Blood, 1996 Nov 15, 88(10), 3675 - 85 Hematopoietic growth factors as adjuncts to the treatment of acute myeloid leukemia; Schiffer CA; A number of randomized trials have recently been completed evaluating the effect of hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor) as adjuncts to the treatment of patients with acute myeloid leukemia . Most studies used the growth factors to decrease the duration of neutropenia with the hope of reducing infectious morbidity and mortality . The results of these trials are generally quite consistent . Virtually all trials showed a modest reduction in the duration of severe neutropenia with a variable effect on the incidence of severe infections, antibiotic usage, and the duration of hospitalization . There was no consistent benefit in terms of improvements in complete response rate, complete response duration, or overall survival . However, it is important that there does not appear to be an increase in the incidence of drug-resistant leukemia in trials in which the growth factor was begun after completion of the chemotherapy . Other trials administered growth factors either before or simultaneous with the chemotherapy in an attempt to enhance chemosensitivity and decrease drug resistance . None of these trials, whether conducted as part of initial induction therapy or in relapse, showed improvements in response rate or survival . Lastly, some anecdotal reports have suggested that occasional patients who receive growth factors as the only therapy for overt leukemia can achieve remission, possibly through a differentiating effect of the growth factor . However, there are very few such reports, and growth factor use in this situation is potentially dangerous and should be performed only in the context of a clinical trial . In summary, there appears to be no role at this time for priming of leukemia cells by growth factors to enhance the effect of chemotherapy, and more in vitro studies should be performed before further clinical trials of this approach . It is clear that growth factors administered after induction and possibly consolidation chemotherapy can shorten the duration of neutropenia, without a significant effect on treatment outcome . It is as yet unclear whether the use of growth factors in this fashion is cost effective. J Biol Chem, 1996 Nov 8, 271(45), 28057 - 63 Processing of colicin V-1, a secretable marker protein of a bacterial ATP binding cassette export system, requires membrane integrity, energy, and cytosolic factors; Zhong X et al.; Extracellular secretion of the peptide antibiotic colicin V (ColV) in Escherichia coli is mediated by a dedicated exporter system consisting of host TolC protein and the products of two specific genes, cvaA and cvaB, the latter being a member of the ATP binding cassette (ABC) superfamily . An amino-terminal export signal of ColV is specific for the CvaA-CvaB-TolC exporter and is processed concomitant with secretion . In this study, we attempt to characterize this processing with a secretable marker protein, ColV-1, using a newly developed in vitro assay . Processing is found to be dependent on both CvaA-CvaB transporters and the TolC protein and to require membrane integrity . An additional cytoplasmic soluble factor(s) is also necessary for the processing . Although the sequence of the cleavage site suggests it could be a substrate, ColV-1 cannot be processed in vitro by the purified leader peptidase I . Moreover, ColV-1 processing is inhibited by antipain and N-ethylmaleimide . Furthermore, the processing requires energy in the form of nucleotide hydrolysis . These results indicate that the processing of ColV-1 is specific and more complex than expected, requiring the CvaA-CvaB-TolC transporter intact in the membrane, energy, and cytosolic factors for rapid cleavage. BMJ, 1996 Nov 2, 313(7065), 1119 - 23 Risk factors for lower respiratory complications of rhinovirus infections in elderly people living in the community: prospective cohort study; Nicholson KG et al.; OBJECTIVE: To assess the role of rhinoviruses in elderly people living in the community . DESIGN: Prospective community based surveillance of elderly people, without intervention . Subjects were telephoned weekly to identify symptomatic upper respiratory tract infections . Symptoms and impact of illnesses were monitored, and specimens were collected for diagnostic serology and human rhinovirus polymerase chain reaction . SETTING: Leicestershire, England . SUBJECTS: 533 subjects aged 60 to 90 . MAIN OUTCOME MEASURES: Symptoms, restriction of activity, medical consultations, and antibiotic use during 96 rhinovirus infections . Adjusted odds ratios for lower respiratory syndromes with respect to smoking and health status . RESULTS: A viral cause was established in 211 (43%) of 497 respiratory illnesses; rhinoviruses were identified in 121 (24%) and as single pathogens in 107 . The median duration of the first or only rhinovirus infection in the 96 people with 107 rhinovirus infections was 16 days; 18 of the 96 patients were confined to bed and 25 were unable to cope with routine household activities . Overall, 60 patients with rhinovirus infections had lower respiratory tract syndromes; 41 patients consulted their doctor, 31 of them (76%) receiving antibiotics . One patient died . Logistic regression analysis showed that chronic medical conditions increased the estimated probability of lower respiratory rhinovirus illness by 40% (95% confidence interval 17% to 68%) and smoking by 47% (14% to 90%) . There were almost six times as many symptomatic rhinovirus infections as influenza A and B infections . CONCLUSIONS: Rhinoviruses are an important cause of debility and lower respiratory illness among elderly people in the community . Chronic ill health and smoking increase the likelihood of lower respiratory complications from such infections . The overall burden of rhinovirus infections in elderly people may approach that of influenza. Rev Hosp Clin Fac Med Sao Paulo, 1996 Nov-Dec, 51(6), 253 - 7 {Lyme disease in Mato Grosso do Sul State, Brazil: report of three clinical cases, including the first of Lyme meningitis in Brazil}; Costa IP et al.; The authors report the occurrence of the first three clinical cases of Lyme disease in Mato Grosso do Sul State, including the first case of Lyme meningitis in Brazil . These were identified by clinical and laboratorial criteria . Anti-Borrelia burgdorferi antibody search was carried out through ELISA and Western Blotting techniques, the former providing identification of IgG class antibodies alone, in one only of those cases . Through Immunoblotting, the following features were found in serum: 5 IgG and 2 IgM bands for the first case; 7 IgG and 2 IgM bands for the second; and 5 IgG and 6 IgM bands for the third . In the latter, presence fo specific antibodies was searched in liquor, due to lymphomonocitary meningitis occurrence, and one IgM band was detected . After antibiotic therapy, all patients exhibited significant clinical and laboratorial improvement in their conditions along with symptom regression to the present moment. Ann Periodontol, 1996 Nov, 1(1), 256 - 321 Periodontal implications: medically compromised patients; Mealey BL; The presence of systemic disease in patients requiring periodontal therapy creates challenges for management . Alteration of treatment plans, with emphasis on physician consultation and preventive periodontal care, is frequently needed to minimize the impact of periodontal disease on the systemic condition . Conversely, detection and treatment of systemic disorders may impact upon the status of the periodontium and the success of periodontal therapy . The goal of holistic patient management is facilitated by a free flow of information between the patients and their medical and dental health care providers. Chirurgia (Bucur), 1996 Nov-Dec, 45(6), 311 - 2 {Single-layer digestive sutures (manual and mechanical) . Observations after 20 years}; Neckell (Necula) T et al.; The experimental study (on rabbits and dogs) and the clinical study followed one layer sutures performed with eversing or inversing separate stitches, with ordinary or nontraumatic needles or mechanical sutures . Sutures were performed on oesophagus, stomach, small and large bowel . Excepting the oeso-jejunal or ileo-colic anastomosis (termino-lateral), the majority of sutures were used to accomplish termino-terminal anastomosis . The results were improved using high-quality materials (resistant, nonhygroscopical, resorbable threads), on correctly evacuated digestive tract, under antibiotic protection, avoiding perioperative hemodynamic fluctuations, with a complex postoperative care and a gradual renutrition. Mikrobiologiia, 1996 Nov-Dec, 65(6), 745 - 8 {Protective effect of a tetracycline-sensitive strain of Escherichia coli on the growth of a tetracyclic-resistant strain in the presence of tetracycline in a coculture}; Nikolaev IuA; The addition of tetracycline to a culture of a tetracycline-sensitive strain of Escherichia coli leads to the appearance in the medium of a chemical compound (or compounds) that in part relieve the inhibition of growth of a tetracycline-resistant strain by a high concentration of the antibiotic . An increase in the growth rate can be as high as 50%. Genes Cells, 1996 Nov, 1(11), 965 - 76 Complete growth inhibition of Escherichia coli by ribosome trapping with truncated cspA mRNA at low temperature; Jiang W et al.; BACKGROUND: CspA, the major cold-shock protein of Escherichia coli, is transiently induced upon temperature downshift and considered to play an important role in low-temperature adaptation . RESULTS: Overproduction of truncated cspA mRNAs retaining translational ability was found to completely block cell growth at low temperatures . This effect was termed 'low-temperature antibiotic effect of truncated cspA expression (LACE)' . In contrast to the significant reduction of polysomes in normal cells upon cold shock, cells under LACE maintained a high polysome profile, producing only truncated cspA products . Growth inhibition of cells under LACE was suppressed when CspA was overproduced together with the truncated cspA mRNA . CONCLUSION: LACE is caused by the overproduction of a truncated cspA mRNA in the absence of CspA production, which in turn traps all the cellular ribosomes in a non-adaptive form incapable of forming initiation complexes with other cellular mRNAs . LACE may provide a novel approach to the development of a new antibiotic. Arch Bronconeumol, 1996 Nov, 32(9), 442 - 6 {Infections in lung transplantation}; Carreno MC et al.; Lung transplantation has become the therapeutic hope of terminal respiratory patients . Infections are among the main causes of morbidity and mortality in these patients . We therefore analyze infections suffered after lung transplants performed at Clinica Puerta de Hierro over a two-year period . The cases of 14 transplanted patients, 6 bilateral and 8 unilateral, were analyzed . Pre-transplant data available for all included analysis of serum antibodies to several viruses, as well as bacterial and fungal cultures, and Ziehl's sputum test . All received prophylactic antibiotic, antifungal and antiviral treatment according to protocol . The bronchial aspirate of the donor, and recipient specimens of bronchial aspirate, bronchoalveolar lavage and biopsies obtained by bronchoscopy after transplantation were cultured . Bronchoscopies were performed according to protocol, based on clinical picture . Other cultures were obtained as needed . We recorded 27 respiratory infections, among which 4 were pneumonia transmitted by the donor, 3 were tuberculosis, 3 were Aspergillus infections, 5 were cytomegalovirus pneumonitis and one, P . carinii pneumonia . Lung infections have a strong impact on outcome of lung transplant patients . Knowledge of the chronological development of infections made appropriate prophylaxis and early detection possible, such that survival during the first two years after transplantation was approximately 70% in our hospital. Gene Ther, 1996 Nov, 3(11), 1018 - 20 A simple and rapid method for the determination of recombinant retrovirus titer by G418 selection; Byun J et al.; We have developed a simple and rapid method for the determination of retroviral titer by G418 selection which is both accurate and reproducible . NIH3T3 cells were transduced with recombinant retroviral vectors harboring the neo gene and selected in the presence of the antibiotic G418 for 3 days . Cells were then trypsinized, harvested, and counted on a hemacytometer . The control NIH3T3 cells were completely dead 3 days after treatment with G418, while cells transduced with retroviral vectors containing the neo gene produced an average of 15 progeny cells per colony . To estimate viral titer, therefore, the total number of trypsinized G418-resistant cells was divided by 15 . Retroviral titers measured by this method did not differ significantly from those determined by the conventional method based on counts of G418-resistant colonies 10-14 days after G418 selection . The method worked well with various retroviral constructs and its efficacy was not influenced by cDNA insert . This method not only reduces the amount of work but also shortens the time needed for determining viral titer. Hautarzt, 1996 Nov, 47(11), 863 - 6 {Postoperative infection with Mycobacterium chelonae}; Engelhardt E et al.; A 70-year-old patient developed Mycobacterium chelonae infection at a donor vein graft site following cardiac bypass surgery . The infection presented as fibrinous, necrotic ulcerations in the scar area . Mycobacterium chelonae and mycobacterium fortuitum are atypical mycobacteria and have been described previously causing infections after injections or surgical procedures . Infection of donor vein graft site is a rare complication after cardiac surgery . As mycobacterium chelonae cannot be cultivated on normal culture media, delayed wound healing might be disinterpretated as a primary wound healing disorder . Treatment of atypical myobacteriosis includes antibiotics, local heat therapy and surgical excision . Clarithromycin is the antibiotic of choice . We obtained complete healing after two months of Clarithromycin treatment, combined with heat therapy. Rev Port Cardiol, 1996 Nov, 15(11), 799 - 803, 772 {Infectious endocarditis caused by Q fever . Apropos of a clinical case}; Almeida M et al.; Endocarditis is a rare, but some times fatal, complication of Q fever . Its diagnosis is difficult and it is based on non-specific cardiac findings and a high title of phase I antibodies . The treatment is based on tetracyclines alone or in combination with cotrimoxazole, for long periods of time . The therapeutic efficacy is evaluated by the measurement of phase I antibodies, every three months . The relapses are frequent despite the long period of antibiotic therapy . We report what is probably the first case of Q fever prosthesis endocarditis in Portugal, as a complication following an acute episode of Q fever. Eur J Cancer, 1996 Nov, 32A(12), 2058 - 63 High-dose melphalan with re-infusion of unprocessed, G-CSF-primed whole blood is effective and non-toxic therapy in multiple myeloma; Ossenkoppele GJ et al.; In order to shorten the pancytopenic period following high-dose melphalan 140 mg/m2 (HDM) treatment of multiple myeloma patients, we studied the effects of re-infusing granulocyte colony stimulating factor (G-CSF) {Filgrastim, Neupogen}-primed unprocessed whole blood . 30 patients with multiple myeloma were treated with HDM . One litre of blood after 5 or 6 days stimulation with G-CSF (10 micrograms/kg) was drawn, kept unprocessed for 1 day and re-infused 24 h after chemotherapy . Time to granulocyte recovery (> 0.5 x 10(9)/1) and platelet recovery (> 20 x 10(9)/1) were assessed as well as length of hospital stay, number of transfusions and antibiotic use . These 30 patients were compared with 20 historical control patients who were similarly treated but without stem cell support . The response rate was 75% (21/28) including a complete remission (CR) rate of 29% (8/28) . Two early deaths due to Aspergillus pneumonia were observed . The median overall survival after HDM has not been reached after a median follow-up of 14 months . 10 patients showed progression at a median of 7 months . Currently, 23 patients are alive with a median follow-up time of 14 months . Haematological recovery was significantly faster in the study group as compared to the historical control group . The neutrophil count reached 0.5 x 10(9)/1 at a median of 14 days after infusion of 1 litre of unprocessed whole blood compared with 38 days in the historical control group . A platelet count of 20 x 10(9)/1 was reached at a median of 26 days compared with 36 days in the historical control group . Length of hospital stay decreased from a median of 43 to 18.5 days . The number of days with antibiotics was reduced from a median of 21 to 6 days . HDM is effective therapy for multiple myeloma . Toxicity of the regimen is considerably reduced by the use of G-CSF-stimulated unprocessed whole blood, an easy to perform and cheap technique to mobilise and collect stem cells. Rev Mal Respir, 1996 Nov, 13(5 Suppl), S41 - 7 {Infectious complications of lung and heart-lung transplantation}; Nicod LP; Thanks to a simplification of surgical techniques, single or double lung transplants have expanded significantly in latter years . Infection remains an important cause for morbidity and mortality, more so in early rather than late stages . Bacterial infections cause approximately fifty per cent of all infections . They can be prevented in part by prophylaxis . Infections to CMV have become less frequent thanks to adequate prophylaxis with ganciclovir . Herpetic infections are prevented by acyclovir or ganciclovir . A better control of immunosuppression seems to be associated with fewer lymphoproliferative disorders secondary to the Epstein-Barr virus . Respiratory viruses remain a serious threat for these patients, although infections due to respiratory syncitial virus may be attenuated by ribavirine . Fungal infections are dangerous but prophylactic prescription of azole derivatives have reduced the incidence and severity . Prophylaxis of infections to Pneumocystis carinii is essential, the use of sulfamethoxazole trimethoprim is efficacious against this as well as nocardiosis . Infections to Mycobacterium tuberculosis are often atypical and should be looked for and anticipated whenever possible. Infection, 1996 Nov-Dec, 24(6), 470 - 2 Lyme borreliosis--problems of serological diagnosis; Hofmann H; As long as test procedures are not standardized, the serological results of IgM- and IgG-antibodies in Lyme borreliosis must be interpreted with caution and always in the context of clinical signs and symptoms . False negative results occur primarily during the first weeks of infection . In erythema migrans of less than 4 weeks' duration, 50% of patients are seronegative even with newly designed ELISAs . At this early stage of the infection the therapeutic decision has to be established on the basis of clinical criteria . Frequently IgM- and/or IgG-antibodies develop during antibiotic therapy . After 4 weeks' duration 80% of patients have elevated borrelial antibodies detectable with recently developed ELISAs . Positive and borderline results should be confirmed by Western blot . False positive results, particularly slightly elevated IgM, may occur in a variety of other diseases . Another problem is the persistence of Borrelia-specific IgM antibodies after therapy . Serological follow-up can only be carried out with the same methods in the same laboratory . Retreatment should be considered if IgM antibodies are increasing significantly and new symptoms are occurring. Clin Ther, 1996 Nov-Dec, 18(6), 1366 - 73 A disease management case study in infectious disease; Wert SM; One of the earliest attempts at risk sharing between a managed-care organization and a pharmaceutical company is the infectious disease management program developed since late 1993 by Intergroup of Arizona and Eli Lilly and Company (Indianapolis, Indiana) in conjunction with the Center for Pharmaceutical Economics at The University of Arizona (Tucson, Arizona) and other entities . In the first phase of the program, protocols were built around eight infectious disease states, and it was recognized that second-line antibiotics were often prescribed when more economical first-line antibiotics would be equally effective . The second phase of the program emphasized developing treatment algorithms focused on patient outcomes, using merged medical and pharmacy claims databases to determine the effects of the antibiotic changes . To implement the program successfully, some significant shifts in corporate, medical, and patient mind-sets had to be addressed . A primary goal was to encourage a movement from a rebate, volume-driven, cost structure to a shared-risk, appropriate-use, reimbursement method in which both managed-care and the pharmaceutical company incentives could mesh as far as possible . Over the long term, it is hoped that this project will lay the groundwork for other disease management programs for high-impact, frequently occurring diseases. Clin Ther, 1996 Nov-Dec, 18(6), 1068 - 79 Use of Broncho-Vaxom in private practice: phase IV trial in 587 children; Berber AC et al.; We conducted a Phase IV, open-label clinical trial to test the efficacy and safety of the immunomodulating agent Broncho-Vaxom in private practice . The trial comprised 587 children younger than 12 years of age who had an acute respiratory tract infection at entry and a history of recurrent respiratory tract infections . The patients were given one capsule daily, 10 days per month, for 3 consecutive months . During the acute phase of the disease the patients also received antibiotic therapy . Comparing the infection present at entry with previous infections, the time to improvement (mean +/- SD) decreased from 6.77 +/- 4.42 days to 3.76 +/- 2.18 days, while the time to cure decreased from 11.86 +/- 8.41 days to 7.36 +/- 4.93 days . During the 3 months of therapy, the number of infections decreased from 1.79 +/- 0.96 1 month before treatment to 0.24 +/- 0.46 in the third month of treatment; absenteeism decreased from 3.17 +/- 3.07 days to 0.16 +/- 0.63 days; and the number of antibiotic treatments decreased from 1.71 +/- 1.06 to 0.16 +/- 0.51 . In the patients who experienced a recurrent respiratory tract infection during the study, the time to improvement decreased from 5.46 +/- 3.28 days before treatment to 2.79 +/- 1.36 days after treatment, and the time to cure decreased from 8.71 +/- 3.96 days to 4.54 +/- 2.26 days . Adverse events included asthenia and adynamia in 3 patients, diarrhea in 3, rash in 2, fever in 2, exacerbation of symptoms in 2, adenitis in 1, and flulike syndrome in 1 . We conclude that Broncho-Vaxom is effective and safe for the treatment of acute episodes of respiratory tract infections and for preventing recurrences. Aust N Z J Ophthalmol, 1996 Nov, 24(4), 361 - 3 Intralenticular metallic foreign body; Lee LR et al.; BACKGROUND: Intralenticular metallic foreign bodies may be well tolerated for many years . CASE REPORT: A 24-year-old caucasian man was referred with an intralenticular metallic foreign body present in the left eye for five days . Following initial treatment with topical steroid and antibiotic, the lens remained clear and visual acuity normal . Two years later the left eye developed an anterior uveitis, with reduced vision . A left phacoemulsification lens extraction with removal of the intralenticular foreign body and insertion of a posterior chamber intraocular lens was performed . CONCLUSION: Management of intralenticular metallic foreign bodies may be conservative till intraocular inflammation or cataract develops. Perit Dial Int, 1996 Nov-Dec, 16(6), 557 - 73 Peritoneal dialysis-related peritonitis treatment recommendations: 1996 update; Keane WF et al.; The recommendations provided in this document represent a distillation of various experiences, as well as data obtained from published studies in the setting of substantial changes in antibiotic sensitivity . It is hoped that this revised compilation will provide a basis upon which future developments and advances can be made in the therapeutic approach to infectious complications of peritoneal dialysis. J Invest Surg, 1996 Nov-Dec, 9(6), 487 - 93 A new experimental model for simultaneous evaluation of aortic and pulmonary allograft performance in a composite graft; Shimokawa S et al.; A model was developed in pigs for simultaneous evaluation of aortic and pulmonary allograft performance in a composite graft . The composite graft consisted of vascular prosthesis and aortic and pulmonary allografts . Following antibiotic preservation, it was anastomosed to the recipient's thoracic descending aorta by an extrapleural approach without using cardiopulmonary bypass . Aortic blood flow was completely diverted into the composite graft . All 12 recipient pigs recovered well, 4 of which were assigned for the initial study to design the suitable experimental schedule . Calcification readily occurred in the aortic allografts and aneurysmal dilatation without calcification developed in the pulmonary allografts . These morphological findings were consistent with those of previous reports . This model has several benefits . First, aortic and pulmonary allograft conduits can be implanted and evaluated simultaneously under the same conditions by making a composite graft . Second, the magnitude of the operation is minimum, and postoperative circulatory and respiratory management is uncomplicated . Third, wound infection rarely occurs, because the skin incision is made on the back . These preliminary studies suggest that this model will allow future study concerning aortic and pulmonary allograft conduits under different conditions. Indian J Med Res, 1996 Nov, 104, 281 - 3 In vitro & in vivo experimental susceptibility of Mycobacterium marinum to augmentin; Chakrabarti A et al.; The effect of augmentin alone and in combination with various beta-lactam antibiotics was studied against a pathogenic Mycobacterium, M . marinum . The in vitro studies did not reveal any additional advantage over that found with augmentin alone and this antibiotic seemed considerably inhibitory to M . marinum at < 1 microgram/ml concentration . In vivo, the effects of augmentin on experimentally produced lesions in the mouse foot pads (MFPs) showed a significant regression of the lesions, which was compatible with an early disappearance of M . marinum from the MFP, in contrast with those of the untreated, control animals. Acta Otolaryngol, 1996 Nov, 116(6), 799 - 804 The alteration of ultrastructure and immunoreactivity of human embryonic organ of Corti tissue culture after exposure to aminoglycoside (neomycin) ototoxicity; Mu MY et al.; Using electron microscopy and GABA immunohistochemistry we evaluated the effects on human embyronic organ of Corti tissue culture of exposure to the ototoxic aminoglycoside antibiotic neomycin at a dose of 1 mM for 48 to 96 hrs . Neomycin induces the formation of multilamellar myeloid structures . These lesions, found only in the basal coil but both in inner and outer hair cells, were characteristic of the membrane-associated neomycin-induced damage . A large amount of lipofucsin and numerous lipoid vacuoles as well as vesicle-filled mound-like protrusions were also observed after exposure to neomycin . It seems there is no obvious effect on GABAergic innervation. J Periodontal Res, 1996 Nov, 31(8), 540 - 4 Use of the polymeric matrix as internal standard for quantitation of in vivo delivery of tetracycline HCl from Actisite tetracycline fiber during periodontal treatment; Litch JM et al.; Actisite (tetracycline hydrochloride) periodontal fiber is a 23 cm monofilament containing 12.7 mg tetracycline HCl homogeneously dispersed in a polymer . This product is indicated as an adjunct to scaling and root planing to reduce pocket depth and bleeding on probing in patients with adult periodontitis . The sustained-release system, placed in the periodontal pocket for 10 d, releases the antibiotic through mechanisms of diffusion and osmosis . A study was conducted in 13 patients with moderate to severe adult periodontitis to evaluate the amount of tetracycline HCl released during therapy (based on residual drug content) . Fibers placed in the pocket remained in place for an average of 9 d . Each patient had 1-4 teeth treated with fiber therapy . At the termination of therapy samples from 29 teeth were retrieved and analyzed . The amount of matrix polymer was used as an internal standard for the quantitation of tetracycline, eliminating any uncertainties with respect to recovery or contamination . An average of 31% (SD 9%) of the tetracycline HCl content was released from the fiber during the treatment period . No single fiber had less than 50% of the original drug remaining . The study demonstrated that a substantial amount of the tetracycline remains in the Actisite fiber at removal (about 70%), which indicates that substantial drug concentrations are maintained in the pocket for the duration of treatment. Carcinogenesis, 1996 Nov, 17(11), 2343 - 5 Sites and types of UV-induced mutations leading to inactivation of the growth-arresting activity in p21 (sdi1/cip1/waf1) cDNA; Lu Y et al.; The p53-regulated gene product p21 (sdi1,cip1,waf1) negatively regulates cell growth and has been suggested to be a potential tumour-suppressor gene . To determine the sites and types of mutations which inactivate the growth-arresting activity in sdi1 cDNA, plasmids containing sdi1 cDNA and the neomycin-resistant gene were irradiated with UV light and transfected into CHO cells . The UV irradiation increased number of the geneticin-resistant colonies which should have the UV-mutated sdi1 cDNA . Sdi1 mRNA was expressed in 23 out of 36 colonies (64%) . In 13 sdi1 cDNA sequences analysed, mutations were found at codon 46 in nine cDNAs, and one each at codons 34, 54, 66 and 73 . All the mutation sites are in the CDK-binding region . Ten mutations (77%) (codons 46 and 66) are C to T transition mutation at the dipyrimidine sequences, which is the major type of the UV-induced mutation. J Antimicrob Chemother, 1996 Nov, 38(5), 799 - 807 Effect of RO 23-9424, cefotaxime and fleroxacin on functions of human polymorphonuclear cells and cytokine production by human monocytes; Matera G et al.; The way in which an antibiotic interacts with host defences could influence the clinical outcome of many infectious diseases . The impact of RO 23-9424, a novel dual-action and extended-spectrum antibiotic, was studied on several functions of human polymorphonuclear neutrophils (PMNs) . A significant (P < 0.05) increase of the superoxide (O2-) released by phorbol-myristate acetate (PMA) -stimulated PMN (10-100 mg/L) can be observed in the RO 23-9424 pre-treated cells . RO 23-9424, particularly at low dosages, showed an interesting but not statistically significant effect on PMN phagocytosis . Higher dosages of RO 23-9424 (50-200 mg/L) and fleroxacin (20-200 mg/L) significantly reduced PMN chemotaxis . Cytokine production by human monocytes were also evaluated after incubation with the antibiotic (100-200 mg/L) in both basal conditions and in response to endotoxin (lipopolysaccharide, LPS) . In the LPS-treated cells, RO 23-9424 (100 mg/L) significantly (P < 0.05) enhanced the tumour necrosis factor-alpha (TNF-alpha) levels, compared with LPS controls after 4 h of incubation . RO 23-9424 (200 mg/L) was able to reduce in a dose-dependent way LPS-induced interleukin-1 beta (IL-1 beta) after 4 and 24 h of incubation . Interleukin-8 (IL-8) release was not significantly changed by RO 23-9424 . Cefotaxime (200 mg/L) significantly (P < 0.05) increased the basal levels of IL-1 beta and reduced basal IL-8 concentration after 24 h of incubation . The lower concentration of cefotaxime reduced the LPS-stimulated IL-8 levels . Fleroxacin (100 mg/L) enhanced basal levels of IL-8 . The potentiated PMN phagocytosis, the significantly enhanced O2- release by PMA-stimulated PMN and the dimetric changes of TNF-alpha and IL-1 beta appeared peculiar for RO 23-9424 and may have useful therapeutical implications. J Antimicrob Chemother, 1996 Nov, 38(5), 787 - 98 Is the uptake of pefloxacin in human blood monocytes a simple diffusion process? Memin E, Panteix G, Revol A. Effective therapy of infections caused by facultative intracellular micro-organisms, which persist after ingestion by mononuclear phagocytic cells, requires antibiotics which inactivate these intraphagocytic bacteria . A previous study demonstrated that intracellular concentrations of normethylpefloxacin, Ci, were the result of simple diffusion and an active efflux involving organic anion transporters . In our work, we studied pefloxacin transport in human monocytes . A kinetic approach was followed to establish the processes involved . Extracellular concentrations, Ce, corresponding to in-vivo pharmacological levels of the drug were used . Uptake of the antibiotic was assessed principally by HPLC . Pefloxacin was accumulated by the cells (Ci/Ce = 3) . The uptake was rapid, non saturable, reversible and temperature dependent . At 4 degrees C, the Ci/Ce was equal to 1 . At high temperatures, an active and initial process appeared that was not visible at lower temperatures and disappeared in presence of energetic metabolism inhibitor: At 42 degrees C, NaCN and 2.4 DNP (1 mM) reduced the initial transport but they had no significant effect on the subsequent curve. J Gastroenterol, 1996 Nov, 31 Suppl 9, 69 - 74 Vaccination against Helicobacter pylori; Lee A; The initial steps have been taken towards the development of a vaccine against the human gastroduodenal pathogen, Helicobacter pylori . Proof of principle was achieved when mice were protected against challenge with living Helicobacter felis, a close relative of the human pathogen, following oral immunization with H . felis sonicate and the mucosal adjuvant, cholera toxin . Similar results with H . pylori antigen have allowed development of possible human vaccines . Recombinant urease protein has been proposed as a major vaccine candidate, together with the heat-labile toxin of Escherichia coli as the adjuvant . Probably the most significant finding in the early vaccine studies was that immunization of already infected mice resulted in a cure of Helicobacter infection . The possibility of a therapeutic vaccine makes commercial development more attractive, as large populations could be immunized without the potential for development of drug-resistant strains that currently restricts widespread antibiotic use . For advanced societies with powerful economies yet a high prevalence of H . pylori, such as Japan, vaccine development should become a high national health priority. Respir Med, 1996 Nov, 90(10), 587 - 92 Time to resolution of morbidity: an endpoint for assessing the clinical cure of community-acquired pneumonia; Daifuku R et al.; Clinical trials of new therapeutics for community-acquired pneumonia (CAP) have typically used a subjective endpoint of clinical response . However, as this endpoint is not quantitative, it is subject to observer bias and renders the conduct of multicenter trials difficult . For the purposes of conducting a clinical trial of filgrastim, as an adjunct to antibiotics for the treatment of CAP, a set of clinical criteria were developed prospectively to determine the time when a clinical cure was achieved, based on respiratory rate, temperature, oxygenation and roentgenographic findings, which was termed the time to resolution of morbidity (TRM) . The TRM was evaluated on the first 100 patients entered in this clinical trial . As no clear reference standard exists, the predictive value for the duration of parenteral antibiotics (AB) and the length of hospital stay (LOS) was compared with that provided by a widely used classification system for severity of disease, APACHE II . The TRM was found to correlate significantly better with AB or LOS than APACHE II (P < 0.001) . Furthermore, TRM offers the benefit over the endpoints of LOS and AB of being specifically designed to measure the patient's response to therapy, and, in fact, may aid physicians in determining the duration of parenteral antibiotic therapy . Hence, TRM is relevant to the clinician and is a useful tool to ensure uniformity in the assessment of the response to a new therapeutic in a multicenter clinical trial. Reg Anesth, 1996 Nov-Dec, 21(6), 595 - 8 Status epilepticus amauroticus secondary to meningitis as a cause of postpartum cortical blindness; Goldstein MJ et al.; BACKGROUND AND OBJECTIVES: A patient who underwent cesarean delivery with epidural anesthesia presented 6 days postpartum with acute cortical blindness . METHODS: Initial studies included an ophthalmology consultation as well as a full neurologic workup, including cranial computed tomography, diagnostic lumbar puncture, magnetic resonance imaging, body fluid cultures, and electroencephalography . Early broad-spectrum antibiotic coverage was initiated, and because of possible epileptic activity on electroencephalogram, phenytoin was added to the treatment regimen . RESULTS: Soon after beginning the initial phenytoin dose, the patient reported full return of her vision . She was eventually discharged from the hospital in good condition . CONCLUSIONS: This case report illustrates how blindness can be related to seizure activity. J Vasc Interv Radiol, 1996 Nov-Dec, 7(6), 921 - 7 Percutaneous transpedicular management of discitis; Arya S et al.; PURPOSE: To present the technique of percutaneous transpedicular biopsy and debridement of discs in diagnosis and management of discitis . MATERIALS AND METHODS: Fifteen patients underwent disc biopsy through a transpedicular approach with local anesthesia and fluoroscopic guidance . An attempt was made to debride the disc as much as possible . A surgical vacuum drain was deployed through the transpedicular tract when there was persistent drainage . RESULTS: Fifteen patients underwent percutaneous transpedicular disc biopsy and debridement of disc for suspected discitis . Three patients underwent biopsy only and 12 underwent percutaneous discectomy . Six patients had at least one positive culture . Eight patients who underwent discectomy had immediate improvement of pain or neurologic symptoms, obviating emergency surgical debridement of the disc . Four patients did not improve and underwent surgical debridement and fusion . CONCLUSIONS: Transpedicular biopsy of the disc is an effective technique for adequate tissue retrieval and diagnosis of discitis . Adequate debridement in selected patients with antibiotic therapy may be definitive . Epidural extension of discitis and massive vertebral destruction precludes percutaneous treatment. Biopharm Drug Dispos, 1996 Nov, 17(8), 675 - 98 The absorption and first-pass metabolism of {14C}-1,3-dinitrobenzene in the isolated vascularly perfused rat small intestine; Adams PC et al.; We tested the hypothesis that the small intestine is capable of the first-pass, reductive metabolism of xenobiotics . A simplified version of the isolated vascularly perfused rat small intestine was developed to test this hypothesis with 1,3-dinitrobenzene (1,3-DNB) as a model xenobiotic . Both 3-nitroaniline (3-NA) and 3-nitroacetanilide (3-NAA) were formed and absorbed following intralumenal doses of 1,3-DNB (1.8 or 4.2 mumol) to isolated vascularly perfused rat small intestine . Dose, fasting, or antibiotic pretreatment had no effect on the absorption and metabolism of 1,3-DNB in this model system . The failure of antibiotic pretreatment to alter the metabolism of 1,3-DNA indicated that 1,3-DNB metabolism was mammalian rather than microfloral in origin . All data from experiments initiated with lumenal 1,3-DNB were fit to a pharmacokinetic model (model A) . ANOVA analysis revealed that dose, fasting, or antibiotic pretreatment had no statistically significant effect on the model-dependent parameters . 3-NA (1.5 mumol) was administered to the lumen of isolated vascularly perfused rat small intestine to evaluate model A predictions for the absorption and metabolism of this metabolite . All data from experiments initiated with 3-NA were fit to a pharmacokinetic model (model B) . Comparison of corresponding model-dependent pharmacokinetic parameters (i.e . those parameters which describe the same processes in models A and B) revealed quantitative differences . Evidence for significant quantitative differences in the pharmacokinetics or metabolism of formed versus preformed 3-NA in rat small intestine may require better definition of the rate constants used to describe tissue and lumenal processes or identification and incorporation of the remaining unidentified metabolites into the models. Fundam Appl Toxicol, 1996 Nov, 34(1), 56 - 66 Nitrofurazone: reproductive assessment by continuous breeding in Swiss mice; George JD et al.; Nitrofurazone (NTFZ), a nitrofuran antibiotic, was evaluated for reproductive toxicity in Swiss CD-1 mice using the Reproductive Assessment by Continuous Breeding protocol . Male and female mice were cohabited for 15 weeks and exposed to NTFZ in feed at concentrations of 0, 100, 375, and 750 ppm (14-102 mg/kg/day) . Fzero 750-ppm breeding pairs had significantly reduced fertility after 7 days of exposure to NTFZ (17% fertile compared to 98% for control pairs) and were infertile after the second litter . Fzero mid-dose pairs had progressively decreasing fertility (47% by the fifth litter), reduced litter size, and reduced proportion of pups born alive . Crossover breeding of control and high-dose Fzero animals confirmed infertility in high-dose males and reduced litter size and pup weight in high-dose females when compared to the control x control group . At necropsy, there were no effects on body weight, but Fzero males had reduced testis weight at the high dose and reduced epididymal sperm concentration and abnormal sperm morphology at all doses of NTFZ . Increased liver as well as kidney and adrenal weights (combined) were observed at 375 and 750 ppm; hepatic hypertrophy was noted microscopically at 750 ppm . Fzero females had reduced body weight, hepatic hypertrophy, and altered estrous cycles at 750 ppm and reduced ovarian weight at all doses . In the second generation, F1 mice at 375 ppm had reduced postnatal survival and body weight and produced smaller F2 litters compared to control mice . At necropsy, F1 males had reduced testes weight and epididymal sperm concentration, abnormal sperm morphology, hepatic hypertrophy at 375 ppm, and borderline nephropathy at 100 and 375 ppm . F1 females had decreased body, liver, and ovarian weight at 375 ppm and altered estrous cycles at 100 and 375 ppm . Thus, NTFZ at > or = 100 ppm (> or = 14 mg/kg/day) caused adverse reproductive effects in Fzero male and female and F1 female mice in the presence of relatively mild systemic toxicity. Transfusion, 1996 Nov-Dec, 36(11-12), 1009 - 15 Alloimmunization after granulocyte transfusions; Stroncek DF et al.; BACKGROUND: Although granulocyte transfusions are recommended for neutropenic patients with bacterial infections that are unresponsive to antibiotic therapy, the presence of white cell (WBC) antibodies in the recipient can render these transfusions ineffective . STUDY DESIGN AND METHODS: A 25-year-old man with chronic granulomatous disease experienced a pulmonary transfusion reaction while receiving granulocyte transfusions, and he was found to be immunized to neutrophil antigen NA2 . A retrospective study of alloimmunization to HLA and neutrophil antigens in 18 patients with chronic granulomatous disease who had also received repeated granulocyte transfusions was then performed . Sera were tested in lymphocytotoxicity, granulocyte agglutination, granulocyte immunofluorescence, monoclonal antibody immonobilization of granulocyte antigen, and immunoprecipitation assays . RESULTS: After the granulocyte transfusions, sera from 14 of the 18 patients contained WBC antibodies . Seven sera samples reacted in the lymphocytotoxicity, granulocyte immunofluorescence, and granulocyte agglutination assays; seven reacted in the lymphocytotoxicity and granulocyte immunofluorescence assays but not the granulocyte agglutination assay, and four did not react . When the monoclonal antibody immobilization of granulocyte antigen assay was used, three sera samples reacted with Fc gamma receptor III, three with the 58- to 64-kDa protein carrying the neutrophil antigen NB1, one with CD11a, and one with CD18 . Antibodies from three patients immunoprecipitated a neutrophil protein of 60 kDa . Overall, antibodies to neutrophil antigens other than HLA could be detected in sera from eight patients . Transfusion reactions occurred in 11 of the 14 individuals with WBC antibodies and in none of the 4 without antibodies . Seven pulmonary reactions occurred in patients with WBC antibodies . The patients with WBC antibodies were given significantly more granulocyte concentrates (78 +/- 65 vs . 29 +/- 15 units, p < 0.05) . CONCLUSION: Recipients of granulocyte transfusions often become alloimmunized . Screening for WBC antibodies periodically during transfusions, after adverse reactions, or before subsequent transfusions is indicated . If WBC antibodies are present, no further granulocyte transfusions should be given unless the granulocytes are collected from HLA- and/or neutrophil antigen-compatible donors. Gastrointest Endosc, 1996 Nov, 44(5), 554 - 61 Evaluation of initial noninvasive therapy in pediatric patients presenting with suspected ulcer disease; Olson AD et al.; OBJECTIVE: To compare the clinical and economic effects of five likely treatment strategies in children with dyspepsia: initial diagnostic endoscopy (EGD) with biopsy for Helicobacter pylori infection; initial EGD without biopsy; H . pylori serology screening and treatment for H . pylori if positive; empiric treatment with antisecretory therapy; and empiric treatment for H . pylori with antibiotics and antisecretory therapy . METHODS: Our decision analysis model incorporated data from published literature on the incidence of duodenal ulcer disease and effect of H . pylori infection . Cost inputs were derived from payments made by third-party payers . For the three noninvasive strategies that did not include immediate endoscopy, endoscopy was performed on the first episode of symptom recurrence . RESULTS: The estimated costs per child evaluated for each strategy were: EGD with biopsy, $1458; EGD alone, $1248; H . pylori serology, $1224; antisecretory, $1160; and antisecretory-antibiotic, $1164 . Results were sensitive to the costs of EGD and the likelihood of recurrent symptoms in children . When the cost of endoscopy fell below $950 or if over 65% of patients without ulcers eventually underwent endoscopy, there was no longer a cost advantage for initial noninvasive treatment when compared with EGD alone strategy . CONCLUSION: In a decision analysis model, empiric antisecretory treatment in children with dyspepsia was most cost-effective, eliminating 40% of endoscopies and leading to antibiotic use in only those patients with H . pylori (4%) . Further studies to determine the actual recurrence rate of symptoms after empiric antisecretory treatment of children with dyspepsia are required. Mol Reprod Dev, 1996 Nov, 45(3), 255 - 63 Unexpected behavior of a gene trap vector comprising a fusion between the Sh ble and the lacZ genes; Camus A et al.; A new gene trap vector has been designed, comprised of a fusion between the Sh ble gene, which confers resistance to the antibiotic phleomycin, and the lacZ gene (phleal fusion gene) . A synthetic splice acceptor, made of the yeast branchpoint followed by a pyrimidin-rich sequence of 27 nucleotides, is included at the 5' extremity . The linearized gene trap vector was introduced into mouse embryonic stem cells (ES cells), and 40 phleomycin resistant (phleo') cell lines possessing a single copy of the insert were selected . They were stable in expressing the lacZ gene . Reporter gene expression was studied at days 8.5 and 10.5 of embryonic development in chimeric embryos obtained after injection of phleo' ES clones into 8-cell stage embryos . Out of 20 phleal lines examined, 14 exhibited beta-galactosidase expression at day 10.5 . Use of the phleal fusion gene trap vector to select genes expressed in ES cells, therefore, is compatible with the isolation of genes expressed at midgestation . However, and most intriguingly, 10 out of these 14 cell lines (71%) displayed reporter gene expression mostly in heart and liver . Two of them exhibited, in addition, expression in central nervous system (CNS) or in CNS and limb buds, respectively . Germline chimeras were subsequently obtained and 15 mouse lines have been established . Intercrosses of animals heterozygous for the insertion revealed a mutant phenotype in several lines. Am J Otol, 1996 Nov, 17(6), 850 - 2 Topical gentamicin-induced hearing loss: a mitochondrial ribosomal RNA study of genetic susceptibility; Chen JM et al.; Mitochondrial ribosomal RNA mutation has been shown to predispose affected individuals to aminoglycoside-induced hearing loss (AIHL) . An A-to-G nucleotide substitution at the 1555 position within the 12S ribosomal RNA gene has been identified with a maternally inherited pattern in affected Asian pedigrees . The aim of this study was to identify the frequency of this DNA polymorphism in subjects who appear to show hypersensitivity to topical (middle ear) application of aminoglycoside . In this pilot study, 10 subjects with AIHL were recruited . Eight underwent vestibular ablative therapy with middle ear instillation of gentamicin for disabling vertigo, and two were treated with topical antibiotic drops for otitis media in the presence of a tympanic perforation . DNA samples were extracted, and polymerase chain reaction (PCR) technique was used for gene amplification and purification, searching for 1555 A-to-G substitution in the 12S ribosomal RNA gene . None of the subjects demonstrated this specific mutation. Arch Surg, 1996 Nov, 131(11), 1136 - 40 Host defense mechanisms of surgical patients . Friend or foe? Christou NV. Surgeons and members of this society commonly deal with 2 types of infections of great concern in hospitalized patients . These are hospital-acquired pneumonia and intra-abdominal infections . Both of these infections have the potential for severe morbidity and mortality . We have learned how to classify the types of intra-abdominal infections into primary peritonitis, localized abscess with or without peritonitis, diffuse suppurative peritonitis, or combinations of these classifications . Each of these conditions carries a different mortality risk proportional to its severity . We have also learned how to diagnose surgical infections by properly taking medical history and performing physical examination, appropriate laboratory testing, and sophisticated imaging techniques . The treatment of intra-abdominal infections has become fairly standardized and includes surgical or percutaneous drainage of the infected material, correction of the underlying pathologic symptoms, and broad-spectrum empirical antibiotic therapy. Diabetes Care, 1996 Nov, 19(11), 1257 - 60 Treatment of osteomyelitis in the diabetic foot . Contribution of conservative surgery; Ha Van G et al.; OBJECTIVE: To compare the duration of healing of foot ulcers with osteomyelitis in diabetic patients treated by medical treatment versus medical treatment associated with conservative orthopedic surgery . RESEARCH DESIGN AND METHODS: We entered into the study 67 diabetic patients who had a foot ulcer with osteomyelitis without ischemia requiring a peripheral arterial reconstruction . Thirty-two diabetic patients were included in a first historic group from 1986 to 1993, treated by antibiotic therapy, offloading, and wound care . Thirty-two patients were included from September 1993 to March 1995, treated by the same medical treatment and conservative orthopedic surgery . RESULTS: The healing rate was 57% in the group treated by the medical treatment alone versus 78% in the surgical group (P < 0.008) . The duration of healing was 462 +/- 98 days versus 181 +/- 30 days (P < 0.008) . CONCLUSIONS: Conservative surgery contributes to an increase in the healing rate of foot ulcers with osteomyelitis compared with a medical treatment alone. Neurosurgery, 1996 Nov, 39(5), 958 - 64 Spinal epidural abscess: evaluation of factors influencing outcome; Khanna RK et al.; OBJECTIVE: The goal of this study was to critically evaluate the predictive efficacy of various clinical factors in spinal epidural abscess influencing outcome after surgical and/or medical treatment . METHODS: A retrospective analysis of 41 cases of spinal epidural abscess treated at Henry Ford Hospital between 1984 and 1992 was performed . RESULTS: Thirty patients underwent open surgery and received antibiotic therapy, and 11 patients received medical treatment alone . After a mean follow-up period of 20.9 months (range, 4-45 mo), 24 patients (58.5%) had no or minimal deficits, 9 patients (22%) had severe paresis or plegia and/or bowel/bladder dysfunction, and 8 patients (19.5%) died . Univariate analysis revealed patient age, degree of thecal sac compression, spinal location, surgical findings, and septic presentation to be significantly associated with outcome . In multiple logistic regression analysis, increasing age and degree of thecal sac compression were the only factors with significant independent association with poor outcome (P = 0.01 for both) . A simple grading system (Grades 0-III) was developed, with patient age, degree of thecal sac compression, and duration of symptoms as the determining criteria . The incidence of poor outcome for patients with Grade 0 was 0%, compared to 85.7% for patients with Grade III . CONCLUSION: We conclude that long-term outcome after treatment of spinal epidural abscess can be predicted with the use of the proposed grading scheme . Surgical drainage plus parenterally administered antibiotics remains the recommended treatment, although medical treatment alone can also be used for certain patients. Circulation, 1996 Nov 1, 94(9 Suppl), II235 - 8 Genetically engineered smooth muscle cells as linings to improve the biocompatibility of cardiovascular prostheses; Scott-Burden T et al.; BACKGROUND: The seeding of the blood-contacting surfaces of cardiovascular prostheses with autologous endothelial cells to improve their biocompatibility has had little success . In most instances, cells have sloughed off under flow conditions . The performance of left ventricular assist devices (LVADs) designed to stabilize patients awaiting donor hearts for transplantation has been remarkably good . After prolonged implantation, pump surfaces become covered with a pannus of smooth muscle-like cells (myofibroblasts) . Occasional islands of endothelial cells have been identified on top of such cell layers . Therefore, in an attempt to accelerate the beneficial conditioning and improve biomaterial-blood compatibility of LVAD internal surfaces, their seeding with autologous, genetically engineered smooth muscle cells (SMCs) was investigated . METHODS AND RESULTS: Since routine testing of the Thermocardiosystems HeartMate LVAD is carried out in calves, SMCs were isolated from calves, propagated in culture, and transduced with NO synthase genes to yield stable production of NO . Previous studies had demonstrated that SMCs attached strongly to the biomaterials that compose the internal surfaces of LVADs . Transduction of NO synthase gene expression in the SMCs was achieved by electroporation and antibiotic (G418) selection . Inhibition of smooth muscle cell proliferation by NO has been documented, and the same molecule has been shown to inhibit platelet adhesion to cell surfaces . Cells transduced with NO synthase expressed enzyme protein at consistently high levels for several passages in culture; however, NO production was dependent on the supplementation of culture medium with a source of tetrahydrobiopterin (sepiapterin) . Under such conditions, transduced cells were growth-inhibited compared with mock-transfected controls . Induction of GTP cyclohydrolase (the rate-limiting enzyme for the production of tetrahydrobiopterin) expression also resulted in NO production by NO synthase-transduced cells . CONCLUSIONS: Preliminary studies have shown that SMCs form strong attachments to the surface materials of LVADs and that their proliferation rates could be controlled after transformation with NO synthase under conditions that support production of NO . Therefore, genetically engineered SMCs may provide an improved blood biomaterial interface for cardiovascular prostheses. FEMS Microbiol Lett, 1996 Nov 1, 144(2-3), 207 - 11 Induction of L-lysine epsilon-aminotransferase by L-lysine in Streptomyces clavuligerus, producer of cephalosporins; Rius N et al.; L-Lysine epsilon-aminotransferase (LAT) catalyzes the first reaction in the two-step conversion of L-lysine (Lys) to 1-alpha-aminoadipic acid (Aaa), a direct precursor of cephalosporins (including cephamycin C) in Streptomyces clavuligerus . Previous work showed that addition of Lys to chemically defined medium improved antibiotic production . We show that in S . clavuligerus cultures supplemented with high concentrations of Lys, Lys enhances antibiotic production by a dual effect, i.e . as a substrate of LAT thus providing Aaa and also as an inducer of LAT yielding even more Aaa . On the other hand, LAT is not induced by Aaa. FEMS Microbiol Lett, 1996 Nov 1, 144(2-3), 177 - 84 Expression of the Streptomyces coelicolor A3(2) ptpA gene encoding a phosphotyrosine protein phosphatase leads to overproduction of secondary metabolites in S . lividans; Umeyama T et al.; A DNA fragment that caused pigment production in Streptomyces lividans was isolated from a gene library of PstI-digested chromosomal fragments of S . coelicolor A3(2) . Subcloning and nucleotide sequencing proved the identity of the cloned gene to ptpA encoding a low-molecular-mass phosphotyrosine protein phosphatase . The S . lividans transformant containing ptpA on pIJ41 with a copy number of 3 4 per genome produced large amounts of undecylprodigiosin and A-factor, in addition to the pigmented antibiotic actinorhodin, whereas the transformant containing ptpA on an SCP2* derivative with a copy number of 1-2 did not . The PtpA protein produced as a fusion to the maltose binding protein in Escherichia coli showed phosphatase activity toward o-phosphotyrosine, but not toward o-phosphoserine or a-threonine . Introduction of a mutant ptpA gene encoding an inactive protein with serine instead of the 9th cysteine caused no pigmentation . Disruption of the chromosomal ptpA gene of S . coelicolor A3(2), however, appeared to cause no detectable effect on the production of the pigmented antibiotics or A-factor and the ptpA disruptants developed aerial mycelium and spores normally. Appl Environ Microbiol, 1996 Nov, 62(11), 4233 - 7 Neomycin resistance as a selectable marker in Methanococcus maripaludis; Argyle JL et al.; We cloned the aminoglycoside phosphotransferase genes APH3'I and APH3'II between the Methanococcus voltae methyl reductase promoter and terminator in a plasmid containing a fragment of Methanococcus maripaludis chromosomal DNA . The resulting plasmids encoding neomycin resistance transformed M . maripaludis at frequencies similar to those observed for pKAS102 encoding puromycin resistance . The antibiotic geneticin was not inhibitory to M . maripaludis. Am J Surg Pathol, 1996 Nov, 20(11), 1368 - 77 Osseous manifestations of SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome; Reith JD et al.; The SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome includes a complex group of disorders characterized by peculiar bone lesions, most commonly involving the anterior chest wall, and sometimes accompanied by dermatologic manifestations . The clinical and radiographic features of this syndrome are well described, but few studies have examined the histologic features of the bone lesions . We describe the clinical, radiographic, and histologic features of the osseous lesions encountered in eight patients with a clinical diagnosis of SAPHO syndrome . The patients included five female and three male patients ranging in age from 5 to 63 years (mean, 35.3 years) . The most common clinical presentation was pain related to the sites of osseous involvement . Two patients also had some form of pustular dermatosis . The radiographic features of the osseous lesions varied but often suggested the possibility of a neoplasm . Nine pathologic specimens were available for review, five from the clavicle, two from the first rib, one from the calcaneus/cuboid, and one from the tibia . The histologic features varied but seemed related to the duration of the patients' musculoskeletal symptoms . Early lesions contained acute inflammation, edema, and prominent periosteal bone formation, histologically indistinguishable from ordinary bacterial osteomyelitis, whereas late lesions demonstrated markedly sclerotic bone trabeculae with prominent marrow fibrosis and only mild chronic inflammation; one of these biopsies appeared virtually identical to Paget's disease . One biopsy was performed after an intermediate duration of symptoms and contained prominent chronic inflammation only . The histologic findings in SAPHO are variable and nonspecific and may depend on the duration of disease, but it is important to recognize the spectrum of histologic changes possible in the syndrome and to realize that clinicopathologic correlation is necessary to avoid misdiagnosis and unnecessary long-term antibiotic therapy. Fertil Steril, 1996 Nov, 66(5), 712 - 7 Laparoscopic management of adnexal abscesses: consequences for fertility; Raiga J et al.; OBJECTIVE: To study fertility of patients with adnexal abscesses treated by laparoscopy, antibiotic therapy, and second-look laparoscopy . DESIGN: A retrospective clinical study . SETTING: Department of Obstetrics Gynecology and Reproductive Medicine, University of Auvergne, University Hospital of Clermont Ferrand, France . PATIENT(S): Thirty-nine patients treated for adnexal abscesses between January 1983 and December 1992 . INTERVENTION(S): Laparoscopic drainage of adnexal abscesses was performed in all patients; 35 patients underwent a second laparoscopy 3 to 6 months later . MAIN OUTCOME MEASURE(S): Immediate and long-term clinical results, anatomical data obtained at second-look laparoscopy, spontaneous fertility . RESULT(S): No immediate reoperation was necessary within the first 2 months after the initial laparoscopic surgery . At second-look laparoscopy, an adhesiolysis was necessary in all cases . A distal tuboplasty was performed in 17 patients and 6 patients were referred to IVF-ET . Subsequently, 12 of 19 patients not using any contraception obtained a spontaneous intrauterine pregnancy (63%) . CONCLUSION(S): This study confirms that laparoscopic surgery is a safe and efficient technique for treating adnexal abscesses . Anatomical results observed at second-look laparoscopy suggest that this second surgical step is essential for patients desiring future pregnancy. Biophys Chem, 1996 Oct 30, 61(2-3), 93 - 100 Daunomycin unfolds compactly packed DNA; Yoshikawa Y et al.; Daunomycin is an antitumor antibiotic known to inhibit DNA replication and transcription . Although the inhibition is assumed to be caused by a direct interaction of the drug with DNA, the exact effect of daunomycin on the higher order DNA structure remains uncertain . We studied the effect of daunomycin on DNA compacted states using fluorescence and electron microscopies . Structural changes in individual DNA molecules were examined under the following conditions . T4 phage DNA (166 kbp) was first compacted by spermidine followed by the addition of daunomycin to the compacted DNA . A direct observation of individual single duplex DNAs by fluorescence microscopy indicated that daunomycin induced unfolding of the compacted DNA . Electron microscopic observation of the morphological changes of the higher order DNA structure supported the results obtained by fluorescence microscopy . We discuss here the mechanisms of the unfolding of the compacted structure following intercalation of daunomycin into DNA particularly in terms of the free energy. Brain Res, 1996 Oct 28, 738(1), 121 - 30 Cell size and geometry of spinal cord motoneurons in the adult cat following the intramuscular injection of adriamycin: comparison with data from aged cats; Liu RH et al.; Adriamycin (ADM), an antineoplastic antibiotic, when injected intramuscularly, is taken up by motoneuron axonal terminals and retrogradely transported to the motoneuron soma where it exerts its neurotoxic effect . In the present study, ADM was injected into the hindlimb muscles of five adult cats . Measurements of the electrophysiological properties of the lumbar motoneurons innervating these muscles were obtained using intracellular techniques . Based upon these data the equivalent cylinder model of motoneurons was employed to evaluate ADM-induced changes in cell size and cell geometry . The size of cell somas in the ventral horn was also measured using light microscopy and computer imaging software . There were significant increases in the membrane time constant (25%) and input resistance (50%) in motoneurons whose muscles were treated with ADM (ADM-MNs) compared with data from control motoneurons (control-MNs) . The increase in membrane time constant is attributed to an increase in membrane resistance; the increase in input resistance appears to depend upon both an increase in membrane resistance and a decrease in total cell surface area . Cell capacitance, which is proportional to the total cell surface area, was significantly reduced (15%) in ADM-MNs . Calculations based on cable theory indicate that while there was no significant change in the length of the equivalent cylinder for ADM-MNs, there was a significant decrease (17%) in the diameter of the equivalent cylinder . These data indicate that there is a decrease in total cell surface area which can be attributed to the shrinkage of branches throughout the dendritic tree . There was also a small (7%) but statistically significant decrease in the electrotonic length of ADM-MNs . Morphological analysis also revealed that the mean cross-sectional area of the somas of those ventral horn neurons which are likely to correspond to the motoneuron population was significantly reduced on the ADM-treated side compared to that of neurons on the control side . We conclude that significant geometrical changes were induced in lumbar motoneurons of adult cats after ADM was injected to their muscles . In old cats, spinal cord motoneurons exhibit similar patterns of changes in their electrophysiological characteristics which have also been suggested to be correlated with changes in cell geometry . The question then arises as to whether the response of motoneurons to ADM and the aging process reflects a stereotypic reaction of motoneurons to a variety of insults or whether the response to ADM mirrors specific aspects of the aging process. Med J Aust, 1996 Oct 21, 165(8), 433 - 4 Roxithromycin-induced digoxin toxicity; Corallo CE et al.; A 76-year-old women presented with digoxin toxicity four days after starting a course of roxithromycin . In 10%-15% of the population, digoxin is degraded extensively by bacteria in the gastrointestinal tract, and antibiotic-induced changes in the bacterial flora may lead to digoxin toxicity. J Biotechnol, 1996 Oct 18, 51(1), 97 - 105 Characterization of a protease deficient strain of Penicillium roqueforti generated by heterologous plasmid integration: potential use for protein production; Durand-Poussereau N et al.; A strain of Penicillium roqueforti was transformed with a plasmid which confers resistance to phleomycin . Stable transformants were selected . They all present a high resistance to the antibiotic . Their proteolytic activity was tested . One transformant is a proteolytic deficient strain unable to degrade casein . It is characterized by a tandem integration of the transformant vector in one site of the genome . The extracellular proteins profile of the strain reveals the absence of a 43 kDa polypeptide which probably corresponds to the aspartyl protease of Penicillium roqueforti . The aspA gene which encodes aspartyl protease is not expressed in the transformant and Southern analyses show that the aspA gene is not disrupted by the transformation vector. Structure, 1996 Oct 15, 4(10), 1153 - 9 An alpha to beta conformational switch in EF-Tu; Abel K et al.; BACKGROUND: The bacterial elongation factor EF-Tu recognizes and transports aminoacyl-tRNAs to mRNA-programmed ribosomes . EF-Tu shares many structural and functional properties with other GTPases whose conformations are regulated by guanine nucleotides . RESULTS: An intact form of Escherichia coli EF-Tu complexed with GDP has been crystallized in the presence of the EF-Tu-specific antibiotic GE2270 A . The three-dimensional structure has been solved by X-ray diffraction analysis and refined to a final crystallographic R factor of 17.2% at a resolution of 2.5 A . The location of the GE2270 A antibiotic-binding site could not be identified . CONCLUSIONS: The structure of EF-Tu-GDP is nearly identical to that of a trypsin-modified form of EF-Tu-GDP, demonstrating conclusively that the protease treatment had not altered any essential structural features . The present structure represents the first view of an ordered Switch I region in EF-Tu-GDP and reveals similarities with two other GTPases complexed with GDP: Ran and ADP-ribosylation factor-1 . A comparison of the Switch I regions of the GTP and GDP forms of EF-Tu also reveals that a segment, six amino acids in length, completely converts from an alpha helix in the GTP complex to beta secondary structure in the GDP form . The alpha to beta switch in EF-Tu may represent a prototypical activation mechanism for other protein families. EMBO J, 1996 Oct 15, 15(20), 5726 - 36 Mof4-1 is an allele of the UPF1/IFS2 gene which affects both mRNA turnover and -1 ribosomal frameshifting efficiency; Cui Y et al.; The mof4-1 (maintenance of frame) allele in the yeast Saccharomyces cerevisiae was isolated as a chromosomal mutation that increased the efficiency of -1 ribosomal frameshifting at the L-A virus frameshift site and caused loss of M1, the satellite virus of L-A . Here, we demonstrate that strains harboring the mof4-1 allele inactivated the nonsense-mediated mRNA decay pathway . The MOF4 gene was shown to be allelic to UPF1, a gene whose product is involved in the nonsense-mediated mRNA decay pathway . Although cells harboring the mof4-1 allele of the UPF1 gene lose the M1 virus, mutations in other UPF genes involved in nonsense-mediated mRNA decay maintain the M1 virus . The mof4-1 strain is more sensitive to the aminoglycoside antibiotic paromomycin than a upf1 delta strain, and frameshifting efficiency increases in a mof4-1 strain grown in the presence of this drug . Further, the ifs1 and ifs2 alleles previously identified as mutations that enhance frameshifting were shown to be allelic to the UPF2 and UPF1 genes, respectively, and both ifs strains maintained M1 . These results indicate that mof4-1 is a unique allele of the UPF1 gene and that the gene product of the mof4-1 allele affects both -1 ribosomal frameshifting and mRNA turnover. EMBO J, 1996 Oct 15, 15(20), 5647 - 58 Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities; McKercher SR et al.; PU.1 is a member of the ets family of transcription factors and is expressed exclusively in cells of the hematopoietic lineage . Mice homozygous for a disruption in the PU.1 DNA binding domain are born alive but die of severe septicemia within 48 h . The analysis of these neonates revealed a lack of mature macrophages, neutrophils, B cells and T cells, although erythrocytes and megakaryocytes were present . The absence of lymphoid commitment and development in null mice was not absolute, since mice maintained on antibiotics began to develop normal appearing T cells 3-5 days after birth . In contrast, mature B cells remained undetectable in these older mice . Within the myeloid lineage, despite a lack of macrophages in the older antibiotic-treated animals, a few cells with the characteristics of neutrophils began to appear by day 3 . While the PU.1 protein appears not to be essential for myeloid and lymphoid lineage commitment, it is absolutely required for the normal differentiation of B cells and macrophages. Proc Natl Acad Sci U S A, 1996 Oct 15, 93(21), 11487 - 92 Structure and function in rhodopsin: high level expression of a synthetic bovine opsin gene and its mutants in stable mammalian cell lines; Reeves PJ et al.; Stable mammalian cell lines harboring a synthetic bovine opsin gene have been derived from the suspension-adapted HEK293 cell line . The opsin gene is under the control of the immediate-early cytomegalovirus promoter/enhancer in an expression vector that also contains a selectable marker (Neo) governed by a relatively weak promoter . The cell lines expressing the opsin gene at high levels are selected by growth in the presence of high concentrations of the antibiotic geneticin . Under the conditions used for cell growth in suspension, opsin is produced at saturated culture levels of more than 2 mg/liter . After reconstitution with 11-cis-retinal, rhodopsin is purified to homogeneity in a single step by immunoaffinity column chromatography . Rhodopsin thus prepared (> 90% recovery at concentrations of up to 15 microM) is indistinguishable from rhodopsin purified from bovine rod outer segments by the following criteria: (i) UV/Vis absorption spectra in the dark and after photobleaching and the rate of metarhodopsin II decay, (ii) initial rates of transducin activation, and (iii) the rate of phosphorylation by rhodopsin kinase . Although mammalian cell opsin migrates slower than rod outer segment opsin on SDS/polyacrylamide gels, presumably due to a different N-glycosylation pattern, their mobilities after deglycosylation are identical . This method has enabled the preparation of several site-specific mutants of bovine opsin in comparable amounts. Cancer Res, 1996 Oct 15, 56(20), 4735 - 42 Gene-directed enzyme prodrug therapy with a mustard prodrug/carboxypeptidase G2 combination; Marais R et al.; The gene for the bacterial enzyme carboxypeptidase G2 (CPG2) was expressed internally in mammalian cells . Mammalian-expressed CPG2 had kinetic properties indistinguishable from bacterially expressed CPG2 . Human tumor cell lines A2780, SK-OV-3 (ovarian adenocarcinomas), LS174T, and WiDr (colon carcinomas) were engineered to express constitutively either CPG2 or bacterial beta-galactosidase . These cell lines were subjected to a gene-directed enzyme prodrug therapy regime, using the prodrug 4-{(2-chloroethyl)(2-mesyloxyethyl)amino}benzoyl-L-glutamic acid (CMDA) . The lines which expressed CPG2 had enhanced sensitivity to CMDA . Comparing IC50S, WiDr-CPG2 and SK-OV-3-CPG2 were 11-16-fold more sensitive, whereas A2780-CPG2 and LS174T-CPG2 were approximately 95-fold more sensitive than the corresponding control lines . CPG2-expressing cells and control cells were mixed in differing proportions and then treated with prodrug . Total kill occurred when only approximately 12% of cells expressed CPG2 with the WiDr and SK-OV-3 lines and when only 4-5% of cells expressed CPG2 with the LS174T and A2780 lines, indicating a substantial bystander effect . These results establish this CPG2 enzyme/CMDA prodrug system as an effective combination for the gene-directed enzyme prodrug therapy approach. J Biol Chem, 1996 Oct 11, 271(41), 25604 - 10 Mechanism responsible for oligomycin-induced occlusion of Na+ within Na/K-ATPase; Arato-Oshima T et al.; The mechanism whereby oligomycin occludes Na+ within Na/K-ATPase was investigated to study Na+ and K+ transport mechanisms . Oligomycin stimulated Na+ binding to Na/K-ATPase but inhibited Na-K and Na-Na exchange . The oligomycin concentration required to stimulate Na+ binding to half-maximal was 4.5 microM, which was close to the concentration that reduced Na-Na and Na-K exchange and ATPase activity to half-maximal, suggesting that Na/K-ATPase possesses an oligomycin binding site responsible for stimulating Na+ binding and reducing ion exchange and ATPase activity . In contrast, neither K+ binding nor K+ transport was affected by oligomycin . Limited tryptic digestion of Na/K-ATPase showed that, unlike Na+, K+, and ouabain, oligomycin treatment did not result in a specific digestion pattern . Oligomycin appeared to inhibit ouabain binding in a noncompetitive manner, whereas it did not affect ATP binding . Na/K-ATPase isoforms with low and high sensitivities to ouabain were equally sensitive to oligomycin . These results suggest that the oligomycin binding site is located on the extracellular side of Na/K-ATPase, at a different position from the ouabain binding site, and this antibiotic did not induce a conformational change of Na/K-ATPase . We propose that oligomycin interacts with the Na+ occlusion site from the extracellular side of Na/K-ATPase, which delays Na+ release to the extracellular side without inducing a conformational change, suggesting that the pathways responsible for Na+ and K+ transport differ. Biochemistry, 1996 Oct 8, 35(40), 13240 - 9 Physical and biological characteristics of the antitumor drug actinomycin D analogues derivatized at N-methyl-L-valine residues; Takusagawa F et al.; The crystal structure of the DNA-actinomycin D (AMD) complex and a simple molecular modeling study indicated that AMD analogues derivatized at N-methyl-L-valine residues (fifth amino acid residue in the cyclic depsipeptide of AMD) could bind to DNA as strongly as the parent AMD . The analogues in which N-methyl-L-valine residues were replaced with L- and D-forms of N-methylvalines, N-methylthreonines, N-methylphenylalanies, N-methyltyrosines, and N-methyl-O-methyltyrosines have been totally synthesized . The characteristics of binding of the analogues to various DNAs including DNA-1 {d(TATATATGCATATATA)}, DNA-2 {d(TATATACGCGTATATA)}, DNA-3 {d(ATATATAGCTATATAT)}, and DNA-4 {d(ATATATGGCCATATAT)} have been examined by using visible absorption spectrum methods . The association constants calculated from the absorption spectra indicate that the modifications of the N-methyl-L-valine residues in the AMD molecule do affect the DNA binding characteristics of the analogues . The L-aromatic analogues bind slightly better than the L-aliphatic analogues except for binding to DNA-1 (-TGCA-), whereas the D-aliphatic analogues bind consistently better than the D-aromatic analogues . In the L-form analogues, the L-Tyr analogue has the highest overall association constant, whereas the D-Val analogue has the highest association constant among the D-form analogues . In spite of substitution of bulky aromatic groups, the D-aromatic analogues bind to the DNA-1 quite well . However, D-aromatic analogues have significantly reduced their binding capacities to the other DNAs, indicating that the substitution of the D-aromatic residues creates a unique four-base sequence preference (-TGCA-) . The RNA polymerase inhibitory activities of the AMD analogues in vivo have been examined using human cells (HeLa) . All AMD analogues except for the L-Thr analogues severely inhibit RNA synthesis at relatively low drug concentrations . The D-Val, L-OMT, L-Phe, and D-Phe analogues inhibit RNA synthesis more strongly than the natural antibiotic (AMD itself). Ugeskr Laeger, 1996 Oct 7, 158(41), 5749 - 53 {Risk factors of surgical wound infection}; Bay-Nielsen M; The risk of developing a surgical wound infection depends on the balance between factors determining the number of bacteria contaminating the wound and factors determining the resistance of the wound against infection . Some of these factors are responsive to interventive strategies, aiming at lowering the frequency of surgical wound infection . It has been shown, that the use of prophylactic antibiotics and ultraclean-air operation room techniques are beneficial in certain types of surgery, while the use of blood transfusion increases the risk of wound infection . Evidence suggests that the use of laparoscopic techniques in abdominal surgery will decrease the risk of infection . Research in immunological factors and hypoxia have not yet contributed any clinically applicable types of prophylactic strategies. J Mol Biol, 1996 Oct 4, 262(4), 421 - 36 RNA sequence determinants for aminoglycoside binding to an A-site rRNA model oligonucleotide; Recht MI et al.; The codon-anticodon interaction on the ribosome occurs in the A site of the 30 S subunit . Aminoglycoside antibiotics, which bind to ribosomal RNA in the A site, cause misreading of the genetic code and inhibit translocation . Biochemical studies and nuclear magnetic resonance spectroscopy were used to characterize the interaction between the aminoglycoside antibiotic paromomycin and a small model oligonucleotide that mimics the A site of Escherichia coli 16 S ribosomal RNA . Upon chemical modification, the RNA oligonucleotide exhibits an accessibility pattern similar to that of 16 S rRNA in the 30 S subunit . In addition, the oligonucleotide binds specifically aminoglycoside antibiotics . The antibiotic binding site forms an asymmetric internal loop, caused by non-canonical base-pairs . Nucleotides that are important for binding of paromomycin were identified by performing quantitative footprinting on oligonucleotide sequence variants and include the C1407.G1494 base-pair, and A.U base-pair at positions 1410/1490, and nucleotides A1408, A1493 and U1495 . The asymmetry of the internal loop, which requires the presence of a nucleotide in position 1492, is also crucial for antibiotic binding . Introduction into the oligonucleotide of base changes that are known to confer aminoglycoside resistance in 16 S rRNA result in weaker binding of paromomycin to the oligonucleotide . Oligonucleotides homologous to eukaryotic rRNA sequences show reduced binding of paromomycin, suggesting a physical origin for the species-specific action of aminoglycosides. Ginekol Pol, 1996 Oct, 67(10), 526 - 8 {Obstruction of biliary tracts in infants}; Zajadacz B et al.; Three cases with the biliary tracts obstruction in infants are reported . Similar early clinical symptoms were subsequently distinguished by the serious of the diagnostic examinations . That allowed for undertaking proper treatment . The prognosis in congenital biliary tract obstruction depends on the child's age time of the operation and in the cases of the inflammatory ethiology depends on the proper antibiotic therapy. Trop Gastroenterol, 1996 Oct-Dec, 17(4), 230 - 2 Risk factors for wound infection following elective cholecystectomy; Chandrashekhar C et al.; A study of risk factors for wound infection among patients undergoing elective cholecystectomy was undertaken . Over a 2-Year period 177 patients who underwent elective cholecystectomy for symptomatic gall stone disease were randomized into groups, one receiving antibiotics (96 patients) and the other not receiving antibiotics (81 patients) . Gall bladder bile and wound swab were cultured to detect bacterial growth . Duration of preoperative hospital stay, type of skin incision and operating time were noted for each patient . Postoperatively wound infection developed in 22/177 (12%) patients . The infection rate was lower in the antibiotic group 3/96 (3%) as compared to the non-antibiotic group 19/81 (23.5%) . Wound sepsis occurred in 11/37 (23%) of patients with bactibilia as compared to 11/140 (7.8%) patients with sterile bile . Stepwise logistic regression analysis showed that bactibilia and use of prophylactic antibiotics were the most significant predictors of wound infection in low risk patients undergoing elective cholecystectomy. Neurotoxicology, 1996 Fall-Winter, 17(3-4), 883 - 95 Selective neurotoxicity induced by the ionophore lasalocid in rat dissociated cerebral cultures, involvement of the NMDA receptor/channel; Safran N et al.; An in vitro model of dissociated cerebral cultures, prepared from prenatal 15-16-days rat fetuses, was used to further characterize the neurotoxic effects caused by the antibiotic ionophore lasalocid-X-537A . The damage caused by lasalocid (1-2 microM, 2-4 hr) included swelling of perikarya, followed by cytolysis of most neurons present in the cultures . The neuronal damage was dose-dependent, noticeable at concentrations above 0.5 microM, and was more pronounced in established cultures (14 days in vitro-DIV) than in younger ones (7 DIV) . Unlike neurons, no damage was observed in glia and other non-neuronal cells present in the cultures by exposure to 2 microM lasalocid . Moreover, the drug was not toxic for cultures of rat astrocytes and C6 glioma cells . Another calcium ionophore A-23187 (calcimycin, 1 microM), destroyed both neuronal and non-neuronal cells within 1 hr . Ca2+ influx was increased by 140% in cultures exposed to lasalocid (1.5 microM) . The lasalocid neurotoxic effects were neither inhibited by 10 microM nimodipine (a calcium channel antagonist) nor by 10 microM 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX)(a non-N-methyl-D-aspartic acid (NMDA) receptor antagonist), but were exclusively blocked by 10 microM MK-801 (a non-competitive NMDA receptor/channel antagonist) . The neurotoxicity induced by lasalocid was further confirmed by measurements of lactate dehydrogenase (LDH) released into the media . Lasalocid (1.5 microM) induced the release of both LDH and arachidonic acid (AA) (by 8 and 4 fold of control values, respectively), and this was blocked by MK-801 but not by CNQX . These results are in according with the observations that activation of calcium influx through the NMDA receptor leads to activation of phospholipase A2 (PLA2) and release of AA . In contrast, MK-801 did not block the release of either LDH or AA mediated by the calcium ionophore A-23187 (1 microM) in these cultures . {3H}-MK-801 binding to washed rat cortical membranes, a measure of direct interaction with the NMDA receptor/channel complex, was not affected by lasalocid either alone or in the presence of glutamate and glycine . {3H}-D-aspartate release, a measure of excitatory amino acid (EAA) secretion mediated by NMDA receptor activation, was increased by lasalocid and could be blocked by MK-801 . These observations suggest that lasalocid induces selective neurotoxicity, which involves the NMDA receptor/channel complex, possibly indirectly, resulted in elevated intracellular Ca2+ levels and the subsequent glutamate or aspartate release. Indian J Exp Biol, 1996 Oct, 34(10), 949 - 53 Effect of nalidixic acid on recombination and DNA repair of Escherichia coli K-12 strains; Inan S et al.; Bacterial DNA gyrase enzyme plays a role in replication, transcription, recombination and repair . Escherichia coli gyrase enzyme is composed of two types of subunit, the gyr A and gyr B gene products called subunit A and B . Each type of subunit can be inhibited with temperature-sensitive mutations or by treating cells with specific antibiotic . Quinolones class of drugs such as nalidixic acid, oxonilic acid and norfloxacin affect gyr A protein . This effect due to inactivation of gyrase arises from the change in DNA superhelical tension . Mutant bacteria resistant to nalidixic acid show structural alterations in subunit A . Nalidixic acid resistant mutants of E . coli strains showed lower recombination efficiency, linkage, DNA repair, and mutation frequency than their wild types. Radiologe, 1996 Oct, 36(10), 805 - 12 {Diagnostic imaging in osteomyelitis . Characteristics in childhood}; Wandl-Vergesslich KA et al.; The prognosis of acute hematogenous osteomyelitis in children is mainly influenced by early diagnosis and prompt initiation of antibiotic and surgical therapy . In this age group, two forms of manifestation are differentiated: osteomyelitis in infants up to 18 months and juvenile osteomyelitis until the closure of the epiphyseal plate . Osteomyelitis in infants is often accompanied by septic arthritis of the adjacent joint . In juvenile osteomyelitis, the disease is mostly confined to the metaphysis . Plain films and ultrasonography represent the basic imaging modalities . Depending on the age of the child, the clinical course of the disease and the availability of the various methods, MRI and multiphase bone scintigraphy can be performed for further imaging . CT is of only limited value and should only be used for special cases concerning chronic osteomyelitis. Sangre (Barc), 1996 Oct, 41(5), 395 - 7 {Fungal infections in leukemic patients: our experience during 5 years}; Torre MA et al.; The use of high-dose chemotherapy and the subsequent prolonged neutropenia in patients with haematological diseases have resulted in an increased incidence of fungal infections . These infections are associated with a high mortality rate . There are several predisposing factors including broad-spectrum antibiotic, central venous access . Diagnosis remains difficult . Characteristic clinical manifestations are not constant and they appear only after neutrophil recovery . Responsible organisms are infrequently isolated . The use of invasive procedures is far from being justified in patients who suffering usual severe thrombocytopenia . The unique drug with proven efficiency in the treatment of fungal infections is amphotericin B or liposomal amphotericin B . A favourable outcome strongly correlated with complete leukemia remission . We describe our findings in seven leukemic patients with fungal infections. Clin Podiatr Med Surg, 1996 Oct, 13(4), 701 - 24 Update on the diagnosis and management of osteomyelitis; Mader JT et al.; Osteomyelitis can be classified by duration, pathogenesis, location, extent, and host status . Bone infections are currently classified by the Waldvogel or the Cierny-Mader classification . Because the Waldvogel classification is an etiologic system and the Cierny-Mader classification is descriptive, both classifications can be simultaneously used . The Cierny-Mader classification is based on the anatomy of the bone infection and the physiology of the host . Cierny-Mader staging allows stratification of long bone osteomyelitis and the development of comprehensive treatment guidelines for each stage . Current trends in long bone osteomyelitis therapy emphasize early diagnosis and aggressive treatment . Radiographs and bone cultures are the mainstays of diagnosis . Imaging with radionuclide scans, computerized tomography, and magnetic resonance imaging are used when the diagnosis of osteomyelitis is equivocal or to help guage the extent bone and soft tissue infection . Surgical treatment involves debridement of necrotic bone and tissue, obtaining appropriate cultures, managing dead space, and, when necessary, obtaining bone stability . Medical therapy includes improving any host deficiencies, initial antibiotic selection, and antibiotic modification based on culture results . Antibiotic delivery has expanded to include effective oral agents and local therapy with antibiotics mixed in polymethylmethacrylate . Cierny-Mader staging was developed to describe long bone osteomyelitis . This staging system has to be modified to describe diabetic foot osteomyelitis and vertebral osteomyelitis . Osteomyelitis in patients with diabetes mellitus involves the bones of the feet or ankles . The vascular and neurologic status of the patient must be carefully accessed . Patients may be managed with local debridement surgery or ablative surgery plus 2 to 4 weeks of antibiotic therapy depending on whether all of the osteomyelitis is surgically removed . If the patient does not wish surgery or is not a surgical candidate, suppressive antibiotic therapy can be used . Vertebral osteomyelitis is usually hematogenous in origin . The diagnosis is made by bone cultures, histology, and radiographs . Magnetic resonance imaging and technetium scans are useful in making the diagnosis and in gauging the extent of the bone and soft tissue infection . Therapy requires parenteral antibiotic therapy and may include early surgery and stabilization . The choice of an antibiotic therapy is guided by the bone biopsy or debridement culture results. Rinsho Shinkeigaku, 1996 Oct, 36(10), 1179 - 82 {A case of paranasal sinusitis-cavernous sinusitis with ophthalmoplegia externa}; Nagata A et al.; A 15-year-old man was admitted because of diplopia and bilateral ptosis which occurred a few days after initial clinical signs, such as fever up, nausea, vomiting and headache . His pupils were anisocoric (Rt . phi 3.5 mm < Lt . phi 6.0 mm) . In his left eye, light reflex was absent and its movements were limited in all directions . Brain MRI revealed the findings of paranasal sinusitis in bilateral ethmoidal and sphenoidal sinuses and swelling of bilateral cavernous sinus . Combination of intravenous antibiotic therapy and drainage improved his clinical symptoms and MRI findings . It was diagnosed as the inflammation originated in the sphenoid and ethmoid sinuses, which extended to the cavernous sinus and then involved III, IV, and VI cranial nerves . In conclusion, MRI was very useful to detect the cavernous sinusitis secondary to sphenoidal sinusitis. Minerva Med, 1996 Oct, 87(10), 475 - 8 {Unusual case of acute suppurative thyroiditis}; Gimondo P et al.; Acute suppurative thyroiditis is an acute disease of the thyroid gland . In this paper the authors report a case of acute suppurative thyroiditis complicated by abscessual evolution in an addict patient study with ultra-sonography and treated with fine needle aspiration and antibiotic therapy . The patient reached our observation for a swelling of the neck . Ultrasonography showed diffuse hypoechogenicity in both thyroid lobes and mixed nodule with hyperechoic trabeculas inside . This nodule underwent fine needle aspiration (FNA) for cytologic and cultural evaluation . Diagnosis was acute suppurative thyroiditis . Ultrasonography presented features similar to other thyroid pathology (sub-acute thyroiditis, haemorrhagic cyst, thyroid lymphoma and anaplastic carcinoma) . In our case none of the ultrasonographic features were diagnostic except hyperechoic trabeculas inside . Ultrasonographic features of acute suppurative thyroiditis are very rare in the literature . Ultrasonography and fine needle aspiration are the only methods that confirm this diagnosis. West J Med, 1996 Oct, 165(4), 215 - 20 Prognosis and treatment of burns; Mann R et al.; Survival rates for burn patients in general have improved markedly over the past several decades . The development of topical antibiotic therapy for burn wounds, the institution of the practice of early excision and grafting, and major advances in intensive care management have all contributed to this success . In this review we address these 3 important advances in the modern treatment of burn injuries and provide a brief historical overview of these accomplishments and others, emphasizing specific achievements of note and promises for the future . We also discuss 3 topics of interest to burn physicians, including the special problems and high mortality of elderly burn patients, the disturbingly high mortality in burn patients with inhalation injury, and the possible use of artificial skin to facilitate rapid wound closure. West J Med, 1996 Oct, 165(4), 197 - 204 Sputum gram's stain in community-acquired pneumococcal pneumonia . A meta-analysis; Reed WW et al.; The usefulness of the sputum Gram's stain is controversial . This meta-analysis was designed to evaluate the sensitivity and specificity of the sputum Gram's stain in community-acquired pneumococcal pneumonia . Using a predetermined protocol, articles were discovered through a MEDLINE search (1966 to 1993) and the examination of bibliographies and were graded for quality by three blinded reviewers . Information on the reference standard, blinding, stain interpreter, control for antibiotic use, and definition of a positive test was collected . We found 12 articles containing 17 test characteristics to evaluate . The number of patients in each study ranged from 16 to 404 . Sputum culture was the most common reference standard (10 of 17 estimations) . Sensitivity ranged from 15% to 100% and specificity from 11% to 100% . Test characteristics varied markedly among studies and appeared related partly to the test interpreter . The sputum Gram's stain may yield misleading results in community-acquired pneumonia, as its sensitivity and specificity vary substantially in different settings . A practitioner electing to use the study should be well trained and use a specific definition for a positive test. Int J Parasitol, 1996 Oct, 26(10), 1111 - 4 Freeze-fracture cytochemistry of membrane cholesterol in Blastocystis hominis; Yoshikawa H et al.; Membrane cholesterol in Blastocystis hominis was detected by freeze-fracture methods using a polyene antibiotic, filipin . Since the intramembrane particles (IMP) were distributed heterogeneously on both plasma and vacuole membranes, many IMP-free areas were observed . Even in filipin-treated cells, filipin-cholesterol complexes were not detected in IMP-free areas on the plasma membrane, whereas on the central vacuole membrane the complexes were mainly observed in IMP-free regions . These results indicate the different organization of the membrane cholesterol between the plasma membrane and central vacuole membrane . Most of the granules in the central vacuole were densely labeled with filipin, indicating the accumulation of cholesterol in the vacuole. Br J Ophthalmol, 1996 Oct, 80(10), 911 - 4 Temporary corneal stem cell dysfunction after radiation therapy; Fujishima H et al.; BACKGROUND: Radiation therapy can cause corneal and conjunctival abnormalities that sometimes require surgical treatment . Corneal stem cell dysfunction is described, which recovered after the cessation of radiation . METHODS: A 44-year-old man developed a corneal epithelial abnormality associated with conjunctival and corneal inflammation following radiation therapy for maxillary cancer . He experienced ocular pain and loss of vision followed by conjunctival epithelialisation of the upper and lower parts of the cornea . RESULTS: Examination of brush cytology samples showed goblet cells in the upper and lower parts of the cornea, which showed increased fluorescein permeability, and intraepithelial lymphocytes . Impression cytology showed goblet cells in the same part of the cornea . Specular microscopy revealed spindle type epithelial cells . Patient follow up included artificial tears and an antibiotic ophthalmic ointment . The corneal abnormalities resolved after 4 months with improved visual acuity without any surgical intervention, but the disappearance of the palisades of Vogt did not recover at 1 year after radiation . CONCLUSION: Radiation therapy in this patient caused temporary stem cell dysfunction which resulted in conjunctivalisation in a part of the cornea . Although limbal stem cell function did not fully recover, this rare case suggested that medical options should be considered before surgery. J Protein Chem, 1996 Oct, 15(7), 607 - 19 Tet repressor-tetracycline interaction; Kaszycki P et al.; Previous studies {Wasylewski et al . (1996), J . Protein Chem . 15, 45-58} have shown that the W43 residue localized within the helix-turn-helix structure domain of Tet repressor can exist in the ground state in two conformational states . In this paper we investigate the fluorescence properties of W43 of TetR upon binding of tetracycline inducer and its chemical analogs such as anhydro- and epitetracycline . Binding of the drug inducer to the protein indicates that the W43 residue still exists in two conformational states; however, its environment changes drastically, as can be judged by the changes in fluorescence parameters . The FQRS (fluorescence-quenching-resolved spectra) method was used to decompose the total emission spectrum . The resolved spectra exhibit maxima of fluorescence at 346 and 332 nm and the component quenchable by KI (346 nm) is shifted 9 nm toward the blue side of the spectrum upon inducer binding . The observed shift does not result from the changes in the exposure of W43, since the bimolecular quenching rate constant remains the same and is equal to about 2.7 x 10(9) M-1 sec-1 . The binding of tetracycline leads to drastic decrease of the W43 fluorescence intensity and increase of the tetracycline intensity as well as the decrease of fluorescence lifetime, especially of the W43 component characterized by the emission at 332 nm . The observed energy transfer from W43 to tetracycline is more efficient for the state characterized by the fluorescence emission at 332 nm (88%) than for the component quenchable by iodide (53%) . Tetracycline and several of its derivatives were also used to observe how chemical modifications of the hydrophilic groups in tetracycline influence the mechanism of binding of the antibiotic to Tet repressor . By use of pulsed-laser photoacoustic spectroscopy it is shown that the binding of tetracyclines to Tet repressor leads to significant increase of tetracycline fluorescence quantum yields . Steady-state fluorescence quenching of tetracycline analogs in complexes with Tet repressor using potassium iodide as a quencher allowed us to determine the dependence of the exposure of bound antibiotic on the modifications of hydrophilic substituents of tetracycline . Circular dichroism studies of the TetR-{Mg.tc}+ complex do not indicate dramatic changes in the secondary structure of the protein; however, the observed small decrease in the TetR helicity may occur due to partial unfolding of the DNA recognition helix of the protein . The observed changes may play an important role in the process of induction in which tetracycline binding results in the loss of specific DNA binding. Schweiz Rundsch Med Prax, 1996 Oct 1, 85(40), 1258 - 60 {Infections of the lower airways}; Russi EW; Lower airway infections are very common . A distinction should be made between acute tracheobronchitis, exacerbation of chronic bronchitis and pneumonia, since prognosis and therapy of these diseases are different . Community-acquired pneumonia has to be treated without delay by an antibiotic which is efficient against pneumococci. Nihon Rinsho Meneki Gakkai Kaishi, 1996 Oct, 19(5), 498 - 504 {Drug induced hemolytic anemia associated with agranulocytosis}; Satoh S et al.; A 27-year-old female was admitted to a hospital because of severe anemia (hemoglobin 4.9 g/dl) after taking PL (a drug for common cold consisted of Salicylamide, Acetaminophen, Caffeine and Promethazine methylene di-salicylate) and Cefadroxil (an oral antibiotic) for ten days . History and laboratory data leaded to a diagnosis of drug induced hemolytic anemia . 6 units of concentrated red blood cells were transfused and the suspected drugs were discontinued immediately . Though resolution of anemia and no further hemolysis were observed, progressive leukocytopenia developed since four days after the admission . Bone marrow aspiration revealed marked decrease of granulocytic series . The patient was transferred to our hospital and was isolated under laminar air-flow to prevent her from bacterial and fungal infections . She was treated with prednisolone and granulocyte-colony stimulating factor . She recovered from leukocytopenia in two weeks without suffering from any life-threatening infection . We extensively analyzed the suspected drugs and mechanism of hemolysis and granulocytopenia . Cefadroxil is turned out to be contributed to hemolysis by an immune complex mechanism . Cefadroxil and Salicylamide were suggested to be involved in granulocytopenia by the induction of antibodies against the leukocytes to which these drugs were bound . Thus Cefadroxil was regarded as a causative drug of both hemolysis and granulocytopenia . This case is of interest for analyzing drug-induced blood abnormality because it is very rare that two lineage of blood were injured by one drug at the same time as far as we know. Br J Surg, 1996 Oct, 83(10), 1413 - 4 Conservative management of infective mastitis and breast abscesses after ultrasonographic assessment; O'Hara RJ et al.; Current practice in this unit for a suspected breast abscess is preliminary ultrasonographic scan, aspiration of any pus, antibiotic therapy and repeat aspiration in the outpatient clinic if necessary . Inflammatory masses are treated with antibiotics alone . A retrospective review of this strategy has been made . Over a 2-year interval 53 patients were admitted to hospital with a suspected breast abscess . Twenty-two abscesses were aspirated, of which 19 resolved and three required subsequent incision and drainage . Eight patients underwent primary incision and drainage, one of whom required a second drainage procedure . In five patients the abscess discharged spontaneously before intervention . The remaining 18 patients were found on ultrasonography to have inflammation without evidence of focal pus which settled with antibiotic therapy in all but two patients . One of these was found to have an inflammatory cancer and the other developed an abscess, which was drained . Aspiration combined with ultrasonographic imaging is an effective alternative to incision and drainage. J Clin Pathol, 1996 Oct, 49(10), 857 - 8 Ocular spherulocystosis; Kini U et al.; Spherulocystosis (myospherulosis), a rare entity, is characterised by histopathological changes of sac-like refractile structures in soft tissue and presents clinically as an inflammatory lesion . It is caused by trauma or is induced iatrogenically by the topical application of fat based ointments . A case of myospherulosis confined to the region of the lacrimal caruncle, which developed soon after topical antibiotic application for suspected conjunctivitis, in a 49 year old woman is reported . Though this lesion is uncommon, this report illustrates the importance of recognising this condition to avoid confusion with and treatment for fungal infection. J Cardiovasc Surg (Torino), 1996 Oct, 37(5), 505 - 9 Sternotomy infection with Mycoplasma hominis: a cause of "culture negative" wound infection; Mossad SB et al.; Wound infections with Mycoplasma species are unusual; diagnosis may be delayed because of the growth characteristics of this organism . We report Mycoplasma hominis infection of sternotomy wounds in two patients . The first presented with fever and drainage from the incision 1 week after coronary artery bypass grafting . The other patient presented with drainage from the incision three weeks after double-lung transplantation . In both cases, initial cultures were negative, but the typical colonial morphology of M . hominis was subsequently detected . Successful treatment consisted of debridement and long courses of antibiotic therapy; omental flap grafting was eventually required for the second patient . Other published cases were reviewed and compared with the newly reported cases. Nippon Kyobu Geka Gakkai Zasshi, 1996 Oct, 44(10), 1840 - 6 {Mitral reconstruction in patients with infective endocarditis}; Mizuno T et al.; Between June 1992 and October 1993, 5 patients with infective endocarditis in native mitral valve underwent open heart surgery . The patients ranged in age from 51 to 64 years and were all males . According to NYHA functional classification, 4 patients were class II and one was class III . Surgery was indicated because of hemodynamic deterioration (2 pts), echocardiographic mobile vegetation with or without previous emboli (2 pts) and both condition (1 pt) . Before surgery the patients were afebrile and had negative serum CRP and negative blood cultures for at least one week after adequate medical treatment . The leaflet lesions found in the 5 patients were vegetation (2 pts), perforation (1 pt), calcification (1 pt) and thickening (2 pts) . The chordal lesions found were rupture (5 pts) and thickening (1 pt) . The infective lesions did not extend to the annulus . The mitral leaflets, including all apparently infectious lesions, were resected in a V-shaped fashion and then valve reconstruction was performed . The resected parts were sutured together with anchoring chordae . The annuloplasty with Teflon-tapes was also added . Postoperatively, all 5 patients showed a dramatic improvement in hemodynamics and endocarditis did not recur during 22 to 38 months of follow-up . The patients who received the repair did not require Warfarin . This study shows that mitral valve repair is an acceptable operation in patients with infective endocarditis, giving the patients better quality of life than mitral valve replacement when (1) infectious lesion are limited to mitral leaflet and chordae, (2) there is no severe calcification of the mitral valve, (3) the infection is healed by the adequate antibiotic therapy. J Craniomaxillofac Surg, 1996 Oct, 24(5), 263 - 70 Perioperative morbidity in maxillofacial orthopaedic surgery: a retrospective study; Van de Perre JP et al.; The data of 2049 patients, who underwent maxillofacial orthopaedic surgery, were retrospectively analysed for major intra- and immediate postoperative complications . Immediate life-threatening complications were very rare . They can in most cases be avoided by good anaesthetic and surgical techniques and adequate postoperative care . The most frequently encountered problem in maxillary surgery is excessive blood loss, whilst a compromised airway due to swelling is the most frequent complication in mandibular surgery . Good co-operation between anaesthetist and surgeon is essential to prevent major intraoperative and immediate postoperative problems. Clin Otolaryngol, 1996 Oct, 21(5), 393 - 5 Facial palsy in acute otitis media; Ellefsen B et al.; During the 17-year period from 1977 to 1994 a total of 23 patients in Copenhagen County were admitted to hospital with facial palsy, developed during acute otitis media . This corresponds to an annual incidence of 2.3 per million inhabitants . In the pre-antibiotic era it was estimated that 0.5% of patients with acute otitis media developed facial palsy . Our figures indicate a decrease of this complication by a factor of 100, to 0.005% . Although fourteen of the patients were children, the risk of an acute otitis media being complicated by facial palsy seems to be highest in adults (who have a low incidence of acute otitis media) . All the children were < or = 3 years of age and 2/3 of the adults > or = 50 years of age . Complete remission was seen in all patients, except one . The time interval to complete remission was correlated significantly with the degree of the facial palsy on admission, as it was longest in the most severe facial palsies. Intensive Care Med, 1996 Oct, 22 Suppl 4, S462 - 7 Interferon gamma in trauma-related infections; Dries DJ; OBJECTIVE: The efficacy of interferon gamma therapy in reducing infection and improving outcome from infection in patients sustaining major injury was examined . DESIGN: Randomized double-blind placebo control trial SETTING: Nine level one university affiliated trauma centers in the United States . PATIENTS AND PARTICIPANTS: Four hundred sixteen patients with injury severity score (ISS) > or = 25 or ISS > or = 20 with evidence of wound contamination . INTERVENTION: Recombinant human interferon gamma 100 ug or placebo was given subcutaneously daily for up to 21 days in addition to standard antibiotic