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