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J Laryngol Otol, 1997 Aug, 111(8), 766 - 8
Patient with primary tonsillar and gastric syphilis; Ishimaru T et al.; A male patient with syphilitic lesions in the tonsil and stomach is presented . The patient was infected while practising oral sex with heterosexual friends . He complained of nausea and snoring; his left tonsil was enlarged . Spirochetes were detected in a smear preparation from the left tonsil . As a gastric lesion, initially believed to be cancer, appeared to result from spirochete ingestion, the case is considered to represent primary syphilis . After antibiotic therapy with ampicillin, the left tonsil returned to normal size and gastric changes were no longer evident endoscopically . Gastroscopy should be considered if syphilis of the tonsil is observed, particularly when gastrointestinal symptoms are present . Both the oral and the gastric lesion can be mistaken for malignant neoplasm.

Thorax, 1997 Aug, 52(8), 702 - 8
Optimal treatment of descending necrotising mediastinitis; Corsten MJ et al.; BACKGROUND: Descending necrotising mediastinitis is caused by downward spread of neck infection and has a high fatality rate of 31% . The seriousness of this infection is caused by the absence of barriers in the contiguous fascial planes of neck and mediastinum . METHODS: The recent successful treatment of seven adult patients with descending necrotising mediastinitis emphasises the importance of optimal early drainage of both neck and mediastinum and prolonged antibiotic therapy . The case is also presented of a child with descending necrotising mediastinitis, demonstrating the rapidity with which the infection can develop and lead to death . Twenty four case reports and 12 series of adult patients with descending necrotising mediastinitis published since 1970 were reviewed with meta-analysis . In each case of confirmed descending necrotising mediastinitis the method of surgical drainage (cervical, mediastinal, or none) and the survival outcome (discharge home or death) were noted . The chi 2 test of statistical significance was used to detect a difference between cases treated with cervical drainage alone and cases where mediastinal drainage was added . RESULTS: Cervical drainage alone was often insufficient to control the infection with a fatality rate of 47% compared with 19% when mediastinal drainage was added (p < 0.05) . CONCLUSIONS: Early combined drainage with neck and chest incisions, together with broad spectrum intravenous antibiotics, should be considered standard care for this disease.

Chest, 1997 Oct, 112(4), 1130 - 2
Bronchopleural fistula and lymphocytic empyema due to Histoplasma capsulatum; Richardson JV et al.; A patient presented with chest pain, fever, and chills and developed a large pleural effusion while receiving antibiotic therapy . On a CT scan of the chest, multiple loculi of fluid were noted, and at surgery, a complex empyema with an associated bronchopleural fistula related to a granulomatous process in the lower lobe of the right lung was demonstrated . Cultures revealed Histoplasma capsulatum in the pleural fluid as well as in the pulmonary parenchymal process.

Clin Cardiol, 1997 Oct, 20(10), 829 - 36
Chronic infection in the etiology of atherosclerosis--the case for Chlamydia pneumoniae; Gupta S et al.; Established cardiovascular risk factors do not fully explain the variations in the prevalence and severity of coronary heart disease . Recent evidence suggests that common chronic infections may contribute, either by direct or indirect mechanisms, to the etiology and/or progression of coronary atherosclerosis . Of the candidate infectious agents implicated, Chlamydia pneumoniae has emerged as the most likely pathogen to have a causal role . Evidence for this is based on seroepidemiologic, pathologic, and laboratory-based evidence, in addition to recent small-scale antibiotic intervention studies . Concerted efforts are now focused on the design of large prospective trials with antibiotics active against C . pneumoniae in the secondary prevention of coronary heart disease.

Am J Surg, 1997 Oct, 174(4), 422 - 4
Preventing infection of the incision after appendectomy by using metronidazole preoperatively to infiltrate tissues at the incision; Shubing W et al.; METHODS: From January 1991 to July 1995, 260 patients with acute appendicitis were operated on . After excluding 21 patients, the remaining 239 cases were randomly divided into two groups . Group A was given the treatment and group B was the control group . Precisely 0.915 g metronidazole disodium phosphate injection (Tongzhen Pharmaceutical Co., Shan Xi Province, P . R . China) or 25% metronidazole glucose solution was added to 100 mL 0.9% normal saline . After anesthetizing the patients in group A, 60 to 80 mL of the solution was injected into the subcutaneous tissue and muscle . The control group B was given intravenous injection of metronidazole disodium phosphate and cephazolin postoperatively . RESULTS: In the 119 cases in group A, the rate of incision infection was 0.8% . By contrast, the rate of infection among the 120 cases in group B was 11.6% . The statistical analysis (chi square) was significant, with P < 0.001 showing that preincisional or intraincisional infiltration with metronidazole was effective.

Br J Nurs, 1997 Aug 14-Sep 10, 6(15), 846 - 8, 850, 852 passim
Infection control and related issues in intravascular therapy; Vost J et al.; The use of Intravascular (i.v.) catheters has become an increasingly common practice in today's healthcare setting . This increase, however, brings associated problems . An overview of the current literature surrounding i.v . devices and infection control issues was undertaken . This included: the pathogenesis of infection with reference to local and systemic complications; the importance of handwashing; the influence of catheter material and type on infection rates; the controversy over skin preparation and whether it is best to use povidone-iodine, chlorhexidine or an antibiotic ointment; insertion techniques; the duration of line placement; the dilemma over the choice of dressing, i.e . gauze vs transparent; nurses' responsibilities in relation to the UKCC standards and professional accountability; safety issues; and the main principles surrounding the safe disposal of sharps . To conclude, this overview finds that all healthcare professionals must be held accountable for every aspect of i.v . therapy, including the control of infection.

Klin Monatsbl Augenheilkd, 1997 Jun, 210(6), 402 - 4
{Endophthalmitis after intra-oral block of the infraorbital nerve}; Weinand FS et al.; BACKGROUND: Most penetrating needle puncture injuries occur in retro- or peribulbar anesthesia . Hereby only a small percentage of patients develop endophthalmitis . Ocular penetration after enoral infraorbital nerve block has not yet been reported in literature . HISTORY AND FINDINGS: In June 1995 a 74-year-old man presented with a fulminant fibrinous and purulent endophthalmitis . Because he suffers from trigeminal neuralgia his anesthesiologist performed an infraorbital nerve block from enoral two days ago . During this procedure the patient felt a sharp ocular pain . THERAPY AND OUTCOME: We suspected an ocular penetration and performed a vitrectomy with intravitreal antibiotic instillation on the admission-day . A needle penetration site near the inferior rectus muscle was detected and after exocryocoagulation a 5 mm wide radial buckle was sutured over penetration site . Three months postoperatively vision recovered from hand moving to 20/50 and all infiltrations had been disappeared . Only preexisting cataract prevented a better vision . 10 months later after successful cataract extraction with intraocular lens implantation patient left hospital with a vision of 20/30 . CONCLUSION: Careful anamnesis would have prevented this accidental globe penetration . Right upper palate is absent presumably due to congenital cleft malformation or surgery . This allowed needle penetration through smooth tissue into the right globe . Fortunately, endophthalmitis develops only in a small percentage after needle puncture . We recommend immediate pars-plana-vitrectomy and intravitreal antibiotics in case of endophthalmitis after ocular penetration.

Ann Ital Med Int, 1997 Apr-Jun, 12(2), 63 - 6
{Pancreatitis caused by Cryptosporidium parvum in patients with severe immunodeficiency related to HIV infection}; Calzetti C et al.; Up to the present, pancreatic complications due to cryptosporidium parvum infection have been described only in a few patients with acquired immunodeficiency syndrome (AIDS) . We report our experience with 3 subjects with AIDS who presented with acute or chronic pancreatitis related to cryptosporidiosis . All 3 patients had abdominal pain resistant to analgesics, increased serum amylase and abnormalities at both sonography and computed tomography . Endoscopic retrograde cholangiopancreotography revealed papillary stenosis in all patients; one patient also had stenosis of the Wirsung duct . Cryptosporidium was found in both bile and stool samples in all patients, while viral cultures were negative, even in the 2 patients who had cytomegalovirus retinitis . Endoscopic sphincterotomy temporally relieved abdominal pain in all patients, but did not prevent either acute or recurrent pancreatic inflammation . Several antibiotic therapeutic protocols were ineffective against the parasite.

Gene, 1997 Sep 15, 197(1-2), 83 - 9
Improved EBV-based shuttle vector system: dicistronic mRNA couples the synthesis of the Epstein-Barr nuclear antigen-1 protein to neomycin resistance; Ramage AD et al.; Use of EBV-based vector systems has been limited by the requirement to generate EBNA+ cells which are 'permissive' for replication of an oriP-vector . In current constructs, selectable marker and EBNA-1 are not always co-expressed . This is a significant problem since the EBNA-1 gene product can be toxic in some cell types and may be selected against . In this paper, we describe a gene construct that overcomes this limitation . We have exploited the piconaviral internal ribosome entry site to allow the genes for Epstein-Barr nuclear antigen-1 and G-418 resistance to be transcribed as a dicistronic fusion mRNA under the control of the phosphoglucokinase promoter . This construct can be routinely integrated into human cell lines . The presence of EBNA-1 protein was reflected by a large increase in transfection frequencies (1000-fold) using an oriP-based vector which was shown to replicate stably in these cells with no apparent gross rearrangements detected after 8 weeks in culture . Using this system, G-418 resistance should directly reflect integration, as well as expression of the EBNA-1 gene, which, in turn, increases transfection frequencies and stability of EBV-based vector systems and should result in its increased use.

Mol Pharmacol, 1997 Oct, 52(4), 560 - 70
Molecular properties of amphotericin B membrane channel: a molecular dynamics simulation; Baginski M et al.; Amphotericin B is a powerful but toxic antifungal antibiotic that is used to treat systemic infections . It forms ionic membrane channels in fungal cells . These antibiotic/sterol channels are responsible for the leakage of ions, which causes cell destruction . The detailed molecular properties and structure of amphotericin B channels are still unknown . In the current study, two molecular dynamic simulations were performed of a particular model of amphotericin B/cholesterol channel . The water and phospholipid environment were included in our simulations, and the results obtained were compared with available experimental data . It was found that it is mainly the hydrogen bonding interactions that keep the channel stable in its open form . Our study also revealed the important role of the intermolecular interactions among the hydroxyl, amino, and carboxyl groups of the channel-forming molecules; in particular, some hydroxyl groups stand out as new "hot spots" that are potentially useful for chemotherapeutic investigations . Our results also help to clarify why certain antibiotic derivatives, with a blocked amino group, are less active . We present a hypothesis for the role of membrane lipids and cholesterol in the channel.

Gene, 1997 Sep 1, 196(1-2), 187 - 9
A new retroviral vector, CA1, to identify and select for cells expressing an inserted gene in vitro and in vivo; Abram CL et al.; A new retroviral vector has been constructed that expresses genes encoding three different activities from a single transcript . This feature has been exploited to enable the efficient marking and selection of cells that express a gene of interest . The marker gene lacZ, encoding beta-galactosidase, and neo, encoding neomycin phosphotransferase, for selection by the antibiotic G418, are expressed as a fusion, beta Geo . The expression of beta Geo is coordinated with expression of a gene of interest at the mRNA level using an Internal Ribosome Entry Site (IRES) from the Encephalomyocarditis Virus (EMCV) . The IRES promotes cap-independent initiation of translation therefore two reading frames can be translated from a single transcript . In vitro, the vector has been shown to confer beta-galactosidase activity, transformation by v-src and resistance to G418, following infection of cells . To show that the retrovirus was able to mark infected cells in vivo, cells infected with the retrovirus were transplanted into mouse mammary gland where they grew and were successfully located by staining for beta-galactosidase over 2 months after transplantation.

Aust N Z J Surg, 1997 Oct, 67(10), 689 - 91
Leg wound infections associated with coronary revascularization; Wong SW et al.; BACKGROUND: Wound infections after saphenous vein harvest for coronary revascularization are common but they are infrequently examined . The aim of the present study was to investigate the risk factors for infection and the possible beneficial effects of saline lavage . METHODS: From April 1996 to July 1996, 152 consecutive patients who underwent saphenous vein harvest for coronary artery bypass graft were recruited . Factors that may influence infection rates were analysed . RESULTS: A total of 22 of the 125 (18%) patients included in the present study developed a wound infection . The length of the wound was the only variable found to have a statistically significant association with wound infection . In the analysis of patients with multiple leg wounds, the development of infection correlated with the absence of mechanical wash-out . CONCLUSION: The use of saline lavage may prevent wound infections by diluting the bacterial population prior to closure . The use of antiseptic or antibiotic lavage may offer an additional benefit.

Enzyme Microb Technol, 1997 Oct, 21(5), 314 - 20
Response surface analysis of chlortetracycline and tetracycline production with K-carrageenan immobilized Streptomyces aureofaciens; Asanza Teruel ML et al.; A full-factorial experimental design at three levels with two independent variables, carrageenan concentration (1.0, 1.5, and 2.0%) and potassium chloride concentration (0.3, 0.7, and 1.1 M) was studied in order to analyze the effect of both factors on the antibiotic production of K-carrageenan-immobilized mycelia of Streptomyces aureofaciens . The response surfaces obtained have indicated that both carrageenan and potassium chloride concentrations have a pronounced effect on the yield of chlortetracycline (CTC) and tetracycline (TC) produced by S . aureofaciens . By exclusively varying the immobilization conditions, the tetracycline production can be enhanced more than eight times (12.3 mg g-1 biomass for immobilized cells vs . 1.5 mg g-1 biomass for free cells) in comparison with free-cell mycelial cultures.

J Hosp Infect, 1997 Sep, 37(1), 55 - 64
Amoxycillin/clavulanic acid prophylaxis in elective colorectal surgery: a prospective randomized trial; Mosimann F et al.; In a randomized trial of 440 patients undergoing elective colorectal surgery, the prophylactic efficacy and the safety of amoxycillin/clavulanic acid were compared with that of a control regimen of clindamycin and gentamicin . Surgical wound healing was assessed by the ASEPSIS points scale; it was normal in 86% of patients and the scores for both groups were not statistically different (amoxycillin/clavulanic acid: 11.1; clindamycin + gentamicin: 10.9) . Intra-abdominal infections were more frequent in the clindamycin + gentamicin arm of the study (Fisher's exact test, P = 0.035) . It is concluded that amoxycillin/clavulanic acid is as effective and safe as clindamycin + gentamicin in the prevention of wound infection and may provide better protection against intra-abdominal infections.

Am J Gastroenterol, 1997 Sep, 92(9), 1492 - 5
Prevalence of serum antibodies to Helicobacter pylori and to CagA protein in liver transplant recipients; Rudi J et al.; OBJECTIVE: To study Helicobacter pylori seroepidemiology before and after orthotopic liver transplantation . METHODS: Serum samples obtained from 118 liver transplant recipients before and after transplantation were examined for the presence of IgG antibodies to H . pylori whole cell extract and to the CagA protein of H . pylori . RESULTS: Of 118 patients, 64 (54.2%) were H . pylori positive, and 36 (56.3%) of these had CagA antibodies . Of the 64 seropositive patients, 22 (34.4%) remained positive and 42 (65.6%) became negative for H . pylori antibodies a median of 39 months after transplantation . Patients who seroreverted showed a tendency to lower pretransplantation antibody levels and had received antibiotic therapy for at least 4 days . Seroreversion or antibody persistence was not affected by age, sex, CagA antibody status, CagA antibody titer, duration of antibiotic therapy, or immunosuppressive drugs administered after liver transplantation . CONCLUSIONS: The prevalence of H . pylori infection, as detected by serological screening, in patients selected for liver transplantation is not different from that in the general population . In these patients, the seroprevalence of H . pylori drops after liver transplantation . This is largely due to the intake of antibiotics and immunosuppressants by transplant recipients . Seroreversion seems to be independent of the type of H . pylori bacteria.

J Clin Microbiol, 1997 Oct, 35(10), 2546 - 50
Laboratory investigation of enteroaggregative Escherichia coli O untypeable:H10 associated with a massive outbreak of gastrointestinal illness; Itoh Y et al.; A massive outbreak of gastrointestinal illness occurred in Tajimi city, Gifu prefecture, in June of 1993 in which 2,697 children in elementary and junior high schools developed severe diarrhea . Stool specimens from 30 children with severe protracted diarrhea were studied . Twenty-seven strains of enteroaggregative Escherichia coli (EAggEC) isolated from 12 of 30 patients all belonged to the same serotype, O untypeable (OUT):H10, and showed the same biochemical characteristics and antibiotic susceptibility pattern . These strains were negative for the virulence factors of the four standard categories of diarrheagenic E . coli (enterotoxigenic, enteropathogenic, enteroinvasive, and enterohemorrhagic) . However, the isolates showed an aggregative pattern of adherence to HEp-2 cells and had a 60-MDa plasmid and an astA gene, which encodes heat-stable enterotoxin-1 production . These data suggested that the EAggEC serotype OUT:H10 was associated with this massive outbreak of gastrointestinal illness.

Am J Physiol, 1997 Sep, 273(3 Pt 1), L612 - 7
Integrin activation protects pulmonary endothelial cells from the genotoxic effects of bleomycin; Hoyt DG et al.; Integrin activation promotes the survival of endothelial cells undergoing diverse forms of stress . Here we determined the ability of integrins to inhibit DNA strand breakage by bleomycin (BLM), a DNA-cleaving antitumor antibiotic that causes acute endothelial injury and subsequent pulmonary fibrosis . We found that BLM produced DNA breakage in cultured murine lung endothelial cells (MLEC) within 45 min of treatment as measured by DNA sedimentation and in situ labeling of 3'-OH by nick translation (ISNT) . Two hours after the removal of BLM, we found a marked but incomplete reduction in DNA strand breakage as measured by ISNT, indicating that the damage was reversible . DNA sedimentation and ISNT demonstrated that strand breakage due to BLM was inhibited in MLEC cultured on fibronectin, and no evidence of breakage was found 2 h after removal of the drug in ISNT experiments . Gelatin, type IV collagen, laminin, and the integrin ligand peptide Gly-Arg-Gly-Asp-Ser-Pro, but not the inactive Gly-Arg-Ala-Asp-Ser-Pro peptide, also inhibited DNA strand breakage . Activation of integrins, either by coating surfaces with antibodies to alpha 5-, beta 1-, or beta 3-integrin subunits or by receptor clustering with the soluble antibodies, inhibited BLM-induced DNA breakage . Inhibition of BLM-induced DNA strand breakage by soluble beta 1-integrin antibody increased with increasing antibody concentration and duration of receptor clustering before BLM treatment . Thus integrin activation protects pulmonary endothelial cells from the genotoxic effects of BLM.

Trop Doct, 1997 Oct, 27(4), 222 - 6
A 1-day survey of drug prescribing patterns in the District General Hospital of the Wassa West District of Ghana; Bosu WK et al.; A 1-day prevalence survey of the drug prescribing patterns for 45 in-patients of the Tarkwa Government Hospital was undertaken in November 1995 . An average of 3.6 drugs were prescribed per patient . The commonest prescribed drugs were paracetamol, chloroquine, amoxycillin, gentamicin and ampicillin . Of 162 drug items prescribed, 93.2% were on the national Essential Drugs List (EDL) and 61.1% were prescribed by their generic names . Over 60% of the patients received one or more injectable drugs or antibiotics . The use of injectable drugs on the wards ranged from nil on the male surgical ward to 90.9% on the male medical ward . The most frequently prescribed injectable drugs were gentamicin, ampicillin, chloroquine, benzylpenicillin, dextrose and pethidine . The main indications for antibiotic use were post-Caesarean delivery, pneumonia, accidents, abscesses and meningitis . The findings provide the basis for monitoring drug prescribing patterns and for evaluating any interventions to improve prescribing behaviour and the treatment of diseases.

J Antibiot (Tokyo), 1997 Aug, 50(8), 671 - 6
Borrelidin is an angiogenesis inhibitor; disruption of angiogenic capillary vessels in a rat aorta matrix culture model; Wakabayashi T et al.; Borrelidin, an antibiotic from Streptomyces rochei, was found to be an angiogenesis inhibitor in a rat aorta matrix culture model which forms capillary vessels in vitro . Borrelidin strongly inhibited capillary tube formation with a 50%-inhibitory concentration value of 0.8 nM, and decreased the number of capillary tubes within 24 hours when added after maturation of tube formation . Borrelidin remarkably disrupted capillary tubes in a dose-dependent manner, by inducing apoptosis of the tube-forming cells.

Clin Infect Dis, 1997 Sep, 25(3), 608 - 13
Candidal mediastinitis: an emerging clinical entity; Clancy CJ et al.; Candidal mediastinitis is rare . We report nine cases encountered at our institutions since 1985; seven cases were diagnosed since 1993 . All cases followed thoracic surgery, with a median time from surgery to disease onset of 11 days (range, 6-100 days) . All patients received prior antibiotic therapy . Common clinical manifestations were chest wall erythema in 4 cases (44%), drainage in 5 (56%), fever in 4 (44%), and sternal instability in 4 (44%) . Failure to obtain appropriate intraoperative specimens for cultures and the dismissal of cultures positive for Candida as contaminants delayed diagnosis in three cases (33%) . Mediastinitis was complicated by contiguous or hematogenous spread in seven cases (78%); five patients (56%) had two or more complications . The mortality rate was 56% . Optimal therapy remains undefined, but on the basis of our experience, aggressive surgical debridement combined with antifungal therapy for at least 6 weeks is recommended . Prompt recognition and institution of therapy appear to be the keys to improving prognosis.

Bone Marrow Transplant, 1997 Sep, 20(6), 431 - 4
High-dose chemotherapy followed by autologous blood cell transplantation: a safe and effective outpatient approach; Gluck S et al.; High-dose chemotherapy (HDCT) followed by autologous blood cell (ABC) transplantation has been used widely for patients with metastatic breast cancer (MBC) . It has been shown by our group and others to be an effective means of achieving very high response rates including complete remission . Therefore, further reduction in toxicity and increased patient satisfaction is necessary . Fifty-three patients with MBC were enrolled in a feasibility study at our cancer centre with a three-step approach to outpatient observation after HDCT and ABC transplantation discharging our patients from hospital 6 days after reinfusion of ABC, 1 day after reinfusion of ABC and 1 day prior to reinfusion of ABC . The supportive care consisted of the use of 5-HT3 antagonists for nausea and vomiting, DMSO depletion, through body hygiene, prophylactic antibiotic, antifungal and virustatic drugs . In the event of febrile neutropenia, a standard evaluation and treatment was used . Only 22 patients were admitted for febrile neutropenia and two for haemorrhage . The median hospital stay was 2 days (range 1-7) . The time to engraftment, need for transfusion and other toxicities were not different in patients who stayed entirely as outpatients . No toxic deaths occurred . In conclusion, HDCT followed by ABC transplantation can be safely administered to patients in the clinic with outpatient post-transplant observation.

Biol Neonate, 1997, 72(1), 28 - 31
Antinociception induced by verapamil and chloramphenicol in mice; Yildiran G et al.; The analgesic effects of verapamil, a calcium channel blocker, and chloramphenicol, a phenicolated antibiotic, were compared using the test of acetic-acid-induced writhing and the hot-plate test in mice . The results suggest that both drugs have antinociceptive properties comparable to salicylate analgesia . No significant difference was found between verapamil- and chloramphenicol-induced analgesia (p < 0.05).

Rev Clin Esp, 1997 Aug, 197(8), 560 - 3
{Animal bites . Study of 606 cases}; Knobel Freud H et al.; BACKGROUND: There is scarce information on animal bites in Spain . The objective of this study was to know the incidence, characteristics of the bitten persons, characteristics of biting animals, location of wounds and therapeutic behavior in our environment . PATIENTS AND METHODS: Descriptive study of patients who visited a rabies service after having been bitten by animals . Study period: from March, 1st, 1995, to February, 29th, 1996 . During the study period 606 patients were visited and 2,400 telephone consultations answered . RESULTS: The incidence was 100 animal bites per 100,000 inhabitants/year . The male/female distribution of attended patients was 347/251 (47.3 vs 42.7%, respectively), a mean age of 32.5 +/- 21 years; 25% of cases were aged less than 15 years . The offending animals were: dogs 450 (74.3%), cats 97 (16%), rats 32 (5.3%), hamsters 16 (2.6%) and other animals 11 (1.8%) . In 52.8% of cases the offending animals were owned by the bitten persons or domestic; in children 64.2% of cases were animals with these characteristics (p < 0.007); in this group of patients the rabies vaccination was correct in 61% of dogs and 40% of cats . The hand was the most frequent location of the wound, although face and neck locations were not uncommon in children (13.2%) compared with adults (4.4%) (p < 0.0002) . The therapeutic behavior includes antitetanic prophylaxis in virtually all cases; antibiotic therapy was inappropriate in 44.4 of cases; a correct diversion towards the rabies service occurred in 42.4% of cases . The post-exposition rabies vaccine was administered in 218 patients, with a rate of 7.3/100,000 inhabitants/year . CONCLUSIONS: In the Barcelona province area animal bites are relatively common; in general populations preventive measures and health education are required, particularly among domestic animal owners, as well as health care personnel on the proper behavior when faced with animal bites.

Dtsch Tierarztl Wochenschr, 1997 Jul, 104(7), 254 - 6
{Chemical-physical risks originating from dead animals or animal products for the health of humans and animals and for the environment}; Klein W; On-farm burial of dead stock principally may lead to an exclusively local contamination of groundwater by nitrogen species and dissolved organic matter . This definitively is a local risk, the size of which, however, depends on the amounts of dead animals buried and the hydrogeological conditions of the site . Emission mitigation by rendering companies has resulted in emissions, which do not present a hazard to humans, animals and the environment . The valuable recycling products contain ubiquitous pollutants in minor concentration not resulting in a effective relevant risk . The role which recycling in rendering plays, as regards redispersion of pollutants and active ingredients, also is very low for the chemicals which have been assessed so far . The role of veterinary medicinal drugs, however, especially of antibiotics for the risk in the environment needs attention.

Dermatology, 1997, 195 Suppl 1, 10 - 4; discussion 38-40
How cost-effective is oral isotretinoin?
Newton JN.
PURPOSE: To consider whether oral isotretinoin (Roaccutane/Accutane) represents good value compared with typical alternative treatments for moderate or severe acne . PROCEDURES: Published reports were reviewed on the comparative effectiveness of oral isotretinoin and its alternatives and on their relative costs . RESULTS: Observational studies of clinical and patient-assessed outcomes suggest that oral isotretinoin is much more effective than available alternatives . The costs of treatment with isotretinoin are greater in the first year, but substantial cost savings accrue in subsequent years . CONCLUSIONS: Isotretinoin is more cost-effective than long-term antibiotic therapy mainly because of its greater efficacy but also because of long-term cost savings . MESSAGE: The costs and benefits of alternative treatments for acne should be assessed over a period of at least 2 years, preferably longer . The higher initial cost of oral isotretinoin should not be a barrier to its use where the drug is clinically indicated.

Blood, 1997 Sep 15, 90(6), 2273 - 81
Clonal variability in beta-globin mRNA content in an interleukin-3-dependent bone marrow cell line transfected with the erythropoietin receptor before and after stimulation with erythropoietin; Ishiguro K et al.; Unexpected clonal variability was observed in the content of beta-globin mRNA in erythropoietin receptor (EpoR)-transfected Ba/F3 cells before and after exposure to erythropoietin (Epo) . Of 11 clones selected by virtue of G418 resistance and positive EpoR expression, 5 clones showed high levels of beta(major)-globin mRNA before Epo exposure, with subsequent Epo treatment causing little or no increase in globin mRNA . Five clones had undetectable levels of globin mRNA before Epo stimulation, and they did not accumulate globin mRNA when exposed to Epo, exhibiting resistance to the differentiation inducing action of Epo . Only one clone exhibited the expected phenotype, a low level of globin mRNA before exposure to Epo, and a significant Epo-dependent accumulation of globin mRNA . Phosphorylation of tyrosyl residues of the EpoR, Stat5, and JAK2 occurred upon Epo stimulation in clones representing each category . Furthermore, electrophoretic mobility shift assays using a Stat5 consensus sequence showed a difference in the nuclear binding component among these clones . These findings indicate that (1) the attainment of EpoR+ Ba/F3 clones with the anticipated sensitivity to both the growth and differentiation inducing actions of Epo is a rare event and (2) STAT5 transcription factors were differently activated by Epo in clones that differed in sensitivity to Epo.

Curr Genet, 1997 Jul, 32(1), 66 - 72
Transfer of an autonomously replicating vector between vegetatively incompatible biotypes of Colletotrichum gloeosporioides; Poplawski AM et al.; Previous research has indicated that biotypes A and B of Collectotrichum gloeosporioides that infect Stylosanthes spp . in Australia are asexual and vegetatively incompatible . Selectable marker genes conferring resistance either to hygromycin or phleomycin were introduced into isolates of these biotypes . Vectors conferring resistance to hygromycin and carrying telomeric sequences from Fusarium oxysporum replicated autonomously in C . gloesoporioides and gave frequencies of transformation 100-times higher than vectors that integrated into the genome . Monoconidial colonies resistant to both antibiotics were recovered when hygromycin-resistant biotype-A transformants carrying an autonomously replicating vector were paired in culture with a phleomycin-resistant biotype-B transformant carrying integrative vector sequences . Molecular analysis of double antibiotic-resistant progeny indicated that they contained the autonomous vector in a biotype-B genetic background . Results indicate that transfer of the autonomous vector had occurred from biotype A to biotype B, demonstrating the potential for transfer of genetic information between these biotypes.

Surgery, 1997 Sep, 122(3), 546 - 7
Toe amputation in the diabetic patient; Kerstein MD et al.; BACKGROUND: We considered whether it is more practical to amputate the toe of a diabetic patient with osteomyelitis and good circulation or to treat the patient with antibiotics for a prolonged period . METHODS: We undertook a retrospective study of 141 diabetic patients who had undergone a toe-ray amputation for proven or documented osteomyelitis . RESULTS: The mean ankle/brachial index of all patients was 0.81 (range, 0.68 to 1.14); the mean functional days lost on antibiotic therapy was 39 (range, 7 to 84 days) . The cost of 6 to 8 weeks of preoperative antibiotic therapy was $900 to $2240 (mean, $1440) . CONCLUSIONS: Diabetic patients with good circulation and osteomyelitis of the toe may benefit from prompt toe amputation.

Postgrad Med J, 1997 Aug, 73(862), 509 - 11
Sudden death in Whipple's disease; McGettigan P et al.; Despite antibiotic therapy, some patients with uncomplicated Whipple's disease die suddenly and inexplicably . We describe one such patient who died following unexplained cardiorespiratory arrest and was found to have chronic active myocarditis related to the causative organism . We postulate myocarditis as a cause of sudden death.

Microb Drug Resist, 1997 Fall, 3(3), 277 - 82
Effect of Mycobacterium avium infection on the influx, accumulation, and efflux of KRM-1648 by human macrophages; Bermudez LE et al.; KRM-1648 is a new benzoxazinorifamycin with activity in vitro and in vivo against organisms of the Mycobacterium avium complex . We investigated the ability of 14C-KRM-1648 to concentrate within human monocyte-derived macrophages in vitro . KRM-1648 is rapidly taken up by uninfected macrophages, with 90% of the initial concentration added to the monolayer found within macrophages by 1 h and approximately 80% at 2 h . Comparable results were obtained in assays using macrophages that have been infected with an AIDS-related strain of M . avium for 24 h . In contrast, macrophages infected with M . avium for 3 days, showed an impaired ability to concentrate KRM-1648, primarily because of a significant efflux of the antibiotic (intracellular concentration of 86% of the available drug was present within macrophages at 1 h vs . 47% at 2 h) . Daily administrations of KRM-1648 to a macrophage monolayer for 3 consecutive days resulted in significant accumulation of the drug within phagocytic cells . Although the efflux was greater in M . avium-infected macrophages than in uninfected cells, consecutive administration of KRM-1648 led to a total intracellular accumulation of drug that exceeded the initial level and appeared to continue to accumulate . The ability of KRM-1648 to rapidly accumulate in human macrophages, including M . avium-infected cells, may explain, in part, the improved therapeutic effectiveness in animal models against M . avium and M . tuberculosis.

Aliment Pharmacol Ther, 1997 Aug, 11(4), 705 - 10
Seven-day treatment for Helicobacter pylori infection: ranitidine bismuth citrate plus clarithromycin and tetracycline hydrochloride; Williams MP et al.; BACKGROUND: Dual therapy with ranitidine bismuth citrate plus clarithromycin twice daily for 14 days is an effective regimen for eradicating Helicobacter pylori infection . AIM: To determine whether this regimen can be improved by the addition of a second antibiotic, tetracycline hydrochloride, whilst reducing the duration of treatment to 7 days . METHODS: Sixty-one out-patients were enrolled to this open treatment study . All had H . pylori infection, as determined by 13C-urea breath test and, for those undergoing endoscopy, by rapid urease test . Patients were treated with ranitidine bismuth citrate 400 mg . clarithromycin 500 mg and tetracycline hydrochloride 500 mg all twice daily for 7 days . Eradication of H . pylori was assessed by two separate 13C-urea breath tests, the first 28-68 days after the completion of treatment, the second 28-162 days later . H . pylori infection was considered cured if both tests were negative . RESULTS: All 61 patients were included in the intention-to-treat efficacy analysis . Successful eradication of H . pylori was achieved in 55/61 patients (90%; 95% CI; 82-98%) . Fifty-nine out of sixty-one patients reported 100% compliance; one patient missed a single dose of medication and the other withdrew at 48 h due to nausea and vomiting . Minor adverse events were reported by 30/61 patients . CONCLUSION: One-week triple therapy with ranitidine bismuth citrate, clarithromycin and tetracycline, all twice daily, is a safe and well-tolerated regimen which eradicates H . pylori in 90% of infected patients.

J Biotechnol, 1997 Aug 11, 56(2), 115 - 28
Cloning and analysis of a peptide synthetase gene of the balhimycin producer Amycolatopsis mediterranei DSM5908 and development of a gene disruption/replacement system; Pelzer S et al.; A gene cloning system for Amycolatopsis mediterranei DSM5908, the producer of the glycopeptide antibiotic balhimycin, was developed for analysis of peptide synthetase genes . A modified direct transformation procedure was used to introduce DNA . The efficiency of DNA uptake depended on the age of the culture: mycelium of early stationary phase (52-55 h) cultures resulted in optimal transformation frequencies . Using the novel non-replicative integration vector pSP1, gene disruption plasmids were constructed . Highest integration frequencies were observed when the DNA was isolated from the dam/dcm Escherichia coli strain JM110 . The efficiency of integration depended directly on the size of the cloned insert . Plasmids with fragments smaller than 1 kilobase (kb) were difficult to integrate . In gene replacement experiments a high double cross-over rate (31%) was demonstrated . Oligonucleotides derived from conserved regions of peptide synthetases were designed to identify balhimycin biosynthesis genes . Using these gene probes in plaque hybridization experiments, we identified peptide synthetase homologous DNA fragments in a lambda library of A . mediterranei . One peptide synthetase gene fragment was characterized by DNA sequencing and the results revealed a complete amino acid activating domain of a peptide synthetase gene, designated aps . The disruption of aps neither influenced balhimycin biosynthesis nor generated another apparent phenotype.

J Eukaryot Microbiol, 1997 Sep-Oct, 44(5), 454 - 6
Heterogeneous distribution of membrane cholesterol at the attachment site of Cryptosporidium muris to host cells; Yoshikawa H et al.; Distribution of membrane cholesterol at the attachment site of Cryptosporidium muris was investigated by freeze-fracture cytochemistry using a polyene antibiotic filipin . Since the host plasma membrane enveloped C . muris, the inner and outer membranes were continuous with the parasite plasma membrane at the annular ring and with host membrane at the dense band, respectively . Although many filipin-cholesterol complexes were observed on the plasma membrane of host cells and parasites, a line showing no complexes was evident at the above two membrane junctures . These observations indicate that parasitic infection of C . muris altered the organization of membrane cholesterol.

Salud Publica Mex, 1997 May-Jun, 39(3), 207 - 16
{Ethnography of acute respiratory infections in a rural zone of Mexican highlands}; Martinez H et al.; OBJECTIVE: To identify the terms used by mothers to refer to diseases, signs and symptoms related to acute respiratory illnesses (ARI), alarming signs which should motivate them to seek medical attention, and to describe common home practices of disease care and treatment . MATERIAL AND METHODS: An ethnographic study was performed in six rural communities of the Mexican central highlands . Interviews were collected from 12 key informers, six mothers of children who had died from ARI and 24 mothers of children younger than five years of age, with several ethnographic techniques to complement information ("triangulation") . RESULTS: The most commonly identified diseases were cold, sore throat, cough, bronchitis, pneumonia and "bronchopneumonia" . Key signs to establish diagnosis included nasal discharge, sore throat, cough, head and body ache, fever . "bubbling" chest, general malaise and shortness of breath . Tachypnea was referred to as "strong breathing", "much breathing", "rapid breathing" or "sizzle"; intercostal depression as "the chest sinks", stridor as "chest moan or chest snore", sibilance as "chest snore" and cyanosis as "he turns purple" . Home treatments include herbal teas, lemon, green or red tomato or potato applied to the throat externally, as well as creams applied to chest or back . Antibiotic prescription was not common, contrary to antipyretics . Most mothers recognized mild illnesses: severe illnesses were recognized less frequently . When faced with a severe ARI, mothers sought attention firstly at the project clinic, second in frequency with a private physician in the capital of the province and then at the Health Ministry of the district . The reasons to choose these possibilities were mainly proximity and lower costs . CONCLUSIONS: This information can be useful to improve communication with mothers.

Z Geburtshilfe Neonatol, 1997 May-Jun, 201(3), 99 - 101
{Postpartum ovarian vein thrombosis}; Goretzlehner U et al.; An 28 years old women came on his 7 . post partum day with an lower abdominal pain on the right hand side with the diagnosis of an unilateral rotating ovarian tumor . After computed tomography, ultrasound and laparoscopy the adnectomia dextra by laparotomy was performed . In the histology we find an ovarian vein thrombosis . The following therapy was made with an therapeutic anticoagulation with heparin combined with an antibiotic therapy and later with an oral anticoagulation.

Ann Otol Rhinol Laryngol, 1997 Sep, 106(9), 759 - 66
Efficacy of sinus irrigation versus sinus irrigation followed by functional endoscopic sinus surgery; Hartog B et al.; Sinus irrigation is the traditional treatment for chronic maxillary sinusitis . Functional endoscopic sinus surgery (FESS) restores aeration and allows secretions to be removed from an infected sinus . This study compares the efficacy of sinus irrigation with that of sinus irrigation followed by FESS in 89 patients . We measured the effects by way of sinus radiographs, nasendoscopic findings, and patient complaints . When we analyzed the data in terms of intent to treat, we found significantly favorable results for sinus irrigation followed by FESS at the end point, though only for loss of smell and purulent rhinitis . Treatment consisting of sinus irrigation alone prevented surgery in 58% of all patients for 1 year . Both treatment methods were combined with a 10-day course of loracarbef, which might have contributed to the outcome . We conclude that a good option for treatment of chronic maxillary sinusitis seems to be sinus irrigation in combination with a broad-spectrum antibiotic followed by FESS.

Rev Saude Publica, 1996 Dec, 30(6), 527 - 35
{Use of medicines by children attending nursery schools}; Bricks LF et al.; In order to study the pattern of the use of medicines by children, 1,382 children seen at 15 of the 16 day-care centers of Pinheiros, S . Paulo city (SP) (Brasil), were followed-up for 2 months . Of these, 37% received 1,409 drugs . Average drug use was 50.9 medicines/100 children/month and the number of medicines used by each child ranged from 0 to 13 . Younger children (0-2 years) received more medicines and more frequently than older children; over 80% of the younger children received one or more medicines, and more than 20% received 5 or more medicines vs . less than 45% and 5%, respectively, in the group of children aged 2-7 years . The medications most frequently employed were anti-infective, respiratory medicines and antipyretics used by, respectively . 20.1%, 19.0% and 14.0% of the children studied (usually for respiratory problems) . Physicians prescribed 93% of medicines, but there were many inappropriate therapies for benign conditions, such as bronchitis and common colds . Antibiotic measure was observed (66%) including an excessive number of cloramphenicol prescriptions . Also, there were many prescriptions of doubtful value (decongestants, expectorants, vitamin and mineral supplements) and usage of as yet un approved medications for children (diclofenac, benzidamin, iodides).

Int J Cancer, 1997 Sep 4, 72(5), 865 - 70
Circumvention of glutathione-mediated mitomycin C resistance by a novel mitomycin C analogue, KW-2149; Ishida T et al.; A novel antitumor antibiotic 7-N-{2-{{2-(gamma-L-glutamylamino)ethyl}dithio}ethyl} mitomycin C (KW-2149), an analogue of mitomycin C (MMC), is activated by thiol molecules, such as glutathione (GSH) . To clarify the relationship between cellular GSH levels and the cytotoxicity of KW-2149, a murine fibroblast cell line (NIH/3T3) was transfected with human gamma-glutamylcysteine synthetase (gamma-GCS) cDNA, which codes a rate-limiting enzyme of GSH synthesis . Transfected cells (3T3/GCS) displayed increased gamma-GCS mRNA levels, gamma-GCS activity and GSH content, compared with NIH/3T3 cells . 3T3/GCS cells exhibited a 4.4-fold resistance to MMC, but not to KW-2149 (x 0.69), using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, suggesting that the increased cellular GSH levels did not affect the growth-inhibitory effect of KW-2149 . KW-2149 exerted a greater growth-inhibitory effect than MMC on cisplatin- and doxorubicin-resistant cells with cross-resistance to MMC . KW-2149 exhibited a greater growth inhibitory effect than MMC not only on cells with GSH-mediated MMC resistance but also on cells with acquired resistance . We thus conclude that KW-2149 might be a clinically useful drug.

Ann Vasc Surg, 1997 Sep, 11(5), 529 - 32
Infection of a chronically implanted iliac artery stent; Bunt TJ et al.; Pseudoaneurysm formation and infection at the site of iliac artery stenting are uncommon complications that occur soon after stent placement . We describe a case in which an infected pseudoaneurysm developed 22 months following stent implantation . Stent infection, although rare, has potentially disastrous implications, as made evident by a review of the literature . Prophylactic antibiotic therapy at the time of stent placement is recommended.

Anticancer Drugs, 1997 Jul, 8(6), 588 - 96
Phase I study with the DNA sequence-specific agent adozelesin; Burris HA et al.; Adozelesin, a synthetic analog of the antitumor antibiotic CC-1065, is a novel cytotoxic agent which inhibits DNA synthesis by binding to the minor groove of the DNA helix . Preclinical studies have shown a broad spectrum of activity against a variety of murine and human tumor xenograft models . We conducted a phase I study of adozelesin to (i) determine a recommended dose for phase II testing using a 10 min i.v . infusion, (ii) characterize the toxic effects of the drug using this schedule and (iii) document any antitumor activity observed . Adozelesin was administered as an i.v . infusion every 6 weeks . CBC and biological parameters were performed weekly . The starting dose of 10 microg/m2, corresponding to 1/30 the mouse equivalent lethal dose, was escalated, according to a modified Fibonacci scheme, until dose-limiting toxicity was encountered . Forty-seven adult patients with solid malignancies were entered in the study . Successive dose levels used were 10, 20, 33, 50, 70, 105, 120, 150 and 180 microg/m2 . The main toxic effect was myelosuppression, which was dose limiting . The maximally tolerated dose was defined as 180 microg/m2 . A minor response with a 4 month duration was reported in one previously treated patient with melanoma . We conclude that the recommended phase II dose of adozelesin given as a 10 min infusion is 150 microg/m2, repeated every 4 weeks.

J Cardiol, 1997 Aug, 30(2), 79 - 87
{Clinical analysis of infective endocarditis with aneurysmal formation of the mitral or aortic valve}; Kinoshita N et al.; Echocardiographic findings, clinical features, and pathophysiology of mitral and aortic valve aneurysms were evaluated in four patients with pathologically proven aneurysms of the mitral and/or aortic valves associated with infective endocarditis . These four were selected from 20 patients hospitalized in our institute from April 1990 to May 1995 because of infective endocarditis . All four patients had received repeated, inadequate antibiotic treatments at other medical institutions prior to admission, and underwent surgical repair because of acute hemodynamic exacerbation associated with aneurysmal perforation . Six aneurysms (three mitral and three aortic valve aneurysms) were detected before surgery, including two by transthoracic echocardiography and four by transesophageal echocardiography . The echocardiographic findings typical of aortic valve aneurysm were: ringed echo at the level of the aortic annulus in the short-axis view; turbulent flow within the ringed echo; and dome formation of the aortic valve that persisted throughout the cardiac cycle . All mitral valve aneurysms were true aneurysms without active inflammatory changes or significant destructive lesions, and were associated with severe infective aortic regurgitation . Histologic examination of the aortic valve in these patients showed active inflammation and extensive destruction, suggesting that these valves were the primary focus of infection . One patient had an aortic valve aneurysm without apparent mitral involvement, indicating that another mechanism had mediated aneurysmal formation . We conclude that: diagnosis of mitral or aortic valve aneurysms in patients with infective endocarditis has important therapeutic implications, and therefore, transesophageal echocardiographic examination should be done in such patients: there are three key echocardiographically diagnostic findings of aortic valve aneurysm as mentioned above; and several unknown factors may contribute to aneurysmal formation of the mitral or aortic valve in patients with infective endocarditis.

Pharm World Sci, 1997 Aug, 19(4), 202 - 7
Evaluation of drug use and cost of hospital care for AIDS patients between 1990 and 1994; Peyron F et al.; This study was designed to evaluate drug use and drug costs of treatment of 1112 AIDS patients at the Infectious Diseases Unit at F . Houphouet Boigny Hospital in Marseilles, France, between January 1, 1990 and December 31, 1994 . All drug expenditures directly or indirectly related to AIDS treatment were recorded for both inpatients and outpatients . There were 1952 hospital stays . For each stay baseline characteristics including age, sex risk factors, costs, and duration of hospitalization were noted . Patients were mainly young male drug addicts around thirty years of age . Reason for admission was also noted . The overall number of admissions per year has decreased since 1991 probably due to development of outpatient care . The number of stays per patient per year has decreased since 1993 because of the use of more appropriate therapeutic and prophylactic protocols . The number of drugs used was high increasing from 750 in 1990 to 868 in 1994 . Cost of treatment doubled between 1990 and 1994 due to the introduction of many expensive new drugs . Closer analysis showed that the greatest increase in expenditure involved 'antibiotic/antiviral', 'psychiatry/neurology' and 'specialized therapy' . Although not frequently prescribed, costly drugs such as immunoglobulins, hematopoietic growth factors, and parenteral nutrition solutions accounted for a high proportion of total costs . Since AZT, ddI and ddC were used mainly for outpatient treatment, their cost was low in inpatients . Cytomegalovirus-related retinitis, tuberculosis, and multiple infections were cost-intensive complications . The increasing number of cytomegalovirus infections underlines the need for cost evaluation and surveillance of this complication . This study demonstrates that cost of treating AIDS patients is rising due to the use of more and costlier drugs . This finding underlines the need to evaluate and compare new therapeutic modalities in terms of cost effectiveness.

Prikl Biokhim Mikrobiol, 1997 May-Jun, 33(3), 257 - 61
{Effect of the kinetic selectivity of eremomycin adsorption on the concentration of components in chromatographic bands}; Pisarev OA et al.; The adsorption dynamics of antibiotic eremomycin to structurally segregated carboxylic adsorbents was studied . It was shown that effects of the kinetic selectivity of adsorption lead to an additional narrowing of bands containing the component to be separated . This narrowing provides the possibility of superpurification of biologically active compounds by the "small shift" method of quasiequilibrium chromatography.

Clin Ter, 1996 Dec, 147(12), 621 - 6
{Rokitamycin tolerance in patients with adverse reactions to chemotherapeutic agents}; Cenci L et al.; The main task in the drug intolerance reactions is the choice of "alternative" drug by oral challenge . The tolerance of rokitamycine (RKM), a new macrolide with a wide activity spectrum in 133 antibiotic-intolerant patients has been studied by open oral challenge with incremental dosage until a cumulative dose of 406 mg . The RKM in 96.2% of cases has been well tolerated . Only 5 patients (3.8%) have had reactions, mainly "atypical" and of minor clinical importance, at cumulative doses ranging from 31.25 to 250 mg . The RKM has been well tolerated also by 6 patients who have had reactions to macrolides belonging to the same group (16 membered) . Finally, the use of RKM as alternative drug in chemotherapeutics-intolerant patients has been proposed.

Cesk Slov Oftalmol, 1997 Jun, 53(3), 155 - 67
{Mitomycin C in glaucoma filtering surgery}; Vasa M et al.; Authors evaluate application of mitomycin C (0.2-0.4 mg/ml) on the sclera during glaucoma filtering surgery . Mean follow-up was 19.5 months in the group of 67 patients (75 eyes) . The most serious complication was an early endophthalmitis in 2 cases with the loss of residual visual field and vision, 1x hemophthalmus followed with the development of traction retinal detachment, 1x hypotonic maculopathy, 1x traction retinal detachment for progression of proliferative vitreoretinopathy of neovascular glaucoma . Higher rate of the complications was noted in the group of mitomycin C 0.4 mg/l . Visual acuity was better one line Snellen optotypes in 3 cases, and worse in 26 cases . Intraocular pressure (IOP) compensation up to 20 mmHg was reached in 32 cases without therapy (45.1%), in 28 cases therapy, (39.6%) . IOP above 20 mmHg was in 11 cases (15.4%) and the data are not known in 4 cases (5.41%) . IOP was compensated after mitomycin C application in 84.7%.

J Oral Maxillofac Surg, 1997 Sep, 55(9), 941 - 5;discussion 945-6
A bioabsorbable poly-L-lactide miniplate and screw system for osteosynthesis in oral and maxillofacial surgery; Bessho K et al.; PURPOSE: The purpose of this study was to evaluate the usefulness of a bioabsorbable poly-L-lactide (PLLA) miniplate system for osteosynthesis . MATERIALS AND METHODS: Ultra-high-strength PLLA rods were fabricated using a drawing technique . This osteosynthesis system, consisting of bioabsorbable PLLA miniplates and screws, was used clinically on 50 patients . RESULTS: The only post operative complications were two cases of postoperative infection, but these were controlled by an oral antibiotic regimen or plate removal . Bone healing was satisfactory in all cases, without delay of bony union or obvious displacement of segments after surgery . CONCLUSION: The PLLA miniplates provided effective osteosynthesis of the maxillofacial skeleton.

J Cataract Refract Surg, 1997 Jul-Aug, 23(6), 889 - 93
Association between nonadministration of subconjunctival cefuroxime and postoperative endophthalmitis; Lehmann OJ et al.; PURPOSE: To determine whether not administering subconjunctival cefuroxime during cataract surgery is associated with postoperative endophthalmitis . SETTING: Southampton Eye Unit, Southampton General Hospital, England . METHODS: This retrospective, case-control study comprised nine patients who developed endophthalmitis after cataract surgery in a single ophthalmic unit over a 21 month period . Ten control patients for each case were randomly chosen from patients having cataract surgery within 1 week of the endophthalmitis case . RESULTS: None of the nine endophthalmitis patients received peroperative subconjunctival cefuroxime compared with 43 of 90 control patients (47.8%) (P = 0.008) . No other variables were found to be associated with development of endophthalmitis in this study . CONCLUSION: Nonadministration of subconjunctival cefuroxime was associated with subsequent endophthalmitis . A further study to determine whether the observed association is causal is therefore warranted.

Blood, 1997 Sep 1, 90(5), 2075 - 83
Induction of gamma-globin by histone deacetylase inhibitors; McCaffrey PG et al.; The short-chain fatty acid butyrate has been shown to elevate fetal hemoglobin (HbF) by inducing expression of the gamma-globin gene . Regulation of gene expression by butyrate is thought to proceed via inhibition of the enzyme histone deacetylase, leading to elevated levels of core histone acetylation which affect chromatin structure and transcription rates . To determine whether changes in histone acetylation are critical for the regulation of the gamma-globin gene, we tested three potent and specific inhibitors of histone deacetylase, the cyclic tetrapeptides trapoxin and Helminthsporium carbonum toxin (HC toxin), and the antifungal antibiotic trichostatin A for their ability to induce fetal hemoglobin expression in erythroid cells . These compounds induced fetal hemoglobin in both primary erythroid cell cultures and human erythroleukemia (K562) cells . A butyrate-responsive element spanning the duplicated CCAAT box region of the gamma-globin promoter has been identified in transient transfection assays using a reporter construct in K562 cells, and we show that the same promoter region is required for response to trapoxin and trichostatin . Mutational analysis of the gamma-globin promoter indicates that the distal CCAAT box and 3' flanking sequence (CCAATAGCC) is critical for activation by butyrate, trapoxin, and trichostatin, whereas the proximal element (CCAATAGTC) plays a less important role . These results show that inhibition of histone deacetylase can lead to transcriptional activation of gamma-globin promoter reporter gene constructs through proximal promoter elements, and suggest that butyrate induces gamma-globin expression via such changes in histone acetylation.

J Microencapsul, 1997 Sep-Oct, 14(5), 577 - 91
Sustained-release of oxytetracycline from chitosan microspheres prepared by interfacial acylation and spray hardening methods; Mi FL et al.; Chitosan microspheres containing oxytetracycline (OTC), an antibiotic agent, were prepared by spray hardening and interfacial acylation methods . The object of this study was to prepare oxytetracycline-containing microspheres for oral administration and injection using different molecular weight (Mw 70,000 approximately 2,000,000) of chitosan . By the spray hardening method, microspheres with particle sizes between 5 and 30 microns could be obtained and might be suitable for intramuscular injection . On the other hand, chitosan microspheres with the ability to extend the dissolution period of oxytetracycline in low pH medium were also prepared by the interfacial acylation method . The result indicated that the releasing of oxytetracycline from various acylated chitosan microspheres was decreased with increasing the molecular weight of chitosan and would show well sustained-release property . Besides, the morphology of various microspheres and crystalline form transition of oxytetracycline were also studied using electron scanning microscope and X-ray analysis.

J Clin Pharm Ther, 1997 Feb, 22(1), 21 - 5
Therapeutic drug monitoring of gentamicin: a 6-year follow-up audit; Ismail R et al.; BACKGROUND AND OBJECTIVE: In 1984 a therapeutic drug monitoring (TDM) service was established in Hospital Universiti Sains Malaysia (HUSM) and gentamicin concentrations were measured and used to design optimal regimens for the antibiotic . In this study we report on a 6-year follow-up audit since our first assessment of the service . METHOD: Records of 733 requests for gentamicin monitoring were reviewed . RESULTS: Of the 592 patients involved, 39% were neonates and 42% were adults . Peak gentamicin concentrations were within the therapeutic range in 65% of the patients at first monitoring and 79% of the corresponding trough concentrations were within the non-toxic range . After dosage adjustment, 81% of the peak concentrations were within the therapeutic range and trough concentrations rose to levels regarded as toxic in 7% of patients . In patients with therapeutic peak concentrations at the first monitoring point, the average duration of gentamicin therapy was statistically shorter than in those patients who failed to achieve a therapeutic peak concentration . The distribution of gentamicin peak and trough concentrations in terms of therapeutic ranges were also better than those found in 1990 . CONCLUSION: TDM for gentamicin is well accepted in HUSM and its application has contributed to improved gentamicin administration . Furthermore, our physicians are now able to choose more appropriate dosage regimens for their patients because the majority of gentamicin concentrations attained even at the first monitoring were within the therapeutic range.

J Laryngol Otol, 1997 Jan, 111(1), 77 - 9
Oral botryomycosis: a case report; Devaiah AK et al.; We present a 42-year-old male with botryomycosis initially presenting with left-sided proptosis due to an infraorbital mass . A biopsy through an anterior orbitotomy yielded indeterminate histopathology . The patient later developed a similar oral lesion which was biopsied and found to be botryomycosis . The oral lesion recurred after initial surgical treatment, but responded to antibiotic therapy . Discussion of this case along with a review of the literature is presented to offer guidelines for recognition and management of this rare disorder.

J Laryngol Otol, 1997 Jan, 111(1), 73 - 4
Peritonsillar abscess--an unusual presentation of Kawasaki disease; Ravi KV et al.; Kawasaki disease (KD) is a paediatric illness characterised by prolonged high fever, mucocutaneous lesions and lymphadenopathy . It is potentially fatal as coronary arteritis occurs in up to a third of affected children . We present a seven-year-old child who was admitted to hospital with neck pain and fever . Despite intravenous antibiotic therapy and a quinsy right tonsillectomy on the sixth day after admission, the patient's symptoms persisted . With the appearance of further signs and symptoms the diagnosis of KD was made two days after operation . The patient's symptoms resolved with aspirin and intravenous gammaglobulin therapy . A literature review of the various aspects of KD is presented.

Ann Allergy Asthma Immunol, 1997 Aug, 79(2), 119 - 24
Open trial of intravenous immune serum globulin for chronic sinusitis in children; Ramesh S et al.; BACKGROUND: Chronic sinusitis in children is a complex clinical problem . Some patients do not improve with medical therapy and some fail surgery as well . OBJECTIVE: A therapeutic trial of intravenous immune serum globulin (IVIG) was given to children whose sinus disease was recalcitrant to the usual therapeutic modalities . The objective of IVIG administration was to modulate the inflammatory process contributing to the chronicity of the sinusitis . METHODS: Six patients were given a 12-month trial of monthly (400 mg/kg) IVIG infusions . Entry criteria included persistence of sinusitis after 3 months of full course antibiotics, or two episodes of sinusitis within a 3-month period while on prophylactic antibiotics . All patients had abnormal sinus CT (computerized tomography) scans at entry . Three of the six patients remained symptomatic despite prior sinus surgery . Patients with primary immune deficiencies were excluded . Each patient served as his own control based on their previous 12-month history and clinical course . Four of the 6 patients were atopic as demonstrated by prick skin testing; however, all patients had nasal eosinophilia . RESULTS: Full course antibiotic use decreased in five of the six patients (183 to 84 days); correspondingly, the episodes of sinusitis decreased (average 9 to 4 per year) . In addition, sinus CT scans showed significant improvement . CONCLUSION: This preliminary open-trial of IVIG suggests its usefulness as adjunct therapy to medical management in selected patients with chronic sinus disease . The mechanism(s) by which IVIG may be helpful is probably not based on the concept of replacement therapy, but more likely as an immune or inflammatory modulating agent.

Am J Manag Care, 1997 Oct, 3(10), 1528 - 34
Evolving therapy for Helicobacter pylori infection: efficacy and economic impact in the treatment of patients with duodenal ulcer disease; Cutler AF et al.; Helicobacter pylori infection is present in most patients with duodenal ulcer disease, and cure of H pylori infection has been shown to dramatically reduce ulcer recurrence . Therapeutic strategies for duodenal ulcer disease have rapidly evolved over the past several years in an effort to consistently cure H pylori infection in a safe, cost-efficient manner . This paper reviews the effectiveness of treatments for H pylori infection in patients assessed with duodenal ulcer disease . The impact of clinical success on economic effectiveness has been determined in a recent prospective outcomes trial . Treatments with clarithromycin plus omeprazole or clarithromycin plus ranitidine-bismuth-citrate (RBC) provide consistent cure of H pylori infection, with eradication rates of 70% to 80% . Recent studies suggest that higher rates of eradication are possible with triple combination therapy (e.g., clarithromycin plus a second antibiotic and a proton pump inhibitor or RBC), but the optimal triple therapy regimen (including the combination of drugs, dosage, and duration of treatment) has not yet been defined . A recent 1-year prospective outcomes trial has demonstrated that eradication therapy with clarithromycin and omeprazole, compared with standard antisecretory therapy, provides measurable savings in utilization of ulcer-related health-care resources . Combination therapy with clarithromycin plus omeprazole, clarithromycin plus RBC, or clarithromycin plus lansoprazole and amoxicillin have been approved for the treatment of H pylori infection in patients with duodenal ulcer disease . Economic analysis has confirmed that cure of H pylori infection not only contributes to the clinical resolution of duodenal ulcer disease, but also provides economic advantages by reducing costs associated with recurrence.

J Bacteriol, 1997 Sep, 179(17), 5511 - 5
Environmental signals triggering methylenomycin production by Streptomyces coelicolor A3(2); Hayes A et al.; Methylenomycin production by Streptomyces coelicolor A3(2) may be triggered by either of two environmental signals: alanine growth-rate-limiting conditions and/or an acidic pH shock . The production of this SCP1-encoded antibiotic was studied by using batch and chemostat cultures . Batch cultures indicated a role for both nutritional status and culture pH in its regulation . Steady-state methylenomycin production and transcription of an mmy gene under alanine but not glucose growth-rate-limiting conditions was demonstrated in chemostat culture . Transient mmy expression and methylenomycin production occurred following an acidic pH shock . This stimulation of methylenomycin production occurred independently of the nutritional status of the growth environment . Antibiotic production was partially suppressed under alanine compared with glucose growth-rate-limiting conditions following the acidic pH shock . A low specific growth rate was a prerequisite for both steady-state and transient production of methylenomycin.

Am J Vet Res, 1997 Sep, 58(9), 942 - 8
Ultrasound biomicroscopy of globes from young adult pigs; Bartholomew LR et al.; OBJECTIVE: To determine anterior chamber ocular measurements of adult porcine globes without histologic fixation by use of ultrasound biomicroscopy scanning . SAMPLE POPULATION: 25 porcine globes obtained at an abattoir . PROCEDURE: Globes were packed on ice for transport . In the laboratory, globes were trimmed, rinsed with antibiotic solution, secured on a single gauze-fold in a latex holder, then were ultrasonogrammed unreformed . Ultrasound biomicroscopy scanning was done, using a 50-MHz transducer, 17-mm cup, and 2% methyl cellulose . RESULTS: Average young adult pig external ocular measurements were: nasal-temporal corneal diameter, 16.61 mm; superior-inferior corneal diameter, 14.00 mm; nasal-temporal globe diameter, 25.48 mm; superior-inferior globe diameter, 24.48 mm; and axial length 21.64 mm . Ultrasound biomicroscopy anterior chamber measurements were: iris sulcus, 30.45 degrees; ciliary sulcus, 18.89 degrees; central corneal thickness, 0.98 mm; corneal thickness at limbus, 1.19 mm; central iris thickness, 0.58 mm; iris tip to ciliary apex, 1.73 mm; iris tip to iris sulcus origin, 3.83 mm; iris tip to ciliary sulcus origin, 2.98 mm; anterior chamber depth from iris tip to cornea, 2.21 mm; central anterior chamber depth, 2.47 mm; ciliary process mid-thickness, 0.65 mm; ciliary process apex to origin of iris sulcus, 2.32 mm; ciliary process apex to origin of ciliary sulcus, 1.34 mm; zonular bundle diameter, 0.10 mm; and interzonular bundle space, 0.11 mm . CONCLUSIONS: Anatomic anterior chamber measurements and relations in porcine globes can be used to describe trauma, confirm existence of lesions, and help explain theory . CLINICAL RELEVANCE: Ultrasound biomicroscopy is a clinical decision aid facilitating noninvasive anatomic or pathologic description without histologic fixation.

Pediatrics, 1997 Sep, 100(3 Pt 1), 330 - 3
Parents can dose liquid medication accurately; McMahon SR et al.; OBJECTIVE: To determine whether parental errors in dosing liquid medication can be decreased through education . DESIGN: Randomized convenience sample stratified to three study groups . SETTING: General pediatric clinic, largely indigent and Latino . PATIENTS: A total of 45 English-speaking and 45 Spanish-speaking children diagnosed with otitis media and treated with an antibiotic suspension . INTERVENTION: Group 1 patients received the prescription and verbal instructions . Group 2 patients received the prescription and a syringe, then the correct dose was demonstrated . Group 3 patients received the prescription, a syringe with a line marked at the correct dose, and a demonstration . After returning from the pharmacy, parents administered the medication under observation . Parents in group 1 used a dispensing device similar to that planned for home use . The other groups used the syringe . After observation but before discharge, everyone received a syringe with a line marked at the correct dose . Patients were seen again at approximately 1 month, and parents demonstrated how much medication they had administered . MAIN OUTCOME MEASURE: Percent of parents who administered the correct dose . RESULTS: Patients in group 1 received between 32% and 147% of the correct dose, with only 11 of 30 (37%) receiving the correct dose (+/-0.2 mL) . In group 2, 25 of 30 (83%) parents administered the correct dose, and in group 3, 30 of 30 (100%) gave the correct dose . Simultaneous logistic regression indicated that accuracy of dosage differed across instructional groups and language . At follow-up, 23 of 26 parents demonstrated the correct dose . CONCLUSION: Education can decrease medication dosing errors made by both Spanish-speaking and English-speaking parents . Effectiveness was also shown at follow-up.

Radiology, 1997 Sep, 204(3), 622 - 6
Peripherally inserted central catheters in infants and children; Dubois J et al.; PURPOSE: To determine prospectively the feasibility, complications, and mid- and long-term advantages of peripheral insertion of central catheters in infants and children . MATERIALS AND METHODS: During a 15-month period between March 1995 and June 1996, a total of 285 catheter placement attempts were made to peripherally insert central catheters in 183 pediatric patients (89 boys, 94 girls) . Phlebographic guidance was used, and the catheters were inserted below the elbow in 99% of cases . Catheter insertion was indicated for prolonged antibiotic therapy in 108 patients (158 catheter placement attempts), hematologic or oncologic care in 24 patients (40 attempts), total parenteral nutrition in 16 patients (46 attempts), and venous access for fluid or blood in 35 patients (41 attempts) . The success rate and complications were recorded along with the indication, patient age, and duration of catheter placement . RESULTS: One hundred fifty-two of 158 (96%) catheter placement attempts were successful in outpatients (n = 108), 124 of 127 (98%) in hospitalized patients (n = 75), and 70 of 73 (96%) in patients aged less than 1 year . Infection and pericatheter venous thrombosis were the main complications and were seen in 17 of 276 (6%) and one of 276 (0.3%) catheter placement attempts, respectively . Catheter occlusion occurred in 23 of 276 (8%) catheter placement attempts . CONCLUSION: Peripheral insertion of central catheters was highly feasible in infants and children with this protocol . Such catheters were well tolerated in the pediatric population with a low frequency of complications.

J Urol, 1997 Sep, 158(3 Pt 2), 1232 - 5
The use of renal parenchymal area in children with high grade vesicoureteral reflux; Pruthi RS et al.; PURPOSE: We sought to apply 2-dimensional sonographic measurements of renal parenchymal area in children with high grade vesicoureteral reflux to assess reliability and accuracy in estimating differential renal function, and in predicting clinical outcome compared to traditional 1-dimensional sonographic measurements . MATERIALS AND METHODS: We retrospectively evaluated 121 sonograms from 30 patients with a grade 4 or 5 primary vesicoureteral reflux, including 14 who underwent ureteral reimplantation during followup and 16 who were followed on prophylactic antibiotic therapy . One-dimensional sonographic measurements of longitudinal length and bipolar thickness were determined in refluxing and contralateral kidneys, as were 2-dimensional measurements of longitudinal parenchymal area using computer planimetry . Renal length, bipolar thickness and parenchymal area were compared to renal function data determined by nuclear renography . Renal length and area was also represented as a percent of age adjusted normal values using previously published nomograms . RESULTS: Differential renal function correlated well with differential parenchymal area for all patients (r = 0.924) . This correlation persisted in patients with (r = 0.917) and without scarring (r = 0.890), as determined by dimercapto-succinic acid scan . Differential length did not correlate as well (r = 0.661) and bipolar parenchymal thickness did not correlate at all (r = 0.021) . Sonographic age adjusted area of the refluxing kidneys was approximately two-third normal . No statistically significant difference was observed among age adjusted renal area of the observation, preoperative and postoperative groups . Contralateral kidney area was not significantly different than normal . CONCLUSIONS: Our data indicate that serial sonographic measurements of longitudinal renal parenchymal area provide a simple and accurate method of monitoring renal growth and function in patients with high grade vesicoureteral reflux . In contrast to 1-dimensional measurements of renal length and bipolar parenchymal thickness, renal parenchymal area correlates well with renal function . Area also appears to be a more sensitive method of monitoring renal growth in children with vesicoureteral reflux.

Biochemistry, 1997 Aug 19, 36(33), 9995 - 10005
Interactions of deglycosylated cobalt(III)-pepleomycin (green form) with DNA based on NMR structural studies,; Caceres-Cortes J et al.; Pepleomycin (PEP)1 is a metalloglycopeptide antitumor antibiotic that has improved pharmacological properties than does bleomycin (BLM) . Both PEP and BLM bind to and degrade DNA in a sequence-selective manner . The binding interactions of HO2--Co(III)-CodPEP (CodPEP) with CGTACG have been studied by 2D NMR and molecular modeling . Inspection of the 2D-NMR data revealed 60 notable intermolecular NOEs between CodPEP and CGTACG which place the drug's metal binding domain and peptide linker in the minor groove of the DNA close to G8 and T9 . On the basis of the NOEs, the drug's DNA binding domain is located close to the T9.A4 and A10.T3 base pairs . Intercalation of the bithiazole tail between these base pairs is indicated by the loss of DNA symmetry upon complexation with CodPEP, by a break in the sequential connectivity at the TpA steps, and by the upfield shift of the bithiazole H-H5 and H-H5' proton resonances . Intercalation of the bithiazole moiety unfolds the CodPEP molecule and exposes its hydroperoxide group to the DNA . The hydroperoxide group in the refined model of CodPEP-CGTACG is close to the C4' proton of T9, consistent with cleavage at this position . The NOE pattern between the pyrimidine ring of CodPEP and G8 of DNA suggests a specific pairing recognition via hydrogen bonds between these groups, thus establishing a 5'-GT-3' sequence preference . The structural elucidation of the free CodPEP and CoPEP {Caceres-Cortes et al . (1997) Eur . J . Biochem . 244, 818-828}, and of the complex of CodPEP-CGTACG afford a plausible mechanism for the recognition and its subsequent cleaving of DNA by the drug . The process involves the unfolding of the compact CodPEP, recognition of a guanine base using the metal binding domain, threading of the bithiazole tail between base pairs, and finally positioning of the HO2- group close to the T or C found 3' to the specific G site.

Cancer, 1997 Aug 15, 80(4), 656 - 60
Neutropenic enterocolitis in a patient with colorectal carcinoma: unusual course after treatment with 5-fluorouracil and leucovorin--a case report; Kronawitter U et al.; BACKGROUND: Neutropenic enterocolitis is observed in approximately 25% of patients with acute leukemia, but has been reported rarely in patients with solid tumors . If treatment is not initiated promptly, the mortality is high . The incidence of this disease is rising in patients with hematologic malignancies . Increasing numbers of patients with solid tumors are subject to high dose chemotherapy regimens or new drugs known to cause severe neutropenia . Therefore, the frequency of this disease can be expected to increase . METHODS: The authors report a patient with colorectal carcinoma who developed neutropenic enterocolitis after treatment with 5-fluorouracil and leucovorin . RESULTS: The patient developed the typical clinical picture of abdominal pain, diarrhea, and neutropenia . The course was complicated by a recurrence of symptoms after initially successful antibiotic therapy without the patient receiving further chemotherapy . CONCLUSIONS: This case indicates that neutropenic enterocolitis may occur in patients with colorectal carcinoma receiving 5-fluorouracil and leucovorin.

Lancet, 1997 Aug 9, 350(9075), 404 - 7
Randomised trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS Pilot Study . ROXIS Study Group; Gurfinkel E et al.; BACKGROUND: There is serological evidence for an association between Chlamydia pneumoniae and coronary heart disease . We investigated the hypothesis that an antichlamydial macrolide antibiotic, roxithromycin, can prevent or reduce recurrent major ischaemic events in patients with unstable angina . METHODS: The effect of roxithromycin was assessed in a double-blind, randomised, prospective, multicentre, parallel-group, placebo-controlled pilot study of 202 patients with unstable angina or non-Q-wave myocardial infarction . Patients were randomly assigned either roxithromycin 150 mg orally twice a day (n = 102) or placebo orally twice a day (n = 100) . The treatment was for 30 days . Patients were followed up for 6 months . We report the primary clinical endpoints (cardiac ischaemic death, myocardial infarction, and severe recurrent ischaemia), assessed at day 31, in 202 patients on an intention-to-treat basis . FINDINGS: A statistically significant reduction in the primary composite triple endpoint rates was observed in the roxithromycin group: p = 0.032 . The rate of severe recurrent ischaemia, myocardial infarction, and ischaemic death was 5.4%, 2.2%, and 2.2% in the placebo group and 1.1%, 0%, and 0%, in the roxithromycin group, respectively . No major drug-related adverse effects were observed . INTERPRETATION: Antichlamydial antibiotics may be useful in therapeutic intervention in addition to standard medication in patients with coronary-artery disease . Large-scale trials are needed to confirm these preliminary observations.

Fogorv Sz, 1997 Aug, 90(8), 241 - 5
{Prophylactic use of roxithromycin in dental procedures}; Gaspar L et al.; In this study roxithromycin was applied for prophylactic treatment of 104 patients (implantology, dentoalveolar surgery, risk patients etc.) underwent dental surgery . The efficacy and side effects of roxithromycin were studied . The efficacy of this antibiotic was 92%, gastrointestinal complains, as the most common side effects were obtained in 2.8% of the patients treated with roxithromycin.

Eur J Biochem, 1997 Aug 1, 247(3), 1190 - 6
Identification of an ubiquitin-ligation system for the epidermal-growth-factor receptor--herbimycin A induces in vitro ubiquitination in rabbit-reticulocyte lysate; Mori S et al.; Some receptor tyrosine kinases such as the receptors for epidermal-growth factor (EGF) and platelet-derived growth factor undergo polyubiquitination as a consequence of ligand binding . The EGF receptor is also ubiquitinated by treatment with herbimycin A, an ansamycin antibiotic widely used as a tyrosine kinase inhibitor . To investigate the mechanism of the receptor ubiquitination, we have established an assay system in which herbimycin-A-induced ubiquitination processes can be analyzed in vitro . We now show that herbimycin A treatment of the purified EGF receptor induces polyubiquitination of the receptor in rabbit-reticulocyte lysate . Both DEAE unadsorbed material (fraction I) and high salt eluate (fraction II) of the reticulocyte lysate are involved cooperatively in the ubiquitination process, where the ubiquitin-conjugating enzyme UBC4 can functionally substitute for fraction I . A ubiquitin-protein ligase-like activity, partially purified from fraction II by DEAE anion-exchange chromatography, also functions in concert with UBC4 . The precise mechanism of herbimycin A-induced ubiquitination of the EGF receptor is not fully understood, however, our present findings suggest that direct interaction with herbimycin A results in some modification of the receptor which is recognized by the ubiquitin-conjugating system in rabbit-reticulocyte lysate.

Anesthesiology, 1997 Aug, 87(2), 268 - 76
Diagnosis of ventilator-associated pneumonia: an evaluation of direct examination and presence of intracellular organisms; Papazian L et al.; BACKGROUND: Ventilator-associated pneumonia (VAP) requires early diagnosis and adequate antibiotic therapy . The aim of this prospective postmortem study was to assess the accuracy of direct examination and quantification of intracellular organisms (ICO) for the diagnosis of VAP . METHODS: Total and differential cell counts were performed on fluids recovered using nonbronchoscopic sampling techniques (blind bronchial sampling {BBS}, mini-bronchoalveolar lavage {mini-BAL}) and from bronchoalveolar lavage (BAL) performed during fiberscopy . These 3 sampling techniques were done within 15 min of death without discontinuing mechanical ventilation . Quantification of ICO was performed on each sample recovered from the various sampling procedures . Gram reaction and morphology of bacteria were evaluated on Gram smears . RESULTS: The results of each technique were compared with histology and culture of lung tissue specimens obtained by surgical pneumonectomies in 28 patients who died after at least 72 h of mechanical ventilation . Histology was positive in 13 patients and negative in 15 patients . When only VAP with positive lung culture was considered (histologic signs of bronchopneumonia plus positive lung tissue culture), the sensitivity of Gram staining on BAL, mini-BAL, and BBS was 56%, 44%, and 56%, respectively . If all samples were considered, the sensitivity and the specificity of the determination of the percentage of ICO were low (less than 70%) whatever the sampling technique . CONCLUSIONS: For initial therapeutic guidance, direct examination and presence of ICO do not contribute for establishing the diagnosis of VAP, essentially because of a lack of sensitivity . However, when positive, Gram staining can obviously guide initial antibiotherapy.

Gan To Kagaku Ryoho, 1997 Aug, 24(10), 1263 - 71
{Menogaril (TUT-7) late phase II study for malignant lymphoma, adult T-cell leukemia and lymphoma (ATLL)}; Taguchi T et al.; A late Phase II multicenter study with menogaril was conducted nationwide in patients with malignant lymphoma {non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD)}, and ATLL, menogaril was orally administered at 100 mg daily after breakfast, for seven consecutive days with two- or three-week drug withdrawal, then menogaril administration was repeated . For malignant lymphoma, in 81 patients with NHL and 5 patients with HD registered, 70 and 5 patients were evaluable for efficacy, respectively . The efficacy rates were 32.9% (6 CRs + 17 PRs/70) for NHL and 20.0% (1 PR/5) for HD, respectively; that for the NHL patients with prior anthracycline antibiotic chemotherapy was 30.5% (5 CRs and 13 PRs/59) . For ATLL, among the 16 patients registered, 15 were evaluable for efficacy, and the efficacy rate was 40.0% (2 CRs and 4 PRs/15) . Adverse drug reactions frequently observed in the patients with malignant lymphoma and ATLL included bone-marrow suppression and gastrointestinal symptoms such as anorexia, and nausea/vomiting . With these results, menogaril was considered to be effective for the treatment of non-Hodgkin's lymphoma and ATLL.

Gan To Kagaku Ryoho, 1997 Aug, 24(10), 1253 - 61
{TUT-7 early phase II clinical study for various solid tumors and hematologic malignancies}; Taguchi T et al.; An early Phase II study with TUT-7 (menogaril), a new anthracycline antitumor antibiotic, was conducted in patients with various malignant tumors at 81 departments of 65 institutions nationwide . One course of TUT-7 treatment consisted of seven (7) or fourteen (14) consecutive days of administration at 75 or 100 mg/body/day with two-week drug withdrawal; at least two courses of treatment were given in principle . Among the 165 patients registered, 145 patients were eligible and 128 patients were evaluable for antitumor efficacy . In 11 patients with malignant lymphoma, one (1) had CR and five (5) had PR (54.5%); in three (3) patients with prostate cancer, one (1) had PR (33.3%); and in 12 patients with uterine cervical cancer, two (2) had PR (16.7%) . Adverse drug reactions frequently observed were digestive organ disorders (anorexia and nausea/vomiting) and malaise . The abnormality in laboratory tests observed frequently was myelosuppression (leukopenia and neutropenia).

Arch Pathol Lab Med, 1997 Aug, 121(8), 869 - 73
Disseminated toxoplasmosis . Unusual presentations in the immunocompromised host; Arnold SJ et al.; OBJECTIVE: Owing to the increasing number of patients with acquired immunodeficiency syndrome and immunosuppressed transplant patients, disseminated Toxoplasma gondii has emerged as a potentially fatal pathogen . Common presentations include encephalitis, pneumonia, and myocarditis . The objective of this report is to describe the clinical course, histologic features, and outcome in two immunocompromised patients with disseminated toxoplasmosis presenting with parasitemia and panniculitis . MATERIALS AND METHODS: Two cases of disseminated toxoplasmosis presenting with parasitemia (patient 1) and panniculitis (patient 2) were retrieved from the clinical, surgical, and autopsy pathology archives of Vanderbilt University Medical Center, Nashville, Tenn . The histology and diagnostic approaches used are reported . Charts were reviewed for primary diagnosis, therapy protocols, clinical presentation of infection, and outcome . RESULTS: Patient 1 developed a clinically unexplained sepsis syndrome shortly after heart transplantation; T gondii parasitemia was diagnosed by examination of peripheral blood smears . The diagnosis was confirmed at autopsy . Patient 2 was a child undergoing induction chemotherapy for lymphoma who developed rapidly progressive neurologic deterioration accompanied by a maculopapular skin rash; T gondii panniculitis was diagnosed retrospectively when histologic examination was combined with immunohistochemistry . Autopsies performed in both cases confirmed widely disseminated infection . CONCLUSIONS: Disseminated toxoplasmosis should be considered in the differential diagnosis of immunocompromised patients with culture-negative sepsis syndrome, particularly if combined with neurologic, respiratory, or unexplained skin lesions . Examination of Wright's-stained peripheral blood smears or antitoxoplasma immunoperoxidase studies of skin biopsies may be diagnostic and allow rapid initiation of antibiotic therapy . Autopsy findings contributed to both of our cases by documenting the wide-spread heavy parasite burden and demonstrating numerous diagnostic T gondii cyst forms.

Postgrad Med, 1997 Aug, 102(2), 253 - 8
Acute sinusitis in adults . Difficult to diagnose, essential to treat; Kankam CG et al.; Acute sinusitis is difficult to diagnose . Diagnosis depends on obtaining a complete history and physical examination in addition to use of radiographic diagnostic aids and, if necessary, sinus aspiration . Once the diagnosis is made, empirical treatment with antibiotic agents and adjunctive measures should be started . Because most acute sinus infections are caused by H influenzae and S pneumoniae, the preferred antibiotic for treatment is amoxicillin or TMP-SMZ . Timely and appropriate therapy prevents complications . Symptoms persisting after completion of an appropriate course of treatment are an indication for referral to an otolaryngologist.

Dis Colon Rectum, 1997 Aug, 40(8), 973 - 6
Pneumocystis carinii pneumonia postrestorative proctocolectomy for ulcerative colitis: a role for perioperative prophylaxis in the cyclosporine era? Report of a case and review of the literature; Scott AM et al.; PURPOSE: Medical management of severe ulcerative colitis has used cyclosporine with increasing frequency as an adjuvant to systemic steroids and mercaptopurine . However, the effects of combined management with cyclosporine and prednisone may lead to significant immune compromise and adversely affect operative morbidity in the event urgent surgery is required . METHODS: A case is reported of a 43-year-old white male who presented with severe ulcerative colitis . The patient had been initially treated with prednisone and cyclosporine for six weeks before surgical intervention . The intractability of his ulcerative colitis caused the patient to present to surgery, where he underwent restorative proctocolectomy . RESULTS: On initial presentation, the patient manifested systemic signs of severe ulcerative colitis with hypoalbuminemia, anemia, and weight loss, despite continuous prednisone and cyclosporine management . Before surgical intervention, a chest x-ray and the patient's respiratory status were normal . A total abdominal colectomy with ileal pouch reconstruction and temporary loop ileostomy were performed without incident . On the fifth postoperative day, the patient developed respiratory failure, which was subsequently diagnosed as Pneumocystis carinii pneumonia . Although ventilator support and both aggressive medical and surgical management eventually resulted in successful outcome, significant perioperative morbidity occurred . CONCLUSIONS: In the era of aggressive medical management for ulcerative colitis with both steroids and cyclosporine, the complications of immunosuppression may be significant, including opportunistic pneumonia . Prophylaxis against P . carinii pneumonia with sulfa antibiotics should be considered, especially in patients for whom proctocolectomy is a potential end point.

J Cardiovasc Surg (Torino), 1997 Aug, 38(4), 371 - 5
Infected abdominal aortic aneurysm: in situ replacement with cryopreserved arterial homograft; Alonso M et al.; Infected aortic aneurysms are a rare (1.3% of all abdominal aortic aneurysms) but life-threatening disease . At present controversy continues about the specific diagnosis and the best surgical management . We present one case of infected aortic aneurysm treated with in situ reconstruction with cryopreserved arterial homograft . He was a 50-year-old man with recent history of pneumococcal meningitis who is readmitted because he suffered a stroke and during physical examination a pulsatile abdominal mass was discovered . Blood cultures were done and the result was repeatedly negative . Radiological studies were performed: the abdominal CT scanning showed a non ruptured 5 cm infrarenal aortic aneurysm with irregular wall and in the aortography it appeared eccentric, multilobulated with a clear neck in an otherwise normal size aorta but with some arteriosclerotic lesions . The diagnosis of infected aneurysm was suspected and the patient received antibiotic therapy and was operated on: aneurysm resection with wide debridement of surrounding tissues and in situ aortic replacement with aortobifemoral cryopreserved arterial homograft . Cultures of the aneurysm wall and contents were negative but aneurysm wall biopsy suggested an infected aortic aneurysm . The postoperative course was uneventful and antibiotics were continued for 6 weeks . The patient is doing well 7 months after surgery without signs of recurrent infection and normal appearance of the cryopreserved arterial homograft . We conclude that specific diagnosis of infected aortic aneurysms is essential for correct treatment but may be difficult, in these cases a history of infection supported by radiologic findings and aneurysm wall biopsy are of great value . Cryopreserved arterial homografts constitute a good alternative to prosthetic grafts for in situ reconstructions in the treatment of infected aortic aneurysms, decreasing the risk of re-infection or septic complications.

Am J Perinatol, 1997 Aug, 14(7), 419 - 22
Fetal but not maternal serum cytokine levels correlate with histologic acute placental inflammation; Salafia CM et al.; Our objective was to determine if placental histologic acute inflammation is related to maternal and fetal serum cytokine levels in preterm labor, using a data set previously constructed blinded to histopathologic information . To this goal in 1992, 32 consecutive patients at 20-36 weeks with progressive labor and tocolytic failure were recruited . Maternal serum sampled during the active phase of labor, and fetal (umbilical vein) serum were assayed by ELISA for levels of soluble interleukin-1 beta (IL-1 beta), soluble interleukin-2 receptor (IL-2 R), and interleukin 6 (IL-6) (T-Cell Diagnostics) . Acute placental inflammation was scored by two groups blinded to clinical data, and the average scores analyzed for relationships to serum cytokine levels . Weighted kappa values, reflecting interobserver agreement in scoring of acute inflammation, were: amnion 0.84; choriodecidua 0.84; umbilical cord 0.85; and chorionic plate 0.73 . Fetal levels of IL-1 beta and IL-2 R were higher with grade 3-4 acute amnionitis than with grades 0-2 (p = 0.022 and p = 0.023) . Fetal levels of all three cytokines were higher in grade 3-4 umbilical vasculitis (IL-1 beta p = 0.008, IL-2 R p = 0.01, and IL-6 p = 0.03) . In contrast, maternal serum cytokine levels were not associated with presence or severity of histologic evidence of acute placental inflammation . Histologic acute inflammation was not related to duration of labor, interval from membrane rupture to delivery, and presence or duration of antibiotic therapy . We conclude that fetal serum, but not maternal serum cytokine levels, are correlated with histologic evidence of acute placental inflammation, and may reflect a predominant placental origin of the cytokines.

Pediatr Res, 1997 Aug, 42(2), 232 - 6
The presence and significance of the Pi class glutathione S-transferase isoenzyme in cerebrospinal fluid during the course of meningitis in children; Wylie-Modro S et al.; A rise in the concentration of the Pi class isoenzyme of glutathione S-transferase (GST) in the cerebrospinal fluid (CSF) during meningitis may be an early indicator of inflammation and cell damage . Pi class GST concentrations were measured in 48 samples of CSF from 46 children with proven or suspected meningitis using a commercially available immunoassay . Forty-four fetal brain samples were assayed by isoelectric focusing to determine the nature and number of isoenzymes likely to be released . Twenty-four percent of children had measurable amounts of the isoenzyme in their CSF during the initial stages of the disease . One child, for whom CSF samples were taken pre-, mid-, and post-antibiotic treatment, had measurable Pi class GST in the CSF only in the mid-treatment sample, when bacterial lysis and inflammation are likely to be at their peak . Where follow-up data were available, two of three children with measurable Pi class GST in their CSF at the initial stages had recordable disabilities at 5 y of age compared with 4 of 11 of those in whom no Pi class GST was detected . Two proteins analogous to Pi class GST were detected in frozen brain tissue, but only one was active with a known substrate; only the active protein was seen in fresh tissue . We conclude that 1) initial high levels of CSF Pi class GST may be an indicator of the severity of inflammation and thus of prognostic significance and 2) only one Pi class GST occurs in brain tissue.

Antimicrob Agents Chemother, 1997 Aug, 41(8), 1715 - 20
Inducible expression of human hepatitis B virus (HBV) in stably transfected hepatoblastoma cells: a novel system for screening potential inhibitors of HBV replication; Ladner SK et al.; We report the development and isolation of a cell line, termed HepAD38, that replicates human hepatitis B virus (HBV) under conditions that can be regulated with tetracycline . In the presence of the antibiotic, this cell line is free of virus due to the repression of pregenomic (pg) RNA synthesis . Upon removal of tetracycline from the culture medium, the cells express viral pg RNA, accumulate subviral particles in the cytoplasm that contain DNA intermediates characteristic of viral replication, and secrete virus-like particles into the supernatant . Since the HepAD38 cell line can produce high levels of HBV DNA, it should be useful for analyses of the viral replication cycle that depend upon viral DNA synthesis in a synchronized fashion . In addition, this cell line has been formatted into a high-throughput, cell-based assay that permits the large-scale screening of diverse compound libraries for new classes of inhibitors of HBV replication.

RNA, 1997 Aug, 3(8), 870 - 81
Translational misreading: mutations in translation elongation factor 1alpha differentially affect programmed ribosomal frameshifting and drug sensitivity; Dinman JD et al.; The translation elongation feactor 1alpha (EF-1alpha) catalyzes the critical step of delivering aminoacyl-tRNAs to the elongating ribosome . A series of Saccharomyces cerevisiae strains containing mutant alleles of the TEF2 gene encoding EF-1alpha have phenotypes consistent with effects on cellular processes related to translation . These include (1) conditional growth defects, (2) antibiotic sensitivity or resistance, (3) altered +1 or -1 ribosomal frameshifting efficiencies, and (4) altered maintenance of the killer phenotype . Although all the mutant alleles were isolated as dominant +1 frameshift suppressors, the effects of these mutations on the cell are quite different when present as the only form of EF-1alpha . Allele-specific effects are observed with regard to their ability to alter the efficiency of programmed +1 frameshifting as opposed to programmed -1 ribosomal frameshifting . The significantly altered efficiency of -1 frameshifting in strains containing the TEF2-4 and TEF2-9 mutant alleles further correlates with a reduced ability to maintain the killer phenotype and the M1 satellite virus of L-A, an in vivo assay of translational fidelity . In light of the proposed models regarding the different A- and P-site occupancy states required for +1 or -1 ribosomal frameshifting, these results aid analysis of interactions between EF-1alpha and the translational apparatus.

Am J Clin Oncol, 1997 Aug, 20(4), 338 - 41
Cellulitis of the breast as a complication of breast-conserving surgery and irradiation; Hughes LL et al.; Breast-conserving therapy (BCT) has become a standard treatment option for patients with early-stage breast cancer . We have observed cellulitis of the treated breast as a complication occurring before, during, and after breast irradiation . The cases of five women (median follow-up, 28 months; range, 24-65 months) who developed cellulitis before (n = 1), during (n = 2), or after (n = 2) breast irradiation were reviewed . A consecutive series of BCT patients at Emory University was reviewed to determine the incidence of this complication . Four of five women had an axillary dissection, yielding a median of 14 negative lymph nodes (range, 6-22 nodes) . Two of four patients developed axillary seromas requiring aspiration . In these four patients, only the breast was irradiated . A fifth patient had no axillary dissection and had breast and supraclavicular/axillary irradiation . The median whole breast dose was 50 Gy (range, 46-50.4 Gy) . The clinical features of cellulitis included erythema, edema, tenderness, and warmth in all patients . Cellulitis was a relapsing problem for four of the five patients . The incidence of this complication in our series of BCT patients was approximately 1% . Cellulitis in the ipsilateral breast can be a relapsing complication of BCT and can be seen before, during, or after breast irradiation . Axillary seromas and aspiration seem to indicate a subset of patients at risk of early cellulitis . Late cellulitis may be caused by a variety of factors related to modifications of vascular and skin integrity by surgery and radiotherapy . Prompt diagnosis and appropriate antibiotic therapy is recommended . This problem need not interrupt a course of breast irradiation, and does not necessarily lead to a poor cosmetic result.

Appl Environ Microbiol, 1997 Aug, 63(8), 3189 - 98
Physiological and biochemical characterization of Trichoderma harzianum, a biological control agent against soilborne fungal plant pathogens; Grondona I et al.; Monoconidial cultures of 15 isolates of Trichoderma harzianum were characterized on the basis of 82 morphological, physiological, and biochemical features and 99 isoenzyme bands from seven enzyme systems . The results were subjected to numerical analysis which revealed four distinct groups . Representative sequences of the internal transcribed spacer 1 (ITS 1)-ITS 2 region in the ribosomal DNA gene cluster were compared between groups confirming this distribution . The utility of the groupings generated from the morphological, physiological, and biochemical data was assessed by including an additional environmental isolate in the electrophoretic analysis . The in vitro antibiotic activity of the T . harzianum isolates was assayed against 10 isolates of five different soilborne fungal plant pathogens: Aphanomyces cochlioides, Rhizoctonia solani, Phoma betae, Acremonium cucurbitacearum, and Fusarium oxysporum f . sp . radicis lycopersici . Similarities between levels and specificities of biological activity and the numerical characterization groupings are both discussed in relation to antagonist-specific populations in known and potential biocontrol species.

J Gastroenterol, 1997 Aug, 32(4), 543 - 7
Regression of atypical lymphoid hyperplasia after eradication of Helicobacter pylori; Tanahashi T et al.; A rare case of endoscopic and histological regression of a gastric lymphoid mucosal lesion after eradication of Helicobacter pylori is reported . A 72-year-old man was suspected of having a low-grade B-cell gastric mucosa-associated lymphoid tissue (MALT) lymphoma by endoscopic and histological findings . Histology of biopsy specimens showed massive infiltration of atypical lymphocytes and lymphoepithelial lesions . Immunohistochemical staining revealed kappa light chain expression in the infiltrated atypical lymphocytes to be twofold that of lambda light chain . The above diagnosis was thus highly suspected but not confirmed . Antibiotic therapy was given on the basis of evidence of H . pylori infection . Successful eradication of H . pylori resulted in remarkable improvement of endoscopic and histological findings . Follow-up studies were carried out 8 months after eradication, with no evidence of relapse . The eradication of H . pylori appears to be an effective alternative therapy for B-cell lymphoproliferative disease, although longer follow-up and further studies are needed before this treatment can be established.

Mamm Genome, 1997 Aug, 8(8), 559 - 63
Linkage assignment of eleven genes to the porcine genome; Hu Z et al.; We report comparative linkage mapping of eleven genes in the swine genome by RFLP analysis . These genes include: Acid phosphatase type 5 (ACP5), Cholecystokinin Type B Receptor (CCKBR), Antibiotic Peptide (FALL39), Insulin-like Growth Factor 1 Receptor (IGF1R), Integrin Alpha M (ITGAM), Integrin Beta 2 (ITGbeta2), Opioid Receptor Mu-1 (OPRM1), Pro-hormone Converter (PC1/3), Retinol Binding Protein 3 (RBP3), Ribosomal DNA (RNR1), and Zona Pellucida Glycoprotein 1 (ZP1) . The CCKBR and ITGbeta2 loci define the ends of the linkage groups on Chromosomes (Chro) (SSC) 9p and 13qter, respectively.

Gastroenterology, 1997 Aug, 113(2), 442 - 8
Defects of monocyte interleukin 12 production and humoral immunity in Whipple's disease; Marth T et al.; BACKGROUND & AIMS: Whipple's disease (WD) is a systemic infection in which the causative bacteria typically accumulate within macrophages . The aim of this study was to test whether this macrophage dysfunction is the cause or result of previously shown T-cell defects . METHODS: In vitro production of interleukin (IL)-12, IL-10, tumor necrosis factor alpha, interferon gamma (IFN-gamma), and transforming growth factor beta (TGF-beta) from purified monocytes and peripheral blood mononuclear cells, cytokine expression on duodenal biopsy specimens, and serum cytokine and immunoglobulin (Ig) levels were tested in 9 patients with WD . RESULTS: Reduced monocyte IL-12 production and decreased IFN-gamma secretion by peripheral blood mononuclear cells in vitro were found, as well as reduced immunohistological staining for IL-12 and IFN-gamma, but no decrease in other cytokines in patients with WD . A similar but less severe defect in 2 relatives with WD argued for a genetic basis of this abnormality . Serum IgG2, an IFN-gamma-dependent Ig subclass, and serum TGF-beta levels were reduced in patients with WD . CONCLUSIONS: The described monocyte defects in WD may result in a secondary reduction of IFN-gamma production and IgG2 serum levels . This provides a rationale for additive immunotherapy in patients with antibiotic-refractory WD.

Clin Immunol Immunopathol, 1997 Aug, 84(2), 171 - 6
Cerebrospinal fluid cytokines in patients with tuberculous meningitis; Mastroianni CM et al.; The level of tumor necrosis factor (TNF)-alpha, soluble TNF receptors p75 (sTNFR-75) and sTNFR-55, interferon (IFN)-gamma, and interleukin (IL)-10 and IL-12 were measured in 59 cerebrospinal fluid (CSF) samples from 15 patients with tuberculous meningitis (TBM) . TBM was associated with elevated concentrations of TNF-alpha, sTNFR-75, sTNFR-55, IFN-gamma, and IL-10, while CSF IL-12 was undetectable in all TBM patients . A significant correlation between cytokines and CSF adenosine deaminase activity was also found . The levels of TNF-alpha did not decrease over time, being still detectable in the CSF 16 months after starting antibiotic therapy, whereas IFN-gamma along with anti-inflammatory mediators sTNFR-75, sTNFR-55, and IL-10 remained elevated in the CSF for 4-8 months . The chronic release of cytokines in the CSF compartment was related neither to the TBM stage nor to the clinical outcome of the disease, thus suggesting the presence of a continuous activity of the inflammatory process at the site of infection.

Arch Microbiol, 1997 Aug, 168(2), 102 - 13
Identification of stsC, the gene encoding the L-glutamine:scyllo-inosose aminotransferase from streptomycin-producing Streptomycetes; Ahlert J et al.; Eight new genes, strO-stsABCDEFG, were identified by sequencing DNA in the gene cluster that encodes proteins for streptomycin production of Streptomyces griseus N2-3-11 . The StsA (calculated molecular mass 43.5 kDa) and StsC (45.5 kDa) proteins - together with another gene product, StrS (39.8 kDa), encoded in another operon of the same gene cluster - show significant sequence identity and are members of a new class of pyridoxal-phosphate-dependent aminotransferases that have been observed mainly in the biosynthetic pathways for secondary metabolites . The aminotransferase activity was demonstrated for the first time by identification of the overproduced and purified StsC protein as the L-glutamine:scyllo-inosose aminotransferase, which catalyzes the first amino transfer in the biosynthesis of the streptidine subunit of streptomycin . The stsC and stsA genes each hybridized specifically to distinct fragments in the genomic DNA of most actinomycetes tested that produce diaminocyclitolaminoglycosides . In contrast, only stsC, but not stsA, hybridized to the DNA of Streptomyces hygroscopicus ssp . glebosus, which produces the monoaminocyclitol antibiotic bluensomycin; this suggests that both genes are specifically used in the first and second steps of the cyclitol transamination reactions . Sequence comparison studies performed with the deduced polypeptides of the genes adjacent to stsC suggest that the enzymes encoded by some of these genes {strO (putative phosphatase gene), stsB (putative oxidoreductase gene), and stsE (putative phosphotransferase gene)} also could be involved in (di-)aminocyclitol synthesis.

J Biol Chem, 1997 Jul 25, 272(30), 18694 - 701
The function of steroid hormone receptors is inhibited by the hsp90-specific compound geldanamycin; Segnitz B et al.; The ansamycin antibiotic geldanamycin,