Eur Urol, 1981, 7(6), 343 - 5 Creation of caverno-glandular shunt for treatment of priapism; Chary KS et al.; Caverno-glandular shunt was performed in 8 patients with priapism during the past 3 years . Complete and sustained detumescence was achieved immediately in all patients . Only one case developed a complication, viz . cavernositis which responded to antibiotic administration systemically as well as locally . This procedure was performed under local anaesthesia in 5 patients . The technical details and advantages of this procedure over conventional operations for priapism are discussed. Toxicology, 1981, 21(1), 59 - 69 Determinants of the toxicity of L-alanosine to various organs of the mouse; Tyagi AK et al.; Toxicologic and biochemical properties of the antitumor antibiotic, alanosine {L-2-amino-3-(N-hydroxy,N-nitrosamino)propionic acid}, were studied in mice . The LD50 of L-alanosine (given intraperitoneally) was approximately 2 g/kg; L-5178Y/AR tumor, small intestine, liver, and lung were the tissues more consistently or severely damaged by the drug . L-5178Y/AR tumor, small intestine, liver, and lung, which were more susceptible to damage by L-alanosine, showed high concentrations of the putative active antimetabolite of L-alanosine, "L-alanosyl-AICOR", and either high concentrations of SAICAR synthetase, which forms this conjugate or low specific activities of adenylosuccinate lyase, the enzyme believed to decompose it . In addition, a low specific activity of the enzyme, adenylosuccinate synthetase, appeared to predispose an organ to the toxicity of alanosine . These data are compatible with the hypothesis that "L-alanosyl-AICOR" is the molecule responsible both for the therapeutic and toxicologic effects of L-alanosine and suggest that it is the dynamic interplay of the synthesizing enzyme, the catabolizing enzyme, and the target enzyme which determines whether this anabolite accumulates to a concentration capable of inflicting cellular damage. Zentralbl Chir, 1981, 106(11), 734 - 41 {Gallbladder decompression in acute cholecystitis (author's transl)}; Dederer JM et al.; Decompression of the acute inflamed gallbladder via laparoscopy and inserting a small catheter not only allow to reduce the pressure on the wall but to instill antibiotic solutions into the gallbladder as well . In this way the inflammatory process will fade away and the operation (cholecystectomy) can be performed with much lesser risk . In old aged people the authors recommend so called "minioperations" like laproscopic cholecystotomy and -cholecystostomy. J Bone Joint Surg Br, 1981, 63-B(3), 413 - 6 The importance of cephradine in hip surgery; Wicks MH et al.; Effective concentrations of antibiotic in the fluid bathing implanted hip prostheses are essential to prevent infection by micro-organisms . Twenty patients undergoing total hip replacement were given one gram of Cephradine intramuscularly one hour before operation and one other received a single bolus of Cephradine intravenously before operation and one other received a single bolus of Cephradine intravenously before operation . The concentrations of antibiotic were greater and persisted longer in the tissue fluid than in the blood . The antibiotic was sufficient to inhibit most micro-organisms causing contamination . We recommend that Cephradine is given intramuscularly one hour before operation and at six-hourly intervals after operation until the drainage tubes and intravenous lines have been removed. Clin Gastroenterol, 1981 Jan, 10(1), 177 - 89 Recurrent or chronic intestinal pseudo-obstruction; Anuras S et al.; Recurrent or chronic intestinal pseudo-obstruction is not a rare problem . More cases will be recognized and diagnosed when clinicians are more aware of this problem . Medical treatment is unsatisfactory in most cases unless the patients have such treatable associated systemic diseases as myxoedema, hypoparathyroidism or phaeochromocytoma . Intermittent antibiotic therapy may be needed to alleviate diarrhoea or steatorrhoea due to bacterial overgrowth in the small intestine . Surgery may help to relieve the symptoms in those cases with short segmental dilatation of the bowel . Most patients will have an exploratory laparotomy to rule out an organic obstructing lesion . Either a drainage procedure or resection of a short dilated segment should be carried out . Once the diagnosis of chronic intestinal pseudo-obstruction is made, repeated exploratory operations must be avoided . Preoperative antibiotic therapy to treat bacterial overgrowth in the small bowel will reduce postoperative peritonitis from peritoneal soiling by septic small bowel contents. Ann Ophthalmol, 1981 Jan, 13(1), 95 - 100 Clindamycin therapy for toxoplasmosis; Ferguson JG Jr; Clindamycin hydrochloride hydrate (Cleocin), a semisynthetic antibiotic shown experimentally to be effective in ocular toxoplasmosis in the rabbit, was used in the treatment of four patients with active retinochoroiditis secondary to toxoplasmosis . The drug was administered subjunctivally on alternate days for 30 days . Both subjective and objective evidence indicated beneficial results in these patients during the first 30 days . One of the four did not respond during the first 30 days but did respond during an extended period . One of those who responded initially had exacerbations when the drug was stopped and required treatment. Acta Obstet Gynecol Scand, 1981, 60(2), 121 - 3 Persistance of ampicillin in the intrauterine content following single and multiple doses to pregnant women; Philipson A; Cord plasma, and amniotic fluid (AF), as well as maternal plasma from women who had been given ampicillin in single or multiple doses prior to delivery were assayed for levels of the antibiotic . If medication had been discontinued two days prior to delivery or less, ampicillin could still be demonstrated in AF, where it remained demonstrable longer than in cord plasma . Ampicillin, when given during pregnancy, crosses the placenta, enters the fetal circulation, and is excreted by the fetal kidneys into the AF . The results of the present study indicate that as medication is continued, the level of ampicillin in AF rises through continuous renal excretion by the fetus . Once medication is discontinued, ampicillin is slowly cleared from the AF mainly through absorption from AF to fetal circulation and further passage to maternal circulation. Jpn J Antibiot, 1981 Jan, 34(1), 16 - 20 {The effects of fosfomycin on antigenicity (author's transl)}; Shibata U et al.; The antigenicity of fosfomycin (FOM), a new antibiotic agent, was studied . The binding of 3H-FOM with human serum protein was measured by the short term dialysis method . The binding was very weak only by 2.16% and reversible . The rabbits were immunized subcutaneously by fosfomycin as sodium salt (FOM-Na) with FREUND'S complete adjuvant . Antigenicity of IgG was examined by means of agar gel precipitation, passive cutaneous anaphylaxis and passive hemagglutination . To study the antigenicity of IgE, the BALB/cA mice were immunized intraperitoneally by FOM-Na with aluminum hydroxide gel and, passive cutaneous IgG and IgE . Consequently, it can be concluded that FOM does not conjugate with human serum protein to form its hapten and has not antigenicity. Biomaterials, 1981 Jan, 2(1), 3 - 8 Synthesis and characterization of PVNO and PVNO-PVP hydrogels; Hasirci VN; Hydrogels of crosslinked poly(2-vinylpyridine-1-oxide), PVNO, and poly(2-vinylpyridine-1-oxide)-poly(N-vinyl-pyrrolidone), PNVO-PVP, were synthesized . PVNO hydrogels were found to be degradable in a pseudo-biological medium and their stability could be increased by increasing the relative concentration of the crosslinking agent . PVNO-PVP hydrogels were also degradable and their stability could be increased by increasing the relative concentration of crosslinking agent and/or poly(N-vinylpyrrolidone) . Swelling ratio and percent solvent content for both types of gels were determined . In addition, for PVNO-PVP gels, swelling properties in solvents with different dielectric constants, at different temperatures and ionic strengths were determined . Antibiotic releasing and water vapour behaviour were also investigated . From the data obtained, the free energy change involved in water vapour adsorption was calculated. Zh Nevropatol Psikhiatr Im S S Korsakova, 1981, 81(2), 47 - 52 {Clinical picture and pathogenesis of generalized forms of herpes zoster}; Smirnov IuK et al.; Clinical examination of 83 patients with generalized herpes zoster has given the authors grounds to regard this disease as a result of activation of latent varicella-zoster virus . This assumption was confirmed by the results of indirect hemagglutination inhibition tests with 37 serum specimens taken from 18 patients . Treatment with antibiotics, the drug proper-myl, and by dehydration was the more effective, the earlier the patients were admitted to the clinic . Dehydration, proper-myl and combination of chloramphenicol with dehydration produced a more beneficial effect than the antibiotic alone . Five patients died . Problems of pathogenesis are discussed. Sex Transm Dis, 1981 Jan-Mar, 8(1), 12 - 5 Rosaramicin and tetracycline treatment in Chlamydia trachomatis-positive and -negative nongonococcal urethritis; Juvakoski T et al.; Rosaramicin, a new macrolide antibiotic, is active in vitro against Chlamydia trachomatis and Ureaplasma urealyticum . Its efficacy in the treatment of uncomplicated nongonococcal urethritis was evaluated in 78 men . There were two parallel groups, one receiving rosaramicin and the other receiving tetracycline (dosage of either drug, 250 mg four times daily for seven days); all data were evaluated blindly . The follow-up period was six weeks . C . trachomatis was eliminated from all of 21 patients receiving rosaramicin and from 25 of 26 patients receiving tetracycline . C . trachomatis-negative patients responded clinically to both treatments . The results suggest that these two antibiotics yield similar clinical outcomes in the treatment of nongonococcal urethritis in adult men. Int Ophthalmol Clin, 1981 Spring, 21(1), 41 - 6 Iridectomy with scleral cautery; Scheie HG; I have described modifications that have evolved over the years in doing iridectomy with cautery and have reviewed some of my experiences with the method . All filtering operations leave a great deal to be desired . Each technique has certain advantages and disadvantages . A great advantage of the cautery procedure is its safety and simplicity . It is as effective in lowering pressure as most other procedures . Even if the operation fails to control pressure, little harm is done to the eye, and it can be repeated . One of the great advances in management of open-angle glaucoma in recent years has been the adoption of stringent indications for surgery . Surgery should not be advised until a thorough trial of maximal medical therapy has been made . In many instances, however, the pendulum has been allowed to swing too far . When medical treatment has failed, and the patient is faced with progressive loss of vision if control of pressure is not achieved, the ophthalmic surgeon should resist the temptation to procrastinate . Surgery should be done promptly and deterioration should not be allowed to occur . Should a cataract occur, it can be removed . Endophthalmitis can be prevented or cured by antibiotic therapy . Although filtering operations leave a great deal to be desired, when effective, they will preserve a functioning optic nerve. Chemotherapy, 1981, 27(1), 18 - 28 Biliary excretion of cefuroxime . Experimental and human study; Brogard JM et al.; The biliary excretion of cefuroxime was studied experimentally, using a preparation of isolated rabbit liver (n = 5) perfused in vitro during 3 h; 0.92% of the cefuroxime (10 mg) added to the circulating blood was found in the bile, while peak antibiotic activity reached a mean value of 8.0 +/- 1.1 microgram/ml . In man, 1 h after a single intravenous injection of cefuroxime (0.5 g), a maximum concentration of 4.0 +/- 1.6 microgram/ml was found in the duodenal aspiration fluid collected from 5 healthy subjects . In 10 patients with T-tube drainage, a mean biliary peak of 10.3 +/- 2.4 microgram/ml was observed 2 h after intravenous injection of the same dose; the biliary excretion of cefuroxime during the 12-hour experiment corresponded to 0.13% of the administered dose . Assays performed during cholecystectomy in 10 patients 1 h after cefuroxime intravenous injection of 0.5 g showed concentrations of 11.9 +/- 0.8 microgram/ml in the serum, 12.0 +/- 1.5 microgram/ml in the common duct bile and 7.4 +/- 1.1 microgram/ml in the gallbladder bile . These results were compared with those observed after administration of 11 other beta-lactam antibiotics in identical experimental and clinical conditions. Antibiotiki, 1981 Jan, 26(1), 50 - 5 {Pharmacokinetic analysis of the nephrotoxic effect of sisomycin}; Firsov AA et al.; The kinetics of the urea nitrogen in serum was studied on anesthetized cats with constant concentrations of sisomycin in the blood . A correlation between the nephrotoxic effect of sisomycin and its concentration in the blood serum was found . High nephrotoxicity of sisomycin as compared to that of gentamicin, kanamycin or streptomycin under conditions of their equal levels in the blood was revealed on the basis of the above correlation . Still, when the antibiotic concentrations in the blood serum were maintained at the respective therapeutic levels, the nephrotoxic effects of sisomycin and gentamicin were almost equal . The above correlation was used for calculation of the maximum value of the sisomycin safe concentration in blood serum . The safe concentration of gentamicin in blood serum is 8 micrograms/ml, while that of sisomycin in 6 micrograms/ml . This approach may be used in estimation of safe concentrations for new aminoglycosides. J Cell Biol, 1981 Jan, 88(1), 199 - 204 Inhibition of fusion of embryonic muscle cells in culture by tunicamycin is prevented by leupeptin; Olden K et al.; The carbohydrate requirement for alignment and fusion of embryonic quail muscle cells has been examined in tissue culture by use of tunicamycin (TM) . The mononucleated, spindle-shaped proliferating myoblasts were treated with TM at various times before fusion and differentiation into multinucleated muscle fibers capable of spontaneous contraction . Tm blocked protein glycosylation and expression of glycoproteins on the cell surface, and strongly inhibited fusion when added to cultures of differentiating muscle cells before the fusion "burst," but had no apparent effect on cell alignment . The inhibition of fusion was partially prevented when TM was administered in the presence of protease inhibitors such as leupeptin and pepstatin, but the inhibition of glycosylation was not prevented . Both glycosylation and fusion were completely restored to normal by the removal of the antibiotic from the medium . These studies provide strong support for the idea that myoblast fusion is partially mediated by glycoproteins with asparagine-linked oligosaccharides . However, the requirement for the carbohydrate portion of the glycoprotein appears to be indirect in that it acts to stabilize the protein moiety against proteolytic degradation . Our findings do not rule out the possibility that oligosaccharide units of surface glycolipids have some role in myoblast fusion. J Int Med Res, 1981, 9(1), 52 - 7 Safety and efficacy of netilmicin in neonates with serious systemic infections; Trujillo H et al.; Twenty-five hospitalized neonates, each with two or more serious symptomatic infections, were given netilmicin by intramuscular injection . The antibiotic was administered usually at 1.5 or 3.0 mg/kg twice a day (q 12 hr) for 7 to 13 days . At the end of therapy the signs and symptoms of infection were completely resolved in twenty-four of the twenty-five patients and markedly improved in the remaining one . Thirty-five causative organisms were isolated from 30 of the 59 infection sites; after netilmicin therapy 31 causative organisms were completely eliminated and 4 were markedly reduced in number . One of the babies had a slight increase in serum creatinine level, possibly related to therapy, and a mild transient rash which was doubtfully related to netilmicin . None of the other neonates had adverse reactions. Arzneimittelforschung, 1981, 31(12), 2116 - 7 Comparison of distribution of doxycycline in mice after oral and intravenous application measured by a high-performance liquid chromatographic method; Bocker R et al.; Doxycycline levels in various organs of mice after i.v . and p.o . administration were measured by a high-performance liquid chromatography method . When given as a single dose (50 mg/kg) i.v . doxycycline accumulated in the lung . High concentrations were also measured in liver and kidneys . When 50 mg/kg doxycycline were administered by stomach tube to fed mice the antibiotic accumulated to a lesser degree in the lung . On the other hand, the antibiotic levels in the liver and the kidneys were higher as after i.v . injection . The absorption of doxycycline administered p.o . was about 92% and seemed not to be influenced by food in the stomach . The elimination half-life in mice was 170 min independent of the route of administration. Arzneimittelforschung, 1981, 31(12), 2085 - 8 Biotransformation of reproterol in the intestinal tract of the rat; Kucharczyk N et al.; The major metabolite of reproterol (Broncho-spasmin) in rat feces is 2-{3-theophyllinyl(7)-propyl}-4,6,8-trihydroxy-1,2,3,4-tetrahydroisoquinoline . It was also found in the bile of orally or intravenously dosed rats in the form of glucuronides . The biotransformation of an oral dose of reproterol to this metabolite occurred mostly in the cecum-colon section of the intestinal tract . Experiments in antibiotic treated rats showed no significant effect of the treatment on the extent of metabolite formation . This metabolite was also formed by incubation of reproterol with cecum-colon homogenates under aerobic as well as anaerobic conditions . The pharmacological action after an oral dose must be attributed to reproterol absorbed as intact form, since the metabolite is inactive. Arzneimittelforschung, 1981, 31(9), 1456 - 8 Effect of unilateral nephrectomy on the pharmacokinetics of rolitetracycline in rabbits; Wojcicki J et al.; An analysis of the single-dose pharmacokinetics of rolitetracycline in rabbits after unilateral nephrectomy is presented . Rolitetracycline was injected i.v . 3.5 mg/kg before operation and after 2 weeks, 3 months and 6 months from unilateral nephroctomy . The concentration of the antibiotic in plasma was estimated by the fluorimetric method of Kohn . The two-compartment open model was applied to calculate rolitetracycline concentration changes . The calculations of pharmacokinetic parameters were performed using the Hewlett-Packard 9830B computer and fitting the concentrations of the antibiotic in blood to the general biexponential equation . AUC of rolitetracycline was increased in operated animals by 130% after 6 months . The mean kel at this time decreased, while t0.5 beta was prolonged from 1.0 h to 3.0 h . It is assumed that the dosage regimen of rolitetracycline should be changed in subjects possessing one kidney. Arch Geschwulstforsch, 1981, 51(5), 398 - 404 {Antineoplastic activity of lambdamycin in different murine test models compared with cyclophosphamide, 6-mercaptopurine and 5-fluorouracil (author's transl)}; Gutsche W et al.; Lambdamycin, a chromoglycoside antibiotic like chartreusin was found to be very active against leukemias L 1210 and P 388 and moderate effective against melanoma B 16 and Lewis lung carcinoma of mice . It was nearly without any effect when tested on Walker 256 carcinoma of rats . The effectiveness of lambdamycin was compared with that of cyclophosphamide, 5-fluorouracil and 6-mercaptopurine. Arzneimittelforschung, 1981, 31(7), 1165 - 8 Penetration into human urogenital tissues, muscle tissues, rib and cerebrospinal fluid of thiamphenicol; Plomp TA et al.; The penetration of D(+)-threo-2-dichloroacetamido-1-(p-methylsulfonylphenyl)-1,3-propanediol (thiamphenicol, TAP, Urfamycine) into human renal, ureter, prostatic, testicular and muscle tissue, perirenal fat, rib as well as cerebrospinal fluid (CSF) after a single i.v . injection of 1.0 g of thiamphenicol glycinate ester was investigated . 2 h after TAP administration to 17 patients with severely diseased kidneys, the antibiotic concentration in renal tissue ranged from 9.8 to 138.7 microgram/g (mean value 40.4 +/- 29.9 microgram/g), in ureter tissue from 6.3 to 62.0 microgram/g (mean value 20.8 +/- 17.0 microgram/g), in muscle tissue from 1.7 to 13.7 microgram/g (mean value 8.2 +/- 3.6 microgram/g), in rib from 0.8 to 3.4 microgram/g (mean value 2.4 +/- 1.5 microgram/g) and in perirenal fat from 0.6 to 5.7 microgram/g (mean value 2.1 +/- 1.5 microgram/g) . At the same time the TAP serum level varied from 4.6 to 15.2 microgram/ml (mean value 9.4 +/- 3.1 microgram/ml) . Prostatic tissue concentration, measured in 16 patients with prostate adenomas, varied at 2 h after dosing, from 2.1 to 15.1 microgram/g (mean value 5.7 +/- 3.8 microgram/g) . The simultaneous serum level was between 4.6 and 14.5 microgram/ml (mean value 8.9 +/- 3.4 microgram/ml) . In 6 of these patients additionally CSF level was measured at 1.5 h post inj . and ranged from 0.11 to 0.65 microgram/ml (mean value 0.32 +/- 0.19 microgram/ml) . Testicular tissue concentration assessed in 7 patients with prostate carcinomas varied at 2 h after i.v . injection from 3.4 to 8.4 microgram/g (mean value 6.1 +/- 1.9 microgram/g) . The respective serum level in these patients was between 5.2 and 10.4 microgram/ml (mean value 8.5 +/- 1.7 microgram/ml) . Several factors affecting the diffusion of TAP into the reported tissues and CSF are discussed . TAP should be regarded as an antibiotic with good penetration into urogenital tissues. Arzneimittelforschung, 1981, 31(5), 816 - 22 Preclinical toxicologic studies of netilmicin; Weinberg EH et al.; 1-N-Ethylsisomicin (netilmicin), a semisynthetic aminoglycoside antibiotic, was given parenterally to mice, rats, guinea pigs, rabbits, and dogs for toxicological evaluation . Acute signs of toxicity were consistent with neuromuscular blockade . Results of teratological studies in rats and rabbits were negative; the only effect observed was wavy ribs, a minor developmental variation, in rats . No effects were found on fertility, reproduction, or development of offspring . Single daily doses of 60 mg/kg s.c . for 10 weeks in young rats and 30 days in young dogs were non-toxic . No indication of toxicity was found in rats and dogs given single daily doses of 7.5 mg/kg i.v . for 2 weeks . Daily i.m . doses caused signs of neuromuscular blockade in rats after 2 weeks at 100 mg/kg and after 1 month at 50 mg/kg, and in dogs after 2 months at 75 mg/kg; dose levels of 150 mg/kg did not cause renal failure . No ocular changes or impairment of vestibular or auditory function were evident at any dose studied . Comparison with tobramycin, gentamicin, and kanamycin at s.c . doses of 50 or 150 mg/kg per day for 4 weeks showed netilmicin to be less nephrotoxic in rats than tobramycin or gentamicin and only slightly more nephrotoxic than kanamycin . Only mild changes were seen microscopically in kidneys of dogs given netilmicin at daily doses of 75 mg/kg i.m . for 3 months . The renal effects of netilmicin given at high multiples of the human therapeutic dose were one-half to one-third less that those of gentamicin and were not severe at any dosage. Folia Microbiol (Praha), 1981, 26(1), 8 - 13 Mucidin-nonproducing mutants of oudemansiella mucida; Semerdzieva M et al.; Mutants of Oudemansiella mucida, blocked in the biosynthesis of the antibiotic mucidin, were obtained at a 0.28% frequency after the application of N-methyl-N'-nitro-N-nitrosoguanidine (MNG) to basidiospores under conditions leading to 0.5--5.0% survival rates . Loss of antibiotic activity was in most isolates accompanied by a decrease in mycelium growth rate and a suppression of dikaryotizing and fructification ability . Recombination analysis of two stable mutants revealed that the block in mucidin synthesis is the result of mutation in the same chromosomal gene (muc) . In contrast to the action of MNG, UV-irradiation leads neither to the loss of biosynthetic activity nor to any morphological change. Br Heart J, 1981 Jan, 45(1), 20 - 8 Rastelli procedure for transposition of the great arteries, ventricular septal defect, and left ventricular outflow tract obstruction . Early and late results in 41 patients (1971 to 1978); Moulton AL et al.; Forty-one children with transposition of the great arteries, ventricular septal defect, and left ventricular outflow tract obstruction underwent a Rastelli operation between 1971 and 1978 . A homograft valve preserved in an antibiotic solution and extended with A dacron tube was the conduit of choice . Alternatively, conduits with porcine heterografts or valves constructed from calf pericardium were used . They were positioned to the left of the aorta whenever possible . The intraventricular tunnel from the left ventricle to the aorta was constructed from Dacron velour . There were four early and seven late deaths . The last 13 consecutive patients have survived . Early deaths were related to unfavourable anatomy, conduit compression, and sepsis . Residual ventricular septal defects and postoperative infection were the main factors contributing to the late deaths. Bull Los Angeles Neurol Soc, 1981, 46, 36 - 40 Neurological sequelae of cervical spine trauma; Rubin BD et al.; It is estimated that there will be 5,000 new spinal cord injured patients each year . Prolonged survival has resulted from better understanding of the pathophysiology of cord damage, as well as from the advances in antibiotic and ventilatory therapy . Most well-motivated patients with lesions at or below C5 can attain a level of independence which obviates institutional care . Regional spinal injury centers have done much to increase the survival of and quality of life of cord injured patients . These realities make initial care of patients with acute traumatic lesions of the cervical spine of paramount importance . Neurologic function at both the nerve root and cord levels can be adversely affected by excessive motion of the unstable spine . Early evaluation of X-rays must therefore be carried out in an attempt to determine the stability of the spine. Mol Gen Genet, 1981, 183(1), 197 - 8 Synergistic action of genetic and phenotypic suppression of nonsense mutations in yeast Saccharomyces cerevisiae; Surguchov AP et al.; It was found that the phenotypic suppression induced by the paromamine-containing antibiotic paromomycin could be significantly strengthened by a ribosomal suppressor mutation in yeast Saccharomyces cerevisiae . As a result the suppressor efficient towards ochre mutations in the presence of paromomycin acquired the ability to suppress both amber and opal mutations . It is suggested that phenotypic suppression by paromomycin and genotypic suppression by sup 1 both involve a similar mechanism of misreading. Adv Otorhinolaryngol, 1981, 27, 144 - 58 Drug-induced sudden hearing loss and vestibular disturbances; Federspil P; Today the number of potentially ototoxic substances in high, but the most important class is that of the aminoglycoside antibiotics . The clinical symptoms and signs of the aminoglycoside antibiotic ototoxicity are considered as well as the symmetry of these lesions, their possible reversibility or progressiveness . The data collected up to now concerning the main factors influencing ototoxicity of the aminoglycoside antibiotics are perused . In special paragraphs the intrinsic ototoxic potential of the newer aminoglycoside antibiotics, the influence of the dosage and route of administration, of renal function, preexisting hearing disturbances, individual and familial sensitivity, pregnancy, newborn age and the combination with sound exposure, diuretics and cephalosporins are considered . Finally, the treatment of ototoxic damage is indicated. Microbios, 1981, 31(123), 7 - 16 On the uptake of nystatin by Saccharomyces cerevisiae . 2 Effects of pH, ionic strength, sterol concentration and "protecting" ions; Beezer AE et al.; Uptake of nystatin by sensitive cells of Saccharomyces cerevisiae was studied as a function of pH and ionic strength . The pH was shown to affect radically uptake kinetics and extent, whilst ionic strength variation appeared not to modify uptake at all . The effects of variation in the sterol concentration of the cells employed showed a decrease in nystatin uptake as sterol concentration increased . This was not the anticipated observation . Calcium ions were shown to "protect" the yeast cells by associating with the cell and not the antibiotic . Possible explanations are discussed. Microbios, 1981, 30(120), 109 - 30 Plasmid-determined resistance to tetracycline; Sompolinsky D et al.; A general concept is proposed to explain the mechanism of bacterial resistance to tetracycline, and is essentially based on experimental date and a review of recently of recently published studies . It is assumed that tetracyclines are accumulated in the bacterial cell by an energy-demanding, carrier-mediated influx-mechanism, at a rate depending on the concentration of the antibiotic in the medium . Tetracyclines seep out of the cell by facilitated diffusion at a rate depending on the concentration inside the cell . At steady state, when no net alteration of the intracellular concentration is evident, the molecules of the antibiotic, inside and outside the cell, are exchanged by influx and efflux . In the resistant organism, an additional energy-demanding and carrier-mediated efflux-mechanism is assumed . The total efflux rate is therefore increased, and the steady state is obtained at a lower intracellular level of tetracyclines . It is possible that, in addition, the influx is decreased in the resistant organism. Ther Drug Monit, 1981, 3(2), 167 - 9 Quantitation of tobramycin by solid-phase immunofluorescence; Gerson B et al.; Tobramycin usage, as for most aminoglycoside antibiotic usage, may require careful monitoring to avoid irreversible toxicity . Several methods for tobramycin quantitation are available . The purpose of this study was to evaluate the performance of solid-phase immunofluorescence as an alternative . Tobramycin was quantitated in the sera of 81 patients by radioimmunoassay and solid-phase immunofluorescence . No statistically significant or medically important difference was demonstrated (bias, 0.006 micrograms/ml, t = 0.09, s = 1.02, r = 0.97) . Within-run and run-to-run precision for the two methods were comparable . Interference by gentamicin could not be demonstrated . Solid-phase immunofluorescence may be an acceptable alternative method for tobramycin quantitation in some laboratories. Med Cutan Ibero Lat Am, 1981, 9(1), 67 - 71 {Multiple applications of closed permanent wet dressings . Their mode of action}; Mirande LM et al.; New applications and forms of Darier's humid permanent closed cures are analysed specially in connection with concepts of cutaneous hydratation . The multiplicity of their application however makes it necessary to find an explanation for their excellent effects which are probably related to the anti-inflammatory, antipruritic and antiinfectious actions as well as the permanent draining effect from the deeper layers to the surface of the epidermis . The hydratation affected by HPCC is very important in dry and exudative stasis dermatitis with both a complete or a partial loss of stratum corneum . Cutaneous eutrophia is restored quite rapidly and an anti-infectious effect is brought about simultaneously . Especially in cases of stasis dermatitis with excessive secretions and pus formation the permanent drainage and hydratation make possible rapid healing . The preference for sodium borate does not exclude the use of other substance both alone or in combination . On the contrary, HPCC may be employed with especific antibiotics . Topical corticosteroid and antibiotic combination is frequently used in stasis dermatitis . In cases of pyoderma, the results obtained are definitively better when antibiotics are of the treatment . Eventually systematic corticoids may be included in the therapeutic arsenal. J Int Med Res, 1981, 9(4), 274 - 6 Prospective clinical trial on the efficacy of amoxycillin administered twice or four times daily in children with respiratory tract infections; Daschner FD et al.; Thirty-four children with upper or lower respiratory tract infections were randomly allocated to receive either a twice daily or four times daily dose of 50 mg amoxycillin/kg body-weight/day . Mean duration of therapy was identical in both groups . Peak and trough antibiotic concentrations were determined . Eradication of bacteria, clinical improvement and side-effects were comparable in both groups. Circ Shock, 1981, 8(3), 291 - 300 Survival of primates in lethal septic shock following delayed treatment with steroid; Hinshaw LB et al.; We recently developed a methylprednisolone sodium succinate (MPSS)/gentamicin sulfate (GS) regimen that prevented death in baboons given a 2-hour infusion of LD100 E coli (J . Surg . Res . 28:151, 1980) . Steroid treatment was begun in that study 30 minutes after initiation of E coli . Our current aim was to determine if baboons would survive if MPSs treatment was delayed until all E coli were infused and severe hypotension had ensued . Fourteen lightly anesthetized baboons (P.c . cynocephalus) were administered E . coli and seven were then treated with MPSS and GS for 10 hours . All nontreated baboons died, while six of seven treated animals survived . In the treated group, hypoglycemia and hypoinsulinemia were reversed, tachycardia was reduced and neutrophil recovery was improved . Baboons with delayed MPSS, however, evidenced diminished perfusion and recovered more slowly than those with earlier MPSs treatment . In conclusion, primates in septic shock are clearly protected with delayed steroid/antibiotic therapy. Mol Gen Genet, 1981, 181(3), 390 - 4 A novel form of suppression due to an altered RNA polymerase; Ephrati-Elizur E et al.; A group of mutants isolated from E coli K12(tif-1) display a very pleiotropic phenotype . The main characteristic of these mutants, temporarily designated 'S' strains, is their ability to suppress a large number of mutations . High efficiency of suppression is correlated with increased thermolability of cellular proteins, indicating an impairment in the fidelity of protein synthesis . Efficient suppression is also accompanied by the appearance of new characteristics like simultaneous resistance to several antibiotic drugs (Sm, Spc, and Mer), and plasmid-like DNA circles . Genetic studies show that the suppressor character is located in the rpoBC region . In a large number of spontaneous Rifr mutants, isolated from these strains, suppression or resistance to drugs is lost . The findings suggest that the phenotype of 'S' strains is due to an altered RNA polymerase causing erroneous transcription. J Reprod Fertil Suppl, 1981, 29, 159 - 72 Embryonic and uterine factors in delayed implantation in rodents; Surani MA et al.; An hypothesis for delayed implantation and embryonic quiescence is proposed on the basis of adaptation of blastocysts to changes in their environment . The environmental factors considered consist of macromolecules and essential ions and metabolites such as Ca2+, Mg2+ and glucose . Macromolecules appear to induce an influx of these essential metabolites which is followed by metabolic enhancement in blastocysts in the absence of any of the essential factors, the initial stages of embryonic diapause follow . The prevention of influx of metabolites such as Ca2+ by specific inhibitors, D600 or papaverine, also prevents activation of blastocysts . Early cleavage stage embryos show little or no response to changes in environmental macromolecules which may explain why embryos usually enter into quiescence at the blastocyst stage when the environmental constraints on blastocyst development become very marked . This also coincides with termination of cleavage and initiation of cell growth in embryos . The increase in responsiveness of embryos is attributed to several inherent changes including cell surface and functional changes in the plasma membrane . The conditions for embryonic quiescence in vivo are not species specific . Trophoblastic vesicles without the inner cell mass can also enter into quiescence . Studies using the antibiotic, tunicamycin, which inhibits protein glycosylation and prevents trophoblast adhesion and giant cell outgrowths, suggest that the cell surface interactions may involve glycoproteins . Such interactions may be crucial for implantation as well as for maintaining embryos in diapause for prolonged periods of time . A short sojourn in diapause for certain blastocysts which do not normally develop to an advanced stage, appears to have a beneficial effect on subsequent development . The overall significance of this suggestion for other species showing obligatory diapause is unclear. Pathol Biol (Paris), 1981 Jan, 29(1), 25 - 30 {Experimental and clinical study of the biliary excretion of cefamandole (author's transl)}; Brogard JM et al.; Using the isolated rabbit liver perfusion model, it could be shown that 11.1% of 10 mg of cefamandole added to the circulating blood were recovered in the 3 hours collected bile . The maximal biliary antibiotic activity averaged 214 +/- 37 microgram/ml . In humans a peak concentration of 19.0 +/- 6.1 microgram/ml could be measured in the aspirated duodenal fluid (n = 5) 1 hour after a single intravenous injection of 1 g of cefamandole . In 10 patients provided with a Kehr's drainage, a mean biliary peak of 141.4 +/- 86.4 microgram/ml was observed at the 2nd hour after administration of the same dose of cefamandole . Assays performed during cholecystectomy showed 1 after the intravenous injection of 1 g of cefamandole mean values of 64.0 +/- 18.0 microgram/ml in the gallbladder bile and 87.2 +/- 16.1 microgram/ml in the common duct bile . These data are compared with those obtained by administration of 11 other beta-lactamines under similar experimental and clinical conditions. J Bacteriol, 1981 Jan, 145(1), 654 - 6 Preferential selection of deletion mutations of the outer membrane lipoprotein gene of Escherichia coli by globomycin; Zwiebel LJ et al.; Globomycin is an antibiotic which inhibits the processing of the prolipoprotein . Eighty globomycin-resistant mutants were independently isolated from Escherichia coli K-12 which had a deletion mutation in chromosomal lipoprotein gene (lpp), but contained a plasmid carrying the wild-type lpp gene . Twenty-six of the mutants did not have the lipoprotein in the membrane fractions . From the analysis of the plasmids of these mutants, all of the lipoprotein-deficient mutations were found to be due to deletion mutations around the lpp gene. Laryngoscope, 1981 Jan, 91(1), 17 - 29 Hemophilus influenzae type B soft tissue infections of the head and neck; Simpson GT et al.; Hemophilus influenzae soft tissue infections produce a variety of specific and dangerous pathologic manifestations in the head and neck . Problems include periorbital cellulitis and abscess, sinusitis, supraglottitis and otitis media . Complications include meningitis, airway obstruction and death . Pediatric patients are especially susceptible to these infections and complications . Effective management includes correct diagnosis, prevention of complications, and high doses of appropriate antibiotics . Increasing ampicillin resistance necessitates alternative antibiotic regimens . Specific physical findings, diagnostic studies and appropriate current treatments are discussed with illustrative cases from Children's Hospital Medical Center, Boston, and reference to pertinent recent literature. J Immunol, 1981 Jan, 126(1), 270 - 5 Biosynthesis and cell surface localization of nonglycosylated human histocompatibility antigens; Ploegh HL et al.; The effects of the inhibitor of N-linked glycosylation, tunicamycin, on the synthesis of HLA-A and -B antigens in the human lymphoblastoid cell line JY are described . HLA-A and -B antigens are membrane glycoproteins that consist of a two chain complex, the heavy chain being glycosylated at Asn 86, whereas the light chain, identical to beta 2-microglobulin, is not glycosylated . HLA-A and -B antigens synthesized in the presence of the antibiotic are devoid of carbohydrate . This lack of carbohydrate does not affect the association of the heavy and light chains, nor does it affect the reactivity with human alloantisera, or a mouse monoclonal antibody W6/32, that reacts with all HLA-A and -B specificities examined so far . Nonglycosylated HLA-A and -B antigens are no more susceptible to proteolysis with trypsin, chymotrypsin, or papain than their fully glycosylated counterparts . Thus it may be concluded that the carbohydrate side chains of HLA-A and -B antigens do not contribute significantly to the conformation of HLA-A and -B antigens, at least as measured by these procedures . Pulse-chase experiments, in conjunction with the isolation of cell-surface HLA-A and -B antigens by adsorbing the monoclonal antibody W6/32 to intact cells, indicate that nonglycosylated molecules reach the cell surface at a rate indistinguishable from that of fully glycosylated molecules (although the absolute amount synthesized in the presence of tunicamycin was decreased) . Thus glycosylation is also not required for membrane insertion of HLA antigens, nor for their subsequent transport to the cell surface. J Cell Physiol, 1981 Jan, 106(1), 41 - 7 Amphotericin B resistance is recessive in Chinese hamster hybrid cells; Hidaka K et al.; Previous studies from our laboratory have shown that Chinese hamster V79 cells mutated to high level resistance to amphotericin B have a lower cellular level of cholesterol, the target molecule for the polyene antibiotic . Two amphotericin B-resistant (AMBR) mutants were each hybridized to their parental amphotericin B-sensitive (AMBS) V79 cells . All the hybrids derived from AMBR/AMBS fusions were as sensitive to polyene antibiotics (amphotericin B, filipin, and pimaricin) as AMBS cells or AMBS/AMBS hybrids . The AMBR/AMBS hybrids were found to contain cholesterol per phospholipids that is comparable to those in AMBS or AMBS/AMBS . The analysis of hybrids formed between mutant and wild-type cells thus indicated that resistance to amphotericin B is a recessive marker, and that the cellular level of cholesterol is compensated in the AMBS/AMBR hybrids . Hybrids of AMBR and AMBR cells were all resistant, so that the three AMBR mutants all fell into a single complementation group. Transfusion, 1981 Jan-Feb, 21(1), 74 - 6 Altered platelet function and circulation induced by amphotericin B in leukemic patients after platelet transfusion; Kulpa J et al.; Four adults, recently diagnosed, acute leukemic patients received 40 separate platelet transfusion treatments before, during, and after intravenous administration of amphotericin B . Fourteen of these platelet transfusions were administered while the patients also received amphotericin B; 26 platelet transfusions were given before or after amphotericin B therapy . The mean platelet increment for platelet transfusions administered while the patients were untreated with amphotericin B was 58 +/- 6 per cent . While the same patients were being treated with amphotericin B, the mean platelet increment was significantly decreased to 29 +/- 8 per cent (t = 3.1; p less than 0.005) . In addition, when the patients were not being given amphotericin B, a highly significant negative relationship (r = -0.77; p less than 0.001) between the values for bleeding time and venous platelet count was present . In contrast, during amphotericin B treatment there was no correlation between the patients' bleeding times and venous platelet counts . We propose that amphotericin B therapy has a direct toxic effect on the function and circulation of transfused platelets . These toxic effects are quickly corrected by discontinuing this antifungal antibiotic. Albrecht Von Graefes Arch Klin Exp Ophthalmol, 1981, 216(3), 191 - 203 Effects of commercial ophthalmic drugs on rabbit corneal epithelium . A scanning electron-microscopic study; Maudgal PC et al.; Surface changes on rabbit cornea were studied by scanning electron-microscopy after instillation of commercial corticosteroid and antibiotic collyria extensively used in ophthalmic practice . All the collyria caused loss of surface microvilli and cell damage . The collyrium containing dexamethasone, neomycin, and benzalkonium chloride caused less damage than similar collyrium with polymyxin, but without dexamethasone . On the other hand the collyrium containing dexamethasone and neomycin was still less damaging than similar collyrium with benzalkonium chloride as preservative . Chloramphenicol with dexamethasone caused damage similar to collyria containing dexamethasone, neomycin, polymyxine B sulphate, and benzalkonium chloride. Int J Oral Surg, 1981, 10(Suppl 1), 168 - 77 Hyperbaric oxygen therapy with subtotal extirpation surgery in the management of radionecrosis of the mandible; Guernsey LM et al.; Radiation-induced obliterative endarteritis causes ischemia and hypoxia in tissue wounds, making them prone to dehiscence, infection and delayed healing . The successful use of hyperbaric oxygen as an adjunct to intensive antibiotic and surgical therapy in the treatment of radionecrosis of the mandible is well established . This report details our experience in four cases of radionecrosis of the mandible of long duration, prior to acceptance of the patients into our hyperbaric oxygen protocol. Derm Beruf Umwelt, 1981, 29(6), 151 - 6 {Allergy to ed-edta and formaldehyde (author's transl)}; Pevny I et al.; 1 . Comparison of the ED/EDTA allergies as determined by epicutaneous testing from 1977-79 with the test results from 1980 . An increase in the sensitization indices for ED as well as for EDTA is evident . 2 . Additional information concerning the occurrence of ED/EDTA . 3 . EDTA and formaldehyde allergy . 4 . ED/EDTA and antibiotic allergy. Ann Chir Gynaecol, 1981, 70(5), 292 - 6 Management of massive defects of the abdominal wall; Hockerstedt K et al.; Full-thickness abdominal wall defects are mainly traumatic or infectious in origin . After adequate resuscitation, treatment of associated visceral trauma, antibiotic therapy and careful debridement to vital tissues, primary repair of the abdominal wall should be carried out by simple methods by using synthetic mesh and/or split skin grafts . Local pedicle skin flaps or musculocutaneous flaps are advocated for secondary repair of the abdominal wall and also used in elective tumour surgery when total resection of the abdominal wall is indicated. Mol Gen Genet, 1981, 184(2), 249 - 54 Vectors for cloning in cyanobacteria: construction and characterization of two recombinant plasmids capable of transformation of Escherichia coli K12 and Anacystis nidulans R2; Kuhlemeier CJ et al.; Two plasmids were constructed consisting of the E . coli vector pACYC184 and the cyanobacterial plasmid pUC1 . These recombinants, designated pUC104 and pUC105, can be transformed to E . coli K12 as well as to the cyanobacterium Anacystis nidulans R2 and in both hosts they express their antibiotic markers . pUC104 and pUC105 differ with respect to the location and the orientation of the pACYC184 segment in pUC1 . pUC104 was found to be stable under all circumstances . Transformation of pUC105 to A . nidulans R2 gave intact plasmids when chloramphenicol was the selective agent, but upon ampicillin selection a deletion derivative was produced identical to pUC1 . Further characteristics of pUC104 and pUC105 are described and their usefulness as cloning vectors is discussed. Allergol Immunopathol (Madr), 1981 Jan-Feb, 9(1), 29 - 36 The viral factor in the etiology of acute asthma attacks in children; Oehling A et al.; Over the last decade firm proponents of a viral etiology have risen, alongside those considering mycoplasma as prime agent in the induction of bronchospasm . Since we are not convinced as to the validity of the viral hypothesis, we decided to study a group of asthmatics to detect the different viral antigens serologically, in order to determine which can play a decisive role in the pathogenesis of the asthmatic crisis . Without previous etiologic selection, 37 children admitted as emergency cases with severe asthmatic crises, were chosen for the study . All were being treated as asthmatics and were diagnosed as bacterial or mixed asthmatics according to the Ciba Symposium criteria; the ages ranged from one to eleven years . Four patients presented infections by RS virus and of these, two showed an accompanying infection by Coxsackie B3 and B5 . Only one patient presented antibodies against mycoplasma pneumoniae . The incidence of maxillary sinusitis was 75.6% . We found the only 13.5% of the children showed specific antibodies, against any of the 16 viral antigens tested . That is, we find that in parallel with the bacterial infection, there exists a viral infection which is manifested by the increment of specific antibody titers after ten days . The asthmatic symptoms disappeared after antibiotic and corticoid therapy, as opposed to the resistance to this form of treatment reported by McIntosh. Antimicrob Agents Chemother, 1981 Jan, 19(1), 22 - 8 Suction skin blister, skin window, and skin chamber techniques to determine extravascular passage of cefotaxime in humans; Frongillo RF et al.; We report the results obtained in comparative study on the extravascular passage of cefotaxime, employing three different methods: suction skin blister, skin window, and skin chamber . Applying the skin blister method in two different ways, we also studied the influence that suction pressure and time lapse between blister formation and antibiotic injection had on the results obtained in order to standardize the method and establish repeatability of the results . Using the skin chamber method, we studied the influence that the different protein contents in the fluid used to fill the skin chamber had on extravascular concentrations. J Virol, 1981 Jan, 37(1), 307 - 16 Mutational changes in the vesicular stomatitis virus glycoprotein affect the requirement of carbohydrate in morphogenesis; Chatis PA et al.; The role of carbohydrate in the morphogenesis of vesicular stomatitis virus was studied, using the antibiotic tunicamycin to inhibit glycosylation . It has been reported previously (Gibson et al., J . Biol . Chem . 254:3600-3607, 1979) that the San Juan strain of vesicular stomatitis virus requires carbohydrate for efficient migration of the glycoprotein (G) to the cell surface and for virion formation, whereas the prototype or Orsay strain of vesicular stomatitis virus is less stringent in its carbohydrate requirement at 30 degrees C . However, there are many differences between the two strains . We found that mutational changes within the G protein of the same strain of virus (prototype or Orsay) alters the requirement for carbohydrate at 30 degrees C . Group V or G protein mutants tsO45 and tsO44, like their prototype parent, did not require carbohydrate for efficient morphogenesis . In contrast, the G protein of another group V mutant, tsO110, was totally dependent upon carbohydrate addition for migration to the cell surface . Furthermore, no tsO110 particles were released in the absence of glycosylation . The wild-type prototype strain did require carbohydrate at 39.5 degrees C for insertion of the G protein into the plasma membrane and virion formation . However, a pseudorevertant of tsO44 (tsO44R), unlike the prototype parent, no longer exhibited this temperature-sensitive requirement for carbohydrate . At 39.5 degrees C in the presence of tunicamycin, tsO44R-infected cells released normal yields of particles and the unglycosylated G reached the cell surface very efficiently . In contrast to tsO110, which absolutely requires carbohydrate, mutational change in the tsO44R G protein has eliminated the requirement for carbohydrate . Thus, simple mutational changes, as opposed to many changes in the molecule, are sufficient to alter the carbohydrate requirement. J Rheumatol, 1981 Jan-Feb, 8(1), 100 - 9 Septic Discitis; McCain GA et al.; The clinical and laboratory findings in 15 patients with septic discitis are reported . The clinical picture was that of a sub-acute illness characterized by back pain, spinous process tenderness, and sciatic nerve root irritation . There was a considerable delay from clinical presentation to diagnosis (average 14 wk) . The erythrocyte sedimentation rate was the most useful diagnostic laboratory blood test and the best indicator of disease activity . The relative value of plain radiographs, tomography, and radionuclide bone scans is discussed . Needle aspiration of the disc space was found to be a useful diagnostic test . We found that a diagnosis of septic discitis could be made even in the absence of positive bacterial cultures from various biologic fluids or from the disc space . Long-term oral and intravenous antibiotic therapy with controlled rest resulted in a favourable outcome. Eur J Immunol, 1981 Jan, 11(1), 48 - 55 Role of glycosylation in the H-2-restricted cytolysis of virus-infected cells; Black PL et al.; The role of the oligosaccharide portions of cell surface glycoproteins in the susceptibility of virus-infected cells to H-2-restricted cytolysis was investigated by using the antibiotic tunicamycin (TM) . TM inhibits the addition of sugars to the polypeptides of glycoproteins . TM treatment of P815 cells before and during infection with vesicular stomatitis virus (VSV) inhibited glycosylation of proteins and reduced by about 50% the lysis of infected P815 cells by VSV-immune, H-2-identical killer cells . In contrast, TM treatment had a modest inhibitory effect on cytolysis of P815 cells by alloimmune effector cells . TM treatment did not inhibit the surface expression of either H-2 or VSV glycoprotein . Thus, glycosylation of H-2 and/or viral glycoprotein is a prerequisite for the lysis of infected cells by H-2-identical, VSV-immune cytotoxic cells. Eur J Biochem, 1981 Jan, 113(2), 391 - 6 Inhibition of the links between electron transfer and proton translocation in mitochondria; Tu SI et al.; The mechanism by which proton extrusion is linked to electron transfer in mitochondria was investigated by means of the primary amine-specific reagent fluorescamine, and of compounds obtained from the reaction of fluorescamine with simple amines (e.g . benzylamine) and with the mycosamine-containing antibiotic amphotericin B . The effect of these 'modifiers' (i.e . fluorescamine transfer chain were assayed separately using specific inhibitors to block the action associated with the other site . Both types of modifiers inhibited the proton extrusion across the membrane to a significantly greater extent than the electron transfer process in both sites II and III . In contrast, the lactone derivative (or cyclic form) of the amine-fluorescamine compounds had no significant inhibitory effect on the proton extrusion and its associated electron transfer . These results are consistent with the hypothesis that the link between proton extrusion and electron transfer in mitochondria is indirect in nature . The results show that: (a) the links involved in sites II and III are identical or very similar in nature; (b) a covalent modification of primary amino groups in the inner membrane is not essential for the expression of these differential inhibitory effects; (c) specific structural features in the amine-fluorescamine compounds, and in the mitochondria-fluorescamine derivatives, are crucial for the expression of the inhibitory effects . Our results contradict the 'redox loop' model of Mitchell, and are compatible with the proton pump concept for the linked proton translocation in oxidative phosphorylation. Anticancer Res, 1981, 1(3), 175 - 86 Neocarzinostatin in cancer chemotherapy (review); Maeda H; This article describes previous studies on a unique protein antitumor antibiotic, neocarzinostatin . Namely, its chemical nature, mode of action at molecular and cellular levels, toxicity and pharmacology, and recent results in clinical trials obtained primarily in Japan have been reviewed briefly. Pediatr Pharmacol (New York), 1981, 1(4), 357 - 64 Alterations induced by Nesdonal and Revrin on the heptic and nervous tissues of chick embryo; Farid M; The effect of two common drugs, namely, Nesdonal (a general anesthetic drug containing thiobarbitone) and Revrin (a common antibiotic containing tetracycline) on the glycogen content of the hepatocytes and the motor neurones of the lumbosacral region of 10-day-old chick embryos was studied in the present investigation . These drugs had been selected as they are frequently prescribed to pregnant women and their cytopathologic action in chick embryos had not been studied before . It was found that both drugs lead to the degeneration of the cells, pyknosis of the nuclei, and vacuolation of the cytoplasm . The glycogen content of the cells under investigation markedly decreased, fragmented, or disappeared . In these respects Revrin seems to exert a more powerful effect than Nesdonal. Trans R Soc Trop Med Hyg, 1981, 75(3), 394 - 8 Bleomycin-induced life prolongation of mice infected with Trypanosoma brucei brucei EATRO 110; Nathan HC et al.; The antitumour antibiotic bleomycin, supplied as commercial BlenoxaneR (a mixture of bleomycinic acids), at 7 or 14 mg/kg prolonged life greater than 30 days beyond death of controls without relapse or sign of trypanosomes in the peripheral blood of mice infected with Trypanosoma b . brucei EATRO 110 . Control mice died in three to four days . The purified A2 and B2 bleomycin congeners were also active at this dose . Spermidine, spermine and hirudonine (1,8-diamidinospermidine) but not putrescine, co-administered with drug, annulled the curative effects of these compounds, as signalled by appearance of trypanosomes in the blood and death of the animals. Folia Microbiol (Praha), 1981, 26(5), 345 - 50 The mechanism of resistance to streptomycin in Escherichia coli . Functional analysis of the permeability barrier of cells harbouring the R1 drd-19Km- plasmid; Brana H et al.; The mechanism of phenotypically altered SM resistance in mutants of Escherichia coli JC5455 (Rldrd-19Km-) lrs and JC5455 (pON5300) was compared with that of the standard strain JC5455 (Rldrd-19Km-) . On analyzing the membrane polypeptides in polyacrylamide gel both mutants were found to possess a protein spectrum different from that of ths standard strain . Transport of D-xylose and L-arginine was the same in all strains, transport of L-proline was decreased in JC5455 (pON5300) which may indicate a mutational interference with energy metabolism . The basic uptake of dihydrostreptomycin was the same in all strains but there were differences after preincubation of cells with streptomycin or glucose . The increased resistance of JC5455 (Rldrd-19Km-) lrs may be due to observed quantitative differences in membrane polypeptides that might play a role in the binding and functional expression of aminoglycoside-3'adenylyl transferase which modifies streptomycin . The increased sensitivity toward streptomycin in JC5455 (pON5300) can be explained by a mutation due to N-methyl-N'-nitro-N-nitrosoguanidine in the host cell since this change of sensitivity to streptomycin could not be transferred by transformation into a nonmutagenized strain . The coincidence of inducibility of increased transport of streptomycin by this antibiotic and the altered frequency of reversion to high levels of streptomycin resistance in JC5455 (pON5300) and in the transformant JC5455 (pON5302) may indicate that the altered reversibility toward phenotypically high resistance to streptomycin is a property of pON5300 and is transferred by transformation. Antibiotiki, 1981 Jan, 26(1), 5 - 7 {New actinomycin from Actinomyces sp . No . 2}; Kuznetsova VS et al.; A new actinomycin was isolated from a mixture of actinomycins formed by Actinomyces sp . No . 2, an organism producing auranthin, an actinomycetous antibiotic . The peptide chains of the new actinomycin contain such amino acids as threonine, valine, proline and sarcosine in a ratio of 2 : 4 : 2 : 2 . N-Methyl-valine characteristic of all actinomycins is replaced in position 5 of both pentapeptide chains of the new actinomycin by valine . The new actinomycin is actinomycin D undermethylated in position 5 by valine . When the growing culture of Actinomyces olivobrunneus producing actinomycin D was exposed to sulfadimesine, an inhibitor of biological methylation, production of actinomycin D0 (sarcosine replaced by glycine in one of the pentapeptide chains) markedly increased, which indicated impairment of the glycine residue methylation . Still, no impairment of the valine residue methylation in position 5 of the pentapeptide chains was observed an no actinomycin with N-methyl-valine replaced by valine was formed. Endoscopy, 1981 Jan, 13(1), 27 - 30 ERCP: Complications and prophylaxis a controlled study; Brandes JW et al.; Prophylactic measures for the prevention of complications (pancreatitis, pancreatic and biliary sepsis) after an ERCP examination were investigated in a controlled study . A total of 118 patients were selected at random and divided into three groups by post-ERCP treatment (Group A: no treatment, Group B: oral prophylaxis with broad spectrum tetracycline, Group C: bedrest for 36 hours, fasting, stomach catheter and infusion prophylaxis . The total rate of complications in the study as a whole was 5% (2.5% pancreatitis, 2.5% bacterial complications) . Statistical comparison of the groups produced no significant differences, i.e . neither the antibiotic nor the infusion prophylaxis proved advantageous with respect to the frequency of pancreatitis and bacterial complications . In addition to this, prophylactic measures after ERCP had no influence on the frequency, duration and extent of such temporary symptoms as abdominal discomfort, fever, leukocytosis, hyperamylasemia, hyperamylasuria and cholestasis . It is worth considering carrying out ERCP on an out-patient basis in special cases. Dtsch Med Wochenschr, 1980 Dec 19, 105(51), 1776 - 9 {Treatment of severe febrile neutropenia (author's transl)}; Meuret G et al.; Random allocation of 22 patients with benign and malignant diseases with neutrophil counts of up to 1 X 10(9)/l blood and probably infection-caused fever of more than 38 degrees C to intravenous treatment with one of the following antibiotic combinations was performed: carbenicillin (6 g/m(2) . 6 h) plus sisomicin (45 g/m2 . 6 h) or mezlocillin (3 g/m2 . 6 h) plus sisomicin (45 g/m2 . 6 h) . Both combinations were tolerated equally well . Patients became afebrile in 16 out of 23 treatment periods . Seven out of 11 patients responded to carbenicillin - sisomicin, and 9 out of 12 to mezlocillin - sisomicin . Mezlocillin thus leads to equal success of treatment in febrile neutropenia as the double dose of carbenicillin when both antibiotics are combined with the same aminoglycoside. Fed Regist, 1981 Jan 2, 46(1), 28 - 30 Prescription drug products; patient package insert requirements--Food and Drug Administration . Final rule; Purification and properties of adenylosuccinate synthetase from Yoshida sarcoma ascites tumor cells; Adenylosuccinate synthetase (IMP:L-aspartate ligase (GDP-forming), EC 6.3.4.4) was purified about 750-fold to a homogeneous state from Yoshida sarcoma ascites tumor cells . A yield of 38% purified enzyme was achieved by a procedure including affinity chromatography on hadacidin-Sepharose 4B . Ultracentrifugal analyses showed that the molecular weight of the native enzyme was 102 000 with an s20,w value of 4.5 and that the molecular weight in 6 M guanidine-HCl was 47 000 . These values indicate that the native enzyme is composed of two subunits . The isoelectric point was determined to be 5.9 by isoelectric focusing . The optimum pH for activity was 6.8-7.0 . The Km values for IMP, aspartate and GTP were calculated to be 4.1, 9.8 and 0.7 . 10(-4) M, respectively . The antibiotic, hadacidin was strongly inhibitory, causing competitive inhibition with respect to aspartate with a Ki value of 2.5 . 10(-6) M . Nucleoside mono- and diphosphate also inhibited the enzyme activity, but their inhibitions were not apparently specific . The purified enzyme showed full activity in the presence of Mg2+, and Mg2+ could be partially replaced by Mn2+, Co2+, Ca2+ or Cu2+ . Divalent metal ions, such as Cd2+, Pb2+, Zn2+, Cu2+ and Mn2+, interfered with the activity by antagonizing Mg2+ . Hg2+ or PCMB inactivated the enzyme, suggesting that an SH-group may be important for activity. Antibiotiki, 1980 Dec, 25(12), 928 - 31 {Action of levorin on amino acid transport in the rat small intestine}; Lishnevskaia EB et al.; Levorin, a polyenic antibiotic, in concentration of 2.10(-6) M markedly inhibited the active transport of amino acids in the cells of rat thin intestine, thus decreasing the oxygen dependent transfer of 14C-glycine and 14C-leucine and antigradient accumulation of glycine in the enterocytes . The effect increases with an increase in the period of the intestine mucosa contact with the antibiotic . Introduction of levorin from th serous side had no effect on the glycine transport . Inhibition of the transmembrane transport of glycine by levorin is due to its effect on transfer and accumulation of amino acids in the cells. Angiology, 1980 Dec, 31(12), 846 - 56 Echocardiographic abnormalities in acute rupture of the aortic valve due to infective endocarditis; Chia BL et al.; The M-mode echocardiographic findings seen in 5 patients with acute rupture of the aortic valve leaflets due to infective endocarditis are described . These findings embrace a wide spectrum of abnormalities seen in the aortic root in diastole and they are (1) fine, high frequency oscillating echoes, (2) thick oscillating bands of echoes, and (3) dense shaggy echoes loosely attached to the aortic valve leaflets . Three patients showed persistence of these aortic root echoes right up to the level of the left ventricular outflow tract . All 5 patients demonstrated early closure of the mitral valve and exaggerated motion of the interventricular septum and the posterior wall of the left ventricle . Two patients died from the illness and the remaining 3 had successful aortic valve replacement after appropriate antibiotic therapy . The aortic valve and the aortic root were carefully examined in all 5 patients either at necropsy or at operation . Two patients had leaflet perforation alone, whereas the remaining 3 had both leaflet perforations as well as vegetations . An attempt was made to correlate morphologic findings with the echocardiographic abnormalities . It is concluded that it is frequently difficult from abnormal echoes in the aortic root alone to differentiate between ruptured leaflets and vegetations . However, the presence of the combination of early closure of the mitral valve, exaggerated motion of the interventricular septum and the posterior wall of the left ventricle, together with abnormal aortic root echoes as described above should strongly suggest acute rupture of the aortic valve leaflets due to infective endocarditis, or in rare cases myxomatous degeneration of the aortic valve. Br J Dermatol, 1980 Dec, 103(6), 681 - 4 Primary cutaneous aspergillosis in a premature neonate; Granstein RD et al.; A case of primary cutaneous aspergillosis in a 3-week-old premature infant is reported . The lesion, which presented as a solitary nodule surmounted by three pustules, occurred following the use of elasticized and cloth adhesive tape and was cured by surgical excision . Factors predisposing to this infection included maceration, antibiotic usage, and prematurity. Am J Obstet Gynecol, 1980 Dec 1, 138(7 Pt 1), 755 - 8 Intrauterine irrigation with cefamandole nafate solution at cesarean section: a preliminary report; Long WH et al.; The effectiveness of intrauterine irrigation with an antibiotic solution of cefamandole nafate in reducing the incidence of endometritis after cesarean section was studied in a prospective, double-blind fashion . Ninety patients who underwent cesarean section at Tripler Army Medical Center were divided into three equal groups . Each group received one of the following treatments at the time of operation: (1) intrauterine irrigation with the antibiotic solution, (2) irrigation with normal saline solution, or (3) no irrigation . The resulting incidences of endometritis were 0%, 26.7%, and 23.3%, respectively . Intrauterine irrigation with cefamandole nafate solution at the time of cesarean section significantly reduced the incidence of endometritis. J Bone Joint Surg Am, 1980 Dec, 62(8), 1345 - 50 Late hematogenous infection of total joint replacement; Stinchfield FE et al.; Late deep wound infection secondary to hematogenous spread of bacteria from a distant focus is an infrequent but devastating complication of total joint replacement . Nine patients (ten implants) with documented late hematogenous infection are reported, all of whom demonstrated several characteristic features . The initial operation was free of clinical evidence of infection and a long asymptomatic interval ensued, followed by a definite febrile illness and acute joint pain . The source of the infection often was not recognized until late and prophylactic antibiotics were not given when it was identified . Seven of the ten implants had to be removed . The primary responsibility for the prevention of this devastating complication lies with the surgeon, who must inform each patient of the risk of late hematogenous seeding from infection elsewhere in the body . It is also important to pay special attention to patients who are at particularly high risk, such as those with rheumatoid arthritis or other systemic diseases . A knowledge of the bacterial flora of the various areas of the human body is essential in choosing the appropriate prophylactic antibiotic. Cancer Res, 1980 Dec, 40(12), 4390 - 7 Identification of the antimetabolite of L-alanosine, L-alanosyl-5-amino-4-imidazolecarboxylic acid ribonucleotide, in tumors and assessment of its inhibition of adenylosuccinate synthetase; Tyagi AK et al.; The conjugate of L-alanosine {L-2-amino-3-(N-hydroxyN-nitrosamino)propionic acid} and 5-amino-4-imidazolecarboxylic acid ribonucleotide has been synthesized in good yield by enzymatic means, using partially purified chicken liver 5-amino-4-imidazole-N-succinocarboxamide ribonucleotide synthetase (EC 6.3.2.6) . The chromatographic behavior of this molecule was characterized, as was its ability to inhibit adenylosuccinate synthetase, an enzyme long considered to be the locus of action of the drug . The Ki of-L-alanosyl-5-amino-4-imidazolecarboxylic acid ribonucleotide versus a partially purified adenylosuccinate synthetase frm the L5178y/AR leukemia of C57BL X DBA/2 F1 (hereafter called BD2F1) mice was 0.228 microM, whereas the Ki of L-alanosine was 57.23 mM . Administration of 50 microCi of DL-{1-14C}alanosine along with unlabeled L-alanosine (500 mg/kg) to BD2F1 mice bearing s.c . nodules of Leukemia L5178Y/AR resulted in the accumulation in tumors of a material with properties compatible with those of L-alanosyl-5-amino-4-imidazolecarboxylic acid ribonucleotide . It coeluted with L-alanosyl-5-amino-r-imidazolecarboxylic acid ribonucleotide in the high-resolution chromatographic system used, was Bratton-Marshall positive, and inhibited adenylosuccinate synthetase strongly . In tumor nodules 2 hr after dosage, the concentration of this compound approximated 70 microM . Under the same circumstances, the intratumoral concentration of L-alanosine was found to be 440 microM . At this concentration, the antibiotic itself exerts only a marginal inhibition of leukemic adenylosuccinate synthetase . In ancillary studies, it was shown for the first time in vivo that the parenteral administration of L-alanosine reduces the specific activity of intratumoral adenylosuccinate synthetase by 70% and depresses the synthesis of DNA to an equivalent or greater extent; adenine but not hypoxanthine (both at 250 mg/kg) was able to reverse the latter inhibition . No effect on purine salvage enzymes was exerted by L-alanosine . Viewed in concert, these experiments establish that the adduct of L-alanosine with 5-amino-4-imidazolecarboxylic acid is formed by neoplastic cells in vivo and that this anabolite is most probably responsible for the inhibition of adneylosuccinate synthetase and, in turn, for the diminished synthesis of DNA seen after a therapeutic dose of L-alanosine. J Thorac Cardiovasc Surg, 1980 Dec, 80(6), 909 - 20 Calcification of aortic homografts used for reconstruction of the right ventricular outflow tract; Saravalli OA et al.; Calcification of aortic homografts used for reconstruction of the right ventricular outflow tract was studied in assess the frequency of occurrence, location, extent, speed of progression, and clinical and hemodynamic implications . Radiologic follow-up by means of penetrated posteroanterior and lateral radiograms ranged from 2 to 10 years in two groups of patients . Group 1 comprised 40 patients with cyanotic congenital heart disease in whom an aortic homograft was used to restore continuity between the right ventricle and pulmonary arteries . Results from this group were correlated with those from Group 2, which included 80 patients who had a homograft implanted as a substitute for their own pulmonary valve, which had been used as an autograft for replacing the diseased aortic or mitral valve . In Group 1, 92% of the grafts were calcified 6 months to 4 years after operation . Calcification was severe in two cases, moderate in 33, and mild in two . One of the grafts had to be removed in the tenth postoperative year for progressive obstruction . In Group 2, 27% showed signs of calcification, never before the second year after implantation . Calcium development was severe in two, moderate in 12, and mild in eight . Two obstructed homografts were removed . Aortic homograft calcification has been more common, developed earlier, and been more severe in patients operated upon for congenital lesions . The lower age, the peculiar metabolism, the distorted anatomy, and the development of pulmonary hypertension in this group may account for this fact . In 96% of the patients who were followed, calcification has not yet meant clinical disability or hemodynamic dysfunction . Use of "fresh," antibiotic-sterilized homografts has reduced the incidence of calcification in Group 2 and is expected to decrease its severity in all cases. Ophthalmology, 1980 Dec, 87(12), 1309 - 13 Ocular pathology for clinicians . 8 . Orbital cellulitis; Macy JI et al.; Orbital cellulitis secondary to sinusitis has been the most common cause of proptosis in children . A case report is presented which emphasizes that the signs and laboratory findings in orbital cellulitis may be confusing, especially when modified by prior antibiotics . When orbital cellulitis is a possibility, adequate antibiotic therapy should be instituted while diagnostic studies are being performed . CT scanning is a new and useful modality for the evaluation of these patients, but cautious and experienced interpretation is essential . In patients who do not respond promptly to appropriate medical therapy, surgical intervention is indicated for drainage and biopsy. Jpn J Antibiot, 1980 Dec, 33(12), 1318 - 31 Pharmacokinetics of ribostamycin in healthy volunteers and patients with impaired renal function; Yamasaku F et al.; Ribostamycin is an aminoglycoside antibiotic produced by Streptomyces ribosidificus, and extracted and isolated by NIIDA et . al . It has been used widely clinically with its characteristic of low ototoxicity . UMEMURA et al . studied the pharmacokinetics of this antibiotic in animals and reported that it has a similar pharmacokinetic behavior in vivo to kanamycin . In the present studies, the pharmacokinetic behavior of ribostamycin was studied in 5 healthy adult volunteers receiving different doses (0.5 g, 1.0 g and 1.5 g) by intramuscular injection, and 0.5 g by intravenous drip infusion . In addition, a similar study was conducted with 11 patients with varying degrees of renal dysfunction in order to study the application of ribostamycin in such patients. Ann Neurol, 1980 Dec, 8(6), 631 - 3 Mollaret meningitis: report of a case with recovery after colchicine; Mora JS et al.; A 13-year-old boy developed closely spaced episodes of recurrent febrile meningitis that persisted for 22 months despite antibiotic therapy . During exacerbations the cerebrospinal fluid contained up to 2,500 leukocytes per cubic millimeter, including up to 20% activated monocytoid cells, with high IgM and IgG levels . No cause for the disorder was found, but steroids improved the condition and colchicine therapy apparently cured it. Southeast Asian J Trop Med Public Health, 1980 Dec, 11(4), 572 - 81 Prevalence of enterotoxigenic Escherichia coli in patients with diarrhoea in Bangkok; Khusmith S et al.; Enterotoxigenic Escherichia coli (ETEC) were recovered from 17 of 82 patients (20.7%) with diarrhoea admitted to Bamrajnaradura Hospital . Six patients (7.3%) were infected with LT + ETEC, 6 patients (7.3%) with ST + ETEC, 2 patients (2.4%) with LT + ST + ETEC and 3 patients with mixed ETEC infection, two of them had LT + ST + and LT + and one had LT + and ST + ETEC infections . There was no significant differences between the age group and the positive isolation of ETEC . Only 33 of 63 isolates could be typed . Two of 4 patients with LT + ST + ETEC had 078 serotype . There was no correlation between enteroxigencity and enteropathogenicity as determined by the antisera used . Antibiotic sensitivity testing showed that 51.6% of ETEC isolates were resistant to ampicillin, chloramphenicol, streptomycin and tetracycline, and all ETEC were sensitive to gentamicin and cotrimoxazole. Am J Obstet Gynecol, 1980 Dec 1, 138(7 Pt 2), 1078 - 81 Problems and proposals for the surveillance and control of sexually transmitted diseases associated with pelvic inflammatory disease in South America; de la Torre LA; PIP: The number of women at risk for gonococcal pelvic inflammatory disease has increased greatly in South America as has the incidence rates for gonorrhea . IN an effort to summarize the problems encountered in the control of sexually transmitted disease (STD) agents associated with pelvic inflammatory disease (PID), official documents prepared for the Pan American Health Organization and articles published in South American journals were reviewed . The problem of PID essentially involves fertile women between the ages of 15 and 49 years . Fertile women are at greater risk for STD, and the number of such women has increased markedly . Between 1970 and 1975, the reported incidence rates of gonoccal infection increased 29% in Bolivia, 25% in Uruguay, 15% in Argentina, and 13% in Colombia . The rates in Paraguay declined by 50% . Surveillance systems for STD are inaccurate in South American countries, and the health care services offer highly variable population coverage . In most South American countries, programs for the control of STD are limited to the control of prostitution and evaluation and treatment of prostitutes, prenatal serologic screening for syphilis, and studies performed in women attending hospital gynecology clinics . The other factors contributing to poor STD control are: the medical care system; medical care coverage; professional STD training; laboratory system; antibiotic misuse; and public education . Ignorance regarding STD on the part of physicians works as a major barrier to more effective control programs . It is essential that clinical services for STDs be available for the majority of a country's population . J Pediatr Surg, 1980 Dec, 15(6), 790 - 6 Corticosteroid therapy in hemorrhagic and septic shock in puppies; Connors RH et al.; The efficacy of corticosteroid therapy in the treatment of shock remains controversial . In order to evaluate this question, the following controlled experimental study was undertaken . There were 44 puppies (2-6 kg) used to examine the effects of methylprednisolone (30 mg/kg) in both hemorrhagic and live Escherichia coli septic shock . In order to isolate the effects of steroid treatment, no volume or antibiotic therapy was given . Arterial, venous, and pulmonary artery catheterization allowed continuous hemodynamic and metabolic monitoring . One control group received steroid treatment and was not subjected to shock . Septic shock was achieved by a rapid bolus infusion of 10(9) live E . coli organisms . Hemorrhagic shock was produced by bleeding the puppy an average of 43% of his blood volume . Four septic and four hemorrhagic shock groups received either no treatment, steroids at the time of shock, or steroids 30 min before or after shock . Cardiac outputs of less than 50% of control values and significant lactic acidosis were documented in all of the shock animals . The septic groups showed more profound alterations in these parameters and a decreased overall survival . No statistically significant differences could be found, however, in the hemodynamic, metabolic or survival figures among the different septic shock groups, or among the various hemorrhagic shock animals . The anticipated preservation of cardiac output and decrease in leakage of lysosomal acid phosphatase were not seen with any treatment schedule . The theoretical benefits of corticosteroid treatment in shock could not be documented in these two models of severe septic and hemorrhagic shock in puppies. Chest, 1980 Dec, 78(6), 867 - 9 Counterimmunoelectrophoresis in the diagnosis of Hemophilus influenzae pleural effusion; Holsclaw DS Jr et al.; A child with a sterile pleural effusion resulting from an infection with Hemophilus influenzae type b (Hi b) is described . The diagnosis was established by use of counterimmunoelectrophoresis (CIE) . The alarming increase in incidence of pneumonia due to Hi b is noted, as is the large number of associated pleural effusions . CIE provides a rapid, reliable, and sensitive means by which to establish the exact etiology of such bacterial infections so that optimal antibiotic therapy can be started promptly. J Allergy Clin Immunol, 1980 Dec, 66(6), 447 - 51 The effect of troleandomycin on methylprednisolone elimination; Szefler SJ et al.; Troleandomoycin (TAO), a macrolide antibiotic, has an apparent "steroid-sparing" effect when used in the treatment of severe steroid-dependent asthma . This study was designed to investigate the effect of TAO on methylprednisolone elimination . Pharmacokinetic studies were performed before and 1 wk after starting TAO in 10 severe steroid-dependent asthmatics . Baseline total body clearance of methylprednisolone was 406 +/- 139 (mean +/- SD) ml/min/1.73 m2 and decreased significantly (p < 0.001) to 146 +/- 57 ml/min/1.73 m2 1 wk after TAO therapy was initiated . Methylprednisolone half-life was 2.46 +/- 0.75 hr before TAO and increased significantly (p < 0.01) to 4.63 +/- 1.35 hr after 1 wk on TAO therapy . A follow-up evaluation of methylprednisolone pharmacokinetics in three patients after at least 1 mo on TAO therapy demonstrated continuation of the reduced methylprednisolone elimination . TAO inhibition of methylprednisolone clearance may contribute to the beneficial effects observed initially with combined methylprednisolone-troleandomycin therapy in severe steroid-dependent asthma. J Allergy Clin Immunol, 1980 Dec, 66(6), 438 - 46 Efficacy of troleandomycin in outpatients with severe, corticosteroid-dependent asthma; Zeiger RS et al.; Sixteen severe, corticosteroid-dependent yet resistant outpatient asthmatics were treated with troleandomycin (TAO), a macrolide antibiotic, in an attempt to both induce a clinical remission and reduce methylprednisolone requirements . Within the first 2 wk of initiating TAO therapy, 50% of the patients experienced a greater than 20% increase in forced expiratory volume in 1 sec (FEV1) and 80% noted a greater than 20% increase in forced vital capacity between 25% and 75% (FVC 25%-75%) . Maximal increases in FEV1 and FVC 25%-75% were noted in all patients within the first 6 wk on TAO and methylprednisolone . There was a concomitant clinical improvement in all patients . Corticosteroid-induced side effects, gastrointestinal tract discomfort, and elevated serum glutamic pyruvic transaminase (SGPT) were common yet generally transient during TAO and methylprednisolone therapy . After a 4- to 18-mo follow-up 15/16 patients were well-controlled on TAO and methylprednisolone . Methylprednisolone requirements were reduced at least four- to fivefold in most patients during TAO therapy . Normal morning serum cortisol levels were documented after varying intervals in most patients when both TAO (250 mg) and methylprednisolone (4 to 16 mg) could be reduced to alternate-day administration . Only one patient was forced to discontinue therapy due to side effects . The present study extends the effectiveness of TAO therapy to ambulatory asthmatics, establishes a clinical strategy that maximizes benefit/risk factors, and provides practical guidelines for the long-term use of TAO and methylprednisolone. Aust N Z J Surg, 1980 Dec, 50(6), 622 - 3 A case of Fournier's gangrene; Bruce M; Fournier's gangrene of the scrotum is an uncommon condition . Its aetiology remains obscure . It has a potentially serious and possibly fatal outcome if not treated quickly and effectively . The following case history demonstrates that a combination of early surgical intervention and intravenous antibiotic therapy will substantially reduce morbidity and mortality. Proc Natl Acad Sci U S A, 1980 Dec, 77(12), 7049 - 53 DNA polymerase alpha mutants from a Drosophila melanogaster cell line; Sugino A et al.; Aphidicolin, a tetracyclic diterpenoid antibiotic, is a specific inhibitor of DNA synthesis in vivo and DNA polymerase (deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase, EC 2.7.7.7) alpha of eukaryotic organisms . After ethyl methanesulfonate mutagenesis, we have recovered mutants of Drosophila melanogaster Schneider cell line no . 2 that grow at concentrations of aphidicolin that completely inhibit wild-type cells . The DNA polymerase alpha from one of these mutants, aph-10, is much more resistant to inhibition by the drug; the apparent Ki of the wild-type enzyme is 12 nM aphidicolin, whereas the apparent Ki of the aph-10 polymerase is more than 100 nM . (The apparent Km for dCTP is the same for both enzymes.) Another mutant, aph-13, overproduces DNA polymerase alpha at least 8-fold . The DNA polymerase of this mutant has the same apparent Km and Ki for dNTPs and aphidicolin as does wild-type polymerase. AJR Am J Roentgenol, 1980 Dec, 135(6), 1205 - 10 Neonatal candidiasis: renal and pulmonary manifestations; Patriquin H et al.; A description of three newborns with renal candidiasis and a review of 14 others suggest the following pathogenesis: antibiotic therapy in a premature baby with an intravascular catheter is followed by hematogenous renal spread, candiduria, and acute obstructive nephropathy by mycotic bezoars . The radiologic appearance is often characteristic . Prompt therapy is the only possibility for survival . Primary thoracic candidiasis occurs more frequently in the full term baby and is probably aspirated during birth . One patient is described and 20 cases from the literature are reviewed . The radiologic appearance is nonspecific. Antimicrob Agents Chemother, 1980 Dec, 18(6), 933 - 8 Pharmacokinetics of moxalactam in subjects with various degrees of renal dysfunction; Bolton WK et al.; We have examined the pharmacokinetics of moxalactam (LY127935) in 36 subjects with various degrees of renal dysfunction . Creatinine clearance (Ccr)/1.73 m2 ranged from zero to 135.8 ml/min . After a 1-g administration of moxalactam intravenously, the volume of distribution was 20.6 /+- 9.5 liters (0.28 liter/kg), and the mean half-life ranged from 3.1 h for subjects with Ccr greater than 65 ml/min to 19.3 h for subjects with Ccr less than 10 ml/min . The moxalactam clearance was closely correlated to Ccr (r = 0.93, P less than 0.0001) and excretion of antibiotic was 73.6 +/- 13% in normal subjects . Renal clearance accounted for 90% of moxalactam clearance in the normal subjects . A dosage schedule for administering moxalactam to patients with various degrees of renal dysfunction is provided. Antibiotiki, 1980 Dec, 25(12), 924 - 7 {Antitumor activity of bleomycetin against ascitic tumors in mice}; Bazhanov VS et al.; When used intraperitoneally in doses of 18.0-0.006 mg/kg daily bleomycetin inhibited th growth of lymphadenosis NK/Li by 90-100 per cent . When used subcutaneously or intravenously in maximum tolerated doses the antibiotic inhibited the development of lymphadenosis NK/Li by 90 and 70 per cent respectively . The antitumor effect of bleomycetin on Ehrlich's carcinoma was somewhat less pronounced . Inhibition of Ehrlich's carcinoma growth by 50-90 per cent was observed with intraperitoneal and subcutaneous use of the antibiotic in doses of 0.2-1.0 and 5.0-13.0 mg/kg respectively . When used intraperitoneally bleomycetin markedly prolonged the life span of mice with lymphocytic leucosis P-388 and was superior by its efficiency to methotrexate used as a reference . On subcutaneous administration the efficiency of the antibiotic was almost the same as that of methotrexate and on intravenous administration it amounted to 70 per cent of the methotrexate efficiency . No effect of bleomycetin on its intraperitoneal use was observed with respect to lymphoid leucosis L-1210. Nucleic Acids Res, 1980 Nov 25, 8(22), 5519 - 31 Counterion dependent variation of DNA secondary structure in (A . T) clusters: evidence by use of netropsin as a structural probe; Reinert KE et al.; The interaction of the oligopeptide antibiotic netropsin (Nt) with (A . T) regions of DNA is characterized by a spectrum of discrete modes . This has been revealed by viscometric analysis, at 20 degrees C and 0.2 M "counterions", for NaDNA in a preceding and for NH4DNA in this paper . The increase of DNA contour length as induced by one Nt molecule was found to depend on the special mode only, while the respective stiffening is generally higher for NH4DNA . The latter property is interpreted in terms of an enhanced flexibility, relative to that of NaDNA, of the (A . T) cluster segments before complex formation . For some of the interaction modes of the DNA-Nt systems a difference in the number of corresponding binding sites has been observed . This phenomenon is understood by assuming an influence of the counterion species upon existing equilibria between different forms of the (A . T) cluster secondary structure . Not less than 5 to 10% of the total DNA are effected in this manner . Upper limits for the local differences in the axial rise per base pair are 0.04 nm and 0.02 nm. C R Seances Acad Sci D, 1980 Nov 24, 291(11), 897 - 9 {Visceral localization of 14C gentamicin in the rat after administration of a single dose}; Fresel J et al.; When administered intravenously to Rats, 14C Gentamicin decreased very fast in all tissues, except in kidney and cartilage . Some flexures of the small intestine contained radioactive carbon, and that was evidence for the biliary elimination of a part of the aminoglycoside . In animals with water restriction, the distribution of the antibiotic in tissues was similar to the distribution in animals with free access to water. MMW Munch Med Wochenschr, 1980 Nov 14, 122(46), 1651 - 4 {Pharmacokinetics of cefotaxim in geriatric patients (author's transl)}; Naber K et al.; The behavior of plasma concentrations after intravenous and intramuscular administration of 2 g cefotaxim (Claforan) was determined in an intra-individual cross-over comparison in 10 geriatric patients . The half-lives measured of about 2 hours were approximately twice as long as in healthy subjects . Thus an effective level is maintained over the same period with half the recommended dose of antibiotic compared with younger patients, which could be clinically relevant. Biochemistry, 1980 Nov 11, 19(23), 5411 - 6 Nonenzymic translocation and spontaneous release of noncognate peptidyl transfer ribonucleic acid from Escherichia coli ribosomes; Cabanas MJ et al.; Poly(uridylic acid)-programmed ribosomes have been used to synthesize the noncognate peptidyl-tRNA Ac-Phe-Tyr-tRNATyr and its cognate counterpart Ac(Phe)2-tRNAPhe . After synthesis, Ac(Phe)2-tRNAPhe remains, as expected, in the ribosomal acceptor (A) site, but the noncognate AcPhe-Tyr-tRNATyr does not; part of it spontaneously falls off the ribosome and the rest translocates, without elongation factor (EF) G, to the ribosomal donor site . The inhibitor of translocation viomycin prevents both the spontaneous release and the nonenzymatic translocation by confining the noncognate peptidyl-tRNA to the A site . Under these conditions, the interaction of AcPhe-Tyr-tRNATyr with the A site appears to be similar to that of Ac(Phe)2-tRNAPhe without the antibiotic, and EF-G promotes the translocation and subsequent elongation of both peptidyl-tRNAs to comparable extents . The results indicate that, without viomycin, the noncognate peptidyl-tRNA is weakly held in the ribosomal A site and support the proposal that the release of peptidyl-tRNA occurring during protein synthesis in vivo is related to a ribosomal editing mechanism which discards mistranslated nascent proteins {Menninger, J . R . (1977) Mech . Ageing Dev . 6, 131}. J Biol Chem, 1980 Nov 10, 255(21), 10517 - 22 Mutants of Escherichia coli lacking ribosomal protein L11; Stoffler G et al.; Three mutants with ribosomes apparently lacking Protein L11, AM68, AM76, and AM77, were investigated using a variety of immunological techniques to determine whether L11 was indeed lacking . Ouchterlony double diffusion, modified immunoelectrophoresis, and dimer formation on sucrose gradients all gave results indicating Protein L11 was missing from the ribosome in these mutants . Electron micrographs of ribosomes of the mutants were indistinguishable from those of wild type . Ribosomes of AM68, AM76, and AM77, did not bind the antibiotic thiostrepton, but binding was recovered upon reconstitution with wild type Protein L11. Sem Hop, 1980 Nov 8-15, 56(41-42), 1748 - 53 {Studies on liver abscesses (author's transl)}; Ragnaud JM et al.; The authors report 25 observations of liver abscesses in the same service over a 5 years period . Diagnostic difficulties are pointed out and the value of echography, a simple and well tolerated examination, are emphasized immunologic studies allow the differentiation of the two types off liver abscesses i.e., pyogenic and amoebic, thus orientating their different treatments . The treatment of pyogenic abscesses (12 cases) is chiefly surgical, supported with suitable antibiotic therapy . Amoebic abscesses require medical treatment in collected abscesses of little or mean volume . In our series the number of patients requiring surgery is important (13 cases) . This is due to persisting residual pouches or to the absence of well defined cliical improvement with medical treatment and the occurence of pre-burst or burst symptoms. Biochim Biophys Acta, 1980 Nov 4, 602(2), 260 - 8 Application of differential spectra in the ultraviolet-visible region to study the formation of amphotericin B-sterol complexes; Gruda I et al.; The extent of complex formation between the polyene antibiotic, amphotericin B, and cholesterol or ergosterol was investigated and a method for a quantitative measurement of the complex formation was developed . The effect of experimental conditions on the magnitude of the amphotericin B-sterol interaction and on the selectivity of this interaction showed that there was only a narrow range of solvent composition in which the differential selectivity of amphotericin B towards these two sterols could be observed. Br J Cancer, 1980 Nov, 42(5), 692 - 6 Survival of intestinal crypts after treatment by adriamycin alone or with radiation; Moore JV et al.; A survival curve has been established for jejunal crypts of BDF1 mice treated by single i.p . doses of the antibiotic agent adriamycin . The threshold dose and Do were twice that for marrow CFU-S of these mice . The overall extrapolation number of the crypt survival curve was very low (1.3 +/- 0.13) compared to the value for gamma radiation . This observation is discussed with respect to the interpretation of crypt survival curves . We were unable to demonstrate any enhancement by adriamycin (reduction in Dq) of the response of microcolony-forming cells to radiation given immediately before the drug. Anaesth Intensive Care, 1980 Nov, 8(4), 402 - 3 The period of nasotracheal intubation in acute epiglottitis; Phelan PD et al.; Experience during the last three years with nasotracheal intubation in children with acute epiglottitis indicates that a period of intubation of 8-12 hours after the institution of appropriate antibiotic therapy is satisfactory in most patients . Shortening the period of intubation should have benefits to the patient . A shorter period of intubation should provide less opportunity for complications to develop and allow earlier discharge. J Am Vet Med Assoc, 1980 Nov 1, 177(9), 849 - 51 Coccidial infections in ranch mink; Myers GH et al.; A field study was conducted from April through June of 1976 to determine whether coccidial infections adversely affect the growth and survivability of young mink . Two anticoccidials, lasalocid (62 mg/kg of feed) and an antibiotic-sulfonamide preparation (220 mg/kg of feed), were incorporated into a standard pelleted ration . Comparisons of weight gains, mortality, and oocyst numbers were made between control and treated groups . Treatment reduced mortality (P < 0.001) but did not significantly affect weight gains . The antibiotic-sulfonamide preparation and, to a lesser extent lasalocid, reduced oocyst discharge . Increased oocyst shedding was detected among adult female mink from parturition to weaning of their kits. Cell, 1980 Nov, 22(2 Pt 2), 459 - 67 Role of ATP in binding and migration of 40S ribosomal subunits; Kozak M; Two assays have been devised to demonstrate ATP-dependent migration of 40S ribosomal subunits on messenger RNA . The first is a two-step runoff assay . Reovirus mRNA was initially loaded with 40S subunits by incubation with wheat germ ribosomes in the presence of the antibiotic edeine . During the second phase of the incubation, in which further attachment of ribosomes was inhibited, the preformed complexes were shown to dissociate (presumably by runoff) only if ATP was included in the reaction . A more direct demonstration of ATP-dependent migration of 40S subunits was carried out using 3' end-labeled brome mosaic virus mRNA . In the presence of edeine and ATP, 40S ribosomal subunits were shown to advance all the way to the 3' end of the message, as shown by protection of the labeled 3'-proximal segment against nuclease digestion . Depletion of ATP by the addition of hexokinase prevented this migration . A variety of observations has raised the possibility that attachment of eucaryotic ribosomes to messenger RNA proceeds via a "scanning mechanism." The hypothesis is that a 40S subunit binds initially at or near the 5' terminus of the message and subsequently migrates toward the interior, stopping when it encounters the first AUG triplet . If migration of 40S subunits requires ATP, as the present studies suggest, the scanning mechanism predicts that in a system depleted of ATP a single 40S ribosome should be trapped near the 5' terminus of the message--upstream of the AUG initiator codon . This prediction was confirmed by analyzing binding of wheat germ ribosomes to a synthetic ribopolymer in which the 5'-proximal region (lacking AUG codons) and the AUG-containing segment near the 3' end of the molecule were differentially labeled. Antimicrob Agents Chemother, 1980 Nov, 18(5), 691 - 5 Stimulation of leucomycin production by magnesium phosphate and its relevance to nitrogen catabolite regulation; Omura S et al.; Addition of magnesium phosphate {Mg3(PO4)2 x 8H2O} to a complex medium or to an ammonium ion-containing, chemically defined medium stimulated leucomycin production by Streptomyces kitasatoensis . Ammonium ions in high concentrations inhibited leucomycin production, but their limitation by magnesium phosphate led to the high production of the antibiotic. Antibiotiki, 1980 Nov, 25(11), 868 - 70 {14C-alanine incorporation into rat thymus nuclear proteins on actinomycin D administration at different times of day}; Savina MI; Actinomycin D was administered to rats at various day periods and it was observed that the levels of the nuclear protein synthesis in the thymus cells significantly lowered depending on the period of the drug administration . This was most pronounced with respect to histones H1 and nonhistone proteins . The antibiotic effect was determined by the stage of the lymphocyte living cycle: G1 period was most sensitive to the actinomycin block. Antibiotiki, 1980 Nov, 25(11), 850 - 4 {Action of levorin on glucose transport in the rat small intestine}; Roshchina GM et al.; The technique of accumulating preparation of the mucosa and "turned out sac" was used to show that levorin, a polyenic antibiotic in a concentration of 10(-6) M, lowered the transport rate and accumulation of glucose by the epithelial cells of the rat thin intestine under conditions of oxygenation . Suppression of the glucose transport in the first stages resulted in partial inhibition of the transmembrane transfer . It is suggested that levorin suppression of the glucose transport through the erythrocyte apical membrane in the thin intestine is associated with a decrease in the electrochemical gradient of Na+. Antibiotiki, 1980 Nov, 25(11), 822 - 8 {Morphological and biochemical characteristics of Streptomyces hygroscopicus mutants induced by streptomycin and hygromycin B}; Pronina MI et al.; Under the effect of streptomycin and hygromycin B there were obtained morphological mutants of Str . hygroscopicus differing in their capacity for synthesis of the antibiotic and a complex of proteolytic enzymes, as well as their resistance to high concentrations of the antibiotics . The mutation of resistance to the aminoglycosides with preservation of the initial phenotype did not result in significant changes in biosynthesis of hygromycin B and the enzyme . At the same time the antibiotic resistant mutants with changed morphology of the colonies were characterized by different capacity for the biosynthesis of the enzyme and antibiotic . Mutants with high, productivity of hygrolytin, not producing hygromycin B were most valuable . Production of hygromycin B correlated with the culture capacity to form aerial mycelium and spores . On the contrary, synthesis of hygrolytin by Str . hygroscopicus did not depend on the morphological characteristics of the culture: strains active with respect to hygrolytin synthesis were found among both the mutants forming abundant aerial mycelium and those not forming it . The study on the biochemical characteristics of the cultures showed that by the lipid content and fatty acid composition they belonged to the same group. South Med J, 1980 Nov, 73(11), 1473 - 5 Use, misuse, and cost of parenteral cephalosporins at a county hospital; Appleby DH et al.; We reviewed total usage of parenteral cephalosporins at a county hospital during 1978 with regard to appropriateness, pattern of use, and cost . In addition, we determined the impact of replacing cephalothin with cephapirin in the hospital formulary . During the 12-month study 366 patients received 409 courses of parenteral cephalosporins: 167 received cefazolin, 160 received cephapirin, and 35 received a combination of cefazolin and cephapirin . The surgical service prescribed 87% of the cephapirin and 92% of the cefazolin . Parenteral cephalosporins were used 62% of the time for prophylaxis and 38% of the time for therapy . Usage was judged inappropriate in 47% of all courses based on our criteria; 25% of the therapeutic courses were judged inappropriate, compared to 60% of the prophylactic courses . Pharmacy costs of cefazolin used as prophylaxis were more than twice the cost for cephapirin . Cost of a mean therapeutic course for cefazolin was 43% higher than for cephapirin . Antibiotic audits and continued education combined with judicial substitution of therapeutic equivalents should limit the inappropriate use and expense of parenteral cephalosporins for large as well as small hospitals. Johns Hopkins Med J, 1980 Nov, 147(5), 182 - 5 Unrecognized Candida brain abscess in infancy: two cases and a review of the literature; Haruda F et al.; Two infants with presumed Candida species brain abscesses are presented . Six other infants with the same problem were found in a search of the literature, and some of the clinical and pathologic features of these patients are presented and discussed . All diagnoses were made post-mortem . There was frequent association with gastrointestinal pathology and subsequent surgery, and with antibiotic administration . Central nervous system signs and symptoms were not a prominent feature, and although most patients had disseminated candidiasis, one patient had an isolated macroscopic cerebral abscess. Arch Ophthalmol, 1980 Nov, 98(11), 2050 - 2 Intraocular penetration of sisomicin in rabbits; Faris BM et al.; The intraocular penetration of sisomicin, an aminoglycoside antibiotic, was studied in 47 normal rabbits following subconjunctival and/or intramuscular (IM) injections . Sisomicin levels were determined in the cornea and the aqueous humor of the injected eye as well as in the aqueous of the fellow eye by means of the cylinder-plate bioassay technique . When the IM route alone was used, the eye tissue concentrations remained negligible . One hour after subconjunctival injection, highly therapeutic sisomicin concentrations were achieved in the aqueous humor of both injected and fellow eyes, but the level dropped to very low concentrations 12 hours after the injection . The concomitant administration of sisomicin intramuscularly and subconjunctivally resulted in a significant delay of the clearance of sisomicin from the eye tissues . The use of the combined subconjunctival-IM regimen for administering aminoglycoside antibiotics needs further evaluation. Surg Gynecol Obstet, 1980 Nov, 151(5), 604 - 8 Candidal abscess of the spleen in patients with acute leukemia; Page CP et al.; Between January 1974 and July 1976, three adult patients with leukemia, therapy-associated granulocytopenia and febrile courses unresponsive to broad spectrum antibiotic therapy were operated upon for a preoperative diagnosis of candidal abscess of the spleen . The diagnosis was based upon a high index of suspicion of invasive candidiasis in this immunosuppressed group of patients; the failure of the patients to respond to the empiric administration of broad spectrum antibiotics, salicylates and steroids, and the presence of discrete scintiscan defects on liver-spleen scan with both 99Tc sulfur colloid and 67Ga citrate . Multiple splenic abscesses containing candidal organisms were confirmed in all three patients, and two of the three also had multiple small abscesses of the liver . The fourth patient, whose liver-spleen scintiscans were abnormal only in showing splenomegaly and whose febrile course responded to aspirin, did not have a candidal abscess of the spleen at the time of celiotomy which was undertaken for fever of unknown cause . The antemortem diagnosis and treatment of candidal splenic abscess in patients with leukemia is dependent upon a high index of suspicion and appropriate clinical correlation with diagnostic tests . Although the prophylactic oral administration of mycostatin to patients at high risk may prevent this once fatal complication, only prompt and aggressive treatment can cure it. J Bacteriol, 1980 Nov, 144(2), 666 - 71 Role of vacuolar ion pool in Saccharomyces carlsbergensis: potassium efflux from vacuoles is coupled with manganese or magnesium influx; Lichko LP et al.; Saccharomyces carlsbergensis cells accumulated Mn2+ (or Mg2+) ions in the presence of glucose, fructose, or mannose, but not of deoxyglucose, 3-O-methylglucose, and sorbose . Accumulation of one equivalent of Mn/2+ was coupled with the efflux of two equivalents of K+ from the cells . Mg/2+ did not exit during Mn2+ uptake . Preliminary treatment of cells with various proton conductors or glucose led to the loss of K+ and to the proportional inhibition of Mn2+ uptake . Polyene antibiotic candicidin together with glucose elicited rapid efflux of K+ and completely inhibited Mn2+ accumulation . Exogenous K+ (more than 1 mM), 100 microM N,N'-dicyclohexylcarbodiimide, and 30 mM sodium arsenate inhibited both K+ efflux and Mn2+ influx . K+ efflux from S . carlsbergensis cells affected the vacuolar pool of K+ both during the accumulation of Mn2+ or Mg2+ and during glucose uptake. Am J Obstet Gynecol, 1980 Nov 1, 138(5), 541 - 4 Contraceptive practice and tuboovarian abscess; Edelman DA et al.; PIP: In an effort to evaluate the possible relationship between contraceptive usage and the occurrence of tubovarian abscess (TOA), the hospital records of 346 women who were treated as inpatients at the North Carolina Memorial Hospital over the January 1970 to June 1979 period and were discharged with a diagnosis of TOA were reviewed retrospectively . A TOA diagnosis was made by review of the operative notes and pathology reports for patients who were surgically treated or by review of the reports of physicians contained in the hospital records for patients who were not surgically treated . 28 women were excluded from the analysis . Comparisons were made only between women using IUDs or oral contraceptives (OCs) and those using no contraceptive method . Compared to women using OCs or no contraceptive method, a signifi