hospital with a temperature of more than 39 degrees C, intense dyspnea on exertion and a strong dry cough under the persumed diagnosis pneumonia . The laboratory values showed nonspecific signs of inflammation, the blood gas analysis was changed to a heavy hypoxemia (pO subset2 49.2 mmHg) and in the chest x-ray there were seen miliary and partly reticular alterations . The chest computed tomography showed extensive densities in both upper and lower parts of the lungs and the pulmonary function test corresponded with a low-grade to middle-grade restriction (VC subsetin = 67%, TLC = 69%) . A high dose of corticosteroids produced an improvement of the radiological findings and of the pulmonary function . Also the specialized diagnostic in a hospital for pulmonary diseases yielded no new knowledge, and an interstitial pneumonia was diagnosed . Only the new formation of an acute pneumonic clinical picture on the day of returning to the patients own habitation suggested a noxious substance in the domestic environment . The inspection of the rooms finally showed the source of antigen to be from a condensation water soaked, moulded tapestry on the embrasure of a small unopenable window in the bedroom just on the head of the bed . The nutritive mediums left in the rooms furnished evidence of the mould-species Penicillium, Cladosporium and Botrytis, in the bedroom however mostly Penicillium . The RAST of specific IgG proved a positive result of all three mould species (Penicillium sp . 1 : 100, Cladosporium sp . 1 : 200 and Botrytis sp . 1 : 200) . The diagnosis of an extrinsic allergic alveolitis caused by mould was confirmed by a controlled re-exposure test, which promptly gave rise to a relapse and forced the patient to change habitation with the result of no further ailments . - Characteristic for the extrinsic allergic alveolitis in the described case is the inefficiency of antibiotic therapy, the immediate recovery by corticosteroids and furthermore the outbreak of relapses caused by re-exposure . If the source of antigens is unclear, the inspection of the habitation by an experienced allergologist may lead to success.

Int J Antimicrob Agents, 2000 Feb, 13(4), 243 - 8
A comparison of the activities of three amphotericin B lipid formulations against experimental visceral and cutaneous leishmaniasis; Yardley V et al.; The polyene antibiotic, amphotericin B, the gold standard for systemic fungal infections is also a recommended second line treatment for visceral, cutaneous and mucocutaneous leishmaniasis . Acute toxicity has limited the use of amphotericin B but less toxic lipid formulations, AmBisome, Amphocil and Abelcet, have shown potential for the treatment of clinical visceral and mucocutaneous leishmaniasis . This study compares the in vitro and in vivo anti-leishmanial activity of Fungizone and the three lipid formulations . AmBisome and Amphocil were more active (ED50 values 0.3 and 0.7 mg/kg, respectively) than Abelcet (ED50 2.7 mg/kg) against L . donovani in a mouse model . Against L . major in vivo, AmBisome at a dose of 25 mg/kg was the most successful at reducing lesion size, with Amphocil also showing activity while Abelcet was inactive . In the L . donovani--peritoneal macrophage (PEM) model Fungizone and Amphocil were significantly more active (ED50 values 0.013 and 0.02 microg/ml, respectively) than AmBisome and Abelcet (ED50 values 1.5 and 2.6 microg/ml) . This trend was similar in the L . major--PEM model (Fungizone > Amphocil > AmBisome > Abelcet) . THP-1 macrophages infected with L . donovani amastigotes showed a different profile with Amphocil = Abelcet > AmBisome > Fungizone . Differences could be due to the interaction of the formulations with the biological milieu and uptake into different cell types.

Spine, 2000 Mar 1, 25(5), 626 - 8
Mycobacterium xenopi infection of the spine: a case report and literature review; Danesh-Clough T et al.; STUDY DESIGN: A case report of Mycobacterium xenopi . OBJECTIVES: To present a case report of a vertebral osteomyelitis caused by M . xenopi and to review the world literature on the subject . SUMMARY OF BACKGROUND DATA: M . xenopi is most commonly a pulmonary pathogen in immunosuppressed patients or those with underlying lung disease . Infection of the spine is very rare, with only four cases reported . Three of these cases occurred in immunosuppressed patients, and the fourth in a patient with previous tuberculosis osteomyelitis of the spine . METHODS: The information was obtained from a review of the patient's clinical notes and follow-up appointments . RESULTS: The patient was a 73-year-old woman with an M . xenopi osteomyelitis of T6-T7, confirmed by magnetic resonance imaging and a computed tomography-guided biopsy . She was treated with surgical decompression and stabilization before a 2-year antibiotic regimen was begun . At follow-up assessment 1 year after the antibiotics were finished, she still had some ongoing back pain, but no evidence of relapse . CONCLUSIONS: This is the first reported case of an M . xenopi infection of the spine in a patient with no predisposing factors . This type of infection can be difficult to treat, with a high relapse rate reported despite prolonged courses of antibiotics.

Med Pregl, 1999 Nov-Dec, 52(11-12), 505 - 7
{A quiet clinical course in an otogenic brain abscess}; Deric D et al.; INTRODUCTION: The occurrence of otogenic intracranial complications has been significantly diminished by introduction of antibiotic therapy, improved diagnostic methods and surgical treatment of chronic otitis . Meningitis is still the most frequent otogenic intracranial complication, otogenic brain abscesses are following, while other complications occur rarely (1,2,3) . Otogenic meningitis and brain abscesses are often associated, which makes the on time diagnosis of each complication harder . Mortality from otogenic brain abscesses is still relatively high, despite diagnostic and therapeutic achievements (4.5) . CASE DESCRIPTION: The aim of this study is to present a patient with brain abscess, which arose quietly, as a consequence of chronic suppurative otitis and to point at possibilities of diagnostics and treatment of this complication . The diagnosis of brain abscess by clinical methods of examination is not always reliable . It is often accompanied by most severe form of meningitis, so that neurological examination, in most cases, reveals only signs of meningitis . In our patient, the abscess has been detected by computerized tomography, in its late stage, when it already had completely formed a capsule and had shown clinically manifesting focal signs . This case is interesting because of quiet and unperceived evolution of brain abscess . In the active phase of chronic suppurative otitis, the patient was receiving antibiotic therapy, which has most likely hidden the early symptoms of evolution of intracranial infections . The appearance of signs of focal intracranial infection (photophobia) required applying computerized tomography revealing brain abscess, which was clearly bounded, with a developed capsule, pointing at its late stage (about two months) . These findings lead to a conclusion that an otologist should always keep in mind and check whether there is an intracranial infection in cases of active phase chronic otitis.

Eur J Clin Microbiol Infect Dis, 2000 Feb, 19(2), 146 - 8
Evaluation of the E test for antifungal susceptibility testing of Candida glabrata; Favel A et al.; The E test was compared to the reference NCCLS broth macrodilution method for susceptibility testing of Candida (Torulopsis) glabrata . The MICs of amphotericin B, flucytosine, fluconazole and itraconazole were determined using the appropriate culture media (RPMI 1640 agar with 2% glucose, Casitone agar or Antibiotic Medium 3 agar) according to the drug tested . Agreement between the two methods was within plus/minus two dilutions for 77-100% of test results, according to the drug/medium combination . The study revealed problems in determining the MICs of azoles using the E test, and confirmed the suitability of Casitone agar for susceptibility testing of fluconazole even if results were read within 24 h.

Rozhl Chir, 1999 Nov, 78(11), 587 - 9
{Drainage of the abdominal cavity using a simple and reliable system}; Serclova Z et al.; Experience with drains is more than 2000 years old, but instructive . In abdominal surgery nowadays indications for prophylactic drainage are diminishing as peroperative antibiotic administration has a similar effect . Therapeutic drainage is however still important and drainage is also useful after extensive operations, surgery of the lesser pelvis and operations with major bacterial contamination . The authors present their practical experience with a simple system of wrapped drains (Medisillen-Rubena, Brno) and a cover with an adhesive plate (B-Braun-Biotrol) which they used in 660 abdominal drainages with a very good effect.

Int J Hematol, 2000 Feb, 71(2), 136 - 43
Efficacy of a new formulation of lenograstim (recombinant glycosylated human granulocyte colony-stimulating factor) containing gelatin for the treatment of neutropenia after consolidation chemotherapy in patients with acute myeloid leukemia; Takeshita A et al.; The efficacy and safety of a new formulation of lenograstim (recombinant glycosylated granulocyte colony-stimulating factor) prepared by switching the stabilizer from human serum albumin (HSA) to gelatin was investigated for the treatment of neutropenia after consolidation chemotherapy in patients with acute myeloid leukemia (AML) . The results obtained in the study using the gelatin-containing formulation (gelatin-lenograstim) were retrospectively compared to those obtained from a placebo-controlled double-blind randomized study (AML-DBT) using the HSA-containing formulation (HSA-lenograstim) . The median time of neutrophil recovery to > or = 1000/mm3 was significantly shorter in the gelatin-lenograstim group (14 days) than in the placebo group (21 days, P = .0001), and there was no significant difference between the gelatin-lenograstim group and the HSA-lenograstim group (14.5 days of AML-DBT, P = .5462) . The incidences of febrile neutropenia were significantly reduced in the gelatin-lenograstim group (24/43, 55.8%) compared to the placebo group (58/64, 90.6%, P < .0001) . The incidence of fever and antibiotic use was also significantly lower in the gelatin-lenograstim group (69.8% and 83.7%, respectively) than in the placebo group (92.2%, P = .0034, and 96.9%, P = .0285, respectively) . However, between the 2 groups there were no differences in the number of patients who had infectious episodes . No serious adverse drug reactions ascribed to gelatin-lenograstim were encountered . These results demonstrate that gelatin-lenograstim exerted beneficial effects in the acceleration of neutrophil recovery and in the reduction of fever, febrile neutropenia, and antibiotic use, and its efficacy was equivalent to HSA-lenograstim . Therefore, we concluded that the gelatin-lenograstim formulation, which offers no risk of virus contamination and can be stored at room temperature, is more beneficial than the HSA-lenograstim formulation.

Oral Oncol, 2000 Mar, 36(2), 242 - 7
Induction of apoptosis in KB cells by pingyangmycin; Tai KW et al.; Pingyangmycin (PYM; Bleomycin A(5)), an antitumour antibiotic is currently used during anticancer therapy . Previous experiments demonstrated that the therapeutic efficiency of PYM for treatment of malignant tumours is considered to be related to its ability to cause DNA strand breaks in vitro . However, very little is known about the interaction of PYM with the target cells, and it is still unclear how PYM enters the cells . In this study, cell death induced by PYM was studied in a human squamous cell carcinoma cell line (KB cells) . In order to determine if cell death occurred by necrosis (reproductive cell death) or apoptosis (programmed cell death), KB cells were exposed to different concentrations of PYM and evaluated by biochemical and morphological criteria . Our results indicate that KB cells displayed an arrest in the G(2)-M phase of the cell cycle and became enlarged and polynucleated before dying at the low concentrations of PYM . In contrast, when cells were exposed to high concentrations of PYM, morphological changes identical to those usually associated with apoptosis were observed as well as internucleosomal digestion of genomic DNA . In conclusion, we demonstrate that PYM is able to induce two distinct modes of cell death depending on the doses of PYM.

Magn Reson Imaging, 2000 Apr, 18(3), 255 - 62
The diagnostic role of gadolinium enhanced MRI in distinguishing between acute medullary bone infarct and osteomyelitis; Umans H et al.; The objective of the study was to evaluate the diagnostic utility of contrast enhanced magnetic resonance imaging (MRI) for distinguishing between acute medullary bone infarct and osteomyelitis . There were 11 patients (age 6-34 years) presented to our institution between December 1994 and February 1998 with a clinical differential diagnosis of acute bone infarct versus osteomyelitis and inconclusive radiographs were imaged using MRI . All but one received i.v . gadolinium . Nine of the patients had homozygous Sickle Cell disease (SCD) and two had Systemic Lupus Erythematosus (SLE), the latter requiring chronic methylprednisolone . Osteomyelitis was confirmed either by biopsy alone or by the combination of Gallium(67) scan in conjunction with positive blood cultures and clinical resolution following antibiotics . Infarcts without osteomyelitis were confirmed either by biopsy or resolution of symptoms without antibiotic therapy . All patients had at least six months clinical follow-up . The results found that seven of nine patients with SCD had acute infarct only . One patient with SCD had osteomyelitis only . Three patients (two SLE and one SCD) had both acute-on-chronic infarcts and superimposed osteomyelitis, one with an adjacent soft tissue abscess . Accurate distinction between infarct and osteomyelitis was impossible for one patient with SLE who did not receive contrast . All other cases were correctly diagnosed prospectively based on distinct patterns of MRI contrast enhancement . In all adult patients, acute infarcts demonstrated thin, linear rim enhancement on MRI while osteomyelitis revealed more geographic and irregular marrow enhancement . Two of four cases of osteomyelitis also demonstrated subtle cortical defects with abnormal signal traversing marrow and soft tissue . The single pediatric patient demonstrated elongated, serpiginous central medullary enhancement with periostitis . We concluded that the pattern of MR contrast enhancement may allow accurate distinction between acute infarct and osteomyelitis, or recognition of osteomyelitis superimposed on bone infarction.

Obes Surg, 1994 Aug, 4(3), 232 - 237
Clinical Benchmark for Gastric Stapling Procedures; Graves HA Jr; To help answer the call to cut costs of surgical care, hospitals and physicians have joined to compare methods of care for the more common Diagnosis Related Group (DRG) diagnoses to form a Benchmark . Since many bariatric surgeons are the only ones performing this surgery in their primary hospitals, they do not have two or more surgical routines for comparison . This presentation compares data for the preoperative work-up, operating-room, and methods of postoperative care used by 29 members of the American Society for Bariatric Surgery (ASBS) . There was representation of both academic and private surgeons and hospitals . To target areas for possible savings, the hospital bills of 16 patients without complication were compared . The synthesis of this information revealed significant differences in the extent and cost of preoperative work-up, antibiotic coverage, other postoperative care, and length of stay . These differences are examined under the assumption that patient outcome was the same.

Eur J Gastroenterol Hepatol, 2000 Feb, 12(2), 183 - 6
An audit of percutaneous endoscopic gastrostomy in a general hospital in Singapore; Yim HB et al.; OBJECTIVE: We conducted an audit on 50 percutaneous endoscopic gastrostomies (PEGs) performed by physician endoscopists from January 1996 up to November 1997 . DESIGN: A retrospective cohort study was conducted . RESULTS: The mean age of the patients was 68.5 years (range 20-101) and the main indications were cerebrovascular accident in 40 (80%), neurological dysphagia in six (12%) and head injury in three (6%) . The interval between the diagnosis of dysphagia and PEG was > 60 days in 19 patients (38%), 31-60 days in eight (16%) and < or = 30 days in 23 (46%) . The commonest reason for PEG insertion was intolerance to nasogastric tube in 49 patients (98%) . Twelve patients had antibiotics given concurrently for other infections and two had antibiotics given specifically to cover PEG insertion . There was evidence of post-PEG infection in two of 14 patients given antibiotics (14%) and in 14 of 36 patients not given antibiotics (39%) . By Cox regression, the adjusted relative risk of infection in patients receiving antibiotics versus those not receiving was 0.6927 (95% CI 0.3396-1.4130; not significant) . The 30-day mortality was 7/48 patients (15%), with two patients lost to follow-up before 30 days . There were no deaths directly attributable to PEG . CONCLUSIONS: PEG is still not adequately requested by doctors for patients needing enteral feeding for more than 30 days . The use of antibiotics in this retrospective cohort study failed to show any benefit in reducing the rate of infective complications.

Int Orthop, 1999, 23(6), 348 - 50
Total hip arthroplasty for tuberculous coxitis; Caparros AB et al.; We report a case of tuberculous arthritis of the hip in a 22 year old male patient, treated with arthrotomy and antituberculous antibiotic therapy for 9 months; the joint deteriorated and 2 years later he underwent uncemented total hip arthroplasty . He received antibiotic therapy for 3 months preoperatively and for 6 months postoperatively . At 5 year follow-up there was no evidence of recurrent infection.

J Biochem (Tokyo), 2000 Apr, 127(4), 585 - 9
Mutational analysis of tyrosine-191 in the catalysis of Cephalosporium acremonium isopenicillin N synthase; Loke P et al.; Isopenicillin N synthase (IPNS) is a key enzyme responsible for the catalytic conversion of delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV) to isopenicillin N in the beta-lactam antibiotic biosynthetic pathway . The Aspergillus nidulans IPNS crystal structure implicated amino acid residues tyrosine-189, arginine-279, and serine-281 in the substrate-binding of the valine carboxylate portion of ACV via hydrogen bonds . In previous reports, we provided mutational evidence for the critical involvement of the corresponding arginine-281 and serine-283, which constitute a conserved R-X-S motif, for the catalysis of Cephalosporium acremonium IPNS (cIPNS) . In this study, we report the site-directed mutagenesis of the corresponding tyrosine-191 in cIPNS to four amino acids from different amino acid groups, namely, phenylalanine, serine, histidine, and aspartate . The mutants Y191F, Y191H, and Y191R respectively yielded specific activities at levels of 3, 8.6, and 18.8% relative to the wild-type when enzyme bioassays were performed using purified protein fractions . These results were surprising, as previous mutational analyses involving arginine-281 and serine-283 resulted in non-measurable specific activities, thus suggesting that tyrosine-191 is important but not critical for the activity of cIPNS due to its involvement in ACV binding . Hence, it is likely that tyrosine-191 is the least critical of the three residues involved in binding the ACV valine carboxylate moiety.

Lakartidningen, 2000 Feb 16, 97(7), 688 - 91
{Help to children and adolescents with malnutrition or eating disorders . Percutaneous endoscopic gastrostomy with button: simple, safe and cost-effective}; Casswall T et al.; Percutaneous endoscopic gastrostomy (PEG) has gained great popularity for children with malnutrition and eating disorders secondary to chronic illness . However, the procedure is not without risks . We report on 62 infants and children, median age 4 years (1 month-20 years), who underwent PEG placement . Cerebral palsy with or without mental retardation was the most common diagnosis (50%) . No complications related to the PEG procedure itself occurred, but postoperative pneumonia was seen in 10% . Late complications were few: intraperitoneal migration of the button in one child and prolapse of the stoma in another . At the time of button placement, after median 14 weeks, mean weight had increased from a standard deviation score of -2.7 to -2.2 (P < 0.001) . We consider PEG to be a safe procedure for children with malnutrition requiring enteral feeding . Due to potential risks and complications related to this method, a multidisciplinary approach, as found in a "nutritional support team", is recommended.

J Pediatr Orthop, 2000 Mar-Apr, 20(2), 163 - 5
Pin site care during external fixation in children: results of a nihilistic approach; Gordon JE et al.; We prospectively followed 27 consecutive children with tibial circular external fixators applied between July 1, 1995, and June 30, 1997 . A simple pin care system with no physical pin cleansing except that provided by daily showers was used . Children with inflamed or infected pin sites were placed on an oral antibiotic (cephalexin) for 10 days . Pin sites were graded according to the system of Dahl et al . on a 0 to 5 scale . A total of 4,473 observations was made . Patients developed 178 pin tract infections (4.0% per observation), with 151 (85%) grade 1 and 27 (15%) grade 2 infections . No pin was removed because of infection . Diaphyseal half pin sites were less commonly infected (1.6%) than periarticular wire or half pin sites (4.5%) . We recommend only showering without other physical pin cleaning procedures in children undergoing external fixation procedures.

Laryngorhinootologie, 2000 Feb, 79(2), 77 - 80
{Bilateral malfunction of peripheral vestibular organs . Observations of 20 cases of Dandy syndrome}; Lange G et al.; BACKGROUND: Dandy's Syndrome initially provokes dizziness and vertigo . Later on patients suffer from motion unsteadiness especially in dark surroundings and from oscillopsies . Gentamicin is ototoxic mostly for the vestibular part of the inner ear, and it is nephrotoxic . It may cause transitory renal dysfunction . Chronic or acute renal insufficiencies inhibit gentamicin clearance . PATIENTS: Among 20 cases we found 15 who had previously been treated with aminoglycosides (13 with gentamicin and two with streptomycin) . Ten of our patients showed symptoms of preexistant chronic nephrosis or of transitory renal insufficiency caused by gentamicin therapy . In all 13 cases, peripheral vestibular function was destroyed or severely damaged by antibiotic . The same patients had no hearing loss . CONCLUSIONS: The different reactions of the cochlear and the vestibular end organs support the theoretical basis for transtympanic gentamicin treatment of Meniere's disease.--Other reasons for Dandy's Syndrome were bilateral Meniere's disease, skull fractures, and bilateral vestibular disorders.

Aliment Pharmacol Ther, 2000 Mar, 14(3), 299 - 303
Furazolidone versus metronidazole in quadruple therapy for eradication of Helicobacter pylori in duodenal ulcer disease; Malekzadeh R et al.; OBJECTIVE: Furazolidone, an old but cheap antibiotic, was shown to be a good alternative to metronidazole in triple therapy for Helicobacter pylori eradication in areas where metronidazole resistant bacteria are common, but randomized studies are lacking . AIM: A randomized controlled trial to determine the efficacy and safety of furazolidone compared to metronidazole in classic quadruple therapy for eradication of H . pylori infection in duodenal ulcer patients . METHODS: Patients with endoscopically proven duodenal ulcer and positive urease test were randomized to receive ranitidine 300 mg, amoxycillin 1000 mg and bismuth subcitrate 240 mg b.d, with either furazolidone 200 mg b.d (RABF), or metronidazole 500 mg b.d . (RABM) for 2 weeks . Compliance and side-effects were monitored and recorded by table diary . H . pylori eradication was assessed at least 4 weeks after the completion of therapy with 14C-urea breath test . RESULTS: A total of 106 patients were enrolled and 101 (59 male, 42 female, mean age=40 +/- 11 years) completed the study . Endoscopic findings and demographic data were comparable in both groups . Intention-to-treat eradication rates were 75% and 55% (P=0.03) and per protocol eradication rates were 82 and 56% (P=0 . 006) in the RABF and RABM groups, respectively . Side-effects were reported by 13 patients (27%) in the RABF group (one stopped treatment) compared to five patients (10%) in the RABM group (P=0 . 04) . CONCLUSION: Quadruple therapy containing furazolidone, instead of metronidazole, results in a significantly higher H . pylori eradication rate in Iranian duodenal ulcer patients.

Theriogenology, 1999 Nov, 52(7), 1117 - 22
Effect of clavulanic acid-potentiated amoxycillin on semen quality in dogs; England GC; Two different doses of clavulanic acid-potentiated amoxycillin were evaluated for their effect upon semen quality and libido in dogs . There was no significant difference in either parameter between control dogs and dogs treated with clavulanic acid-potentiated amoxycillin at either 12.5 mgkg-1 or 25 mgkg-1 orally twice daily for 28 d . Despite the marked effect of certain antibiotic agents upon spermatogenesis, it appears that clavulanic acid-potentiated amoxycillin can be used in dogs at up to twice the therapeutic dosage recommended by the manufacturer without a deleterious effect upon semen quality.

Eur J Cardiothorac Surg, 2000 Feb, 17(2), 184 - 6
Multiple mycotic arch-thoraco-abdominal aortic aneurysms: a successful case of in situ graft replacement; Kuki S et al.; Mycotic aortic aneurysms are an uncommon yet still life-threatening pathology . We report on a 67-year-old male who had a persistent fever and back pain . Contrast enhanced computed tomography (CT) showed multiple aortic aneurysms located in the aortic arch, the descending thoracic aorta and the supraceliac abdominal aorta . After 2 months of antibiotic therapy, a staged operation was carried out with 2-week interval, which includes a graft replacement of aortic arch with elephant trunk technique and a graft replacement of thoraco-abdominal aorta with omental transfer . The postoperative course was uneventful . This case seems to be quite rare in terms of multiplicity and location of mycotic aneurysms . Surgical strategy for this pathology is discussed.

Int J Parasitol, 2000 Apr 10, 30(4), 427 - 39
Impact of a plastid-bearing endocytobiont on apicomplexan genomes; Sato S et al.; Both the chromosomal and extrachromosomal components of the apicomplexan genome have been supplemented by genes from a plastid-bearing endocytobiont: probably an algal cell . The sequence of the apicomplexan plastid's vestigial genome indicates that a large number (>100) of genes of endocytobiotic origin must have transferred laterally to the host cell nucleus where they control maintenance of the plastid organelle and supply its functional components by means of post-translational protein trafficking . Should the nuclear genes prove to be less divergent phylogenetically than those left on the plastid genome, they might give better clues than we have at present to the origin of the plastid-bearing endocytobiont . Most of these nuclear genes still await discovery, but the on-going genome sequencing project will reveal the function of the organelle, as well as many "housekeeping" processes of interest on a wider front . The plastid's own protein synthetic machinery, being cyanobacterial in origin, offers conventional targets for antibiotic intervention, and this is discussed here using a structural model of elongation factor Tu . Uncovering the vital function(s) of the plastid organelle will provide new drug targets.

Theriogenology, 1998 Apr 1, 49(5), 933 - 42
In vitro maturation of domestic dog oocytes cultured in advanced preantral and early antral follicles; Bolamba D et al.; Initial studies in our laboratory demonstrated that a large proportion of domestic dog advanced preantral (APAN) and early antral (EAN) follicles contained grown oocytes that had acquired the dense cytoplasmic lipid characteristic of preovulatory oocytes . The objective of this study was to assess nuclear maturation of those oocytes after in vitro culture . Both APAN and EAN follicles (152 to 886 microns in diameter) were isolated from ovaries by treatment with collagenase and DNase . The follicles were cultured in Dulbecco's Modified Eagle's medium/nutrient mixture F-12 Ham culture medium supplemented with 20% (v/v) fetal bovine serum (FBS), 2 mM L-glutamine, 1% (v/v) antibiotic-antimycotic, 1 microgram FSH/ml, 10 IU hCG/ml and 1 microgram estradiol/ml . Within each group (APAN or EAN), control follicles were not cultured (0 h), and 2 to 12 follicles per well were incubated under a humidified atmosphere of 5% CO2 in air at 37 degrees C for 24, 48 or 72 h . After 24 h of culture, significantly more (5.3%, 20/374; P < 0.05) oocytes from APAN follicles reached the metaphase I to metaphase II stages (MI to MII) than the percentage of control follicles observed at 0 h (0.9%, 3/318) . Continued culture resulted in a further increase (P < 0.05) in the percentage of oocytes reaching MI to MII by 48 h (11.5%, 47/407), which remained unchanged at 72 h (9.9%, 40/404) . The percentage of oocytes from EAN follicles reaching MI to MII did not significantly increase after 24 h of culture . However, there was an increase (P < 0.05) by 48 h of culture (8.7%, 11/126), which remained unchanged at 72 h (7.5%, 8/106) . These results show that dog oocytes cultured within advanced preantral and early antral follicles in vitro are competent to resume meiosis to the metaphase stage.

J Am Anim Hosp Assoc, 2000 Mar-Apr, 36(2), 111 - 4
The effects of sodium ampicillin, sodium cefazolin, and sodium cefoxitin on blood pressures and heart rates in healthy, anesthetized dogs; Morgan MR et al.; This study determined the effects of intravenous ampicillin, cefazolin, and cefoxitin on blood pressures and heart rates in healthy, anesthetized dogs . Forty dogs were each randomly assigned to a control, ampicillin, cefazolin, or cefoxitin group . Antibiotics or saline was delivered by intravenous bolus prior to surgical stimulation . Heart rate; systolic, mean, and diastolic arterial pressures; oxygen saturation; end-tidal halothane; and end-tidal carbon dioxide (CO2) were recorded before and every minute for 10 minutes after the test drug was administered . No significant differences were recorded between the antibiotic and control groups . The prophylactic use of these antibiotics should be considered safe in healthy, anesthetized dogs.

Obes Surg, 1996 Oct, 6(5), 416 - 420
Complications of Biliopancreatic Diversion Surgery as Proposed by Scopinaro in the Treatment of Morbid Obesity; Michielson D et al.; BACKGROUND: This study concerns 33 patients treated for morbid obesity with the procedure proposed by Scopinaro . Results are reviewed retrospectively in terms of complication rates . METHODS: The group consisted of ten men and 23 women with a mean age of 34 years (range 20-51 years), and a mean BMI of 49.5 kg/m(2) (range 37-77) . Adequate attempts at medical management had failed repeatedly . The operative procedure involved a 2/3 partial gastrectomy and biliopancreatic diversion by Roux-en-Y reconstruction 50 cm before the ileocecal valve . In one patient, a cholecystectomy was added . RESULTS: The mean weight loss after 6 months was 18.9% of the initial weight, with mean BMI 41 kg/m(2) (range 29-60) . Early complications included four wound infections (15%), while two patients complained of an early dumping syndrome (6%), treated by dietary measures . There were no respiratory infections and no pulmonary embolism, likely as a result of the thoracic epidural anesthesia and high doses of prophylactic heparin used . There was no mortality . As to late complications, nine patients complained of diarrhea due to bacterial overgrowth (27%) and were treated with antibiotic therapy . There were five incisional hernias (15%) . Five patients had a peptic ulcer (15%) and required medical treatment . Two patients had acute cholecystitis (6%) . One patient had an afferent loop obstruction (3%), requiring reoperation . CONCLUSIONS: Overall, this series of intestinal diversion procedures by the method of Scopinaro had a larger complication rate than generally accepted.

Spectrochim Acta A Mol Biomol Spectrosc, 2000 Jan, 56A(1), 181 - 91
NMR, UV-vis and CD study on the interaction of pradimicin BMY-28864 with divalent cations of alkaline earth metal; Hu M et al.; In order to clarify the mechanism of the calcium-activated anti-fungal action of pradimicin derivatives, we investigated the compatibility of four divalent metal cations, Ca2+, Mg2+, Sr2+ and Ba2+, when combined with pradimicin BMY-28864 in an aqueous solution . The 1H NMR studies suggest that all the tested cations can induce a chemical exchange between two types of aggregation of BMY-28864 in an aqueous solution . The exchange rate, however, varies according to the cation species . In descending order they are: Ba2+ > Sr2+ > Ca2+ > Mg2+ . The differences in the binding ability of BMY-28864 to the cations and the solubility of the chloride salts are explained by the electronegativity of these cations . The UV-Vis and CD spectra of these solutions show isosbestic points that correspond to an exchange process in the cations' binding to BMY-28864 . The results provide experimental support for the hypothesis that there is a common mechanism underlying their cations interactions with the antibiotic . The CD study also provided evidence about the stoichiometric relation of the divalent metal ions to the antibiotic, 1:2, which was obtained by NMR analyses.

Postgrad Med, 2000 Mar, 107(3), 69 - 70, 73-6, 79-80
Topical therapy for acne vulgaris . How do you choose the best drug for each patient?
Johnson BA, Nunley JR.
Although management of acne is sometimes difficult, primary care physicians can offer a number of treatment plans to patients with this skin condition . Comedonal acne usually responds to topical keratolytics, such as salicylic acid, benzoyl peroxide, adapalene, and tretinoin . Inflammatory acne is usually treated with topical therapy plus a systemic antibiotic . Nodulocystic acne generally requires an 8-week course of systemic antibiotics . If the nodulocystic acne does not improve, minocycline or isotretinoin may be needed . Topical therapy is often helpful in the long-term management of nodulocystic acne . New products are available that deliver topical agents in novel ways that decrease skin irritation . With the proper tools and instructions in use, most patients have significant improvement in their acne.

Biochem J, 2000 Apr 1, 347 Pt 1, 205 - 9
Novel inhibitors of the condensing enzymes of the type II fatty acid synthase of pea (Pisum sativum); Jones AL et al.; The type II fatty acid synthases (FASs) of higher plants (and Escherichia coli) contain three condensing enzymes called beta-ketoacyl-ACP synthases (KAS), where ACP is acyl-carrier-protein . We have used novel derivatives of the antibiotic thiolactomycin to inhibit these enzymes . Overall de novo fatty acid biosynthesis was measured using {1-(14)C}acetate substrate and chloroplast preparations from pea leaves, and {1-(14)C}laurate was used to distinguish between the effects of the inhibitors on KAS I from those on KAS II . In addition, the activities of these enzymes, together with the short-chain condensing enzyme, KAS III, were measured directly . Six analogues were tested and two, both with extended hydrocarbon side chains, were found to be more effective inhibitors than thiolactomycin . Incubations with chloroplasts and direct assay of the individual condensing enzymes showed that all three compounds inhibited the pea FAS condensing enzymes in the order KAS II > KAS I > KAS III . These results demonstrate the general activity of thiolactomycin and its derivatives against these FAS condensation reactions, and suggest that such compounds will be useful for further detailed studies of inhibition and for use as pharmaceuticals against Type II FASs of pathogens.

Bioconjug Chem, 2000 Mar-Apr, 11(2), 219 - 27
Sequence-recognition and cleavage of DNA by a netropsin-phenazine-di-N-oxide conjugate; Helissey P et al.; We report the synthesis, DNA-binding and cleaving properties, and cytotoxic activities of R-128, a hybrid molecule in which a bis-pyrrolecarboxamide-amidine element related to the antibiotic netropsin is covalently tethered to a phenazine-di-N-oxide chromophore . The affinity and mode of interaction of the conjugate with DNA were investigated by a combination of absorption spectroscopy, circular dichroism, and electric linear dichroism . This hybrid molecule binds to AT-rich sequences of DNA via a bimodal process involving minor groove binding of the netropsin moiety and intercalation of the phenazine moiety . The bidentate mode of binding was evidenced by linear dichroism using calf thymus DNA and poly(dA-dT).(dA-dT) . In contrast, the drug fails to bind to poly(dG-dC).poly(dG-dC), because of the obstructive effect of the guanine 2-amino group exposed in the minor groove of this polynucleotide . DNase I footprinting studies indicated that the conjugate interacts preferentially with AT-rich sequences, but the cleavage of DNA in the presence of a reducing agent can occur at different sequences not restricted to the AT sites . The main cleavage sites were detected with a periodicity of about 10 base pairs corresponding to approximately one turn of the double helix . This suggests that the cleavage may be dictated by the structure of the double helix rather than the primary nucleotide sequence . The conjugate which is moderately toxic to cancer cells complements the tool box of reagents which can be utilized to produce DNA strand scission . The DNA cleaving properties of R-128 entreat further exploration into the use of phenazine-di-N-oxides as tools for investigating DNA structure.

J Antibiot (Tokyo), 1999 Sep, 52(9), 809 - 14
Enzymatic 1-N-acetylation of paromomycin by an actinomycete strain #8 with multiple aminoglycoside resistance and paromomycin sensitivity; Sunada A et al.; An actinomycete strain #8 with multiple aminoglycoside (AG) resistance and paromomycin (PRM) sensitivity was examined for its capability of enzymatic modification of AGs . Cell free extracts from the strain converted all of the examined AGs including PRM in the presence of acetyl CoA . PRM was completely modified to at least two products (major and minor spots upon TLC) without significant reduction of the antibiotic activity of the reaction mixture . The structure determination and antibiotic assay of the purified major product revealed l-N-acetylPRM and its antibiotic activity (12% activity of PRM), indicating the existence of AAC(1) . It was thus obvious that the 1-N-acetylation of PRM did not cause PRM resistance . Apramycin, the substrate of the known AAC(1), was not readily acetylated, suggesting that the AAC(1) of strain #8 is a new type . Two diacetylated products (1,2'-di-N-acetylPRM and 1,6"'-di-N-acetylPRM) were found in the minor spot, suggesting the existence of additional AACs.

J Drug Target, 2000, 7(5), 393 - 406
Synthesis, characterisation and in vivo behaviour of a norfloxacin-poly(L-lysine citramide imide) conjugate bearing mannosyl residues; Gac S et al.; With the aim of promoting the targeting of macrophage mannose receptors and the internalisation of the norfloxacin antibiotic, which is active against some intracellular bacteria, a macromolecular prodrug was synthesised where the antibiotic and mannosyl moieties were coupled to a polymeric carrier, namely poly(L-lysine citramide imide) . This carrier, which derived from two metabolites, citric acid and L-lysine, is known to be biocompatible and slowly degradable under slight acidic conditions . Norfloxacin was coupled onto the acid groups present along the polymer chains, and conjugates were characterised by UV, TLC and SEC . The mannosyl groups selected to promote the targeting of the mannose-specific lectin present on the outer membrane of macrophages were incorporated through a biodegradable glycolic spacer arm . Two different strategies were considered to synthesise the full conjugates, namely coupling norfloxacin onto mannosylated conjugates, and coupling mannose onto PLCAI/Nflx conjugates . The second pathway led to better results regarding mannosylation . The presence of norfloxacin and mannose caused chain aggregation, especially for conjugates with a high content of mannosyl residues . The targeting ability of the prodrug was investigated using a method based on the competition between the mannosylated macromolecules and glucose oxidase, a mannosyl-bearing non-human protein . This method showed that prodrug macromolecules competed effectively with glucose oxidase and thus should be able to bring the drug up to the mannosyl receptor-bearing membranes of macrophages infected by intracellular bacteria.

Aust Fam Physician, 2000 Jan, 29(1), 19 - 23
Acute sinusitis . Who should we be treating?
Beavis M.
BACKGROUND: The diagnosis of acute sinusitis has been regarded as a serious condition that requires the use of antibiotics . However the increasing incidence of resistant organisms means antibiotics need to be used carefully . OBJECTIVE: To look at the evidence available regarding antibiotic use for sinusitis, and to discuss its application to general practice . DISCUSSION: There have been surprisingly few randomised double blind placebo controlled trials for sinusitis, and fewer still have been based in a representative population of primary care patients . This article discusses studies relevant to general practice . Several practical clinical symptoms and signs have been shown to increase the likelihood of a patient having acute bacterial sinusitis, and therefore benefit from antibiotics . When antibiotics are used, comparative data suggest that amoxycillin should be used first line . The issue of patient experience, expectations and satisfaction is also raised.

J Infect Dis, 2000 Mar, 181(3), 1185 - 8
Soluble CD14 levels in the serum, synovial fluid, and cerebrospinal fluid of patients with various stages of Lyme disease; Lin B et al.; Levels of circulating soluble CD14 (sCD14) in patients with various stages of Lyme disease (LD) were examined . Patients with early or untreated late LD had significantly higher levels of sCD14 than did healthy controls (P=.0001 and .0007, respectively); levels returned to normal within 3 months after antibiotic therapy . Patients with persistent posttreatment symptoms of LD had sCD14 levels equivalent to those of healthy controls . Differences in the serum sCD14 levels in patients with various stages of LD are likely to be directly correlated with differences in bacterial burden, suggesting that posttreatment symptoms may not require continued presence of the organism . sCD14 levels in the cerebrospinal fluid (CSF) of patients with any stage of LD were no different from those of control subjects . Levels of synovial fluid sCD14 from patients with Borrelia burgdorferi in their joints were elevated, compared with levels in normal serum, and may play a role in the pathogenesis of arthritis.

Jpn J Clin Oncol, 1999 Nov, 29(11), 571 - 5
Surgical management of primary lung cancer in an elderly patient with preoperative empyema; Harada M et al.; A 74-year-old man with primary lung cancer developed preoperative empyema but was successfully managed surgically . The patient was given a diagnosis of c-T2N1M0, stage IIB, moderately differentiated squamous cell carcinoma, but before surgery pneumothorax and empyema developed, resulting from rupture of the carcinoma . Thoracic drainage, lavage and systemic administration of antibiotics improved his empyema . As there were no malignant cells in the drainage fluid, right middle-lower bilobectomy, empyemal cavity resection and lymph node dissection were performed . The bronchial stump was covered with an intercostal muscle flap . Thoracic drainage, lavage and systemic administration of antibiotics were performed for 6 days following the operation . The patient was discharged on the 27th postoperative day without any complications having developed . The pathological diagnosis of the tumor was p-T4N2(#7)M0, stage IIIB, br(-), ly(+), v(+), p3(pleura), pm1 and d0 . He died of recurrence at home 18 months after the operation . We believe the following to be the minimum requirements for surgical management of such patients: (1) immediate thoracic cavity drainage and lavage with systemic antibiotic therapy, aiming at infection control before surgery; (2) prophylactic lavage of the thoracic cavity during and after surgery and (3) coverage of the bronchial stump with an adequate flap . Six reported cases of primary lung cancer with preoperative empyema are also discussed.

Semin Neurol, 1999, 19(2), 201 - 11
Neurologic manifestations of toxoplasmosis in AIDS; Cohen BA; Central nervous system (CNS) toxoplasmosis is the most common cause of cerebral mass lesions in AIDS patients . Toxoplasma gondii is commonly acquired through ingestion of contaminated meats resulting in latent infection . With the onset of immunosuppression, it may preferentially infect the CNS, resulting in a wide range of clinical presentations . Effective antibiotic therapy is available and capable of producing rapid remission of active infection but must be continued throughout life to prevent recurrence . Characteristic presentations and rapid therapeutic response permit presumptive diagnosis and initiation of specific antibiotics in many cases; however, appropriate clinical and radiographic monitoring to detect alternative or mixed pathologies is necessary . Unusual presentations may hinder rapid diagnosis and should be considered in AIDS patients with cryptic CNS symptoms . Despite increasing attention to primary prophylaxis, the worldwide distribution of this parasite, its potential to be the presenting illness in previously unidentified human immunodeficiency virus-infected individuals, and failures of prophylaxis are likely to make toxoplasmosis an important continuing source of neurologic morbidity in AIDS.

Proc Natl Acad Sci U S A, 2000 Mar 14, 97(6), 2674 - 9
The genetics of ivermectin resistance in Caenorhabditis elegans; Dent JA et al.; The ability of organisms to evolve resistance threatens the effectiveness of every antibiotic drug . We show that in the nematode Caenorhabditis elegans, simultaneous mutation of three genes, avr-14, avr-15, and glc-1, encoding glutamate-gated chloride channel (GluCl) alpha-type subunits confers high-level resistance to the antiparasitic drug ivermectin . In contrast, mutating any two channel genes confers modest or no resistance . We propose a model in which ivermectin sensitivity in C . elegans is mediated by genes affecting parallel genetic pathways defined by the family of GluCl genes . The sensitivity of these pathways is further modulated by unc-7, unc-9, and the Dyf (dye filling defective) genes, which alter the structure of the nervous system . Our results suggest that the evolution of drug resistance can be slowed by targeting antibiotic drugs to several members of a multigene family.

Perit Dial Int, 2000 Jan-Feb, 20(1), 76 - 9
A retrospective study of seven cases of Candida parapsilosis peritonitis in CAPD patients: the therapeutic implications; Wong PN et al.; BACKGROUND: Candida peritonitis accounts for the majority of fungal peritonitis in continuous ambulatory peritoneal dialysis (CAPD), but the Candida species were not routinely subtyped in previous studies.The clinical course and the outcome of Candida parapsilosis peritonitis remain unclear . OBJECTIVE: To study the clinical course and outcome of C . parapsilosis peritonitis in CAPD patients . SETTING: Peritoneal dialysis unit in a regional hospital . PATIENTS AND DESIGN: A retrospective study on seven cases of C . parapsilosis peritonitis occurring in a single center over 3 years . RESULTS: The 7 patients included 4 males and 3 females . Their mean age was 62 +/- 11.5 years . Two (29%) were diabetic . Three (43%) had a history of preceding peritonitis and 5 (71 %) had received broad spectrum antibiotic within the previous 1 month . All presented with cloudy dialysate, abdominal pain, and fever . The mean dialysate white cell count was 300 +/- 168/mm3 with a predominance of neutrophils (81.4% +/- 13.1%).The mean time from onset of symptoms to diagnosis was 5.7 +/- 3.1 days . All had been treated with immediate catheter removal within 24 hours of diagnosis and antifungal therapy, including oral fluconazole, intravenous (IV) amphotericin, or their sequential combination . Environmental samplings were negative for C . parapsilosis . The overall complication rate was exceptionally high (71%), with three (43%) complicated by abscess formation requiring surgical drainage, one peritoneal adhesion (14%), and one mortality (14%) . In the end, only two (29%) could resume CAPD . CONCLUSIONS: The outcome of this study group appeared worse than those previously described in the literature, and the optimal treatment for this group of patients remains unclear.

J Dairy Sci, 2000 Feb, 83(2), 338 - 44
The influence of long-term supplementation with biotin on the prevention of lameness in pasture fed dairy cows; Fitzgerald T et al.; In a double-blind study, the influence of biotin supplementation on lameness in dairy cows was investigated over a 13-mo period . The experimental site was a tropical upland environment and involved over 2705 Holstein and Friesian cows on 20 participating farms . Cows on 10 farms received biotin at a rate of 20 mg/head per day in the concentrate, and cows on 10 other farms received feed without the biotin supplement . Premixes with or without biotin were incorporated into a grain concentrate that was fed at a constant rate to cows at milking . Farmers maintained accurate records of the nature of hoof problems and any treatment applied . Each herd was evaluated for locomotion scores at 8-wk intervals . Locomotion scores were significantly correlated with the number of days with measurable rainfall per month (r = 0.88) . The biotin-supplemented herds exhibited better locomotion scores than the unsupplemented herds . In the wet summer period the number of lame cows, as observed by the farmer, were significantly fewer during the rainy period for the biotin-supplemented herds and required fewer antibiotic treatments than unsupplemented herds . Most hoof lesions were most commonly observed in the outer claws of the hind limb . Daily milk production (17.3 vs . 18.5 L) was not affected by biotin supplementation . Reduced milk fat percentage and somatic cell counts of bulk milk were recorded in the biotin supplemented herds during the wet, summer period.

Physiol Behav, 2000 Feb, 68(4), 533 - 41
Temporal modulation of nephrotoxicity, feeding, and drinking in gentamicin-treated rats; Julien N et al.; Gentamicin-induced nephrotoxicity varies temporally, with a peak being observed when this antibiotic is administered during the resting period and a trough when given during the activity period of rats . These nychthemeral variations are modified by fasting and by restricted feeding schedules . In this study, food and water intakes of adult female Sprague-Dawley rats were measured during pretreatment (Days 1 to 5) and during treatment (Days 6 to 10) with gentamicin (80 mg/kg/day, i.p.) injected at 1300 or 0100h . A significantly higher level of serum creatinine was observed when gentamicin was administered at 1300 h compared to 0100 h, and a significantly lower creatinine clearance was found in rats treated with gentamicin at 1300 h compared to those treated with saline at the same time . Gentamicin treatment at 1300 or 0100 h resulted in a decrease in the 24-h food intake . In addition, in the gentamicin-treated group at 0100 h, the maximal food intake observed at late dark during the pretreatment period decreased during treatment, and early dark rather than late dark maximal intake occurred . Our data demonstrate that gentamicin induces a nephrotoxicity that varies temporally, and that gentamicin treatment inhibits food intake and alters its nocturnal variations.

Chest, 2000 Mar, 117(3), 734 - 7
Errors in the treatment of tuberculosis in Baltimore; Rao SN et al.; BACKGROUND: Incomplete or incorrect antibiotic therapy, especially in the initial phase of antituberculosis (anti-TB) treatment, is a major cause of acquired drug resistance and treatment failure . We determined the extent of errors in anti-TB treatment regimens by way of nonadherence to recommended treatment protocols among patients with TB in Baltimore, MD, a city with declining rates of disease . An error was defined as using too few drugs or the wrong drugs, giving inadequate doses of drugs, or prescribing an inadequate duration of treatment . METHODS: We reviewed the records of all patients with culture-positive, pulmonary TB reported in the city of Baltimore from January 1, 1994, to December 31, 1995 . We determined demographic information, initial anti-TB regimen, doses and duration of therapy, history or presence of resistance to anti-TB drugs, injecting-drug or alcohol abuse, HIV status, and whether treatment was given by a private physician or by the Tuberculosis Clinic of the Baltimore City Health Department (BCHD) . RESULTS: Of the 110 cases of active pulmonary TB, 17 cases (15.4%) had errors in treatment for control of their current disease . Thirteen of 34 privately treated patients (38%) had some error in their initial anti-TB regimen, compared with 4 of 76 patients (5.2%) treated by the Tuberculosis Clinic of the BCHD (p < 0.0001) . Patients were otherwise similar as determined by age, sex, HIV status, drug-resistance characteristics, and injecting-drug use, regardless of whether they had erroneous anti-TB regimens . CONCLUSION: In a low-prevalence area, private physicians make frequent errors in prescribing anti-TB therapy . Additional educational resources for physicians and increased use of expert consultation may contribute to improved TB control.

Mutat Res, 2000 Feb 16, 459(1), 29 - 41
Cellular and molecular effects of bleomycin are modulated by heat shock in Saccharomyces cerevisiae; Keszenman DJ et al.; To study some mechanisms underlying the stress responses in eukaryotic cells, we investigated the effect of heat shock (HS) on the induction of DNA double strand breaks as well as on potentially lethal and mutagenic events induced by the radiomimetic antibiotic bleomycin (BLM) in Saccharomyces cerevisiae . Haploid wild-type yeast cells in the logarithmic phase of growth were exposed to different concentrations of BLM (0-30 microg/ml, 1.5 h) without and with a previous HS (38 degrees C, 1 h) . Immediately after treatments, survival as well as mutation frequency were determined, and quantitative analysis of chromosomal DNA by laser densitometry were performed both immediately after treatments and after incubation of cells during different time intervals in liquid nutrient medium free of BLM . Our results indicate that HS induces resistance to potentially lethal and mutagenic effects of BLM . Quantitative analysis of chromosomal DNA performed immediately after treatments showed the same DNA fragmentation, either upon BLM as single agent or preceded by HS . However, HS pretreated cells incubated during 4 h in liquid nutrient medium free of BLM repaired DNA double strand breaks more efficiently as compared to non-pretreated cells . On this basis, we propose that the observed HS-induced resistance to BLM depends on a regulatory network acting after DNA-induced damage, which includes genes involved in DNA repair, HS response and DNA metabolism.

J Spinal Disord, 2000 Feb, 13(1), 42 - 5
Postoperative deep wound infection in adults after posterior lumbosacral spine fusion with instrumentation: incidence and management; Picada R et al.; The authors reviewed 817 instrumented lumbosacral fusions in adults and found an incidence of 3.2% deep wound infections . The primary focus of this study was the management of these infections, with particular attention to whether the implants needed to be removed . A consulting infectious disease specialist indicated that an acute infection of a low back fusion wound could not be healed without removal of the metallic implants . This opinion was in contrast to the authors' daily experience and prompted this study . The authors identified and reviewed 817 cases of instrumented posterior lumbosacral arthrodeses in adults . A detailed analysis of any case with a deep wound infection was performed and yielded and infection rate of 3.2% (26 patients) . Of these, 24 achieved a clean, closed wound without removal of instrumentation through a protocol of aggressive debridement and secondary closure . Instrumentation removal is not necessary to obtain a clean, closed wound using an aggressive approach with early diagnosis, vigorous debridement in the operative room under general anesthesia, delayed primary or secondary closure, and appropriate antibiotic coverage.

Implant Dent, 1999, 8(4), 355 - 9
Dental implants in the diabetic patient: a retrospective study; Balshi TJ et al.; It has become increasingly common for controlled diabetic patients to be considered as candidates for dental implants . This study reports on the results of placing implants in 34 patients with diabetes who were treated with 227 Branemark implants . At the time of second-stage surgery, 214 of the implants had osseointegrated, a survival rate of 94.3% . Only one failure was identified among the 177 implants followed through final restoration, a clinical survival rate of 99.9% . Screening for diabetes and trying to ensure that implant candidates are in metabolic control are recommended to increase the chances of successful osseointegration . Antibiotic protection and avoidance of smoking should also be considered.

Biochem Biophys Res Commun, 2000 Mar 16, 269(2), 574 - 9
Spectinomycin inhibits the self-splicing of the group 1 intron RNA; Park IK et al.; Effects of the aminoglycoside spectinomycin on the self-splicing of primary transcripts of the phage T4 thymidylate synthase gene (td) have been investigated . The kinetic analysis demonstrated that spectinomycin acts as a mixed noncompetitive inhibitor for the td intron RNA with a K(i) of 7.2 mM . Increasing the spectinomycin concentration raised the K(m) values with the corresponding decrease of V(max) and k(cat) values . The specificity of the splicing inhibition by spectinomycin is due to changes in both K(m) and k(cat) . The splicing inhibition by spectinomycin is dependent on pH changes and Mg(2+) concentration, indicating electrostatic interactions with the intron RNA . It has been proposed that the key structural features in spectinomycin responsible for the inhibition of splicing may be the hydroxyl groups on the antibiotic .

J Am Acad Orthop Surg, 1994 Jan, 2(1), 44 - 53
Infected Total Knee Replacements; Windsor RE et al.; Deep infection is a devastating complication following total knee arthroplasty . Prompt diagnosis and definitive treatment of this complication are essential for a successful outcome . The treatment options for an infected total knee replacement include (1) antibiotic suppression alone; (2) aggressive wound debridement, drainage, and antibiotic suppression therapy; (3) resection arthroplasty; (4) arthrodesis; (5) two-stage reimplantation; and (6) amputation . Successful salvage of this complication can be accomplished only by extensive investment of surgical and infectious disease efforts in eradicating the infection . Two-stage reimplantation has been the most successful functional option and should be used whenever possible to definitively eradicate the infection and ensure good function of the knee joint.

Microbiology, 2000 Feb, 146 ( Pt 2), 297 - 303
A new single-copy mycobacterial plasmid, pMF1, from Mycobacterium fortuitum which is compatible with the pAL5000 replicon; Bachrach G et al.; A 9.2 kb cryptic Mycobacterium fortuitum plasmid, pMF1, was isolated from strain 110 and its restriction map constructed . A 4.2 kb HindIII fragment of pMF1 was found to support replication in mycobacteria and this fragment was cloned and sequenced to characterize the replication elements of the plasmid . Computer analysis identified a putative Rep protein (362 amino acids) with high homology to the putative Rep protein of the Mycobacterium celatum plasmid pCLP and limited homology, mostly in the N-terminal region, to the Rep proteins of Mycobacterium avium pLR7, M . fortuitum pJAZ38 and Mycobacterium scrofulaceum pMSC262 . A region containing a putative ori site was located upstream of the rep gene; this region displayed high homology at the nucleotide level with the predicted ori of pCLP and pJAZ38 . A plasmid carrying the 4.2 kb HindIII fragment and a kanamycin resistance marker, designated pBP4, was maintained as a single-copy plasmid in Mycobacterium smegmatis and was stably inherited in the absence of antibiotic selection . Plasmid pBP4 was incompatible with the pJAZ38 replicon but was compatible with the widely used pAL5000 replicon, indicating that among the mycobacterial vectors now available there are two incompatibility groups . Significantly, the plasmid was able to replicate in the pathogen Mycobacterium tuberculosis, making it a useful tool for gene expression studies . To provide a choice of restriction sites and easy manipulation, a 2.1 kb fragment containing the minimal replication region was cloned to make the mycobacterial shuttle vector pBP10, which showed similar stability to pBP4.

Antibiot Khimioter, 2000, 45(2), 5 - 9
{The effect of heat shock on the formation and composition of actinomycins}; Liui Kh et al.; The effect of various conditions of heat shock on production of actinomycins by Streptomyces chrysomallus 2 and their composition was studied . The actinomycin biosynthesis was shown to be the function of the growing mycelium and changed in accordance with changes in the volume of the mycelium and its morphological features after heat shock at various suboptimal temperatures . The temperature shock had a specific action on the antibiotic synthesis: the index of the actinomycin maximum quantity increased after the heat shock at 35 and 38 degrees C and lowered more sharply than that of the biomass volume after the heat shock at the temperatures of 40, 42, 45 and 50 degrees C for 1 hour . After the shock at 38 degrees C the component composition of the actinomycin complex did not significantly change while with addition of exogenic amino acids such as L-valine, L-leucine and L-isoleucine the shock effect on the component composition of the actinomycin complex was marked.

Ned Tijdschr Geneeskd, 2000 Feb 12, 144(7), 305 - 8
{Acute abdomen: consider also the thorax}; van der Eerden MM et al.; Three patients, 2 men aged 22 and 62 years en 1 woman aged 49, presented with symptoms of an acute abdomen . While infiltrative signs were described on radiodiagnostic images two patients underwent laparotomies . In all three subsequently the diagnosis of pneumonia was established and the patients made full recovery after antibiotic therapy . When a patient presents with symptoms of an acute abdomen, the possibility of an existing pneumonia should always be borne in mind . It is therefore recommended to make a chest radiograph with frontal and lateral view . In the presence of infiltrative signs the existence of pneumonia as the cause of abdominal symptoms should be considered in order to avoid unnecessary laparotomy.

J Postgrad Med, 1995 Apr-Jun, 41(2), 40 - 2
Disseminated mucormycosis in healthy adults; Verma GR et al.; Three patients of disseminated mucormycosis are described . None had predisposing factors . Two of them presented with nonspecific symptoms along with acute renal failure and peritonitis . Third patient had fulminating primary cutaneous mucormycosis which disseminated later . Development of acute renal failure with smooth enlargement of both kidneys in an apparently healthy individual or appearance of mould in a wound should raise the suspicion of mucormycosis . The hallmark of the infection was vascular invasion and thrombosis . Antemortem diagnosis could be made in one patient only . All patients had progressive downhill course despite supportive treatment, antibiotic and amphotericin in-B in one patient.

Vet Clin North Am Food Anim Pract, 2000 Mar, 16(1), 1 - 22
Interpretation of basic gross pathologic changes of the digestive tract; Helman RG; The necropsy is a valuable diagnostic tool . When presented with a dead animal, it is not uncommon for the necropsy to be the springboard for the entire diagnostic evaluation . Not only is important information gained from gross examination of the organs but during necropsy, tissue and fluid samples for supportive tests--bacterial culture, antibiotic sensitivity, virus isolation, serology, parasite burden, and toxicologic and histopathologic studies--are collected . It is not essential for a veterinarian to be a pathologist to get good information from a necropsy . This article attempted to identify a number of basic lesions that occur with the most common diseases of the digestive tract of food animals . Additionally, associations between lesions and certain etiologies as well as diseases have been made so that when one identifies a particular lesion (in a live or dead animal), a prioritized list of possible differential diagnoses comes to mind . The necropsy does not stand alone or above the other sources of diagnostic information . The information gained from a necropsy must be correlated with the other information to arrive at either a specific diagnosis or a short list of possible diagnoses . The veterinarian must seek further input, in the latter situation, from additional clinical examinations, laboratory tests, or interviews with the client to arrive at the diagnosis.

Biol Pharm Bull, 2000 Jan, 23(1), 116 - 8
Role of endogenous endotoxin on tumor necrosis factor-hypersensitivity caused by D-galactosamine challenge; Sakaguchi S et al.; We examined the role of endotoxin in the mechanism of recombinant human tumor necrosis factor (rhTNF)-hypersensitivity caused by D-galactosamine (GalN) . We used polymyxin B, an antibiotic with anti-endotoxin activity, to determine the participation of endogenous endotoxin . The glycogen and blood glucose level of rhTNF (1 x 10(4) units/mouse, i.v.)-injected mice was lower at 7 h post-intoxication than that in the control . Administration of rhTNF to GalN (700 mg/kg, i.p.)-treated mice resulted in lower levels of glycogen and blood glucose than those in animals treated with rhTNF alone . In mice pretreated with polymxin B (20 mg/kg, i.p.), the level at 7 h after rhTNF/GalN-injection was markedly increased compared to that in mice treated with rhTNF/GalN alone . The injection of a low endotoxin dose (0.1 mg/kg, i.p.) markedly decreased the rectal temperature in mice treated with rhTNF (5 x 10(3) units/mouse, i.v.) and GalN, and none of these animals survived after treatment for 18 h . These findings suggest that endogenously produced endotoxin may contribute to the extent of rhTNF-hypersensitivity caused by GalN.

Chemosphere, 2000 Apr, 40(7), 759 - 65
Stability of Tylosin A in manure containing test systems determined by high performance liquid chromatography; Loke ML et al.; Tylosin is a widely used antibiotic for the treatment of infections in swine . Tylosin consists of a mixture of Tylosin A, Tylosin B, Tylosin C and Tylosin D . All components contribute to the potency of tylosin but Tylosin A is by far the major component (usually about 90% and not less than 80%) . A fast, robust and easily performed HPLC method has been developed for determination of Tylosin A in the presence of tylosin residues; Tylosin B, Tylosin C and Tylosin D in manure containing incubation media . The separation was performed using a YMC-Pack ODS-AQ column (250 x 4.6 mm i.d., 5 microns particle size) operated at 35 degrees C . The mobile phase consisted of 2.25% (w/v) sodium perchlorate pH 2.5-acetonitrile (60:40 v/v) . Detection was performed by measuring the UV absorption at a wavelength of 290 nm . Calibration curves of tylosin made in the incubation medium containing 6.4% manure were linear in the range from 0.375 to 128.0 mg/l (R2 = 0.999) . The limit of quantitation (at the RSD 20% level) for Tylosin A was found to be 0.4 mg/l in incubation media containing 6.4% manure . The recovery of Tylosin A was in the range from 100% to 108% depending on the concentration of manure . The reproducibility was good as the relative standard deviation (n = 4) in each matrix tested was in the range from 0.7 to 1.9 at the 25 mg/l level . The stability of Tylosin A was studied under methanogenic conditions and the half-life was found to be less than two days . Studies under aerobic conditions showed that the degradation rate was found to increase with increasing concentrations of manure particles in the incubation medium . It is, however, not clear whether the decrease in the concentration of Tylosin A is caused by sorption, abiotic or biotic chemical degradation . The major degradation product of Tylosin A in methanogenic as well as aerobic incubation media has a UV-spectrum and a retention time corresponding to Tylosin B . Furthermore, Tylosin D is believed to be a minor degradation product.

Chemosphere, 2000 Apr, 40(7), 715 - 22
Sorption and mobility of metronidazole, olaquindox, oxytetracycline and tylosin in soil; Rabolle M et al.; Laboratory studies were conducted to characterise four different antibiotic compounds with regard to sorption and mobility in various soil types . Distribution coefficients (Kd values) determined by a batch equilibrium method varied between 0.5 and 0.7 for metronidazole, 0.7 and 1.7 for olaquindox and 8 and 128 for tylosin . Tylosin sorption seems to correlate positively with the soil clay content . No other significant interactions between soil characteristics and sorption were observed . Oxytetracycline was particularly strongly sorbed in all soils investigated, with Kd values between 417 in sand soil and 1026 in sandy loam, and no significant desorption was observed . Soil column leaching experiments indicated large differences in the mobility of the four antibiotic substances, corresponding to their respective sorption capabilities . For the weakly adsorbed substances metronidazole and olaquindox the total amounts added were recovered in the leachate of both sandy loam and sand soils . For the strongly adsorbed oxytetracyline and tylosin nothing was detected in the leachate of any of the soil types, indicating a much lower mobility . Results from defractionation and extraction of the columns (30 cm length) showed that 60-80% of the tylosin added had been leached to a depth of 5 cm in the sandy loam soil and 25 cm in the sand soil.

Eur J Pharm Biopharm, 2000 Mar, 49(2), 191 - 4
In vitro and in vivo characterization of biodegradable enoxacin microspheres; Abazinge M et al.; The in vitro release and plasma concentration profiles of sustained release enoxacin microspheres intended for the treatment of bone and systemic infections due to sensitive strains of bacteria were investigated . Microspheres of enoxacin were prepared by using poly(glycolic acid-co-DL-lactic acid) (PLGA) by the emulsion solvent evaporation technique and characterized by in vitro release in an incubator, and in vivo release in the rat subcutaneous model . The microspheres were spherical in nature, and particle size range had a significant influence on the in vitro release . The enoxacin plasma concentration 2 h after the administration of treatments was two-fold higher in animals who received the free drug compared with those who received microspheres of size range 125-250 microm . The plasma of animals who received the free drug was depleted of enoxacin by the end of the first day . However, the plasma concentration of enoxacin in the animals who received microspheres was sustained above 0.5 microg/ml for about 8 days . The results show that biodegradable microspheres of enoxacin can be prepared which release the antibiotic in vivo for days following a subcutaneous administration . This should provide a means for the sustained treatment of infections due to sensitive strains of bacteria.

Rev Med Suisse Romande, 2000 Jan, 120(1), 43 - 6
{Infective Chlamydia pneumoniae and coronary disease: where is the truth?}; Malinverni R; Chlamydia pneumoniae has been associated with atherosclerosis and coronary heart disease for several years . This association is based upon 4 research areas: 1 . seroepidemiological studies, 2 . detection of the pathogen in diseased arteries, 3 . experimental studies in vitro and in animal models, and 4 . human intervention trials with antibiotics . We review and discuss recent data from these four areas . Although the infectious hypothesis of atherosclerosis is not new, the bulk of evidence supporting a role for C . pneumoniae is important . However, a definite pathogenic role for initiating or accelerating the athreosclerotic process remains unproven . Several large clinical trials with antibiotic interventions in patients with coronary heart disease are ongoing . Treatment of C . pneumoniae infection and the perspectives for a vaccine remain, however, problematic.

Rev Med Interne, 2000 Feb, 21(2), 187 - 90
{Atypical presentation of tuberculosis in the elderly: a case report of pleuropericarditis}; Asseray N et al.; INTRODUCTION: The incidence of tuberculosis is increasing, particularly in the elderly, and has various clinical presentations . EXEGESIS: We describe the case of a 78-year-old woman who presented tuberculous pleuropericarditis . This case is atypical, due to infection localisation, negativity of the tuberculin skin test, and mixed pleural effusion . Following antituberculosis antibiotic therapy and corticotherapy, the outcome was favorable . CONCLUSION: Due to atypical and non-specific clinical presentation, diagnosis of tuberculosis may be particularly difficult in the elderly.

J Chromatogr A, 2000 Feb 4, 868(2), 197 - 207
Enantiomeric and diastereomeric high-performance liquid chromatographic separation of cyclic beta-substituted alpha-amino acids on a teicoplanin chiral stationary phase; Schlauch M et al.; High-performance liquid chromatographic (HPLC) separation of stereomeric cyclic beta-substituted or-quaternary alpha-amino acids was performed on a chiral stationary phase based on the glycopeptide antibiotic teicoplanin . The investigated amino acids are the 1-amino-2-methylcyclohexanecarboxylic acids, the 1-amino-2-hydroxycyclohexanecarboxylic acids, Ala, Cha, Phe and Tle . The effects of the mobile phase composition (type and content of organic modifier, pH) and of the temperature on the enantio- and diastereoselectivity were studied and the conditions were optimised to resolve the four stereomers of one amino acid in a single chromatographic run . The influence of the modifier concentration and the pH of the mobile phase reveal two enantiomeric and diastereomeric discrimination mechanisms based on different interactions with the stationary phase . For optimal separation of diastereomers the column has to be conditioned with an acidic eluent.

J Pharm Biomed Anal, 1999 Nov, 21(3), 473 - 82
Simultaneous spectrophotometric and volumetric determinations of amoxycillin, ampicillin and cloxacillin in drug formulations: reaction mechanism in the base catalysed hydrolysis followed by oxidation with iodate in dilute acid solution; Qureshi SZ et al.; A method for the analysis of degraded products of amoxycillin, ampicillin and cloxacillin in drug formulations, obtained as a result of their base hydrolysis is described . Simultaneous spectrophotometric and volumetric determinations of the antibiotic is based on the neutralization of the degraded product by dilute hydrochloric acid to get a pH approximately 2 to be conducive for redox titration using potassium iodate as titrant . A red purple colour is developed in carbon tetrachloride at the end point . Spectrophotometry is done after separating the organic layer and measuring the absorbance of red-purple colour at lambda(max) 520 nm . The pathways of different degraded products and their oxidation mechanism is described on IR, TLC and UV spectroscopic studies.

Nat Struct Biol, 2000 Mar, 7(3), 215 - 9
Structural basis of gene regulation by the tetracycline inducible Tet repressor-operator system; Orth P et al.; The tetracycline repressor (TetR) regulates the most abundant resistance mechanism against the antibiotic tetracycline in grain-negative bacteria . The TetR protein and its mutants are commonly used as control elements to regulate gene expression in higher eukaryotes . We present the crystal structure of the TetR homodimer in complex with its palindromic DNA operator at 2.5 A resolution . Comparison to the structure of TetR in complex with the inducer tetracycline-Mg2+ allows the mechanism of induction to be deduced . Inducer binding in the repressor core initiates conformational changes starting with C-terminal unwinding and shifting of the short helix a6 in each monomer . This forces a pendulum-like motion of helix a4, which increases the separation of the attached DNA binding domains by 3 A, abolishing the affinity of TetR for its operator DNA.

Nat Biotechnol, 2000 Mar, 18(3), 326 - 32
A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks; Schuster S et al.; A set of linear pathways often does not capture the full range of behaviors of a metabolic network . The concept of 'elementary flux modes' provides a mathematical tool to define and comprehensively describe all metabolic routes that are both stoichiometrically and thermodynamically feasible for a group of enzymes . We have used this concept to analyze the interplay between the pentose phosphate pathway (PPP) and glycolysis . The set of elementary modes for this system involves conventional glycolysis, a futile cycle, all the modes of PPP function described in biochemistry textbooks, and additional modes that are a priori equally entitled to pathway status . Applications include maximizing product yield in amino acid and antibiotic synthesis, reconstruction and consistency checks of metabolism from genome data, analysis of enzyme deficiencies, and drug target identification in metabolic networks.

Biotechnol Bioeng, 2000 Apr 5, 68(1), 31 - 43
Influence of bcl-2 on cell death during the cultivation of a Chinese hamster ovary cell line expressing a chimeric antibody; Tey BT et al.; The influence of Bcl-2 expression on the robustness of a CHO cell line (22H11) developed for the industrial production of a chimeric antibody was evaluated . Western blot analysis following transfection with the expression vector unexpectedly revealed upregulation of endogenous Bcl-2 expression in the control (Neo) cell line in response to exposure to the selection drug G418 . This indicated that geneticin may function by inducing apoptosis in cells not carrying the control plasmid or expressing very low levels of survival genes . Thus, exposure to the drug enriched the culture for a population of cells which expressed enhanced levels of endogenous Bcl-2 . In batch cultures, ectopic bcl-2 expression resulted in a 75% increase in maximum viable cell density over control cultures . Moreover, the rate of decrease in viability in the Bcl-2 cultures was significantly lower than that in the control cultures . After 18 days, the Bcl-2 viability was around 90%, compared to 20% in the control cultures . Evaluation of the mechanism of cell death revealed very few cells with classical apoptotic morphology . Around 10% were clearly necrotic, but the majority of dead cells were seen as chromatin free but otherwise relatively intact structures . Because of the relatively low rate of cell death in both cell lines, few cells were observed in the transitional, easily identifiable early stages of apoptosis . However, DNA gel electrophoresis revealed a clear ladder-pattern, but only in the control cultures, thus confirming high levels of apoptotic death . Antibody concentrations during both sets of cultures were very similar, both during the growth and death phases, with a maximum titer of around 40 microgram/ml . Analysis of Bcl-2 expression by flow cytometry revealed that the cultures contained two populations of cells: a large population which expressed high levels of Bcl-2 and a relatively smaller low-expressing population . During the course of the batch, the smaller, low-expressing population declined in frequency, suggesting that these cells were more sensitive to cell death . In addition, the mean level of Bcl-2 expression in the overexpressing population also declined significantly, presumably reflecting the exhaustion of precursors for protein synthesis following nutrient depletion . Importantly, when cells were taken from day 40 of the significantly extended Bcl-2 batch cultures, they immediately proliferated, confirming that they had retained their replicative potential . Cultivation of the cells in basal medium lacking (individually) serum, all amino acids, glutamate/asparagine, and, finally, glucose, resulted in relatively lower viable cell numbers and viability in the control cell line compared to the Bcl-2 cell line . Exposure of cells to ammonia toxicity also revealed the relative robustness of the bcl-2 transfected cells . When growth was arrested by treatment with 4 mM thymidine, Bcl-2 overexpressing cells exhibit a viability of over 80% after 5 days in culture, compared to only 40% in the control cell line . However, under growth-arrested conditions, there was no major difference in antibody titer between the two cell lines .

Int J Oral Maxillofac Implants, 2000 Jan-Feb, 15(1), 125 - 38
Treatment of peri-implantitis defects with autogenous bone grafts: six-month to 3-year results of a prospective study in 17 patients; Behneke A et al.; As part of an ongoing prospective study, the treatment of peri-implantitis defects using autogenous bone grafts was evaluated . This present report is based on data from 25 ITI screw implants in 17 patients with progressive peri-implant tissue destruction during the maintenance phase . Treatment of these lesions included raising flaps, removal of the surrounding granulation tissue, and air-polishing of the implant surface . Subsequently, corticocancellous bone grafts or particulate bone were placed into the peri-implant osseous defects, and the flaps were sutured around the cervical segment of the implants, allowing for transmucosal healing . Two of the 25 cases resulted in a negative outcome of the procedure . One of the transplants had to be removed 40 days after augmentation because of flap dehiscence and graft mobility . In another patient, the healing period was uneventful until the re-entry surgery, but when the site was reopened, the total graft volume was resorbed . The primary therapeutic success at re-entry surgery evaluated by intraoperative measurements resulted in a median defect depth reduction of 6.9 to 0.7 mm (P = .001), corresponding to a bone repair of 90% . The change in defect width was 1.9 mm (P = .002, repair 100%) . A positive result of the reconstructive therapy has been observed during a re-evaluation time of up to 3 years . Median marginal bone loss was reduced from 6.2 to 2.3 mm after 2 and 3 years, respectively . The median vertical bone resorption of 4.5 mm was completely repaired . The crevicular fluid volume, a parameter of the level of marginal inflammation, along with probing depths and attachment levels, were reduced to a physiologic rate . The implant observation period until the first appearance of the lesion seems to be crucial to the effectiveness of the therapy . Early failures appearing within the first 2 years after implant placement showed a more stable therapeutic result over time.

Ear Nose Throat J, 2000 Feb, 79(2), 94 - 5
Osteoradionecrosis of the temporal bone in nasopharyngeal carcinoma after radiotherapy: a case report; Tsang WS et al.; Osteoradionecrosis of the temporal bone after external-beam radiotherapy for nasopharyngeal carcinoma is not uncommon following a long posttreatment interval . We describe the case of a man who had experienced this complication 13 years after he had undergone such radiotherapy . His condition resolved after removal of dead bone from the external auditory canal, followed by antibiotic therapy and periodic aural toileting.

Aust N Z J Surg, 2000 Jan, 70(1), 43 - 6
Factors that influence length of stay after appendicectomy in children; Foulds KA et al.; BACKGROUND: The length of hospital stay following appendicectomy in children at Christchurch Hospital has decreased in recent years . The aim of the present study was to identify those factors that contributed to this change . METHODS: A retrospective review of children admitted to Christchurch Hospital between 1994 and 1998 inclusive who underwent appendicectomy for suspected appendicitis was conducted . Data recorded included standard demographic information, symptom duration, operative details, analgesia, antibiotics, pathology, complications and postoperative length of stay (LOS) . RESULTS: Postoperative LOS decreased significantly during the period reviewed across all degrees of appendiceal inflammation, from a mean of 70.5 to 50.1 h . The main determinant of postoperative hospital stay was the severity of the appendiceal inflammatory process . Other factors that influenced LOS included surgical approach (open vs . laparoscopic), use of intra-operative local anaesthesia, type and mode of postoperative analgesia, and age of the child . Longer duration of antibiotic use and symptom duration of greater than 24 h were associated with a longer LOS, primarily as a reflection of the severity of inflammation of the appendix . Factors that appeared to have little or no influence included gender and the experience of the surgeon . CONCLUSION: The severity of the inflammatory process appeared to be the main determinant of postoperative hospital LOS; advanced appendicitis with abscess formation or peritonitis was associated with the longest LOS, irrespective of the surgical approach, although the LOS after appendicectomy was reduced by a laparoscopic approach . Intra-operative local anaesthesia during open appendicectomy reduced hospital stay, probably because it reduced the need for postoperative narcotics . Early diagnosis (< 24 h) was associated with a shorter postoperative LOS for acutely inflamed appendices.

J Toxicol Clin Toxicol, 2000, 38(1), 59 - 62
Pulse steroid therapy in adult respiratory distress syndrome following petroleum naphtha ingestion; Kamijo Y et al.; CASE REPORT: A suicide attempt by a 23-year-old woman involved ingestion of 1000 mL of petroleum naphtha . Early chemical pneumonitis was complicated by life-threatening, diffuse interstitial lung consolidation with pneumatoceles . Pulse steroid therapy beginning on day 17 was associated with remarkable resolution of interstitial consolidation, although an enlarging secondarily infected pneumatocele ruptured to produce a bronchopleural fistula . Thoracic surgery and antibiotic therapy resulted in improvement of the patient's respiratory condition, and she was discharged with no residual respiratory symptoms . High-dose corticosteroid therapy appears to be a useful addition to aggressive supportive treatment in late adult respiratory distress syndrome following hydrocarbon ingestion.

J, Exp . Mar . Biol . Ecol. . 2000 Mar 15, 245(2), 171 - 182
Relationship between specific dynamic action and protein deposition in calanoid copepods; Thor P; The link between specific dynamic action (SDA) and protein deposition was investigated in copepodites stage V of two calanoid copepod species, the neritic Acartia tonsa and the oceanic Calanus finmarchicus . This was done by measuring respiration before, during, and after a specific feeding period and measuring the incorporation of carbon into proteins . These were also measured on individuals incubated with cycloheximide, an antibiotic that inhibits protein synthesis . The cycloheximide treatment significantly diminished the magnitude of SDA in both A . tonsa and C . finmarchicus, and inhibited carbon incorporation into protein in both species . This provides evidence that the rate at which protein deposition takes place greatly affects the magnitude of SDA . The specific respiration rates of both starving and feeding copepods were generally higher in A . tonsa than in C . finmarchicus . This influenced SDA, the magnitude of SDA normalised to an 8 h feeding period being threefold higher in A . tonsa (78.7+/-25.7 nlO(2) microgC(-1)) than in C . finmarchicus (27.5+/-11.6 nlO(2) microgC(-1)) . This difference may arise due to differences in energy allocation in the organisms of the copepodite V stage of the two species . In this stage C . finmarchicus deposits large quantities of storage lipids, predominately wax esters, whereas A . tonsa deposits proteins during somatic growth.

N Z Med J, 1999 Nov 26, 112(1100), 445 - 7
Ophthalmomyiasis and nasal myiasis in New Zealand: a case series; Macdonald PJ et al.; We report three cases of ophthalmomyiasis in New Zealand, due to the larvae of Oestrus ovis . All three patients reported eye injury caused by a fly . The larvae were removed from the conjunctival sac without difficulty under local anaesthesia . Presenting ocular symptoms of foreign body sensation, irritation, redness and photophobia all resolved swiftly . Topical antibiotic and steroid eye drops were administered . All three patients also developed nasal symptoms such as sneezing, nasal discharge and epistaxis . Otolaryngology follow-up demonstrated nasal myiasis in two patients which was treated with nasal decongestants . In addition, all three patients were treated with ivermectin (Mectizan).

J Periodontol, 2000 Jan, 71(1), 79 - 89
Repeated metronidazole and amoxicillin treatment of periodontitis . A follow-up study; Lopez NJ et al.; BACKGROUND: The prevailing concept is that little or no clear benefit is derived from antibiotic therapy in chronic periodontitis . Studies to determine the effect of metronidazole plus amoxicillin (M+A) on adult periodontitis are questionable because standard design for clinical trials was usually not used . In addition, there is no information about the effect of M+A as the sole therapy for periodontitis . METHODS: A randomized, triple-blind, controlled clinical trial was used to determine the effect of systemic administration of M+A, as the sole therapy, in progressive adult periodontitis . Forty-six subjects with moderate to advanced adult periodontitis who showed > or =2 mm attachment loss in at least 2 sites in the previous 2 months were entered in the study . Subjects were randomly distributed to a group who received 21 tablets of metronidazole 250 mg plus amoxicillin 500 mg, or to a group receiving a placebo (1 tablet every 8 hours for 1 week) . Patients were examined every 2 months for 12 months . The M+A or placebo regimen was repeated at 4 and 8 months . No effort was made to change the oral habits of patients and they received no additional therapy . Differences between groups were assessed using the Mann-Whitney U test . The differences at every 2-month interval within each group were assessed using the ANOVA test . RESULTS: Seven subjects abandoned the study; at 12 months the M+A group had 20 subjects and the placebo group 19 . There were no significant differences in the clinical parameters at baseline between the 2 groups . After 2 months and thereafter, the M+A group showed significant clinical improvement while the placebo group showed a progressive deterioration of periodontal status . At 12 months compared to baseline, subjects of the M+A group showed: 1) a significant overall mean attachment gain of 0.43 mm (P = 0.005); 2) a significant decrease of active sites (P< or =0.03); 3) a significant increase of sites gaining attachment level (P< or =0.01); 4) a significant reduction of pocket depth (P< or =0.00006); and 5) a significant decrease in percentage of bleeding on probing sites (BOP) (P< or =0.0005) . Significant differences between both groups at all 2-month evaluations were found in overall mean attachment level (P < or =0.000004), in percent of active sites (P< or =0.03), and in percent of BOP sites (P< or =0.02) . Sites exhibiting > or =2 mm of attachment loss in 2 successive or alternate evaluations, and periodontal abscess were noticed only in the placebo group . CONCLUSIONS: A 1-week course of systemic M+A every 4 months, as the only therapy, arrests the progression of adult periodontitis and significantly improves the clinical parameters of the disease.

Am Surg, 2000 Feb, 66(2), 133 - 7
Postoperative pneumonia; Croce MA; Despite the advances made in surgical critical care, the diagnosis of one of the most common infections seen in critically ill patients remains a challenge . Ventilator-associated pneumonia is associated with a 20 to 25 per cent mortality rate . There are numerous risk factors for ventilator-associated pneumonia, including underlying disease, prolonged mechanical ventilation, direct lung injury, and shock . The standard clinical criteria for pneumonia are inaccurate . Quantitative cultures of bronchoalveolar lavage effluent are accurate for the diagnosis, and it is safe to base antibiotic therapy on the results of the quantitative cultures.

Przegl Lek, 1999, 56(9), 584 - 7
{Infections with Chlamydia pneumoniae, Helicobacter pylori or cytomegalovirus and atherosclerosis}; Grabczewska Z et al.; It's known that common risk factors of atherosclerosis can explain only 50% of its etiology . In only 40% patients risk factors modification inhibits progression of atherosclerosis . Therefore looking for new risk factors of atherosclerosis is necessary . In recent years the inflammatory-infectious hypothesis of atherosclerosis has been reevaluated . The discovery of heavy infections load in the serum of patients with acute coronary syndromes might suggest a potential immunological mechanism triggered by bacterial proteins . Chlamydia pneumoniae, Helicobacter pylori and cytomegalovirus infections are very common in human population and therefore they are suspected as the main infectious pathogen in the coronary disease . Clinical studies have demonstrated higher anti-Chlamydia and ani-Helicobacter antibody titres in patients with myocardial infarction (60-70% pts), stable and unstable angina (50-60% pts) than in control groups (12-15% pts) . Two studies were performed with antibiotic (azotromycin, roxitromycin) influence on the prevalence of acute coronary syndromes after myocardial infarction and unstable angina . These studies have shown statistically significant reduction of the prevalence of acute coronary episodes in follow-up period.

Cent Afr J Med, 1999 Jul, 45(7), 169 - 73
Risk factors for neonatal mortality: Harare Central Hospital Neonatal Unit--Zimbabwe; Kambarami RA et al.; OBJECTIVE: To assess risk factors for neonatal mortality in a tertiary level neonatal unit . DESIGN: Case control analysis of routine neonatal data for 1998 . SETTING: Harare Central Hospital Neonatal Unit . SUBJECTS: All neonates delivered at Harare Maternity Hospital and admitted to the neonatal unit for care between January and December 1998 . MAIN OUTCOME MEASURE: Neonatal mortality in hospital . RESULTS: A total of 5,305 neonatal admissions were studied of which 19.3% died in hospital . The median age at death was two days (Q1 = 1, Q3 = 3) and the median age at hospital discharge was 3 days (Q1 = 1, Q3 = 6) . Risk factors for mortality were un-booked mother odds ratio (OR) 2.36 (95% CI = 1.98 to 2.81), breech delivery OR: 1.76 (95% CI = 1.39 to 2.22), low birth weight OR: 4.67 (95% CI = 3.92 to 5.57), prematurity OR: 2.36 (95% CI = 2.09 to 2.66), congenital malformations OR: 2.80 (95% CI = 1.72 to 4.53) and birth asphyxia OR: 1.79 (95% CI = 1.51-2.12) . Being admitted for respiratory distress was associated with better survival OR: 0.22 (95% CI = 0.17 to 0.28) . Having a Caesarian section was also protective OR: 0.60 (95% CI = 0.47 to 0.76) . Mother's age, parity, time of delivery and sex were not significantly associated with mortality odds ratios (95% CI) of 1.07 (0.86 to 1.34), 0.94 (0.78 to 1.13), 1.10 (0.93 to 1.30) and 0.89 (0.78 to 1.03) respectively . On regression analysis birth weight greater than 2,500 g, being un booked and breech delivery were predictive of mortality with OR (95% CI) of 0.99 (0.99 to 0.99), 1.31 (1.12 to 1.61) and 1.15 (1.04 to 1.28) respectively . CONCLUSION: Low birth weight is the highest risk factor for mortality in this tertiary level hospital . Strategies targeted at low birth weight infants such as antenatal corticosteroid use, improved intrapartum care, appropriate antibiotic use, improved efficiency and access to neonatal intensive care will have the most impact on neonatal mortality.

Int J Clin Pract, 1999 Jul-Aug, 53(5), 396 - 7
The use of recombinant human G-CSF in the treatment of propylthiouracil-induced agranulocytosis; Altunbas H et al.; A 43-year-old female patient with Basedow-Graves' disease developed agranulocytosis in the eighth month of propylthiouracil therapy . After discontinuing the drug, a broad spectrum antibiotic regimen plus recombinant human granulocyte colony-stimulating factor (G-CSF), a human haematopoietic growth factor, were started . Her granulocyte count returned to normal with the second dose of G-CSF, and ulcerating pharyngitis improved rapidly . We think that in patients with propylthiouracil-induced agranulocytosis, G-CSF will reduce the risk and severity of infection, and should be accepted as a part of the standard therapy.

Rinsho Ketsueki, 2000 Jan, 41(1), 32 - 6
{CD56-positive adult T-cell leukemia manifested by abnormal lung shadows}; Koike M et al.; A 54-year-old woman was admitted to Juntendo Izunagaoka Hospital on Aug . 29, 1998, after experiencing cough and fever for 19 days . Chest X-ray films disclosed infiltrates in the left lung field . The abnormal lung shadows progressed despite antibiotic therapy, and enlargement of superficial lymph nodes and hepatosplenomegaly developed . Peripheral blood examination disclosed cleaved lymphoid cells without granular cytoplasm . Anti-HTLV-I antibody titer was x320, and the monoclonal integration of HTLV-I provirus was confirmed by Southern blot analysis . Surface marker analysis of lymph node cells was positive for CD2, CD3, CD4, CD5, CD56, and HLA-DR . The above results yielded a diagnosis of adult T-cell leukemia . LSG-4 therapy alleviated the lung infiltrations and dyspnea . This case was considered unusual because of the expression of the natural killer cell marker CD56 on leukemic cells and the presentation of abnormal lung shadows possibly due to leukemic cell infiltration.

Epidemiol Infect, 1999 Dec, 123(3), 403 - 11
Bordetella pertussis surveillance in England and Wales: 1995-7; Van Buynder PG et al.; Available data sources on disease due to Bordetella pertussis, including notifications, hospital admissions, deaths, and an enhanced laboratory-based surveillance system commenced in January 1994, were reviewed for the period 1995-7 . Pertussis notifications continued their approximately 3-year cycle although at historically reduced levels . A slight seasonal increase in late summer/early autumn existed over and above a relatively constant background rate . Over time, the proportion of pertussis cases in younger, unvaccinated children, and to a lesser extent, adolescents and young adults, is increasing . There is a continuing significant and underreported mortality associated with pertussis in the very young age group . Disease due to serotype 1,2 is on the increase despite persistent high vaccination levels and this serotype causes more severe disease . The provision of preventative antibiotics prior to disease onset reduced the severity of the disease but its use remains uncommon in England and Wales . While overall levels of pertussis notifications have declined in recent times, vaccination efficacy wanes with increasing age, and pertussis remains a significant cause of mortality and severe morbidity in the very young . This could be reduced by timely booster vaccination and increased recognition of mild disease in older cases followed by early antibiotic therapy for the very young household contacts.

J Pediatr Surg, 2000 Feb, 35(2), 239 - 44; discussion 244-5
Historical changes in the postoperative treatment of appendicitis in children: impact on medical outcome; Lelli JL Jr et al.; BACKGROUND/PURPOSE: The introduction of managed care in the 1980s caused increased pressure to reduce costs for hospitalized patients . The authors hypothesized that these market forces have resulted in a decreased hospital stay and utilization of sophisticated diagnostic testing in children treated for appendicitis . If true, the impact of this paradigm shift on patient outcome is unknown . METHODS: Hospital records for 913 pediatric patients treated for appendicitis from 1974 to 1998 were reviewed retrospectively . Patients were stratified into those with perforated appendicitis (PA) and nonperforated appendicitis (NPA) . Demographics, perioperative hospital course, diagnostic testing, complications, and long-term outcomes were analyzed after stratification into time intervals . RESULTS: Over time, children with NPA were treated with shorter antibiotic courses (P<.05) and were placed on a regular diet earlier (P<.05) . These changes in treatment resulted in an earlier discharge (P<.05) . The amount of time to become afebrile with a normal white blood cell count (WBC) did not change over time . Children with PA exhibited similar results with shorter antibiotic courses (P<.05), earlier dietary intake (P<.05) and earlier hospital discharge (P<.05) over time . In all children with appendicitis there was no significant difference in the rate of wound infections, abscesses requiring drains, readmission, or reoperations overtime . The utilization of abdominal radiographs (83%) and ultrasonography (USN; 40%) was high and remained unchanged over time . Utilization of computed tomography (CT scan) was low (4.3%) in the early decades and was not used as a preoperative test from 1991 to 1994 . Given the high diagnostic accuracy of a pediatric surgeon for this disease, Bayesian analysis indicates that USN utilization rates should be 15% . CONCLUSIONS: The market pressures of managed care have resulted in a new treatment paradigm with an earlier discharge of all children with appendicitis . There has been no concomitant increase in the complication rate in either group as a result of this paradigm shift . Bayesian analysis indicates that USN and abdominal radiographs are overutilized in our institution.

Proc R Soc Lond B Biol Sci, 1999 Dec 22, 266(1437), 2539 - 49
Invasion thresholds for fungicide resistance: deterministic and stochastic analyses
Gubbins S, Gilligan CA.
Fungicide resistance is an important practical problem, but one that is poorly understood at the population level . Here we introduce a simple nonlinear model for fungicide resistance in botanical epidemics which includes the dynamics of the chemical control agent and the host population, while also allowing for demographic stochasticity in the host-parasite dynamics . This provides a mathematical framework for analysing the risk of fungicide resistance developing by including the parameters for the amount applied, longevity and application frequency of the fungicide . The model demonstrates the existence of thresholds for the invasion of the resistant strain in the parasite population which depend on two quantities: the relative fitness of the resistant strain and the effectiveness of control . This threshold marks a change from definite elimination of the resistant strain below the threshold to a finite probability of invasion which increases above the threshold . The fungicide decay rate, the amount of fungicide applied and the period between applications affect the effectiveness of control and, consequently, they influence whether or not resistance develops and the time taken to achieve a critical frequency of resistance . All three parameters are amenable to control by the grower or by coordinating the activity of a population of growers . Providing crude estimates of the effectiveness of control and relative fitness are available, the results can be used to predict the consequences of changing these parameters for the risk of invasion and the proportion of sites at which this might be expected to occur . Although motivated for fungicide resistance, the model has broader application to herbicide, antibiotic and antiviral resistance . The modelling approach and results are discussed in the context of resistance to chemical control in general.

J Biol Chem, 2000 Mar 3, 275(9), 6201 - 6
Biosynthetic studies of the glycopeptide teicoplanin by (1)H and (13)C NMR; Heydorn A et al.; The biosynthesis of the glycopeptide antibiotic teicoplanin was studied by growing a teicoplanin producing strain of Actinoplanes teichomyceticus (ATCC 31121) on glucose containing either 34.0% {1-(13)C}glucose or 9.7% {U-(13)C}glucose . The fractional enrichment pattern of teicoplanin produced in the medium containing {1-(13)C}glucose was obtained from a one-dimensional (13)C spectrum . The enrichment pattern showed characteristic peaks indicating that amino acids 3 and 7 are derived from acetate, whereas amino acids 1, 2, 4, 5, and 6 are derived from tyrosine . Multiplet structures in heteronuclear single quantum coherence spectra of teicoplanin produced in the medium containing {U-(13)C}glucose showed characteristic coupling patterns supporting these results . Fractional enrichment patterns and multiplet structures of the three sugars in teicoplanin showed that about 50% of the sugars have the same labeling pattern as the glucose substrate whereas the rest have a labeling pattern showing that they are reassembled, probably from precursors in the primary metabolism.

Diabet Med, 2000 Jan, 17(1), 74 - 7
'Sausage toe': a reliable sign of underlying osteomyelitis; Rajbhandari SM et al.; AIMS: To follow-up patients with a 'sausage' deformity of the toe associated with local neuropathic ulceration to confirm the diagnosis of underlying osteomyelitis . This was based on our observation that some diabetic patients with suspected pedal osteomyelitis with a local neuropathic ulcer have a 'sausage' deformity of a toe . METHODS: Over a period of 2 years, 14 patients with foot ulcers, who were observed to have the 'sausage' deformity of a toe in the diabetic foot clinic were followed up and investigated . RESULTS: Underlying osteomyelitis was confirmed in six on the very first X-ray examination . A further seven had osteomyelitis diagnosed on bone scanning . Both the X-ray and the bone scan were equivocal in one patient, whose ulcer only healed after an 8-week course of antibiotics . Antibiotic therapy was successful in 11 patients and three patients required amputation of the affected toe . Following successful treatment, there was full resolution of the 'sausage toe' in the majority . CONCLUSIONS: The appearance of a 'sausage toe' should alert the physician of the possibility of underlying osteomyelitis in diabetic foot, so that prompt treatment can be commenced with antibiotics.

Ophthalmology, 2000 Feb, 107(2), 315 - 7
Prevention of cellulitis after open lacrimal surgery: a prospective study of three methods; Vardy SJ et al.; OBJECTIVE: Soft-tissue cellulitis after open lacrimal surgery, almost exclusively caused by infection, is associated with a reduced surgical success rate, inconvenience for the patient, and may predispose to secondary hemorrhage . Although postoperative oral antibiotics have been shown to significantly reduce the infection rate, this investigation was designed to compare this regimen with two other methods for the prevention of postoperative infection . DESIGN: A prospective nonrandomized comparative trial of three methods for prevention of postoperative infection . PARTICIPANTS: Patients, recruited over a 16-month period from the Lacrimal Clinic at Moorfields Eye Hospital, who required primary open dacryocystorhinostomy . METHOD: Two hundred and sixty-five patients were assigned, on the basis of hospital number, to one of three groups: to receive either an intravenous broad-spectrum antibiotic immediately after induction of anesthesia (group 1), intraoperative lavage of the rhinostomy site just after suture of the anterior mucosal flaps (group 2), or a postoperative course of oral antibiotics (group 3) . OUTCOME MEASURES: Cellulitis was considered to be present when there was marked tenderness along a swollen and erythematous incision line, evidence of frank pus from the suture line, or late postoperative hemorrhage occurred . Patients were reviewed within a week of surgery . RESULTS: Signs of infective cellulitis occurred in 1 of 127 (0.8%) cases in group 1, 7 of 41 (18%) cases in group 2, and 2 of 127 (1.5%) cases in group 3 . Whereas the infection rate in group 2 was significantly greater than that in group 1 (P << 0.001) or group 3 (P<0.001), no significant difference was found between that in groups 1 and 3 (0.75>P>0.5; chi-square test with Yates' correction) . CONCLUSION: Compared with intraoperative saline lavage, intraoperative or postoperative broad-spectrum antibiotics have comparable efficacy in the prevention of postoperative soft-tissue cellulitis after open lacrimal surgery . Intraoperative administration of antibiotics has the advantages of compliance and economics.

Ugeskr Laeger, 2000 Feb 7, 162(6), 795 - 7
{Invasive aspergillosis in two hematological patients}; Rask CU et al.; We present two cases of invasive aspergillosis in patients with acute myeloid leukemia . In neutropenic patients with antibiotic resistent fever, without specific symptoms or signs, invasive aspergillosis should be considered . Diagnostic approaches such as X-ray/CT-scan of the thorax and sinuses, relevant cultures and antigen detection should be performed . Due to diagnostic difficulties and the rapid progression of the infection empirical antifungal therapy should be given . During subsequent neutropenic episodes prophylactic antifungal therapy can possibly preempt recurrence.

Z Gastroenterol, 2000 Jan, 38(1), 39 - 43
Mechanic intestinal obstruction--a possible presentation of perforated appendicitis; Miehsler W et al.; A 61-year-old man presented with diffuse abdominal pain, diarrhea, vomiting and fever . On the initial diagnosis of gastroenteritis the patient received the antibiotic ofloxacine for one week . On admission plain abdominal radiograph suggested a mechanic intestinal obstruction . In computed tomography a conglomerate tumor in the ileocecal region was seen and the patient underwent laparotomy . The conglomerate tumor was mobilized and an abscess opened, which was caused by a perforated appendicitis . After the operation the patient improved immediately and had an uneventful postoperative course . He was released and did not suffer from gastrointestinal symptoms the following 16 months of follow-up . The present case shall set forth that perforated appendicitis can clinically present as intestinal obstruction . Although a rare complication, perforated appendicitis should therefore even be considered in cases of mechanic intestinal obstruction of unknown cause.

Chest Surg Clin N Am, 2000 Feb, 10(1), 45 - 53, viii
The history of surgery of empyema, thoracoplasty, Eloesser flap, and muscle flap transposition; Miller JI Jr; This article discusses the surgical history of empyema, thoracoplasty, the Eloesser flap, and muscle flap transfer . Little has changed in the 2000 years since the treatment of empyema was originally described by Hippocrates . The basic concepts of drainage of the infected empyema and obliteration of the space by allowing the lung to come up to the chest wall, taking the chest wall down to the lung, or by using muscle flaps or antibiotic solution remain the stabilizing forces in the treatment of postresection or postinfectious empyemas.

Eur J Pharmacol, 2000 Feb 18, 389(2-3), 141 - 6
Cellular uptake and interaction with purified membranes of rebeccamycin derivatives; Goossens JF et al.; Rebeccamycin is an antitumor antibiotic possessing a DNA-intercalating indolocarbazole chromophore linked to a glycosyl residue . The carbohydrate moiety of rebeccamycin and related synthetic analogues, such as the potent antitumor drug NB-506 (6-N-formylamino-12,13-dihydro-1, 11-dihydroxy-13-(beta-D-glucopyranosyl)-5H-indolo{2,3-a}pyrrolo- {3,4-c}carbazole-5,7-(6H)-dione), is a key element for both DNA-binding and inhibition of DNA topoisomerase I . In this study, we have investigated the cellular uptake of rebeccamycin derivatives and their interaction with purified membranes . The transport of radiolabeled {3H}dechlorinated rebeccamycin was studied using the human leukemia HL60 and melanoma B16 cell lines as well as two murine leukemia cell lines sensitive (P388) or resistant (P388CPT5) to camptothecin . In all cases, the uptake is rapid but limited to about 6% of the drug molecules . In HL60 cells, the uptake entered a steady-state phase of intracellular accumulation of about 0.26+/-0.05 pmol/10(6) cells, which persisted to at least 90 min . The efflux of exchangeable radiolabeled molecules was relatively weak . Fluorescence studies were performed to compare the interaction of a rebeccamycin derivative and its aglycone with membranes purified from HL60 cells . The glycosylated drug molecules bound to the cell membranes can be extracted upon washing with buffer or by adding an excess of DNA . In contrast, the indolocarbazole drug lacking the carbohydrate domain remains tightly bound to the membranes with very little or no exchange upon the addition of DNA . The membrane transport and binding properties of indolocarbazole drugs related to rebeccamycin are reminiscent to those of other DNA-intercalating antitumor agents . The uptake most likely occurs via a passive diffusion through the plasma membranes and the glycosyl residue of the drug plays an essential role for the translocation of the drug from the membranes to the internal cell components, such as DNA.

Biochemistry, 2000 Feb 22, 39(7), 1734 - 8
Intact aminoacyl-tRNA is required to trigger GTP hydrolysis by elongation factor Tu on the ribosome; Piepenburg O et al.; GTP hydrolysis by elongation factor Tu (EF-Tu) on the ribosome is induced by codon recognition . The mechanism by which a signal is transmitted from the site of codon-anticodon interaction in the decoding center of the 30S ribosomal subunit to the site of EF-Tu binding on the 50S subunit is not known . Here we examine the role of the tRNA in this process . We have used two RNA fragments, one which contains the anticodon and D hairpin domains (ACD oligomer) derived from tRNA(Phe) and the second which comprises the acceptor stem and T hairpin domains derived from tRNA(Ala) (AST oligomer) that aminoacylates with alanine and forms a ternary complex with EF-Tu . GTP . While the ACD oligomer and the ternary complex containing the Ala-AST oligomer interact with the 30S and 50S A site, respectively, no rapid GTP hydrolysis was observed when both were bound simultaneously . The presence of paromomycin, an aminoglycoside antibiotic that binds to the decoding site and stabilizes codon-anticodon interaction in unfavorable coding situations, did not increase the rate of GTP hydrolysis . These results suggest that codon recognition as such is not sufficient for GTPase activation and that an intact tRNA molecule is required for transmitting the signal created by codon recognition to EF-Tu.

Surgery, 2000 Feb, 127(2), 136 - 41
Gangrenous and perforated appendicitis: a meta-analytic study of 2532 patients indicates that the incision should be closed primarily; Rucinski J et al.; BACKGROUND: Surgical incisions after appendectomy for complicated (gangrenous or perforated) acute appendicitis are often managed with delayed closure (DC) rather than primary closure (PC) . This study synthesizes the results of other studies in the surgical literature and supports the routine use of PC . METHODS: Studies dealing with complicated appendicitis were reviewed to assess the results of PC in comparison with DC . The rate of incision (wound) infection in groups of patients managed by PC and DC were compared with the use of a statistical technique that defined the probability of expected results by incorporating data derived from all of the various study groups . RESULTS: Of the 2532 patients who had been treated for complicated appendicitis and who were assessed, 1724 patients underwent PC and 808 patients underwent DC . The rate of incision infection was 4.7% and 4.6% in the PC and DC groups, respectively . With a 95% confidence interval, there was no demonstrable difference between the 2 types of operative site management (P < .01) . CONCLUSIONS: PC of the skin and subcutaneous tissue after appendectomy for gangrenous or perforated appendicitis, combined with the use of antibiotic therapy in the perioperative period, is not associated with an increased risk of incision infection when compared with DC.

Presse Med, 2000 Jan 29, 29(3), 128 - 34
{Procalcitonin in pediatric emergencies: comparison with C-reactive protein, interleukin-6 and interferon alpha in the differentiation between bacterial and viral infections}; Lorrot M et al.; OBJECTIVE: Procalcitonin concentration increases in bacterial infections but remains low in viral infections and inflammatory diseases . The change is rapid and the molecule is stable making it a potentially useful marker for distinguishing between bacterial and viral infections . PATIENTS AND METHODS: Procalcitonin (PCT) was determined with an immunoluminometric assay on plasma collected at admission in 436 infants and children hospitalized for bacterial or viral infection . It was compared with C reactive protein, interleukin-6 and interferon-alpha measured on the same sample . RESULTS: PCT was 41.3 +/- 77.4 micrograms/l in children with septicemia or bacterial meningitis (n = 53), 0.39 +/- 0.57 microgram/l in children with viral infection (n = 274) and 3.9 +/- 5.9 micrograms/l in children with a localized bacterial infection who had a negative blood culture (n = 109) . PCT was > 1 microgram/l in 126 children with a localized or systemic bacterial infection (sensitivity 78%) . PCT was < 1 microgram/l in 258 children with a viral infection (specificity 94%) . For differenciation between viral and bacterial infections, CRP value > or = 20 mg/l, IL-6 > 100 pg/ml and interferon-alpha > 0 Ul/ml have 85, 48 and 76% sensitivity and 73, 85 and 92% specificity respectively . CONCLUSIONS: In this study, a PCT value of 1 microgram/l or greater had better specificity, sensitivity and predictive value than CRP, IL-6 and interferon-alpha in children for distinguishing between viral and bacterial infections . PCT may be useful in pediatric emergency room for making decision about antibiotic treatments.

Eur Neurol, 2000, 43(2), 107 - 9
Chronic fatigue syndrome in patients with Lyme borreliosis; Treib J et al.; Several authors have reported a chronic fatigue-like syndrome in patients that have suffered from Lyme borreliosis in the past . To further investigate this suspicion of an association without sample bias, we carried out a prospective, double-blind study and tested 1, 156 healthy young males for Borrelia antibodies . Seropositive subjects who had never suffered from clinically manifest Lyme borreliosis or neuroborreliosis showed significantly more often chronic fatigue (p = 0.02) and malaise (p = 0.01) than seronegative recruits . Therefore we believe it is worth examining whether an antibiotic therapy should be considered in patients with chronic fatigue syndrome and positive Borrelia serology .

Biochem Pharmacol, 2000 Mar 15, 59(6), 719 - 26
Inhibitory effects of aclarubicin on nitric oxide production in aortic smooth muscle cells and macrophages; Wakabayashi I et al.; The effects of aclaruhicin (ACR), an anthracycline antibiotic, on inducible nitric oxide (NO) synthesis was investigated in rat aortic smooth muscle cells (RASMCs) and RAW macrophages . ACR at concentrations as low as 0.1 microM significantly inhibited NO production induced by interleukin-1beta in RASMCs . About 5- to 10-fold higher concentrations of ACR were required for inhibition of interferon-gamma and lipopolipopolysaccharide-induced NO production in RAW cells . When ACR was subsequently administered to inducible NO synthase (iNOS) induction, the NO production was barely suppressed in RASMCs . Moreover, ACR (up to 10 microM) lacked direct inhibitory effects on iNOS activity in homogenates of these cells . ACR (0.1 microM) inhibited the expression of iNOS protein and mRNA in RASMCs without concomitant cytotoxic effects . ACR (>0.5 microM)-induced inhibition of NO production in RAW cells was associated with substantial cytotoxic effects as shown by measurement of lactate dehydrogenase release . These results suggest that ACR is a potent inhibitor of iNOS induction in vascular smooth muscle, but inhibits iNOS induction in macrophage only at high cytotoxic

JAMA, 2000 Feb 9, 283(6), 749 - 55
A controlled trial of a critical pathway for treatment of community-acquired pneumonia . CAPITAL Study Investigators . Community-Acquired Pneumonia Intervention Trial Assessing Levofloxacin; Marrie TJ et al.; CONTEXT: Large variations exist among hospitals in the use of treatment resources for community-acquired pneumonia (CAP) . Lack of a common approach to the diagnosis and treatment of CAP has been cited as an explanation for these variations . OBJECTIVE: To determine if use of a critical pathway improves the efficiency of treatment for CAP without compromising the well-being of patients . DESIGN: Multicenter controlled clinical trial with cluster randomization and up to 6 weeks of follow-up . SETTING: Nineteen teaching and community hospitals in Canada . PATIENTS: A total of 1743 patients with CAP presenting to the emergency department at 1 of the participating institutions between January 1 and July 31, 1998 . INTERVENTION: Hospitals were assigned to continue conventional management (n = 10) or implement the critical pathway (n = 9), which consisted of a clinical prediction rule to guide the admission decision, levofloxacin therapy, and practice guidelines . MAIN OUTCOME MEASURES: Effectiveness of the critical pathway, as measured by health-related quality of life on the Short-Form 36 Physical Component Summary (SF-36 PCS) scale at 6 weeks; and resource utilization, as measured by the number of bed days per patient managed (BDPM) . RESULTS: Quality of life and the occurrence of complications, readmission, and mortality were not different for the 2 strategies; the 1-sided 95% confidence limit of the between-group difference in the SF-36 PCS change score was 2.4 points, which was within a predefined 3-point boundary for equivalence . Pathway use was associated with a 1.7-day reduction in BDPM (4.4 vs 6.1 days; P = .04) and an 18% decrease in the admission of low-risk patients (31% vs 49%; P = .01) . Although inpatients at critical pathway hospitals had more severe disease, they required 1.7 fewer days of intravenous therapy (4.6 vs 6.3 days; P = .01) and were more likely to receive treatment with a single class of antibiotic (64% vs 27%; P<.001) . CONCLUSION: In this study, implementation of a critical pathway reduced the use of institutional resources without causing adverse effects on the well-being of patients.

J Biotechnol, 2000 Feb 17, 77(2-3), 209 - 18
Intracellular glucose 6-phosphate content in Streptomyces coelicolor upon environmental changes in a defined medium; Mira de Orduna R et al.; A new, chemically defined medium providing dispersed growth and high biomass formation and a method for quantitative extraction of intracellular metabolites was used to investigate the cellular response of Streptomyces coelicolor A3(2) during growth and upon changes in nutrient utilization . Fast changes of the glucose 6-phosphate content precisely signaled transitions in the flow of carbon sources . The results indicate that intracellular pool sizes may be used to detect early nutrient limitations in view of the onset of antibiotic production . Additionally the results disclose characteristics of the regulation of maltose and glutamic acid uptake and degradation in S . coelicolor A3(2).

Laryngoscope, 2000 Feb, 110(2 Pt 1), 246 - 9
Saline irrigation in the prevention of otorrhea after tympanostomy tube placement; Gross RD et al.; OBJECTIVES: Comparison of intraoperative saline irrigation to otic drops in the prevention of postoperative otorrhea in children with middle ear effusion undergoing bilateral myringotomy with ventilation tubes . STUDY DESIGN: This study was designed as a blinded, controlled, prospectively randomized trial . METHODS: Study children were randomly assigned to receive either otic drops for 3 days postoperatively or saline irrigation of the middle ear space at the time of myringotomy . Only children with effusion present at the time of surgery were included . All children were evaluated for drainage 7 to 14 days postoperatively, and the degree of drainage was graded from 0 to 4 . RESULTS: Of the 84 patients entered into the study, 62 patients were eligible for data analysis (16 failed follow-up, 6 records were lost) . Of the patients who completed the study, not all had bilateral effusions, resulting in 111 ears for inclusion in the study . Fifty-two ears underwent irrigation, and 10 were noted to have otorrhea (19.2%) . Fifty-nine ears received otic drops, resulting in 21 ears with otorrhea (35.6%) . Evaluating the degree of otorrhea with a five-point Leichert scale, the average score per ear was 0.42 for the saline irrigation group and 1.07 for the control group . The rate and degree of drainage were both statistically reduced in the saline irrigation group (P < .05) . CONCLUSIONS: Using middle ear irrigation at the time of tympanostomy may be more effective than antibiotic drops in preventing postoperative otorrhea.

Phytochemistry, 2000 Jan, 53(2), 231 - 7
Trans-4-aminoproline, a phytotoxic metabolite with herbicidal activity produced by Ascochyta caulina; Evidente A et al.; A phytotoxic metabolite, characterized through NMR techniques and synthetic methods as trans-4-aminoproline, was isolated from the culture filtrates of Ascochyta caulina, a promising mycoherbicide for biological control of Chenopodium album . The metabolite, which shows interesting phytotoxic properties, together with ascaulitoxin (recently characterized as N.2-beta-D-glucoside of the unusual bis-amino acid 2,4,7-triamino-5-hydroxyoctandioc acid) and another unidentified compound, compose an active fraction of A . caulina culture filtrates with promising herbicidal properties . When assayed on leaves of host and non host dicots, including wild and cultivated plants, the trans-4-aminoproline showed a wide range of toxicity, with leaves of C . album being the most sensitive . Other interesting aspects were its inefficacy on several monocots, both cultivated and wild, and its lack of antifungal, antibiotic and zootoxic activities . This is the first report on trans-4-aminoproline as naturally occurring compound and phytotoxic metabolite produced by A . caulina.

Antimicrob Agents Chemother, 2000 Mar, 44(3), 574 - 7
Faropenem transport across the renal epithelial luminal membrane via inorganic phosphate transporter Npt1; Uchino H et al.; We previously showed that the mouse inorganic phosphate transporter Npt1 operates in the hepatic sinusoidal membrane transport of anionic drugs such as benzylpenicillin and mevalonic acid . In the present study, the mechanism of renal secretion of penem antibiotics was examined by using a Xenopus oocyte expression system . Faropenem (an oral penem antibiotic) was transported via Npt1 with a Michaelis-Menten constant of 0.77 +/- 0.34 mM in a sodium-independent but chloride ion-sensitive manner . When the concentration of chloride ions was increased, the transport activity of faropenem by Npt1 was decreased . Since the concentration gradient of chloride ions is in the lumen-to-intracellular direction, faropenem is expected to be transported from inside proximal tubular cells to the lumen . So, we tested the release of faropenem from Xenopus oocytes . The rate of efflux of faropenem from Npt1-expressing oocytes was about 9.5 times faster than that from control water-injected Xenopus oocytes . Faropenem transport by Npt1 was significantly inhibited by beta-lactam antibiotics such as benzylpenicillin, ampicillin, cephalexin, and cefazolin to 24.9, 40 . 5, 54.4, and 26.2% of that for the control, respectively . Zwitterionic beta-lactam antibiotics showed lesser inhibitory effects on faropenem uptake than anionic derivatives, indicating that Npt1 preferentially transports anionic compounds . Other anionic compounds, such as indomethacin and furosemide, and the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid significantly inhibited faropenem uptake mediated by Npt1 . In conclusion, our results suggest that Npt1 participates in the renal secretion of penem antibiotics.

J Gynecol Obstet Biol Reprod (Paris), 2000 Feb, 29(1), 102 - 4
{Granulomatous recurrent mastitis during pregnancy}; Laghzaoui Boukaidi M et al.; We report a case of granulomatous mastitis during pregnancy which raised important diagnostic and therapeutic problems . Several diagnoses were suspected and subsequently different therapeutic regimen were tried (antibiotic therapy associated with nonsteroidal antiinflammatory drugs, progestogens, vein tonicity drugs and bromocriptine) . All were ineffective and the patients status worsened . Histology confirmed the diagnosis of granulomatous recurrent mastitis . Corticosteroid therapy and interruption of pregnancy successfully controlled the disease process.

Int J Pharm, 2000 Feb 25, 196(1), 115 - 25
Gentamicin encapsulation in PLA/PLGA microspheres in view of treating Brucella infections; Prior S et al.; In view of treating intracellular Brucella infections, microspheres made of poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) were developed as delivery system for the cationic and highly hydrophilic antibiotic gentamicin sulphate . Drug microencapsulation by spray drying yielded microspheres with regular morphology, an average particle size of approximately 3 micrometer and encapsulation efficiencies of up to 45% . Different copolymers of similar molecular weights gave varying encapsulation efficiencies and particle size distributions . The encapsulation efficiency generally increased with polymer hydrophilicity, except for the hydrophilic copolymer PLGA50:50H carrying carboxylic end groups . Encapsulation also depended on the pH value of the aqueous drug solution to be encapsulated . Moreover, increasing nominal gentamicin sulphate loading yielded lower efficiencies . For comparison, some formulations were also prepared by a (W(1)/O)W(2)-solvent evaporation method, which yielded lower encapsulation efficiencies, in the order of 13% . Finally, drug bioactivity was found to remain intact after microencapsulation, MS storage and MS incubation in aqueous medium . The results suggest that PLA/PLGA microspheres prepared by spray drying may be an appropriate delivery system for gentamicin sulphate to be used in the treatment of intracellular Brucella infections.

J Neurol Sci, 2000 Feb 1, 173(1), 40 - 4
Changes in uptake of vitamin B(12) and trace metals in brains of mice treated with clioquinol; Yassin MS et al.; Clioquinol is a hydroxyquinoline antibiotic that has been associated with severe side-effects in the CNS . The syndrome caused by clioquinol treatment, subacute myelo-optic neuropathy (SMON), is considered as one of the worst drug disasters of this century . The precise biochemical mechanism behind SMON is not fully understood . Clioquinol can form strong lipophilic chelates with divalent cations and therefore it has been speculated that the drug may disturb the retention of vitamin B(12) through chelation of Co(2+) . In the present study, the tissue distribution and uptake capacity of {57Co}cyanocobalamin were estimated in mice treated with clioquinol or saline . The concentrations of some trace metals were also determined in brain tissue . Accumulation of vitamin B(12) in the brain and its concentration in blood were decreased by clioquinol treatment . The mean concentrations of several trace metals were also lowered in the brain while the concentration of cobalt in the brain was not affected, suggesting that clioquinol does not bind to the cobalt in vitamin B(12) . Moreover, a significant decrease in the levels of S-adenosylmethionine (SAM) was observed in the brain after clioquinol treatment . This may be a consequence of decreased vitamin B(12) levels . From these results, it can be concluded that chronic treatment with clioquinol may alter the tissue homeostasis of vitamin B(12) in the brain.

Biochim Biophys Acta, 2000 Feb 15, 1463(2), 323 - 32
Deuterium NMR investigation of an amphotericin B derivative in mechanically aligned lipid bilayers; Hing AW et al.; The methyl-d(3) amide derivative of the polyene antibiotic amphotericin B was synthesized, assayed for biological activity, incorporated into mechanically aligned bilayers of dipalmitoylphosphatidylcholine (DPPC), and examined by deuterium and phosphorus NMR . The amide derivative has a lesser, but qualitatively similar, biological activity relative to amphotericin B . Incorporation of the amide derivative and ergosterol into aligned DPPC bilayers resulted in a single, stable bilayer phase, as shown by phosphorus NMR of the DPPC headgroups . Deuterium NMR spectra revealed one major (2)H quadrupolar splitting and one major (2)H-(1)H dipolar splitting in the liquid-crystalline phase, consistent with a high degree of alignment and a single, averaged physical state for amphotericin B methyl-d(3) amide in the bilayer . Variations of the quadrupolar and dipolar splittings as a function of macroscopic sample orientation and temperature indicated that the amide derivative undergoes fast rotation about a motional axis that is parallel to the bilayer normal.

Ann Chir Plast Esthet, 1999 Dec, 44(6), 617 - 24; discussion 625-6
{Skin and muscle flaps to cover and fill chronic open osteitis of the tibia . Results with 10 cases}; Goncalves J et al.; Chronic osteomyelitis is a severe long-term bone infection which retains its mechanical qualities . The authors report 10 cases of osteomyelitis of the tibia treated by muscular and fascio-cutaneous flaps and reviewed at one year follow-up . Four cases concerned the third upper part of the tibia, 3 the middle and 3 the lower third . Two total failures at the third lower part and three complications which finally healed with delay were observed . The results of this small series compared with the reports in the literature suggest the value of large excision with coverage by a well vascularized flap and the need for antibiotics . The choice of flap is related to type and site of the bone defect . Another question should be raised concerning the surgical strategy in one--or two--stage management and the duration of antibiotic therapy.

Curr Opin Obstet Gynecol, 1999 Dec, 11(6), 541 - 7
Role of amniocentesis for the diagnosis of subclinical intra-amniotic infection in preterm premature rupture of the membranes; Blackwell SC et al.; The clinical role of amniocentesis in the management of pregnancies that are complicated by preterm premature rupture of the membranes remains unclear . The indiscriminant use of expectant management, corticosteroids, and empiric antibiotic therapy without knowledge of the presence or absence of intra-amniotic infection poses underappreciated risks to the fetus . This clinical opinion presents the argument that amniocentesis should be an integral part of the management of patients with preterm premature rupture of the membranes . The technical aspects of amniocentesis, the associations between subclinical infection and neonatal morbidity, and the limitations of current interventions are reviewed, and suggestions for future studies that are sorely needed are offered.

Eur J Radiol, 2000 Jan, 33(1), 63 - 5
Laryngopyocele: signs on computed tomography; Nazaroglu H et al.; A laryngocele is an air-filled dilation of the saccule of the larynx . An infected laryngocele is called a laryngopyocele . Our experience with a case of laryngopyocele with signs on computed tomography before and after antibiotic therapy is presented since laryngopyocele is more unusual.

Vet Rec, 2000 Jan 15, 146(3), 61 - 5
Therapeutic efficacy of water-soluble lincomycin-spectinomycin powder against porcine proliferation enteropathy in a European field study; McOrist S et al.; Controlled clinical trials to a standardised protocol were conducted into the effect of a water-soluble antibiotic on proliferative enteropathy and its causative agent (Lawsonia intracellularis) on commercial pig farms at six sites in four European countries . Clinical signs of the disease and L intracellularis-specific polymerase chain reaction (PCR)-positive pigs were detected in pens of six- to 12-week-old pigs (weighing 5 to 55 kg) immediately before each trial . Matched pens of randomised pigs were either left unmedicated (32 to 59 pigs per trial), or medicated orally with 10 mg/kg of a water-soluble combination of lincomycin and spectinomycin powder (21 and 42 mg, respectively, of antibiotic activity per litre) for either seven days (33 to 61 pigs per trial), or 14 days (33 to 61 pigs per trial), delivered via the drinking water . Investigators did not know which pens received which treatment In most of the affected pigs in each trial, diarrhoea due to L intracellularis resolved within three to seven days after the medication began, whereas most unmedicated pigs remained diarrhoeic for at least 10 days . On average the medicated pigs gained more weight than the unmedicated pigs over the 21-day trial period (P=0.01) . In two trials, the absence of L intracellularis after the treatment ended was confirmed by the PCR.

Br J Radiol, 1999 Oct, 72(862), 1006 - 11
Magnetic resonance imaging of actinomycosis presenting as pelvic malignancy; Hawnaur JM et al.; Pelvic actinomycosis is associated with long-standing use of an intrauterine contraceptive device and may present with clinical signs and symptoms of pelvic malignancy . Diagnostic imaging can confirm the presence of a pelvic mass and tissue infiltration but findings are often non-specific . We present a case of pelvic actinomycosis with tubo-ovarian abscess in which magnetic resonance imaging demonstrated lower signal intensity tissue on T2 weighted sequences than would be typical for pelvic malignancy or infection and was useful in confirming regression of pelvic disease in response to antibiotic therapy.

Bone Marrow Transplant, 2000 Feb, 25(3), 319 - 20
Sequential vidarabine infusion in the treatment of polyoma virus-associated acute haemorrhagic cystitis late after allogeneic bone marrow transplantation; Vianelli N et al.; Late onset haemorrhagic cystitis (HC) occurs in 20-30% of allogeneic bone marrow transplant patients . Human polyomavirus BK (BKV) (or less frequently adenovirus) may be involved in the pathogenesis of viral HC and can represent a serious post-transplant complication . Diagnosis and treatment of viral HC can be difficult and has an uncertain outcome . We report the efficacy of sequential vidarabine in the treatment of a patient with severe BKV-associated HC, despite the delay in implementing therapy . Bone Marrow Transplantation (2000) 25, 319-320.

Biophys Chem, 2000 Jan 17, 83(2), 83 - 8
Dimerization kinetics of violamycin BI anthracycline--the influence of ionic strength; Oncescu T et al.; Violamycin BI is an anthracycline derivative with two sugars hanging on, each of them carries one positive charge . It dimerizes under conditions, which depend on the concentration of the antibiotic, pH and the ionic strength of the solution . By keeping a constant pH in a phosphate-EDTA buffer, the rate constants of violamycin BI dimerization were determined at various ionic strengths by temperature jump method . The dimerization constant Kd, resulting from the ratio of these rate constants, confirmed the values obtained spectrophotometrically in this study or elsewhere . The influence of ionic strength (0.02-0.2 M) on the rate constant values suggested to us some speculations on the reaction mechanism of the dimerization, in which, the specific mutual orientation of the monomers in the encounter, and perhaps a specific conformation of their side groups is required before a stabilizing action of the binding forces sets in.

Anaesthesist, 1999 Dec, 48(12), 900 - 3
{Bilateral hydrothorax with hydromediastinum after accidental catheter dislocation}; Dobel KU et al.; We report a complication during the insertion time of a central venous catheter in a patient with intracerebral bleeding . This complication was caused by an inadvertent dislocation of a subclavian catheter . Hydromediastinum and bilateral hydrothorax developed . There was a clear diagnosis followed by removal of the central venous catheter after radiological investigations could explain the cause of the complication and the clinical symptoms . In the course of events mediastinitis was diagnosed . The clinical condition improved under antibiotic therapy . The patient could be transferred to another clinical unit for endovascular treatment of an arterio-venous cerebral malformation.

Mol Microbiol, 2000 Feb, 35(3), 623 - 34
Promoter discrimination by the related transcriptional activators MarA and SoxS: differential regulation by differential binding; Martin RG et al.; MarA and SoxS are closely related proteins ( approximately 45% identical) that transcriptionally activate a common set of unlinked genes, resulting in multiple antibiotic and superoxide resistance in Escherichia coli . Both proteins bind as monomers to a 20 bp degenerate asymmetric recognition sequence, the 'marbox', located upstream of the promoter . However, the proteins differ widely in the extents to which they activate particular promoters, with the consequence that overexpression of SoxS leads to greater superoxide resistance than does overexpression of MarA . This 'discrimination' between activators by promoters was demonstrated in vivo, using promoters fused to lacZ, and in vitro, using purified RNA polymerase, promoter DNA and MarA or SoxS . The marbox was found to be a critical element in discrimination by in vivo and in vitro assays of hybrid promoters containing the marbox from one gene and the core promoter from another . Furthermore, by sequential mutation of its marbox, a promoter that discriminated 35-fold in favour of SoxS was converted into one that did not discriminate . The relative activation of a promoter by MarA or SoxS was paralleled by the relative binding of the two activators to the promoter's marbox as assayed by band shift experiments . Thus, differential recognition of closely related marbox sequences by the closely related activators is the primary basis for promoter discrimination . Discrimination enables the cell to customize its response to the stresses that trigger synthesis of the activators.

Minim Invasive Neurosurg, 1999 Dec, 42(4), 204 - 6
Pituitary abscess secondary to isolated sphenoid sinusitis; Shono T et al.; Intracranial complications from isolated sphenoid sinusitis are rare but nevertheless demonstrate both a high morbidity and mortality . We herein report a case of a pituitary abscess secondary to sphenoid sinusitis in a 12-year-old boy . This patient presented with an acute onset of moderate fever and headache, followed by progressive right ptosis . An emergency endoscopic endonasal sphenoidotomy with sinus drainage and postoperative antibiotic therapy resulted in a satisfactory recovery.

Wien Klin Wochenschr, 1999 Dec 10, 111(22-23), 945 - 50
Has the presence or absence of Borrelia burgdorferi sensu lato as detected by skin culture any influence on the course of erythema migrans?
Logar M, Lotric-Furlan S, Maraspin V, Cimperman J, Jurca T, Ruzic-Sabljic E, Strle F.
The aim of this prospective study was to compare epidemiological and clinical data in patients with a positive Borrelia burgdorferi sensu lato culture and culture-negative erythema migrans skin lesions . Of the 546 adult patients with erythema migrans seen at our institution in 1997 in whom a skin biopsy was performed and the specimen cultured for the presence of B . burgdorferi sensu lato, 235 (43%) had a positive and 311 (57%) a negative skin culture . More women than men were present in both groups and women were also significantly older than men . Tick bites resulting in culture-positive erythema migrans predominated in May (p = 0.012), while in August and September tick bites with subsequent culture-negative skin lesions were more common (p = 0.018 and 0.011, respectively) . Similarly, erythema migrans lesions noticed by our patients in May were significantly more often Borrelia culture positive than negative (p = 0.004), while lesions appearing in October were significantly more often culture negative (p = 0.004) . In addition to these seasonal differences, the comparison of the large number of Borrelia skin culture-positive and -negative patients with erythema migrans also revealed differences in several clinical parameters including a larger diameter of skin lesions in the culture-positive group (p = 0.007 at presentation, and p = 0.039 at registration, respectively), a lesser number of multiple skin lesions (7/235 versus 27/311, p = 0.006), and a lower frequency of signs/symptoms (p = 0.039) associated with erythema migrans lesions in culture-positive than in culture-negative patients . We have no plausible explanation for the majority of these rather unexpected findings . Of the 59 patients who, prior to biopsy, had received brief courses of antibiotics known to be effective in the treatment of erythema migrans, 12 (20.3%) were culture positive . As anticipated, the ratio of culture positivity in pretreated patients was significantly lower (p < 0.001) than in those without antecedent antibiotic therapy.

Wien Klin Wochenschr, 1999 Dec 10, 111(22-23), 941 - 4
The outcome of Lyme borreliosis in children; Aberer E et al.; Austria is an endemic area for Lyme borreliosis . The IgG seroprevalence of healthy blood donors as investigated by a DAKO flagellum-ELISA in Graz/Styria is 13% . In order to determine whether this high seroprevalence is caused by infection in childhood, 36 children aged 3 to 18 years (mean, 10.1 years) were followed up over 2 to 20 months (mean, 11.1 months) and reinvestigated for clinical symptoms and antibodies against B . burgdorferi by a commercial flagellum ELISA and a commercial B . garinii Western blot (WB) . Twenty-seven children had erythema migrans (EM), one of them with reinfection, 5 had borrelia lymphocytoma (BL), 2 EM and BL, 1 acrodermatitis chronica atrophicans and 1 ACA/circumscribed scleroderma . Before treatment with either phenoxymethylpenicillin, amoxicillin, or minocyclin for 3-4 weeks, 64% of the patients were IgM and 44%, IgG seropositive . Clinically, all but 5 patients with EM recovered from Lyme borreliosis . Among these 5 patients--one of them with reinfection of EM--3 had mild arthralgia, 1 recurrent headache and 1 concentration disturbance . Only 2 children with arthralgia were IgM positive by ELISA and WB . One of 5 BL patients had a persistent swelling of the ear lobe although with a negative serology before and after several antibiotic treatments and at follow up . In 16 children serological investigations were performed after more than 12 months (range, 13-20 months) . Eighteen percent of them had IgM antibodies by ELISA, 25% by WB, and 6% IgG antibodies by ELISA and 6% by WB . Although there was a decline of antibody response from 64% to 18% for IgM and from 44% to 6% for IgG as measured by ELISA, children remain seropositive for more than 1 year with or without clinical symptoms . The relevance of the association with clinical symptoms can be raised by combining several diagnostic methods . It is assumed that recurrent, often silent, infections might increase antibody titres . It should be noted that antibody titres also generally increase with the age of individuals.

J Am Acad Orthop Surg, 2000 Jan-Feb, 8(1), 21 - 36
Ballistics and gunshot wounds: effects on musculoskeletal tissues; Bartlett CS et al.; As a result of the increasing number of weapons in this country, as many as 500,000 missile wounds occur annually, resulting in 50,000 deaths, significant morbidity, and striking socioeconomic costs . Wounds are generally classified as low-velocity (less than 2,000 ft/sec) or high-velocity (more than 2,000 ft/sec) . However, these terms can be misleading; more important than velocity is the efficiency of energy transfer, which is dependent on the physical characteristics of the projectile, as well as kinetic energy, stability, entrance profile and path traveled through the body, and the biologic characteristics of the tissues injured . Although bullets are not sterilized on discharge, most low-velocity gunshot wounds can be safely treated nonoperatively with local wound care and outpatient management . Typically, associated fractures are treated according to accepted protocols for each area of injury . Treatment of low-velocity, low-energy fractures is generally dictated by the osseous injuries, as these are similar in many regards to closed fractures . Soft tissues play a more critical role in high-velocity and shotgun fractures, which are essentially open injuries . Aside from perioperative prophylaxis, antibiotics are probably required only for grossly contaminated wounds; however, because contamination is not always apparent, most authors still recommend routine prophylaxis . High-energy injuries and grossly contaminated wounds mandate aggressive irrigation and debridement, including a thorough search for foreign material . Open fracture protocols including external fixation or intramedullary nailing and intravenous antibiotic therapy for 48 to 72 hours should be instituted . If there is vascular damage, exploration and repair are best performed after prompt fracture stabilization . Evaluation of the "four Cs"-color, consistency, contractility, and capacity to bleed-provides valuable information regarding the viability of muscle . Skin grafting is preferable when tension is required for wound closure, although other soft-tissue procedures, such as use of local rotation flaps or free tissue transfer, may be necessary, especially for shotgun wounds . Distal neurologic deficit alone is not an indication for exploration, as it often resolves without surgical intervention.

Acta Crystallogr D Biol Crystallogr, 2000 Jan, 56 ( Pt 1), 101 - 3
Crystallization of type I chloramphenicol acetyltransferase: an approach based on the concept of ionic strength reducers; Andreeva AE et al.; Chloramphenicol acetyltransferase (CAT) is responsible for bacterial resistance to chloramphenicol . It catalyzes inactivation of the antibiotic by acetyl-group transfer from acetyl CoA to one or both hydroxyl groups of chloramphenicol . Type I CAT possesses some unique properties which are not observed in other CAT variants . Type I CAT overexpressed in Escherichia coli was purified and crystals with a resolution limit of 2.22 A have been obtained using a novel procedure which is based on the concept of 'ionic strength reducers' . The crystals have the symmetry of space group P1 and unit-cell parameters a = 96.46, b = 113.86, c = 114.21 A, alpha = 119.9, beta = 94.1, gamma = 98.6 degrees . These dimensions are consistent with four to six trimers per unit cell, corresponding to a solvent fraction ranging from 65 to 47%.

Arch Biochem Biophys, 2000 Feb 15, 374(2), 279 - 85
Carvedilol inhibits the exogenous NADH dehydrogenase in rat heart mitochondria; Oliveira PJ et al.; There are several reports on the oxidation of external NADH by an exogenous NADH dehydrogenase in the outer leaflet of the inner membrane of rat heart mitochondria . Until now, however, little was known about its physiological role in cellular metabolism . The present work shows that carvedilol ( inverted question mark1-{carbazolyl-(4)-oxy}-3-{2-methoxyphenoxyethyl)amino}-pro - panol-(2) inverted question mark) is a specific inhibitor of an exogenous NADH dehydrogenase in rat heart mitochondria . Carvedilol does not affect oxygen consumption linked to the oxidation of succinate and internal NADH . It is also demonstrated that the inhibition of exogenous NADH dehydrogenase by carvedilol is accompanied by the inhibition of alkalinization of the external medium . In contrast to the addition of glutamate/malate or succinate, exogenous NADH does not generate a membrane potential in rat heart mitochondria, as observed with a TPP(+) electrode . It is also demonstrated that the oxygen consumption linked to NADH oxidation is not due to permeabilized mitochondria, but to actual oxidase activity in the inner membrane . The enzyme has a K(m) for NADH of 13 microM . Carvedilol is a noncompetitive inhibitor of this external NADH dehydrogenase with a K(i) of 15 microM . Carvedilol is the first inhibitor described to this organospecific enzyme . Since this enzyme was demonstrated to play a key role in the cardiotoxicity of anticancer drugs of the anthracycline family (e.g., adriamycin), we may suggest that the administration of carvedilol to tumor patients treated with adriamycin might be of great help in the prevention of the cardioselective toxicity of this antibiotic .

J Vasc Surg, 2000 Feb, 31(2), 325 - 42
Preoperative treatment with doxycycline reduces aortic wall expression and activation of matrix metalloproteinases in patients with abdominal aortic aneurysms; Curci JA et al.; PURPOSE: Matrix metalloproteinases (MMPs) are considered to play a central role in the pathogenesis of abdominal aortic aneurysms (AAAs) . Doxycycline (Dox) has direct MMP-inhibiting properties in vitro, and it effectively suppresses the development of elastase-induced AAAs in rodents . The purpose of this study was to determine if treatment with Dox suppresses MMPs within human aneurysm tissue and to elucidate the molecular mechanisms underlying this effect . METHODS: Aneurysm tissues were obtained from 15 patients with an AAA, eight of whom had been treated with Dox before surgery (100 mg orally twice a day for 7 days) . Protein extracts were examined by means of gelatin zymography and immunoblot analysis, and RNA was examined by means of reverse transcription-polymerase chain reaction (RT-PCR) . The effects of Dox on MMP production were further examined in human THP-1 mononuclear phagocytes in vitro . RESULTS: No detectable difference was found between groups by using substrate zymography as a means of assessing total MMP activity, but Dox treatment was associated with a slight (24.4%) reduction in the activated fraction of 72-kDa gelatinase (MMP-2; P <.05) . In contrast, a 2.5-fold reduction in the amount of extractable 92-kDa gelatinase (MMP-9) protein in Dox-treated patients was revealed by means of immunoblot analysis (P <.05) . Also, a 5.5-fold (81.9%) reduction in MMP-9 messenger RNA (mRNA) in Dox-treated patients was demonstrated by means of quantitative competitive RT-PCR (mean +/- SE, mol MMP-9/mol beta-actin: 1.3 +/- 0.5 vs 7.2 +/- 3.1; P <.04) . There was no significant difference between groups in the relative expression of MMP-2 protein or mRNA . In cultured THP-1 monocytes stimulated with phorbol ester, the expression of MMP-9 protein and mRNA were both decreased after exposure to relevant concentrations of Dox in vitro . CONCLUSION: In addition to its recognized effects as a direct MMP antagonist, Dox may influence connective tissue degradation within human aneurysm tissue by reducing monocyte/macrophage expression of MMP-9 mRNA and by suppressing the post-translational processing (activation) of proMMP-2 . Through this complementary combination of mechanisms, treatment with Dox may be a particularly effective strategy for achieving MMP inhibition in patients with an AAA.

J Hepatobiliary Pancreat Surg, 1999, 6(4), 418 - 21
Gallbladder torsion: case report and review of 245 cases reported in the Japanese literature; Nakao A et al.; We report here a case of torsion of the gallbladder in a 73-year-old woman . The patient was admitted to our hospital with right hypochondralgia . Ultrasonography and computed tomography demonstrated a distended gallbladder, with a multilayered wall, which contained no stones . Since the symptoms did not respond to antibiotics, laparotomy was performed . The gallbladder was found to be twisted around its pedicle and to be gangrenous . Cholecystectomy was performed, and the patient had an uneventful postoperative course . We also reviewed 245 cases reported in the Japanese literature . The clinical features of gallbladder torsion, which include low frequency of fever and jaundice, poor response to antibiotic therapy, and acute onset of abdominal pain, may be helpful in the differential diagnosis from acute cholecystitis . Moreover, a highly suggestive sign of gallbladder torsion observed by ultrasonography or computed tomography is a markedly enlarged "floating" gallbladder with a continuous hypoechoic line indicating edematous change in the wall.

Intensive Care Med, 2000 Jan, 26(1), 20 - 30
The diagnosis of ventilator-associated pneumonia using non-bronchoscopic, non-directed lung lavages; Flanagan PG et al.; OBJECTIVES: (1)To assess the diagnostic utility of quantitative cultures of non-bronchoscopic lung lavage (NBL) in ventilator-associated pneumonia and evaluate the role of the Bacterial Index; (2) To assess the predictive value of NBL surveillance quantitative cultures in ventilated patients; (3) To evaluate the Clinical Pulmonary Infection Score (CPIS) system in ventilated patients . DESIGN: A prospective comparison of NBL with bronchoscopic bronchoalveolar lavage and protected specimen brush . SETTING: Three intensive care units in academic tertiary care centres . PATIENTS: 145 adults ventilated for 72 h, with and without clinical signs of pneumonia . INTERVENTIONS: Sampling of lower airway secretions by NBL, bronchoalveolar lavage and protected specimen brush . MAIN OUTCOME MEASURES: Diagnostic reliability of quantitative cultures, Bacterial Index and CPIS . RESULTS: 34 episodes of clinical ventilator-associated pneumonia were documented in 32 patients . 9 episodes were confirmed by concordant blood/pleural culture or post-mortem lung examination . Qualitative concordance of the predominant pathogen between sequential NBL: bronchoalveolar lavage and protected specimen brush was 83 % . Sensitivity and specificity of non-directed bronchial lavage at a threshold of 10(4) CFU/ml were 68 % and 70 % respectively (p = 0 . 003) and were comparable with the bronchoscopic methods . However, the low positive predictive value of NBL indicates that quantitation in the absence of clinical signs is unlikely to be useful . Bacterial Index did not improve discriminatory power of quantitation compared with bacterial load of predominant organism . Mean CPIS for confirmed pneumonia cases was 8.4 +/- 1.01, significantly higher than for non-pneumonia observations (p = < 0.0001) . CONCLUSION: NBL is a simple, safe, cheap, readily-available method of diagnosing ventilator-associated pneumonia with comparable diagnostic accuracy to bronchoscopic techniques . Quantitation of respiratory tract cultures can exclude pneumonia in patients with equivocal clinical signs . The diagnostic threshold should vary depending on the length of ventilation, likelihood of pneumonia and antibiotic administration . The Bacterial Index is a flawed mathematical device that has no contributory role in pneumonia diagnosis . The CPIS has some diagnostic role in selected cohorts of ventilated patients.

HNO, 2000 Jan, 48(1), 18 - 21
{Antimycotic therapy in otomycosis with tympanic membrane perforation}; Dyckhoff G et al.; Especially after prolonged antibiotic ototopic therapy otomycosis is not rare . An inoculation of fungi into the tympanic cavity however may have serious sequelae . Therefore an eradication of fungi from the external auditory canal is imperative before surgery . In addition to thorough cleaning of the outer ear canal antimycotic preparations are recommended in treating otomycosis . However, all of the commercially available ear drops contain ototoxic agents . In the case of defects of the tympanic membrane a damage of the inner ear may result . Alternatively, we suggest an aqueous solution of Miconazol 0,5%.

Chirurg, 2000 Jan, 71(1), 93 - 7
{Actinomycosis of the colon as a rare differential diagnosis of colonic carcinoma}; Rose G et al.; INTRODUCTION: Abdominal actinomycosis is an uncommon disease . Nevertheless it should be considered in case of unclear tumor-like abdominal masses . METHODS: We report a case of a 49-year-old patient with an intrauterine device . The patient was submitted with a solid and painful tumor in the upper abdomen . After sonography, computerized tomography, gastroduodenoscopy and colonoscopy the preoperative presumptive diagnosis was a carcinoma of the transvers colon invading the abdominal wall . Pathological examination after a right hemicolectomy surprisingly revealed an actinomycosis . RESULTS: Based on this case diagnostic tools and therapeutic options of actinomycosis of the colon are discussed . CONCLUSIONS: This case illustrates the importance to consider the possibility of actinomycosis when finding an unclear abdominal mass . After a surgical excision an abdominal actinomycosis requires antibiotic therapy.

Chem Biol, 2000 Feb, 7(2), 133 - 42
Function of glycosyltransferase genes involved in urdamycin A biosynthesis; Trefzer A et al.; BACKGROUND: Urdamycin A, the principle product of Streptomyces fradiae Tu2717, is an angucycline-type antibiotic . The polyketide-derived aglycone moiety is glycosylated at two positions, but only limited information is available about glycosyltransferases involved in urdamycin biosynthesis . RESULTS: To determine the function of three glycosyltransferase genes in the urdamycin biosynthetic gene cluster, we have carried out gene inactivation and expression experiments . Inactivation of urdGT1a resulted in the predominant accumulation of urdamycin B . A mutant lacking urdGT1b and urdGT1c mainly produced compound 100-2 . When urdGT1c was expressed in the urdGT1b/urdGT1c double mutant, urdamycin G and urdamycin A were detected . The mutant lacking all three genes mainly accumulated aquayamycin and urdamycinone B . Expression of urdGT1c in the triple mutant led to the formation of compound 100-1, whereas expression of urdGT1a resulted in the formation of compound 100-2 . Co-expression of urdGT1b and urdGT1c resulted in the production of 12b-derhodinosyl-urdamycin A, and co-expression of urdGT1a, urdGT1b and urdGT1c resulted in the formation of urdamycin A . CONCLUSIONS: Analysis of glycosyltransferase genes of the urdamycin biosynthetic gene cluster led to an unambiguous assignment of each glycosyltransferase to a certain biosynthetic saccharide attachment step.

Int J Epidemiol, 1999 Dec, 28(6), 1167 - 71
Incidence of trichiasis in a cohort of women with and without scarring; Munoz B et al.; BACKGROUND: Blindness from trachoma is a significant problem for many underdeveloped countries . While active trachoma is common in children, trichiasis, the potentially blinding sequella, develops in adulthood and affects mainly women . Little is known about factors associated with the development of trichiasis . METHODS: The 7-year incidence of trichiasis and its association with ocular chlamydia infection was examined in a cohort of women from a hyperendemic area . A total of 4,932 women 18 years and older, living in 11 villages in Central Tanzania, were examined in 1989 . A follow-up examination in 1996 was performed on all women with scars living in six of the 11 villages and on a random sample of women without scars from the same villages . Trachoma was graded clinically, chlamydia infection was ascertained at follow-up using polymerase chain reaction-enzyme immunoassay (PCR-EIA) . RESULTS: A total 523 of the women with scars and 503 of the women without scars were re-examined . Forty-eight of the women with scars (incidence, 9.2%) and three of the women without scars (0.6%) developed trichiasis in the 7-year period . Prevalence of chlamydia infection was significantly higher in the group with scars (11.7% versus 7.1%) . Trichiasis cases were more likely to be older, and to have chlamydia infection at follow-up odds ratio (95% confidence interval) 2.5 (1.1-5.7) . CONCLUSION: The 7-year incidence rate in the population with scars was high, over 1% per year . Ocular chlamydia infection was more common in the group with scars at baseline and was also associated with being a trichiasis case, suggesting the importance of potentially long-term chlamydia infection in the progression to trichiasis . Antibiotic distribution programmes for trachoma control should include women with scars.

Microbiology, 2000 Jan, 146 ( Pt 1), 139 - 46
The mycarose-biosynthetic genes of Streptomyces fradiae, producer of tylosin; Bate N et al.; The tylCK region of the Streptomyces fradiae genome was sequenced, revealing an incomplete set of five tylC genes encoding all-but-one of the enzymes involved in the biosynthesis of mycarose . The latter is a 6-deoxyhexose sugar required during production of the macrolide antibiotic, tylosin . The missing mycarose-biosynthetic gene, tylCVI, was found about 50 kb distant from its functional partners, on the other side of the tylG (polyketide synthase) gene complex . Mutational analysis, involving targeted gene transplacement, was employed to confirm the functions of specific genes, including tylCVI . Particularly interesting was the similarity between the tylosin-biosynthetic mycarosyltransferase enzyme, TylCV, and proteins of the macrolide glycosyltransferase (MGT) family that inactivate macrolides via glycosylation of attached sugar residues and are involved in resistance and/or antibiotic efflux . The arrangement of genes within the 'mycarose cluster' would allow their expression as two short operons with divergent, and perhaps co-regulated, promoters . Whether displacement of tylCVI relative to the other tylC genes provides additional regulatory opportunities remains to be established.

Eur J Cancer, 1999 Sep, 35(9), 1349 - 55
Toxicity, supportive care and costs of two chemotherapy protocols for treatment of childhood ALL in Russia: BFM 90m and MB 91; von Stackelberg A et al.; Since the late 1980s, polychemotherapy protocols for the treatment of childhood acute lymphoblastic leukaemia (ALL) derived from Western European and American regimens have been introduced in Russian paediatric oncology centres . Whereas treatment results were significantly improved compared with the results of former non-standard treatment strategies, the substantial toxicity of these protocols required a high standard of supportive care, and the high costs of treatment became a major problem . In 1991, a new protocol was developed with the aim of reducing toxicity and costs without affecting efficacy of the treatment . Since 1991, a single-centre study comparing the new Russian Protocol, Moscow-Berlin 91 (MB), with a modified version of the protocol ALL BFM 90 (BFM) of the Berlin-Frankfurt-Munster group was performed in Moscow to evaluate possible advantages of the new protocol under Russian conditions . The aim of the present analysis was to compare toxicity, need of supportive care and expense of both regimens (BFM, 25 pts; MB, 32 pts) . Hepatotoxicity (liver enzymes), nephrotoxicity (creatinine), duration of neutropenia, and platelet transfusions were similar in both protocols . The median erythrocyte transfusion level was greater in the BFM (1000 ml/m2) than the MB patients (505 ml/m2, P < 0.01), as was the length of intravenous (i.v.) antibiotic therapy (22 days BFM versus 9 days MB, P < 0.01), treatment delays (39 days BFM versus 21 days MB, P < 0.001), and duration of in-patient treatment (47 days BFM versus 18 days MB, P < 0.001) . Side-effects of the MB protocol occurred mainly during induction therapy . Total costs (mean cost/person/m2 body surface) of treatment including supportive care were 1.73-fold higher for the BFM protocol than MB, whereas costs of cytostatic drugs were comparable in both groups . In Russia both protocols were feasible . During consolidation therapy tolerance to treatment was better in MB 91 compared with BFM 90m, whereas toxicity during induction therapy was similar in both protocols . With respect to costs and side-effects, the MB 91 protocol appears to be an alternative to established protocols for countries with limited financial and clinical resources.

Med Pediatr Oncol, 2000 Feb, 34(2), 92 - 6
Cost analysis of filgrastim for the prevention of neutropenia in pediatric T-cell leukemia and advanced lymphoblastic lymphoma: a case for prospective economic analysis in cooperative group trials; Bennett CL et al.; BACKGROUND: Growth factor use has been shown to ameliorate chemotherapy-induced neutropenia, leading to shorter hospital stays and lower use of parenteral antibiotics, two costly areas of cancer treatment . Prior reports on pediatric patients have shown evidence of cost savings in some studies, but no such evidence in others . In this study a retrospective analysis compared the costs of inpatient supportive care for pediatric patients with T-cell leukemia and advanced lymphoblastic lymphoma enrolled in a Pediatric Oncology Group trial . PROCEDURE: Patients 1-22 years of age were randomized to receive either granulocyte colony-stimulating factor (G-CSF; n = 45) or no G-CSF (n = 43) following induction and two cycles of maintenance therapy . There were no significant differences in neutropenia-related outcomes during the induction phase . During maintenance therapy, G-CSF patients had significantly fewer days to an ANC >500 cells/microl and a trend towards fewer days of hospitalization . Data on resource utilization were tabulated from case report forms . Costs were imputed from national data on hospitalization costs, average wholesale prices of pharmaceuticals, and patient billing information from a single institution . RESULTS: Total median costs of supportive care were $34,190 for patients receiving G-CSF and $28,653 for patients not receiving G-CSF (P > 0 . 05 for the cost difference) . Sensitivity analyses demonstrated that the total cost difference was not statistically significant, even in scenarios that included reasonable variations in estimates of the range of the length of stay, antibiotic regimen, and dosage and cost of G-CSF . CONCLUSIONS: In the setting of pediatric leukemia, the cost of growth factor may offset potential savings from shorter hospital stays or lower antibiotic use, a finding consistent with that from the Children's Cancer Study Group .

Surg Endosc, 2000 Feb, 14(2), 175 - 8
Video-assisted thoracoscopic surgery in the management of loculated empyema; Cunniffe MG et al.; BACKGROUND: Fibropurulent empyema (stage II of Light) does not respond to antibiotic therapy and simple drainage . If the condition is inadequately treated, restrictive pulmonary deficit develops, necessitating thoracotomy and decortication . We report our experience with the videoscopic management of stage II and limited stage III disease . METHODS: Ten consecutive patients underwent videoscopic debridement of fibropurulent empyema; three of them required removal of limited visceral and parietal rind . RESULTS: The mean operating time was 42 +/- 8.1 min . Postoperative pyrexia and leucocytosis settled within 4.2 +/- 2.1 days and 13.1 +/- 3.2 days, respectively . Intercostal chest tubes were removed by 4.5 +/- 1.0 days . The mean fall in hematocrit following surgery was 4.9% . Parenteral analgesics were required for 1.0 +/- 0.5 days and oral analgesics for 3 +/- 1.6 days . The mean postoperative stay was 11 +/- 8.1 days . No patient required any further intervention . CONCLUSIONS: Videoscopic debridement of empyema produces excellent results, with minimal patient morbidity and a short hospital stay . We recommend it as the preferred method for first-line management of fibropurulent (stage II) empyema.

Ophthalmic Res, 2000 Jan-Feb, 32(1), 13 - 8
The effect of propolis extract in experimental chemical corneal injury; Ozturk F et al.; PURPOSE: To investigate the effect of propolis, a natural resin produced by honeybees, in the treatment of alkali-injured rabbit eyes . METHOD: A corneal alkali burn was induced by applying filter paper immersed in 1 N NaOH on the central axis of the right corneas of 24 rabbits for 30 s . The animals were divided into three treatment groups: group 1 (control) was given 0.3% tobramycin and phosphate-buffered solution; group 2 was treated with antibiotic coverage and topical 1% ethanolic extract of propolis; group 3 received antibiotic coverage and topical 1% dexamethasone . The dexamethasone-treated group was maintained as the positive control . Drugs were instilled 4 times a day for 7 days . The corneal inflammation was evaluated by calculating the average inflammatory index obtained from clinical observation of the ciliary hyperemia, central and peripheral corneal edema at 24 h, 48 h, on day 5 and day 7, before sacrificing the animals . Then, the corneas underwent routine histological examination . RESULTS: The effects of dexamethasone and propolis on healing of injured corneas were similar (p>0.05) and significantly better than controls at 24 h (p<0.01, p< 0.05, respectively), and on day 7 (p<0.05) with respect to the inflammatory index . On histological observation, inflammatory cell infiltration was lower as compared to control in both the dexamethasone and propolis groups (p<0.001) and similar with each other (p>0.05) . CONCLUSIONS: Our study shows that propolis has an anti-inflammatory effect comparable to dexamethasone in chemical corneal injury .

J Cell Biochem, 2000 Jan, 76(4), 674 - 85
Circular YAC vectors containing short mammalian origin sequences are maintained under selection as HeLa episomes; Nielsen TO et al.; pYACneo, a 15.8-kb plasmid, contains a bacterial origin, G418-resistance gene, and yeast ARS, CEN, and TEL elements . Three mammalian origins have been cloned into this circular vector: 343, a 448-bp chromosomal origin from a transcribed region of human chromosome 6q; X24, a 4.3-kb element containing the hamster DHFR origin of bidirectional replication (oribeta), and S3, a 1.1-kb human anti-cruciform purified autonomously replicating sequence . The resulting constructs have been transfected into HeLa cells, and G418-resistant subcultures were isolated . The frequency of G418-resistant transformation was 1.7-8.7 times higher with origin-containing YACneo than with vector alone . After >45 generations under G418 selection, the presence of episomal versus integrated constructs was assessed by fluctuation assay and by PCR of supercoiled, circular, and linear genomic cellular DNAs separated on ethidium bromide-cesium chloride gradients . In stable G418-resistant subcultures transfected with vector alone or with linearized constructs, as well as in some subcultures transfected with circular origin-containing constructs, resistance was conferred by integration into the host genome . However, several examples were found of G418-resistant transfectants maintaining the Y.343 and the YAC.S3 circular constructs in a strictly episomal state after long-term culture in selective medium, with 80-90% stability per cell division . The episomes were found to replicate semiconservatively in a bromodeoxyuridine pulse-labeling assay for </=130 cell generations after transfection . Furthermore, after </=172 cell generations rescued episomal DNA could be isolated intact and unrearranged, and could be used to retransform bacteria . These versatile constructs, containing mammalian origins, have the capacity for further modification with human telomere or large putative centromere elements, in an effort to move towards construction of a human artificial chromosome .

Biophys J, 2000 Feb, 78(2), 571 - 83
Continuum solvent model calculations of alamethicin-membrane interactions: thermodynamic aspects; Kessel A et al.; Alamethicin is a 20-amino acid antibiotic peptide that forms voltage-gated ion channels in lipid bilayers . Here we report calculations of its association free energy with membranes . The calculations take into account the various free-energy terms that contribute to the transfer of the peptide from the aqueous phase into bilayers of different widths . The electrostatic and nonpolar contributions to the solvation free energy are calculated using continuum solvent models . The contributions from the lipid perturbation and membrane deformation effects and the entropy loss associated with peptide immobilization in the bilayer are estimated from a statistical thermodynamic model . The calculations were carried out using two classes of experimentally observed conformations, both of which are helical: the NMR and the x-ray crystal structures . Our calculations show that alamethicin is unlikely to partition into bilayers in any of the NMR conformations because they have uncompensated backbone hydrogen bonds and their association with the membrane involves a large electrostatic solvation free energy penalty . In contrast, the x-ray conformations provide enough backbone hydrogen bonds for the peptide to associate with bilayers . We tested numerous transmembrane and surface orientations of the peptide in bilayers, and our calculations indicate that the most favorable orientation is transmembrane, where the peptide protrudes approximately 4 A into the water-membrane interface, in very good agreement with electron paramagnetic resonance and oriented circular dichroism measurements . The calculations were carried out using two alamethicin isoforms: one with glutamine and the other with glutamate in the 18th position . The calculations indicate that the two isoforms have similar membrane orientations and that their insertion into the membrane is likely to involve a 2-A deformation of the bilayer, again, in good agreement with experimental data . The implications of the results for the biological function of alamethicin and its capacity to oligomerize and form ion channels are discussed.

Pediatrics . 2000 Feb;105(2):E24.
Effect of cisapride on the QT interval in infants with gastroesophageal reflux; Khoshoo V et al.; OBJECTIVE: We prospectively studied the effect of cisapride per se on QT interval in young infants (3-6 months) with gastroesophageal reflux (GER) in a controlled setting . STUDY DESIGN: The infants diagnosed with GER and deemed to require therapy with cisapride were divided into 2 groups . Group A comprised infants with GER who underwent an electrocardiogram (ECG) before initiation of therapy with cisapride in the dose of 1 mg per kg per 24 hours, divided into 3 doses . They were reweighed after 7 to 10 days, and the dose was adjusted for their new weight . A repeat ECG was performed after approximately 2 weeks (12-18 days) of therapy . The QT interval was measured in each ECG and then the corrected QT interval was calculated by Bazett's formula . Group B comprised infants with GER who had already been on therapy with cisapride for over 1 month . All infants in group B received cisapride in an approximate dose of 1 mg per kg per 24 hours (.8-1.1 mg/kg/24 hours) given in 3 divided doses . They underwent only 1 ECG, ie, at 1 to 4 months after initiation of therapy . The measurement of the actual dose of cisapride was demonstrated to every parent and a marked measuring syringe was provided . The following categories of infants were not included: those with any underlying cardiopulmonary, renal, or hepatic problem; those with a history of apnea; those using a macrolide antibiotic or azole antifungal at any stage during the study; and infants hospitalized for any reason during the course of the study . RESULTS: Cisapride therapy in the dose of 1 mg/kg/day frequently resulted in a slight increase in the QT interval (pretreatment: 390 +/- 18 milliseconds; posttreatment: 400 +/- 20 milliseconds) but the increase was still below the accepted upper limit of 440 milliseconds and not statistically significant . Even with prolonged therapy, the pattern of change in QT interval was similar to that with therapy for 2 weeks . Overall, 2 of 100 (2%) infants developed a prolongation of corrected QT interval beyond the normal range (456 and 486 milliseconds) . Neither infant had evidence of any arrhythmia or conduction defect on ECG . No additional factor could be identified in either infant to explain prolongation of the QT interval . CONCLUSION: Our experience suggests that cautious cisapride therapy in young infants in a modest dose does not result in arrhythmias or conduction defects . We recommend that: 1) the dose of cisapride in infants be <1.2 mg/kg/day and preferably between.8 and 1 mg/kg/day; 2) the right measure of the dose be actually demonstrated to the parents; and 3) parents be provided a list of drug interactions with cisapride . One should think twice before denying the use of an effective drug simply because of the need for closer monitoring and extra time spent for parent education.

Pediatrics, 2000 Feb, 105(2), 316 - 9
Cerebrospinal fluid findings in aseptic versus bacterial meningitis; Negrini B et al.; BACKGROUND: Aseptic meningitis is often reported to be characterized by a mononuclear cell predominance in the cerebrospinal fluid (CSF), whereas bacterial meningitis is characterized by a polymorphonuclear (PMN) cell predominance . In contrast, other studies suggest that PMNs can be the most prevalent cell in early aseptic meningitis followed by a shift to mononuclear cells within 24 hours . These contradictory reports may lead to uncertainty in the diagnosis and treatment of meningitis . OBJECTIVES: To assess 1) the characteristics of the CSF differential in aseptic versus bacterial meningitis, 2) the influence of duration of illness on the CSF differential, and 3) the role of the CSF differential in discriminating between aseptic versus bacterial meningitis . METHODS: A retrospective chart review was conducted of all cases of meningitis in children >30 days of age hospitalized during the peak months for enteroviral meningitis (April to October) between 1992 to 1997 . Cases of aseptic meningitis were defined as having at least 20 white blood cells/mm(3) and the absence of bacterial growth on culture . Patients were excluded if they received antibiotic therapy within the previous 5 days . Cases of bacterial meningitis were defined as having a positive culture of the CSF or the presence of a CSF pleocytosis with positive cultures of the blood . CSF variables including white blood cell differential and time from the onset of symptoms to the performance of a lumbar puncture were analyzed . PMNs were considered to be predominant when the percentage of neutrophils added to juvenile forms was >50% of cells . RESULTS: One hundred fifty-eight cases of meningitis were reviewed: 138 were aseptic and 20 were bacterial . The patients ranged in age from 30 days to 18 years; 61% were male . Fifty-seven percent of cases of aseptic meningitis had a PMN predominance . The percentage of PMNs in the CSF in patients with aseptic meningitis was not statistically different for patients who had a lumbar puncture performed either within or beyond 24 hours of the onset of symptoms . Fifty-one percent of the 53 patients with aseptic meningitis and duration of illness >24 hours had a PMN predominance . The ability of a PMN predominance to differentiate between aseptic and bacterial meningitis was assessed . The sensitivity of a PMN predominance for aseptic meningitis is 57% whereas the specificity is 10% . The positive predictive value of a PMN predominance for aseptic disease is 81% but the negative predictive value is 3% . Alternative definitions of PMN predominance from 60% to 90% were not useful as a clinical indicator of bacterial disease . CONCLUSIONS: The majority of children with aseptic meningitis have a PMN predominance in the CSF . The PMN predominance is not limited to the first 24 hours of illness . Because the majority of children with a PMN predominance during enteroviral season will have aseptic disease, a PMN predominance as a sole criterion does not discriminate between aseptic and bacterial meningitis.

Am J Ophthalmol, 2000 Jan, 129(1), 96 - 8
Congenital trigeminal anesthesia in two siblings and their long-term follow-up; Wong VA et al.; PURPOSE: To alert ophthalmologists to congenital trigeminal anesthesia as a cause of corneal scarring and amblyopia and its effective treatment with tarsorrhaphies . METHODS: Case reports . A 2-month-old infant presented with bilateral corneal erosions and complete corneal anesthesia . Her sister presented at age 3 years with a corneal ulcer and corneal hypoesthesia (sensation markedly decreased) . The father and paternal grandmother of the siblings also had corneal hypoesthesia . RESULTS: Further investigation of the infant revealed bilateral hearing loss, swallowing difficulties, and decreased sensation in the trigeminal nerve distribution . A diagnosis of congenital trigeminal anesthesia was made . The corneal erosions of the patient resolved with bilateral two-thirds width tarsorrhaphies . The girl continues to do well now at 10 years of age with ocular lubrication and superficial corneal scar removal . Her older sister initially required antibiotic ointment for her corneal ulcer but now requires only ocular lubrication for congenital trigeminal anesthesia . CONCLUSION: This study describes the earliest reported use of tarsorrhaphies in an infant with congenital trigeminal anesthesia . The presence of this condition in her sister and relatives makes it one of the few reports of congenital trigeminal anesthesia in more than two generations . Early recognition of this condition is essential in the preservation of useful vision.

Ann Emerg Med, 2000 Feb, 35(2), 131 - 7
Safety and efficacy of diclofenac ophthalmic solution in the treatment of corneal abrasions; Szucs PA et al.; STUDY OBJECTIVE: To determine whether the use of diclofenac ophthalmic solution is a safe and effective analgesic in the treatment of traumatic corneal abrasions in the emergency department . METHODS: We conducted a prospective, randomized, double-blinded, placebo-controlled clinical trial . Consenting consecutive patients with corneal abrasions who presented to a community-based ED from August through February 1998 were randomly assigned to receive either diclofenac or control vehicle drops . Pain relief was measured using a visual Numeric Pain Intensity Scale (NPIS) before and after treatment . Exclusion criteria were as follows: age younger than 18 years, pregnancy, history of glaucoma, ocular infection, recent eye surgery, other signs of ocular trauma, narcotics within 6 hours, minimal pain (NPIS score <3), and any allergy to diclofenac or nonsteroidal anti-inflammatory drugs . Patients were discharged with study drug or control vehicle solution, a topical antibiotic, oxycodone-acetaminophen as a rescue analgesic, and a pain diary . The outcome measurements were improvement in NPIS score 2 hours after treatment, use of oxycodone-acetaminophen, and occurrence of any adverse effects . RESULTS: Forty-nine patients were enrolled in the study; 25 received diclofenac and 24 received control vehicle drops . Both groups were similar in gender, age, pretreatment pain duration, NPIS score, and analgesic use . There was significantly greater improvement in the 2-hour NPIS score in the diclofenac group (3.1; 95% confidence interval {CI} 2.3 to 4) compared with the control group (1.0; 95% CI 0.1 to 2.0) . The difference between the 2 groups was 2.1+/-1.3 (95% CI 0.8 to 3.4) . There was a trend toward fewer patients taking rescue oxycodone-acetaminophen in the diclofenac group (20%; 95% CI 4% to 36%) versus the control group (42%; 95% CI 22% to 62%) . Other than transient mild stinging, there were no complications associated with diclofenac use . CONCLUSION: Diclofenac ophthalmic solution appears to be a safe and effective analgesic in the treatment of traumatic corneal abrasions in the ED.

Can J Ophthalmol, 1999 Dec, 34(7), 389 - 93
Visual outcome following penetrating globe injuries with retained intraocular foreign bodies; Lam SR et al.; BACKGROUND: In our institution the occurrence of endophthalmitis related to intraocular foreign bodies has been rare . In this review we analyse the outcome of eyes with retained intraocular foreign bodies presenting to two vitreoretinal surgeons over nearly 7 years . METHODS: Review of the records of 26 patients who presented to two surgeons in a tertiary care vitreoretinal service in Toronto between January 1989 and November 1995 . Information documented included mechanism of injury, time from injury to definitive surgery, entry site, presence of vitreous hemorrhage, type of surgery performed, initial and final visual acuity, and development of endophthalmitis . RESULTS: All the injuries occurred in male patients, with a mean age of 36.1 (range 15 to 55) years . Most of the injuries occurred in the workplace, and in most cases (17 {65.4%}) the mechanism of injury was "metal on metal." The entry site was via a perforating wound of the cornea in 16 cases (61.5%) . Almost all cases were repaired within 48 hours by means of pars plana vitrectomy . Concurrent lensectomy was required in 18 cases (69.2%) for lens damage at the time of the original injury . Vitreous hemorrhage was present in 22 cases (84.6%) . One patient (3.8%) manifested clinically apparent endophthalmitis, which responded to intravitreal antibiotic therapy . Nineteen eyes (73.1%) had a final visual acuity of 6/24 or better . Eyes with coexisting or subsequent retinal detachment had significantly worse vision than those without retinal detachment (p < 0.001) . INTERPRETATION: The incidence of endophthalmitis in our series is lower than that in other published series . Prompt definitive treatment was associated with a good prognosis in most cases.

Microb Drug Resist, 1999 Winter, 5(4), 259 - 64
Identification and characterization of a new intermediate in the ribosylative inactivation pathway of rifampin by Mycobacterium smegmatis; Imai T et al.; Mycobacterium smegmatis DSM 43756 inactivates rifampin by ribosylation . To study this process of rifampicin, all possible inactivated forms of the antibiotic were extracted and purified . Structural studies showed the presence of a new inactivation product, designated RIP-TAp(23-phosphoribosyl-rifampin) . Formation of 23-(O-ADP-ribosyl)rifampin (RIP-TAs) is the first step, followed by removal of AMP to give rise to the newly identified compound . Lastly, dephosphorylation leads to formation of 23-ribosyl-rifampin (RIP-Mb) . Feeding experiments with the ADP-ribosylated antibiotic obtained from the cell homogenates of an Escherichia coli strain carrying the cloned M . smegmatis gene confirmed this rifampin inactivation process.

J Hematother Stem Cell Res, 1999 Dec, 8(6), 645 - 52
T lymphocyte transduction with herpes simplex virus-thymidine kinase (HSV-tk) gene: comparison of four different infection protocols; Di Ianni M et al.; In this study, we assessed the efficiency of T lymphocyte transduction with a retroviral vector carrying the herpes simplex virus thymidine kinase (HSV-tk) and neomycin phosphotransferase (neo) genes by four different protocols: standard supernatant infection, supernatant infection plus centrifugation steps, supernatant infection on fibronectin fragment-coated wells, and cocultivation . After retrovirus-mediated gene transfer of tk-neo in PHA/IL-2-stimulated primary T lymphocytes and G418 selection, T cells retained their proliferative activity, alloresponsiveness, ability to produce and to respond to IL-2, and ganciclovir (gcv)-specific sensitivity . When the four different transduction techniques were compared, no significant differences were seen in terms of cellular viability, proliferation capacity, and immunophenotyping . tk gene expression was the same in all transduced selected populations, as indicated by gcv sensitivity . Transduction efficiency was evaluated by semiquantitative PCR . Using the standard supernatant infection method, the rate of infection was extremely low (<5%) . After adding the centrifugation step or performing supernatant infection on fibronectin fragment-coated wells, PCR analysis showed a 30%-40% rate of transduced cells . After infection by cocultivation, the rate of transduced cells was 30%-40% . These results demonstrate that supernatant infection plus centrifugation, supernatant infection on fibronectin fragment-coated wells, and cocultivation methods provide equivalent rates of transduced cells . The lack of reproducibility and safety indicates that cocultivation is not suitable for clinical studies . In our view, supernatant infection plus centrifugation is easier to perform than using fibronectin fragments, and it is currently the optimal method for clinical studies when large quantities of T lymphocytes are being processed.

Vestn Khir Im I I Grek, 1999, 158(5), 48 - 9
{Use of constant electric current in prevention of postoperative bronchopulmonary complications in patients with hiatal hernia}; Alekseenko AV et al.; The prophylactics of bronchopulmonary complications was performed by the authors original method of intrapulmonary electrophoresis . It was shown to be effective and allowed the amount of postoperative bronchitis and pneumonia to be reduced from 15-20% to 4.4%.

J Am Acad Dermatol, 2000 Feb, 42(2 Pt 1), 295 - 7
Pyoderma gangrenosum and Chlamydia pneumoniae infection in a diabetic man: pathogenic role or coincidence?
Vannucci SA, Mitchell WM, Stratton CW, King LE Jr.
Chlamydia Pneumoniae is not a known cause of skin infections, but unusual pathogens cause chronic infections in diabetic patients . Multiple idiopathic pyoderma gangrenosum-like (PG-like) lesions were refractory to multiple therapeutic agents in a diabetic patient who had C pneumoniae identified by serologic tests and polymerase chain reaction . Based on complete resolution by prolonged anti-chlamydial antibiotic therapy and concomitant decrease in serologic and titers determined by polymerase chain reactions, the PG-like lesions were presumed to be due to C pneumoniae.

Naturwissenschaften, 1999 Dec, 86(12), 559 - 70
The significance of lichens and their metabolites; Huneck S; Lichens, symbiontic organisms of fungi and algae, synthesize numerous metabolites, the "lichen substances," which comprise aliphatic, cycloaliphatic, aromatic, and terpenic compounds . Lichens and their metabolites have a manifold biological activity: antiviral, antibiotic, antitumor, allergenic, plant growth inhibitory, antiherbivore, and enzyme inhibitory . Usnic acid, a very active lichen substance is used in pharmaceutical preparations . Large amounts of Pseudevernia furfuracea and Evernia prunastri are processed in the perfume industry, and some lichens are sensitive reagents for the evaluation of air pollution.

J Indian Med Assoc, 1999 Jul, 97(7), 265 - 70
Dilemmas in the management of rheumatic heart disease; Victor S; Rheumatic heart disease (RHD) is a major health care problem in India and will continue to be so for few more decades . As there is no vaccine against RHD, it is difficult to control the disease . Besides RHD, most children have other preventable ailments as well . Hence the schools, specially for the poor, must act as primary and preventive health care centres . Prevention of RHD starts with school prophylaxis . Primary, secondary and tertiary prophylaxis play their roles afterwords . After the heart valves have been damaged, tertiary prevention might minimise further damage . For mitral stenosis, closed mitral valvotomy (CMV), open mitral valvotomy (OMV) and interventional mitral valvotomy (IMV) are the different options but none is curative . Valve replacement poses many problems and therefore valvotomy is deferred as far as possible . Mild or moderate mitral regurgitation (MR) is best treated medically . For more advanced disease repair or replacement is the option . For aortic stenosis (AS), valvotomy may be preferred to replacement wherever feasible and for aortic regurgitation (AR) repair is not yet well established . In combined mitral and aortic valve disease it is important to assess both the valves carefully and try to repair one or both the valves and to avoid double valve replacement as far as possible . Once the heart valve is damaged any treatment is palliative, hence all efforts should be directed towards prevention of RHD . Indian Medical Association can play a major role in this endeavour and help children in India to grow up free from RHD.

Z Kardiol, 1999 Nov, 88(11), 885 - 95
{Role of Chlamydia pneumoniae in the pathogenesis of coronary disease}; Kahler J et al.; Several studies have demonstrated an association Chlamydia pneumoniae with coronary artery disease, suggesting that infection with C . pneumoniae increases the risk for coronary artery disease by factor 2 or more . Since atherosclerosis is considered to be a chronic inflammatory process, these data would fit into the response-to-injury hypothesis of atherosclerosis rather than representing a completely novel concept . Several pathomechanisms as increased cytokine synthesis, proliferative and proaggregatory effects could transmit the effects of chronic C . pneumoniae infection . Animal models and first clinical trials using antibiotic therapy seem to support an etiological role of C . pneumoniae in coronary artery disease . In this paper the current knowledge of the role of C . pneumoniae in coronary artery disease is reviewed and possible pathomechanisms are discussed.

J Eur Acad Dermatol Venereol, 1999 Nov, 13(3), 214 - 7
Treatment of cutaneous leishmaniasis with 20% paromomycin ointment; Stanimirovic A et al.; Cutaneous leishmaniasis is an infectious disease caused by flagellate protozoa of the genus Leishmania . In Mediterranean countries, the most common causative agents are Leishmania (L.) major, L . infantum and L . tropica . In Croatia, cutaneous leishmaniasis is a rare disease, the last case being reported in 1988 . Our patient was a 5-year-old boy with a left cheek skin lesion in the form of papule with central exulceration, hyperkeratotic crust and erythema of a 6-month duration . The diagnosis of cutaneous leishmaniasis was based on history data (stay in the southernmost region of Croatia and multiple mosquito bites), light microscopic histology (dense infiltrates of large histiocytes with extracellular bodies), and positive Montenegro (leishmanin) test . A new therapy with aminosidine (paromomycin), an aminoglycoside antibiotic, in the form of ointment at a concentration of 20%, was for the first time used in Croatia . Four-week therapy resulted in complete regression of the skin lesions with residual hyperpigmentation . During therapy, no local or systemic side effects were observed . Thus, topical therapy with paromomycin could be considered an efficient therapeutic alternative in the management of cutaneous leishmaniasis.

J Anim Sci, 1999 Dec, 77(12), 3168 - 75
Health of finishing steers: effects on performance, carcass traits, and meat tenderness; Gardner BA et al.; The impact of respiratory disease during a 150-d feedlot finishing period on daily gain, carcass traits, and longissimus tenderness was measured using 204 steer calves . Feedlot health status was monitored in two ways . First, clinical signs of respiratory infection were evaluated each day; treatment with antibiotic was based on degree of fever (if rectal temperature exceeded 40 degrees C then calves were treated) . Steers that were treated (n = 102) had lower (P<.05) final live weights, ADG, hot carcass weights (HCW), less external and internal fat, and more desirable yield grades . Steers that were treated had a higher prevalence of carcasses that graded U.S . Standard than steers that were never treated . Second, as an alternative index of health status, lungs of all steers were evaluated at the processing plant using a respiratory tract lesion classification system; this health index included presence or absence of preexisting pneumonic lesions in the anterioventral lobes plus activity of the bronchial lymph nodes (inactive vs active) . Lung lesions were present in 33% of all lungs and were distributed almost equally between treated (37%) and untreated cattle (29%) . Steers with lesions (n = 87) had lower (P<.05) daily gains, lighter HCW, less internal fat, and lower marbling scores than steers without lesions . Compared to steers with lesions but inactive bronchial lymph nodes (n = 78), steers with lung lesions plus active lymph nodes had lower (P<.01) ADG and dressing percentage . Longissimus shear force values for steaks aged 7 d were lower (P = .05) from steers without lung lesions than those for steaks from steers with lung lesions . Overall, morbidity suppressed daily gains and increased the percentage of U.S . Standard carcasses . Compared to health assessment by clinical appraisal (based on elevated body temperature), classification based on respiratory tract lesions at slaughter proved more reliable statistically and, thereby, more predictive of adverse effects of morbidity on production and meat tenderness.

Surg Today, 1999, 29(12), 1287 - 9
Descending necrotizing mediastinitis with sternocostoclavicular osteomyelitis and partial thoracic empyema: report of a case; Sonobe M et al.; We present herein the case of a 50-year-old woman in whom descending necrotizing mediastinitis originating from an anterior neck abscess spread to the left upper bony thorax, resulting in osteomyelitis of the left sternocostoclavicular articulation and left partial thoracic empyema . Transcervical mediastinal irrigation and drainage was performed with aggressive antibiotic therapy, followed by resection of the left sternocostoclavicular joint and debridement of the anterior mediastinum . The patient had an uneventful postoperative course, and her left arm and shoulder mobility was well preserved.

Antimicrob Agents Chemother, 2000 Feb, 44(2), 421 - 4
Detection of florfenicol resistance genes in Escherichia coli isolated from sick chickens; Keyes K et al.; Florfenicol is an antibiotic approved for veterinary use in cattle in the United States in 1996 . Although this drug is not used in poultry, we have detected resistance to florfenicol in clinical isolates of avian Escherichia coli . Molecular typing demonstrated that the florfenicol resistance gene, flo, was independently acquired and is plasmid encoded.

N Engl J Med, 2000 Jan 20, 342(3), 161 - 7
Supplemental perioperative oxygen to reduce the incidence of surgical-wound infection . Outcomes Research Group; Greif R et al.; BACKGROUND: Destruction by oxidation, or oxidative killing, is the most important defense against surgical pathogens and depends on the partial pressure of oxygen in contaminated tissue . An easy method of improving oxygen tension in adequately perfused tissue is to increase the concentration of inspired oxygen . We therefore tested the hypothesis that the supplemental administration of oxygen during the perioperative period decreases the incidence of wound infection . METHODS: We randomly assigned 500 patients undergoing colorectal resection to receive 30 percent or 80 percent inspired oxygen during the operation and for two hours afterward . Anesthetic treatment was standardized, and all patients received prophylactic antibiotic therapy . With use of a double-blind protocol, wounds were evaluated daily until the patient was discharged and then at a clinic visit two weeks after surgery . We considered wounds with culture-positive pus to be infected . The timing of suture removal and the date of discharge were determined by the surgeon, who did not know the patient's treatment-group assignment . RESULTS: Arterial oxygen saturation was normal in both groups; however, the arterial and subcutaneous partial pressure of oxygen was significantly higher in the patients given 80 percent oxygen than in those given 30 percent oxygen . Among the 250 patients who received 80 percent oxygen, 13 (5.2 percent; 95 percent confidence interval, 2.4 to 8.0 percent) had surgical-wound infections, as compared with 28 of the 250 patients given 30 percent oxygen (11.2 percent; 95 percent confidence interval, 7.3 to 15.1 percent; P=0.01) . The absolute difference between groups was 6.0 percent (95 percent confidence interval, 1.2 to 10.8 percent) . The duration of hospitalization was similar in the two groups . CONCLUSIONS: The perioperative administration of supplemental oxygen is a practical method of reducing the incidence of surgical-wound infections.

Antimicrob Agents Chemother, 2000 Feb, 44(2), 396 - 9
Identification of a cyclase gene dictating the C-9 stereochemistry of anthracyclines from Streptomyces nogalater; Torkkell S et al.; Nogalamycin is an anthracycline antibiotic produced by Streptomyces nogalater . Its aglycone has a unique stereochemistry (7S, 9S, 10R) compared to that of most other anthracyclines (7S, 9R, 10R) . The gene snoaL, encoding a nogalonic acid methyl ester cyclase for nogalamycin, was used to generate nogalamycinone, demonstrating that the single cyclase dictates the C-9 stereochemistry of anthracyclines.

Gene Ther, 1999 Dec, 6(12), 1982 - 7
In vivo cell type-specific gene delivery with retroviral vectors that display single chain antibodies; Jiang A et al.; Cell type-specific gene delivery will be essential for in vivo gene therapy . Our laboratory has previously developed retroviral vector particles, derived from spleen necrosis virus, SNV, which display the antigen-binding site of an antibody on the viral surface . Such particles infected only human cells in vitro, which expressed a receptor recognized by the antibody . To test cell type-specific gene delivery in vivo, a mouse model system has been developed . Antibiotic resistant human target and non-target cells were injected into the peritoneum of SCID mice . Subsequently, a vector solution containing 106 infectious particles, which display scAs against the human her2neu cell surface protein, was injected . Cells were recovered from the peritoneum, subjected to antibiotic selection, and tested for the expression of a lacZ gene transduced by the retroviral vector . We found that human target cells, which express her2neu, were infected in vivo . However, neither human cells that do not express her2neu, nor normal mouse cells were infected by such viral particles . These data give proof of principle that retroviral vector-mediated, cell type-specific gene delivery can be obtained in vivo.

Antibiot Khimioter, 1999, 44(10), 8 - 12
{The capacity of the mycelia of Streptomyces chrysomallus variants to bind exogenous actinomycin D and the synthesis by these variants of macrotetralides}; Orlova TI et al.; Streptomyces chrysomallus is known as an organism producing macrotetrolides (MTL) and actinomycin C . The dynamics of the MTL biosynthesis by some variants of S . chrysomallus in the process of their growth in liquid media was studied . In parallel the ability of the culture mycelium (washed or suspended in physiological solution) to bind exogenous actinomycin D (AMD) was estimated . An inverse correlation between the dynamics of MTL biosynthesis and the rate of the AMD binding by the washed mycelium during the whole period of the culture development was observed: a decrease in the culture ability to bind AMD corresponded to active biosynthesis of MTL and an increase in the culture ability to bind AMD corresponded to lower biosynthesis of MTL . It was suggested that the active biosynthesis of MTL correlated not only with a decrease in the ability of the suspended mycelium to bind AMD but also with a decrease in binding of actinomycin synthesized and excreted to the medium by the culture . A decrease in the reflux of the synthesized antibiotic to the cells was likely one of the components of the system of the S . chrysomallus insensitivity to its own antibiotic.

Arch Ophthalmol, 2000 Jan, 118(1), 125 - 6
Acute unilateral corneal immunoprotein deposition in IgM monoclonal gammopathy; Schelonka LP et al.; A healthy 43-year-old officer of a merchant ship at sea developed pain, redness, and photophobia in his right eye . During the next 2 weeks, he noted the presence of a band of opacity spreading from his temporal limbus toward his central cornea . His episcleral vessels were engorged in a distribution contiguous with the peripheral, sectorial, fleck-like corneal opacities . The opacity had progressed during topical and systemic antibiotic therapy, but halted with use of topical corticosteroids . Systemic evaluation showed mild IgM monoclonal gammopathy . Transmission electron microscopy of a corneal biopsy specimen revealed electron-dense fibrils identified as immunoprotein . To our knowledge, this is the first report of a case of acute unilateral deposition of corneal immunoprotein in a patient with monoclonal gammopathy . Clinicians should begin with a broad differential diagnosis when evaluating patients with corneal opacity.

Arch Ophthalmol, 2000 Jan, 118(1), 13 - 6
The spectrum of ocular inflammation caused by euphorbia plant sap; Eke T et al.; OBJECTIVE: To report the spectrum of clinical findings in patients with ocular inflammation caused by plant sap from Euphorbia species . DESIGN: Clinical case series . SETTING: Ophthalmology emergency referrals in the United Kingdom . PATIENTS: We examined 7 patients, all of whom gave a history of recent ocular exposure to the sap of Euphorbia species . INTERVENTIONS: All patients were treated with antibiotic drops or ointment (chloramphenicol) . Cycloplegic and steroid drops were also used for some patients . Patients were observed until all signs and symptoms had resolved . MAIN OUTCOME MEASURES: Symptoms, visual acuity, and clinical signs of inflammation . All patients provided a specimen of the plant for formal identification . RESULTS: Initial symptoms were generally burning or stinging pain with blurred vision . In most cases, visual acuity was reduced between 1 and 2 Snellen lines . In 1 patient with age-related maculopathy, acuity dropped from 20/80 to hand motions before recovering . Clinical findings varied from a mild epithelial keratoconjunctivitis to a severe keratitis with stromal edema, epithelial sloughing, and anterior uveitis . All signs and symptoms had resolved by 1 to 2 weeks . CONCLUSIONS: These cases illustrate the range of severity of Euphorbia sap keratouveitis . The condition seems to be self-limiting when managed supportively . People who work with Euphorbia plant species should wear eye protection . Clinicians managing keratopathy caused by Euphorbia species should be aware of the danger of sight-threatening infection and uveitis, particularly during the first few days.

Acta Otorhinolaryngol Belg, 1999, 53(3), 241 - 4
Risk factors for surgical wound infections in patients undergoing head and neck oncologic surgery; Barry B et al.; Risk factors for surgical wound infection are difficult to establish in head and neck surgery . Flap reconstruction, which correlates with tumour size and surgical procedure, appears to be the main risk factor . Attempts should be made by the surgical staff to improve surgical procedures in terms of duration of surgery and choice of the procedure . The intraoperative choice between primary closure and flap reconstruction should be studied further . More subtle risk factors may appear in studies of large groups of patients and/or if a distinction is drawn between early and late SWI.

Rev Med Interne, 1999 Dec, 20(12), 1126 - 31
{Acrodystrophic neuropathy of Bureau and Barrière}; Dilhuydy MS et al.; INTRODUCTION: The acrodystrophic neuropathy described by Bureau and Barriere in the 1950s is a rare trophic complication of chronic, analgesic neuropathy due to alcohol abuse, which is at the origin of perforating ulcers of the foot, vasomotor disorders with dysautonomia, and leads to mutilating arthropathy of the lower limb . This neuroacropathy, also termed vagabonds' or vagrants' disease, usually occurs in subjects with a debilitated condition, chronic alcoholism, and unfavourable socioeconomic conditions . EXEGESIS: We report four cases of Bureau-Barriere disease which occurred in male subjects who were on average 55 years of age . The clinical presentation was close to that reported in the literature . Indeed, all four patients were alcoholic, nondiabetic and lived under conditions of precarious hygiene . Therapeutic management of the patients was difficult due to bad compliance with the treatment and persistence of alcohol abuse . Immobilization of the foot is considered to be the primary treatment . Local care including baths and bandages with hydrocolloids must be continued during several months, and associated with antibiotic therapy, administered by infusion when necessary . The outcome is often chronic, with poor prognosis . Given the limited therapeutic possibilities, acrodystrophic neuropathy is an invalidating disease with high morbidity . CONCLUSION: Bureau-Barriere disease is a rare, serious invalidating disease . The clinical symptomatology is usually based on the diagnostic triad: analgesia of the foot, perforating ulcers of the foot, and deforming and mutilating arthropathy of the lower limb . Treatment is often hampered due to poor compliance with local care and persistence of alcohol abuse.

J Paediatr Child Health, 1999 Dec, 35(6), 545 - 8
Bacterial endocarditis in neonatal intensive care; Opie GF et al.; OBJECTIVES: To ascertain the incidence of bacterial endocarditis in a level III neonatal nursery . To document the clinical features, assess survival, and evaluate the role of central venous catheters in neonates with bacterial endocarditis . METHODOLOGY: Index cases were identified by retrospective review of the echocardiographic records of infants admitted to the neonatal nursery from 1983 to 1995 . Data obtained by review of the clinical records of these infants, and case-matched controls . RESULTS: From January 1983 to December 1995, 12,249 infants were admitted to the Special Care Nursery . Eight infants with endocarditis were identified, an incidence of 0.07% . Presenting symptoms and signs were often vague and nonspecific . Gestation less than 32 weeks, birthweight less than 1500 g, thrombocytopenia and neutropenia or neutrophilia were common features . Infants with endocarditis had a significantly higher Clinical Risk Index for Babies score than those without endocarditis . The tricuspid valve was involved in seven infants, six of whom had a percutaneous central venous catheter in situ before diagnosis . Mitral valve involvement occurred in two infants, neither of whom had central lines inserted . However, compared to infants without endocarditis, the placement of a central venous line was not of statistical significance . Seven of the eight infants survived following prolonged antibiotic therapy . CONCLUSIONS: Bacterial endocarditis is a rare but serious condition which is usually not fatal . In the premature newborn infant, presenting signs and symptoms are often nonspecific . Endocarditis should therefore be considered in the unwell very low birthweight infant.

J Med Genet, 2000 Jan, 37(1), 38 - 40
Prevalence of mitochondrial gene mutations among hearing impaired patients; Usami S et al.; The frequency of three mitochondrial point mutations, 1555A-->G, 3243A-->G, and 7445A-->G, known to be associated with hearing impairment, was examined using restriction fragment length polymorphism (RFLP) analysis in two Japanese groups: (1) 319 unrelated SNHL outpatients (including 21 with aminoglycoside antibiotic injection history), and (2) 140 cochlear implantation patients (including 22 with aminoglycoside induced hearing loss) . Approximately 3% of the outpatients and 10% of the cochlear implantation patients had the 1555A-->G mutation . The frequency was higher in the patients with a history of aminoglycoside injection (outpatient group 33%, cochlear implantation group 59%) . One outpatient (0.314%) had the 3243A-->G mutation, but no outpatients had the 7445A-->G mutation and neither were found in the cochlear implantation group . The significance of the 1555A-->G mutation, the most prevalent mitochondrial mutation found in this study of a hearing impaired population in Japan, among subjects with specific backgrounds, such as aminoglycoside induced hearing loss, is evident.

Minerva Anestesiol, 1999 Nov, 65(11), 799 - 805
{Septic pancreatic necrosis in intensive care}; Cominotti S et al.; BACKGROUND: Infected necrotizing pancreatitis is the most fulminant variety of this disease . The reported mortality is up to 50% . The haemodynamic features of cardiovascular instability has many similarities to sepsis syndrome, septic shock and multiple organ dysfunction syndrome (MODS) . The purpose of this study is to review personal experience in the ICU (hospital of Varese) to determine etiology, treatment and complications . METHODS: Twenty patients treated since 1988 with infected necrotizing pancreatitis required surgical treatment and mechanical ventilation . RESULTS: The mortality rate was 60% and ICU-stay was 26.5 +/- 12.3 days, the median age was 54 +/- 13 . Ranson's criteria at admission to the ICU was 6.6 +/- 1.2, Glasgow point was 4.6 +/- 1.2 (5.5 +/- 0.87 died, 3.2 +/- 0.8 survived p < 0.01), Baltazar score 6.2 +/- 2.1 (7.4 +/- 2.1 died, 5.5 +/- 0.9 survived p < 0.05) and SAPS II score 43.4 +/- 12.1 (50.1 +/- 7.8 died, 34 +/- 5.5 survived p < 0.01) . The etiology was: gallstones (45%), alcoholism (15%), ERCP (15%) and idiopathic in 25% . Serum pancreatic amylase was 342 +/- 113.9 U/l (550 +/- 100 died, 155 +/- 60 survived p < 0.01), lipase was 334 +/- 176 U/l and transaminases GOT was 123 +/- 46 u/l (156 +/- 90 died, 29 +/- 7 survived p < 0.05) . High initial amylase and GOT levels were frequently found in non survived patients . MODS occurred in 17 cases (85%), ARDS in 2 patients (10%), abdominal bleeding in 6 (30%) and septic syndrome in 8 (40%) . CONCLUSIONS: It is thus possible that a target-oriented approach including fluid replacement, rapid correction of intestinal underperfusion, inotropic and antibiotic therapy, supply of specific nutrients and other therapeutic strategies as open laparostomy must be employed to prevent MODS or septic syndrome in pancreatic infection after acute necrotizing pancreatitis.

Pediatr Dent, 1999 Nov-Dec, 21(7), 459 - 62
Conservative treatment of severely luxated maxillary primary central incisors: case report; Holan G; The treatment and follow-up evaluation of two orally luxated maxillary primary central incisors in a three-year-old girl is described . The injured teeth were displaced into a cross-bite with their mandibular opposing teeth . They were repositioned shortly after the injury and splinted with composite resin for two weeks . Oral hygiene instructions and antibiotic therapy were prescribed . Two weeks after the injury a necrotic pulp was removed and the root canals filled with a resorbable paste . Thirty months after the injury, the teeth and the surrounding tissues were clinically and radiographically asymptomatic and physiologic root resorption could be noted . The permanent successors erupted soon after natural exfoliation of the injured primary teeth . Only mild hypocalcified defects were observed on the permanent incisors.

Eur J Biochem, 2000 Jan, 267(2), 527 - 34
Permeation of tetracyclines through membranes of liposomes and Escherichia coli; Sigler A et al.; Uptake of tetracycline (tc), 2-tetracyclinonitrile (CN-tc), and 9-(N, N-dimethylglycylamido)-6-demethyl-6-deoxytetracycline (DMG-DMDOT) by liposomes containing Tet repressor (TetR) and by Escherichia coli cells overexpressing TetR was examined . TetR specifically binds to tetracyclines, enhances their fluorescence and thereby allows selective detection of tetracyclines that have crossed the membranes . Analysis of the diffusion of tc and DMG-DMDOT into liposomes yielded permeation coefficients of (2.4 +/- 0.6) x 10-9 cm.s-1 and (3.3 +/- 0.8) x 10-9 cm.s-1, respectively . Similar coefficients were obtained for uptake of these tetracyclines by E . coli, indicating that diffusion through the cytoplasmic membrane is the rate-limiting step . The permeation coefficients translate into half-equilibration times of approximately 35 +/- 15 min and explain how efflux pumps can mediate resistance against tetracyclines . Furthermore, diffusion of CN-tc into liposomes was at least 400-fold slower than that of tc, indicating that the carboxamide group at position C2 is required for efficient permeation of tc through lipid membranes and thereby explaining the lack of antibiotic activity of CN-tc.

Aliment Pharmacol Ther, 2000 Jan, 14(1), 79 - 83
Efficacy of a multistep strategy for Helicobacter pylori eradication; Gasbarrini A et al.; BACKGROUND: Helicobacter pylori eradication therapies do not achieve 100% success rates . Antibiotic resistant strains are among the major causes of failure . Current recommendations concerning the management of treatment failures are not fully clear . AIM: To evaluate the efficacy of a multi-step therapeutic strategy in a large group of infected patients . METHODS: A total of 2606 H . pylori-positive patients were administered tinidazole, clarithromycin and a proton pump inhibitor for 1 week . Patients with continuing infection were then given a second 1-week course of amoxycillin, clarithromycin and ranitidine bismuth citrate . Patients still infected after the second course underwent upper gastrointestinal endoscopy with H . pylori culture, and then received a 1-week quadruple proton pump inhibitor-bismuth based scheme established on H . pylori antibiotic sensitivity . RESULTS: After the first step, eradication was achieved in 2063 out of 2413 patients {86% per protocol analysis (PP); 79% intention-to-treat analysis (ITT)} . First-step failures (350 out of 2413; 14.5% PP) showed second-step eradication rates of 82% (271 out of 329 patients, PP; 77% ITT) . The specific quadruple therapy for second-step failures (58 out of 329, 18% PP) achieved 77% (30 out of 39 patients, PP) or 52% (ITT) success . This algorithm led to overall eradication rates of 99% (PP) or 91% (ITT) . CONCLUSIONS: This multi-step strategy succeeded in a high percentage of H . pylori infected patients . Given the lack of precise guidelines on treatment failures, assessing H . pylori sensitivity to antibiotics only after failure of the second treatment could be suggested in clinical practice.

J Chemother, 1999 Oct, 11(5), 410 - 3
Cyclosporin A and imipenem associated seizure activity in allogeneic bone marrow transplantation patients; Turhal NS; Imipenem is an antibiotic used with cilastatin in the bone marrow transplant (BMT) setting . Cyclosporin A (CsA) is an immunosuppressive agent . Seizures can be seen with both imipenem/cilastatin and CsA . Our hypothesis for study was that CNS toxicity and seizures are increased by the concomitant administration of CsA and imipenem/cilastatin . Between December of 1989 and 1996, all of the 166 stem cell BMTs performed at Mount Sinai Hospital in New York were evaluated for this study . Three groups were studied: 77 patients received CsA alone (Group 1); 89 patients received imipenem/cilastatin, and of these, 45 received concomitant CsA (Group 2); and 44 patients who underwent autologous BMT received imipenem/cilastatin only (Group 3) . We observed a total of 5 seizure episodes . There were no statistical differences in frequency between the groups . Adverse effects may be difficult to relate to a particular drug, especially for patients on multidrug regimens but the use of imipenem/cilastatin and CsA did not cause a significant rise in the frequency of seizures when compared to CsA alone.

Am J Hematol, 2000 Feb, 63(2), 90 - 3
Ticlopidine-induced aplastic anemia and quick recovery with G-CSF: case report and literature review; Taher A et al.; We report here a case of ticlopidine-induced aplastic anemia that responded to G-CSF and review the literature . An 83-year-old woman was started on ticlopidine for coronary artery disease after an episode of upper gastrointestinal bleeding secondary to aspirin . She developed aplastic anemia seven weeks after initiation of ticlopidine . She was hospitalised and received empiric antibiotic therapy and granulocyte colony stimulating factor (G-CSF) . Her bone marrow started to recover quickly, and white blood cell and platelet counts returned to normal within three weeks . A review of medical literature revealed 20 similar cases of ticlopidine-induced aplastic anemia resulting in death in seven cases . G-CSF has been used previously with variable success . Ticlopidine is associated with serious, sometimes fatal hematological side effects . This risk should be seriously taken into consideration when prescribing ticlopidine . G-CSF may be helpful in the treatment of ticlopidine-induced aplastic anemia .

Nippon Geka Gakkai Zasshi, 1999 Nov, 100(11), 761 - 4
{Pleural empyema complicated by spontaneous pneumothorax treated with thoracoscopic debridement and pleural irrigation: case report}; Inoue N et al.; A 69-year-old man who had experienced spontaneous left pneumothorax one week previously was admitted to our hospital for the management of left empyema thoracis . Because the symptoms did not resolve with antibiotic therapy and chest tube drainage, thoracoscopic debridement and pleural irrigation were performed in the fibrinopurulent phase 4 days after admission . The postoperative course was uneventful . This procedure is minimally invasive and effective in the treatment of acute empyema.

Otolaryngol Head Neck Surg, 2000 Jan, 122(1), 1 - 7
Diagnosis and treatment of uncomplicated acute bacterial rhinosinusitis: summary of the Agency for Health Care Policy and Research evidence-based report; Benninger MS et al.; PURPOSE: The goal was to critically examine evidence regarding the performance of diagnostic tests and the efficacy of antibiotic and other treatments for uncomplicated acute bacterial rhinosinusitis (ABR) . METHODS: Scientific literature was reviewed, and meta-analysis methods were used to assess diagnostic test and antibiotic efficacy . A decision analysis and cost-effective analysis were performed . RESULTS: Although more sensitive than clinical examination for diagnosis of ABR, sinus radiograms are not cost-effective as an initial management strategy . Antibiotics reduce the incidence of clinical failures by one half compared to no treatment and, when coupled with clinical criteria-based diagnosis, present the most cost-effective treatment strategy . However, without antibiotics, symptoms in two thirds of patients improve by 14 days with no serious complications . The risk of treatment failure does not differ significantly between amoxicillin or folate inhibitors and newer, more expensive antibiotics . CONCLUSIONS: The current literature shows that treatment of uncomplicated ABR with amoxicillin or folate inhibitors and based on clinical criteria is the most cost-effective strategy.

Nucleic Acids Res . 2000 Dec 15;28(24):E108.
Controlling gene expression in yeast by inducible site-specific recombination; Cheng TH et al.; An intron module was developed for Saccharomyces cerevisiae that imparts conditional gene regulation . The kanMX marker, flanked by loxP sites for the Cre recombinase, was embedded within the ACT1 intron and the resulting module was targeted to specific genes by PCR-mediated gene disruption . Initially, recipient genes were inactivated because the loxP-kanMX-loxP cassette prevented formation of mature transcripts . However, expression was restored by Cre-mediated site-specific recombination, which excised the loxP-kanMX-loxP cassette to generate a functional intron that contained a single loxP site . Cre recombinase activity was controlled at the transcriptional level by a GAL1::CRE expression vector or at the enzymatic level by fusing the protein to the hormone-dependent regulatory domain of the estrogen receptor . Negative selection against leaky pre-excision events was achieved by growing cells in modified minimal media that contained geneticin (G418) . Advantages of this gene regulation technique, which we term the conditional knock-out approach, are that (i) modified genes are completely inactivated prior to induction, (ii) modified genes are induced rapidly to expression levels that compare to their unmodified counterparts, and (iii) it is easy to use and generally applicable.

Surg Endosc, 2000 Nov, 14(11), 1028 - 30
A simple scoring system to reduce intraabdominal septic complications after laparoscopic appendectomy; Serralta A et al.; BACKGROUND: The development of intraabdominal abscess (IAA) following laparoscopic appendectomy (LA) is associated with significant morbidity . The aim of the present study was to validate an IAA risk score constructed from a previous review of 156 consecutive LA . METHODS: The score was tested in 250 subsequent consecutive LA and in patients with a positive risk score . Broad-spectrum antibiotics were administered in order to avoid IAA . RESULTS: Factors related to IAA included clinically complicated appendicitis, leucocytosis >15,000/microl, a difference of >1 degrees C between axillary and rectal temperature, intraoperative findings such as (gangrenes and perforation), and intraoperative perforation of the appendix . In this series, broad-spectrum antibiotic therapy in patients with a positive IAA risk score reduced the incidence of IAA from 7.05% to 1.60% . CONCLUSION: This policy of identifying high-risk patient via the scoring system and instituting subsequent antibiotic therapy in patients at risk reduces the incidence of IAA following LA.

Arch Pediatr, 1999 Dec, 6(12), 1338 - 44
{Controversies concerning acute otitis media}; Mudry A; Acute otitis media is the subject of many unresolved points of controversy: 1) correct diagnosis; 2) whether or not bacteria are present in each case of acute otitis media; 3) spontaneous course; 4) indication of antibiotherapy; 5) treatment of recurrent acute otitis media; and 6) the place of alternative medicine, such as homeopathy . There is no ideal response . It is important, however, to take into account the knowledge of the different otoscopic stages of acute otitis media and the fact that the course of the disease is spontaneously favorable in the majority of cases . Selective prescription of an antibiotic in cases of purulent otitis only, and attention directed towards early recognition of complications, appear to be the most appropriate attitudes in the management of the disease, helping to reduce the alarmingly increasing numbers of resistant bacteria.

Bone Marrow Transplant, 1999 Dec, 24(12), 1279 - 83
Clinical significance of CD34+ cell dose in long-term engraftment following autologous peripheral blood stem cell transplantation; Perez-Simon JA et al.; The number of CD34+ cells has been described as the best parameter for predicting the quality of engraftment in peripheral blood progenitor cell (PBPC) transplantation in the early post-transplant period . In this study we have determined the optimal number of CD34+cells in order to maintain engraftment in the long term in a series of 100 patients receiving autologous PBPC transplantation . Based on our previous experience on the speed of early hematopoietic recovery, four subgroups of patients were established: patients infused less than 0.75 x 106/kg CD34+ (n = 9), 0.75 to 1.25 (n = 24), 1.25 to 2.0 (n = 37) and more than 2.0 (n = 30) . These groups were designated as low, intermediate-low, intermediate-high and high CD34 groups, respectively . Transitory loss of neutrophil engraftment was observed in 67%, 30%, 16% and 6% of patients in the four mentioned CD34 groups respectively, with statistically significant differences between the different groups . Significant differences were also observed between the low CD34 group and the rest of the groups as regards platelet and red blood cell transfusion requirements, fever episodes, days of hospitalization and antibiotic requirements throughout the first year . Our results show that the dose of CD34+ cells influences engraftment also in the late post-transplant period, and correlates with transfusion and antibiotic requirements, fever episodes and days of hospitalization during the first year post-transplant.

J Comp Pathol, 2000 Jan, 122(1), 3 - 8
MS-8209, an amphotericin B analogue, delays the appearance of spongiosis, astrogliosis and PrPres accumulation in the brain of scrapie-infected hamsters; Adjou KT et al.; The histopathological response of scrapie-infected hamsters treated at the late stage of the infection with an "anti-scrapie" drug, a polyene macrolide antibiotic designated MS-8209, was evaluated in the brain . The results showed that (1) MS-8209 prolonged significantly the incubation time of the experimental disease, (2) MS-8209 delayed the appearance of spongiosis and astrogliosis in the brain, (3) immunodetection of abnormal prion protein and glial fibrillary acidic protein was significantly reduced in the central nervous system . In addition, this report indicates that polyene antibiotics markedly delay the development of the classical brain lesions that result from scrapie infection .

Mol Endocrinol, 2000 Jan, 14(1), 27 - 39
The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution; Jones SA et al.; Transcription of genes encoding cytochrome P450 3A (CYP3A) monooxygenases is induced by a variety of xenobiotics and natural steroids . There are marked differences in the compounds that induce CYP3A gene expression between species . Recently, the mouse and human pregnane X receptor (PXR) were shown to be activated by compounds that induce CYP3A expression . However, most studies of CYP3A regulation have been performed using rabbit and rat hepatocytes . Here, we report the cloning and characterization of PXR from these two species . PXR is remarkably divergent between species, with the rabbit, rat, and human receptors sharing only approximately 80% amino acid identity in their ligand-binding domains . This sequence divergence is reflected by marked pharmacological differences in PXR activation profiles . For example, the macrolide antibiotic rifampicin, the antidiabetic drug troglitazone, and the hypocholesterolemic drug SR12813 are efficacious activators of the human and rabbit PXR but have little activity on the rat and mouse PXR . Conversely, pregnane 16alpha-carbonitrile is a more potent activator of the rat and mouse PXR than the human and rabbit receptor . The activities of xenobiotics in PXR activation assays correlate well with their ability to induce CYP3A expression in primary hepatocytes . Through the use of a novel scintillation proximity binding assay, we demonstrate that many of the compounds that induce CYP3A expression bind directly to human PXR . These data establish PXR as a promiscuous xenobiotic receptor that has diverged during evolution.

Photochem Photobiol, 1999 Dec, 70(6), 957 - 9
The phototumorigenic fluoroquinolone lomefloxacin photosensitizes pyrimidine dimer formation in human keratinocytes in vitro; Traynor NJ et al.; The fluoroquinolone antibiotic lomefloxacin is phototoxic, photogenotoxic, photomutagenic and photosensitizes tumorigenesis in mouse skin . We have used T4 endonuclease V to demonstrate that lomefloxacin photosensitizes pyrimidine dimer formation in a human keratinocyte line (HaCaT) . A possible mechanism for this effect would be triplet-triplet energy transfer . However, there is indirect evidence that the lomefloxacin triplet yield is very low, making this reaction less likely . The finding that lomefloxacin photosensitizes production of highly mutagenic pyrimidine dimers correlates with its ability to initiate skin tumor formation in mice . Until the potential of other fluoroquinolones to photosensitize dimer formation is explored it may be unadvisable to prescribe these antibiotics to patients with defective DNA repair capacity (e.g . xeroderma pigmentosum).

Wilderness Environ Med, 1999 Winter, 10(4), 242 - 6
Catfish spine envenomation: a case report and literature review; Blomkalns AL et al.; Catfish spine envenomations are common injuries, reported in both freshwater and saltwater . Such injuries are complex puncture wounds, often complicated by severe infection . Signs and symptoms range from simple local pain and bleeding to systemic manifestations with hemodynamic compromise . Care and treatment involve aggressive pain management, judicious wound cleansing, prophylactic antibiotics, and close follow-up . A case of catfish spine envenomation from a freshwater catfish is presented here.

Neurosci Lett, 1999 Dec 31, 277(3), 193 - 7
Overexpression of bcl-2, bcl-XL or hsp70 in murine cortical astrocytes reduces injury of co-cultured neurons; Xu L et al.; Astrocytes perform many functions that protect neurons during stress, including transmitter uptake, metabolic support, and protection from oxidative stress . We asked whether astrocytes overexpressing either the anti-apoptotic genes bcl-2, or bcl-XL, or the inducible heat shock protein hsp70, could better protect neurons grown with them in co-culture than normal astrocytes or astrocytes expressing beta-galactosidase . Retroviral vectors were used to express these genes in primary astrocyte cultures . After antibiotic selection to eliminate untransformed astrocytes, neurons were plated on top of the astrocytes . Overexpression of any of the three genes in astrocytes reduced neuronal injury induced by combined oxygen-glucose deprivation, or glucose deprivation . Hsp70 overexpression reduced glutamate toxicity . As none of the genes studied is thought to be secreted, the likeliest explanation for the protection observed is improved astrocyte function.

Acta Paediatr, 1999 Dec, 88(12), 1385 - 91
Very low birthweight, bronchopulmonary dysplasia and health in early childhood; Korhonen P et al.; The impact of very low birthweight (<1500g) and bronchopulmonary dysplasia (BPD) on respiratory morbidity, on need of medical resources and rehabilitation at 2-8 y of age, and on the everyday life of the child's family was evaluated by means of a questionnaire addressed to parents of 143 very low birthweight children, 36 of whom had had BPD at 28 d postnatal age, and 131 term controls . In the preceding year, respiratory symptoms provoked by exercise, use of inhaled medications, regular follow-up visits and hospitalizations, need for physiotherapy, occupational therapy, technical aids and financial support from society had been more common in the very low birthweight groups compared to children born at term . Children with BPD suffered respiratory infections and needed antibiotic courses more frequently than term controls . Repeated antibiotic courses, physiotherapy and occupational therapy were more common among very low birthweight children with BPD than among those without . Concern for the child and the impact of the child's health on his or her everyday life and the parents' work and education were more often reported in target families than in term controls . Compared to term families, more parents in the BPD group felt that the child's health affected the pasttimes of other family members . To the families concerned, very low birthweight and BPD constitute a significant burden far beyond the neonatal period . Validated scales for the assessment of their quality of life are needed to develop supportive measures and to evaluate the effects of such interventions.

Acta Paediatr, 1999 Dec, 88(12), 1373 - 9
Asthma and respiratory infections in school children with special reference to moisture and mold problems in the school; Taskinen T et al.; AIM OF THE STUDY: Initially, we performed a questionnaire study on 622 school children aged 7 to 13 y . The study was supplemented with a clinical study including skin prick tests to 13 molds in 212 (34%) children with doctor-diagnosed asthma or parental-reported wheezing or prolonged cough . These children were attending one of two elementary schools, one with moisture problems (index) school, the other being the control school . The objective of the study was to evaluate whether exposure to moisture and sensitization to molds are associated with respiratory manifestations in school children . RESULTS: The prevalence of asthma was 4.8%, which was similar in the children from both schools . The children from the index school more often had wheezing (16% vs 6%; p <0.001) and cough (21% vs 9%: p < 0.001) symptoms than control children . Positive skin reactions to molds were rare (2.4%), being present in 7% of asthmatic and in 1-2% of non-asthmatic children (NS) . Lower respiratory tract infections were more common in the spring than in the fall in children from the index school, but not in control children, and the difference between the schools was significant in emergency visits (OR =2.0, p <0.01) and antibiotic courses (OR = 2.1, p < 0.01) . CONCLUSIONS: We found evidence of an association between moisture or mold problems in the school building and the occurrence of respiratory infections, repeated wheezing and prolonged cough in school children.

Biochemistry, 2000 Jan 11, 39(1), 237 - 47
Characterization of peroxisomal 3-hydroxy-3-methylglutaryl coenzyme A reductase in UT2 cells: sterol biosynthesis, phosphorylation, degradation, and statin inhibition; Aboushadi N et al.; We have previously identified a CHO cell line (UT2 cells) that expresses only one 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase protein which is localized exclusively in peroxisomes {Engfelt, H.W., Shackelford, J.E., Aboushadi, N., Jessani, N., Masuda, K., Paton, V.G., Keller, G.A., and Krisans, S.K . (1997) J . Biol . Chem . 272, 24579-24587} . In this study, we utilized the UT2 cells to determine the properties of the peroxisomal reductase independent of the endoplasmic reticulum (ER) HMG-CoA reductase . We demonstrated major differences between the two proteins . The peroxisomal reductase is not the rate-limiting enzyme for cholesterol biosynthesis in UT2 cells . The peroxisomal reductase protein is not phosphorylated, and its activity is not altered in the presence of inhibitors of cellular phosphatases . Its rate of degradation is not accelerated in response to mevalonate . Finally, the degradation process is not blocked by N-acetyl-Leu-Leu-norleucinal (ALLN) . Furthermore, the peroxisomal HMG-CoA reductase is significantly more resistant to inhibition by statins . Taken together, the data support the conclusion that the peroxisomal reductase is functionally and structurally different from the ER HMG-CoA reductase.

J Ethnopharmacol, 1999 Dec 15, 68(1-3), 3 - 37
Aloe vera leaf gel: a review update; Reynolds T et al.; Research since the 1986 review has largely upheld the therapeutic claims made in the earlier papers and indeed extended them into other areas . Treatment of inflammation is still the key effect for most types of healing but it is now realized that this is a complex process and that many of its constituent processes may be addressed in different ways by different gel components . A common theme running though much recent research is the immunomodulatory properties of the gel polysaccharides, especially the acetylated mannans from Aloe vera, which are now a proprietary substance covered by many patents . There have also been, however, persistent reports of active glycoprotein fractions from both Aloe vera and Aloe arborescens . There are also cautionary investigations warning of possible allergic effects on some patients . Reports also describe antidiabetic, anticancer and antibiotic activities, so we may expect to see a widening use of aloe gel . Several reputable suppliers produce a stabilized aloe gel for use as itself or in formulations and there may be moves towards isolating and eventually providing verified active ingredients in dosable quantities

Drug Des Discov, 1999 Nov, 16(3), 243 - 50
Synthesis of combinatorial libraries of 3,4,5-trisubstituted 2(5H)-furanones . Part Two: Construction of a library of 4-amino-5-alkoxy-2(5H)-furanones; Lattmann E et al.; A three dimensional combinatorial library of 3-halogen-4-amino-5-alkoxy-2(5H)-furanones has been prepared by applying solution phase combinatorial chemistry techniques . The substituents in the 3-4-5-positions of a butenolide scaffold were varied independently to generate with 3 butenolides, 4 alcohols and 24 amines a library of 288 compounds using a 2 stage synthetic protocol . Typical representives of the library were purified and fully characterized . Biological evaluation resulted in the discovery of a lead structure for a new class of antibiotic agents . The 4-benzylamino-2(5H)-furanone, Dr, of this library has shown a promising antibiotic activity against the multiresistant Staphillococcus aureus (MRSA 96-7778).

Lippincotts Prim Care Pract, 1999 Jul-Aug, 3(4), 419 - 27
Management of the patient with a total joint replacement: the primary care practitioner's role; Palmer LM; The primary care practitioner assumes chief responsibility for patients with arthritis . More than 40 million Americans experience some form of arthritis . Management of the patient with arthritis may include a referral to an orthopedic surgeon for surgical intervention . As estimated, up to 500,000 total joint replacement procedures are performed by orthopedic surgeons each year in the United States . Presurgical evaluation for a total joint replacement is imperative to ensure that the patient can safely undergo this surgical procedure . Postsurgical care of a patient with total joint replacement involves coordinating care with the physical therapist and orthopedic surgeon to ensure adequate follow-through with the recommended rehabilitation program, prophylactic antibiotic coverage, and observation for any complications including infection, deep-vein thrombosis, or loosening of the total-joint prosthesis.

J Clin Oncol, 2000 Jan, 18(1), 43 - 53
Randomized trial of filgrastim, sargramostim, or sequential sargramostim and filgrastim after myelosuppressive chemotherapy for the harvesting of peripheral-blood stem cells; Weaver CH et al.; PURPOSE: The purpose of this study was to compare the effects of filgrastim, sargramostim, or sequential sargramostim and filgrastim on CD34(+) cell yields and morbidity after myelosuppressive mobilization chemotherapy (MC) . PATIENTS AND METHODS: One hundred fifty-six patients were randomized to receive filgrastim (n = 51), sargramostim (n = 52), or sargramostim for 5 days followed by filgrastim (n = 53) after MC with either cyclophosphamide and etoposide (n = 75) or paclitaxel and cyclophosphamide (n = 81) . RESULTS: Compared with those who received sargramostim, patients who received filgrastim had faster recovery of an absolute neutrophil count of 0.5 x 10(9)/L or greater (a median of 11 v 14 days; P = . 0001), with fewer patients requiring RBC transfusions (P =.008), fewer patients with fever (18% v 52%; P = 0.001), fewer hospital admissions (20% v 42%; P =.013), and less intravenous antibiotic therapy (24% v 69%; P =.001) . Patients who received filgrastim yielded more CD34(+) cells (median, 7.1 v 2.0 x 10(6)/kg/apheresis; P =.0001), and a higher fraction achieved 2.5 x 10(6) (94% v 78%; P =.021) and 5 x 10(6) (88% v 53%; P =.001) or more CD34(+) cells/kg with fewer aphereses (median, 2 v 3; P =.002) and fewer days of growth-factor treatment (median, 12 v 14; P =.0001) . There were no major differences in outcomes between the filgrastim alone and the sequential regimens . After high-dose chemotherapy, patients who had peripheral-blood stem cells (PBSCs) mobilized with filgrastim or the sequential regimen received higher numbers of CD34(+) cells and had faster platelet recovery (P =.015), with fewer patients (P =.014) receiving fewer platelet transfusions (P =.001) than patients receiving sargramostim-mobilized PBSCs . CONCLUSION: It was concluded that filgrastim alone or sequential sargramostim and filgrastim were superior to sargramostim alone for the mobilization of CD34(+) cells and reduction of toxicities after MC.

Biochem Biophys Res Commun, 2000 Jan 7, 267(1), 54 - 8
Herbimycin A induces G1 arrest through accumulation of p27(Kip1) in cyclin D1-overexpressing fibroblasts; Endo N et al.; The ansamycin antibiotic herbimycin A is a potent tyrosine kinase inhibitor and reduces the growth rate of various types of mammalian cells . When quiescent Rat6 fibroblast cells were treated with herbimycin A, serum-induced expression of cyclin D1 was inhibited, and this was associated with inhibition of G1 phase progression . However, herbimycin A also inhibited serum-induced G1 progression in derivatives of the Rat6 fibroblast cell line that stably overexpress a human cyclin D1 cDNA (R6ccnD1#4 cells), without affecting the expression levels of G1 cyclins . We found that herbimycin A prevented serum-induced downregulation of the cyclin-dependent kinase inhibitor p27(Kip1), thereby leading to inactivation of the protein kinase activity of CDK2 . These results suggest that herbimycin A inhibits a tyrosine kinase(s) that plays a role in degradation of the p27(Kop1) protein .

Biochem J, 2000 Jan 15, 345 Pt 2, 307 - 14
Geldanamycin disrupts platelet-membrane structure, leading to membrane permeabilization and inhibition of platelet aggregation; Suttitanamongkol S et al.; Geldanamycin (GA), a benzoquinoid ansamycin antibiotic, has been used as a tyrosine kinase inhibitor and an anti-tumour agent and is known to bind to heat-shock protein 90 . In the present study on human platelets we have found that GA inhibited platelet aggregation induced by ADP, thrombin and the thrombin-receptor-activating peptide and caused platelet plasma-membrane damage, detected by leakage of adenine nucleotides as well as serotonin . Scanning electron microscopy (SEM) revealed that platelet exposure to GA led to the formation of holes or fenestrations in the platelet plasma membrane, confirming GA's ability to initiate membrane damage . In addition, GA itself caused both the dephosphorylation and phosphorylation of proteins in resting platelets and prevented agonist-induced phosphorylation of pleckstrin, the 20-kDa myosin light chain and other proteins . Another ansamycin, herbimycin A, also inhibited platelet aggregation, but caused minimal membrane permeabilization, as detected by (3)H release from platelets labelled previously with {(3)H}adenine, and much less membrane damage, revealed by SEM . Overall, GA is able to disrupt membrane structure and inhibit platelet aggregation, an ability which may be linked to alterations in the activity of protein kinases and phosphatases.

Int J Clin Pract, 1999 Sep, 53(6), 460 - 6
Chronic infections and coronary heart disease; Smith D et al.; The rapidly changing patterns of coronary heart disease (CHD) prevalence and presentation fail to be explained by conventional cardiovascular risk factors alone . An infectious basis to atherosclerosis may, at least in part, be contributing to the variable rates of prevalence of CHD in different parts of the world . The evidence for such an association appears to be strongest for Chlamydia pneumoniae . Results of recent anti-chlamydia antibiotic intervention pilot studies have renewed interest in the role of C . pneumoniae, and corroborated the evidence from sero-epidemiological, pathological and animal-model studies . The results of larger, on-going, purpose-designed intervention studies should help to increase our understanding of the role of infection in atherogenesis and potentially lead to a novel and effective treatment strategy for patients with CHD--broad spectrum antibiotics.

Postgrad Med J, 1999 Nov, 75(889), 645 - 9
Necrotizing soft tissue infections; Urschel JD; Necrotizing soft tissue infections are a group of highly lethal infections that typically occur after trauma or surgery . Many individual infectious entities have been described, but they all have similar pathophysiologies, clinical features, and treatment approaches . The essentials of successful treatment include early diagnosis, aggressive surgical debridement, antibiotics, and supportive intensive treatment unit care . The two commonest pitfalls in management are failure of early diagnosis and inadequate surgical debridement . These life-threatening infections are often mistaken for cellulitis or innocent wound infections, and this is responsible for diagnostic delay . Tissue gas is not a universal finding in necrotizing soft tissue infections . This misconception also contributes to diagnostic errors . Incision and drainage is an inappropriate surgical strategy for necrotizing soft tissue infections; excisional debridement is needed . Hyperbaric oxygen therapy may be useful, but it is not as important as aggressive surgical therapy . Despite advances in antibiotic therapy and intensive treatment unit medicine, the mortality of necrotizing soft tissue infections is still high . This article emphasizes common treatment principles for all of these infections, and reviews some of the more important individual necrotizing soft tissue infectious entities.

Clin Radiol, 1999 Dec, 54(12), 792 - 7
Medical treatment of renal and perirenal abscesses: CT evaluation; Dalla Palma L et al.; AIM: A retrospective study of our experience of CT evaluation and follow-up of 16 solitary and multiple renal abscesses treated successfully with antibiotics alone and evaluated with CT at the onset of symptoms and after therapy . MATERIALS AND METHODS: Seven patients had a solitary renal abscess, five had multiple renal abscesses and four had renal and perinephric abscess . None of the abscesses were larger than 5 cm . RESULTS: In all 16 patients, the CT examination showed total renal and extrarenal regression of the abscesses . In four patients, scarring of the renal outline was observed on follow-up . CONCLUSIONS: The study demonstrates the opportunity to avoid aggressive interventional or surgical treatment of renal and perirenal abscesses of 5-cm diameter or less which can completely regress after antibiotic therapy of at least 4 weeks . The CT examination results are important both in the diagnostic phase to establish the extent of the lesions and in the follow-up to check the results of medical treatment.

Proc Natl Acad Sci U S A, 2000 Jan 4, 97(1), 418 - 23
Treatment of Mycobacterium tuberculosis with antisense oligonucleotides to glutamine synthetase mRNA inhibits glutamine synthetase activity, formation of the poly-L-glutamate/glutamine cell wall structure, and bacterial replication; Harth G et al.; New antibiotics to combat the emerging pandemic of drug-resistant strains of Mycobacterium tuberculosis are urgently needed . We have investigated the effects on M . tuberculosis of phosphorothioate-modified antisense oligodeoxyribonucleotides (PS-ODNs) against the mRNA of glutamine synthetase, an enzyme whose export is associated with pathogenicity and with the formation of a poly-L-glutamate/glutamine cell wall structure . Treatment of virulent M . tuberculosis with 10 microM antisense PS-ODNs reduced glutamine synthetase activity and expression by 25-50% depending on whether one, two, or three different PS-ODNs were used and the PS-ODNs' specific target sites on the mRNA . Treatment with PS-ODNs of a recombinant strain of Mycobacterium smegmatis expressing M . tuberculosis glutamine synthetase selectively inhibited the recombinant enzyme but not the endogenous enzyme for which the mRNA transcript was mismatched by 2-4 nt . Treatment of M . tuberculosis with the antisense PS-ODNs also reduced the amount of poly-L-glutamate/glutamine in the cell wall by 24% . Finally, treatment with antisense PS-ODNs reduced M . tuberculosis growth by 0 . 7 logs (1 PS-ODN) to 1.25 logs (3 PS-ODNs) but had no effect on the growth of M . smegmatis, which does not export glutamine synthetase nor possess the poly-L-glutamate/glutamine (P-L-glx) cell wall structure . The experiments indicate that the antisense PS-ODNs enter the cytoplasm of M . tuberculosis and bind to their cognate targets . Although more potent ODN technology is needed, this study demonstrates the feasibility of using antisense ODNs in the antibiotic armamentarium against M . tuberculosis.

J Biol Chem, 2000 Jan 7, 275(1), 167 - 76
Disruption of vma-1, the gene encoding the catalytic subunit of the vacuolar H(+)-ATPase, causes severe morphological changes in Neurospora crassa; Bowman EJ et al.; By using the process of Repeat-induced Point mutation (Selker, E . U., and Garrett, P . W . (1988) Proc . Natl . Acad . Sci . U . S . A . 85, 6870-6874), we inactivated vma-1, the gene encoding subunit A of the V-ATPase of Neurospora crassa . Two vma-1 mutant strains were characterized . One was mutated at multiple sites, did not make a protein product, and produced spores that only rarely germinated . The other had four point mutations, made a protein product, and produced viable spores . Neither strain had detectable V-ATPase activity . The vma-1 mutant strains did not grow in medium buffered to pH 7.0 or above or in medium supplemented with the cation Zn(2+) . They were completely resistant to inhibition by concanamycin C, supporting our hypothesis that the V-ATPase is the in vivo target of this antibiotic . Inactivation of the vma-1 gene had a pronounced effect on morphology and development of the organism . In the mutants tip growth was inhibited, and multiple branching was induced . The vma-1 mutant strains could not differentiate conidia or perithecia . They could grow slowly as mycelia and could donate nuclei in a sexual cross . A mutation in the plasma membrane ATPase, which suppressed the sensitivity of wild type N . crassa to concanamycin, also proved effective in suppressing the sensitivity of a vma-1 null mutant to basic pH but did not correct the morphological defects.

J Neurosurg, 2000 Jan, 92(1), 31 - 8
Risk factors for repeated cerebrospinal shunt failures in pediatric patients with hydrocephalus; Tuli S et al.; OBJECT: Repeated cerebrospinal fluid (CSF) shunt failures in pediatric patients are common, and they are a significant cause of morbidity and, occasionally, of death . To date, the risk factors for repeated failure have not been established . By performing survival analysis for repeated events, the authors examined the effects of patient characteristics, shunt hardware, and surgical details in a large cohort of patients . METHODS: During a 10-year period all pediatric patients with hydrocephalus requiring CSF diversion procedures were included in a prospective single-institution observational study . Patient characteristics were defined as age, gender, weight, head circumference, American Society of Anesthesiology class, and cause of hydrocephalus . Surgical details included whether the procedure was performed on an emergency or nonemergency basis, use of antibiotic agents, concurrent surgical procedures, and duration of the surgical procedure . Details on shunt hardware included: the type of shunt, the valve system, whether the shunt system included multiple or complex components, the type of distal catheter, the site of the shunt, and the side on which the shunt was placed . Repeated shunt failures were assessed using multivariable time-to-event analysis (by using the Cox regression model) . Conditional models (as established by Prentice, et al.) were formulated for gap times (that is, times between successive shunt failures) . There were 1183 shunt failures in 839 patients . Failure time from the first shunt procedure was an important predictor for the second and third episodes of failure, thus establishing an association between the times to failure within individual patients . An age younger than 40 weeks gestation at the time of the first shunt implantation carried a hazard ratio (HR) of 2.49 (95% confidence interval {CI} 1.68-3.68) for the first failure, which remained high for subsequent episodes of failure . An age from 40 weeks gestation to 1 year (at the time of the initial surgery) also proved to be an important predictor of first shunt malfunctions (HR 1.77, 95% CI 1.29-2.44) . The cause of hydrocephalus was significantly associated with the risk of initial failure and, to a lesser extent, later failures . Concurrent other surgical procedures were associated with an increased risk of failure . CONCLUSIONS: The patient's age at the time of initial shunt placement and the time interval since previous surgical revision are important predictors of repeated shunt failures in the multivariable model . Even after adjusting for age at first shunt insertion as well as the cause of hydrocephalus, there is significant association between repeated failure times for individual patients.

Epidemiology, 2000 Jan, 11(1), 81 - 3
Simpson's paradox: an example from hospital epidemiology; Reintjes R et al.; Simpson's paradox was first recognized at the beginning of the 20th century, but few examples with real data have been presented . In this paper we present an example of this phenomenon from a multicenter study on nosocomial infections, and we try to explain intuitively this type of extreme confounding.

J Arthroplasty, 1999 Dec, 14(8), 952 - 6
The role of intraoperative gram stain in the diagnosis of infection during revision total hip arthroplasty; Spangehl MJ et al.; A total of 202 revision hip arthroplasties in 178 patients, over a 2-year period, were evaluated prospectively . Intraoperative Gram stains were obtained from periprosthetic tissues in all cases . Of these, a definitive diagnosis of infection, using defined criteria, was established in 35 cases . Of these 35 patients, 17 had received antibiotics before surgery . The intraoperative cultures were positive in 8 of the 17 patients who had received antibiotics and 17 of the 18 patients who had not received preoperative antibiotics . In 1 infected case, intraoperative cultures of periprosthetic tissues failed to reveal bacterial growth, despite the fact that the patient received no preoperative antibiotics . Overall, there were 5 true-positive Gram stain results, 172 true-negative results, 3 false-positive results, and 22 false-negative results . The sensitivity of the Gram stain was 19%, specificity was 98%, predictive value of a positive test was 63%, and predictive value of a negative test was 89% . These results suggest that the intraoperative Gram stain is not a sensitive tool for the diagnosis of infection and should not be used when attempting to diagnose infection intraoperatively.

Pediatr Pulmonol, 2000 Jan, 29(1), 1 - 7
Randomized controlled trials in cystic fibrosis (1966-1997) categorized by time, design, and intervention; Cheng K et al.; The improved prognosis of cystic fibrosis (CF) over the last three decades has been associated with an increased use of a range of treatments, but it is important that the use of an individual treatment is based on evidence . Well-designed randomized controlled trials (RCTs) are a robust method for evaluating the effectiveness of such treatments . We have developed a register of RCTs in CF and have studied when they were performed, their design, and what interventions were investigated . We identified 506 RCTs; 37.5% were identified solely as abstract reports in conference proceedings . There has been about a 30-fold increase in the number of RCTs in CF since 1966 . A high proportion of the RCTs (72.7%) had a sample size of 30 or less, and only 8.7% were multicenter trials . Reporting of study design was poor: in 51.4% the report did not state whether there was any blinding in the trial design; 53.6% of studies were of crossover design . The most common interventions studied were antibiotic treatments and physiotherapy, but a number of commonly used therapies had been evaluated only in a small number of patients . Although the number of RCTs of interventions in CF patients has increased over the last 25 years, the sample sizes of these trials are generally too small to indicate whether the intervention was effective, and very few were multicenter . Future RCTs in CF are more likely to provide clinically useful answers if higher numbers of patients are recruited into large, well-designed multicenter trials . This should be a priority of the organization of future research in CF .

Dis Colon Rectum, 1999 Dec, 42(12), 1644 - 8
Fournier's gangrene after hemorrhoidectomy: association with drug-induced agranulocytosis . Report of a case; Cihan A et al.; An unusual case of Fournier's gangrene after hemorrhoidectomy and drug-induced agranulocytosis, as the predisposing condition, is described . The patient had severe granulocytopenia that was attributed to the recent use of dipyrone . Together with hemodynamic resuscitation, broad-spectrum antibiotic and recombinant human granulocyte colony-stimulating factor were started . Wide surgical excision of all the gangrenous tissues, in addition to laparoscopic formation of a defunctioning sigmoid loop colostomy, was performed . The white blood cell count rose steadily and the patient experienced a rapid recovery . We emphasize that radical surgery must be accompanied by pharmacologic interventions for a successful outcome in such cases.

Ned Tijdschr Geneeskd, 1999 Nov 27, 143(48), 2401 - 3
{Family doctor: acrobat or drugstore clerk?}; Mazel JA et al.; In four cases there existed a discrepancy between the patient's request and the views of the GP who went by the guidelines of the Dutch College of General Practitioners . The requests concerned were those of a woman aged 56 who wanted a serum cholesterol determination and a youth aged 17 with a sprained ankle who asked for an X-ray--they were not satisfied until their wishes had been fulfilled--and those of a man aged 43 with recurrent low back pain who wanted to be referred to physical therapy and a woman aged 39 with a common cold who wanted a prescription for an antibiotic--they were only satisfied after a favourable development . The general practitioner has to choose whether to fulfill the patient's wishes or try to explain that the advice--based on medical evidence--is preferable . Good patient information is necessary for a better understanding of each other's points of view and, moreover, gives the doctor more satisfaction in his or her work.

Clin Orthop, 1999 Dec, (369), 144 - 56
The treatment of the infected hip replacement . The complex case; Haddad FS et al.; The treatment of the infected total hip replacement remains expensive, leads to a long difficult course for the patient, and frequently results in a suboptimal functional outcome . Various treatment techniques are available, and may be suitable for the more straightforward case . These include one-stage exchange arthroplasty, two-stage exchange arthroplasty, resection arthroplasty, and debridement and irrigation . The complex infected total hip replacement encompasses numerous host and organism factors . These include unusual or multiple organisms, diagnostic difficulties, bone loss, immunocompromise, and reinfection . In the authors' experience, the problem of the complex infected hip replacement is best addressed using the prosthesis of antibiotic-loaded acrylic cement approach . This interval arthroplasty is a modular, custom-made, immediate fit, antibiotic selective, temporary spacer system that allows the surgeon to reconstruct even the most deficient bone stock safely and effectively using two-stage exchange arthroplasty . It affords the patient rapid pain relief, allows them to mobilize quickly while successfully eradicating infection in 96% of hips with severe bone loss, and sets an appropriate soft tissue environment for a relatively straightforward second stage procedure . The prosthesis of antibiotic-loaded acrylic cement system affords the benefits of two-stage exchange without the functional disadvantages of an excision arthroplasty particularly when the proximal femur is severely deficient . It allows flexibility for the interval period and the type of fixation used, and the potential for allograft reconstruction at the final stage.

Clin Orthop, 1999 Dec, (369), 139 - 43
One-stage revision surgery of the infected hip . A minimum 10-year followup study; Callaghan JJ et al.; Between 1977 and 1983, 24 one-stage revision surgeries were performed for septic failure of a total hip arthroplasty in 24 patients by one surgeon . Twelve patients died and none were lost to followup at a minimum of 10 years after the procedure . Infection reoccurred around two hips (8.3%) . If the selected criteria (patients without draining sinuses, without immunocompromise, and with adequate bone quality after debridement) and the standard approach (meticulous debridement, use of antibiotic-impregnated cement, and use of 3 to 6 months postoperative oral antibiotic therapy) used in this study are implemented, direct exchange of an infected total hip arthroplasty construct is a reasonable and cost-effective alternative for some patients with infection after total hip arthroplasty.

J Mol Biol, 1999 Dec 3, 294(3), 785 - 94
Thermodynamics of the alpha-helix-coil transition of amphipathic peptides in a membrane environment: implications for the peptide-membrane binding equilibrium; Wieprecht T et al.; Amphipathic alpha-helices are the membrane binding motif in many proteins . The corresponding peptides are often random coil in solution but are folded into an alpha-helix upon interaction with the membrane . The energetics of this ubiquitous folding process are still a matter of conjecture . Here, we present a new method to quantitatively analyze the thermodynamics of peptide folding at the membrane interface . We have systematically varied the helix content of a given amphipathic peptide when bound to the membrane and have correlated the thermodynamic binding parameters determined by isothermal titration calorimetry with the alpha-helix content obtained by circular dichroism spectroscopy . The peptides investigated were the antibiotic magainin 2 amide and three analogs in which two adjacent amino acid residues were substituted by their d-enantiomers . The thermodynamic parameters controlling the alpha-helix formation were found to be linearly related to the helicity of the membrane-bound peptides . Helix formation at the membrane surface is characterized by an enthalpy change of DeltaH(helix) approximately -0.7 kcal/mol per residue, an entropy change of DeltaS(helix) approximately -1.9 cal/molK residue and a free energy change of DeltaG(helix)=-0.14 kcal/mol residue . Helix formation is a strong driving force of peptide insertion into the membrane and accounts for about 50 % of the free energy of binding . An increase in temperature entails an unfolding of the membrane-bound helix . The temperature dependence can be described with the Zimm-Bragg theory and the enthalpy of unfolding agrees with that deduced from isothermal titration calorimetry .

J Mol Biol, 1999 Dec 3, 294(3), 627 - 37
Mutant EF-Tu species reveal novel features of the enacyloxin IIa inhibition mechanism on the ribosome; Zuurmond AM et al.; For clarification of the action of a new antibiotic, the analysis of resistant mutants is often indispensable . For enacyloxin IIa we discovered four resistant elongation factor Tu (EF-Tu) species in Escherichia coli with the mutations Q124K, G316D, Q329H, and A375T, respectively . They revealed that enacyloxin IIa sensitivity is dominant in a mixed population of resistant and wild-type EF-Tus . This points to an inhibition mechanism in which EF-Tu is the dominant target of enacyloxin IIa and in which a ribosome with a sensitive EF-Tu blocks mRNA translation for upstream ribosomes with resistant EF-Tus, a mechanism similar to that of the unrelated antibiotic kirromycin . Remarkably, the same mutations are also linked to kirromycin resistance, though the order of their levels of resistance is different from that for enacyloxin IIa . Among the mutant EF-Tus, three different resistance mechanisms can be distinguished: (i) by obstructing enacyloxin IIa binding to EF-Tu . GTP; (ii) by enabling the release of enacyloxin IIa after GTP hydrolysis; and (iii) by reducing the affinity of EF-Tu.GDP . enacyloxin IIa for aminoacyl-tRNA at the ribosomal A-site, which then allows the release of EF-Tu.GDP.enacyloxin IIa . Ala375 seems to contribute directly to enacyloxin IIa binding at the domain 1-3 interface of EF-Tu.GTP, a location that would easily explain the pleiotropic effects of enacyloxin IIa on the functioning of EF-Tu .

Klin Monatsbl Augenheilkd, 1999 Nov, 215(5), 311 - 4
{Penetrating and perforating eye injuries with foreign bodies during motorized brush-cutting while wearing head protection gear}; Gau M et al.; BACKGROUND: Protective clothing is prescribed concerning gloves, shoes, protective trousers and a helmet for protection of hearing and the face during brush-cutter work . PATIENTS AND METHODS: Seven patients were observed in a time period from 1994 to 1998 . Mostly a nylon head protection had been used . The side of the helmet has no protection shield . The 1- to 4-mm large foreign bodies passed the head protection shield from the side or by entering through the holes of the nylon mesh which may be not small enough to stop the foreign body . A pars plana vitrectomy with foreign body removal was performed after primary wound repair . RESULTS: An endophthalmitis was diagnosed in two patients after primary wound treatment . In these cases, a pars plana vitrectomy and antibiotic instillation was performed . In 5 patients visual acuity increased postoperatively . We measured a postoperative visual acuity from 1/50 to 1.6 . The development of proliferative vitreoretinopathy with retinal detachment in 4 patients was the main complication observed after pars plana vitrectomy . CONCLUSIONS: A cosmetically satisfactory appearance of the injured eye was reached by pars plana vitrectomy in all patients . Anatomic and functional success was reached in most of the patients . For prophylaxis, a head-protection seems not safe enough . The additional usage of eye protection glasses may be imperative for the prevention of these eye injuries.

J Cataract Refract Surg, 1999 Dec, 25(12), 1685 - 7
Recurrent anterior uveitis and glaucoma associated with inadvertent entry of ointment into the anterior chamber after radial keratotomy; Garzozi HJ et al.; Anterior uveitis and elevated intraocular pressure (IOP) occurred after radial keratotomy that was complicated by microperforation and penetration of antibiotic ophthalmic ointment into the anterior chamber . Anterior uveitis and IOP elevation were observed during the early postoperative follow-up and 41 and 61 months after surgery . All 3 attacks responded well to topical anti-inflammatory and antiglaucoma treatment . The probable causes of the uveitis and glaucoma in this case are discussed.

J Bone Joint Surg Am, 1999 Dec, 81(12), 1662 - 70
Differentiating between septic arthritis and transient synovitis of the hip in children: an evidence-based clinical prediction algorithm; Kocher MS et al.; BACKGROUND: A child who has an acutely irritable hip can pose a diagnostic challenge . The purposes of this study were to determine the diagnostic value of presenting variables for differentiating between septic arthritis and transient synovitis of the hip in children and to develop an evidence-based clinical prediction algorithm for this differentiation . METHODS: We retrospectively reviewed the cases of children who were evaluated at a major tertiary-care children's hospital between 1979 and 1996 because of an acutely irritable hip . Diagnoses of true septic arthritis, presumed septic arthritis, and transient synovitis were explicitly defined on the basis of the white blood-cell count in the joint fluid, the results of cultures of joint fluid and blood, and the clinical course . Univariate analysis and multiple logistic regression analysis were used to compare groups . A probability algorithm for differentiation between septic arthritis and transient synovitis on the basis of independent multivariate predictors was constructed and tested . RESULTS: Patients who had septic arthritis differed significantly (p < 0.05) from those who had transient synovitis with regard to the erythrocyte sedimentation rate, serum white blood-cell count and differential, weight-bearing status, history of fever, temperature, evidence of effusion on radiographs, history of chills, history of recent antibiotic use, hematocrit, and gender . Patients who had true septic arthritis differed significantly (p < 0.05) from those who had presumed septic arthritis with regard to history of recent antibiotic use, history of chills, temperature, erythrocyte sedimentation rate, history of fever, gender, and serum white blood-cell differential . Four independent multivariate clinical predictors were identified to differentiate between septic arthritis and transient synovitis: history of fever, non-weight-bearing, erythrocyte sedimentation rate of at least forty millimeters per hour, and serum white blood-cell count of more than 12,000 cells per cubic millimeter (12.0 x 10(9) cells per liter) . The predicted probability of septic arthritis was determined for all sixteen combinations of these four predictors and is summarized as less than 0.2 percent for zero predictors, 3.0 percent for one predictor, 40.0 percent for two predictors, 93.1 percent for three predictors, and 99.6 percent for four predictors . The chi-square test for trend and the area under the receiver operating characteristic curve indicated excellent diagnostic performance of this group of multivariate predictors in identifying septic arthritis . CONCLUSIONS: Although several variables differed significantly between the group that had septic arthritis and the group that had transient synovitis, substantial overlap in the intermediate ranges made differentiation difficult on the basis of individual variables alone . However, by combining variables, we were able to construct a set of independent multivariate predictors that, together, had excellent diagnostic performance in differentiating between septic arthritis and transient synovitis of the hip in children.

Med Hypotheses, 1999 Oct, 53(4), 350 - 60
Niacinamide therapy for osteoarthritis--does it inhibit nitric oxide synthase induction by interleukin 1 in chondrocytes?
McCarty MF, Russell AL.
Fifty years ago, Kaufman reported that high-dose niacinamide was beneficial in osteoarthritis (OA) and rheumatoid arthritis . A recent double-blind study confirms the efficacy of niacinamide in OA . It may be feasible to interpret this finding in the context of evidence that synovium-generated interleukin-1 (IL-1), by inducing nitric oxide (NO) synthase and thereby inhibiting chondrocyte synthesis of aggrecan and type II collagen, is crucial to the pathogenesis of OA . Niacinamide and other inhibitors of ADP-ribosylation have been shown to suppress cytokine-mediated induction of NO synthase in a number of types of cells; it is therefore reasonable to speculate that niacinamide will have a comparable effect in IL-1-exposed chondrocytes, blunting the anti-anabolic impact of IL-1 . The chondroprotective antibiotic doxycycline may have a similar mechanism of action . Other nutrients reported to be useful in OA may likewise intervene in the activity or synthesis of IL-1 . Supplemental glucosamine can be expected to stimulate synovial synthesis of hyaluronic acid; hyaluronic acid suppresses the anti-catabolic effect of IL-1 in chondrocyte cell cultures, and has documented therapeutic efficacy when injected intra-articularly . S-adenosylmethionine (SAM), another proven therapy for OA, upregulates the proteoglycan synthesis of chondrocytes, perhaps because it functions physiologically as a signal of sulfur availability . IL-1 is likely to decrease SAM levels in chondrocytes; supplemental SAM may compensate for this deficit . Adequate selenium nutrition may down-regulate cytokine signaling, and ample intakes of fish oil can be expected to decrease synovial IL-1 production; these nutrients should receive further evaluation in OA . These considerations suggest that non-toxic nutritional regimens, by intervening at multiple points in the signal transduction pathways that promote the synthesis and mediate the activity of IL-1, may provide a substantially superior alternative to NSAIDs (merely palliative and often dangerously toxic) in the treatment and perhaps prevention of OA.

Helicobacter, 1999 Dec, 4(4), 243 - 8
Practice patterns for peptic ulcer disease: are family physicians testing for H . pylori?
Zoorob RJ, Jones GN, Mainous AG 3rd, Hagen MD.
BACKGROUND: Peptic ulcer disease (PUD) is a problem common in family medicine . Recent evidence of Helicobacter pylori as an etiological agent of PUD has led to National Institutes of Health recommendations for treatment to eradicate H . pylori through antibiotic therapy . The purpose of this study is to examine practice patterns of family physicians in treating PUD, their use of H . pylori testing, and knowledge of current recommendations for PUD . MATERIALS AND METHODS: A mail survey was sent to a random sample of 1,500 members of the American Academy of Family Physicians . Six hundred thirty useable surveys (49.1%) were available for analysis . Descriptive statistics were obtained, as were inferential statistics focusing on the relationship of physician background characteristics to practices . RESULTS: Thirty-eight percent of the respondents order diagnostic procedures for the majority (50% or more) of their suspected PUD cases . Of the physicians who reported ordering any diagnostic tests, 52% ordered the combination of upper gastrointestinal series and endoscopic gastroduodenoscopy . For patients with clinical diagnoses of PUD, 77% of doctors reported ordering a diagnostic test for H . pylori . Approximately 68% were aware that some kind of guidelines existed; only 11% reported that they were familiar with the National Institutes of Health recommendations for PUD . CONCLUSIONS: Although some of the practices of family physicians for treatment of PUD deviate from current recommendations, the majority of practices are consistent with current evidence.

FEBS Lett, 1999 Dec 17, 463(3), 241 - 4
Inhibition of yeast inositol phosphorylceramide synthase by aureobasidin A measured by a fluorometric assay; Zhong W et al.; Inositol phosphorylceramide synthase (IPC synthase) is an essential and unique enzyme in fungal sphingolipid biosynthesis and is the target of the cyclic nonadepsipeptide antibiotic aureobasidin A . As a first step towards understanding the mechanism of aureobasidin A inhibition, we developed a fluorometric HPLC assay for IPC synthase using the Saccharomyces cerevisiae enzyme and the fluorescent substrate analog 6-{N-(7-nitro-2,1, 3-benzoxadiazol-4-yl)amino}-hexanoyl ceramide (C(6)-NBD-cer) . The kinetic parameters for C(6)-NBD-cer were comparable to those for the synthetic substrate N-acetylsphinganine used previously . Aureobasidin A acted as a tight-binding, non-competitive inhibitor with respect to C(6)-NBD-cer and had a K(i) of 0.55 nM.

Med Tr Prom Ekol, 1999, (11), 20 - 4
{Analysis of immunological indices of occupational sensibilization to tylosin}; Baltadzhieva D et al.; The authors studied sensibilization to antibiotic Tilosine and determined several immunologic parameters in Tilosine production workers, searching for criteria of the sensibilization's occupational etiology . The results prove that skin allergic reactivity, antibodies production and lymphocytes proliferation response are diagnostic for immune changes in workers exposed to occupational allergens and useful for assessing risk of allergic disorders.

An Med Interna, 1999 Oct, 16(10), 527 - 9
{Leptospirosis . Review of 5 cases}; Resano Igal AB et al.; Five cases of leptospirosis diagnosed from 1978 to 1996 were retrospectively reviewed . The five patients were male and their mean age was 34.2 years . Epidemiologic factors were found in the 5 patients . The 3 common clinical findings: fever, myalgia and jaundice were found in the 5 patients . Hepatorenal involvement was observed in 4 cases (80%), bleeding episodes in 4 patients (80%), cardiac involvement in 4 (80%); in none case was observed central nervous system involvement . In one case (20%) was observed septic shock with acute respiratory failure . The Leptospira serogroups identified were icterohaemorrhagiae in 3 cases and could not be determined in 2 . All the patients were amelioration with antibiotic therapeutic . The epidemiologic, clinical, analytical and therapeutic aspects are discussed.

Respir Med, 1999 Nov, 93(11), 770 - 8
Intra-tracheal delivery strategy of gentamicin with partial liquid ventilation; Cullen AB et al.; Patients with pulmonary infection often present with ventilation and perfusion abnormalities, which can impair intravenous antibiotic therapy . Intra-tracheal (i.t.) administration has met with obstacles, such as inadequate delivery to affected lung regions and the disruption of gas exchange . We hypothesized that i.t . administration of a gentamicin (G)/perfluorochemical (PFC) suspension (G/PFC) would effectively deliver and distribute gentamicin to the lung, while maintaining gas exchange and non-toxic serum levels . In addition, we sought to compare serum G and lung levels and distribution of G when G/PFC is administered at the initiation of partial liquid ventilation (PLV) vs . during PLV . To test this hypothesis, 17 newborn lambs were ventilated by PLV with perflubron (LiquiVent) for 4 h using three different G (5 mg kg-1) administration techniques: i.t . slow-fill (SF) (n = 6; G/PFC over 15 min at start of PLV), i.t . top-fill (TF) (n = 6; G/PFC 10-65 min after start of PLV), intravenous (i.v.) (n = 5, aqueous injection at start of PLV) . Serum levels of gentamicin were obtained 1, 15, 30 and 60 min after administration, and hourly there after for the remainder of the protocol (4 h) . Arterial blood gas and pulmonary function measurements were obtained throughout the protocol . At the conclusion of the protocol, representative samples from each lung lobe, the brain and kidney were homogenized and assayed for gentamicin . All results are presented as the mean +/- SEM; P < 0.05 . Over time, serum gentamicin levels were greatest (P < 0.05) in i.v . (11.0 +/- 2.3 micrograms ml-1), followed by TF (2.3 +/- 0.1 micrograms ml-1) and SF (0.8 +/- 0.1 microgram ml-1) . The percentage of the administered dose remaining in the lungs after 4 h was greater (P < 0.05) following i.t . delivery (SF 23.8 +/- 4.3%, TF 13.7 +/- 2.5%) as compared to i.v . (3.7 +/- 0.5%) . These findings suggest that for a given dose of G, both SF and TF delivery methods of G/PFC can enhance pulmonary, relative to systemic, antibiotic coverage.

Infect Immun, 2000 Jan, 68(1), 192 - 6
Subclinical chlamydial infection of the female mouse genital tract generates a potent protective immune response: implications for development of live attenuated chlamydial vaccine strains; Su H et al.; Chlamydia trachomatis is a major cause of sexually transmitted disease (STD) for which a vaccine is needed . CD4(+) T-helper type 1 (Th1) cell-mediated immunity is an important component of protective immunity against murine chlamydial genital infection . Conventional vaccine approaches have not proven effective in eliciting chlamydial-specific CD4 Th1 immunity at the genital mucosa . Thus, it is possible that the development of a highly efficacious vaccine against genital infection will depend on the generation of a live attenuated C . trachomatis vaccine . Attenuated strains of C . trachomatis do not exist, so their potential utility as vaccines cannot be tested in animal models of infection . We have developed a surrogate model to study the effect of chlamydial attenuation on infection and immunity of the female genital tract by treating mice with a subchlamydiacidal concentration of oxytetracycline following vaginal infection . Compared to untreated control mice, antibiotic-treated mice shed significantly fewer infectious organisms (3 log(10)) from the cervico-vagina, produced a minimal inflammatory response in urogenital tissue, and did not experience infection-related sequelae . Antibiotic-treated mice generated levels of chlamydia-specific antibody and cell-mediated immunity equivalent to those of control mice . Importantly, antibiotic-treated mice were found to be as immune as control untreated mice when rechallenged vaginally . These findings demonstrate that subclinical chlamydial infection of the murine female genital tract is sufficient to stimulate a potent protective immune response . They also present indirect evidence supporting the possible use of live attenuated chlamydial organisms in the development of vaccines against chlamydial STDs.

Angew Chem Int Ed Engl, 1999 Nov 15, 38(22), 3334 - 3339
Total Synthesis of Everninomicin 13,384-1-Part 1: Synthesis of the A(1)B(A)C Fragment; Nicolaou KC et al.; The powerful antibiotic everninomicin 13,384-1 (1, Ziracin) has been prepared for the first time through a total synthesis . The 1-->1'-disaccharide and the two orthoesters of this target molecule were introduced by new methodologies using a tin acetal and 1,2-phenylseleno migrations . The reaction sequence also relies on stereoselective glycosidations and subtle manipulations of protecting groups . In addition to the introduction of new synthetic methodologies, this total synthesis should allow the preparation of combinatorial libraries of semisynthetic analogues of this highly promising antibiotic for biological screening purposes.

J Neurophysiol, 1999 Dec, 82(6), 3168 - 74
Gentamicin blocks both fast and slow effects of olivocochlear activation in anesthetized guinea pigs; Yoshida N et al.; The medial olivocochlear (MOC) efferent system, which innervates cochlear outer hair cells, suppresses cochlear responses . MOC-mediated suppression includes both slow and fast components, with time courses differing by three orders of magnitude . Pharmacological studies in anesthetized guinea pigs suggest that both slow and fast effects on cochlear responses require an initial acetylcholine activation of alpha-9 nicotinic receptors on outer hair cells and that slow effects require additional intracellular events downstream from those mediating fast effects . Gentamicin, an aminoglycoside antibiotic, has been reported to block fast effects of sound-evoked OC activation following intramuscular injection in unanesthetized guinea pigs, without changing slow effects . In the present study, we show that electrically evoked fast and slow effects in the anesthetized guinea pig are both blocked by either intramuscular or intracochlear gentamicin, with similar time courses and/or dose-response curves . We suggest that sound-evoked slow effects in unanesthetized animals are fundamentally different from electrically evoked slow effects in anesthetized animals, and that the former may arise from effects of the lateral OC system.

Pharmacotherapy, 1999 Dec, 19(12), 1456 - 8
Trimethoprim-sulfamethoxazole-induced tremor in an immunocompetent patients; Patterson RG et al.; Trimethoprim-sulfamethoxazole (TMP-SMX) is a widely administered antibiotic that is well tolerated by most patients . Hypersensitivity reactions and gastrointestinal intolerance are the most common adverse events associated with it . Central nervous system adverse effects such as tremors are less common and occur primarily in patients with acquired immune deficiency syndrome . A 29-year-old immunocompetent man developed a tremor while taking TMP-SMX . The tremor resolved within 2 days after the drug was discontinued.

Immunopharmacology, 1999 Nov, 44(3), 255 - 65
Hypothemycin inhibits the proliferative response and modulates the production of cytokines during T cell activation; Camacho R et al.; Hypothemycin, a resorcylic acid lactone antibiotic, was identified as active in a screen for inhibitors of T cell activation . It was found to inhibit the proliferation of mouse and human T cells stimulated with anti-CD3 mAb + PMA and of human PBMC stimulated with anti-CD3 mAb alone . This inhibition was partially reversed by exogenous IL-2 indicating that it is not due to non-specific toxicity . Hypothemycin potently suppressed the production of IL-2 (IC50: 9 nM) but affected IL-2-induced proliferation to a lesser extent (IC50: 194 nM) . Hypothemycin also inhibited IL-6, IL-10, IFN-gamma and TNF-alpha production . By contrast, it markedly enhanced the production of IL-4, IL-5 and IL-13 . These effects were seen both at the mRNA and protein secretion levels . Analysis of the effect of hypothemycin on CD69 induction suggested that it disrupts calcineurin-independent rather than calcineurin-dependent signaling . Furthermore, hypothemycin was able to inhibit the phosphorylation of ERK1/2 induced by PMA treatment of T cells . Therefore, hypothemycin represents an inhibitor of T cell activation with a novel mode of action and unique modulatory activity on cytokine production.

J Pediatr Hematol Oncol, 1999 Nov-Dec, 21(6), 475 - 8
Rebirth of granulocyte transfusions: should it involve pediatric oncology and transplant patients?
Strauss RG.
Several methodologic advances, particularly use of recombinant granulocyte colony stimulating factor to stimulate donors, have made it possible to collect extraordinarily large numbers of normal neutrophils for transfusion into neutropenic patients with life-threatening infections . Because larger doses of neutrophils can be transfused, renewed interest has arisen in the use of neutrophil (granulocyte) transfusions to treat adult oncology patients and progenitor cell transplant recipients, in whom neutropenia complicated by severe infections persists as a significant problem, despite combination antibiotic therapy, recombinant cytokines, myeloid growth factors, and use of mobilized peripheral blood progenitor cells . In this commentary, consideration is given as to whether pediatric oncology and transplant patients might benefit from modern granulocyte transfusion therapy . If children are found to experience significant morbidity or mortality from neutropenic infections despite modern supportive care, it is logical to explore the efficacy, potential toxicity, and cost-effectiveness of granulocyte transfusion therapy by properly designed, randomized clinical trials.

J Cardiovasc Surg (Torino), 1999 Oct, 40(5), 675 - 7
Mediastinitis due to Gordona sputi after CABG; Kuwabara M et al.; Genus Gordona is included in mycolic acid containing bacteria . This genus infection is very rare and occurs classically in immuno-compromised patients . We report a patient who developed mediastinitis due to Gordona sputi after coronary artery bypass grafting (CABG) using left internal mammary artery . Immunocompromised factors were not noticed in this case but postoperative bleeding, the most important risk factor of mediastinitis, was found in his course . The treatment was antibiotic therapy, surgical soft tissue debridement and open irrigation with dilute povidone-iodine solution . However, infectious reaction continued and Gordona sputi repeated cultured from wound . Next procedure, debridement of sternal bone and omental transfer, was performed and skin was closed primarily . Inflammatory reaction was attenuated and the wound was healed Broad debridement and omental transfer were very effective for mediastinitis due to Gordona sputi after CABG.

AIDS, 1999, 13 Suppl 2, S3 - 9
Granulocyte colony-stimulating factor: its potential role in infectious disease; Hartung T; Studies on the role of endogenous granulocyte colony-stimulating factor (G-CSF) in host defense indicate that, in addition to its anti-infectious role, this cytokine has an immunomodulatory function and also augments antibiotic efficacy . Pre-clinical and clinical trials with Filgrastim, recombinant-methionyl human G-CSF, in neutropenic and non-neutropenic infections demonstrate a reduction in morbidity and mortality . This is attributed to Filgrastim's ability to control infectious complications and permit continuation of immunosuppressive therapies.

Rozhl Chir, 1999 Aug, 78(8), 371 - 4
{Subacute appendicitis in children}; Horn F et al.; Over the period of 4 years from 1993 to 1996 the authors recorded a 6% incidence of patients with periappendicular mass (PM) in a group of 786 patients with acute appendicitis . The aim of the study is to compare the two methods in the management of patients (operation-A, conservative treatment-B) by applying the same criteria . In the subacute phase of the disease 22 patients (group A) were operated on, while 24 patients (group B) were successfully treated conservatively, with recommendation of elective appendectomy after 6 months . In group A indication for operation was PM in 7 patients, diagnostic problems (tumour, hydronephrosis) or complications (peritonitis, intestinal obstruction) in 15 patients . Antibiotic therapy was nearly the same in both group . Peritoneal drainage in postoperative care was performed in 10 patients of group A for 4.7 days on the average . In this group, secondary wound healing was recorded in 3 patients . In group B, elective appendectomy was performed only in 12 patients (50%) . In 2 patients, however, a diagnostic error was revealed, i.e . Crohn's disease and an ovarian cyst had been suspected to be a periappendicular mass . Conservative treatment with subsequent elective appendectomy after 6 months seems to be an effective method in the treatment of patients with a typical clinical picture and well bordered periappendicular mass . Appendectomy in the subacute phase of the disease appears to be a safety technique of PM treatment in patients with complications or diagnostic problems.

Cancer Res, 1999 Nov 1, 59(21), 5461 - 3
Apoptotic conversion: evidence for exchange of genetic information between prostate cancer cells mediated by apoptosis; de la Taille A et al.; Changes in the outer membrane of apoptotic cells can induce neighboring cells to become phagocytic . Using genetically marked prostate cancer cell lines, we explored the possibility that genetic information might be transferred from an apoptotic cell to a phagocytic neighbor . Neomycin-resistant LNCaP cells that overexpress bcl-2 (LNCaP(bcl-2/neo-r)) were cocultured with hygromycin-resistant LNCaP cells (LNCaP(hygr-r)) . The cocultures were then transiently exposed to serum starvation to induce apoptosis of LNCaP(hygr-r) cells . Surviving cells were then coselected in medium containing both antibiotics . Whereas monocultures of LNCaP(bcl-2/neo-r) or LNCaP(hygr-r) treated this way yielded no colonies, cocultures yielded dual-antibiotic-resistant clones at a frequency of approximately 1 in 10(5) . Pre-exposure to an apoptotic agent was required; cocultures not exposed to serum starvation yielded no dual-selectable colonies . Analysis of DNA extracted from a dual-resistant clone demonstrated that the restriction endonuclease pattern of the neo-r gene was unaltered when compared with the parental LNCaP(bcl-2/neo-r) . However the hygr-r gene demonstrated an altered restriction endonuclease pattern in the dual-resistant derivative compared with the parental LNCaP(hygr-r) cell line . This is evidence that genetic information can be transferred from one prostate cancer cell to another through the process of apoptosis, and we term this form of genetic transfer "apoptotic conversion."

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