No To Shinkei, 1990 Jul, 42(7), 651 - 4 {A case of syphilitic meningitis presenting the seventh nerve and the eighth nerve palsies}; Komachi H et al.; Here we described a case of syphilitic meningitis presenting the seventh nerve and the eighth nerve palsies . A 56-year-old man was admitted because of left facial palsy and hearing loss of bilateral ears . He had a penile chancre five months before admission . Cerebrospinal fluid examination showed high pressure, pleocytosis predominantly with mononuclear cells and high protein content . STS and TPHA of serum and CSF were positive . High dose penicillin G was effective, and he was discharged with only mild hearing loss in the left . Considering the penetration of penicillin G into the CSF and the minimum fully treponemicidal concentration of penicillin, the administration of large doses of aqueous penicillin G intravenously or intramuscularly was effective in such a case to prevent permanent deafness, though CDC recommends relatively low dose. Protein Eng, 1990 Jul, 3(7), 635 - 9 Expression, purification and crystallization of penicillin G acylase from Escherichia coli ATCC 11105; Hunt PD et al.; The penicillin acylase gene (pac) from Escherichia coli ATCC 11105 was cloned into pUC 9 and the resulting vector (pUPA-9), when transformed into E . coli strain 5K, allowed the constitutive overproduction of mature penicillin acylase when grown at 28 degrees C . The enzyme was purified from the periplasmic fraction of E . coli pUPA-9 by hydrophobic interaction chromatography and anion exchange . Crystals of penicillin acylase were grown in batch using polyethylene glycol 8000 as a precipitant . The crystals (space group P1) diffracted to beyond 2.3 A. Ann Allergy, 1990 Jul, 65(1), 1 - 13 Lyme disease; Duffy J; Lyme disease is a complex multisystem disorder recognized on six continents that is epidemic in some parts of the world during spring, summer, and fall seasons . It is an infectious disease caused by a spirochete, B . burgdorferi, which is transmitted chiefly by I . dammini and pacificus ticks in the United States and I . ricinis in Europe . It is a disease with early and late cutaneous manifestations plus involvement of the nervous system, heart, eye, and joints in variable combinations . Diagnosis is based on patient contact with an endemic area, one or more characteristic clinical features, particularly erythema migrans rash, and a positive serologic test for B . burgdorferi infection in the majority of cases with illness greater than 4 to 6 weeks' duration . Although infection is the primary cause, immune mechanisms almost certainly play a synergistic role in some manifestations during late stages . Prompt diagnosis and treatment are important for full recovery . Therapy with doxycycline or amoxicillin is effective in the earliest stages but serious late complications require high doses of intravenous penicillin or ceftriaxone . Some sequelae respond well to antibiotic therapy while others such as chronic arthritis or advanced central nervous system disease may not . Anti-B . burgdorferi antibodies appear to be protective in certain experimental studies but data are limited and inconclusive in humans. Aust Vet J, 1990 Jul, 67(7), 258 - 60 Treatment of virulent footrot with lincomycin and spectinomycin; Venning CM et al.; A mixture of lincomycin and spectinomycin was investigated as a treatment for footrot in sheep . In a controlled clinical trial 92.5% of acute and chronic cases of virulent footrot were cured following a single intramuscular injection of a mixture containing 50 mg lincomycin and 100 mg spectinomycin/ml at a dose rate of 1 ml/10 kg bodyweight . No improvement in clinical response was observed in groups of sheep treated on 3 successive days with this dose rate nor in another group treated once at a dose rate 1 ml/3.3 kg bodyweight . Cure effectiveness of each of the 3 treatment groups relative to untreated controls was 89%, 95% and 95% . Efficacy of lincomycin/spectinomycin was compared with that of penicillin/streptomycin in the treatment of footrot on 2 farms in south western New South Wales . Assessments made 14 to 17 d after treatment showed that on one farm all 122 ewes treated with lincomycin/spectinomycin had recovered while 170 of 175 ewes treated with penicillin/streptomycin recovered in the same period . On the second farm 87 of 90 ewes treated with lincomycin/spectinomycin recovered, compared with 184 of 190 sheep in the same flock treated with penicillin/streptomycin . Supportive footbathing did not seem to improve the clinical response in either treatment group and the paring done was sufficient only to establish diagnosis and to remove grossly overgrown horn. Biochem J, 1990 Jul 1, 269(1), 247 - 53 Homocitrate synthase from Penicillium chrysogenum . Localization, purification of the cytosolic isoenzyme, and sensitivity to lysine; Jaklitsch WM et al.; Subcellular fractionation of cell-free extracts obtained by nitrogen cavitation showed that Penicillium chrysogenum Q176 contains a cytosolic as well as a mitochondrial homocitrate synthase activity . The cytosolic isoenzyme was purified about 500-fold, and its kinetic and molecular properties were investigated . Native homocitrate synthase shows a molecular mass of 155 +/- 10 kDa as determined by gel filtration and a pH of 4.9 +/- 0.1 as determined by chromatofocusing . The kinetic behaviour towards 2-oxoglutarate is hyperbolic, with Km = 2.2 mM; with respect to acetyl-CoA the enzyme shows sigmoidal saturation kinetics, with {S}0.5 = 41 microM and h = 2.6 . The enzyme was inhibited strongly by L-lysine (Ki = 8 +/- 2 microM; 50% inhibition by 53 microM at 6 mM-2-oxoglutarate), competitively with 2-oxoglutarate, in protamine sulphate-treated and desalted cell-free extracts and in partially purified preparations . The extent of this inhibition was strongly pH-dependent . Both isoenzymes are equally susceptible to inhibition by lysine . The same inhibition pattern is shown by the enzyme from strain D6/1014A, which is a better producer of penicillin than strain Q176. J Chromatogr, 1990 Jun 27, 510, 149 - 54 Rapid protein purification using phenylbutylamine-Eupergit: a novel method for large-scale procedures; Kasche V et al.; Electrophoretic desorption was used to compare the protein binding capacities of some hydrophobic adsorbents {the phenylbutylamine (PBA) derivatives of Eupergit C and agarose and Phenyl-Sepharose} for low-pressure chromatography . The highest capacity was observed for the bifunctional adsorbent PBA-Eupergit . The hydrophobically adsorbed proteins can be selectively desorbed by decreasing the pH of the eluent due to electrostatic repulsion between positive charges on the adsorbed proteins and positively charged secondary amines on the adsorbent . This was used to purify 1500 U penicillin amidase from E . coli homogenates per gram wet weight of PBA-Eupergit in 50 adsorption-desorption cycles without organic solvents (greater than 90% yield, purification factor = 5.3). J Chromatogr, 1990 Jun 27, 510, 115 - 21 Novel media for chromatography and immobilization using a radiation grafting technique; Muller-Schulte D; Radiation grafting onto polyamide and poly(vinyl alcohol) was performed using different vinyl monomers . This grafting technique permits the synthesis of carrier media with a wide range of physical and chemical properties . A number of immobilization tests with antibodies and enzymes e.g., penicillin acylase, glucose isomerase and formate dehydrogenase, are described, exhibiting binding capacities which are distinctly higher than those achieved with commercial media . The epoxy- and isocyanate-activated grafted copolymers were used for the affinity chromatographic separation of insulin, factor VIII and human serum albumin using antibodies as affinity ligands . The radiation-modified media allow a high antibody coupling, thus overcoming drawbacks of currently available commercial media . The separation of blood group antibodies can be performed by using novel antibody-specific oligosaccharide ligands, which permit a much more specific separation than protein G coupled media. Eur J Biochem, 1990 Jun 20, 190(2), 365 - 9 pH-induced insertion of the amphiphilic alpha-helical anchor of Escherichia coli penicillin-binding protein 5; Phoenix DA et al.; By treating vesicles prepared from Escherichia coli K12 with various reagents, we have investigated the mechanism by which penicillin-binding protein 5 anchors to the inner membrane . The results indicate that there are two forms of anchoring; one which is inaccessible to urea and probably inserted into the bilayer and one which is accessible . Association of the accessible form with the membrane seems to involve significant hydrophobic interaction and this form is triggered to undergo reversible 'insertion' by a decrease in pH. Brain Res, 1990 Jun 11, 519(1-2), 65 - 72 Biphasic action of dextrorphan on penicillin induced bursting in rat hippocampal slice; Aryanpur J et al.; Effects of dextrorphan (DX), a metabolite of the over-the-counter antitussive, dextromethorphan, were investigated in rat hippocampal slices exposed to the epileptogenic agent penicillin . At 50 microM and 100 microM concentrations dextrorphan suppressed late components of the epileptiform CA1 field potential elicited by afferent electrical stimulation, and partially suppressed the intracellularly recorded paroxysmal depolarization shift . These effects were not due to non-specific changes in cell excitability, since resting cell membrane potential, input resistance, and the ability of cells to fire action potentials in response to direct depolarizing current were unaffected . The depressant effect of 100 microM dextrorphan was probably due to actions at the NMDA receptor, since pretreatment with the competitive NMDA antagonist D-APV prevented any further depressant effects of dextrorphan in this model . In contrast, at a 10 microM concentration DX enhanced the amplitude of evoked epileptiform field potentials and intracellularly recorded EPSPs . These findings support a role for dextrorphan and similar agents as anticonvulsants at high concentrations, but raise a caution regarding possible excitatory actions of dextrorphan at low concentrations. Antimicrob Agents Chemother, 1990 Jun, 34(6), 1020 - 5 Role of sodium in protection by extended-spectrum penicillins against tobramycin-induced nephrotoxicity; Sabra R et al.; Salt depletion is known to potentiate aminoglycoside nephrotoxicity, while salt replacement attenuates it . Recent studies have shown that ticarcillin protects against tobramycin and gentamicin nephrotoxicity . It has been suggested that this protection is due to an interaction between ticarcillin and the aminoglycoside . However, it can also be explained by the salt load associated with ticarcillin administration . This study was conducted to examine this question . Tobramycin was administered to eight groups of rats at 100 mg/kg per day intraperitoneally for 10 days . Group 1 rats were salt depleted, while group 2 rats were on a normal salt diet . Rats in groups 3 through 8 were also salt depleted but received, in addition, the following interventions intraperitoneally: group 3, ticarcillin, 300 mg/kg per day (0.37 to 0.39 meq of Na supplement per day); group 4, ticarcillin, 300 mg per day (1.56 meq of Na supplement per day); group 5, ticarcillin, 300 mg/kg per day, and NaCl supplement (1.17 to 1.19 meq/day), resulting in a total load of 1.56 meq/day; group 6, piperacillin, 400 mg/day (0.76 meq of Na supplement per day and equimolar to the ticarcillin dose {300 mg/day} in group 4 rats); group 7, piperacillin, 400 mg/day, and NaCl supplement (0.8 meq/day) for a total Na load of 1.56 meq/day; and group 8, 1.56 meq of Na per day as NaCl . Rats in groups 2, 4, 5, 7, and 8, which received a normal salt diet or its equivalent Na supplement, had no significant change in creatinine clearance (CLCR) over the 10-day period . The remaining groups sustained significant reductions in CLCR, as follows: group 1, -53.0% (P < 0.05); group 3, -66.2% (P < 0.05); group 6, -79.8% (P < 0.05) . A positive correlation was found between the concentration of tobramycin in the kidneys and the percent change in CLCR at the end of the study . Concentrations of drugs in plasma were highest in group 1 rats, lowest in the rats in groups in which protection was observed, and moderately elevated in the remaining groups of rats . The results of this study suggest the following: (i) that the protective effect of ticarcillin against tobramycin nephrotoxicity is secondary to the obligatory sodium load associated with it, (ii) pharmacokinetic and pharmacodynamic interactions between salt and tobramycin are proposed to explain this effect, (iii) the nephrotoxicity of tobramycin is probably related to the degree of accumulation of the drug in the kidney, and (iv) an in vivo interaction between tobramycin and ticarcillin does not contribute to the protective effect of the penicillin but may influence concentrations in plasma, especially under conditions of severe renal impairment. J Vet Pharmacol Ther, 1990 Jun, 13(2), 179 - 85 The effect of phenylbutazone on the plasma disposition of penicillin G in the horse; Firth EC et al.; A pilot study in two ponies showed that the plasma concentrations of intramuscularly administered procaine penicillin were higher if phenylbutazone was administered concurrently . In two other trials, each involving five horses, intravenous sodium penicillin was administered with and without concurrent intravenously injected phenylbutazone, and procaine penicillin was injected intramuscularly with and without oral phenylbutazone . In both cases the plasma concentrations of penicillin were higher when phenylbutazone was given . The pharmacokinetic parameters indicated that the effect was probably due to a lower peripheral distribution because the penetration of penicillin into the tissues was greatly reduced. Hear Res, 1990 Jun, 46(1-2), 95 - 9 Organic acids do not alter the cochlear effects of ethacrynic acid; Rybak LP et al.; Previous studies have shown a reduction of the ototoxicity of furosemide in chinchillas pretreated with organic acid transport inhibitors . The current studies were designed to investigate whether such a protective effect could be observed in chinchillas receiving ethacrynic acid . Chinchillas weighing 400-600 g were injected with saline followed by ethacrynic acid 12.5 mg/kg i.v . (controls) or one of three organic acids (probenecid, penicillin G and or sodium salicylate) 50 mg/kg i.v., thirty minutes prior to ethacrynic acid injection (experimentals) . Endocochlear potential (EP) and compound action potential of the eighth nerve (CAP) elicited by click stimuli were simultaneously monitored before and after injection in both groups . The mean change in EP and CAP findings are consistent with observations by other investigators of the actions of these loop diuretics in the isolated loop of Henle . In the latter tissues, the 'furosemide-like loop diuretics' appear to have a different mechanism of action than does ethacrynic acid . It appears from the findings of the present study that the actions of furosemide and ethacrynic acid on the cochlea are by different mechanisms as well. Tijdschr Kindergeneeskd, 1990 Jun, 58(3), 94 - 9 {Chorea mollis, a rare variant of chorea minor}; Bernsen PL et al.; A 15-year-old boy was admitted at age 10 because of muscle weakness, choreatic involuntary movements, and a profound hypotonia . He was diagnosed as having chorea mollis, a rare variant of Sydenham's chorea . He made a full recovery and received prophylaxis with monthly injections of benzathinebenzyl penicillin for the next 5 years . Six months after discontinuation of the prophylaxis he had a recurrence . The choreatic movements were successfully treated with haloperidol . However, a hypotonia and mild psychiatric symptoms still persist one year later . The clinical course, observed in our patient, is in concordance with the results of recent studies, reporting, that a number of patients with Sydenham's chorea may be left with mild to moderate neurologic and psychiatric sequelae. J Am Acad Dermatol, 1990 Jun, 22(6 Pt 1), 1061 - 7 The spectrum of syphilis in patients with human immunodeficiency virus infection; Gregory N et al.; Five patients infected with the human immunodeficiency virus (HIV) with unusual manifestations of syphilis are reported . The high prevalence of HIV seropositivity among our patients with syphilis, the rapid progression to tertiary disease, the increased severity of the clinical manifestations, inappropriate antibody responses to infection, relapse without reexposure despite "adequate" treatment, and lack of response to penicillin therapy have been observed in these and in other patients . Data are presented to explain these unusual observations. Genitourin Med, 1990 Jun, 66(3), 202 - 4 Tumorous syphilid; Lee ES et al.; An unusual form of secondary syphilis, characterised by oozing tumours on the forehead and scalp concomitantly with plaques in the genital area, is presented . The patient was diagnosed as having secondary syphilis by dark-field examination, serologic tests for syphilis, and demonstration of spirochetes in the tissues by the immunoperoxidase technique with avidin-biotin peroxidase complex . Treatment with benzathine penicillin led to rapid resolution of the skin lesions one month later . This case of tumorous syphilid, a variant of papular syphilid, which appears not to have been described in the literature previously. Genitourin Med, 1990 Jun, 66(3), 159 - 64 Syphilis intervention in pregnancy: Zambian demonstration project; Hira SK et al.; Despite availability of simpler serologic tests for syphilis and near cure with penicillin, unacceptably high prevalence of infectious maternal syphilis exist in many developing countries, including Zambia . It is the foremost risk factor for mid-trimester abortions, stillbirths, prematurity and morbidity and mortality among infants born with congenital syphilis in Zambia . An intervention project was conducted in Lusaka aimed at demonstrating the effectiveness of new health education methods and prenatal screening for syphilis in reducing the adverse outcomes during pregnancy . During pre-intervention phase, approximately 150 consecutive pregnant women from each of the three study and the three control centres were recruited when they presented in labour at the University Teaching Hospital . The intervention phase lasted for one year at the three study centres during which new methods of health education were introduced to improve early attendances during pregnancy . Also, on-site syphilis screening was performed twice during pregnancy and seroreactive women, and in many cases their sexual partners, were treated by the existing prenatal clinic staff . During the post-intervention phase the steps of pre-intervention phase were repeated to evaluate the impact of intervention . Overall, 8.0% of women were confirmed seroreactive for syphilis; there was no difference between the study and the control centres (p greater than 0.05) . Fifty seven percent (132/230) of syphilitic pregnancies ended with an adverse outcome, that is, abortion (RR 5.0), stillbirth (RR 3.6), prematurity (RR 2.6) and low birth weight (RR 7.8) . The overall risk of adverse outcomes due to syphilis was 8.29 (95% confidence interval 6.53, 10.53) . The new methods of health education were effective and the percentage of women who had their first prenatal visit under 16 weeks of gestation improved from 9.4 to 42.5 . Although screening and treatment during intervention was suboptimal, the adverse outcomes attributable to syphilis were reduced to 28.3%; this is almost a two-third reduction when compared with 72.4% of adverse outcomes at control centres (p < less than 0.001) . The intervention is culturally and politically acceptable in Zambia . The cost of each prenatal screening is US$0.60 and of averting each adverse outcome US$12 . In countries with high rates of syphilis, there is an urgent need for STD control and Maternal and Child Health (MCH) programmes to pool their resources together to revitalise the prenatal carePIP: Researchers at the University Teaching Hospital in Lusaka, Zambia implemented their syphilis intervention project in 3 phases: preintervention phase (September 1985-January 1986), intervention phase (February 1986-January 1987), and postintervention phase (February-June 1987) . To evaluated the effectiveness of the project, they followed 491 women from 3 periurban health centers serving as study centers and 434 from 3 similar control centers . 8% of all women tested positive for syphilis which was lower than seroprevalence for prenatal patients in 1980 and 1983 (12.5% and 12.8% respectively) . Before intervention, 9.4% of the women visited a health center for the 1st prenatal visit before 16 weeks gestation . Following health education during the intervention phase, this percentage climbed to 42.5% . Health workers conducted a syphilis test on 58.6% and 14.3% of the women during their 1st visit to a study center and control center respectively . Prior to intervention, adverse outcomes occurred in 58% of syphilitic pregnancies . Total relative risk (RR) for adverse outcomes stood at 8.29 . Specifically, RR was 7.76 for low birth weight, 5.03 for abortion, 3.57 for stillbirth, and 2.61 for premature birth . 2.2% of the syphilitic pregnancies resulted in congenital syphilis . Before penicillin was available for treatment these percentages were 20-40% abortions, 20-30% stillbirths, and 25% congenital infections . After the intervention phase, syphilitic pregnancies resulted in 28.3% adverse outcomes (p.001) . The percentage of adverse outcomes at the control centers stood at 72.4% . Further, nonsyphilitic pregnancies resulted in 11.1% adverse outcomes before intervention and 8.1% following intervention (p.05) . This study showed that syphilis intervention is effective and not costly (US$12 to prevent each adverse outcome) . Jpn J Psychiatry Neurol, 1990 Jun, 44(2), 424 - 5 Effect of complete section of corpus callosum and massa intermedia on feline penicillin-induced thalamic focus; Soga T et al.; ECoG and depth EEG changes before and after the complete section of CC and MI were investigated in the Pc-induced thalamic focus model . The results suggested that the mesencephalic reticular formation might be necessary for the generalization and maintenance of ictal discharges from the thalamic focus in cats. P N G Med J, 1990 Jun, 33(2), 159 - 60 A case of pseudoanaphylactic reaction to intramuscular procaine penicillin G (Hoigne's syndrome); Phelps G et al.; A personal record of a pseudoanaphylactic reaction to procaine penicillin G is presented, together with a brief discussion of the topic . Since procaine penicillin is widely used in Papua New Guinea the reaction may be more common than is generally realized . The reaction is not a true anaphylaxis and is probably caused by the procaine component after inadvertent intravenous injection of the drug. Biokhimiia, 1990 Jun, 55(6), 1124 - 31 {Kinetic characteristics and enantioselective action of penicillinase in the hydrolysis reaction of N-phenylacetyl derivatives of 1-aminoethylphosphonic acid and its esters}; Mironenko DA et al.; Penicillin acylase from E . coli (EC 3.5.1.11) was found to hydrolyze N-phenylacetylated 1-aminoethylphosphonic acid and its esters . The enzyme preferentially converts the R-form of the substrates: the ratios of the bimolecular rate constants of penicillin acylasecatalyzed hydrolysis of R- and S-forms of 1-(N-phenylacetamino)-ethylphosphonic acid and its dimethyl- and diisopropyl-esters are 58000, 2300, 1800; these derivatives were shown to have the greatest values of the catalytic constants for enzymatic hydrolysis of all known substrates for penicillin acylase: 237, 148 and 134 s-1; the corresponding Km values are 3.7 10(-5), 6.8 10(-4) and 6.2 10(-4) M at pH 7.0 . The kinetics of enzymatic hydrolysis of 1-(N-phenylacetamino)-ethylphosphonic acid was investigated up to high degrees of conversion . The inhibition of penicillin acylase by high concentrations of the R-form of the substrate (with substrate inhibition constant of 0.07 M) and competitive inhibition by the reaction product, phenylacetic acid (Ki = 3.5 10(-5) M), was observed. Semin Dermatol, 1990 Jun, 9(2), 178 - 84 Sexually transmitted diseases and enteric infections in the male homosexual population; Law C; There are certain special considerations in the management of sexually transmitted diseases (STDs) in homosexual men, with the impact of human immunodeficiency virus (HIV) infection on the presentation, diagnosis, and management of certain STDs just becoming apparent recently . Rectal and pharyngeal gonorrhea are usually asymptomatic and also more difficult to treat . The serological diagnosis of syphillis may be unreliable in acquired immunodeficiency syndrome (AIDS) patients, and HIV-seropositive homosexual men may be at risk of accelerated progression to neurosyphilis, despite treatment with benzathine penicillin . Chlamydia trachomatis is infrequently detected in patients with proctitis so therapy should be directed only at culture-positive cases . Herpes simplex is usually severe and persistent in immunosuppressed patients and may be further complicated by the development of acyclovir-resistance . Concurrent HIV infection may be associated with increased infectivity of homosexual chronic hepatitis B carriers, but milder hepatic injury and reduced efficacy of hepatitis B vaccines and immodulatory or antiviral agents . Although there is some concern regarding the possibility of increased risk of anal cancer in homosexual men, conservative management of human papilloma-virus-associated conditions is advised . The carriage of Entamoeba histolytica in this group is rarely associated with any deleterious effects and treatment should be directed only at symptomatic patients in whom other enteric pathogens have been excluded. J Antibiot (Tokyo), 1990 Jun, 43(6), 684 - 91 Biosynthesis of benzylpenicillin (G), phenoxymethylpenicillin (V) and octanoylpenicillin (K) from glutathione S-derivatives; Ferrero MA et al.; "In vitro" synthesis of benzylpenicillin and phenoxymethylpenicillin has been carried out by direct N-acylation of 6-aminopenicillanic acid (6-APA) with S-phenylacetyl- and (S-phenoxyacetyl)glutathione . The reactions were catalyzed by the enzyme acyl-CoA: 6-APA acyltransferase (AT) from Penicillium chrysogenum and in both cases the synthesis of antibiotics was enhanced by CoA . Penicillin K, a natural penicillin, was also synthesized "in vitro" by incubating (S-octanoyl)glutathione, 6-APA and AT, but in this case the formation of antibiotic required the presence of CoA . Furthermore, benzylpenicillin was obtained from (S-phenylacetyl)cysteinylglycine and 6-APA, suggesting that some intermediates of the gamma-glutamyl cycle are directly involved in the biosynthesis of penicillins . To explain "in vivo" formation of this beta-lactam antibiotic, a biosynthetic pathway which includes several glutathione-S-derivatives and a non-enzymatic reaction, is proposed. Brain Res Bull, 1990 Jun, 24(6), 765 - 8 NMDA receptor antagonists attenuate a portion of the penicillin-induced epileptiform burst; Watson GB et al.; In the CA1 region of the rat hippocampal slice, epileptiform activity was induced by the GABAA antagonist penicillin (PEN, 3.4 mM) . The competitive N-methyl-D-aspartate (NMDA) receptor antagonists D-2-amino-7-phosphonoheptanoate (D-AP7) and D-2-amino-5-phosphonovolerate (D-AP5) attenuated extracellularly recorded evoked burst duration, the number of population spikes per evoked bursts and the frequency of spontaneously occurring bursts, but did not affect the sum of the population spike amplitudes or the evoked burst coastline measures due to increases in amplitude of the remaining secondary population spikes . Intracellular recordings showed that many of the secondary action potentials in the PEN burst were decreased in amplitude and broadened in duration, perhaps due to spike inactivation . D-AP7 allowed these secondary action potentials to increase in amplitude, which could explain the increases in secondary population spike amplitude seen extracellularly . Decrements in stimulus strength can mimic the effect of D-AP7 on PEN bursts . These data suggest that there is a portion of the PEN-induced epileptiform burst which is sensitive to NMDA antagonists. J Chromatogr, 1990 May 16, 507, 177 - 85 Determination of penicillin G in milk by high-performance liquid chromatography with automated liquid chromatographic cleanup; Moats WA; Specific confirmatory tests are needed to identify and quantify beta-lactam antibiotic residues detected in milk at levels of less than 10 parts per 10(9) (ppb) by screening tests . A liquid chromatographic method for penicillin G was developed using the liquid chromatography system for cleanup as well as analysis . Milk was deproteinized with two volumes of acetonitrile . The acetonitrile was extracted with hexane-methylene chloride (1:1) and the remaining water layer was concentrated by evaporation . The water layer (2 ml = 5 ml milk) was injected onto a Polymer Laboratories PLRP-S column using a WISP autosampler with the solvent, 0.01 M pH 7.0 phosphate buffer (A) . Penicillin G was eluted with acetonitrile (B) gradient A-B (100:0) (0-3 min)-(40:60) (25 min) . Penicillin G eluted as a narrow band in less than 0.5 min . A narrow fraction containing penicillin G was collected and rechromatographed on the same type of column at low pH (1.96) . This effectively separated penicillin G from interferences . Recoveries were 92 +/- 9% with a sensitivity limit near 2 ppb . The approach used is applicable to determination of other beta-lactam antibiotics but specific conditions for analysis must be determined for each one . The cleanup procedure can be automated using an autosampler, gradient controller, and fraction collector. Brain Res, 1990 May 7, 515(1-2), 87 - 93 Substantia nigra-mediated anticonvulsant action: a possible role of a dopaminergic component; La Grutta V et al.; A number of neural pathways may mediate nigral control of epilepsy . According to the literature, a GABAergic nigrotectal pathway may be responsible for the control exerted by the substantia nigra on the diffusion of discharges toward spinal targets, while the nigrothalamic projection may transfer nigral influence on premotor neocortical epilepsy . Since there is probably an anatomical nigrohippocampal pathway arising from dopaminergic cells in the substantia nigra, we tested the effects of stimulating the substantia nigra pars compacta (SNpc) on focal hippocampal epilepsy induced by penicillin injection in the cat . The possibility of dopamine involvement was further tested by studying the effects of intraperitoneal injection of haloperidol, a dopamine receptor blocking agent on nigrohippocampal influences, while to verify the precise site of action, in other groups of cats, sulpiride and apomorphine (D-receptor antagonist and agonist, respectively) were locally administered in the dorsal hippocampus . Furthermore, modifications of hippocampal epileptiform EEG were studied in control conditions and following SNpc electrolytic lesions . Results showed a strong nigral suppressive effect on focal hippocampal epilepsy . Nigral stimulation induced a significant decrease in both frequency and amplitude of hippocampal spikes, which disappeared either about 10 min after i.p . injection of haloperidol 1 mg/kg or about 5 min after intrahippocampal administration of sulpiride, and did not return during a further hour or more of experimental observation . It should be emphasized that in the absence of nigral stimulation, both haloperidol and sulpiride did not modify hippocampal spike frequency . Apomorphine application to dorsal hippocampus induced a marked reduction of hippocampal epileptiform activity parallel to the effect observed during SNpc stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) Ann Acad Med Singapore, 1990 May, 19(3), 413 - 5 Secondary syphilis presenting with optic perineuritis and uveitis; Lim SH et al.; We describe a 40 year-old man with optic perineuritis due to secondary syphilis . This condition which is due to inflammation of the optic nerve sheath is often mistaken for papilloedema or papillitis . We discuss its diagnosis and stress the importance of recognising it because it is easily treated by a course of Penicillin. Indian Pediatr, 1990 May, 27(5), 447 - 52 Empyema in infancy and childhood; Padmini R et al.; A study of 108 cases of empyema during 18 months period showed the incidence of empyema to be 2.17% . Staph . aureus (17.6%) was the common causative organism . Response to a combination of cloxacillin and gentamicin was better than that of crystalline penicillin and gentamicin . Only 30.3% cases needed intercostal drainage for more than 2 weeks . Almost 43% cases could be discharged by 3-4 weeks after hospitalisation and 38.1% by 30-57 days . The mortality rate was 12.1% . Among the survivors, excluding 8 children who left against medical advice, all had complete recovery excepting one child in whom AFB was isolated and who developed bronchiectasis and recurrent hemoptysis, inspite of antituberculous treatment . Age of the child, antibiotic combination given and nutritional status appear to be the main factors influencing the recovery and prognosis. Allergol Immunopathol (Madr), 1990 May-Jun, 18(3), 141 - 8 Study of various immunological parameters in the diagnosis of allergy to penicillin G and its derivatives; Prieto Lopez C et al.; The objective of this paper was to draw up an efficient and safe study protocol to diagnose allergy to beta-lactam antibiotics . Seven hundred and fifty patients with clinical histories suggesting penicillin allergy were studied . RAST to penicilloyl G/V, skin tests with PPL, MDM, penicillin G and ampicillin, epicutaneous tests with differed type reactions and a provocation test (in case of the negative results of the other tests) were performed on the patients . The incidence of this pathology is very low (6.5%) and atopic patients do not present greater predisposition to suffer from it than the general population . By carrying out RAST and skin tests with PPL, MDM, penicillin G and ampicillin we arrived at the diagnosis, in the anaphylactic type charts, in 97.5% of the cases . In reactions of a differed type, by performing patch tests we arrived at the diagnosis in 50% of the cases. J Clin Microbiol, 1990 May, 28(5), 1057 - 9 Isolation, identification, and characterization in Israel of Brucella melitensis biovar 1 atypical strains susceptible to dyes and penicillin, indicating the evolution of a new variant; Banai M et al.; During characterization by conventional biotyping tests of numerous Brucella melitensis isolates obtained in Israel in the last 2 years, we identified several strains of the biovar 1 serotype that are atypically susceptible to dyes and penicillin . Their coisolation from two brothers in a family that rears sheep and from the milk of one of their sheep and the prevalence of such strains in two distinct geographical zones in Israel provide epidemiological support for the notion that a new variant has been identified. Drug Saf, 1990 May-Jun, 5(3), 168 - 78 Immunotoxic side-effects of drug therapy; Mitchell JA et al.; Adverse reactions to drugs in which an immune mechanism is responsible for toxicity have been described as idiosyncratic . Understanding these toxic effects is important to enable the identification of patients at risk . The specific toxic side effects considered are heparin-induced thrombocytopenia, penicillin-induced haemolytic anaemia, hepatitis as a result of halothane and tienilic acid therapy, quinine- and quinidine-dependent thrombocytopenia, methyldopa-induced haemolytic anaemia and immune-complex disease following administration of hydralazine, procainamide and penicillamine . The molecular mechanisms of immunotoxicity are presented where such information is available although more than one effect may contribute to the observed pattern of toxicity . The initial events leading to antibody production in certain individuals in response to drug therapy are not understood and, in many of the examples described, antibody production occurs in some patients who do not subsequently experience clinical problems . Clinically serious adverse effects involving immune reactions are infrequent, and a range of genetic and environmental circumstances need to be present simultaneously in an individual before toxicity develops . The ability to metabolise a particular drug has been shown to be one major predisposing factor in toxicity; the immunocompetence of the patient is likely to be another . Both of these considerations are subject to genetic and environmental controls, including infection and disease. J Urol, 1990 May, 143(5), 1012 - 4 Disseminated actinomycosis presenting as a testicular mass: a case report; Jani AN et al.; Actinomycosis of the testicle is a rare clinical entity . A review of the literature reveals only 7 case reports . Patients require prolonged therapy with antibiotics, usually penicillin . Many patients with less severe forms of the disease improve on antibiotics alone . Surgical intervention is reserved for confirming the diagnosis, treatment of abscesses, excision of sinus tracts and drainage . We report case 8 in the literature and review the previous reports. Fiziol Zh SSSR Im I M Sechenova, 1990 May, 76(5), 595 - 603 {Respiratory regulation during neuronal hyperactivation of the respiratory center}; Kryzhanovskii GN et al.; The responses of breathing and of respiratory neurons to microinjections of penicillin into the respiratory center area were studied in anesthetized and spontaneously breathing rats . The injections caused different alterations of the respiration, of the activity of respiratory neurons and their spatial distribution, and initiated respiratory moments of apneustic and gasping types . the hyperactivation of the respiratory center neurons by penicillin seems to cause a reversible development of pathological types of respiration. Mol Gen Genet, 1990 May, 221(3), 322 - 30 Cloning, characterization of the acyl-CoA:6-amino penicillanic acid acyltransferase gene of Aspergillus nidulans and linkage to the isopenicillin N synthase gene; Montenegro E et al.; The penDE gene encoding acyl-CoA:6-amino penicillanic acid acyltransferase (AAT), the last enzyme of the penicillin biosynthetic pathway, has been cloned from the DNA of Aspergillus nidulans . The gene contains three introns which are located in the 5' region of the open reading frame . It encodes a protein of 357 amino acids with a molecular weight of 39,240 Da . The penDE gene of A . nidulans shows 73% similarity at the nucleotide level with the penDE gene of Penicillium chrysogenum . The A . nidulans gene was expressed in P . chrysogenum and complemented the AAT deficiency of the non-producer mutants of P . chrysogenum, npe6 and npe8 . The penDE gene of A . nidulans is linked to the pcbC gene, which encodes the isopenicillin N synthase, as also occurs in P . chrysogenum . Both genes show the same orientation and are separated by an intergenic region of 822 nucleotides. Przegl Dermatol, 1990 May-Jun, 77(3), 193 - 6 {Incidence and the results of treatment of beta-lactamase-positive gonorrhea with spectinomycin (trobicin)}; Wojtowicz U et al.; Beta-lactamase-positive gonorrhoea was rather sporadic in Poland . In spring 1988 a marked rise was observed in the proportion of therapeutic failures in the treatment of gonorrhoea with procaine penicillin (4.8 million u) with probenecid among patient treated in the outpatient clinic of the Venereology Institute in Warsaw . The cause was infection with beta-lactamase producing gonococci . Up to June 1989 beta-lactamase production ability was tested in gonococci cultured from 415 patients (363 men and 52 women) with positive results in 73 cases (61 men and 11 women) that is in 18% . Most (85%) patients were treated with spectinomycin (2 g intramuscularly in men and 4 g in women in one dose) with cure in all cases . Treatment with tetracycline (2 g daily for 7 days) given to 12 patients failed in 2 cases . These results, if confirmed in other parts of the country, will cause the necessity of revision of the presently accepted indications for gonorrhoea treatment with penicillin with probenecid as the basic method. Indiana Med, 1990 May, 83(5), 330 - 1 Making a rash diagnosis: amoxicillin therapy in infectious mononucleosis; Pauszek ME; The ampicillin analog, amoxicillin, can potentially produce the same hypersensitivity reaction as the ampicillin . The case of a patient treated with amoxicillin for a sore throat, who later presented with a rash, is reviewed . Infectious mononucleosis was considered and then supported by a positive mono spot . It would appear therefore that amoxicillin can produce the same hypersensitivity reaction as ampicillin in the setting of acute infectious mononucleosis . The clinical decision to use antibiotics in acute pharyngitis is complicated by the identical presentation of both viral and bacterial illnesses . If empiric therapy is elected, the incidence of hypersensitivity reaction is less common with penicillin or tetracycline compared to ampicillin or its analog, amoxicillin. Gastrointest Endosc, 1990 May-Jun, 36(3), 247 - 52 Whipple's disease: endoscopic aspects before and after therapy; Geboes K et al.; This report describes the utility and the advantages of endoscopy in diagnosing and following the course of Whipple's disease . Sixteen patients, diagnosed over a period of 22 years, were identified via pathology records and retrospectively reviewed . Five patients were diagnosed before 1980 by means of peroral suction biopsy of the small intestine . The 11 patients diagnosed after 1980 all had upper gastrointestinal endoscopy and endoscopic small intestinal biopsies . Gross endoscopic lesions were observed in 9 of the 11 patients and disappeared in 5 of 6 treated patients at 6 months . These lesions include erosions, yellow plaques, and a pale yellow shaggy mucosa . The latter two lesions are macroscopically suggestive of Whipple's disease . After endoscopic "healing," periodic acid-Schiff-positive macrophages remained present in the endoscopic biopsies for years . The patients were followed for a median period of 4 years and 5 months . All patients were treated with antibiotics (eight tetracycline alone, four tetracycline + streptomycin + penicillin, and four trimethoprim) . Five patients (four of the tetracycline alone group, none of the trimethoprim group) relapsed 2 to 11 years after the initial treatment. FEBS Lett, 1990 Apr 24, 263(2), 237 - 40 Identification of the binding sites of benzyl penicilloyl, the allergenic metabolite of penicillin, on the serum albumin molecule; Yvon M et al.; Tryptic digests of fragment A299-585 of penicilloylated serum albumin obtained from two penicillin-treated patients or prepared by in vitro conjugation, were analyzed by a tandem immunoaffinity reversed-phase HLPC . Determinations of benzyl penicilloyl groups (BPO) were performed on the different fractions . Three BPO containing peptides were identified by their amino acid sequence and the bound BPO were located on lysines 432, 541 and 545 . Six major BPO binding sites were thus identified on the whole albumin molecule . All of them are lysine residues and correspond to a limited number of definite structures in which lysine and serine residues appear to be closely associated. J Chromatogr, 1990 Apr 20, 504(2), 359 - 67 Precolumn derivatization technique for high-performance liquid chromatographic determination of penicillins with fluorescence detection; Iwaki K et al.; A precolumn derivatization method was developed for the high-performance liquid chromatographic (HPLC) determination of penicillins using fluorescence detection . Penicillins were derivatized by a two-step reaction, the beta-lactam ring being opened by hydrolysis in aqueous sodium carbonate solution in the first step to give a secondary amine functionality, and the secondary amino group being reacted with 7-fluoro-4-nitrobenzo-2-oxa-1,3-diazole in the second step to give a fluorescent derivative . The resulting reaction mixture was injected directly onto a reversed-phase column and analysed by HPLC . At a penicillin concentration of 10 micrograms/ml, the precision (relative standard deviation) ranged from 1.49 to 2.20% . In the concentration range 0.2-100 micrograms/ml, a linear response was observed . The detection limits of this method were 30-85 ng/ml for five different penicillins at a signal-to-noise ratio of 3:1 . The proposed method was applied to the determination of penicillins added to serum following pretreatment by deproteinization and removal of compounds containing amino functionalities with a cation-exchange resin. Eur J Pharmacol, 1990 Apr 10, 179(1-2), 111 - 8 The effect of GABA on the frog optic tectum is sensitive to ammonium and to penicillin; Mazda GY et al.; Excitatory postsynaptic potentials (termed U1 and U2) were extracellularly recorded from the frog optic tectum in vitro following electrical stimulation of the contralateral optic nerve . Gamma-Aminobutyric acid (GABA) and glycine elicited a large and sustained enhancement of these synaptic waves . In the presence of the Cl- transport inhibitor ammonium (NH+4) the effects of GABA or glycine were progressively reduced to about 50% of their initial action without changes in the control synaptic waves . In 50% Cl- media the depression of GABA and glycine responses by NH+4 was more intense . Other Cl- transport inhibitors such as bumetanide, piretanide and 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonate (SITS) were inactive against responses to GABA or glycine . Penicillin, a Cl- channel blocker, antagonized the action of GABA and glycine, while increasing the amplitude of the U2 waveform . The present results provide pharmacological evidence in support of the Cl- dependence of the unusual action of GABA or glycine in facilitating excitatory synaptic transmission in the optic tectum. Med Clin (Barc), 1990 Apr 7, 94(13), 502 - 4 {Syphilitic arthro-osteitis}; Blanch J et al.; We report a black female with past history of sexual promiscuity who developed arthroosteitis of clavicula and sternoclavicular joint and cranial osteitis during secondary syphilis . Spirochaeta were identified in the material from osteoarticular biopsy . The patient was treated with benzathine penicillin, 2,400,000 U weekly for three weeks . There was a complete clinical recovery . We emphasize the uncommon occurrence of osteoarticular involvement in secondary syphilis and the exceptional character, according to the literature, of the finding of spirochaeta in the biopsy material . We discuss the differential diagnosis and we review the literature on secondary syphilis . We suggest that syphilis should be considered in the differential diagnosis of any acute arthritis or osteitis, particularly when the involved joint is the sternoclavicular and the patient is sexually promiscuous. Dtsch Med Wochenschr, 1990 Apr 6, 115(14), 534 - 8 {Bone pain in adults as the first symptom of late congenital syphilis}; Rauh G et al.; A 20-year-old woman developed multifocal bone pain . Diagnostic radiology revealed thickened periosteum, and syphilis serology was positive (T . pallidum haemagglutination test 1:5120) . She also had discrete signs of congenital syphilis, with retinitis pigmentosa and Hutchinson's incisors . Skeletal scintigraphy demonstrated increased uptake even in radiologically unremarkable bones . The bone pain decreased after four-week administration of 1 M units of penicillin G daily . Scintigraphy one year later showed regression of the increased uptake, skeletal radiology did not reveal significant changes . This case shows that late manifestations of congenital syphilis still occur today . The stigmata of such an infection can be minute and easily missed . Skeletal scintigraphy is better for demonstrating active bone involvement than conventional radiology. Br J Psychiatry, 1990 Apr, 156, 554 - 9 Acute psychotic reactions and stress response syndromes following intramuscular aqueous procaine penicillin; Ilechukwu ST; Acute non-anaphylactic reactions to procaine penicillin include fear of death, sensations of disintegration, perceived changes of body shape, and visual and auditory hallucinations . Fragments of the original reaction experience, or elaborations of it, feature prominently in a chronic syndrome which persists if the initial reaction is not supported emotionally or professionally . The cultural acceptance of the reality of 'mysterious' forces played a role in the syndrome . Compatible diagnostic labels were panic disorder, post-traumatic disorder, mixed phobic disorder, and depressive illness . The observed period prevalence rate is 5.9 per 1,000. Sheng Li Xue Bao, 1990 Apr, 42(2), 141 - 8 {Effect on electroacupuncture on experimental epilepsy--power spectrum analysis of EEG}; He XP et al.; The present study was undertaken to investigate the effect of electroacupuncture (EA) on electroconvulsive shock (ECS) and penicillin-induced convulsions in rats, using power spectrum analysis technique . Under quiet state, delta and theta bands were found to be predominant in the power spectrum of spontaneous EEG's with the peak of the main power in the delta band . During ECS and penicillin-induced convulsions, the power percentage of the delta band decreased, while those of alpha and beta bands increased . The bands with the peak of the main power shifted to the right, and the total power was distinctly enhanced . No marked change in background EEG activity was observed during EA stimulation . In the case of EA plus ECS or penicillin-induced convulsions, the power percentage of the delta band increased, while those of alpha and beta bands decreased . The peak of the main power returned to the delta band with a decreased total power . The compressed power spectrum array showed distinct suppression of convulsions by EA audio-visually . These results suggest that EA enables the EEG to synchronize and enhances the inhibitory process of the brain, thereby plays its anticonvulsant role. J Trop Pediatr, 1990 Apr, 36(2), 56 - 62 Symptom-free intervals in sicklers: does pneumococcal vaccination and penicillin prophylaxis have a role? el-Hazmi MA, Bahakim HM, Babikar MA, al-Swailem AM, Warsy AS. To investigate the combined effect of pneumococcal vaccination and penicillin prophylaxis on the progress of sickle cell disease, two groups of sickle cell disease patients, presenting with severe clinical manifestations of the disease were selected as cohorts . One group was vaccinated with the polyvalent pneumococcal vaccine and given penicillin prophylaxis, while the other group was not given the vaccine and penicillin . Clinical manifestations, frequency of hospitalization, crises and blood transfusion requirements, haematological parameters, and differential counts were recorded for each patient in the two groups . The 'severity index' of the sickle cell disease was calculated for each patient . No significant differences were encountered in the values of the haematological parameters except for the white cell count which was significantly higher in the non-vaccinated group . However, the frequency of hospitalization, crisis, and blood transfusion were significantly higher in the non-vaccinated group compared to the vaccinated group . Clinical symptoms frequently associated with severe sickle cell disease, were also encountered at a higher frequency in the non-vaccinated group . These results show that pneumococcal vaccination and penicillin prophylaxis increase the crisis-free interval in sickle cell disease patients, and play a significant role in decreasing the morbidity associated with sickle cell disease. J Neurophysiol, 1990 Apr, 63(4), 832 - 40 Laminar analysis of extracellular field potentials in rat vibrissa/barrel cortex; Di S et al.; 1 . A 16-channel electrode array was used to record simultaneously extracellular laminar field potentials evoked by displacement of contralateral vibrissa from vibrissa/barrel cortex in five rats . Current source-density (CSD) analysis combined with principal component analysis (PCA) was used to determine the time course of laminar-specific transmembrane currents during the evoked response . 2 . The potential complex consisted of biphasic fast components followed by long-lasting slow waves . It began with activity in supragranular cells consisting of a source in layers I-II and a sink in layers IV-V; this was followed by activation of the infragranular cells with a paired sink and source in layers I-IV and V-VI, respectively . The slow-wave sequences also began in the supragranular cells followed by infragranular neurons . 3 . We propose that the fast components reflect sequential intralaminar depolarization processes, and the slow waves, hyper- or repolarization processes . These results suggest that a basic neuronal circuit, consisting of sequential activation of the supragranular and then the infragranular pyramidal cells, gives rise to the field potentials evoked by physiological stimulation . This is consistent with our previous studies of direct cortical responses (DCR) and pathological discharges of the penicillin focus. Am J Nurs, 1990 Apr, 90(4), 68 - 70 Syphilis . A new look at an old killer; Nettina SL; Thirty-four-year-old George Talbot was admitted to your medical/surgical unit with deep vein thrombosis of his left leg, probably related to intravenous drug abuse . So it's no surprise that Mr . Talbot is receiving heparin IV . Today, however, you notice that his physician has prescribed one dose (2.4 million units) of benzathine penicillin IM . You're not sure why until you check the patient's lab work . Mr . Talbot's rapid plasma reagin (RPR) test was reactive . The physician is treating Mr . Talbot for syphilis. Int J Syst Bacteriol, 1990 Apr, 40(2), 160 - 4 Mycoplasma somnilux sp . nov., Mycoplasma luminosum sp . nov., and Mycoplasma lucivorax sp . nov., new sterol-requiring mollicutes from firefly beetles (Coleoptera: Lampyridae); Williamson DL et al.; Strain PYAN-1T (T = type strain), which was isolated from a pupal gut of the firefly beetle Pyractonema angulata, and strains PIMN-1T and PIPN-2T, which were isolated from guts of adult Photinus marginalis and Photinus pyralis fireflies, respectively, were demonstrated to be sterol-requiring mollicutes . Cells of the three strains were shown by electron and dark-field microscopy to be small, pleomorphic, nonhelical, nonmotile bodies surrounded by single membranes . No evidence of a cell wall was observed, and the organisms were not susceptible to 500 U of penicillin per ml . The three strains grew rapidly in SP-4 broth medium . Strains PIMN-1T and PIPN-2T grew in medium supplemented with bovine serum fraction, but strain PYAN-1T did not . All three strains grew on solid media when the cultures were incubated aerobically, but only strains PYAN-1T and PIPN-2T formed colonies when anaerobic conditions were employed . The three strains catabolized glucose but hydrolyzed neither arginine nor urea . All of the strains grew at temperatures of 18 to 32 degrees C; strains PYAN-1T and PIMN-1T also grew at 10 degrees C . The optimal temperature for growth for strains PYAN-1T and PIPN-2T was 30 degrees C; strain PIMN-1T grew equally well at 30 or 32 degrees C . None of the three strains grew at 37 degrees C . The genome sizes of strains PYAN-1T, PIMN-1T, and PIPN-2T were about 527 (478 to 589), 570 (480 to 630), and 762 (635 to 871) megadaltons, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) Pharmacol Biochem Behav, 1990 Apr, 35(4), 999 - 1001 Inhibitory influence of excitatory amino acid antagonists on penicillin-induced epileptiform bursting in rat hippocampal slices; Sagratella S et al.; The inhibitory influence of excitatory amino acid (E.A.A.) antagonists such as kynurenic acid, 2-amino-5-phosphonopentanoic acid (AP5), cis-2,3-piperidine dicarboxylic acid (cis-2,3 PDA) and (+)-5-methyl-10,11,-dihydro-5H-dibenzo(a,d)cyclo-hepten-5,10-imine maleate (MK 801), has been studied on the epileptiform activity elicited in rat hippocampal slices, bathed in penicillin (1 mM) . The rank of the inhibitory potency was: MK 801 greater than kynurenic acid greater than cis 2,3 PDA greater than AP5 . Moreover, only MK 801 was able to block the last population spike of the penicillin-induced epileptiform bursting in 100% of the experiments . The data indicate that the antiepileptic activity of E.A.A . antagonists on the penicillin epileptiform bursting in CA1 pyramidal cells is low and limited, indicating that the hippocampal area is not the primary site of the anticonvulsant activity of E.A.A . antagonists. Proc Natl Acad Sci U S A, 1990 Apr, 87(7), 2823 - 7 Altering enzymatic activity: recruitment of carboxypeptidase activity into an RTEM beta-lactamase/penicillin-binding protein 5 chimera; Chang YH et al.; The D-Ala-D-Ala carboxypeptidases/transpeptidases (penicillin-binding proteins, PBPs) share considerable structural homology with class A beta-lactamases (EC 3.5.2.6), although these beta-lactamases have no observable D-Ala-D-Ala carboxypeptidase activity . With the objective of recruiting such activity into a beta-lactamase background, we have prepared a chimeric protein by inserting a 28-amino acid segment of PBP-5 of Escherichia coli in place of the corresponding region of the RTEM-1 beta-lactamase . The segment thus inserted encompasses two residues conserved in both families: Ser-70, which forms the acyl-enzyme intermediate during beta-lactam hydrolysis, and Lys-73, whose presence has been shown to be necessary for catalysis . This chimera involves changes of 18 residues and gives a protein that differs at 7% of the residues from the parent . Whereas RTEM beta-lactamase has no D-Ala-D-Ala carboxypeptidase activity, that of the chimera is significant and is, in fact, about 1% the activity of PBP-5 on diacetyl-L-Lys-D-Ala-D-Ala; in terms of free energy of activation, the chimera stabilizes the transition state for the reaction to within about 2.7 kcal/mol of the stabilization achieved by PBP-5 . Furthermore, the chimera catalyzes hydrolysis exclusively at the carboxyl-terminal amide bond which is the site of cleavage by D-Ala-D-Ala carboxypeptidase . Though containing all those residues that are conserved throughout class A beta-lactamases and are thought to be essential for beta-lactamase activity, the chimera has considerably reduced activity (approximately 10(-5) on penams such as penicillins and ampicillins as substrates . As a catalyst, the chimera shows an induction period of approximately 30 min, reflecting a slow conformational rearrangement from an inactive precursor to the active enzyme. J Bacteriol, 1990 Apr, 172(4), 2187 - 90 Dissociation of the ampicillin-induced lysis of amino acid-deprived Escherichia coli into two stages; Pisabarro AG et al.; The ampicillin-induced lysis of amino acid-deprived relA+ Escherichia coli was dissociated into two separate stages . The early stage ("priming") requiring the presence of ampicillin apparently involved the interaction of ampicillin with a target penicillin-binding protein . The later stage ("lysis induction") was ampicillin independent and required only chloramphenicol to relax the RelA-dependent control of peptidoglycan hydrolase activity. In Vitro Cell Dev Biol, 1990 Apr, 26(4), 369 - 78 Alpha-1, alpha-2, and beta adrenergic signal transduction in cultured uterine myocytes; Phillippe M et al.; The following studies were undertaken to develop a cultured uterine myocyte model which would allow further clarification of the adrenergic signal transduction mechanisms utilized by these myocytes . After mechanical removal of the endometrium, rabbit uterine myocytes were isolated by an overnight enzymatic disaggregation using collagenase and DNase I . The isolated myocytes were maintained in culture in 75-cm2 flasks containing Waymouth's MB 751/1 medium-10% fetal bovine serum along with 10(-8) M estradiol, penicillin, streptomycin, and Fungizone . The phase contrast and electron micrographic appearance of these cells was consistent with that previously reported for smooth muscle myocytes in culture . Immunocytochemical studies utilizing monoclonal anti-alpha-smooth muscle actin antibodies confirmed the presence of smooth muscle actin in these cultured myocytes . Western blot studies similarly confirmed the presence of alpha-smooth muscle actin in rabbit myometrial tissue and the cultured myocytes, both the primary and F1 generation . After prelabeling the myocytes with {3H}inositol, adrenergic stimulation experiments demonstrated alpha-1 receptor mediated stimulation of inositol phosphates . Beta receptor stimulation experiments confirmed cAMP production in these cultured myocytes, and the ability of clonidine, an alpha-2 agonist, to inhibit forskolin stimulated cAMP production confirmed the presence of functional alpha-2 adrenergic receptors in these myocytes . In conclusion, these cultured rabbit uterine myocytes have provided an in vitro model which can be utilized to further clarify the adrenergic receptor signal transduction mechanisms in genital tract smooth muscle. Indian J Med Res, 1990 Apr, 92, 120 - 7 Seizure susceptibility & intra rectal sodium valproate induced recovery in developing undernourished rats; Sharma SK et al.; The seizure threshold and therapeutic potential of intrarectal sodium valproate were studied in young developing normal and undernourished rats, using the penicillin model . Undernourished rats were highly susceptible to seizure discharge . They exhibited generalised electrocortical inhibition and repeated episodes of epileptic discharges even after temporary neuronal recovery . Delayed spontaneous and drug induced neuronal recovery, low spike frequency and amplitude (P less than 0.001) reduced background EEG and marked electrocortical silence in response to intrarectal (25 mg/kg) sodium valproate treatment, was observed in the undernourished animals . Rehabilitated animals exhibited partial neuronal recovery which was related to the improvement in body weight . Analysis of spike frequency, spike amplitude and neuronal recovery time showed that both normal and undernourished animals behaved in a similar fashion at lower doses of penicillin (2.5 to 15 IU) . Significant differences in the electrophysiological parameters were observed between the two groups at higher doses of penicillin (20 to 30 IU). Harefuah, 1990 Apr 1, 118(7), 392 - 3 {Anaphylactic reaction to oral penicillin}; Guberman D; Anaphylactic reactions are often caused by parenterally administered penicillin . However, oral penicillin can also produce severe reactions . A 34-year-old man developed anaphylaxis 30 minutes after oral intake of 400,000 units of phenoxymethyl penicillin . He developed hypotension and angioedema which responded well to subcutaneous adrenalin and to intravenous fluids. Rev Esc Enferm USP, 1990 Apr, 24(1), 31 - 40 {An experimental study of the tissue reactions in rats induced by different concentrations of benzathine penicillin G}; Massad MR et al.; The search of scientific answers to problems due to procedures involving professional actions is a permanent challenge to the nurses committed with the improving of nursing care . In face of the intensive muscle soreness provoked by penicillin G benzatin shots, an experimental evaluation of this procedure was carried out in order to observe the influences of concentration and volumes used . This evaluation could give some insights to improve the nursing care, particularly those linked to the manipulation of the penicillin injection . The study was performed in the Faculty of Medicine of the University of Sao Paulo, in 27 Male Wistar rats . After the injection of the drug or saline solution in the right and left limb, respectively, the animals were sacrificed and the muscles in which the solution were injected were histologically examined . The use of penicillin provoked intensive inflammatory reaction, the peak intensity being attained after 48 hours . A remaining effect lasted about thirty days . The inflammatory reaction was similar for the three concentrations of penicillin . Nevertheless, the present research does not bring data that should modify the current injection procedures. J Formos Med Assoc, 1990 Apr, 89(4), 275 - 80 Clinical features of rheumatic carditis in adolescents and adults; Vun PN et al.; A retrospective study on the clinical features of acute rheumatic fever (RF) with carditis in 45 patients, 15 years of age and older (range 15-61), is described . Nineteen patients were seen at initial attack; the remaining 26 patients (28 recurrences) were admitted because of RF recurrence . Of the total 47 episodes, carditis was manifested by a significant murmur without previous RF or any known rheumatic heart disease in 40%; change in the character of a murmur under observation or the appearance of a new murmur in 15%; and acute pericarditis in 19% . Congestive heart failure of recent onset was noted in 85% of the episodes, while classical polyarthritis or polyarthralgia occurred in 57% . The aortic valve was newly damaged or preexisting aortic regurgitation worsened in 12 episodes . Twenty-nine patients were followed for 1/2-16 years . Of 11 patients with an initial attack who were maintained on regular prophylaxis (intramuscular benzathine penicillin 1,200,000 units every 4 weeks), the mitral valve murmur disappeared in 3 and none of the patients had recurrence . Of the remaining 18 patients with no or incomplete prophylaxis, 1 died from congestive heart failure 6 months later, and 3 had recurrences with involvement of the aortic valve . In conclusion, RF with carditis in adolescents and adults in our practice at the National Taiwan University Hospital is likely to show more cardiac problems and complications than that seen in the West . Although active rheumatic carditis among this patient population is relatively uncommon, recurrences with subsequent involvement of the aortic valve (aortic regurgitation) do occur.(ABSTRACT TRUNCATED AT 250 WORDS) Neurosci Lett, 1990 Mar 26, 111(1-2), 99 - 101 Paroxysmal depolarization shifts induced by bicuculline in CA3 neurons of hippocampal slices: suppression by the organic calcium antagonist verapamil; Straub H et al.; Organic calcium antagonists have been reported to abolish epileptic neuronal discharges elicited by pentylenetetrazol and penicillin . It was tested whether the organic calcium antagonist verapamil is able to suppress also paroxysmal depolarization shifts (PDS) induced by bicuculline . This is of special interest, since bicuculline is assumed to produce PDS by blocking GABAergic synaptic inhibition . The experiments were performed on CA3 neurons of hippocampal slices (guinea pig) . Verapamil (40, 60, and 80 microM) reduced amplitude, duration and frequency of appearance of PDS until the generation of PDS failed . The results indicate that calcium currents are also involved in bicuculline PDS, and that bicuculline exerts its epileptogenic action, at least in part, on extrasynaptic sites. FEBS Lett, 1990 Mar 26, 262(2), 342 - 4 Acyl coenzyme A: 6-aminopenicillanic acid acyltransferase from Penicillium chrysogenum and Aspergillus nidulans; Whiteman PA et al.; A study of the final stages of the biosynthesis of the penicillins in Penicillium chrysogenum has revealed two types of enzyme . One hydrolyses phenoxymethyl penicillin to 6-aminopenicillanic acid (6-APA) . The other, also obtained from Aspergillus nidulans, transfers a phenylacetyl group from phenylacetyl CoA to 6-APA . The acyltransferase, purified to apparent homogeneity, had a molecular mass of 40 kDa . It also catalyses the conversion of isopenicillin N (IPN) to benzylpenicillin (Pen G) and hydrolyses IPN to 6-APA . In the presence of SDS it dissociates, with loss of activity, into fragments of ca 30 and 10.5 kDa, but activity is regained when these fragments recombine in the absence of SDS. Vet Med (Praha), 1990 Mar, 35(3), 155 - 64 {Use of semisynthetic penicillin in the treatment of infectious mastitis in cows during the dry period}; Vasil' M et al.; During two years in a herd of dairy cows with an average number of 94 cows the effects on infection level were investigated of single nonselective antibiotics treatment of cow's udder in the dry period . The treatment influenced favourably the results of complex periodic three-months examinations: --level of infection with infectious mastitis was reduced from 38.3% to 9.8%; --occurrence of clinical forms of mastitis dropped from 17.4% to 5.9%;--occurrence of NK-test positive reactions decreased from 55.8% to 21.8% . An investigation into therapeutic efficiency of three intramammary preparations revealed the highest total therapeutic effect of Stapenor retard (Bayer, FRG)--93.2%; Syntarpene 500 (Polfa, Poland) had the total therapeutic efficiency of 92.6% and the efficiency of Oxaclene foam (Spofa, CSSR) made 86.5% . The results demonstrate good efficiency of the method because the levels of mastitis infection in the herd were positively influenced, and excellent therapeutic efficiency of semisynthetic penicillins containing intramammary preparations used for mastitis treatment of dairy cows in the dry period. Neurology, 1990 Mar, 40(3 Pt 1), 541 - 3 Neurosyphilis in AIDS patients: initial CSF VDRL may be negative; Feraru ER et al.; We report 2 HIV-seropositive patients with neurosyphilis whose initial CSF VDRL tests were negative . The CSF VDRL became positive after 12 days of IV penicillin treatment for syphilitic meningitis in the 1st patient . The 2nd patient developed syphilitic polyradiculopathy and a positive CSF VDRL 3 months after treatment with IV penicillin . Serial CSF VDRL determinations may be required in AIDS patients when a diagnosis of neurosyphilis is suspected. Obstet Gynecol, 1990 Mar, 75(3 Pt 1), 375 - 80 The Jarisch-Herxheimer reaction complicating syphilotherapy in pregnancy; Klein VR et al.; Thirty-three gravidas with syphilis were monitored with hourly vital signs and examinations for 24 hours after treatment with benzathine penicillin G . Fifteen (45%) of the subjects had a Jarisch-Herxheimer reaction, including all three, 12 of 20 (60%), and none of ten of those with primary, secondary, and latent syphilis, respectively . The most common symptoms were fever (73%), uterine contractions (67%), and decreased fetal movement (67%) . The signs or symptoms began 2-8 hours after treatment; fevers peaked at 6-12 hours post-therapy and the events usually abated by 16-24 hours after treatment . Uterine contractions and decreased fetal activity began concurrent with maternal fever in eight of ten women reporting contractions . Transient late decelerations were detected in three of 11 monitored patients . Three of the women with Jarisch-Herxheimer reactions delivered infants with congenital syphilis, including one stillbirth, but none of those without a detectable reaction had fetal treatment failures . Prostaglandin F2 alpha and prostacyclin metabolites were elevated transiently in the one subject studied, suggesting their role in mediating the cardiovascular and uterine events in the post-treatment period . The Jarisch-Herxheimer reaction in pregnancy is similar in frequency, character, and intensity to that in nonpregnant adults, but gravidas may have increase uterine activity and transient alterations in fetal well-being . The pregnant patient with a severely affected fetus with congenital syphilis may experience preterm labor, preterm delivery, or fetal death in association with the Jarisch-Herxheimer reaction. Nihon Kyobu Shikkan Gakkai Zasshi, 1990 Mar, 28(3), 481 - 6 {Foreign body-induced bronchial actinomycosis with severe stenosis that must be distinguished from lung cancer}; Umeki S et al.; A 59-year-old woman who accidentally swallowed a foreign body (fish bone) 9 months ago was admitted to our hospital because of cough, hemosputum and sleep wheezing for two months . Chest roentgenograms and chest CT scanning revealed severe stenosis of the right lower lobe bronchus and truncus intermedius, suggesting lung cancer . Bronchoscopic examination revealed an intrabronchial foreign body . The biopsy specimen from granulation tissue revealed bronchial actinomycosis . The foreign body was removed bronchoscopically after an extensive chemotherapy with penicillin G (for actinomycosis) and prednisolone (for granulation tissue of the bronchus) . This was considered to be a rare case of bronchial actinomycosis without a pulmonary lesion produced by a foreign body. Hautarzt, 1990 Mar, 41(3), 155 - 7 {Morphaea profunda}; Buchner SA et al.; A 47-year-old woman with a solitary morphoea profunda on the flexor aspect of the left thigh is described . Clinically the lesion is characterized by a circumscribed, deeply indurated sclerotic plaque . The main histopathological features were sclerotic collagen changes and a striking accumulation of inflammatory cells in the deep dermis as well as in the subcutaneous tissue . Plasma cells and T- and B-lymphocytes were the predominant cellular components of the infiltrate . The patient had an elevated serum titre of antibodies to Borrelia burgdorferi . The patient was treated with penicillin, which brought about a remarkable improvement . These findings provide further support for the concept that in some cases morphoea profunda may be a manifestation of Borrelia infection. Prim Care, 1990 Mar, 17(1), 183 - 94 The politics of STDs . Dwindling resources for a growing problem; Wertheimer WJ; Although the 1920s witnessed little progress in combating sexually transmitted diseases, the staggering dimensions of the problem had nonetheless been clarified . Increased reticence, declining government commitment, and a continued insistence on solving the venereal problem through moral uplift rather than medical means all combined to ensure that these diseases reached epidemic proportions . Thus Dr . Allan Brandt, in his book No Magic Bullet: A Social History of Venereal Disease in the United States since 1880, described the post World War I era of the social hygiene movement in the United States . Today, nearly 70 years later and more than 40 years after the widespread availability of penicillin, virtually every one of the more than 30 recognized sexually transmitted diseases (STDs) still defies control in the United States . Cases of STDs are increasing at dramatic rates, at enormous societal and personal cost . The epidemic of AIDS has diverted needed funds, personnel, and other resources from the nation's programs of research, training, prevention, and control of STDs . Ironically, the epidemics of STDs, the diseases themselves and the sexual and drug-using behaviors surrounding them, are now fueling the HIV epidemic . Although it is often said that education is the only prevention for AIDS, in fact there is another important and cost-effective component of HIV prevention: the control of other STDs . STDs are not only public health concerns, but issues of biomedical research, economics, access to care, public and professional education, drug use, poverty, and last but not least politics . Their prevention and control demands new research approaches, the development of necessary expertise, and a major and sustained investment of resources. Zh Vyssh Nerv Deiat Im I P Pavlova, 1990 Mar-Apr, 40(2), 362 - 8 {Unilateral epilepsy and the asymmetry of postepileptic sleep}; Aslanova MA et al.; In the paper the analysis is given of "penicillin" epilepsy in animals (cats) in conditions of different forms of deafferentation of one of the halves of the fore brain . It is shown, that in conditions of combined section of one half of the operculum of the midbrain and commissural systems of the endbrain, diencephalon and midbrain, under large doses of penicillin, unilateral convulsive activity is recorded in summate electrical activity of one of the brain halves at the side of the midbrain lesion . After the completion of unilateral organization of the epileptic process an asymmetrical sleep takes place: at the side, at which epileptiform activity was recorded, a more deep phase of the sleep appears than in the opposite brain half. Nihon Kyobu Shikkan Gakkai Zasshi, 1990 Mar, 28(3), 448 - 56 {Respiratory infections caused by Branhamella catarrhalis in 5 different hospitals}; Matsumoto K et al.; During 9 months (from January 1988 to September 1988), we experienced 82 patients (94 episodes) of respiratory infections with Branhamella catarrhalis in 5 different hospitals . There were 11 patients of acute bronchitis, 8 patients of pneumonia, 56 patients of chronic bronchitis (68 episodes), 3 patients of bronchiectasis, 3 patients of bronchial asthma with infection and chronic pulmonary emphysema in one patient . Ten cases of acute bronchitis and 3 cases of pneumonia had a recent history of common cold, with no underlying disease . There were 68 episodes of acute exacerbation of chronic bronchitis, the highest among 94 episodes of all respiratory infection . In chronic bronchitis the single pathogen B . catarrhalis was more than B . catarrhalis associated with other pathogens . H . influenza was associated with B . catarrhalis in in most cases of polymicrobial infection . beta-lactamase producing B . catarrhalis was 71% and oral penicillin was not effective in 8 cases of infection by beta-lactamase producing strains . These results show that B . catarrhalis is very important as a common pathogen of respiratory infection. Curr Genet, 1990 Mar, 17(3), 213 - 21 Cloning and expression of a hybrid Streptomyces clavuligerus cefE gene in Penicillium chrysogenum; Cantwell CA et al.; A hybrid cefE gene was constructed by juxtaposing promoter sequences from the Penicillium chrysogenum pcbC gene to the open reading frame of the Streptomyces clavuligerus cefE gene . In S . clavuligerus the cefE gene codes for the enzyme penicillin N expandase {also known as deacetoxycephalosporin C synthetase (DAOCS)} . To insert the hybrid cefE gene into P . chrysogenum the vector pPS65 was constructed; pPS65 contains the hybrid cefE gene and the Aspergillus nidulans amdS gene . The amdS gene encodes acetamidase and provides for dominant selection in P . chrysogenum . Protoplasts of P . chrysogenum were transformed with pPS65 and selected for the ability to grow on acetamide medium . Extracts of cells cultivated in penicillin production medium were analyzed for penicillin N expandase activity . Penicillin N expandase activity was detected in approximately one-third of the transformants tested . Transformants WG9-69C-01 and WG9-61L-03 had the highest specific activities of penicillin N expandase: 4.3% and 10.3%, respectively, relative to the amount of penicillin N expandase in S . clavuligerus . Untransformed P . chrysogenum exhibited no penicillin N expandase activity . Analysis of the penicillin V titer revealed that WG9-61L-03 produced titers equal to that of the recipient strain while the amount of penicillin V produced in WG9-69C-01 was reduced by five fold. Appl Biochem Biotechnol, 1990 Mar, 23(3), 187 - 203 Thermodynamics of industrially-important, enzyme-catalyzed reactions; Tewari YB; The thermodynamics of 10 industrially-important, enzyme-catalyzed reactions are examined . The reactions discussed are: the conversions of penicillin G to 6-amino-penicillinic acid using the enzyme penicillin acylase; starch to glucose using amylases; glucose to fructose using glucose (xylose) isomerase; cellulose to glucose using cellulase; fumaric acid and ammonia to L-aspartic acid using L-aspartase; transcinnamic acid and ammonia to L-phenylalanine using L-phenylalanine ammonia lyase; L-histidine to urocanic acid and ammonia using L-histidine ammonia lyase; lactose to glucose and galactose using lactase; and the reactions catalyzed by amino acylases and proteases . The selection of these processes was based on the economic value of the products and their intrinsic industrial importance . The available thermodynamic properties, such as equilibrium constants, Gibbs energies (delta G degrees), enthalphies (delta H degrees), and heat capacity changes (delta Cp degrees) of these enzyme-catalyzed reactions, are reviewed and summarized . Recommendations are made for future research in this area. Schweiz Rundsch Med Prax, 1990 Feb 20, 79(8), 202 - 6 {Father's medicine of the 40s}; Russbach A; A general practitioner practising from 1940 onwards on the Gruyere region describes visually his former task: permanence on call, daily journeys of 80 km for house calls, often on skis or by sleigh, surgery under most primitive conditions, serious decisions taken lonely, diphtheria-epidemics, frequent tuberculosis, penicillin as a major break-through, picturesque human encounters...A lively testimony of times gone by. Clin Ter, 1990 Feb 15, 132(3), 201 - 2 {Fever caused by penicillin . Description of a clinical case}; Baratta E et al.; A case of drug-provoked fever is described in a scleroderma patient on penicillamine . The drug was withdrawn because of the severity and recurrence of the fever . Both our personal experience and a review of the literature, show this side effect to be markedly less frequent than reported by German researchers. BMJ, 1990 Feb 10, 300(6721), 371 - 4 Assessment of care of children with sickle cell disease: implications for neonatal screening programmes; Milne RI; OBJECTIVE--To assess the quality of care provided by hospitals for young children with sickle cell disease . DESIGN--Retrospective survey . SETTING--Teaching hospital in London . PATIENTS--31 Children (mean age 4 years 4 months, range 4 months to 7 years 5 months) born with sickle cell disease between 1978 and 1985 identified from Hospital Activity Analysis data, an outpatient diagnostic register, and registers of the haematology department . Eight had been diagnosed on neonatal screening and at least four of these had not been followed up . MAIN OUTCOME MEASURES--Aspects of quality of outpatient care (blood testing, clinic attendance, and prophylactic drug treatment) and family care (adequate support and carers' knowledge about the disease) as assessed by reviewing the notes and administering a semistructured questionnaire to the carers, in relation to a devised list of standards deemed necessary to ensure achievement of the aims of screening . RESULTS--There were 93 outpatient attendances during the previous 12 months, but 13 children had not attended at least every six months and four not at all for more than a year . Only eight children had had three of the blood tests considered to be necessary for good care; three had had none . Prophylactic treatment with penicillin and folic acid was erratic; three children with sickle cell anaemia were not receiving regular prophylactic penicillin . IMPLICATION--Diagnosis of sickle cell disease on neonatal screening must be linked with follow up to ensure optimal management. Biochim Biophys Acta, 1990 Feb 9, 1037(2), 133 - 9 Thermodynamic profiles of penicillin G hydrolysis catalyzed by wild-type and Met----Ala168 mutant penicillin acylases from Kluyvera citrophila; Martin J et al.; The Met-168 residue in penicillin acylase from Kluyvera citrophila was changed to Ala by oligonucleotide site-directed mutagenesis . The Ala-168 mutant exhibited different substrate specificity than wild-type and enhanced thermal stability . The thermodynamic profiles for penicillin G hydrolysis catalyzed by both enzymes were obtained from the temperature dependence of the steady-state kinetic parameters Km and kcat . The high values of enthalpy and entropy of activation determined for the binding of substrate suggest that an induced-fit-like mechanism takes place . The Met----Ala168 mutation unstabilizes the first transition-state (E..S not equal to) and the enzyme-substrate complex (ES) causing a decrease in association equilibrium and specificity constants in the enzyme . However, no change is observed in the acyl-enzyme formation . It is concluded that residue 168 is involved in the enzyme conformational rearrangements caused by the interaction of the acid moiety of the substrate at the active site. S Afr Med J, 1990 Feb 3, 77(3), 152 - 3 A return to Conybeare; Dubb A; The chapter on infectious diseases in Conybeare's Textbook of Medicine is reviewed 40 years after the author studied it as a medical student . The sulphonamides were then in general use, penicillin had recently been introduced and there were high hopes for the development of other chemotherapeutic substances . Congenital defects had recently been described in babies born to mothers who contracted rubella in early pregnancy . The varicella-zoster virus had not yet been isolated, chloramphenicol was not available for treating typhoid fever and the cause of infectious mononucleosis was unknown - but in many diseases little has changed . Modern medicine has produced a new spectrum of disease, opportunistic infections, and also a host of resistant organisms. Postgrad Med, 1990 Feb 1, 87(2), 33 - 5, 39, 41 Proving penicillin allergy; Erffmeyer JE et al.; Allergic reactions to penicillin are usually short-lived and reversible, but they can be fatal . What causes these reactions? Can they be avoided? How is the risk of penicillin allergy evaluated? Drs Erffmeyer and Blaiss describe the full spectrum of allergic, immune, and nonimmune reactions to penicillin and discuss how to assess and treat patients with suspected penicillin allergy. Ophthalmology, 1990 Feb, 97(2), 196 - 203 The ocular manifestations of syphilis in the human immunodeficiency virus type 1-infected host; McLeish WM et al.; Nine patients with active ocular or optic nerve involvement by syphilis who also had concurrent human immunodeficiency virus type-1 (HIV-1) infection are described . The ocular manifestations of syphilis led to the discovery of HIV-1 seropositivity in four of nine cases . Fifteen eyes were affected . Ocular manifestations were: iridocyclitis in three eyes, vitreitis in one eye, retinitis or neuroretinitis in five eyes, papillitis in two eyes, optic perineuritis in two eyes, and retrobulbar optic neuritis in two eyes . Three patients diagnosed with acquired immune deficiency syndrome (AIDS) had the worst initial visual acuities . Six of nine patients had evidence of concomitant central nervous syndrome (CNS) involvement with syphilis . Benzathine penicillin was administered intramuscularly to three patients . All three had relapses . Seven of nine patients treated intravenously with high-dose penicillin had dramatic responses to therapy with improvement in vision and serologies and no evidence of relapse . Regimens accepted for the treatment of neurosyphilis appear to be adequate for the treatment of ocular syphilis in HIV-1-infected patients though further long-term follow-up will be required. J Neurophysiol, 1990 Feb, 63(2), 225 - 39 Role of Na-K pump potassium regulation and IPSPs in seizures and spreading depression in immature rabbit hippocampal slices; Haglund MM et al.; 1 . Using the immature (8-12 days postnatal) rabbit hippocampal slice preparation, we investigated regional extracellular potassium concentration {( K+}o) changes that occur during spontaneous and evoked spreading depression (SD) episodes . We report here a difference between the CA1 and CA3 cell populations in the immature hippocampus with regard to 1) resting {K+}o, 2) magnitude of the {K+}o change during seizurelike events and SDs, and 3) susceptibility to SD episodes . Experiments were also performed to elucidate the roles that the Na-K pump and synaptic inhibition play in controlling SD onset, duration, and recovery . We demonstrated a major role for potassium regulation by the Na-K pump and a lesser modulatory role for inhibitory postsynaptic potentials (IPSPs) in preventing SD in the CA3 region . 2 . Simultaneous intra- and extracellular recordings were made in the CA1 and CA3 regions of the immature rabbit hippocampus during spontaneous or evoked SD, while potassium ion-sensitive microelectrodes (K-ISMs) monitored changes in {K+}o . The CA1 region had 1) a higher frequency of spontaneous SD episodes than CA3, 2) a lower threshold to potassium-triggered SD, 3) a longer duration SD episode, and 4) smaller post-SD membrane potential and {K+}o undershoots (below the original resting membrane potential and resting {K+}o) . 3 . During the onset of a SD episode in the CA1 region, the local {K+}o rose either before or at the same time as the membrane potential depolarization . 4 . In the CA3 region, spontaneous ictallike events consisting of tonic cell depolarization with repetitive activity followed by clonic afterdischarges were more likely to occur than SD episodes . During these ictallike episodes, {K+}o rose above the 10- to 12-mM ceiling level reported for adult CNS tissue during seizures . Increases in {K+}o evoked by repetitive stimulation were regulated at a lower level in CA3 (average {K+}o rise to 11.4 mM) than in CA1 (average {K+}o rise to 18.3 mM) . 5 . In CA3, bath application of 10 microM bicuculline or 3.4 mM penicillin did not change the frequency of spontaneously occurring SDs or the SD response threshold to local pressure ejection of 2 M KCl . However, blockade of IPSPs did lead to lower thresholds for SD or seizurelike episodes elicited by stimulation of the mossy fibers . 6 . A single application of ouabain (10 microM) to CA3 by local pressure ejection caused a slow rise in local {K+}o measured with K-ISMs . The ouabain treatment also increased the frequency of spontaneous postsynaptic potential activity and decreased the amplitude and duration of CA3 pyramidal cell afterhyperpolarizations (AHPs).(ABSTRACT TRUNCATED AT 400 WORDS) Transplantation, 1990 Feb, 49(2), 261 - 4 Optimal cardioplegia and 24-hour heart storage with simplified UW solution containing polyethylene glycol; Wicomb WN et al.; Recent work has shown that UW may be better than standard cardioplegic solutions for short-term heart preservation . In this study we have used a rabbit heart model to evaluate a simplified UW solution in which penicillin, dexamethasone, insulin, allopurinol, and adenosine were omitted and 5% polyethylene glycol (PEG20M) was substituted for hydroxyethyl starch . The test systems consisted of 4-hr cardioplegic storage at 15 degrees C with repeated flushing every 30 min for 2 hr and 24-hr hypoxic low-flow microperfusion (3 ml/g/24 hr) at 0 degrees C . Control groups were arrested with a 15-25 ml flush in iced saline and immediately tested . Cardiac output (CO)* after preservation was measured in a working heart model using an acellular perfusate at 37 degrees C at an aortic pressure of 100 cm H2O . The CO (ml/g heart wt/min) were as follows--Controls: St . Thomas II 20.5 +/- 8.3 (5), UW 34.7 +/- 11.7 (16), PEG20M 41.8 +/- 4.4 (14); 4-hr cardioplegia: St . Thomas II 17.4 +/- 0.9 (4), Bretschneider HTK 14.9 +/- 7.0 (4), UW 25.2 +/- 11.5 (9), PEG20M 41.1 +/- 7.8 (8); 24-hr microperfusion: UW 25.4 +/- 11.1 (18), PEG20M 37.1 +/- 8.2 (18) . Following cardioplegic or microperfusion preservation, PEG20M hearts functioned at control levels (P greater than 0.05) and were significantly superior to all other solutions, with approximately double the CO (P less than 0.05, all other groups) . We conclude that for heart preservation, 5 components can be eliminated from UW and substitution of PEG20M for HES appears to have improved its performance. J Invest Dermatol, 1990 Feb, 94(2), 230 - 4 Cultured porcine epithelial grafts: an improved method; Regauer S et al.; An improved method of in vitro cultivation of porcine keratinocytes by which keratinocyte sheets suitable for grafting can be generated rapidly is described . Epidermis from split-thickness porcine skin is enzymatically separated from dermis with 0.25% Dispase solution (37 degrees C) within 3 h, and trypsinized to a single cell suspension . Keratinocytes are grown in Dulbecco-Vogt modified Eagle medium supplemented with 20 ng/ml hydrocortisone, 100 micrograms/ml penicillin, 100 micrograms/ml streptomycin, and 20% (cells from six-month-old pigs) or 10% fetal calf serum (cells from two-month-old pigs) . Freshly isolated keratinocytes are plated at a density of 1.25 X 10(6) cells/ml since their plating efficiency is about 15 times lower than that of human keratinocytes grown under comparable conditions . Primary keratinocytes plated on plastic grow to confluence faster than those plated on lethally irradiated 3T3-J2 feeder layer cells . Porcine keratinocytes grown on plastic reach senescence in the third passage but, when subsequently cultivated on a lethally irradiated 3T3-J2 feeder layer, can be passaged up to seven times . Nevertheless, plating efficiency of second-passage porcine keratinocytes is only about 5%-7%, whereas that of human newborn foreskin keratinocytes is 20%-30% . Confluent stratified primary cultures grown on plastic, or secondary cultures grown on feeder layers, are used for grafting . The sheets are detached with Dispase solution and stapled to vaseline gauze to facilitate handling . Epidermal regeneration from porcine grafts produced by this method has been demonstrated after transplantation to full-thickness wounds excised to muscle fascia in donor animals. Mol Microbiol, 1990 Feb, 4(2), 209 - 19 Cloning and characterization of mepA, the structural gene of the penicillin-insensitive murein endopeptidase from Escherichia coli; Keck W et al.; The putative structural gene mepA of the penicillin-insensitive murein endopeptidase from Escherichia coli was cloned and sequenced . N-terminal sequence determination with the isolated endopeptidase protein showed that this enzyme is coded by the mepA gene and that it is synthesized initially with an N-terminal signal peptide . No significant sequence homology with the other (penicillin-sensitive) murein endopeptidase (dacB) or any other protein was found . The precise chromosomal mapping position of mepA relative to two other genes, aroC and fabB, was shown to be 50.4 min . E . coli strains carrying multicopy plasmids with the mepA gene produced 5-6-fold more endopeptidase and secreted it into the periplasm, where it appeared to function normally in vivo since the release of cell wall peptides into the medium increased in parallel . The transformed cells were, however, not unusually sensitive to penicillin and their murein had a normal degree of cross-bridges. Farmaco, 1990 Feb, 45(2), 203 - 14 E . coli penicillin acylase: purification by affinity chromatography and covalent binding to nylon; Boccu E et al.; Penicillin acylase (EC 3.5.1.11) from E . coli, both in solution and immobilized on solid supports, has been commercially exploited for the large scale production of 6-aminopenicillanic acid (6-APA), which is an important intermediate for the manufacturing of semisynthetic penicillins . In this paper a very simple procedure of penicillin acylase purification is reported, which employs only one affinity chromatographic step (Sepharose-phenylacetic column) . The enzyme was obtained at a high degree of purity and could be used for immobilization on partially hydrolyzed and activated nylon . Since the support is chemically inert and mechanically stable the catalyst can be used several times without any significant loss of activity, making the process of great commercial importance. Br J Oral Maxillofac Surg, 1990 Feb, 28(1), 12 - 5 Prophylactic use of phenoxymethylpenicillin and tinidazole in mandibular third molar surgery, a comparative placebo controlled clinical trial; Happonen RP et al.; A clinical double-blind placebo controlled trial was carried out in 136 patients to test the value of the prophylactic use of phenoxymethylpenicillin and tinidazole in mandibular third molar surgery . The three patient groups were uniform with regard to the background data such as age and weight of the patients and the clinical status of the operated tooth, as well as to the observations made at surgery . No statistically significant differences were found between the study groups in the parameters used for evaluation . The results indicate that neither penicillin nor tinidazole have more effect on postoperative complications following operative extraction of wisdom teeth, than placebo tablets. Schweiz Rundsch Med Prax, 1990 Jan 30, 79(5), 111 - 3 {Weight loss, fever, dyspnea}; Grohe C et al.; A 41-year-old homosexual man complained about weight loss of 14 kg over a period of 6 months . He developed exertional dyspnea and fever up to 39.6 degrees C . The ESR was elevated and the fraction of immature neutrophils increased . Penicillin was administered with no effect, chest X-ray showed basal pulmonary infiltrates, P . carinii was found in bronchioalveolar fluid . HIV-serology was positive . Sulfamethoxazole/trimethoprim (1600/320 mg daily) and 100 mg of prednisolone/die led to reduction of fever . Prevention of P . carinii pneumonia relapse is currently underway with bi-weekly inhalation of pentamidine-isethionate aerosol. Brain Res, 1990 Jan 29, 508(1), 105 - 17 Laminar interactions in rat motor cortex during cyclical excitability changes of the penicillin focus; Barth DS et al.; Laminar interactions between neurons in rat motor cortex during cyclical seizure episodes in the penicillin focus were studied using a combination of current source-density (CSD) and principal component analysis (PCA), combined with computer-based physical modeling . These data suggest that all phases of cyclical seizure phenomena are produced by interactions between two distinct populations of neurons, the same neuronal circuits previously reported to give rise to the direct cortical response (DCR) and electrically evoked interictal penicillin spikes (EIIS) . The first population consists of small pyramidal cells in the supragranular layer, and the second population consists of larger pyramidal cells in the infragranular layers with apical dendrites extending to the cortical surface . The supragranular cells serve as a trigger zone for initiating both spontaneous interictal spikes (IIS) and polyspike bursts (PSB) during seizures . Fast activity in the supragranular cells is typically followed by a hyperpolarizing slow wave that may be the result of Ca2+-activated K+ currents . This slow wave increases during seizures, possibly reflecting changes in extracellular Ca2+ associated with seizure onset and termination . The monophasic response of infragranular cells is similar for both IIS and PSB and consists of a large depolarizing shift followed by a rapid but partial repolarization period and a subsequent gradual repolarization period lasting several hundred milliseconds . The infragranular response is similar in polarity and morphology to the intracellularly recorded paroxysmal depolarization shift (PDS) and may indicate that these deeper neurons are mainly responsible for this phenomena in neocortex . Finally, there is a marked postictal slow oscillation between the supra- and infragranular layers . This oscillation appears first and largest in the supragranular cells and may reflect a disturbance in excitatory feedback in these cells produced by the disinhibitory effect of penicillin, a disturbance capable of pathologically synchronizing the epileptic neuronal aggregate sufficiently for activation of the spike-generating mechanism and subsequent seizures. Rev Neurol (Paris), 1990, 146(1), 41 - 4 {Amyotrophic lateral sclerosis syndrome of syphilitic origin . 5 cases}; el Alaoui-Faris M et al.; We studied 5 cases of syphilitic lateral amyotrophic sclerosis . The diagnosis was based on the presence of a lymphocytic reaction in the CSF and positive VDRL and TPHA reactions in both blood and CSF . Clinically, the disease affected the arms in 3 cases and produced paraplegia in 2 cases . The gradual extension of amyotrophy over several months, the diffusion of electromyographic abnormalities and the finding of spinal cord atrophy at myelography and CT suggested a subacute ischemic mechanism with meningo-myelic arteritis involving the anterior horns . After treatment with penicillin G in high doses, the outcome was constantly favourable, with improvement of motor deficit in 4 cases and stabilisation in 1 case in a 5 to 13 years' follow-up. J Bacteriol, 1990 Jan, 172(1), 63 - 70 Interaction of monoclonal antibodies with the enzymatic domains of penicillin-binding protein 1b of Escherichia coli; den Blaauwen T et al.; Monoclonal antibodies (MAbs) against four different antigenic determinants of penicillin-binding protein (PBP) 1b were used to study the transglycosylase and transpeptidase activities of PBP 1b . Enzyme kinetics in the presence of and without the MAbs were determined, and the synthesized murein was analyzed . Two MAbs against the transglycosylase domain of PBP 1b appeared to inhibit this reaction . One MAb inhibited only the transpeptidase reaction, and one inhibited both enzymatic activities of PBP 1b . The latter two MAbs bound to the transpeptidase domain of PBP 1b . The following major conclusions were deduced from the results . (i) Transpeptidation is the rate-limiting step of the reaction cascade, and it is dependent on the product of transglycosylation . (ii) PBP 1b has only one type of transpeptidase activity, i.e., a penta-tetra transpeptidase activity . (iii) PBP 1b is probably a globular protein which has two intimately associated enzymatic domains. J Bacteriol, 1990 Jan, 172(1), 125 - 35 Localization of penicillin-binding protein 1b in Escherichia coli: immunoelectron microscopy and immunotransfer studies; Bayer MH et al.; We report the localization of penicillin-binding protein 1b (PBP 1b) in Escherichia coli KN126 and in an overproducing construct containing plasmid pHK231 . We used PBP 1b-specific antiserum for the immunoelectron microscopy of ultrathin sections of whole cells and for immunoelectrophoresis of cytoplasm and isolated membrane fractions . We studied ultrathin sections of both glutaraldehyde-fixed cells that had been embedded after progressively lowering the temperature and cryofixed cells that had been freeze-substituted in Lowicryl K4M and HM20 . Most of the PBP 1b-specific label was observed in the inner membrane (IM) and the adjacent cytoplasm, much less was observed in the outer membrane (OM); appreciable amounts were also seen in the bulk cytoplasm . Distribution and intensity of label were both temperature dependent: temperature shift-up to 37 degrees C, causing PBP 1b overproduction in the construct, showed a statistically highly significant increase in label of the IM, including a cytoplasmic zone (of at least 30 nm in depth) adjacent to the IM, a zone we termed the membrane-associated area . Concomitant with the temperature shift-up, a decrease in label density was observed in the bulk cytoplasm . Increased label was also found in IM-OM contact areas (zones of membrane adhesion) . The periplasm did not show significant label . Western blotting (immunoblotting) revealed PBP 1b in most of the isolated membrane fractions; however, the highest label density was found in membrane fractions of intermediate density, supporting the suggestion of an increased concentration of PBP 1b in the membrane adhesion zones . In summarizing, we propose that PBP 1b is present in the membrane-associated area of the cytoplasm, from where proteins (such as PBP 1b or thioredoxin) gain access to their specific insertion sites in the envelope . The use of several methods of immunoelectron microscopy provided the first unequivocal evidence for localization of PBP 1b at membrane adhesion sites . Since such sites are specifically labeled with anti-PBP 1b serum, we hypothesize that they contain parts of the machinery for assembly and growth of the murein layer. Am J Nephrol, 1990, 10(3), 222 - 30 Drug-induced hypersensitivity nephritis: lymphocyte stimulation testing and renal biopsy in 10 cases; Joh K et al.; The pathomorphological and clinical findings were investigated in 10 cases of drug-induced hypersensitivity nephritis . Hypersensitivity due to drugs was strongly suggested by the lymphocyte stimulation test in all patients . The offending drugs included penicillin, cephem derivatives, nonsteroidal anti-inflammatory drugs, and minocycline . All patients developed acute renal failure shortly after administration of regular doses of the drugs . Allergic symptoms plus a raised level of serum IgE or eosinophilia were seen in 7 patients . The remaining 3 patients receiving nonsteroidal anti-inflammatory drugs had no allergic symptoms, but developed severe proteinuria . Eight patients without severe glomerular damage recovered after withdrawal of the offending drugs and temporal dialysis and/or steroid therapy . Renal biopsies revealed tubulitis and tubular epithelial degeneration with interstitial edema as the common characteristic findings . Granulomatous lesions were occasionally observed . Multinucleated giant cells found in the granulomas were positive for LN-3 which is compatible with HLA-DR antigen . The glomeruli appeared normal, except in 2 cases in whom crescentic glomerulonephritis and thrombotic microangiopathy were seen . Our study suggests that the lymphocyte stimulation test and renal biopsy are the most useful means to confirm the diagnosis and provides further evidence for the participation of cell-mediated immunity in the pathogenesis of drug-induced hypersensitivity nephritis. J Perinat Med, 1990, 18(2), 145 - 8 Penicillin-tetracycline prophylaxis in cesarean delivery: prospective and randomized comparison of short and long term therapy; Neuman M et al.; A prospective and randomized study was undertaken to determine the safety and efficacy of low price and discouraging bacterial resistance agents, given for 12 hours versus 72 hours, as prophylaxis at cesarean section . Ninety six patients received penicillin (ten million units) intravenously and tetracycline (0.25 g) intramuscularly at cord clamping and 12 hours postoperatively (table I) . Among them 14% of febrile morbidity was recorded (table II) . Eighty seven patients received the same treatment followed by oral ampicillin (2 g) and tetracycline (1.5 g) per day, for a further 60 hours (table I) . Maternal febrile morbidity was not further reduced by the oral additional treatment (table II) . This regiment prophylactic effect is comparable to previous reported data concerning other protocols, and even better, while expenses are reduced and efficacy for important pathogens such as chlamydia and mycoplasma is obtained . No side effects of the drugs were recorded. Soc Sci Med, 1990, 30(10), 1049 - 63 Sorcery and penicillin: treating illness on a Papua New Guinea island; Lepowsky M; Research on a remote and culturally conservative Papua New Guinea island before and after the introduction of biomedical primary health care in the form of government aid posts shows that beliefs in the supernatural causation of serious illness and death by sorcery, witchcraft or taboo violation remain largely unchanged after a decade . Most islanders first seek treatment from traditional healers who can identify and combat the underlying supernatural causes of illness . A healer, traditional or modern, must be greatly trusted by patient and kin due to fears of sorcery and witchcraft attack, and aid post orderlies, from a different cultural and linguistic group, find it difficult to gain the confidence of the community . Orderlies and other health care providers should not present themselves as being in competition with traditional healers but concentrate on earning the trust of community members . Individuals from the local community should be offered training as aid post orderlies and primary health care workers . The islanders' hierarchy of resort to medical treatment is variable, and biomedicine and traditional healing have not assumed complementary functions . Traditional theories of disease causation and treatment are part of indigenous religious beliefs and thus highly resistant to change . Acceptance of biomedical treatment can occur without rejection of supernatural theories of disease causation . The rate of acceptance may vary among ethnic groups within the same country or region due to underlying cultural or religious differences . The constraints of inter-ethnic differences and of traditional beliefs concerning health and illness within which the health system must function in this case are found in many multi-ethnic developing countries. Scand J Thorac Cardiovasc Surg, 1990, 24(1), 93 - 4 Actinomycosis simulating pulmonary neoplasm in a previously healthy man . Case report; Aarnio P et al.; In a 41-year-old, previously healthy man, a pulmonary opacity presented diagnostic difficulties . Thoracotomy with resection of lung and ribs revealed actinomycosis . Postoperatively the patient responded well to long-term penicillin therapy. Vestn Dermatol Venerol, 1990, (2), 47 - 50 {A clinico-immunological assessment of the efficacy of combined methods of treating patients with different immunopathological forms of focal scleroderma}; Suchkova TN et al.; To help the physicians choose a rational scheme of combined therapy of patients with various immunopathologic forms of focal scleroderma, the authors present a clinical and immunologic assessment of the efficacies of 2 combined therapeutic courses, enzyme immunotherapy and penicillin immunotherapy, as well as of the individual course of tactivin immunotherapy . Inclusion of tactivin in any complex therapeutic scheme appears to be necessary . In patients suffering from the condition for a long time, with multiple foci of involvement, tactivin should be combined with enzymic drugs, like hyaluronidase (lydase) . Enzyme immunotherapy promoted a more active resolution of the skin process . Penicillin<