Lipids, 1987 Oct, 22(10), 757 - 9 The differential effect of polymyxin B1 on guinea pig lung mitochondrial and microsomal glycerophosphate acyltransferase; Das SK et al.; The activities of guinea pig lung mitochondrial and microsomal glycerophosphate acyltransferase differed in sensitivity to polymyxin B1 . At an antibiotic concentration of 1 mg/ml, the mitochondrial enzyme activity was stimulated twofold, but the microsomal enzyme activity was completely inhibited . Furthermore, the mitochondrial enzyme activity was stimulated by polymyxin B1 without the addition of exogenous acyl-CoA . Additional experiments ruled out the possibility of polymyxin B1 acting as a substrate for the mitochondrial acyltransferase . These results suggest either that the polymyxin B1 sensitivity of mitochondrial and microsomal glycerophosphate acyltransferase is different or that their accessibility to substrates is different because the two isoenzymes are located differently in the different phospholipid microenvironment of the membranes. Antibiot Med Biotekhnol, 1987 Oct, 32(10), 738 - 43 {Structural and functional research on polymyxins . 1H NMR analysis of the conformation of polymyxin M in water}; Okhanov VV et al.; Spatial structure of polypeptide antibiotic polymyxin M in water was studied by one-and two-dimensional (COSY, COSY-45, RELAY) H NMR spectroscopy . Analysis of the signal spectral parameters revealed two intramolecular hydrogen bonds in the cyclic part of the molecule which was analogous to the structure of polymyxin B . However, configuration of both the beta-turns in the polymyxin M structure differed from that of the detected earlier beta-turns in the structure of polymyxin B. Proc Natl Acad Sci U S A, 1987 Oct, 84(20), 7203 - 7 Saccharomyces cerevisiae mutants that tolerate centromere plasmids at high copy number; Tschumper G et al.; Two yeast (Saccharomyces cerevisiae) mutants that tolerate centromere (CEN) plasmids at high copy number have been isolated . The mutations relieve the restraint normally imposed on plasmid copy number by a cloned CEN sequence . Our CEN plasmids specify resistance to G418 and are high copy plasmids only when the mutant host cells are grown on medium containing this antibiotic . The high copy number of the plasmids is independent of the specific cloned CEN sequence and recovered plasmids show no alteration in structure or function of the CEN DNA . The efficiency with which CEN plasmids go to high copy number is increased if the mutant cell is cotransformed by another CEN plasmid . The genomic mutation responsible for the high copy number (COP) is dominant and stable, and it segregates in a Mendelian manner . Homozygous COP/COP a/alpha diploids do not tolerate CEN plasmids at high copy number, suggesting that the mutation is regulated by mating type . The genomic DNA from both mutant cells contains an altered transposon (Ty) restriction fragment that cosegregates with the COP phenotype in crosses of mutant and wild-type strains . The mutations may be transposon-mediated events that identify a gene involved in centromere or mitotic spindle function. Biochem Pharmacol, 1987 Oct 1, 36(19), 3293 - 7 Coordinate increases and decreases in mitochondrial RNA and ATP syntheses produced by propranolol and rifampicin; Buss WC et al.; A variety of compounds were examined for their capacity to alter RNA synthesis in isolated rat cardiac and hepatic mitochondria . The beta-adrenergic blocking agents propranolol and butoxamine, and the antiarrhythmic agent quinidine, produced a concentration-dependent stimulation of RNA synthesis in cardiac and hepatic mitochondria . In contrast, the antitubercular antibiotic rifampicin produced a concentration-dependent inhibition of RNA synthesis in cardiac and hepatic mitochondria . Propranolol, as a representative compound which stimulated RNA synthesis, was also found to stimulate ATP synthesis in isolated mitochondria, whereas rifampicin inhibited ATP synthesis . Coordinate increases and decreases in RNA and ATP syntheses suggest that agents which stimulate or inhibit RNA synthesis may rapidly alter ATP synthesis . This finding is consistent with the rapid turn-over of mitochondrial RNA with a messenger function (1.4 and 3.3 min in isolated rat cardiac and hepatic mitochondria), and it suggests that mitochondrial RNA must continue to be synthesized to maintain inner membrane systems required for ATP synthesis . Stimulation of RNA and ATP syntheses by propranolol through membrane stabilization or other actions represents a heretofore unrecognized action of propranolol which may contribute to its beneficial therapeutic effects. J Mol Biol, 1987 Sep 20, 197(2), 257 - 71 Binding of Hoechst 33258 to the minor groove of B-DNA; Pjura PE et al.; An X-ray crystallographic structure analysis has been carried out on the complex between the antibiotic and DNA fluorochrome Hoechst 33258 and a synthetic B-DNA dodecamer of sequence C-G-C-G-A-A-T-T-C-G-C-G . The drug molecule, which can be schematized as: phenol-benzimidazole-benzimidazole-piperazine, sits within the minor groove in the A-T-T-C region of the DNA double helix, displacing the spine of hydration that is found in drug-free DNA . The NH groups of the benzimidazoles make bridging three-center hydrogen bonds between adenine N-3 and thymine O-2 atoms on the edges of base-pairs, in a manner both mimicking the spine of hydration and calling to mind the binding of the auti-tumor drug netropsin . Two conformers of Hoechst are seen in roughly equal populations, related by 180 degrees rotation about the central benzimidazole-benzimidazole bond: one form in which the piperazine ring extends out from the surface of the double helix, and another in which it is buried deep within the minor groove . Steric clash between the drug and DNA dictates that the phenol-benzimidazole-benzimidazole portion of Hoechst 33258 binds only to A.T regions of DNA, whereas the piperazine ring demands the wider groove characteristic of G.C regions . Hence, the piperazine ring suggests a possible G.C-reading element for synthetic DNA sequence-reading drug analogs. Biochim Biophys Acta, 1987 Sep 18, 903(1), 78 - 88 A study of the structure of polymyxin B-dipalmitoylphosphatidylglycerol complexes by vibrational spectroscopy; Babin Y et al.; The effect of the antibiotic polymyxin B on dipalmitoylphosphatidylglycerol (DPPG) bilayers has been studied by Raman and infrared spectroscopies and small-angle X-ray diffraction . Each polymyxin B molecule binds five DPPG molecules at physiological pH and induces a macroscopic phase separation of the complex rather than a lateral phase separation . Below the phase transition of DPPG/polymyxin B bilayers, the results obtained show that the intermolecular vibrational coupling is high and suggest that the acyl chains of the bound lipid are interdigitated and that the hydrophobic tail of the antibiotic does not penetrate this tight assembly . On the other hand, the phase transition of DPPG is shifted down from 41 degrees C to 37 degrees C in the complexes and remains highly cooperative . Above the phase transition of the complexes, the conformation of the acyl chains of DPPG is slightly more disordered as a result of the penetration of the polymyxin chain, but the structure of the glycerol backbone of the lipid does not seem to be affected . However, the rotational rate of the lipid appears to be restricted by the peptide. Minerva Med, 1987 Sep 15, 78(17), 1281 - 9 {Prevention of recurrent respiratory infections in adults}; Vettori G et al.; The authors compared the results obtained by using antibiotic therapy, vaccine, thymomodulin (a calf thymus acid lysate) and association of vaccine-thymomodulin in order to prevent acute infectious episodes in a group of 85 patients suffering with recurrent respiratory infections . The use of thymomodulin, alone and in association with vaccine, at the dose of 120 mg/die for 20 days/month during the period of observation (4 months), determined a higher reduction, (p less than 0.001) if compared with the other treatments, of the number and the duration of infectious episodes and moreover of the antibiotics' intake . Also the respiratory symptoms, and in particular the fits of coughing, showed an improvement . The pulmonary function indices and the laboratory parameters were unchanged in all groups studied. No Shinkei Geka, 1987 Sep, 15(9), 983 - 8 {Intracranial bacterial aneurysms--report of two cases with special reference to operative indications}; Okabe S et al.; Two cases of intracranial bacterial aneurysms caused by bacterial endocarditis are reported . Case 1 was a 20-year-old male who underwent mitral valve annuloplasty because of mitral regurgitation due to mitral valve prolapse syndrome 3 year prior to this admission . He was referred when a large intracerebral hemorrhage of the right frontal lobe ruptured into the lateral ventricle was seen in computed tomography (CT) scan on admission . An aneurysm at the distal portion of precentral artery of the middle cerebral artery (MCA) was found by right carotid angiography . Emergency evacuation of the hematoma and trapping of the aneurysm were performed . Another three aneurysms, located at the distal portion of contralateral left precentral artery of MCA, the left posterior cerebral artery (PCA) and the right anterior falx artery were found in the subsequent angiogram . The latter two aneurysms developed while receiving antibiotics . The aneurysms of PCA and MCA were trapped surgically . However, the aneurysm of anterior falx artery disappeared spontaneously under antibiotic therapy without surgery . Case 2 was a 21-year-old female who underwent cardiac surgery one month prior to presentation for aortic insufficiency and coarctation of the aorta . She was referred to our clinic because of sudden loss of consciousness, aphasia and right hemiparesis . CT scan and left carotid angiography showed a large hematoma in the left frontal lobe and an aneurysm at the distal portion of the opercular-frontal artery . Emergency ventricular drainage was performed . The operation for evacuation of the hematoma and clipping of aneurysm was performed 10 days later . However, at the operation the aneurysm neck was only partially clipped in order to prevent the obstruction of efferent vessels.(ABSTRACT TRUNCATED AT 250 WORDS) Jpn J Antibiot, 1987 Sep, 40(9), 1624 - 7 {Fundamental and clinical studies on cefuzonam in the field of obstetrics and gynecology}; Horii T et al.; Fundamental and clinical studies on cefuzonam (CZON, L-105), a new cephem antibiotic, were carried out . The results obtained are summarized as follows: 1 . Upon drip infusion of 1 g CZON, a good transfer of the drug into female genital organ was observed . The transfer of CZON into exudates of the pelvic dead space was also good . 2 . Clinical efficacy of CZON was good in 1 case we tested . No side effect was observed. Jpn J Antibiot, 1987 Sep, 40(9), 1617 - 23 {Clinical studies on cefuzonam in the field of obstetrics and gynecology}; Souma A et al.; Cefuzonam (CZON, L-105), a cephem type antibiotic, was clinically studied in the field of obstetrics and gynecology . The results are summarized as follows: CZON 1-2 g was administered by injection twice daily to 11 cases of infections (4 of endometritis, 2 of pyometra, 3 of adnexitis and peritonitis, 1 of abdominal abscess, and 1 of puerperal fever) . Clinical efficacy was excellent in 2 cases and good in 9 cases, with a very high overall efficacy rate of 100% . Slight elevations of GOT and GPT in 1 case were noted in clinical laboratory tests . No side effects attributable to the drug were noted . CZON is considered to be a useful drug for obstetric and gynecological infections. Semin Respir Infect, 1987 Sep, 2(3), 146 - 5 Community-acquired pneumonia in children; Gilsdorf JR; The clinical findings and etiologic agents of childhood pneumonia vary, dependent upon the age of the child, with major differences seen in neonates, young infants 1 to 3 months of age, older infants or young children 3 months to 5 years of age, and older children or adolescents . Appropriate medical management and antibiotic therapy of children with pneumonia require consideration of these various age-dependent factors . Commonly the bacterial or viral etiologic agent causing community-acquired childhood pneumonia is not identified and thus antibiotic therapy is based on the probability of the most likely causative organisms . The choice of antibiotic for continuation of therapy is based on the clinical response to empiric therapy. J Antibiot (Tokyo), 1987 Sep, 40(9), 1303 - 15 Synthesis and antitumor activity of spergualin analogues . II . Chemical modification of the spermidine moiety; Umeda Y et al.; Chemical modifications of the spermidine moiety of an antitumor antibiotic, spergualin (Ia), and the structure-activity relationship are described . Replacement of spermidine with other polyamines decreased the antitumor activity against mouse leukemia L1210 . Analogues containing an oxidized spermidine moiety that probably formed during oxidation with amine oxidase were inactive . Spermidine is indispensable for the antitumor activity . A facile method for the synthesis of glyoxyloyl polyamine, a key intermediate of spergualin-related compounds, is also reported. Can J Surg, 1987 Sep, 30(5), 329 - 31 Clagett open-window thoracostomy in patients with empyema who had and had not undergone pneumonectomy; Bayes AJ et al.; Patients with empyema not responding to simple chest-tube drainage and antibiotic therapy have been managed by a "Clagett"-type procedure that consists of open-window thoracostomy, antibiotic irrigation and closure of the window . The results of such treatment were reviewed . Of the 103 patients with empyema treated between 1967 and 1983, 41 underwent open-window thoracostomy . Twenty-eight (group 1) had empyema after pneumonectomy, 13 (group 2) did not; however, 9 of the 13 in group 2 had undergone lobectomy . The mean follow-up was 46 months for group 1 and 42 months for group 2 . When surgical closure of the open-window thoracostomy was attempted, the success rate in group 1 was 85% for those without concomitant bronchopleural fistula, but only 36% in patients with a fistula . In group 2 the respective success rates were 50% and 57% . Unsuccessful closure resulted in chronic fistulas in four patients in each of the two groups . Six deaths in group 1 and two in group 2 were related to the original disease, but one was an operative death . These results demonstrate both the effectiveness and limitations of open-window thoracostomy in the management of these difficult cases. J Vet Pharmacol Ther, 1987 Sep, 10(3), 241 - 7 Distribution of cephapirin into a tissue chamber implanted subcutaneously in horses; Short CR et al.; The pharmacokinetics of cephapirin sodium and its distribution into a tissue chamber implanted subcutaneously in the neck of mature horses are described . Cephapirin was administered as an intravenous bolus dose of 20 mg/kg . The serum concentration vs time curve was best described by a two-compartment open model . Cephapirin disappeared from serum rapidly (t1/2 beta = 18.8 min), and had only a modest volume of distribution (Vd(area) approximately equal to 346 mg/kg, Vd(ss) approximately equal to 204 ml/kg) . Total clearance was also rapid (approximately equal to 13 ml/min.kg) . Concentrations of the antibiotic in tissue chamber fluid, however, were quite constant from 30 min to 3 h post-injection, and did not decay in parallel with either the concentration of the drug in serum or the estimated concentration of drug in the peripheral compartment . The ratio of area under the curve (AUC0-3 h) for serum: chamber fluid was 13.8 : 1, while that for peripheral compartment : chamber fluid was 11 : 1 . The slow rate of cephapirin transport into, and out of, the chamber may be related to its hydrophilic nature . The lack of parallelism between the chamber fluid decay curve and that of serum is characteristic of drugs with a very short half-life. J Pediatr, 1987 Sep, 111(3), 349 - 52 Corticosteroids in treatment of obstructive lesions of chronic granulomatous disease; Chin TW et al.; Two patients with chronic granulomatous disease had obstructive lesions of the gastrointestinal tract, esophagus, and genitourinary tract, which were successfully treated with corticosteroids . These obstructive lesions, caused by local granuloma formation, have been reported in 18 other patients with chronic granulomatous disease, none of whom received steroids . Our first patient, a 3-year-old boy, had emesis and weight loss associated with antral narrowing and delayed gastric emptying at age 2 years . Antibiotic therapy was ineffective, but intravenous and oral corticosteroid therapy for 10 weeks resulted in clinical cure . One year later, dysuria associated with bladder neck obstruction was also treated successfully with corticosteroids . The second child, a 10-year-old boy, had dysphagia caused by distal esophageal stenosis . Corticosteroid therapy (with concomitant antibiotics) on two occasions reversed this obstruction . Granulomatous cystitis with ureteropelvic obstruction then developed, which also responded to treatment with corticosteroids and antibiotics . Despite the risk of increased susceptibility to infection, corticosteroid therapy is justified in preventing life-threatening obstruction of vital organs. Arch Otolaryngol Head Neck Surg, 1987 Sep, 113(9), 992 - 4 Cervical osteomyelitis . An unusual complication of tonsillectomy; Tami TA et al.; Tonsillectomy is one of the most common operations performed by the otolaryngologist . Deep-neck infections are among the possible complications associated with this procedure . We encountered a case of osteomyelitis of the cervical spine occurring subsequent to an otherwise uncomplicated tonsillectomy . Although never previously reported with tonsillectomy to our knowledge, cervical osteomyelitis has been associated with other procedures and infections of the head, neck, and maxillofacial regions . Mechanisms that might explain this occurrence include direct extension via fascial planes, direct venous and lymphatic spread, and hematogenous dissemination from the contaminated surgical site . Treatment consisted of drainage and debridement of the infection, cervical immobilization, and long-term antibiotic administration . Healing was complete and cervical mobility and stability were normal at three months . Early recognition of this unusual complication of tonsillectomy is imperative to avoid potential neurologic sequelae. Surg Gynecol Obstet, 1987 Sep, 165(3), 217 - 22 Role of surgical treatment in the management of complications of the gastrointestinal tract in patients with leukemia; Villar HV et al.; The clinical course of patients with leukemia, specifically after treatment, is complicated by opportunistic infections, often derived from the gastrointestinal tract . Four hundred and thirty-eight patients with leukemia were treated at the Arizona Health Sciences Center from 1976 to 1985 . Fifty-five (13 per cent) had 60 major gastrointestinal complications develop . Thirty-seven were treated medically with a mortality rate of 51 per cent, while 18 who were treated surgically had a 17 per cent mortality rate . These infections usually occur during induction or consolidation chemotherapy . Positive blood cultures and white blood cell counts of less than 2,500 per millimeter are a frequent occurrence . The most common complications of the gastrointestinal tract are enterocolitis, perirectal sepsis and bleeding . Because of the combined defects in phagocytosis (neutropenia), antibody production and cell mediated immunity, opportunistic infections (such as viral, fungal, parasitic or bacterial) are frequent and often lethal, despite routine antibiotic coverage . A protocol to identify a subset of patients with septic leukemia who may require emergency surgical treatment is vital since death in this group is most commonly from undiagnosed sepsis or progression of hematologic defects . This protocol should include repeated physical examinations, daily roentgenograms of the abdomen, liberal use of endoscopy, contrast roentgenography and computed tomography (CT) or ultrasound . Extensive surgical procedures can be safely carried out in patients with leukemia . The diagnosis of leukemia should not be a deterrent to emergency surgical exploration. Geriatrics, 1987 Sep, 42(9), 29 - 36, 41 Bacterial pneumonia: specific diagnosis and treatment of the elderly; Gleckman RA et al.; Community-acquired bacterial pneumonia remains a formidable problem for the elderly . Patients' clinical presentations do not invariably coincide with those "classically" described . Predisposing factors, clinical manifestations, laboratory assessment, and differential diagnosis are discussed . The pivotal role of the technically adequate chest x-ray and the potential limitations of its interpretation are underscored . A comprehensive treatment program is presented, including supportive measures and specific antibiotic strategies . Immunoprophylaxis, its advantages and limitations, is also outlined. Rev Infect Dis, 1987 Sep-Oct, 9(5), 1013 - 9 Disseminated infection with Trichosporon beigelii; Walling DM et al.; Two cases of systemic infection with Trichosporon beigelii are reported . Both patients had acute leukemia and were receiving cytotoxic and antibiotic drug therapy, which included amphotericin B, at the time of sepsis . Although clinical isolates of the organisms were found to be sensitive to amphotericin B in vitro, both patients died from severe, widespread fungal infection . The pathologic findings in these two cases suggest that the host response to trichosporon infection is a granulomatous inflammation . Trichosporon is a virulent opportunistic pathogen that may originate from the gastrointestinal tract damaged by cytotoxic therapy in the patient with aplasia . Despite aggressive antifungal therapy, survival is most closely related to recovery of the host's hematopoietic system. Onderstepoort J Vet Res, 1987 Sep, 54(3), 507 - 8 A preliminary investigation into the efficacy of intraperitoneal vaccination of sheep and goat kids against heartwater; Hurter LR; The intraperitoneal route was explored both as an alternative to the intravenous route for the vaccination of sheep and goat kids against heartwater and for the administration of an antibiotic to animals suffering from the disease . Only 8 (57%) of the 14 adult sheep, and none of the 7 goat kids, were found to be immune after intraperitoneal vaccination with infective blood . However, this route was found to be very suitable and effective for the administration of tetracyclines to reacting animals. J Pharmacobiodyn, 1987 Sep, 10(9), 431 - 5 Antitumor activity of quinocarmycin against carcinoma of the lung in human tumor clonogenic assay; Chiang CD et al.; Quinocarmycin monocitrate is a novel antitumor antibiotic isolated from Streptomyces melanovinaceus . We have utilized a human tumor clonogenic assay to test the antitumor activity of this drug against carcinoma of the lung and to compare its activity with those of mitomycin C or cisplatin, which are components of the clinically effective regimens in therapy for this disease . The overall in vitro response rate (defined as less than 50% survival of tumor colony forming units) for quinocarmycin at 0.1 and 1.0 microgram/ml continuous exposure was 42% and 72%, respectively, which was superior to that of other drugs . Quinocarmycin and other antitumor drugs do not have identical spectra of antitumor activities in vitro, suggesting that this compound with good in vitro activity should be further developed for clinical trials. Antibiot Med Biotekhnol, 1987 Sep, 32(9), 700 - 2 {Effect of bruneomycin on the immune response induced in mice by various antigens}; Vatin OE; The effect of the antitumor antibiotic bruneomycin on antibody formation in response to immunization with sheep red blood cells and E . coli lipopolysaccharide was studied on mice . Marked suppression of the primary immune response following parenteral injection of the antibiotic before antigen stimulation and activation of antibody genesis due to oral administration of the drug in doses of 1 to 2 mg/kg was observed . An increase in the absolute and relative numbers of the antibody forming cells (AFC) in the spleen after the antibiotic oral administration in spite of a lowered total number of lymphocytes in it suggested that the AFC precursors (B-lymphocytes) were resistant to bruneomycin. Vestn Khir Im I I Grek, 1987 Sep, 139(9), 41 - 6 {Use of computerized tomography and echography in the diagnosis and treatment of abscesses of the abdominal cavity and retroperitoneal space}; Krylov NL et al.; An analysis of complex use of computer tomography and echography for diagnostics, aimed biopsy and following measures in 32 patients with foci of purulent infection in organs of the abdominal cavity and retroperitoneal space has been made . In 11 patients with small abscesses not more than 5 cm in diameter percutaneous aimed punctures of the pus cavity were fulfilled followed by the aspiration of the content and introduction of an antibiotic . In 21 patients percutaneous drains were introduced into the abscesses by Seldinger's method or through a trocar . Curative punctures and percutaneous drainage in 85.7% of the patients gave successful results. Trop Med Parasitol, 1987 Sep, 38(3), 236 - 8 Acute infectious diarrhea; Gyr K et al.; This review deals with the epidemiology of acute infectious diarrhea mainly with regard to third world countries . It also reports on advances in modern case management, oral rehydration, antibiotic therapy and problems of host resistance and transmission. Mol Gen Mikrobiol Virusol, 1987 Sep, (9), 41 - 4 {Kanamycin sulfate--an inducer of recA gene in Escherichia coli}; Kiselev VI; Kanamycin sulphate causes the efficient induction of recA gene, being an inhibitor of protein synthesis . Kanamycin is not known to damage the DNA structure . Possibly, the antibiotic ability to induce the SOS-genes is explained by activation of endogenous nucleases activity or by the increase of "alarmone" synthesis, the latter playing the "trigger" role in derepression of SOS-operon. J Antimicrob Chemother, 1987 Sep, 20 Suppl A, 111 - 8 Prevention of infective endocarditis: the view from the United States; Shulman ST; The American Heart Association's recommendations for the prevention of infective endocarditis were first published in February, 1955, and the most recent (fifth revision) in December, 1984 . The somewhat controversial nature of these recommendations reflects several issues, including the degree to which infective endocarditis in man is preventable and the relative safety of alternative regimens . Nevertheless, it is apparent that a reasonable fraction of cases are preventable and that antibiotics for this purpose are appropriate . It is also clear that certain patient groups, i.e . those with prosthetic valves or surgically constructed systemic-pulmonary shunts, are at greatest risk and warrant more intensive, primarily parenteral antibiotic regimens . Particularly controversial are recommendations related to the very large group of patients with mitral valve prolapse . The latest American Heart Association recommendations are presented in detail. Int J Clin Pharmacol Ther Toxicol, 1987 Sep, 25(9), 519 - 21 Efficacy and tolerance of ceftazidime in the treatment of post-operative respiratory tract infections; Tinozzi S et al.; Ceftazidime proved particularly effective in the treatment of acute respiratory tract infections arising in the immediate post-operative period, affording complete clinical cures in 88.8% of cases and a substantial improvement in the pathological picture in the other 11.2% of cases treated . The authors also draw attention to the excellent tolerance of the antibiotic, as evaluated on the basis of liver and kidney function and blood chemistry parameters and the total absence of adverse reactions. Eur J Cancer Clin Oncol, 1987 Sep, 23(9), 1379 - 84 Combination chemotherapy including epirubicin for the management of non-Hodgkin's lymphoma; Al-Ismail SA et al.; One hundred patients with untreated non-Hodgkin's lymphoma were entered in a prospective randomized study in South and West Wales designed to assess the value of the anthracycline antibiotic, epirubicin (4'-epidoxorubicin), in their management . Patients with low grade histology and progressive disease were randomized to receive either epirubicin, vincristine and prednisolone (EVP) or cyclophosphamide, vincristine and prednisolone (CVP) . The response rate of 81% in patients receiving EVP with complete remission rate of 52% were similar to a response rate of 88% and complete remission rate of 58% for patients receiving CVP . No difference was observed in survival between the two groups . Patients with high grade lymphoma were randomized to receive either cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) or cyclophosphamide, epirubicin, vincristine and prednisolone (CEOP) . The response rate was 71% for CHOP and 84% for CEOP . The complete remission rates were 46% for CHOP and 61% for CEOP . The cardiotoxicity of the two anthracyclines were monitored closely in 45 patients using measurements of systolic time intervals . Patients receiving epirubicin tolerated higher dose per course and higher total cumulative dose with less evidence of compromised left ventricular function than patients receiving doxorubicin . Epirubicin is an effective agent when used in combination chemotherapy in both low grade and high grade lymphoma with less toxicity than doxorubicin. JPEN J Parenter Enteral Nutr, 1987 Sep-Oct, 11(5), 486 - 7 Repeated rescue of a Broviac catheter: fixation of exposed cuff by a skin flap; Pineschi A et al.; A cutaneous infection exposed the cuff of a Broviac catheter employed for home-TPN in a 3-month-old child with ultra-short bowel syndrome . In order to avoid removal of the catheter, sepsis was abated by antibiotic administration through its lumen, then the exposed cuff was covered and fixed by a skin flap . The advantages proceeding from this sort of "emergency rescue" of the Broviac catheter have been: (1) to avoid a new cutdown in a child already submitted to several attempts of cannulation with sacrifice of major vessels; (2) to resume home total parenteral nutrition (TPN) in a short time, being the patient strictly dependent upon his parenteral intake and to spare a well-functioning catheter . Ten months after the last cuff covering by skin flap, the catheter is safely fixed in place and currently employed for home TPN. Eur J Immunol, 1987 Sep, 17(9), 1371 - 4 Transcription of a T cell receptor beta chain gene in L cell fibroblasts following DNA-mediated gene transfer; Sensi M et al.; Functionally rearranged T cell receptor alpha and beta-chain genes from a fluorescein-specific cytotoxic T cell clone have been introduced, together with the selectable marker gene neo, into mouse fibroblasts (L cells) by electroporation . Transformed cells were selected for neo gene expression by growth in medium containing the antibiotic G418 . Southern blot analysis of DNA from transformed L cell clones revealed that the endogeneous T cell receptor alpha and beta-chain genes were in germ-line configuration and that in 4 of the 6 clones examined the exogenously introduced rearranged alpha and beta chain genes were present . The introduced beta-chain gene is transcriptionally active in two L cell clones examined whereas no transcription of the alpha-chain gene could be detected in the same transformants. Neurochirurgia (Stuttg), 1987 Sep, 30(5), 143 - 8 {Local treatment of infections in neurosurgery with gentamicin PMMA chains (Septopal)}; Zumkeller M et al.; Treatment of infections after neurosurgical operations at the head and vertebral column is lengthy and stressful for the patient . Hence, we implanted--as has been routine in septic bone surgery for a long time--carriers of antibiotics for local antibiotic therapy in the form of Septopal chains . The course of treatment and the results obtained in 16 patients are presented . In all patients the wound cavities were filled with Septopal chains after debridement . In the course of 6-12 days the chains projecting from the skin by a stab incision were extracted sphere by sphere . The treated wound healed immediately in 14 patients; healing was delayed in 2 patients, but there were no complications . Since the use of Septopal chains results in local gentamicin levels which are so high that the conventional classification of germs into gentamicin-sensitive/gentamicin-resistant is of minor importance, the wounds healed without complications even in those patients where the germs had been classified as "resistant" in the routine antibiogram . Thus, Septopal offers the advantage of primary wound closure without secondary contamination or scatter into the environment (intensive-care ward!), shorter treatment time, reduced stress for the patient and more rapid mobilisation. Mol Cell Biol, 1987 Sep, 7(9), 3297 - 305 Development of a fungal transformation system based on selection of sequences with promoter activity; Turgeon BG et al.; A novel strategy was used to develop a transformation system for the plant pathogenic fungus Cochliobolus heterostrophus . Sequences capable of driving the expression of a gene conferring resistance to the antibiotic hygromycin B in C . heterostrophus were selected from a library of genomic DNA fragments and used, with the selectable marker, as the basis for transformation . The library of random 0.5- to 2.0-kilobase-pair fragments of C . heterostrophus genomic DNA was inserted at the 5' end of a truncated, promoterless Escherichia coli hygromycin B phosphotransferase gene (hygB) whose product confers resistance to hygromycin B . C . heterostrophus protoplasts were transformed with the library and selected for resistance . Resistant colonies arose at low frequency . Each colony contained a transformation vector stably integrated into chromosomal DNA . When the transforming DNA was recovered from the genome and introduced into C . heterostrophus, resistant colonies appeared at higher frequency . We determined the sequences of two of the C . heterostrophus DNA fragments which had been inserted at the 5' end of hygB in the promoter library and found that both made translational fusions with hygB . One of the two fusions apparently adds 65 and the other at least 86 amino acids to the N-terminus of the hygB product . Plasmids containing hygB-C . heterostrophus promoter fusions can be used unaltered to drive hygB expression in several other filamentous ascomycetes . This approach to achieving transformation may have general utility, especially for organisms with relatively undeveloped genetics. Somat Cell Mol Genet, 1987 Sep, 13(5), 553 - 61 Molecular cloning of MER-2, a human chromosome-11-encoded red blood cell antigen, using linkage of cotransfected markers; Bill J et al.; We report the molecular cloning of a human gene MER-2 located on chromosome 11 that encodes a cell surface antigen which is polymorphic on red blood cells . An essential element of the cloning strategy was cotransfection-induced linkage of pSV2-neo, which encodes resistance to the antibiotic G418, to the human MER-2 gene . An important feature of the pSV2-neo construct is that the same gene (the transposon, Tn5) that encodes G418 resistance in eukaryotic cells confers neomycin resistance in bacteria . Chinese hamster ovary (CHO) cells were cotransfected with pSV2-neo and genomic DNA from a CHO X human cell hybrid containing a single human chromosome (chromosome 11) . Transfectants expressing both the human MER-2 gene and G418 resistance were isolated by selection in the antibiotic G418, followed by indirect immunofluorescence using the monoclonal antibody 1D12, which recognizes the MER-2 antigen, manual enrichment, and single-cell cloning . Genomic DNA from a primary transfectant positive for MER-2 expression and G418 resistance was used to construct a cosmid library and cosmid clones able to grow in neomycin were isolated . Of 150,000 cosmid clones screened, 90 were resistant to neomycin and of these, 11 contained human repetitive sequences . Five neomycin-resistant cosmid clones containing human repetitive DNA were able to transfect CHO cells for G418 resistance and MER-2 expression. Proc Natl Acad Sci U S A, 1987 Sep, 84(18), 6412 - 6 Demonstration of the asymmetric effect of CC-1065 on local DNA structure using a site-directed adduct in a 117-base-pair fragment from M13mp1; Hurley LH et al.; Using DNase I and Alu I endonuclease analysis of a site-directed CC-1065-{N3-adenine}DNA adduct in a 117-base-pair fragment from M13mp1 DNA, we have demonstrated that CC-1065 produces an asymmetric effect on DNA conformation that extends more than one helix turn to the 5' side of the covalently modified adenine . CC-1065 is a potent antitumor antibiotic produced by Streptomyces zelensis, which is believed to mediate its cytotoxic effects through covalent binding to DNA . Previous studies have demonstrated that CC-1065 binds covalently to N3 of adenine and lies within the minor groove of DNA spanning a 4-base-pair sequence to the 5' side of the modified adenine . DNase I footprinting of this site-directed CC-1065-DNA adduct on the noncovalently modified strand shows that inhibition of cleavage occurs over a 12-base region, which is bordered on the 3' side by a site of 2-fold enhancement of cleavage . On the covalently modified strand a much less pronounced inhibition/enhancement pattern of cleavage occurs as far as 11 bases to the 5' side of the covalently modified adenine . While Hae III is able to cleave the DNA on both strands on the 3' side of the covalently modified adenine, Alu I is only able to cleave the covalently modified strand on the 5' side of the adduct . By taking into account the recently published structure of DNase I, we are able to interpret these results and develop a model for the effect of CC-1065 on local DNA structure . In this model, we propose selective drug-induced distortion of the covalently modified strand as a consequence of the alkylation of adenine by CC-1065. Eur J Biochem, 1987 Aug 17, 167(1), 59 - 64 Kinetics of binding of lucensomycin to natural and artificial membranes; Capuozzo E et al.; The binding of the polyenic antibiotic lucensomycin to native or modified human erythrocyte ghosts and to model membranes has been studied by monitoring the absorbance variations of the polyene at 320 nm . The non-steroidal components of the membranes (such as proteins and phospholipids) seem to affect the rate of the individual reaction steps leading to the formation of cholesterol-lucensomycin complexes rather than the ratio among these heterologous aggregates at equilibrium. Science, 1987 Aug 14, 237(4816), 779 - 81 Stable integration and expression of a bacterial gene in the mosquito Anopheles gambiae; Miller LH et al.; Foreign DNA was successfully introduced into the germline of the African mosquito vector of malaria Anopheles gambiae . Stable integration of genes into the germlines of insects had been achieved previously only in Drosophila melanogaster and related species and required the use of the P element transposon . In these experiments with Anopheles gambiae, the plasmid pUChsneo was used, which contains the selectable marker neo gene flanked by P element inverted repeats . Mosquitoes injected with this plasmid were screened for resistance to the neomycin analog G-418 . A single event of plasmid insertion was recovered . Integration appears to be stable and, thus far, resistance to G-418 has been expressed for eight generations . The transformation event appears to be independent of P. Brain Res, 1987 Aug 11, 417(2), 380 - 4 Cultured cerebellar cells as an in vitro model of excitatory amino acid receptor function; McCaslin PP et al.; Primary cultures of neurons from 8-day-old rat pups were grown for 10 days in vitro in antibiotic-free media and then analysed for changes in cyclic guanosine monophosphate (cGMP) in response to several excitatory amino acid (EAA) agonists or related antagonists . Kainic acid (KA), N-methyl-D-aspartic acid (NMDA) and quisqualic acid (QA) produced dose- and calcium-dependent increases in cGMP with KA producing the largest and QA the least increase in this cyclic nucleotide . The increase induced by NMDA was additive with both KA and QA; however, KA and QA were not additive with each other . In fact, QA completely antagonized the effects of KA and to a much greater degree than did the EAA antagonists, glutamylaminomethylsulfonic acid (GAMS) or cis-2,3-piperidine dicarboxylic acid (PDA) . 2-Amino-7-phosphonoheptanoic acid completely prevented the NMDA-induced elevations of cGMP yet had little effect on either the KA- or QA-induced elevations of this parameter . GAMS and PDA, on the other hand, were more effective in blocking the effects of KA and QA than of NMDA . These data show that cGMP levels in cerebellar granule cells provide an excellent model for studying the subtypes of EAA receptors. Med J Aust, 1987 Aug 3, 147(3), 139 - 41 Alloimmune neonatal neutropenia--a neglected diagnosis? Minchinton RM, McGrath KM. Alloimmune neonatal neutropenia is due to maternal IgG neutrophil-specific antibodies that cross the placenta to sensitize fetal neutrophils and cause neutropenia in the neonate . Within the first few weeks of life, the infant may succumb to localized or generalized bacterial infections . Haematologically, the mother is normal, but the infant is severely neutropenic . The incidence of this condition is one in 2000 neonates, but it can be overlooked easily if specialized testing is not performed in neonates with unexplained neutropenia . It is generally a self-limiting disorder, but severe infection may result in a 5% mortality . The clinical and serological features of four cases are described . The treatment of severe infections in infants with alloimmune neonatal neutropenia is essential, but the use of prophylactic antibiotic therapy during the period of neutropenia is not warranted. J Immunol Methods, 1987 Aug 3, 101(2), 279 - 85 High efficiency gene transfer and expression in normal murine B lymphocytes; Wu DD et al.; The introduction of new genetic information into hematopoietic cells offers a new approach for investigating the molecular events controlling differentiation . Retrovirus vectors have been used to transfer new genes with high efficiency into murine hematopoietic cells, primarily of the myeloid lineage . In this report, we show that vectors carrying the dominant, selectable gene for neomycin resistance (neo gene) can successfully infect normal murine B lymphocytes (CFU-B) . The infected CFU-B formed colonies in vitro in high concentrations (750 micrograms/ml) of G418, a neomycin analogue . That B lymphocytes contained the neo gene was confirmed by the findings that the putative B cell colonies growing in G418 contained antibody-producing cells and that the cells responding to the B cell mitogen, LPS, were resistant to G418 . Infection of normal spleen cells with different vectors containing a variety of transcriptional regulatory sequences resulted in 7-40% of the CFU-B becoming G418 resistant . Introduction of the immunoglobulin heavy chain enhancer into NEO vectors appeared to augment the expression of the neo gene, since the level of G418 resistance was higher in B cells infected with a NEO vector containing the enhancer than in cells infected with a vector lacking the enhancer. Arzneimittelforschung, 1987 Aug, 37(8), 969 - 71 Ambroxol plus amoxicillin in the treatment of exacerbations of chronic bronchitis; Peralta J et al.; Twenty-three patients with exacerbations of chronic bronchitis were divided in two groups in a randomized fashion receiving either amoxicillin 1500 mg/d (n = 13) or amoxicillin 1500 mg/d associated with the mucolytic drug ambroxol 90 mg/d (n = 10) . The improvement in cough, expectoration difficulties and sputum purulence was statistically more evident and occurred earlier in the ambroxol + amoxicillin group than in the amoxicillin only group . Although amoxicillin plasma and sputum levels were similar in both groups, the differences in daily sputum volume, which was also statistically greater in patients receiving ambroxol, suggests that this drug favours the bronchial mucus clearance of the antibiotic which could be related to the more favourable clinical evolution . No changes were observed in lung function tests and blood gases. Arzneimittelforschung, 1987 Aug, 37(8), 967 - 8 Influence of ambroxol on amoxicillin levels in bronchoalveolar lavage fluid; Gene R et al.; Amoxicillin levels were measured in bronchoalveolar lavage (BAL) fluid samples obtained from patients who after randomization were treated in double-blind fashion either with amoxicillin 1000 mg p.o.t.i.d . or with amoxicillin 1000 mg + ambroxol 60 mg p.o.t.i.d . Antibiotic levels were higher in the group receiving ambroxol (0.32 +/- 0.02 micrograms/ml; n = 8) than in the other one (0.19 +/- 0.02 micrograms/ml; n = 6) . This difference was statistically significant (p less than 0.001) . Comparisons of protein concentrations in BAL fluid samples and of amoxicillin plasma levels did not show significant differences in the two groups . These results seem to prove that ambroxol is able to increase the antibiotics concentration in the lungs, although the mechanism of action is still unclear . In addition it could be shown that the BAL technique is suitable for exploring the lung concentration of antibiotics. Arzneimittelforschung, 1987 Aug, 37(8), 965 - 6 Influence of ambroxol on lung tissue penetration of amoxicillin; Spatola J et al.; Lung amoxicillin levels were assessed in tissue obtained from 16 patients who underwent lung resection due to different pulmonary diseases . In this double-blind placebo controlled study patients were allocated to two groups in randomized order; one group received amoxicillin 1000 mg t.i.d . (n = 8) and the other amoxicillin 1000 mg + ambroxol 60 mg t.i.d . (n = 8) . A trend towards higher antibiotic lung tissue levels was observed in patients who received the antibiotic together with the mucolytic agent . The ratio pulmonary tissue/serum amoxicillin levels reached a significant difference being higher in the amoxicillin plus ambroxol group than in the other one (0.411 +/- 0.04 vs 0.672 +/- 0.07; p less than 0.01), even if the amoxicillin plasma levels were lower . A possible effect of ambroxol on lung tissue penetration of amoxicillin is suggested and discussed. Antibiot Med Biotekhnol, 1987 Aug, 32(8), 579 - 83 {Intracellular ATP content and nonactin biosynthesis}; Negrin S et al.; The effect of potassium orthophosphate on growth of the mycelium, its ATP contents and biosynthesis of the macrotetrolide antibiotic nonactin by Str . chrysomallus var . macrotetrolidi was studied . Direct dependence of the ATP contents in the mycelium on the amount of the phosphate added to the medium and consumed by the developing actinomycete was shown . Changes in the intracellular content of ATP depended also on the mycelium age . It was characterized by two peaks . Hemin was detected in the actinomycete mycelium . Its levels were sufficiently high and depended on the mycelium age and cultivation conditions, in particular on the phosphate content in the medium . Higher levels of nonactin biosynthesis were characteristic of the mycelium with lower contents of ATP, proteins and hemin . Intensive production of the antibiotic proceeded at the background of decreasing levels of ATP in the mycelium. Teratology, 1987 Aug, 36(1), 51 - 8 Fate of adriamycin-induced dilated renal pelvis in the fetal rat: functional and morphological effects in the offspring; Kavlock RJ et al.; Previously we reported that gestational exposure to Adriamycin, an anthracycline antibiotic used in the treatment of neoplasms, reduced renal function in the neonatal rat, and we suggested that alterations in the development of the renal papilla might be responsible for the dysfunction . In this study we exposed groups of Sprague-Dawley rats to 0, 1.0, 1.25, or 1.5 mg/kg of Adriamycin on gestation days 10-12, a period previously shown to be effective in altering postnatal renal function with this compound . Offspring were evaluated at several developmental periods in order to 1) precisely define the morphological status of the urogenital system in Adriamycin-treated offspring; 2) replicate the finding of a decreased renal concentrating ability in the neonates; 3) determine the transience/permanence of any morphological effect; and 4) correlate any permanent alterations in urogenital morphology with our indicator of neonatal functional competence . Maternal Adriamycin treatment induced alterations in the development of the renal papilla that persisted well into the postnatal life of the offspring . The first appearance of the morphological alteration occurred in the absence of other general indicators of developmental toxicity such as growth retardation . The determination of the ultimate fate and functional consequences of the structural alterations required postnatal evaluations of the renal system . Finally, a relatively simple test of renal function in the neonate proved to be predictive of the permanence of the morphological effect, and the absolute test result showed a strong correlation with the incidence of the morphological effect in the overall population. Laryngol Rhinol Otol (Stuttg), 1987 Aug, 66(8), 416 - 9 {Nasal concentrations of fusafungin following administration of a dosage aerosol (Locabiosol)}; Rohdewald P et al.; Following investigations on content uniformity and of the drug content delivered per each dose from a pressurised aerosol (Locabiosol) the concentration of the locally acting antibiotic fusafungin was determined in nasal secretions of volunteers . Quantitative HPLC-assay of fusafungin was performed following the extraction of cotton swabs used to collect nasal secretions . The volume of the nasal secretions results from the mass difference of the swabs before and after application . The concentrations of fusafungin measured on 41 volunteers over a period of 3 hrs were evidently higher than the minimum inhibitory concentrations reported in literature . The results of controlled clinical studies of other authors are in agreement with these results. J Behav Med, 1987 Aug, 10(4), 367 - 76 The effect of verbal commitment and treatment choice on medication compliance in a pediatric setting; Kulik JA et al.; This experiment examined the manner in which verbal commitment and treatment choice affect medication compliance in a pediatric setting . Parents (N = 89) of children suffering from an inner ear infection (otitis media) were asked or not asked for a verbal promise to give their child all prescribed antibiotic medication (commitment manipulation) and allowed or not allowed to choose between two equally appropriate antibiotics as the treatment for their child (choice manipulation) . Self-reports at follow-up visits, which were supported by urinalysis results, indicated that obtaining a verbal commitment significantly increased medication compliance . Verbal commitment also nonsignificantly increased the likelihood of a resolved infection at follow-up . Providing the parent with a choice of treatments had no effect on compliance or health outcome. J Rheumatol, 1987 Aug, 14(4), 852 - 3 Monoarthritis due to Mycobacterium chelonei; Gran JT et al.; A 48-year-old woman with infection of the tendon sheaths and proximal interphalangeal joint by Mycobacterium chelonei is described . Antibiotic therapy was not administered, and the patient recovered spontaneously. Eur J Haematol, 1987 Aug, 39(2), 182 - 4 A case of Bernard-Soulier syndrome: study of platelet glycoprotein Ib in a kindred; Ingerslev J et al.; The Bernard-Soulier syndrome is characterized by low platelet counts, abnormally large (giant) platelets, and impaired or absent platelet aggregation by the inducer antibiotic ristocetin . The recent discovery of the inherited biochemical defect and the deficient synthesis of platelet glycoprotein Ib (GP-Ib), has contributed greatly to the understanding of the disease . We report a case of the Bernard-Soulier syndrome presenting with bleeding from the pharynx after adenotomy . The patient and nearest family members were studied by a novel immunoperoxidase method for quantification of platelet glycoprotein Ib using a specific monoclonal antibody (AN51). Biochem Med Metab Biol, 1987 Aug, 38(1), 36 - 43 Inhibitory effect of gentamicin on gluconeogenesis from pyruvate, propionate, and lactate in isolated rabbit kidney-cortex tubules; Michalik M et al.; The effect of gentamicin on glucose production in isolated rabbit renal tubules was studied with lactate, propionate, malate, 2-oxoglutarate, and succinate as substrates . This antibiotic at 5 mM concentration inhibited gluconeogenesis from lactate by about 60% and that from either pyruvate or propionate by about 30% . In contrast, it did not alter the rate of glucose formation from other substrates studied . The rate of gluconeogenesis was higher at 1 mM propionate than at increasing concentrations of this substrate and was stimulated in the presence of 1 mM carnitine . However, the addition of carnitine did not affect the degree of inhibition of glucose formation by gentamicin . Since the mitochondrial free coenzyme A level was significantly lower in the presence of 10 than 1 mM propionate and increased on the addition of carnitine to the reaction medium, the inhibitory effect of propionate concentrations above 1 mM on gluconeogenesis in rabbit renal tubules may be due to a depletion of the free mitochondrial coenzyme A level, resulting in an inhibition of the mitochondrial coenzyme A-dependent reactions . In intact rabbit kidney cortex mitochondria incubated in State 4 as well as in Triton X-100-treated mitochondria, 5 mM gentamicin inhibited by about 30-40% the incorporation of 14CO2 into both pyruvate and propionate . The results indicate that the inhibitory effect of gentamicin on glucose formation in isolated kidney tubules incubated with lactate, pyruvate, or propionate is likely due to a decrease of the rate of carboxylation reactions. Anasth Intensivther Notfallmed, 1987 Aug, 22(4), 191 - 3 {ARDS in Mycoplasma pneumonia}; Holtermann W et al.; In this paper we describe a case of bilateral broncho-pneumonia due to invasion by mycoplasma pneumoniae, leading to ARDS . A high serum level of cold agglutinins, a mild haemolysis and a rash resembling that of an erythema multiforme were noted . The initial treatment was non-specific . After pathogen identification tetracycline therapy was initiated . Bacterial superinfections were treated with appropriate antibiotic schemas . The observed biphasic clinical course could be explained as an immunological phenomenon. Exp Cell Res, 1987 Aug, 171(2), 321 - 30 Influence of the membrane undercoat on filipin perturbation of the red blood cell membrane; Clark MR et al.; Filipin, a polyene antibiotic, interacts with beta-hydroxy sterols such as cholesterol in most cell membranes, forming bumps and pits that are visible by electron microscopy of freeze-fracture replicas . The markedly reduced perturbability of the red blood cell (RBC) membrane, compared to other cells, has been attributed to the constraining influence of the red cell membrane skeleton, the undercoat composed of spectrin, actin, and protein 4.1 . To test the influence of the membrane skeleton on filipin-induced perturbation of the RBC membrane, we studied the interaction of filipin with red cells that were inherently devoid of spectrin and RBC in which spectrin had been crosslinked or denatured . These spectrin-deficient, crosslinked, and denatured cells have a fivefold increase in the number of filipin-induced perturbations as compared to control cells, despite equivalent membrane cholesterol content . These findings confirm that the spectrin-based membrane skeleton strongly influences the organization of the membrane so as to limit perturbation by filipin:cholesterol interaction and that for membranes in which the cholesterol content is known, filipin is a useful probe for testing the avidity of spectrin-based cytoskeletal attachment. Chest, 1987 Aug, 92(2), 213 - 8 Percutaneous small bore catheter drainage in the management of lung abscesses; Parker LA et al.; For patients with pyogenic lung abscesses who do not respond to medical therapy, thoracotomy with pulmonary resection is the widely-accepted treatment of choice . Six patients with lung abscess who failed to respond to conservative medical management were treated by percutaneous catheter drainage using small catheters (10 Fr or smaller) . Five patients showed prompt clinical improvement and the sixth improved after a modification in antibiotic therapy . All patients recovered with radiographic resolution of the abscess and were well at followup periods from two months to two years . In such patients, percutaneous drainage with small catheters provides an excellent clinical result with minimal risk and trauma. J Urol, 1987 Aug, 138(2), 312 - 4 Salvage of the eroded inflatable penile prosthesis: a new concept; Furlow WL et al.; Most surgeons consider erosion of any component of an inflatable penile prosthesis as an indication for total device removal . However, it has been our contention that in selected cases conservative management can be used and the device can be salvaged . In 32 patients with erosion of various device components we performed conservative salvage techniques, consisting of immediate component replacement, repositioning of the eroded component or removal of only the eroded component in conjunction with closed drainage and antibiotic irrigation . Early success with device salvage resulted in the development of a rigid protocol for patient selection and management . Salvage techniques were successful in 16 of 22 cases of scrotal pump erosion and in all 8 cases of reservoir erosion . In 2 cases of cylinder erosion salvage attempts failed. Proc Natl Acad Sci U S A, 1987 Aug, 84(15), 5335 - 9 Retroviral gene transfer into primary hepatocytes: implications for genetic therapy of liver-specific functions; Ledley FD et al.; The liver is an important target for potential gene therapy because of the critical role it plays in intermediary metabolism and synthesis of serum proteins . We report the use of retroviral vectors for transfer of recombinant genes into primary mouse hepatocytes . Hepatocytes were grown in a defined serum-free medium and expressed liver-specific functions for up to 14 days . Hepatocytes were transformed to Genticin (G418) resistance by infection with recombinant retroviruses carrying the Tn5 neomycin-resistance gene . The G418-resistant cells exhibited characteristic hepatocyte morphology and continued to express liver-specific gene function . A retrovirus that expresses neomycin resistance driven by a herpes simplex thymidine kinase promoter produced the most efficient transformation compared with viruses using the retroviral long terminal repeat promoter or the simian virus 40 early-region promoter . These experiments indicate that primary hepatocytes can be successfully cultured and transformed with recombinant genes using retroviral vectors . These results provide a model for future somatic gene replacement therapy in which functional genes can be introduced into hepatocytes by viral-mediated gene transfer. Proc Natl Acad Sci U S A, 1987 Aug, 84(15), 5087 - 91 Conformation of a 16-residue zervamicin IIA analog peptide containing three different structural features: 3(10)-helix, alpha-helix, and beta-bend ribbon; Karle IL et al.; Boc-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib-Pro-Ala-Aib-Pro-Aib-Pro-Phe-OMe (where Boc is t-butoxycarbonyl and Aib is alpha-aminoisobutyric acid), a synthetic apolar analog of the membrane-active fungal peptide antibiotic zervamycin IIA, crystallizes in space group P1 with Z = 1 and cell parameters a = 9.086 +/- 0.002 A, b = 10.410 +/- 0.002 A, c = 28.188 +/- 0.004 A, alpha = 86.13 +/- 0.01 degrees, beta = 87.90 +/- 0.01 degrees, and gamma = 89.27 +/- 0.01 degrees; overall agreement factor R = 7.3% for 7180 data (F0 greater than 3 sigma) and 0.91-A resolution . The peptide backbone makes a continuous spiral that begins as a 3(10)-helix at the N-terminus, changes to an alpha-helix for two turns, and ends in a spiral of three beta-bends in a ribbon . Each of the beta-bends contains a proline residue at one of the corners . The torsion angles phi i range from -51 degrees to -91 degrees (average value -64 degrees), and the torsion angles psi i range from -1 degree to -46 degrees (average value -31 degrees) . There are 10 intramolecular NH...OC hydrogen bonds in the helix and two direct head-to-tail hydrogen bonds between successive molecules . Two H2O and two CH3OH solvent molecules fill additional space with appropriate hydrogen bonding in the head-to-tail region, and two additional H2O molecules form hydrogen bonds with carbonyl oxygens near the curve in the helix at Pro-10 . Since there is only one peptide molecule per cell in space group P1, the molecules repeat only by translation, and consequently the helices pack parallel to each other. Pharmazie, 1987 Aug, 42(8), 519 - 20 Investigation of stability of tetracycline hydrochloride in methylcellulose gel; Kubis A et al.; The investigations proved that granulation of tetracycline hydrochloride with ethanol, methanol or acetone does not reduce the antibiotic activity of the preparation . At room temperature the activity of the granular preparation decreases by 10% within the time range from 994 to 1074 d . Gel containing 0.7% of methylcellulose, 5% of 1,2-propylene glycol and 5% of dimethyl acetamide proved to be very stable in respect to viscosity and pH over 3 years . Application of 20% excess of tetracycline hydrochloride and storage of the gel at 4 degrees C enables maintaining it active over 21 d. Jpn J Antibiot, 1987 Aug, 40(8), 1477 - 85 {Clinical evaluation of flomoxef in pediatrics and a study on the penetration into cerebrospinal fluid}; Okada T et al.; The transfer to cerebrospinal fluid of a new oxacephem antibiotic flomoxef (FMOX, 6315-S) and its clinical efficacy against bacterial infections were investigated . 1 . In 3 cases of purulent meningitis, cerebrospinal fluid concentrations of FMOX after one shot intravenous injection of 100 mg/kg during the acute stage of infections were 5.12-6.32 micrograms/ml and ratios of FMOX in cerebrospinal fluid in serum were about 5% . During the recovery stage, cerebrospinal fluid concentrations were about 3.8 micrograms/ml and cerebrospinal fluid/serum ratios were about 3.5% . 2 . In 1 case of purulent meningitis, the treatment with FMOX was clinically effective but this case was classified as "unevaluable" because other drug was used concomitantly . FMOX was rated effective in other 2 cases of purulent meningitis . Of 9 cases of pneumonia, FMOX was rated very effective in 8 cases and it was rated only effective in the other . Of 4 cases of bronchitis, the drug was rated very effective in 3 cases and only effective in the other . FMOX was rated very effective against 2 cases of tonsillitis, also . 3 . As side effects, thrombocytosis was observed in 3 of 20 cases examined . All cases, however, were deemed unrelated to the FMOX treatment and the side effect was only transient as are often found in courses of recovery from infections. Am J Obstet Gynecol, 1987 Aug, 157(2), 502 - 6 Single-dose versus multiple-dose piperacillin prophylaxis in primary cesarean operation; Gall SA et al.; A prospective, randomized double-blind study was undertaken to determine the safety and efficacy of single-dose versus multiple-dose piperacillin for primary cesarean operation prophylaxis . After informed consent was obtained, patients received either 4 gm of piperacillin intravenously as a single dose or three 2 gm doses of piperacillin intravenously 4 hours apart . One hundred sixteen patients were evaluated for response; postoperative infection at the operative site was prevented in 52/60 (86.6%) who received the single dose and 53/56 (94.6%) who received multiple doses . The types of postoperative infections that occurred were similar in those patients in each group who developed infection and all responded well to therapeutic drugs . No adverse reactions to piperacillin were noted . Demographic characteristics and risk factors for infection were comparable for the two groups . These data support the efficacy of single-dose prophylaxis with an appropriate antibiotic agent. J Surg Oncol, 1987 Aug, 35(4), 266 - 8 Short-term prophylaxis with cefuroxime in colorectal surgery for cancer; Colizza S et al.; A controlled study of short-term prophylaxis with cefuroxime was performed on a group of 52 patients with colorectal neoplasms who underwent elective surgery . The patients were divided into two groups, A and B . Group A received the antibiotic immediately before surgery, intraincisionally and immediately after the end of operation; group B was treated only postoperatively . Each patient received a total of 5,250 mg of cefuroxime . Wound sepsis was demonstrated in 11.5% of cases of group A and 23.0% of group B (P less than 0.01); another type of sepsis was observed in 34% of group A and 11.5% of group B (P less than 0.001) . There was no difference in the operative mortality in the two groups. Surg Neurol, 1987 Aug, 28(2), 114 - 8 Nocardial brain abscess: diagnostic and therapeutic use of stereotactic aspiration; Hall WA et al.; Three cases of nocardial brain abscess are presented . All three patients were receiving immunosuppressive therapy at the time of diagnosis . Two patients had cardiac transplantation and the third had periarteritis nodosa . The patients presented with generalized seizures or focal weakness . Accurate localization of the intracerebral mass lesion was obtained from computed tomography (CT) scans, but CT-guided stereotactic aspiration was required for diagnosis and treatment in every case . After Nocardia asteroides was seen on Gram's stain and subsequently identified by culture, appropriate antibiotic therapy was initiated . Both heart transplant patients survived in good neurological condition . We believe that stereotactic aspiration followed by prolonged antibiotic therapy may significantly improve the outcome of patients with nocardial brain abscess. Biochimie, 1987 Aug, 69(8), 849 - 56 Structure-activity relationships of sparsomycin: modification at the hydroxyl group; Lazaro E et al.; Ten analogues of the antibiotic sparsomycin were prepared and evaluated in several in vitro tests . Nine of them carry a modification at the hydroxymethylene group of the molecule, two have a disulfide bond instead of the S(O)-CH2-S moiety at the sulfur-containing side chain of the molecule . While the presence of the S-S group decreases the activity of the analogues in all the tests performed, the modification at the OH group has no deleterious effects on the activity when a polyphenylalanine synthesis assay is used in an Escherichia coli extract . The same modifications, however, diminish drastically the activity of the analogues when tested in a similar Saccharomyces cerevisiae extract . A polymerization system in the archaebacterium Halobacterium halobium extract behaves like the eukaryotic preparations . A discrepancy is also found between the results of the polymerization tests and those of the 'puromycin reaction' which is also less sensitive to the modified sparsomycin analogues . The results of cell growth inhibition tests in bacteria as well as in eukaryotic organisms agree only partially with the in vitro data. Proc Natl Acad Sci U S A, 1987 Aug, 84(16), 5848 - 52 Complete nucleotide sequence of a gene conferring polymyxin B resistance on yeast: similarity of the predicted polypeptide to protein kinases; Boguslawski G et al.; Polymyxin B is an antibiotic that kills sensitive cells by disrupting their membranes . We have cloned a wild-type yeast gene that, when present on a high-copy-number plasmid, renders the cells resistant to the drug . The nucleotide sequence of this gene is presented . A single open reading frame within the sequence has the potential to encode a polypeptide (molecular mass of 77.5 kDa) that shows strong homologies to polypeptides of the protein kinase family . The gene, PBS2, located on chromosome X, is not allelic to the previously described PBS1 gene (where PBS signifies polymyxin B sensitivity) . Although pbs1 mutations confer resistance to high levels of polymyxin B, double mutants, pbs1 pbs2, are not resistant to the drug, indicating that PBS2 is essential for pbs1 activity . Models based on the proposed protein kinase activity of the PBS2 gene product are presented to explain the interaction between PBS1 and PBS2 gene products involved in conferring polymyxin B resistance on yeast cells. Biochimie, 1987 Aug, 69(8), 885 - 9 Spectinomycin resistance at site 1192 in 16S ribosomal RNA of E . coli: an analysis of three mutants; Makosky PC et al.; Three different single base substitutions were constructed at residue C-1192 in 16S rRNA on a plasmid-coded rrnB operon of E . coli using site-directed mutagenesis . All 3 mutants conferred different levels of resistance to spectinomycin in transformed cells but none affected the growth rate in the absence of the antibiotic . The G-1192 mutant conferred remarkable resistance, permitting growth in 40 mg/ml of spectinomycin. Biochim Biophys Acta, 1987 Jul 22, 892(3), 320 - 30 Effects of adriamycin on respiratory chain activities in mitochondria from rat liver, rat heart and bovine heart . Evidence for a preferential inhibition of complex III and IV; Nicolay K et al.; The inhibition of respiratory chain activities in rat liver, rat heart and bovine heart mitochondria by the anthracycline antibiotic adriamycin was measured in order to determine the adriamycin-sensitive sites . It appeared that complex III and IV are efficiently affected such that their activities were reduced to 50% of control values at 175 +/- 25 microM adriamycin . Complex I displayed a minor sensitivity to the drug . Of the complex-I-related activities tested, only duroquinone oxidation appeared sensitive (50% inhibition at approx . 450 microM adriamycin) . Electron-transfer activities catalyzed by complex II remained essentially unaltered up to high drug concentrations . Of the activities measured for this complex, only duroquinone oxidation was significantly affected . However, the adriamycin concentration required to reduce this activity to 50% exceeded 1 mM . Mitochondria isolated from rat liver, rat heart and bovine heart behaved essentially identical in their response to adriamycin . These data support the conclusion that, in these three mitochondrial systems, the major drug-sensitive sites lie in complex III and IV . Cytochrome c oxidase and succinate oxidase activity in whole mitochondria exhibited a similar sensitivity towards adriamycin, as inner membrane ghosts, suggesting that the drug has direct access to its inner membrane target sites irrespective of the presence of the outer membrane . By measuring NADH and succinate oxidase activities in the presence of exogenously added cytochrome c, it appeared that adriamycin was less inhibitory under these conditions . This suggests that adriamycin competes with cytochrome c for binding to the same site on the inner membrane, presumably cardiolipin. J Immunol Methods, 1987 Jul 16, 101(1), 51 - 6 Induction of human interleukin-1 production by polymyxin B; Damais C et al.; Lipopolysaccharide (LPS) is a well known interleukin-1 inducer . Polymyxin B sulphate (PMB) is a cyclic antibiotic which neutralizes different biological properties of LPS . Under the conditions used in our laboratory, we were able to show that PMB alone could stimulate human monocytes to produce and release interleukin-1 activity, and that PMB was unable to inhibit the production of interleukin-1 by human monocytes stimulated with LPS . On the contrary, a synergistic effect was obtained which was not observed with another stimulant such as muramyl dipeptide. Cancer, 1987 Jul 15, 60(2), 165 - 9 Toxicity of high dose Ara-C in children and adolescents; Barrios NJ et al.; The toxicity of high dose cytosine arabinoside (Ara-C) in 23 leukemic children aged 1.5 years to 16 years 11 months was evaluated . The group included 11 children with acute lymphoblastic leukemia (ALL), nine with acute nonlymphoblastic leukemia (ANLL), two with chronic myelocytic leukemia (CML) in blastic crisis, and one with Burkitt's lymphoma . Toxicity consisted of bone marrow suppression in all patients, with a mean nadir time of 11 days for platelets and granulocytes . All patients experienced nausea and vomiting; 12 of 23 had drug induced fever; seven of 23 conjunctivitis; five of 23 mucositis; four of 23 diarrhea, and one of 23 elevated transaminase with hyperbilirubinemia . Adverse reactions were mild and reversible in all patients . No serious neurologic toxicity was seen . The toxicity observed in four patients with prior cranial irradiation was not any different from nonirradiated patients . The only life-threatening effect was neutropenia, the consequences of which were generally well controlled with antibiotic therapy . While this agent was effective in induction of remission in AML patients resistant to standard doses of Ara-C, it had no significant effect in a very small number of patients with relapsed ALL and CML in blast crisis . Side effects of high dose Ara-C though relatively substantial are manageable enough to warrant wider scale efficacy trials of this agent in childhood leukemias and solid tumors. Biochemistry, 1987 Jul 14, 26(14), 4213 - 9 Purification, characterization, and amino acid composition of rabbit pulmonary bleomycin hydrolase; Sebti SM et al.; Bleomycin (BLM) hydrolase, a protective enzyme that inactivates the antitumor antibiotic BLM, was purified (6000-fold) to homogeneity from rabbit lungs by DEAE-Sephacel, phenyl-Sepharose chromatography, BLM-Sepharose affinity chromatography, and Mono Q fast protein liquid chromatography . The enzyme had a molecular mass of 250,000 daltons as demonstrated by Superose gel permeation chromatography and polyacrylamide gel electrophoresis (PAGE) under native conditions . Sodium dodecyl sulfate-PAGE revealed a single band of 50,000 daltons, suggesting a pentameric structure . The Km and Vmax for BLM A2 were 1.3 mM and 5.9 mumol mg-1 h-1, respectively . BLM hydrolase activity was labile, had a half-life of 25 min at 56 degrees C, 10 h at 37 degrees C, and 5 days at 4 degrees C, and was stabilized by 2 mM dithiothreitol . The enzyme had a pH optimum of 7.0-7.5 and was inhibited by N-ethylmaleimide, leupeptin, puromycin, and divalent cations such as Cu2+, Cd2+, Zn2+, and Co2+ but was unaffected by chelating agents . On the basis of Mono P chromatofocusing chromatography, three isoforms of BLM hydrolase (apparent pI's of 5.3, 4.5, and 4.3) were present in rabbit pulmonary cytosol . The elution profiles of BLM hydrolase from phenyl-Sepharose and Mono P chromatofocusing indicated that this enzyme is hydrophobic and acidic . This was confirmed by amino acid composition analysis, which demonstrated that 48% of the total amino acids of bleomycin hydrolase were hydrophobic and 37% were acidic. Life Sci, 1987 Jul 13, 41(2), 235 - 40 Analgesic effect of actinonin, a new potent inhibitor of multiple enkephalin degrading enzymes; Hachisu M et al.; Actinonin, previously isolated as an antibiotic and shown to be an inhibitor of aminopeptidase M (EC 3.4.11.2), has now been shown to inhibit three enkephalin-degrading enzymes from guinea-pig striatum . The values of IC50 were 0.39 microM for striatal membrane aminopeptidase ("enkephalin-aminopeptidase") and 5.6 microM striatal membrane neutral endopeptidase ("enkephalinase A") . Furthermore, soluble dipeptidylaminopeptidase in a rat whole brain homogenate was also inhibited by actinonin with the IC50 value of 1.1 microM . Actinonin administered intracisternally (i.cist., 50 micrograms) or intraperitoneally (i.p., 100 mg/kg), potentiated the analgesic action of met-enkephalin (50 micrograms i.cist.) . analgesia by a tail-flick test . The potentiating activity of actinonin i.p . to met-enkephalin analgesia was almost the same potency as that of thiorphan, whereas the inhibitory activity of actinonin against enkephalinase A was 1/1000 that of thiorphan . Actinonin alone, administered either i.cist . or i.p., showed an analgesic action as estimated by the tail-flick test. Sex Transm Dis, 1987 Jul-Sep, 14(3), 160 - 4 Effect of prior sexually transmitted disease on the isolation of Chlamydia trachomatis; Katz BP et al.; In developed nations, Chlamydia trachomatis is the most common sexually transmitted pathogen . To determine whether prior disease affects the probability of subsequent chlamydial infection, we took culture specimens from 2,546 men and 1,998 women attending a sexually transmitted diseases clinic . The men had nongonococcal urethritis and the women were contacts of men who had a positive chlamydial culture or nongonococcal urethritis . Significantly lower isolation rates for those with a history of sexually transmitted diseases were found for both men (29% vs . 38%; P less than 0.0001) and women (27% vs . 36%; P less than 0.0001) . In addition, both men and women with previously documented chlamydial infections had a lower isolation rate at the index visit, if the previous infection occurred less than, as opposed to more than, six months earlier (men: 20% vs . 41%; P = 0.0006; women: 14% vs . 35%; P = 0.003) . These relationships were found to be independent of age . However, the effect of partial immunity due to prior infection could not be distinguished from that of prior antibiotic therapy, and if such immunity does confer protection against reinfection, that protection appears to be both partial and of relatively short duration. Acta Anaesthesiol Scand, 1987 Jul, 31(5), 397 - 404 Predictive value of skin testing, neutrophil migration and C-reactive protein for postoperative infections in cardiopulmonary bypass patients; Kress HG et al.; Despite antibiotic cover for cardiac surgery the development of postoperative infection remains a feared complication . The present prospective study was designed to evaluate whether it is possible to identify preoperatively those individuals in whom the risk of a postoperative infection is significantly greater . Skin test response, chemotaxis and random migration of neutrophils, and serum levels of C-reactive protein (CRP) were chosen as indicators of host resistance . Pre-operatively and at defined postoperative time intervals, 80 patients undergoing open-heart surgery with the aid of cardiopulmonary bypass were examined . Of all the immunological variables measured in this study, the state of anergy proved the most reliable predictor of postoperative infection . Six of the nine pre-operatively anergic patients developed infections (P = 0.00026) representing one half of the postoperatively infected patients . No predictive role of CRP level or neutrophil chemotaxis can be derived from our data . The pre-operatively decreased random migration of polymorphonuclear leukocytes (PMN) from postoperatively infected patients, however, along with the significant defects in chemotactic and random PMN motility seen after cardiac surgery may partly explain the predisposition to bacterial infection in these patients . In conclusion, a pre-operative skin test makes a valuable contribution to the assessment of the patient's postoperative infectious risk. J Antibiot (Tokyo), 1987 Jul, 40(7), 1036 - 43 Physico-chemical interaction of mycobacillin with Aspergillus niger protoplast membrane, the site of its action; Das SK et al.; Mycobacillin partially quenched the strong fluorescence when 1-anilino naphthalene 8-sulfonate (ANS) was added to protoplast or plasma membrane but is without any effect on weak fluorescence when added to cell-free extract . There are two classes of ANS binding sites on protoplast or plasma membrane of which one class is sensitive to mycobacillin, being competitively abolished by it . Mycobacillin also non-competitively inhibits the binding of pyrene, a lipid specific probe . Thus it follows from the inhibition by mycobacillin of ANS or pyrene binding to protoplast or plasma membrane that the site of action of the antibiotic is located in the plasma membrane . Interaction between mycobacillin and the plasma membrane is physico-chemical in nature. J Antibiot (Tokyo), 1987 Jul, 40(7), 1023 - 7 Amides of polyene macrolide aureofacin . Synthesis and biological properties; Czerwinski A et al.; Synthesis and biological properties of a number of amides of polyene macrolide antibiotic aureofacin obtained in the reaction of the antibiotic with various glycine esters are described. Equine Vet J, 1987 Jul, 19(4), 295 - 8 Luxation of the metacarpophalangeal and metatarsophalangeal joints in horses; Yovich JV et al.; Lateral or medial luxation of the metacarpophalangeal or metatarsophalangeal (fetlock) joint in 10 horses is presented . Closed and open fetlock luxation each occurred in five horses . Horses were treated by cast immobilisation after debridement of soft tissue and joint lavage in cases of open luxations . Suture apposition of a ruptured collateral ligament was attempted in three cases . Antibiotic therapy was used in all cases of open fetlock luxation but non-steroidal anti-inflammatory medication was used inconsistently . Whether closed or open, fetlock luxations had a good prognosis for return to breeding status . After treatment, seven horses were used for breeding, one horse was ridden for nine years, one horse remained lame and was destroyed and one horse was lost to follow up. Biull Eksp Biol Med, 1987 Jul, 104(7), 113 - 6 {Morphological manifestations of anthracycline cardiomyopathy in the ventricular myocardium of the rat}; Semenov DE et al.; Cardiomyopathy and plastic contractile myocardial insufficiency were simulated in Wistar rats by an anthracycline antibiotic rubomycin . The myocardium in conditions of DNA-dependent RNA synthesis suppression was studied using polarization, electron microscopy and the method of cardiomyocyte isolation . During anthracycline cardiomyopathy in the absence of necrotic and necrobiotic myocardial injuries there was a smaller depression of cardiomyocyte population and their nuclei in the right ventricle (23 and 22% respectively) than in the left ventricle (38 and 39% respectively) . It was concluded that a smaller amount of cardiomyocyte population was in the phase of intensive protein synthesis in the right than in the left ventricular myocardium. Tijdschr Diergeneeskd, 1987 Jul 1, 112(13), 795 - 9 {Mycoplasma bovis arthritis in a herd of dairy cattle}; Wentink GH et al.; Cases of severe arthritis due to M . bovis in a herd of dairy cattle are reported . M . bovis was also isolated from the mammary tissues and lungs of one of the lame animals at autopsy; this animal did not show any symptoms of respiratory disease or mastitis . M . bovis was detected in milk samples of eight animals in which mastitis was present or absent, though not in any of the animals affected with arthritis . Antibiotic therapy failed to produce permanent results in the lame animals . Ultimately, spontaneous recovery occurred in these cases . M . bovis was no longer isolated following the short period during which lameness was present. Med Hypotheses, 1987 Jul, 23(3), 253 - 7 Glutathione: is it an evolutionary vestige of the penicillins? Spallholz JE. Glutathione is structurally similar to the precursor of the antibiotics found in the fungi of the genus Penicillium and Cephalosporium . The structural similarity is such to permit the rearrangement of glutathione to form the beta-lactam ring, common to many antibiotics . The possibility exists that glutathione may have evolved away from an antibiotic role in cells with the evolutionary development of specialized cells of immune systems. Am J Kidney Dis, 1987 Jul, 10(1), 62 - 5 The use of intracatheter instillation of streptokinase in the treatment of recurrent bacterial peritonitis in continuous ambulatory peritoneal dialysis; Norris KC et al.; Recurrent bacterial peritonitis resistant to therapy with antibiotics is seen in a small percentage of patients maintained on continuous ambulatory peritoneal dialysis . In these patients, removal of the Tenckhoff catheter is necessary to achieve a cure . Sequestration of bacteria within fibrin clots located on the catheter has been postulated to contribute to this resistance to standard therapy . We, therefore, examined the efficacy of intraperitoneal streptokinase in combination with antibiotic therapy in the treatment of two patients with recurrent bacterial peritonitis . After addition of streptokinase to the therapeutic regimen, no further episodes of peritonitis were observed after 6 to 8 weeks follow-up . These data suggest that intraperitoneal streptokinase may be useful as adjunctive therapy in the treatment of recurrent bacterial peritonitis. J Thorac Cardiovasc Surg, 1987 Jul, 94(1), 12 - 9 Evaluation of long-term results of homograft and heterograft valves in extracardiac conduits; Bull C et al.; Between 1971 and 1982, 249 patients received right heart extracardiac conduits . The 173 patients who survived 30 days were reviewed retrospectively; 72 had antibiotic-sterilized aortic homografts, 97 had xenografts of various types, and four had valveless tubes . Reoperation for conduit obstruction was required as early as 13 months after the original operation, but actuarial analysis showed no differences in overall performance of homograft and heterograft conduit groups with respect to late death or survival free of conduit obstruction . More important risk factors for late death or the need for reoperation were the severity of the underlying cardiac lesions and the influence of early postoperative complications . When analyzed statistically, the performance of conduits bearing homografts was disappointing, influenced sometimes by complications in the Dacron extension tubes . Repairs dispensing with conduits entirely should be evaluated. AJR Am J Roentgenol, 1987 Jul, 149(1), 59 - 62 Percutaneous drainage of periappendiceal abscesses: review of 20 patients; Jeffrey RB Jr et al.; Twenty patients with periappendiceal abscesses diagnosed by CT underwent percutaneous catheter drainage . Eighteen (90%) of the 20 patients were successfully treated by percutaneous drainage and antibiotic therapy alone . In two of these patients, however, small recurrent abscesses were diagnosed by CT 4 and 6 weeks after drainage, but these abscesses resolved with additional antibiotic therapy . Surgery was performed in two patients in whom percutaneous drainage failed . One was a diabetic patient who had a gas-forming abscess that extended into the posterior pararenal space . Surgery was necessary in a second patient because of a technical failure of catheter insertion, which resulted in perforation of the abscess cavity and peritonitis . Abscess sinograms in eight (44%) of 18 patients showed fistulas between the abscess cavity and the base of the cecum or appendix . However, the fistulas did not pose a problem in clinical management, and all closed within 14 days . Percutaneous drainage is an effective alternative to surgery in selected patients with periappendiceal abscesses. J Oral Maxillofac Surg, 1987 Jul, 45(7), 577 - 82 Intraosseous wire fixation versus rigid osseous fixation of mandibular fractures: a preliminary report; Theriot BA et al.; While wire osteosynthesis has been the accepted modality to use with open reduction of mandibular fractures, several authors have suggested the use of more rigid techniques to achieve the same result while also eliminating adverse effects associated with prolonged maxillomandibular fixation . Few studies have directly compared the two techniques in a prospective manner . The purpose of this paper was to evaluate complications seen with wire osteosynthesis versus a small bone plating system in management of mandibular fractures . The results suggest that small bone plating systems similar to the one used in this study may serve as a suitable alternative to wire osteosynthesis for the management of mandibular parasymphysis, body, and angle fractures . The length of the procedure, the length of hospital stay, and patient comfort were comparable with the two techniques . Factors that may contribute to failure are: location of the fracture, poor patient compliance, length of time from the trauma to the repair, antibiotic choice, and most importantly, operator skill and experience. Clin Pharmacol Ther, 1987 Jul, 42(1), 33 - 41 Enoxacin-warfarin interaction: pharmacokinetic and stereochemical aspects; Toon S et al.; The interaction between the new quinoline-azaquinoline antibiotic enoxacin and the oral anticoagulant warfarin was investigated in six healthy male volunteers . Enoxacin was found not to affect the hypoprothrombinemic response produced by warfarin but did produce a decrease in the clearance of the less pharmacologically potent enantiomer of warfarin, (R)-warfarin . The decreased clearance of (R)-warfarin produced by concomitant enoxacin administration was found to be a consequence of inhibition by enoxacin of the (R)-6-hydroxywarfarin metabolic pathway. Eur J Drug Metab Pharmacokinet, 1987 Jul-Sep, 12(3), 215 - 8 Fusidic acid in tear fluid: pharmacokinetic study with fusidic acid viscous eye drops; van Bijsterveld OP et al.; Fusidic acid viscous eye drops, Fucithalmic (R), is a new eye antibiotic preparation which shows sustained-release properties . The long-lasting antibiotic concentrations in tear fluid can be ascribed to the carbomer used in the vehicle . Fusidic acid viscous eye drops was found to give significantly higher tear fluid concentrations than chloramphenicol viscous eye drops, the latter based on methylcellulose when investigated in rabbit eyes and dog eyes . In volunteers the excretion half-life of fusidic acid from tears was found to be 1.9 h . From a pharmacokinetic point of view and from already available clinical data, fusidic acid viscous eye drops would seem to be effective when given only twice daily. Rev Argent Microbiol, 1987 Jul-Sep, 19(3), 91 - 100 {Production of thermolabile exotoxin by strains of Escherichia coli isolated in Argentina}; Rivas M et al.; The production of heat-labile enterotoxin (LT) by E . coli strains was studied . Four strains isolated from acute infant diarrhea cases in Argentina and one reference strain, all of them producers of different levels of LT, were employed . GM1-ELISA was used as titration method . The production was assayed in two culture media; Evans (Ev) and Trypticase Soy Broth (CTS) with or without glucose and with different concentrations of lincomycin (0; 30; 45 y 90/micrograms/ml) . The effects of pH and inoculum concentration were also examined . Higher levels of LT were found to be produced in Ev (mean production value X = 233.1 ng/ml) than in CTS (X = 133.8 ng/ml), although the difference was statistically not significant (P = 0.22) . Lincomycin addition stimulated toxin synthesis and release in both media, and these effects were found to increase with the concentration of the antibiotic (P less than 0.01) . Glucose increased the LT levels of low-producing strains and also the growth rate, cellular yield and LT levels of 40T and CC2e strains . Levels of LT released were found to be independent of inoculum concentration . In CTS without pH control, the LT production was one half the levels attained with regulated pH . This was not an effect on the release of the toxin as the determination included both the extracellular LT and the intracellular toxin accumulated in the periplasmic space, which is released by polymyxin B treatment . A pH-dependent inactivation of the synthetized and release toxin was demonstrated. Biofizika, 1987 Jul-Aug, 32(4), 638 - 41 {Characteristics of copper-induced streptomycin transport in Escherichia coli}; Lebedev VS et al.; Copper dependent uptake of streptomycin by resting E . coli cells was studied . It was shown that copper stimulates the aminoglycoside uptake only when bacteria possess endogenic energy sources . Additional accumulation of positive charged molecules of the antibiotic is accompanied by partial depolarisation of the membrane, its steady state distribution between cells and the medium corresponding to the resulted value of the membrane potential . On the basis of the data obtained it was suggested that under the influence of copper membrane permeability for streptomycin increases. Radiol Med (Torino), 1987 Jul-Aug, 74(1-2), 81 - 7 {Percutaneous pancreato-gastrostomy in the treatment of pancreatic pseudocysts . Presentation of 2 cases}; Gandini G et al.; The authors describe a new method for the treatment of pancreatic pseudocysts using a personal technique: the percutaneous pseudocystogastrostomy . Under US and fluoroscopy guidance at first a percutaneous drainage is introduced in the pseudocyst using a transgastric approach . For seven days the drainage catheter is flushed with antibiotic solution (Rifocin), then under fluoroscopy and endoscopy guidance doubled pig-tail catheter is placed with its curlend ends in the lumen of the stomach and pseudocyst respectively . After 60 days the double pig-tail catheter is removed endoscopically . Two patients with pancreatic pseudocysts were treated successful by this method . No complications or recurrences were observed. Arch Ophthalmol, 1987 Jul, 105(7), 922 - 4 Topical vs systemic gentamicin penetration into the human cornea and aqueous humor; Insler MS et al.; Twenty-two patients undergoing penetrating keratoplasty received either topical fortified gentamicin (13.6 mg/mL) or a loading dose of intramuscular gentamicin before surgery . Cornea and aqueous humor samples were obtained and assayed by radioimmunoassay for gentamicin . In the topical group, the average gentamicin levels in the cornea and aqueous were 16.2 micrograms/g and 0.3 microgram/mL, respectively . Parenteral drug levels were less variable and averaged 6.1 micrograms/g in the cornea and 0.4 microgram/mL in the aqueous . Although this study demonstrates that parenteral therapy can be used to deliver adequate drug levels to the cornea, it requires far more antibiotic and subjects the patient to potentially toxic systemic side effects . Therefore, topical administration is the preferred route of delivery of antibiotic to the cornea. Fertil Steril, 1987 Jul, 48(1), 33 - 8 Pulsatile intravenous gonadotropin-releasing hormone for ovulation-induction in infertile women . I . Safety and effectiveness with outpatient therapy; Jansen RP et al.; Pulsatile intravenous gonadotropin-releasing hormone (IV-GnRH) was used in 36 infertile patients with primary amenorrhea (n = 5), secondary amenorrhea due to hypothalamic chronic anovulation (HCA) (n = 22), hyperprolactinemia (n = 1) or polycystic ovary syndrome (PCOS) (n = 5), and oligomenorrhea (n = 3) . Treatment was commonly initiated in the hospital but was then continued outside, with patients and local physicians accepting responsibility for maintaining IV-GnRH delivery systems . Twenty-eight of 113 treatment cycles (24.8%) resulted in pregnancy, with four spontaneous abortions (14.3%) and four twin pregnancies (16.7%) among 24 births . Probability of pregnancy per treatment cycle was significantly higher for primary amenorrhea (0.30) and for HCA (0.33) than for PCOS (0.07; P less than 0.05) and for oligomenorrhea (no conceptions; P = 0.01) . Ovulatory cycles were not achieved in five patients (primary amenorrhea, n = 1; PCOS, n = 3; oligomenorrhea, n = 1) . There were no serious complications; six patients recorded eight febrile episodes, which responded quickly to antibiotic therapy and cannula change . The authors conclude that outpatient IV-GnRH is safe, practical, and effective for follicular stimulation and ovulation induction in women presumed to have GnRH deficiency and in whom clomiphene therapy fails, and that less intensive monitoring is needed compared with gonadotropin ovulation induction therapy. Am J Hosp Pharm, 1987 Jul, 44(7), 1625 - 8 Stability of penicillins in total parenteral nutrient solution; Perry M et al.; The stability of ticarcillin, mezlocillin, and piperacillin in total parenteral nutrient (TPN) solutions at concentrations commonly used in adults was determined . Each antibiotic was added separately to three different amino acids-dextrose TPN solutions in two concentrations: 10 and 20 mg/mL . Amino acids concentration ranged from 25 g/L to 50 g/L . Dextrose concentration ranged from 100 g/L to 350 g/L . Solutions were assayed for antibiotic concentration immediately after mixing (time 0) and at 4, 8, 24, and 48 hours by high-performance liquid chromatography . The effect of the added penicillins on the stability of amino acids and other TPN additives was not investigated . Mezlocillin and piperacillin 10 and 20 mg/mL exhibited stability in TPN solution at 24 hours . Ticarcillin was stable for 24 hours at a concentration of 10 mg/mL, but at 20 mg/mL it was unstable at all times tested . The three antibiotics demonstrated the same characteristic stability in all three TPN solutions, suggesting that the concentrations of dextrose and amino acids did not affect stability . Ticarcillin, mezlocillin, and piperacillin are stable for 24 hours in the TPN solutions studied. Otolaryngol Head Neck Surg, 1987 Jul, 97(1), 18 - 23 Successful replantation of amputated nose and auricle; Fuleihan NS et al.; Amputations of the nose and of the auricle present difficult management problems . Application of simple reattachment techniques, followed by aggressive medical therapy which consists of cooling, anticoagulation, antibiotic coverage, and multiple stab incisions in the amputated tissues, have resulted in the successful replantation of major portions of an amputated nose and an amputated auricle with satisfactory cosmetic results. J Clin Microbiol, 1987 Jul, 25(7), 1239 - 43 Whole chromosomal DNA probes for rapid identification of Mycobacterium tuberculosis and Mycobacterium avium complex; Roberts MC et al.; Whole chromosomal DNA probes were used to identify clinical isolates of Mycobacterium tuberculosis, Mycobacterium avium complex, and Mycobacterium gordonae . The probe for M . tuberculosis was prepared from Mycobacterium bovis BCG, which has been shown to be closely related to M . tuberculosis . A probe for the M . avium complex was prepared from three strains representing each of the three DNA homology groups in the M . avium complex . The probes were used in dot blot assays to identify clinical isolates of mycobacteria . The dot blot test correctly identified 57 of the 61 (93%) cultures grown on solid media, and 100% of antibiotic-treated broth-grown cells were correctly identified . Identification by dot blot required a maximum of 48 h . When the probes were tested against 63 positive BACTEC (Johnston Laboratories, Inc., Towson, Md.) cultures of clinical specimens, 59% were correctly identified . However, of the 14 BACTEC cultures that had been treated with antibiotics before being lysed, 13 (93%) were correctly identified. J Anal Toxicol, 1987 Jul-Aug, 11(4), 175 - 8 A simple enzymic digestion procedure of intact tissue samples in pharmacokinetic drug analysis; de Groot G et al.; A simple procedure is described for the enzymic digestion of intact solid tissue samples . The samples are digested in an enzyme suspension containing collagenase and subtilisin Carlsberg without additional grinding or homogenizing . Bacterial growth during digestion is reduced by addition of an antibiotic solution . The resulting digests contain only very small tissue fragments . The total digestion is carried out at physiological conditions of temperature and pH, which makes the procedure suitable for inclusion in extraction procedures in a broad pH range . Since a minimum of sample manipulation is required, the procedure can be appropriately included in pharmacokinetic studies in which large series of samples are involved. Antibiot Med Biotekhnol, 1987 Jul, 32(7), 517 - 20 {57Co-bleomycetin distribution in the body of experimental animals with hyperglycemia}; Ul'ianenko SE et al.; Distribution of 57Co-bleomycetin in organs and tissues of rats with experimental short-term hyperglycemia was studied . Hyperglycemia was induced by intraperitoneal administration of 40 per cent glucose solution in doses of 1 to 10.4 g/kg . The labeled antitumor antibiotic was also administered intraperitoneally (0.2-0.8 MBq per animal) . The data on both the external radiometry in the area under the animal limb and the radiometry of separate organs and tissues showed that hyperglycemia markedly altered pharmacokinetics of the labeled antibiotic and retarded its elimination . With respect to the lungs it even increased the drug tropism and accumulation . This information may be useful in radionuclide diagnosis and therapy in particular of lung cancer . The time course of glucose concentration in blood was not an adequate criterion of hyperglycemia influence since the influence of hyperglycemia on retarding the drug elimination was also observed when the level of glucose in blood did not differ from the initial one. Biochem Biophys Res Commun, 1987 Jun 30, 145(3), 1149 - 57 Stimulation of transcription and translation by aurin tricarboxylic acid in mitochondrial lysates from Ehrlich ascites cells; Kulkarni GR et al.; We have prepared a submitochondrial fraction from Ehrlich ascites tumor cell mitochondria which shows transcription and translation activities . The antibiotic aurin tricarboxylic acid (ATA) at low concentrations induces both RNA and protein synthetic activities of the mitochondrial lysate by several fold . At high concentrations, however, ATA inhibits the translation activity but continues to stimulate the transcription activity in a dose dependent manner up to 0.5 mM concentration tested . The lysate system transcribes endogenous DNA yielding RNA species resembling control mitochondrial RNA and synthesizes authentic cytochrome oxydase I and cytochrome oxidase II subunits. Lancet, 1987 Jun 27, 1(8548), 1477 - 9 Corticosteroids as adjunctive therapy in treatment of Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome; MacFadden DK et al.; 10 patients with the acquired immunodeficiency syndrome whose respiratory failure due to Pneumocystis carinii pneumonia (PCP) was deteriorating rapidly had 7 days of intravenous methylprednisolone added to their antibiotic regimen . 8 similar patients were treated with antibiotic therapy alone . 9 of the 10 methylprednisolone-treated patients survived their episode of PCP, compared with 2 of the 8 conventionally treated patients . Clinical improvement was evident within 2 days of the start of steroid therapy, and in none of the 10 patients did clinical deterioration or recurrence of PCP occur on cessation of steroid therapy . In 1 steroid-treated patient disseminated herpes zoster developed 2 days after discontinuation of methylprednisolone . Methylprednisolone seems to be a useful adjunctive therapeutic agent for patients with AIDS in whom Pneumocystis carinii is the sole respiratory pathogen. Cell, 1987 Jun 19, 49(6), 825 - 33 Mutations in the gene for EF-G reduce the requirement for 4.5S RNA in the growth of E . coli; Brown S; A general strategy is described for the isolation of suppressors of essential genes whose functions are unknown . This strategy was used to analyze the role of 4.5S RNA, an essential RNA of E . coli . In this strategy, the structural gene for 4.5S RNA is fused to the Ptac promoter in such a way that the strain becomes dependent upon inducers of lac for growth . Mutants mapping to fus, the structural gene for protein synthesis elongation factor G, appear as spontaneous, inducer-independent revertants . These mutants alter the intracellular distribution of 4.5S RNA such that it sediments at 70S or greater . Furthermore, the increased sedimentation velocity is sensitive to the antibiotic puromycin . These results show that 4.5S RNA physically associates with the ribosome in performing its essential function, and that this association is mediated by elongation factor G. J Biol Chem, 1987 Jun 15, 262(17), 7967 - 72 A proton and carbon 13 nuclear magnetic resonance study of neomycin B and its interactions with phosphatidylinositol 4,5-bisphosphate; Reid DG et al.; The entire proton NMR spectrum of the aminoglycoside antibiotic neomycin B has been assigned at physiological pH by a combination of two-dimensional J-resolved and J-correlated and nuclear Overhauser enhancement difference spectroscopy . Unambiguous assignment of all four ring systems is possible without recourse to model or derivative compounds by observing nuclear Overhauser enhancements between as well as within rings . The subsequent assignment of the carbon 13 spectrum is simply achieved using two-dimensional heteronuclear J-correlated techniques . The proton NMR spectrum of a sonicated aqueous dispersion of the intracellular second messenger precursor phosphatidylinositol 4,5-bisphosphate is reported for the first time . The spectrum is consistent with a high degree of side chain unsaturation and a conformation for the myo-inositol head group, which appears highly mobile, in which all bulky substituents are equatorial (except the 2-hydroxyl) . Addition of aliquots of phosphatidylinositol 4,5-bisphosphate to an aqueous buffered solution of neomycin B induces complex changes in the whole spectrum of the latter, including downfield shifts of differential magnitude for several well-resolved signals, viz . the anomerics, and the pair of methylene protons of the substituted cyclohexane . The complexation kinetics are fast on the NMR time scale at 25 degrees C . The binding results are discussed in terms of a tentative complexation geometry. Minerva Med, 1987 Jun 15, 78(11), 777 - 84 {Collateral effects of 9-alpha-fluor-prednisolone acetate and kanamycin, administered by nasal spray . Clinical experience and experimental data}; Petrini MT et al.; Iatrogenic pathology due to treatment with steroid drugs used by systemic route is well known . On the contrary iatrogenic pathology due to topical use of these drugs is rarely reported . Two cases of abuse of 9-alpha- fluor-prednisolone and kanamycin administered by endonasal route are reported . The same treatment has been carried out in patients and rabbits . Clinical and bio-humoral data in patients and anatomo-pathological findings in rabbits are reported . The risks, sometimes underestimated, of an overdose of corticosteroid and antibiotic drugs used by endonasal route are pointed out. Biochim Biophys Acta, 1987 Jun 12, 900(1), 145 - 56 Structure of planar membrane formed from liposomes; Kolomytkin OV; Lipid vesicles with incorporated ion channels from polyene antibiotic amphotericin B were used to investigate structures of planar membranes formed by Shindler's techniques . A planar membrane assembled on the aperture in a lavsan film from two layers generated at the air-aqueous liposome suspension interface is not a simple bilayer but a bimolecular membrane containing numerous partly fused liposomes . A complete fusion of liposomal membranes with the planar bilayer is an unlikely event during membrane formation . A planar bimolecular lipid membrane without incorporated liposomes can be made by a method consisting of three stages: formation of a lipid layer on the air-water interface of a suspension containing liposomes, transfer of this layer along the surface of the solution into a chamber containing a solution without liposomes where a lipid monomolecular layer forms gradually (within about 20 min) at the air-water interface, assembling of the planar bilayer membrane from this monolayer . The knowledge of the planar membrane structure may be useful in experiments on incorporation of membrane proteins into a planar lipid bilayer. Hosp Pharm, 1987 Jul, 22(7), 698 - 700, 718 Cost savings with a new combination clindamycin-gentamicin admixture policy; Rogers RC et al.; Clindamycin and gentamicin are frequently prescribed by obstetricians and gynecologists (OB-GYN) for various pelvic infections in women . These two antibiotics maintain chemical stability when admixed in a small-volume parenteral . The institution of an admixture policy that recommends combining these agents when both drugs are prescribed in OB-GYN patients would decrease the frequency of administration, improve patient convenience, reduce risk of administration errors and intravenous line contamination, and reduce costs of antibiotic therapy . The authors analyzed antibiotic use in OB-GYN patients over a 3-month period and found that the anticipated cost savings appeared sufficient to warrant an admixture policy change . Six months after initiating the new policy, the authors found an increase in the use of clindamycin and gentamicin, but a decrease in the overall cost for providing antibiotic therapy to OB-GYN patients . Savings for the second quarter were due to the pharmacy providing less expensive clindamycin-gentamicin therapy. J Biol Chem, 1987 Jun 5, 262(16), 7927 - 31 Acetoacetyl-acyl carrier protein synthase, a potential regulator of fatty acid biosynthesis in bacteria; Jackowski S et al.; The first condensation reaction in the fatty acid biosynthetic pathway in Escherichia coli was rate-limiting as judged by analysis of the relative pool sizes of acyl carrier protein (ACP) thioester intermediates in vivo . Comparable concentrations of acetyl-ACP, malonyl-ACP, and nonesterified ACP were present during logarithmic growth, whereas long-chain acyl-ACP comprised a minor fraction of the total ACP pool . The antibiotic cerulenin was used to irreversibly inhibit both beta-ketoacyl-ACP synthases I and II . However, acyl-ACP formation in vivo was not blocked by this antibiotic, and short-chain (4-8-carbon) acyl-ACPs increased to 60% of the total ACP pool in cerulenin-treated cells . These data suggested that existence of a cerulenin-resistant condensing enzyme that was capable of catalyzing the initial steps in chain elongation . A unique enzymatic activity, acetoacetyl-ACP synthase, that specifically catalyzed the condensation of malonyl-ACP and acetyl-ACP was detected in E . coli cell extracts . Acetoacetyl-ACP synthase activity was not inhibited by cerulenin and was present in extracts prepared from a double mutant harboring genetic lesions in beta-ketoacyl-ACP synthases I and II (fabB20 fabF3) . These data point to the condensation of malonyl-ACP and acetyl-ACP as the ra