Antibiotics

Plast Reconstr Surg, 1997 Apr, 99(5), 1324 - 8
The fate of preserved autogenous bone graft; DeLuca L et al.; Certain clinical conditions exist in which a section of cranial bone is removed but not immediately replaced at the initial procedure . Preservation of this bone can provide a valuable autogenous donor source for a future reconstructive procedure . The purpose of our study was to compare the volume retention of fresh autogenous bone with that of preserved autogenous bone as inlay and onlay cranial grafts . Two bone grafts were harvested from the skull of 15 adult New Zealand White rabbits . The graft volumes were calculated, and the graft were preserved in a normal saline-antibiotic solution at -20 degrees C . Three months later, during the second procedure, a fresh graft was harvested and then placed in the preexisting occipital defect as an inlay graft . Also at this time, the preserved grafts were placed, one as an inlay graft in the fresh occipital defect and the other as an onlay graft in the frontal region . The animals were sacrificed 3 months later, and the percentage of graft volume retention was determined . The fresh inlay grafts had a mean volume retention of 85.1 percent, while the preserved inlay nad onlay grafts had 61.8 and 75.9 percent mean volume retention, respectively . It is concluded that while fresh cranial autograft remains the "gold standard" for craniofacial reconstruction, preserved autogenous cranial bone is a viable alternative for inlay and onlay grafting of the craniofacial region.

Ophthalmic Surg Lasers, 1997 Apr, 28(4), 321 - 4
New ophthalmic manifestations of presumed rifabutin-related uveitis; Arevalo JF et al.; Rifabutin-related uveitis has been reported in AIDS patients who take a daily dose of 300 to 1800 mg of this drug . Presumed rifabutin-related uveitis is characterized by unilateral or bilateral anterior chamber inflammation with hypopyon accompanied by hyperemia, pain, photophobia, and vitritis . However, retinal manifestations or vitreous cytology of this entity have never been reported . This report describes a patient who had retinal vascular changes associated with uveitis while being treated with oral rifabutin . Fundus photographs and fluorescein angiograms documented resolved retinal vasculitis . Vitreous cytology of this case showed acute inflammatory cells . To the authors' knowledge, this is the first report of retinal vasculopathy in a patient with rifabutin-related uveitis and the first analysis of the vitreous cytologic aspects of this disease.

J Bacteriol, 1997 Apr, 179(8), 2668 - 77
Transposon mutagenesis reinforces the correlation between Mycoplasma pneumoniae cytoskeletal protein HMW2 and cytadherence; Krause DC et al.; A new genetic locus associated with Mycoplasma pneumoniae cytadherence was previously identified by transposon mutagenesis with Tn4001 . This locus maps approximately 160 kbp from the genes encoding cytadherence-associated proteins HMW1 and HMW3, and yet insertions therein result in loss of these proteins and a hemadsorption-negative (HA-) phenotype, prompting the designation cytadherence-regulatory locus (crl) . In the current study, passage of transformants in the absence of antibiotic selection resulted in loss of the transposon, a wild-type protein profile, and a HA+ phenotype, underscoring the correlation between crl and M . pneumoniae cytadherence . Nucleotide sequence analysis of crl revealed open reading frames (ORFs) orfp65, orfp216, orfp41, and orfp24, arranged in tandem and flanked by a promoter-like and a terminator-like sequence, suggesting a single transcriptional unit, the P65 operon . The 5' end of orfp65 mRNA was mapped by primer extension, and a likely promoter was identified just upstream . The product of each ORF was identified by using antisera prepared against fusion proteins . The previously characterized surface protein P65 is encoded by orfp65, while the 190,000 Mr cytadherence-associated protein HMW2 is a product of orfp216 . Proteins with sizes of 47,000 and 41,000 Mr and unknown function were identified for orfp41 and orfp24, respectively . Structural analyses of HMW2 predict a periodicity highly characteristic of a coiled-coil conformation and five leucine zipper motifs, indicating that HMW2 probably forms dimers in vivo, which is consistent with a structural role in cytadherence . Each transposon insertion mapped to orfp216 but affected the levels of all products of the P65 operon . HMW2 is thought to form a disulfide-linked dimer, formerly designated HMW5, and examination of an hmw2 deletion mutant confirms that HMW5 is a product of the hmw2 gene.

Biochemistry, 1997 Apr 1, 36(13), 3917 - 29
DNA cleavage by topoisomerase I in the presence of indolocarbazole derivatives of rebeccamycin; Bailly C et al.; DNA topoisomerase I has been shown to be an important therapeutic target in cancer chemotherapy for the camptothecins as well as for indolocarbazole antibiotics such as BE-13793C and its synthetic derivatives NB-506 and ED-110 {Yoshinari et al . (1993) Cancer Res . 53, 490-494} . To investigate the mechanism of topoisomerase I inhibition by indolocarbazoles, we have studied the induction of DNA cleavage by purified mammalian topoisomerase I mediated by the antitumor antibiotic rebeccamycin and a series of 20 indolocarbazole derivatives . The compounds tested bear (i) various functional groups on the non-indolic moiety (X = CO, CH2, CHOH), (ii) a hydrogen or a chlorine atom at positions 1 and 11 (R2), and (iii) different substituents on the maleimido function (R1 = H, OH, NH2, NHCHO) . Half of the ligands have the same carbohydrate moiety as rebeccamycin whereas the other ligands have no sugar residue . The inhibitory potency of the test compounds was assessed in vitro by comparing the cleavage of {32P}-labeled restriction fragments by the enzyme in the absence and presence of the drug . In addition, the DNA-binding properties of these compounds were investigated by means of complementary spectroscopic techniques including electric linear dichroism, and the DNA sequence selectivity was probed by DNase I footprinting . The study shows that the sugar residue attached to the indolocarbazole chromophore is critical for the drug ability to interfere with topoisomerase I as well as for the formation of intercalation complexes . Structure-activity relationships indicate that the presence of chlorine atoms significantly reduces the effects on topoisomerase I whereas the substituents on the maleimido function and the functional group on the non-indolic moiety can be varied without reduction of activity . The results suggest that the inhibition of topoisomerase I by indolocarbazoles arises in part from their ability to interact with DNA . Analysis of the base preferences around topoisomerase I cleavage sites in various restriction fragments indicated that, in a manner similar to camptothecin, the rebeccamycin analogue R-3 stabilized topoisomerase I preferentially at sites having a T and a G on the 5' and 3' sides of the cleaved bond, respectively . By analogy with models previously proposed for camptothecin and numerous topoisomerase II inhibitors which intercalate into DNA, a stacking model for the interaction between DNA, topoisomerase I and indolocarbazoles is proposed . These findings provide guidance for the development of new topoisomerase I-targeted antitumor indolocarbazole derivatives.

Ann Intern Med, 1997 Apr 1, 126(7), 520 - 7
Diagnosis and monitoring of Whipple disease by polymerase chain reaction; Ramzan NN et al.; BACKGROUND: Whipple disease is a chronic, multisystem disorder associated with infection with Tropheryma whippelii, an organism that has not yet been grown on artificial media . In some cases, the diagnosis of Whipple disease is uncertain if it is based on histology alone . Although antibiotic regimens of various durations have been used, the disease recurs in about one third of cases . No test for cure is available . OBJECTIVE: To develop a test that is more sensitive and specific than histologic examination to diagnose Whipple disease and monitor the effects of antibiotic therapy . DESIGN: Retrospective, laboratory-based evaluations of stored tissue specimens . PATIENTS: 30 patients with clinically diagnosed, histologically confirmed Whipple disease and 8 patients in whom Whipple disease was clinically suspected but who did not have definitive histologic evidence . MEASUREMENTS: Pretreatment and post-treatment biopsy specimens of the small bowel and lymph node were tested by polymerase chain reaction for the presence of T . whippeli DNA . RESULTS: Results on PCR were positive in 29 of the 30 specimens from patients with histologically confirmed disease (sensitivity, 96.6%; specificity, 100%) and in 7 of the 8 specimens from patients in whom disease was clinically suspected . Small-bowel biopsy specimens were obtained after treatment from 17 patients (median duration of follow-up, 119 months); specimens from 12 of these patients had positive results on PCR . When these cases were correlated with therapeutic outcome, it was found that 7 of the 12 patients had clinical relapse during subsequent follow-up or had never responded to treatment (positive predictive value, 58% {95% CI, 28% to 85%}) . In contrast, none of the 5 patients whose post-treatment biopsy specimens had negative results on PCR had relapse (negative predictive value, 100% {CI, 48% to 100%}; P = 0.044) . No correlation was found between post-treatment histology and clinical outcome (P > 0.2) . CONCLUSIONS: Polymerase chain reaction is highly sensitive and specific when used to confirm the diagnosis of Whipple disease, to identify inconclusive and suspicious cases, and to monitor response to therapy . A negative result on PCR may predict a low likelihood of clinical relapse; a positive test result that remains positive despite therapy may be associated with a poor clinical outcome . Histopathologic evaluation of post-treatment specimens does not predict clinical cure or relapse.

Antimicrob Agents Chemother, 1997 Apr, 41(4), 752 - 6
Activity of liposomal amphotericin B against experimental cutaneous leishmaniasis; Yardley V et al.; The polyene antibiotic amphotericin B is currently a second-line treatment for visceral leishmaniasis (VL) and mucocutaneous leishmaniasis . Lipid-amphotericin B formulations with lower toxicity than the parent drug that were developed for the treatment of systemic mycoses have proved to be an effective treatment for VL, especially AmBisome, a small unilamellar negatively charged liposome . In vitro, free amphotericin B was three to six times more active than the liposomal formulation AmBisome against both Leishmania major promastigotes in culture and amastigotes in murine macrophages . In a BALB/c L . major model of cutaneous infection, liposomal amphotericin B administered once a day on six alternate days by the intravenous route produced a dose-response effect between 6.25 and 50 mg/kg . Liposomal amphotericin B administered subcutaneously close to a lesion had no significant activity . Free drug was ineffective at nontoxic doses . The results suggest that liposomal amphotericin B may be useful in the treatment of cutaneous leishmaniasis.

Hum Gene Ther, 1997 Mar 20, 8(5), 555 - 61
Intracellular delivery of lipopolysaccharide during DNA transfection activates a lipid A-dependent cell death response that can be prevented by polymyxin B; Cotten M et al.; The presence of lipopolysaccharide (LPS) as a contaminant in plasmid DNA prepared from Escherichia coli is well documented, and we have previously demonstrated that LPS internalization during adenovirus-mediated gene transfer can generate a toxicity in some primary cell types . We demonstrate here that in addition to adenoviral systems, several commonly used nonviral methods of gene transfer also activate this cell death response in the presence of LPS . Subcomponents of LPS were analyzed and the toxicity was found to be due to the lipid A component of LPS . The LPS-chelating antibiotic polymyxin B, when present at concentration of 10-30 micrograms/ml, can block this toxicity.

Biochemistry, 1997 Mar 18, 36(11), 3050 - 5
Fosfomycin resistance protein (FosA) is a manganese metalloglutathione transferase related to glyoxalase I and the extradiol dioxygenases; Bernat BA et al.; The enzyme conferring resistance to the antibiotic fosfomycin {(1R,2S)-1,2-epoxypropylphosphonic acid} originally reported by Suarez and co-workers {Area, P., Hardisson, C., & Suarez, J . E . (1990) Antimicrob . Agents Chemother . 34, 844-848} is demonstrated in this study to be a metalloglutathione transferase . The apoenzyme is a dimer of 16 kDa subunits . Electron paramagnetic resonance spectroscopy and water proton nuclear magnetic resonance longitudinal relaxation rates suggest that each subunit contains a mononuclear Mn2+ center that interacts strongly with the substrate fosfomycin (Kd = 17 microM) more weakly with the product (Kd = 1.1 mM) and very weakly or not at all with GSH . Inhomogeneous broadening of the EPR signals of enzyme-bound Mn2+ in the presence of H2(17)O indicates that three of the coordination sites on the metal are occupied by water . Sequence alignments, three-dimensional structures, and mechanistic considerations suggest that FosA is related to at least two other metalloenzymes, glyoxalase I and the Mn2+- or Fe2+-containing extradiol dioxygenases . The mechanistic imperative driving the evolution of this previously unidentified superfamily of metalloenzymes is proposed to be bidentate coordination of a substrate or intermediate to the metal center in the enzyme-catalyzed reactions.

Nucleic Acids Res, 1997 Mar 15, 25(6), 1219 - 24
Interaction of tetracycline with RNA: photoincorporation into ribosomal RNA of Escherichia coli; Oehler R et al.; Photolysis of {3H}tetracycline in the presence of Escherichia coli ribosomes results in an approximately 1:1 ratio of labelling ribosomal proteins and RNAs . In this work we characterize crosslinks to both 16S and 23S RNAs . Previously, the main target of photoincorporation of {3H}tetracycline into ribosomal proteins was shown to be S7, which is also part of the one strong binding site of tetracycline on the 30S subunit . The crosslinks on 23S RNA map exclusively to the central loop of domain V (G2505, G2576 and G2608) which is part of the peptidyl transferase region . However, experiments performed with chimeric ribosomal subunits demonstrate that peptidyltransferase activity is not affected by tetracycline crosslinked solely to the 50S subunits . Three different positions are labelled on the 16S RNA, G693, G1300 and G1338 . The positions of these crosslinked nucleotides correlate well with footprints on the 16S RNA produced either by tRNA or the protein S7 . This suggests that the nucleotides are labelled by tetracycline bound to the strong binding site on the 30S subunit . In addition, our results demonstrate that the well known inhibition of tRNA binding to the A-site is solely due to tetracycline crosslinked to 30S subunits and furthermore suggest that interactions of the antibiotic with 16S RNA might be involved in its mode of action.

BMJ, 1997 Mar 8, 314(7082), 722 - 7
Open randomised trial of prescribing strategies in managing sore throat; Little P et al.; OBJECTIVE: To assess three prescribing strategies for sore throat . DESIGN: Randomised follow up study . SETTING: 11 general practices in the South and West region . SUBJECTS: 716 patients aged 4 years and over with sore throat and an abnormal physical sign in the throat; 84% had tonsillitis or pharyngitis . Patients were randomised to three groups: prescription for antibiotics for 10 days (group 1,246 patients); no prescription (group 2,230 patients); or prescription for antibiotics if symptoms were not starting to settle after three days (group 3; 238 patients) . MAIN OUTCOME MEASURES: Duration of symptoms; satisfaction and compliance with and perceived efficacy of antibiotics; time off school or work . Outcomes were documented in 582 subjects (81%) . RESULTS: Median duration of antibiotic use differed significantly in the three groups (10 v 0 v 0 days, P < 0.001); 69% of patients in group 3 did not use their prescription . The proportion of patients better by day 3 did not differ significantly (37% v 35% v 30%, P = 0.28), nor did the duration of illness (median 4 v 5 v 5 days, P = 0.39), days off work or school (median 2 v 2 v 1, P = 0.13), or proportion of patients satisfied (96% v 90% v 93%, P = 0.09), although group 1 had fewer days of fever (median 1 v 2 v 2 days, P = 0.04) . More patients in group 1 thought the antibiotics were effective (87% v 55% v 60%, P < 0.001) and intended coming to the doctor in future attacks (79% v 54% v 57%, P < 0.001) . "Legitimation" of illness-to explain to work or school (60%) or family or friends (37%)-was an important reason for consultation . Patients who were more satisfied got better more quickly, and satisfaction related strongly to how well the doctor dealt with patient's concerns . CONCLUSION: Prescribing antibiotics for sore throat only marginally affects the resolution of symptoms but enhances belief in antibiotics and intention to consult in future when compared with the acceptable strategies of no prescription or delayed prescription . Psychosocial factors are important in the decision to see a general practitioner and in predicting the duration of illness.

Virology, 1997 Mar 3, 229(1), 228 - 39
Construction and characterization of herpes simplex virus type 1 mutants with conditional defects in immediate early gene expression; Preston CM et al.; The herpes simplex virus type 1 (HSV-1) mutant in 1814 contains an insertion mutation in the coding sequence for the virion transactivator protein VP16 and is thus impaired for the activation of immediate early (IE) gene expression . This virus was modified further by introducing the Moloney murine leukemia virus LTR promoter in place of the upstream sequences controlling expression of the IE regulatory protein ICPO, to yield mutant in 1820 . In almost all cell types tested, in 1820 initiated infection less efficiently than in 1814, behaving as if lacking both VP16 and ICPO functions, but in BHK cells in 1820 was less impaired than in 1814 . A rescuant of in 1820 at the VP16 locus, in 1825, also exhibited a host range phenotype, initiating replication as efficiently as wild-type HSV-1 in BHK cells but inefficiently in other cell types . In 1825 was unable to complement an ICPO null mutant in restricted cells, demonstrating that the promoter exchange prevented the expression of ICPO protein in functionally significant amounts . The novel host range properties of in 1820 provided a basis for the construction of additional viruses conditionally impaired for IE gene expression and assessment of their value as prototype vectors . Production of an HSV-1 mutant multiply defective in the expression of IE gene products was achieved by introduction of the temperature-sensitive mutation of HSV-1 tsK, which inactivates the IE transcription activator ICP4 at nonpermissive temperatures, into in 1820 to produce in 1820K . This mutant could be propagated effectively in BHK cells at 31 degrees but was effectively devoid of the major regulators ICPO, ICP4, and VP16 in other cells types at 38.5 degrees . Cultures could withstand infection with 5 PFU of in 1820K per cell without detectable cytopathology and could be reseeded to form colonies at approximately 90% efficiency . A derivative of in 1820K containing the Escherichia coli lacZ gene controlled by the human cytomegalovirus (HCMV) major IE promoter expressed low but detectable levels of beta-galactosidase in almost all cells after infection of cultures at 5 PFU per cell and incubation at 38.5 degrees . Cultures infected with 5 PFU per cell of an in 1820K derivative expressing neomycin phosphotransferase (npt) controlled by the HCMV IE promoter were resistant to killing by the antibiotic G418 for up to 3 days, and cell survival correlated with the retention of functional levels of npt . Mutants based on in 1820K can thus express foreign gene products in virtually all cells in a culture under conditions in which cytotoxicity is eliminated, demonstrating that progressive reduction of IE gene expression is an important step in the design of HSV-1-derived vectors.

J Card Surg, 1997 Mar-Apr, 12(2 Suppl), 256 - 60; discussion 260-1
The infected aorta; von Segesser LK et al.; BACKGROUND: Despite the improvements achieved in antibiotic therapy, severe aortic infection resulting in mycotic aneurysms is still a highly lethal disease and surgical management remains a challenging task . PATIENTS AND METHODS: A total of 43 patients with severe aortic infections were analyzed and separated in four groups: (1) Infections of the aortic root Ventriculo-aortic disconnection due to deep aortic infection (6 patients) . Two patients were operated using homo-composit grafts . Of the 6 patients total, one died early and two died late during a mean follow-up of 6 years . The two patients with homografts are still alive . (2) Infections of the ascending aorta and the aortic arch . In situ repair for mycotic aneurysmal lesions of the ascending aorta was performed in 6 patients using synthetic graft material in 4/6, biological material in 1/6 and direct suture in 1/6 . Two patients had to be reoperated; one of them died early . There was no recurrent infection during a mean follow-up of 6 years . (3) Infections of the descending thoracic and thoraco-abdominal aorta in-situ repair for mycotic aneurysmal lesions of the descending and thoraco-abdominal aorta was performed in 12 patients using homografts in five . Two patients died early and two other patients died late during a mean follow-up of 6 years . (4) Infections of the infrarenal abdominal aorta . In this series of 19 patients with mycotic infrarenal aortic aneurysms, in situ reconstruction was performed in 12 (5/12 with homografts) and extra-anatomic reconstruction (axillo-femoral bypass) was performed in 7 . Hospital mortality was 5/19 patients and another 5/19 patients died during a mean follow-up of 6 years . One of the early deaths was due to aortic stump rupture . Two patients with axillo-femoral reconstructions were later converted to descending-thoracic-aortic-bifemoral bypasses . Five thromboses of axillo-femoral bypasses were observed in three of the seven patients with extra-anatomic repairs . RESULTS: Infections of the aortic root, the ascending aorta and the aortic arch are approached with total cardio-pulmonary bypass, using cardioplegic myocardial protection and deep hypothermia with circulatory arrest if necessary . Proximal unloading and distal support using partial cardiopulmonary bypass is preferred for repair of infected descending and thoracoabdominal aortic lesions, whereas no such adjuncts are required for repair of infected infrarenal aortic lesions . CONCLUSIONS: The anatomical location of the aortic infection and the availability of homologous graft material are the main factors determining the surgical strategy.

Vestn Oftalmol, 1997 Mar-Apr, 113(2), 19 - 21
{Clinical and laboratory assessment of therapeutic efficacy of maxaquin in treatment of chlamydial conjunctivitis}; Maichuk IF et al.; Maxaquin (lomefloxacin), a new fluoroquinolone antibiotic, was used in combined therapy of chlamydial conjunctivitis . The results of treatment of 72 patients were assessed by the clinical manifestations and the laboratory time course of Chlamydia trachomatis antigen in smears from the conjunctiva, detected by enzyme immunoassay . Clinical and laboratory findings proved the high efficacy of the drug and its advantages over traditional therapy and other fluoroquinolones.

Mikrobiol Z, 1997 Mar-Apr, 59(2), 20 - 4
{The induction of mutations in Streptomyces aureofaciens by UV rays and nitrosoguanidine and the identification of the mutants obtained}; Lavrinchuk VIa et al.; Streptomyces aureofaciens 019(8), chlortetracycline producent was subjected to the effect of UV-light and nitrosoguanidine and after that its 121520 colonies have been analyzed by the methods of replicas and 57 mutants were isolated: sensitive to the effect of UV radiation--14; auxotrophs--30; antibiotic-inactive --13 . The induction frequency of mutations is within the limits of 0.016 to 0.067% . Auxotrophic mutants manifested genetic instability . Mutants with a block chlortetracyclin biosynthesis are stable.

Minerva Cardioangiol, 1997 Mar, 45(3), 101 - 6
{Surgical therapy for prosthetic infections of the thoracic aorta . Conservative approach}; Spirito R et al.; The prosthetic graft infection of the thoracic aorta is a dreaded complication and it is associated with a high mortality rate . There is not substantial agreement in literature about how to manage a vascular graft infection, except for local anti-septic irrigation with a systemic antibiotic therapy . The main point of discussion is if it is mandatory to remove or not the infected thoracic aorta prosthesis: some authors prefer to eliminate all the thoracic aortic prostheses which may be infected, while others propose graft removal only when the sutures lines are involved . In this paper we report our experience on the conservative management of infected thoracic aorta prostheses using a local antiseptic irrigation, a perigraft debridement and leaving the original graft "in situ" when there is evidence of graft damage especially or involvement of the sutures lines . This approach has been performed in three patients: two had an infected aortic arch prosthesis, while one had a descending thoracic aorta prosthesis infection.

Urologe A, 1997 Mar, 36(2), 157 - 61
{Treatment and follow-up of patients with squamous epithelial carcinoma of the penis}; Lummen G et al.; Since squamous cell carcinoma of the penis is rare, prospective trials do not exist . Therefore, new treatment strategies have to be developed . Based on our experience with the treatment of 22 patients with penile squamous cell carcinoma, we describe our therapeutic approaches . Ten patients with superficial disease (T1-2N0M0) were treated with partial penectomy . The 3-year survival rate amounted to 90% . In patients with extensive disease (T3-4 or N1-3) a partial or total penectomy was performed . After initial antibiotic therapy for 4 weeks, patients underwent inguinal lymph-node dissection and if the nodes were positive, additional pelvic lymph-node dissection . In patients with ulcerous inguinal lymph-node metastases surgical resection was performed, covering the wound with a musculocutaneous flap (tensor fascia lata flap n = 2; rectus abdominis flap n = 1) . The 3-year survival rate of patients with T1-2N1 tumours (n = 4) was 67% and with T3-4N1-3 (n = 8) 25% . Patients with distant metastases received inductive systemic chemotherapy with cisplatin, methotrexate and bleomycin . Objective responses occurred in 22% (1 CR, 1 PR) of 9 patients . These results suggest that immediate radical surgery with lymph-node dissection is the best treatment for squamous cell carcinoma of the penis.

Minerva Urol Nefrol, 1997 Mar, 49(1), 45 - 9
{Emphysematous pyelonephritis . A clinical case successfully treated with percutaneous drainage}; Appignanesi P et al.; Emphysematous pyelonephritis is an unusual and serious infection, associated with the formation of gas by choliphormi bacteria . The authors present a case of monolateral emphysematous pyelonephritis in an obese and diabetic patient, put under observation and treated successfully through percutaneous drainage and antibiotic therapy.

Zhonghua Yi Xue Za Zhi (Taipei), 1997 Mar, 59(3), 171 - 6
Clarithromycin in the combination therapy for the eradication of Helicobacter pylori in peptic ulcer disease; Lo WC et al.; BACKGROUND: Clarithromycin is a new macrolide antibiotic which is known to be highly effective in eradicating Helicobacter pylori (H . pylori) . In Chinese, the role of clarithromycin for H . pylori is still unclear . METHODS: Between January 1995 and February 1996, 75 patients with active H . pylori-positive duodenal ulcer were enrolled in this study . Three groups were randomized to have (1) 2 x 150 mg nizatidine twice daily, 2 x 250 mg amoxicillin four times daily, and 2 x 250 mg clarithromycin three times daily for two weeks (niz-amox-clar group, N = 25); or (2) 20 mg omeprazole twice daily plus 2 x 250 mg clarithromycin three times daily for two weeks (ome-clar group, N = 25); or (3) 300 mg bismuth subsalicylate four times daily, and 2 x 250 mg amoxicillin four times daily, 250 mg metronidazole four times daily for two weeks (triple therapy group, N = 25) . All the patients received H2 receptor antagonist (150 mg nizatidine or ranitidine, or 400 mg cimetidine, twice daily) for the consecutive six weeks . RESULTS: The eradication rate of H . pylori eight weeks after the entry of study was 80%(20/25) in the niz-amox-clar group, 76%(19/25) in the ome-clar group, 88%(22/25) in the triple therapy group (p < 0.05 among the three groups) . The ulcer healing rates eight weeks after the entry of study for the niz-amox-clar, the ome-amox, and the triple therapy groups were 84%(21/25), 80%(20/25), and 80%(20/25), respectively (p < 0.05 among the three groups) . The number of patients experiencing adverse effects in the niz-amox-clar group, the ome-clar group, and the triple therapy group were 10(40%), 7(28%), and 4(16%), respectively (p > 0.05 among the three groups) . CONCLUSIONS: Both nizatidine/amoxicillin/clarithromycin and omeprazole/clarithromycin regimens can achieve good eradication rates and may provide an effective alternative anti-H . pylori treatment in duodenal ulcer diseases.

J Hand Surg {Am}, 1997 Mar, 22(2), 338 - 40
Flexor tenosynovitis in the hand caused by Mycobacterium malmoense: a case report; Gabl M et al.; This report analyzes a rare case of flexor tenosynovitis caused by Mycobacterium malmoense . A synovectomy was carried out on the index finger (no other finger was afflicted) of a 66-year-old farmer, followed by antibiotic therapy with ethambutol, rifampin, and clarithromycin . Because of strong side effects, the treatment with ethambutol and rifampicin had to be discontinued after 4 months . There was no recurrence after 14 months, and the patient's finger had a full range of motion.

Changgeng Yi Xue Za Zhi, 1997 Mar, 20(1), 1 - 10
Management of infected total knee arthroplasty; Wang CJ; BACKGROUND: Deep wound infection after total knee arthroplasty is an infrequent but very serious complication . Treatment is difficult and challenging . Antibiotic therapy alone can not replace surgery in the management of infected total knee arthroplasty . METHODS: Fourteen infected total knee arthroplasties in 13 patients were treated by the author . Nine patients underwent two-stage reimplantation, one patient one-stage reimplantation, one patient arthroscopic debridement, and one patient knee fusion . Four knees in three patients were excluded because of less than 12 months follow-up . This study retrospectively analyzed the results of treatment in 10 infected total knee arthroplasties in 10 patients . RESULTS: All patients were followed up for 12 months or longer . The length of follow-up ranged from 12 months to 69 months with an average of 28 months . All infections were successfully controlled, and there was no recurrence of infection . However, only 67% of the patients showed satisfactory functional results . CONCLUSION: Based upon the results in this study, most of the infection after total knee arthroplasty could be successfully controlled by combined surgical treatment and intravenous antibiotic therapy . The result of two-stage reimplantation was more consistent and predictable . The functional result of infected total knee arthroplasty was less satisfactory as compared with that of the non-infected counterpart . Furthermore, the impact of infection or the longevity of total knee prosthesis could only be determined by long-term follow-up.

Am J Crit Care, 1997 Mar, 6(2), 141 - 4
Control of infections caused by drug-resistant organisms in critical care; Hoppe B; The emergence of antibiotic-resistant pathogens has been an ongoing concern of infection-control and infectious disease practitioners . Infections caused by these organisms increase costs and may result in poorer outcomes for patients . Efforts to contain the problem of infections caused by drug-resistant organisms have two objectives: to optimize antibiotic use and to prevent transmission through effective infection-control practices.

Z Naturforsch {C}, 1997 Mar-Apr, 52(3-4), 217 - 26
Isolation and analysis of moenomycin and its biosynthetic intermediates from Streptomyces ghanaensis (ATCC 14672) wildtype and selected mutants; Subramaniam-Niehaus B et al.; Streptomyces ghanaensis (ATCC 14672) produces the phosphoglycolipid antibiotic moenomycin consisting of several components . A solid phase extraction procedure was developed which allowed a rapid isolation of both moenomycin and its biosynthetic intermediates from culture filtrates . Semi-preparative high performance liquid chromatography followed by high performance liquid chromatography-mass spectrometry provided structural data on the different moenomycin components . In order to obtain initial information on the biosynthetic pathway, moenomycin non-producing mutants were isolated . They were shown to release intermediates with shorter lipid chains suggesting that the lipid chain synthesis probably takes place at a later stage of the moenomycin biosynthesis . Based on the biological activity and the analytical data, we assume that a modification and in particular a shorter lipid portion drastically influences the inhibitory activity of this antibiotic.

Semin Neurol, 1997 Mar, 17(1), 63 - 8
Immunologic mechanisms in Lyme neuroborreliosis: the potential role of autoimmunity and molecular mimicry; Sigal LH; Most of the clinical manifestations of Lyme disease are due to the local presence of the causative agent, Borrelia burgdorferi, in the affected tissues . However, the precise means of tissue damage are not well understood and there is no proof that the organism, live or dead, is always present . An understanding of the complex interaction between the organism, the immune response elicited by the organism, and the host can explain manifestations of the disease and persistence of symptoms and signs after the antibiotic-induced death of the organism . It is possible that dead spirochetes, or fragments thereof may persist and act as a focus of ongoing inflammation . Different immunogenetic types may predispose to different immunologic responses, with distinct clinical outcomes . Vascular changes induced by the infection, either by local infection or the effects of cytokines on the vessel wall, may underlie tissue pathology . Finally, the immune response to B . burgdorferi may elicit the production of antibodies capable of recognizing and damaging or modifying normal host tissues . Only by establishing the mechanisms causing tissue damage in Lyme disease can rational therapeutic strategies be developed . Only by understanding these mechanisms can physicians and patients interpret clinical responses to therapy and accurately appreciate the clinical prognosis.

J Laryngol Otol, 1997 Mar, 111(3), 274 - 6
Central nervous system complications of acute tonsillitis; Morgan N et al.; Acute tonsillitis is a common infection of early childhood which may even run a self-limiting course without antibiotic therapy in some cases . Complications are encountered infrequently and rarely assume a life-threatening propensity . Central nervous system involvement has not to our knowledge been described in association with tonsillitis without local abscess formation . We describe three cases in which acute tonsillitis/peritonsillitis was complicated by major central neurological sequelae . The neurological complications encountered in young previously healthy adults were: facial palsy and hemiplegia; superior sagittal sinus thrombosis with communicating hydrocephalus and papilloedema; Guillain-Barre syndrome and facial palsy . The pathogenesis and management is discussed . All patients made satisfactory recoveries, though with minor residual neurological disabilities.

Orthop Nurs, 1997 Mar-Apr, 16(2), 31 - 46
Acute management of patients with hip fracture . A research literature review; Anders RL et al.; PURPOSE: To provide the orthopaedic nurse a summary of the significant research concerning the management of patients with a fractured hip . DESIGN: Meta-Analysis . SAMPLE: 135 articles reviewed for possible inclusion, 57 original research reports and publications are reported . METHODS: For the years 1985 to March 1996 Medline, MEDLARS, and CINAHL data bases were searched . Twenty-seven search terms were used, including hip fractured), orthopedic standards, and length of stay . MAIN RESEARCH CLASSIFICATIONS: Preoperative, Operative and Postoperative . Studies arranged by author, outcomes, focus, data source and year, sample, and findings . FINDINGS: Research reports were found concerning: preoperative care including the use of MRI, predictors of complications and transfusion needs, and impact of skin traction on pain; operative studies including spinal anesthesia and oxygen saturation rates, use of blankets to keep patient warm, prophylactic antibiotic use, and impact of delaying surgery; and postoperative reports including the incidence of DVT, nutritional status, cauterization, management protocols, morbidity and mortality risks, length of stay, functional status, and ambulation . CONCLUSION: The scientific merit of each study was not evaluated in depth . With some degree of comfort the review did find one study or several studies to support the findings presented . IMPLICATIONS FOR NURSING RESEARCH: Current research concerning the impact of pressure sores, incontinence, management of falls risk, and the impact the fear of falling on postinjury patients are just a few of the topics not adequately addressed.

Br J Pharmacol, 1997 Mar, 120(5), 841 - 50
The effects of bradykinin on K+ currents in NG108-15 cells treated with U73122, a phospholipase C inhibitor, or neomycin; Hildebrandt JP et al.; 1 . Bradykinin has multiple effects on differentiated NG108-15 neuroblastoma x glioma cells: it increases Ins(1,4,5)P3 production and intracellular Ca2+ concentration {Ca2+}i evokes a Ca2+ activated K+ current (IK(Ca)) and inhibits M current (IM) . We studied the effect of the aminosteroid U73122 and the antibiotic neomycin, both putative blockers of phospholipase C (PLC), on these four bradykinin effects . 2 . Preincubation with 1 or 5 microM U73122 for 15 min partly suppressed Ins(1,4,5)P3 generation and the increase in {Ca2+}i induced by 1 microM bradykinin . U73122 10 microM caused total and irreversible inhibition . The inactive analogue U73343 was without effect . 3 . Resting levels of Ins(1,4,5)P3 were not affected . However, resting {Ca2+}i was increased by 10 microM U73122, but not by U73343 . Individual cells responded to 10 microM U73122 with a small increase in {Ca2+}i, followed in some cells by a large further rise . 4 . Pretreatment of whole-cell clamped cells with 1 microM U73122 for 30 min reduced the bradykinin-induced IK(Ca) to a fifth of its normal size . To suppress it totally, a 7-12 min pretreatment with 5 microM U73122 was required . Again, U73343 was without effect . 5 . U73122 and U73343 at concentrations of 5-10 microM irreversibly decreased the holding current (Ih) which at a holding potential of -30 or -20 mV mainly flows through open M channels . The decrease was often preceded by a transient increase . 6 . M current (IM) measured with 1 s pulses, was also decreased by 5-10 microM U73122 and U73343, but short applications of U73122 could cause a small increase . The bradykinin-induced inhibition of IM was not affected by U73122 . 7 . Preincubation with 1 or 3 mM neomycin for 15 min did not affect Ins(1,4,5)P3 generation and the increase in {Ca2+}i induced by bradykinin . Pretreatment with 3 mM neomycin for about 20 min diminished the bradykinin-induced IK(Ca) to a fifth of its normal size . 8 . The four main conclusions drawn from the results are: (a) U73122 suppresses bradykinin-induced PLC activation and IK(Ca), but not IM inhibition . (b) This indicates that the transient outward current IK(Ca), but not the decrease of IM in response to bradykinin, is mediated by PLC . (c) U73122 itself inhibits IM and mobilizes Ca2+ from intracellular stores . (d) Externally applied neomycin is not an effective inhibitor of PLC-mediated signalling pathways in NG108-15 cells.

J Microencapsul, 1997 Mar-Apr, 14(2), 175 - 87
Biodegradable microparticles for sustained delivery of tetracycline to the periodontal pocket: formulatory and drug release studies; Esposito E et al.; This paper describes the production and characterization of biodegradable microparticles containing tetracycline, designed for periodontal disease therapy . The influence of production parameters on microparticle characteristics and antibiotic release modality was studied . Microparticles were made by using different preparation procedures and different polyesters, namely poly(L-lactide), {L-PLA} poly(DL-lactide), {DL-PLA} and poly(DL-lactide-co-glycolide) 50:50, {DL-PLG} . A double emulsion preparation method together with a concentrated salt solution as external phase gave the best results in terms of tetracycline incorporation efficacy . In vitro release experiments demonstrated that tetracycline is slowly and appropriately released from microparticles . Release kinetics were found to be influenced by the type of polymer utilized for microparticle production . In vitro experiments, simulating in vivo conditions were carried out for up to 30 days . Only DL-PLG microparticles showed significant changes in their morphology, whereas L-PLA and DL-PLA were found almost intact after the same period of time.

Clin Biochem, 1997 Mar, 30(2), 135 - 42
Distribution of sirolimus in rat tissue; Napoli KL et al.; OBJECTIVES: To examine the distribution of sirolimus (SRL, rapamycin), an immunosuppressive macrolide antibiotic, in the tissues of adult male Wistar-Furth rats following continuous intravenous infusion (CIVI) and repeated daily peroral gavage (PO) . DESIGN AND METHODS: Animals received 14-day courses of SRL by either CIVI (0.04-0.4 mg/kg/day) or PO (0.4-1.6 mg/kg/day) administration . Samples of whole blood and homogenates of five solid organs (heart, kidney, liver, lung and spleen), and portions of intestinal, muscle and testicular tissues were prepared on day 13 of CIVI treatment or 24 hours after administration of the 14th PO dose . SRL concentrations were determined by high performance liquid chromatography with reference to calibration curves produced from SRL-spiked whole blood or tissue homogenates prepared from drug-free animals . RESULTS: Following PO but not CIVI administration, SRL concentrations in whole blood and all tissues increased linearly in relation to dose . SRL was extensively distributed among most tissues tested (tissue partitions coefficients of > 40 were observed in some cases) . Comparatively, SRL whole blood concentrations were low . The ratio between the SRL whole blood concentrations after PO versus after CIVI administration (at like doses of 0.4 mg/kg/day) was 0.04 . Therefore, we inferred that the oral bioavailability of SRL was low . CONCLUSIONS: The linear relationships between PO dose and SRL concentrations in whole blood and tissues may be attributed to the low oral bioavailability of SRL, which is indicated by the low levels of SRL observed in whole blood and tissues after PO administration . The nonlinear relationships between CIVI dose and SRL concentrations in whole blood and tissues may result because although whole blood depots may be saturated with SRL, the tissues continue to absorb SRL as the dose of SRL increases . Thus, because a high percentage of SRL is widely distributed into tissues stores, caution must be used when administering this drug in humans.

Dis Colon Rectum, 1997 Mar, 40(3), 370 - 1
Bullous pemphigoid at colostomy site: report of a case; Vande Maele DM et al.; PURPOSE: Pemphigoid is a well-recognized cutaneous lesion, occurring rarely in peristomal skin . We report the diagnosis and successful treatment of localized pemphigoid lesions adjacent to a colostomy . METHODS: We review the chart, immunofluorescence study, treatment, and follow-up of a patient with bullous lesions at a colostomy site . RESULT: Pemphigoid of the pericolostomy skin was diagnosed by immunofluorescence study and successfully treated with antibiotic . CONCLUSION: Diagnosis of bullous pemphigoid should be considered in the differential diagnosis of a bullous lesion adjacent to a colostomy site . Diagnosis is easily made, and treatment is simple and efficacious.

Am J Emerg Med, 1997 Mar, 15(2), 161 - 3
Simultaneous uvulitis and epiglottitis in adults; McNamara R et al.; The emergency physician must be aware of the varied ways in which epiglottitis can present . This report discusses two adult patients who presented with symptoms and signs indicative of uvulitis who were found to have associated epiglottitis . Neither patient reported respiratory difficulty but both experienced significant pain upon swallowing and were febrile with an enlarged, erythematous uvula . Management consisted of close observation and treatment with an intravenous antibiotic and corticosteroid . The emergency physician should consider the possibility of coexistent epiglottitis in the adult patient who presents with uvulitis.

Clin Infect Dis, 1997 Mar, 24(3), 468 - 70
Infectious diseases consultation: impact on outcomes for hospitalized patients and results of a preliminary study; Classen DC et al.; In the absence of detailed and specific data on outcomes, specialists are thought to contribute excessively to the cost of care . Infectious diseases physicians are at further risk of heavy utilization of medical resources because their patients often are those with serious complications or expensive underlying diseases (e.g., AIDS) . By using readily available information in a sophisticated computer database, we examined the crude economic impact of an inpatient infectious diseases consultation and identified important matching variables for more refined analysis . The study was performed at LDS Hospital (Salt Lake City), a tertiary care facility with four full-time infectious diseases physicians . A total of 496 cases (patients who were seen by an infectious diseases consultant) were matched with 3,117 controls (patients who were not seen by an infectious diseases consultant) . Matching was performed on the basis of age, sex, exact discharge diagnosis-related group, minimum length of hospital stay equal to the interval from admission to consultation for cases, and measures of the severity of illness (nursing acuity score and the number of secondary diagnoses) . Cases had longer lengths of hospital stays, longer intensive care unit lengths of stays, and higher antibiotic costs than did matched controls, and if the consultation occurred in the last one-third of hospitalization, cases had shorter lengths of hospital stay and lower antibiotic costs than did controls.

Presse Med, 1997 Mar, 26 Suppl 2, 27 - 9
{Asthma and Chlamydia pneumoniae . A future prospect for macrolides in general and roxithromycin in particular?}; Mayaud C; A LOGICAL HYPOTHESIS: Recent publications raise the question of an association between Chlamydia pneumoniae and asthma . There has been no formal proof justifying routine search for C.pneumoniae in patients with uncontrolled asthma nor for systematic treatment with an antibiotic . OPEN QUESTIONS: Can Chlamydia pneumoniae infection initiate or aggravate asthma? Are acute manifestations of asthma associated with an overly high frequency of recent C.pneumoniae infection? Is a past history of C.pneumoniae infection abnormally frequent in patients with chronic asthma? PERSPECTIVES: Rigorously controlled clinical trials evaluating the efficacy of antibiotics such as macrolides which are active against C.pneumoniae are warranted to further elucidate these questions.

Patient Educ Couns, 1997 Mar, 30(3), 257 - 70
Design, development, and evaluation of visual aids for communicating prescription drug instructions to nonliterate patients in rural Cameroon; Ngoh LN et al.; In this study, culturally sensitive visual aids designed to help convey drug information to nonliterate female adults who had a prescription for a solid oral dosage form of antibiotic medications were developed and evaluated . The researchers conceptualized the educational messages while a local artist produced the visual aids . Seventy-eight female ambulatory patients were evaluated for comprehension and compliance with antibiotic prescription instructions . The study was conducted in three health centers in Cameroon, West Africa and followed a pre-test, post-test, and follow-up format for three groups: two experimental, and one control . All participants were randomly assigned to either experimental or control groups, 26 patients to each group . Subjects in the experimental groups received visual aids alone or visual aids plus an Advanced Organizer . A comparison of the three groups showed that subjects in the experimental groups scored significantly higher than the control group in both the comprehension and compliance measuresPIP: A study in rural Cameroon evaluated culturally sensitive visual aids designed to convey instructions for use of prescription antibiotics to illiterate women . The study, conducted in 3 health centers, used a pre-post test and follow-up format in 3 random groups (2 experimental and 1 control) of 26 patients each to test compliance with short-term prescriptions of antibiotics (ampicillin, sulfamethoxazole, trimethoprim, metronidazole, and tetracycline) . The introduction to this report reviews the literature on use of essential drugs by ambulatory patients and the problems of communicating directions for use to patients, especially illiterate patients in developing countries . Visual aids can use pictorial, graphic, or verbal symbols and must get the audience's attention, be culturally appropriate, and be relevant to the population to be served . The theoretical framework for the use of visual aids is found in Albert Bandura's Social Learning Theory of Identificatory Processes, which explains how to achieve behavior modification using modeling . This study involved use of a literacy test, visual aids, and an "advanced organizer." The advanced organizer (introductory information used to explain why the drug is needed) used farming as an analogy and described a body as a crop field, disease as weeds, and antibiotics as a farmer . Visual aids were developed through a conceptual and a design phase and were field tested . It was found that the experimental groups (1 with only visual aids, 1 with visual aids and the advanced organizer) scored significantly higher than the controls in measures of comprehension and compliance and that use of the advanced organizer improved scores significantly . It is concluded that, to be effective, visual aids must be population-specific but that their preparation and use contributes significantly to achieving desired results in patients .

J Periodontol, 1997 Mar, 68(3), 299 - 305
Abscess formation around a hydroxyapatite-coated implant placed into the extraction socket with autogenous bone graft . A histological study using light microscopy, image processing, and confocal laser scanning microscopy; Takeshita F et al.; The purpose of this study was to evaluate the radiologic, histologic, and histometric findings for a retrieved hydroxyapatite (HA)-coated implant which had been placed into a fresh extraction socket with autogenous bone graft 3 months previously . A periapical radiography disclosed a vertical bone loss around the implant cervix . Examination of histologic section disclosed that granulation tissue including bone chips around the cervix, and newly-formed bone tissue around the grafted bone tissue on the HA coated surface . In the confocal laser scanning microscopic findings toluidine blue-negative bone tissue showed autofluorescence . Histometric analysis indicated that the average percent bone contact was 29.2% (ranged 26.4% to 34.1%) . Suspected reasons for failure were an early exposure of the barrier membrane, its early removal, the implant placement into an infected site, inadequate antibiotic premedication, and/or poor control of infections around teeth prior to implant surgery and around implants before and after placement of barrier membrane.

Semin Respir Infect, 1997 Mar, 12(1), 7 - 11
Psittacosis; Gregory DW et al.; Pneumonia caused by Chlamydia psittaci likely occurs considerably more frequently than is suggested by the mere 100 to 200 cases reported annually to public health authorities . Parrots and other psittacine birds still are regarded as the major reservoir of the infectious agent and most recognized cases are associated with owning pet birds or working in a pet store . It was once thought that birds imported from abroad, often illegally, were a principal source, but many domestic breeder flocks of pet birds now have become infected . There is little that is distinctive in the clinical presentation of psittacosis . Therefore, a careful history of bird contact is often the first clue to the diagnosis . The diagnosis frequently is first considered in evaluating a patient whose pneumonia has not responded to therapy with a beta-lactam antibiotic . The diagnosis usually is established serologically . Tetracycline is the preferred therapy and is administered for three weeks to prevent relapses.

Rinsho Ketsueki, 1997 Mar, 38(3), 228 - 30
{Positive seroconversion syphilis in a patient with acute lymphocytic leukemia after allogeneic bone marrow transplantation}; Naohara T et al.; An acute lymphocytic leukemia patient underwent allogeneic bone marrow transplantation (BMT) from a sibling who was serologically positive for syphilis . After the donor was administered antibiotic therapy, the titration of treponema pallidum hemagglutination (TPHA) decreased from x1260 to x320 . Thereafter, the graft consisting of mononuclear cells was transplanted . TPHA of the recipient turned positive on day +63, but became negative 1.5 years after BMT . Although the cause of the seroconversion of TPHA seemed to be the contamination of treponema to the graft, the adoptive transfer could not be ruled out as an another possible cause.

Masui, 1997 Mar, 46(3), 384 - 7
{Aspiration pneumonia during the endotracheal intubation on the occasion of bladder perforation by TUR}; Fukuhara H et al.; We report on two cases of aspiration pneumonia which developed during the endotracheal intubation after bladder perforation during TUR . The first case was a 79 y.o . male, who underwent TUR-P and lithotripsy under spinal and epidural anesthesia . The second case was a 69 y.o . male, who had undergone TUR-Bt under nitrous oxide-oxygen-enflurane anesthesia . General anesthesia was selected to perform an laparotomy when the diagnosis was made . They vomited a considerable amount of gastric content just after giving the drugs for induction . The chest X-rays revealed signs of aspiration pneumonia . These X-ray findings improved in a week using antibiotic therapy . Although TUR is performed as scheduled, vomiting may occur in the case of unexpected bladder perforation, which can cause aspiration pneumonia . In such emergency, we should insert a nasal tube before induction, press the cricoid (crush induction), or intubate with the patient awake.

Anticancer Drugs, 1997 Mar, 8(3), 238 - 44
In vitro inhibition of endothelial cell growth by the antiangiogenic drug AGM-1470 (TNP-470) and the anti-endoglin antibody TEC-11; Maier JA et al.; Angiogenesis plays a key role in tumor growth, progression and metastasis . The modulation of angiogenesis represents a potentially useful target for novel forms of anticancer therapy . Two such modulators are AGM-1470 (TNP-470, angioinhibin), which is a synthetic analog of the antibiotic fumagallin, and the monoclonal antibody TEC-11 to endoglin . We investigated the mechanisms of action of these modulators on human microvascular and macrovascular endothelial cells and on the transformed endothelial cell line ECV-304 in vitro . The administration of AGM-1470 or TEC-11 resulted in a significant inhibition of cell proliferation in all cell types used; this effect was reversible upon removal of these compounds from the culture medium . Furthermore, biochemical and morphological analyses showed that neither AGM-1470 or TEC-11 induce apoptosis . Both AGM-1470 and TEC-11 inhibited the production of urokinase-type plasminogen activator (u-PA), an enzyme involved in the early steps of neovascularization . Finally, the incubation of endothelial cells with both AGM-1470 and TEC-11 did not produce an additive effect on growth cell inhibition, apoptosis or u-PA production . Since both AGM 1470 and TEC-11 inhibit crucial events such as endothelial cell growth and protease production, our results provide a basis for their therapeutic use as angiostatic molecules in cancer.

J Pediatr Surg, 1997 Mar, 32(3), 486 - 8
Hepatic transplantation in children under 3 months of age: a single centre's experience; Bonatti H et al.; Liver transplantation in neonates represents a major medical and technical challenge particularly in babies weighing less than 5 kg . The authors report the experience of 10 liver transplants in 9 babies (6 boys and 3 girls), mean age, 6 weeks (range, 2 to 11); median weight, 3.7 kg (range, 2.4 to 5) . All had fulminant hepatic failure caused by neonatal haemochromatosis (n = 3), non-A non-B hepatitis (n = 3), total parenteral nutrition induced (n = 1), hepatitis B (n = 1), and hepatic haemangio-endothelioma (n = 1) . One child underwent retransplantation for hepatic artery thrombosis . Immunosuppression was by Cyclosporine A-based triple therapy in all cases . All received a reduced size graft consisting of left lobe (n = 1), left lateral segment (n = 6) and monosegment III (n = 3) . In nine cases the donor hepatic artery was anastomosed to an iliac artery conduit from the infrarenal aorta, and a Roux loop was used for bile duct reconstruction . Primary abdominal wound closure was possible in six patients, skin closure alone in one, and a silastic patch was used in three . Complications included infection (n = 5), bowel perforation (n = 2), diaphragmatic perforation (n = 2), bile leak (n = 1), hepatic artery thrombosis (n = 1), and portal vein thrombosis (n = 1) . None of the babies experienced acute rejection . Currently five of the nine recipients are alive with good graft function at a mean follow-up of 22 months (range, 5 to 58) . Of the four deaths, two were related to infection (one in combination with portal vein thrombosis), one to multiorgan failure and fluid overload, and one to early graft dysfunction and sepsis after undergoing retransplantation for hepatic artery thrombosis . From our experience liver transplantation offers a promising option for the treatment of severe liver disease in children less than 3 months old.

J Comput Aided Mol Des, 1997 Mar, 11(2), 114 - 28
Structure-affinity relationships for the binding of actinomycin D to DNA; Gallego J et al.; Molecular models of the complexes between actinomycin D and 14 different DNA hexamers were built based on the X-ray crystal structure of the actinomycin-d(GAAGCTTC)2 complex . The DNA sequences included the canonical GpC binding step flanked by different base pairs, nonclassical binding sites such as GpG and GpT, and sites containing 2,6-diamino-purine . A good correlation was found between the intermolecular interaction energies calculated for the refined complexes and the relative preferences of actinomycin binding to standard and modified DNA . A detailed energy decomposition into van der Waals and electrostatic components for the interactions between the DNA base pairs and either the chromophore or the peptidic part of the antibiotic was performed for each complex . The resulting energy matrix was then subjected to principal component analysis, which showed that actinomycin D discriminates among different DNA sequences by an interplay of hydrogen bonding and stacking interactions . The structure-affinity relationships for this important antitumor drug are thus rationalized and may be used to advantage in design of novel sequence-specific DNA-binding agents.

Int J STD AIDS, 1997 Mar, 8(3), 187 - 91
Demographic data on prostitutes from Bulgaria--a recruitment country for international (migratory) prostitutes; Tchoudomirova K et al.; The study was aimed at investigating the conditions and circumstances for the recruitment of prostitutes, as well as their reproductive history, working conditions, knowledge of and attitudes to sexually transmitted diseases (STDs), and use of prophylactic antibiotic therapy of these diseases . Two hundred prostitutes were investigated by in-depth interviews at STD clinics, private practices and hotels . Of the 200 prostitutes, 8 (4%) were less than 15 years old and 32 (16%) more than 25 years old . Most of the women came from rural villages . Half of them were gypsies . Most had a boyfriend (often the pimp) . One-quarter had been or were on their way abroad to prostitute . Half were migrating within Bulgaria to prostitute . They claimed a high rate of condom use with customers, but seldom with their pimps or boyfriends . About one-tenth used antibiotics prophylactically . They had knowledge of classical STDs and HIV/AIDS but only in exceptional cases had they heard about chlamydial and human papillomavirus infections . They often cohabited with a female friend also often practising prostitution . It was concluded that recruitment is often easy as the prostitute can earn more from only one contact with a customer than their parents earn from work in a month . Symptoms suggestive of STD were very common in the prostitutes, i.e . in 43% . Bulgaria is a recruitment area for international prostitutes.

J Am Podiatr Med Assoc, 1997 Mar, 87(3), 125 - 30
Unusual presentation of calcaneal osteomyelitis . Twenty-five years after inoculation; Rogoff RS et al.; An unusual presentation of calcaneal osteomyelitis is described, where-by the infection remained undiagnosed for 25 years . The 36-year-old patient recently sought medical treatment for a reported ankle sprain, but the pain was recalcitrant to conservative care . Further investigation yielded a history significant for stepping on a chicken bone as a child, which entered the inferior lateral heel . Magnetic resonance imaging revealed what plain radiographs did not: a well demarcated lytic lesion in the body of the calcaneus . Intraoperative findings were consistent with an abscess of chronic osteomyelitis . The treatment included incision and drainage, antibiotic beads, and a tricortical bone graft.

Pharmacotherapy, 1997 Mar-Apr, 17(2), 375 - 8
Phenytoin-oxacillin interactions in normal and uremic sera; Dasgupta A et al.; Displacement of phenytoin (90% bound to albumin) by other strongly albumin-bound drugs such as salicylate and valproic acid may result in an increase in pharmacologically active free concentrations . The antibiotic oxacillin is also strongly bound to albumin and is often administered to patients receiving phenytoin . Oxacillin at a concentration of 15 micrograms/ml caused no significant displacement of phenytoin in a serum pool prepared from patients receiving phenytoin . However, a significant increase in the free phenytoin concentration was seen at an oxacillin concentration of 50 micrograms/ml . We also prepared a serum pool from uremic patients and another from patients with hypoalbuminemia and supplemented both of them with phenytoin . Significant increases in the free phenytoin concentration occurred with both 15- and 50-microgram/ml concentrations of oxacillin . In one hypoalbuminemic patient receiving both phenytoin and intravenous high-dose oxacillin, the free phenytoin fraction was 22.5% before oxacillin therapy, 24.1% 12 hours after first dose of oxacillin, and 27.2% after 60 hours, indicating the possibility of in vivo displacement of phenytoin by oxacillin . We conclude that the phenytoin-oxacillin interaction is not significant at lower dosages of oxacillin usually prescribed for oral therapy . However, the interaction may be significant at high concentrations of oxacillin, especially in patients with hypoalbuminemia or uremia.

Microbiology, 1997 Mar, 143 ( Pt 3), 875 - 83
Gene disruption and replacement in the rapamycin-producing Streptomyces hygroscopicus strain ATCC 29253; Lomovskaya N et al.; A system for gene disruption and replacement based on a streptomycete temperate phage vector was developed to introduce DNA in the rapamycin-producing Streptomyces hygroscopicus strain ATCC 29253 . This will be useful in attempts to produce, through genetic manipulation, novel forms of the therapeutically important immunosuppressive drug rapamycin . Recombinant phages were constructed from the phi C31 phage derivative KC515 (C+ attp) carrying a thiostrepton or viomycin resistance gene along with segments of the S . hygroscopicus chromosome . Each of the cloned segments also contained the aphll neomycin/kanamycin resistance gene to enable gene replacement by loss of the phage-derived DNA . Specific deletion of the entire polyketide synthase (PKS) believed to govern rapamycin biosynthesis resulted in the loss of rapamycin production . In contrast, disruption or deletion of a region predicted to encode four PKS open reading frames, or another region predicted to encode another PKS plus a cytochrome P450 hydroxylase and ferredoxin, had no effect on the production of rapamycin or nigericin, a polyether antibiotic also produced by S . hygroscopicus . Therefore, S . hygroscopicus may have the capacity to produce polyketides additional to rapamycin and nigericin.

Microbiology, 1997 Mar, 143 ( Pt 3), 867 - 74
A novel fusidic acid resistance gene from Streptomyces lividans 66 encodes a highly specific esterase; von der Haar B et al.; Resistance to fusidic acid in Streptomyces lividans is due to secretion of an extracellular enzyme (FusH) that converts the steroid antibiotic into an inactive derivative . NH2-terminal and several internal amino acid sequences were prepared from the purified enzyme . Using one of the deduced oligonucleotides to probe a subgenomic DNA library, the fusH gene was cloned and sequenced . Sequence analysis located an ORF which, owing to the presence of two putative start codons, indicates a predicted protein with 520 or 509 amino acids . A signal peptide was identified by aligning the deduced amino acids with the N-terminal sequence determined for the mature enzyme . The C-terminal part of the deduced FusH contains a region of three tandemly repeated stretches of 50 amino acids, which is preceded and followed by amino acids showing high homology with the repeats . FusH was found to share a GDS motif with some deduced esterases . S . lividans transformants carrying fusH on a multicopy vector synthesized high levels of FusH . Purified FusH cleaved equally well an acetyl, a thioacetyl or a formyl group from the 16 beta-position of fusidic acid and its derivatives . However, a propionyl group at the 16 beta-position was attacked with difficulty and a 16 alpha-acetyl group was not hydrolysed at all . These data indicate that FusH is a highly specific esterase . The fusH gene is widely distributed among streptomycetes that modify fusidic acid to its inactive lactone derivative.

J Vasc Interv Radiol, 1997 Mar-Apr, 8(2), 197 - 202
Replacement of accidentally removed tunneled venous catheters through existing subcutaneous tracts; Egglin TK et al.; PURPOSE: The authors describe their experience with reinsertion of accidentally removed tunneled venous catheters using existing subcutaneous tracts . MATERIALS AND METHODS: Replacement of 13 dislodged tunneled venous catheters was attempted a median of 12 hours (range, 3 hours to 5 days) after accidental removal . The catheters were needed for hemodialysis (n = 11), plasmapheresis (n = 1), or antibiotic therapy (n = 1) . The tunnel exit was probed in the same fashion as for a dislodged nephrostomy tube, and new catheters were reinserted once a guide wire was advanced into the central veins . The medical record was reviewed to determine materials used and occurrence of complications, if any . RESULTS: Replacement was successful in 12 of 13 patients . The remaining patient had a new catheter placed through a fresh puncture during the same visit . There were no infections associated with re-use of existing tunnels . In five patients, after probing the tract with a guide wire, new catheters were simply advanced into the desired position . Seven other successes required additional manipulations with use of dilators and peel-away sheaths . CONCLUSIONS: Tunneled catheters that "fall out" can be readily replace even when reinsertion is attempted up to 5 days later . This represents an important contribution that radiologists can offer in the management of venous access cases.

Hear Res, 1997 Mar, 105(1-2), 191 - 201
Otoconial formation in the chick: changing patterns of tetracycline incorporation during embryonic development and after hatching; Kido T; The antibiotic tetracycline (TC) is incorporated into calcifying tissues and serves as a fluorescent marker for identifying calcifying sites in bone and otoconia . Fluorescent labeling was performed at different stages in chick embryos and newly hatched chicks . The stagewise changes in the intensity, location and time course of fluorescent labeling were assessed . TC/egg (1-2 mg) was injected into the yolk sacs of embryos on the 4th, 8th and 11th embryonic days (ED), and the embryos were then killed at specified times after injection . In newly hatched chicks, TC was injected daily intraperitoneally with 0.06 mg TC/g body weight for 7 days and the chicks were killed on the 8th day after hatching . Embryos injected on the 4th ED and killed on the 6th ED showed intense fluorescence in the saccular otoconial layer . All maculae from embryos killed after injection on the 4th ED showed uniformly intense fluorescence throughout the otoconial layer . By the 9th ED, otoconia in all three maculae (saccular, utricular, and lagenar) fluoresced . Maculae from embryos killed after injection on the 8th ED showed uniformly intense fluorescence throughout the otoconial layer or intense localized fluorescence mainly in the upper half of the otoconial layer . All maculae from embryos killed after injection on the 11th ED showed moderate to weak fluorescence primarily in the lower half of the otoconial layer . All maculae from posthatched chicks showed very weak fluorescence throughout the otoconial layer . Otoconia at the periphery of the maculae generally showed weak fluorescence in embryos that had been injected on the 4th and 8th ED, but not in embryos injected on the 11th ED . TC, which competes for calcium binding sites, may inhibit the formation of some otoconia . The formation of giant otoconia may reflect subtle changes in the crystallization microenvironment on these occasions . In brief, the results suggest that: (a) otoconial formation in the saccule precedes that of the utricle and lagena; (b) otoconial formation occurs during the early period (beginning the 6th ED); (c) otoconial formation is stratified, with those in the upper layer forming first and those in the lower layer forming last.

Cancer Gene Ther, 1997 Mar-Apr, 4(2), 118 - 28
Purified herpes simplex thymidine kinase Retrovector particles . I . In vitro characterization, in situ transduction efficiency, and histopathological analyses of gene therapy-treated brain tumors; Kruse CA et al.; Replication-defective, highly purified retroviral vectors (Retrovector), at titers of 10(8) colony forming units/mL, were prepared that conferred either beta-galactosidase or herpes simplex thymidine kinase (HSV-TK) activity . 9L gliosarcoma cells, transduced efficiently in vitro, were highly sensitive to ganciclovir (GCV) . The mean frequency of in situ transduction, measured by flow cytometry of single-cell tumor suspensions isolated from rat brains, was 3.2 +/- 0.6%; similar assessments were made by staining of beta-galactosidase or by immunohistochemistry with anti-HSV-TK . In vitro HSV-TK-transduced and G418-selected 9L-TK gliosarcoma tumors treated with GCV were eradicated in approximately 53% of the animals (10/19) at day 26, however, 89% (17/19) histologically showed < 1% tumor volume . Histologic evaluation at day 26 of animals with established 9L tumors treated with intralesional injection of HSV-TK vector followed by GCV treatment showed that 29% (4/14) had no tumor; 50% (7/14) had < 1% tumor volume . Regression of tumors proceeded over the time since the complete rate was increased at day 60 . Neither HSV-TK vector particles nor GCV alone altered the histological profile of 9L tumors, but substantial numbers of CD4+ and CD8+ lymphocytes infiltrated the tumors of animals treated with both . In cured animals, the former tumor bed contained cell debris, immune cells, and fibroblasts and was without damage to adjacent brain . The efficacy of suicide gene therapy for rat gliosarcoma using highly purified virion vectors approaches that of packaging cell lines.

Ophthalmic Surg Lasers, 1997 Mar, 28(3), 236 - 8
Gentamicin retinal toxicity after cataract surgery in an eye that underwent vitrectomy; Rosenbaum JD et al.; A cataract developed in a 23-year-old man 4 months after a vitrectomy to repair a traumatic retinal detachment . An uneventful phacoemulsification was performed, using antibiotic-fortified infusion solution . Afterward, a large area of atrophic retina, consistent with gentamicin toxicity, was observed in the macula . The patient remains stable with 20/200 best-corrected acuity . The authors suggest that because the vitreous had been removed, gentamicin was able to settle over the macula during the entire cataract procedure . Therefore, gentamicin should be used intracamerally with caution, especially in eyes in which vitrectomy has been performed.

Drugs, 1997 Mar, 53(3), 453 - 82
Epirubicin . An updated review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of breast cancer; Coukell AJ et al.; Epirubicin, an anthracycline antitumour antibiotic which is structurally related to doxorubicin, is among the most active single agents used in the management of patients with breast cancer . The drug may be administered alone or in combination with other agents both to patients with early breast cancer and to those with metastatic disease . There is a clear relationship between epirubicin dose and tumour response . Dose intensified regimens have produced improved response rates in patients with advanced breast cancer compared with standard dose therapy; however, improved overall survival has not yet been demonstrated . The combination of epirubicin with newer agents such as vinorelbine or paclitaxel shows considerable promise, as does the use of epirubicin in high dose regimens with peripheral blood progenitor cell support . The major adverse effects of epirubicin are acute dose-limiting haematological toxicity and cumulative dose-related cardiac toxicity . These effects are less severe after epirubicin administration than after equimolar doses of doxorubicin . Other major adverse effects of epirubicin administration include mucositis, nausea and vomiting, reversible alopecia and local cutaneous and vesicant reactions . In summary, epirubicin has an established role in the treatment of both early and advanced breast cancer . Incombination with other highly active agents or in dose intensified regimens administered with haemopoietic growth factor and/or peripheral blood progenitor cell support, epirubicin may play a significant role in emerging breast cancer treatment strategies.

Acad Emerg Med, 1997 Mar, 4(3), 179 - 83
Prevalence of positive serology for acute Chlamydia pneumoniae infection in emergency department patients with persistent cough; Wright SW et al.; OBJECTIVE: To determine the prevalence of acute Chlamydia pneumoniae infection in ED patients presenting with a persistent cough . METHODS: This was a case series consisting of a convenience sample of 65 patients > or = 18 years of age who presented with a chief complaint of a cough lasting > or = 2 weeks . Patients were treated in the ED of an urban university hospital . Patients with immunosuppression, lung disease, pneumonia, or a cough lasting > or = 3 months were excluded . Acute and convalescent sera were assayed for antibody to C . pneumoniae . Subjects with C . pneumoniae antibody titers showing a fourfold rise in either immunoglobin M (IgM) or immunoglobin G (IgG) antibody, an IgM titer of > or = 16, or an IgG titer of > or = 512 were considered to have evidence of acute C . pneumoniae infection . RESULTS: Thirteen (20%; 95% CI, 11% to 32%) of the 65 subjects had serologic evidence of acute C . pneumoniae infection . Except for an increased rate of fever, clinical signs and symptoms and laboratory studies did not differentiate those who had C . pneumoniae from those who did not have the disease . Patients diagnosed as having Bordetella pertussis or Mycoplasma pneumoniae infection did not have serologic evidence of concurrent C . pneumoniae infection . CONCLUSIONS: C . pneumoniae infection appears to be associated with a persistent cough in ED patients . Clinicians should consider this organism when evaluating these patients . It is unclear whether antibiotic therapy is indicated for these patients . If antibiotics are used, a tetracycline or macrolide antibiotic would be most appropriate.

J Clin Oncol, 1997 Mar, 15(3), 1163 - 70
Granulocyte colony-stimulating factor in established febrile neutropenia: a randomized study of pediatric patients; Mitchell PL et al.; PURPOSE: Infection in neutropenic patients is potentially life-threatening and carries important implications for hospital resource use . Prophylactic administration of cytokines may reduce the severity of neutropenia, but involves the treatment of all patients for the possible benefit of a minority . This study evaluates whether treatment with cytokines in the setting of established febrile neutropenia will influence outcome and be potentially more cost-effective . PATIENTS AND METHODS: In a double-blind study, pediatric patients with fever and severe neutropenia were randomized to receive granulocyte colony-stimulating factor ({G-CSF} filgrastim; 5 microg/kg/d) or placebo, in addition to antibiotics . The study protocol required a resolution of fever and a neutrophil count > or = 0.2 x 10(9)/L for hospital discharge . Patients could be randomized for up to four independent febrile episodes . A total of 186 episodes of febrile neutropenia were investigated . RESULTS: Patients randomized to G-CSF had a shorter hospital stay (median, 5 v 7 days; P = .04) and fewer days of antibiotic use (median, 5 v 6 days; P = .02) . G-CSF-treated patients also had more rapid neutrophil recovery and higher neutrophil levels at discharge . The 2-day reduction in hospital stay reduced the median bed cost by 29% per patient admission (P = .04) . CONCLUSION: Under the clinical guidelines of our institution, the use of G-CSF in the treatment of established febrile neutropenia produced a small but significant reduction in the time that children required antibiotics and hospital admission, with possible cost savings.

J Rheumatol, 1997 Mar, 24(3), 531 - 5
Misleading clinical aspects of hydroxyapatite deposits: a series of 15 cases; Claudepierre P et al.; OBJECTIVE: To study the characteristics of radiographs in diagnosis of hydroxyapatite deposits in sites other than the shoulders and hips . METHODS: We reviewed the records of patients hospitalized during the last 3 years whose final diagnosis was apatite deposits in sites other than the shoulders and hips . RESULTS: Ten women and 5 men were studied . The initial presentation mimicked septic arthritis or periarticular soft tissue abscess in 12 patients, corresponding to calcifications in the fingers (6), toes (2), wrists (2), elbow (1), and ankle (1) . One patient presented with a spontaneous coccygeal pain (precoccygeal deposit), one with a pseudotumoral process of the thigh (paradiaphyseal calcification), and one with acute cervical pain and dysphagia (longus coli muscle calcification) . Complete clinical healing was observed after an average of 4.9 days; 11 patients used nonsteroidal antiinflammatory drugs (NSAID), 2 used colchicine, one used oral steroids, and one had brief antibiotic therapy and used NSAID . CONCLUSION: Initial clinical aspects of apatite deposits in sites other than the shoulders and hips can often be misleading, especially by mimicking an infectious process . Careful analysis of immediate radiographic films can help to rapidly ascertain the diagnosis and thus avoid useless investigations or treatment.

Mol Pharmacol, 1997 Mar, 51(3), 448 - 61
Copper-dependent oxidative and topoisomerase II-mediated DNA cleavage by a netropsin/4'-(9-acridinylamino)methanesulfon-m-anisidide combilexin; Henichart JP et al.; A conjugate molecule was synthesized by linking the DNA-intercalative antitumor drug 4'-(9-acridinylamino)methanesulfon-manisidide (mAMSA) via a 4-carboxamide side chain to a dipyrrolecarboxamide moiety structurally related to the minor groove-binding antibiotic netropsin . The molecule (netropsin/ mAMSA) behaves as a threading intercalator . Its netropsin-like tail becomes located in the minor groove of the double helix and serves to drive the hybrid molecule preferentially to AT-rich sites on various DNA fragments as revealed by DNase I footprinting . The hybrid retains the susceptibility to copper-dependent oxidation characteristic of the parent mAMSA moiety as well as its ability to generate oxygen radicals, which can mediate DNA damage, mainly at cytidine and guanosine nucleotides . It also retains the property of stimulating the formation of cleavable complexes with DNA in the presence of topoisomerase II, but its netropsin-like moiety confers little or no influence on the reaction with topoisomerase I . Although netropsin/mAMSA is less potent than mAMSA at producing cleavable complexes with topoisomerase II, it promotes the appearance of cleavage sites at much the same nucleotide sequences as does the parent compound . The dipyrrolecarboxamide tail is not silent, however, since it modifies the concentration-dependence of cleavable complex formation.

Mol Pharmacol, 1997 Mar, 51(3), 422 - 30
Involvement of activator protein-1 and nuclear factor-kappaB transcription factors in the control of the DT-diaphorase expression induced by mitomycin C treatment; Yao KS et al.; The antitumor antibiotic mitomycin C is activated by several bioreductive enzymes, including DT-diaphorase . In HT29 cells, mitomycin C treatment results in the induction of DT-diaphorase as reflected in elevated steady state DT-diaphorase mRNA levels . An increase in the transcriptional rate was demonstrated by nuclear run-on assay . To investigate the molecular basis of the change in transcriptional activity caused by mitomycin C treatment, electrophoretic mobility shift assays were used to demonstrate the induction of nuclear factor binding to elements in the 5' flanking region of the DT-diaphorase gene . Treatment of HT29 cells with mitomycin C resulted in the dose-dependent induction of binding activity directed to the activator protein-1 (AP-1) binding element with a time course similar to that of mRNA elevation . Supershift assays using specific antibodies to Jun and Fos demonstrated the participation of both proteins in the binding activities generated . A binding activity for the nuclear factor-kappaB (NF-kappaB) site was induced with a similar time course . Both competitor and supershift experiments indicated that a heterodimer of the NF-kappaB proteins p50 and p65 was contained in the bound complex . To further investigate the functional consequences of such binding, we transfected HT29 cells with a plasmid containing 3 kb of the DT-diaphorase 5' region upstream of a reporter gene, chloramphenicol acetyltransferase . Treatment with mitomycin C resulted in a 5.5-fold increase in the expression of a chloramphenicol acetyltransferase construct containing 3 kb of DT-diaphorase promoter sequence . Using a series of deletion mutations based on this full-length construct, we found that two regions of the DT-diaphorase promoter region, positions -346 to -588 (containing the AP-1 element) and positions -785 to -890 (containing the NF-kappaB element) are required for the full expression of the mitomycin C response . The specific involvement of these binding elements was confirmed using mutational analysis . The results demonstrate that mutation of either element alone or of both diminishes the response, indicating an additive interaction between the elements at a minimum . However, inducibility characterizes a promoter fragment as small as 78 base-pairs from the transcription start site . Treatment of cells with mitomycin C induced binding to a 38-base-pair region (-40 to -78) devoid of known transcription factor binding elements . These data suggest that mitomycin C induces the overexpression of DT-diaphorase through a mechanism involving both the AP-1 and NF-kappaB response elements and that inducibility depends on a novel factor binding element.

Antimicrob Agents Chemother, 1997 Mar, 41(3), 661 - 4
Development of a high-performance liquid chromatographic assay for G418 sulfate (Geneticin); Bethune C et al.; We have developed a chromatographic assay with high sensitivity and specificity to quantify G418 sulfate (Geneticin), an antibiotic used routinely in molecular genetics experiments for selecting eukaryotic transformants . With this method, G418 in tissues and plasma samples can be quantitated without the confounding factors often associated with biological assays . After removal of proteins in homogenized tissue or plasma samples with methanol (2:1, vol/vol), the amino group of G418 was derivatized with 1-fluoro-2,4-dinitrobenzene (DNFB) to form the UV-visible G418-DNFB product . The DNFB-derivatized G418 was separated on a reversed-phase C18 column with an acetonitrile and water gradient as the mobile phase . Under these assay conditions, the detection limit for G418 sulfate in buffer, plasma, and tissues was recorded at 78 ng/ml and the linearity was recorded for concentrations up to 100 micrograms/ml . The data obtained from this analysis indicate that this assay can be used for the quantitative determination of G418 sulfate in plasma and tissue samples.

J Bacteriol, 1997 Mar, 179(5), 1796 - 804
Characterization of a mitomycin-binding drug resistance mechanism from the producing organism, Streptomyces lavendulae; Sheldon PJ et al.; In an effort to characterize the diversity of mechanisms involved in cellular self-protection against the antitumor antibiotic mitomycin C (MC), DNA fragments from the producing organism (Streptomyces lavendulae) were introduced into Streptomyces lividans and transformants were selected for resistance to the drug . Subcloning of a 4.0-kb BclI fragment revealed the presence of an MC resistance determinant, mrd . Nucleotide sequence analysis identified an open reading frame consisting of 130 amino acids with a predicted molecular weight of 14,364 . Transcriptional analysis revealed that mrd is expressed constitutively, with increased transcription in the presence of MC . Expression of mrd in Escherichia coli resulted in the synthesis of a soluble protein with an Mr of 14,400 that conferred high-level cellular resistance to MC and a series of structurally related natural products . Purified MRD was shown to function as a drug-binding protein that provides protection against cross-linking of DNA by preventing reductive activation of MC.

J Infect Dis, 1997 Mar, 175(3), 720 - 2
A population-based seroepidemiologic study of human granulocytic ehrlichiosis and Lyme borreliosis on the west coast of Sweden; Dumler JS et al.; Ehrlichioses are emerging infections in the United States . Human granulocytic ehrlichiosis (HGE) and Lyme borreliosis (LB) are acquired after Ixodes ricinus-complex tick bites . An ongoing seroepidemiologic study of the 185 of the 356 permanent residents of the Koster Islands in Sweden was expanded to include ehrlichioses . Ehrlichial antibodies were measured by IFA using Ehrlichia equi and Ehrlichia chaffeensis . Borrelia burgdorferi IgG ELISA-seropositive subjects were confirmed by Western blot . E . equi and E . chaffeensis antibodies (titer > or = 80) were found in 21 (11.4%) and 2 (1.1%) of 185 samples, respectively . Antibodies to B . burgdorferi were found in 25 (13.5%) of 185 . Six persons were seropositive for both HGE and LB . Among data from questionnaires, clinical symptoms, antibiotic treatments, or tick bites were not more frequent in E . equi- or B . burgdorferi-seropositive than -seronegative persons . The seroprevalence of HGE was similar to that of Lyme borreliosis . Prospective studies of European HGE are needed.

Gastroenterology, 1997 Mar, 112(3), 991 - 4
Low albumin gradient ascites complicating severe pseudomembranous colitis; Zuckerman E et al.; Pseudomembranous colitis (PMC) is a frequently severe, sometimes fatal iatrogenic disease that is antibiotic-associated in almost all cases . The most common clinical features of PMC include abdominal pain, watery diarrhea, fever, leukocytosis, hypoalbuminemia, and hypovolemia . Ascites, not considered a well-known feature of PMC, is fairly common, based on a review of the English language literature but has not been characterized fully . This case report describes 5 patients with PMC who presented with low serum-ascites albumin gradient (SAAG) and neutrocytic ascites, without evidence of infectious, malignant, or inflammatory peritoneal disease, which has not been reported previously . In 1 patient, massive low SAAG ascites was the presenting manifestation of PMC, a feature also not reported previously . Three of the 5 (60%) patients had acquired immunodeficiency syndrome . The characteristics of the fluid specimens in these 5 patients and the possible pathogenetic mechanisms are proposed . The findings suggest that PMC should be included in the differential diagnosis of low SAAG ascites, especially in patients with acquired immunodeficiency syndrome.

Chem Phys Lipids, 1997 Feb 28, 85(2), 145 - 55
The effect of aggregation state of amphotericin-B on its interactions with cholesterol- or ergosterol-containing phosphatidylcholine monolayers; Barwicz J et al.; Amphotericin B (AmB) is the most effective antibiotic used in the treatment of systemic fungal infections . It is generally thought that the activity of this drug results from its interaction with ergosterol, the main sterol of fungi membranes . However, AmB also interacts with cholesterol, the major sterol of mammal membranes, thus limiting the usefulness of this drug due to its relatively high toxicity . The aim of the present work is to study the molecular basis of the interactions of AmB with these sterols contained in a DOPC film by using the monolayer technique . Two different concentrations of the sterols in the film (13 and 30%) at an initial surface pressure of 30 mN/m were studied, which correspond to conditions found in various biological membranes . Four concentrations of AmB in the subphase, ranging from a molecularly dispersed to a highly aggregated state of the drug were studied . Our results show that the monomeric form of AmB interacts with the ergosterol containing film solely . On the other hand, when AmB is dispersed as a pre-micellar or as a highly aggregated state in the subphase, a very significant selectivity of its interactions between the two sterols is observed which is shown in our experimental results by a difference of 8 mN/m in the surface pressure when AmB interacts with ergosterol as compared to cholesterol . We show that the activity of AmB is most likely related to the micellar form of the antibiotic . In addition, we observe that upon increasing the amount of ergosterol in the film, the insertion of AmB is largely promoted, results that are discussed in terms of the molecular organization of the sterols within the monolayer film . We show that these results provide a better understanding of the action of AmB (activity/toxicity) at the membrane level.

J Med Chem, 1997 Feb 28, 40(5), 771 - 84
Synthesis, antiproliferative and antiviral activity of imidazo{4,5-d}isothiazole nucleosides as 5:5 fused analogs of nebularine and 6-methylpurine ribonucleoside; Swayze EE et al.; A series of imidazo{4,5-d}isothiazole nucleosides related to the antibiotic nebularine and the highly cytotoxic 6-methyl-9-beta-D-ribofuranosylpurine have been synthesized from the corresponding heterocycles . The sodium salt glycosylation of the imidazo{4,5-d}isothiazoles proceeded smoothly, giving mixtures of N-4 and N-6 regioisomers in generally good yields . The protected derivatives were deblocked using standard conditions to afford the desired imidazo{4,5-d}-isothiazole nucleosides, usually as crystalline solids . None of the new nucleosides or heterocycles displayed selective activity against human cytomegalovirus (HCMV) or herpes simplex virus type 1 (HSV-1) . The N-6 glycosylated imidazo{4,5-d}isothiazoles were completely inactive up to the highest concentration tested . The N-6 glycosylated imidazo{4,5-d}isothiazoles also were inactive in antiproliferative and cytotoxicity assays, except for 3-methyl-6-beta-D-ribofuranosylimidazo{4,5-d}isothiazole (15a) and 5-(benzylthio)-6-(2-deoxy-beta-D-ribofuranosyl)imidazo{4,5-d}isothiaz ole (5e), which showed moderate inhibition of L1210 cell growth . However, the heterocycles and several of the N-4 glycosylated derivatives were toxic to HFF, KB and L1210 cells; compounds with 5-benzylthio substituents were the most cytotoxic agents in this series.

Biochemistry, 1997 Feb 25, 36(8), 2291 - 9
Differential interactions of the Mg2+ complexes of chromomycin A3 and mithramycin with poly(dG-dC) x poly(dC-dG) and poly(dG) x poly(dC); Majee S et al.; The interaction of the two anticancer antibiotics, chromomycin A3 and mithramycin, with the polynucleotides poly(dG-dC) x poly(dC-dG), representative of B-DNA, and poly(dG) x poly(dC), representative of A-DNA, in the presence of Mg2+ is studied by spectroscopic techniques such as absorbance, fluorescence, and dircular dichroism (CD) . The studies were done with both drug x Mg2+ complexes, I and II, having 1:1 and 2:1 stoichiometries with respect to drug and Mg2+, respectively {Aich, P., Sen, R., & Dasgupta, D . (1992) Biochemistry 31, 2988-2997} . The objective of the present work is 2-fold . First, an attempt is made to understand the structural basis of the ligand-DNA interaction, particularly the role of DNA backbone conformation with its groove size and the accessibility of the 2-amino group in the minor groove of guanosine . Second, the role of the antibiotic saccharide moieties in the association with DNA was studied . For this purpose, the spectroscopic characterization of the binding was done followed by the evaluation of binding parameters and associated thermodynamics . Analysis of the observed thermodynamics for the ligand-DNA interactions in terms of the different structures of the polynucleotides was done . The salient results are as follows . Complex I does not discriminate significantly among the A- and B-forms of DNA when it binds to them in an entropy-driven process . On the other hand, complex II for both drugs recognizes B- and A-forms of DNA in different ways . This observation implies that the sequence specificity shown by this complex is a sequel to the difference in the parameters such as groove size and accessibility of the guanosine amino group . Another important finding is that binding with the same polynucleotide is not comparable for the complex II of the two drugs . It emphasizes the involvement of the sugar moieties, when the drug x Mg2+ complex binds to DNA . The presence of an acetoxy group in the sugars of chromomycin A3 imparts some distinctive specific features of the association of the chromomycin dimer x Mg2+ complex with DNA . Finally, the results are compared with those available from NMR studies of different drug-oligonucleotide complexes under conditions where complex II is the ligand.

J Chromatogr A, 1997 Feb 21, 762(1-2), 327 - 33
High-performance liquid chromatographic separation of beta-methyl ADC-13 enolphosphate diphenyl ester and its alpha-methyl diastereomer; Wang T; The development of a high-performance liquid chromatographic (HPLC) separation of beta-methyl ADC-13 enolphosphate diphenyl ester, an intermediate compound in the synthesis of a carbapenem antibiotic drug candidate, and its alpha-methyl diastereomer is reported . The method development involved separation on different columns in both normal- and reversed-phase modes . The use of normal-phase mode resulted in the desired elution order of the two diastereomers . The influence of different polar modifiers and their concentrations on resolution, capacity factor and separation factor was investigated . Different stationary phases were compared for their efficiency and resolution . The optimized separation was applied to the determination of the minor diastereomer in the bulk intermediate, and 0.1% minor diastereomer was detectable.

Proc Natl Acad Sci U S A, 1997 Feb 18, 94(4), 1160 - 5
Novel pyridinium surfactants for efficient, nontoxic in vitro gene delivery; van der Woude I et al.; Novel, double-chained pyridinium compounds have been developed that display highly efficient DNA transfection properties . The transfection efficiency of several of these compounds is enhanced by an order of magnitude, when compared with the transfection efficiency accomplished with the widely used cationic lipid system, lipofectin . Most importantly, the pyridinium compounds were found to be essentially nontoxic toward cells . Using various reporter genes, such as beta-galactosidase and pNEO (a gene construct that renders cells resistent to antibiotic derivatives of neomycin like G418), we demonstrate that the enhanced efficiency relates to the fact that a relative higher number of cells in the population is transfected (approximately 50% in the case of COS cells) by the pyridinium derivatives, whereas the delivery of DNA per cell is also enhanced . Furthermore, application of the pyridinium derivatives shows little cellular preference in their ability to transfect cells . By systematically modifying the structure of the pyridinium amphiphile, i.e., by changing either the headgroup structure or the alkyl chains, some insight was obtained that may lead to unraveling the mechanism of amphiphile-mediated transfection, and thus to protocols that further optimize the carrier properties of the amphiphile . Our results reveal that unsaturated alkyl chains enhance the transfection properties of the pyridinium-based amphiphiles . Preliminary experiments suggest that the structure-dependent improvement of transfection efficiency, when comparing pyridinium derivatives with lipofectin, likely relates to the mechanism of delivery rather than the packaging of the amphiphile/DNA complex.

J Clin Invest, 1997 Feb 15, 99(4), 608 - 17
Prevention of bleomycin-induced pulmonary fibrosis after adenovirus-mediated transfer of the bacterial bleomycin resistance gene; Tran PL et al.; A serious limitation in the use of the DNA-cleaving, antitumoral-antibiotic, bleomycin during chemotherapy is pulmonary toxicity . Lung injury induced by bleomycin is characterized by an increased deposition of interstitial extracellular matrix proteins in the alveolar wall that compromises respiratory function . Several drugs have been tested in animal models to prevent the pulmonary toxicity of bleomycin, but have not led to a useful clinical treatment because of their adverse effects on other tissues . We have shown that transgenic mice expressing Streptoalloteichus hindustanus (Sh) ble bleomycin resistance protein in pulmonary epithelial cells in the lungs are protected against bleomycin-induced toxicity in lungs . In the present study, we used intranasal administration by adenovirus-mediated gene transfer of the bleomycin resistance Sh ble gene to mouse lung for prevention of bleomycin-induced pulmonary fibrosis . We constructed recombinant adenoviruses Ad.CMVble and Ad.RSVble harboring the bleomycin resistance Sh ble gene under the control of the cytomegalovirus early promoter and the Rous sarcoma virus early promoter, respectively . Transgene expression was detected in epithelia of conducting airways and alveolar septa by immunostaining with a rabbit polyclonal antibody directed against the bleomycin resistance protein and persisted for the duration of drug treatment; i.e., up to 17 d . No toxic effect was seen in adenovirus-treated mice . Pretreatment of mice with Ad.CMVble or Ad.RSVble completely prevented collagen deposition 42-133 d after bleomycin treatment, as measured by lung OH-proline content . Histologic studies indicated that there was little or no lung injury in the adenovirus/bleomycin-treated mice compared with the bleomycin-treated mice . These observations may lead to new approaches for the prevention of bleomycin-induced pulmonary fibrosis.

Toxicol Lett, 1997 Feb 7, 90(2-3), 217 - 21
Poly-l-aspartic acid protects cultured human proximal tubule cells against aminoglycoside-induced electrophysiological alterations; Todd JH et al.; Cultured human proximal tubule cell monolayers maintained on permeable supports were treated simultaneously with the aminoglycoside antibiotic, gentamicin, and poly-L-aspartic acid (PAA), an inhibitor of aminoglycoside nephrotoxicity . Following 4 days of exposure, cell monolayers were placed into Ussing chambers to allow monitoring of transepithelial electrical properties . For each of the three cell isolates examined, aminoglycoside-induced alterations in electrogenic transport, reflected by changes in short-circuit current (Isc), as well as alterations in paracellular properties, indicated by changes in transepithelial electrical resistance (RT), were diminished in the presence of PAA . Alterations resulting from selective basolateral exposure to gentamicin were unchanged in the case of apically applied PAA and attenuated only when PAA acid was added basolaterally . This is the first demonstration of PAA inhibition of aminoglycoside-induced cellular alterations involving human cells.

Am J Ophthalmol, 1997 Feb, 123(2), 252 - 4
Primary varicella-zoster keratitis: diagnosis by polymerase chain reaction; Power WJ et al.; PURPOSE: To report the value of polymerase chain reaction in the diagnosis of a worsening corneal ulcer . METHODS: A 6-year-old boy underwent an emergent penetrating keratoplasty for a corneal ulcer that continued to worsen despite intensive antibiotic therapy . RESULTS: Examination of the corneal specimen by polymerase chain reaction was positive for varicella-zoster virus but negative for herpes simplex . Based on polymerase chain reaction studies, we diagnosed primary varicella-zoster keratitis with corneal perforation . Electron microscopy showed herpetic virus particles in the cornea . CONCLUSIONS: Polymerase chain reaction analysis of corneal buttons at the time of penetrating keratoplasty may benefit patients with undiagnosed recalcitrant corneal ulcers.

Arch Mal Coeur Vaiss, 1997 Feb, 90(2), 285 - 9
{Giant aneurysm of the interventricular septum . Value of imaging techniques}; Revel F et al.; A pseudosubaortic left ventricular aneurysm was discovered in a 32 year old African presenting with pyrexia after a long history of chest pains and dyspnea . Echographic and radiological techniques showed a large pulsatile mediastinal mass and the patient was referred for aneurysmorrhaphy . The actiology of this pseudo-aneurysm is discussed with reference to data in the literature . Infection is the first cause to be excluded in view of the pyrexia truncated by "blind" anti-inflammatory and antibiotic therapy . The hypothesis of an interventricular septal abscess secondary to septicaemia with secondary rupture into the pericardium is discussed . Precessive endocarditis with an aseptic abscess is unlikely because of the minimal aortic valve lesions, the absence of vegetations and the very long clinical evolution . Finally, idiopathic pseudo-aneurysms in sub-Saharian Africans, due to a congenital defect of the fibrous aortico-mitral and subannular zones must be considered . The risk of complications of these pseudo-aneurysms justifies surgical intervention on the accurate anatomical description of the lesions provide by transthoracic and transoesophageal echocardiography and magnetic resonance imaging.

Genetika, 1997 Feb, 33(2), 284 - 6
{Role of the rpoS gene in the regulation of expression of plasmid genes determining the synthesis of C51 microcin}; Fomenko DE et al.; In cells mutant for the rpoS gene coding the sigma s subunit of RNA polymerase, synthesis of antibiotic microcin C51, which is produced by Escherichia coli, is absent or extremely reduced . In experiments with a cloned promoter of the microcin operon, the sigma s subunit was shown to participate in regulation of transcription of plasmid genes that determine microcin synthesis.

Allerg Immunol (Paris), 1997 Feb, 29(2), 36 - 8
{Clinico-immunological study of 16 cases of benzoate intolerance in children}; Petrus M et al.; The authors report a sery of 16 cases of intolerance to the benzoates in children . Sixteen children (9 boys and 7 girls) were directed to the Hospital of Tarbes from June 1995 to July 1995, for recurring urticaria (7/16) combined with asthma (1/16), atopic eczema (2/16), dermorespiratory syndrome (2/16) and asthma (1/16) . All were subject to an immunological examination comprising alimentation inquiry, prick test, IgE determination, RAST, oral provocation test to benzoates, which establishes the diagnosis, whose confirmation is certified by the benefit of the food eviction . To conclusion, the authors underline several points: the presumable underestimation of the intolerance, the often mentioned atopic familial context, the observed pathology (urticaria, asthma, eczema), the importance of the provocation test . Finally, besides food such as grey shrimps, sodas and antibiotic syrups, one finds benzoates in the antiallergic syrups initially prescribed as a preventive measure.

Unfallchirurg, 1997 Feb, 100(2), 111 - 8
{Seidel humerus intramedullary nailing . Clinical results of 100 surgeries}; Kelsch G et al.; Between 01.01.88 and 30.07.94 we treated 81 traumatic and 19 pathologic humeral shaft fractures with the Seidel humeral locking nail (HLN) . The majority of the 100 patients (60 women, 40 men) were older than 60 years of age . The dominant fracture type according to AO was type A . Operative stabilization was considered indicate because of fracture distraction during functional bracing in most cases . In general, patients choose surgical intervention in preference to conservative management . Radiological consolidation was observed within 10 weeks . In 48 cases sonography revealed motor disturbances between the gliding sheath of the rotator cuff, but there was no correlation between this and the shoulder mobility . In 7 cases an additional fracture was created during introduction of the nail . This complication can be avoided by using the right technique . There were no cases of non-union or radial nerve lesion . There were 2 patients who developed an infection, which disappeared after removal of the nail and introduction of antibiotic-loaded beads . Functional results were recorded in 63 patients: 53 patients (84%) had an excellent or satisfactory result (NEER score > 80) . Among the others, problems at the site of nail insertion predominated . In our view, the Seidel humeral locking nail is an implant that provides exercise stability without intraoperative positioning problems or risk of injury to nerves or vessels . Nevertheless, this method needs a skilled surgeon with special training to handle typical technical nailing problems.

Br J Neurosurg, 1997 Feb, 11(1), 75 - 7
Spontaneous drainage of an infratentorial extradural empyema: case report; Nathoo N et al.; We describe a 21-year-old male who presented with spontaneous drainage of an infratentorial extradural empyema secondary to mastoiditis . Following eradication of the primary source, the patient was commenced on high dose intravenous antibiotics . Serial computed tomography (CT) revealed complete resolution of the pus collection . Antibiotic therapy was successful and no neurosurgical intervention was necessary.

Genitourin Med, 1997 Feb, 73(1), 59 - 62
Non-cultural detection of rectal and pharyngeal gonorrhoea by the Gen-Probe PACE 2 assay; Young H et al.; OBJECTIVE: To assess the sensitivity and specificity of the Gen-Probe PACE 2 assay, which uses a chemiluminescent labelled single-stranded DNA probe to detect gonococcal ribosomal RNA (rRNA), for the non-cultural detection of rectal and pharyngeal gonorrhoea in homosexual men . SUBJECTS: 161 homosexual men attending the Department of Genitourinary Medicine, Edinburgh Royal Infirmary during the latter half of 1995 and the first quarter of 1996 . METHODS: Duplicate rectal and pharyngeal swabs were collected for culture on modified New York City (MNYC) medium and detection of gonococcal nucleic acid by the Gen-Probe assay . Repeatedly reactive Gen-Probe specimens from culture negative patients were also tested by the Gen-Probe competition assay (PCA) . RESULTS: Of the 161 patients, 23 (14.3%) gave a positive culture at one or both sites (rectum 10, throat 8, rectum and throat 5) compared with 28 (16.7%) who gave a positive Gen-Probe result at one or both sites (rectum 9, throat 11, rectum and throat 8) . After resolution of discrepant results by PCA the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Gen-Probe was 94.1%, 100%, 100% and 99.3% for rectal specimens while the corresponding values for pharyngeal specimens were 86.4%, 100%, 100%, and 97.9% . The sensitivity and NPV of rectal culture were 88.2% and 98.6% while the corresponding values for pharyngeal culture were 59% and 93.9% . Gen-Probe was significantly more sensitive than throat culture (p < 0.05) but not rectal culture (p > 0.2) . The average Relative Light Units (RLU) value for the cut-off was 386 (range 351-450) while the average for a positive result was 20306 (range 403-110104): this was, however, significantly higher (p = 0.019) in rectal specimens 31325 (range 1705-110104) than in throat specimens 10447 (range 403-15633) . CONCLUSIONS: Gen-Probe PACE 2 assay is a sensitive and specific method for the detection of rectal and pharyngeal gonorrhoea . As the Gen-Probe assay may detect nucleic acid from non viable gonococci the clinical significance of a probe positive culture negative specimen from a patient without culture evidence of gonorrhoea at another site is uncertain and requires further consideration . Nevertheless a positive result does indicate exposure to infection and could be important in ensuring appropriate partner notification action . If non-cultural methods are used to screen for gonococcal infection cultures should be obtained from patients with positive results in order that the antibiotic susceptibility and molecular epidemiology of the gonococcal population can be monitored.

Clin Infect Dis, 1997 Feb, 24 Suppl 2, S181 - 3
Penetration of meropenem in plasma and abdominal tissues from patients undergoing intraabdominal surgery; Condon RE et al.; We assessed the penetration of a new carbapenem antibiotic, meropenem, into abdominal tissues . A single 1,000-mg intravenous dose was administered to 66 patients undergoing elective intraabdominal surgery . Plasma, body fluid (peritoneal fluid and bile), and tissue samples (colon, gallbladder, omentum, stomach, fascia, muscle, and skin) were taken at various times up to 8 hours after administration of the dose . Meropenem concentrations were determined by means of validated bioassay techniques . Peak meropenem concentrations in most tissue specimens and one body fluid occurred within approximately 1 hour; the exceptions were bile and muscle specimens, in which peak concentrations were present in approximately 2 to approximately 4 hours . The bile concentration increased with time, thus indicating active excretion of drug into bile . Only one adverse event (mild nausea) was attributable to meropenem . Our results show that meropenem achieves adequate tissue concentrations for the treatment of intraabdominal infections due to susceptible bacteria.

Clin Infect Dis, 1997 Feb, 24 Suppl 2, S178 - 80
Tissue penetration of Meropenem in patients undergoing gynecologic surgery; Gall S et al.; The purpose of this study was to assess the tissue-penetrating ability of a new beta-lactam antibiotic, meropenem, in 64 patients undergoing elective gynecologic surgery . Patients received a single 500-mg dose intravenously before surgery . Plasma and tissue concentrations of meropenem were highest at approximately 1 hour, and good tissue penetration was seen in the variety of specimens evaluated . The median plasma concentration at approximately 1 hour was 13.3 micrograms/mL . The median fluid and tissue concentrations at approximately 1 hour were as follows: cervix, 8.5 micrograms/g; endometrium, 2.3 micrograms/g; fallopian tube, 1.9 micrograms/g; myometrium, 3.6 micrograms/g; ovary, 2.3 micrograms/g; and uterus, 2.3 micrograms/g . These tissue concentrations exceed the MICs of meropenem for 90% of typical pathogens associated with gynecologic infections . Meropenem readily penetrates gynecologic tissue . A single 500-mg dose provides adequate tissue concentrations for treatment of gynecologic infections caused by susceptible pathogens.

J Dairy Res, 1997 Feb, 64(1), 1 - 11
Management practices associated with high mortality among preweaned dairy heifers; Losinger WC et al.; In a national survey of US dairy operations, 1685 dairy operations reported 47,057 new dairy heifers (either births or acquisitions) and 4427 deaths (9.4%) of preweaned dairy heifer calves over a 3 month period . Stepwise logistic regression was used to identify management practices associated with high mortality among preweaned heifers in dairy operations where at least three dairy heifer calves were born alive or moved on to the operation . Analysis was done twice: once by separating all operations by size into high or low mortality; again using only operations with < 2 and > 10% mortality to eliminate dairy operations with intermediate levels of mortality from the comparisons . Results were similar . Dairy operations in the West were more likely to fall in the high mortality category than dairy operations in the rest of the country . In addition, the following dairy operation characteristics were associated with high death levels in both models: rolling herd average milk production < 7710 kg . preweaned heifers placed in groups of seven or more, a male having primary responsibility for the care and feeding of preweaned heifers, calves not receiving hay or other roughages until > 20 d old, calves fed on mastitic or antibiotic milk after colostrum and calves not given whole milk after colostrum.

Sex Transm Dis, 1997 Feb, 24(2), 61 - 3
How can industry, academia, public health authorities, and the sexually transmitted diseases diagnostics initiative work together to help control sexually transmitted diseases in developing countries?
Chernesky MA.
PIP: More than 300 million new cases of gonorrhea, chlamydia, syphilis, and chancroid will develop in 1997, with 85% occurring in developing countries . While diagnostic tests for sexually transmitted diseases (STDs) are sensitive and specific, their expense has led the World Health Organization to promote syndromic management of STDs . This approach, however, can lead to overtreatment with expensive drugs and may result in development of antibiotic-resistant strains of infection . Also, gonococcal and chlamydial infections are often asymptomatic in women . Because the presence of an STD facilitates HIV transmission, STD treatment is an important strategy in HIV/AIDS prevention and control . Since 1990, the STD Diagnostics Initiative (SDI) has sought to identify sensitive, specific, simple, stable, and inexpensive means of diagnosing STDs . Since 1994, 8 research proposals have received a total of $850,000 for a 3-year period . The efficient diagnostic tests sought by the SDI would encourage greater expenditures on STD treatment . The SDI believes that collaboration with industry should remove most of the constraints to product development and market penetration that exist in developing countries . Incentives to achieve the goals of the SDI include a million dollar prize offered by the Rockefeller Foundation for development of a rapid, sensitive, specific, simple, stable, and inexpensive assay . SDI can provide research funds, controlled access to pedigreed clinical specimens, and guidelines for effective evaluations . Industry has the market and the challenge to join with SDI in this effort .

Eur J Clin Microbiol Infect Dis, 1997 Feb, 16(2), 153 - 5
Characterization of Escherichia coli serotype O12:K1:H7 isolates from an immunocompetent carrier with a history of spontaneous abortion and septicemia; Blum-Oehler G et al.; Escherichia coli isolates from an immunocompetent woman with a history of repeated amnion infections and spontaneous abortion were characterized . Escherichia coli were isolated from stool, blood and cervix swab samples taken over a 21-month period after the last abortion which followed septicemia during pregnancy . All samples except the last cervix swab contained isolates of serotype O12:K1:H7, which produced adhesins, P fimbriae, type I fimbriae and the iron-chelator aerobactin . Pulsed-field gel electrophoresis revealed identical Xbal restriction patterns of the O12:K1:H7 isolates, suggesting that one particular Escherichia coli strain was responsible for the severe extraintestinal infections during pregnancy . The strain was able to persist in the intestine of the woman despite antibiotic therapy.

Intern Med, 1997 Feb, 36(2), 113 - 7
Idiopathic hypoparathyroidism with fungal seminal vesiculitis; Matsuyama W et al.; A 23-year-old man was suffering from high fever and general fatigue 6 months before admission . The levels of serum Ca and intact-parathyroid hormone (PTH) were low . His brain computed tomography (CT) revealed marked calcifications of the basal ganglia, and pelvis magnetic resonance imaging (MRI) showed inflammation of his seminal vesicle . His candida antigen titer was high and antibiotic therapy was unsuccessful . High fever persisted despite fluconazole treatment, however he recovered after treatment with fluconazole and vitamin D (alfacalcitol) . Idiopathic hypoparathyroidism hinders the activation of vitamin D via insufficient PTH secretion, and vitamin D has some immunological effects . His decreased natural killer (NK) cell activity improved after alfacalcitol treatment . We suggest the possible immunological effects of vitamin D in this fungal infection.

Prep Biochem Biotechnol, 1997 Feb, 27(1), 19 - 38
New macrolactone of the desertomycin family from Streptomyces spectabilis; Ivanova V; The non-polyenic macrocyclic antibiotic complex 1012 was isolated from the culture broth of a strain Streptomyces spectabilis 1 . The complex was found to belong to the desertomycin complex . Three main compounds of complex 1012 were separated and purified by preparative chromatographic methods . The identification was performed by UV, IR, NMR and mass-spectrometric studies . It was proved that two of the compounds with MW . 1191, C61H109NO21 and MW . 1190, C61H106O22 were identical to desertomycin A and D . The other com-pound with MW.1028, C55H96O17 is new macrolactone, named deser-tomycin E . The structures were established by detailed spectroscopic analysis.

Pharm World Sci, 1997 Feb, 19(1), 35 - 44
Neuromuscular transmission and its pharmacological blockade . Part 3: Continuous infusion of relaxants and reversal and monitoring of relaxation; Booij LH; Continuous infusion is an attractive method of administration when muscle relaxation is needed for a longer period . The pharmacokinetic behaviour of a drug is an important determining factor for the suitability of relaxants for continuous infusion . At present mainly intermediately long acting relaxants are used for this purpose . At the end of surgery residual curarization may exist and thus anaesthesiologists prefer to be able to reverse the relaxants . The anticholinesterases neostigmine, pyridostigmine, and edrophonium are used clinically for this reason . Their effect is prolonged in patients with renal failure, and also affected during acid-base disturbances . Some other drugs have been used experimentally for the reversal of neuromuscular blockade, but are inadequate . Special problems can arise when reversal of a mivacurium-induced or antibiotic-induced blockade is wanted, or mivacurium was administered . Monitoring neuromuscular transmission is an important feature to determine the effect of relaxant administration or to detect residual curarization . It is based on stimulation of peripheral nerves with either single twitch, train of four, tetanic or double burst stimulation . The evoked response can be quantitated with mechanomyography, electromyography, or accelerography . The response of the various muscles to nerve stimulation varies due to the different characteristics of the muscles . Clinically, the use of the adductor pollicis muscle is advised.

J Biochem Biophys Methods, 1997 Feb 1, 34(1), 1 - 10
Isolation of tRNA isoacceptors by affinity chromatography with immobilized elongation factor Tu from Escherichia coli; Chinali G; Elongation factor Tu (EF-Tu) from E . coli was coupled to activated CH Sepharose 4B . The immobilized EF-Tu maintained most of the guanosine nucleotide binding activity, but its ability to bind aminoacyl-tRNA depended on the type of complex used in the coupling reaction . The EF-Tu.GTP.aminoacyl-tRNA.kirromycin complex yielded an immobilized factor that was much more active in binding aminoacyl-tRNA than that obtained by coupling EF-Tu.GDP or EF-Tu.GDP.kirromycin to CH Sepharose 4B . Like the free factor, the immobilized EF-Tu.GTP did bind aminoacyl-tRNAs, but not unacylated tRNAs or N-acylated-aminoacyl-tRNAs . The antibiotic kirromycin was used to obtain the rapid conversion of EF-Tu.GDP to EF-Tu.GTP and the release of aminoacyl-tRNA from the matrix-bound EF-Tu by GDP . When total tRNA was aminoacylated by one amino acid only, a column of immobilized EF-Tu-GTP.kirromycin allowed the isolation of the aminoacylated tRNA from bulk tRNA . A rapid and nearly quantitative recovery of highly purified tRNA isoacceptors for various amino acids was obtained in one chromatographic step.

Gene Ther, 1997 Feb, 4(2), 150 - 5
A simple procedure to determine the biological titer of recombinant retroviral vectors; Tavoloni N; Retroviral vectors are widely used to deliver genetic material to live cells both in experimental and clinical settings . The ability of these vectors to transduce target cells is an important aspect of their clinical applicability and one of the factors determining their transduction efficiency is vector functional titer . Current methods for titrating retroviral vectors involve measuring the number of target cells in culture transduced by a given volume of vector solution . In this report, we describe a new procedure which allows one to estimate the actual number of infectious particles capable of transducing a permissive cell type . Vector biological titer is calculated from the fractional decline in transduction efficiency observed when a given volume of vector solution is sequentially added to multiple dishes containing permissive cells . Values determined this way are greater than those obtained from a single transduction experiment, with the difference being inversely proportional to the degree of cell permissiveness for vector entry . The present procedure is simple, reliable and expeditious . It will be useful to standardize vector biological titers determined in different laboratories, and help implement strategies for efficient gene delivery protocols.

Am J Surg, 1997 Feb, 173(2), 95 - 8
Surgical approaches to low anovaginal fistula in Crohn's disease; Hull TL et al.; BACKGROUND: Anovaginal fistula due to Crohn's disease can be surgically repaired in some women . The purpose of this study was to analyze the types of fistula along with the features that point to success or failure in treating these patients . METHODS: Women with anovaginal fistula and Crohn's disease treated surgically by one surgeon from 1988 to 1992 were retrospectively studied . RESULTS: Forty-eight women underwent treatment for anovaginal fistula caused by Crohn's disease . This represented 55% of the total patients seen for anovaginal fistula from all causes . Nine patients had severe anorectal and/or colonic disease and underwent total proctocolectomy with ileostomy . Four other patients had seton placement only . The remaining 35 patients underwent transanal repair of their fistula and are the basis of this study . Three types of flap repairs were performed: curvilinear advancement rectal flap (n = 24), linear advancement rectal flap (n = 6), and advancement sleeve flap (n = 5) . The type of surgery selected depended on the associated anal and colorectal disease . Diverting ileostomies were used in nine patients with a successful outcome in eight . Healing occurred with the initial repair in 19/35 (54%) . An additional five patients underwent successful repeat procedures for an overall success rate of 24/35 (68%) . CONCLUSION: Surgical closure of anovaginal can be offered to selected women with Crohn's disease, thus avoiding a permanent stoma in this group . The type of flap chosen for repair depends on the characteristics of the fistula.

Gan To Kagaku Ryoho, 1997 Feb, 24(4), 443 - 53
{Biochemical mechanisms of NCS-chromophore-induced DNA cleavage and inhibition of protein kinase activity}; Ohtsuki K et al.; A NCS-chromophore (molecular weight: approximately 695) can be extracted from an antitumor antibiotic neocarzinostatin (NCS) (approximately 11,000, pI 3.3) with methanol as a DNA cleavaging molecule . Recently, the Goldberg research group (Harvard University, USA) proposed two distinct mechanisms of DNA cleavages (thiol-dependent DNA cleavage and thiol-independent base-catalyzed (bc) cleavage of ssDNA) by NCS-chromophore in vitro . Therefore, it is concluded that the ability of NCS-chromophore to cleave DNA is its primary action, which selectively inhibits DNA synthesis in cultured cells . Furthermore, we found that NCS-chromophore inhibits protein phosphorylation by CK-II (casein kinase II) involved in transcriptional regulation in a dose-dependent manner . Disruption of the repair systems of the NCS-chromophore-induced biological damages results in the positive induction of apoptosis, because the drug is greatly activated by thiols at the intracellular level, and it inhibits the activities of several transcriptional factors through their specific phosphorylation by nuclear kinases, such as CK-II . Taken together, all these biological and biochemical data suggest that the NCS-chromophore could be an effective chemotherapeutic drug for human cancer if its toxicity can be appropriately controlled.

J Hand Surg {Br}, 1997 Feb, 22(1), 133 - 4
Hand infections in the diabetic patient; Pinzur MS et al.; Between 1984 and 1994, 23 diabetic patients were admitted to a university hospital/Department of Veterans Affairs (DVA) Medical Centre with a primary or secondary diagnosis of hand infection . We also identified 726 patients admitted to all DVA Medical Centres during the years 1989 through 1994 with co-diagnoses of diabetes mellitus and hand infection . Contrary to previously published literature, most diabetic hand infections are non-specific, confined to the soft tissues, and respond to broad spectrum parenteral antibiotic therapy . When surgery is necessary, most patients do not require amputation.

Fam Pract, 1997 Feb, 14(1), 34 - 9
Sore throat management practices of Canadian family physicians; McIsaac WJ et al.; OBJECTIVES AND METHODS: A survey was conducted of Canadian family physicians about their usual sore throat management practices . Physician knowledge, attitudes, beliefs and the effect of selected patient factors on variation in practices was assessed . RESULTS: The majority of physicians did not follow North American expert recommendations to usually take a throat culture and wait for culture results before prescribing an antibiotic . Similarly to the practices of family physicians in many countries, they favoured a clinical policy of selective use of throat cultures and decisions about the need for antibiotics based on clinical judgement . CONCLUSIONS: Physician practice site, demographics, knowledge, attitudes, beliefs and patient factors did not explain differences in approach . The implications for antibiotic utilization in the management of upper respiratory tract infections are discussed.

Thorax, 1997 Feb, 52(2), 153 - 6
How general practitioners manage acute asthma attacks; Neville RG et al.; BACKGROUND: The management of asthma attacks by general practitioners in 1992/93 was compared with 1991/92 in relation to recommended guidelines . METHODS: The findings from a postal survey of 299 UK general practitioners who managed 2332 patients with an asthma attack in 1992/93 were compared with those from 218 practitioners who managed 1805 attacks in 1991/92 . Management by a subgroup of practitioners from a special interest group was analysed separately . RESULTS: In 1992/93 2031 (87%) of attacks were managed entirely by general practitioners, 251 (11%) were referred for admission to hospital, and 50 (2%) were managed by an accident and emergency department . There was no change in the pattern of management relative to 1991/92 . Compared with recommended guidelines there was underuse of systemic steroids and nebulised bronchodilators . Between 1991/92 and 1992/93 use of systemic steroids in acute attacks increased from 56% to 71%, nebulised bronchodilators from 31% to 32%, and an increase in prophylactic medication after an acute attack from 41% to 49% . Contrary to guidelines, antibiotic use increased from 32% to 40% of attacks . Practitioners from a special interest asthma group gave more of their patients systemic steroids and nebulised bronchodilators both in 1991/92 and 1992/93 . CONCLUSIONS: Some aspects of the management of asthma attacks by general practitioners has changed in line with guidelines, but there is still a large gap between actual and recommended management.

Rinsho Ketsueki, 1997 Feb, 38(2), 108 - 16
{The effects of preventive regimens for the prophylaxis of infection after bone marrow transplantation}; Morishima Y et al.; The effects of regimens on the prevention of infection in 42 adult leukemia patients receiving bone marrow transplantation was analyzed . Standard risk patients (transplantation in 1st remission of acute leukemia and chronic phase of chronic myelogeneous leukemia received marrow from HLA compatible sibling or autologous marrow) showed shorter febrile days than high risk patients (transplantation in more advanced stage of leukemia and transplantation from unrelated donor), 1.33 mean days vs . 4.93 mean days respectively . Poorer intake of non-absorved antibiotics resulted in higher rate of bacterial colonization in stool after transplantation . And that, the degree of gut sterilization correlated with the duration of febrile days during the period of less than 100/microliter peripheral neutrophil count in high risk patients . Thus, prophylactic regimens of infection in bone marrow transplantation should be considered according to the risk of patient, that is, more practical and complete prophylaxis in risk patients and more conventional one in standard risk patients.

Semin Vet Med Surg (Small Anim), 1997 Feb, 12(1), 22 - 7
Inflammatory liver disease; Weiss DJ et al.; The histopathologic and clinical features of feline inflammatory liver disease are incompletely under-stood . Results of recent studies indicate that feline inflammatory liver diseases can be classified as acute (suppurative) and chronic (nonsuppurative) cholangiohepatitis and lymphocytic portal hepatitis . Histopathologic features of cholangiohepatitis include infiltration of neutrophils into walls and lumens of bile ducts and portal areas, periportal necrosis, and variable degrees of fibrosis and bile duct hyperplasia . Lymphocytic portal hepatitis is characterized by increased numbers of lymphocytes and plasma cells in portal areas, bile duct hyperplasia, and fibrosis . Liver biopsy is needed to establish a definitive diagnosis but trends in clinical laboratory test results may be helpful in establishing a tentative diagnosis . Specific treatment for cholangiohepatitis include antibiotic therapy . Corticosteroids have been recommended for treatment of lymphocytic portal hepatitis.

J Clin Oncol, 1997 Feb, 15(2), 660 - 6
Prospective randomized placebo-controlled study of granulocyte-macrophage colony-stimulating factor without stem-cell transplantation after high-dose melphalan in patients with multiple myeloma; Moreau P et al.; PURPOSE: To evaluate the impact of granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo on the durations of intravenous (IV) antibiotic use, hospitalization, neutropenia, and fever, as well as remission rates, after high-dose melphalan (HDM) without stem-cell transplantation (SCT) in patients with multiple myeloma (MM) . PATIENTS AND METHODS: One hundred two patients with high-risk MM were randomized 2:1 in a prospective multicenter trial to receive 5 microg/kg/d GM-CSF (69 patients) or placebo (33 patients) starting the day after 140 mg/m2 IV melphalan for up to 21 days . RESULTS: GM-CSF significantly reduced neutropenia after HDM (median, 23.5 v 29 days; P = .0468), with a trend to reduce the duration of hospitalization (median, 32 v 38 days; P = .0841) . Nevertheless, GM-CSF did not significantly reduce infectious toxicity as regards the number of days with fever (median, 5 v 3; P = .359), the number of days with IV antibiotics (median, 22 v 27; P = .14), or early deaths, with an 11.5% treatment-related mortality rate in the GM-CSF group (eight of 69 v two of 32 patients in the placebo group; P = .686) . There was no difference in response rates between the two groups of patients . CONCLUSION: GM-CSF after HDM without SCT is feasible and significantly shortens neutropenia with a trend toward reduction of hospitalization duration, but does not significantly reduce the morbidity and mortality of such therapy . Thus, when intensive therapy is indicated, given that the mortality of HDM followed by SCT reported in the literature is less than 5% and patients are discharged at approximately day 15, despite the risk of contamination by clonogenic malignant cells, SCT appears to be preferable to GM-CSF after HDM.

J Clin Oncol, 1997 Feb, 15(2), 451 - 7
Low-dose filgrastim significantly enhances neutrophil recovery following autologous peripheral-blood stem-cell transplantation in patients with lymphoproliferative disorders: evidence for clinical and economic benefit; McQuaker IG et al.; PURPOSE: To assess the clinical and economic benefit of low-dose (50 microg/m2) filgrastim after peripheral blood stem-cell transplantation (PBSCT) in a randomized, placebo-controlled double-blinded study . PATIENTS AND METHODS: Thirty-eight patients with lymphoproliferative disorders were randomized to receive low-dose filgrastim (19 patients) or placebo (19 patients) beginning on the first day after stem-cell reinfusion and continuing until absolute neutrophil count (ANC) was greater than 0.5 x 10(9)/L . All patients received greater than 2.5 x 10(6) CD34+ cells/kg, which was mobilized with chemotherapy and filgrastim 300 microg from the fifth day . An economic analysis was performed based on the outcome in the two groups . RESULTS: Neutrophil engraftment was significantly more rapid in patients who received filgrastim with a median number of days until ANC was greater that 0.5 x 10(9)/L of 10 (9 to 13) versus 14 (9 to 19; P < .0001) . The time to reach an ANC greater than 1 x 109/L was 12 (9 to 14) versus 16 days (10 to 25; P < .0001) . The total number of patients who required intravenous antibiotic therapy was lower in the filgrastim-treated group (68%) compared with the placebo group (89%); also, the median number of days with fever and the duration of antibiotic therapy were shorter, although these differences did not reach statistical significance . However, although only three of 19 (16%) patients who received filgrastim required amphotericin, 11 of 19 (58%) who received placebo did require it, and amphotericin usage was significantly less in the filgrastim group (P = .029) . Finally, in-patient stay was significantly shortened in those who received filgrastim from 16 (13 to 23) to 13 days (11 to 18; P = .0003) . CONCLUSION: Low-dose filgrastim significantly reduces neutrophil engraftment time post-PBSCT and also reduces in-patient stay and costs, which makes it economically viable for patients who are undergoing high-dose chemotherapy.

Dig Dis Sci, 1997 Feb, 42(2), 289 - 92
H . pylori infection in HIV-positive patients . A serohistological study; Fabris P et al.; Sixty-seven consecutive patients infected with the human immunodeficiency virus (HIV-1), 72% of which with overt AIDS, were examinated by upper endoscopy due to various indications and evaluated for the prevalence of H . pylori infection . The infection was studied by performing both histological examination of gastric biopsies and serological testing for anti-H . pylori IgG antibodies . The H . pylori prevalence rate was 55% in histology; no significant differences were observed in HIV-infected subjects and those with overt AIDS (52% vs 63%, respectively; P = NS) . Positive histological testing appeared to be directly related to the peripheral CD4+ lymphocyte count (minimum rates of 43% were detected in patients with CD4+ < 100 x 10(6)/liter and maximum rates of 78% in patients with CD4+ > 200 x 10(6)/liter, respectively; P < 0.05) and inversely related to the frequency of antibiotic treatments performed over the six months prior to endoscopy . Low CD4+ counts were also apparently associated with low-grade H . pylori infection . Serological testing was positive for anti-H . pylori IgG antibodies in 39% of patients; compared to histology, serology displayed a sensitivity of 57% and a specificity of 81% . The discrepancy between histological and serological positive results for H . pylori was noted to be higher in the more advanced phases of HIV infection . Based upon our results, the serological testing for anti-H . pylori IgG antibodies seems to require cautious interpretation in HIV-positive patients.

Genome Res, 1997 Feb, 7(2), 179 - 86
Retrofitting vectors for Escherichia coli-based artificial chromosomes (PACs and BACs) with markers for transfection studies; Mejia JE et al.; P1-based artificial chromosomes (PACs) and bacterial artificial chromosomes (BACs) have significantly expanded the size of fragments from eukaryotic genomes that can be stably cloned in Escherichia coli as plasmid molecules . Functional characterization of a gene within a given PAC or BAC clone often requires transferring the DNA into eukaryotic cells for transient or long-term expression . To facilitate transfection studies, we have developed protocols using the Notl restriction sites of any PAC or BAC clone to introduce a transfection reporter gene, lacZ, together with a selectable marker, neo . This enables transfected cells to be detected by X-Gal staining to verify DNA uptake, and clones of stably transformed cells may be selected for in the presence of the antibiotic G418 . The same retrofitting protocols may be applied with other markers of interest to extend the functionality of PAC and BAC libraries, and specialized aspects of such manipulation of E . coli-based artificial chromosomes are outlined.

Microbiology, 1997 Feb, 143 ( Pt 2), 617 - 24
Natural kirromycin resistance of elongation factor Tu from the kirrothricin producer Streptomyces cinnamoneus; Cappellano C et al.; The antibiotic kirromycin (Kr) inhibits bacterial protein synthesis by binding to elongation factor Tu (EF-Tu) . Streptomyces cinnamoneus and Nocardia lactamdurans, producers of antibiotics of the Kr class, are known to possess an EF-Tu resistant to Kr . Both micro-organisms appear to possess a single tuf gene and we have characterized the one from S . cinnamoneus, which belongs to the tuf1 family . To assess the molecular determinants of Kr resistance, the S . cinnamoneus tuf gene was expressed in Escherichia coli as a translational fusion to malE, which enabled the recovery by affinity chromatography of the recombinant protein uncontaminated by the host factor . The recombinant EF-Tu was able to catalyse polyU-directed polyPhe synthesis in two heterologous cell-free systems, even as an uncleaved fusion . When tested for antibiotic sensitivity it behaved like the natural S . cinnamoneus protein, showing equivalent resistance to Kr but sensitivity to the antibiotic GE2270, indicating that all the determinants for Kr resistance are intrinsic to the EF-Tu sequence . Multiple sequence analysis of EF-Tu proteins, together with knowledge of mutations conferring Kr resistance, allowed the identification of key residues as likely candidates for the natural Kr resistance of the S . cinnamoneus EF-Tu . One of these, Thr378, was mutated to the consensus Ala and the resulting mutant protein was sensitive to Kr . Interestingly, it retained some activity (30% of the control) even at high Kr concentrations.

J Trauma, 1997 Feb, 42(2), 337 - 40
Surgical management of cutaneous infection caused by atypical mycobacteria after penetrating injury: the hidden dangers of horticulture; Holland J et al.; We identified two patients in a 12-month period who presented with cutaneous infection and secondary lymph node involvement from atypical mycobacterial infection after minor gardening injuries . One patient had a coinfection with Nocardia asteroides . Both patients required multiple surgical interventions, despite appropriate antibiotic therapy, before resolution of the disease . The course of the infection was characterized by chronic relapses with complete healing at 12 to 18 months after the original injury . The identification and management of this clinical problem are reviewed.

J Pediatr, 1997 Feb, 130(2), 324 - 6
Facial sporotrichoid infection with Mycobacterium marinum; Brady RC et al.; We report a case of Mycobacterium marinum facial sporotrichoid infection in an otherwise healthy 2-year-old child, probably acquired through contact with pets in an aquarium . The M . marinum isolate was susceptible to clarithromycin, and the child was successfully treated with oral antibiotic therapy . This unusual case emphasizes the importance of a thorough history in the evaluation of a patient with chronic sporotrichoid skin lesions.

J Allergy Clin Immunol, 1997 Feb, 99(2), S773 - 80
Overview of comorbid associations of allergic rhinitis; Spector SL; Allergic rhinitis affects approximately 20% of the U.S . population . An association between allergic rhinitis and conditions including asthma, sinusitis, otitis media, nasal polyposis, respiratory infections, and even orthodontic malocclusions has been observed . Clinical research has identified shared pathogenic mechanisms, epidemiologic correlations, and findings from allergy testing to indicate that these conditions represent long-term physical consequences in allergic individuals . The positive response of patients afflicted with these conditions to antiallergic treatment further enhances the association between allergic rhinitis and other airway diseases . The use of nasal corticosteroids in patients with rhinitis and asthma reduces not only rhinitis symptoms but also asthma symptoms and airway reactivity to methacholine challenge . Similarly, antihistamines, with or without decongestants, result in improvement of objective measurements of pulmonary function . In the treatment of acute sinusitis, the combination of an intranasal corticosteroid and an antibiotic provides greater benefit than an antibiotic alone . Treatment strategies for allergic rhinitis should be directed at controlling the symptoms of allergic rhinitis and reducing the development of physical complications in susceptible persons . Three techniques for the treatment of allergic rhinitis are used, including avoidance of offending allergens, selection of appropriate pharmaceuticals, and allergy immunotherapy . Appropriate treatment may spare some patients of related airway diseases and may also reduce the overall cost of care . The broadened scope of allergic rhinitis and increased prevalence of IgE-mediated diseases have heightened awareness regarding the profound consequences of allergic rhinitis and the importance of effective treatment.

J Thorac Cardiovasc Surg, 1997 Feb, 113(2), 242 - 7
Aggressive surgical management of sternoclavicular joint infections; Carlos GN et al.; BACKGROUND: Although the sternoclavicular joint is an unusual site for infection, thoracic surgeons may preferentially be called on to coordinate management of cases refractory to antibiotic therapy because of the anatomic relationship of this joint to major vascular structures . METHODS: Since 1994 we have surgically managed nine sternoclavicular joint infections in eight patients . Associated medical problems were frequent and included diabetes mellitus (n = 2), end-stage renal disease (n = 2), hematologic disorders (n = 2), and multiple joints affected by sepsis (n = 4) . Open joint exploration with drainage and debridement with the use of general anesthesia was performed in four patients . The remaining four patients (one with bilateral sternoclavicular joint infections) had computed tomographic evidence of diffuse joint and surrounding bone destruction with infection extending into mediastinal soft tissues . Surgical therapy for these five joint infections involved en bloc resection of the sternoclavicular joint with an ipsilateral pectoralis major muscle covering the bony defect . RESULTS: There were two deaths unrelated to the surgical procedure . After a mean follow-up of 20 months, the remaining six survivors (seven joints) have complete healing with no apparent limitation in the range of motion even after en bloc resection . CONCLUSIONS: Most cases of early sternoclavicular joint infections will respond to conservative measures . However, when radiographic evidence of infection beyond the sternoclavicular joint is present, en bloc resection, although seemingly aggressive, results in immediate eradication of all infection with negligible functional morbidity . Prolonged antibiotic therapy or continued local drainage procedures appear to have little value in these cases, adding only to patient care costs and the potential sequelae of chronic infections.

Ann Thorac Surg, 1997 Feb, 63(2), 504 - 9
Undertreatment and overtreatment of patients with infected antiarrhythmic implantable devices; Molina JE; BACKGROUND: Infection of implantable defibrillators or pacemakers is a serious complication, reported with increasing frequency probably because of an increase in the total number of devices implanted due to a change in trends in the treatment of arrhythmias . This review is aimed to provide guidelines on how to deal with these infections and which method is most likely to be successful . METHODS: This is a review of 38 patients with infected antiarrhythmic implantable devices under three different plans of therapy . There were 17 implantable cardioverter defibrillators and 21 pacemakers . In 27, infection occurred after primary implantation (15 pacers, 12 implantable cardioverter defibrillators), and in 11 after replacement (six pacers, five implantable cardioverter defibrillators) . Three therapeutic plans were identified . Group I (n = 12) received intravenous antibiotics without removal of the antiarrhythmic implantable device, but with relocation to a different area or plane, and with or without the use of a topical irrigating-suction system . Group II (n = 19) had complete removal of the system, 2 weeks of intravenous antibiotics, and implantation of a new unit followed by 10 more days of antibiotics . Group III (n = 7) underwent complete removal, 6 weeks of antibiotics, implantation of a new unit, and another 6 or more weeks of antibiotic therapy . RESULTS: Failure occurred in 100% of cases in group I . Groups II and III had complete clearing of infection and successful reimplantation of new systems with no recurring infections . Follow-up was 8 months to 5 years . Two deaths occurred, both in group I . Hospitalization for groups I and III was 104 days and 65 days, respectively, versus 22 days for group II . No deaths occurred in group II or III . CONCLUSIONS: With an infected antiarrhythmic implantable device, immediate removal of the entire unit is recommended, followed by 2 weeks of intravenous antibiotics, implantation of a new system, and 10 more days of postoperative antibiotics . This regimen is sufficient to cure the problem . No attempts should be made to save an infected system from removal because it endangers the patient's life, prolongs hospitalization, increases costs, and most likely will fail.

Am J Vet Res, 1997 Feb, 58(2), 136 - 9
Oral administration of tylosin phosphate for treatment and prevention of proliferative enteropathy in pigs; McOrist S et al.; OBJECTIVE: To evaluate the efficacy of orally administered tylosin phosphate for prevention and treatment proliferative enteropathy (PE) in pigs . ANIMALS: Crossbred pigs weaned at 24 days of age . PROCEDURE: Pigs were challenge exposed with an inoculum of Lawsonia intracellularis strain LR189/5/83 . Seven control pigs received buffer solution . Of 33 challenge-exposed pigs, 8 were untreated . Two groups of challenge-exposed pigs were dosed orally with tylosin phosphate via a 2% stabilized premix, starting with 100 or 40 ppm 4 days before challenge exposure and continuing for 16 days, when the dose was reduced to 40 or 20 ppm, respectively, which was continued for 12 more days . Another group of challenge-exposed pigs was dosed orally with 100 ppm of tylosin phosphate commencing 7 days after challenge exposure and continuing for 21 days . Pigs were euthanatized and necropsied 4 weeks after challenge exposure . RESULTS: The 8 untreated pigs had reduced weight gain, 3 of them had moderate diarrhea 3 weeks after challenge exposure . Five pigs had gross lesions of PE at necropsy . Seven pigs had histologic lesions of PE with numerous L intracellularis organisms . None of the pigs in the control, nonchallenge-exposed, or the 3 groups given tylosin phosphate before or after challenge exposure had clinical signs or lesions of PE . CONCLUSION AND CLINICAL IMPLICATIONS: Tylosin phosphate can be effective for prevention and for treatment of PE, using reported dosing schedules . We can experimentally induce PE, using the pure culture challenge-exposure model, for use in testing of treatments.

No Shinkei Geka, 1997 Feb, 25(2), 169 - 75
{Lymphocytic infundibulo-hypophysitis with diabetes insipidus as a new clinical entity: a case report and review of the literature}; Miyagi K et al.; In 1992, we reported a lymphocytic adenohypophysitis (LIH) (Neurol Med Chir) . We considered this case unusual in that the case was that of a menopausal female and that it was accompanied with diabetes insipidus as classical lymphocytic adenohypohysitis (LAH) . Subsequently, Ahmed reported two cases which presented a similar pathological manifestation, except for necrosis, as did our case and named them "necrotizing infundibulo-hypophysitis." Recently we encountered another similar case, which is reported hereunder . A female, 34 years of age, had suffered from headache, polyuria, and amenorrhea . CT scan showed a pituitary mass, and pituitary tumor was surgically removed transcranially at a local hospital . The pathological examination revealed the findings of chronic inflammation and necrosis . One month after the operation, however, she was an in-patient again under the suspicion of meningitis for fever and, when antibiotic therapy at the local hospital resulted in no improvement, she was referred to our hospital . Endocrinological studies showed low FSH, LH, ACTH and plasma cortisol level . Antibodies of serum to RNP, Sm, mitochondria, nucleus, AChR, and DNA were all negative . Because of an intrasellar mass with suprasellar extension on MRI, transsphenoidal operation was conducted four months after the initial operation . The pathological examination revealed the infiltration of lymphocytes, plasma cells, and foamy macrophages, and necrosis . After this operation, the headache was cured and the patient was discharged . Two months subsequent to the second operation, headache recurred and temporal upper quadrantic anopsia was noted . An enlarged tumor was found, but prednisolone worked to cure the pain and the visual field defect was found to have been remedied . The patient's diabetes insipidus is presently persisting, and she still relies on the use of desmopressin acetate and is still in need of cortisol replacement therapy . Including our cases, ten cases of lymphocytic hypophysitis, not related to pregnancy or delivery but with diabetes insipidus, have been reported . Several clinical and anatomical features distinguish these 10 cases from classical LAH . The classical LAH was predominantly related to pregnancy or delivery . However 6 of 10 cases were male in LIH . LAH related to pregnancy or delivery does not accompany diabetes insipidus, but all reported cases of LIH had a diabetes insipidus . Visual field and/or ocular movement disturbance are LAH's chief complaints (15 out of 25 cases) but visual field disturbance seldom occurs in LIH (1 out of 10 cases) . Hypopituitarism is more serious in LAH, and 4 cases became fatal from an adrenal crisis . Anatomically, inflammatory change of LIH is located anterior and posterior to the pituitary gland and extends to the pituitary stalk and, at times, hypothalamus . On the other hand, LAH relates to pregnancy or delivery, the inflammatory change localizes to the adenohypophysis . Ahmed emphasized necrosis, while necrosis was not a prominent histological finding in LIH . Necrosis was noted only in 3 of 10 cases . To be stressed, rather, are the inflammatory changes seen on the neurohypophysis and the pituitary stalk, together with the characteristic diabetes insipidus . We believe, in view of the above, that what Ahmed named necrotizing infundibulo-hypophysitis should be named "LIH with diabetes insipidus." Whereas differential diagnosis is necessary between this said new disorder and the conventional LAH, we advocate that the latter, which is related to pregnancy or parturition but is free from neurohypophysitis be identified as "LAH related to pregnancy or delivery." With respect to treatment, steroid therapy is essential . If the symptoms do not improve, a transsphenoidal operation for diagnosis (LIH and LAH) and decompression (the case of LAH with visual or external ocular movement disturbance) is advisable . However, extensive surgery is not recommended, because per

J Pharmacol Exp Ther, 1997 Feb, 280(2), 669 - 76
Active transport of nitrofurantoin across a mouse mammary epithelial monolayer; Toddywalla VS et al.; The antibiotic nitrofurantoin is transported against an electrochemical gradient into milk . A monolayer of CIT3 cells, a subline of the Comma 1D normal mouse mammary epithelial cell line, transports {14C}-nitrofurantoin against a concentration gradient from the basal to the apical solution when grown on membrane filters . In a side-by-side diffusion chamber with well-stirred solutions on both sides, the transfer rate is 50% higher in the basal-to-apical than in the apical-to-basal direction . Nonlabeled nitrofurantoin (500 microM) in the basal chamber equalized the transport in both directions, suggesting that a specific transporter is responsible for the basal-to-apical increment in flux . From inhibition studies, the apparent affinity of this transporter for nitrofurantoin is 50 microM . Changes in pH between 6.4 and 7.8 had no effect on the active transport component of the flux but did affect the passive flux component . Passive flux of the nonionized molecule was 2.6 times faster than that of the ionized molecule, but the ionized molecule did appear to cross the membrane passively . Our findings show that nitrofurantoin is actively transported across a mammary epithelial cell monolayer by a transporter whose affinity for nitrofurantoin does not depend on the anionic charge on nitrofurantoin . The pH dependence of a parallel passive pathway suggests that both nonionized and ionized forms of nitrofurantoin cross the membranes of the mammary epithelial cell by passive diffusion.

J Bacteriol, 1997 Feb, 179(4), 1385 - 92
Purification and preliminary characterization of (E)-3-(2,4-dioxo-6-methyl-5-pyrimidinyl)acrylic acid synthase, an enzyme involved in biosynthesis of the antitumor agent sparsomycin; Parry RJ et al.; Sparsomycin is an antitumor antibiotic produced by Streptomyces sparsogenes . Biosynthetic experiments have previously demonstrated that one component of sparsomycin is derived from L-tryptophan via the intermediacy of (E)-3-(4-oxo-6-methyl-5-pyrimidinyl)acrylic acid and (E)-3-(2,4-dioxo-6-methyl-5-pyrimidinyl)acrylic acid . An enzyme which catalyzes the conversion of (E)-3-(4-oxo-6-methyl-5-pyrimidinyl)acrylic acid to (E)-3-(2,4-dioxo-6-methyl-5-pyrimidinyl)acrylic acid has been purified 740-fold to homogeneity from S . sparsogenes . The molecular mass of the native and denatured enzyme was 87 kDa, indicating that the native enzyme is monomeric . The enzyme required NAD+ for activity but lacked rigid substrate specificity, since analogs of both NAD+ and 3-(4-oxo-6-methyl-5-pyrimidinyl)acrylic acid could serve as substrates . The enzyme was very weakly inhibited by mycophenolic acid . Monovalent cations were required for activity, with potassium ions being the most effective . The enzyme exhibited sensitivity toward diethylpyrocarbonate and some thiol-directed reagents, and it was irreversibly inhibited by 6-chloropurine . The properties of the enzyme suggest it is mechanistically related to inosine-5'-monophosphate dehydrogenase.

Clin Orthop, 1997 Feb, (335), 268 - 74
Treatment of open tibial fractures with primary suture and Ilizarov fixation; Shtarker H et al.; Thirty-two open tibial fractures were treated by irrigation, debridement, antibiotic therapy, primary closure when possible, and fixation with Ilizarov device . In the Gustilo classification, 11 were Grade I, 10 Grade II, 8 Grade IIIA, and 3 were Grade IIIB . No Grade IIIC fractures were treated in the period studied . Fifteen were in patients with multiple trauma, and in 17 patients the fracture was a single injury . All fractures healed with good anatomic alignment, except for 1 with 5 degrees angulation and another with 1-cm shortening . The healing time was 21.9 weeks in the single injury and 25.7 weeks in the patients with multiple trauma . Eleven patients had pin tract infection, and in 4 the pin had to be replaced . One patient had dermatitis near the fracture site . This treatment of open tibial fractures proved to be successful for anatomic restoration of the tibia and had a low complication rate . Primary closure should be considered a possible method of treatment in Types I to IIIA open fractures, together with the Ilizarov external fixator, if the wound edges can be approximated easily with no tension at the suture line.

J Neurosurg, 1997 Feb, 86(2), 197 - 202
Chronic electrical stimulation of the gasserian ganglion for the relief of pain in a series of 34 patients; Taub E et al.; The use of an implanted system for chronic electrical stimulation of the gasserian ganglion for relief of facial pain was described in 1980 by Meyerson and Hakansson . Between 1982 and 1995, the senior author (R.R.T.) performed gasserian ganglion stimulation in 34 patients for the relief of chronic medically intractable facial pain . The etiology of pain was peripheral damage to the trigeminal nerve in 22 patients (65%), central (stroke) damage in seven (21%), postherpetic neuralgia in four (12%), and unclassifiable cause in one (3%) . All patients received a trial of transcutaneous stimulation (Stage 1) . Successful trials in 19 patients (56%) were followed by implantation of a permanent system (Stage II) . Trial and postimplantation stimulation were deemed successful when there was a reduction of pain by at least 50% whenever the stimulator was on . Success rates varied from five (71%) of seven patients for central pain to five (23%) of 22 for peripheral pain and none (0%) of four for postherpetic neuralgia . The median follow-up duration in successful cases was 22.5 months . Infections occurred in seven patients, all of whom had undergone Stage II treatment . Infections were more frequent when the stimulating electrode from Stage I was left in place for Stage II (six {43%} of 14) than when completely new hardware was used and prophylactic antibiotic drugs were administered (one {20%} of five) . Other complications included iatrogenic injury to the trigeminal nerve or ganglion in three cases (9%), transient diplopia in two (6%), increased pain in two (6%), and various technical problems in 10 (29%) . It is concluded that pain of central origin (stroke) is the type most likely to be relieved by this procedure . This finding is new, as the few other clinical series reported to date contain no patients with this type of pain . The risk of infection seems to be lower when completely new hardware is used for Stage II and prophylactic antibiotic drugs are administered.

J Bacteriol, 1997 Feb, 179(3), 705 - 13
Pristinamycin I biosynthesis in Streptomyces pristinaespiralis: molecular characterization of the first two structural peptide synthetase genes; de Crecy-Lagard V et al.; Two genes involved in the biosynthesis of the depsipeptide antibiotics pristinamycins I (PI) produced by Streptomyces pristinaespiralis were cloned and sequenced . The 1.7-kb snbA gene encodes a 3-hydroxypicolinic acid:AMP ligase, and the 7.7-kb snbC gene encodes PI synthetase 2, responsible for incorporating L-threonine and L-aminobutyric acid in the PI macrocycle . snbA and snbC, which encode the two first structural enzymes of PI synthesis, are not contiguous . Both genes are located in PI-specific transcriptional units, as disruption of one gene or the other led to PI-deficient strains producing normal levels of the polyunsaturated macrolactone antibiotic pristinamycin II, also produced by S . pristinaespiralis . Analysis of the deduced amino acid sequences showed that the SnbA protein is a member of the adenylate-forming enzyme superfamily and that the SnbC protein contains two amino acid-incorporating modules and a C-terminal epimerization domain . A model for the initiation of PI synthesis analogous to the established model of initiation of fatty acid synthesis is proposed.

J Bacteriol, 1997 Feb, 179(3), 627 - 33
bldA dependence of undecylprodigiosin production in Streptomyces coelicolor A3(2) involves a pathway-specific regulatory cascade; White J et al.; The production of the red-pigmented tripyrrole antibiotic undecylprodigiosin (Red) by Streptomyces coelicolor A3(2) depends on two pathway-specific regulatory genes, redD and redZ . RedD is homologous to several other proteins that regulate antibiotic production in streptomycetes; RedZ is a member of the response regulator family . redZ transcripts were detected during exponential growth and increased in amount during transition and stationary phases; transcription of redD was confined to the two latter stages of growth . Whereas mutation of redD had no effect on redZ transcription, transcription of redD was highly dependent on redZ, suggesting that RedZ is a transcriptional activator of redD . bldA, which encodes the only tRNA of S . coelicolor that can efficiently translate the rare leucine codon UUA, is required for Red production at higher phosphate concentrations . While the redD transcript contains no UUA codons, the redZ mRNA contains one . Transcription of redZ appeared to be unaffected in a bldA mutant; in contrast, redD transcription was undetectable, consistent with the translational dependence of redZ on bldA and the transcriptional dependence of redD on redZ . Red production in a bldA mutant was restored by multiple copies of redZ, presumably reflecting a low level of mistranslation of the redZ UUA codon, while multiple copies of redD had no effect, presumably a consequence of the severe dependence of redD transcription on RedZ . Transcription of redZ appears to be negatively autoregulated.

Biophys Chem, 1997 Jan 31, 63(2-3), 201 - 9
Kinetics of cleavage of intra- and extracellular simian virus 40 DNA with the enediyne anticancer drug C-1027; Kirk CA et al.; A kinetic analysis of cleavage of simian virus DNA (SV40 DNA) inside and outside green monkey BSC-1 cells by the enediyne-protein antibiotic C-1027 and its free chromophore is described . Information on rate constants was obtained by fitting populations of forms I (closed circular DNA), II (nicked circular DNA) and III (linear DNA) SV40 DNA as a function of drug concentration to a kinetic model which includes: cutting of form I to give form II with rate constant k1, cutting of form I to give form III with rate constant K4, and cutting of form II to give form III with rate constant k2 . The ratio of single-strand (ss) to double-strand (ds) cutting for the holoantibiotic and the free chromophore, k1/k4, is approximately 1.8 for extracellular SV40 DNA . For intracellular DNA and extracellular DNA which has been post-treated with putrescine, ds cutting is much more probable, with k4 about four times as large as k1 . This observation suggests that amine groups present in the cell are able to convert abasic sites opposite an ss break into a ds break in SV40 chromatin . The overall rate of cleavage of form-I DNA inside the cell is much larger than the rate outside, the sum k1 + k4 being about three times as large for intracellular DNA as for extracellular DNA.

J Biol Chem, 1997 Jan 31, 272(5), 3036 - 41
Substrate-binding lipoprotein of the cyanobacterium Synechococcus sp . strain PCC 7942 involved in the transport of nitrate and nitrite; Maeda S et al.; Of the four genes (nrtABCD) required for active transport of nitrate in the cyanobacterium Synechococcus sp . strain PCC 7942, nrtBCD encode membrane components of an ATP-binding cassette transporter involved in the transport of nitrite as well as of nitrate, whereas nrtA encodes a 45-kDa cytoplasmic membrane protein, the biochemical function of which remains unclear . Characterization of the nrtA deletional mutants showed that the 45-kDa protein is essential for the functioning of the nitrate/nitrite transporter . A truncated NrtA protein lacking the N-terminal 81 amino acids, expressed in Escherichia coli cells as a histidine-tagged soluble protein, was shown to bind nitrate and nitrite with high affinity (Kd = 0.3 microM) . Immunoblotting analysis using the antibody against the 45-kDa protein revealed a 48-kDa precursor of the protein, which accumulated in the cyanobacterial cells treated with globomycin, an antibiotic that specifically inhibits cleavage of the signal peptide of lipoprotein precursors . These findings indicated that the nrtA gene product is a nitrate- and nitrite-binding lipoprotein . The N-terminal sequences of putative cyanobacterial substrate-binding proteins suggested that lipoprotein modification of substrate-binding proteins of ATP-binding cassette transporters is common in cyanobacteria.

Ned Tijdschr Geneeskd, 1997 Jan 25, 141(4), 204 - 5
{Ophthalmic preparations Polyspectran (combination of neomycin, polymyxin B and bacitracin/gramicidin) and Terramycin (oxytetracycline with polymyxin B) mistakenly no longer reimbursed}; Brandenburg HC et al.; The Netherlands' Ministry of Health and the health insurance companies have drawn up a list of preparations which will no longer be reimbursed . The ocular antibiotic preparations Polyspectran and Terramycin are on the list . However, there are no satisfactory alternative with respect to the broadness of the antibiotic spectrum required . In addition, some alternatives have serious side effects or may induce bacterial resistance.

Proc R Soc Lond B Biol Sci, 1997 Jan 22, 264(1378), 1 - 7
Burial and seed survival in Brassica napus subsp . oleifera and Sinapis arvensis including a comparison of transgenic and non-transgenic lines of the crop; Hails RS et al.; The creation of transgenic plants through genetic engineering has focused interest on how the fitness of a plant species may be altered by small changes in its genome . This study concentrates on a key component of fitness: persistence of seeds overwinter . Seeds of three lines of oilseed rape (Brassica napus subsp . oleifera DC Metzger) and of charlock (Sinapis arvensis L.) were buried in nylon mesh bags at two depths in four habitats in each of three geographically separated sites: Cornwall, Berkshire and Sutherland . Seeds were recovered after 12 and 24 months . Charlock exhibited much greater seed survival (average 60% surviving the first year and 32.5% surviving the second year) than oilseed rape (1.5% surviving the first year and 0.2% surviving the second) at all sites . Charlock showed higher survival at 15 cm burial than 2 cm burial at certain sites, but oilseed rape showed no depth effect . Different genetic lines of oilseed rape displayed different rates of seed survival; non-transgenic rape showed greater survival (2%) than the two transgenic lines, one developed for tolerance to the antibiotic kanamycin (0.3%) and one for tolerance to both kanamycin and the herbicide glufosinate (0.25%) . The absolute and relative performances of the different genetic lines of oilseed rape were context specific, illustrating the need to test hypotheses in a wide range of ecological settings.

Virology, 1997 Jan 20, 227(2), 488 - 92
Entry of Semliki forest virus into cells: effects of concanamycin A and nigericin on viral membrane fusion and infection; Irurzun A et al.; Semliki forest virus (SFV) was biosynthetically labeled with pyrene phospholipids and used to investigate two alternative routes of entry of SFV into BHK-21 cells: (1) receptor-mediated endocytosis followed by fusion of the viral envelope with the endosomal membrane and (2) direct fusion of SFV with the plasma membrane induced by low pH treatment . The selective inhibitor of the vacuolar proton-ATPase, concanamycin A, abolished fusion and subsequent infection only when the virus utilized the endocytic route to enter cells . The inhibitory effect of this macrolide antibiotic was bypassed by low pH treatment of cells . However, the ionophore nigericin was inhibitory irrespective of the route used by the virus to infect cells, suggesting the necessity of a transmembrane pH gradient for the entry process . According to our results, concanamycin A emerges as a suitable tool for selectively investigating the involvement of endosomal function in animal virus entry.

BMJ, 1997 Jan 18, 314(7075), 187 - 9
Comparison of out of hours care provided by patients' own general practitioners and commercial deputising services: a randomised controlled trial . I: The process of care; Cragg DK et al.; OBJECTIVE: To compare the process of out of hours care provided by general practitioners from patients' own practices and by commercial deputising services . DESIGN: Randomised controlled trial . SETTING: Four urban areas in Manchester, Salford, Stockport, and Leicester . SUBJECTS: 2152 patients who requested out of hours care, and 49 practice doctors and 183 deputising doctors (61% local principals) who responded to those requests . MAIN OUTCOME MEASURES: Response to call, time to visit, prescribing, and hospital admissions . RESULTS: 1046 calls were dealt with by practice doctors and 1106 by deputising doctors . Practice doctors were more likely to give telephone advice (20.2% v 0.72% of calls) and to visit more quickly than deputising doctors (median delay 35 minutes v 52 minutes) . Practice doctors were less likely than deputising doctors to issue a prescription (56.1% v 63.2% of patients) or to prescribe an antibiotic (43.7% v 61.3% of prescriptions issued) and more likely to prescribe genetic drugs (58.4% v 32.1% of drugs prescribed), cheaper drugs (mean cost per prescription pounds 3.28 v pounds 5.04), and drugs in a predefined out of hours formulary (49.8% v 41.1% of drugs prescribed) . There was no significant difference in the number of hospital admissions . CONCLUSIONS: By contrast with practice doctors, deputising doctors providing out of hours care less readily give telephone advice, take longer to visit at home, and have patterns of prescribing that may be less discriminating.

J Mol Biol, 1997 Jan 17, 265(2), 187 - 201
Solution structure of the calicheamicin gamma 1I-DNA complex; Kumar RA et al.; Calicheamicin gamma 1I is an enediyne antibiotic possessing antitumour activity associated with its ability to bind and following activation, affect double-strand cleavage at oligopyrimidine-oligopurine tracts on DNA . Footprinting and chemical modification studies have identified the (T-C-C-T).(A-G-G-A) sequence as a preferred calicheamicin gamma 1I binding site and established the importance of the 5'-guanine residue as critical for high affinity binding . The sequence specificity of intermolecular recognition has been identified with the aryltetrasaccharide component of the drug together with an important contribution from the iodine atom on the thiobenzoate ring to the affinity of complex formation . Calicheamicin gamma 1I binds to the minor groove of the DNA duplex and in the process positions the enediyne ring to abstract hydrogen atoms from partner strands leading to double-strand cleavage . We report on the solution structure of the calicheamicin gamma 1I-DNA hairpin duplex complex containing a central (T-C-C-T).(A-G-G-A) segment based on a combined analysis of NMR and molecular dynamics calculations including intensity refinement in a water box . The refined solution structures of the complex provide a molecular explanation of the sequence specificity of binding and cleavage by this member of the enediyne family of antitumor antibiotics . Calicheamicin gamma 1I binds to the DNA minor groove with its aryltetrasaccharide segment in an extended conformation spanning the (T-C-C-T).(A-G-G-A) segment of the duplex . Further, the thio sugar B molecule and the thiobenzoate ring C molecule are inserted in an edgewise manner deep into the minor groove with their faces sandwiched between the walls of the groove . A range of intermolecular hydrophobic and hydrogen-bonding interactions account for the sequence specific recognition in the complex . These include critical intermolecular contacts between the iodine and sulfur atoms of the thiobenzoate ring of the drug with the exposed exocyclic amino protons of the 5' and 3'-guanine bases, respectively, of the A-G-G-A segment on the DNA . The bound aryltetrasaccharide in turn positions the enediyne ring deep in the minor groove such that the pro-radical carbon centers of the enediyne are proximal to their anticipated proton abstraction sites . Specifically, the pro-radical C-3 and C-6 atoms are aligned opposite the abstractable H-5' (pro-S) and H-4' protons on partner strands across the minor groove, respectively, in the complex . The DNA duplex is right-handed with Watson-Crick base-pairing in the complex . The helix exhibits a B-DNA type minor groove width at the aryltetrasaccharide binding-site while there is widening of the groove at the adjacent enediyne binding-site in the complex . The DNA helix exhibits localized perturbations at the binding-site as reflected in imino proton complexation shifts and specific altered sugar pucker geometrics associated with complex formation . Sequence-specific binding of calicheamicin gamma 1I to the (T-C-C-T).(A-G-G-A) containing DNA hairpin duplex is favored by the complementarity of the fit through hydrophobic and hydrogen-bonding interactions between the drug and the floor and walls of the minor groove of a minimally perturbed DNA helix.

J Mol Biol, 1997 Jan 17, 265(2), 173 - 86
Solution structure of the esperamicin A1-DNA complex; Kumar RA et al.; Esperamicin A1 is an enediyne antibiotic possessing antitumor activity associated with its ability to bind and, following activation, affect strand cleavage of DNA . We report on the solution structure of the esperamicin A1-d(C-G-G-A-T-C-C-G) duplex complex based on a combined analysis of NMR and molecular dynamics calculations including intensity refinement in a water box . The refined solution structures of the complex provide a molecular explanation of the sequence specificity for binding and cleavage by this member of the enediyne family of antitumor antibiotics . Esperamicin A1 binds to the DNA minor groove with its methoxyacrylyl-anthranilate moiety intercalating into the helix at the (G2-G3)-(C6'-C7') step . The methoxyacrylyl-anthranilate intercalator and the minor groove binding A-B-C+ risaccharide moieties rigidly anchor the enediyne in the minor groove such that the pro-radical centers of the enediyne are proximal to their anticipated proton abstraction sites . Specifically, the pro-radical C-3 and C-6 atoms are aligned opposite the abstractable H-5' (pro-S) proton of C6 and the H-1' proton of C6' on partner strands, respectively, in the complex . The thiomethyl sugar B residue is buried deep in an edgewise manner in the minor groove with its two faces sandwiched between the walls of the groove . Further, the polarizable sulfur atom of the thiomethyl group of sugar B residue is positioned opposite and can hydrogen-bond to the exposed amino proton of G3' in the complex . There is little perturbation away from a right-handed Watson-Crick base-paired duplex in the complex other than unwinding of the helix at the intercalation site and widening of the minor groove centered about the enediyne-binding and anthranilate intercalation sites . Sequence-specific binding of esperamicin A1 to the d(C-G-G-A-T-C-C-G) duplex is favored by the complementarity of the fit between the drug and the floor of the minor groove, good stacking between the intercalating anthranilate ring and flanking purine bases and intermolecular hydrogen-bonding interactions.

Nucleic Acids Res, 1997 Jan 15, 25(2), 339 - 46
Distamycin prolongs E-selectin expression by interacting with a specific NF-kappaB-HMG-I(Y) binding site in the promoter; Ghersa P et al.; The E-selectin cell adhesion protein plays a critical role in mediating adherence of leukocytes to endothelium at sites of inflammation . Cytokine-induced E-selectin expression on the surface of endothelial cells is transient; mRNA expression peaks at 3-4 h after induction and returns to basal levels within 24 h . The mechanism for this transcriptional down-modulation is not known . Promoter binding factors responsible for induced gene expression include NF-kappaB, which binds at three sites within the E-selectin promoter, and HMG-I(Y), which binds to the A/T-rich core found at the centre of these binding sites . Distamycin is an antibiotic that also binds A/T-rich DNA and inhibits HMG-I(Y) DNA binding . To study the role of HMG-I(Y) in E-selectin expression, we have examined the effect of distamycin on the cytokine-induced E-selectin expression cycle . We found that distamycin prolonged E-selectin expression, both by sustaining mRNA transcription and by extending the transcript's half-life . The distamycin effect on transcription was mediated through one of the three NF-kappaB-HMG-I(Y) binding sites (NF-kappaBII) within the promoter . This suggests that the NF-kappaB-HMG-I(Y) complex interacting at the NF-kappaBII site plays a role not only in cytokine induction of E-selectin expression, but also in its down-modulation.

Int J Pediatr Otorhinolaryngol, 1997 Jan 3, 38(3), 247 - 54
Management of medial subperiosteal abscess of the orbit in children--a 5 year experience; Pereira KD et al.; A medial subperiosteal abscess (SPA) of the orbit is the most common serious complication of sinusitis in children . The distinction between SPA and the more benign pre-septal disease is difficult to make especially in a young child in whom an ophthalmological evaluation is often difficult . Computerised tomography (CT) is the investigation of choice in making this distinction . Subperiosteal inflammatory disease of the orbit is initially treated with intravenous antibiotic therapy with surgery reserved for those patients who do not respond to medical treatment and in whom a medial SPA is confirmed by CT . Conventionally, the abscess is drained via an external incision and an ethmoidectomy is performed at the same time . More recently, successful drainage of SPA's has been accomplished endoscopically via a intranasal approach with less morbidity and superior cosmesis . We present a 5 year experience of 24 patients with CT scans suggestive of medial SPA who underwent endoscopic exploration of the medial subperiosteal orbital space . We discuss the current management of medial subperiosteal disease of the orbit in children and include a review of the literature . Also included is a clinical staging system which aids the management of orbital complications of sinusitis.

Gene, 1997 Jan 3, 184(1), 89 - 97
High copy number integration into the ribosomal DNA of the yeast Phaffia rhodozyma; Wery J et al.; This report describes a transformation system leading to stable high copy number integration into the ribosomal DNA (rDNA) of the astaxanthin-producing yeast Phaffia rhodozyma . A plasmid was constructed that contains the transposon Tn5 encoded kanamycin resistance gene (KmR) fused in frame to the 5'-terminal portion of the Phaffia actin gene . This marker, driven by the Phaffia actin promoter, confers resistance to G418 (Geneticin) . The plasmid also contains a rDNA portion that comprises the 18S rDNA and promotes high copy integration leading to stable Phaffia transformants that maintained the plasmid at high copy number after 15 generations of non-selective growth . Phaffia, strain CBS 6938, was found to contain the rDNA units in clusters distributed over three chromosomes with a total copy number of 61 . Phaffia transformants were shown to have over 50 copies of pGB-Ph9 integrated in tandem in chromosomes that contain rDNA loci . The chromosomal shifts that occur as a result of these integrations as shown by pulsed field electrophoresis strongly suggest that Phaffia is haploid.

Mutat Res, 1997 Jan 3, 373(1), 125 - 37
Molecular spectrum of mutations induced by 5-hydroxymethyl-2'-deoxyuridine in (CHO)-PL61 cells; Chaung W et al.; We have utilized (CHO)-PL61 cells to characterize the mutations produced in mammalian cells by exogenous treatment with the nucleoside 5-hydroxymethyl-2'-deoxyuridine (hmdUrd) . HmdUrd is incorporated into DNA as a thymidine analogue and is removed by the repair enzyme hmUra-DNA glycosylase . PL61 cells are hprt(-) and contain adjacent single copies of the Escherichia coli gpt and neo genes (gpt+, neo+) separated by 2 kb, rendering the cells thioguanine sensitive (TGs) and geneticin resistant (G418r) . Cells were exposed to hmdUrd and the colonies resistant to thioguanine or thioguanine and G418 were selected . Selection in thioguanine alone (TGr/gpt(-)) allows the growth of all gpt(-) mutants (small, intermediate and large deletions/insertions and point mutations) while selection in thioguanine and G418 (TGr/gpt(-), G418r/neo+) prevents survival of colonies containing vary large deletions of the gpt gene that include the neo gene . To confirm the types of mutation at the molecular level, the gpt gene was amplified from mutants' genomic DNA by PCR, and the amplified DNA was sequenced directly by the dideoxy method . Our study showed that 4 microM hmdUrd induced mutations to TGr/gpt(-) at a rate 3-4 times that of control, but showed no marked increase in mutation to TGr/gpt(-), G418r/neo+ . The predominant type of hmdUrd induced mutation in the thioguanine resistant cells at the gpt locus was complete loss of the gpt gene resulting from a large deletion . Background mutations were generally point mutations or small insertion/deletion mutations . We propose that hmdUrd induces large/intermediate deletions as a major type of mutations in mammalian cells as a consequence of DNA repair, and not as a result of misincorporation or mispairing, suggesting that base excision repair by itself can lead to large deletion mutagenesis.

Mutat Res, 1997 Jan 3, 373(1), 17 - 29
Targeted base substitutions and small deletions induced by neocarzinostatin at the APRT locus in plateau-phase CHO cells; Wang P et al.; Treatment of confluence-arrested CHO-D422 cells for 48 h with low concentrations (0.5-3 nM) of the radiomimetic antibiotic neocarzinostatin resulted in an increase in up to 11-fold in the frequency of mutations at the hemizygous APRT locus . Analysis by PCR and DNA sequencing revealed that the mutations were a mixture of base substitutions, small deletions, and large-scale rearrangements . base substitutions occurred preferentially at sequence positions where the drug is known to produce abasic sites with closely opposed strand breaks, e.g., AGT, TGT and AGC, where the abasic site occurs at the underlined base and the strand break occurs opposite the first base in each triplet . These results suggest that the substitutions were produced by replicative bypass of the abasic sites, perhaps during attempted repair of the accompanying strand break . Single-base deletions, which comprised nearly half of all deletions, were targeted to these same sequence positions, suggesting that they may have been generated either by replicative bypass of the abasic sites, or by end-joining repair of double-strand breaks, which are induced the same sites . Quantitative analysis of neocarzinostatin-induced damage to APRT DNA in vitro confirmed the association between lesions involving concommitant damage to both DNA strands, and mutations . The results are consistent the hypothesis that agents which induce such bistranded DNA damage can produce biologically significant levels of mutagenesis even in nondividing cells.

Acta Otolaryngol Suppl, 1997, 529, 241 - 4
Squamous cell cancer cell lines: sensitivity to bleomycin and suitability for animal xenograft studies; Jaaskela-Saari HA et al.; Bleomycin (BLM) is a natural antibiotic, toxic to dividing cells (G2/M-phase), also proven effective in squamous cell carcinomas (SCC) . We have clinically shown that a short-range beta-emitting radionuclide combined to bleomycin (In-111-BLMC) is a tumor-targeting agent in SCCs . With higher radionuclide activities it may be possible to develop a more effective agent, to be tested in animal studies . Using a 96-well clonogenic assay we investigated three SCC cell lines, grown in our own laboratory . IC20, IC50 and IC90 values for BLM were determined . The UT-SCC-12A and UT-SCC-12B cells were originated from a primary tumor and a metastasis of the same patient . UT-SCC-12A cells were also inoculated subcutaneously into nude mice and the tumor growth was analysed . The IC50 value for UT-SCC-19A cell line was 4.0 +/- 1.3 nM . UT-SCC-12A and UT-SCC-12B were both more resistant to BLM; IC50 values were 14.2 +/- 2.8 nM and 13.0 +/- 1.1 nM, respectively . Within 35 days the weight of nude mice increased 2.8 +/- 0.6g . At 25 and 35 days after tumor inoculations the tumor volumes were 111 +/- 51 mm3 and 874 +/- 577 mm3, respectively . The calculated doubling time was 3.86 +/- 0.76 days . SCC cell lines demonstrate different sensitivity to BLM . Our SCC tumor xenograft model showed a rapid growth proper for radiochemotherapeutic studies using In-111-BLMC . The uptake of In-111-BLMC in vivo has been directly proportional to proliferation activity, and the tumors with high binding capacity could be predicted from animal model dose calculations.

Swiss Surg, 1997, 3(3), 107 - 11
{Value of Hartmann's operation as an emergency intervention in sigmoid diverticulitis}; Rothlin M et al.; INTRODUCTION: Improvements in antibiotic and intensive care treatment have facilitated the conservative therapy of patients suffering from complicated diverticulitis of the sigmoid for the time necessary for preparation in view of early elective resection of the sigmoid colon . Consequently, early elective resection of the sigmoid colon with primary anastomosis has become very popular as the treatment of choice in complicated diverticulitis . This has led us to a retrospective evaluation of our own results with both Hartmann's operation and resection with primary anastomosis . PATIENTS AND METHODS: 55 patients with complicated diverticulitis of the sigmoid colon were operated on at our institution between 1981 and 1990 . Group I consisted of 33 patients (17 females and 16 males) aged 39 to 89 years who underwent Hartmann's operation . Group II included 11 patients (6 females and 5 males) aged 39 to 85 years treated by resection and primary anastomosis . The remainder of the patients was treated by a three-step procedure and should not be considered here . RESULTS: In group I 25 patients (76%) suffered complications either at the Hartmann's operation or at descendorectostomy or both . Mortality was 6% . Only 76% of patients had their stoma closed after an average of 3.8 months . The average hospital stay of both operations combined amounted to 61 days . In group II 3 patients had complications, one of which was lethal (lung emboly) . The total hospital stay in this group averaged 22 days . CONCLUSIONS: For Hinchey stages I and II conservative treatment, bowel preparation and early elective resection with primary anastomosis should be attempted . In cases of general peritonitis (Stages III and IV) Hartmann's operation is still the treatment of our choice.

Ann Med Interne (Paris), 1997, 148(3), 226 - 9
{Prevention of tuberculosis in immunocompromised patients}; Perronne C; Immunosuppressed patients have an increased risk of developing active tuberculosis, either by reactivation of an old infection, or by horizontal acquisition during a contact with a contagious tuberculous patient . The diagnosis of tuberculosis requires a clinical examination and the realization of a PPD skin test and a pulmonary radiograph . Symptomatic tuberculosis is a contra-indication to chemoprophylaxis and requires a full curative treatment . The decision to undertake chemoprophylaxis should be individual . When indicated, it relies classically on a 6-month regimen of isoniazid . Short term chemoprophylactic regimens, such as rifampicin-isoniazid during 3 months or rifampicin-pyrazinamide during 2 months, have shown some efficacy . The interaction of rifampicin with corticosteroids or ciclosporin often impedes the use of this antibiotic . Apart from HIV infection, no clinical study of chemoprophylaxis is available in immunosuppressed patients.

Dermatology, 1997, 194(4), 351 - 7
Roaccutane treatment guidelines: results of an international survey; Cunliffe WJ et al.; BACKGROUND: Oral isotretinoin (Roaccutane) revolutionized the treatment of acne when it was introduced in 1982 . METHODS: Twelve dermatologists from several countries with a special interest in acne treatment met to formally review the survey of their last 100 acne patients treated with oral isotretinoin . The primary purpose of the survey was to identify the types of acne patients who were prescribed oral isotretinoin and how the patients were managed . RESULTS: Of the 1,000 patients reviewed, 55% of those who received oral isotretinoin had those indications treated historically, i.e . severe nodular cystic acne or severe inflammatory acne, not responding to conventional treatment . Forty-five percent of patients who were prescribed oral isotretinoin however had either moderate or mild acne . Most patients in this group had moderate acne (85%) . However, 7.3% had mild acne on physical examination . The criteria for prescribing oral isotretinoin in this less severe group of patients included acne that improves < 50% after 6 months of conventional oral antibiotic and topical combination therapy, acne that scars, acne that induces psychological distress and acne that significantly relapses during or quickly after conventional therapy . Treatment is usually initiated at daily doses of 0.5 mg/kg (but may be higher) and is increased to 1.0 mg/kg . Most of the physicians aimed to achieve a cumulative dose of > 100-120 mg/kg . Mucocutaneous side-effects occur frequently but are manageable while severe systemic side-effects are rarely problematic (2%) . The teratogenicity of oral isotretinoin demands responsible consideration by both female patients and their physicians . Significant cost savings when treating acne patients with oral isotretinoin as compared to other treatment modalities were further proven in this study . CONCLUSIONS: Our recommendation is that oral isotretinoin should be prescribed not only to patients with severe disease but also to patients with less severe acne, especially if there is scarring and significant psychological stress associated with their disease . Acne patients should, where appropriate, be prescribed isotretinoin sooner rather than later.

Cancer Invest, 1997, 15(4), 353 - 7
The role of granulocyte colony-stimulating factor in hematopoietic stem cell transplantation; Tabbara IA et al.; Recombinant granulocyte colony-stimulating factor (G-CSF) has been shown to decrease the duration of severe neutropenia, the incidence of febrile neutropenic episodes, the overall duration of intravenous antibiotic therapy, and the length of hospitalization in patients receiving myelosuppressive chemotherapy . G-CSF has also been shown to accelerate myeloid recovery after autologous and allogeneic bone marrow transplantation, and to mobilize stem cells in peripheral blood for hematopoietic rescue . However, the optimal dose, schedule, and method of administration of G-CSF in these settings remain to be standardized . This review focuses on the role of G-CSF in bone marrow and peripheral blood stem cell transplantation, and in hematopoietic stem cell mobilization.

Stomatologiia (Mosk), 1997, 76(3), 41 - 3
{The prevention and treatment of complications related to the removal of the mandibular third molar when it is retained}; Grigor'iants LA et al.; The lower third molars were removed in 52 patients by the method developed by the authors because of these teeth's retention or half-retention . Control group consisted of 22 patients in whom the teeth were removed traditionally . In 35 patients of the main group with acute inflammations of soft tissues adjacent to the tooth to be removed the operation was performed without preliminary arrest of inflammation . Bone cavity formed after removal of the tooth was filled with hydroxyapatite . In some cases Maillefer turbine drill or Lancet high-intensity laser device were used for cutting the diseased tooth into pieces . After surgery laser and antibiotic therapy were carried out . Four (7.7%) patients with inflammations before surgery developed complications . The operation wound healed in 9-10 days in patients with inflammations and in 7-8 days in those without inflammations, in contrast to the controls, in whom recovery ensued only in 4-6 weeks . Hence, the new method is recommended for clinical use irrespective of inflammatory changes in the adjacent tissues.

Digestion, 1997, 58(3), 211 - 7
Antral mucosal Helicobacter pylori infection density as a risk factor of duodenal ulcer; Talamini G et al.; OBJECTIVE: Duodenal ulcer is regarded as the end result of alterations in which Helicobacter pylori (HP) plays a major role as a pathogenetic agent . The aim of this prospective study was to evaluate duodenal ulcer risk factors such as alcohol intake, smoking, use of non-steroidal anti-inflammatory drugs, age and sex in relation to HP colonization density . PATIENTS AND METHODS: 495 patients consecutively examined by diagnostic upper digestive endoscopy were assessed; none of them had had previous upper digestive endoscopy or peptic ulcer, recent anticulcer-antibiotic treatment, upper gastrointestinal surgery, or cancer . The HP colonization on antral bioptic specimens was graded semi-quantitatively as follows: HP--- (absence of HP); HP+--(focal presence of small amounts of HP); HP++- (intermediate situation between HP+-- and HP+++), and HP+++ (diffuse presence of large amounts of HP) . RESULTS: Logistic regression analysis identified only male sex (odds ratio 1.88, p < 0.02), smoking more than 10 cigarettes/day (odds ratio 2.53, p < 0.01), and HP grade (HP +-- odds ratio 0.79, p = NS; HP++- odds ratio 2.42, p < 0.02; HP+++ odds ratio 3.66, p < 0.001) as independent risk factors of duodenal ulcer . CONCLUSION: The duodenal ulcer risk was found to correlate with HP density, male sex, and smoking, but not with non-steroidal anti-inflammatory drug use.

Acta Otorhinolaryngol Belg, 1997, 51(2), 113 - 8
Acute mastoiditis with complications: a report of two cases; Dallari S et al.; The authors report two cases of lateral sinus thrombosis (LST) which were recently observed after more than a 20-year absence of such pathology at their Institutions . After reviewing the epidemiologic data, the clinical observations are described in detail . Changes in symptomatology mainly due to the improper use of antibiotics are then discussed as well as the diagnostic improvement offered by modern imaging techniques . Problems still under debate concern the therapeutic strategy: internal jugular vein ligation or anticoagulation therapy versus aminoglycoside administration for patients refractory to the conventional antibiotic therapy . The necessity of close cooperation between general practitioner, pediatrician and otolaryngologist is stressed.

Probl Tuberk, 1997, (2), 30 - 2
{Features of development, clinical picture and surgical treatment policy of destructive forms of pulmonary tuberculosis in the North}; Vinokurov II et al.; In 135 patients, follow-up clinical, X-ray, immunological, and pathomorphological studies revealed that destructive changes in the form took place as an extensive specific process involving more than one lobe with bronchogenic dissemination and, commonly, as caseous pneumonia . Despite the extensive destructive changes, a tuberculous process is torpid, by showing mild clinical manifestations of the onset of the disease . Early lung tissue fibroplastic changes lead to an irreversible process after 4-5 months of antibiotic therapy, which suggests failure to cure them and makes it necessary to apply surgical treatments.

Membr Cell Biol, 1997, 10(5), 553 - 63
Conformational analysis of amphotericin B molecule; Silberstein AYa et al.; Conformational analysis of a cyclic molecule of a channel-forming antibiotic amphotericin B was conducted by the methods of molecular mechanics . A number of conformers differing in both hydroxyl group orientation and lactone ring conformation were obtained . The stable states of the conformers have close intrinsic energies . The conformational analysis supports the conclusion by Mazerski and Borowski (Biophys . Chem . 54:49-60 (1995)) on the flexibility of the amphotericin B lactone ring.

Antibiot Khimioter, 1997, 42(1), 17 - 22
{The effect of calcium gluconate on the acute and chronic toxicity of doxorubicin in mice}; Bogush TA et al.; The effect of calcium gluconate on the toxicity of the anthracycline antibiotic doxorubicin (DOX) in mice was studied . Calcium gluconate showed a significant protective action with respect to the DOX acute toxicity . When DOX was used in the lethal doses, up to the LD50s calcium gluconate protected all the mice from death . At the DOX LD100 or higher the antitoxic effect of calcium gluconate manifested itself in a lower death rate and/or in a higher lifespan of the animals (at least 2-fold) . When DOX was used for the treatment course its chronic toxicity in the presence of calcium gluconate was 2 or more times lower by all the quantitative indices: the lifespan of the animals that died, the maximum and minimum total lethal doses of DOX, the latent period before the first mouse death, the overall duration of the DOX treatment course . The antitoxic effect of calcium gluconate also manifested itself in a lower DOX acute and chronic toxicity with respect to the gastrointestinal tract . Thus, calcium gluconate proved to be an effective DOX antitoxic modificator which provided the use of about 2 times higher single and courses doses of DOX in mice.

Somat Cell Mol Genet, 1997 Jan, 23(1), 9 - 17
Expression of human O6-methyl guanine methyl transferase (MGMT) in post replication repair (PRR) deficient CHO-UV-1 cells: compensation for hypersensitivity to methylating and ethylating agents but not to mitomycin C; Gustafson DL et al.; The cDNA for human MGMT was transfected into and expressed in CHO cells and the post-replication repair deficient mutant CHO-UV-1 cell, both of which are devoid of endogenous MGMT activity . Expression of MGMT activity was demonstrated by measurement of activity and by immunoblot analysis . The mutant phenotype of UV-1 is characterized by extreme hypersensitivity to killing by methylating and ethylating agents as well as the antitumor antibiotic mitomycin C (MMC) . MGMT expression conferred equivalent, supra-normal levels of resistance to killing by MNNG (N-methyl-N'-nitro-nitrosoguanidine) or EMS (ethyl methanesulfonate) on CHO and UV-1, but had no effect on the lethality of MMC . So, even though a mutated gene other than MGMT is known to underlie the pleiotropic phenotype of UV-1, expression of MGMT compensates for part of this phenotype . This result indicates that attempts to concordance map and clone the gene(s) responsible for the UV-1 phenotype can be complicated when using MNNG selection due to compensation by the MGMT gene . These results also indicate that the post-replication repair deficient phenotype characterized in CHO-UV-1 cells, will be masked in cells normally expressing MGMT due to MGMT-mediated resistance to methylating and ethylating agents.

Tex Med, 1997 Jan, 93(1), 81 - 8
Searching for preventable causes of infant mortality in Texas; Kerr GR et al.; Texas' health objectives include reducing the infant mortality rate from 8.1 per 1000 live births in 1990 to no more than 7 per 1000 by the year 2000 . To help target potentially preventable causes of infant mortality, we examined the underlying cause of each of the 2545 infant deaths that occurred in Texas during 1990 . Potential existed for primary prevention of the underlying cause of at least some of 778 infant deaths and for secondary prevention by treating the underlying causes of 1127 . The following appear to be the most promising targets and strategies for prevention: causes of neonatal mortality by improving the clinical care of high-risk newborns; sudden infant death syndrome by having infants sleep in the supine position; respiratory complications of preterm birth by preventive and therapeutic surfactant; death from bacterial infections by optimal antibiotic therapy; injuries and accidents by optimal parental supervision; preterm birth and adverse pregnancy outcomes by optimal prenatal, obstetric, and neonatal care; and neural tube defects by adequate paraconceptual folic acid.

Biomed Pharmacother, 1997, 51(4), 156 - 60
Eradication of Helicobacter pylori and regression of B-cell lymphoma; Vanagunas A; There is an increasing body of evidence implicating a causal association between Helicobacter pylori and the development of mucosa-associated lymphoid tissue (MALT) associated B-cell gastric lymphoma . Investigators have noted that almost all patients with H pylori-associated chronic gastritis develop lymphoid follicles . Some of these patients demonstrate infiltration of B cells and lymphoepithelial lesions typical of MALT lymphoma . When gastric tissue from patients with gastric B-cell lymphoma is analyzed for H pylori infection, the overwhelming majority of patients demonstrate this condition . Epidemiologic nested case-control studies have shown that patients with gastric non-Hodgkin's lymphoma are substantially more likely that matched controls to have H pylori infection . This situation may be analogous to the linkage between chronic Epstein-Barr virus and lymphoma . The mechanisms inducing the development of lymphoma are not clear, but it has been suggested that chronic infection with H pylori results in the stimulation of H pylori-responsive T cells which in turn activate B cells with the subsequent development of a mutation to a monoclonal B-cell population . Recent evidence indicates that cure of H pylori infection produces regression of MALT lymphoma within 3 to 12 months in approximately 75% of antibiotic-treated patients . Individual responsiveness remains unpredictable, however, and careful and prolonged endoscopic and histologic follow-up is needed . Large, well-controlled studies are necessary, however, to determine the duration of 'cure' and the appropriate setting for treatment.

Tex Heart Inst J, 1997, 24(2), 129 - 30
Infection of a pacemaker by Brucella melitensis; de la Fuente A et al.; We report a case that, to the best of our knowledge, is the only published instance of infection of a pacemaker and its leads by Brucella melitensis . Furthermore, this case suggests that B . melitensis may be able to persist around pacemaker devices despite its having been eliminated from the rest of the body . The patient was a sheep shearer who had just undergone a 45-day course of antibiotic therapy for brucella and had been considered cured on the basis of negative blood cultures.

Isr J Med Sci, 1997 Jan, 33(1), 50 - 2
Transient hepatocellular injury during attacks of cholinergic urticaria; Niv Y et al.; Cholinergic urticaria presents as wheals and erythroderma that develop in response to a variety of factors which stimulate muscarinic receptors, including exercise, heat, cold, sweat and emotional stress . We describe a 25-year-old man with ulcerative colitis who developed cholinergic urticaria diagnosed by a metacholine test . He had had seven previous attacks over 8 years, and the finding of elevated liver enzymes required admission to four different hospitals . The clinical picture was identical: urticaria, hepatosplenomegaly, lymphadenopathy and elevation of liver enzymes . The causative agent was never identified and recovery was complete, with or without antibiotic therapy . To the best of our knowledge, this is the first description of liver involvement in cholinergic urticaria noted in the English-language medical literature.

Neoplasma, 1997, 44(2), 91 - 5
Increased efficacy of aphidicolin killing of human neuroblastoma cells in vitro by encapsulation in liposomes; Cinatl J Jr et al.; Aphidicolin is a tetracyclic diterpene antibiotic which kills human neuroblastoma cells (NB) in vitro while it has no significant effect on the viability of different human cell types including normal embryonal cells . In the present study, we tested whether aphidicolin encapsulated in liposomes kills NB cells with the efficacy superior to that of unencapsulated aphidicolin . The drug was entrapped in vesicles composed of phosphatidylcholine, phosphatidylserine and cholesterol in a molar ratio of 83:5:12 . The treatment with encapsulated aphidicolin at a concentration of 200 nmol for 5 days killed all cells of three human NB cell lines . In contrast, at least 30% of the cells survived 5 days of treatment with 200 nmol unencapsulated aphidicolin . The results showed that aphidicolin killing of human NB cells may be increased by encapsulation in liposomes.

Chir Narzadow Ruchu Ortop Pol, 1997, 62(1), 55 - 8
{Cefamandole for perioperative prophylaxis in total hip alloplasty}; Jackowiak M et al.; The aim of this paper was to present the use of Cefamandole as one of the elements in perioperative prophylactics in total hip replacement . One hundred patients operated between 1993 and 1995 were followed-up for mean 13.5 months . There were 33 males and 67 females, mean age was 61.4 years . Cefamandole was administered according to fixed protocol for three days (first dose along with premedication) . Mono-antibiotic therapy was sufficient in most cases . No septic complication occurred, no side-effects of Cefamandole were recorded . The patients are still being followed-up . Results achieved resemble these from the literature so conclusion can be made, that Cefamandole is safe and efficient drug for peri-operative prophylactics in total hip replacement.

Adv Exp Med Biol, 1997, 412, 47 - 51
Pathogenesis of O157:H7 Escherichia coli infection in neonatal calves; Dean-Nystrom EA et al.; Cattle have been implicated as an important reservoir of Shiga-like toxin-producing Escherichia coli (SLTEC) O157:H7, enterohemorrhagic E . coli (EHEC) that cause hemorrhagic colitis and hemorrhagic uremic syndrome in humans . Naturally- or experimentally-infected cattle can shed low levels of E . coli O157:H7 long-term, but little is known about the pathogenesis of E . coli O157:H7 infection in cattle . E . coli O157:H7 induce characteristic attaching and effacing (A/E) mucosal lesions in ceca and colons of 1-day-old gnotobiotic piglets and this model is used to study the pathogenesis of SLTEC infections . A/E lesions were not detected in histologic sections of the intestines from adult cattle or 3- to 14-week-old calves infected with E . coli O157:H7 . Our objective was to determine if E . coli O157:H7 induce A/E lesions in neonatal calves . Colostrum-deprived calves (< 12-h-old) were bottle-fed with antibiotic-free milk replacer containing 10(10) colony forming units (CFU) of O157:H7 (SLT-I+, SLT-II+) or nonpathogenic E . coli, necropsied 18 h postinfection and their intestines examined histologically . Bacterial attachment, effacement of microvillous borders, and destruction of epithelium were observed in the intestines of the neonatal calves inoculated with E . coli O157:H7 . No lesions were observed in calves inoculated with nonpathogenic E . coli . The distribution of intestinal lesions in neonatal calves resembled that in gnotobiotic pigs . Neonatal calves are apparently more susceptible to A/E lesions induced by E . coli O157:H7 than are older calves or adult cattle and provide a model for studying the pathogenesis of E . coli O157:H7 infections in cattle.

Przegl Lek, 1997, 54(1), 70 - 2
{Foreign body imitating bronchial neoplasm}; Ochmanski W et al.; A case of 53 year-old male admitted to the Clinic with fever and persisting cough with a muco-purulent secretion, varying in intensity for about 4 months, was presented . Prior to the admission to the Clinic the patient was treated with antibiotics, which only slightly relieved the symptoms mentioned above . The patient was admitted to the Clinic with diagnosis of chronic bronchitis, right sided bronchopneumonia with a suspicion of lung cancer . Performed chest X-ray seemed to confirm this diagnosis . Later on, tomography scans and bronchoscopy demonstrated a foreign body in the bronchus . Bronchoscopy not only allowed to exclude neoplastic change but also enabled us to "treat" the patient by extracting his molar tooth remained in the main right bronchus, which caused purulent inflammatory changes in this bronchus . After subsequent antibiotic therapy patient's general condition improved and radiological chest image returned to normal . Persistent cough and recurrent fever are often the symptoms of the lung cancer . It should be emphasised that in the observed case longterm treatment of these changes lasted for 4 months without chest radiological examination.

Antibiot Khimioter, 1997, 42(4), 8 - 11
{Metabolites produced by Streptomyces kanamyceticus mutants with impaired biosynthesis of kanamycin}; Golets LM et al.; Metabolites produced by Streptomyces kanamyceticus mutants with impaired kanamycin biosynthesis (kan mutants) were investigated by thin layer chromatography . With spectrophotometric scanning of the chromatograms the quantitative content of kanamycin A and 2-desoxystreptamine (2-DOS) in the culture fluid was determined . Five groups of the S.kanamyceticus mutants with impaired kanamycin biosynthesis at various stages were identified: kanA produced no D-glucosamine, kanB and kanC produced no 2-DOS, kanD was not able to transfer 2-DOS to the metabolites with the antibiotic activity, kanG synthesized no kanosamine.

Antibiot Khimioter, 1997, 42(4), 12 - 5
{Calcium ions in the life cycle of Streptomyces albogriseolus 444}; Danova ST et al.; The influence of Ca2+ on the growth, antibiotic production and differentiation of Streptomyces albogriseolus 444 was studied . Consumption of the calcium ions by the strain was followed up . It was shown that Ca2+ changed the dynamics of the biomass accumulation and had no significant effect on the antibiotic production . Calcium present in the medium was assimilated more intensively during the first 24 hours of the strain growth . The own antibiotic nigericin exogenously added to the medium increased the calcium assimilation . In the presence of Ca2+ the nigericin stimulation of the strain differentiation was higher.

Actas Urol Esp, 1997 Jan, 21(1), 75 - 7
{Bilateral abscess of cavernous bodies}; Fernandez Gomez JM et al.; Report of a rare case of abscess in both cavernous bodies . Its peculiarity is based on the location, the bilateral nature and the absence of a clear causative factor, although it was probably related of a local septic focus (rectal or prostatic) . Diagnosis was established with CAT because of the primarily posterior location and the significant peripheral inflammatory reaction . The patient was treated successful with a vigorous antibiotic therapy and open drainage from both cavernous bodies with no development of sequelae such as fibrosis and penial incurvation or impotence.

Rev Pneumol Clin, 1997, 53(1), 27 - 30
{A rare cause of Pierre Marie hypertrophic osteoarthropathy: subacute infectious endocarditis}; Urban T et al.; Secondary hypertrophic osteoarthropathy occurred in a patient with subacute endocarditis . Chest x-ray in this smoker with ethylic cirrhosis showed a pulmonary opacity . Clinical signs of osteoarthropathic inflammation resolved with antibiotics before surgical cure of the aortic insufficiency . The diagnosis was retained on the basis of outcome after antibiotic therapy and the absence of any other etiology, notably bronchogenic cancer . Endocarditis or infectious endarteritis should be entertained in case of hypertrophic osteoarthropathy in patients with an infectious syndrome . Pathogenic hypotheses are discussed . In congenital cardiopathies, intrapulmonary shunts, megacaryocytes and activation of the vascular-platelet endothelium unit may be involved . Bacterial factors and platelet aggregation could play a role in initiating hypertrophic osteoarthropathy in patients with infectious endocarditis.

J Asthma, 1997, 34(3), 211 - 7
Roxithromycin attenuates acid-induced cough and water-induced bronchoconstriction in children with asthma; Shimizu T et al.; In the present study, we evaluated the effect of roxithromycin, a semisynthetic macrolide antibiotic, on the cough response to inhaled acetic acid (AA) and on the bronchoconstriction induced by ultrasonically nebulized distilled water (UNDW) in children with asthma . Ten hospitalized asthmatic children (8 boys and 2 girls, mean +/- SEM age 12.6 +/- 0.4 years) were enrolled in this study . They were treated with 150 mg of roxithromycin once a day orally for 8 weeks without any side effects . All the patients underwent AA inhalation challenge before and 2, 4, and 8 weeks after the administration of roxithromycin . Seven of the 10 patients, who had a fall in FEV1 of at least 20% after UNDW inhalation, underwent UNDW inhalation challege at the same time . The cough threshold values, the lowest concentrations of AA eliciting coughs, and UNDW provocative dose producing a 20% fall in FEV1 (UNDW PD20) values 4 or 8 weeks after the administration of roxithromycin increased significantly over the initial values (p < 0.05) . No significant change was observed in baseline FEV1 or serum theophylline concentrations throughout the study . These results support the notion that administration of roxithromycin may have favorable results in the treatment of childhood asthma.

Laryngorhinootologie, 1997 Jan, 76(1), 23 - 7
{Effects of standardized Myrtol in therapy of acute sinusitis--results of a double-blind, randomized multicenter study compared with placebo}; Federspil P et al.; BACKGROUND: In the management of non-purulent acute sinusitis, alpha adrenergic substances are administered topically and secretolytics systemically . Antibiotic therapy should be restricted to purulent forms . This study was designed to demonstrate the importance of the maintenance of permanent ventilation and drainage of the sinuses as a therapeutic concept . PATIENTS/METHODS: In a multicentric trial the efficacy and safety of myrtol standardized and another essential oil were investigated in 331 patients with acute sinusitis in comparison to placebo . Three hundred thirty patients were evaluated in an intent-to-treat-analysis and 291 patients remained for statistical analysis . The study was conducted in 16 centers in a double-blind, double-dummy, randomized design versus placebo . During an observation-period of 14 days the patients were treated for 6 +/- 2 days with the respective study medication . RESULTS: With respect to efficacy, both myrtol standardized and the other essential oil proved to be significantly superior to placebo . As to the tolerance, a slight advantage of myrtol standardized was demonstrated in comparison to the other verum substance . CONCLUSION: These results which do support the value of essential oils like myrtol as an effective treatment in acute, uncomplicated sinusitis instead of antibiotics as first choice, are confirmed by the existing literature.

Instr Course Lect, 1997, 46, 165 - 9
Wound complications in total knee arthroplasty; Dennis DA; Wound problems are a dreaded complication following TKA and the ideal is to avoid them . Preventive measures include proper choice of the skin incision, gentle handling of the soft tissues, meticulous hemostasis, and wound closure without excessive tension . Should persistent wound drainage or soft-tissue necrosis occur, early intervention is imperative, because delay risks deep infection and failure of the TKA . Cases associated with full-thickness soft-tissue necrosis often require transfer of well-vascularized tissue, such as a medial gastrocnemius myocutaneous flap reconstruction.

Instr Course Lect, 1997, 46, 15 - 24
Complications of humeral head replacement for proximal humeral fractures; Muldoon MP et al.; The indications for humeral head replacement in acute fractures and in chronic fracture problems have been studied over many decades and are reasonably well defined . Complications have probably been understudied . Many different complications occur, and their frequency and the need for reoperation is quite high . Because of the variety of complications that occur, familiarity with preventive measures and treatment options is important, not only to deal with complications arising from endoprostheses, but also to treat musculoskeletal infections, nerve injuries, fractures, instability, nonunion of tuberosities, malunion, and rotator cuff or capsule contracture or tearing . Physicians also must be able to integrate reparative/reconstructive surgery with a program of postoperative rehabilitation . The challenges are many . Treatment often provides considerable improvement for the patient, but often the extent of the improvement is somewhat less than optimal.

Annu Rev Immunol, 1997, 15, 63 - 92
Lyme disease: a review of aspects of its immunology and immunopathogenesis; Sigal LH; Lyme disease, caused by Borrelia burgdorferi, causes a multisystem inflammatory ailment, although the precise means of tissue damage are not well understood . It is clear that the organism is present at the site of inflammation in many organs and that many of the features of the illness are relieved by antibiotic therapy . A complex interaction between spirochete and immune systems of a number of mammalian hosts, in human disease and animal models, has been described . It is clear that T cells and macrophages are intimately associated with the pathogenesis of arthritis and that immune mechanisms are involved in other aspects of disease . Inflammation directed at persistence of Borrelial antigens is a plausible explanation for persisting arthritis . Autoimmunity based on molecular mimicry may play a role in the pathogenesis of Lyme disease . Humoral immunity plays a protective role, prompting interest in vaccine development . Significant variation in certain of the outer surface proteins suggests that multiple proteins, peptides, or chimeric vaccines may be needed to provide a sufficiently broad humoral protective response.

Bioorg Khim, 1997 Jan, 23(1), 3 - 17
{Gene-directed biologically active substances (antisense oligonucleotides and their derivatives)}; Knorre DG; Results of studies carried out over the last eight years under the Russian State Scientific and Technical Program "New Methods in Bioengineering" are reviewed . New addressing constructions formed by a tandem of two or more oligonucleotides on a target nucleic acid are described . The reactivity of the tandem is enhanced due to the stabilization of some components, either by attachment of polyaromatic systems (method of effectors) or by the formation of a reaction center, which occurs when the components of the active center draw together into a tandem . Reagents which are oligonucleotide derivatives are also described, in particular a derivative of the antibiotic bleomycin, which is capable of catalytic cleavage of the target . Evidence is presented that oligonucleotides interact with the proteins of cells and living organisms, including the receptor proteins discovered in the course of this research, the T-helper CD4 receptor, immunoglobulins, and some growth factors.

Psychopharmacol Bull, 1997, 33(1), 143 - 7
Methylphenidate patterns among Medicaid youths; Zito JM et al.; Treatment of attentional disorders in America has increased dramatically in recent years . This trend is accounted for partly by lengthening the duration of treatment into adulthood for some individuals as well as by increased treatment among girls . Beyond these factors, the role of economic status, race, and geographic region to explain the variation in methylphenidate use is not well understood . Computerized administrative data were used to explore the influence of several sociodemographic factors on the prevalence of methylphenidate use . The data source consisted of Maryland Medicaid prescription drug reimbursement claims data for FY1991 for children ages 5 to 14 years . In effect, the study was restricted to a sample of patients with limited income . The study aims included (1) measuring gender-, age-, race-, and region-specific methylphenidate prevalence for this restricted income population; (2) comparing the Caucasian:African-American (C:A-A) ratio for methylphenidate with the C:A-A ratio for several drug therapies having non-psychotropic uses, specifically the anti-asthma drug, theophylline, and antibiotics for infections; and (3) estimating the average daily dose of methylphenidate from prescription claims data . Total drug-specific prevalence among the 5-14 year olds was 2.2 percent for methylphenidate while age-specific prevalence varied from 0.4 percent (5 year olds) to 3.4 percent (9 year olds) . The gender ratio was 3.7:1 (M:F), confirming the increasing trend for girls to receive this medication . Substantial variation across eight defined regions of the state was observed . Racial differences were pronounced: African-Americans were 2.5 times less likely to receive methylphenidate than Caucasian youths . As hypothesized, non-psychotropic drug use was distinctly different from psychotropic drug use in terms of race: theophylline was 1.5 times more likely to be found for African-Americans than Caucasians, whereas antibiotic prescriptions were 1.5 times more likely to be prescribed to Caucasian youths . Average daily dose of methylphenidate was estimated to be 18.7 +/- 10.4 mg for 5-9 year olds and 26.8 +/- 14.0 mg for 10-14 year olds . This brief report confirms the typically lower rate among African-American Medicaid youths for most prescription drugs . The dramatic racial disparity for the psychotropic agent methylphenidate is a new and compelling finding which should be verified among other economic groups . Diagnostic, referral, and cultural bias should be ruled out as possible explanations for the observed differences.

Wien Med Wochenschr, 1997, 147(1), 2 - 5
{Acute pancreatitis--conservative versus surgical therapy}; Gebhardt C et al.; Based on own studies and on results of other centers the multiorgan failure (MOF) resp . the systemic inflammatory response syndrome (SIRS) in acute necrotizing pancreatitis seems to be no longer an compelling reason for surgery in the absence of proven infection of pancreatic necrosis . Growing experience of continuous veno-venous hemofiltration (CVVH) facilitates successful conservative treatment of-formerly often lethal-cases of serious necrotizing pancreatitis . If infection of necrosis is documented surgical intervention should be performed . Our present regime of therapy of necrotizing pancreatitis consists in conservative intensive medical treatment, immediately after admission; a pancreas penetrating antibiotic medication starting on admission; early use of continuous veno-venous hemofiltration if MOF or SIRS occurs, surgical intervention, if infection of necrosis is proved . Other indications for surgery are massive bleeding or bowel perforation due to tryptic lesions.

Ophthalmologe, 1997 Jan, 94(1), 41 - 4
{Ultrasound biomicroscopy for localization of artificial lens haptics after trans-scleral suture fixation}; Steiner A et al.; Correct positioning of transscleral haptics for sulcus fixation of IOL haptics may be difficult due to lack of visual control by the surgeon . We determined the haptic sites in eyes which underwent secondary IOL implantation with transscleral suturing using ultrasound biomicroscopy (UBM) (Humphrey Instruments, Inc., San Leandro, CA, USA) . Eighteen eyes of 17 patients were included in the study . The follow-up time ranged from 1 to 36 months (mean: 7 months) . The positions of 36 IOL-haptics were documented by UBM examination . Twelve haptics (33%) were found in the sulcus, whereas 18 haptics (50%) were located posteriorly to the sulcus . Six haptics (17%) were identified anteriorly to the sulcus . There were no complications resulting from dislocation . In one of the eyes, suture infection occurred requiring surgical revision and antibiotic therapy.

Acta Otolaryngol Suppl, 1997, 526, 54 - 7
When and how to use gentamicin in the treatment of Menière's disease; Odkvist LM et al.; Gentamicin given as local therapy for severe Meniere's disease is of considerable value in the control of vertigo . The ototoxic antibiotic is instilled through the tympanic membrane causing a peripheral vestibular loss and possibly also diminished endolymph production . In order to achieve the best results with gentamicin treatment it is of utmost importance that the diagnosis is correct . Given to a patient with vertigo of other than peripheral origin, the outcome would be worsening of the existing symptoms and addition of new ones . The method should be used only by physicians who are very familiar with vertigo and otology, and only in patients with such a disturbing degree of vertigo that they are well motivated to receive treatment . Thorough information regarding the disease, the treatment procedure and the symptoms caused by a unilateral peripheral vestibular loss should be given to the patient . Vestibular rehabilitation, including movement therapy, should be given by the physician or preferably, a well trained physiotherapist on an individual basis or in patient groups together with written practice programmes for use at home . Vertigo attacks are usually relieved in 95% of patients . Twenty percent of patients experience an added hearing loss in the treated ear, although this number is reduced if the treatment is given as a single installment on consecutive days with extra installments given one month later if the vertigo remains.

Adv Biochem Eng Biotechnol, 1997, 58, 1 - 14
Optimizing industrial enzymes by directed evolution; Arnold FH et al.; Enzymes can be tailored for optimal performance in industrial applications by directing their evolution in vitro . This approach is particularly attractive for engineering industrial enzymes . We have created an efficient para-nitrobenzyl esterase over six generations of random point mutagenesis and recombination coupled with screening for improved variants . The best clones identified after four generations of sequential random mutagenesis and two generations of random recombination display more than 150 times the p-nitrobenzyl esterase activity of wild type towards loracarbef-p-nitrobenzyl ester in 15% dimethylformamide . Although the contributions of individual effective amino acid substitutions to enhanced activity are small (< 2-fold increases), the accumulation of multiple mutations by directed evolution allows significant improvement of the biocatalyst for reactions on substrates and under conditions not already optimized in nature . The positions of the effective amino acid substitutions have been identified in a pNB esterase structural model . None appear to interact directly with the antibiotic substrate, further underscoring the difficulty of predicting their effects in a 'rational' design effort.

Br J Cancer, 1997, 75(8), 1205 - 12
High-dose carboplatin, etoposide and melphalan (CEM) with peripheral blood progenitor cell support as late intensification for high-risk cancer: non-haematological, haematological toxicities and role of growth factor administration; Benedetti Panici P et al.; The present report describes the non-haematological toxicity and the influence of growth factor administration on haematological toxicity and haematopoietic recovery observed after high-dose carboplatin (1200 mg m(-2)), etoposide (900 mg m(-2)) and melphalan (100 mg m(-2)) (CEM) followed by peripheral blood progenitor cell transplantation (PBPCT) in 40 patients with high-risk cancer during their first-line treatment . PBPCs were collected during the previous outpatient induction chemotherapy programme by leukaphereses . CEM administration with PBPCT was associated with low non-haematological toxicity and the only significant toxicity consisted of a reversible grade III/IV increase in liver enzymes in 32% of the patients . Haematopoietic recovery was very fast in all patients and the administration of granulocyte colony-stimulating factor (G-CSF) plus erythropoietin (EPO) or granulocyte-macrophage colony-stimulating factor (GM-CSF) plus EPO after PBPCT significantly reduced haematological toxicity, abrogated antibiotic administration during neutropenia and significantly reduced hospital stay and patient's hospital charge compared with patients treated with PBPCT only . None of the patients died early of CEM plus PBPCT-related complications . Low non-haematological toxicity and accelerated haematopoietic recovery renders CEM with PBPC/growth factor support an acceptable therapeutic approach in an adjuvant or neoadjuvant setting.

J Fr Ophtalmol, 1997, 20(3), 195 - 9
{Does the dosage of mitomycin-C applied during filtering surgery of glaucoma vary with the individual surgeon?}; Mehel E et al.; PURPOSE: The purpose of this study was to estimate the quantity of mitomycin-C contained in sponges prepared by different surgeons as compared to that in applicators of the type used in Schirmer's test graduation (5 x 5 mm) . MATERIALS AND METHODS: Four surgeons each cut and prepared 10 sponges for intraoperative use according to their usual method . The same procedure was performed with 10 Schirmer's test graduations . Each sponge and each graduation was immersed in a solution of mitomycin-C 0.2 mg/ml, and the quantity of antibiotic (microgram) in each was calculated as the difference between wet and dry weight . RESULTS: The mean quantity (+/-SEM) of mitomycin-C contained in cut sponges was 9.6 +/- 4.4 micrograms (range 1.9-17.3), and differences between surgeons were statistically significant (p < 0.0001) . The mean quantity of antibiotic in Schirmer's test graduation was 1.7 +/- 0.3 micrograms (range 1.1-2.5), and the differences between surgeons were not statistically significant (p = 0.79) . CONCLUSION: The quantities of mitomycin-C contained in sponges prepared for glaucoma surgery differed for a given surgeon and between surgeons . Thus, variations in the doses applied to the sclera could account for certain complications due to mitomycin-C . The use of a Schirmer's test graduation improves predictability for the quantity of mitomycin-C applied to the sclera.

J Periodontal Res, 1997 Jan, 32(1 Pt 2), 183 - 8
Tetracycline inhibits Porphyromonas gingivalis lipopolysaccharide-induced lesions in vivo and TNF alpha processing in vitro; Shapira L et al.; Lipopolysaccharides (LPS) are considered one of the more important virulence factors related to the pathogenesis of periodontal diseases . Based on tetracycline (TTC) ability to bind divalent metal ions, the present study was designed to examine the effect of TTC on P . gingivalis LPS-induced lesions in vivo and on LPS-induced TNF alpha production in vitro . Subcutaneous injection of 50-100 micrograms of P . gingivalis LPS into BALB/C mice induced a visible lesion within 24 h with evident tissue necrosis . Daily systemic administration of TTC for the first 4 d following LPS challenge reduced the size of the lesion, and total inhibition of lesion formation was observed in 75-100% of the treated mice . A non-related broad spectrum antibiotic, ampicillin, or the IL-1 inhibitor ML-20, had no effect on the lesion size . In order to explore some aspects of the mechanism involved, we tested the effect of TTC on LPS-induced TNF alpha secretion by human monocytes in vitro . TTC (1 mM) was found to block LPS-stimulated TNF alpha secretion . Western blotting of monocyte cytoplasmic membranes for membrane-bound TNF alpha show that TTC causes the retention of membrane-associated TNF alpha on monocyte membranes, thereby preventing the release of TNF alpha into the culture media . The results suggest the TTC is an effective in vivo therapy for preventing P . gingivalis LPS-induced subcutaneous lesion formation in the murine model . The mechanism of TTC treatment probably involves blocking the activity of metalloproteinases, including TNF alpha processing enzyme, thereby preventing LPS-induced tissue destruction.

Anaesthesist, 1997 Jan, 46(1), 14 - 20
{Intubation conditions and the development of neuromuscular blockade with rocuronium in endoscopic ORL surgery}; Lullwitz E et al.; Rocuronium is a new nondepolarizing muscle relaxant for which a fast onset has been described . The goal of this study was to examine whether the characteristics of rocuronium could make it an appropriate relaxant for the anaesthetic management of operations of intermediate duration such as endoscopic upper airway surgery . These operations, which require the anaesthesiologist and surgeon to "share" the patient's airway, require good muscle relaxation for endotracheal intubation and placement of endoscopic instruments . In addition, the time course of neuromuscular blockade and its relation to the quality of intubating conditions were analysed . METHODS: The study was approved by the local ethics committee; 30 patients (ASA status 1-3) scheduled for elective endoscopic upper airway surgery were included after written informed consent . Exclusion criteria were suspected difficult intubating conditions, neuromuscular disease, or antibiotic therapy with aminoglycosides during the last 24 h . Anaesthesia was induced by propofol 2 mg/kg and alfentanil 1 mg after volume loading with 500 ml Ringer's lactate and preoxygenation, and was maintained by propofol infusion 5-8 mg/kg/h and repetitive alfentanil injections according to clinical needs . Endotracheal intubation was performed by a senior anaesthesiologist 90 s after injection of rocuronium 0.6 mg/kg (2 x ED95) . Intubating conditions were graded 1 to 4 (1 = excellent, 2 = good, 3 = sufficient, 4 = inadequate) . Acceleromyography was used for neuromuscular monitoring by means of the TOF-guard (organon Teknika/Biometer) . The adduction movement of the thumb was measured by an acceleration transducer while stimulating the ulnar nerve at the wrist via surface electrodes in a supramaximal train-of-four (TOF) mode (2 Hz every 15 s) . Twitch height and TOF ratio were documented during the course of neuromuscular blockade . Data are presented as mean +/- standard deviation . RESULTS: Patients were aged 37 to 64 years (mean 54 +/- 7) . Intubating conditions were excellent in 17 cases and good in 7 . In 2 cases intubating conditions were graded sufficient, as patients could be easily intubated but showed clear diaphragmatic movements at intubation . In 4 patients intubating conditions could not be judged, as a laryngoscopic view of the glottic structures was impossible for anatomic reasons . Neuromuscular block at intubation was 78 +/- 22%, onset time 152 +/- 62 s, clinical duration 30 +/- 8 min, and recovery index 11 +/- 4 min . The TOF ratio required 51 +/- 14 min to return to 0.7 . CONCLUSIONS: Good to excellent intubating conditions can be expected 90 s after injection of rocuronium 0.6 mg/kg . Diaphragmatic reactions cannot be excluded . Complete relaxation of the adductor pollicis muscle is not necessary for endotracheal intubation . Intubation at a certain time interval, for example, 90 s after injection of rocuronium 0.6 mg/kg, can be recommended . Onset and recovery characteristics of rocuronium make it an appropriate relaxant for the anaesthetic management of operations of intermediate duration such as endoscopic upper airway surgery . Care should be given, however, to detect inadequate recovery of neuromuscular transmission, as there are considerable interindividual differences in recovery.

J Dent, 1997 Jan, 25(1), 31 - 4
Early management of dental pain in children and adolescents; Mason C et al.; OBJECTIVES: There is little information regarding the initial management of dental pain in children and adolescents . The present study investigated the early management of 155 children and adolescents with dental pain prior to definitive treatment in the Eastman Dental Institute and Hospital for Oral Health Care Sciences, London, UK . METHOD: Prior to the child being examined by a qualified dentist in the casualty department, the accompanying parents or guardians were requested to complete a self-administered questionnaire regarding the duration and severity of pain, presence of swelling, professional advice sought and medication taken . RESULTS: Of the attending children, 83% were in pain, 20% having been in pain for over 1 month . Most parents sought professional health care advice, particularly from a dentist; however, 15% initially obtained advice from a medical practitioner and 5% from a pharmacist . Simple analgesics were taken by 74% of patients; however, these rarely produced complete pain relief . Of concern, 10 children were inappropriately given aspirin, three of whom had taken the aspirin on the advice of a pharmacist . Sixty-seven children received systemic antibiotic therapy; however, 31% of these patients did not have any local swelling . CONCLUSION: It is evident that children and adolescents often receive inappropriate initial treatment for dental pain and may thus suffer unnecessary symptoms for several weeks . There is thus a need to educate healthcare workers more appropriately on aspects of the management of oral pain and to promote oral health care and hence reduce the incidence of caries in children.

Chem Res Toxicol, 1997 Jan, 10(1), 49 - 58
Mechanism for the anti-thyroid action of minocycline; Doerge DR et al.; Administration of minocycline (MN), a tetracycline antibiotic, produces a black pigment in the thyroids of humans and several species of experimental animals and antithyroid effects in rodents . We have previously shown that these effects appear to be related to interactions of MN with thyroid peroxidase (TPO), the key enzyme in thyroid hormone synthesis . In the present study, the mechanisms for inhibition of TPO-catalyzed iodination and coupling reactions by MN were investigated . MN was stable in the presence of TPO and H2O2, but adding iodide or a phenolic cosubstrate caused rapid conversion to several products . TPO-dependent product formation, characterized by on-line LC-APCI/MS and 1H-NMR, involved oxidative elimination to form the corresponding benzoquinone with subsequent dehydrogenation at the aliphatic 4-(dimethylamino) group . Addition of thiol-containing polymers (bovine serum albumin or thiol-agarose chromatographic beads) had a minimal effect on MN oxidation by TPO, but substantially reduced product formation and produced concomitant losses in free thiols . Covalent bonding through a thioether linkage of a reactive intermediate, the benzoquinone iminium ion, was inferred from these findings . Iodide- and phenolic cosubstrate-dependent oxidation of tetracycline to demethylated and dehydrogenated products was also observed, although at a slower rate than MN . The products and kinetics observed with MN were consistent with oxidation of MN by either the enzymatic iodinating species formed by reaction of TPO compound I with iodide or phenoxyl radicals/cations generated by TPO-mediated oxidation of a phenolic cosubstrate . The proposed reaction mechanism is consistent with alternate substrate inhibition of TPO-catalyzed iodination of tyrosyl residues in thyroglobulin (Tg) by MN, as previously reported . Furthermore, the observed phenoxyl radical-mediated oxidation of MN is consistent with its previously reported potent inhibition of the coupling of hormonogenic iodotyrosine residues in Tg in the reaction that forms thyroid hormones . The proposed reaction mechanism also implicates a reactive benzoquinone iminium ion intermediate that could be important in toxicity of MN.

Nihon Kyobu Shikkan Gakkai Zasshi, 1997 Jan, 35(1), 117 - 23
{Cough-variant asthma successfully treated with a peptide leukotriene receptor antagonist}; Nishi K et al.; A 47-year-old woman complained of coughing for over 5 weeks . The coughing was not relieved by bronchodilators (theophylline, beta 2-adrenoceptor agonist; procaterol), anti-allergic agents (azelastine, ozagrel), an inhaled corticosteroid (beclomethasone dipropionate), a macrolide antibiotic (clarithromycin), or codeine phosphate . A peptide leukoriene receptor antagonist (pranlukast) completely abolished the coughing and increased the cough threshold to capsaicin . The patient was given a diagnosis of cough-variant asthma because her sputum contained many eosinophils and her airway responsiveness to methacholine was slightly higher than normal . Peptide leukotriene may have contributed to the coughing . The fact that coughing associated with cough-variant asthma was abolished by a peptide leukotriene receptor antagonist is clinically important.

Ophthalmologica, 1997, 211 Suppl 1, 68 - 76
Prophylactic use of topical anti-infectives in ophthalmology; Kramer A et al.; The prophylactic use of topical anti-infectives is indicated on the eye (1) prior to any surgery on the eye, by periorbital and conjunctival administration and, if required, intraoperatively as well; (2) in the form of the Crede prophylaxis against ophthalmia neonatorum; (3) with accidental pathogenic contamination of the eye; (4) to prevent conjunctivitis by intensive care surgical patients; (5) for the antiseptic irrigation of donor bulbi prior to keratoplasty, and (6) if required, to prevent ocular infection in a given epidemiological situation . The drug of first choice is polyvinylpyrrolidone-iodine at a concentration ranging from 1.5 to 5% . Another topical anti-infective is a 0.02 or 0.01% solution of polyhexanide, a promising medication, currently in the process of being approved.

Eur J Clin Microbiol Infect Dis, 1997 Jan, 16(1), 98 - 107
Economic aspects of treatment for fungal infections in cancer patients; Torfs K; Although health care expenditure has increased steadily over the past decennium, the general feeling is that resources are more limited than ever . One reason for this may be that the range of treatment options has grown so wide that the need to make rational choices has become apparent . Since treatments vary with respect to both effectiveness and cost, economic evaluations are becoming an important tool for assessing new and existing treatment strategies . The basic concepts of economic evaluation will be introduced here and the key economic questions with respect to treatment of fungal infections in cancer patients identified . Some of these concepts are explained using findings from a pilot survey carried out among participants in the symposium "Trends in Invasive Fungal Infections-3" 7-9 held September, 1995, in Brussels, Belgium . The conclusion will offer recommendations for assessing economic evaluations.

Eur J Clin Microbiol Infect Dis, 1997 Jan, 16(1), 32 - 41
Practical modalities for prevention of fungal infections in cancer patients; De Pauw BE; Invasive fungal infections have become a major obstacle to the treatment of patients with malignancies . Candida spp . and Aspergillus spp . now rank among the ten most prominent pathogens in these patients . Currently, there are no adequate means of detecting these infections at an early stage, and optimal hygiene and elimination of well-known sources of infection remain the most important preventive measures . Due to the lack of reliable, randomized studies, the role of antifungal drugs in the prevention of invasive fungal infections is difficult to judge . The clinical impact of the older oral antifungal agents is questionable, and compliance with therapeutic regimens of these drugs is often limited . In prospective studies in bone marrow transplant recipients, fluconazole was effective in preventing candidiasis but offered no prophylaxis against infections due to Aspergillus spp . and other molds . Initial trials on the use of sprays and aerosols of amphotericin B and on infusions of low doses of this drug appeared beneficial, but the number of patients included was too small to allow any definite conclusion . Itraconazole offers promise, but it can only be given orally; adequate, reliable absorption is not yet guaranteed . While the lack of data justifies a wait-and-see approach in patients at low or moderate risk of developing a fungal infection, it seems reasonable to administer prophylaxis to high-risk patients, even though there is presently no single agent suitable for all prophylactic purposes.

Zentralbl Bakteriol, 1997 Jan, 285(2), 212 - 33
Polyphasic taxonomic study of clinically significant actinomadurae including the description of Actinomadura latina sp.nov; Trujillo ME et al.; Thirty-one strains received either as Actinomadura madurae or Actinomadura pelletieri were assigned to four phena, clusters 1 to 4, in a numerical phenetic survey of the genus Actinomadura . Clusters 2 and 4 corresponded to the validly described species A . madurae and A . pelletieri whereas clusters 1 and 3 encompassed strains received as A . madurae and A . pelletieri, respectively . The two clusters that contained A . madurae strains formed a single taxon when a dataset lacking the antibiotic sensitivity entries was examined . Results from pyrolysis mass spectrometric and DNA amplification fingerprinting analyses underpinned the taxonomic status of clusters 2, 3 and 4 and suggested that the A . madurae strains accounted for a relatively wide range of variation . It is proposed that the cluster 3 strains be given species status within the genus Actinomadura given the congruence found between the chemical, molecular and numerical phenetic data . The name Actinomadura latina is proposed for the new taxon . The type strain is DSM 43382.

Acta Neurochir (Wien), 1997, 139(1), 33 - 6
Propionebacterium acnes in cultures from ventriculo-peritoneal shunts: infection or contamination?
Westergren H, Westergren V, Forsum U.
We have examined the accuracy of our present CSF sampling technique in 14 referred patients with suspect shunt dysfunction . The study was performed comparing culture results from shunt reservoir punctures and sham samples from skin tissue fluid close to the reservoirs . Propionebacterium acnes (P acnes) was found in five of fifteen cultures from reservoir punctures and in five of fifteen sham procedures . Positive cultures correlated in two cases . Thirteen of the fourteen patients included in the study were followed clinically and their symptoms disappeared without antibiotic or surgical treatment . One patient was treated surgically . We conclude that bacterial growth in cultures from shunt reservoirs in cases with P acnes should be interpreted with great caution, as our findings indicate that they may be skin contaminations.

Am J Nephrol, 1997, 17(1), 42 - 5
Evaluation of acute renal failure in bacterial allograft pyelonephritis using abdominal CT and graft biopsy; Yang CW et al.; The causes of acute renal failure in bacterial allograft pyelonephritis were evaluated using abdominal CT and graft biopsy . Twenty-one recipients, who showed a poor response to antibiotic therapy, comprised this study group . The diagnostic approach taken with this poor responder group was first to perform abdominal CT . If a focal lesion was identified on abdominal CT, a diagnosis of acute focal bacterial nephritis or renal abscess was made . If no focal lesion was found, a graft biopsy was performed for diagnosis . Abdominal CT revealed focal lesions in 9 of the 21 recipients, and renal biopsy showed superimposed acute rejection in 8 of the 12 recipients biopsied . In conclusion, acute renal failure in allograft pyelonephritis is associated with not only severe infection but also a superimposed acute rejection process . Therefore, imaging study and graft biopsy are recommended in the poor responder group.

Biomed Chromatogr, 1997 Jan-Feb, 11(1), 11 - 5
HPLC-fluorescence determination of individual free and conjugated bile acids in human serum; Gatti R et al.; A method for the quantitative analysis of unconjugated and conjugated bile acids (BA) in serum of patients with primary biliary cirrhosis (PBC) before and after therapy with antibiotic or ursodeoxycholic acid (UDCA) is described . After separation of the free, glycine and taurine conjugated (F, G and T conjugated) fractions by solid-phase extraction, the isolated T conjugates were hydrolysed enzymatically using cholyglycine hydrolase . The BA fractions were derivatized using 2-bromoacetyl-6-methoxynaphthalene (Br-AMN) and detected fluorimetrically (lambda exc = 300 nm, lambda em = 460 nm) . The derivatization reaction was performed under mild conditions (10 min at 40 degrees C) in an aqueous medium in the presence of tetrakis (decyl) ammonium bromide (TDeABr) . The HPLC separation was achieved using an ODS column and with a mobile phase gradient mixture of A-B, where A is water and B is acetonitrile:methanol (60:40 v/v) for elution at a flow-rate of 1.2 mL/min . The reproducibility, recovery and separation of individual BA under gradient elution conditions were satisfactory, allowing a sensitive detection of each BA in serum samples with a detection limit of about 1-2 pmol.

J Antimicrob Chemother, 1997 Jan, 39(1), 63 - 9
Evaluation of hypersensitivity to microencapsulated ampicillin in guinea pigs; Barsoum IS et al.; The purpose of this study was to determine if the sustained release of ampicillin from a biodegradable drug-delivery system (microencapsulated ampicillin anhydrate (MEAA)) will increase or decrease the intensity of a hypersensitivity reaction compared with that observed with free drug . Ovalbumin, which is known to elicit a marked hypersensitivity reaction in guinea pigs, and microencapsulated ovalbumin (MOVA) were tested in parallel with ampicillin and MEAA . Guinea pigs were sensitized biweekly by subcutaneous and intramuscular injections of ampicillin, MEAA, ovalbumin, MOVA or placebo microspheres (test articles), each mixed with Freund's adjuvant, and challenged 2 weeks later, intradermally, with the free compounds . In a separate set of experiments, guinea pigs were sensitized by implantation of the same agents in the caudal thigh of anaesthetized animals . Skin allergic reactions were tested at 1 and 3 weeks following local implantation of the test articles . Sera of sensitized guinea pigs were tested for specific IgG antibodies by enzyme-linked immunosorbent assay, and skin samples from the site of the inflammatory reaction were fixed, stained and evaluated histologically . Guinea pigs sensitized systemically with MEAA or MOVA showed smaller, but not statistically different skin allergic response than animals given corresponding free compounds . However, guinea pigs sensitized by local implantation of MEAA showed a significantly lower inflammatory response (P < 0.0001) than those given an equivalent dose of the free drug . Guinea pigs sensitized with placebo microspheres showed a low inflammatory skin reaction which was similar to those sensitized with all doses of MEAA . There was no significant difference in specific IgG antibody response in the sera of guinea pigs sensitized locally with either free or microencapsulated ampicillin or ovalbumin . Histology of skin revealed a milder inflammatory reaction with MEAA or MOVA than with ampicillin or ovalbumin, respectively . We conclude that the encapsulated ampicillin or ovalbumin and subsequent release of each agent will elicit a reduced hypersensitivity reaction in guinea pigs than will the free agent.

Br J Cancer, 1997, 75(5), 656 - 9
Intratibial injection of an anti-doxorubicin monoclonal antibody prevents drug-induced myelotoxicity in mice; Morelli D et al.; With few exceptions, the major limit to high-dose chemotherapeutic treatments is the severity and duration of drug-induced myelosuppression . We have recently developed a monoclonal antibody, MAD11, which reacts with the potent anti-tumour antibiotic doxorubicin and other anthracyclines . To protect directly pluripotent stem cells and cells of the haematopoietic microenvironment in the bone marrow against doxorubicin cytotoxicity, the monoclonal antibody MAD11 was injected into the tibial bone of mice before chemotherapeutic treatment . All mice pretreated intratibially with MAD11 and injected with 14 mg kg(-1) body weight of doxorubicin survived, whereas 41% of mice treated with doxorubicin alone died . At a higher dose of doxorubicin (18 mg kg(-1)), early mortality (first 6 days) was similar in the groups, but no deaths were observed thereafter in the intratibially MAD11-treated group, whereas most of the mice treated with doxorubicin alone died . Data obtained in mice injected with P388 leukaemia cells showed that the intratibial injection of MAD11 did not compromise the anti-tumoral activity of doxorubicin . Moreover, the administration of the anti-doxorubicin monoclonal antibody before chemotherapeutic treatment effectively reduced apoptosis induced by doxorubicin in the bone marrow cells . These data suggest the usefulness of monoclonal antibodies against chemotherapeutic drugs in the local protection of bone marrow without influencing the anti-tumour properties of the drug.

Cell Transplant, 1997 Jan-Feb, 6(1), 39 - 45
Effect of fusidic acid on pancreatic islet allograft rejection; Mendola JF et al.; We examined in fully mismatched rats, the survival of pancreatic islet allografts in recipients treated with either fusidic acid (FA), an antistaphyllococcal antibiotic that has been shown to possess an immunosuppressive effect in vitro and in vivo, or cyclosporin-A (CsA) . Islets were isolated by collagenase digestion, separated from acinar tissue by handpicking under a dissecting microscope and transplanted into the liver by portal vein injection of streptozotocin(STZ)-induced diabetic rats . The results indicated that while a temporary immunosuppression with CsA achieved an indefinite islet allograft survival, FA administered to recipients daily was not able to prevent islet allograft rejection across a major histocompatibility barrier . We conclude that despite the fact that fusidic acid has been claimed to act as an-immunosuppressant drug in vitro with effects similar to those of CsA, unlike CsA, FA given either orally or by s.c . injection was not effective to prolong islet allograft survival in vivo.

Skeletal Radiol, 1997 Jan, 26(1), 64 - 6
Malignant hemangioendothelioma of the left calcaneus associated with fever and hematological abnormalities; Rong Y et al.; A case of malignant hemangioendothelioma of the left calcaneus associated with unique system manifestations is reported here . The severe toxic manifestations included: high fever, anemia, leukocytosis, coagulation abnormalities, and other signs . Because of poor response to many antibiotic regimens, the confusion of diagnosis, and severe coagulation abnormalities with clinical signs that the life of the patient was endangered, below the knee amputation was performed . Pathological studies revealed a malignant hemangioendothelioma . A review of the case suggests that the signs and symptoms were possibly due to an immune response to the tumor rather than to secondary infection, although the latter possibility cannot be completely excluded.

Parasitol Res, 1997, 83(2), 198 - 202
Biochemical alterations in paromomycin-treated Leishmania donovani promastigotes; Maarouf M et al.; Paromomycin is used for the treatment of leishmaniasis in humans, but little is known about its mechanism of action . Investigating the effect of this antibiotic on promastigotes of Leishmania donovani, we showed that inhibition of the multiplication of these parasites could be related to its effect on RNA synthesis and to modifications of membranous polar lipids and membrane fluidity, leading to altered membrane permeability.

Thorax, 1997 Jan, 52(1), 98 - 9
Thromboembolism related to a Port-a-Cath device in a patient with cystic fibrosis; Yung B et al.; The case is described of a potentially life threatening complication relating to the use of a totally implantable venous access device (Port-a-Cath) in a 28 year old patient with cystic fibrosis . The device was inserted in 1990 and used repeatedly for antibiotic therapy without any complications . In 1995, during assessment for double lung transplantation, a 3 cm thrombus was found at the tip of the catheter in the right atrium . Embolisation of the thrombus to the pulmonary arteries occurred after the infusion of recombinant tissue plasminogen activator (rt-PA) . Thrombus formation may be associated with totally implantable venous access devices and thromboembolism may occur following the use of thrombolytic agents in the treatment of such thrombosis.

J Am Optom Assoc, 1997 Jan, 68(1), 38 - 42
Swelling of collagen intracanalicular implants; Lowther GE et al.; BACKGROUND: Absorbable intracanalicular collagen implants are used to attempt to determine if permanent closure of the tear drainage system will diminish or alleviate the signs and symptoms of dryness . The rate of swelling of the collagen implants was measured in vitro in this study . METHODS: Collagen implants were submersed in saline, Refresh Plus artificial tears or Tobrex antibiotic solution on a hanging drop microscope slide . The diameter of the collagen rod was measured over time using videotaping and image processing . RESULTS: The 0.3- and 0.4-mm diameter collagen implants swelled approximately 55% to 65% in Unisol 4 Preservative Free saline and Refresh Plus artificial tear solution, with the majority of the swelling occurring over the first 30 minutes . The 0.4-mm diameter implants took slightly longer to reach the fully swollen state than did the 0.3-mm implants . They swelled somewhat less in Tobrex Ophthalmic Solution . CONCLUSIONS: Collagen implants swell approximately 60%, with the majority of the swelling occurring in the first 30 minutes . Thus, it will take approximately 30 minutes after insertion of the implants for the full occlusive effect to occur.

Public Health, 1997 Jan, 111(1), 5 - 10
Diarrhoeal disease morbidity and home treatment practices in Egypt; Jousilahti P et al.; Diarrhoeal disease is a major cause of death in children in the developing world . In developing countries a quarter of infant and childhood mortality is related to diarrhoea . The World Health Organization started the Diarrhoeal Disease Control Programme (CDD) in 1980 with the objective to decrease diarrhoeal mortality and morbidity among young children in developing countries . The aim of this study was to measure the prevalence and incidence of diarrhoeal diseases among young children and to assess the quality of home case management of diarrhoeal cases . Particular emphasis was put on the assessment of drug use during diarrhoea . The survey included also the assessment of breast feeding practices . Geographically the survey was limited to two governorates, Dakahlia and Gharbia, in lower Egypt, which have the largest population (7.12 million) and were thought to be representative of lower Egypt . The total sample size was 11032 . Seasonally adjusted diarrhoea incidence was 3.6 episodes per child under five years of age per year . This means a minimum estimate of 30 million cases annually in Egypt . Although the majority of the caretakers knew of Oral Rehydration Salts (ORS), only 22% of cases with diarrhoea in the last 24 h received ORS . 54% of cases had received drugs, and many of the children with diarrhoea received more than one drug . The source of drug prescription was most often a private doctor and the use of drugs was common among government doctors and health workers . The high proportion of cases treated with drugs, other than ORS, is the major problem in diarrhoeal home case management in Egypt . The message of ORS has penetrated into the general population well, but the practices of health professionals have not changed . To improve the situation further, training of health workers in correct case management is needed . Paediatric forms of symptomatic antidiarrhoeal drugs should also be withdrawn from the marketPIP: In August 1992, interviews were conducted with 9711 caretakers, usually mothers, living in Kakahlia and Gharbia governorates, Egypt, so researchers could determine the prevalence and incidence of diarrheal diseases among 11,032 children aged under 5 years and examine the quality of home treatment practices among 958 children who had had diarrhea in the previous 24 hours . The point prevalence of diarrhea for the previous 24 hours was 8.7% (958 children) . 4.1% of these diarrhea cases had had persistent diarrhea (14 days in duration) . 3.8% had had blood in the stool . Only 2 of the 36 children with blood in the stool had received an antibiotic or an antiparasitic drug . 21.9% had received oral rehydration solution (ORS) . 77.1% of their caretakers prepared ORS correctly . The mean quantity of ORS was 351 ml/child, probably too little for effective rehydration . 95.8% of caretakers of all cases of diarrhea in the last 24 hours were familiar with ORS . The 2-week diarrheal incidence rate was 20.4% . The seasonally adjusted incidence rate was 3.6 episodes/child/year . Rural areas had higher incidence and prevalence rates than urban areas (2-weeks incidence, 22.7% vs . 16.9%; point prevalence, 10% vs . 6.6%) . 96.3% of lactating mothers continued to breast feed during their child's diarrhea episode . 69.8% of diarrhea cases receiving solid or semi-solid foods before the illness received the same amount during the diarrhea episode . Only 24.4% of cases who received fluids other than breast milk before diarrhea received more fluids during diarrhea . 54.2% of all cases were given at least one drug during the diarrhea episode; more than 50% of these were given more than one drug . 17.6% received ORS and drugs . Only 5% received ORS alone . A private physician and a government physician or health worker, respectively, prescribed a drug for 50% and 23.3% of cases who were given drugs . A pharmacy provided 90.4% of the drugs . The continued breast feeding rate (i.e., any breast feeding in last 24 hours) was 78.2% among children aged 12-15 months and 48.9% among those aged 20-23 months . Training of health workers in correct case management is needed .

J Periodontol, 1997 Jan, 68(1), 84 - 91
Minocycline-induced intraoral pharmacogenic pigmentation: case reports and review of the literature; Westbury LW et al.; Minocycline, a semi-synthetic tetracycline antibiotic, is well documented as being associated with pharmacogenic pigmentation of various tissues in humans and other mammals . The most obvious of these are skin pigmentation, but intraorally include "green" roots of erupted teeth, "black" roots of extracted teeth, a dark stain of the crowns of fully developed teeth, and "black" alveolar bone . This article presents five cases of "black" alveolar bone with photographic documentation of its progress . It also reviews the available English language literature on this phenomenon . The incidence of minocycline staining of alveolar bone is probably 2% of that population taking the drug for 2 months or longer . Presently, minocycline is most widely used in the young adult population for the treatment of acne . With the recent interest in minocycline as a palliative treatment for rheumatiod arthritis, an entirely different population could be experiencing this effect . If minocycline use becomes widespread as a treatment for rheumatoid arthritis, it is likely that more practitioners will be asked to diagnose this sometimes striking, though apparently benign, condition . Recognition of this condition will save the practitioner and the patient from unnecessary concern and surgery.

J Bone Joint Surg Br, 1997 Jan, 79(1), 161 - 6
Contamination of bone allografts: analysis of incidence and predisposing factors; Deijkers RL et al.; We analysed the bacterial contamination of 1999 bone allografts retrieved from 200 cadaver donors under sterile operating conditions . The effect of various factors on the relative risk of contamination was estimated using a multiple logistic regression model . Organisms of low pathogenicity were cultured from 50% of the grafts and of high pathogenicity from 3% . The risk of contamination with low pathogenic organisms (mainly skin commensals) increased by a factor of 1.6 for each member added to the procurement team . The risk of contamination with high pathogenic organisms (mainly contaminants from the gastrointestinal tract) was 3.4 times higher in donors with a traumatic cause of death and 5.2 times higher in those with a positive blood culture . Preceding organ procurement did not significantly influence the risk of contamination . Rinsing the graft with an antibiotic solution was not an effective decontamination method . The major source of contamination is exogenous and is strongly influenced by the procurement team . Contamination from endogenous sources can be controlled by donor selection . We discuss methods that can be used to decrease contamination and the rate of discarding of bone allografts.

J Bone Joint Surg Br, 1997 Jan, 79(1), 31 - 5
One-stage revision surgery for infected megaprostheses; Holzer G et al.; We have reviewed the results of one-stage revision surgery in 18 patients for infection of megaprostheses implanted after the resection of malignant bone and soft-tissue tumours . At a mean follow-up of 52.0 +/- 35.0 months (18 to 135) infection was eliminated in 14 of the 18 patients . The infection-free patients showed no abnormal tests for inflammation and had a mean Enneking score of 20.6 +/- 5.0 points (maximum 30 points) . We suggest that one-stage revision without exchange of the anchorage parts is justified in patients with megaprostheses infected by antibiotic-sensitive micro-organisms.

Eur J Cell Biol, 1997 Jan, 72(1), 61 - 9
Influence of N-methylformamide on the intracellular transport of doxorubicin; Calcabrini A et al.; The polar solvent N-methylformamide proved to be capable of enhancing the cytotoxic potential of various antitumoral compounds, both in vitro and in vivo . In many cases, this ability depended on the sequence of treatment, and the enhancement of the cytotoxic effect occurred only when N-methylformamide administration succeeded anticancer drug treatment . The results obtained in the present study indicate that N-methylformamide interferes with the mechanisms of intracellular transport and efflux of the antitumoral drug doxorubicin . In particular, laser scanning confocal microscopy observations performed on melanoma cells (M14) after N-methylformamide administration revealed evident alterations of the microtubular network, including numerous interruptions of the microtubules . Moreover, when doxorubicin-treated cells were recovered in the presence of the polar solvent, the normal efflux of the anthracyclinic antibiotic appeared to be hampered, and the drug was localized mainly in well delimited perinuclear regions . Double staining experiments demonstrated the colocalization of the doxorubicin molecules and the WGA-stained regions as well as a close structural relationship between them and the microtubule system . These results indicate that N-methylformamide interferes with the doxorubicin transport inducing a damage in the microtubular network and the consequent persistence and entrapment of the drug in the regions likely occupied by the Golgi apparatus of tumor cells . This finding could account for the chemosensitizing properties exerted by N-methylformamide.

J Am Soc Nephrol, 1997 Jan, 8(1), 61 - 9
The effect of transfection of antisense cDNA for procollagen alpha 1 (IV) on stimulated proliferation in rat glomerular endothelial cells; Artishevsky A et al.; Glomerular endothelial cells were stably transfected with a pMAMneo-Blue vector recombinant for procollagen alpha 1 (IV) cDNA in the sense (S) or antisense (AS) orientation utilizing a calcium phosphate precipitation technique . Cellular clones resistant to G418 antibiotic were selected and expanded for further analysis . Immunofluorescence microscopy demonstrated less Type IV collagen in the AS clones (1.0 +/- 0.3) than in control parent (P) and S clones (2.0 +/- 0.4) (P < 0.05) . Western analysis showed that the AS clones synthesized 20 +/- 10% of the 205-kd alpha 1 (IV) chain of Type IV collagen compared with P cells (P < 0.05) . As transfected clones demonstrated similar basal proliferation rates as control cells when cultured in 0.5% fetal calf serum (FCS), but failed to undergo fetal calf serum (FCS)-stimulated hyperplasia when grown on standard fibronectin-coated surfaces in 40% FCS (P < 0.05, compared with P- and S-transfected control cells) . There were significant linear relationships between the presence of Type IV collagen as detected by either immunofluorescence microscopy or alpha 1 (IV) peptide chain quantitation by Western analysis and the ability of cells to undergo FCS-stimulated hyperplasia when grown on fibronectin (P < 0.05) . Growth on a surface comprised of fibronectin plus Type IV collagen restored the capacity of AS transfected cells to respond to FCS stimulation (P < 0.001), but had no significant effect on the proliferative behavior of P or S cells . Measurements of AS RNA levels in these cells suggest that the inhibition of stimulated proliferation is determined by the presence of a threshold quantity of cellular AS RNA . These data demonstrate that Type IV collagen plays a critical role in conditioning glomerular endothelial cells to respond to proliferative stimuli.

Clin Diagn Lab Immunol, 1997 Jan, 4(1), 23 - 32
Mycobacterium tuberculosis efpA encodes an efflux protein of the QacA transporter family; Doran JL et al.; The Mycobacterium tuberculosis H37Rv efpA gene encodes a putative efflux protein, EfpA, of 55,670 Da . The deduced EfpA protein was similar in secondary structure to Pur8, MmrA, TcmA, LfrA, EmrB, and other members of the QacA transporter family (QacA TF) which mediate antibiotic and chemical resistance in bacteria and yeast . The predicted EfpA sequence possessed all transporter motifs characteristic of the QacA TF, including those associated with proton-antiport function and the motif considered to be specific to exporters . The 1,590-bp efpA open reading frame was G+C rich (65%), whereas the 40-bp region immediately upstream had an A+T bias (35% G+C) . Reverse transcriptase-PCR assays indicated that efpA was expressed in vitro and in situ . Putative promoter sequences were partially overlapped by the A+T-rich region and by a region capable of forming alternative secondary structures indicative of transcriptional regulation in analogous systems . PCR single-stranded conformational polymorphism analysis demonstrated that these upstream flanking sequences and the 231-bp, 5' coding region are highly conserved among both drug-sensitive and multiply-drug-resistant isolates of M . tuberculosis . The efpA gene was present in the slow-growing human pathogens M . tuberculosis, Mycobacterium leprae, and Mycobacterium bovis and in the opportunistic human pathogens Mycobacterium avium and Mycobacterium intracellular . However, efpA was not present in 17 other opportunistically pathogenic or nonpathogenic mycobacterial species.

Arch Pediatr Adolesc Med, 1997 Jan, 151(1), 35 - 40
Economic impact of pertussis; Pichichero ME et al.; OBJECTIVE: To assess the economic consequences of pertussis in Monroe County, New York (population, 713969), during a 6-year period (1989-1994) . METHODS: Cases of pertussis were identified retrospectively by passive reporting and diagnosis based on culture, positive results of direct fluorescent antibody testing, or Centers for Disease Control and Prevention clinical criteria (cough for > 14 days otherwise unexplained or for > 7 days with paroxysms or whoop epidemiologically linked to a laboratory-confirmed case) . One hundred seven (50%) of 216 subjects with identified cases of pertussis completed questionnaires and had medical records reviewed to ascertain the costs of illness, including physician office visits, laboratory tests, medications, hospitalization, emergency department visits, additional child care, and lost days from school (children) or from work (parents or adult cases) . RESULTS: Ninety-three (87%) of the pertussis case occurred in children . The average duration of illness before diagnosis was 21.3 days (range, 12-37 days) . One hundred one patients (94%) saw a physician at least once; overall, the average number of visits per case was 3.2 (range, 1-15) . Ninety-seven patients (91%) received at least 1 course of antibiotic therapy (average cost for all antibiotics, $95/case), and all took symptomatic treatment (average cost, $48/case) . Fifteen patients (14%) required hospitalization; average cost per admission was $13425 (range, $1732-$69637) . Thirty patients (28%) were seen in emergency departments; average cost was $202 (range, $69-$289) . Additional child care costs ranged from $12 to $2688 . For 50 families, 1 adult lost workdays because of illness or to provide child care for an average of 8.3 days (range, 1-45 days) . For 4 families, 2 adults lost an average of 44 days from work (range, 10-120 days) . The cumulative number of lost workdays was 758 in association with the 107 cases of pertussis . The average full recovery time from illness was 72.9 days (range, 25-115 days) . CONCLUSIONS: Total direct and indirect cost for 107 cases of pertussis in Monroe County was $381052 . The economic burden of pertussis is substantial and encourages broader use of vaccination to prevent disease.

Am Heart J, 1997 Jan, 133(1), 108 - 11
QT interval prolongation and risk of life-threatening arrhythmias during toxoplasmosis prophylaxis with spiramycin in neonates; Stramba-Badiale M et al.; We recently reported two cases of QT interval prolongation and cardiac arrest in newborns receiving antibiotic therapy with spiramycin, a macrolide agent extensively used for toxoplasmosis prophylaxis . In this study we assessed the effects of this drug on ventricular repolarization and on the potential risk of lethal arrhythmias in eight newborn infants in whom toxoplasmosis prophylaxis after birth was necessary . Electrocardiograms (ECGs) and echocardiograms were recorded during spiramycin therapy (350,000 i.u./kg/ day) and after its withdrawal . In a control group of eight healthy newborns matched for age and sex, no differences were found between two ECGs analogously recorded . The QT interval corrected for heart rate (QTc) was longer during spiramycin therapy than after drug withdrawal (448 +/- 32 msec vs 412 +/- 10 msec, +9%, p = 0.021) . QTc dispersion, expressed as the difference between the longest and the shortest value in 12 different leads (QTcmax-min), was also higher during spiramycin therapy (60 +/- 32 msec vs 34 +/- 8 msec, +76%, p = 0.021), mainly because of a major lengthening of the longest QTc (QTcmax) . QTc and QTc dispersion were markedly increased in the two newborns who experienced cardiac arrest after beginning treatment compared with the six neonates who had no drug-induced symptoms . During therapy seven of eight newborns had a rare abnormality in the thickening of the left ventricular posterior wall similar to that observed in patients with congenital long QT syndrome . This abnormality disappeared after drug withdrawal . Thus antibiotic therapy with spiramycin in the neonatal period may induce QT interval prolongation and increase QT dispersion . When this effect on ventricular repolarization is more marked, it may favor the occurrence of torsades des pointes and lead to cardiac arrest.

Mayo Clin Proc, 1997 Jan, 72(1), 33 - 6
Mycoplasma-associated pericarditis; Farraj RS et al.; Mycoplasma pneumoniae-associated pericarditis may result in pronounced morbidity unless appropriate therapy is administered . In this report, we describe a patient who had recurrent episodes of chest pain, intermittent constitutional symptoms, and, eventually, cardiac tamponade due to pericarditis despite treatment with nonsteroidal anti-inflammatory drugs . Immunofluorescence antibody titers were consistent with recent M . pneumoniae infection, and antibiotic therapy resulted in rapid and complete resolution of the patient's symptoms . This treatable entity may be underrecognized and can now be diagnosed with sensitive serologic testing.

South Med J, 1997 Jan, 90(1), 16 - 22
Ceftriaxone versus cefazolin in peripheral arterial operations: a randomized, prospective trial; Ross CB et al.; Serious morbidity and mortality are associated with postoperative wound infections in peripheral vascular surgery . The use of prophylactic antibiotics is considered the standard of care, with attention focused on the most efficacious agent . A prospective, randomized study was conducted to evaluate the efficacy of ceftriaxone versus cefazolin in prevention of postoperative wound infections in a group of patients who had peripheral arterial operations between October 1991 and February 1993 . Patient characteristics associated with an increased risk of postoperative wound infection were evaluated . Prophylaxis was provided for 105 operations with cefazolin and 103 operations with ceftriaxone . The overall wound infection rate was 3.85% . Six operations (5.7%) in the cefazolin group were complicated by wound infection versus 2 operations (1.9%) in the ceftriaxone group . Diabetes (6 infections/64 operations; infection rate, 9%) and a personal history of previous aortocoronary bypass (5 infections/49 operations; infection rate, 10%) were characteristics associated with an increased chance for postoperative wound infection . Ceftriaxone is therapeutically equivalent to cefazolin in the prevention of postoperative wound infections in peripheral vascular surgery.

Obstet Gynecol, 1997 Jan, 89(1), 65 - 70
Pelvic inflammatory disease and human immunodeficiency virus infection; Barbosa C et al.; OBJECTIVE: To identify the effect of human immunodeficiency virus (HIV) infection on the clinical course of pelvic inflammatory disease (PID) . METHODS: Women hospitalized with PID at an urban hospital serving a population at high risk for HIV were studied cross-sectionally . Data abstracted from medical records of 349 women, admitted between July 1992 and April 1994 were linked anonymously to HIV serology . Main outcome measures were length of hospital stay, prolonged fever, tubo-ovarian abscess, surgery, and change in antibiotics . RESULTS: Among the 349 women with PID, 27 were HIV-positive . These HIV-positive women had lower mean white blood cell counts at admission (7411 versus 11,266, P < .01), lower mean lymphocyte counts (1411 versus 1928, P < .01), greater febrile morbidity (54 versus 28.3%, P < .01), and longer hospital stays (10.5 versus 6.4 days, P < .01) than HIV-negative women . Women who were HIV-positive required more time for defervescence and needed to change their antibiotic regimen more frequently (41 versus 12.7%, P < .01); differences in tubo-ovarian abscesses (19 versus 14%, P = .52) or surgery (15 versus 6.2%, P = .10) were not significant . The differences in hospital course between HIV-positive and HIV-negative women were modest, and they were resolved largely by the fourth or fifth hospital day . All HIV-positive women were treated successfully with first- or second-line antibiotic regimens . CONCLUSION: Despite more severe initial presentation and a prolonged hospital course, HIV-positive women with PID, but without other acute illnesses, were treated successfully with standard therapeutic regimens . These observations support current recommendations for hospitalization of HIV-positive women with PID and treatment according to current standards.

J Orthop Trauma, 1997 Jan, 11(1), 45 - 9
Open total talus dislocation: case report and review of the literature; Palomo-Traver JM et al.; An open pure total lateral dislocation of the right talus with extrusion of the whole talar body is reported . Immediately surgical debridement, reduction, and primary closure were accomplished under antibiotic coverage . The ankle was immobilized for 6 weeks, and weight-bearing was restricted for 6 more weeks . Neither avascular necrosis (AVN) of the talus nor infection developed . Both ankle and foot regained full pain-free range of motion at 16 weeks, except for a mild restriction of the last 5 degrees of supination . Four years postinjury, the patient continues in the same preinjury occupation . A thorough review of the literature suggested that (a) immediate closed or open reduction is preferable; (b) if AVN develops, it can be treated in most cases by weight-bearing restrictions; and (c) talectomy, alone or associated with a tibiocalcaneal arthrodesis, should be reserved for an eventual reconstructive procedure, particularly in the event of talus infection.

Can J Anaesth, 1997 Jan, 44(1), 59 - 72
Septic shock; Baxter F; PURPOSE: Many patients with sepsis require surgery for their management, often on an urgent or emergency basis . Anaesthetists are commonly required to manage patients with sepsis and septic shock in the operating room, past anaesthesia recovery area, and the intensive care unit . Since little has been written in the Anaesthesia literature on sepsis and septic shock, a review of this topic was considered appropriate . SOURCE: References were obtained from computerized searches on the National Library of Medicine (English language), recent review articles and personal files . PRINCIPLES FINDINGS: Septic shock is a common cause of morbidity and mortality . Its presentation may be subtle or catastrophic . Successful management depends on an understanding of the pathophysiology of the syndrome, allowing rapid, appropriate resuscitation . This often requires aggressive correction of volume deficit, maintenance of adequate perfusion pressure with inotropic and vasopressor therapy, mechanical ventilation and correction of coagulopathy . Appropriate cultures must be taken and antibiotic therapy started, often empirically . Anaesthetic management should include careful haemodynamic monitoring . Anaesthesia induction and maintenance must be tailored to the haemodynamically unstable patient . CONCLUSIONS: The management of the septic patient in the perioperative period presents a challenge for the anaesthetist . Haemodynamic and respiratory instability should be anticipated . Management requires multisystem intervention and careful anesthetic management.

Antimicrob Agents Chemother, 1997 Jan, 41(1), 141 - 7
Prednisolone at anti-inflammatory or immunosuppressive dosages in conjunction with doxycycline does not potentiate the severity of Rickettsia rickettsii infection in dogs; Breitschwerdt EB et al.; Dogs were experimentally inoculated with Rickettsia rickettsii to determine if anti-inflammatory or immunosuppressive dosages of prednisolone, when administered in conjunction with an antirickettsial antibiotic (doxycycline), induced therapeutically relevant pathophysiological consequences that ultimately influence disease outcome . Although the duration of rickettsemia was prolonged in dogs receiving immunosuppressive, but not anti-inflammatory, corticosteroids, concurrent administration of doxycycline and corticosteroids conferred no other detected detrimental effects . Treatment with doxycycline or doxycycline in conjunction with prednisolone resulted in decreased R . rickettsii-specific antibody titers; however, examination of appropriately timed acute- and convalescent-phase serum samples would have facilitated an accurate diagnosis of Rocky Mountain spotted fever (RMSF) in all 16 dogs . We conclude that the concurrent use of anti-inflammatory or immunosuppressive doses of prednisolone in conjunction with doxycycline, early in the course of experimental RMSF, confers no clinically relevant detrimental effects and that additional studies might be indicated to detect possible beneficial effects in cases of severe or potentially fulminant RMSF . However, because the illness induced in these dogs was of mild to moderate severity, the results of this study should definitely not be construed as supporting the safety or efficacy of prednisolone for treatment of severe canine or human RMSF.

J Invest Dermatol, 1997 Jan, 108(1), 30 - 4
Complementation of hypopigmentation in p-mutant (pink-eyed dilution) mouse melanocytes by normal human P cDNA, and defective complementation by OCA2 mutant sequences; Sviderskaya EV et al.; Mutations in the P gene of humans and the homologous p-locus of mice, respectively, result in the homologous disorders oculocutaneous albinism type 2 (OCA2) and pink-eyed dilution . Although clearly required for melanin biosynthesis, the specific function of the P gene product, a melanosomal transmembrane protein expressed in melanocytes of the skin, hair, and eyes, is not yet known . Here we describe lines of immortal melanocytes and melanoblasts from mice of the null genotype p(cp)/p(25H) . These p-null melanocytes were severely hypopigmented, although they and the melanoblasts expressed mRNAs for a number of melanosomal proteins . Proliferation of the p-null melanoblasts was normal . Both diploid and immortal p-null melanocytes grew more slowly than wild-type melanocytes, however, and were unusually susceptible to the antibiotic G418; these abnormalities were corrected by culture in high concentrations of L-tyrosine . Transfection of the p-null melanocytes with full-length normal human P cDNA resulted in complementation of deficient melanin biosynthesis and hypopigmentation . In contrast, transfection with mutant human P cDNAs containing amino acid substitutions (A481T, V443I) found in patients with OCA2 resulted in minimal or partial correction, consistent with the corresponding pigmentation phenotypes in patients with these mutations . These results demonstrate the utility of this model system for distinguishing true OCA2 mutations from nonpathologic polymorphisms and for quantitating the effect of these mutations on P function.

J Clin Microbiol, 1997 Jan, 35(1), 197 - 200
High rates of genital mycoplasma infection in the highlands of Papua New Guinea determined both by culture and by a commercial detection kit; Clegg A et al.; Duplicate vaginal swabs were collected from 100 women, and comparisons were made between an in-house broth-agar culture system and a commercially available kit, the Mycoplasma IST kit (bioMerieux), for the detection of Mycoplasma hominis and Ureaplasma urealyticum . There was good agreement between the two systems for detection of the genital mycoplasmas in terms of sensitivity, with values of > 92% being obtained . In terms of specificity, the mutual comparisons were less favorable, though specificity values of > 72% were obtained . Statistically there was no significant difference in the performance of the two tests (P < 0.1 for both M . hominis and U . urealyticum) . While the broth-agar culture system was considerably less expensive than the kit, the Mycoplasma IST kit provided additional information on antibiotic susceptibilities and had the advantages of a shelf life of up to 12 months and not requiring the preparation of culture media . The prevalences of colonization obtained for M . hominis and U . urealyticum were extremely high in this randomly selected group of women from periurban and rural settlements in the Eastern Highlands of Papua New Guinea, being > or = 70% for M . hominis and > or = 78% for U . urealyticum . colonization with both genital mycoplasmas simultaneously was also very common, with > or = 60% of women being colonized by both M . hominis and U . urealyticum.

Eur J Pharmacol, 1996 Dec 27, 318(1), 93 - 6
Potent inhibition of angiogenesis by wortmannin, a fungal metabolite; Oikawa T et al.; Wortmannin ({1S-(1 alpha, 6b alpha, 9a beta, 11 alpha, 11b beta)}-11-(acetyloxy)-1,6b,7,8,9a,10,11,11b-octahydro-1- (methoxymethyl)-9a, 11b-dimethyl-3 H-furo{4,3,2-de}indeno{4,5-h}-2-benzopyran-3,6,9-trione), a fungal metabolite that is as a selective inhibitor of phosphatidylinositol 3-kinase, was evaluated for its potential as an inhibitor of in vivo angiogenesis in a bioassay system involving growing chick embryo chorioallantoic membranes . It showed dose-dependent inhibitory activity against embryonic angiogenesis . This inhibition occurred at a dose as low as 1 ng (2.3 pmol) per egg and the ID50 value was 30 ng/egg . These findings suggest that wortmannin is a new angiogenesis inhibitor, and that it may be a lead antibiotic for a novel class of therapeutic agents for angiogenesis-dependent diseases like cancer, diabetic retinopathy and rheumatoid arthritis.

Vet Rec, 1996 Dec 21-28, 139(25), 615 - 8
Treatment and prevention of porcine proliferative enteropathy with oral tiamulin; McOrist S et al.; The effect of an oral treatment or prevention programme, incorporating the antibiotic tiamulin, on the development of proliferative enteropathy in experimentally challenged pigs was studied . Twenty weaner pigs were challenged orally with a virulent inoculum of Lawsonia intracellularis strain LR189/5/83, a British isolate of the causative agent of porcine proliferative enteropathy, and seven control pigs were dosed with a buffer solution . Seven of the 20 challenged pigs were left untreated; they gained less weight than the controls and three of them developed mild to moderate diarrhoea two weeks after the challenge . All seven developed lesions, six visible grossly, of proliferative enteropathy, and numerous intracellular L intracellularis were detected in sections of the intestines examined three weeks after the challenge . To test a 'prevention' dosing strategy for tiamulin, six of the challenged pigs were dosed orally with 50 ppm tiamulin, incorporated in a 2 per cent stabilised premix, given from two days before the challenge until they were euthanased . To test a 'treatment' strategy, the remaining group of seven challenged pigs were dosed orally with 150 ppm tiamulin given in the premix from seven days after challenge until they were euthanased . All the control pigs and the 13 pigs treated with tiamulin, either before or after challenge, remained clinically normal and had no specific lesions of proliferative enteropathy in sections of the intestines examined post mortem.

J Mol Biol, 1996 Dec 13, 264(4), 757 - 69
Solution structure of a parallel left-handed double-helical gramicidin-A determined by 2D 1H NMR; Chen Y et al.; The structure of a parallel left-handed double-helical form of gramicidin was detected by circular dichroism spectroscopy and determined using 500 and 600 MHz NMR in CaCl2/methanol solution . Measurements of TOCSY, DQF-COSY and NOESY spectra were converted into 604 distance and 48 torsional angle constraints for structure calculations . Stereospecific assignments and chi 1 angles were calculated using 3J alpha beta, d alpha beta (i,i), dN beta(i,i) and dN gamma(i,i) . chi 2 angles were determined using d alpha beta(i,i), dN beta(i,i), d beta delta(i,i), dN gamma(i,i) and d alpha gamma(i,i) . The calculations of initial structures were performed using the distance geometry/simulated annealing method in XPLOR . The initial structures were further refined and energy minimized using simulated annealing/molecular dynamics methods . Back-calculations for every generated structure were also performed to check their consistency with the experimental data . 187 final structures with no violations above the threshold conditions (0.05 A, 5 degrees, 5 degrees, 0.5 A and 5 degrees for bonds, angles, improper, NOE and cdihe, respectively) were produced from the 200 initial structures . Twenty structures with the lowest NOE energies were used for further analysis . The average r.m.s . deviations for the 20 structures are 0.64 A for backbone and 1.1 A for all non-hydrogen atoms . Gramicidin in this form, with approximately 5.7 residues per turn, is a parallel double helical dimer . The length along the helix axis is about 30 A and the inner pore diameter varies from 1 to 2 A . It is different from all other gramicidin structures determined to date . The presence of Ca2+ stabilises a conformation that prevents the binding of monovalent cations . It is likely that this structure is related to a non-channel, antibiotic role of gramicidin.

Stud Health Technol Inform, 1997, 43 Pt A, 358 - 62
Implementation problems of decision support system for nosocomial infection; Rems M et al.; Decision support system for nosocomial infection therapy Ptah can reduce antibiotic misuse with data about bacteria resistance and antibiotic ineffectiveness . Resistance vectors in time series show epidemiological problems with resistant bacterias, named house-bacteria . Most important implementation factors are integrated hospital information system and doctors, nurses and managers interested in problems of nosocomial infection.

Gene, 1996 Dec 5, 182(1-2), 145 - 50
Development of a VSV-G protein pseudotyped retroviral vector system expressing dominant oncogenes from a lacO-modified inducible LTR promoter; Wang S et al.; We report the development of a retroviral vector system in which two dominant oncogenes are expressed inducibly in human cells using the lac repressor/lac operator regulatable promoter system . First, the parent vector, pLoCRNLo, was constructed to contain a retroviral long terminal repeat (LTR) promoter that has been modified by incorporation of a lac operator sequence (lacO) . This promoter, LTRo, was shown to mediate IPTG-inducible cat expression in rat cells expressing the lac repressor . The pLoCRNLo backbone was used to develop the retroviral vector LoTPRRNLo which expresses SV40 T antigen and H-ras val12 oncogenes as a dicistronic unit separated by a poliovirus internal ribosome entry sequence (PO-IRES) . LoPRRNLo retrovirus was produced as a VSV-G protein pseudotype and used to infect primary human cells, resulting in the efficient formation of transformed cell lines . Subsequent introduction into the transformed cells of the lac repressor, expressed from a second retroviral vector, MSCV-In(S), resulted in IPTG-responsive oncogene expression and cell growth . This vector system is useful for introducing multiple genes under inducible control into mammalian cells.

Biochem Biophys Res Commun, 1996 Dec 4, 229(1), 295 - 8
IRES bicistronic expression vectors for efficient creation of stable mammalian cell lines; Gurtu V et al.; Stable transfection of mammalian cells is a widely used technique for the study of gene expression and protein purification . However, selection of cell lines expressing desired genes from a large number of candidate clones is often labor-intensive and time consuming . To improve the efficiency of stable cell line production, we have used a bicistronic mammalian expression vector, pIRES1hyg, which contains the internal ribosome entry site (IRES) of the encephalomyocarditis virus (ECMV) . The IRES element permits the translation of two open reading frames from one messenger RNA: one reading frame encoding the recombinant protein of interest and the other an antibiotic resistant marker (e.g . hygromycin) . We demonstrate that the use of the bicistronic vector significantly facilitates the creation of stable mammalian cell lines, because all selected antibiotic-resistant colonies express the recombinant gene of interest . Therefore, the use of the pIRES1hyg bicistronic vector for stable transfection eliminates the need to screen large numbers of colonies to find functional clones . We conclude that the IRES bicistronic vector provides a powerful tool for efficient selection of stable transformants in mammalian cells.

Rev Sci Tech, 1996 Dec, 15(4), 1415 - 29
Diagnosis and control of contagious caprine pleuropneumonia; Thiaucourt F et al.; The diagnosis of contagious caprine pleuropneumonia (CCPP) has often been considered difficult . This is because of the confusion that can arise with other mycoplasmoses of small ruminants . Symptoms and lesions can be similar and the isolation of M . capricolum subsp . capripneumoniae (MccF38) requires skilled technicians . Once MccF38 strains are isolated, their identification should not be difficult . New techniques, such as polymerase chain reaction, now offer the possibility of identifying MccF38 directly from dried samples . However, the isolation of MccF38 strains is always required for an official declaration of infection . Until now, the official serological test has been the complement fixation test; the main drawbacks being lack of sensitivity and specificity and also the short persistence of antibodies detected by this technique . The specific competition enzyme-linked immunosorbent assay has now been developed and should enable wide serological enquiries to determine the real prevalence of the disease . Antibiotic treatments are effective but may not prevent persistence in latent carriers . An inactivated vaccine with saponin as an adjuvant has been produced in Kenya, which protects goats for approximately one year.

Baillieres Clin Haematol, 1996 Dec, 9(4), 727 - 41
Gut lymphomas; Zucca E et al.; Gut lymphoma still remains the subject of much debate and controversy with respect to pathological classification, clinical staging and treatment . This is mainly due to the fact that most studies reported retrospective non-randomized evaluations of small series and lacked uniformity in histological classification, patients' characteristics and type of treatment . Moreover, most of the historical series were published before the recognition of MALT as the origin of most GI lymphomas . Hence, there is a compelling need for the use of modern histological criteria for primary GI lymphomas because of their unique histology, special features and origin in mucosal tissue . General adoption of the histological classification proposed in 1988 by Isaacson et al (Table 1) can be recommended which follows the general principles of the Kiel Classification and includes the MALT lymphomas as a particular disease entity . Combination chemotherapy is the treatment of choice for gut lymphomas with aggressive histology and multiple node involvement or disseminated disease . The effectiveness of combination chemotherapy in advanced disease has excited a reconsideration of the role of primary surgery in less advanced cases where surgery has, historically, been the initial procedure of choice . This is particularly true for gastric lymphomas where it is possible that, in future, surgery will be resorted to as a potential approach for salvage when complete remission is not achieved with conservative therapy . For primary intestinal lymphoma, however, there are as yet no studies which clearly demonstrate that surgery is not necessary . With respect to the group of localized low-grade MALT lymphomas of the stomach and the indolent nature of the disease make plausible a conservative approach, with antibiotic eradication of H . pylori as the sole initial treatment . This may avert or at least postpone the indication for surgical resection in the majority of patients.

Arch Esp Urol, 1996 Dec, 49(10), 1029 - 33
{Polycystic kidney in the adult and kidney transplantation . Our experience}; Monreal Garcia de Vicuna F et al.; OBJECTIVES: To determine the need for nephrectomy prior to renal transplantation in patients with adult polycystic renal disease . METHODS: We reviewed the records of 54 (31 females, 23 males) of 62 patients with polycystic renal disease that had been treated at our center from 1951 to 1994 . Eight of the earlier cases, whose complete clinical data were unavailable, were excluded from the study . The patients were classified into three groups: nephrectomized transplanted, nephrectomized non-transplanted and non-nephrectomized transplanted patients . RESULTS: No patient had required nephrectomy due to a tumor . No surgical difficulty during transplantation had been reported in the non-nephrectomized patients . Nephrectomy had been performed in most of the cases for hematuria or preparatory to renal transplantation . The infections complications (11.76%) were resolved with antibiotic therapy . CONCLUSIONS: In the absence of renal tumor and given the low prevalence of complicated cysts, in our view it is unnecessary to perform nephrectomy routinely prior to renal transplantation in patients with adult polycystic renal disease . Nephrectomy should be reserved for cases with severe cystic complications, such as severe intracystic hemorrhage, hematuria causing anemia, pyonephrosis, or patients with grossly enlarged kidneys in whom we suspect that technical difficulties might arise at the time of transplantation.

Unfallchirurg, 1996 Dec, 99(12), 914 - 24
{Infected pseudarthrosis}; Ekkernkamp A et al.; Sequestrectomy, fragment fixation, wound treatment and bone grafting are the old principles of infected non union surgery . Today these principles are the frame, which contents a more aggressive treatment . Sequestrectomy is a radical excision of the complete infected bone-soft-tissue-scar, the resulting defects are covered by one of the various techniques (skin-traction, flap surgery, bone shifting, etc.) . Out of 71 infected non unions, treated by radical resection and bone segment transport, healing rate without recurrence of infection was 94%, in 3 additional patients (4%) amputation was performed . For bone fragment fixation, a non devastating implant, like external fixateur, is preferred . To close the wound, the law of avoiding a dead space is used . Defects are closed by muscle flaps, by fragment shortening or by a antibiotic spacer temporarily . The skin is closed by skin-traction techniques or with flap surgery . After soft tissue healing, small bone defects are filled by autografts, defects of more than 3-4 cm with transported segments . Previous limb shortening to close bone defects, with a lengthening later in a "healthy" region, is also possible . Local antibiotic wound treatment cases a significant reduction of the contamination rate, improved dressing techniques support wound healing free of infection . This therapeutic techniques are comparable to open fracture treatment, where by similar surgery a very low infection rate can be achieved.

Ophthalmologe, 1996 Dec, 93(6), 680 - 7
{Phenocopies of hereditary retinal degenerations}; Kellner U et al.; BACKGROUND: Phenocopies of retinal degenerations mimic the clinical signs of inherited retinal dystrophies . The purpose of this study is to discuss the difficulties of differential diagnosis . METHODS: Four patients were examined ophthalmologically and by standard electroretinography (ERG) . RESULTS: (a) A 19-year-old woman presented with progressive visual loss, bone spicules, concentric narrowing of visual fields and extinguished ERG responses . At 3 years of age, she had developed a retinopathy induced by an infection with measles . (b) A 27-year-old man had bilateral visual loss, night blindness, pigmentary retinal changes, marked attenuation of visual fields and a reduced ERG . All signs of syphilitic retinopathy were regressive under antibiotic therapy . (c) A 59-year-old man showed a visual loss in the left eye, bilateral photophobia, color vision disturbances and a ring scotoma . Cone responses were nonrecordable in the ERG . A birdshot chorioretinopathy was suggested by ophthalmoscopic appearance and HLA typing . (d) A 40-year-old woman presented with paravenous pigmented retinochoroidal atrophy associated with Behcet disease . CONCLUSION: Systemic viral or bacterial inflammation as well as autoimmune disorders may present as phenocopies of hereditary retinal degenerations . A faulty diagnosis may have serious consequences, because necessary therapy may be withheld . Moreover, the misdiagnosis of a hereditary retinal degeneration may have severe effects on the psychic and social status of the patient.

Br J Biomed Sci, 1996 Dec, 53(4), 294 - 301
Anaerobic cocci of clinical importance; Wren MW; The current knowledge is reviewed concerning the anaerobic cocci, in particular those of clinical relevance . The anaerobic cocci are defined and their current taxonomic positions discussed . It is clear that new genera and species await to be characterised fully . The overwhelming majority found in clinical material belong to the genus Peptostreptococcus, with the remainder belonging to the veillonellae and, possibly, ruminococci . Human infections with other anaerobic cocci are extremely rare . Their morphology, metabolism and culture, and role in clinical infections are assessed . The methods for isolation and identification, which for some species are difficult, are presented, together with brief summaries of the clinically important species . The review concludes with the current status of antibiotic susceptibilities and the methods used to test susceptibility in vitro . There is no current consensus as to which susceptibility test method is the method of choice.

Exp Eye Res, 1996 Dec, 63(6), 739 - 45
Endothelial toxicity of ceftazidime in anterior chamber irrigation solution; Duch-Samper AM et al.; Due to the high toxicity of aminoglycoside antibiotics, many authors prefer to use third generation cephalosporines in the prophylaxis and treatment of intraocular infections . The aim of the present study was to determine safe ceftazidime levels in anterior chamber irrigation solution . Twenty-two eyes of 12 white New Zealand rabbits were divided into six groups of two animals each . Double paracentesis was performed in both eyes, irrigating the right eye with 250 ml of BSS-Plus (BSS+) solution, and the left eye with 250 ml of BSS+ solution with increasing concentrations of ceftazidime (2, 3, 4, 6 and 8 mg ml-1) . Each rabbit was killed at the end of surgery, except the last group, which received BSS+ and BSS+ with 8 mg ml-1 of ceftazidime, respectively, in one eye, and were then killed 24 hr later . Endothelial lesions were assessed by silver nitrate staining . We considered lesions endothelial silver affinity ranging from minimal (1-2+) to intense (3-4+) . 1-2+ silver affinity was found in 4 +/- 1.35% of endothelial cells in the controls; this percentage in turn increased with antibiotic concentration (6.1 +/- 1.13%, 6.7 +/- 0.4%, 7.2 +/- 1.36%, 7.3 +/- 1.93% and 7.5 +/- 1.83%, respectively) . The percentage of 3-4+ silver affinity was 0.18 +/- 0.17% in the controls, and likewise increased with antibiotic concentration (0.22 +/- 0.11%, 0.37 +/- 0.09%, 2.8 +/- 0.63% and 3.1 +/- 0.46%, respectively) . The increase in affinity was greatest up to the 4 mg ml-1 concentration . In the last group there were zones of endothelial alterations in morphology and size, with signs of attempted repair in the eye treated with antibiotic, but none in the case treated only with BSS+ . Ceftazidime concentrations above 3 mg ml-1 in intraocular infusions induce endothelial cell toxicity.

Leuk Lymphoma, 1996 Dec, 24(1-2), 93 - 101
Immunosuppressive toxicity of CAMPATH1H monoclonal antibody in the treatment of patients with recurrent low grade lymphoma; Tang SC et al.; We have studied, as part of a group of international multicenter phase II clinical trials, the toxicity and effectiveness of CAMPATH1H administered intravenously three times a week in an outpatient setting to patients with recurrent or progressive low grade lymphoma . We report here on the toxicity and therapeutic results of the first seven patients treated before the study was closed prematurely because of unacceptable toxicity . Classical complete or partial responses of treatment were seen in three of seven patients . One complete response lasted 8.5 months and the other complete response is ongoing at 1 year . Responses occurred in nodal sites as well as in skin and peripheral blood . The first three or four antibody infusions in each patient was associated with grade 1 or 2 side-effects including rigor, fever, facial flushing, nausea, vomiting, hives, wheezes, hypotension, and/or diarrhea but these subsequently decreased or disappeared . The most significant toxicity was profound lymphopenia and associated infection, usually viral . Six of seven patients had culture or serologically documented infections and four patients had two or more such episodes . All infections responded to temporary discontinuation of antibody therapy and appropriate antiviral or antibiotic agents . We conclude that CAMPATH1H monoclonal antibody has therapeutic activity against low grade non-Hodgkin's lymphoma but that this activity is limited by marked lymphopenia and an unacceptably high frequency of serious infection at the dose and schedule used in this trial.

Nippon Geka Gakkai Zasshi, 1996 Dec, 97(12), 1042 - 7
{Basic and clinical control of nosocomial infections}; Furuya N et al.; Nosocomial infections, especially opportunistic infections and occupationally acquired infections, are causing major problems in perioperative period . Opportunistic infections are increased by opportunism secondary to antibiotic therapy and lower body defences . Organisms that cause opportunistic infections come from either exogenous or endogenous sources . Exogenous infections result from transmission of organisms from a source other than the patient . Control of person-to-person spread, such as handwashing and gown technique, disinfection and sterilization of equipment, and environmental cleaning are necessary to prevent exogenous infections . Endogenous infections are caused by the patient's own flora . Antibiotic policies are required to prevent endogenous infections . The main preventive measure of occupationally acquired infections, especially blood-borne infections, is practices of universal precautions . Universal precautions are intended to prevent parenteral, mucous membrane, and nonintact skin exposures to blood-borne pathogens in health care settings.

Intern Med, 1996 Dec, 35(12), 957 - 60
Crohn's disease associated with colo-bronchial fistula; Mera A et al.; An 18-year-old female patient with Crohn's disease presented with left lower lobe pneumonia and pleural effusion which were resistant to treatment with antibiotics . Colo-bronchial fistula had not been recognized until she coughed up yellow sputa with feculent odor and developed acute respiratory distress syndrome . This type of fistula is a rare complication of Crohn's disease, but the present case certainly alerts physicians to search for a fistula between the bronchus and gastrointestinal tract when encountering patients with Crohn's disease accompanied by antibiotic-resistant chronic pneumonia.

J Antimicrob Chemother, 1996 Dec, 38(6), 1049 - 53
Inhibition of the respiration of multi-drug resistant clinical isolates of Mycobacterium tuberculosis by thioridazine: potential use for initial therapy of freshly diagnosed tuberculosis; Amaral L et al.; Chlorpromazine and thioridazine are phenothiazines employed in the treatment of psychosis . These agents inhibited the respiration of clinical isolates of Mycobacterium tuberculosis resistant to streptomycin, rifampin, isoniazid, ethambutol and/or pyrazinamid, all first line drugs . Since any adverse reaction to thioridazine is generally less severe than to chlorpromazine, the possibility is attractive that thioridazine may have a potential in the initial management of patients with newly diagnosed tuberculosis with an as yet undetermined antibiotic susceptibility profile.

J Antimicrob Chemother, 1996 Dec, 38(6), 969 - 76
A comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in humans: a study of once daily administration by intramuscular and intravenous routes; Goonetilleke AK et al.; Pleural fluid and serum pharmacokinetics of ceftriaxone were performed in thirteen patients with pleural effusion . One gram of ceftriaxone was administered once daily intravenously in six patients and intramuscularly in seven patients . Ceftriaxone concentrations were measured in serum and pleural fluids in both groups on the first day of administration and in four patients of the intramuscular group on the fourth day of administration . The mean serum peak concentration at 1 h was 199 mg/L (S.E.M . 63.2) in the iv group and 80.5 mg/L (S.E.M . 12.0) in the im group . The mean serum trough concentrations in the two groups at 24 h were 27.5 mg/L (S.E.M . 12.6) and 29.7 mg/L (S.E.M . 5.2) respectively . In the pleural fluid, mean peak concentration was 20.1 mg/L (S.E.M . 4.7) at 6 h in the iv group and 15.3 mg/L (S.E.M . 5.1) at 12 h in the im group . The mean trough concentration was 9.6 mg/L (S.E.M . 1.9) and 13.3 mg/L (S.E.M . 3.1) at 24 h in the two groups respectively . On the fourth day of intramuscular administration the serum and pleural fluid peak and trough concentrations were higher when compared with the first day, consistent with a cumulative effect . The serum and pleural fluid concentrations of ceftriaxone following intravenous and intramuscular administration were well above the MIC90 of most common respiratory pathogens indicating good penetration into extracellular spaces . Further, these serum and pleural fluid antibiotic concentrations could be maintained even after a single intramuscular injection of the drug, thus indicating its usefulness as a parenteral mode of therapy on a domicilliary basis with a significant cost-saving potential . In conclusion, intramuscular administration of ceftriaxone would appear to be a convenient method of administering parenteral therapy in lower respiratory tract infections in the hospital and community, with pharmacokinetics very similar to those exhibited by the intravenous route.

J Biomol Struct Dyn, 1996 Dec, 14(3), 303 - 16
Molecular dynamics simulation of conformational flexibility of alamethicin fragments in aqueous and membranous environment; Kothekar V et al.; We present here results on molecular dynamics (MD) simulation on two fragments of channel forming antibiotic peptide Alamethicin, containing isoamino butyric acid (Aib) . Simulations are carried out in aqueous and membranous environment in a bilayer of 39 molecules of Dimyristoyl phosphatidyl choline (DMPC) . The peptides Boc-Pro-Aib-Ala-Aib-OBzl (Alam 1) and Boc-Leu-Aib-Pro-OBzl (Alam 2) were simulated from their crystallographic coordinates . The bilayers were built from two different conformations (A and B) of DMPC reported in crystal data . The P-N dipoles were arranged hexagonally with surface area per lipid molecule 66.5 A degrees 2 and P-P separation across the bilayer 34 A degrees . They were hydrated by 28.6 and 25.5 water molecules per DMPC molecule . Simulations are done using AMBER 4.0 package in constant number volume temperature (NVT) condition for 100 pico seconds (ps) in aqueous environment and 250 ps of equilibrated bilayer . Geometric parameters of lipids as: bilayer thickness, order parameter of the chains, transfraction of chain torsional angles were monitored . We also monitored geometric parameters of the peptides as backbone torsional angles, distances amongst C alpha atoms, angles between C alpha atoms, movement of center of gravity (CG) along and perpendicular to bilayer normal . We find that membrane bilayer is slightly disturbed due to the presence of peptides . In case of alam 2 in water angles phi 1 and phi 3 showed larger variation in water compared to same in the bilayer . The peptide conformation is more stable in DMPC bilayer . However the peptides showed movement along and perpendicular to bilayer normal . This we believe is due to hydrophobic nature of these peptides.

Mol Med Today, 1996 Dec, 2(12), 499 - 502
Drug-resistant bacteria: responding to the infectious disease crisis; Jack DB; The 1990s have been a period of growing anxiety about the emergence of antibiotic-resistant bacteria . Public health, society and the research community must respond quickly to safeguard existing drugs and develop new ones to prevent resistance overwhelming healthcare systems worldwide.

J Laryngol Otol, 1996 Dec, 110(12), 1166 - 8
Spontaneous internal jugular vein thrombosis and recurrent laryngeal nerve palsy: a rare simultaneous presentation of an occult malignant neoplasm; Kalan A et al.; Internal jugular vein thrombosis is an uncommon potentially life-threatening disorder caused by various conditions . Non-spontaneous internal jugular vein thrombosis is an uncommon condition associated in the pre-antibiotic area with deep-neck infections . Currently iatrogenic trauma to the internal jugular vein from catheterisation and repeated intravenous injections by drug abusers are the leading causes of thrombosis . Spontaneous internal jugular vein thrombosis may occur when there are no apparent pre-disposing mechanical or inflammatory causes although a few of these patients may harbour an occult malignant neoplasm . Hence, careful investigation and follow-up are vital . Thrombosis in Trousseau's syndrome is usually confined to the vascular system of the extremities and the viscera . However, secondary to the paraneoplastic hypercoagulable state, thrombosis can occur in the large veins of the head and neck region . We understand this to be the first case where spontaneous internal jugular vein thrombosis and ipsilateral recurrent laryngeal nerve paralysis were the only initial manifestations of an occult malignancy.

Trends Pharmacol Sci, 1996 Dec, 17(12), 445 - 9
Amphotericin B: new life for an old drug; Hartsel S et al.; Interest in amphotericin B has undergone a renaissance of sorts over the past few years despite the advent of the newer less-toxic azole antifungal drugs . This is, in part, owing to the unfortunate increase in fungal diseases worldwide . It is also, however, owing to the reduction of toxicity via innovative liposomal delivery systems, better understanding of drug mechanism and distribution and a surprising expansion of the antibiotic spectrum of amphotericin B to include select virus, parasite and possibly prion infections . In this article, Scott Hartsel and Jacques Bolard summarize the recent leaps in pharmaceutics, spectrum and molecular mechanistic knowledge of this surprising molecule.

J Clin Pharmacol, 1996 Dec, 36(12), 1154 - 60
Effect of dirithromycin on human CYP3A in vitro and on pharmacokinetics and pharmacodynamics of terfenadine in vivo; Goldberg MJ et al.; Terfenadine is metabolized by the cytochrome P-450 3A subfamily of enzymes (CYP3A) . Certain macrolide antibiotic agents inhibit CYP3A and, when coadministered with terfenadine, result in a drug interaction . The authors compared the abilities of dirithromycin (a new macrolide antibiotic agent), its major metabolite erythromycylamine, and the known CYP3A substrate terfenadine to inhibit CYP3A in vitro . The hydroxylation of midazolam in human liver microsomes was used as a probe for CYP3A activity . Dirithromycin and erythromycylamine were low affinity inhibitors of CYP3A (inhibitory binding affinities of 493 mumol/L and 701 mumol/L, respectively); conversely, terfenadine was a moderate affinity inhibitor (inhibitory binding affinity of 28 mumol/L) . Based on these data, the authors tested the hypothesis that dirithromycin would not interact with terfenadine in humans . Six healthy men received terfenadine alone (60 mg twice daily) for 8 days, after which dirithromycin (500 mg once daily) was added to the terfenadine regimen for an additional 10 days . The pharmacokinetics of terfenadine (and its acid metabolite) and the QTc interval were measured during both treatments, and it was found that neither parameter was affected . In this study, dirithromycin was found to have low affinity for human CYP3A in vitro, which is in accordance with the study's finding that in vivo dirithromycin has no major effect on the metabolism of the CYP3A substrate terfenadine in humans.

Cardiovasc Surg, 1996 Dec, 4(6), 792 - 5
Expeditious management of ischemic invasive foot infections; Chang BB et al.; Management of infected ischemic diabetic limbs requires antibiotic therapy, abscess drainage, and revascularization . However, revascularization is often delayed for several days or weeks as the infection is controlled . In an effort to decrease hospital stay and costs and to increase limb salvage, a series of 974 extremities with distal occlusive disease were managed with autogenous distal bypass . Some 136 of these limbs (125 diabetic) had severe invasive infections . These patients received intravenous antibiotics in all cases and abscess drainage if necessary . Vascular reconstruction was carried out as soon as possible, within 48 h of admission . An in situ bypass was used preferentially (107 cases) . Patients were maintained on intravenous antibiotics in the perioperative period . Partial foot amputations, when necessary, were performed in 111 cases, usually 3-5 days after vascular reconstruction . There were no graft infections or major wound infections . There were two cases of skin edge necrosis requiring reoperation due to flap mobilization and consequent ischemia . Urgent revascularization with an autogenous conduit may be carried out in patients with invasive foot infections expeditiously, with high rates of limb salvage . Graft and wound infections are not common in this setting . Costly prolonged pre-bypass hospitalization in these cases is unnecessary.

Kansenshogaku Zasshi, 1996 Dec, 70(12), 1242 - 53
Effect of recombinant human granulocyte colony-stimulating factor on combination therapy with aztreonam and clindamycin for infections in neutropenic patients with hematologic diseases; Toyama K et al.; The present multicenter study was performed to evaluate the effect of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on combination therapy using aztreonam (AZT) and clindamycin (CLDM) to treat severe infection in neutropenic patients with hematologic diseases . Forty-three neutropenic patients with infections (rhG-CSF group) were treated with AZT (2 g) and CLDM (600 mg) 2-3 times daily as well as rhG-CSF (Lenograstim or Filgrastim: 2-5 mu/kg/day) . The clinical efficacy of this regimen was compared to that obtained in 44 febrile neutropenic patients, with hematologic diseases, who received only AZT and CLDM in a previous study (historical control group) . The overall efficacy rate was 69.8% (30/43) in the rhG-CSF group and 65.9% (29/44) in the historical control group . Although the neutrophil count was significantly increased and C-reactive protein tended to be lower in the rhG-CSF group, the daily maximum body temperature profiles of the 2 groups were nearly the same . These results suggest that rhG-CSF is of little benefit in the treatment of single infectious episodes in neutropenic patients, and that appropriate antibiotic therapy is more important.

Minim Invasive Neurosurg, 1996 Dec, 39(4), 108 - 12
Stereotactic aspiration and drainage of brain abscesses . Experience with 9 cases; Skrap M et al.; The first-line treatment for brain abscesses is still a much-debated argument . Recently, stereotactic aspiration of these lesions has gained ground as a valid alternative to the traditional medical and/or surgical therapeutical treatments . From 1991 to 1995, 9 patients affected by intracranial abscesses were surgically treated by stereotactic puncture of the lesion and drainage of pus, using the Kelly-Goerss stereotactic system . Multiple abscesses were present in one case . Specific antibiotic therapy was used in the post-operative stage, when possible . One death occurred four weeks after surgery for acute ischemia of the brain stem . Follow-up CT demonstrated gradual resolution of the abscesses in all the cases and a successful return to normal daily life in all the surviving patients . In one case, recurrence of the abscess occurred two months after resolution: a successful result was obtained by steroids and broad-spectrum antibiotic therapy alone . Possible advantages of this technique are discussed and compared with the traditional routes . The literature concerning this argument is reviewed.

J Paediatr Child Health, 1996 Dec, 32(6), 525 - 31
Risk-stratified nosocomial infection surveillance in a neonatal intensive care unit: report on 24 months of surveillance; Ferguson JK et al.; OBJECTIVE: To document the nosocomial infection rate in a single neonatal intensive care unit (NICU) in terms of patient workload and device utilization . METHODOLOGY: Nosocomial infections have been identified and documented by the methodology described by the National Nosocomial Infection Surveillance System (NNIS), Centres for Disease Control, Atlanta . In addition, antibiotic usage has been surveyed in the NICU and standardized measures of patient exposure to antibiotics stratified by birthweight and gestational age have been described . RESULTS: Overall nosocomial infection rates compared favourably with the published NNIS figures at 6.2 infections per 100 admissions or 4.8 per 1000 patient days . Infection rates were significantly higher in lower birthweight groups . Device-related infection rates in each birthweight cohort were also very close to published figures and varied less with birthweight group . Antibiotic exposure averaged 12% of total admission days, less than previously published data . CONCLUSIONS: The NNIS system is applicable to Australian NICU and provides an effective tool for monitoring infection episodes.

Minerva Urol Nefrol, 1996 Dec, 48(4), 189 - 91
{Renal agenesis and homolateral seminal vesicle cyst . Case report}; Casetta G et al.; The authors present a case of renal agenesis and seminal vesicle cyst in a young man, diagnosed because of several micturion disorders partially cleared up with antibiotic therapy . We discuss about the diagnosis technique which includes Ultrasound Scanner, Computed Tomography, Magnetic Resonance and pelvic arteriography . Then we describe the surgical approach and finally we discuss about embryogenesis.

Microbiology, 1996 Dec, 142 ( Pt 12), 3407 - 14
Identification of an overexpressed yeast gene which prevents aminoglycoside toxicity; Prezant TR et al.; Aminoglycoside antibiotics, used to treat bacterial infections by interfering with proofreading during protein synthesis, cause sensorineural hearing loss in genetically susceptible individuals . The only aminoglycoside-hypersensitivity mutations which have been described in humans are in the mitochondrial 125 rRNA gene, potentially allowing increased antibiotic binding to mitochondrial ribosomes . To identify additional predisposing mutations, a yeast model system was used to isolate genes which interact with or bypass the effects of aminoglycoside antibiotics . A novel yeast gene was isolated which, in high copy, confers neomycin resistance to yeast transformants . The neomycin-resistance 1 gene (NEO1) encodes a potential 1151 as integral membrane protein, most homologous to the yeast DRS2 gene product, a Ca(2+)-ATPase involved in cytoplasmic ribosome assembly . The N-terminus of Neo1p is partially homologous to abrin A-chain, another protein which interacts with cytoplasmic ribosomes . Mutagenesis experiments demonstrate that the NEO1 product is essential for vegetative growth and that the drug-resistance phenotype requires ATPase function.

Int J Hematol, 1996 Dec, 65(1), 31 - 40
Herbimycin A down-regulates messages of cyclin D1 and c-myc during erythroid differentiation of K562 cells; Yamada H et al.; The ansamycin antibiotic, herbimycin A, is a potent tyrosine kinase inhibitor, and induces the erythroid differentiation of bcr-abl-possessing K562 cells . The growth of K562 cells was cytostatically reduced to less than 50% of the control level at 48 h by 0.5 microgram/ml of herbimycin A treatment . A total of 12% and 53% of the treated cells were benzidine-positive at 24 h and 48 h, respectively . The percentage of cells in the S phase decreased rapidly from 60% to 15% after 12 h of treatment . The reduction of S phase cells persisted until 24 h, whereas the G1 population conversely increased . Then underphosphorylated retinoblastoma gene product increased from 6 h to 24 h, but returned to baseline at 48 h . Most cell cycle controlling genes were unchanged by herbimycin A treatment . However, both cyclin D1 and c-myc were prominently down-regulated in the early phase of treatment, corresponding to the decline of the S phase population . Cyclin D1 was initially down-regulated to an undetectable level at 6 h, although its expression recovered gradually from 12 h and returned to baseline at 24 h . c-myc was also down-regulated from 1 h to 6 h . These data suggest that signals originating from bcr-abl kinase are at least partly transduced through both c-myc and cyclin D1, and that herbimycin A-induced erythroid differentiation occurs during or after the cessation of growth due to interference with these signals.

Can J Microbiol, 1996 Dec, 42(12), 1263 - 6
A Saccharomyces cerevisiae phleomycin-sensitive mutant, ph140, is defective in the RAD6 DNA repair gene; He CH et al.; The antibiotic bleomycin is used as an anticancer agent for treating a variety of tumours . The antitumour effect of bleomycin is related to its ability to produce lesions such as apurinic/apyrimidinic sites and single- and double-strand breaks in the cellular DNA . Phleomycin is a structurally related form of bleomycin, but it is not used as an anticancer agent . While phleomycin can also damage DNA, neither the exact nature of these DNA lesions nor the cellular process that repairs phleomycin-induced DNA lesions is known . As a first step to understand how eukaryotic cells provide resistance to phleomycin, we used the yeast Saccharomyces cerevisiae as a model system . Several phleomycin-sensitive mutants were generated following gamma-radiation treatment and among these mutants, ph140 was found to be the most sensitive to phleomycin . Molecular analysis revealed that the mutant ph140 harbored a mutation in the DNA repair gene RAD6 . Moreover, a functional copy of the RAD6 gene restored full phleomycin resistance to strain ph140 . Our findings indicate that the RAD6 protein is essential for yeast cellular resistance to phleomycin.

Spine, 1996 Dec 1, 21(23), 2806 - 8
Spinal osteomyelitis presenting with a life-threatening pleural empyema; Jari S et al.; STUDY DESIGN: This case report illustrates a rare presentation of spinal osteomyelitis that initially manifested as a life-threatening pleural empyema leading to misdiagnosis . OBJECTIVES: A high index of suspicion is required to make the correct diagnosis of spinal osteomyelitis, especially with unusual presentations . Appropriate antibiotic management should be commenced immediately the diagnosis is made . SUMMARY OF BACKGROUND DATA: A review of the literature reveals five previous cases of vertebral osteomyelitis associated with pleural effusions . In three of these, the effusions were reactive and sterile . There is only one previous case of a pleural empyema related to primary spinal osteomyelitis . There also is one case report of vertebral osteomyelitis presenting as a mediastinal abscess . METHODS: A case is presented of a man thought to have bronchogenic carcinoma with a destructive vertebral metastasis who was sent for palliative radiation therapy . A life-threatening pleural effusion subsequently developed, and after additional investigation, he was found to have spinal osteomyelitis with a pleural empyema . RESULTS: The empyema was drained through an indwelling chest tube, and the patient was administered appropriate antibiotics . He made a complete and uneventful recovery . CONCLUSIONS: The case illustrates a rare presentation of spinal osteomyelitis . It exemplifies the dictum that if a malignant disease is suspected, every effort has to be made to establish a histologic diagnosis to prevent inappropriate management and the potentially devastating consequences of an incorrect diagnosis . It also high-lights the difficulties in diagnosis of vertebral osteomyelitis with empyema . With correct management, the prognosis is excellent.

Gan To Kagaku Ryoho, 1996 Dec, 23(14), 1916 - 9
{Characteristic and effective usage of adriamycin}; Horiuchi K et al.; The utility of adriamycin (doxorubicin), an anti-cancer antibiotic, for the treatment of transitional cell carcinoma of the bladder has been appreciated . Adriamycin is still used intravesically for superficial bladder cancer to avoid implantation of floating cancer cells after transurethral resection, to decrease the incidence of recurrence and treat an unresected part of the tumor . On the other hand, cisplatin-based multi-drug chemotherapies including adriamycin have proven effective in treating locally and systemically advanced bladder cancer.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 1996 Dec, 82(6), 610 - 2
Amoxicillin-related postextraction bleeding in an anticoagulated patient with tranexamic acid rinses; Bandrowsky T et al.; This report describes a patient who had significant postoperative bleeding 4 days after undergoing surgery while using a tranexamic acid (4.8%) mouth rinse protocol for local control of hemostatis . Patients undergoing dentoalveolar surgery who are receiving chronic oral anticoagulants are treated with a tranexamic acid mouth rinse at our hospital . No systemic modification of their coagulation status is attempted . The postoperative bleeding problem that developed was determined to be caused by an antibiotic-induced vitamin K deficiency rather than a failure of the tranexamic acid protocol.

Bone Marrow Transplant, 1996 Dec, 18(6), 1175 - 8
An economic evaluation of peripheral blood stem cell transplantation as an alternative to autologous bone marrow transplantation in multiple myeloma; Duncan N et al.; Autologous peripheral blood stem cell transplantation (PBSCT) is increasingly being utilised as an alternative to autologous bone marrow transplantation (ABMT) in the treatment of malignant diseases . We have performed a pharmacoeconomic study using cost-minimisation analysis to evaluate the two techniques in a population of multiple myeloma patients undergoing PBSCT (n = 37) or ABMT (n = 14) . In the PBSCT group, the time to > 0.5 x 10(9)/l neutrophils was significantly shorter (16 vs 22 days; P = 0.0019) as was the time to > 50 x 10(9)/l platelets (19 vs 27 days; P = 0.0019) . The faster haematopoietic recovery resulted in a reduced period of intravenous antibiotic therapy (12 vs 19 days; P < 0.0001), reduced requirements for platelet transfusions (12 vs 31.5 units; P = 0.0005), and ultimately, a significant reduction in duration of hospitalisation (19 vs 27.5 days; P < 0.0001) . These clinical benefits translated into economic benefits such that the total cost in the PBSCT group was 27.5% less than in the ABMT group (< Pounds 7995 vs < Pounds 11026; P = 0.0001) . We conclude that the use of PBSCT as an alternative to ABMT in patients with multiple myeloma is associated with demonstrable economic advantages in addition to clinical benefits.

Anaesth Intensive Care, 1996 Dec, 24(6), 647 - 50
Acute renal failure in cardiac surgical patients, potentiated by gentamicin and calcium; Schneider M et al.; A retrospective study in coronary artery bypass graft patients was undertaken to assess the effect of gentamicin and a bypass prime with a high calcium on the incidence of renal failure . Patients who received both Haemaccel (polygeline, Hoechst Marion Roussel) (calcium concentration 6.25 mmol/l) in the bypass prime and gentamicin perioperatively had a higher incidence of renal failure compared with those who received only Haemaccel (P = 0.005), only gentamicin (P = 0.002) or neither (P = 0.0001) . We suggest that the combination be avoided in this group of patients.

Pediatr Infect Dis J, 1996 Dec, 15(12), 1123 - 4
Frequency of respiratory syncytial virus in hospitalized infants with lower acute respiratory tract infection in Colombia; Bedoya VI et al.; PIP: In Colombia, health workers obtained a nasopharyngeal wash from 103 infants aged less than 12 months hospitalized for acute lower respiratory infection (ALRI) at the General Hospital of Medellin during April 1994 to April 1995 so researchers could determine the frequency of ALRI caused by respiratory syncytial virus (RSV) in hospitalized children . Immunofluorescence detected RSV infection in 43 (41.7%) patients . The presence of the following signs and symptoms allowed a clinical diagnosis of a viral infection: rhinorrhea, prolonged expiration, expiratory wheezing, interstitial infiltrates, and hyperinflation on chest radiographs as well as negative tests for 3 or 4 acute phase reactants . The physicians initiated antibiotic therapy (for 1-3 days) in 12 cases (27.9%) based on acute phase reactant findings who actually had an RSV infection . When the physicians learned that the laboratory confirmed RSV infection, they stopped antibiotic therapy . Antibiotics were continued in 16 (37.2%) other RSV infected infants, all of whom were less than 2 months old, due to mixed pneumonia (viral and bacterial) . 39.4% of RSV-infected children whose clinical findings strongly suggested RSV received no antibiotics . None of these children or other ALRI patients with a viral disease suffered complications . They required less hospitalization time--since no further diagnostic tests were needed--than ALRI patients with a bacterial infection . Admissions for both ALRI and RSV infection peaked during November to January . RSV incidence peaked in January (23.3%) . The leading reasons for hospitalization were pneumonia and bronchiolitis . These findings show that RSV diagnosis is useful and it lessens the indiscriminate use of antibiotics .

J Fam Pract, 1996 Dec, 43(6), 577 - 80
Treatment of a patient with an infected hepatic cyst; Purvis JR et al.; Symptomatic hepatic cysts are infrequently seen by family physicians . We review the literature and describe the diagnosis and management of a patient with cystic liver disease and a dominant infected hepatic cyst . The treatment included percutaneous drainage, intravenous antibiotic therapy, and sclerotherapy infusion using sterile alcohol (95% ethanol).

Biophys J, 1996 Dec, 71(6), 2984 - 95
Ion coordination in the amphotericin B channel; Khutorsky V; The antifungal polyene antibiotic amphotericin B forms channels in lipid membranes that are permeable to ions, water, and nonelectrolytes . Anion, cation, and ion pair coordination in the water-filled pore of the "barrel" unit of the channels was studied by molecular dynamics simulations . Unlike the case of the gramicidin A channel, the water molecules do not create a single-file configuration in the pore, and some cross sections of the channel contain three or four water molecules . Both the anion and cation are strongly bound to ligand groups and water molecules located in the channel . The coordination number of the ions is about six . The chloride has two binding sites in the pore . The binding with water is dominant; more than four water molecules are localized in the anion coordination sphere . Three motifs of the ion coordination were monitored . The dominant motif occurs when the anion is bound to one ligand group . The ion is bound to two or three ligand groups in the less favorable configurations . The strong affinity of cations to the channel is determined by the negatively charged ligand oxygens, whose electrostatic field dominates over the field of the hydrogens . The ligand contribution to the coordination number of the sodium ion is noticeably higher than in the case of the anion . As in the case of the anion, there are three motifs of the cation coordination . The favorable one occurs when the cation is bound to two ligand oxygens . In the less favorable cases, the cation is bound to three or four oxygens . In the contact ion pair, the cation and anion are bound to two ligand oxygens and one ligand hydrogen, respectively . There exist intermediate solvent-shared states of the ion pair . The average distances between ions in these states are twice as large as that of the contact ion pair . The stability of the solvent-shared state is defined by the water molecule oriented along the electrostatic field of both ions.

Infect Dis Clin North Am, 1996 Dec, 10(4), 879 - 98
Focal intracranial infections; Heilpern KL et al.; Focal intracranial infections are relatively rare, but the consequences of a missed or delayed diagnosis are significant . The clinician is urged to consider these diagnoses in patients with headaches or focal neurologic examinations, particularly in the setting of known or suspected otorhinologic disease . For diagnosis, gadolinium-enhanced MR imaging or MR imaging with angiography are the procedures of choice; CT is far less sensitive and specific . Lumbar puncture is contraindicated in most of these infections . Management of suspected elevation of intracranial pressure and broad empiric antibiotic therapy should be instituted emergently . Early involvement of surgical services is recommended.

Drugs, 1996 Dec, 52(6), 875 - 81; discussion 882
Erdosteine; Dechant KL et al.; Erdosteine is a thiol derivative developed for the treatment of chronic obstructive bronchitis, including acute infective exacerbation of chronic bronchitis . Erdosteine contains 2 blocked sulfhydryl groups which are released following first-pass metabolism . The 3 active metabolites exhibit mucolytic and free radical scavenging activity . Erdosteine modulates mucus production and viscosity and increases mucociliary transport, thereby improving expectoration . It also exhibits inhibitory activity against the effects of free radicals produced by cigarette smoke . Clinical studies in patients with chronic obstructive lung disease have demonstrated the efficacy and tolerability of erdosteine . Erdosteine 300mg twice daily reduced cough (both frequency and severity) and sputum viscosity more quickly and more effectively than placebo and reduced the adhesivity of sputum more effectively than ambroxol 30mg twice daily . Co-administration of erdosteine and amoxicillin in patients with acute infective exacerbation of chronic bronchitis resulted in higher concentrations of the antibiotic in the sputum, leading to earlier and more pronounced amelioration of clinical symptoms compared with placebo . Erdosteine is associated with a low incidence of adverse events, most of which are gastrointestinal and generally mild.

Drugs, 1996 Dec, 52(6), 799 - 804
Prospects for the development of a vaccine against Helicobacter pylori; Telford JL et al.; Over 50% of the world population is chronically infected by the gastric pathogen, Helicobacter pylori, which is responsible for most peptic ulcer disease and is closely associated with adenocarcinoma of the stomach . Current therapies for peptic ulcer disease include antibiotic eradication of H . pylori infection . While effective, the high cost, difficulty of patient compliance with the treatment regimens, and risks of selection for resistant strains make these therapies impractical on a large scale . Studies of the pathogenesis of H . pylori have led to the identification of bacterial antigens as candidates for inclusion in novel vaccines against this disease . Both prophylactic and therapeutic vaccination have been demonstrated in animal models of Helicobacter infection . Preclinical evaluations of several antigens are at present under way and trials of vaccination in humans are planned.

Arch Otolaryngol Head Neck Surg, 1996 Dec, 122(12), 1326 - 9
Descending necrotizing mediastinitis . Surgical drainage and tracheostomy; Brunelli A et al.; OBJECTIVE: To outline the most appropriate treatment of descending necrotizing mediastinitis . DESIGN: Case series . SETTING: General community, institutional practice, hospitalized care . PATIENTS: Five consecutive cases of descending necrotizing mediastinitis that were treated at our institution from 1983 to 1995 . Selection criteria included clinical manifestations of severe cervical infection, characteristic radiographic features, documentation of the mediastinal infection at operation, and establishment of the relationship of the oropharingeal infection with the mediastinal process . Cases of mediastinitis due to perforation of the cervical esophagus were excluded . A cervicothoracic computed tomographic scan was obtained in the last 4 patients on admission . In the first case, computed tomographic scanning was not yet available at our institution . INTERVENTIONS: All patients underwent drainage of the cervical infection through a cervical incision . Mediastinitis was drained by thoracotomy in 2 patients, since the lower mediastinum was involved, whereas 3 patients underwent cervicomediastinal drainage alone . Tracheostomy was performed in 2 patients . RESULTS: All patients survived, with a short hospital stay (mean, 35 days) . CONCLUSIONS: Cervicomediastinal drainage is adequate when the descending mediastinitis is limited to the upper mediastinum . Thoracotomy has to be performed only when the process has diffusely spread below the carina . Early diagnosis is crucial, and we strongly recommend a cervicothoracic computed tomographic scan in every patient with deep cervical infection . We consider tracheostomy not always necessary . Adequate early drainage, with the cervical wounds left open, and antibiotic and anti-inflammatory therapy should prevent upper airway obstruction.

J Bacteriol, 1996 Dec, 178(24), 7276 - 84
Induction of actinorhodin production by rpsL (encoding ribosomal protein S12) mutations that confer streptomycin resistance in Streptomyces lividans and Streptomyces coelicolor A3(2); Shima J et al.; A strain of Streptomyces lividans, TK24, was found to produce a pigmented antibiotic, actinorhodin, although S . lividans normally does not produce this antibiotic . Genetic analyses revealed that a streptomycin-resistant mutation str-6 in strain TK24 is responsible for induction of antibiotic synthesis . DNA sequencing showed that str-6 is a point mutation in the rpsL gene encoding ribosomal protein S12, changing Lys-88 to Glu . Gene replacement experiments with the Lys88-->Glu str allele demonstrated unambiguously that the str mutation is alone responsible for the activation of actinorhodin production observed . In contrast, the strA1 mutation, a genetic marker frequently used for crosses, did not restore actinorhodin production and was found to result in an amino acid alteration of Lys-43 to Asn . Induction of actinorhodin production was also detected in strain TK21, which does not harbor the str-6 mutation, when cells were incubated with sufficient streptomycin or tetracycline to reduce the cell's growth rate, and 40 and 3% of streptomycin- or tetracycline-resistant mutants, respectively, derived from strain TK21 produced actinorhodin . Streptomycin-resistant mutations also blocked the inhibitory effects of relA and brgA mutations on antibiotic production, aerial mycelium formation or both . These str mutations changed Lys-88 to Glu or Arg and Arg-86 to His in ribosomal protein S12 . The decrease in streptomycin production in relC mutants in Streptomyces griseus could also be abolished completely by introducing streptomycin-resistant mutations, although the impairment in antibiotic production due to bldA (in Streptomyces coelicolor) or afs mutations (in S . griseus) was not eliminated . These results indicate that the onset and extent of secondary metabolism in Streptomyces spp . is significantly controlled by the translational machinery.

Ther Drug Monit, 1996 Dec, 18(6), 698 - 705
A simplified whole blood enzyme-linked immunosorbent assay (ProTrac II) for tacrolimus (FK506) using proteolytic extraction in place of organic solvents; MacFarlane G et al.; Tacrolimus (FK506) is a macrolide antibiotic with potent immunosuppressive properties . FK506 is 10- to 100-fold more potent than cyclosporin A in preventing organ rejection and in toxicity . Extreme inter- and intrapatient variability and lack of correlation between drug dosage and drug blood levels necessitate consistent and reliable therapeutic drug monitoring . Previous methods for monitoring drug levels have been lengthy and labor intensive and have required organic solvents for sample extraction . We have developed a manual enzyme-linked immunosorbent assay (ProTrac II ELISA) that employs standardized reagents and a nonorganic solvent extraction and yields good assay sensitivity and precision . The calculated mean sensitivity of the assay was 0.18 ng/ml . Interassay precision ranged from 6.3% to 13.1% (coefficient of variation) for FK506 in whole blood (concentration range, 1.0-25.0 ng/ml) . Recovery of the drug from spiked EDTA whole blood was 91-98% over the same concentration range . Mean recovery of the drug from clinical samples spiked with kit standards was 99.5% . Dilutions of high-concentration spiked EDTA whole blood samples and high-concentration samples from patients exhibited linearity of observed versus expected values (y = 0.86x - 1.15; r = 0.99) . Comparison of ProTrac II with the INCSTAR ProTrac FK506 ELISA by paired Student's t test showed no statistical difference between the methods (p = 0.46) . Comparison of ProTrac II ELISA to the IMx microparticle enzyme immunoassay (MEIA) by linear regression resulted in a line with a slope of 1.22 (r = 0.91) . Analysis by t test resulted in a p value < 0.001, indicating that the absolute values obtained in these assays are significantly different . The mean (+/-SD) difference in the absolute values was 4.2 +/- 2.6 ng/ml, with the MEIA values consistently higher . These results indicate that ProTrac II is a sensitive, precise ELISA for the determination of tacrolimus in whole blood; it can be performed in < 4 h.

Mol Cell Biol, 1996 Dec, 16(12), 6744 - 51
Rapamycin resistance tied to defective regulation of p27Kip1; Luo Y et al.; The potent antiproliferative activity of the macrolide antibiotic rapamycin is known to involve binding of the drug to its cytosolic receptor, FKBP12, and subsequent interaction with targets of rapamycin, resulting in inhibition of p70 S6 kinase (p70S6K) . However, the downstream events that lead to inhibition of cell cycle progression remain to be elucidated . The antiproliferative effects of rapamycin are associated with prevention of mitogen-induced downregulation of the cyclin-dependent kinase inhibitor p27Kip1, suggesting that the latter may play an important role in the growth pathway targeted by rapamycin . Murine BC3H1 cells, selected for resistance to growth inhibition by rapamycin, exhibited an intact p70S6K pathway but had abnormally low p27 levels that were no longer responsive to mitogens or rapamycin . Fibroblasts and T lymphocytes from mice with a targeted disruption of the p27Kip1 gene had impaired growth-inhibitory responses to rapamycin . These results suggest that the ability to regulate p27Kip1 levels is important for rapamycin to exert its antiproliferative effects.

Plast Reconstr Surg, 1996 Dec, 98(7), 1242 - 6
Risk factors for complications in pediatric tissue expansion; Friedman RM et al.; Tissue expansion in children has been associated with complication rates of 20 to 40 percent . A critical analysis of 6 years' (1988-1993) experience with 180 expanders placed in 82 consecutive children was performed to identify those factors which predispose to complications . Major and minor complications each occurred in 9 percent of patients . The factors associated with a statistically significant increase in complications were burns and soft-tissue loss, patient age under 7 years, use of internal expander ports, and a history of two or more prior expansions . In addition, complications were significantly more likely to occur within the first 90 days than during any subsequent expansion . Factors that did not influence complication rate included patient gender, wound drainage upon expander insertion or removal, intraoperative use of antibiotic irrigation, number of expanders placed, use of customized expanders, and operating surgeon.

J Infect Dis, 1996 Dec, 174(6), 1271 - 8
Reduction of nasopharyngeal carriage of pneumococci during the second year of life by a heptavalent conjugate pneumococcal vaccine; Dagan R et al.; Children 12-18 months old were randomized to receive one dose of a conjugate heptavalent pneumococcal vaccine, two doses of the same vaccine, or one dose of a 23-valent native polysaccharide vaccine . Before immunization, pneumococci included in the conjugate vaccine were isolated from 24% of the children, and an antibiotic-resistant pneumococcus was isolated from 22% of the children . The vaccines had no effect on carriage of non-vaccine-type pneumococci . In contrast, there was a significant reduction in carriage of vaccine-type pneumococci 3 months after one dose and 1 month after a second dose of conjugate vaccine (from 25% to 9% and 7%, respectively; P < .001) . No effect was seen after vaccination with the nonconjugate vaccine . One year after immunization, carriage of antibiotic-resistant vaccine-type pneumococci in children receiving conjugate vaccine was lower than that in children receiving the nonconjugate vaccine (4% vs . 14%, P = .042) . Conjugate pneumococcal vaccines may reduce spread of pneumococci in the community.

Prim Care, 1996 Dec, 23(4), 821 - 35
The diagnosis and management of bacterial pneumonias in infants and children; Churgay CA; The majority of pediatric pneumonias are viral in origin, but a bacterial source always must be considered in the differential diagnosis because antibiotic administration may be crucial to the patient's management . There is no gold standard for differentiating between pediatric bacterial and viral pneumonias, but signs and symptoms from the clinical presentation, laboratory tests, and appearance of the chest radiograph can be used to help make the distinction . The most important factors governing which antibiotics to choose when treating a child with bacterial pneumonia are the child's age and whether any underlying illnesses are present . Surgical intervention may be needed in addition to antibiotic therapy if complications develop.

Biochemistry, 1996 Nov 26, 35(47), 14800 - 5
Cell surface protein disulfide-isomerase is involved in the shedding of human thyrotropin receptor ectodomain; Couet J et al.; In human thyroid glands the TSH receptor undergoes a cleavage reaction which yields to an extracellular alpha subunit and a membrane spanning beta subunit linked together by disulfide bridges . A similar reaction is observed in transfected L cells although some uncleaved monomers persist in these cells . We have recently shown that the alpha subunit of the TSH receptor undergoes partial shedding in human thyroid cells and heterologous cells permanently transfected with an expression vector encoding the receptor . This shedding is a two-step process . The first step consists in the cleavage of the proreceptor at the cell surface probably by a matrix metalloprotease and the second step in the reduction of the disulfide bridge(s) (Couet, J., Sar, S., Jolivet, A., Vu Hai, M . T., Milgrom, E., & Misrahi, M . 1996, J . Biol . Chem . 271, 4545-4552) . We have used the transfected L cells to study the second step involved in sTSHR shedding . The membrane impermeant sulfhydryl reagent DTNB (5,5'-dithiobis(2-nitrobenzoic acid) allowed us to confirm that the reduction of the TSH receptor disulfide bonds occurred at the cell surface . The antibiotic bacitracin even at low concentrations also elicited a marked inhibition of TSH receptor shedding . This led us to implicate the enzyme protein disulfide isomerase (PDI, EC 5.3.4.1) in this process . We thus tested the inhibitory activity of specific monoclonal antibodies raised against PDI . All antibodies elicited a marked inhibition of sTSHR shedding . This confirmed that cell surface PDI is involved in the shedding of the TSH receptor ectodomain . The shed alpha subunit may be at the origin of circulating TSH receptor ectodomain detected in human blood.

Exp Cell Res, 1996 Nov 25, 229(1), 7 - 13
Clonal nature of spontaneously immortalized 3T3 cells; Rittling SR; Mouse embryo fibroblasts (MEFs), when plated at appropriate densities, proliferate vigorously for several passages, and then the growth rate of the culture slows considerably . If the cells are plated at a high enough density and continuously passed, the cultures will eventually overcome this "crisis" period and resume rapid growth . Here, we have addressed the question of what the changes are that cells undergo in overcoming the growth restraints of crisis . Primary MEF cells were infected with a retrovirus which confers G418 resistance and selected in G418 . The resultant pre-crisis population comprised cells which each contained a retrovirus integrated at a unique genomic location . These cells were then passed according to the 3T3 protocol until immortal, rapidly growing cells emerged . The integration pattern of the retrovirus in the immortal population was examined . In two independent experiments, the immortal population of cells grown in the presence of G418 comprised two independent clones of cells, with additional clones undetectable at the level of detection of the assays used . The integration pattern was also examined in parallel infected cultures grown in the absence of selection . In one experiment the unselected immortal population contained the same labeled clone that appeared in the sister infected culture, indicating that an immortal precursor was present in the precrisis population . These results are consistent with the idea that a mutation is responsible for the immortal phenotype.

Gene, 1996 Nov 21, 180(1-2), 173 - 6
Molecular analysis of tlrD, an MLS resistance determinant from the tylosin producer, Streptomyces fradiae; Gandecha AR et al.; The macrolide antibiotic, tylosin (Ty), is produced by Streptomyces fradiae . Two resistance determinants (tlrA, synonym ermSF, and tlrD) conferring resistance to macrolide, lincosamide and streptogramin B type (MLS) antibiotics were previously isolated from this strain, and their products shown to methylate 23S ribosomal RNA (rRNA) at a common site, thereby rendering the ribosomes MLS resistant . However, the TlrA and TlrD proteins differ in their action; the former dimethylates, and the latter monomethylates, the target nucleotide . Here, 2.2 kb of DNA from the tylLM region of the tylosin biosynthetic gene cluster of S . fradiae has been sequenced and shown to encompass tlrD . Comparison of the sequences of tlrA and tlrD (and of their deduced products) with those of related ('erm-type') genes from other actinomycetes suggests that the combined presence of tlrA and tlrD in S . fradiae is not the result of recent gene duplication.

Thromb Res, 1996 Nov 15, 84(4), 253 - 66
Aggregated-disaggregated, refractory platelets retain sensitivity to ristocetin; White JG et al.; The present investigation has used an aggregation-disaggregation-reaggregation model to determine if exposure to potent aggregating agents causing a refractory state in deaggregated platelets results in down-regulation and clearance of GPIb/IX, the receptor for von willebrand factor . Thrombin, the thrombin receptor activating peptide (TRAP) and the thromboxane A2 mimic, U46619, caused irreversible aggregation and secretion when stirred on an aggregometer with plateletrich plasma (PRP) . Addition of prostaglandin E1 (PGE1) after the plateau of maximum aggregation was reached caused rapid dissociation of platelet aggregates . Dissociated platelets were refractory to a second exposure to the primary stimulus or to other aggregating agents . Exposure of the refractory cells to epinephrine before the primary agent restored sensitivity resulting in a second wave of irreversible aggregation . Deaggregated, refractory platelets, however, retained their sensitivity to ristocetin . Amounts of the antibiotic causing agglutination of resting PRP also caused agglutination of disaggregated, refractory platelets . Addition of epinephrine to samples of refractory platelets less sensitive to low concentrations of the antibiotic restored their capacity to undergo irreversible ristocetin-induced agglutination . Analysis of the frequency of gold particles associated with monoclonal antibodies directed against GPIb/IX on control platelets and disaggregated, refractory platelets showed no significant difference in the number of receptors . The findings indicate that significant numbers of GPIb/IX receptors remain on platelet surfaces following exposure to potent aggregating agents.

EMBO J, 1996 Nov 15, 15(22), 6301 - 10
Smooth muscle alternative splicing induced in fibroblasts by heterologous expression of a regulatory gene; Roberts GC et al.; Alternative splicing is a common mechanism for regulating gene expression in different cell types . In order to understand this important process, the trans-acting factors that enforce the choice of particular splicing pathways in different environments must be identified . We have used the rat alpha-tropomyosin gene as a model system of tissue-specific alternative splicing . Exon 3 of alpha-tropomyosin is specifically inhibited in smooth muscle cells allowing the alternative inclusion of exon 2 . We have used a novel gene transfer and selection strategy to detect a gene whose expression in fibroblasts is sufficient to switch them to smooth muscle-specific splicing of alpha-tropomyosin and also alpha-actinin . Extracts from the regulating fibroblasts contain an apparently novel 55 kDa protein which binds to RNA elements required for regulation of tropomyosin splicing . This protein is not detected in extracts of non-regulating cells and is therefore a strong candidate cell-specific splicing regulator . These experiments advance our understanding of smooth muscle splicing regulation as well as establishing a means for direct cloning of tissue-specific splicing regulators which have so far been refractory to biochemical analysis.

J Clin Invest, 1996 Nov 15, 98(10), 2277 - 83
Rapamycin inhibits vascular smooth muscle cell migration; Poon M et al.; Abnormal vascular smooth muscle cell (SMC) proliferation and migration contribute to the development of restenosis after percutaneous transluminal coronary angioplasty and accelerated arteriopathy after cardiac transplantation . Previously, we reported that the macrolide antibiotic rapamycin, but not the related compound FK506, inhibits both human and rat aortic SMC proliferation in vitro by inhibiting cell cycle-dependent kinases and delaying phosphorylation of retinoblastoma protein (Marx, S.O., T . Jayaraman, L.O . Go, and A.R . Marks . 1995 . Circ . Res . 362:801) . In the present study the effects of rapamycin on SMC migration were assayed in vitro using a modified Boyden chamber and in vivo using a porcine aortic SMC explant model . Pretreatment with rapamycin (2 ng/ml) for 48 h inhibited PDGF-induced migration (PDGF BB homodimer; 20 ng/ml) in cultured rat and human SMC (n = 10; P < 0.0001), whereas FK506 had no significant effect on migration . Rapamycin administered orally (1 mg/kg per d for 7 d) significantly inhibited porcine aortic SMC migration compared with control (n = 15; P < 0.0001) . Thus, in addition to being a potent immunosuppressant and antiproliferative, rapamycin also inhibits SMC migration.

J Am Vet Med Assoc, 1996 Nov 15, 209(10), 1714 - 5
Cost effectiveness of use of a solution of 6% dextran 70 in young calves with severe diarrhea; Wall PL et al.; OBJECTIVE: To determine whether intravenous administration of 6% dextran 70 solution to young calves with severe diarrhea is cost effective . DESIGN: Randomized, prospective, clinical trial . ANIMALS: 22 calves < 2 months old that were hospitalized for diarrhea and that did not have pneumonia . PROCEDURE: All calves received antibiotics, were fed by use of an orogastic tube, were supplied with radiant heat, and were given crystalloids, i.v., as deemed appropriate by an attending veterinarian . A group of 12 calves also received 500 ml of 6% dextran 70 solution, i.v., over a 1-hour period as part of the initial treatment . Data were collected to determine whether early treatment with 6% dextran 70 solution resulted in a similar end cost for treatment because of a decrease in the volume of fluids administered i.v., a decrease in antibiotic usage, a decrease in the amount of time hospitalized, or a decrease in mortality . RESULTS: Capillary refill times, heart rates, respiratory rates, and rectal temperatures; and scores for dehydration, mucous membrane color, lung sounds, mental status, and suckling response were not different between the 2 groups of calves at admission . Differences were not detected in client charges or in hospitalized time (6% dextran 70 group, $89.68 +/- 11.05 and 36 +/- 3 hours; control group $88.02 +/- 4.93 and 36 +/- 4 hours), but those charges did not include costs for the 6% dextran 70 solution . CLINICAL IMPLICATIONS: Use of 6% dextran 70 solution as part of the resuscitation of most young calves with diarrhea requiring hospitalization is not likely to be cost effectivePublication Types:

	Clinical Trial
	Randomized Controlled Trial

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