Antibiotics

Postgrad Med, 1993 Aug, 94(2), 105 - 11
Gonorrhea . Finding and treating a moving target; Hawley HB; Gonorrhea is the most common reportable disease in the United States . In recent years, the epidemiology of this infection has changed as a result of increasing drug abuse, exchange of money and drugs for sex, and sexual promiscuity among teenagers, particularly blacks . Significant numbers of asymptomatic male carriers have been identified, which presents an additional challenge to disease control . Gonococcal infection has become increasingly resistant to traditional antibiotic therapy and now requires the use of newer, more expensive agents . Single-dose oral treatment with cefixime (Suprax) or a quinolone appears to be effective, safe, and practical for patients with uncomplicated gonorrhea . Serious infection and new syndromes caused by gonococci continue to be reported . Because disseminated infections can be fatal, hospitalization and treatment with intravenous antibiotics such as ceftriaxone sodium (Rocephin) or cefotaxime sodium (Claforan) are required.

J Lab Clin Med, 1993 Aug, 122(2), 202 - 7
Plasma defensin concentrations are elevated in patients with septicemia or bacterial meningitis; Panyutich AV et al.; We measured concentrations of defensins (human neutrophil peptides) in the plasma of healthy volunteers and patients with sepsis and meningitis . When a sensitive enzyme immunoassay was used, defensins were detected in plasma samples from 13 of 24 healthy blood donors, with a mean +/- SD of 42 +/- 53 ng/ml . Defensin levels in plasma samples from seven patients with sepsis at the onset of disease ranged from 900 ng/ml to 170,000 ng/ml . In 10 patients with meningitis in the initial phase of disease, plasma defensin concentrations ranged from 120 ng/ml to 910 ng/ml . Defensin concentrations in the plasma of both patient groups were significantly higher than those in healthy blood donors (p << 0.01), and patients with sepsis had higher defensin levels than patients with meningitis (p < 0.01) . Defensin levels were significantly (p < 0.01) lower after the beginning of specific antibiotic therapy . Defensin concentrations in the plasma of patients with sepsis and meningitis correlated only weakly (r = 0.38) with blood neutrophil count . In vitro studies of defensin added to plasma indicated that all defensin was bound to plasma proteins . At high concentrations (1000 micrograms/ml), defensins caused precipitation of plasma proteins . Because plasma defensin levels may reflect neutrophil activation at sites of infection and inflammation, studies of the clinical utility of defensin ELISA are indicated.

J Virol, 1993 Aug, 67(8), 4732 - 41
Deletion of the vaccinia virus B5R gene encoding a 42-kilodalton membrane glycoprotein inhibits extracellular virus envelope formation and dissemination; Wolffe EJ et al.; The structure, formation, and function of the virion membranes are among the least well understood aspects of vaccinia virus replication . In this study, we investigated the role of gp42, a glycoprotein component of the extracellular enveloped form of vaccinia virus (EEV) encoded by the B5R gene . The B5R gene was deleted by homologous recombination from vaccinia virus strains IHD-J and WR, which produce high and low levels of EEV, respectively . Isolation of recombinant viruses was facilitated by the insertion into the genome of a cassette containing the Escherichia coli gpt and lacZ genes flanked by the ends of the B5R gene to provide simultaneous antibiotic selection and color screening . Deletion mutant viruses of both strains formed tiny plaques, and those of the IHD-J mutant lacked the characteristic comet shape caused by release of EEV . Nevertheless, similar yields of intracellular infectious virus were obtained whether cells were infected with the B5R deletion mutants or their parental strains . In the case of IHD-J, however, this deletion severely reduced the amount of infectious extracellular virus . Metabolic labeling studies demonstrated that the low extracellular infectivity corresponded with a decrease in EEV particles in the medium . Electron microscopic examination revealed that mature intracellular naked virions (INV) were present in cells infected with mutant virus, but neither membrane-wrapped INV nor significant amounts of plasma membrane-associated virus were observed . Syncytium formation, which occurs in cells infected with wild-type WR and IHD-J virus after brief low-pH treatment, did not occur in cells infected with the B5R deletion mutants . By contrast, syncytium formation induced by antibody to the viral hemagglutinin occurred, suggesting that different mechanisms are involved . When assayed by intracranial injection into weanling mice, both IHD-J and WR mutant viruses were found to be significantly attenuated . These findings demonstrate that the 42-kDa glycoprotein of the EEV is required for efficient membrane enwrapment of INV, externalization of the virus, and transmission and that gp42 contributes to viral virulence in strains producing both low and high levels of EEV.

J Laparoendosc Surg, 1993 Aug, 3(4), 325 - 9
Laparoscopic vs . open wedge biopsy of the liver; Falcone RE et al.; This study was a post-hoc evaluation of laparoscopic versus open wedge biopsy of the liver performed as part of prospective phase I antibiotic trial . Consenting patients undergoing elective cholecystectomy were enrolled in a protocol which required samples of bile, blood, the gallbladder, and 1 gram of liver tissue . The study occurred during the evolution of laparoscopic surgery . Liver biopsy was done in standard fashion and laparoscopic liver biopsy was accomplished with cauterized scissors . Twenty-four patients, 4 male and 20 female averaging 42.1 years of age, were entered in this study . Eighteen patients underwent laparoscopic surgery and six patients underwent open surgery . They did not differ significantly in age (43.9 vs 42.1 years), operating room time (58.3 min vs 55.8 min), or complications (2/18 vs 2/6) . Patients undergoing laparoscopic surgery, however, did have a shorter hospital stay (1.1 days vs 3.5 days, p < 0.001) . All liver specimens were considered adequate . There were no complications related to the liver biopsy . Laparoscopic wedge biopsy of the liver is both a feasible and viable alternative to open wedge biopsy.

Singapore Med J, 1993 Aug, 34(4), 309 - 12
Excimer laser photorefractive keratectomy in Singapore--a new treatment modality for myopia; Balakrishnan V et al.; BACKGROUND: Myopia is a national epidemic in Singapore . Photorefractive Keratectomy (PRK) for the treatment of myopia using the Argon Fluoride Excimer Laser commenced in January 1992 at the Singapore National Eye Centre . METHODS: An open, prospective, non randomised clinical trial to assess the efficacy, predictability, stability, and safety of PRK for the correction of myopia between -2.0 to -6.0 dioptres . RESULTS: One hundred and fifty-five eyes of one hundred and thirty-five patients underwent PRK between January and September 1992, of which thirty-one had completed at least six months of follow-up . Twenty-nine of the thirty-one patients (93.5%) achieved an unaided visual acuity of at least 6/12 . Twenty-six patients (83.9%) were within 1 dioptre of emmetropia . There was an initial over-correction in all patients which regressed to a plateau at around three or four months . Corneal haze did not pose a significant problem . Three patients had ocular hypertension, and another developed a mild allergic reaction to the antibiotic-steroid ointment . CONCLUSIONS: Excimer Laser Photorefractive Keratectomy is a very effective, fairly predictable, stable and safe surgical method for the treatment of myopia.

Khirurgiia (Mosk), 1993 Aug, (8), 35 - 9
{Treatment of generalized purulent appendicular peritonitis in children}; Tsuman VG et al.; Experience in the treatment of 137 children with a most severe and complicated course of generalized purulent peritonitis of appendicular genesis is generalized . It is shown that such patients must be concentrated in centers of pediatric surgery providing the possibility of applying a complex of diagnostic examinations and therapeutic measures, including purposeful antibiotic therapy, differentiated immunocorrection, and effective detoxification . The detoxification and immunocorrection effect of discrete plasmapheresis with two-stage "washing out" of the red cells is illustrated in the discussion of 22 cases . It is pointed out that in operations for generalized purulent peritonitis the abdominal cavity must not only be cleansed but also drained adequately and intubation of the intestine must be carried out with aspiration of its content for 3-5 days and application of enterosorption through an intestinal tube . A complex of organizational and therapeutic measures made it possible to reduce considerably the mortality rate in acute appendicitis and its complications in the Moscow Region.

J Toxicol Sci, 1993 Aug, 18(3), 203 - 6
Effects of rokitamycin on bilirubin-albumin binding: a study in vitro; Yamamura H et al.; The effects of rokitamycin, a macrolide antibiotic, on the binding of bilirubin to albumin were examined in vitro using blood plasma from young rats with hyperbilirubinemia, bilirubin-supplemented serum separated from human cord blood, and the human serum from a newborn infant with icterus gravis neonatorum . Rokitamycin at concentrations from 1 to 500 micrograms/ml (the entire range over which experiments could be conducted) had little or no effect on the concentration of unbound bilirubin in any of the incubation mixtures used . This result suggests that rokitamycin has no effect on the binding of bilirubin to albumin.

Ir J Med Sci, 1993 Aug, 162(8), 301 - 5
Early experience with leg lengthening by callotasis and chondrodiastasis; O'Beirne J et al.; Over a four year period, 20 segments in 16 patients were treated by lengthening by callotasis or chondrodiastasis . The indications for treatment were leg length discrepancy in 13 patients and short stature in three . Patients with leg length discrepancy were all treated by femoral lengthening; the mean length gained was 4.4 cm (range 2.5 to 6.Ocm) . For patients with short stature, the mean femoral length gain was 10.0 cm (9.0 to 10.5 cm), and the mean tibial length gain was 8.0 cm (6.5 to 9.0 cm) . The commonest problem was pin tract infection, but this always settled with antibiotic therapy . Most other complications were also successfully dealt with, and did not compromise the outcome of treatment . At the time of review, 13 of the 16 patients said they were very happy with the result; two patients were reserving judgement until completion of treatment, and, only one thought the treatment had been of no benefit . Our initial experience, with callotasis in particular, has been that it is a highly satisfactory method of limb lengthening, has an acceptable complication rate, and involves minimal hospitalization as compared with older techniques.

Mol Microbiol, 1993 Aug, 9(4), 897 - 905
The maturation pathway of microcin B17, a peptide inhibitor of DNA gyrase; Yorgey P et al.; The maturation pathway of microcin B17 (MccB17), a ribosomally synthesized peptide antibiotic which inhibits DNA gyrase, has been characterized . Synthesis of MccB17 involves several steps beginning with the translation of the MccB17 structural gene, mcbA, to yield a 69 amino acid precursor, preMccB17 . Pre-MccB17 is then modified and folded by the action of three gene products, McbBCD, to yield proMccB17 . Mutations in mcbA were isolated that permit modifications of the resulting mutant peptides, but prevent folding, suggesting that modification and folding are sequential steps . ProMccB17 is subsequently converted to MccB17 by removal of the N-terminal 26-amino-acid leader by a chromosomally encoded protease . Removal of the leader resulted in aggregation of the peptide, suggesting that the leader may function to maintain peptide solubility during synthesis in the cell . Finally, polyclonal antibodies raised against MccB17 recognize both MccB17 and proMccB17, but do not recognize preMccB17 . This demonstrates the dramatic structural changes that result from the modifications and has been used to distinguish intermediates in the steps of maturation.

J Spinal Disord, 1993 Aug, 6(4), 296 - 9
Serum cefazolin levels during spinal fusion: effect of blood loss and duration of surgery; Lopez-Sosa FH et al.; Perioperative cefazolin prophylaxis is commonly employed in posterior spinal fusion (PSF) procedures, which are often lengthy and involve significant blood loss . In this study, serum levels of prophylactically administered cefazolin were measured serially during spinal fusion procedures, and the possible relationship of antibiotic concentrations to blood loss and fluid therapy were examined . Serum antibiotic levels, measured at 30-min intervals, declined with a half-life of 90 min, similar to the previously reported experience with normal adult volunteers . There was no relationship between serum half-life and blood loss or fluid replacement . An explanation for these findings is offered, along with recommendations for dosing.

Ann Med, 1993 Aug, 25(4), 349 - 52
Late Lyme borreliosis: epidemiology, diagnosis and clinical features; Wahlberg P et al.; Lyme borreliosis is endemic in the Aland Islands . Exposure of the inhabitants to bites of the tick Ixodes ricinus is heavy . The purpose of this study was to describe symptoms and signs of patients with late Lyme borreliosis in this area, and to correlate the findings with the epidemiological setting . The first 100 consecutive patients with late Lyme borreliosis found in the region since 1984 are included in this study . Neurological, articular and muscular symptoms and signs dominate . General screening for Lyme disease is not recommended in the area due to uncertainty about how to deal with seropositive healthy persons in this heavily exposed population . The recognition and prompt treatment of erythema migrans and other manifestations of primary Lyme borreliosis is important in order to avoid the late stages of the disease . Treatment of all those suffering tick-bites with an antibiotic would be an option in view of the incidence of infected ticks, but cannot be considered because tick-bites are extremely common among the inhabitants . The region would be suitable for general immunization against Borrelia burgdorferi if the means for doing this becomes available in the future.

Ann Plast Surg, 1993 Aug, 31(2), 141 - 5
Crotalidae envenomation in children; Weber RA et al.; Poisonous snakebites cause a severe envenomation syndrome in children, yet treatment remains controversial . Sixty-seven patients were treated for poisonous snakebites at our institution between 1975 and 1990; 18 were children < or = 12 years old . There were 13 rattlesnake bites, 4 copperhead bites, and 1 unidentified bite . Initial management included intravenous fluids and antibiotic administration, laboratory studies, tetanus prophylaxis, affected limb elevation, and a limited excision of the bite site in the emergency room . Antivenin was administered only if signs of systemic involvement such as shock, coagulopathy, gastrointestinal cramping, or neurological involvement were present . Children developed systemic involvement 72% of the time, 9 children (50%) developed coagulopathy . Consequently, 11 (61%) children received antivenin . The dose of antivenin they received was 3.2 ml/kg and the children tolerated it well with only 36% of them demonstrating adverse reactions to the antivenin . Clinically, the pediatric patients demonstrated signs and symptoms of a fulminant envenomation syndrome (8 days, average hospital stay), yet, they had a good eventual outcome . Only 11% of children reported long-term morbidity . No deaths occurred and 100% of patients were able to return to full preinjury activities . We conclude that Crotalidae envenomation in children is a serious disease and warrants hospitalization, early surgical involvement, and frequent use of antivenin.

Arch Fam Med, 1993 Aug, 2(8), 841 - 6
Effect of patient characteristics and disease manifestations on the outcome of acute otitis media at 2 months; Froom J et al.; BACKGROUND: Optimal therapy for acute otitis media (AOM) is controversial and there is no consensus regarding which antibiotic to use, how long to administer it, or whether antibiotics are effective at all . Knowledge of the effects of patient characteristics and disease manifestations is needed to individualize treatment and to evaluate large-scale trials . METHODS: Data originated from 2251 patients with AOM, aged newborn to 15 years, who participated in a prospective primary care study in eight countries . At the initial visit, medical history, symptoms, physical findings, and treatment data were recorded . Follow-up 2 months later identified changes in treatment and outcome . RESULTS: Patients younger than 13 months were less likely to have recovered than those aged 13 months to 15 years (P = .05) . Using univariate analysis for infants aged 12 months or younger, male sex, prior episodes of AOM, and serous otitis media were associated with poor outcome . For older patients, poor outcome was associated with initial history of ear tubes, prophylactic antibiotic use, ear discharge, decreased hearing, serous otitis media; and past episodes of AOM; the symptom of decreased hearing; and the finding of pus exuding from the tympanic membrane . Using multivariate analysis for infants aged 12 months or younger, a history of serous otitis media (odds ratio {OR}, 2.3; 95% confidence interval {CI}, 0.95-5.7), past episodes of AOM (OR, 1.9; 95% CI, 0.82-4.5), and male sex (OR, 1.7; 95% CI, 1.0-3.0) made independent contributions to poor outcome . For children aged 13 months to 15 years, significant variables included pus drainage (OR, 2.2; 95% CI, 1.5-3.3), a history of ear tubes (OR, 2.3; 95% CI, 1.5-3.6), past episodes of AOM (OR, 1.8; 95% CI, 1.3-2.34), and a history of serous otitis media (OR, 1.4; 95% CI, 1.0-1.9) . CONCLUSIONS: Patient characteristics and disease manifestations are significant determinants of AOM outcome.

J Oral Maxillofac Surg, 1993 Aug, 51(8), 868 - 73; discussion 873-4
Management of maxillofacial infections: a review of 50 cases; Krishnan V et al.; Maxillofacial infections often place the oral and maxillofacial surgeon in situations where timely decisions have to be made . These decisions can be life-saving . This study reviews 50 infections treated over a 3-year period . The results reveal rapid resolution of the infections by adhering to fundamental principles in their management: recognition of airway compromise, surgical intervention, and the administration of the appropriate antibiotic . A protocol for the management of maxillofacial infections is described.

Cardiovasc Surg, 1993 Aug, 1(4), 419 - 25
Preoperative management and surgical therapy in complicated acute infective endocarditis: a 5-year experience; Arena V et al.; Twenty-five patients underwent early and elective valve replacement for infective endocarditis during a 5-year period between April 1985 and March 1991 . Indications for urgent surgical intervention performed at a mean 32 (range 6-47) days after admission were intractable heart failure, systemic emboli, septic multiorgan failure and the presence of vegetations . Indication for elective surgery was persistent (mean 42 (range 17-56) days) infection after appropriate antibiotic therapy . Twenty patients (80%) had a native valve endocarditis; five (20%) had prosthetic valve involvement . A total of 30 valvular prostheses were implanted: 22 (73.3%) were aortic (21 mechanical and one biological); eight (26.7%) were mitral (all mechanical) . All unstable patients referred were treated before surgery in the intensive care unit and subjected to blood ultrafiltration to restore satisfactory circulatory parameters . No patient underwent cardiac catheterization; all patients were operated upon on the basis of echocardiographic data alone . One patient (4%) died during hospitalization; two (8%) died later at 48 and 12 months after the first intervention . The reoperation rate was 12% . After a mean follow-up of 49 (range 1-71) months, 21 of the survivors (95%) were in New York Heart Association functional class I or II; the actuarial 5-year survival rate was 87% . Precise preoperative assessment of early operative indications and timely association of medical therapy in unstable patients could represent a step forward in the treatment of acute infective endocarditis.

J Pharm Pharmacol, 1993 Aug, 45(8), 745 - 7
Protective effects of cyclodextrin sulphates against gentamicin-induced nephrotoxicity in the rat; Uekama K et al.; The effects of cyclodextrin sulphates on the development of rat renal dysfunction induced with gentamicin, an aminoglycoside antibiotic, were studied . Daily subcutaneous injection of gentamicin (100 mg kg-1, 14 days) developed nephrotoxicity in the rat as assessed by an increase in serum urea nitrogen and histopathological changes in the renal cortex . When cyclodextrin sulphates were given intraperitoneally at 300 mg kg-1 at 6 h intervals after gentamicin administration, they protected the rat against the drug-induced renal impairment, while the parent cyclodextrins were ineffective . Since post-administration of cyclodextrin sulphates did not reduce the total amount of gentamicin accumulated in the kidney, the protection may occur through interference with intracellular events leading from the drug accumulation to nephrotoxicity . These results suggest that cyclodextrin sulphates are particularly effective in preventing renal failure associated with aminoglycoside treatment.

Int J Gynaecol Obstet, 1993 Aug, 42(2), 121 - 5
Tinidazole prophylaxis in elective abdominal hysterectomy; Dhar KK et al.; OBJECTIVE: To determine whether a single dose (2 g) of tinidazole before abdominal hysterectomy could reduce the incidence of postoperative infection . METHOD: A randomized double-blind placebo-controlled study was undertaken with a single oral dose (2 g) of tinidazole, 12 h before surgery, in 100 patients undergoing abdominal hysterectomy for various benign diseases . Other antibiotic use was withheld until there was no postoperative infection . RESULT: A significant reduction (P < 0.05) of infectious morbidity (28% vs . 8%) as well as a decrease in additional antibiotic use (P < 0.01) and duration of hospital stay (P < 0.001) was observed . Febrile morbidity was also reduced from 36% to 14% (P < 0.05) . Tinidazole was tolerated well by all the patients . CONCLUSION: Tinidazole prophylaxis (2 g oral dose) is considered to be a simple, safe and effective way to reduce postoperative infection in abdominal hysterectomy.

Int J Gynaecol Obstet, 1993 Aug, 42(2), 117 - 20
Single dose tinidazole prophylaxis in vaginal hysterectomy; Dhar KK et al.; OBJECTIVE: To determine the efficacy and side effects of a single dose of tinidazole for infection following vaginal hysterectomy . METHOD: A randomized double-blind placebo-controlled trial using 2 g tinidazole 12 h before vaginal hysterectomy in 50 patients was conducted . No other antibiotic was used until the development of infection . RESULT: There was a significant reduction (P < 0.01) of post-operative vaginal cuff cellulitis (54-16%) . A similar reduction (P < 0.05) in febrile morbidity was also observed . The duration of postoperative hospital stay (P < 0.001) and use of additional antibiotics (P < 0.01) were also reduced . No adverse effect of tinidazole was noted . CONCLUSION: A single dose of tinidazole appears to be a safe and effective alternative prevention against infection in vaginal hysterectomy.

Am J Clin Oncol, 1993 Aug, 16(4), 323 - 6
Low toxicity with continuous infusion of high-dose bleomycin in poor prognostic testicular cancer; Gerson R et al.; Bleomycin is a powerful antitumoral antibiotic whose utilization has been limited by pulmonary toxicity . At the Medical Oncology Department of the Hospital General de Mexico, SS, 17 patients with high-risk testicular cancer were treated with therapeutic regimens based on cisplatin and bleomycin in continuous infusion . The mean bleomycin dose was 813 mg . Adequate renal function was observed in all patients during and after chemotherapy . During a minimum 4-year follow-up period, no patient experienced pulmonary toxicity; 3 patients died due to tumoral progression . The remaining 14 patients are alive and none of them had shown x-ray abnormalities nor a significant reduction in pulmonary vital capacity (PVC) or carbon monoxide diffusion capacity (DLCO) . Bleomycin in continuous infusion can be an appropriate alternative for reducing pulmonary toxic effects . Therefore, randomized controlled studies should be conducted in order to determine if this treatment regime could enhance the therapeutic index.

Acta Med Port, 1993 Aug-Sep, 6(8-9), 377 - 82
{Acute appendicitis in children}; Goncalves M et al.; From January 1st, 1987 to December 31st, 1989, 267 patients were operated upon for acute appendicitis representing 97% of emergency laparotomies at the Pediatric Surgery Department of Santa Maria Hospital (HSM); of these, 207 records were analysed using a retrospective protocol and the results were as follows: most frequent symptoms were abdominal pain (99% of cases) and anorexia (86%) . Referral for surgical evaluation was made in 35.8% of cases 48 hours after the onset of symptoms; surgery was performed in 129 patients (62.4%) in advanced stages of disease, with histopathological examinations of necrotic, perforated and gangrenous appendices . 15 patients (7.2%) had no appendicitis-11 were found to have follicular hyperplasia and 4 normal histology; of these, luminal distention by parasitic eggs was found in 4 . Antibiotic therapy was used in 89 patients preoperatively and in 200 patients postoperatively; cefoxitin was the most commonly used in 89.9% and 83.0% respectively . There were 19 complications (9.2%): 8 parietal, 5 pelvic and 1 subphrenic abscesses, 4 total or partial obstructions and 1 lost drain; 4 patients (1.9%) were reoperated and there was no mortality.

Int J Cancer, 1993 Jul 30, 54(6), 952 - 8
Infection with a transforming growth factor alpha anti-sense retroviral expression vector reduces the in vitro growth and transformation of a human colon cancer cell line; Ciardiello F et al.; Transforming growth factor alpha (TGF alpha) is a growth factor produced by colon cancer cells which may function as an autocrine growth regulator . Therefore, the proliferation and transformation of colon cancer cells might be attenuated by blocking the production of endogenous TGF alpha . GEO cells, from a human colon carcinoma cell line that expresses TGF alpha and functional epidermal growth factor (EGF) receptors, were infected with a replication-defective, recombinant amphotropic retroviral expression vector containing the neomycin-resistance gene and a 435-bp ApaI-EcoRI coding fragment of the human TGF alpha cDNA oriented in the 3' to 5' direction under the transcriptional control of the heavy-metal-inducible mouse metallothionein I promoter . Following antibiotic selection, G418-resistant colonies were pooled and expanded into a cell line (GEO TGF alpha AS cells) . A 50 to 70% inhibition in the production of secreted and cell-associated TGF alpha protein was observed in GEO TGF alpha AS cells that had been maintained in CdCl2-supplemented medium . Moreover, a growth inhibition of 70% and 50% was observed in CdCl2-treated GEO TGF alpha AS cells under anchorage-dependent and anchorage-independent culture conditions, respectively . In contrast, CdCl2 treatment of parental GEO cells had no significant effect upon these parameters . Our results suggest that TGF alpha may be involved in modulating the in vitro cell growth and transformation of human colon cancer cells that express both this growth factor and its cognate receptor.

Biochemistry, 1993 Jul 6, 32(26), 6656 - 63
Tetracenomycin F1 monooxygenase: oxidation of a naphthacenone to a naphthacenequinone in the biosynthesis of tetracenomycin C in Streptomyces glaucescens; Shen B et al.; Tetracenomycin (Tcm) F1 monooxygenase, which catalyzes the oxidation of the naphthacenone Tcm F1 to the 5,12-naphthacenequinone Tcm D3 in the biosynthesis of the anthracycline antibiotic Tcm C in Streptomyces glaucescens, has been purified to homogeneity and characterized . Gel filtration chromatography yields a molecular weight of 37,500 whereas SDS-PAGE gives a single band with a molecular weight of 12,500, indicating that the Tcm F1 monooxygenase is a homotrimer in solution . The N-terminal sequence of the enzyme establishes that it is encoded by the tcmH gene . The monooxygenase displays an optimal pH of 7.5 and has a Km of 7.47 +/- 0.67 microM and Vmax of 473 +/- 10 nmol.min-1.mg-1 . Formally, the Tcm F1 monooxygenase can be classified as an internal monooxygenase that requires only O2 for the enzymatic oxidation . Yet, it apparently does not possess any of the prosthetic groups of known monooxygenases, such as flavin or heme groups, nor does it utilize metal ions . It is inactivated by p-chloromercuribenzoic acid, N-ethylmaleimide, and diethyl pyrocarbonate, suggesting that sulfhydryl groups and histidine residues are essential for the enzyme activity.

Oncogene, 1993 Jul, 8(7), 1731 - 5
Method of identifying inhibitors of oncogenic transformation: selective inhibition of cell growth in serum-free medium; Li PM et al.; We developed a new method for evaluating inhibitors of oncogenic signal transduction pathways based on different growth abilities between normal and transformed cells in a defined serum-free medium . The growth rates of src, abl or ras oncogene-transformed cells, activated raf proto-oncogene transformed cells, and normal NIH-3T3 cells were 60-90%, 20-30% and 10% in a serum-free medium, respectively, compared to the growth rates in a serum-containing medium . An addition of a growth factor (PDGF, FGF or TGF-beta) stimulated the growth of normal NIH3T3 cells by 40-80% in a serum-free medium . Herbimycin A, a specific cytoplasmic protein tyrosine kinase inhibitor, selectively inhibited the growth of src or abl transformed cells in the serum-free medium resulting in about 10-fold or fivefold lower IC50 than those in the serum-containing medium . The antibiotic did not show such an effect on ras transformed cells, and the treatment of src transformed cells with other protein kinase inhibitors or cytotoxic drugs showed little IC50 shifts between the two media . Thus, this method of comparing growth inhibition in the serum-free and the serum-containing media may be useful in evaluating specific inhibitors of signaling pathways mediated by growth factors and certain oncogene products.

Circ Res, 1993 Jul, 73(1), 3 - 9
Gene targeting . The precise manipulation of the mammalian genome; Robbins J; Genetics is a powerful tool for studying the function of different gene products as well as the physiological consequences of a normal or aberrant polypeptide . Until recently, the most powerful genetic applications have been restricted to relatively simple organisms whose genomes are more easily manipulated . For a number of years, in lower organisms, it has been possible to create defined genetic changes that are targeted to a specific locus or even to a defined codon or transcriptional regulatory sequence . With the development of gene targeting using embryonic stem cells derived from the preimplantation blastocyst of a mouse, it has become possible to extend these experiments to a mammalian system . Via homologous recombination, one can ablate, or "knock out," a defined genetic locus or mutate a particular set of nucleotides that encodes a peptide domain of interest . These techniques, when applied to genes that underlie normal cardiovascular function, promise to define the exact role(s) different proteins play during the development, growth, and maintenance of the heart . The ability to generate defined animal models of human disease in which the primary genetic defect is known should lead to fundamental advances in the study of the normal and failing heart.

Prikl Biokhim Mikrobiol, 1993 Jul-Aug, 29(4), 542 - 6
{Identification of aurofusarin in Fusarium graminearum isolates, causing a syndrome of worsening of egg quality in chickens}; Medentsev AG et al.; Twenty isolates of Fusarium graminearum have been isolated from infested grain . When laying hens were fed with biomass of most isolates, the quality of eggs deteriorated . It was found that all the isolated produced a yellow-orange metabolite with an antibiotic activity against mycelial fungi and yeasts . The metabolite was identified by physico-chemical methods as the dimeric naphthoquinone aurofusarin . The production of the other mycotoxins zearalenone and deoxynivalenol by the fungal isolates did not evoke the syndrome of egg quality deterioration.

Pediatr Pulmonol, 1993 Jul, 16(1), 69 - 73
Unusual form of endobronchial Aspergillosis in a patient with cystic fibrosis; Sammut PH et al.; The isolation of Aspergillus fumigatus from airway secretions from patients with cystic fibrosis (CF) is common and usually denotes asymptomatic colonization or allergic broncho-pulmonary aspergillosis (ABPA) . A 12-year-old boy with CF acutely developed moderately severe symptoms of unremitting cough, fever, dyspnea, weight loss, and cyanosis . Chest radiographs demonstrated widespread unilateral infiltrates and volume loss . By bronchoscopy tenacious mucous plugs were seen occluding the left lower lobe bronchus . Cultures from sputum and sequential bronchoalveolar lavage grew Aspergillus fumigatus, but other significant criteria for diagnosing ABPA were lacking . No improvement was seen with a 3 week course of systemic corticosteroid and antibiotic therapy . Treatment with amphotericin B and short-term mechanical ventilation resulted in rapid resolution of all symptoms . This form of endobronchial aspergillosis has not been described previously.

Hum Reprod, 1993 Jul, 8(7), 1143 - 4
Induced regeneration of endometrium following curettage for abortion: a comparative study; Farhi J et al.; A significant increase in endometrial thickness and volume was observed in 30 patients given oestrogen and progestin supplementation following curettage for first trimester abortions, compared with 30 women who received no treatment . This indicates an enhanced regeneration of the endometrium following treatment . The ability to induce this response, creating a space between the intra-cavity surface area a short time after abortion, may theoretically be suggested as preventative treatment to reduce the risk of intrauterine adhesionsPIP: In Israel, gynecologists randomly assigned 60 women who underwent dilatation and curettage (D&C) during the 1st trimester of pregnancy at either the Golda Medical Centre in Petah Tikva or Sackler Medical School of Tel Aviv University to the estrogen and progestin treatment group or the no-treatment group . They wanted to examine the effect of estrogen-progestin therapy on endometrial response after surgical abortion . All the women received prophylactic oral antibiotic therapy after the D&C . 30 women received daily 2 mg estradiol valerate for 21 days and 0.5 mg norgestrel for the last 10 days during the 1st cycle after the D&C . None of the women had any complications during or after the abortion . Women who underwent estrogen-progestin therapy experienced significantly greater endometrial thickness (0.84 cm vs . 0.67 cm; p = 0.02), endometrial width (0.81 cm vs . 0.64 cm; p = 0.002), and endometrial volume (3.85 sq . cm vs . 1.97 sq . cm) than the control group . These findings suggested that estrogen-progestin therapy may overcome curettage's adverse effect on endometrial regeneration . Even though the literature does not show that enhanced regeneration of the endometrium prevents intrauterine adhesions, this treatment does cause significant increase in endometrial thickness and volume which might play a significant role in preventing intrauterine adhesions in women at high risk of developing them .

Zentralbl Hyg Umweltmed, 1993 Jul, 194(4), 392 - 7
{Detection of intracellular multiplication of Legionella pneumophila in protozoa by antigen quantification using ELISA}; Helbig JH et al.; Legionellae and Acanthamoeba castellanii were co-cultivated (37 degrees C, 2 days) to study the intracellular multiplication of Legionella pneumophila strains (n = 37) derived from different sources . The quantification of intracellular growth was observed by both traditional counting of colony forming units and antigen detection by ELISA using polyclonal and monoclonal antibodies . There was a good correlation between the two methods . Depending on detection antibodies chosen, the correlation coefficient ranged from 0.86 to 0.91 . Clinical and water isolates associated with legionellosis exhibited significant higher multiplication rates than water isolates without association with legionelloses . Utilization of antigen estimation by ELISA proved to have the following advantages: (1) Availability of results within a few hours after lysis of cells, and (2) simple handling of co-cultivation owing to omission of killing non-ingested bacteria and elutriate the antibiotic . Therefore, the procedure described is recommended for virulence screening, particularly for large number of colonies of Legionella-positive water samples or genetically manipulated legionellae.

Am J Perinatol, 1993 Jul, 10(4), 323 - 6
Central venous line thrombosis in premature infants: a case management and literature review; Alkalay AL et al.; Increased risk of central venous line thrombosis in tiny premature infants occurs because the size of the catheter relative to the cross-sectional area of the vessel is large, decreased plasma levels of plasminogen and antithrombin III, and relative low flow of the infusate through the catheter, in comparison with larger infants . A potentially fatal complication of central venous catheters is an intracardiac thrombus . The yield of detecting right atrial thrombi by routine echocardiographic monitoring is very low . Persistent positive blood cultures in infants with central venous lines, in spite of appropriate antibiotic therapy, or signs of catheter occlusion, may increase the yield of echocardiographic detection of intracardiac thrombi . Surgical removal of intracardiac thrombi in infants weighing less than 1500 gm carries a high mortality rate because of the need to use cardiopulmonary bypass with total circulatory arrest and profound hypothermia during surgery . It is in these infants that thrombolysis with urokinase should be considered . A successful therapy with urokinase of a complete occlusion of the right pulmonary artery by an embolus originating from the right atrium is described in a premature infant . For thrombolysis, a loading dose of urokinase of 4400 U/kg followed by 4400 to 8800 U/kg/hr for a few days was used . The thrombolytic effect was manifested by decreased thrombus echogenicity followed by its disappearance, by increased fibrinogen split products, and by decreased plasma fibrinogen . Urokinase therapy may cause massive bleeding, dislodge an intracardiac thrombus causing obstruction of cardiac valves or main vessels or causing embolization to the pulmonary or systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

J Microencapsul, 1993 Jul-Sep, 10(3), 367 - 74
Decrease in the placental transfer of chloramphenicol when administered in albumin microspheres into rats; Onur MA et al.; Chloramphenicol is an antibiotic which can pass across the human placenta and has teratogenic effects in the foetus . When this antibiotic is entrapped in albumin microspheres and administered to pregnant rats intravenously its placental transport is significantly lowered when compared with that of free drug . Drug modifications such as entrapment are suggested as an alternative way to prevent harmful effects of drugs in case of consumption during pregnancy.

HNO, 1993 Jul, 41(7), 335 - 8
{Lumbar cerebrospinal fluid drainage for prevention of cerebrospinal fluid fistulas}; Raquet F et al.; Leakage of cerebrospinal fluid may complicate surgical procedures of the temporal bone and skull base . This presentation details experience utilizing 7 days lumbar drainage in an attempt to prevent the occurrence of a postoperative CSF fistula . Thirty-nine patients underwent surgery for various intracranial pathologies and were felt to be at high risk for the development of postoperative CSF fistulae . None of the patients was given prophylactic antibiotics . Ten patients developed clinical and laboratory findings consistent with early meningitis and were treated with appropriate antibiotics . Three patients eventually developed a CSF fistula, with two resolving spontaneously and the third requiring a second surgical procedure to repair the dura (again using lumbar drainage postoperatively) . Our conclusions suggest that prophylactic placement of a lumbar catheter in high risk patients increases the likelihood of successful dural closure with an acceptable morbidity . Is these patients routine antibiotic coverage is not indicated.

Ginekol Pol, 1993 Jul, 64(7), 336 - 9
{Occurrence of correlation between occurrence of genital tract candidiasis in young girls and some subjective and objective examination parameters}; Golab-Lipinska M et al.; The authors tried to find the correlation between the occurrence of genital tract candidiasis in adolescents and some subjective and objective examination parameters . The highest correlation rates were found for pudendal pruritus, lower abdominal pains and early applied antibiotic therapy material: 188 adolescent girls.

J Rheumatol, 1993 Jul, 20(7), 1250 - 2
Interleukin 8: the major neutrophil chemotaxin in a case of pseudogout; Miller EJ et al.; A patient with traumatic osteoarthritis secondary to a pinning procedure, developed monoarthritis following gall bladder surgery . Although the neutrophil count within the synovial fluid (SF) (> 36,000 cells/microliters) suggested an infectious arthritis, there was no improvement following antibiotic therapy . Radiographs indicated the presence of chondrocalcinosis, and calcium pyrophosphate dihydrate crystals were detected within the granulocytes of the SF . The condition was alleviated after administration of colchicine . Before the treatment with colchicine, the neutrophil chemotactic and activating peptide, interleukin 8 (IL-8), was the major neutrophil chemotaxin within the SF . During the course of the treatment, the IL-8 concentration continued to rise in the synovium, while the neutrophil count decreased . Our data indicate that IL-8 was the major neutrophil chemotaxin in the SF, and that while the condition was alleviated with colchicine, the underlying disorder still existed, with the potential that discontinuance of the colchicine would result in the unrestrained action of the IL-8.

Br J Surg, 1993 Jul, 80(7), 917 - 21
Prophylactic use of cefuroxime in biliary tract surgery: randomized controlled trial of single versus multiple dose in high-risk patients . Galant Trial Study Group; Meijer WS et al.; To assess the efficacy of a single-dose short-acting antibiotic in the prevention of septic complications after biliary surgery, a randomized controlled double-blind multicentre trial was conducted . One dose of cefuroxime before operation (1.5 g intravenously) was compared with a three-dose regimen of the drug as control (1.5 g before and two doses of 0.75 g after operation) . The study group comprised 1004 patients with risk factors for infection, who were followed for 4-6 weeks after surgery . The characteristics of both treatment groups were comparable . No significant difference was found between the one- and three-dose antibiotic regimens in preventing postoperative wound infection: 6.6 versus 6.2 per cent for minor wound infection (P = 0.78) and 4.6 versus 3.8 per cent for major wound infection (P = 0.52) . The estimated difference in major wound infection rate between the two groups was 0.8 per cent (95 per cent confidence interval -1.7 to 3.3 per cent).

Berl Munch Tierarztl Wochenschr, 1993 Jul, 106(7), 230 - 5
{Clinical indications of an auxiliary effect of antihistamines (parenteral benadryl) in the treatment of RSV infections of cattle}; Heckert HP et al.; The BRSV-infection belongs to the Bovine Respiratory Disease (BRD) complex . Because of its clinical features as well as pathomorphological and histopathological lesions it can be considered an independent disease . Therefore, concepts of treatment deviating from conventional BRD have to be applied . In addition to antibiotic therapy, therefore, the effect of treatment with the antihistamine Diphenylhydramin (Benadryl-parenteral, Parke Davis) was checked . For the evaluation the internal body temperature was used as measure . With the additional daily application of the antihistamine to the antibiotic therapy the animals were faster without fever . The difference was significant.

Arch Oral Biol, 1993 Jul, 38(7), 601 - 6
Effect of dietary vitamin E supplementation and rotational stress on alveolar bone loss in rice rats; Cohen ME et al.; The effect of this supplementation on bone loss (distance from the cementum-enamel junction to the alveolar crest measured at the midline of the lingual aspect of each of the mandibular molar roots) was studied in rats that were either not stressed or stressed on a rotational device for 90 days . In the first study, neither vitamin E nor stress condition had statistically significant effects but there was substantial bone loss and bone-loss variability in all groups . Before the start of the second study, to reduce differences in bone loss that might otherwise exist before introduction of the treatments, rats received an antibiotic in their drinking water . In addition, rotational stress was introduced more abruptly than in the first study to reduce the likelihood of adaptation . Bone loss and bone-loss variability were substantially reduced in the second study . Analysis of these data indicated that vitamin E supplementation had a statistically significant protective effect, which was most pronounced at sites most susceptible to loss . Stressed subjects tended to lose more bone, but this effect was not significant . These findings suggest some role for vitamin E supplementation in the maintenance of periodontal health but also a sensitivity in this effect to initial periodontal status.

Nippon Jibiinkoka Gakkai Kaiho, 1993 Jul, 96(7), 1133 - 40
{Clinical observation of acute otitis media in children}; Tomiyama M; The efficacy of a combination of cefaclor and fosfomycin otic solution was investigated in 81 children with acute otitis media, who needed myringotomy for severe erythema and swelling of the tympanic membrane . The patients were followed up for one year to investigate correlations between test findings of early treatment and both clinical course and prognosis . These drugs were used for 10 days, and the effects of combined use were evaluated from findings in the tympanic membrane after the 10-day period . Three stages were assessed; cured, recovered and unchanged . In cured and recovered cases, the administration was evaluated to be effective . Within 2 weeks after the start of treatment, views of the ears, nose and epipharynx were roentgenographically examined for shadows of mastoid pneumatization and the paranasal sinuses, and the presence or absence of adenoid vegetation . After the antibiotic administration, the patients were instructed to visit us at least once every 3 months to rule out recurrence of acute otitis media and otitis media with effusion (possibly occurring one year after treatment) . The following results were obtained . 1 . The two drug combination was effective in 99% of patients, produced no side effects, and was deemed extremely useful . 2 . The course of acute otitis media tended to be significantly prolonged in patients with mastoid pneumatization and paranasal sinus shadows as revealed by roentgenography.(ABSTRACT TRUNCATED AT 250 WORDS)

Clin Pediatr (Phila), 1993 Jul, 32(7), 401 - 4
Efficacy of a protocol to distinguish risk of serious bacterial infection in the outpatient evaluation of febrile young infants; Bonadio WA et al.; A study of 534 febrile infants ages 4 to 8 weeks evaluated for sepsis assessed the efficacy of the Milwaukee Protocol (MP) for selecting patients at low risk for serious bacterial infection (SBI) who might benefit from outpatient management . Two groups were compared: 1) Infants with uncompromised presentation (UP) who met all MP criteria received ceftriaxone 50 mg/kg and were discharged, then reevaluated within 24 hours . 2) Infants with compromised presentation (CP) who did not meet MP criteria were hospitalized for antibiotic therapy pending culture results . Of 391 CP patients, 23 (5.9%) had SBI; of 143 UP patients, 1 (0.7%) had SBI (P < .02) . The MP criteria had a sensitivity of 96% and a 99% negative predictive value for distinguishing SBI outcome . The only UP patient with SBI was afebrile and had a negative repeat blood culture after 24 hours, and recovered with no complications . Managing UP infants as outpatients avoided 48 to 72 hours of hospitalization, decreasing health-care costs by an estimated total of $465,170.

Ann Pharmacother, 1993 Jul-Aug, 27(7-8), 967 - 71
Ceftazidime dosing in the elderly: economic implications; Vlasses PH et al.; OBJECTIVE: This study evaluated the prevalence and resulting costs of ceftazidime dosing in excess of product labeling recommendations in elderly hospitalized patients . Ceftazidime is a beta-lactam antibiotic excreted via glomerular filtration . According to product labeling, ceftazidime dosing can frequently be decreased in the elderly because glomerular filtration declines with age . METHODOLOGY: A multicenter, retrospective utilization audit involving 11 US academic medical centers examined 221 medical records of patients 65 years of age or older receiving ceftazidime (any brand, any indication) . The creatinine clearance of each patient was estimated using the Cockcroft-Gault formula . RESULTS: Renal insufficiency, defined as an estimated creatinine clearance of less than 50 mL/min, was present in 111 of the patients (50 percent) . Ceftazidime dosing in excess of product labeling recommendations was noted in 75 of those 111 (68 percent) . The cost of excess ceftazidime dosing for those 75 patients (i.e., extra drug acquisition, preparation, administration) was $13,822.50 . CONCLUSIONS: Although the dosage of ceftazidime required in a specific patient is based on many factors, ceftazidime is frequently overdosed in the elderly because renal function is not considered . Ceftazidime dose-adjustment in the elderly, based on the estimated creatinine clearance, can lead to cost savings . In the US, where hospital reimbursement by Medicare is based on diagnosis, institutions can realize direct cost savings.

J Antibiot (Tokyo), 1993 Jul, 46(7), 1069 - 75
R1128 substances, novel non-steroidal estrogen-receptor antagonists produced by a Streptomyces . III . Pharmacological properties and antitumor activities; Hori Y et al.; R1128 B (1,3,6-trihydroxy-8-n-butylanthraquinone), a new antibiotic produced by Streptomyces sp . No . 1128, inhibited estrogen binding to its receptor . The IC50 value of R1128 B for partially purified rat uterine cytosol receptor was 1.2 x 10(-7) M . However, the IC50 value of R1128 B against androgen-receptor binding was about 50-fold greater than that against estrogen-receptor binding . R1128 B was a competitive inhibitor against estrogen-receptor binding . R1128 B inhibited the growth of estrogen-responsive human mammary adenocarcinoma MCF-7 cells in soft agar . This inhibition, however, was reversed when estradiol was added to the culture medium . R1128 B showed antitumor activities against MCF-7 both xenografted to nude mice and implanted in subrenal capsule of mice (SRC assay) . The potency of R1128 B was about 8-fold lower than that of tamoxifen both in vitro and in vivo.

Ann Plast Surg, 1993 Jul, 31(1), 78 - 81
Control of hemorrhage during renal failure with triglycyl-lysine-vasopressin; Garner WL et al.; A 35-year-old man with chronic renal failure developed toxic epidermal necrolysis due to combination antibiotic therapy for a community acquired pneumonia . During wound care for his toxic epidermal necrolysis, he developed massive bleeding, a 4 to 6 unit blood loss at each dressing change, due to uremia-associated platelet dysfunction and thrombocytopenia . After failure of standard therapy, the man was treated with intravenous triglycyl-lysine-vasopressin, a selective peripheral vasoconstrictor . Transfusion requirements stopped during treatment . This man went on to full recovery with complete wound healing . Triglycyl-lysine-vasopressin effectively reduced skin blood loss in this man with toxic epidermal necrolysis and an intrinsic hemostatic defect, and may be useful in other patients with cutaneous blood loss.

J Am Board Fam Pract, 1993 Jul-Aug, 6(4), 333 - 9
Acute otitis media in adults: a report from the International Primary Care Network; Culpepper L et al.; BACKGROUND: Of 22 million visits annually to United States physicians for acute otitis media, almost 4 million are by patients 15 years old or older . Yet the clinical spectrum and variables related to recovery have not been reported for adults . METHOD: Data originated from 3224 primary care patients with acute otitis media, of whom 500 were 15 years old or older, who were enrolled in a prospective study in eight countries . At the initial visit, history, symptoms, physical findings, and treatment were recorded . At a 2-month follow-up visit, changes in treatment and recovery were recorded . RESULTS: Compared with children, adults sought care more quickly after symptom onset; were more likely to have had a tonsillectomy or adenoidectomy; and were more likely to complain of ear pain, decreased hearing, sore throat, and ear discharge . Children were more likely to have a history of recent upper respiratory tract infection, serous otitis media, and ear tubes; symptoms of fever, diarrhea, and vomiting; and tympanic membrane findings of redness, bulging, and ear tubes in place . History of reduced hearing, allergy, prophylactic antibiotics, and tympanic membrane findings characterized as opaque or dull, fluid, draining pus, perforation, and not visualized were equally frequent in both age groups . For adults, neither type nor duration of antibiotic affected outcome . Patients receiving antibiotics had lower rates of recovery than those who did not . The likelihood of a poor outcome increased with an increasing number of past episodes of acute otitis media and with increasing age . CONCLUSION: Although history and symptoms differ in adults and children, the similarity of tympanic membrane findings is consistent with previous reports of a similar bacterial spectrum in both groups . Recovery is related more to individual patient characteristics and history than to antibiotic therapy . Adults have an increased rate of poor outcome at 2 months compared with children.

Pediatr Infect Dis J, 1993 Jul, 12(7), 574 - 7
Risk factors associated with fungal peritonitis in very low birth weight neonates with severe necrotizing enterocolitis: a case-control study; Karlowicz MG; Fungal peritonitis is uncommon in infants with severe necrotizing enterocolitis with intestinal perforation . In our institution we noted a significant (P < 0.01) increase in fungal peritonitis from 7% (3 of 45 cases of peritonitis) from January, 1980, to June, 1989, to 35% (8 of 23 cases of peritonitis) from July, 1989, to December, 1991 . The mean birth weight of 11 infants with fungal peritonitis (946 +/- 70 g) (mean +/- SE) was significantly less (P = 0.008) than that of 57 infants with bacterial peritonitis (1282 +/- 52 g) . In a case-control study to identify risk factors associated with fungal peritonitis, 11 infants with bacterial peritonitis were matched to the 11 infants with fungal peritonitis by age at bowel perforation and birth weight . Infants with fungal compared with bacterial peritonitis had significantly longer (P < 0.05): median duration of umbilical vessel catheterization before bowel perforation, 10 vs . 3 days, respectively; median duration of antibiotic therapy before bowel perforation, 23 vs . 14 days, respectively; and median duration of intubation, 13 vs . 5 days, respectively . Other potential risk factors that were not significant in this study included duration of central venous catheterization, total parenteral nutrition, intravenous lipid administration, aminoglycoside use, dexamethasone use or methyl xanthine therapy . In summary fungal peritonitis in neonates with necrotizing enteritis was significantly related to extremely low birth weight, prolonged umbilical vessel catheterization, prolonged exposure to antibiotics and prolonged intubation.

Pediatr Infect Dis J, 1993 Jul, 12(7), 571 - 3
Mycoplasma hominis and Ureaplasma urealyticum in neonates with suspected infection; Valencia GB et al.; The role of genital mycoplasmas in the pathogenesis of neonatal infection is incompletely understood . We performed nasopharyngeal, blood and cerebrospinal fluid (CSF) cultures for Mycoplasma hominis and Ureaplasma urealyticum in 69 neonates who underwent a diagnostic workup for suspected sepsis . The mean gestational age was 35.9 weeks (range, 25 to 42 weeks) with a mean birth weight of 2386 g (range, 652 to 4420 g) . Twenty-seven infants (39.1%) had positive nasopharyngeal cultures; 6 were positive for M . hominis, 10 for U . urealyticum and 11 for both organisms . Seven (26%) of these 27 patients developed chronic lung disease compared with 2 (4.7%) infants in the non-colonized group . Nine infants had positive CSF cultures for M . hominis and one infant had a positive CSF culture for U . urealyticum . All blood cultures were sterile . One of the infants with a positive CSF culture for M . hominis had clinical evidence of systemic infection . All of the infants were treated with antibiotic agents that were not active against mycoplasmas . These data indicate that genital mycoplasmas can be found commonly in the CSF and nasopharynx of infants with suspected sepsis . Their etiologic role in the causation of infection and chronic lung disease, however, remains unclear.

J Fam Pract, 1993 Jul, 37(1), 23 - 7
The effect of parental expectations on treatment of children with a cough: a report from ASPN; Vinson DC et al.; BACKGROUND . A previous retrospective study of children with cough raised questions about how physicians diagnose acute bronchitis . We hypothesized that if the physician perceives a parental expectation that an antibiotic is needed, it is more likely that a child with a cough will be diagnosed as having bronchitis and treated with an antibiotic . METHODS . Data were collected prospectively in 44 primary care practices in the Ambulatory Sentinel Practice Network . Variables examined included elements of the patient's history and physical examination, diagnoses made, and treatments prescribed . RESULTS . Data regarding 1398 patients were collected . A parental expectation that a prescription for an antibiotic would be given was associated with an increased likelihood of a diagnosis of bronchitis (relative risk 2.04, 95% confidence limits, 1.76 to 2.35, P < .001), and was second only to the physical finding of rales in the magnitude of its association with that diagnosis . The only other diagnosis associated with parental expectation of an antibiotic was viral upper respiratory tract infection, where parental expectation of treatment with an antibiotic was associated with a 49% reduction in the probability of that diagnosis . CONCLUSIONS . The expectations of parents of children with a cough appear to influence physician decision making.

Transplantation, 1993 Jul, 56(1), 15 - 9
Effects of rapamycin in experimental organ allografting; Ochiai T et al.; The immunosuppressive effect of rapamycin (RAPA), a macrolide antibiotic produced by Streptomyces hygroscopicus, was tested using allografts in the rat and dog . It was immunosuppressive at a dose of 3.0 mg/kg/day for 8 days in skin allografts and 0.1 mg/kg/day for 11 days using cardiac allografts in the rat . It prevented rejection of renal allografts in beagle dogs at a dose of 0.3 mg/kg; however, emaciation and gastrointestinal toxicity resulted in some deaths in dogs . Mucosal necrosis and vasculitis in the submucosal layer were the predominant findings at autopsy in dogs receiving RAPA . Serum amylase values rose soon after commencement of RAPA treatment . Combined drug treatment with CsA at a nonimmunosuppressive dose of 3.2 mg/kg in the rat or 2.5 mg/kg in the dog was synergistic, with a low dose of 0.1 mg/kg/week RAPA . Combined therapy of CsA and RAPA also inhibited the frequency of vasculitis and emaciation in dogs . The present data suggest that RAPA is immunosuppressive in organ allografting and that the combination of CsA and RAPA would be effective clinically.

Am J Med, 1993 Jul, 95(1), 16 - 22
Nosocomial Legionnaires' disease: aspiration as a primary mode of disease acquisition; Blatt SP et al.; PURPOSE: Nosocomial Legionnaires' disease remains a significant problem with many unresolved questions regarding transmission of legionella organisms to patients . We performed a case-control and environmental study to identify risk factors and modes of transmission of Legionella infection during an outbreak of nosocomial Legionnaires' disease in a military medical center . PATIENTS AND METHODS: During the calendar year 1989, 14 cases of nosocomial Legionnaires' disease were identified by active surveillance following the discovery of 2 culture-proven cases among organ transplant recipients . Four control patients were matched to each case by age, sex, and date of admission . Cases and controls were compared with respect to past medical history and hospital exposure variables . Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for matched variables . Environmental culturing of air and water supplies in and around the medical center was also performed . RESULTS: The case-control study revealed the following significant risk factors for the acquisition of nosocomial Legionnaires' disease: immunosuppressive therapy (OR = 32.7, CI = 4.5 to 302.6), nasogastric tube use (OR = 18.4, CI = 2.6 to 166.2), bedbathing (OR = 10.7, CI = 2.2 to 59.0), and antibiotic therapy (OR = 14.6, CI = 2.9 to 84.4) . Shower use (OR = 0.1, CI = 0 to 0.4) appeared to be a negative risk factor . Water cultures revealed Legionella pneumophila serogroup 1, monoclonal antibody subtype Philadelphia (identical to all patient isolates) in the ground-water supply to the hospital, 1 hot-water tank, and 15% of 85 potable water sites tested . Air sampling of cooling towers, hospital air intakes, and medical air and oxygen supplies were negative for Legionella organisms . CONCLUSIONS: This study confirms the importance of potable water in transmitting nosocomial Legionnaires' disease and suggests that the organism gains access to the hospital via external water supplies . The risk factors identified in this case-control study provide evidence that Legionnaires' disease may act as a superinfection in a nosocomial setting and is likely acquired by aspiration, similar to other nosocomial pneumonias.

J Clin Epidemiol, 1993 Jul, 46(7), 625 - 30
Cefazolin compared with cefoxitin for cesarean section prophylaxis: the use of a two-stage study design; Currier JS et al.; The authors used a two-stage design to compare the risk of endometritis in women undergoing non-elective cesarean section who received cefazolin prophylaxis (n = 481) with those who received cefoxitin prophylaxis (n = 1799) . The primary data source for this study was an automated record linkage system which allowed the ascertainment of exposure(antibiotic prophylaxis) and preliminary ascertainment of outcome (post-partum endometritis) on a consecutive sample of women undergoing cesarean section between 1 April 1987 and 30 September 1989 . Potentially important covariates not available in the automated data source were sampled by review of complete medical records of a random sample of each exposure-disease category of the cohort . Of the 2280 women studied, 99 (4.3%) developed postpartum endometritis . After control for age, race, anemia, presence of ruptured membranes, parity, labor, number of vaginal examinations and payor status the adjusted odds ratio for cefazolin compared to cefoxitin was 0.95 (95% C.I . 0.5-1.9) . The cost of prophylaxis was significantly higher for women who received cefoxitin prophylaxis ($56/patient vs $9.55/patient) . These results suggest that cefazolin prophylaxis should be favored over cefoxitin due to lower cost and similar efficacy . This study also demonstrates the efficiency of a two-stage design in the setting where exposure and outcome are available for an entire cohort but information about important covariates is more difficult to obtain.

Clin Plast Surg, 1993 Jul, 20(3), 551 - 7
Management of intrathoracic defects; Clay RP et al.; Most intrathoracic transpositions involve the serratus anterior, pectoralis major, and latissimus dorsi muscles . These muscles provide an adequate mass and length of muscle for coverage of most structures in the mediastinum and have a single, dominant vascular axis . Winging of the scapula can occur with the harvest of the serratus anterior unless this is prevented by the maintenance of the upper two or three muscle slips as described previously . Even if winging does occur, we believe it to be a reasonable price to pay for control of the ongoing infection . Transposition of the latissimus dorsi and pectoralis major produce little if any significant cosmetic or functional defect in these ill patients . These muscles are transposed to assist in sealing of fistulas and to bolster vascular or visceral repair . We do not think that complete soft-tissue obliteration of the pleural cavity is necessary, and we continue to use the Clagett method of antibiotic-solution filling of the chest cavity at closure . In the irradiated patient with poor healing potential, intrathoracic muscle flaps may provide a means to salvage situations previously considered unsalvageable when the flaps are combined with sound principles of infection control; when used prophylactically, the flaps may prevent those same situations.

Am Surg, 1993 Jul, 59(7), 465 - 9
Optimal regional coverage of exposed in situ vein bypass by muscle flaps; Hans SS; Three patients with exposed in situ saphenous vein bypass resulting from major wound breakdown in the groin, thigh, and calf are reported . Successful coverage of the exposed arterial bypass was accomplished by appropriately placed myocutaneous or muscle flaps at three different anatomical locations in combination with antibiotic therapy and aggressive debridement.

Cancer Res, 1993 Jul 1, 53(13), 3052 - 7
Anticancer efficacy of Magainin2 and analogue peptides; Baker MA et al.; Linear helical channel-forming peptides structurally similar to the Xenopus-derived antibiotic, Magainin2-amide, were synthesized . Because activity resides in the physicochemical properties of the peptides, an all-D-amino acid as well as an all-L-amino acid sequence were tested for anticancer activity . In vitro activity against carcinoma cells and in vivo efficacy against four murine ascites tumors were determined . The novel peptides proved to have enhanced potency in vitro and in vivo as compared to the parent compound . The 50% inhibitory concentrations against A549 cells for the all-D, the all-L, and Magainin2 were 6, 10, and 110 micrograms/ml, respectively . All three peptides had activity against P388 leukemia, S180 ascites, and a spontaneous ovarian tumor when injected i.p . Increase in life span of over 100% was produced for the analogues in the latter two models . The maximally effective concentrations for the analogues were 20 to 25 mg/kg while Magainin2 required 50-60 mg/kg for in vivo efficacy . The all-D-amino acid peptide, MSI-238, proved as effective as doxorubicin at a more advanced stage of the ovarian tumor and this activity may be attributed to its resistance to proteolytic degradation . Therefore, this class of amphiphilic alpha-helical cationic peptides has potential in the peritoneal treatment of ovarian cancer.

Vojnosanit Pregl, 1993 Jul-Aug, 50(4), 359 - 64
{Clinical characteristics of Lyme disease}; Bojic I et al.; Clinical characteristics of Lyme disease were analysed in 22 patients . Erythema migrans was found in 20 (91%), arthralgia in 18 (81%), neuralgia in 8 (36%), encephalitis in 3 (13%), carditis in 2 (9%) and arthritis in 2 (9%) patients . The positive antibody titer was found in 14 (63%) patients . Favourable effects of antibiotic therapy was achieved in all patients . Erythema migrans has been manifested up to 12 days after tick sting and arthralgia, arthritis, neuralgia, hepatitis and chronic dermatitis within a year . Carditis and encephalitis have been developing from a month to ten years after tick sting . Lyme borreliosis is commonly manifested as a systemic disease . Together with the skin, most commonly have been involved ankle joints, heart and nervous system . The time from tick sting to the onset of first signs of the diseases varies by the involved organs.

J Heart Valve Dis, 1993 Jul, 2(4), 380 - 4
Aortic infective endocarditis managed by the Ross procedure; Oswalt JD et al.; The excellent clinical results with homografts inserted for aortic endocarditis encouraged us to take this method one step further, believing that the placement of a pulmonary autograft which is totally viable and antibiotic-perfused would be an even better choice for valve replacement . We applied this technique in 13 consecutive patients with infective aortic endocarditis, achieving excellent early results . Our follow up extending to 30 months continues to show excellent results with 0% re-infection and 0% mortality . We conclude from our experience that this technique affords excellent results in curing the infection with the lowest chance of thromboembolism, the lack of need for anticoagulation and only a small chance of reoperation in the future.

Ann Vasc Surg, 1993 Jul, 7(4), 343 - 6
Candida thrombosis of the innominate vein with septic pulmonary emboli; Kelly RF et al.; Thrombosis of central veins has become more prevalent because of increased use of long-term central venous catheterization . Candida superinfection of the thrombus can occur particularly in patients on long-term antibiotic therapy and on parenteral nutrition . Removal of the catheter, thrombolytic therapy, anticoagulation, and antifungal therapy with amphotericin B will usually eradicate the candidemia and restore venous patency . Occasionally this therapeutic regimen fails . This case report illustrates such a failure in which multiple pulmonary emboli could have caused death . Surgical thrombectomy of the innominate vein effectively removed the source of the Candida sepsis and maintained patency of a major vein . Thrombectomy should be considered as a therapeutic option in septic central vein thrombosis.

Infection, 1993 Jul-Aug, 21(4), 223 - 8
Ceftazidime versus ceftazidime plus tobramycin in febrile neutropenic children; Jacobs RF et al.; Although the effectiveness of antibiotic monotherapy in febrile neutropenic patients remains unproven, ceftazidime has been shown previously to be effective monotherapy for the empiric treatment of selective patients . The efficacy and safety of ceftazidime versus ceftazidime plus tobramycin was evaluated in the treatment of febrile children (range 8 months to 18 years) with neutropenia secondary to cancer chemotherapeutic agents . Of the evaluable 89 patients, 45 received ceftazidime and 44 received ceftazidime plus tobramycin for 5 to 10 days . At the end of therapy, 30 (67%) of the 45 ceftazidime-treated patients were clinically cured compared with 38 (86%) of 44 combination-treated patients . Thirteen (29%) of the patients treated with ceftazidime failed to respond clinically to treatment, versus four (9%) of the patients treated with ceftazidime/tobramycin (p = 0.046) . This study suggests that ceftazidime as monotherapy in febrile neutropenic children may be inferior to combination therapy for optimal clinical response in these patients.

Z Naturforsch {C}, 1993 Jul-Aug, 48(7-8), 632 - 9
X-ray studies on phospholipid bilayers . XIII . Interactions with gentamicin; Suwalsky M et al.; This study deals with the structural perturbations that the aminoglycoside antibiotic gentamicin (GENT) can produce to phospholipid bilayers . Two multi-bilayer systems, one built-up of dimyristoylphosphatidylcholine (DMPC) and the other of dimyristoylphosphatidylethanolamine (DMPE) were allowed to interact with GENT . The experiments were performed in both a hydrophobic and a hydrophilic medium below the phospholipid main transition temperatures . X-ray diffraction techniques were used to determine the extent of the perturbation induced by GENT . The maximum effect was attained when GENT interacted with DMPC in the hydrophobic medium . On the other hand, GENT in aqueous solutions was unable to perturb in any significant extent the structure of the phospholipids under study.

J Postgrad Med, 1993 Jul-Sep, 39(3), 134 - 6
Effect of pre-operative skin preparation on post-operative wound infection; Shirahatti RG et al.; A prospective randomised trial was carried out to compare the efficacy of method of scrubbing the operative site for ten minutes with an antiseptic (GpA; n = 68) with a simplified method where the antiseptic was merely painted onto the operation site (GpB; n = 67) . The median age, sex distribution and the types of procedures done in each group were similar as was the antibiotic policy . There were a total of 11 patients who got infected, 6 in the group A and 5 in the group B . No significant difference could be demonstrated in the infection rates between the two groups . It is concluded that the old method of prolonged scrubbing the operation site can safely be omitted to a more simplified version.

Wiad Lek, 1993 Jul, 46(13-14), 506 - 10
{Borreliosis}; Lukasik S et al.; Borreliosis which incidence and epidemic range are constantly increasing is an infectious zoonosis, detected in the town of Lyme, Connecticut, USA in 1975 . This disease is caused by Borrelia burgdorferi transmitted by ticks . It relatively easily responds to antibiotic therapy . Making of correct diagnosis, however, causes more problems . The disease has often atypical course, its phases overlap . It may also mimic collagen diseases and other spirochetoses . The relatively low specificity of serological tests additionally makes the diagnosis more difficult.

Comp Biochem Physiol C, 1993 Jul, 105(3), 521 - 4
In vivo evaluation of reuterin and its combinations with suramin, melarsoprol, DL-alpha-difluoromethylornithine and bleomycin in mice infected with Trypanosoma brucei brucei; Yunmbam MK et al.; 1 . Trypanosoma brucei brucei-infected mouse models treated with a new antibiotic, reuterin, showed reduction of the levels of parasitemia and prolonged survival of the mice . 2 . Cures of the parasitemia were observed in groups of mice treated with combinations of reuterin and suramin or melarsoprol . 3 . Reuterin administered in combination with bleomycin or DL-alpha-difluoromethylornithine showed temporary remission of the parasitemia in groups of mice.

Infect Immun, 1993 Jul, 61(7), 2774 - 9
Association of treatment-resistant chronic Lyme arthritis with HLA-DR4 and antibody reactivity to OspA and OspB of Borrelia burgdorferi; Kalish RA et al.; Chronic Lyme arthritis that is unresponsive to antibiotic therapy is associated with an increased frequency of the HLA-DR4 specificity . To determine whether the immune response to a particular polypeptide of Borrelia burgdorferi may be associated with treatment-resistant chronic Lyme arthritis, we correlated the clinical courses and HLA-DR specificities of 128 patients with Lyme disease with their antibody responses to spirochetal polypeptides . Antibody reactivity was determined by Western blotting (immunoblotting) with sonicated whole B . burgdorferi and recombinant forms of its outer surface proteins, OspA and OspB, as the antigen preparations . Of 15 patients monitored for 4 to 12 years, 11 (73%) developed strong immunoglobulin G responses to both OspA and OspB near the beginning of prolonged episodes of arthritis, from 5 months to 7 years after disease onset . When single serum samples from 80 patients with Lyme arthritis, were tested, 57 (71%) showed antibody reactivity to recombinant Osp proteins; in contrast, none of 43 patients who had erythema migrans or Lyme meningitis (P < 0.00001) and 1 of 5 patients who had chronic neuroborreliosis but who never had arthritis (P = 0.03) showed antibody reactivity to these proteins . Among the 60 antibiotic-treated patients with Lyme arthritis, those with the HLA-DR4 specificity and Osp reactivity had arthritis for a significantly longer time after treatment than those who lacked Osp reactivity (median duration, 9.5 versus 4 months; P = 0.009); a similar trend was found for the HLA-DR2 specificity . For other HLA-DR specificities, arthritis resolved within a median duration of 2 months in both Osp-reactive and nonreactive patients . We conclude that the combination of the HLA-DR4 specificity and OspA or OspB reactivity is associated with chronic arthritis and the lack of a response to antibiotic therapy.

Int J Food Microbiol, 1993 Jun 25, 19(1), 1 - 14
Selective media for detecting and enumerating foodborne yeasts; Beuchat LR; No one medium is satisfactory for detecting, isolating and enumerating all yeasts in all foods . Antibiotic-supplemented media such as dichloran rose Bengal chloramphenicol agar, tryptone glucose yeast extract chloramphenicol agar, oxytetracycline glucose yeast extract agar and rose Bengal chloramphenicol agar are superior to acidified potato dextrose agar and other acidified media for enumeration of the vast majority of spoilage yeasts . Dichloran glycerol (18%) agar performs well for enumerating moderately xerotolerant yeasts . Malt extract yeast extract glucose (up to 60%) can be used for detecting and enumerating moderate and extreme xerophiles . These media also support the growth of moulds . Lysine agar, Schwarz differential agar and Lin's wild yeast differential agar are used by the brewing industry to differentiate wild yeasts from brewer's strains . Lysine agar is selective for apiculate yeasts and ethanol sulfite yeast extract agar is selective for Saccharomyces . Both have application in wineries . Modified molybdate agar can be used to selectively isolate yeasts from tropical fruits . Preservative-resistant yeasts can be detected on malt acetic agar . The recommended incubation temperature is 25 degrees C, but incubation time between plating and counting colonies ranges from 5 days for determination of general populations of yeasts to 10 days for more for xerotolerant yeasts . There is need for new and improved media for selectively isolating various groups, genera, species and strains of yeasts capable of growing only under specific environmental conditions in specific types of foods and beverages.

Schweiz Med Wochenschr, 1993 Jun 12, 123(23), 1203 - 6
{Drug-induced liver disease: experiences of the Swiss Center for Adverse Drug Effects 1989-1991}; Werth B et al.; Drug-induced liver disease can mimic any form of acute or chronic liver disease . Suspected drug-induced liver disease makes up between 4 and 7% of all reports of adverse drug effects voluntarily reported to central registries . We report on all patients with drug-induced hepatotoxic reactions voluntarily reported to the Swiss Adverse Drug Reaction Center from 1989 to 1991 . In that period there was a total of 2084 reports of which 140 (6.7%) concerned the liver . In 16 cases two drugs were simultaneously involved, so that 156 investigations were carried out . We found a causal relationship in 123 cases . Antibiotic and chemotherapeutic agents were the drugs most frequently involved . There were seven fatal cases (5%) . Our data correspond with the data in the literature . Regarding the amount of drugs prescribed, the hepatic adverse effect can be regarded as common.

Nucleic Acids Res, 1993 Jun 11, 21(11), 2613 - 7
Introduction of a point mutation into the mouse genome by homologous recombination in embryonic stem cells using a replacement type vector with a selectable marker; Rubinstein M et al.; The introduction of small mutations instead of null alleles into the mouse genome has broad applications to the study of protein structure-function relationships and the creation of animal models of human genetic diseases . To test a simple mutational strategy we designed a targeting vector for the mouse proopiomelanocortin (POMC) gene containing a single nucleotide insertion that converts the initial tyrosine codon of beta-endorphin 1-31 to a premature translational termination codon and introduces a unique Hpal endonuclease restriction site . The targeting vector also contains a neo cassette immediately 3' to the last POMC exon and a herpes simplex virus thymidine kinase cassette to allow positive and negative selection . Homologous recombination occurred at a frequency of 1/30 clones of electroporated embryonic stem cells selected in G418 and gancyclovir . 10/11 clones identified initially by a polymerase chain reaction (PCR) strategy had the predicted structure without evidence of concatemer formation by Southern blot analysis . We used a combination of Hpa I digestion of PCR amplified fragments and direct nucleotide sequencing to further confirm that the point mutation was retained in 9/10 clones . The POMC gene was transcriptionally silent in embryonic stem cells and the targeted allele was not activated by the downstream phosphoglycerate kinase-1 promoter that transcribed the neo gene . Under the electroporation conditions used, we have demonstrated that a point mutation can be introduced with high efficiency and precision into the POMC gene using a replacement type vector containing a retained selectable marker without affecting expression of the allele in the embryonic stem cells . A similar strategy may be useful for a wide range of genes.

Biochim Biophys Acta, 1993 Jun 5, 1148(2), 269 - 77
CD and NMR studies on the aggregation of amphotericin-B in solution; Balakrishnan AR et al.; We report in this paper the aggregation properties of amphotericin-B (amp-B) in solution using CD and 1H-NMR techniques . Our results indicate that the preferred structure of amp-B in dimethylsulfoxide is a monomer at low concentrations (10(-4) M and below) and a stable dimer at higher concentrations (range 5.10(-3) M to 10(-2) M) . In a DMSO/ethanol mixture (1:1 (v/v)), the antibiotic is monomeric, irrespective of the concentration within the range studied . We propose a head-to-tail model based on NMR data . An understanding of the head-to-tail dimer, is, we believe important, particularly in view of the recent report wherein it is proposed that the drug inserts into bilayers as head-to-tail oligomers.

Biochim Biophys Acta, 1993 Jun 5, 1148(2), 257 - 62
Alamethicin as a permeabilizing agent for measurements of Ca(2+)-dependent ATPase activity in proteoliposomes, sealed membrane vesicles, and whole cells; Ritov VB et al.; The channel-forming antibiotic peptide alamethicin was used in measurements of Ca-ATPase activity in sarcoplasmic reticulum (SR) vesicles, proteoliposomes containing Ca(2+)-ATPase from SR, and native human platelets . Alamethicin was used as a permeabilizing agent providing for a free access of the whole cells or sealed vesicles interiors for ions, ATP, and other reactants . The experiments were carried out with the use of alamethicin preparations obtained in our laboratory and that purchased from the Upjohn Company (antibiotic U-22,324) . A comparative study of the effects of Ca(2+)-ionophore A23187 and alamethicin was performed on native SR vesicles containing Ca(2+)-ATPase molecules with right orientation and SR vesicles treated with cholate in order to randomize Ca(2+)-ATPase molecules orientation in the membrane . It was found out that alamethicin, like A-23187, prevents the ATP-dependent Ca2+ accumulation by the vesicles and therefore activates the Ca(2+)-ATPase . Maximal specific activities of the Ca(2+)-ATPase in native SR vesicles in the presence of either alamethicin, or A23187, or both of them, are equal in all cases to 20 activity units (mumol Pi per min per mg protein) . The operative range of alamethicin concentrations is 5-25 micrograms/ml and is a little wider than that for A23187 . The ATPase activity of the SR vesicles treated with cholate reached 20 units in the presence of alamethicin while in the presence of A23187 it was only 10 units . These data suggest that alamethicin unlike A23187 allows ATP to reach the ATPase's active centers from the inside of the SR vesicles with 'randomized' membranes, the ATP transport through the membrane not being the rate-limiting stage of ATP hydrolysis . It was shown that diffusion flux of ATP through a BLM in the presence of alamethicin may reach 10% of the flux through the hole without the BLM . With the use of alamethicin it was found out that the quality of randomization of the ATPase molecules orientation in the membrane depends on the proteoliposome preparation technique . The ATP transport through the alamethicin pores makes possible the use of alamethicin in accurate measurements of Ca(2+)-ATPase activity in whole cells . A method was developed for determination of the activity of human platelets was found to be 90-100 nmol Pi per min per mg protein.

J Clin Invest, 1993 Jun, 91(6), 2791 - 5
Herbimycin A, a pp60c-src tyrosine kinase inhibitor, inhibits osteoclastic bone resorption in vitro and hypercalcemia in vivo; Yoneda T et al.; Since absence of expression of the c-src gene product in mice indicates that the pp60c-src tyrosine kinase is required and essential for osteoclastic bone resorption, we tested the effects of the antibiotic herbimycin A, which is an inhibitor of pp60c-src on osteoclastic bone resorption in vitro and on hypercalcemia in vivo . We examined the effects of herbimycin A on the formation of bone resorbing osteoclasts in mouse long-term marrow cultures, on isolated rodent osteoclasts and on bone resorption in organ cultures of fetal rat long bones stimulated by parathyroid hormone . We found that herbimycin A in concentrations of 1-100 ng/ml inhibited bone resorption in each of these systems . We determined the effects of herbimycin A (100 ng/ml) on src tyrosine kinase activity in mouse marrow cultures and found that it was decreased . Herbimycin A also decreased elevated blood calcium levels that were induced either by repeated subcutaneous injections of recombinant human interleukin-1 alpha or by a human tumor . There was no evidence for toxicity in any of these culture systems or in mice treated with herbimycin A . A different tyrosine kinase inhibitor that does not inhibit pp60c-src was used as a control and caused none of these effects . These data suggest that pp60c-src tyrosine kinase inhibitors may be useful pharmacologic inhibitors of osteoclastic bone resorption and hypercalcemia.

Am J Obstet Gynecol, 1993 Jun, 168(6 Pt 2), 2033 - 41
Contraception and sexually transmitted diseases: interactions and opportunities; McGregor JA et al.; Today "safe sex" means protection from both unintended pregnancy and sexually transmitted disease and human immunodeficiency virus . These parallel complications of sexual activity have serious biologic and clinical sequelae that should be considered at the time of contraceptive selection . In addition, there is ongoing debate regarding potential interactions between antibiotic intervention and contraceptive steroids . This article assesses the impact of hormonal contraception, spermicides, barrier methods, intrauterine devices, and douching on the pathogenesis of sexually transmitted disease and the human immunodeficiency virus infection . It discusses the direct and indirect effects of contraception methods on clinical physiology and host immune responses while also considering the possible consequences on maternal and infant health if pregnancy results from the use of ineffective contraception . Counseling and care for both family planning and infectious disease protection must be provided to all sexually active individualsPIP: The notion of safe sex currently denotes protection from unintended pregnancy, HIV, and other sexually transmitted diseases (STD) . Modern parallel complications of sexual activity should therefore be considered when selecting contraceptives . This article assesses the impact of hormonal contraception, spermicides . barrier methods, IUDs, and douching on the pathogenesis of STDs and HIV . It discusses the direct and indirect effects of contraception methods on clinical physiology and host immune responses while considering the possible consequences on maternal and infant health if pregnancy results from the use of ineffective contraception . It is concluded that significant interactions exist between forms of contraception and STDs and HIV which may be beneficial or harmful to women . For example, oral contraceptive (OC) use may reduce risks of pelvic inflammatory disease and its sequelae, but may increase risks of chlamydia infection . Barrier methods, especially when combines with spermicides, can reduce the risk of STDs/HIV if used consistently . The combined use of OCs and condoms offers serious defense against both unintended pregnancy and STDs/HIV . IUDs also seem safe and effective in women at low risk for reproductive tract infection . Periodic screening and treatment for prevalent STDs and possible bacterial vaginosis can protect the health of individuals and their sexual contacts . Finally, more research is needed on the reproductive and infectious disease repercussions of human sexuality, while counseling and care for family planning and infectious disease protection are recommended for those who are sexually active .

Invest Ophthalmol Vis Sci, 1993 Jun, 34(7), 2210 - 9
Studies of human uveal melanocytes in vitro: isolation, purification and cultivation of human uveal melanocytes; Hu DN et al.; PURPOSE . To develop the methods for isolation and cultivation of human uveal melanocytes (UM) from adult donor eyes . METHODS . After removal of the pigment epithelium, the uvea was pretreated in trypsin solution at 4 degrees C overnight, incubated at 37 degrees C with trypsin for 1 hr, then incubated with collagenase for 3 hr . Released cells were collected each hour during the incubation and cultured with F12 medium supplemented with fetal bovine serum, basic fibroblast growth factor, isobutylmethylxanthine and cholera toxin . Contaminant cells were eliminated by adding a selective cytotoxic agent, geneticin, when necessary . RESULTS . These methods provide pure melanocyte cultures with high cell yields, good viability, and rapid growth rates . UM isolated and maintained using these methods can be passaged 23 times for a period of 7 mo for more than 35 population doublings . This is comparable to results obtained with cultured neonatal dermal melanocytes and exceeds results obtained with adult dermal melanocytes cultured in media supplemented with phorbol ester, isobutylmethylxanthine, and cholera toxin . CONCLUSION . A method for isolation and cultivation of UM has been developed that yields satisfactory results . Cultured UM may be useful in in vitro studies of UM physiology and may allow development of in vitro models of the pathogenesis of uveal malignant melanoma.

Biochemistry, 1993 Jun 1, 32(21), 5591 - 7
Coralyne binds tightly to both T.A.T- and C.G.C(+)-containing DNA triplexes; Lee JS et al.; Coralyne is a DNA-binding antitumor antibiotic whose structure contains four fused aromatic rings . The interaction of coralyne with the DNA triplexes poly(dT).poly(dA).poly(dT) and poly{d(TC)}.poly{d(GA)}.poly{d(C+T)} was investigated by using three techniques . First, Tm values were measured by thermal denaturation analysis . Upon binding coralyne, both triplexes showed Tm values that were increased more than those of the corresponding duplexes . A related drug, berberinium, in which one of the aromatic rings is partially saturated, gave much smaller changes in Tm . Second, the fluorescence of coralyne is quenched in the presence of DNA, allowing the measurement of binding parameters by Scatchard analysis . The binding isotherms were biphasic, which was interpreted in terms of strong intercalative binding and much weaker stacking interactions . In the presence of 2 mM Mg2+, the binding constants to poly(dT).poly-(dA).poly(dT) and poly{d(TC)}.poly{d(GA)}.poly{(C+T)} were 3.5 x 10(6) M-1 and 1.5 x 10(6) M-1, respectively, while the affinity to the parent duplexes was at least 2 orders of magnitude lower . In the absence of 2 mM Mg2+, the binding constants to poly{d(TC)}.poly{d(GA)}.poly{d(C+T)} and poly-{d(TC)}.poly{d(GA)} were 40 x 10(6) M-1 and 15 x 10(6) M-1, respectively . Thus coralyne shows considerable preference for the triplex structure but little sequence specificity, unlike ethidium, which will only bind to poly(dT).poly(dA).poly(dT) . Further evidence for intercalation of coralyne was provided by an increase in the relative fluorescence quantum yield at 260 nm upon binding of coralyne to triplexes as well as an absence of quenching of fluorescence in the presence of Fe{(CN)6}4-.(ABSTRACT TRUNCATED AT 250 WORDS)

J Thorac Cardiovasc Surg, 1993 Jun, 105(6), 1106 - 13
Prosthetic valve endocarditis with ring abscesses . Surgical management and long-term results; Jault F et al.; From January 1978 to December 1988, 71 patients underwent surgical intervention at our institution for prosthetic valve endocarditis with ring abscesses . These procedures involved 59 aortic prostheses and 12 mitral prostheses . No causative agent could be identified in 19 patients (26.7%) . The operation was performed during antibiotic therapy in 63 patients and after a planned course of antibiotic therapy in 8 patients . At the aortic level, abscesses were remedied by suturing in 3 cases, by pericardial patches in 34 cases, and by complex procedures in 22 cases (subcoronary valved conduit in 11 cases, supracoronary valved conduit with coronary bypass grafts in 10 cases, apicoaortic valved conduit in 1 case) . At the mitral level, ring abscesses were cured in 10 cases by intraatrial implantation of the prosthesis . In one case, the prosthesis was anchored inside the left ventricle; and in one case the valve could be seated on the anulus . The overall operative mortality rate was 17% . Long-term survival was 54% +/- 8% at 6 years . Fifteen (26%) of the survivors needed a third valve replacement (four operative deaths); a complex reconstruction was performed in seven patients . Better detection of ring abscesses and earlier surgical intervention before annular destruction and hemodynamic failure can improve the operative mortality rate for prosthetic valve endocarditis . When it is necessary, complex reconstruction, in spite of a high mortality rate, seems to eradicate the infectious seat, and the outlook for the patient's condition appears good.

J Thorac Cardiovasc Surg, 1993 Jun, 105(6), 1095 - 105
Inhibition of adenosine deaminase and nucleoside transport . Utility in a model of homograft cardiac valve preimplantation processing; Abd-Elfattah AS et al.; Human cardiac valves are increasingly used in the reconstruction of ventricular outflow tracts and offer performance advantages over porcine and mechanical prostheses; the durability of these replacements has been associated with leaflet interstitial cell viability and a presumed sustained function after implantation . Preimplantation tissue preparation entails sequential steps that are potentially cytotoxic and may therefore affect functional cell survival at thaw . We defined the metabolic consequences of each interval using semilunar cusps from 118 porcine valves to model a homograft preparation with 40 minutes of fixed cadaveric (harvest) ischemia . Fifty-eight valves served as controls and were first processed according to standard cryopreservation protocol; nucleosides were extracted at the end of each step to differentiate independent contributions to high-energy phosphate depletion . Sixty simultaneously harvested leaflets were administered the nucleoside transport inhibitor p-nitrobenzy-thionosine (NBMPR) and the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) at procurement, to attempt adenosine salvage and restitution of processing-incurred adenine nucleotide losses . High-performance liquid chromatography was used to compare adenosine triphosphate, diphosphate, and monophosphate and diffusible nucleopurines of the control and EHNA/NBMPR-treated groups . Control results indicate that disruption of the adenosine triphosphate-diphosphate cycle occurs independently with antibiotic disinfection and cryopreservation . However, throughout all preparation steps, adenine nucleotides were maintained at harvest (baseline) concentrations in the EHNA/NBMPR valves . This suggests that salvage therapy may protect a significant number of cells from net high-energy phosphate catabolism . If, with further study, the durability of transplanted valves is concluded to benefit from retained leaflet interstitial cell viability, such enhancement of metabolic tolerance to the obligatory processing may facilitate functional recovery.

Mol Pharmacol, 1993 Jun, 43(6), 863 - 9
Effect of pH on DNA alkylation by enzyme-activated mitomycin C and porfiromycin; Yu F et al.; DNA adduct formation by enzyme-activated antibiotics, mitomycin C (MMC) or porfiromycin (PFM), at pH 7.6 or pH 6.0 under anaerobic conditions was analyzed by a 32P-postlabeling method . Antibiotic activation by rat liver NADPH-cytochrome P-450 reductase (EC 1.6.2.4) and bovine milk xanthine oxidase (EC 1.2.3.2) produced similar results . Five 32P-labeled MMC adducts were separated by thin layer chromatography and high performance liquid chromatography from DNA alkylated at either pH . Four of the radioactive spots separated by thin layer chromatography were identified as two monofunctional monoadducts {1" alpha and 1" beta forms of N2-(2" beta,7"-diaminomitosen-1"-yl)-2'-deoxyguanylic acid}, one bifunctional monoadduct {N2-(10"-decarbamoyl-2",7"-diaminomitosen-1" alpha-yl)-2'-deoxyguanylic acid}, and one cross-linked adduct {N2-(2" beta,7"-diamino-10"-deoxyguanyl-N2-yl-mitosen- 1" alpha-yl)-2'-deoxyguanylic acid} . One minor radioactive spot was not identified . By comparing DNA alkylated at the two pH values, based on equal amounts of 32P radioactivity, similar amounts of cross-links were detected . However, the DNA showed different ratios of the alpha and beta isomers of the monofunctional monoadduct . Furthermore, the DNA alkylated at pH 6.0 showed more bifunctional monoadducts than did the DNA alkylated at pH 7.6 . Analysis of alkylated DNA by enzyme-activated PFM showed a similar spectrum of DNA adduct formation . The effect of pH on the distribution of the five PFM-DNA adducts was similar to that observed for the five MMC-DNA adducts . The distribution of adducts in DNA alkylated at the same pH was similar irrespective of which enzyme activated MMC or PFM . The pH of the reaction during DNA and MMC interaction was the determining factor for the quantitative distribution of the adducts . This pH effect may be important for the cytotoxicity of MMC and PFM in tumor cells that have high levels of reductive enzymes with low optimal pH values.

Am J Med, 1993 Jun, 94(6), 577 - 82
Nosocomial acquisition of Candida parapsilosis: an epidemiologic study; Sanchez V et al.; OBJECTIVE: The purpose of this study was to determine aspects of the epidemiology of nosocomial infection due to Candida parapsilosis . Candida species are important nosocomial pathogens; however, little epidemiologic information is available . PATIENTS AND METHODS: We prospectively cultured specimens from 98 patients admitted to the bone marrow transplant unit and a medicine intensive care unit (ICU) of a tertiary care hospital . Specimens from hands of personnel and environmental surfaces were also cultured . Environmental cultures were done before patients were admitted to a studied unit . Restriction enzyme analysis (REA) of chromosomal DNA was used as a typing system to determine the relatedness of strains . RESULTS: C . parapsilosis was identified from five patients, six hand cultures from four hospital staff, and two environmental surfaces . All five patients had negative initial cultures and acquired C . parapsilosis after admission to the study unit . There were no significant differences between patients and control subjects in age, underlying disease, immunosuppressive therapy, and instrumentation . The duration of antibiotic therapy (median: 32.8 versus 11.8 days, p = 0.05) and the duration in the unit (means: 30.1 versus 16.1 days, p = 0.048) was longer in patients than in controls . No common source was identified . REA revealed three strain types; however, one strain type was identical in four patients, three staff members, and two environmental surfaces . CONCLUSION: These results suggest exogenous acquisition of C . parapsilosis . Based upon isolation of identical patient strains of C . parapsilosis from inanimate surfaces before patients were admitted to a study unit, there is evidence that the organism may have been acquired from the hospital environment . The principal mechanism of transmission was probably indirect contact via the hands of hospital personnel.

Helv Chir Acta, 1993 Jun, 59(5-6), 955 - 63
{Proximal femoral fractures: trochanteric area (classification 31 A1-A3)}; Rosso R et al.; The increasing incidence of trochanteric fractures renders their treatment a challenging task concerning both medical and increasingly socio-economical questions as well . The majority of these fractures occurs in elderly patients compromised by various preexisting medical problems . The primary goal of treatment therefore has to be early mobilisation to avoid secondary complications . This can only be achieved by operative treatment . Regarding the perioperative management an antibiotic as well as an antithrombotic prophylaxis is advisable . Recent data also suggest to add an enteral nutritional supplement during the postoperative period . The social reintegration depends however primarily upon the rapid restoration of the walking capacity . In this concern the Dynamic Hip Screw (DHS) is an optimal implant for ORIF, since it allows early full weight-bearing and shows a lower complication rate than static implants (e.g . the condylar blade plate).

J Chemother, 1993 Jun, 5(3), 181 - 5
Treatment of intracranial abscesses: experience with sulbactam/ampicillin; Akova M et al.; In an open prospective study, the efficacy of sulbactam/ampicillin (50 and 100 mg/kg, respectively, qid) was evaluated in 21 patients with intracranial abscess(es) . Sixteen patients had cerebral, 3 epidural, and 2 cerebellar abscesses . Multiple lesions were found in 7 patients . Sixteen patients underwent surgical intervention, others were treated with antibiotic alone . The mean duration of antibiotic therapy (+/- SD) was 48 +/- 10 days (range 26-65 days) . The mean duration of follow-up after completion of therapy (+/- SD) was 6 +/- 2.4 months . All patients had at least some reduction in size of abscess(es) within 3 weeks of the initiation of therapy as monitored by computerized tomography . Seventeen patients were cured, three patients died due to causes unrelated to their infection . One patient was reoperated since no clear improvement either clinically or radiologically was observed 18 days after the first operation . Side effects of sulbactam/ampicillin were minor and transient . Results obtained in this study indicate that sulbactam/ampicillin can be used in the treatment of intracranial abscesses, alone or with surgical intervention.

Ann Plast Surg, 1993 Jun, 30(6), 545 - 8
Carpal tunnel release complicated by necrotizing fasciitis; Greco RJ et al.; We report a 31-year-old diabetic woman who underwent carpal tunnel release for median nerve compression followed by a laparoscopic tubal ligation . The procedure was complicated by a severe postoperative necrotizing fasciitis infection of the carpal tunnel release incision . This has not been previously reported . The wound was poorly responsive to antibiotic therapy and serial wound debridements . Control of the woman's infection required total excision of the palmar skin and fascia . Complicating factors in this case included the woman's long history of insulin-dependent diabetes and a concomitant clean-contaminated procedure.

West Indian Med J, 1993 Jun, 42(2), 79 - 81
Wiskott-Aldrich syndrome in a Jamaican; Walters JP et al.; A 3-week-old boy presented with severe thrombocytopenia and recurrent infections . He was subsequently found to have Wiskott-Aldrich Syndrome, a rare X-linked disorder . Splenectomy was performed and he died of post-splenectomy sepsis despite prophylactic antibiotic therapy . This is the first recorded case in the English-speaking Caribbean.

J Gen Microbiol, 1993 Jun, 139 ( Pt 6), 1353 - 62
Partial purification and properties of carminomycin 4-O-methyltransferase from Streptomyces sp . strain C5; Connors NC et al.; A methyltransferase that acts on carminomycin and 13-dihydrocarminomycin, and that is postulated to be the terminal enzyme in the daunomycin biosynthesis pathway, was purified to near-homogeneity from the daunomycin- and baumycin-producing Streptomyces sp . strain C5 . The enzyme was obtained in approximately 5% yield with a purification of 114-fold in specific activity over the sample precipitated with 30-50% ammonium sulphate . Polyacrylamide gel electrophoresis under denaturing conditions indicated a subunit M(r) of about 41,000 . The enzyme was shown by gel filtration chromatography to have an M(r) of approximately 166,000, suggesting that it is a homotetramer . Kinetic analysis indicated an affinity for S-adenosyl-L-methionine typical of antibiotic methyltransferases; the enzyme had a slightly higher affinity for carminomycin than for 13-dihydrocarminomycin . The reaction product from methylation of carminomycin was confirmed by chromatography and mass spectral analysis to be daunomycin . The purified enzyme did not catalyse methylation of the aglycones carminomycinone or 13-dihydrocarminomycinone . S-Adenosyl-L-homocysteine inhibited the methyltransferase, whereas homocysteine, adenosine, adenine, epsilon-rhodomycinone, daunomycin, and daunomycinone showed little or no inhibitory activity.

Eur J Clin Microbiol Infect Dis, 1993 Jun, 12(6), 449 - 53
Meropenem versus imipenem/cilastatin in the treatment of intraabdominal infections requiring surgery; Kanellakopoulou K et al.; In a prospective randomized study meropenem was compared with imipenem/cilastatin in the treatment of 62 patients with intraabdominal infections requiring surgery . The patients were suffering from diffuse or local peritonitis of moderate severity complicating in most cases gangrenous appendicitis, stomach perforation or gallbladder disease . There were 30 patients in the meropenem group and 32 patients in the imipenem/cilastatin group . Both antibiotic regimens were given intravenously at a dosage of 1 g every 8 h for a mean duration of 7.7 days in the meropenem group versus 8.6 days in the imipenem/cilastatin group . Fifty-nine aerobic strains and 15 anaerobic strains were isolated from cultures of pus taken intraoperatively, the meropenem MICs ranging from < or = 0.25 to 2 micrograms/ml . At follow-up at least one month after treatment the outcome was considered successful in all of 27 evaluable patients given meropenem and in all of 29 evaluable patients given imipenem/cilastatin . Both antibiotic regimens were well tolerated.

J Clin Pharm Ther, 1993 Jun, 18(3), 171 - 7
Pharmacokinetics of fusidic acid after a single dose of a new paediatric suspension; Bourget P et al.; The pharmacokinetics of fusidic acid (Fucidine, Leo Laboratories) were studied in 10 children after single oral dosing with 20 mg/kg of a new banana-flavoured paediatric suspension (titrating at 50 mg/ml) . Nine blood samples were drawn from each child at 0, 1, 2, 3, 6, 8, 12, 24 and 48 h following dosing with the antibiotic . Serum fusidic acid levels were measured by high-performance liquid chromatography (HPLC) . A model-independent method was used for the pharmacokinetic analysis . Results were compared with those obtained after dosing eight healthy adult volunteers with 500 mg of sodium fusidate by parenteral administration (infusion) then per os . The acceptability of the single dose was good . The terminal elimination half-life t1/2 (h) and the mean residence time (MRT, h) of fusidate were similar to those determined in healthy adults after oral dosing, i.e . 16.0 +/- 14.5 versus 16.0 +/- 3.5 and 17.7 +/- 12.1 versus 17.7 +/- 2.5, respectively . In contrast, the oral bioavailability of the suspension (Fapprox., %) was relatively low: of the order of 22.5 versus 91.0% for tablets in the healthy adult, which justifies the use of a relatively higher dose in the child . This led to the calculation of an estimated total clearance (Clest., ml/min) significantly less than that in the healthy adults, while the estimated apparent volume of distribution (Vd, litre/kg) was significantly increased (10.4 +/- 9.1 versus 21.8 +/- 2.1 and 0.73 +/- 0.53 versus 0.30 +/- 0.04, respectively) . Fusidic acid is normally excreted in metabolized form (98%) . The decrease in clearance could be attributed to the almost immediate saturation of liver enzymes in immature infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Unfallchirurg, 1993 Jun, 96(6), 332 - 40
{Experiences with closed irrigation-suction drainage and simultaneous administration of an antiseptic}; Pfister A et al.; In 47 patients a closed instillation drainage system was used with concomitant systemic antibiotic therapy . The schedule was strictly followed and is described in detail in the text . Prerequisites for a successful therapy are thorough surgical debridement, good coverage with soft tissue and a very careful skin closure . We propose a shortened duration of instillation of 3 to a maximum of 5 days . The Draintec suction pumps now used evidently create less problems than the classic pumps . During a mean follow-up of 3 years a definite recurrence was observed in two cases and a possible recurrence in one . In view of these results we consider this mode of treatment is still valid . Lavasept was added as an antiseptic drug in three quarters of the cases and was tolerated well . In view of the low rate of recurrence in all cases its potential cannot yet be fully estimated . We recommend the instillation-drainage system for use in thigh, upper arm and pelvic areas in the hands of a fully cooperating management team with some experience in the application of instillation-drainage systems.

Br J Dermatol, 1993 Jun, 128(6), 674 - 8
Cutaneous fibroses induced by Borrelia burgdorferi; Marsch WC et al.; Three cases of chronic infection with Borrelia burgdorferi are described . The patients presented with nodular or discoid fibrosis, partly in conjunction with acrodermatitis chronica atrophicans (ACA) . Juxta-articular fibrotic nodules may develop within a few months of the onset of ACA . Nodular, discoid morphoea-like, and widespread cutaneous fibroses in chronic Borrelia infection may be provoked by trauma, surgery or electromagnetic radiation . They respond well to antibiotic therapy . These lesions offer an in vivo model for studying the evolution of immunologically induced fibrosis.

Ophthalmic Surg, 1993 Jun, 24(6), 382 - 8
Effect of subconjunctival daunorubicin on glaucoma surgery in rabbits; Xu Y et al.; Daunorubicin (DNR), an antibiotic-antimetabolite, was used as an adjunct to standardized partial-thickness filtration surgery in 21 rabbits to determine its effects on that surgery . Postoperatively, one of the eyes of each rabbit received subconjunctival injections of DNR 25 micrograms or 50 micrograms, while the fellow eyes received only diluent, daily for 2 to 14 days . Bleb survival, fistula patency, the thickness of the subconjunctival connective tissue, and postoperative complications were investigated . The filtration blebs lasted significantly longer (P < .005), the rate of fistula closure was significantly lower (P < .005), and the subepithelial connective tissue was much looser and thicker in the experimental eyes than in the control eyes . Corneal toxicity occurred more frequently in the eyes treated with the higher-dose DNR than in those treated with the lower dose and in the control eyes.

J Arthroplasty, 1993 Jun, 8(3), 269 - 71
Reinfusion of whole blood following addition of tobramycin powder to the wound during total knee arthroplasty; Lux PS et al.; This study prospectively examined nine human volunteers who underwent unilateral cementless total knee arthroplasty and had 600 mg of tobramycin powder added to their wound just prior to fascial closure . Serum levels of tobramycin were measured at 30 minutes, 4 hours, 8 hours, and 12 hours after surgery . Tobramycin levels in the reinfused whole blood were measured with each reinfusion . Patients were reinfused up to 12 hours after surgery and then the reservoir was left to suction drainage . All patients had significant levels of serum tobramycin 30 minutes after surgery . The average serum level was 5.5 micrograms/ml (range, 3.0-10.6 micrograms/ml) . This level was achieved prior to any reinfusion and represented systemic absorption of tobramycin from the bleeding surfaces of the muscle and bone . All patients received at least one reinfusion of 400 ml of whole blood in the first 8 hours after surgery . Two thirds of the patients received a second reinfusion within the same time frame . Serum tobramycin levels measured post-reinfusion indicated that the risk of attaining potential toxic levels of aminoglycoside was not dependent on reinfusion, but on absorption from the wound . The dose of tobramycin in the drain was measured and found to be excessive and potentially toxic (range, 27-312 mg; average, 132 mg) . Despite this fact, reinfusion was not as likely to produce toxic serum levels as was local uptake of the antibiotic . Although no patient in this series had any complaints relating to the high dose of tobramycin (deafness or renal failure), caution should be exercised when using antibiotics in a reinfusion system.(ABSTRACT TRUNCATED AT 250 WORDS)

Gen Physiol Biophys, 1993 Jun, 12(3), 249 - 57
The interaction of amphotericin B with cell membrane of rat thymocytes; Sabirov RZ et al.; Amphotericin B (AB) at micromolar concentrations increases cell membrane permeability and induced swelling of rat thymus lymphocytes . Potassium efflux is a precondition for AB to induce swelling of the cells . The rate constants for potassium loss and volume changes were proportional to the 1.24th and the 2nd power of the antibiotic concentration respectively . The reflection coefficients for nonelectrolytes with different hydrodynamic radii were determined, and the equivalent radius of the amphotericin pore in the thymocyte cell membrane was estimated to be 4.1 +/- 0.3 A at polyene concentrations varying between 2.5 mumol/l and 80 mumol/l . It is suggested that channel formation by AB in cell membranes is actually able to modulate immune responses.

Zhongguo Yi Xue Ke Xue Yuan Xue Bao, 1993 Jun, 15(3), 212 - 6
{Cytotoxicity to hepatoma BEL-7402 cells of an antitumor monoclonal antibody-streptonigrin conjugate}; Liu Y et al.; Streptonigrin, a highly active antitumor antibiotic, was covalently conjugated to anti-human hepatoma monoclonal antibody 3A5 via the active ester method . The conjugate showed biological activities and UV spectra characteristics of streptonigrin and McAb 3A5 . The molar ratio of streptonigrin to 3A5 was 2-6:1, with protein recovery of 76% . The conjugate retained 12.5% of drug activity and nearly full antibody activity, though as the number of streptonigrin molecules in the conjugate increased, the antibody activity of the conjugate decreased . As determined by clonogenic assay with human hepatoma BEL-7402 cells in vitro, the inhibitory potency of the conjugate was 63-fold stronger than that of free streptonigrin . For KB cells (which react weakly with 3A5) the cytotoxicity was 11-fold weaker . The results indicate that the McAb 3A5-streptonigrin conjugate is selective for target cells.

Hum Cell, 1993 Jun, 6(2), 137 - 42
{Effective removal of the contaminating host fibroblasts for establishment of human-tumor cultured lines}; Inagaki T et al.; We report a useful method for the establishment of cell lines in vitro from human tumors . One of the obstacles to establishing pure human cancer cells in vitro is contaminating fibroblasts in cultures . This obstacle could be overcome by selective-growth control of fibroblasts treated with serum-free GIT medium and their selective elimination with antibiotic Geneticin (G418-sulfate) . In this study, the process of establishing cultured cell lines from two oral cavity cancers is demonstrated using GIT medium and Geneticin . The comparative study of the growth of cells of the two oral cavity cancers and of two control normal fibroblast cell lines supported the selective growth inhibition and elimination of normal fibroblasts by the "G-G method".

Zentralbl Veterinarmed A, 1993 Jun, 40(5), 345 - 58
Immune functions of veal calves fed low amounts of iron; Gygax M et al.; Immune functions were studied in male calves fed milk replacer (MR) containing 10 or 50 mg iron (Fe)/kg . Calves fed 10 mg Fe/kg MR developed marked hypoferremia and anemia, whereas serum-Fe and haemoglobin concentration of calves fed 50 mg Fe/kg MR were normal . Growth performance was reduced, while feed/gain ratio, incidence of infections (especially pneumonias), febrile body temperatures and antibiotic treatments were higher in calves fed 10 than 50 mg Fe/kg MR (p < 0.05) . Whereas antibody production (to horse erythrocytes) and lymphocyte stimulation (by mitogens) were not significantly altered, cell-mediated immunity (measured as cutaneous delayed-type hypersensitivity reaction to dinitrofluoro-benzene), number of neutrophils with phagocytic capacity, activity of the Fe-containing enzyme myeloperoxidase, blood serum IgG concentration and the number and diameter of germinal centres as a measure of the number and production of B-cells in cervical superficial lymph nodes in calves fed 10 mg Fe/kg MR were reduced when compared with calves fed 50 mg Fe/kg MR (p < 0.05) . In conclusion, severe Fe deficiency caused reduced growth performance, associated with and partly due to higher incidence of infections because of defective immune reactions.

Antibiot Khimioter, 1993 Jun, 38(6), 41 - 5
{Analysis of ceftazidime and ampicillin tissue distribution using physiologic models of pharmacokinetics}; Manuilov KK; Physiological models of ceftazidime and ampicillin pharmacokinetics were used to study accumulation of the antibiotics in the tissue interstitial space and to analyze the influence of the regional blood flow rate on the accumulation . For the control of the model adequacy, the published pharmacokinetic data on the distribution of ceftazidime and ampicillin in serum and "skin blister" fluid were used . The pharmacokinetic profiles calculated from the equations of the physiological models including Kp corresponded to the kinetics of the changes in the content of the cephalosporins and penicillins in the tissue homogenates . To estimate the antibiotic accumulation in the tissue interstitial space, it was necessary to use the equations where Kp = 1 . Introduction of the coefficient regulating the regional blood flow rate to the equations made it possible to analyze the influence of the blood supply characteristics on the local pharmacokinetics.

Antibiot Khimioter, 1993 Jun, 38(6), 19 - 24
{High performance liquid chromatography in studies of component composition of polyene macrolides}; Shenin IuD et al.; The published data on the use of HPLC in studies on the chemistry of polyene macrolide antibiotics are summarized and the conditions for HPLC, the use of various sorbents, the impact of the ratio of the organic solvents and buffer solutions, etc . are discussed comparatively . Several aspects of the use of HPLC are indicated i.e . the identification of polyene antibiotics (heptaenes, pentaenes and hexaenes), the standardization and investigation of the antibiotic homogeneity and quality, the purification of the antibiotics and the determination of the amphotericin B content in tissues and plasma.

Am J Physiol, 1993 Jun, 264(6 Pt 1), C1532 - 7
Novobiocin forms cation-permeable ion channels in rat fetal distal lung epithelium; O'Brodovich H et al.; The antibiotic novobiocin has been previously reported to increase Na+ transport in frog skin, presumably by attenuation of Na+ self-inhibition of Na+ channels . To determine whether novobiocin had similar effects and utilized a similar mechanism in mammalian Na(+)-transporting tissues, we studied its effect on ion transport by primary cultures of fetal distal lung epithelium (FDLE) cultured from 20-day gestationally aged rats (term = 22 days) . Novobiocin (10 mM) increased short-circuit current and markedly decreased the resistance in FDLE monolayers mounted in Ussing chambers . Fura-2 single-cell studies showed that novobiocin increased intracellular Ca2+ concentration and that this resulted from extracellular sources . Nystatin-perforated patch-clamp techniques demonstrated that novobiocin increased nonrectifying cation whole cell currents without inducing detectable anion currents . Novobiocin created nonrectifying monovalent cation-selective channels in lipid bilayers . These studies demonstrated that novobiocin affects the bioelectric properties of Na+ transporting lung epithelium and that this likely occurs by the formation of ion-permeant channels in their lipid membranes.

Mutat Res, 1993 Jun, 287(2), 141 - 56
Ultraviolet light, mitomycin C and nitrous acid induce genetic instability in Streptomyces ambofaciens ATCC23877; Volff JN et al.; In Streptomyces ambofaciens ATCC23877, pigment-negative (Pig-) mutants occur at high frequency (about 0.7 x 10(-2)) in the progenies of wild-type colonies . Furthermore, the offspring of these Pig- mutants can either be phenotypically homogeneous or hypervariable (with no preponderant phenotype) . Pig- mutants can also lack antibiotic production and present aerial mycelium deficiency, auxotrophy for arginine, oversensitivity to either ultraviolet (UV) light or mitomycin C and resistance to either novobiocin or nosiheptide . This genetic instability is related to both amplified DNA sequences and deletions . Mutagens such as UV light, mitomycin C and nitrous acid induced genetic instability and increased the Pig- mutant frequency to almost 30% even at a high survival rate . Induced Pig- mutants exhibited the same features as the spontaneous ones at both phenotypic and molecular levels . The frequency of detected genomic rearrangements after treatment was higher than 10% . We postulate that an SOS-like system is involved in the induction of genetic instability in S . ambofaciens.

Hosp Pract (Off Ed), 1993 Jun, 28 Suppl 1, 11 - 5
Outpatient parenteral therapy . Management of serious infections . Part I: Medical, socioeconomic, and legal issues . Selecting the patient; Brown RB; Careful patient selection is vital to the success of outpatient parenteral antibiotic therapy . As more experience has been gained, criteria for acceptance have expanded . Up to 50% of patients now originate from physicians' offices and other nonhospital settings . Currently, medical stability, insurance coverage, and availability of experienced personnel are the major selection criteria.

Gene, 1993 May 30, 127(2), 267 - 8
The complete sequences of plasmids pFNeo and pMH-Neo: convenient expression vectors for high-level expression of eukaryotic genes in hematopoietic cell lines; Hahn WC et al.; The eukaryotic expression vector, pFNeo, confers resistance to the antibiotic G418 and directs hematopoietic-specific expression of proteins under the control of the long terminal repeat from the Friend spleen focus-forming virus . Here, we report the entire nucleotide sequence of pFNeo . We have also constructed and sequenced a pFNeo-based expression vector (pMH-Neo) that carries an improved multiple cloning site region for easier subcloning . The utility of both vectors was demonstrated by transfection of murine T-cell hybridomas by electroporation . Transfection with either pFNeo or pMH-Neo yielded a high frequency (1 in 2 x 10(4)) of G418-resistant cell lines.

Gene, 1993 May 30, 127(2), 233 - 6
Construction of a retrotransposition indicator sequence using a neomycin resistance-encoding gene containing a functional intron; Schwartz DA et al.; An intron from a Syrian hamster gene was inserted into a neo gene such that splicing of the neo gene mRNA results in the synthesis of active aminoglycoside phosphotransferase . The unspliced construct is inactive in Escherichia coli, but confers resistance to G418 when transfected into mouse and hamster cells . This selectable marker is designed to aid in the cloning and identification of genomic integration sites following retrotransposition.

Tidsskr Nor Laegeforen, 1993 May 30, 113(14), 1730 - 4
{Diagnosis and treatment of infections in a neonatal unit--bacterial and fungal infections}; Hansen TW et al.; Following an outbreak of Candida septicemia in our intensive care nursery we reviewed our routines for diagnosis and treatment of neonatal infections . The revision resulted in a set of written guidelines for septic work-ups, initiation and discontinuation of antibiotic therapy, and choice of antibiotics . In this article we present the guidelines for dealing with bacterial and fungal infections, along with relevant comments.

J Med Chem, 1993 May 28, 36(11), 1548 - 61
A molecular dynamics study of the bis-intercalation complexes of echinomycin with d(ACGT)2 and d(TCGA)2: rationale for sequence-specific Hoogsteen base pairing; Gallego J et al.; The behavior of the complexes of echinomycin with the DNA tetramers d(ACGT)2 and d(TCGA)2, in which the terminal AT base pairs are in either a Hoogsteen or a Watson-Crick conformation, has been explored by molecular dynamics taking into account experimental data from NMR studies (Gao and Patel . Biochemistry 1988, 27, 1744-1751) . The DNA binding specificity of echinomycin appears to be the result of a subtle balance between stabilizing and destabilizing forces . Among the former is a number of hydrogen bonds between the alanine residues of echinomycin and both the N3 and 2-amino groups of the guanine bases which decisively determine the strong affinity of the antibiotic for CpG steps . On the other hand, there appears to be an unfavorable dipolar interaction between the chromophores of the antibiotic and the CpG step . This electrostatic component of the stacking interactions also contributes to explaining the conformational preferences of the flanking sequences: upon Hoogsteen pairing, the dipole moment of an AT base pair is found to increase significantly and alter its relative orientation . In the d(ACGT)2:echinomycin complex, this arrangement helps to improve the stacking interactions with the quinoxaline-2-carboxamide system, but would lead to unfavorable dipolar interactions in the d(TCGA)2 complex . The bearing of these findings on the binding of echinomycin to several sequences as well as on the altered binding selectivity of other members of the quinoxaline family of antibiotics is also discussed.

N Z Med J, 1993 May 26, 106(956), 201 - 3
Ventilation tubes, swimming and otorrhoea: a New Zealand perspective; Davison MJ et al.; OBJECTS . To compare advice given by specialist otolaryngologists to patients following ventilation tube insertion and the management of purulent otorrhoea in these patients . METHODS . A postal questionnaire was sent to all 59 specialists currently listed in the New Zealand Otolaryngology Specialist Register . RESULTS . 96.5% of specialist otolaryngologists replied, 88% in sufficient detail for analysis in this study . The vast majority (96%) allowed patients to swim with tubes in situ, and all allowed hair washing . Advice for ear protection varied . If otorrhoea develops with ventilation tubes in situ, 90% of specialists advise patients to stop swimming, but allow hair washing to continue with ear protection . Ninety percent of specialists' initial treatment of otorrhoea involves a combination of suction toilet and topical steroid/antibiotic drops . CONCLUSION . In general, specialist otolaryngologists in New Zealand give similar advice to patients with ventilation tubes . However, the specific methods of ear protection advised when swimming and hair washing varies markedly.

J Biol Chem, 1993 May 25, 268(15), 11152 - 9
N-linked glycosylation of the ligand-binding domain of the human urokinase receptor contributes to the affinity for its ligand; Moller LB et al.; Variations in glycosylation exist among urokinase plasminogen activator receptors (u-PARs) from different cell types . We have studied the functional role of N-linked carbohydrate within the ligand-binding domain of u-PAR . Treatment with glycosidases demonstrated that all the N-linked carbohydrates on u-PAR are complex-type oligosaccharides . Substitution of a single Asn (Asn52) to Gln by means of site-directed mutagenesis led to an active receptor mutant with a ligand-binding domain devoid of carbohydrate . The cellular distribution, the glycosyl-phosphatidylinositol anchoring, and the conformational stability after solubilization were unaffected by this single substitution . However, ligand binding analysis demonstrated a 4- 5-fold decrease in affinity as compared with the wild type receptor . Two different strategies were used in order to obtain a u-PAR type completely devoid of N-linked carbohydrates . 1) Tunicamycin treatment of wild type u-PAR-expressing cells . 2) Mutation of all glycosylation sites (Hu-PARN5-mut) . In neither case, unglycosylated receptors with ligand binding activity were identified . However, immunofluorescence studies demonstrated that the Hu-PARN5-mut was retained inside the cells in the endoplasmic reticulum . The same result was found for Hu-PARN4-mut, where only the glycosylation sites outside the binding domain were mutated . These results demonstrate that some extent of glycosylation of u-PAR is necessary for cellular transport and for molecular maturation events leading to ligand binding activity . Glycosylation of the binding domain per se affects only the affinity of the receptor . The positive modulation of the Asn52 carbohydrate side chain on ligand affinity suggests that the u-PAR glycosylation variants observed in various cell types may have different functional roles.

Blood, 1993 May 15, 81(10), 2496 - 502
A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia; Dale DC et al.; Patients with idiopathic, cyclic, and congenital neutropenia have recurrent severe bacterial infections . One hundred twenty-three patients with recurrent infections and severe chronic neutropenia (absolute neutrophil count < 0.5 x 10(9)/L) due to these diseases were enrolled in this multicenter phase III trial . They were randomized to either immediately beginning recombinant human granulocyte colony-stimulating factor (filgrastim) (3.45 to 11.50 micrograms/kg/d, subcutaneously) or entering a 4-month observation period followed by filgrastim administration . Blood neutrophil counts, bone marrow (BM) cell histology, and incidence and duration of infection-related events were monitored . Of the 123 patients enrolled, 120 received filgrastim . On therapy, 108 patients had a median absolute neutrophil count of > or = 1.5 x 10(9)/L . Examination of BM aspirates showed increased proportions of maturing neutrophils . Infection-related events were significantly decreased (P < .05) with approximately 50% reduction in the incidence and duration of infection-related events and almost 70% reduction in duration of antibiotic use . Asymptomatic splenic enlargement occurred frequently; adverse events frequently reported were bone pain, headache, and rash, which were generally mild and easily manageable . These data indicate that treatment of patients with severe chronic neutropenia with filgrastim results in a stimulation of BM production and maturation of neutrophils, an increase in circulating neutrophils, and a reduction in infection-related events.

Gene, 1993 May 15, 127(1), 63 - 9
Analysis of the self-defense gene (fmrO) of a fortimicin A (astromicin) producer, Micromonospora olivasterospora: comparison with other aminoglycoside-resistance-encoding genes; Ohta T et al.; The nucleotide (nt) sequence of a 3409-bp PvuII fragment carrying the self-defense gene (fmrO) of a fortimicin A (FmA; astromicin) producer, Micromonospora olivasterospora, was determined; four open reading frames (ORFs) exist in this region . Expression analysis of fmrO using the lac promoter in Escherichia coli revealed that ORF-3 encodes fmrO . ORF-1 was considered to encode a FmKH epimerase (fms11) . ORF-2, ORF-3 and ORF-4 seemed to form an operon . No homology was detected between fmrO and the resistance-encoding gene fmrT of Streptomyces tenjimariensis, a producer of the Fm-group antibiotic, istamycin . Gene organization around the fmr genes differed considerably between M . olivasterospora and S . tenjimariensis . The deduced amino acid sequence of fmrO showed an identity of 30.8% to grmA of M . purpurea and 35.8% to grmB of M . rosea, respectively, suggesting that fmrO encodes a 16S rRNA methyltransferase . We found in M . purpurea a novel resistance gene distinct from grmA and highly similar to fmrO which conferred a resistance phenotype similar to that of fmrO . These results suggest that fmrO of M . olivasterospora and the two resistance-encoding genes of M . purpurea were derived from a common ancestral gene.

Gene, 1993 May 15, 127(1), 117 - 20
Cloning and sequence analysis of an Escherichia coli gene conferring bicyclomycin resistance; Bentley J et al.; We have cloned and sequenced DNA from Escherichia coli that, when present in a high-copy-number plasmid, confers resistance to the diketopiperazine antibiotic, bicyclomycin (Bc) . The DNA includes a 378-amino-acid open reading frame (ORF), disruption of which results in the loss of Bc resistance . This ORF contains the BcR gene . Studies using the minicell expression system reveal that a polypeptide of 31 kDa is produced from this cloned region . The ORF maps at 47.1 min on the E . coli genome map . Sequence comparison between the translated ORF and a protein database reveal between 26.5 and 23.4% aa sequence homology to bacterial transmembrane (TM) proteins including those mediating chloramphenicol (Cm) and tetracycline (Tc) resistance and an arabinose-proton symport protein . Sequence analysis using the Diagon program showed the BcR gene product (BcR) had homology with the N-terminal regions of the CmR and TcR-encoded proteins and weak N-terminal homology with the arabinose-proton symport protein . Hydropathy profiles of the BcR protein and CmR products show a striking similarity, both having twelve predicted TM domains.

Biochemistry, 1993 May 4, 32(17), 4487 - 95
A-tract and (+)-CC-1065-induced bending of DNA . Comparison of structural features using non-denaturing gel analysis, hydroxyl-radical footprinting, and high-field NMR; Sun D et al.; (+)-CC-1065 is a biologically potent DNA-reactive antitumor antibiotic produced by Streptomyces zelensis . In a previous study we have reported that (+)-CC-1065 produces bending of DNA that has similarities to that intrinsically associated with A-tracts {Lin, C . H., Sun, D., & Hurley, L . H . (1991) Chem . Res . Toxicol, 4, 21-26} . In this article we provide evidence using a combination of non-denaturing gel analysis, hydroxyl-radical footprinting, and high-field NMR for both distinctions between the two types of bends and the importance of junctions in both types of bends . For A-tracts we demonstrate that the locus of bending is at the center of an A-tract and that upon modification of the 3' adenine with (+)-CC-1065 this locus is moved less than 1 base pair to the 3' side, and the bending magnitude is significantly increased . For drug bonding sequences such as 5'-AGTTA* or 5'-GATTA* (where * denotes the drug bonding site), the locus of bending is found to be between the two thymines, and the bending is focused over a 2-base-pair sequence rather than a 5-base-pair sequence, as is the case for the A-tract . An important distinction between an A-tract intrinsic bend and a (+)-CC-1065-induced bend is the effect of temperature . While, as shown previously, the magnitude of A-tract bending increases with decrease in temperature, for drug-induced bending of 5'-AGTTA* the bending magnitude increases with increased temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimicrob Agents Chemother, 1993 May, 37(5), 1167 - 70
Use of an in vivo system to determine the G418 resistance phenotype of bloodstream-form Trypanosoma brucei brucei transfectants; Murphy NB et al.; We determined the level of susceptibility of Trypanosoma brucei brucei to the aminoglycoside G418 in vivo and demonstrated that it is possible to select for G418-resistant transfected T . brucei brucei bloodstream parasites in a mouse host by inoculating the drug intraperitoneally at doses between 40 and 80 mg/kg of body weight daily for 3 days . The ability to select for transfectants in vivo offers new possibilities for studies on genetic recombination in these parasites.

Antimicrob Agents Chemother, 1993 May, 37(5), 1025 - 7
Nonparametric approach to population pharmacokinetics in oncology patients receiving aminoglycoside therapy; Inciardi JF et al.; A nonparametric expectation maximization approach to the study of population pharmacokinetics is described for an aminoglycoside antibiotic . The method is used to explore population estimates for gentamicin clearance (liters per hour per creatinine clearance) and volume of distribution (liters per kilogram) in tumor patients . Joint and marginal probability distributions are plotted and further characterized by using standard descriptors such as mean, median, mode, standard deviation, skewness, and kurtosis . Results of additional analyses using hematologic or solid tumor subpopulations agree with those of a recent larger study which found no significant pharmacokinetic differences between these groups . Nonparametric maximum-expectation analyses are convenient and allow exploratory analysis of population estimates directly from routine laboratory information.

Rheum Dis Clin North Am, 1993 May, 19(2), 379 - 98
Syphilitic arthritis and osteitis; Reginato AJ; Syphilis again has become a significant clinical problem and clinicians must reacquaint themselves with the classic as well as the changing clinical manifestations, new diagnostic methods, interaction with HIV infections, and outcomes of therapy . Musculoskeletal manifestations can be associated with congenital, secondary, and tertiary syphilis and can mimic a wide variety of rheumatic and systemic diseases of worse prognosis . Musculoskeletal manifestations due to congenital and secondary syphilis usually subside completely after accurate diagnosis and antibiotic therapy.

Rheum Dis Clin North Am, 1993 May, 19(2), 351 - 62
Chlamydia-induced reactive arthritis; Silveira LH et al.; Chlamydia trachomatis infection is now recognized as the most prevalent veneral disease in the Western World . The majority of cases of Reiter's syndrome, one type of reactive arthritis, are secondary to sexually transmitted infections . Evidence of urogenital C . trachomatis infection is found in 36% to 61% of cases of Reiter's syndrome . We investigated the prevalence of infection by this organism in a group of patients with spondyloarthropathies . Positive cultures were obtained in 39.4% of patients with Reiter's syndrome, as well as in 22.2% of patients with psoriatic arthritis and in 20% of patients with ankylosing spondylitis . An important percentage of patients also had positive serum antibodies against C . trachomatis (62.1% of patients with Reiter's syndrome), suggesting presence of infection at some point during the course of the disease . Our findings and those from other authors support the use of long-term antibiotic therapy in patients with reactive arthritis, mainly in those in whom positive culture for C . trachomatis has been obtained as well as in their sex partners.

J Clin Microbiol, 1993 May, 31(5), 1303 - 7
Fluorometric quantitation of broth-cultured mycoplasmas by using alkaline ethidium bromide; Schaeffer WI et al.; We developed a fluorometric system which does for broth-grown mycoplasmas what turbidimetric analysis does for broth-grown bacteria . It allows one to monitor the growth of broth-grown mycoplasmas at any interval desired . The entire procedure is quick, taking not more than 20 min . The fluorometric readings correlate with colonial growth on agar, making it possible, for the first time, to take readings which closely estimate the CFU present in the culture at a given moment in time . We show that this system can be used to assess the effectiveness of an antimycoplasmal antibiotic and to optimize medium components and that fluorometer readings taken during the logarithmic phase of growth correlate with the DNA content of the viable cells . Use of this methodology will permit investigators to know absolutely the phase of the growth cycle of the culture concomitant with the growth of the culture itself, and since fluorometer readings of culture aliquots can be converted to DNA equivalents, the standardization of mycoplasmal cultures within and between laboratories will be a possibility.

Cornea, 1993 May, 12(3), 261 - 5
Successful treatment of microsporidial keratoconjunctivitis with topical fumagillin in a patient with AIDS; Rosberger DF et al.; There recently have been several reports of microsporidial keratoconjunctivitis caused by the organism Encephalitozoon hellem . However, treatment of this infection has been largely ineffective . We report a case of a 35-year-old Hispanic woman with AIDS and E . hellem keratoconjunctivitis confirmed with light, electron, and immunofluorescence microscopy that resolved promptly with topical fumagillin, a crystalline antibiotic with proven efficacy against Encephalitozoon species . No corneal or systemic toxicities were noted using the dosage and preparation employed (10 mg/ml suspension in balanced salt solution) . An easily prepared, topical fumagillin suspension appears to be a safe, effective treatment for E . hellem keratoconjunctivitis.

Cornea, 1993 May, 12(3), 216 - 21
A prospective, masked clinical trial of trifluridine, dexamethasone, and artificial tears in the treatment of epidemic keratoconjunctivitis; Ward JB et al.; Epidemics of viral conjunctivitis are a major public health problem in the Far East . No treatment has been shown to shorten the duration of illness . We studied the clinical course of epidemic keratoconjunctivitis in 74 patients during an outbreak of nearly 3,000 cases in late 1988 at a U.S . military base in the Philippines . Patients were randomly assigned to treatment with trifluridine, dexamethasone, or artificial tears, and examined in a double-masked fashion . There was no significant difference between the results of the three treatments . No bacterial cultures were positive . The prompt use of patient isolation, identification of nonadenoviral red eyes, and symptomatic treatment without steroids, antiviral, or antibiotic medication is recommended in cases of epidemic keratoconjunctivitis . This is the largest series of cases of epidemic keratoconjunctivitis with laboratory confirmation reported from the Philippines.

Transplantation, 1993 May, 55(5), 1045 - 8
Potentiation of cyclosporine nephrotoxicity by nafcillin in lung transplant recipients; Jahansouz F et al.; The interaction between nafcillin and cyclosporine was examined in lung transplant recipients receiving cyclosporine-based immunosuppression . Nine recipients received nafcillin for one week posttransplant and 10 recipients did not receive nafcillin . Age, sex, pretransplant renal function, type of transplant procedure, use of cardiopulmonary bypass, and initial cyclosporine dose were not significantly different between groups . The degree of renal dysfunction during the early postoperative period was significantly greater in the lung recipients receiving nafcillin . Although cyclosporine doses were significantly higher in the nafcillin group, this was not reflected by differences in cyclosporine levels . No difference in survival or incidence of allograft rejection was seen--however, the incidence of viral infection was significantly higher in the patients who received nafcillin . Based on our findings the use of an alternative antibiotic for antistaphylococcal prophylaxis in transplant recipients receiving cyclosporine is recommended.

J Trauma, 1993 May, 34(5), 669 - 74; discussion 674-5
Acute ethanol intoxication increases the risk of infection following penetrating abdominal trauma; Gentilello LM et al.; Acute alcohol (ETOH) intoxication as a risk factor for infection in trauma victims to our knowledge has not been previously reported . To determine if ETOH intoxication increases infection risk we examined data from 365 patients with penetrating abdominal trauma who were enrolled in a multi-center antibiotic study . Ninety-four patients sustained an injury to a hollow viscus . To separate acute from chronic ETOH effects, infections were divided into two categories: (1) trauma related; infections caused by bacterial contamination at the time of injury, while blood alcohol level (BAL) was elevated . (2) nosocomial; infections caused by bacteria acquired during hospital stay, after BAL had normalized . A BAL > or = 200 mg/dL was associated with a 2.6-fold increase in trauma-related infections . There was no association between BAL and subsequent nosocomial infection . Since infection rates for intoxicated patients were not higher after BAL had normalized, acute rather than chronic effects of ETOH appear to be responsible.

Psychosomatics, 1993 May-Jun, 34(3), 199 - 207
Psychopharmacologic issues in organ transplantation . Part I: Pharmacokinetics in organ failure and psychiatric aspects of immunosuppressants and anti-infectious agents; Trzepacz PT et al.; This article discusses pharmacokinetics and pharmacodynamics during hepatic, renal, and cardiovascular insufficiencies . Hepatic metabolism of psychotropic drugs and of drugs commonly used in transplant patients that have neuropsychiatric side effects is discussed . Neuropsychiatric effects of immunosuppressant agents, including cyclosporine, corticosteroids, azathioprine, OKT3, and FK 506, are reviewed . Certain infections occur more often in immunosuppressed patients; their treatment with antiviral, antifungal, and antibiotic drugs may have neuropsychiatric consequences . Because of altered drug sensitivities and metabolism, drug interactions, and severe medical illness, most drugs are used in reduced doses.

Emerg Med Clin North Am, 1993 May, 11(2), 495 - 516
Selected white cell disorders; Gin-Shaw S et al.; The emergency physician frequently is confronted with an abnormal white blood cell count when evaluating patients . Leukocytosis may be caused by malignancy, infection, or a variety of other reasons . Leukopenia is an increasingly common finding as the population of immunocompromised patients continues to expand . This article reviews the differential diagnosis of leukocytosis and leukopenia . The management of the neutropenic patient with and without fever is also reviewed and includes currently recommended empiric antibiotic regimens.

South Med J, 1993 May, 86(5), 578 - 80
Pylephlebitis associated with diverticulitis; Perez-Cruet MJ et al.; We have reported the cases of two patients who had acute pylephlebitis associated with portal vein thrombosis and septic hepatic emboli as a result of right colonic diverticulitis . Although rare, pylephlebitis is a treatable but often lethal complication of intra-abdominal sepsis . Several bacterial pathogens, especially Escherichia coli are associated with pylephlebitis . Early suspicion and prompt antibiotic therapy can lead to resolution of portal vein thrombosis and hepatic abscess formation, resulting in full recovery for the patient . Surgery may not be required . Our two patients received ampicillin--the best first-line drug--until specific antibiotic therapy could be given . Early administration of a broad spectrum antibiotic is essential.

Am Fam Physician, 1993 May 1, 47(6), 1435 - 41
Pyogenic hepatic abscess; Vukmir RB; Pyogenic hepatic abscess is a rare condition associated with severe sequelae . The diagnosis may be obvious in patients with fever and leukocytosis who are clearly predisposed to this infectious complication . In patients without known risk factors, diagnosis and treatment are often delayed, usually until numerous health care resources have been consulted . The evaluation of occult hepatic abscess may be improved by a history directed at identifying predisposing conditions, by an appropriate physical examination and by the use of computed tomographic scanning . The standard treatment for pyogenic hepatic abscess is percutaneous or open drainage, accompanied by broad-spectrum antibiotic therapy.

J Urol, 1993 May, 149(5 Pt 2), 1338 - 40
The correlation between round cells and white blood cells in the semen; Sigman M et al.; It is generally recognized that white blood cells in semen are detrimental to sperm function and fertility . Traditionally, pyospermia has been suspected if greater than 10 round cells per high power field or more than 1 million round cells per ml . were identified in the semen . Since immature germ cells and white blood cells appear as round cells under wet mount light microscopy, the relationship between increased numbers of round cells in semen and true pyospermia was examined . Semen analyses were performed on specimens from 627 infertility patients . The numbers of round cells per high power field and the number of round cells per ml . of semen were recorded . Specimens from 57 patients (9%) persistently demonstrated greater than 10 round cells per high power field or more than 1 million round cells per ml . and they were subjected to immunohistochemical staining against white blood cell surface antigens . Greater than 1 million white blood cells per ml . were identified in only 20 patients (35%) and only 8 samples demonstrated more than 3 million white blood cells per ml . Of the patients with greater than 1 million white blood cells per ml . 65% had motilities of less than 60% compared to 49% of the patients with less than this amount of pyospermia . This difference was not statistically significant . Round cells counted on a per milliliter basis correlated better with results of immunohistochemical staining than did round cells counted on a per high power field basis . These data demonstrate that the majority of patients with excess round cells in the semen do not have pyospermia and, therefore, empiric antibiotic therapy without further testing will likely be unproductive.

Obstet Gynecol, 1993 May, 81(5 ( Pt 2)), 876 - 7
Salpingitis or oophoritis: what causes fever following oocyte aspiration and embryo transfer?
Peters AJ, Hecht B, Durinzi K, DeLeon F, Wentz AC.
BACKGROUND: Febrile morbidity following in vitro fertilization and embryo transfer (IVF-ET) is a rare but possibly serious complication . This report describes a case of salpingitis after IVF-ET and discusses the possible reasons for febrile morbidity following this common procedure . CASE: A 37-year-old woman undergoing IVF-ET for tubal factor infertility developed sudden, severe pelvic pain, fever, and leukocytosis 24 hours after ET . Laparoscopy revealed bilateral suppurative pyosalpinges with cystic, hemorrhagic ovaries . Pain, fever, and leukocytosis resolved with conservative surgery and intravenous antibiotic therapy . CONCLUSIONS: This case presents laparoscopic documentation of a rare complication of oocyte aspiration and/or ET, namely, salpingitis . Possibilities for the development of salpingitis following IVF-ET include activation of quiescent bacteria within the fallopian tubes from a previous pelvic infection, puncture of the bowel during oocyte aspiration, inoculation of the pelvis with cervicovaginal flora during oocyte aspiration, and introduction of bacteria-laden secretions or air into the fallopian tubes during ET . Although rare, the possibility of severe pelvic infection following IVF-ET warrants consideration of prophylactic antibiotic coverage.

Plant J, 1993 May, 3(5), 729 - 38
Chloroplast transformation in plants: polyethylene glycol (PEG) treatment of protoplasts is an alternative to biolistic delivery systems; O'Neill C et al.; Nicotiana plumbaginifolia protoplasts were directly transformed by PEG treatment with a cloned 16S rRNA gene isolated from a double antibiotic-resistant Nicotiana tabacum plastid mutant . Putative plastid transformants were selected in cell culture by their spectinomycin resistance and identified by their unselected streptomycin resistance . Alternatively, cell lines were selected in the presence of both antibiotics . The cell line (and its regenerated plants) selected solely for spectinomycin resistance demonstrated an extensive segregation of streptomycin resistance in subsequent tests, while the double-selected line showed stable resistance for both antibiotics . The resistance markers were inherited maternally . In the putative plastid transformants the origin of the resistance mutations was identified by the absence of an AatII site, missing in the donor N . tabacum plastid gene (spectinomycin resistance site) but present in that of wild-type N . plumbaginifolia, and a sequence analysis of the particular nucleotide changes in both resistance sites . Restriction enzyme analysis of total plastid DNA (ptDNA), and the recloning and full sequencing of the fragment introduced, investigated in one of the plastid transformants, showed no DNA rearrangements accompanied with the integration process . Sequence analysis indicated a targeted, homologous integration of the DNA fragment introduced but an unexpectedly complete homology of the parental ptDNA sequences in this region prevented the location of borders . Although the frequency of plastid transformant colonies (2 x 10(-5)) should still be improved, this method for stable chloroplast DNA transformation is comparable with or more efficient than the particle bombardment techniques.

Virology, 1993 May, 194(1), 28 - 36
Activation of phospholipase activity during Semliki Forest virus infection; Perez L et al.; Infection of animal cells by a number of cytolytic viruses leads to increased membrane permeability . Thus, Semliki Forest virus (SFV) infection of susceptible cells modifies the permeability of the membrane for a number of cations and metabolites (Munoz et al . (1985), Virology 146, 203-212) . The molecular basis of this modification of the cell membrane has not been investigated in detail . We report that during the infection of HeLa cells with SFV, or BHK cells with vesicular stomatitis virus, there is a significant increase in the release of choline and arachidonic acid into the culture medium, suggesting that both phospholipases (PLases) C and A2 become activated during infection . Both choline and phosphorylcholine are released into the medium as expected when PLase C is activated . Cells prelabeled with arachidonic acid release a significant amount of radioactivity from the third hour postinfection . Most of this radioactivity is present in the medium of SFV-infected cells in the form of free fatty acid, suggesting that phospholipid hydrolysis has occurred; no intact phospholipids are detected in the culture medium . Finally, the action of several inhibitors of PLases, such as zinc and cadmium ions, chloroquine, chlorpromazine, amantadine, and dansylcadaverine were assayed . Our findings indicate that the release of choline or arachidonic acid is potently blocked by some of these lipase inhibitors . Following infection by SFV HeLa cells become susceptible to the inhibition of protein synthesis by hygromycin B due to increased uptake of this antibiotic . Entry of hygromycin B was prevented by zinc ions or chloroquine, suggesting that the increase in membrane permeability in SFV-infected cells may be mediated in part by lipase activation.

J Virol, 1993 May, 67(5), 2932 - 7
The 23-kilodalton E1 phosphoprotein of bovine papillomavirus type 1 is nonessential for stable plasmid replication in murine C127 cells; Hubert WG et al.; The 23-kDa protein encoded by the 5' segment of the E1 open reading frame of bovine papillomavirus type 1 (BPV1) was previously ascribed a negative regulatory function for the replication of viral plasmid DNA . However, results from recent functional and biochemical studies do not readily support this genetic assignment . Therefore, we have reassessed the role of this protein in papillomavirus DNA replication by using a mutant of BPV1 which is unable to express this E1 protein . This mutant viral DNA was found to replicate extrachromosomally with stability and copy number per cell similar to those of wild-type plasmid DNA . Thus, the absence of expression of the 23-kDa E1 protein did not lead to deregulated viral plasmid replication . We conclude that the 23-kDa E1 protein is nonessential for stable plasmid replication.

Dentomaxillofac Radiol, 1993 May, 22(2), 93 - 6
Periostitis ossificans of the mandible . The value of computed tomography; Larheim TA et al.; Periostitis ossificans in the mandible of a 9-year-old girl was assessed by means of computed tomography . Impaired mandibular function was the most consistent clinical sign and led on to referral for suspicion of a temporomandibular joint disease . Her symptoms improved with antibiotic therapy over a period of 2 months . During this time follow-up computed tomography demonstrated a more or less complete resolution of the new bone formation . The aetiology of the periostitis was considered non-dental due to haematogeneous spread from a pharyngitis.

Mikrobiol Zh, 1993 May-Jun, 55(3), 24 - 30
{Inhibitors of nucleic acid synthesis as a means of identifying the forms of DNA-dependent DNA polymerases in Acholeplasma laidlawii PG-8 and of determining their functions}; Skripal' IG et al.; Antibiotics, inhibitors of nucleic acids' synthesis from the group of chromomycins (olivomycin of sodium salt), anthracyclines (carminomycin and doxorubicin) and streptonigrin (bruneomycin) have been studied for their effect on DNA synthesis in vitro performed by DNA polymerases (1st and 2nd forms) of Acholeplasma laidlawii PG-8 . It has been stated that olivomycin inhibits the function of both the first and second forms of DNA polymerases in proportion to an increase of the antibiotic concentration in the medium . Carminomycin in the concentration of about 1 microgram/ml almost completely inhibited the activity of both DNA polymerases . However, doxorubicin also belonging to the group of anthracyclins completely inhibited the activity of the first form of DNA polymerase in the concentration of 1 microgram/ml and practically has no effect in the concentration up to 100 micrograms/ml on the activity of the second form possessing 3'-->5'-function . Streptonigrin also proved to be suitable for differentiate the forms of DNA polymerases and to determine their functions . The first form of DNA polymerase with 5'-->3'-polymerase and exonuclease functions was not sensitive by this antibiotic in the concentration of 1000 micrograms/ml, while the activity of the second form of DNA polymerase with 3'-->5'-exonuclease functions was fully inhibited by this concentration of the antibiotic in the medium . The combination of doxorhubicin and streptonigrin in the medium can be used to determine the form of DNA polymerases and to identify their 5'-->3'- or 3'-->5'-exonuclease function and for selectivity inhibition of the function of one or another DNA polymerase in the medium.

J Perinatol, 1993 May-Jun, 13(3), 190 - 6
User-friendly computerized quality assurance program for regionalized neonatal care; Donn SM et al.; In October 1983 a computerized data base system was implemented to perform quality assurance in the neonatal referral region of the University of Michigan . This system was customized to match and expand forms and reports already in use . It is menu driven, requires only rudimentary skills, and is compatible with existing computer equipment . To assess the effectiveness of the program in monitoring and improving neonatal care within the region, data from the first full year (1984) were compared with data from the last full year (1990) . Statistically significant changes were found for referring physician presence at transfer, a greater assumption of initial stabilization procedures by community hospital personnel (continuous cardiorespiratory monitoring, orogastric tube placement, provision of respiratory support, blood glucose screening, blood gas evaluation, blood culturing, and antibiotic therapy), and an overall improvement in patient status before transfer . Review of reports generated by data analysis enables design of educational programs that are hospital specific and that focus on problems or deficiencies determined during quality assurance conferences . The chief benefit of this system is the provision of an objective basis for constructive criticism, which leads to both cognitive and behavioral changes in care providers and ultimately improves the delivery of care to neonates.

J Chir (Paris), 1993 May, 130(5), 231 - 6
{Boerhaave syndrome or spontaneous rupture of the esophagus}; Mutter D et al.; Spontaneous rupture of esophagus is a rare affection resulting from barotrauma to lower esophagus during the effort of vomiting . The diagnosis is suggested by the presence of violent retrosternal pain after a bout of vomiting following the partaking of a copious meal by an alcoholic patient . Prognosis is dependent on the rapidity of treatment, always surgical and completed by long-term antibiotic therapy . Complementary examinations should be limited to a standard chest x ray and esophageal imaging with water-soluble contrast . Recovery is now the rule for patients treated within 24 hours . Mortality is high in patients diagnosed at a late stage, but this could be reduced by improved recognition of the syndrome.

J AOAC Int, 1993 May-Jun, 76(3), 549 - 54
Optimization of a liquid chromatographic method for determination of oxytetracycline, tetracycline, and chlortetracycline in milk; White CR et al.; A liquid chromatographic (LC) method was developed for the simultaneous identification and quantitation of oxytetracycline, tetracycline, and chlortetracycline in milk . Milk samples (5 mL) were deproteinized by adding 1 mL 1N HCl and 24 mL acetonitrile, and filtering . Dichloromethane and hexane were added to 15 mL filtrate to separate the water layer . The organic layer was washed with 1 mL deionized water, and the combined water layers were diluted to 4 mL . Sample aliquots of 1000 microL were then injected directly and analyzed on an LC system . The sensitivity limit of the method is 5 ppb for each antibiotic; no interferences are present at their retention times . Mean recoveries from milk spiked at 0.01-1 ppm ranged from 87 to 99%, and precision was good.

Bull Acad Natl Med, 1993 May, 177(5), 749 - 57; discussion 757-9
{Prevention of nosocomial infections}; Mallaret MR et al.; The nosocomial infections prevention have to be subject to a concerted and multidisciplinary policy including the formation development, the specifics resources attribution, a rigorous evaluation reinforcement, and a quality research promotion . The prevention have to be done within tree nosocomial infection, transmissions classical ways: transmission by the health care workers, prevented by the hand washin up, a rigorous "hygienic care" and the isolation of infections patient, transmission by the material, involving to use valid disinfection procedure, transmission within the environment witch control have to grow within an implementation of "prosthetic" material always more used . Two other aspects have to be taken in the nosocomial infection prevention: prophylactic antibiotic use with let to prevent operative site infections, the health employee infection, bacterial or viral, have to be analysed by hygienic strategy in hospital.

Aust N Z J Obstet Gynaecol, 1993 May, 33(2), 204 - 7
Septic pelvic thrombophlebitis: an unusual treatable postpartum complication; Keogh J et al.; Septic pelvic thrombophlebitis is an uncommon but serious postpartum complication occurring in about 1 in 2,000 pregnancies, characterized by pain, antibiotic resistant fever and tachycardia . In about 50% of cases a pelvic mass is present which is usually right-sided (especially when the ovarian vein is involved) . It is estimated to cause 18 maternal deaths per million pregnancies in the United States . Use of contrast enhanced CT scanning and a trial of heparin therapy increases the diagnostic certainty . It is particularly important because surgical management which may otherwise be suggested because of a spiking fever and a mass seems to be associated with a poorer prognosis than does conservative management.

Psychol Med, 1993 May, 23(2), 323 - 6
The role of creatine kinase in the diagnosis of neuroleptic malignant syndrome; O'Dwyer AM et al.; Elevation of serum creatine kinase (CK) concentrations occurs almost invariably in neuroleptic malignant syndrome (NMS) . However, the role of CK levels in the diagnosis of the syndrome remains controversial . This study measured CK levels in patients who became pyrexial while on psychotropic medication and thereby mimicked some of the features of NMS . In all of these cases a diagnosis of infectious illness was made and patients responded to appropriate antibiotic therapy without alteration in psychotropic medication . Two other groups were studied for comparison--patients on psychotropics who were apyrexial and patients who became pyrexial but were not on psychotropics . Significant, unexpected elevations of CK were documented in 70% of those patients who became pyrexial while on psychotropics--in three cases elevation of concentrations to more than 1000 IU/l (ten times reference value) were found . Thirty per cent of patients who became pyrexial but were not on psychotropics also developed elevation of CK but this was of a much smaller magnitude (< 200 IU/l in five out of six cases) . The results of the study suggest that elevation of CK is a non-specific finding, particularly in patients who become pyrexial on psychotropics . Use of CK as a diagnostic criterion may lead to overdiagnosis of NMS.

Biull Eksp Biol Med, 1993 May, 115(5), 550 - 2
{Morphofunctional characteristics of the cat spiral ganglion in neurosensory hypoacusis}; Rakhmanova IV et al.; Morphofunctional disorders in spiral ganglion in animals of different groups of age with neurosensory hardness of hearing due to ototoxic antibiotics have been shown . Antibiotic intoxication in kittens in early postnatal period arouses essential deviation from normal process of development of neurocytes in spiral ganglion . In the first rate low level of their metabolic activity must be shown . Delay of differentiation of neurocytes makes essential influence on the development of spiral ganglion as the unit of transmission of audio-information . The main feature of morphofunctional disorders in neurocytes of ganglion of grown-up animals is inhibition of protein synthesis mechanism activity.

J Gen Microbiol, 1993 May, 139 ( Pt 5), 1003 - 11
Resistance to spiramycin in Streptomyces ambofaciens, the producer organism, involves at least two different mechanisms; Pernodet JL et al.; During its stationary phase, Streptomyces ambofaciens produces the macrolide antibiotic spiramycin, and has to protect itself against this antibiotic . Young mycelia, not yet producing spiramycin, are sensitive to it, but they become fully resistant when production begins . In a sensitive mycelium, resistance could be induced by exposure to sub-inhibitory concentrations of spiramycin, and these induced mycelia, like producing mycelia were resistant not only to spiramycin but also to several other macrolide antibiotics . Ribosomes extracted from these resistant mycelia were shown in vitro to be more resistant to spiramycin than ribosomes extracted from sensitive mycelium, indicating that S . ambofaciens possesses a spiramycin-inducible ribosomal resistance to spiramycin and to macrolide antibiotics . Studies with spiramycin non-producing mutants showed that, in these mutants, resistance to spiramycin also varies during cultivation, in that an old culture was much more resistant than a young one . But with these non-producing mutants, the spectrum of resistance was narrower, and in vitro data showed that resistance was not due to ribosomal modification . These results suggest that S . ambofaciens presents at least two distinct mechanisms for spiramycin resistance; a spiramycin-inducible ribosomal resistance, and a second resistance mechanism which might be temporally regulated and which could involve decreased permeability to, or export of, the antibiotic . The two mechanisms are probably at work simultaneously in the producing mycelium, the spiramycin-inducible resistance being induced by endogenous spiramycin . In non-producing mutants, in the absence of self-induction by spiramycin, only the second mechanism is observed.

Bioconjug Chem, 1993 May-Jun, 4(3), 189 - 93
Synthesis of bleomycin A5 oligonucleotide derivatives and site-specific cleavage of the DNA target; Zarytova VF et al.; A method for coupling bleomycin A5 to oligonucleotides is proposed . The reaction was carried out between an amino group of a spermidine residue of the Cu(II) complex of bleomycin A5 (Cu(II)Blm-RH) and a 5'-phosphate group of the oligonucleotides d(pCCAAACA) (I), d(pCGTCCTC) (II), d(pT)16 (III), d(pCAAACA) (IV), and d(pGCCAAACA) (V) activated with a mixture of triphenylphosphine and 2,2'-dipyridyl disulfide in the presence of 4-(N,N-dimethylamino)pyridine 1-oxide . The yields of the products Cu(II)Blm-R-d(pCCAAACA) (Ia), Cu(II)Blm-R-d(pCGTCCTC) (IIa), Cu(II)Blm-R-d(pT)16 (IIIa), Cu(II)Blm-R-d(pCAAACA) (IVa), and Cu(II)Blm-R-d(pGCCAAACA) (Va) were 60-80% . After removal of the Cu(II) ion from the bleomycin A5 oligonucleotide derivatives Ia-IIIa, compounds Ib-IIIb were obtained . Compounds Ia, IVa, Va, and Ib-IIIb were further used for modification of the target d(pTGTTTGGCGAAGGA) in the presence of Fe(II) ions and 2-mercaptoethanol . Site-specific cleavage of the target by Blm coupled to complementary oligonucleotides was demonstrated . It was shown that efficiency and position of cleavage of the complementary reagents Ia, Ib, IVa, and Va are determined by their oligonucleotide part while the action of thenoncomplementary reagents IIb and IIIb was similar to that of the free antibiotic.

Nucleic Acids Res, 1993 Apr 25, 21(8), 1753 - 60
The 35-kilodalton protein gene (p35) of Autographa californica nuclear polyhedrosis virus and the neomycin resistance gene provide dominant selection of recombinant baculoviruses; Lerch RA et al.; Autographa californica nuclear polyhedrosis virus (AcMNPV) recombinants were constructed to test the effectiveness of the AcMNPV 35-kilodalton protein gene (35K gene) and the bacterial neomycin resistance gene (neo) as dominant selectable markers for baculoviruses . Insertion of the AcMNPV apoptosis suppressor gene (p35) into the genome of p35-deletion mutants inhibited premature host cell death and increased virus yields up to 1200-fold at low multiplicities in Spodoptera frugiperda (SF21) cell cultures . When placed under control of an early virus promoter, the bacterial neomycin resistance gene (neo) restored multiplication of AcMNPV in the same cells treated with concentrations of the antibiotic G418 that inhibited wild-type virus growth greater than 1000-fold . The selectivity of these dominant markers was compared by serial passage of recombinant virus mixtures . After four passages, the proportion of p35-containing virus increased as much as 2,000,000-fold relative to deletion mutants, whereas the proportion of neo-containing viruses increased 500-fold relative to wild-type virus under G418 selection . The strength and utility of p35 as a selectable marker was further demonstrated by the construction of AcMNPV expression vectors using polyhedrin-based transfer plasmids that contain p35 . Recombinant viruses with foreign gene insertions at the polyhedrin locus accounted for 15 to 30% of the transfection progeny . The proportion of desired viruses was increased to greater than 90% by linearizing the parental virus DNA at the intended site of recombination prior to transfection . These results indicate that p35 and neo facilitate the selection of baculovirus recombinants and that p35, in particular, is an effective marker for the generation of AcMNPV expression vectors.

Biochim Biophys Acta, 1993 Apr 23, 1167(3), 303 - 6
Inhibition of oxidized low-density lipoprotein metabolism in macrophage J774 by helvolic acid; Shinohara C et al.; The antibiotic helvolic acid inhibited cholesteryl ester accumulation in macrophage J774 treated with oxidized low-density lipoprotein (LDL) at a concentration of 50-350 microM . The agent reduced oxidized 125I-LDL degradation and {14C}oleate incorporation into cholesteryl ester . In a cell-free assay, ATP-dependent acidification of endosomes and lysosomes was significantly inhibited by 35 microM helvolic acid, suggesting that this activity accounts for the inhibition of oxidized LDL metabolism in the macrophages.

Biochem Pharmacol, 1993 Apr 22, 45(8), 1685 - 94
Activation of the anti-cancer drug ifosphamide by rat liver microsomal P450 enzymes; Weber GF et al.; The NADPH-dependent metabolism of ifosphamide catalyzed by rat liver microsomes was investigated in order to identify individual P450 enzymes that activate this anti-cancer drug and to ascertain their relationship to the P450 enzymes that activate the isomeric drug cyclophosphamide . Pretreatment of rats with phenobarbital or clofibrate increased by up to 8-fold the activation of both ifosphamide and cyclophosphamide catalyzed by isolated liver microsomes . Studies using P450 form-selective inhibitory antibodies demonstrated that constitutively expressed P450s belonging to subfamily 2C (forms 2C11/2C6) make significant contributions to the activation of both oxazaphosphorines in uninduced male rat liver microsomes, while the phenobarbital-inducible P450 2B1 was shown to be a major catalyst of these activations in phenobarbital-induced microsomes . Pretreatment of rats with dexamethasone increased liver microsomal activation of ifosphamide approximately 6-fold without a corresponding effect on cyclophosphamide activation rates . Ifosphamide activation catalyzed by dexamethasone-induced liver microsomes was minimally inhibited by anti-P450 2B or anti-P450 2C antibodies, but was selectively inhibited by anti-P450 3A antibodies . Selective inhibition of liver microsomal ifosphamide activation was also effected by the macrolide antibiotic triacetyloleandomycin, an inhibitor of several dexamethasone-inducible 3A P450s . These studies establish that a dexamethasone-inducible family 3A P450 can make an important contribution to rat liver microsomal ifosphamide activation, and suggest that dexamethasone pretreatment might provide a useful approach for modulation of ifosphamide metabolism in order to improve its therapeutic efficacy in cancer patients.

Biochemistry, 1993 Apr 20, 32(15), 4139 - 44
Lipid-amphotericin B complex structure in solution: a possible first step in the aggregation process in cell membranes; Balakrishnan AR et al.; The interactions between the polyene antibiotic amphotericin B with dipalmitoylphosphatidylcholine were investigated in vesicles (using circular dichroism) and in chloroform solution (using circular dichroism and 1H, 13C, and 31P nuclear magnetic resonance) . The results show that amphotericin B readily aggregates in vesicles and that the extent of aggregation depends on the lipid:drug concentration ratio . Introduction of sterol molecules into the membrane hastens the process of aggregation of amphotericin B . In chloroform solutions amphotericin B strongly interacts with phospholipid molecules to form a stoichiometric complex . The results suggest that there are interactions between the conjugated heptene stretch of amphotericin B and the methylene groups of lipid acyl chains, while the sugar moiety interacts with the phosphate head group by the formation of a hydrogen bond . A model is proposed for the lipid-amphotericin B complex, in which amphotericin B interacts equally well with the two lipid acyl chains, forming a 1:1 complex.

Biochemistry, 1993 Apr 20, 32(15), 4067 - 72
Evidence for a conformational change in the exit site of the Escherichia coli ribosome upon tRNA binding; Lodmell JS et al.; The exit (E) site of the Escherichia coli ribosome was investigated using oligodeoxyribonucleotides complementary to single-stranded regions of ribosomal RNA suggested to be involved in tRNA binding in the E site {Moazed, D., & Noller, H . (1989) Cell 57, 585-597} . Radiolabeled DNA oligomers (probes) were hybridized in situ to complementary sites on the ribosomal RNA of ribosomes or ribosomal subunits, and the effects of simultaneous tRNA or antibiotic binding on probe binding were measured using a nitrocellulose filtration binding assay . Site specificity of probe binding was assured using ribonuclease H to cleave the ribosomal RNA at the site of probe binding . When 50S subunits were hybridized with a probe spanning bases 2109-2119 and deacylated tRNA was added incrementally, probe binding decreased, suggesting that the probe and tRNA competed for the same binding site or that tRNA was allosterically affecting the probe binding site . When 70S ribosomes were substituted for 50S subunits, probe binding to this site initially increased and then decreased at higher concentrations of deacylated tRNA . Titrating probe-ribosome complexes with acylated tRNA, N-acetyl-acylated tRNA, tetracycline, or chloramphenicol had no effect on probe binding . The data presented provide evidence for tRNA/rRNA interaction at or near the E site of the E . coli ribosome and suggest that a conformational change occurs in the E site when deacylated tRNA is bound to the P site . The data suggest that deacylated tRNA in the P site serves as a translocational trigger by causing the E site to change conformations, making it more available for tRNA (and probe) binding and therefore promoting translocation.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemistry, 1993 Apr 20, 32(15), 3902 - 6
Inhibitory effect of modified bafilomycins and concanamycins on P- and V-type adenosinetriphosphatases; Drose S et al.; Various ATPases have been tested for their sensitivity to naturally occurring unusual macrolides and their chemically modified derivatives, which are structurally related to bafilomycin A1 (1), the first specific inhibitor of vacuolar ATPases . The structure-activity study showed that in general the concanamycins, 18-membered macrolides, are better and more specific inhibitors than the bafilomycins of this class of membrane-bound ATPases . The additional carbohydrate residue is not responsible for the improved activity . The importance of an intact hemiketal ring, which is part of an intramolecular hydrogen-bonding network, and the effects of the size of the macrolactone ring are discussed . The structurally related elaiophylin (13), a C2-symmetric macrodiolide antibiotic, proved to be inactive on vacuolar ATPases but still retained its inhibitory effect on P-type ATPases.

Eur J Biochem, 1993 Apr 15, 213(2), 737 - 41
Crystal structure of apo-neocarzinostatin at 0.15-nm resolution; Teplyakov A et al.; The three-dimensional structure of apo-neocarzinostatin, an antitumour antibiotic protein isolated from Streptomyces carzinostaticus, has been determined by X-ray diffraction at 0.15-nm resolution and refined to R = 17.2% . The crystal structure of neocarzinostatin is similar to that of the related proteins actinoxanthin and macromomycin . It is also in good agreement with the solution structure determined by NMR spectroscopy . The protein molecule consists of a seven-stranded antiparallel beta-sandwich and a smaller lobe formed by two beta-ribbons . A deep cleft between the two lobes is a putative chromophore binding site . Side chains of Trp39, Leu45, Phe52, Phe78 and the disulphide Cys37-Cys47 aligning the binding cleft in neocarzinostatin suggest the importance of hydrophobic interactions in stabilizing the chromophore molecule . Comparison of the atomic models of neocarzinostatin, actinoxanthin and macromomycin reveals functional residues which might determine specificity towards different chromophores.

Gene, 1993 Apr 15, 126(1), 141 - 6
A cloned replicon of Saccharopolyspora phages JHJ-1 and JHJ-3 is stably maintained as a plasmid in various actinomycetes; Gaudreau LR et al.; A replicon of phage JHJ-1 (and JHJ-3) was cloned . The autonomously replicating phage element was maintained as a medium-copy-number shuttle plasmid in many actinomycetes, and was efficiently transmitted to spores without antibiotic selection . One gene was shown to be expressed in a vector containing the JHJ-3 replicon.

JAMA, 1993 Apr 14, 269(14), 1812 - 6
The overdiagnosis of Lyme disease; Steere AC et al.; OBJECTIVE--To analyze the diagnoses, serological test results, and treatment results of the patients evaluated in a Lyme disease clinic, both prior to referral and from current evaluation . DESIGN--Retrospective case survey of prescreened patients . SETTING--Research and diagnostic Lyme disease clinic in a university hospital . PATIENTS--All 788 patients referred to the clinic during a 4.5-year period who were thought by the referring physician or the patient to have a diagnosis of Lyme disease . MAIN OUTCOME MEASUREMENTS--Symptoms and signs of disease, immunodiagnostic tests of Lyme disease, and tests of neurological function . RESULTS--Of the 788 patients, 180 (23%) had active Lyme disease, usually arthritis, encephalopathy, or polyneuropathy . One hundred fifty-six patients (20%) had previous Lyme disease and another current illness, most commonly chronic fatigue syndrome or fibromyalgia; and in 49 patients, these symptoms began soon after objective manifestations of Lyme disease . The remaining 452 patients (57%) did not have Lyme disease . The majority of these patients also had the chronic fatigue syndrome or fibromyalgia; the others usually had rheumatic or neurological diseases . Of the patients who did not have Lyme disease, 45% had had positive serological test results for Lyme disease in other laboratories, but all were seronegative in our laboratory . Prior to referral, 409 of the 788 patients had been treated with antibiotic therapy . In 322 (79%) of these patients, the reason for lack of response was incorrect diagnosis . CONCLUSIONS--Only a minority of the patients referred to the clinic met diagnostic criteria for Lyme disease . The most common reason for lack of response to antibiotic therapy was misdiagnosis.

Biochemistry, 1993 Apr 13, 32(14), 3617 - 22
Exclusive production of bistranded DNA damage by calicheamicin; Dedon PC et al.; Bistranded DNA damage produced by the enediyne antitumor antibiotic calicheamicin (CAL) was examined in plasmid DNA and in a model site for CAL-mediated DNA damage containing the sequence AGGA.TCCT . CAL was observed to produce bistranded DNA damage to the virtual exclusion of single-strand (SS) lesions . Without expression of drug-induced abasic sites as strand breaks, CAL activated by 10 mM glutathione produced equal numbers of DS and SS breaks in plasmid DNA . However, cleavage of drug-induced abasic sites with hydrazine and putrescine resulted in a dramatic increase in the appearance of bistranded damage, with ratios of DS to SS breaks of approximately 6:1 and approximately 24:1, respectively . A similar bias for DS lesions was noted in CAL-mediated damage in the AGGA.TCCT model sequence, in which evidence for a 4'-hydroxylated abasic site was observed on the AGGA strand . These model DNA systems revealed three important features of the bistranded damage produced by CAL . First, the major lesion produced by CAL is a bistranded lesion consisting of an abasic site on one strand and a direct strand break on the other . Second, 3'-phosphoglycolate residues resulting from CAL-induced C4'-hydrogen abstraction at the C of AGGATC were restricted to bistranded lesions . This unusual behavior of the C4'-chemistry of both CAL and the related neocarzinostatin (NCS) is consistent with an intermediate in the partitioning that is dependent on bistranded lesions . Finally, 4-hydroxythiophenol activated CAL to produce a ratio of DS to SS lesions of approximately 10:1, as opposed to the approximately 1:30 ratio noted previously for NCS.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemistry, 1993 Apr 13, 32(14), 3564 - 70
Transcription termination factor rho: the site of bicyclomycin inhibition in Escherichia coli; Zwiefka A et al.; Bicyclomycin is a novel, commercially important antibiotic . Information concerning the site of bicyclomycin inhibition in Escherichia coli has been obtained by the production of bicyclomycin resistant mutants by UV irradiation . Selection by growth in the presence of bicyclomycin of a plasmid clone library generated from a highly resistant mutant in recipient antibiotic-sensitive host cells (E . coli strain W3350) has led to the characterization of three different plasmids that confer drug resistance, which contained the gene encoding the transcription termination factor, rho . These mutant rho genes contained single base changes at nucleotide positions 656, 796, and 1009 . Preliminary mechanistic information has been obtained by monitoring the polyC-dependent ATPase activity of rho in the absence and presence of bicyclomycin and dihydrobicyclomycin . Addition of bicyclomycin to aqueous solutions containing rho and ATP led to a decrease in the release of inorganic phosphate with an I50 value of 60-70 microM bicyclomycin . This inhibition is comparable to the drug concentration needed to inhibit bacterial growth on plates . No loss of activity was observed when a similar concentration of dihydrobicyclomycin was used in place of bicyclomycin, while use of 10-fold higher concentrations of this derivative led to partial rho inhibition . PolyC-dependent ATPase activity from partially purified rho isolated from the mutant BCMr108 was not inhibited by bicyclomycin at concentrations (200 microM) found to completely inhibit wild-type rho . These cumulative findings are consistent with the notion that bicyclomycin expresses its activity by interfering with the polyC-dependent ATPase activity of rho.

J Biol Chem, 1993 Apr 5, 268(10), 7036 - 43
BLH1 codes for a yeast thiol aminopeptidase, the equivalent of mammalian bleomycin hydrolase; Enenkel C et al.; We have cloned the BLH1 gene of the yeast Saccharomyces cerevisiae coding for a peptidase with significant homology to rabbit bleomycin hydrolase . Bleomycin is a glycopeptide antibiotic used for the treatment of human cancers . The antitumor activity of the drug is limited by its metabolic inactivation caused by bleomycin hydrolase, a member of the cysteine protease family . The open reading frame of BLH1 consists of 1,449 base pairs encoding a 55.4-kDa protein consistent with the molecular mass found in sodium dodecyl sulfate-polyacrylamide gel electrophoresis . The consensus sequence within the active site region of cysteine proteases is conserved in the yeast enzyme . Biochemical studies on the purified enzyme confirm its classification as a thiol protease . The nonvacuolar enzyme has a molecular mass of 220 kDa, suggesting a homotetrameric structure . It exhibits an aminopeptidase activity with broad substrate specificity . Biochemical and genetic linkage data give evidence that the BLH1 and the LAP3 (Trumbly, R . J., and Bradley, G . (1983) J . Bacteriol . 156, 36-48) encoded aminopeptidases are identical . Deletion of the BLH1 gene is not lethal under normal growth conditions . However, blh1 mutants show hypersensitivity to bleomycin, indicating that bleomycin hydrolase is able to inactivate bleomycin in vivo and to protect cells from bleomycin-induced toxicity.

Presse Med, 1993 Apr 3, 22(12), 585 - 90
{Hematopoietic growth factors . Therapeutic value in oncology}; Archimbaud E et al.; Among haematopoietic growth factors, the granulocyte macrophage colony stimulating factor (GM-CSF), the granulocyte colony stimulating factor (G-CSF) and, more recently, interleukin-3 have been used in therapeutics mainly to try to reduce the duration of aplasia after chemotherapy followed or not by bone marrow transplantation in solid tumours and in leukaemias . In addition, interleukin-3 reduces the need for red cell and platelet transfusions . A concomitant reduction of death from infection, antibiotic use and duration of stay in hospital has been demonstrated by some randomized studies, but data are lacking to evaluate its practical and economic value . In acute myeloid leukaemia haematopoietic growth factors sensitize leukaemic cells to chemotherapy in vitro, but the clinical usefulness of this finding remains to be assessed . The stimulating and differentiating actions of haematopoietic growth factors on the bone marrow in vitro seems to have a clinical value in myelodysplastic syndromes where randomized studies have shown a rise in the number of cells after administration of these factors . However, whether long-term treatment will prolong the survival of patients with myeloplastic syndromes remains to be demonstrated.

Biophys Chem, 1993 Apr, 46(2), 179 - 85
Evaluation of the structural modifications induced by mitomycin C on nucleic acids; Jolles B et al.; The interaction of poly(dG-dC).poly(dG-dC) with mitomycin C, an antitumor antibiotic, has been studied by various spectroscopic methods: circular dichroism, Fourier transform infrared resonance Raman scattering and using fluorescence emission of terbium bound to unpaired guanines as local conformation probe . The results allowed us to confirm the lack of long range modification of the DNA secondary structure upon binding . They also brought first information concerning the modification of the local structure of the nucleic acid at the level of mono- or bifunctional adducts.

Clin Infect Dis, 1993 Apr, 16(4), 550 - 4
Persistent fever due to occult dental infection: case report and review; Siminoski K; Dental sepsis is one potential cause of persistent fever that can escape detection . A patient with febrile episodes due to an occult tooth abscess of 2 years' duration is described . A search of the English-language literature revealed 20 other cases of fever of obscure origin arising from dental sources . This diagnosis may be suggested by repeated questioning of the patient about his or her medical history, repeated physical examination, an elevated erythrocyte sedimentation rate, or a history of failure to respond to antibiotic therapy . Dental infection is unlikely in patients who have a white blood cell count of > 11 x 10(9)/L, a temperature of > 39.5 degrees C, or positive blood cultures . The diagnosis may be made by repeated focused clinical examination, dental roentgenography, or radiolabeled leukocyte scintigraphy . Detection of dental sepsis is worthwhile since the febrile condition can be cured in all instances by tooth extraction and abscess drainage, with or without concurrent antibiotic therapy.

Arch Esp Urol, 1993 Apr, 46(3), 181 - 5
{Fournier's gangrene . Presentation of 11 cases and review of the literature}; Blasco de Villalonga M et al.; Fournier's gangrene is an infectious necrotizing cellulitis of the penis and/or perineoscrotal region, which rapidly progresses and carries a high mortality . Eleven cases of Fournier's gangrene that had undergone an emergency procedure from 1985 to 1992 are described . Excellent results were achieved, with a survival rate of 91% . In our view, treatment of this disease entity is fundamentally based on early diagnosis, wide radical debridement of the affected area, frequent local treatment, debridement at the least sign of recurrence and early antibiotic therapy with three agents.

Can J Microbiol, 1993 Apr, 39(4), 448 - 50
Kasugamycin inhibition of nonsense suppression by thymine-requiring strains of Escherichia coli K12; Tiganos E et al.; Thymine-requiring strains of Escherichia coli suppress nonsense and frame-shift mutations . This appears to occur during translation, suggesting that the lack of activity of an enzyme thymidylate synthase, required for the synthesis of a DNA precursor, alters the fidelity of translation . The aminoglycoside antibiotic kasugamycin, which enhances translational accuracy in vitro, prevents thymine-requiring cells from suppressing . The inhibition of suppression by kasugamycin is not prevented by the introduction of two different kasugamycin-resistance mutations, although the dose required for inhibition increases . These observations support the conclusion that suppression occurs during translation.

Can J Microbiol, 1993 Apr, 39(4), 377 - 83
Accumulation of intracellular carbon reserves in relation to chloramphenicol biosynthesis by Streptomyces venezuelae; Ranade N et al.; Two chloramphenicol-producing strains of Streptomyces venezuelae accumulated small amounts of polyhydroxybutyrate during exponential growth; the compound disappeared from the mycelium as the cultures entered stationary phase . Depletion of polyhydroxybutyrate coincided with chloramphenicol production but the amount of polymer stored in the mycelium was insufficient to supply the precursor requirement for biosynthesis of the antibiotic . Accumulation of polyhydroxybutyrate in the S . venezuelae strains was appreciably lower than in two other streptomycetes examined . Glycogen and lipids accumulated in the mycelium of S . venezuelae 13s during the stationary phase, after nitrogen depletion; under the culture conditions used, they were the principal storage compounds in S . venezuelae . Trehalose was absent from the mycelium in vegetative cultures grown under nonsporulating conditions but it was abundant in spores obtained from submerged and surface cultures . Glycogen and polyhydroxybutyrate were absent from spores.

Biochem Med Metab Biol, 1993 Apr, 49(2), 255 - 64
Purification of nonantibiotic insulinase inhibitors from bacitracin; Medina V et al.; Bacitracin is commonly used in metabolic studies as an insulinase inhibitor . The many isoforms of the commercial preparation were fractionated by charge and size in order to find the most active rat-muscle insulinase inhibitors . CM-Sepharose chromatography revealed that most of the inhibitory activity was contained in a fraction (CM-Inh) that amounted to less than 5% of the mixture . The CM-Inh fraction could be further separated by size on Bio-Gel P4 columns . Six subgroups, each with characteristic specific activity, were isolated . The most potent inhibitor fractions have no antibiotic activity and have molecular weights about twice that of bacitracin A . The peaks isolated by means of Bio-Gel P4 chromatography can be further fractionated by reversed phase HPLC on a C8 column, and by electrophoresis on nonreducing acrylamide gels.

Chirurg, 1993 Apr, 64(4), 279 - 82
{Lung resections for pulmonary infections in intensive care patients}; Kelm C et al.; Pneumonia occurs in about 60% of ventilated patients with a lethality of approximately 40% . Since 1980 we performed a thoracotomy in 16 patients of an intensive care unit suffering from a lung infection (mean age 34 years) . In all patients an adequate antibiotic therapy was unsuccessful . By means of the computed tomography we could ascertain a lung infection limited to one part of the lung, mostly combined by an abscess . We performed 14 lobectomies and one atypical wedge resection and segment resection each . Postoperatively 8 patients died: Three of them because of a persisting septic shock and five because of their multiple injuries . Lung resection is a good treatment in case of a lung infection with septic complications.

J Arthroplasty, 1993 Apr, 8(2), 125 - 8
Reinfusion of whole blood after revision surgery for infected total hip and knee arthroplasties; Lux PS et al.; Because of its proven effectiveness in reducing the need for banked blood transfusions following total joint arthroplasty, the indications for postoperative blood retrieval were expanded to include seven cases of infected total knee or hip arthroplasties where a one-stage exchange procedure was performed . Each joint had been aspirated after surgery and had positive cultures but no gross pus at the time of revision surgery . Each of the operations included debridement with reimplantation of a cementless prosthesis under cover of intravenous antibiotics for 48 hours followed by oral treatment until discharge . Antibiotic-soaked morselized bone graft was used in all patients to restore deficient nonstructural bone . Wound drainage blood was retrieved and reinfused during the first 8 hours after surgery, averaging 958 cc . Banked blood usage averaged 2.4 U (88% homologous) with an average blood loss of 1,974 cc . One patient experienced shaking chills during a second reinfusion of 600 cc of blood without stoppage of the transfusion . Wound hematoma occurred in one patient but did not require surgical evacuation . No patient developed evidence of septicemia.

Infect Control Hosp Epidemiol, 1993 Apr, 14(4), 216 - 8
Comparison of patient telephone survey with traditional surveillance and monthly physician questionnaires in monitoring surgical wound infections; Manian FA et al.; OBJECTIVE: To evaluate the utility of patient telephone surveys in further improving the detection of surgical wound infections (SWIs) postdischarge in the setting of ongoing traditional surveillance system and monthly physician surveys . DESIGN: Prospective surveillance study of randomly selected patients undergoing surgery in inpatient or outpatient settings . SETTING: Tertiary care suburban hospital . RESULTS: Five hundred one patients were randomly selected for telephone contact, of whom 189 (38%) were successfully contacted after three attempts . Eighteen (9.5%) patients reported one or more signs or symptoms of possible SWI . However, none of these patients required antibiotic therapy, was hospitalized with an SWI, or reported by his or her physician (based on the monthly questionnaire) to have had an SWI . Total time spent contacting patients was 47 hours and 48 minutes, or 15 minutes per each successful telephone contact . CONCLUSIONS: Patient telephone surveys as conducted in this study were inefficient and failed to substantially improve the rate of detection of SWIs over traditional surveillance system and monthly physician questionnaires.

J Allergy Clin Immunol, 1993 Apr, 91(4), 873 - 82
Efficacy and safety of low-dose troleandomycin therapy in children with severe, steroid-requiring asthma; Kamada AK et al.; BACKGROUND: Troleandomycin (TAO), a macrolide antibiotic, was studied as an alternative treatment in 18 children with severe, steroid-requiring asthma . METHODS: In this investigation three treatment arms were used in randomized, double-blind, parallel fashion: combination TAO and methylprednisolone (MPn), combination TAO and prednisone, and MPn alone . RESULTS: All groups tolerated a considerable reduction in glucocorticoid dose over the 12 weeks of the study: 80% +/- 6% for TAO-MPn, 55% +/- 8% for TAO-prednisone, and 44% +/- 14% for MPn alone . These reductions are all statistically significant (p < 0.05) within groups, and the differences between groups were statistically significant between the TAO-MPn and MPn alone groups . The concentration of methacholine required to induce a 20% decrease in forced expiratory volume in 1 second and pulmonary function were not significantly improved in any treatment group . Safety parameters including blood chemistry and hematology, adrenal function assessment; bone densitometry, and muscle strength testing, were not altered significantly . Two patients who received TAO had elevated liver enzyme levels; one required discontinuation of TAO and one experienced spontaneous resolution without intervention . Lack of statistically significant changes in the efficacy parameters were likely a result of small sample size and effects of the glucocorticoid dose taper . CONCLUSIONS: TAO is safe and may be a reasonable treatment alternative in a limited trial for patients who are unable to tolerate tapering of their glucocorticoid dosage . Therapy should be guided by the goal of treatment, that is, glucocorticoid dose reduction or improvement of pulmonary function with appropriate monitoring of pulmonary function and adverse effects.

Ann Thorac Surg, 1993 Apr, 55(4), 1016 - 8
Pyoderma gangrenosum after coronary artery bypass grafting; Rand RP et al.; Pyoderma gangrenosum is a rare cutaneous disorder that may complicate recovery after a cardiac operation . The lesions appear to represent a necrotizing infection; however, they do not respond to surgical debridement and antibiotic therapy . The treatment is based on high-dose corticosteroids and concomitant treatment of any underlying systemic disease.

Am Fam Physician, 1993 Apr, 47(5), 1207 - 15
Pressure ulcers in nursing home patients; Spoelhof GD et al.; Pressure, moisture, shear forces and friction lead to skin ulcer formation . Nursing home and home-bound patients with restricted mobility, poor nutrition, incontinence and chronic conditions such as anemia, diabetes and dementia are at risk for ulcer formation . Bedridden patients should be turned from side to side at 30-degree angles at least every two hours . Mattress and chair cushions, splints and cradle boots may reduce pressure . Good hygiene and barrier ointments, condom catheters, absorptive products and scheduled toileting for incontinence may control moisture . Calorie and protein supplements, feeding assistance and serial weight measurements are essential in the management of malnourished patients . Treatment should be based on the stage of the ulcer and the presence of conditions such as necrotic debris, infection and drainage . Saline wet-to-dry dressings and enzymatic and surgical debridement are necessary to remove necrotic tissue . Saline-soaked gauze, hydrogel preparations and occlusive dressings provide the physiologic environment for fibroblasts to grow and form granulation tissue . Patients with sepsis may require hospital admission for both further evaluation and systemic antibiotic therapy.

J Fam Pract, 1993 Apr, 36(4), 449 - 52
Postpartum pyometra: a case report; Deutchman ME et al.; Pyometra is an uncommon result of endometritis . The diagnosis of pyometra is made when a collection of pus is found within the endometrial cavity . Antibiotic administration and drainage of the pus are essential to resolve this condition . A report of a case of pyometra is presented and a technique for drainage is described . This case demonstrates the use of office-based diagnostic ultrasonography to narrow the differential diagnosis and guide the drainage procedure, as well as the use of simple ingenuity to improve patient care.

Circulation, 1993 Apr, 87(4), 1152 - 68
Implantable transvenous cardioverter-defibrillators; Bardy GH et al.; BACKGROUND . Implantable transvenous cardioverter-defibrillators offer a significant opportunity to decrease procedural morbidity and medical costs in the care of patients with life-threatening ventricular arrhythmias who otherwise would have required a sternotomy or thoracotomy for device insertion . The purpose of this study was to examine prospectively the safety, efficacy, and limitations associated with the use of a transvenously implanted, tiered-therapy cardioverter-defibrillator with antitachycardia pacing function in a consecutive population of 84 ventricular fibrillation (VF) and sustained ventricular tachycardia (VT) survivors . METHODS AND RESULTS . The index arrhythmia promoting transvenous cardioverter-defibrillator implantation was VF in 41 patients, VT in 27, and both VF and VT in 16 . In each patient, transvenous defibrillation via a coronary sinus, a right ventricular, a superior vena caval, and/or a subcutaneous chest patch lead system was attempted . The pulsing methods used include two-electrode single-pathway pulsing or three-electrode dual-pathway simultaneous or sequential pulsing . A transvenous cardioverter-defibrillator was inserted if the defibrillation threshold (DFT) was < or = 20 J . Successful implantation of a transvenous cardioverter-defibrillator was possible in 80 of 84 (95%) patients . The mean implant DFT was 10.9 +/- 4.8 J . After cardioverter-defibrillator implantation, all patients were extubated in the operating room and sent to a standard telemetry ward for monitoring . No patient suffered a postoperative pulmonary complication or perioperative flurry of cardiac arrhythmias . Postoperative complications included lead dislodgments in eight, transient long thoracic nerve injury in one, asymptomatic left subclavian vein occlusion in two, asymptomatic small pericardial effusion in one, subcutaneous patch pocket hematomas in four, pulse generator pocket infection in one, and lead fracture in one . As experience was gained with the procedure, it was routine to discharge patients 3 days after surgery . The mean hospital stay was 6.0 +/- 2.4 days . Upon discharge, all patients returned to their prehospital activities including those with complications except for the patient with a pocket infection, who required intravenous antibiotic therapy . Patient survival using an intention-to-treat analysis was 98% over an 11 +/- 7-month follow-up period . During this time period, 31 of the 80 patients (39%) with transvenous lead systems were successfully treated by their device for sustained VT or VF . Antitachycardia pacing was used in 424 episodes of monomorphic VT and was successful in 371 (88%) . All episodes of VF were aborted by the device . Antiarrhythmic drugs were used after device implantation in only eight of 80 patients (10%) . CONCLUSIONS . Transvenous cardioverter-defibrillator implantation is practical in most candidates . Implant DFTs are usually low, surgical morbidity and postoperative complications are modest, therapy of VT and VF is efficient, and survival is excellent.

Otolaryngol Clin North Am, 1993 Apr, 26(2), 203 - 13
Immediate versus delayed repair of skin defects following resection of carcinoma; Thomas JR et al.; Facial defects resulting from excision of skin malignancies may be reconstructed with flaps or grafts immediately or in delayed fashion, or the wound may be allowed to heal by secondary intention . The merits of each option are discussed along with a brief review of the pertinent details of wound healing . A small delay in reconstruction of up to 3 to 4 days can be tolerated safely with no compromise of results . When healing by secondary intention is chosen, fenestration speeds coverage of the wound, and moist dressings with antibiotic ointment effectively prevent infection and expedite epithelialization.

Obstet Gynecol, 1993 Apr, 81(4), 590 - 3
Perioperative complications arising after transvaginal oocyte retrieval; Tureck RW et al.; OBJECTIVE: To determine the incidence of perioperative morbidity in patients undergoing transvaginal oocyte retrieval and to identify those patients at greatest risk for complications . METHODS: A retrospective analysis was performed on 674 patients of reproductive age who underwent transvaginal retrieval of oocytes for assisted reproduction technologies during a 3-year period . All procedures were performed by surgeons with extensive experience with transvaginal retrieval . Patients were entered into the program with a primary diagnosis of unexplained infertility (16%), endometriosis (32%), pelvic adhesions and/or tubal occlusion (38%), or infertility from male or immunologic factors (14%) . RESULTS: Of the 674 patients studied, ten (1.5%) required hospital admission because of perioperative complications . Nine of these patients needed intravenous antibiotics and one required admission and observation for an expanding broad-ligament hematoma . Six of nine women admitted for antibiotic therapy had a history of extensive pelvic adhesions with or without a history of salpingitis . Five of nine patients had a history of salpingitis . In addition, two patients experienced impressive vaginal arterial bleeding during the procedure . CONCLUSION: This study suggests that transvaginal retrieval may not be as innocuous as is often expressed and that the primary factor predisposing to perioperative morbidity is a history of previous pelvic inflammatory disease and/or adnexal adhesions.

J Bacteriol, 1993 Apr, 175(7), 1995 - 2005
Accumulation of bldA-specified tRNA is temporally regulated in Streptomyces coelicolor A3(2); Leskiw BK et al.; Deletion of the bldA gene of Streptomyces coelicolor A3(2), which encodes the only tRNA for the rare UUA codon, had no obvious effects on primary growth but interfered with aerial mycelium formation and antibiotic production . To investigate the possible regulatory role of bldA, its transcription start point was identified, and time courses were determined for the appearance of its primary transcript, the processing of the primary transcript to give a mature 5' end, and the apparent efficiency of translation of ampC mRNA, which contains multiple UUA codons . The bldA promoter was active at all times, but processing of the 5' end of the primary transcript was comparatively inefficient in young cultures . This may perhaps involve an antisense RNA, evidence of which was provided by promoter probing and in vitro transcription . The presence of low levels of the processed form of the tRNA in young cultures followed by increased abundance in older cultures contrasted with the pattern observed for accumulation of a different, presumably typical tRNA which was approximately equally abundant throughout growth . The increased accumulation of the 5' processed form of bldA tRNA coincided with more-efficient translation of ampC mRNA in older cultures, supporting the hypothesis that in at least some physiological conditions, bldA may have a regulatory influence on events late in growth, such as morphological differentiation and antibiotic production.

AJR Am J Roentgenol, 1993 Apr, 160(4), 799 - 802
Therapeutic percutaneous aspiration of hepatic abscesses: effectiveness in 25 patients; Baek SY et al.; OBJECTIVE: The objective of this study was to evaluate the effectiveness of sonographically guided needle aspiration and systemic antibiotic therapy for the treatment of hepatic abscesses . SUBJECTS AND METHODS: From June 1989 to September 1991, sonographically guided needle aspiration and systemic antibiotics were used to treat 25 consecutive patients with 25 hepatic abscesses . Among 36 patients with hepatic abscesses who were admitted to the hospital during that time, six had antibiotic therapy only; of these, three had microabscesses, two had abscesses less than 3.0 cm in diameter, and one refused needle aspiration . Four patients had surgical external drainage (three had cholelithiasis in addition to hepatic abscesses, and one did not respond to needle aspiration) . Two patients treated in 1989 had drainage via an indwelling catheter, which was the preferred method at that time . The remaining 24 patients and one patient who had needle aspiration followed by surgical drainage made up the study group . Seventeen of the hepatic abscesses were caused by pyogenic organisms, six by amoeba, and two by unknown organisms . Eighteen abscesses (72%) were aspirated once, four (16%) were aspirated twice in 8 days, two (8%) were aspirated three times in 14 days, and one (4%) was aspirated four times in 10 days . Persistent fever, pain and tenderness in the right upper quadrant, and leukocytosis were the indications for multiple aspirations . Follow-up sonography was performed to evaluate the outcome of treatment . RESULTS: In 16 cases (64%), the abscesses disappeared within a mean of 84 days . In eight cases (32%) with only partial follow-up, the patients were asymptomatic at the time of discharge and the abscesses were markedly smaller on the last follow-up sonograms (mean, 43 days) . One patient (4%) did not respond to aspiration and had surgical drainage . The length of hospitalization varied from 5 to 42 days (mean, 22 days) . In patients who became afebrile during the treatment, the fever had lasted from 0 to 10 days (mean, 3 days) . Only one patient had a complication of the procedure, a pleural effusion that was treated conservatively . CONCLUSION: Our results show that sonographically guided needle aspiration combined with antibiotic therapy is effective as the initial treatment for hepatic abscesses.

Surgery, 1993 Apr, 113(4), 373 - 9
Peritoneovenous shunting of intractable ascites in patients with cirrhosis: improving results and predictive factors of failure; Hillaire S et al.; BACKGROUND . The clinical results of peritoneovenous shunting have not been entirely satisfactory in spite of dramatic improvement of renal function and decrease of ascites . The purpose of this study is to determine whether certain modifications improved our results . METHODS . A modified LeVeen shunt was electively inserted in 56 patients who had cirrhosis with intractable ascites . In 24 patients (42.9%) the Child-Pugh's score was less than 9, and in 32 patients the score was 9 or above . Fourteen patients (25%) had previous variceal bleeding, and 15 patients (26.8%) had previous spontaneous bacterial peritonitis (SBP) . LeVeen shunt was modified by the addition of a titanium venous catheter tip . Prophylactic antibiotic therapy was administered to all patients . RESULTS . No operative deaths occurred, and one patient had severe postshunt coagulopathy . Five patients (8.9%) experienced recurrent ascites resulting from blockage from the shunt . The cumulative rate of shunt blockage was 5.6% at 1 year and 12% at 2 years . Seventeen patients (30.3%) have recently had variceal bleeding . The cumulative risk of variceal bleeding was significantly higher in patients with a previous hemorrhage than in those patients without (p < 0.05) . Eight patients (14.3%) had SBP after operation . The cumulative risk of SBP was higher in patients with a history of SBP than in those patients without, although the difference was not significant . Fifty-five percent of late deaths were related to variceal bleeding or to SBP . Overall cumulative 1- and 2-year survival rates were 67.2% and 55.2%, respectively . It was 82% and 71% in patients without previous variceal bleeding or SBP . CONCLUSIONS . These data suggest that peritoneovenous shunting might be beneficial only in selected patients . Previous variceal bleeding and/or SBP indicate liver transplantation in suitable patients.

Oncogene, 1993 Apr, 8(4), 1069 - 74
p53 confers a selective advantage on transfected HeLa cells; Ridgway PJ et al.; The p53 gene, which is frequently mutated in various tumors, encodes a phosphoprotein thought to have a key role in the regulation of cell proliferation . To explore their biological effects, the HeLa carcinoma line, which does not express p53, was co-transfected with plasmid constructs expressing wild-type or mutant p53 proteins, or unrelated proteins, along with a plasmid conferring resistance to a neomycin-kanamycin antibiotic analog (G418) . Both wild-type and mutant forms of p53 stimulated the number of G418-resistant colonies between 5- and 36-fold . Further investigation of colony development revealed that p53 enhanced cell survival, leading to increased colony numbers, but did not stimulate cell growth . Nonetheless, we suggest that an initial slowing of cell growth caused by expression of the unintegrated p53 plasmids renders the transfectants resistant to selection with G418, thus causing a higher frequency of G418-resistant colonies . p53 constructs were found to be expressed transiently in HeLa cells as expected, but the G418-resistant colonies frequently failed to express p53 . This loss of p53 expression may be due to negative regulatory effects of p53 on the cytomegalovirus promoter that drives the selection marker.

Cancer Res, 1993 Apr 1, 53(7), 1583 - 9
In vitro cytotoxicity, cellular pharmacology, and DNA lesions induced by annamycin, an anthracycline derivative with high affinity for lipid membranes; Ling YH et al.; Annamycin (AN) is an anthracycline antibiotic with high affinity for lipid membranes which is being developed for clinical studies formulated in liposomes . We studied the in vitro cytotoxicity, cellular pharmacology, and DNA damage induced by AN in P388 cells sensitive and resistant to doxorubicin (DOX) . AN was as cytotoxic as DOX against P388-sensitive cells and about 50 times more cytotoxic than DOX against P388-resistant cells (resistance index 5 for AN versus 250 for DOX) . Cellular uptake of AN by sensitive cells was 2-3-fold higher than that of DOX . In resistant cells, cellular uptake of AN and DOX was approximately 65% and 30%, respectively, of the cellular uptake in sensitive cells . As a result, cellular uptake of AN by resistant cells was higher than uptake of DOX by sensitive cells . DOX was fully retained in sensitive cells while it was effluxed rapidly from resistant cells . In contrast, efflux of AN was similar in sensitive and resistant cells, thus suggesting that it is not mediated by P-glycoprotein . AN was more effective than DOX in inducing single DNA breaks, double DNA breaks, and DNA-protein cross-links, both in sensitive and resistant cells, although DNA damage was lower in resistant cells than in sensitive cells . DNA lesions induced by AN in resistant cells were similar to or greater than those induced by DOX in sensitive cells . These studies indicate that the lack of cross-resistance between DOX and AN appears to be related, at least in part, to the relatively higher cellular uptake of AN compared with DOX and is associated with the ability of AN to induce significant DNA damage in resistant cells.

Toxicol Lett, 1993 Apr, 67(1-3), 3 - 15
Chemistry of drug-induced DNA lesions; Saito I; Recent results on the action mechanisms of naturally occurring DNA-damaging antitumor antibiotics have been described . These antibiotics include neocarzinostatin (NCS) and DNA alkylating, duocarmycin A and kapurimycin A3 . A series of duplex hexanucleotides of modified bases were prepared and their selectivity for C5' and C4' oxidation in the NCS-mediated degradation was investigated . Based on the cleavage data, a new binding model that permits competitive hydrogen abstraction from C5' and C4' of the DNA deoxyribose moiety has been described . Chemistry of alkylation of self complementary octanucleotide d(CGTATACG)2 by antitumor antibiotic duocarmycin A was described . It was demonstrated that N3 of adenine6 attacks the cyclopropane subunit of duocarmycin A to produce the covalently alkylated adduct . In contrast, antibiotic kapurimycin A3 alkylate N7 of guanine4 of d(CGCG)2 to provide the corresponding covalent adduct . Heating at 90 degrees C degraded the adduct to kapurimycin A3-guanine adduct and the respective abasic site-containing oligonucleotide . The structures of heat-induced abasic sites were unambiguously characterized.

J Gen Microbiol, 1993 Apr, 139 ( Pt 4), 735 - 41
Molecular comparison of the IncX plasmids allows division into IncX1 and IncX2 subgroups; Jones CS et al.; We have investigated molecular relationships and evolution of plasmids classified genetically to incompatibility (Inc) group X, in particular by comparison of plasmids from the pre-antibiotic era (PAE) with contemporary R-plasmids . On the basis of restriction analysis, R6K, the best-described and 'prototype' plasmid of the IncX group, exhibited little similarity with the other plasmids in this Inc group . Other contemporary IncX R-plasmids exhibited a substantial degree of interrelationship, and were also related to PAE IncX plasmids . When the origin of plasmid replication of R6K was used as a replicon probe, R6K was the only plasmid tested which exhibited homology . Other contemporary and PAE IncX plasmids exhibited homology with the origin of plasmid R485 . These data suggest that the IncX group should be subdivided . R485 may be regarded as representative of the major subgroup present before and after the advent of antibiotic selection pressure . Plasmids of this subgroup, IncX1, possess an internal region which yields five characteristic EcoRV fragments . R6K may be regarded as representative of subgroup IncX2, of which it is presently the sole well-described member . The antibiotic resistances encoded by contemporary IncX R-plasmids are due to insertion of identifiable transposons in progenitor plasmids identical to the R485 subgroup of PAE IncX plasmids.

J Bacteriol, 1993 Apr, 175(7), 2077 - 82
Transposon mutagenesis by Tn4560 and applications with avermectin-producing Streptomyces avermitilis; Ikeda H et al.; The Tn3-like Streptomyces transposon Tn4560 was used to mutagenize Streptomyces avermitilis, the producer of anthelmintic avermectins and the cell growth inhibitor oligomycin . Tn4560 transposed in this strain from a temperature-sensitive plasmid to the chromosome and from the chromosome to a plasmid with an apparent frequency of about 10(-4) to 10(-3) at both 30 and 39 degrees C . Auxotrophic and antibiotic nonproducing mutations were, however, obtained only with cultures that were kept at 37 or 39 degrees C . About 0.1% of the transposon inserts obtained at 39 degrees C caused auxotrophy or abolished antibiotic production . The sites of insertion into the S . avermitilis chromosome were mapped . Chromosomal DNA fragments containing Tn4560 insertions in antibiotic production genes were cloned onto a Streptomyces plasmid with temperature-sensitive replication and used to transport transposon mutations to other strains, using homologous recombination . This technique was used to construct an avermectin production strain that no longer makes the toxic oligomycin.

Pharmacol Toxicol, 1993 Apr-May, 72(4-5), 336 - 40
Effects of tylosin on the pituitary-gonadal axis in male rats; Meisel ML et al.; Former investigations in rats showed a decrease of thyroid hormone concentrations after treatment with the antibiotic and growth promoter tylosin (Schafer 1984) . In the present study, the effects of tylosin on the pituitary-gonadal axis in adult rats were studied . The substance was administered in two concentrations to rats (0.1 and 5.0 mg tylosin/kg feed) for three different periods: 15, 29 and 65 days . At the end of each period the organ weights were determined and the hormone levels in serum and pituitary gland were measured by radioimmunoassay . After 15 days reduced levels of LH (luteinizing hormone) and FSH (follicle stimulating hormone) in the pituitary gland and LH in serum were found . Moreover, the weight of seminal vesicles was decreased and the weight of pituitary increased . After 29 days an equilibrium between effects of tylosin and endocrine contraregulation seemed to be achieved . The prolonged tylosin administration (65 days) depressed testosterone concentration and increased hypophyseal LH stores . The testing of the pituitary-testicular axis with acute LHRH (luteinizing hormone-releasing hormone) stimulation caused a reduced increase of LH in animals treated with 0.1 mg tylosin . In contrast, the LH responsiveness to LHRH in animals treated with 5.0 mg tylosin was unchanged, while the testosterone response to released LH was reduced . These findings demonstrate that tylosin acts on the pituitary as well as on peripheral functions of the pituitary-gonadal-axis and that its effects depends on the time interval of tylosin administration.

J Chir (Paris), 1993 Apr, 130(4), 200 - 9
{Contribution of imipenem/cilastatin in the treatment of peritonitis: a comparative economic analysis in the case of France}; Levy E et al.; Imipeneme, a molecule chemically related to the carbapenems (beta-lactam), is a potent wide spectrum antibiotic reserved for hospital use . Effective as therapy for major infections, and for use in severely debilitated patients (immunodepressed, etc ...) its efficacy in the treatment of peritonitis has been demonstrated in numerous studies abroad, confirmed by results of a French multicenter trial in 1989 . Its cost-effectiveness ratio was assessed as excellent in a comparative case-controlled study of totally matched patients treated with other antibiotics . As expected, the cost of the treatment itself (imipeneme/cilastatine plus associated products and costs of their administration) was higher by about 1000 F per patient when compared with other antibiotic regimens, but its markedly superior efficacy allowed overall economies of about four and a half times this sum (4300 F) . This cost reduction was related to different factors, some of which could not be individualized because of missing data (personnel) or protocol bias (laboratory examinations) . Nevertheless, the global result was a shortening of hospital stay by more than two days due to a very pronounced decrease in failure rate of the first treatment . This result is even more remarkable in that the peritonitis treated by Tienam was significantly more severe than that treated by the other antibiotics.

Nippon Jinzo Gakkai Shi, 1993 Apr, 35(4), 415 - 9
A case complicated with SLE during maintenance hemodialysis; Shibahara H et al.; A 40-year-old woman suffered from toxemia of pregnancy in 1977 and was admitted to hospital . Thereafter, she developed nephrotic syndrome, underwent a renal biopsy, and a diagnosis of membranoproliferative glomerulonephritis (MPGN) was made . She received steroid therapy, immunosuppressive drug and anticoagulant therapy, and recovered sufficiently to be discharged from hospital in April, 1979 . During subsequent ambulatory treatment at our outpatient department, her renal function deteriorated gradually, and maintenance hemodialysis was started from June, 1990 . In July, 1991, she was admitted to our hospital with pleurisy and pericarditis . There was no improvement despite antibiotic treatments . Laboratory data revealed leukopenia and lymphopenia . Under suspicion of systemic lupus erythematosus (SLE), relevant tests were carried out . Immunological abnormalities such as positive LE cells and the presence of various autoantibodies, together with clinical signs of hypersensitivity to sunlight, stomatitis and serositis, satisfied the diagnostic criteria of the ARA and a diagnosis of SLE was made . This case did not exhibit any clinical or serological abnormalities except for the renal disorder for a 10-year period after the histological diagnosis of MPGN, but was eventually diagnosed as SLE as a result of the manifestation of SLE symptoms for the first time after one year of maintenance hemodialysis . Immunological abnormalities and SLE during maintenance hemodialysis are discussed in relation to other reports.

Mol Microbiol, 1993 Apr, 8(2), 277 - 85
Mycobacterium smegmatis RNA polymerase: DNA supercoiling, action of rifampicin and mechanism of rifampicin resistance; Levin ME et al.; We have isolated RNA polymerase from Mycobacterium smegmatis and established conditions for specific transcription initiation in vitro . The M . smegmatis enzyme has a strong dependence on supercoiling of the DNA substrate for transcription from mycobacterial promoters . We also show that RNA polymerase is the target for rifampicin, and that this antibiotic specifically inhibits the transition from synthesis of short oligoribonucleotides to full-length transcripts . RNA polymerase isolated from a rifampicin-resistant mutant of M . smegmatis is less sensitive to rifampicin in vitro, confirming that one mechanism of rifampicin resistance in mycobacteria is through alteration of RNA polymerase . This in vitro transcription system provides a simple method for the characterization of gene expression in mycobacteria including the pathogens Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium leprae . It also provides a system for evaluating potential anti-mycobacterial drugs.

J Dermatol, 1993 Apr, 20(4), 208 - 13
Pharmacokinetics of meropenem in experimentally burned rats; Yoshida T et al.; The pharmacokinetics of meropenem were investigated to examine its penetration into the skin of third degree burned rats . The rats were divided into two groups . One group acted as the control, and the other group had third degree burns induced by immersing their backs into 80 degrees C water for 20 seconds . The rats in each group were given 20 mg/kg of body weight of meropenem intravenously by one bolus injection seven days after burn inducement or depilation . In the non-burned control group, the maximum concentrations of meropenem in the serum and skin of 6.03 micrograms/ml and 0.12 microgram/g were respectively obtained 15 minutes after the injection and decreased very rapidly thereafter . In the burned rats, the maximum concentrations of meropenem in the serum, skin (eschar), and exudate fluid of 7.07 micrograms/ml, 1.44 micrograms/g and 5.99 micrograms/ml were respectively obtained 15 minutes after the injection and decreased very slowly . The penetration of meropenem into the burned skin was higher than that into the normal skin . These results suggest that meropenem is a very useful antibiotic in the treatment of burn infection.

Zhonghua Wai Ke Za Zhi, 1993 Apr, 31(4), 229 - 31
{Diagnosis and treatment of causes of fever after open heart surgery}; Shi YK; The causes of fever in 171 cases 10 days after 1527 cases of open heart surgery were analysed . The common noninfectious causes of fever were postpericardiotomy syndrome (35.8%) and drug fever (26.9%) . The infectious causes of fever were respiratory system infection (18.1%), chest wall and incision infection (9.9%), infectious endocarditis (7.0%) and transfusion malaria (2.4%) . In this paper, the diagnosis, prevention and treatment of common causes of fever after open heart surgery were discussed . The authors believed that etiologic diagnosis of fever and reasonable antibiotic use were key measures.

J Appl Physiol, 1993 Apr, 74(4), 1885 - 92
Leukocyte CD18 monoclonal antibody worsens endotoxemia and cardiovascular injury in canines with septic shock; Eichacker PQ et al.; We investigated the effects of a murine monoclonal antibody directed against the canine leukocyte CD11/18 adhesion complex (MAb R15.7) in a canine model of septic shock . Awake 2-yr-old purpose-bred beagles were studied 7 days before and 1, 2, 4, and 10 days after intraperitoneal placement of an Escherichia coli-infected fibrin clot . Starting 12 h before clot placement, animals received 0.5-1 mg/kg iv every 12 h (4 doses total) of either MAb R15.7 (MAb group, n = 8) or, as controls, murine serum protein (n = 8) . After infected clot placement, all animals received antibiotic (ceftriaxne, 100 mg.kg-1.day-1 for 4 days) . Two of eight control animals and four of eight MAb animals died (P = 0.4) . During the first 8 h after clot placement, MAb animals, compared with control animals, had greater (P < 0.06) increases in serum endotoxin levels and higher (P < 0.05) neutrophil counts . Day 1 after clot placement, MAb animals, compared with control animals, had decreased (P < 0.05) central venous pressure and arterial pH and increased (P < 0.05) arterial lactate . Day 2 after clot placement, MAb animals, compared with control animals, had decreased (P < 0.05) cardiac index and mean arterial pressure . In summary, MAb R15.7, although associated with increased neutrophil counts, worsened serum endotoxemia, acidosis, and cardiovascular function in this canine model of septic shock . These data suggest that in septic shock, antibody directed against this leukocyte membrane protein complex may be harmful, possibly via impairment of normal leukocyte function.

Arch Biochem Biophys, 1993 Apr, 302(1), 265 - 71
Isopentenoid synthesis in eukaryotic cells . An initiating role for post-translational control of 3-hydroxy-3-methylglutaryl coenzyme A reductase; Giron MD et al.; Using insect (Drosophila) and rodent mammalian cell cultures we demonstrate that acute mevalonate-mediated suppression of 3-hydroxy-3-methylglutaryl coenzyme A was initiated in the absence of protein synthesis . In addition, insect and mammalian cells depleted (1 h) of putative regulatory post-isopentenyl-1-pyrophosphate metabolites by incubation with an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A synthase (L-659,699) accumulated 3-hydroxy-3-methylglutaryl coenzyme A reductase enzyme units . This accumulation resulted primarily from a decrease in the loss of 3-hydroxy-3-methylglutaryl coenzyme A reductase enzyme units rather than from an increase in enzyme synthesis . These observations suggest that the initial phase of mevalonate-mediated suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity was governed primarily by post-translational processes . An unknown rapidly turning over post-isopentenyl-1-pyrophosphate metabolite(s) is proposed as the agonist for these post-translational processes.

Khirurgiia (Mosk), 1993 Apr, (4), 25 - 9
{Dermatoplasty in the treatment of necrotic mastitis and breast erysipelas}; Izmailov GA et al.; The authors had 15 female patients aged from 20 to 35 years with various diseases of the breast which were marked by necrosis of the skin and subcutaneous fat with involvement of 18 to 100% of the breast surface . The necrosis was caused by phlegmonous and infiltrative abscess producing forms of mastitis in 18 and by erysipelas in 7 cases . Necrotic mastitis and erysipelas developed in the first 2 weeks after delivery, as a rule, in patients with marked concomitant diseases of the heart and vessels . The patients were hospitalized 7 to 29 days after the onset of the disease . The development of severe forms of breast diseases was promoted by intensive manual abstraction of milk from the breast and retromammary antibiotic-novocaine blockades . After an operative intervention a complex of therapeutic measures was applied including semisynthetic antibiotics, agents containing protein globulin fractions, and dry and native blood plasma, and artificial polyuria with preceding hemodilution was produced . All patients underwent dermatoplasty with the use of a free split perforated skin graft . Lactorrhea in the region of the granulations was not a contraindication for surgical closure of the wound . Perforation of the skin graft was regarded a forced measure because the secretion of milk led to inevitable rejection of the transplant . The applied treatment produced quite satisfactory cosmetic and functional results.

Cardiovasc Surg, 1993 Apr, 1(2), 103 - 6
Iliofemoral bypass: a 10-year review; Oliveira M et al.; Iliofemoral bypass is available to patients with unilateral iliac occlusive disease . Experience with iliofemoral bypass in terms of graft patency and patient outcome is reviewed . From January 1981 to February 1991, iliofemoral grafts were placed in 19 patients . Of these, 16 had medical records available for review; all were men and the mean age was 65 (range 46-72) years . Risk factors associated with peripheral vascular disease included tobacco use (16 patients), hypertension (ten), coronary artery disease (seven) and diabetes mellitus (four) . Six patients had undergone previous peripheral vascular procedures . Angiography revealed an ipsilateral iliac artery suitable for bypass . Indications for operation included claudication (five patients), rest pain (six) and non-healing ulcer or gangrene (five) . Ten bypasses were placed on the left and six on the right . The mean(s.d.) ankle:brachial pressure index before operation was 0.39(0.24): 0.55(0.19) in patients with claudication and 0.29(0.22) in those treated for threat of limb loss . After surgery patients with claudication demonstrated improvement of this index to a mean(s.d.) of 0.83(0.24); in those with threat of limb loss it improved to 0.60(0.16) . One wound infection resolved with antibiotic therapy alone . Two patients had early (< 30 days) graft failure leading to amputation and subsequent perioperative death . Three other grafts failed, one each at 8, 9 and 13 months . All five grafts failed in patients with preoperative threat of limb loss . The cumulative patency rate was 72% at 1 year and 64% at 2-5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplant, 1993 Apr, 11(4), 307 - 11
Randomised vehicle-controlled dose-finding study of glycosylated recombinant human granulocyte colony-stimulating factor after bone marrow transplantation; Linch DC et al.; A multicentre, randomised vehicle-controlled single-blind dose ranging trial of intravenous recombinant granulocyte colony-stimulating factor (rhuG-CSF) administration after BMT has been performed in 121 patients with non-myeloid malignancies . All the doses of rhuG-CSF used (2-20 micrograms/kg/day) resulted in significant acceleration of neutrophil recovery, and a dose-response effect was apparent (p < 0.05) . At the 20 micrograms/kg/day dose of rhuG-CSF the median time taken to achieve a neutrophil count of > 0.5 x 10(9)/1 was reduced from 19 to 13 days (p < 0.001) and the time to achieve a neutrophil count > 1.0 x 10(9)/1 on the first of 3 consecutive days, from 26 to 14 days (p < 0.001) . There was a trend to less antibiotic use in the rhuG-CSF recipients and the median time in hospital was markedly reduced by 11-15 days (p < 0.01) . There was no toxicity in this study attributable to rhuG-CSF.

EMBO J, 1993 Apr, 12(4), 1499 - 504
Replacement of the L11 binding region within E.coli 23S ribosomal RNA with its homologue from yeast: in vivo and in vitro analysis of hybrid ribosomes altered in the GTPase centre; Thompson J et al.; Replacement of the protein L11 binding domain within Escherichia coli 23S ribosomal RNA (rRNA) by the equivalent region from yeast 26S rRNA appeared to have no effect on the growth rate of E.coli cells harbouring a plasmid carrying the mutated rrnB operon . The hybrid rRNA was correctly processed and assembled into ribosomes, which accumulated normally in polyribosomes . Of the total ribosomal population, < 25% contained wild-type, chromosomally encoded rRNA; the remainder were mutant . The hybrid ribosomes supported GTP hydrolysis dependent upon E.coli elongation factor G, although at a somewhat reduced rate compared with wild-type particles, and were sensitive to the antibiotic, thiostrepton, a potent inhibitor of ribosomal GTPase activity that binds to 23S rRNA within the L11 binding domain . That thiostrepton could indeed bind to the mutant ribosomes, although at a reduced level relative to that seen with wild-type ribosomes, was confirmed in a non-equilibrium assay . The rationale for the ability of the hybrid ribosomes to bind the antibiotic, given that yeast ribosomes do not, was provided when yeast rRNA was shown by equilibrium dialysis to bind thiostrepton only 10-fold less tightly than did E.coli rRNA . The extreme conservation of secondary, but not primary, structure in this region between E.coli and yeast rRNAs allows the hybrid ribosomes to function competently in protein synthesis and also preserves the interaction with thiostrepton.

J Immunol, 1993 Apr 1, 150(7), 2591 - 8
A role for calcineurin in degranulation of murine cytotoxic T lymphocytes; Dutz JP et al.; The immunosuppressive drugs cyclosporin A (CsA) and FK506 bind to distinct families of intracellular proteins, cyclophilins, and FK506 binding proteins (FKBP) respectively, termed immunophilins . Immuno-suppressant-immunophilin complexes bind to and inhibit the activity of calcineurin, a calcium-dependent serine/threonine phosphatase . CsA is known to inhibit degranulation in CTL as assessed by N benzyloxylcarbonyl-L-lysine thiobenzyl ester-esterase release assays . We have investigated whether calcineurin phosphatase activity is involved in this degranulation . Both CsA and FK506 are shown to inhibit N benzyloxylcarbonyl-L-lysine thiobenzyl esteresterase release in murine CTL clones induced either by cognate target or by PMA and the calcium ionophore A23187 . Inhibition is concentration dependent and is observed at drug concentrations that specifically inhibit cellular calcineurin . The FK506-binding immunophilin FKBP12, as well as calcineurin, are shown to be present in these cells by immunoblotting analysis . Rapamycin, a macrolide antibiotic thought to compete with FK506 for binding to common FKBP receptor sites, antagonizes the effects of FK506 on both degranulation and calcineurin activity . Neither the degranulation nor the effect of the immunosuppressants is affected by the protein synthesis inhibitor cycloheximide . These observations suggest a role for calcineurin in CTL degranulation . Thus, in addition to its previously described role in lymphokine gene activation, calcineurin also appears to be involved in T cell activation processes which do not require protein synthesis.

Khirurgiia (Mosk), 1993 Apr, (4), 36 - 8
{Endolymphatic drug infusion in the treatment of complicated acute appendicitis}; Shevkhuzhev ZA et al.; The work is based on lymphogenous methods of treatment, i.e . direct endolymphatic therapy with antibiotics and other agents in complications of acute appendicitis . On the basis of information in the literature, among the antibiotics we chose gentamicin, claforan, and a new antibiotic fortum . In addition to antibiotics, for the correction of disturbed blood rheological properties we gave endolymphatic infusions of trasylol, aspisol, and trental . The purpose of our study was the development of methods and treatment of complications of acute appendicitis . In view of this, we chose the patients according to the nosological groups with appendicular infiltrate, appendicular abscesses, and localized peritonitis of appendicular origin.

Fortschr Med, 1993 Mar 30, 111(9), 152 - 6
{Prevention of traveler's diarrhea with Saccharomyces boulardii . Results of a placebo controlled double-blind study}; Kollaritsch H et al.; BASIC REMARKS: Among travellers to distant countries with a low socioeconomic status and poor hygiene, traveller's diarrhea is a major problem . Once this epidemiological fact had been recognized, intensive efforts were made to reduce the incidence of this illness by prophylactic medication . Among non-antibiotic substances investigated, Saccharomyces boulardii (SB) appeared to show promising results in earlier studies . METHOD: In a placebo-controlled, double-blind study, various dosages (250 mg and 1,000 mg SB) were administered prophylactically to 3,000 Austrian travellers to distant regions . RESULTS: A significant reduction in the incidence of diarrhea was observed, with success depending directly on the rigorous use of the preparation . A tendency was noted for SB to have a varying regional effect, which was particularly marked in North Africa and in the Near-east (Turkey!); in addition, the effect also proved to be dose-dependent . The medication can be classified as low on side effects.

Regul Pept, 1993 Mar 19, 44(2), 233 - 8
Angiotensin II binding sites on micro-organisms contaminating cell cultures; Whitebread S et al.; An angiotensin II (Ang II) binding site, distinct from AT1 and AT2, has been found in cell cultures of rat aortic smooth muscle and rat glomerular mesangium . It is characterized by a high affinity for Ang II (Kd 0.75 +/- 0.13 nM) and Ang I (Ki 0.72 +/- 0.12 nM), but a very low affinity for Ang III (Ki 31 +/- 5 microM) . Ang(1-7) (Ki 1.01 +/- 0.26 nM) and Ang(1-6) (Ki 4.54 +/- 0.24 nM) are very selective for this site, with affinities more than 150- and 10,000-fold greater, respectively, than for AT1 or AT2 . The selective angiotensin receptor subtype ligands losartan and L-158,809 (AT1), PD 123319 and CGP 42112A (AT2) were inactive . Binding to this site was abolished after the cells had been treated with the antibiotic mixture BM-Cyclin, suggesting that the site is located not on the cells, but on a cell culture contaminant . This has been identified as Acholeplasma laidlawii . Caution should therefore be exercised when interpreting Ang II-related data obtained from cells that have not been checked for Mollicute contamination.

Biochemistry, 1993 Mar 16, 32(10), 2498 - 508
Solution structure of a complex between {N-MeCys3,N-MeCys7}TANDEM and {d(GATATC)}2; Addess KJ et al.; {N-MeCys3,N-MeCys7}TANDEM (CysMeTANDEM) is an octadepsipeptide quinoxaline antibiotic that binds specifically by bisintercalation to double-stranded DNA at NTAN sites {Addess, K . J., Gilbert, D . E., Olsen, R . K., & Feigon, J . (1992) Biochemistry 31, 339-350; Addess, K . J., Gilbert, D . E., & Feigon, J . (1992) in Structure and Function Volume 1: Nucleic Acids (Sarma, R . H., & Sarma, M . H., Eds.) pp 147-164, Adenine Press, Schenectady, NY} . We have determined the three-dimensional structure of a complex of CysMeTANDEM and the DNA hexamer {d(GATATC)}2 using two-dimensional 1H NMR derived NOE and dihedral bond angle constraints . This is the first structure of a TpA-specific quinoxaline antibiotic in complex with DNA . Initial structures of the complex were generated by metric matrix distance geometry followed by simulated annealing . Eight of these structures, refined by restrained molecular dynamics, energy minimization, and NOE-based relaxation matrix refinement, have an average pairwise RMSD of 1.11 A for all structures, calculated using all heavy atoms of the drug and the DNA except the terminal base pairs . CysMeTANDEM binds to and affects the structure of the DNA in a manner similar to that observed in complexes of the CpG-specific quinoxaline antibiotics triostin A and echinomycin with DNA {Ughetto, G., Wang, A . H.-J., Quigley, G . J., van der Marel, G . A., van Boom, J . H., & Rich, A . (1985) Nucleic Acids Res . 13, 2305-2323; Wang, A . H.-J., Ughetto G., Quigley, G . J., Hakoshima, T., van der Marel, G . A., van Boom, J . H., & Rich, A . (1984) Science 225, 1115-1121; Wang, A . H.-J., Ughetto, G., Quigley, G . J., & Rich, A . (1986) J . Biomol . Struct . Dyn . 4, 319-342} . The two quinoxaline rings bisintercalate on either side of the two central T.A base pairs and the peptide ring lies in the minor groove . The central A.T base pairs of the complex are underwound (average helical twist angle of approximately -10 degrees) and buckle inward by approximately 20 degrees . There are intermolecular hydrogen bonds between each of the Ala NH and the AN3 protons of the TpA binding site, analogous to those observed between Ala NH and GN3 in the crystal structures of the CpG-specific complexes of echinomycin and triostin A with DNA . However, the structure of the peptide ring of CysMeTANDEM in the complex differs from that of echinomycin and triostin A.(ABSTRACT TRUNCATED AT 400 WORDS)

CMAJ, 1993 Mar 15, 148(6), 961 - 5
Computed tomography before lumbar puncture in acute meningitis: a review of the risks and benefits; Archer BD; OBJECTIVE: To determine the indications, if any, for routine computed tomography (CT) of the brain before lumbar puncture in the management of acute meningitis . DATA SOURCES: Original research papers, reviews and editorials published in English from 1965 to 1991 were retrieved from MEDLINE . The bibliographies of these articles and of numerous standard texts were examined for pertinent references . A survey of local neurologists was conducted, and legal opinion was sought from the Canadian Medical Protective Association . DATA EXTRACTION: There were no studies directly assessing the risks of lumbar puncture in meningitis; however, all sources were culled for other pertinent information . RESULTS: No cases could be found of patients with acute meningitis deteriorating as a result of lumbar puncture . The neurologic consensus refuted the need for CT in typical acute meningitis . All sources stressed speedy lumbar puncture and the early institution of appropriate antibiotic therapy to minimize the severity of the illness and the risk of death . CONCLUSIONS: (a) There is no evidence to recommend CT of the brain before lumbar puncture in acute meningitis unless the patient shows atypical features, (b) for patients with papilledema the risks associated with lumbar puncture are 10 to 20 times lower than the risks associated with acute bacterial meningitis alone, (c) CT may be necessary if there is no prompt response to therapy for meningitis or if complications are suspected, (d) the inability to visualize the optic fundi because of cataracts or senile miosis is not an indication for CT and (e) there are no Canadian legal precedents suggesting liability if physicians fail to perform CT in cases of meningitis.

Somat Cell Mol Genet, 1993 Mar, 19(2), 161 - 9
New vector for transfer of yeast artificial chromosomes to mammalian cells; Markie D et al.; A modification vector has been constructed to facilitate the transfer of yeast artificial chromosomes (YACs) to mammalian cells in culture by targeting a dominant selectable marker (G418 resistance) to the right arm of pYAC4 clones . The ADE2 gene is used for yeast selection with consequent disruption of the URA3 gene, allowing direct modification of YACs within the common host strain AB1380, and providing a simple test for correct targeting . This vector has been tested by modification of a 550-kb YAC containing part of the human MHC class II region and transfer to CHO cells by protoplast fusion . Analysis of 15 independent G418-resistant CHO lines obtained following fusion suggests the majority contain a complete YAC with moderate amplification in some lines.

Enferm Infecc Microbiol Clin, 1993 Mar, 11(3), 139 - 42
{The western immunoblotting technique in atypical situations of Rickettsia conorii infection . Presentation of 2 cases}; Herrero JI et al.; BACKGROUND: During the last few years the application of Western immunoblotting in the study of human infection by Rickettsia conorii has led to the development of a new method of serologic diagnosis of the Mediterranean exanthematous fever . METHODS: The pattern of reactivity of serum samples sequentially obtained in the course of infection versus R . conorii antigens (Malish 7 strain) purified in discontinued density gradient and separated by SDS-PAGE was analyzed by Western immunoblotting . RESULTS: The presence of typical profiles of rickettsial infection similar to those observed in the common forms of presentation of the Mediterranean exanthematous fever was demonstrated in a case of accidental infection transmitted via aerosol and followed by an incomplete clinical picture after the early administration of specific antibiotic therapy and in a patient with signs and symptoms characteristic of Mediterranean exanthematous fever in whom the results of indirect immunofluorescence tests were repeatedly negative . CONCLUSIONS: Western immunoblotting may be a specially useful technique as a complementary procedure in the laboratory to guide in the diagnosis of Mediterranean exanthematous fever in special situations.

Rev Esp Enferm Dig, 1993 Mar, 83(3), 209 - 12
{Hepatic actinomycosis}; Gonzalez Sanchez JA et al.; We present a case of primary liver actinomycosis in a patient who was operated on for a duodenal ulcus seven years before . A gastrectomy was performed . His gallbladder was also removed two years before . After the surgical treatment, followed by antibiotic and chemotherapeutic treatment, with the result of a pretended success, the patient developed a liver pyogenic abscess and portal hypertension . Authors emphasise the seriousness of the illness as well as its rarity even with an accurate treatment.

Bildgebung, 1993 Mar, 60(1), 35 - 8
Pyogenic hepatic abscess: long resolution time despite adequate therapy; Gross M et al.; A 50-year-old male patient with a pyogenic hepatic abscess was successfully treated with an antibiotic regimen and percutaneous drainage of the abscess . Although this treatment was successful, it took more than 3 months for the abscess cavity to be completely resolved . A slow resolution of hepatic abscesses is therefore no evidence for the ineffectiveness of treatment.

Scand J Prim Health Care, 1993 Mar, 11(1), 38 - 43
Frequent attenders in general practice: a study from Slovenia; Svab I et al.; To compare frequent with infrequent attenders at GPs' surgeries in a rural area in Slovenia with respect to morbidity, type of contact with the GP, referral pattern and the prescriptions given, a random sample of 623 records from a population-based register was analysed retrospectively . The frequent attenders had a higher proportion of contacts for malignant disease, mental disorder, and gastrointestinal disease . They also had a greater probability for a "superficial contact", were more likely to be referred to a specialist, were less likely to receive a psychotropic drug, and were more likely to receive a prescription for an antibiotic . We conclude that there are differences in morbidity between the two groups . The high referring pattern and the high proportion of "superficial contacts" of the frequent attenders may reflect poor doctor/patient relationship of this group.

Nippon Kyobu Geka Gakkai Zasshi, 1993 Mar, 41(3), 417 - 20
{Surgical treatment with aortic valve homograft harvested from heart transplant recipients or donors}; Shin H et al.; From March 1988 to November 1991, 24 patients underwent aortic valve replacement or aortic root replacement with an aortic homograft harvested from a heart transplant recipient or donor that was not suitable for heart transplantation . Those patients were followed from 2 to 34 months (mean 12.6 months) . The mean age was 44 years (range 19 to 77 years) . The main lesion was aortic stenosis in 8 patients, aortic regurgitation in eight, mixed lesion in eight, annulo-aortic ectasia in two, active prosthetic valve endocarditis in two, and recurrent LVOTO in one . Cardiac status before operation was NYHA class II in one patient, III in nineteen, IV in four . Aortic valve replacement was performed in 17 patients, and aortic root replacement in seven . There was no early or late death . No structural deterioration was found . Surgical technical error resulted in moderate aortic regurgitation in one patient and mild paravalvular leak in another patient immediately after operation . All patients except one were not given anticoagulants postoperatively, but the entire group was free from thromboembolism . All patients returned to NYHA class I . Most homografts in this series were cryopreserved without antibiotic sterilization immediately after harvest, but homograft valve endocarditis did not occur . The results in this series suggested that homografts from heart transplant recipients or donors were encouraging, but more long-term follow-up was required to be determined whether homografts from heart transplant recipients without antibiotic sterilization were superior to homografts prepared in ordinary manner.

J Antibiot (Tokyo), 1993 Mar, 46(3), 367 - 73
Terpestacin, a new syncytium formation inhibitor from Arthrinium sp; Oka M et al.; Terpestacin, a new antibiotic which inhibits syncytium formation, was isolated from Arthrinium sp . FA1744 (ATCC 74132) . The structure of terpestacin was elucidated as a bicyclic sesterterpene on the basis of spectroscopic data and chemical derivatization.

J Infect, 1993 Mar, 26(2), 127 - 32
Candidaemia: risk factors in patients with cystic fibrosis who have totally implantable venous access systems; Horn CK et al.; Patients with cystic fibrosis who have totally implantable venous access devices often have other consequences of their multi-system disease which predispose them to catheter-associated systemic infection . We describe four episodes of fungaemia in three patients . Each case presented with persistent fever during an acute respiratory exacerbation . The four episodes were successfully treated, but removal of the venous access device was necessary in each case . Identified risk factors for systemic fungal injection were: combinations of a severe background respiratory deficiency; an acute respiratory exacerbation; malnutrition; repeated and frequent broad spectrum antibiotic therapy; parenteral nutrition; and diabetes mellitus . Unexplained fever in high risk patients with cystic fibrosis who have indwelling venous access systems should be treated empirically with antifungal agents while awaiting blood culture results . If fungaemia is confirmed the venous access device must be removed . Daily prophylactic fluconazole may prevent recurrences.

Acta Chir Belg, 1993 Mar-Apr, 93(2), 67 - 9
Pulmonary actinomycosis . Case report; Dossche K et al.; Pulmonary actinomycosis . Case report . Pulmonary actinomycosis is a rare infectious disease . The major difficulty is mainly the diagnosis . A high dose of suspicion is required in each intrathoracic process showing malignant behaviour, despite benign histology . Especially if the process extends through normal tissue planes, actinomycosis should be suspected . The therapy of choice should consist in high dose of antibiotics for several months, occasionally followed by surgery . Often though, surgery is the first treatment because of the unability to differentiate the lesion from malignant tumor . Surgery should always be followed by long term antibiotic therapy.

Br Poult Sci, 1993 Mar, 34(1), 161 - 6
Effect of pyridoxine on the distribution of chloramphenicol and its residues in the chicken; Atef M et al.; 1 . Chickens were given either a single dose of chloramphenicol (50 mg/kg body weight per os) or a dose of chloramphenicol together with pyridoxine (25 mg/kg per os) given 1 h before or 4 h afterwards . 2 . Concentrations of chloramphenicol were determined in samples of serum and the rates of distribution and elimination extrapolated . Concentrations of chloramphenicol in muscle, liver and kidney were also determined . 3 . Serum concentrations of chloramphenicol were lower in chickens given both pyridoxine and chloramphenicol compared with those given only chloramphenicol . 4 . Differences were most pronounced during the post-absorptive phase . The rates of disappearance of chloramphenicol residues from tissues were enhanced by pyridoxine . 5 . The biological half life of chloramphenicol and area under the concentration-time curve were both reduced by the concurrent administration of pyridoxine . 6 . Availability of pyridoxine may be a rate limiting factor in the biotransformation of xenobiotics, though its indiscriminate use could cause failure of antibiotic therapy.

Pharm Res, 1993 Mar, 10(3), 400 - 4
Peptide carrier-mediated transport in intestinal brush border membrane vesicles of rats and rabbits: cephradine uptake and inhibition; Yuasa H et al.; The uptake kinetics of cephradine, an amino-beta-lactam antibiotic, were studied in rat and rabbit intestinal brush border membrane vesicles preparations using both the Ca2+ and the Mg2+ methods of preparation, in the presence of an inward proton gradient . The Ca2+ method demonstrated greater uptake of cephradine in intestinal brush border vesicles prepared from both rat and rabbit and was used for these studies . The transport was observed to be of Michaelis-Menten carrier-mediated type with a passive transport component . The kinetic parameters obtained were as follows: for rat and rabbit, respectively, Km, 1.6 and 1.9 mM; Jmax', 1.7 and 20.7 nmol/mg/min; Pc' (= Jmax'/Km), 1.1 and 10.9 microL/mg/min; and Pm', 0.4 and 0.8 microL/mg/min . The kinetic parameters for the rat vesicles are consistent with those from our previous perfusion study using a conversion factor of 0.71 cm2/mg protein . The rabbit vesicles exhibited a similar Michaelis constant and a 10-fold larger maximal transport velocity, suggesting a quantitative advantage for the study of carrier-mediated transport in the rabbit compared to rat vesicles from the intestine . Cephradine uptake was inhibited by phenylpropionylproline, a proline derivative, and enalapril, an ACE inhibitor, which do not have an alpha-amino group, as well as dipeptides, tripeptides, and amino-beta-lactam antibiotics in both rat and rabbit vesicles . These results support the suggestion that they share the same peptide carrier pathway for oral absorption and that the vesicles may be a useful tool in developing orally effective peptide-type drugs.

Infect Dis Clin North Am, 1993 Mar, 7(1), 37 - 51
Pharmacokinetic and pharmacodynamic aspects of therapy of experimental endocarditis; Carbon C et al.; Bacterial endocarditis is difficult to cure because of poor penetration of antibiotics into infected vegetations, altered metabolic state of bacteria within the lesion, and absence of adequate host-defense cellular response, that could cooperate with antibiotic action . Two main aspects are discussed for their effect on human therapy: (1) the kinetics of antibiotic diffusion into vegetations, with a special reference to the data obtained with autoradiography, and (2) the specificity of some pharmacodynamic aspects of antibiotics in endocarditis, including the clinical consequences of these two parameters on antibiotic dosing regimens and length of therapy.

J Hand Surg {Am}, 1993 Mar, 18(2), 194 - 7
Tension band arthrodesis of small joints in the hand; Stern PJ et al.; Two-hundred three patients underwent 290 tension band arthrodeses of the metacarpophalangeal and proximal interphalangeal joints of the hand . Nine patients (3%) failed to achieve bony union, four had painless pseudarthroses, and one patient had a small finger amputation . Twenty-five fusions (9%) required hardware removal . There were 10 superficial infections (all responded to oral antibiotic therapy), and three fusions were malrotated . Tension band arthrodesis is our choice for fusion of the metacarpophalangeal and proximal interphalangeal joints . It is reliable and provides stable fixation, pins do not protrude, and external splinting is unnecessary in the cooperative patient.

Clin Nucl Med, 1993 Mar, 18(3), 197 - 202
Evaluation of postoperative osteomyelitis of the sternum comparing CT and dual Tc-99m MDP bone and In-111 WBC SPECT; Bessette PR et al.; This article reports on a retrospective study of 32 patients who underwent CT and combined Tc-99m MDP and in-111 WBC SPECT between 1988 and 1991 for post-operative sternal osteomyelitis . Of these 32 patients, 7 patients (Group 1) underwent evaluation for possible sternal osteomyelitis due to persistent fevers, leukocytosis, or changes in the sternal incision; 12 patients (Group 2) had surgically proven osteomyelitis, and in 13 patients (Group 3) there was definite clinical evidence of sternal wound infection (however, surgical specimens of the sternum were not submitted) . There was considerable overlap between the CT findings in the soft tissues adjacent to the sternum in Group 1 and Group 2 patients . Severe demineralization was seen in two patients, and erosion of the sternum was seen in five patients with proven osteomyelitis . Combined Tc-99m MDP bone and in-111 WBC SPECT was positive for osteomyelitis in 11 of 12 patients in Group 2 . One patient with osteomyelitis had negative scintigraphy; however, this patient had a four-week course of IV antibiotic therapy prior to the study . All seven patients in Group 1 had negative SPECT scans and were treated successfully with oral antibiotics and minimal soft tissue debridement . Three patients in Group 3 had negative SPECT scans and were treated successfully with antibiotics and limited debridement . Ten patients with positive SPECT scans were treated with a combination of antibiotics and aggressive surgical intervention . In conclusion, CT findings in the soft tissues offer little specificity in distinguishing soft tissue inflammation from osteomyelitis of the sternum.(ABSTRACT TRUNCATED AT 250 WORDS)

Eur J Clin Nutr, 1993 Mar, 47(3), 174 - 91
The Kingston Project . III . The effects of high energy supplement and metronidazole on malnourished children rehabilitated in the community: morbidity and growth; Heikens GT et al.; In the Kingston Project malnourished children referred from public health clinics to a metabolic ward were treated at home using community health aides within the existing health service . We have previously provided anthropometric results showing significantly greater gains in weight and length for groups given a high energy supplement (3.31 MJ daily) for 3 months during treatment, and greatest gains for a group treated with metronidazole at the beginning of supplementation {Heikens et al., Eur . J . Clin . Nutr . 43, 145-160 (1989); 47, 160-173 (1993)} . We now present findings on morbidity and relate these to the separate interventions and to growth velocities . Although referral was solely on nutritional criteria, 65% of the sample were found to have additional illnesses at enrollment . During the study period (6 months) upper respiratory tract infections (URTI) were the commonest illness in all groups; there were significantly more gastroenteric infections in the group given the supplement, but not the antibiotic, treatment; the children who received only the standard health service care were ill more often and for longer periods than children in the other groups . Diarrhoea, fever and dysentery prevalences were all found to relate significantly to weight velocity, and although prevalences differed between treatment groups, the detrimental effect on velocity was similar whichever the groupPIP: In 1985-86 in Jamaica, a community-based health care project randomly allocated 163 malnourished children (mean age 1.2 years) from the slums of greater Kingston to 1 of 4 groups: group visited at home by community health aides within the existing health service (HC); group receiving HC and a high energy supplement (HES) (790 kcal); group receiving HC and a 5-day course of abroad spectrum antibiotic, metronidazole, for 3 months; or group receiving HC, HES, and metronidazole . The researchers wanted to examine morbidity and to relate morbidity to the various interventions and growth velocity . 65% of all the children at enrollment suffered from an illness in addition to malnutrition, especially upper respiratory tract infections (URTIs) . URTIs continued to be the most frequent illness in all groups throughout the 6-month study . Children receiving HES had significantly more gastroenteric infections, but this was not the case for those receiving metronidazole . Children receiving just HC suffered from morbidity more frequently and were ill for longer durations than the children in the other 3 groups (at 0-3 months, 96.2% vs . 74.3-92.9%, p .04; at 4-6 months, 96.2% vs . 74.3-82.1%, p .06; and 4-7 days, 46.2% vs . 2.9-5.7%, p .0001) . Significant covariates of weight velocity were fever (p .0001), mucoid diarrhea (p .0001), and dysentery (p .0003) . These illnesses had the same effect on weight velocity, even though their prevalences were different between treatment groups . The effect of cold and cough on weight velocity approached significance (p .052 and P .094, respectively) . These findings showed that some illnesses greatly slowed weight gain in malnourished children . They also indicated that antibiotic use reduced the risk of gastroenteric infections in malnourished children, these infections having the most detrimental effect on weight gain .

Qual Assur Health Care, 1993 Mar, 5(1), 67 - 73
An instrument to assess acute respiratory infection case management in Egypt; Harrison LH et al.; To develop an instrument to measure the quality of acute respiratory infection (ARI) case management among Egyptian children . Methods: A baseline survey of all health facilities in a single district, using a multi-data source instrument . Data sources included providers, caretakers, patient records and observation of patient care . Main Results: Physicians did not count the respiratory rate and check for subcostal retraction . Eighty-seven per cent of children who did not require antibiotics received them . Of five children who required antibiotics, four (80%) were prescribed an oral regimen . Three of these should have been admitted to a hospital but were not . Antibiotics were available at the facilities an estimated 7.9 months per year . Oxygen for inpatient treatment was available in one of two hospitals . Conclusions: This instrument was useful for comprehensively evaluating facility capability to provide quality case management . Deficiencies were identified but were not unexpected in a baseline survey . The Egypt ARI program has the potential to have a substantial impact on how children with ARI are diagnosed and treated in health facilitiesPIP: An instrument consisting of 10 questionnaires was developed to assess the ability of facilities to implement acute respiratory infection (ARI) case management guidelines . Data sources included interviews with physicians, nurses and area pharmacists; observation of patient care; review of patient records and an inventory of supplies . All 21 outpatient and two inpatient health facilities as well as 20 of 28 pharmacies in the district were included in the study . Of 93 child assessments observed, physicians asked the age for only 38 (41%) . No child was questioned on ability to drink or experience of seizures . In addition, no physician checked for stridor, wheeze or chest indrawing, or counted the respiratory rate . 81 of 93 (87%) children with ARI were prescribed antibiotics . Among the 88 children assessed as not requiring antibiotics, 77 (88%) received them . Five children (2 pneumonia, 2 severe pneumonia, and 1 very severe disease) were determined to require antibiotics; four were prescribed an oral regimen . Of the four children that both required antibiotics and received them, three should have been admitted to the hospital for parenteral antibiotics, but were not . A variety of prescribed antibiotics were used among the 77 children . 27 (35%) children received two or three antibiotics without specifying the dose, frequency or duration on the prescription . Only two physicians mentioned the antibiotic dosage schedule for home care to the mother . Physicians at each of the outpatient facilities estimated the mean availability of antibiotics at 7.9 +or- 3.9 months . Three facilities (14%) had ampicillin suspension, none had amoxicillin and two (9%) had cotrimoxazole for the treatment of outpatient pneumonia . 19 (90%) had aspirin . Oxygen was available for inpatient care for children with pneumonia in one of the two hospitals, no nebulizers were available for treatment of wheezing, and disposable syringes were available in only one hospital . Parenteral bronchodilators were available in both, oral in neither . This instrument was useful for comprehensively evaluating facility capability to provide quality case management in the Egyptian ARI program .

Surg Endosc, 1993 Mar-Apr, 7(2), 88 - 9
Laparoscopic repair of small bowel and colon . A report of 26 cases; Nezhat C et al.; This is a retrospective review of laparoscopic repair for enterotomies created during therapeutic or diagnostic laparoscopy in 26 women . All patients had mechanical and antibiotic bowel preparation preoperatively . The indication for operative laparoscopy was endometriosis (18), severe abdominal adhesive disease (7), and adhesions with Crohn's disease (1) . Enterotomies were secondary either to CO2 laser vaporization or excision of endometriosis and/or lysis of adhesions (23) and trocar insertion (3) . The injuries included small-bowel enterotomies (9), colotomies (4), and rectotomies (13) . No clinical complications related to enterotomy repair were noted . Twenty-three patients were discharged 1 day after surgery; one was discharged on postoperative day 2; and two were discharged on postoperative day 3 . We concluded that small- and large-bowel enterotomies can be repaired safely via the laparoscope with minimum morbidity in patients with prepared bowel.

Drug Saf, 1993 Mar, 8(3), 213 - 24
Adverse haematological complications of anticancer drugs . Clinical presentation, management and avoidance; Bodensteiner DC et al.; Haematological complications frequently occur in patients treated with chemotherapeutic agents . The degree and duration of bone marrow suppression depends upon the type of agent used . In general, agents that are cell cycle phase-specific tend to cause early myelosuppression with rapid marrow recovery, as compared to the non-phase-specific agents . Host factors including patient age, nutritional status, marrow infiltration or damage, and hepatic and renal function also affect haemotoxicity . Chemotherapeutic agents suppress proliferating or potentially proliferating precursors of neutrophils, platelets and red blood cells to the same extent . With most drugs, neutropenia tends to be dose limiting and more severe than thrombocytopenia . Because of the longer life span of red blood cells, severe anaemia is rarely a problem . The management of myelosuppression is multifaceted, and consists of aggressive antibiotic therapy to treat or prevent the infections that occur with neutropenia, as well as red blood cell and platelet transfusion support to correct anaemia and prevent bleeding . The role of the haemopoietic growth factors including erythropoietin, colony-stimulating factors and the interleukins is currently being evaluated in clinical trials . Haemolytic uraemic syndrome, haemolytic anaemia and therapy-induced myelodysplasia and/or acute leukaemia are uncommon and potentially severe complications of chemotherapeutic agents.

Ann Thorac Surg, 1993 Mar, 55(3), 672 - 6
Completion pneumonectomy and thoracoplasty for bronchopleural fistula and fungal empyema; Utley JR; Achieving sterilization of the postpneumonectomy space and bronchial healing may be difficult when active granulomatous infection of the pleural space and lung parenchyma is present at the time of operation . Three patients with chronic bronchopleural fistula, fungal empyema, and fungal cavities of the remaining ipsilateral lobe were managed with one-stage completion pneumonectomy and modified eight-rib thoracoplasty . Two patients had infection with Aspergillus fumigatis and 1 patient had Coccidioides immitis . Two patients had received mediastinal radiation after prior upper lobectomy for carcinoma of the lung . Two patients were having massive hemoptysis at the time of pneumonectomy . Eight-rib thoracoplasty with suturing of the intercostal muscles to the bronchial stump was performed on all patients . In 2 patients a mass closure of hilar vessels and bronchus was used because of inability to individually close the vessels and bronchus due to ligneous scarring of the hilum . Antibiotic and antifungal irrigations into the operative area were used postoperatively . Chest tubes were left in place 6 to 8 weeks . All wounds healed primarily . Patients were alive without recurrent local infection or tumor at follow-up 3 to 13 years postoperatively.

South Med J, 1993 Mar, 86(3), 311 - 7
Diabetic wound healing and limb salvage in an outpatient wound care program; Keyser JE; Healing wounds and preventing amputations in diabetic patients is a challenge . Baptist Hospital in Nashville, Tennessee, developed an outpatient Wound Care Center program to treat patients with chronic wounds . This comprehensive program includes wound assessment, vascular studies, revascularization, antibiotic therapy, wound debridement, a topical growth factor solution of platelet-derived wound healing factors, protection devices, and patient education . A retrospective study of wound healing and limb salvage was conducted on 54 diabetic patients with 86 wounds . Average previous wound duration was 8 months . Amputation had previously been recommended for 15 limbs . Healing occurred in 88% of the wounds in an average of 15.8 weeks . Ninety-three percent of the limbs for which amputation had been recommended were salvaged . Healing efficacy and amputation reduction have been demonstrated in this program.

Gastroenterol Clin North Am, 1993 Mar, 22(1), 105 - 15
Diagnosis of Helicobacter pylori infection; Brown KE et al.; In conclusion, H . pylori infection can be detected by a variety of methods . The simplest, least expensive noninvasive method is serologic testing . Unfortunately, positive serology can only presume current infection . Urea breath testing is also noninvasive and is positive only in the setting of current infection; it is more expensive than serology and results in low-level radiation exposure when 14C urea is used . Endoscopy with biopsy is invasive and relatively expensive; however, it is readily available and is frequently performed in the evaluation of the symptomatic individual . In such cases, rapid urease testing of biopsy material is simple and less expensive than histologic examination . Histology allows simultaneous evaluation of tissue injury and infection . Frequently, routine hematoxylin-and-eosin staining is sufficient to permit identification of the bacteria; when the results of this stain are inconclusive, special stains such as Giemsa or Warthin-Starry can be used . Finally, direct culture of the organism from gastric tissue is tedious and expensive; therefore, it should generally be reserved for protocol settings or for selected patients in whom antibiotic-resistant organisms are suspected.

Int J Dermatol, 1993 Mar, 32(3), 218 - 20
Amoxicillin and clavulanic acid in the treatment of actinomycetoma; Gomez A et al.; BACKGROUND . Mycetoma is a relatively frequent disease in tropical countries . Drugs commonly used need a long period of treatment, and some cases are resistant to these drugs, especially those with bone or visceral involvement . The combination of amoxicillin-clavulanic acid has shown effectiveness against strains of Nocardia brasiliensis in vitro . METHODS . We have used this combination in two cases of mycetoma caused by N . brasiliensis, both with bone involvement and resistance to the drugs usually used . A dose of three tablets a day for 5 to 6 months was given (each tablet contains 500 mg of amoxicillin and 125 mg of clavulanic acid) . RESULTS . Clinical and mycologic amelioration was observed in the two cases after completing the treatment . There were no side effects or relapses after 3 to 6 months of follow-up after treatment . CONCLUSIONS . We propose this antibiotic as a new option for the treatment of some special cases of actinomycetoma with bone or visceral involvement or resistance to the drugs commonly used in this disease.

Scand J Immunol, 1993 Mar, 37(3), 369 - 76
Intrathecal synthesis of anti-Borrelia burgdorferi antibodies in neuroborreliosis: a study with special emphasis on oligoclonal IgM antibody bands; Wang ZY et al.; Pre- and post-treatment (up to 3-26 months after antibiotic therapy) humoral immune responses were investigated in five neuroborreliosis patients . Anti-Borrelia (B.) burgdorferi IgG and IgM antibodies in CSF and serum were quantitated by capture ELISA . Agarose gel isoelectric focusing (AIF) and protein blotting were used to detect oligoclonal IgG and IgM bands as well as oligoclonal anti-B . burgdorferi IgG and IgM antibodies . These latter components were visualized by transfer to antigen-coated membranes (immunoblot) and immunoenzymatic staining . By ELISA, intrathecal anti-B . burgdorferi IgG and IgM antibody synthesis was detected in all initial specimens and continued 3-26 months after antibiotic therapy in four and three cases, respectively . AIF with protein blotting showed oligoclonal bands of total IgG as well as total IgM in the initial CSF specimens of all patients and persistence of such components occurred in four and five cases, respectively . By AIF and immunoblot, oligoclonal anti-B . burgdorferi IgG and IgM antibody bands could be detected in the CSF of every patient . IgG antibody bands were present in all initial CSF samples . The first specimen of one patient was negative for IgM antibody bands but such components appeared 3 weeks later . Oligoclonal CSF anti-B . burgdorferi IgG antibody components persisted over the entire follow-up periods in all but one case where they disappeared 6 weeks after treatment . The oligoclonal IgM antibodies in CSF vanished in two cases (after being present up to 4 and 11 months after antibiotic therapy) while they persisted over the entire (3-6 months after antibiotic therapy) follow-up periods in three cases . The specificity of the IgM antibody immunoblot technique was corroborated by control experiments, including antibody absorption studies and use of 41 kDa flagellar antigen.

Transfusion, 1993 Mar, 33(3), 243 - 8
Plasma exchange does not improve survival in a canine model of human septic shock; Natanson C et al.; Whether plasma exchange would improve survival in antibiotic-treated canines with septic shock was investigated . Escherichia coli O86H8 (1.4 X 10(10)) was surgically implanted as an intraperitoneal clot in 18 two-year-old (10-12 kg) purpose-bred beagles . Beginning 4 hours after surgery, all animals received cefoxitin and gentamicin for 5 days . Three treatment groups were defined: 1) a no apheresis, or control group, (n = 6); 2) a sham apheresis group, whose whole blood plasma was removed, separated, and then transfused (n = 6); and 3) a plasma exchange group from whom blood and plasma were removed and separated, to whom the blood was returned, and in whom infected plasma was replaced with compatible fresh-frozen canine plasma (n = 6) . For the sham apheresis and plasma exchange groups, a commercial blood cell processor was used to separate 1.5 blood volumes of plasma at 5 and 24 hours after surgery . Serial radionuclide left ventricular ejection fractions and femoral and pulmonary arterial catheter hemodynamics were measured simultaneously in awake animals . All six animals in the plasma exchange group died . In both the sham and control groups, only one of six animals survived . Survival times were ordered (median in hours) (control {372 h} > sham apheresis {48 h} > plasma exchange {24 h} {p < 0.038}) . Decreases in mean cardiac index and mean arterial pressure (from before apheresis to after) at 5 to 7 hours after surgery were ordered (plasma exchange > sham apheresis > control; p < 0.03) . Thus, plasma exchange in this controlled trial of septic shock was associated with decreased survival and worsened hemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)

Int J Dev Biol, 1993 Mar, 37(1), 117 - 24
High efficiency DNA transfection in murine embryonal carcinoma cells: expression of pSV3neo in wild type and retinoid-resistant cell lines; Purpus EJ et al.; Embryonal carcinoma cells provide a convenient and manipulable model for early embryogenesis . Like their counterparts in the inner cell mass, they are refractory to infection by several viruses . In their undifferentiated state, EC cells are resistant to calcium-phosphate DNA transfection . This resistance is compounded by the inefficient and/or actively inhibited expression of transfected genes driven by certain viral promoters . Conversely, the differentiated derivatives do not share this resistance and readily express virally promoted genes . We have developed a protocol for liposome-mediated gene transfer in EC cells and compared its efficiency in wild-type and retinoid-resistant variants . Dose response experiments with the EC cell line PCC4.aza1R showed a linear progression of colony formation when transfected with the vector pSV3neo and selected in medium containing the antibiotic G418 . DNA concentrations of 10 micrograms per plate resulted in over 600 colonies per 10(6) cells . This represents a 20-30 fold greater efficiency over reported values for calcium-phosphate methods even though the neomycin resistance gene in this plasmid is driven by the SV40 viral promoter . The retinoid-resistant line PCC4(RA)-2 also showed enhanced transformation by lipofection, but despite the relatively high efficiency, colony formation rate for the differentiation-defective cells was less than 25% of the parental line . Our data indicates that there is no absolute block of genes driven by the SV40 early region promoter in murine EC cells if enough DNA is introduced to titrate out negative regulatory factors.

Endocrinology, 1993 Mar, 132(3), 959 - 67
The use of genetic manipulation of MA-10 Leydig tumor cells to demonstrate the role of mitochondrial proteins in the acute regulation of steroidogenesis; Stocco DM et al.; The true rate-limiting step in steroidogenesis is the delivery of cholesterol to the inner mitochondrial membrane where it is converted to pregnenolone by the cholesterol side-chain cleavage complex . This process is known to require de novo protein synthesis . We have previously described the synthesis of a family of 37, 32, and 30 kilodalton mitochondrial proteins in response to hormone stimulation in MA-10 mouse Leydig tumor cells and have proposed that these proteins are involved in the acute regulation of steroidogenesis . In this study we have used two subclones of MA-10 cells to further demonstrate the correlation between the quantity of these proteins and the production of steroids in response to hormone treatment . One of these, designated MA-10(K3), has been transfected with a mutant gene of the type 1 regulatory subunit of the cAMP-dependent protein kinase under the control of a metallothionein promoter, whereas the other, designated MA-10(P+29), is a constitutive overproducer of a cAMP-phosphodiesterase (PDE) . MA-10 parent cells designated (P), produce large amounts of progesterone in response to LH, human CG, and (Bu)2cAMP . The MA-10(K3) cells, on the other hand, whereas significantly higher than controls, produce much less steroid than the parent cells in response to hormone stimulation . Activation of the mutant gene with Zn+2 results in yet a further decrease in the amount of steroid produced . The MA-10(P+29) cells display greatly reduced progesterone production when stimulated with LH, because of the presence of high amounts of PDE, but return to maximally stimulated levels when a PDE inhibitor is present . Quantitation of the synthesis of the mitochondrial proteins described above in MA-10(K3) cells in the presence and absence of Zn+2 and in MA-10(P+29) cells in the presence and absence of PDE inhibitor clearly demonstrate that the amount of the 30 kilodalton mitochondrial proteins present in these cells closely parallels that of progesterone production . The high degree of correlation between the appearance and quantity of these mitochondrial proteins and the production of steroids make them strong candidates for the putative proteins involved in acute regulation of steroidogenesis.

Am J Surg Pathol, 1993 Mar, 17(3), 231 - 8
Inflammatory pseudotumor of the liver . Report of four cases and review of the literature; Shek TW et al.; In this report, we describe four cases of inflammatory pseudotumor of the liver and review the literature of this disease entity . The age of our patients ranged from 31 to 35 years (mean, 33 years) . Two had fever, weight loss, and upper abdominal pain . The other had an incidental 1-cm nodule in the liver found during left hemihepatectomy for recurrent attacks of cholangitis . The preoperative clinical diagnoses in the former two cases were hepatocellular carcinoma . The patients had unremarkable recovery after resection . Grossly, the tumors showed a variegated appearance with areas of hemorrhage and necrosis and resembling hepatocellular carcinoma . Microscopically, the tumors were composed of a polyclonal population of reactive plasma cells and abundant plump spindle cells . The latter expressed vimentin but stained negatively for actin, desmin, and myosin . Ultrastructurally, these plump spindle cells showed features of fibroblastic differentiation . Forty-seven cases of inflammatory pseudotumor of the liver have been reported, 35 in males and 12 in females (male-to-female ratio of 2.9) . The patients had a wide age range (10 months to 83 years; mean, 37 years) . The most common symptoms were fever, upper abdominal pain and a space-occupying lesion in the liver . Surgical excision was curative . A few patients responded to antibiotic and steroid treatment . The recognition and distinction of this entity from hepatocellular carcinoma and other malignant tumors is particularly important in order to avoid unnecessary extensive surgery.

Bull Acad Natl Med, 1993 Mar, 177(3), 413 - 21; discussion 422-3
{Current view and outlook for cystic fibrosis therapy}; Navarro J; Cystic fibrosis therapy has obtained in the last few years substantial benefits optimizing nutritional antibiotic and ventilatory techniques . With the discovery of the gene and of CFTR protein pharmacological approach may be initiated: correction of transmembrane ionic exchanges, and of sputum rheology . Gene therapy represents the last development, but rises methodological and ethical problems even if representing an important hope . Pulmonary transplant is only indicated in severe forms of cystic fibrosis.

Southeast Asian J Trop Med Public Health, 1993 Mar, 24(1), 11 - 7
Immunoproliferative small intestinal disease (IPSID) in Thailand; Pramoolsinsap C et al.; Immunoproliferative small intestinal disease (IPSID) is prevalent in the Mediterranean region and in many Third World countries but is rare in Southeast Asia . Between 1980-1990, 4 cases of IPSID were admitted to Ramathibodi Hospital, Bangkok . Three were males and the mean age was 32 +/- 20.2 years . All patients presented with chronic diarrhea of 7 months to 6 years duration, and weight loss of 15 to 31 kg . All were malnourished, three cachectic, and one patient showed growth retardation . Intestinal parasites were found in all cases: two had multiple infections and three had uncommon protozoal infections (coccidium, cryptosporidium) . Barium radiographs revealed intestinal mucosal fold thickening with malabsorption pattern in all cases . Alpha chain IgA was detected in one patient . The remainder underwent exploratory laparotomy and the histological finding was of plasma lymphocytic infiltration of the small intestinal mucosa . All patients responded to oral tetracycline with complete remission occurring in one case . During the follow-up period, 3 cases had progressive retractable clinical courses but all died 2 to 5 years after the diagnosis . The causes of death in these patients were secondary bacterial infection (1 case), intestinal tuberculosis (1 case), fungal infection (1 case) and immunoblastic sarcoma in another case . The results of this study confirm the occurrence of IPSID in Thailand . IPSID responds to oral antibiotic therapy and complete remission may be achieved during the early reversible benign phase, thus an awareness of its occurrence is of clinical importance.

Ginekol Pol, 1993 Mar, 64(3), 165 - 6
{Pregnancy and labor in the patient with arteriovenous congenital fistula}; Florjanski J et al.; The paper presents a case of uncomplicated pregnancy in 26-years old primipara suffering from congenital arteriovenous fistula . The clinical picture of disease was manifested by presence of vaso-dilatations in lower and upper limbs and in the vulva, because of which the pregnancy was terminated by cesarean section . Puerperal and postoperative outcome was uncomplicated . In the puerperal period heparin and large-spectrum antibiotic therapy was administered . No cardiovascular or thromboembolic complications were observed . Authors are of opinion, that in face of menace, the pregnancy and labour in the women presenting arterio-vascular fistula have to be considered as situation of high obstetrical risk.

Minerva Gastroenterol Dietol, 1993 Mar, 39(1), 23 - 7
{Percutaneous endoscopic gastrostomy}; Finocchiaro E et al.; Surgical gastrostomies were first performed in the middle of the 19th century and modified during the following years, but the most important technical improvement was percutaneous endoscopic placement (PEG), in 1980 by Ponsky and Gauderer . This technique doesn't require anesthesia and it in possible also in patients with contraindications to surgical gastrostomy . The simple procedure involves a shorter hospitalization, lower risks and reduced costs . Many authors already reported the good results of this new technique, that can be performed on a day-hospital regimen as well . The main indications are head and neck cancers, neurologic diseases involving food intake capacity, cancer cachexia, obstruction of the GI tract when there is enough space for an endoscopic procedure . Every disease that can compromise food intake for a period longer than 60 days can find an indication in placing a percutaneous gastrostomy . The advantage for the patient is a much better psychological tolerance compared with a naso-gastric tube . Also the incidence of mechanical complications of a PEG is much lower . In our experience from October '90 to July '92 we followed 34 patients with PEG, 22 males and 12 females, with mean age of 69 years (range 41-88) . We used 9-French tube placed using the pull-method technique . All patients received antibiotic therapy for 5 days . About 12 hours after PEG placement all patients began using the gastrostomy, initially with the administration of electrolyte solutions and later with enteral polymeric formulas . The constant increase led all patients to a 1500 non protein calories daily intake in 3-4 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Eksp Klin Farmakol, 1993 Mar-Apr, 56(2), 39 - 42
{A combination of immunostimulants as a method for correcting secondary immunodeficiencies}; Alekhin EK et al.; The specific features of the action of combinations of immunostimulants (levamisole, prodigiozan, methyluracil) on a primary immune response to EB, GST and resistance to experimental infection have been studied . It has been shown that levamisole eliminates stimulation by methyluracil and prodigiozan of a primary immune response, lithium carbonate is also an antagonist of prodigiozan . Vitamin E increases the stimulating effect of prodigiozan rather than oxymethacil . The effect of vitamin A depends on the dose . Levamisole does not change the influence of prodigiozan and methyluracil on GST and, like prodigiozan, suppresses GST stimulated by lithium carbonate . The combination of prodigiozan and methyluracil to a large extent than the agent given alone increases resistance to an infection and efficiency of antibiotic therapy . The combination of methyluracil and levamisole increases only the effect of the antibiotic.

J Am Dent Assoc, 1993 Mar, 124(3), 116 - 8
Avoiding problems in patients with craniotubular bone disorders; Mintz SM et al.; Since osteomyelitis can occur concurrently with osteopetrosis, all craniotubular bone disorder patients should be treated carefully . We recommend preoperative antibiotic coverage and minimizing any excessive force to avoid the risk of osteomyelitis and jaw fractures when surgery is necessary.

Hum Exp Toxicol, 1993 Mar, 12(2), 123 - 5
Poisoning due to insect and scorpion stings/bites; Nhachi CF et al.; 1 . A retrospective study, 1980 to 1989 inclusive, of hospital admission cases due to insect and scorpion stings or bites was carried out in the six main central hospitals of Zimbabwe's four main cities . 2 . A total of 92 cases were recorded and analysed . This constituted 1.5% of all hospital admissions for poisoning which were analysed during that time . 3 . Of the 92 cases the highest number of victims were seen in the 2-to-5-year age group (29.3%), followed by the 6-to-10-year age group (23.9%) . In other age groups the incidence of poisoning was distributed approximately evenly with the 41 to 50 and the over 60-year age groups having the least number of victims, (2.2%) . 4 . The main groups of insects associated with poisoning were bees, 44.6%; wasps, 8.7%; and spiders 8.7% . A further 32.6% of the insect stings were not specified . Scorpion stings accounted for 5.4% of incidences . 5 . No fatalities occurred . 6 . Treatment consisted mainly of the administration of promethazine, as an antihistamine in 35% of the cases, steroids (16.5% of the cases), perhaps for their anti-allergic effects, and paracetamol, a mild analgesic, (14.7% of the cases) . Interestingly, 22.6% of the cases were given an antibiotic (14.1% of which were penicillins) . Adrenaline was administered in only 1.7% of the cases . 7 . The majority of the recorded cases, 49.4%, were hospitalized for at least a day and the average duration of hospitalization was 6.4 days.

Int J Gynaecol Obstet, 1993 Mar, 40(3), 227 - 33
Increased maternal morbidity after cesarean delivery before 28 weeks of gestation; Evans LC et al.; To test the hypothesis that there is increased maternal morbidity associated with cesarean section at very early gestational ages compared to cesarean section at term, a case-control study was performed . Eighty consecutive cases of cesarean section before 28 weeks of gestation were chronologically matched to 80 controls with cesareans at term . Compared to term controls, preterm cases were more frequently complicated by postpartum endomyometritis (32% vs . 9%, P < 0.001) and blood transfusion (14% vs . 1%, P < 0.01), resulting in a significantly longer postpartum stay and longer duration of antibiotic use . One or more major complications occurred in 45% of preterm cases versus 14% of controls (P < 0.001); two major complications occurred in 11% of cases versus 1% of controls (P < 0.05) . Some, but not all, of the higher risk for postpartum complications was attributable to pre-existing differences in risk factors for infection and hemorrhage between the two groups . We conclude that cesarean section before 28 weeks of gestation is associated with a high risk of postoperative complications and that patients should be counseled accordingly.

Arch Environ Health, 1993 Mar-Apr, 48(2), 89 - 93
Immunologic abnormalities in humans exposed to chlorpyrifos: preliminary observations; Thrasher JD et al.; Twelve individuals who were exposed to chlorpyrifos were studied 1-4.5 y following exposure to determine changes in the peripheral immune system . The subjects were found to have a high rate of atopy and antibiotic sensitivities, elevated CD26 cells (p < .01), and a higher rate of autoimmunity, compared with two control groups . Autoantibodies were directed toward smooth muscle, parietal cell, brush border, thyroid gland, myelin, and ANA . Chlorpyrifos exposure was implicated in the immunologic abnormalities reported . The immunologic changes were similar to those reported for other pesticides.

South Med J, 1993 Mar, 86(3), 350 - 5
Granulocyte colony-stimulating factor; Tabbara IA; Recombinant human granulocyte colony-stimulating factor (G-CSF) is a nonglycosylated protein produced in Escherichia coli using recombinant DNA technology . G-CSF was first defined in vitro as a relatively selective stimulator of pure granulocyte colonies from normal marrow and as a factor that induces differentiation of leukemic cell lines . Additional studies have shown that it has significant effects on primitive marrow stem cells as well as on the differentiated cells of the granulocyte-macrophage pathway enhancing phagocytosis, superoxide release, antibody-dependent cellular cytotoxicity, and migration of both neutrophils and monocytes . The most extensively studied clinical application of G-CSF has been in chemotherapy-induced myelosuppression, where it was shown to reduce the duration of severe neutropenia, the incidence of febrile neutropenic episodes, the overall duration of intravenous antibiotic therapy, and the length of hospitalization . G-CSF has also been shown to correct primary and acquired forms of neutropenia, to accelerate neutrophil recovery after bone marrow transplantation, and to mobilize stem cells in peripheral blood or hemopoietic rescue . G-CSF is well tolerated, mild to moderate bone pain being the most frequently reported adverse side effect . The clinical applications of G-CSF are likely to expand as more information emerges from continuing clinical trials.

Gene, 1993 Feb 28, 124(2), 173 - 81
Mutational analysis of the transforming and apoptosis suppression activities of the adenovirus E1B 175R protein; Subramanian T et al.; The role of the adenovirus-2 E1B 19-kDa (175R) T antigen in E1a-cooperative transformation was determined by cotransfection of plasmids expressing E1A or E1B 175R T antigens into primary rat kidney (BRK) cells . Transformed cells were selected by virtue of their resistance to the antibiotic Geneticin (G418) conferred by neo gene co-expression from plasmids coding for 175R . 175R cooperated efficiently with genomic E1a and specifically with the 289R protein coded by the 13S mRNA in the transformation of primary BRK cells . Mutational analysis of the 175R protein revealed that the N terminus and the C-terminal 30 amino acids are not essential for E1a-cooperative transformation . Several conserved sequences located in the middle of the 175R protein are essential for transformation . The effect of various mutants to suppress apoptosis (programmed cell death) induced by an anti-cancer agent, cisplatin, was examined in cells producing the E1A and E1B 175R proteins . Apoptosis was measured by flow cytometric analysis and indicates that the 175R protein efficiently prevents cisplatin-induced apoptosis . This suggests that the 175R function involved in transformation segregates with its ability to suppress cisplatin-induced apoptosis.

FEBS Lett, 1993 Feb 22, 318(1), 88 - 90
Inhibition of protein prenylation by patulin; Miura S et al.; The antibiotic patulin was found to inhibit protein prenylation in mouse FM3A cells . Thus, the agent reduced incorporation of {3H}mevalonate into proteins by 50% at a concentration of 7 microM . In a cell-free assay, patulin inhibited rat brain farnesyl:protein transferase, one of the enzymes responsible for protein prenylation . The inhibition was 50% at a concentration of 290 microM.

Biochemistry, 1993 Feb 16, 32(6), 1488 - 91
EPR spectroscopic investigation of the lability of oxygen in activated bleomycin: implications for the mechanism of bleomycin-mediated DNA degradation; Sam JW et al.; Bleomycin (BLM), an antitumor antibiotic, is capable of degrading DNA through the formation of activated BLM, an activated iron-oxygen complex of the drug with a unique EPR spectrum . A recent study {Rabow, L . E., McGall, G . H., Stubbe, J., & Kozarich, J . W . (1990) J . Am . Chem . Soc . 112, 3203-3208} has cast doubt onto the "hydroxyl-radical-rebound" mechanism, commonly accepted for cytochrome P-450 {McMurray, T.J., & Groves, J.T . (1985) in Cytochrome P-450: Structure, Mechanism, and Biochemistry (Ortiz de Montellano, P., Ed.) pp 1-28, Plenum, New York} and proposed for the anaerobic nucleic base release reaction of BLM, by demonstrating that the source of oxygen in the products of this reaction is solvent molecules and not molecular oxygen . A central issue in this debate is whether the oxygen of activated BLM is available for exchange with that of solvent . The lability of oxygen in activated BLM has been investigated through the use of EPR spectroscopy to measure the exchange of 17O (I = 5/2) between activated BLM and solvent . Evidence for the lack of oxygen exchange between activated BLM and solvent is presented, and the implications of this result for the mechanism of BLM-mediated DNA degradation are discussed.

Tijdschr Diergeneeskd, 1993 Feb 15, 118(4), 116 - 9
{Dermatitis digitalis? Considerations in the evaluation of an intensive therapy}; Suichies HR et al.; A piece of clinical research was performed to illustrate the recovery process of Digital Dermatitis on a chronically contaminated cattle farm . The combined effect of intensive individual treatment and an antibiotic foot-bath was examined . In addition to the classical condition recognized as Mortellaro's disease we found an aspecific form of Digital Dermatitis which failed to respond adequately to the currently recommended therapy.

J Biol Chem, 1993 Feb 15, 268(5), 3420 - 9
Induction of Chinese hamster HSP27 gene expression in mouse cells confers resistance to heat shock . HSP27 stabilization of the microfilament organization; Lavoie JN et al.; Heat shock induces in cells the development of a transient state of thermotolerance thought to result from the induction of heat shock proteins . To assess directly whether a transient overexpression of one of these proteins, HSP27, can contribute to increased cellular resistance, mouse NIH/3T3 cells were cotransfected with a plasmid containing the Chinese hamster HSP27 gene under the control of the metallothionein promoter and a plasmid containing the neo gene . Stable transfectant cell lines were selected for resistance to the antibiotic G418 . Analyses of several stable transfectant cell lines indicated that expression of Chinese hamster HSP27 could be selectively induced by exposure to 3 microM CdCl2, a concentration that had no effect on the induction of the endogenous heat shock proteins (HSP) . In clone 15, the level of HSP27 increased steadily during the first day of exposure to CdCl2, from a concentration of 1 microgram/mg of total protein to 7 micrograms/mg . After withdrawal of CdCl2, the level of HSP27 returned to normal within the next 5 days . Accumulation of the Chinese hamster HSP27 was accompanied by a progressive development of thermoresistance that attained a level approaching heat shock-induced thermotolerance . After CdCl2 removal, thermal resistance and HSP27 decayed in a coordinated manner . In control cells transfected with the neo gene only, increased thermoresistance was not induced by 3 microM CdCl2; in these cells, an exposure to 20 microM CdCl2 was required to induce a level of thermoresistance comparable to that induced by 3 microM CdCl2 in clone 15 . Elevated expression of HSP27 was accompanied by an increased stability of stress fibers during hyperthermia . The protein also partially prevented actin depolymerization during acute exposure to cytochalasin D and reduced cytotoxicity and growth inhibition of chronic exposures to the drug . The results indicated that accumulation of HSP27, as it occurs after a mild heat shock or other inducing treatments, is sufficient for acquisition of thermotolerance that may result in part from a stabilization of actin filaments.

Pharmacoeconomics, 1993 Mar, 3(3), 220 - 7
Economics of home intravenous services; Thickson ND; Home care has become a more attractive option as economic constraints are placed on the total healthcare system . Over the past 25 years, home intravenous service programmes have developed simultaneously with the development of more reliable means of providing intravenous therapy in the home . Reports have been published on a variety of home intravenous programmes including antibiotic therapy, parenteral nutrition support, chemotherapy, blood product administration and pain control . This review examines the economics of home intravenous programmes, including such direct cost items as drugs, medical supplies and equipment, personnel, hospital room, inventory control, and carrying inventory . Indirect costs, assessed as loss of wages, are also analysed . Cost savings have been reported ranging from 18 to 75% for intravenous antibiotic programmes and 60 to 76% for parenteral nutrition programmes . Earlier reports concentrated on analysis of savings derived from comparison of direct costs only, but recent studies have explored a more comprehensive fiscal analysis.

Pharmacoeconomics, 1993 Mar, 3(3), 205 - 19
The cost of asthma: can it be reduced?
Mellis CM, Peat JK, Woolcock AJ.
Asthma is a major public health problem in developed countries, where it consumes a large and increasing share of scarce health resources . Ideally, medical management should be both optimal in terms of improving the patient's quality of life, and cost-effective for society . At present, there is very little information relating to costs and economic efficiency of current asthma management . Although the true total cost of asthma is unknown, current estimates suggest it is high . The main value of recent total cost estimates is that they identify the most expensive areas of asthma costs, and ideally, formal cost-effectiveness analyses should be concentrated on these areas . Asthma is still under- or inappropriately diagnosed, and undertreated . Several national and international consensus plans for the optimal management of asthma in children and adults have been published . If these inadequacies in asthma management were corrected, using current treatment recommendations, the overall cost of asthma from both the community and patient perspective should fall . The situation requires increased use of preventative medications {sodium cromoglycate (cromolyn sodium) or inhaled corticosteroids}, more widespread use of written crisis plans, more proactive medical consultations (rather than reactive or urgent consultations), further expansion of asthma education programmes, and further education of medical practitioners about the optimum management of both long term asthma and the acute exacerbation of asthma in the patient's home, the doctor's office, the hospital emergency room and the hospital inpatient setting . The increased costs associated with these measures would be more than offset by reduced expenditure on bronchodilator drugs, less widespread use of nebulisers at home and in hospitals, reduced antibiotic usage, reduced need for expensive emergency medical care and particularly reduced utilisation of hospital resources . To ensure that resources are being directed into the most cost-effective areas of asthma care, clinical trials of asthma should include utilisation of healthcare resources as an outcome measure, and estimates of the costs of the treatment under study . In addition, since the intangible cost (quality of life) is one of the most important effects of treatment from the patient's perspective, this should be more widely used as an outcome measure in clinical trials . Ultimately, prevention of asthma is the long term goal . If the hypothesis that sensitisation to house dust mite in early infancy is a major contributor to the subsequent development of asthma, then prevention may require drastic and expensive changes to current housing.

Schweiz Rundsch Med Prax, 1993 Feb 2, 82(5), 149 - 53
{Travelers' diarrhea 1992}; von Overbeck J et al.; Traveller's diarrhea is a common problem without consequences for a healthy patient . Correct information, especially about hygiene habits during the trip, is most important . The prescription of an anti-diarrheal medication is usually justified but should not be given without proper information about the possible dangers . A prophylactic antibiotherapy is very seldom necessary . Antibiotic self-medication can be a pragmatic alternative . Patients at risk must be identified before the trip, and appropriate measures are essential . Once the patient is back home again diarrhea will subside spontaneously and both patient and physician should therefore know to be patient.

Biochemistry, 1993 Feb 2, 32(4), 1059 - 66
Concerted DNA recognition and novel site-specific alkylation by duocarmycin A with distamycin A; Yamamoto K et al.; Duocarmycin A, a novel antitumor antibiotic, has a reactive cyclopropane ring, which has been reported to alkylate adenine at the 3' end of sequences of three or more consecutive A or T in DNA {Boger, D . L., et al . (1990) J . Am . Chem . Soc . 112, 8961-8971} . In order to study the DNA recognition, the reaction of DNA with duocarmycin A was performed in the presence of DNA ligands . Distamycin A, berenil, Hoechst 33258, and 4',6-diamidino-2-phenylindole (DAPI), which are minor-groove binders with affinity to A.T-rich sequences, were used . DNA-sequencing experiments showed that treatment of DNA with duocarmycin A plus distamycin A caused alkylation of guanine residues in G.C-rich sequences, which are not alkylated by duocarmycin A alone . Guanine alkylation by duocarmycin A was not observed with berenil, Hoechst 33258, or DAPI . HPLC product analysis showed that duocarmycin A reacted with a double-helical DNA octamer d(CCCCGGGG)2 in the presence of distamycin A to produce duocarmycin A-guanine adduct, while duocarmycin A alone did not react with the octamer . Chromomycin A3, which binds as a Mg(II)-coordinated dimer to G.C-rich sequences in the minor groove, inhibited the guanine alkylation by duocarmycin A in the presence of distamycin A . A footprinting experiment showed that there is a distamycin A-binding site close to the alkylated guanine residue . These results suggest that two different molecules, duocarmycin A and distamycin A, cooperatively recognize DNA sequences including consecutive G.C base pairs resulting in alkylation at the novel guanine sites . The cooperative drug recognition can be designated as "concerted DNA recognition".

J Chir (Paris), 1993 Feb, 130(2), 79 - 86
{Quality control of care in a surgical department . Experience of the Fondation Berganié}; Avril A et al.; Activity in a surgical department can be evaluated quantitatively, but is should also be assessed qualitatively . One way to control the quality of care is to determine as accurately as possible the incidence of pre- peri- and post-operative complications and to analyse these date in a critical comparative study . This was accomplished in the surgical department of the Fondation Bergonie, Bordeaux during three test periods over the last five years--March 1987 (127 patients), June-July 1989 (276 patients), and June 1991 (147 patients) . Results of this analysis cannot validly be compared with those of other departments with different patient recruitment and activity functions . However, this study within a department with regular, homogeneous activity did demonstrate, over a period of several years, a clear reduction in operative mortality, essentially by improved control of infectious complications by the extensive use of prophylactic antibiotic therapy for all surgery with a septic risk or for debilitated patients . Results also demonstrated the low cost effectiveness of routine pre-operative exploratory examinations.

Wei Sheng Wu Xue Bao, 1993 Feb, 33(1), 13 - 21
{Taxonomic study on strain 1254 and its mutant 113}; Zhang Y et al.; The mutant 113 was obtained from a natural non-antibiotic producing Streptomyces sp . 1254 by UV irradiation . It produced a group of novel anthracycline compounds designated mutactimycins . Strain 1254 was placed in the genus Streptomyces on the basis of its morphological characteristics and chemical properties of cells . According to Williams's numerical taxonomical data based on more than 50 physiological tests of a total of 375 type strains, the strain 1254 is considered to be more resemble to S . omiyaensis in the cluster of S . exfoliatus . The whole cell hydrolysate of mutant 113 contains DL-DAP, arabinose, galactose and rhamnose, but its cell envelope does not contain mycolic acids . Comparing with all genera of cell chemotype IV without mycolic acids and with Sacchrothrix which contains taxonomically significant rhamnose, mutant 113 shows differences with them respectively on FA composition or MK and PL patterns . The conclusion we can draw now is that mutant 113 doesn't belong to the same genus Streptomyces as its parent strain 1254 does, and is more close to the genus Sacchrothris.

Biochem Mol Biol Int, 1993 Feb, 29(2), 339 - 47
The generation of stable CHO cell lines expressing very high levels of complement C5A receptors and subsequent modulation of binding affinity for C5A; Pease JE et al.; A single gene fragment encoding for the C5a receptor was produced by reverse transcription of mRNA isolated from differentiated U937 cells and subsequently amplified by means of the polymerase chain reaction . This fragment was introduced into the mammalian expression vector pEE6hCMV.neo and used to transfect a CHO cell line constitutively expressing a viral transactivator protein . Binding characteristics identical to the native neutrophil receptor were observed . A combination of antibiotic selection and cell sorting using anti-C5a receptor antiserum were then used to generate stable cell lines expressing up to 1.2 x 10(7) functional C5a receptors/cell with a lower affinity for C5a . It is postulated that this modulation of receptor affinity is dependent on coupling to native G-proteins in the host cells.

J Post Anesth Nurs, 1993 Feb, 8(1), 21 - 5
Intermediate-term intravenous therapy: a pilot study; Myers JS et al.; Midline catheters provide an effective alternative for intermediate-term intravenous therapy . During a pilot study, 27 midline catheters were inserted in patients who met specific criteria . The insertion success rate was 64%, and the infection rate was 7% . One mechanical phlebitis occurred, but it was resolved by the application of warm, moist heat . One chemical phlebitis occurred during antibiotic therapy . The average dwell time was 8.7 days, and the longest dwell time was 49 days . Patients reported the catheters to be very comfortable and did not experience limitations in mobility.

Hum Reprod, 1993 Feb, 8(2), 244 - 6
Cervical leukocytosis and abnormal post-coital test: a diagnostic and therapeutic approach; Matilsky M et al.; Inflammatory processes and cell-mediated immunological reactions in the cervix and vagina have been implicated as causal factors in some cases of infertility . This investigation examined whether cervical Papanicolaou (PAP) smears in combination with post-coital tests could reveal infertile patients with asymptomatic cervical leukocytosis . Women (n = 56) attending a hospital-based community infertility clinic were subjected to post-coital tests and simultaneous preparation of cervical PAP smears . Those women (n = 18) with both abnormal post-coital tests and asymptomatic cervical leukocytosis, based on abnormally high numbers of leukocytes in the PAP smear, were randomly divided into two groups . One group (n = 10) received antibiotic therapy and the other (n = 8) received no therapy . In the treated group six women became pregnant within 3 months after treatment; none of the eight untreated patients became pregnant within the same period . These results suggest that cervical PAP smears, in cases with abnormal post-coital tests, are useful in detecting couples whose infertility may be due to simple, undetected, asymptomatic bacterial infections.

J Clin Pharm Ther, 1993 Feb, 18(1), 45 - 8
Drug-induced thrombocytosis; Frye JL et al.; Thrombocytosis is generally defined as platelet counts greater than 400,000/mm3 . Thrombocytosis can be either primary or secondary . Adrenalin was one of the first drugs noticed to cause platelet elevations, probably due to demargination of platelets in the pulmonary vasculature . Vinca alkaloids have the most convincing data to show that they can induce thrombocytosis through their thrombocyte-stimulating properties . Miconazole has been implicated in causing thrombocytosis and has a documented case validated by drug rechallenge . Iron, predictably, can cause a transient thrombocytosis . The beta-lactam antibiotic data are very difficult to interpret due to the possibility of an acute-phase reaction in an infected patient being the cause of the thrombocytosis.

Isr J Med Sci, 1993 Feb-Mar, 29(2-3), 89 - 93
A centralized intravenous additive system in an Israeli government hospital; Lustig A; The pharmacy of the Barzilai Medical Center initiated a centralized method for preparation of the sterile i.v . antibiotic dilutions used in the hospital that has proven to be beneficial to the patient and cost-effective to the hospital . With this system, all small-volume bags containing antibiotic dilutions--constituting 58.5% of all the sterile dilutions used in the Medical Center--are prepared centrally in the pharmacy of the hospital rather than in the various wards . Since the method requires professional supervision, it leads to an improvement in the quality of patient care . The solutions are prepared under sterile conditions, and care is taken to ensure their stability as well as to prevent incompatibilities between the antibiotics and the diluents . In addition to the direct benefit to the patient there has been a saving of approximately NIS 200,000/year resulting from the decrease in the number of minibags, syringes and needles, personnel time and wastage.

Hear Res, 1993 Feb, 65(1-2), 164 - 74
Hair cell regeneration in the bullfrog vestibular otolith organs following aminoglycoside toxicity; Baird RA et al.; Adult bullfrog were given single intraotic injections of the aminoglycoside antibiotic gentamicin sulfate and sacrificed at postinjection times ranging from 0.5 to 9 days . The saccular and utricular maculae of normal and injected animals were examined in wholemount and cross-section . Intraotic 200 microM gentamicin concentrations resulted in the uniform destruction of the hair bundles and, at later times, the cell bodies of saccular hair cells . In the utriculus, striolar hair cells were selectively damaged while extrastriolar hair cells were relatively unaffected . Regenerating hair cells, identified in sectioned material by their small cell bodies and short, well-formed hair bundles, were seen in the saccular and utricular maculae as early as 24-48 h postinjection . Immature versions of mature hair cell types in both otolith organs were recognized by the presence or absence of a bulbed kinocilia and the relative lengths of their kinocilia and longest stereocilia . Utricular hair cell types with kinocilia longer than their longest stereocilia were observed at earlier than hair cell types with shorter kinocilia . In the sacculus, the hair bundles of gentamicin-treated animals, even at 9 days postinjection, were significantly smaller than those of normal animals . The hair bundles of utricular hair cells, on the other hand, reached full maturity within the same time period.

Int J Pept Protein Res, 1993 Feb, 41(2), 102 - 17
Partial synthesis of five new analogues of the peptido-lactone Virginiamycine S1, modified in the fifth and/or sixth position ({Xxx5}-VS1 with Xxx = Ala, Asp, Asn and Lys and {Ala5,Gly6}-VS1); Moerman MC et al.; We achieved the reconstruction of VS1-analogues containing a substitute for the fifth residue, gamma-oxo-Pip (Pip = pipecolic acid), starting from VS1-pentapeptide (VS5P;3) the latter being prepared by a two-step degradation process of the native antibiotic VS1 (1a) . Protecting groups during the procedure were chosen in order to realize a minimal number of steps . Most of these gave excellent yields, including final cyclization between the fourth and fifth residue . In total, four analogues were synthesized with Ala, Asp, Asn and Lys (1b) replacing gamma-oxo-Pip . Among these, {Lys5(Tfa salt)}-VS1 is water-soluble, which is an important characteristic for eventual application of VS1 as a pharmaceutical agent . In the proposed reaction sequence, we made sure that residues 4 (MePhe) and 6 (Phg) became partially epimerised . We therefore obtained each time after cyclization a total of four epimers that have been separated by preparative TLC . The chiral identity of the final residues was realized by GC (Chirasil Val-III) on the total hydrolysates.

Br J Haematol, 1993 Feb, 83(2), 270 - 5
Carrageenan-induced activation of human platelets is dependent on the phospholipase C pathway; Hatmi M et al.; Stimulation of washed human platelets by the pro-inflammatory polysaccharide carrageenan is accompanied by shape change, aggregation and release of granule contents and unaccompanied by thromboxane A2 synthesis . Carrageenan triggers platelet activation through a prostaglandin synthetase-independent mechanism . The phospholipase A2 (PLA2) inhibitor, p-bromophenacyl bromide suppresses platelet responses to carrageenan (Vargaftig et al, 1980) probably by mechanism(s) other than those which involve PLA2 activity . Exposure of platelets to carrageenan (2-25 micrograms/ml) induced inositol phosphate formation in a time- and concentration-dependent manner, the level of inositol phosphate formation correlating with the intensity of aggregation . Neomycin, an aminoglycoside antibiotic which inhibits the phospholipase C-mediated phosphatidylinositol 4,5-bisphosphate breakdown, suppressed both platelet activation and inositol phosphate formation . Inhibition was concentration-dependent with an IC50 value of about 180 microM . Platelet-activating factor (PAF) is not responsible for carrageenan-induced platelet activation and inositol phosphate formation, since exposure of platelets to carrageenan (25 micrograms/ml) in the presence of compound WEB 2086 (100 microM), a PAF antagonist, failed to inhibit carrageenan responses . However, compound Ro 19-3704, a structurally related antagonist of PAF reported to be also an inhibitor of phospholipases A2 and C, inhibited concentration-dependently (0.1-10 microM) aggregation and ATP release induced by carrageenan (25 micrograms/ml) . These findings indicate that carrageenan activates human platelets through a phospholipase C-dependent mechanism and show that neomycin, at low concentrations, can be a selective inhibitor of phospholipase C-mediated PIP2-breakdown.

An Med Interna, 1993 Feb, 10(2), 75 - 6
{Common variable immunodeficiency and polyarthritis: a case report}; Gonzalez-Gay MA et al.; We describe a man with common variable immunodeficiency and polyarthritis . He had suffered several infections, including septic arthritis . For this reason we commenced treatment with antibiotics without obtaining a good response . Three weeks' later, and after knowing that the results of all the cultures were negative, we discontinued the antibiotic therapy and started treatment with indomethacin . A dramatic response was rapidly observed . We feel that an arthritis in a patient with a history of previous infections should alert us to the diagnostic possibility of primary antibody deficiency.

Curr Eye Res, 1993 Feb, 12(2), 197 - 203
Treatment of autoimmune uveoretinitis in the rat with rapamycin, an inhibitor of lymphocyte growth factor signal transduction; Roberge FG et al.; Rapamycin (RAPA) is a macrolide antibiotic with unique immunosuppressive properties . RAPA inhibits T-cell function by interfering with IL-2 and IL-4 signal transduction . It does not prevent IL-2 production or IL-2R expression . The efficacy of RAPA in the treatment of autoimmune diseases was evaluated using the experimental autoimmune uveoretinitis (EAU) model . EAU was actively induced in Lewis rats by immunization with S-antigen in Hunter's adjuvant . RAPA and control vehicle were administered by continuous intravenous infusion over a 14 day period by miniosmotic pump . RAPA treatment initiated on the day of immunization or 7 days later was found to efficiently inhibit EAU induction . The minimal effective dose was 0.1 mg/kg/d . EAU inhibition was correlated with reduced number of cells in the immunization site draining lymph nodes, as well as with a shift and lowering of the peak of the lymphocyte proliferative response curve . The anti-S-antigen antibody response was delayed by 3 days under RAPA treatment and the serum levels lowered in a dose dependent manner . An initial body weight loss was observed during the first week of drug administration, but there was a normal weight gain afterward.

Neth J Med, 1993 Feb, 42(1-2), 69 - 72
A rare cause of a hepatic abscess: diverticulitis of the ileum; Posthuma EF et al.; A 41-year-old man with a hepatic abscess due to diverticulitis of the ileum is presented . Drainage of the hepatic abscess and antibiotic therapy resulted in complete recovery . The literature on small bowel diverticulitis and its complications is reviewed . Hepatic abscess is a very rare complication . To our knowledge this is the second case to be described in the literature.

Am J Obstet Gynecol, 1993 Feb, 168(2), 667 - 73
Pharmacokinetics of ampicillin and sulbactam in pregnancy; Chamberlain A et al.; OBJECTIVE: This study evaluated the effects pregnancy had on pharmacokinetic parameters of ampicillin and sulbactam . STUDY DESIGN: Twenty-two women undergoing cesarean section for obstetric indications were randomly assigned to receive a single intraoperative dose of either 1 gm of ampicillin intravenously or 1 gm of ampicillin plus 0.5 gm of sulbactam intravenously after umbilical cord clamping . Blood was drawn from an indwelling intravenous catheter at 15, 30, 45, 60, 120, 240, and 360 minutes after infusion of the antibiotic for determination of serum ampicillin and/or sulbactam levels . Pharmacokinetic parameters were determined by fitting data (serum concentrations versus time) to a single-compartment model that provided elimination rate constants, beta-intercept (calculated concentration at 0 minutes), area under the time-versus-concentration curve, half-life of the drug, total body clearance, and volume of distribution . After the examination 6 weeks post partum, each subject was given an additional dose of the drug she had received during cesarean section, and a second pharmacokinetic study was performed and compared with the previous results . RESULTS: Pregnancy significantly increased the elimination rate constant, decreased the area under the drug-versus-time curve, shortened the serum half-life, and increased the total body clearance in comparison with these parameters in the nonpregnant state for ampicillin . Sulbactam kinetics were similarly affected, although these changes failed to attain statistical significance . CONCLUSION: Because pregnancy is associated with more rapid elimination of beta-lactam drugs, physicians treating infections in pregnant or newly parturient women should consider using shorter intervals between antibiotic doses when a range of dosage intervals is under consideration.

J Clin Periodontol, 1993 Feb, 20(2), 88 - 95
Topical application of tetracycline-HCl in human periodontitis; Christersson LA et al.; Previous in vitro studies have suggested that tetracycline-HCl (TTC-HCl) is adsorbed and actively released from root dentin . The aim of the current study was to evaluate the binding to and release of TTC-HCl from human root dentin surfaces in vivo, and to evaluate the clinical utility of TTC-HCl irrigation as an adjunct to scaling and root planing . Experiment I utilized two contralateral mandibular single-rooted teeth which were examined in four adults with severe generalized periodontitis . One tooth in each patient was carefully scaled and root planed, under local anesthesia, and the other used as an unscaled control . Each subgingival root surface was irrigated for 5 min with an aqueous TTC-HCl solution at a concentration of 100 mg/ml . Gingival crevicular fluid samples were collected on paper strips for the next three weeks . The TTC-HCl concentrations in each sample were determined by the inhibition zone of B . cereus cultured on agar plates . The TTC-HCl concentrations in gingival crevicular fluid collected 15 min after irrigation were 3100 +/- 670 micrograms/ml from the scaled lesions and 4700 +/- 1300 micrograms/ml from the unscaled root surfaces . The antibiotic concentrations decreased logarithmically over the next 7 days; 1500 +/- 270 micrograms/ml and 1100 +/- 330 micrograms/ml at 2 h, 880 +/- 350 micrograms/ml and 1300 +/- 360 micrograms/ml at 6 h and 19 +/- 5 micrograms/ml and 31 +/- 26 micrograms/ml at 1 week for scaled and unscaled root surfaces, respectively . Results for week two and three indicated an average of over 8 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Geriatrics, 1993 Feb, 48(2), 43 - 50
Community-acquired pneumonia: diagnosis and therapy of older adults; Brown RB; Community-acquired pneumonia is a common problem in older adults and is associated with substantial morbidity and mortality . Diagnosis may be difficult, because signs of respiratory involvement may be absent and either constitutional or CNS symptoms may predominate . Elevated respiratory rate may be an important diagnostic clue . No specific pathogen is identified, and therefore empiric therapy is indicated in up to 50% of patients . The decision to hospitalize those over age 65 for parenteral antibiotic therapy is individualized . After 3 to 5 days of i.v . antibiotics oral therapy can be initiated upon favorable clinical response in the absence of proven metastatic foci of infection . Lack of response should prompt reassessment . Immunization with both the pneumococcal and viral influenza vaccines is indicated for most older patients . Discontinuation of smoking should also be encouraged.

Chest, 1993 Feb, 103(2), 641 - 2
Cardiac tamponade due to Nocardia asteroides; Clenney TL et al.; Pericarditis with hemodynamic compromise is a rare manifestation of infection with Nocardia asteroides . To our knowledge, only six cases have been reported previously . In contrast to other cases of pericardial disease due to Nocardia, culture of the pericardial fluid in our case was negative while culture of pericardial tissue led to the diagnosis . Surgical intervention and appropriate antibiotic therapy are essential in the treatment of Nocardia pericarditis.

Ann Thorac Surg, 1993 Feb, 55(2), 413 - 9
Preimplantation alteration of adenine nucleotides in cryopreserved heart valves; Domkowski PW et al.; To assess the initial metabolic phase of cellular injury from cardiac valve processing, high-energy phosphate concentrations were analyzed in valve leaflets subsequent to critical processing steps . Using a porcine model, valves were processed in a manner identical to human homografts, with 58 randomly assigned to five groups representing distinct preparation phases . Group I (controls) sustained 40 minutes of warm ischemia concluded by liquid nitrogen immersion . Remaining groups similarly endured 40 minutes of ischemia, but were subsequently prepared according to stepwise design: II, warm ischemia + 24 hours of 4 degrees C ischemia; III, warm ischemia + 24 hours of 4 degrees C antibiotic disinfection; IV, warm ischemia + 24 hours at 4 degrees C (without antibiotics) + cryopreservation (-1 degrees C/min cryoprotected freezing); and V, warm ischemia+disinfection+cryopreservation . At each regimen's conclusion leaflet extracts were assayed by high-performance liquid chromatography for high-energy adenine nucleotides (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate) and catabolites . A 47% and 86% decrease in cellular adenosine triphosphate level was observed in group III and group V leaflets, respectively . The level of total adenine nucleotides was maintained up to cryopreservation; thereafter a 74% decrease was noted . Catabolite analysis confirmed incomplete degradation of adenine nucleotides indicating cellular metabolic resilience throughout standard homograft preparation in valves previously exposed to 40 minutes of warm ischemia.

What Is Rhizobia?, What Is Protein?, What Is Bioremediation?, What Is Dna?, What Is Environmental Microbiology?, a, Microorganism, s, Microbes, o, Microbe, s, Bacteria, e, Bacteriology, n, Campylobacter, a, Gram negative, r, Microbial, o, Flavobacterium, o, Salmonella typhimurium, n, S. cerevisiae, i, Yeasts, r, Escherichia coli, o, Streptococci, c, Yeasts, r, Pseudomonas, n, Thermophiles, s, Yeasts, a, Prokaryotes, o, Bacteria, e, Streptococcal, i, Kluyveromyces, r, Escherichia coli, c, Streptomycin, i, Escherichia coli, s, Biodegradation

Scientific Publications - Work Done by Microbiology Reader Bioscreen C
Agricultural Microbiology Anaerobic Microbiology Antimicrobial Susceptibility Artificial Atmosphere Bioassay of Antibiotics Biofilm Microbiology Bioreactor Technology Biotechnology Cell Biology Clinical Microbiology Environmental Microbiology Experiments with Yeast	Fermentation Food Microbiology Functional Genomics Gene Technology Growth Media Development Growth Rate and Lag Time Industrial Microbiology Medical/Pharmaceutical Field Microbiological Assay Microbiological Research Microbiology of Cosmetics go to a specific theme...	Military Microbiology Molecular Microbiology Mutagenicity and Genotoxicity Oral Microbiology Patents Postantibiotic Studies Soil Microbiology Spore Microbiology Veterinary Microbiology Waste/Wastewater Treatment Water Microbiology Wine Microbiology

� 2005 Transgalactic Ltd (manufacturer of Bioscreen C software) | Privacy Statement | P.O. Box 1393, 00101 Helsinki, Finland, phone: +358 9 85172920, fax: +358 9 8749481, e-mail: microbiology@bionewsonline.com

Last modified: May 25, 2005