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Ann Intern Med, 1978 Nov, 89(5 Pt 2 Suppl), 743 - 5 Common infections in ambulatory patients; Moffet HL; Most illnesses in ambulatory patients are infections; most of these are upper, middle, or pararespiratory infections . Although these diseases are rarely serious, they result in immense amounts of time lost from work and incalculable expense for over-the-counter medications . Guidelines for antibiotic and other drug therapy for these diseases need a better scientific foundation. J Pharm Sci, 1978 Nov, 67(11), 1579 - 82 Pharmacokinetic evaluation of a drug interaction between kaolin--pectin and clindamycin; Albert KS et al.; The effect of a kaolin--pectin antidiarrheal suspension on the bioavailability of orally administered clindamycin was evaluated by model-dependent pharmacokinetic techniques . Each subject's serum clindamycin concentration--time data in the absence of the kaolin--pectin suspension were fitted to a one-compartment open model with first-order absorption and lag time . The resulting disposition parameters were used to construct individual Wagner-Nelson absorption profiles, expressed as the cumulative relative fraction of clindamycin absorbed versus time following combined antidiarrheal--antibiotic therapy . For each subject, absorption persisted to varying degrees through 14 hr . On the average, the half-time for absorption was prolonged 20-fold (from about 16 min to more than 300 min) . In contrast, extrapolation of the individual time courses of relative absorption to infinity revealed that the antidiarrheal had no effect on the extent of clindamycin absorption. J Neurosurg, 1978 Nov, 49(5), 658 - 68 Decreased mortality from brain abscesses since advent of computerized tomography; Rosenblum ML et al.; No deaths have occurred among 20 consecutive patients with intraparenchyma brain abscesses treated at the University of California, San Francisco, since computerized tomographic (CT) brain scanning became a routine diagnostic procedure (study period: July, 1974, to June, 1977) . These patients have been compared to 18 consecutive cases treated without benefit of CT analysis (January, 1970, to June, 1974) in order to determine the factors responsible for the recently improved prognosis . The mortality rate was 44% for all cases and 36% for all operated patients treated before the availability of CT . Similar morbidity (about 33%) was seen in survivors from both series . No significant differences in the two groups were noted with respect to patient population and antibiotic or corticosteroid therapy . Among the factors that may have contributed to the improved results for patients diagnosed with CT are: less frequent occurrence of multiple abscesses, fewer patients with poor preoperative clinical status, and a greater incidence of total abscess removal . In addition, CT scanning provided more accurate diagnosis and localization of abscesses and aided in the rapid detection of postoperative complications that probably accounted for six out of eight deaths in the earlier series . Serial CT studies provide a means to optimize the timing for surgical intervention and plan appropriate medical therapy . It is noteworthy that two patients have been followed by serial CT scans to non-surgical cures. J Infect Dis, 1978 Nov, 138(5), 690 - 4 Chloramphenicol: an impatient study of use and abuse; Fink TJ et al.; During a six-month period, chloramphenicol was administered systemically to 100 patients and topically to 24 patients who were admitted to the Medical Center Hospital of Vermont, Burlington, Vermont . Seventy-nine percent of the patients receiving the drug systemically were on surgical services, 13% were on the pediatric service, and 8% were on the medical service . In this group, chloramphenicol was administered appropriately in 60.4% of cases as follows: 57.5% on the surgical, 50% on the medical, and 84.6% on the pediatric services . In 19 of 35 instances of inappropriate use on the surgical services, a potentially less toxic antibiotic could have been chosen . Eight cases were treated inappropriately because of dosage errors, and in seven cases no antibiotic should have been used . On the medical services all inappropriate use was due to underdosage, and on the pediatric service there was one case of incorrect dosage and one instance in which a less toxic antibiotic could have been chosen . Ophthalmological use of the drug accounted for all topical use . Of 24 patients treated, 21 received the drug for prophylaxis and three for therapy. Chem Biol Interact, 1978 Nov, 23(2), 141 - 50 Arabinosyl nucleosides . XII . Influence of arabino-furanosylthymine on growth of L5178y cells; Muller WE et al.; The antibiotic 1-beta-D-arabinofuranosylthymine (araThd) is a potent inhibitor of the growth of mouse lymphoma cells (L5178y) . The ED50 concentration was found to be 9.8 muM . The cells die as a consequence of an unbalanced growth . The cytostatic activity of araThd can be abolished by coincubation with dThd and dUrd but not with Urd . At cytostatic concentrations araThd selectively blocks DNA synthesis; RNA- and protein synthesis are unaffected . Intracellularly araThd is rapidly phosphorylated to araTTP . This enzymic phosphorylation does not influence the synthesis of the naturally occuring, related triphosphate dTTP . AraTMP is incorporated into DNA during DNA synthesis; 1 mol of ara-TMP is incorporated/19,500 molecules of dTMP. Arch Inst Cardiol Mex, 1978 Nov-Dec, 48(6), 1224 - 32 {Mycotic anuerysm secondary to bacterial endocarditis . Review apropos of a case}; Almazan V et al.; A case is presented of Subacute Bacterial Endocarditis on a biological Duramater Prosthesis . In the evolution curse, the patient presented an intraparenchimal cerebral haemorrhage, where--upon the angiographic studies demonstrated the existence of a mycotic aneurysm in the left median cerebral arterial territory . With specific antibiotic therapy and replacement of the prosthesis, the clinical evolution of the case, was positive, and later angiographies evidenced the disappearance of the aneurysm . The incidence of intracranial mycotic aneurysm complicating bacterial endocarditis is relatively high (up to 4% in post-mortem series) . There have been very few cases communicated up to now with angiographic demonstration . Mortality is similar in patients under surgical or medical treatment . The aetipothogenic aspects are discussed, as well as the recommended therapeutic measures. Antibiotiki, 1978 Nov, 23(11), 1015 - 7 {Interaction of sibiromycin with soluble chromatin from the cells of murine NK/LI lymphadenosis}; Loz'mian LI; Interaction of sibiromycin with chromatin from NK/Li cells was studied . It was shown that the chromatin proteins had no significant effect on the amount of the antibiotic firmly bound with DNA . The difference observed in the kinetics of the sibiromycin interaction with chromatin and DNA from NK/Li cells was not induced by replacement of a part of the DNA bound proteins . Possibly the chromatin proteins hampered formation of DNA conformation necessary for sibiromycin binding. Ann Thorac Surg, 1978 Nov, 26(5), 421 - 6 Median sternotomy dehiscence; Stoney WS et al.; Sternal dehiscence requiring reoperation occurred in 36 out of 4,531 patients who had a sternotomy incison within an eight-year period . Twisted sternal wire sutures were used for the first four years and a crimped steel plate fixation was used during the second four years with a marked and significant decrease in the incidence of dehiscence from 17 out of 1,000 patients to 3 out of 1,000 patients . Thirty-five of the 36 patients were men, and 4 required reoperation for bleeding . Other factors such as mammary artery dissection, tracheostomy, and body weight of more than 82 kg were not significant . Although infection was noted in 20 patients, it was thought to be secondary . Early reoperation with antibiotic irrigation achieved wound stability in the 34 survivors with only 3 patients requiring additional procedures for chronic osteomyelitis of the sternum. Dtsch Zahnarztl Z, 1978 Nov, 33(11), 814 - 8 {Surgical technic in the treatment of mandibular osteomyelitis}; Luhr HG et al.; Our experience with operative treatment of 70 patients with osteomyelitis of the mandible showed that the incision and drainage of soft-tissue abcesses combined with antibiotic therapy led to healing in 22 patients . More extensive measures, such as sequestectomy, decortication, resection of whole areas of the mandible, and transplantation of autologous cancellous bone, however were necessary with 48 of the patients . A detailed description of the various operative techniques was presented; the respective indications were mentioned. Dtsch Zahnarztl Z, 1978 Nov, 33(11), 819 - 22 {Compression plate osteosynthesis in infected mandibular fractures}; Beckers H et al.; Self-compromising osteosynthesis plates proved satisfactory for 19 patients with infected fractures of the mandible . After immediate stabilization of the fracture with osteosynthesis plates, the abscess was incised and drained, and antibiotic therapy was instituted . All the fractures consolidated without significant complications . Radiologic assessment revealed delayed bony healing . Our findings agree with those in the field of general traumatology for treating infected fractures. Dtsch Zahnarztl Z, 1978 Nov, 33(11), 788 - 93 {Odontogenic soft tissue infections (localization, treatment and course in 1002 cases)}; Koblin I et al.; Between 1965 and 1974, 1002 patients were treated on an in-patient basis for odontogenous soft-tissue infections . Abcesses were observed in 960 patients; inflammatory infiltrate, in 39 patients; a phlegmon, in 3 patients . The relation of male to female patients was 56:44 . The 21- to 30-year-old age group was most frequently affected . Antibiotic therapy was administered over a period of weeks prior to admission in 87% of the patients . Operative procedures prior to admission had been performed on only a few patients. J Lipid Res, 1978 Nov, 19(8), 1063 - 7 Purification of polyphosphoinositides by chromatography on immobilized neomycin; Schacht J; The binding of polyphosphoinositides (phosphatidylinositol phosphate and phosphatidylinositol bisphosphate) to the antibiotic neomycin is utilized for the purification of these lipids . Neomycin is reductively coupled to reactive glass beads (Glycophase-CPG) and serves as the stationary phase in column chromatography . A total lipid extract is prepared from tissues with chloroform-methanol-KC1 or chloroform-methanol-HC1 and washed once with acidified methanol-water . After the addition of an equal volume of methanolic 200 mM ammonium acetate, the extract is directly applied to the column . All lipids but the polyphosphoinositides are removed from the column by rinsing with 150 mM ammonium acetate in chloroform-methanol-water . Increasing the salt concentration to 600 mM elutes phosphatidylinositol phosphate . While further increases in ionic strength are not sufficient for a quantitative removal of phosphatidylinositol bisphosphate, the lipid is completely eluted by the addition of either ammonia or HC1 to the solvent . The column can be recycled and used repeatedly. Antibiotiki, 1978 Nov, 23(11), 1009 - 15 {Antiviral action of carminomycin and some of its derivatives}; Liashenko VA et al.; Carminomycin was shown to inhibit the development of both the DNA-containing variolovaccine virus and the RNA-containing grippe virus in chick embryos . Comparison of the effects of rubomycin, carminomycin, 14-oxy-carminomycin and carminomycin complex with bovine serum albumin in experiments with chick embryos showed that the inhibitory effect of carminomycin and its derivatives on the development of the grippe virus was much higher than that of rubomycin . The carminomycin derivatives proved to be much more active in this respect than the initial antibiotic . Carminomycin and its derivatives had a therapeutic effect on mice with experimental grippe pneumonia also on their oral use. Otolaryngology, 1978 Nov-Dec, 86(6 Pt 1), ORL - 886-7 Permanent threshold shift and cochlear hair cell loss in the kanamycin-treated guinea pig; Prosen CA et al.; The differential contribution of the inner hair cells (IHC) and the outer hair cells (OHC) in the mammalian cochlea to hearing sensitivity was assessed in six behaviorally-trained guinea pigs by comparing audiograms preadministration and postadministration of kanamycin, an antibiotic that predominantly destroys guinea pig OHC while leaving the IHC structurally unchanged . The results support the hypothesis that only the IHC of the cochlea responds to tones approximately 50 to 60 dB above the threshold of the intact cochlea. Oral Surg Oral Med Oral Pathol, 1978 Nov, 46(5), 618 - 27 Histologic study of tooth transplantation in the rabbit; Mirzabagi MH; Tooth transplantation between preimmunized unrelated mismatched animals appears to induce the same immunologic problems that appear in the grafting of other organs . Such transplants showed more inflammatory root resorption and ankylosis and less reattachment of periodontal ligaments than did allografts between compatible animals . It appears that transferring the teeth to the similar side, suturing the gingival soft tissue around the teeth, splinting the transplanted teeth, and antibiotic therapy improve results by minimizing the effects of surgical procedures and trauma . Surgical trauma is confirmed as an important factor, along with immunogenetic differences between donor and recipient, in determining the outcome of tooth transplantation. Lancet, 1978 Oct 28, 2(8096), 917 - 20 Identification of Ureaplasma urealyticum (T-strain Mycoplasma) in patient with polyarthritis; Stuckey M et al.; A 10-year-old boy with confirmed congenital agammaglobulinaemia presented with polyarthritis while on gammaglobulin replacement therapy . Initial cultures of material aspirated from an abscess and of joint fluid were negative, and symptoms progressed despite antibiotic therapy . Synovial-biopsy material, cultured specifically for mycoplasmas, was positive for Ureaplasma urealyticum as were the blood, abscess fluids, throat-swab, and nasopharyngeal secretions . Therapy, based on in-vitro studies of antibiotic susceptibilities of the organism, resulted in the eradication of the infection and resolution of the arthritis . These findings suggest that U . urealyticum may be capable of inducing polyarthritis in man. Biochim Biophys Acta, 1978 Oct 24, 520(3), 481 - 9 Neocarzinostatin induction of DNA repair synthesis in HeLa cells and isolated nuclei; Kappen LS et al.; The antitumor antibiotic neocarzinostatin that causes DNA strand breaks in vivo and in vitro is shown to induce DNA repair synthesis in HeLa S3 cells . In the repair assay, the parental DNA was prelabeled with 32P and a density label (bromodeoxyuridine) was introduced into the new synthesized DNA . Quantitation of the repair synthesis as measured by the incorporation of {3H}thymidine into the light parental DNA at varying doses of the drug indicate that there is a significant repair response at low levels of the drug (0.2--0.5 microgram/ml) which cause DNA strand breakage and inhibition of DNA synthesis . In isolated HeLa nuclei neocarzinostatin stimulates the incorporation of dTMP many-fold . This enhancement of dTMP incorporation, which requires the presence of a sulfhydryl agent, is a consequence of the drug-induced DNA strand breakage and is in the parental DNA . These results suggest that an intact cell membrane is not required for DNA strand breakage and its subsequent repair. Schweiz Med Wochenschr, 1978 Oct 21, 108(42), 1632 - 7 {Strongyloidiasis following kidney transplantation}; Briner J et al.; A 50-year-old Swiss male died from strongyloidiasis 8 weeks after renal allotransplantation . Past history revealed malaria at age 20 years, when the patient had stayed in tropical and subtropical areas, as well as pulmonary tuberculosis . Hypertension, erythrocyturia, proteinuria and unexplained episodes of blood eosinophilia were first noticed age 45, and 4 years later dialysis was started . A mild acute rejection crisis was successfully treated 4 weeks after transplantation . 2 weeks later, however, bilateral pneumonia developed . Despite vigorous antibiotic and tuberculostatic therapy the patient died in septic shock . Autopsy revealed strongyloidiasis with adult females, eggs and rhabditiform larvae of Strongloides stercoralis in the small intestine . Numerous filariform larvae were detected in the lungs, in the walls of bronchi and trachea, in the brain, in the walls of arteries, and in lymphnodes . Massive granulomatous inflammatory reaction and extensive pulmonary hemorrhage were the main pathological findings. Minerva Med, 1978 Oct 13, 69(48), 3311 - 8 {A case of Churg-Strauss granulomatous angiitis: an autonomous clinical entity or a variant of panarteritis nodosa?}; Zanardi F et al.; A fatal case of Churg and Strauss granulomatous angiitis in a 21-yr-old woman is described . Its unusual features included marked personal and familial dysreaction, sudden onset, bronchopulmonitis with distinct eosinophilia and antibiotic- and cortisone-resistant pericarditis, and a terminal picture of generalised septico-pyaemia . The histological findings included necrotising systemic vasculitis with granulomas, some of them extravascular, in various organs . Differential diagnosis and the relation between this form and panarteritis nodosa are discussed. Biochemistry, 1978 Oct 3, 17(20), 4232 - 9 Binding of hedamycin to deoxyribonucleic acid and chromatin of testis and liver; Jernigan HM Jr et al.; The binding of the antibiotic hedamycin to DNA was evaluated by density gradient centrifugation in CsCl to determine the type I binding, which is essentially irreversible at high and low ionic strength . Exhaustive dialysis at low ionic strength was used to determine the sum of type I and type II binding (irreversible at low ionic strength but reversible at high ionic strength) . The maximum ratio of hedamycin to DNA nucleotides (rf) is 0.1 for type I and 0.1 for type II binding to free DNA, but these ratios decrease to 0.07--0.08 in chromatin of rat liver and a testis fraction (spermatogonia plus primary spermatocytes) . The rf for type I binding of hedamycin to monomeric nucleosomes of this testis fraction is considerably less than maximum binding to polymeric nucleosomes or chromatin, suggesting that hedamycin binds more effectively to "linker" DNA than to DNA attached to the core of the nucleosomes . Hedamycin binding to the chromatin of the spermatid fraction of testis is greatly decreased in comparison with chromatin of early stages; this correlates with the change from nucleohistones to nucleoprotamines at the middle to late spermatid stages of spermiogenesis. J Aud Res, 1978 Oct, 18(4), 277 - 91 Hearing impairment in children of low birthweight; Clarke BR et al.; Audiometer evaluations were carried out on a population of 204 low birth weight (LBW) children and 123 controls . In the LBW group, 6 children (3.3%) had a bilateral loss and 5 (2.5%) had a unilateral sensorineural high-frequency hearing loss . No case of sensorineural hearing loss was found among the controls . There were 13 (6.4%) cases of conductive loss among the LBW sample, compared with 3 (2.4%) among the controls . Correlation coefficients showed a relationship between sensorineural impairment and: bilirubin level, incubator time, antibiotic history, and neurological status . Subsequent multiple classification analyses showed that, while incubator time and bilirubin level are each significant predictors of sensorineural loss, this is not the case with antibiotics or neurological status . Neurological status was closely associated with the syndrome of LBW, high bilirubin level, extended incubator time and sensorineural loss . However, no significant relationship could be found between neurological impairment and these predictors nor can it be regarded as useful in predicting hearing loss in this population. Avian Dis, 1978 Oct-Dec, 22(4), 620 - 6 Effect of tiamulin in chickens and turkeys infected experimentally with avian Mycoplasma; Baughn CO et al.; Tiamulin was compared, under a variety of experimental conditions, with 4 water-soluble antibiotic preparations available commercially for the control and treatment of mycoplasmal infections in poultry . In chickens, tiamulin was more effective than the reference antibiotics in preventing and eradicating airsacculitis caused by Mycoplasma gallisepticum and preventing airsacculitis and synovitis caused by M . synoviae . In turkeys, tiamulin and tylosin were equally active in preventing airsacculitis caused by M . gallisepticum . Tiamulin was highly effective in preventing airsacculitis also when administered as a single subcutaneous dose. Orthop Clin North Am, 1978 Oct, 9(4), 1039 - 51 New concepts in the diagnosis and treatment of infections of the cervical spine; Forsythe M et al.; Of the three major areas of the spinal column, the cervical spine is least commonly infected; approximately 3 to 5 per cent of all spinal infections involve the cervical spine . Tuberculous, pyogenic, fungal, and parasitic infections may involve the cervical spine and occur in this order of decreasing frequency . Difficulty in differential diagnosis most commonly involves tumor . Fungal and parasitic infections of the cervical spine are extremely rare, but fungal infections have been increasing over the past three decades . Clinical suspicion, radiologic examination, and definitive diagnosis via tissue biopsy are necessary so that definitive procedures can be instituted . Specific antibiotic coverage, surgery to facilitate the body's defenses and antibiotic penetration, and stabilization of the spine are the most important therapeutic measures to be instituted. J Chir (Paris), 1978 Oct, 115(10), 497 - 500 {A rare abdominal emergency: acute phlegmonous gastritis (author's transl)}; Aurousseau R et al.; In the light of a series of recent observations and a personal case, the authors recall that acute phlegmonous gastritis is a rare disease usually secondary to a bucco-pharyngeal infective focus, characterised by an acute abdominal syndrome accompanied by a very severe infective context . Only laparotomy leads to the diagnosis . Since antibiotics, the mortality has regressed from more than 80% to less than 50% . The prognosis of the antral forms is much less serious than that of the diffuse forms with mortalities of 28% and 71% respectively . In antral gastritis the best therapeutic attitude is early antibiotic therapy associated with 2/3 gastrectomy. Tsitologiia, 1978 Oct, 20(10), 1186 - 91 {Ability of cells in tissue culture to recover from damage caused by chemotherapeutic drugs}; Gotlib VIa et al.; The repair of potential lethal damages was investigated in the LL cell line induced by some chemicals . Three different chemical compounds were used . An inhibitor of DNA synthesis--hydroxyurea, an alkylating agent--methylnitrosourea, and an antibiotic intercalating in DNA--actinomycin D . It was shown that damages induced by hydroxyurea could be repaired . Unlike, the repair of damages induced by methylnitrosourea and actinomycin D was not observed. J Antibiot (Tokyo), 1978 Oct, 31(10), 997 - 1006 Carbon-13 nuclear magnetic resonance assignments of pactamycin and related compounds; Weller DD et al.; All resonances observed in the 13C NMR spectrum of the antitumor antibiotic pactamycin and its degradation product pactamycate have been assigned, employing off-resonance and specific proton decoupling as well as comparison with the 13C NMR spectra of the model compounds m-aminoacetophenone and ethyl 6-methylsalicylate. J Antibiot (Tokyo), 1978 Oct, 31(10), 939 - 44 Trichostatin C, a glucopyranosyl hydroxamate; Tsuji N et al.; In addition to trichostatins A and B, a new antifungal antibiotic, trichostatin C was isolated . The structure was shown to be a glucoside of trichostatin A by spectroscopic examinations and chemical degradations . Trichostatin C is presumably the first example of a glucopyranosyl hydroxamate from nature. J Antibiot (Tokyo), 1978 Oct, 31(10), 1067 - 9 The chemistry of the rubradirins . I . The structures of rubransarols A and B; Hoeksema H et al.; The antibiotic rubradirin, C48H46N4O20 was cleaved at an ester function by aqueous methylamine into rubransarol A, C23H23NO8, and a methyl amide, C26H28N4O12 . Rubradirin B, C40H33N3O15, was similarly cleaved in methanolic ammonia into rubransarol B, C23H23NO8, and the primary amide, C17H13N3O7 . The rubransarols are shown to be unique ansamycins which are isomeric at a double bond in the large ring. J Antibiot (Tokyo), 1978 Oct, 31(10), 1059 - 62 Action of cefoxitin and cefamandole on human neutrophil function; Majeski JA et al.; Polymorphonuclear neutrophilic leukocyte chemotaxis was examined in vitro in the presence to two new antibiotics: cefamandole and cefoxitin . Results indicate that cefamandole inhibited neutrophil chemotaxis to a significant degree only at high antibiotic concentrations of 100 microgram/ml (P less than 0.01) and has no significant effect at normal serum therapeutic range . Cefoxitin was found to produce a 43% inhibition (P less than 0.01) of human in vivo neutrophil chemotaxis at antibiotic concentrations of 100 microgram/ml and have a minimal inhibitory effect (1 approximately 9%) at low concentrations (1 approximately 5 microgram/ml) . Both cefamandole and cefoxitin had no significant effect on opsonophagocytosis. Antibiotiki, 1978 Oct, 23(10), 931 - 4 {Comparative pathomorphological study of the experimental action of carminomycin and rubomycin on the heart}; Vinogorova GF et al.; Comparative histological investigation of the toxic effect of carminomycin and rubomycin on the myocardium was carried out on mice BDF . It was found that the level of the morphological changes in the heart muscle depended on the antibiotic dose . The cardiotoxic effect of carminomycin was less pronounced than that of rubomycin. J Immunol, 1978 Oct, 121(4), 1510 - 7 Double expression of VH region a2 and a3 allotypes in individual rabbit lymphocytes; Wolf B et al.; This study provides evidence that two VH region a group allotypic specificities are synthesized by individual peripheral blood lymphocytes from a2,3 rabbits . After removal of both allotypes from the cell surface with pronase, three types of allotype-bearing cells, a2, a3, and a2,3 were demonstrable after overnight culture in serum-free medium . Frequently, greater than 50% of the cells that contained allotype on the surface resynthesized both allotypes . In culture, reappearance of allotype was first detectable at 4 hr and increased progressively thereafter to a maximum at 18 hr . During regrowth, the relative proportion of cells showing both markers was maintained . The predominance of cells exhibiting only a3 over those displaying only a2 was also maintained . Reappearance of allotype was inhibited by cycloheximide but was manifested when the antibiotic was washed out . Monospecific anti-a2 antibodies could completely suppress the resynthesis of homologous allotype in culture and prevent the regeneration of a2 in double-bearing cells . Likewise, anti-a3 in cultures was usually specifically suppressive for a3 allotype; however, the double producers were only partially depleted. Arch Otolaryngol, 1978 Oct, 104(10), 579 - 84 Comparative ototoxic liability of netilmicin and gentamicin; Brummett RE et al.; Netilmicin sulfate is a new aminoglycoside antibiotic currently undergoing clinical investigation . All of the aminoglycoside antibiotics now in clinical use are ototoxic . This study was done to determine the ototoxic liability of netilmicin when it is compared directly with gentamicin sulfate . Groups of ten guinea pigs each were given doses of 0, 50, 100, or 150 mg/kg of either gentamicin or netilmicin daily for four weeks . After a two-week stabilization period, the Preyer pinna reflex, the cochlea's ability to generate the ac cochlear potential, and the missing hair cells from the cochleas were determined . Additionally, the pharmacokinetics of both drugs in the plasma and perilymph were determined . Little or no cochlear damage was detected with netilmicin, even at the highest dose, while even the smallest dose of gentamicin produced measurable changes in cochlear function. J Thorac Cardiovasc Surg, 1978 Oct, 76(4), 506 - 9 Double-blind comparison of cefazolin and cephalothin in open-heart surgery; Kini PM et al.; Ninety-nine patients undergoing cardiac surgery were randomly assigned to treatment with cefazolin and cephalothin to compare the effectiveness of these cephalosporins in the prevention of postoperative infections . The incidence of infections was low with both antibiotics (cefazolin 2.1 percent, cephalothin 4.6 percent) . Intraoperative serum cefazolin levels were more evenly distributed, whereas a wide dispersion of cephalothin levels was observed . There was no measurable antibiotic detected in cardiac tissue samples in the majority of the cases . Adverse reactions (skin rashes) occurred only in three patients, all receiving cephalothin . It is concluded that cefazolin is as safe and effective as cephalothin in the prevention of postoperative infection in patients undergoing open-heart surgery. Cutis, 1978 Oct, 22(4), 447 - 52 Care of the burn wound; Yarborough MF; The initial therapy of thermal injuries is directed at removal of loose debris and necrotic epidermis, alleviation of pain, and prevention of infection . Following initial wound debridement, bacterial growth in the wound itself is controlled primarily through the use of tropical antibiotic agents and daily hydrotherapy to clean the wounds and remove any loose eschar . Effectiveness of topical therapy is monitored by quantitative burn wound biopsy cultures; growth of greater than 10(4) micro-organisms per gram of tissue indicates invasive burn wound sepsis . Such bacterial invasion may be further controlled through the adjunctive use of antibiotics administered into the sub-eschar space . Once eschar separation has exposed healthy granulation tissue, the burn wound must be covered with suitable biologic dressings prior to autografting . All open wounds may then be autografted with sheet grafts to the face, neck, and areas exposed to trauma or by expansion mesh grafts to cover large areas from limited donor sites . Upon completion of autografting, a vigorous physical therapy program is necessary to rehabilitate victims of massive thermal injury to a functional existence. J Virol, 1978 Oct, 28(1), 368 - 74 Assembly of viral membranes: maturation of the vesicular stomatitis virus glycoprotein in the presence of tunicamycin; Morrison TG et al.; The role of glycosylation in the maturation of the vesicular stomatitis virus (VSV) glycoprotein was studied by use of the antibiotic tunicamycin . Tunicamycin-treated VSV-infected cells synthesize an unglycosylated form of the VSV glycoprotein (R . Leavitt, S . Schlesinger, and S . Kornfeld, J . Virol . 21:375--385, 1977) . We have found that tunicamycin has no effect on the attachment of the glycoprotein to intracellular membranes or on the transport of protein to the lumen of the endoplasmic reticulum . However, tunicamycin prevented the migration of the glycoprotein from the rough endoplasmic reticulum to smooth intracellular membranes. Ann Dermatol Venereol, 1978 Oct, 105(10), 833 - 8 {Clinical evaluation of a topical ethyl lactate treatment of acne vulgaris (author's transl)}; Grosshans E et al.; The efficacy of a lotion containing 10 p . 100 ethyl lactate was evaluated in a double-blind clinical trail during 8 weeks . Test subjects were 45 male and female patients with polymorphous juvenile acne . They were divided into three groups and received the following treatments: Group A: oral antibiotic + topical placebo lotion . Group B: oral antibiotic + topical ethyl lactate lotion . Group C: topical ethyl lactate lotion only . The lotions were applied twice daily with a swab of cotton-wool . The antibiotic doses (tetracycline hydrochloride) were decreased as the trial progressed . Patients were examined before the trial, then after 1, 2, 4, 6 and 8 weeks . At each visit, comedones, microcysts, pustules and nodules were counted on a skin surface of 9 cm2 . Colour photographs were taken before and at the end of the trial and served for counting inflammatory lesions . Also, at each visit, skin lipids were sampled and analysed by I . R . spectrophotometry in order to asses the effect of the treatments on the free fatty acid/triglyceride ratio . The treatments showed similar effectiveness as regards comedones and microcysts, but only treatments A and B succeeded in reducing the number of inflamed lesions . With respect to the latter, the combined treatment B (oral antibiotic + topical ethyl lactate lotion) was more effective than treatment A (oral antibiotic + topical placebo); both treatments were more effective than treatment C (topical ethyl lactate lotion only) . At the end of the trial, all three groups of patients showed significant overall improvement, but acne scores (total number of lesions) did not differ significantly between treatments . When comparing these results with literature data concerning the effects of vitamin A acid and benzoyl peroxide, it appears that ethyl lactate is slightly less effective for topical treatment of acne than vitamin A acid, but slightly more effective than benzoyl peroxide . It should be underlined that ethyl lactate is well tolerated by the skin . Analysis of sebum samples failed to yield evidence of a decrease in the free fatty acid/triglyceride ratio in skin lipids of the patients irrespective of the treatment applied. Cancer, 1978 Oct, 42(4), 1670 - 9 Phase I study with neocarzinostatin: tolerance to two hour infusion and continuous infusion; Ohnuma T et al.; Neocarzinostatin (NCZ), an acidic polypeptide antibiotic, was given to 47 patients with cancer and leukemia, and tolerance to two schedules, a single dose given as a 2 hour infusion and a continuous infusion over 5 days was investigated . Immediate reactions, including fever, chills, rigor, hypertension and mental confusion, were dose-limiting for the 2 hour infusion schedule, occurring at 3000 U/m2 and higher . Continuous administration for 5 days eliminated the immediate reactions and then hematological toxicity--often prolonged leukopenia and thrombocytopenia--became dose-limiting . Other toxicities of NCZ at both dose schedules included anemia, fever and chills, anorexia, nausea and vomiting, hepatic dysfunction, azotemia, hypophosphatemia, aminoaciduria, stomatitis, phlebitis and/or cellulitis at the venous infusion site and pruritus . Patients with solid tumors who had received little or no prior chemotherapy and had good bone marrow reserve tolerated up to 6000 U/m2/24 hours X 5 days . One patient with previously treated acute myelocytic leukemia was induced into a good partial remission lasting 10 weeks. Eur J Biochem, 1978 Oct, 90(2), 261 - 70 The DNA . tyrocidine complex and its dissociation in the presence of gramicidin D; Chakraborty T et al.; The peptide antibiotic tyrocidine affects transcription in vitro by interfering with the initiation process . The complex formed between tyrocidine and native DNA is stable against nucleolytic enzymes . It is sensitive to variations in the salt concentration . Protection of DNA as a function of the tyrocidine concentration follows a curve suggesting cooperative binding of tyrocidine to DNA . The complex formation at low tyrocidine concentrations is accompanied by the presence of single stranded regions of unknown length . With single-stranded DNA, tyrocidine forms a complex which is relatively insensitive to high salt concentrations . Both native and single-stranded DNAs of the complexes become digestible in the presence of gramicidin D, another peptide antibiotic . Breakdown of the complex as a function of the gramicidin D concentration follows a curve which is the reverse of cooperative binding . Gramicidin D acts more effectively on single-stranded rather than on double-stranded DNA . tyrocidine complexes . The DNA . tyrocidine complex, which is broken down by formamide and dimethyl sulfoxide is stabilized by gramicidin D . The implications of these results are discussed with respect to a possible recognition of DNA sequences by tyrocidine and the interaction between DNA, tyrocidine and gramicidin D. J Biol Chem, 1978 Sep 25, 253(18), 6568 - 77 Migration of 40 S ribosomal subunits on messenger RNA in the presence of edeine; Kozak M et al.; The antibiotic edenine induces binding of multiple 40 S ribosomes to reovirus messenger RNAs, producing complexes that sediment rapidly in glycerol gradients . Rapidly sedimenting complexes were also obtained with tobacco mosaic virus RNA and rabbit globin mRNA in the presence of edeine . Following ribonuclease digestion of the heavy complexes, nuclease-resistant 32P-labeled reovirus fragments protected by 40 S ribosomes in the presence of edeine were recovered and fingerprinted . The sequence complexity of the protected material supports the interpretation that 40 S subunits are distributed at many internal sites in each messenger RNA . Additional experiments indicate that binding of the multiple 40 S subunits occurs from a single "entry site" which involves the 5' terminus of the message . This, in turn, implies that in the presence of edeine 40 S ribosomes are able to move along the mRNA chain, attaching initially near the 5' end, then advancing to make room for the next subunit . We suggest that in the absence of antibiotics, also, a 40 S ribosome might bind near the 5' terminus and then advance, stopping where it encounters the first AUG triplet . The effect of edeine might be to interfere with the AUG recognition process, thus allowing the 40 S ribosome to continue unhalted along the message . The present experiments with edeine provide the first direct evidence that 40 S ribosomal subunits are capable of moving along the mRNA chain. Mol Gen Genet, 1978 Sep 20, 165(1), 79 - 86 Gene expression in Escherichia coli B/r during partial rifampicin-mediated restrictions of transcription initiation; Blumenthal RM et al.; The antibiotic rifampicin inhibits transcription initiation, but not the elongation and completion of nascent RNA transcripts . Addition of low concentrations of rifampicin only partially blocks initiation but at the same time specifically alters the general pattern of transcription in the culture . The transcription of genes specifying the beta and beta' subunits of RNA polymerase, and to a lesser extent of the genes specifying the RNA and protein components of the ribosome, was specifically stimulated relative to total transcription . In contrast, the transcription of the lactose operon was selectively reduced . These results are consistent with the ideas that the level of expression of the genes specifying the beta and beta' subunits is sensitive to the general rate of RNA synthesis in the culture, and that the expression of the beta and beta' RNA polymerase genes is related to the expression of ribosome component genes. Biochemistry, 1978 Sep 19, 17(19), 4090 - 6 Transition-metal binding site of bleomycin A2 . A carbon-13 nuclear magnetic resonance study of the zinc(II) and copper(II) derivatives; Dabrowiak JC et al.; The 13C NMR spectra at 25.2 MHz of the Zn(II) and Cu(II) complexes of the antitumor antibiotic bleomycin A2 are discussed . Complexation of the drug to Zn(II) causes 38 of the 52 resonance lines of bleomycin A2 to shift to new positions . All but ten of these shifted lines have been assigned in the Zn(II) bleomycin complex . Although the specific donor sites of the drug cannot be identified from the 13C NMR data, the analysis clearly shows that the pyrimidine-imidazole portion of the molecule is affected by chelation . This finding is in agreement with the previously reported metal-binding site of the antibiotic . The analysis also shows that carbon atoms which have large through-bond distances from the binding site can experience substantial chemical-shift changes upon metal binding . Complexation of the drug to Cu(II) eliminates 23 resonances from the spectrum of the molecule . All of these resonances emanate from carbon atoms which are located in the pyrimidine-imidazole portion of the drug. Chromosoma, 1978 Sep 11, 68(4), 287 - 302 The use of base pair specific DNA binding agents as affinity labels for the study of mammalian chromosomes; Jorgenson KF et al.; The fluorochromes Hoechst 33258 and olivomycin are base pair specific DNA binding agents . The fluorescence enhancement of Hoechst 33258 and olivomycin in the presence of DNA can be directly related to the A--T and G--C content of the interacting DNA respectively . Cytological observations of metaphase chromosomes treated with these two compounds suggest that the fluorescent banding patterns produced are the reverse of one another.--Non-fluorescent base pair specific DNA binding agents have been used as counterstains in chromosome preparations to enhance the contrast of the banding patterns produced by the base specific fluorochromes . The non-fluorescent G--C specific antibiotic actinomycin-D enhanced the resolution of fluorescent bands produced by the A--T specific fluorochrome Hoechst 33258 . Similarly the non-fluorescent A--T specific antibiotic netropsin was found to enhance resolution of the bands produced by the G--C -specific fluorochrome olivomycin . Netropsin was also found to increase the differential fluorescent enhancement of complexes of olivomycin with DNAs of various base composition in solution . These findings suggest that counterstaining agents act through a base sequence dependent inhibition of subsequent binding by base pair specific fluorochromes.--The base specific DNA binding agents have been used to differentiate different types of constitutive heterochromatin in mammalian species, and to facilitate chromosome identification in somatic cell hybrids. J Biol Chem, 1978 Sep 10, 253(17), 5892 - 4 Characterization of ionomycin as a calcium ionophore; Liu C et al.; The ionophorous properties of a new antibiotic, ionomycin, have been studied . It was found that the antibiotic is capable of extracting calcium ion from the bulk of an aqueous phase into an organic phase . The antibiotic also acts as a mobile ion carrier to transport the cation across a solvent barrier . The divalent cation selectivity order for ionomycin as determined by ion competition experiments was found to be: Ca greater than Mg greater than Sr = Ba, where the binding of strontium and barium by the antibiotic is insignificant . The antibiotic also binds La3+ to some extent, but its complexation with monovalent alkali metal ions is negligible . Measurement of the binding of ionomycin with Ca2+ indicates that ionomycin complexes and transports calcium ion in a one to one stoichiometry. Vet Rec, 1978 Sep 9, 103(11), 227 - 9 Infective arthritis of the elbow joint in horses; Edwards GB et al.; Six horses were found to have infective arthritis of one elbow joint . The history, and presence of a small wound on the lateral aspect of the elbow suggested the condition was trauma induced . Two horses recovered following joint lavage under general anaesthesia and antibiotic therapy . The joint changes found post mortem in the others were characteristic of an infective arthritis. Farmaco {Sci}, 1978 Sep, 33(9), 651 - 66 Studies on the mechanism of action of mitomycin C; Rodighiero G et al.; The in vitro formation and properties of the molecular complex between mitomycin C and native DNA were examined by means of various experimental methods; the data obtained indicate that the complex is extremely weak and that the chromophoric moiety of the antibiotic is not involved in its formation . The alkylating activity of mitomycin C was also studied using 3H-mitomycin C; while monofunctional alkylation increases almost in parallel with the concentration of the antibiotic, the difunctional alkylation, causing inter-strand cross-linkages in DNA, rapidly reaches a maximum and then remains constant even when increasing the concentration of the antibiotic and monofunctional alkylation . On the basis of these results, the currently accepted molecular model of the mitomycin--DNA interaction must be revised; a new model of this interaction is presented, which is in better agreement with the properties of mitomycin C and with the latest findings on the subject. J Assoc Off Anal Chem, 1978 Sep, 61(5), 1103 - 6 Determination of neomycin residues in eggs and stability of residues after cooking; Katz SE et al.; The procedure for neomycin residues used a surfactant to improve extraction, a centrifuge step to eliminate solids that interfere with the diffusion of the antibiotic, and a heat treatment to destroy interfering lysozyme activity . The use of Bcillus stearothermophilus and a 65 degree C incubation yielded a rapid assay with a sensitivity of 0.2 microgram neomycin activity/g egg . Frying eggs caused little or no loss of activity, poaching resulted in 25% loss, and soft boiling and hard boiling caused little or no loss of applied activity . Neomycin residues in eggs were quite stable to normal egg preparation procedures. Mikrobiologiia, 1978 Sep-Oct, 47(5), 932 - 8 {Electron microscopic study of the action of submicroscopic levorin structures on Candida guillermondii}; Gerasimov VN et al.; In the course of preparation of aqueous solutions of the polyene antibiotic levorin, the latter is recovered in the solid phase forming granular submicroscopic structures . If the cells of Candida guilliermondii are treated with submicroscopic granular structures (SMGS) of levorin, the structures are adsorbed on the surface of the yeast cell walls . Some visible changes occur in the ultrastructure of the yeast cells incubated with SMGS of levorin for 5 min: the inner layer of the cell wall becomes loose, the periplasmic space appears, the cytoplasmic membrane becomes thicker, the mitochondria swell, and fragmentation of the mitochondrial cristae takes place . Dense round alien bodies 20--40 mn in size can be discerned in the periplasmic space of such cells . If the yeast cells are treated with the levorin structures for a longer period of time (15--60 min), the cell ultrastructure is entirely disorganized. Mikrobiologiia, 1978 Sep-Oct, 47(5), 831 - 40 {Systematic place of the act nomycetes of the Albidus Krassilnikov, 1970 group}; Kuznetsov VD et al.; Detailed studies of the taxonomical characteristics and the complex of produced antibiotics made it possible to establish the identity of Actinomyces albus var . fungatus, Solovieva et Rudaya, 1959 and Actinomyces tumemacerans, Krassilnikov et Koveshnikov, 1962 . Both organisms produce a complex of antibiotics comprising albofungin, albonursin, and a polyene antibiotic belonging to the group of tetraenes . The cultures do not belong to the group of verticillate actinomycetes as was believed earlier (Krassilnikov, 1970) . The later name, Actinomyces tumemacerans, is more appropriate since the organism described under the name of Act . albus var . fungatus differs sharply from other representatives of Act . albus and therefore cannot be regarded as its variety (nomen confusum) . Actinomyces sp . RIA-248 producing albofungin differs from Act . tumemacerans P-42 as well as from Act . albus var . fungatus RIA-247 by the complex of produced antibiotics and other taxonomic properties . Apparently, it should be classed as a new species. J Antibiot (Tokyo), 1978 Sep, 31(9), 875 - 83 Mechanism of action of macromomycin: DNA strand scission, inhibition of DNA synthesis and mitosis; Suzuki H et al.; The effects of macromomycin (MCR), a high molecular weight peptide antibiotic, on cell division, DNA synthesis and DNA fragmentation were examined in cultured mammalian tumor cells . When MCR was added to HeLa cell culture simultaneously with {3H}thymidine, inhibition of DNA synthesis was observed depending on the amount of the drug present, although the inhibition was partial even at a high concentration of the drug . Preincubation of cells with MCR for 2 hours before assay was required for the complete inhibition of DNA synthesis . Cell division of synchronized L5178Y cells, arrested at metaphase, was strongly inhibited by MCR, indicating that the inhibition of cell mitosis by the drug was not dependent on the inhibition of DNA synthesis . Strand scission of DNA in MCR-treated cells was observed by alkaline sucrose gradient centrifugation . The fragmentation of cellular DNA occurred at low concentration of the drug and within a very short incubation time (37 degrees C, 5 minutes) . At high concentrations of the drug, however, the size of the fragmented DNA remained constant . DNA polymerase activity in isolated nuclei from HeLa and L5178Y cells was stimulated by MCR . These data suggest that MCR works directly on cell nuclei and strand scission of DNA is one of the more important actions of the drug. J Antibiot (Tokyo), 1978 Sep, 31(9), 847 - 9 Production, isolation and chemical characterization of mimosamycin; Fukumi H et al.; A procedure is described for the large-scale production of mimosamycin, a satellite antibiotic found in the culture filtrate of Streptomyces lavendulae No . 314 . The 1H and 13C NMR, and mass spectroscopic data, are explained in terms of the structure of mimosamycin. Clin Orthop, 1978 Sep, (135), 69 - 70 Oxacillin induced neutropenia . A case report; Passoff TL et al.; Oxacillin-induced neutropenia is reported in a 16-year-old boy being treated for osteomyelitis . The startling neutropenia developed after 20 days of 200 mg/kg/day of intravenous oxacillin . The neutropenia was not associated with symptoms and was rapidly reversible upon stopping the antibiotic . This reaction may happen with any of the betal lactam antibiotics and is believed to be a direct toxic effect on white cell precursors in the bone marrow. Br J Ophthalmol, 1978 Sep, 62(9), 660 - 2 Penetration of tobramycin sulphate into the human eye; Petounis A et al.; Tobramycin sulphate, a new aminoglycoside antibiotic, was injected intramuscularly (80 and 100 mg) and subconjunctivally (10 mg) into patients, and the concentrations of the drug in serum and aqueous humour were determined 1 hour after the injection by an agar wall diffusion plate method . The intramuscular administration of tobramycin produced insignificant and non-inhibitory concentrations in the aqueous humour, while therapeutically effective levels of the antibiotic appeared in the aqueous after subconjunctival administrationof tobramycin (mean: 18.9 microgram/ml) . These data suggest that tobramycin sulphate may be of value in the treatment of ocular infections. Acta Otolaryngol, 1978 Sep-Oct, 86(3-4), 303 - 8 Aspergillosis of the maxillary sinus . Clinical and histopathological features of 4 cases and a review of the literature; Axelsson H et al.; Four patients with aspergillus maxillary sinusitis are reported and a review of the literature on aspergillus paranasal sinusitis during the last 10 years is presented . The patients had symptoms and X-ray findings similar to a chronic bacterial sinusitis . One patient had been operated upon 6 years previously due to a chronic sinusitis and 3 of the patients had been treated with broad-spectrum antibiotic drugs . Caldwell-Luc operations were performed, also to exclude malignant tumours . The aspergillus etiology of the sinuitis was discovered in routine stained sections by histo-pathological examination of the sinus mucosae . No recurrence of the fungus infection occurred after the Caldwell-Luc operation, which was valuable for the correct diagnosis as well as being the best suited therapy. J Laryngol Otol, 1978 Sep, 92(9), 803 - 10 Malignant otitis externa; Dawson DA; A case is described of malignant otitis externa which was cured by a regime of general and local treatment, including the use of the antibiotic Tobramycin and timely mastoid surgery . The origins, progression, diagnosis and treatment of the disease are discussed with reference to some of the increasingly numerous reports in the literature . Reports disclose an increasing incidence and also an improved prognosis . The former is probably related to the survival of more elderly diabetics and the latter to a better understanding of the disease process and to early medical and, if necessary, surgical treatment . An important feature regarding treatment has been the advent of powerful specific antibiotics including Tobramycin. HNO, 1978 Sep, 26(9), 296 - 7 {Surgical or conservative treatment in orbital complications of sinus inflammations (author's transl)}; Mann W et al.; 47 patients with orbital complications resulting from acute sinusitis have been treated at the Freiburg ENT Department during the last seven years . Acute ethmoiditis predominated in children, while pansinusitis was more common in adults . Previous sinus surgery did not prevent orbital complications arising from the same sinus . Orbital involvement was classified into periostitis, subperiosteal abscess and orbital cellulitis . According to clinical findings, 44.7% of the patients were managed conservatively . Prognosis was best in periostitis, whereas consersative treatment was unsafe in orbital cellulits . Children usually respond well to appropriate antibiotic coverage but the occurrence of common upper respiratory or anaerobic pathogens should be kept in mind. Clin Pharmacokinet, 1978 Sep-Oct, 3(5), 395 - 406 Pharmacokinetics of netilmicin in renal insufficiency and haemodialysis; Pechere JC et al.; The pharmacokinetics of intravenously administered netilmicin, an investigational aminoglycoside antibiotic, were studied in 38 patients with creatinine clearance ranging from 150 to Oml/min/1.73m2 in order to determine the influence of kidney function status on the disposition of the antibiotic . The serum disappearance of netilmicin followed first order kinetics and the elimination rate constant decreased proportionally with decreasing renal function . Half-lives averaged 2.2 hours in normal individuals (creatinine clearance greater than 80ml/min/1.73m2) and reached 42 +/- 10 hours (mean +/- SD) in virtually anephric patients . The elimination rate constant lowered proportionally with decreasing renal function . Several linear relationships between pharmacokinetic parameters and renal function indicators were defined . A clinically useful correlation indicates that the half-life may be approximated as 3 times the serum creatinine concentration and may be used for adjustment of dosage of netilmicin in the treatment of patients with impaired renal function . During haemodialysis, netilmicin extraction from the blood reaches 75 +/- 14% (mean +-/ 95% confidence interval) of that of creatinine and 88 +/- 19% of that of blood urea nitrogen. Antibiotiki, 1978 Sep, 23(9), 833 - 6 {Action of carminomycin on leukemic cell proliferation and some problems of its use in the combined therapy of leukemias}; Egorov LV et al.; The effect of carminomycin on the mitotic cycle of the cells of the transplantable leukemia L-1210 and the therapeutic activity of other antitumor drugs, such as phopurine and cyclophosphane was studied on mice BDF1 . It was found that the cells in phases S and G2 of the mitotic cycle were most sensitive to carminomycin . Transfer G1--S and phase G1 were characterized by resistance to the antibiotic effect . When carminomycin was used in combination with phopurine or cyclophosphane, clear dependence of the therapeutic efficacy on the treatment scheme was noted . Simultaneous administration of all the three drugs resulted in potentiation of the antileukemic effect . An analogous effect was observed when carminomycin was administered prior to phopurine or cyclophosphane . When the order of the drugs use was reverse, the efficacy of the combined therapy was significantly lower than the summation antileukemic effect of the drugs. J Immunol, 1978 Sep, 121(3), 990 - 6 Effect of tunicamycin on IgM, IgA, and IgG secretion by mouse plasmacytoma cells; Hickman S et al.; Tunicamycin, an antibiotic that prevents glycosylation of glycoproteins by blocking the formation of N-acetylglucosamine-lipid intermediates, was used to study the importance of glycosylation for the secretion of immunoglobulins by mouse plasmacytoma lines that produce immunoglobulins of different classes . Biosynthetically labeled secreted and intracellular immunoglobulins were measured by immunoprecipitation assays . Tunicamycin, at a concentration of 0.5 mug/ml produced an 81% inhibition of IgM secretion by MOPC 104E plasma cells without significantly affecting the initial rate of synthesis of intracellular IgM . No increase in the intracellular degradation of nonglycosylated IgM could be demonstrated . Tunicamycin also produced a 64% average inhibition of IgA secretion by several mouse IgA-secreting plasmacytoma lines . In contrast, despite inhibiting the incorporation of D-{14C} glucosamine into newly synthesized IgG, tunicamycin only produced a 28% average inhibition of IgG secretion, which was only slightly more than the nonspecific inhibition of secretion of the normally nonglycosylated lambda2 light chains by variant MOPC 315 plasmacytomas . These data indicate that the extent of inhibition of immunoglobulin secretion produced by tunicamycin depends on the immunoglobulin class produced by the plasma cell. Arch Ophthalmol, 1978 Sep, 96(9), 1650 - 2 Intraocular penetration of topical clindamycin in rabbits . II . Clindamycin phosphate; Devlin JL 3rd et al.; We have obtained comparative data for the intraocular absorption of topically administered clindamycin hydrochloride hydrate and clindamycin phosphate, made feasible with a new gas chromatographic method of analysis . Results indicated that clindamycin phosphate underwent hydrolysis in the eye, liberating the biologically active clindamycin . However, topical clindamycin hydrochloride produced higher levels (two to six times more) of the antibiotic than those achievable with the phosphates ester in the uvea, aqueous humor, and cornea, presumably due to clindamycin hydrochloride's higher lipid solubility . Based on this data, clindamycin hydrochloride appears to be the preferred form of the antibiotic for topical ocular applications. Am J Clin Nutr, 1978 Sep, 31(9), 1594 - 600 Effects of intestinal flora on nitrogen metabolism in patients with chronic renal failure; Mitch WE; Gastrointestinal bacteria have been thought to be beneficial to uremic patients since they could provide an internal source of nitrogen by degrading urea and could function as an alternative means of clearing waste products . Data are presented to indicate that the bacteria of uremic patients do not clear significantly more urea than do the intestinal flora of normal subjects . Analysis of urea metabolism before and during oral administration of aminoglycoside antibiotics demonstrated that nitrogen derived from urea is not used by uremic patients for amino acid synthesis . In addition, it was found that nitrogen balance, on the average -0.98 +/- 0.41, significantly improved to -0.18 +/- 0.29 g N per day during the antibiotic period . The possible explanation for this are discussed . It is concluded that intestinal bacteria adversely affect uremic patients by promoting catabolism and by producing toxins which accumulate in body fluids. J Reprod Med, 1978 Sep, 21(3), 130 - 6 Cephradine and epicillin in body fluids of lactating and pregnant women; Mischler TW et al.; The passage of two antibiotics, cephradine and epicillin, into the milk of 12 lactating women and the amniotic fluid of 48 pregnant women was investigated . All women were given a 500-mg capsule every six hours for at least two days prior to our taking multiple biologic samples from them . Constant levels of both antibiotics were reached in the milk of lactating women as well as in the amniotic fluid of mid-term and full-term pregnant women during the sample period . The ratio of drug concentrations in serum to that in milk was about 5.0 for each antibiotic . In the midtrimester women, the ratio of concentrations in serum to amniotic fluid of both antibiotics was approximately 1.0, suggesting the development of an equilibrium between these two compartments . This ratio was 0.2 for both drugs in the full-term women, demonstrating that the antibiotics concentrated in the amniotic fluid compartment. Klin Monatsbl Augenheilkd, 1978 Sep, 173(3), 407 - 12 {Erosive-ulcerative type of herpes simplex of the lids (author's transl)}; Egerer I et al.; In 14 patients the diagnosis of an erosive-ulcerative type of herpes simplex of the lids was made . It is characterized by erosions of the intermarginal portion of the lid or by erosions or ulcers of the skin, especially close to the lid margin . A combination of both clinical forms is possible . Characteristic herpetic vesicles have been observed only in one case, being situated in close proximity to the erosive lesion of the lid margin . The visualisation of erosions located at the intermarginal portion of the lid can be facilitated by staining with fluorescein . The lack of vesicular eruptions impedes a proper diagnosis; hence one should search for the history of recurrent herpetic infections . A presumptive diagnosis can be confirmed by the immunofluorescence technique . For treatment, topical application of virustatic and antibiotic ointment is recommended. Zh Mikrobiol Epidemiol Immunobiol, 1978 Sep, (9), 82 - 5 {Nutrient medium for the isolation of hemocultures from brucellosis patients}; Grushina TA et al.; To isolate brucellosis causative agent from the blood of patients against the background of antibiotic therapy the authors used for the first time the medium consisting of aminopeptide, beta-globulin agar with glucose, glycerine, and twin-60 . No valuable food products--meat, liver--were required to prepare the medium; by-product of gamma-globulin production being used . With the aid of the suggested medium there was isolated 2.4 times more hemocultures than on the widely used meat-peptone medium . This is attributed to the presence in the medium of human protein, essential amino acids, and blood mineral substances, which, in combination, facilitated adaptation of brucellosis causative agent to the nutrient medium similar to human blood by composition . Economical effect in using the mentioned medium constituted 53.8% annually. Antibiotiki, 1978 Sep, 23(9), 771 - 5 {Density gradient ultracentrifugation method of studying sibiromycin interaction with linear and circular DNA}; Koz'mian LI et al.; Sibiromycin added to linear chromosomal E . coli DNA in vitro leads to the decrease of bouyant density in neutral CsCl density gradient . This decrease is a linear function of sibiromycin/DNA ratio and amounts to about 32 mg/ml at the ratio equal to 0.1 . Binding sibiromycin does not change the degree of hydration of DNA as revealed by centrifugation in metrizamide density gradients . When added to the covalently closed or open circular DNA of PM-2 phage, sibiromycin decreased the bouyant density of these DNA species to a similiar extent . The antibiotic does not induce single-strand breaks in DNA in vitro as follows from the results of ethidium bromide-CsCl density gradient centrifugation of covalently closed PM-2 DNA. Am J Vet Res, 1978 Sep, 39(9), 1438 - 41 In vivo transfer of an Escherichia coli enterotoxin plasmid possessing genes for drug resistance; Gyles C et al.; Experiments were conducted to study transfer of an enterotoxin (Ent) plasmid from a porcine enteropathogenic Escherichia coli to an E coli K12 strain in the intestine of newly weaned pigs . The Ent plasmid carried genes for resistance to tetracycline, streptomycin, and sulfonamides, thereby permitting a selection for tetracycline-resistant exconjugants in the feces of the pigs . In vivo transfer of the Ent plasmid was demonstrated to occur when the pigs were given large oral inocula of donor and recipient cultures, 1 hour apart . Differences in extent of transfer were not detected in pigs given antibiotic-free feed compared with littermates on feed containing oxytetracycline at 50 g/ton . In one experiment, tetracycline-resistant Ent- exconjugants were found which appeared to have received an R plasmid from an enteropathogenic type of E coli resident in the intestine. Antibiotiki, 1978 Sep, 23(9), 829 - 33 {Coamide stimulation of immunogenesis during experimental levomycetin therapy}; Rashidova RA et al.; The effect of various doses of levomycetin on immunogenesis and capacity of coamide for stimulation of immunogenesis in levomycetin therapy was studied . It was found that massive five-fold doses of levomycetin sodium succinate (I and 0.5 g/kg) administered parenterally or orally inhibited immunogenesis, the inhibition being more pronounced on administration of the antibiotic per os . When levomycetin sodium succinate was used in massive doses (1 g/kg) in combination with coamide (0.5 mg/kg) the inhibition of the immune response to the antigenic stimulation was less pronounced. Urologe A, 1978 Sep, 17(5), 355 - 7 {The effect of transurethral electrical stimulation on the paralyzed and incontinent bladder: objective results (author's transl)}; Madersbacher H; Using objective parameters, improvement of the detrusor function and bladder sensitivity can be obtained in most children . A significant improvement in incontinence appears possible in 30--40% of the patients . The method according to Katona is the only one which creates bladder sensitivity . This method is not a cure all but has improved our therapeutic possibilities, especially when it is combined with pharmacotherapy, long term low dose antibiotic therapy and sphincterotomy. Arch Microbiol, 1978 Sep 1, 118(3), 289 - 92 The effect of cycloheximide on Euglena gracilis phenylalanyl-tRNA synthetases; Spare W et al.; The effect of cycloheximide on the chloroplastic, cytoplasmic and mitochondrial phenylalanyl-transfer RNA synthetases of Euglena gracilis was studied by growing both logarithmic and stationary phase cultures in the presence of the antibiotic . Enzyme activity was measured relative to untreated control cultures . At very low concentrations of cycloheximide (1 microgram/ml), all three log phase enzymes showed an increase in activity of 40-50% . At slightly higher concentrations (2.5 microgram/ml), the phenylalanyl-tRNA synthetase activities were comparable to those of the control cultures . At a cycloheximide concentration of 5 microgram/ml the enzyme activities from stationary phase cultures showed only very slight decreases (5-20%) . The cytoplasmic and mitochondrial enzymes behaved similarly in log phase cultures at this concentration . However, the chloroplastic phenylalanyl-tRNA synthetase from log phase cultures treated with 5 microgram/ml cycloheximide showed a marked decrease in activity (70%) . A further increase in antibiotic concentration to 10 microgram/ml resulted in significant losses of activity of all three enzymes, from both growth stages . The implications of the data with regard to identification of the site(s) of chloroplast enzyme synthesis are discussed. J Antibiot (Tokyo), 1978 Sep, 31(9), 884 - 7 Stimulation of prolyl hydroxylase activity by bleomycin; Takeda K et al.; The activity of purified prolyl hydroxylase (proline, 2-oxoglutarate dioxygenase, EC 1 . 14 . 11 . 2) was enhanced 3 approximately 8-fold at a low concentration of ferrous ion (1 X 10(-5 M) by addition of bleomycin, a glycopeptide antibiotic with antineoplastic activity and a side effect of producing pulmonary fibrosis . The maximum stimulation was attained at a concentration of 15 microgram/ml bleomycin (about 1 X 10(-5) M), which was approximately equimolar with the ferrous ion, one of the cofactors of this enzyme . Addition of bleomycin to the assay mixture resulted in a change of the optimal concentration of ferrous ion from 2 X 10(-3) M to 1 X 10(-5) M . Changing the order of addition of ferrous ion, enzyme and bleomycin in assay medium before incubation at 37 degrees C, the stimulatory activity was varied . Blemycin A2Cu++(Cu++-chelated bleomycin), which scarcely complexed with Fe++, had no enhancing effects on the enzymatic activity . We discuss the possible reasons as to why the activity of prolyl hydroxylase was enhanced by addition of bleomycin in the assay mixture. Dtsch Med Wochenschr, 1978 Aug 25, 103(34), 1334 - 8 {Cefamandol: pharmacokinetics with normal and impaired renal function (author's transl)}; Hoffler D et al.; 1.0 g cefamandol was injected in 25 patients with various degrees of renal function . Half-life and distribution volume of this antibiotic and the glomerular filtration rate (GFR) were then measured . The distribution volume was 18.5 +/- 3.5% of body weight, similar to the extracellular space . Half-life and GFR were related in a way which could be expressed in the formula: half-life = 400 sqaure root GFR . Levels of blood concentration of cefamandol could be estimated from half-life and GFR, with the construction of "isoconcentration dosages", by which it is possible to achieve levels similar to those in normal subjects receiving a normal dosage. Eur J Biochem, 1978 Aug 15, 89(1), 125 - 31 Degradation of guanosine 3'-diphosphate 5'-diphosphate in vitro by the spoT gene product of Escherichia coli; Heinemeyer EA et al.; Guanosine 3'-diphosphate 5'-diphosphate (ppGpp) is rapidly degraded to guanosine 5'-diphosphate (ppG) and probably pyrophosphate by an enzyme present in the ribosomal fraction prepared from spoT+ strains of Escherichia coli . The ppGpp-degrading enzyme was released from the ribosomes during dissociation at low ionic strength . Ribosomes are not essential for degradation of ppGpp, and decay of ppGpp is strictly dependent on manganese ions . The reaction is sensitive to inhibition by tetracycline, which can be reversed by MnCl2, indicating that the inhibitory effect is due to the previously described chelating properties of the antibiotic . When the ppGpp-degrading enzyme was complemented with adenosine 5'-triphosphate (pppA) and a nucleoside diphosphate kinase, decay of ppGpp was accelerated yielding pppG and ppG as major products . In the absence of pppA we have been unable to detect the ppGpp-degrading enzyme in various spoT- mutant strains indicating that this enzyme is the spoT gene product. Vet Rec, 1978 Aug 12, 103(7), 130 - 1 A severe outbreak of bovine mastitis assoicated with Mycoplasma bovigenitalium and Acholeplasma laidlawii; Counter DE; An outbreak of clinical mastitis is described in which 75 cows of a herd of 200 Friesian cows were affected in one or more quarters over a period of three months . Sixty animals failed to return to normal despite various intramammary and systemic antibiotic treatments . Heifers, dry cows and lactating animals were affected . The milk of 15 out of 53 animals tested yielded mixed cultures of Mycoplasma bovigenitalium and Acholeplasma laidlawii . Thirteen of 34 sera showed evidence of antibodies to A laidlawii. J Biol Chem, 1978 Aug 10, 253(15), 5332 - 7 Effect of tunicamycin on the secretion of serum proteins by primary cultures of rat and chick hepatocytes . Studies on transferrin, very low density lipoprotein, and serum albumin; Struck DK et al.; Using rat or chick hepatocyte monolayers, we have studied the effect of tunicamycin, a specific inhibitor of protein glycosylation, on the synthesis and secretion of serum proteins . Tunicamycin inhibited glucosamine incorporation into rat liver transferrin and the apoprotein B chain of chick liver very low density lipoprotein (VLDL) by 75 to 90% . In contrasts, amino acid incorporation into these two glycoproteins, as well as into the normally unglycosylated proteins, rat serum albumin and apoprotein A of chick liver VLDL, was decreased by only 10 to 25% in the presence of the antibiotic . Despite the inhibitory effect of tunicamycin on glycosylation, secretion of all four proteins was virtually unimpaired . Thus, the carbohydrate moieties of rat liver transferrin or apoprotein B of chick liver VLDL do not appear to play an essential role in the secretion process. Fortschr Med, 1978 Aug 3, 96(29), 1447 - 51 {Problems with male contraception . 1 . Physiological foundations, male contraception (mechanical procedures, contraceptives)}; Schill WB; PIP: The various aspects of male fertility control are elaborated . A discussion of spermatogenesis and fertilization mechanisms lays the groundwork for determining how these processes can be inhibited . Mechanical male contraceptive methods are coitus interruptus and coitus condomatus . Coitus interruptus can cause neurotic disturbances in both partners and has a failure rate of 10-20/100 use-years . The condom has a failure rate of about 7/100 use-years . Vasectomy is the most practicable operative male contraceptive method . Scrotal hematoma, scrotal abcesses, and congestive epididymitis are possible post-operative complications . 2/3 of the men who have vasectomies develop sperm autoantibodies, and some develop sperm granulomas . Spontaneous recanalization occurs in .8% of the cases . The incipience of azoospermia after vasectomy is dependent on the number of ejaculations but is difficult to predict . Castration and increasing the temperature of the gonads are other operative methods of male contraception . Medicamentive methods of male contraception must be safe, effective, fast, and reversible; they must cause no genetic changes, disturbances in libido or potency, or changes in secondary sex characteristics . Medicamental agents can affect spermatogenesis; the maturation of the spermatozoa; transport, motility, or metabolism of the spermatozoa; capacitation of the spermatozoa; or the penetration enzymes . Heavy metal compounds, cytostatic, or antibiotic compounds are unsuitable as spermatogenic inhibitors due to side effects . 5-Thio-D-Glucose may show promise as an antispermatogenic agent . Postgrad Med J, 1978 Aug, 54(634), 541 - 4 The management of childhood osteomyelitis; Khazenifar M et al.; The management of seventy-six children admitted to Aler Hey Children's Hospital with osteomyelitis is discussed and the indications for surgical intervention are defined . The clinical and pathological course of the disease is examined and the term post-acute osteomyelitis is introduced . The importance of recognition of this stage of the disease and its relevance to the management is highlighted . The use of single antibiotic therapy (clindamycin) is shown to be at least as effective as combinational therapy . Complete resolution was achieved in 94.7% of children, surgical intervention was performed on 74.6%. J Cell Sci, 1978 Aug, 32, 433 - 9 Selecting somatic cell hybrids with hat media and nystatin methyl ester; Fisher PB et al.; The structurally modified polyene antibiotic nystatin methyl ester (NME) has been utilized as a half-selection agent for isolating interspecific mouse--Syrian hamster hybrids . By using HAT media supplmented with NME we have isolated hybrid clones from polyethylene glycol-fused cultures of biochemically defective mouse (A9 or B82) and genetically normal Syrian hamster (KHK/C13) cells . Unfused parental cells were killed in HAT-NME media as a result of their genetic defect, absence of hypoxanthine guanine-phosphoribosyl transferase-HGPRT-(A9) or thymidine kinase--TK-(B82), or innate sensitivity to NME (BHK/C13) . In contrast, hybrid cells proliferated and clones were isolated after 3 weeks growth in HAT-NME media, indicating the genetic complementation had occurred and polyene resistance was expressed as a dominant phenotypic property in the hybrids . The presently described technique is efficient in eliminating unfused parental cells and should prove useful in isolating other types of hybrids formed between genetically defective and normal parental cells. Br J Cancer, 1978 Aug, 38(2), 237 - 49 Thyroid tumours in rats and hepatomas in mice after griseofulvin treatment; Rustia M et al.; Griseofulvin, an antibiotic used to treat dermatophystosis, was tested for carcinogenicity in mice, rats and hamsters . Three groups of mice and rats were given the drug in powdered diet in alternating 5-week periods for life, at dose levels of 3.0%, 1.5% and 0.3% (mice) and 2.0%, 1.0% and 0.2% (rats) . A group of mice and 3 groups of hamsters received continuous daily treatment for life with griseofulvin at 3.0%, 1.5%, 0.3% and 0.1% dose levels respectively . A significant incidence of hepatic tumours was observed at the 2 higher treatment levels in mice . Also, statistically significant rates (P less than or equal to 0.001 and/or P less than or equal to 0.020) of thyroid tumours, indicating a dose-response, were recorded in male rats at the 2.0%, 1.0%, and 0.2% dose levels, and in females at the 2.0% and 1.0% dose levels . Hamsters did not develop neoplasms in response to treatment at any level. Br J Ophthalmol, 1978 Aug, 62(8), 571 - 4 Orbital blood cyst; Sevel D et al.; A blood cyst of the orbit is an unusual cause of proptosis and most likely arises in a pre-existing haemangioma . If the cyst occurs at the apex of the orbit the blood should be aspirated . This is followed by excision of the cyst wall, the dissection being done with the aid of an operating microscope . If there is evidence of intracranial connection of the blood cyst, namely, splayed superior orbital fissure or cerebrospinal fluid leak, then the patient should be treated with an antibiotic to prevent intracranial infection. Antibiotiki, 1978 Aug, 23(8), 690 - 2 {Directed isolation of Micromonospora generic cultures on a selective medium with gentamycin}; Ivanitskaia LP et al.; The results of using selective media with gentamicin for directed isolation of Micromonospora are presented . It was shown that the use of the selective media with gentamicin for isolation of actinomycetes from soils of usual humidity levels markedly increased the frequency of Micronomonospora detection . The use of the selective media with gentamicin for plating out silt substrates containing mainly Micromonospora had practically no effect on the increase in the number of the Micromonospora cultures grown . The number of antibiotic-producing Micromonospora isolated on the media with gentamicin was 3 times higher than that on the control media . The use of the selective media with gentamicin provided directed isolation of Micromonospora. J Clin Invest, 1978 Aug, 62(2), 241 - 7 Gentamicin blockade of slow Ca++ channels in atrial myocardium of guinea pigs; Adams HR et al.; Cardiac dysfunction is occasionally detected in patients undergoing treatment with amino-glycoside antibiotics, however, the mechanism responsible for the negative inotropic effect of these agents has not been identified . In the present investigation electrically driven left atria of guinea pigs were used to study the effects of gentamicin on calcium ion (Ca++)-dependent contractile events in heart muscle isolated from in vivo influences . When atria were first inactivated by excess potassium ion (K+; 22mM) and contractions were then restored by isoproterenol (an experimental model that accentuates the contractile dependence of myocardial fibers on influx of Ca++ through specific "slow channels" of the sarcolemma), the cardiac depressant activity of gentamicin (0.1 mM) was profoundly augmented . Conversely, the negative inotropic effect of tetrodotoxin (23.5 micron) was abolished by the same experimental conditions . Also, gentamicin (1 mM) and La+++ (0.5 mM) markedly decreased the positive inotropic response to increased frequency of stimulation; whereas, D600 (1.05 micron) converted the positive frequency-force relationship to a negative relationship . Present data indicate a direct cardiac depressant action of gentamicin, and suggest that this antibiotic adversely affects either the transport system responsible for Ca++ movement through slow channels of the sarcolemma, the availability of Ca++ for translocation to these sites, or both. J Clin Chem Clin Biochem, 1978 Aug, 16(8), 447 - 50 {A NH(+4)-selective-enzymatic flow-through system . A method for the continuous enzymatic, electrochemical determination of urea, II (author's transl)}; Schindler JG et al.; A flow-through system for the measurement of urea concentrations is described, using soluble urease and consecutive determination of liberated ammonium ions by a selective disc-electrode . The active component of the electrode membrane was the carrier-antibiotic nonactin which was incorporated in a polyvinylchloride matrix. Mutat Res, 1978 Aug, 51(2), 189 - 97 On the mechanisms of induced somatic recombination by certain fungicides in Aspergillus nidulans; Kappas A; Four fungicides interfered with the segregation of chromosomes at mitosis of Aspergillus nidulans by increasing the somatic recombination, shown as colour sectors in green colonies, in a strain heterozygous for spore colour mutations . In an attempt to discover the mechanisms by which these fungicides increased the somatic recombination, a prototrophic diploid strain, heterozygous for colour and several other appropriate markers in all chromosomes, was used which enabled the detection and classification of all colour recombinants to be made by genetic analysis . The fungicides investigated were: benomyl (methyl-1-(butylcarbamoyl)-2-benzimidazole carbamate) a benzimidazole derivative, botran (2,6-dichloro-4-nitroaniline) and chloroneb (1,4-dichloro-2,5-dimethoxybenzene) of the aromatic hydrocarbon group of fungicides, and the antibiotic actinomycin D . At least three different mechanisms, non-disjunction, mitotic crossing-over and breakage-deletion, were found to be responsible for the recombinogenic activity of the compounds studied. J Trauma, 1978 Aug, 18(8), 587 - 95 The burned hand: a planned treatment program; Habal MB; A planned treatment program for burned hands has been developed and was used in 72 burns of the dorsum of the hands . Treatment was individualized on the basis of whether hand burns were superficial or deep . In the former, there was evidence of spontaneous reepithelialization within 14 to 21 days . In the latter, immediate or delayed excision, followed by resurfacing with autografts was done . Both groups received topical antibiotic creaming, elevation, an exercise program as soon as they were able, and splinting of the burned hand in the antideformity position . Hypertrophic scars and unacceptable epithelium were excised when they interfered with function . Initially, this program allowed us to avoid unnecessary surgical procedures in 94% of the second-degree burns of the dorsum of the hand . The third-degree burned hand needed excision and autografting in 100% of the burned hands . This treatment program has as its goals: prevention of deformity by early motion and protection of the unburned and regenerating epithelium by creaming with topical antibiotic ointment. Can J Microbiol, 1978 Aug, 24(8), 1012 - 5 Intracellular cyclic adenosine 3',5'-monophosphate levels and streptomycin production in cultures of Streptomyces griseus; Ragan CM et al.; Changes in the amount of cyclic 3',5'-adenosine monophosphate within the mycelium of Streptomyces griseus were measured as cultures progressed through trophophase and idiophase in a complex medium supporting growth and streptomycin synthesis . Concentrations were highest before the cultures entered stationary phase and had declined 90% by 5 h before the antibiotic was produced . This low conentration was maintained while the antibiotic accumulated during the idiophase . The results indicate that the onset of streptomycin synthesis is not directly mediated by an increase in intracellular cyclic 3',5'-adenosine monophosphate concentration, and thus that antibiotic production in S . griseus is not controlled by catabolite repression. Antibiotiki, 1978 Aug, 23(8), 682 - 6 {Polymyxin B biosynthesis and tricarboxylic acid cycle enzymatic activity}; Nefelova MV et al.; Activity of pyruvate dehydrogenase (PDG), isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase and malate dehydrogenase was found in the extracts of the cells of Bac . polymyxa 153, an organism producing polymyxin B . Dependence of the activity of the above enzymes on the carbon source in the medium, aeration conditions, strain features and culture age was shown . A low level of polymyxin B biosynthesis was observed at high activity of PDG and dehydrogenases of the tricarbonic acid cycle . Increased antibiotic production was recorded against the background of decreases values of the above enzyme activities. Proc Natl Acad Sci U S A, 1978 Aug, 75(8), 3603 - 7 Nucleotide specificity in DNA scission by neocarzinostatin; Hatayama T et al.; Using the DNA sequencing technique of Maxam and Gilbert, we show that the protein antibiotic neocarzinostatin, cleaves double-stranded phiX174 DNA restriction fragments almost exclusively at deoxythymidylic and deoxyadenylic acid residues in a reaction requiring 2-mercaptoethanol . Overall, deoxythymidylic acid residues are attacked much more frequently than are deoxyadenylic acid residues, although there is variability in the attack rate for both nucleotides at different locations in the DNA molecule . While all deoxythymidylic acid residues are sites of scission by neocarzinostatin, not all deoxyadenylic acid residues are cleavage sites . There appears to be no clear-cut nucleotide sequence specificity in determining cleavage frequency . Single-stranded DNA is a very poor substrate for neocarzinostatin-induced scission; with one single-stranded DNA fragment, cleavage occurs at a position that is not attacked in double-stranded DNA . The possible significance for its biological activity of a drug that can attack both members of a DNA base pair is discussed. Nucleic Acids Res, 1978 Aug, 5(8), 2959 - 67 Activation and inactivation of neocarzinostatin-induced cleavage of DNA; Kappen LS et al.; The possible role of free radicals in the mechanism of neocarzinostatin (NCS) action was studied . While mercaptene markedly stimulate the ability of NCS to degrade DNA, they also rapidly inactivate the antibiotic in a preincubation and at higher concentration inhibit the degradation reaction . The radiation protector S,2-aminoethylisothiuronium bromide-HBr is the most potent compound tested . Scavengers of diffusible OH radicals, O2- or H2O2 do not result in significant inhibition of the oxygen-dependent cleavage of DNA by NCS; in fact, alcohols and other organic solvents stimulate the reaction several-fold . By contrast, the potent peroxyl free radical scavenger, alpha-tocopherol, blocks the reaction 50% at 50 micron. Int J Oral Surg, 1978 Aug, 7(4), 380 - 5 Reconstruction of the horizontal rami of the mandible following avulsion in childhood; Holland PS et al.; A 7-year-old boy was involved in a road traffic accident in October 1971, and apparently had been dragged along face downwards with resultant avulsion of the entire horizontal mandibular rami, and most of the mandibular alveolar soft tissue and teeth . Repair by metal implants was attempted but these proved unsatisfactory, and soft tissue replacement for the missing alveolus was carried out by flap raised from arm . Rib grafting was carried out on three occasions at almost yearly intervals, but each time, probably owing to vascular insufficiency, non-union (or more correctly non-replacement) occurred in the left canine region . To "import" a new blood supply, and free some of the scar tissue, a compound muscle/bone/skin flap bearing the clavicle and sternomastoid muscle was transposed to the mandibular bed . This form of grafting was used extensively in World War I to repair facial gunshot wounds, and the transposed blood supply enabled success in the pre-antibiotic period . Bony union is now satisfactory 5 years after injuries and dentures have been recently fitted; speech is normal, the child's facial contours acceptable, and mastication has been satisfactory during this period. Br J Pharmacol, 1978 Aug, 63(4), 643 - 9 Mechanism of histamine release from rat mast cells induced by the ionophore A23187: effects of calcium and temperature; Johansen T; 1 The mechanism of histamine release from a pure population of rat mast cells induced by the lipid soluble antibiotic, A23187, has been studied and compared with data for anaphylactic histamine release reported in the literature . 2 Histamine release induced by A23187 in the presence of calcium 10(-3) mol/l was completed in 10 minutes . By preincubation of the mast cells with A23187 for 10 min in the absence of calcium the histamine release induced by calcium, 10(-3) mol/l or 5 x 10(-3) mol/l, was completed in 90 s and 45 s, respectively . 3 A23187-induced histamine release was maximal with calcium 10(-3) mol/l when the cells were incubated at 33 to 39 degrees C for 10 minutes . 4 The cellular mechanism, which was stimulated by A23187 and calcium for the release of histamine, was irreversibly inactivated by incubation at 45 degrees C . 5 An inhibition of energy metabolism was excluded as the cause of the heat inactivation . 6 The dependence of A23187-induced histamine release on calcium and temperature, the time course of histamine release and the heat inactivation are consistent with the view that the same mechanism is involved in A23187-induced and anaphylactic histamine release. J Biol Chem, 1978 Jul 25, 253(14), 4830 - 2 Effect of light and oxygen on neocarzinostatin stability and DNA-cleaving activity; Burger RM et al.; The in vitro DNA-cleaving activity of neocarzinostatin, a protein antibiotic, is strongly but reversibly inhibited by anaerobiosis . Half-maximal activity is seen in the presence of 0.25 mM O2 . The stability of neocarzinostatin, as demonstrated by its ability to cleave DNA, is significantly reduced in light . Inactivation by light is complete and irreversible. Aust Vet J, 1978 Jul, 54(7), 342 - 4 The influence of the time of treatment in relation to feeding on the efficacy of amoxycillin therapy in dogs and cats; Siwak AD; A field trial comparing the clinically assessed response to amoxycillin therapy in 148 fasted and 129 non-fasted dogs and cats suffering clinically diagnosed bacterial infections is reported . A satisfactory response to treatment was obtained in 88.8% of these cases . The results indicate that the clinical response to amoxycillin therapy was not affected by the concurrent administration of the antibiotic with food. HNO, 1978 Jul, 26(7), 237 - 40 {The clinical presentation and management of otogenic intracranial disease (author's transl)}; von Westernhagen B; Since the introduction of antibiotics in the treatment of ear infection the number of otogenic intracranial complications has decreased . Furthermore the clinical presentation of these complications has likewise since changed . The traditional symptoms and signs as mentioned in the literature are replaced by an indefinite inflammatory course, which is finally succeeded by rapid progress of the disease despite the use of antibiotics . Experiences with 22 patients are reported . Temporal lobe brain abscesses occurred in 11 patients, meningitis occurred in 3 others and lateral sinus thrombophlebitis occurred in 8, in 2 of whom meningitis also occurred . Five patients died as a result of the intracranial complication . After establishing the diagnosis the recommended treatment is the immediate surgical clearance of the primary aural abscess, together with if possible drainage of the intracranial abscess or evacuation of the lateral sinus disease under appropriate antibiotic cover . Whether the patient with intracranial disease is subsequently handled in the ORL or Neurosurgical wards depends upon ward facilities and interdepartmental liaison and cooperation. Gut, 1978 Jul, 19(7), 602 - 5 Alterations of the colonic flora and their effect on the hydrogen breath test; Gilat T et al.; The hydrogen breath test was performed by ingestion of 20 g lactulose and analysis of end-expiratory air . Eighteen patients undergoing colonoscopy, 17 receiving antibiotics, 12 prepared for colon surgery, and 15 controls were examined . The test was repeated under control conditions in the treated patients . Eleven of 55 subjects failed to produce significant amounts of hydrogen under control conditions . This 20% proportion of non-hydrogen producers is much higher than that reported by other investigators . The hydrogen production was very markedly depressed after preparation for colonscopy and antibiotic therapy . The effect of neomycin and enemata as used in preparation for colon surgery was less marked . Hydrogen production by the colonic flora is thus subject to individual variations and may be affected by various therapeutic regimens . All these may cause false negative results when using the hydrogen breath test to evaluate carbohydrate absorption . The test should therefore not be performed for a considerable time after therapeutic manipulation of the colonic flora. Antibiotiki, 1978 Jul, 23(7), 611 - 7 {Effect of the multiple peroral administration of carminomycin on the body of animals}; Gol'dberg LE et al.; Toxicity of carminomycin used orally for many times was mainly evident from suppression of blood formation, the level of the suppression being dependent on the antibiotic dose . Carminomycin had a low suppressing effect on the white blood in rats . At low doses even moderate leucocytosis was observed . The indices of the functional state of the liver, kidneys, sugar blood levels, content of glycogen and fat in the liver, relative mass of the rat organs after repeated oral administrations of karminomycin to the animals remained mainly unchanged . A change in wave T on the ECG of the dogs treated with high doses of the antibiotic was registered . Histological examination of the organs and tissues of the animals killed after repeated oral administrations of carminomycin revealed pathological changes only in the spleen and thin intestine . Such changes were not more pronounced than those after repeated intravenous administration of the equivalent doses of the antibiotic (by the effect on the blood formation) . This allowed the author to recommend the oral administration route for carminomycin trials in clinics. Antibiotiki, 1978 Jul, 23(7), 609 - 11 {Distribution of 3H-carminomycin in the body of mice}; Reznikova MI et al.; Distribution of 3H-carminomycin with the specific activity of 390 mCu/g prepared by the method of isotope exchange in 3H2O was investigated on mice treated with the antibiotic administered intravenously in a dose of 2 mg/kg . It was shown that the antibiotic rapidly accumulated in the mouse tissues, mainly in the liver, kidneys, lungs and spleen . The carminomycin blood levels markedly decreased within the first 5 minutes after the drug administration and remained rather stable during the following 6 hours . The concentrations of carminomycin in the heart muscle were comparatively low . Still, at early periods they were much higher than those in the skeletal muscles . The difference disappeared by 24 hours . Carminomycin penetrated into the tissues of the brain. Antibiotiki, 1978 Jul, 23(7), 593 - 8 {Hydrolysis of the amidine analogs of penicillins}; Veinberg GA et al.; The products of the hydrolytic degradation of 6-beta-(hexahydro-IH-azepenyl-1)methylenamino) penicillanic acid, 6-beta-(N,N-dimethylformamidino-N1)-penicillanic acid and 6-beta-(morpholinyl-1)methylenamino penicillanic acid were identified with the method of thin-layer chromatography and paper electrophoresis in neutral, acid and alkaline solutions and in the presence of penicillinase . The data of the study showed that acid hydrolysis of the amidine analogues of penicillins resulted in cleavage of the beta-lactame cycle and formation of the respective penicillanic acids . In the alkaline medium the secondary amine (hexamethylenimine, dimethylamine, morpholine) was cleaved from the antibiotic side chain and the resulting N-formyl-6-aminopenicillanic acid was further cleaved up to peniciec acid . The beta-lactame cycle of the antibiotics was cleaved under the effect of penicillinase and the resulting penicilloinic acids degraded into peniciec acid, N-formylpeniciec acid and secondary amines . In the nutral solution the antibiotics were transformed into N-formyl-6-aminopenicillanic acid and penicilloinic acids at the first stage of the hydrolysis followed by their further degradation with formation of N-formylpeniciec acid, peniciec acid and secondary amines. South Med J, 1978 Jul, 71(7), 858 - 60 Concurrent primary pneumococcemia, disseminated intravascular coagulation, and sickle cell anemia; McDonald CR et al.; Fulminant pneumococcal infections are rare in teen-agers with sickle cell anemia . A 16-year-old black male with sickle cell anemia was treated as an outpatient for cryptogenic pain crisis, which delayed antibiotic therapy for primary pneumococcal septicemia for seven hours . This patient did not appear ill upon initial presentation but rapidly developed disseminated intravascular coagulation and died. Laryngoscope, 1978 Jul, 88(7 Pt 2 Suppl 10), Suppl 10: 1 - 65 The sublabial transseptal transsphenoidal approach to the hypophysis; Lee KJ; A simple and safe technique for the sublabial transseptal transsphenoidal approach to the hypophysis and parasellar region is described . A review of the literature reveals that this technique and other transsphenoidal routes to the hypophysis were performed more than half a century ago.These procedures fell into disfavor because fo low magnification and insufficient illumination of the operative field, infection and inadequate postoperative endocrine replacement therapy . With today's antibiotic therapy and hormonal replacement, plus the use of the operating microscope, the transsphenoidal route to the hypophysis has gained renewed interest among neurosurgeons and otolaryngologists . Each of the transsphenoidal routes and the advantages of the "from below" approach are described . The applications of transsphenoidal approach and the nonsurgical modalities for hypophysectomy are reviewed . The simplicity and safety of the sublabial transseptal transsphenoidal approach depend on a thorough familiarity with the surgical anatomy, proper positioning of the patient, and the availability of appropriate instrumentation . Photographs of specially prepared whole head anatomical specimens plus skull dissections with radiographic correlation illustrate the pertinent anatomy . Some of the vital structures to be identified and avoided are the optic canals, carotid arteries, circular sinuses, cavernous sinuses, III, IV, V, VI cranial nerves, foramen rotundum, medial walls of the orbits, medial walls of maxillary sinuses, medial pterygoid plates and pterygoid canals . A method for preoperative determination of key distances within the patient's skull is described along with other preoperative tests . This paper discusses the self-retaining speculum and other new instruments for this procedure . A gauge mounted on the front end of the speculum is calibrated to measure the size of the opening at the tip of the speculum . Thirty cases are included in this report, six of which are presented in detail . No operative mortality, CSF rhinorrhea, visual damage carotid or cavernous sinus hemorrhage fracture of the medial pterygoid plates or maxilla were encountered in this series . Three patients developed diabetes insipidus and two patients had meningitis which responded to antibiotic therapy. G Batteriol Virol Immunol, 1978 Jul-Dec, 71(7-12), 198 - 205 {Biological effects of distamycin A}; Pugliese A et al.; In the present review are examined different biological effects of Distamycin A, an antibiotic produced by Streptomyces distallicus . This drug is moderately active on bacteria but it is strongly active on DNA viruses and on some Oncornaviruses, moreover it possesses antineoplastic and antimitotic activity at high doses at which it can result tossic and cause immunodepression. Antibiotiki, 1978 Jul, 23(7), 644 - 7 {Clinical and laboratory comparisons of tetracycline penetration through the blood-cerebrospinal fluid barrier in central nervous system diseases}; Imshenetskaia VF; The data on tetracycline penetration from the blood into the serebrospinal fluid of patients with different diseases of the central nervous system are presented . Clinico-laboratory comparisons showed that the antibiotic penetration did not depend on the character and severity of the main disease of the brain (tumor, trauma, abscess) . No dependence on the surgical intervention was either found . The index of tetracycline penetration from the blood into the liquor did not depend on the drug administration route, i.e . intramuscularly or orally . The presence of the post-operative meningitis increased permeability of the brain membranes for tetracycline. Can Anaesth Soc J, 1978 Jul, 25(4), 303 - 6 Neuromuscular and cardiovascular depression produced by prolonged exposure to Polymyxin B; de Silva AJ et al.; It has been reported previously that in cats pre-treatment for 24 to 48 hours with neomycin sulphate resulted in a change in the pattern of neuromuscular block subsequently produced with this antibiotic . The unique characteristics of neomycin-induced neuromuscular block observed during acute exposure gave way to a pattern of block usually observed with tubocurarine . In a similar experiment on six cats we have demonstrated that with polymyxin B prolonged exposure did not result in a comparable time-dependent change in the nature of the neuromuscular block it produced, in terms of train-of-four, tetanic, and post-tetanic behaviour of the neurally-elicited muscle response . The differing characteristics of neuromuscular block seen with various antibiotics, e.g . the aminoglycoside neomycin as opposed to the polypeptide polymyxin B, during acute and sub-chronic exposure is stressed . Previously observed ability of 4 aminopyridine 0.6 mg/kg to reverse the neuromuscular and cardiovascular depression during acute exposure to polymyxin B persisted in prolonged exposure. Thromb Haemost, 1978 Jun 30, 39(3), 689 - 94 Platelet-binding of the von Willebrand factor; Green D et al.; The aggregation of platelets by the antibiotic, ristocetin, requires a plasma cofactor (VIII:vWF) and one or more specific binding sites on the platelet membrane . The interaction between VII:vWF and the platelet was examined using VIII:vWF labelled with 125I . In the presence of ristocetin (1.5 mg/ml), from 70 to 90% of the 125I-VIII:vWF became platelet-bound . By contrast, only 21% was bound with thrombin (2.5 microgram/ml), and 2.2% with buffer alone . Fractionation of the platelets revealed that peak radioactivity was present in the membrane fraction . Treatment of ristocetin-reacted platelets with either chymotrypsin, 100 microgram/ml, or trypsin, 75 microgram/ml, resulted in the partial release of the membrane-bound radioactivity . It is concluded that VIII:vWF binds to the platelet membrane in the presence of ristocetin. J Membr Biol, 1978 Jun 22, 41(1), 65 - 86 Effects of amphotericin b on the electrical properties of Necturus gallbladder: intracellular microelectrode studies; Reuss L; Intracellular microelectrode techniques were employed to study the mechanism by which amphotericin B induces a transient mucosa-negative transepithelial potential (deltaVms) in the gallbladder of Necturus . When the tissue was incubated in standard Na-Ringer's solution, the antibiotic reduced the apical membrane potential by about 40 mV, and the basolateral membrane potential by about 35 mV, whereas the transepithelial potential increased by about 5 mV . The electrical resistance of the apical membrane fell by 83%, and that of the basolateral membrane by 40%; the paracellular resistance remained unchanged . Circuit analysis indicated that the equivalent electromotive forces of the apical and basolateral membranes fell by 35 and 11 mV, respectively . Changes in potentials and resistances produced by ionic substitutions in the mucosal bathing medium showed that amphotericin B produces a nonselective increase in apical membrane small monovalent cation conductance (K, Na, Li) . In the presence of Na-Ringer's on the mucosal side, this resulted in a reduction of the K permselectivity of the membrane, and thus in a fall of its equivalent emf . During short term exposure to amphotericin B, PNa/PCl across the paracellular pathway did not change significantly, whereas PK/PNa doubled . These results indicate that deltaVms is due to an increase of gNa across the luminal membranes of the epithelial cells (Cremaschi et al., 1977 . J . Membrane Biol . 34:55); the data do not support the alternative hypothesis (Rose & Nahrwold, 1976 . J . Membrane Biol 29:1) that deltaVms results from a reduction in shunt PNa/PCl acting in combination with a rheogenic basolateral Na pump. Biochim Biophys Acta, 1978 Jun 22, 519(1), 31 - 48 Repair of lesions induced by bruneomycin in DNA of isolated mitochondria from the mature eggs of the teleost fish Misgurnus fossilis; Mikhailov VS et al.; Addition of a radiomimetic antibiotic bruneomycin (Streptonigrin) to isolated mitochondria from mature quiescent oocytes of the teleost fish loach Misgurnus fossilis leads to the induction of unscheduled synthesis of mitochondrial DNA . Most of the newly synthesized DNA has the sedimentation properties of open circles and up to 15% of the label is present in the fraction of the covalently closed-circular molecules . The size of the newly synthesized DNA stretches determined from the bouyant shift of DNA labeled with 5-bromouracil and {3H}dAMP and sonicated to fragments of different molecular weight, was found to be equal to about 1000 nucleotides for the labeled covalently closed circles and to about 2000 nucleotides for the labeled open-circular DNA . Experiments with the centrifugation of non-sheared and sonicated 5-bromouracil and {3H}dAMP-labeled mitochondrial DNA (mtDNA) in alkaline CsCl density gradients provided evidence of a covalent linkage between newly-synthesized stretches and the parental DNA strands . It is concluded from these data that the unscheduled mtDNA synthesis induced by bruneomycin does at least in part represent mtDNA repair synthesis. Med Klin, 1978 Jun 16, 73(24), 910 - 3 {Clinical pharmacology of Bacampicillin in comparison to Ampicillin (author's transl)}; Simon C et al.; Equimolecular doses of Ampicillin and Bacampicillin were administrated orally, of Ampicillin also by i.v . injection to 10 healthy adult volunteers (cross over study) . By comparison of areas under serum level curves after i.v . and oral administration absorption rate of Bacampicillin which is hydrolysed rapidly to Ampicillin in the body was determined as 95% . Peaks of serum levels after 0.8 g . Bacampicillin administered orally were higher (15,9 microgram/ml) and earlier (after 60 min) than after 0.556 g . Ampicillin administered orally (3.5 microgram/ml after 150 min) . Concentrations of Ampicillin in skin blister fluid 1 h after i.v . injection of Ampicillin were 20 times higher than after oral administration of Ampicillin and 3-4 times higher than after oral administration of Bacampicillin; after 3 and 4 hours skin blister levels after i.v . injection were only a half of skin blister levels after oral administration of Bacampicillin . Determination of antibiotic concentrations in saliva and tears showed similar relations . Since higher peaks in serum resulted in higher concentrations in the extravascular space Bacampicillin which is absorbed compeltely and more rapidly should be prefered for oral administration. Antibiotiki, 1978 Jun, 23(6), 499 - 503 {Dependence of the component makeup of the gentamicin complex on Micromonospora purpurea var . violacea 1935 cultivation conditions}; Laznikova TN et al.; Dependence of biosynthesis of gentamicin and vitamin B12 on complex and "synthetic" media under conditions of decreased aeration, increased phosphorus levels and non-optimal content of carbon source was studied . The decreased levels of vitamin B12 production under conditions of the non-optimal content of the carbon source and increased phosphorus levels in the medium resulted in decreased production of the antibiotic complex as a whole and decreased relative content of the most methylated gentamicins C1 and C2 in the complex . Decreased aeration lowered the mycelium productivity with respect to the antibiotic production without changing the ratio of the components in the complex and the level of vitamin B12 production. Cell, 1978 Jun, 14(2), 415 - 21 Isolation and characterization of amphotericin B-resistant cell lines in Chinese hamster cells; Hidaka K et al.; Amphotericin B is a polyene macrolide antibiotic which interacts specifically with sterols in mammalian cell membranes . Amphotericin B-resistant (AMBr) lines of stable phenotype have been isolated from cultured Chinese hamster (V79) cells . Three AMBr clones (AMBr-1, -2 and -3) isolated independently after treatment with nitrosoguanidine were resistant to greater than or equal to microgram/ml of the antibiotic, while DNA synthesis as well as the colony-forming ability of the parental V79 cells was blocked by greater than 80% of control in the presence of 20--50 microgram/ml amphotericin B . The AMBr cell line also exhibited increased resistance to other polyene macrolide antibiotics such as nystatin and pentamycin . Other agents, however, such as cytosine arabinoside or ricin, blocked DNA synthesis in AMBr cells to the same extent as in V79 cells . The amphotericin B resistance phenotype was st |