Penicillin

Rev Esp Cardiol, 1991 Oct, 44(8), 556 - 9
{The management by medical treatment of an intracranial mycotic aneurysm in a patient with infectious endocarditis with negative blood cultures and hypertrophic myocardiopathy}; Anguita M et al.; A case of intracranial mycotic aneurysm due to culture-negative infective endocarditis involving a patient with hypertrophic cardiomyopathy is reported . The patient, a 22-year-old woman with no history of known prior disease, had fever, headache and focal neurologic symptoms 3 days before admission . An echocardiogram performed after admission disclosed an obstructive hypertrophic cardiomyopathy and a gross vegetation on septal leaflet of mitral valve . Cerebral angiography revealed a mycotic aneurysm involving a peripheral branch of the left middle cerebral artery . Causal agent was not identified, and empiric treatment with penicillin G and streptomycin achieved medical cure and disappearance of the aneurysm 2 weeks later . Four months after endocarditis had been cured, the patient was electively operated because of progression of mitral regurgitation . Six months later, she is asymptomatic.

Otolaryngol Head Neck Surg, 1991 Oct, 105(4), 578 - 85
Mucosal changes induced by experimental pneumococcal otitis media are prevented by penicillin V; Hermansson A et al.; Penicillin V (pcV) was administered to 50 rats, either before bacterial challenge (prevention group), or after bacterial challenge but before fulminant purulent acute otitis media (AOM) was established (early treatment group) . Five animals from each group were killed on days 4, 8, and 12, and 2 and 6 months after challenge . Middle ear mucosa was sampled at six different sites and studied in the light microscope . Untreated pneumococcal AOM in the rat has been shown to cause persistent structural changes of the middle ear mucosa . Both in the early treatment group and in the prevention group, the structural changes were diminished, as compared with those of untreated infected controls . The persistent structural changes seen after 6 months in untreated controls were not seen in animals that had received pcV in conjunction with the AOM episode . Though the beneficial effect on the mucosal changes during the first 2 weeks was more pronounced when pcV was given prophylactically, its use as early treatment would seem to be almost as effective in preventing the persistence of mucosal changes.

J Microsc, 1991 Oct, 164 ( Pt 1), 29 - 41
A preparation method of specimens of the fungus Penicillium chrysogenum for ultrastructural and immuno-electron microscopical studies; Muller WH et al.; A combination of cryofixation without pre-treatment, freeze-substitution and low-temperature embedding was used to prepare specimens of Penicillium chrysogenum for electron microscopy . To produce specimens which are thin enough for appropriate cryofixation, the P.chrysogenum colonies were grown between dissected-dialysis tubing on an agar plate, which in addition allowed longitudinal sectioning . In contrast to classical chemical fixation, this preparation procedure resulted in excellent preservation of ultrastructure . Furthermore, the penicillin biosynthetic enzyme acyltransferase could be unequivocally located by immunogold labelling, indicating a preservation of antigenic properties of the specimen . Labelling density was not conspicuously affected when using different freeze-substitution media, but it was reduced after embedding in Epon 812.

Acta Paediatr Scand, 1991 Oct, 80(10), 944 - 52
Monitoring of drug prescriptions for children in the county of Jämtland and Sweden as a whole in 1977-1987; Wessling A et al.; One individual-based (Jamtland) and one population-based (Sweden) monitoring system provided information on the prescription sales of drugs for children in ambulatory care . The overall prescription rate decreased between 1977 and 1987 and it was 20-25% lower in Jamtland than in Sweden as a whole . Antibiotics, drugs for ear, nose and throat diseases and respiratory drugs accounted for three out of four prescriptions . Penicillin V dominated among antibiotics and the prescription rate was stable whereas that of other antibiotics increased . During their first year of life one out of ten children in Jamtland had at least one prescription of antibiotics, during their first five years three out of four children . Prescribing of decongestants, especially systemic, decreased during the study period whereas that of anti-asthmatics increased, partly due to the non-approved use of these drugs for common cough . The results from our study underline the need for pharmaco-epidemiological studies linking prescription data to clinical data in order to answer questions on the rational of present drug treatment practices.

Dtsch Tierarztl Wochenschr, 1991 Oct, 98(10), 393 - 4
{A method for the treatment of oviduct obstruction in cattle using CO2 insufflation into the uterus}; Boitor I et al.; The investigations were carried out on 59 cows from Holstein half-breed, establishing that 8 cows suffered salpinx obstruction (5 cases with unilateral obstruction and 3 cases with bilateral obstruction) . The authors are using an apparatus made by themselves, for insufflation of air in the obstructed uterus, and which is useful in desobstruction treatment, too . For diagnosis, CO2 was introduced inside of uterus . The authors used for treatment PBS (saline phosphate buffer) in addition with penicillin G, hydrocortisone and trypsin . Before air insufflation in uterus there will be infused 10-20 ml 2% Lidocaton . The cows must be examined in oestrus period, or 2 days after PGF2 alfa administration . The gas must be introduced under rectal palpation, and pressure must not be higher than 500 mm H2O column . If there is a permeable oviduct, after 15-20 sec . from gas introduction, ist is possible to palpate the filled oviduct . From ovary we can perceive a rustle produced by gas crossing in abdominal cavity . In case of salpinx obstruction, the treatment must be start as soon as possible . The utilized liquid for treatment will be introduce by gas pressure, inside of uterus and oviducts . Using this method, it managed the repermeability of oviducts at 3 from 8 treated cows . In each case, there were used 3 treatments at 48 h interval . After the second insemination (I.A.) 2 cows remained pregnant.

Biochemistry, 1991 Sep 17, 30(37), 9034 - 40
Refolding and assembly of penicillin acylase, an enzyme composed of two polypeptide chains that result from proteolytic activation; Lindsay CD et al.; The in vitro folding and assembly of penicillin acylase (EC 3.5.1.11) (PA) to active enzyme has been studied . PA is a large bacterial protein (Mr = 86,000) comprising two peptides, alpha and beta, produced by proteolytic processing and activation of a 92-kDa precursor . Proteins that result from proteolytic processing are characteristically difficult if not impossible to refold . Different factors that affect folding and assembly of PA, including pH, ionic strength, and temperature, have been studied . Yields of 60% can be obtained, based on recovery of enzyme activity, together with another 20% of folded and associated monomer with conformation closely similar to that of the active enzyme but with the active site not formed . Evidence is presented for in vitro assembly proceeding via initial folding of the N-terminal alpha-peptide with subsequent collapse of the transiently folded beta-chain on to the surface of the former . A slow process of rearrangement follows association in vitro . Competition experiments support the proposal that the linker endopeptide in the precursor serves to increase the probability of productive collision between folded alpha- and beta-peptides . The effect of raised temperature is to interfere with the folding of the alpha-peptide, thus preventing proper folding of the precursor . This finding accounts for the basis of the temperature regulation of PA production in vivo.

Biochem J, 1991 Sep 15, 278 ( Pt 3), 673 - 8
The mutation Lys234His yields a class A beta-lactamase with a novel pH-dependence; Brannigan J et al.; The lysine-234 residue is highly conserved in beta-lactamases and in nearly all active-site-serine penicillin-recognizing enzymes . Its replacement by a histidine residue in the Streptomyces albus G class A beta-lactamase yielded an enzyme the pH-dependence of which was characterized by the appearance of a novel pK, which could be attributed to the newly introduced residue . At low pH, the kcat, value for benzylpenicillin was as high as 50% of that of the wild-type enzyme, demonstrating that an efficient active site was maintained . Both kcat . and kcat/Km dramatically decreased above pH 6 but the decrease in kcat./Km could not be attributed to larger Km values . Thus a positive charge on the side chain of residue 234 appears to be more essential for transition-state stabilization than for initial recognition of the substrate ground state.

Eur J Biochem, 1991 Sep 15, 200(3), 767 - 73
Purification of penicillin-binding protein 4 of Escherichia coli as a soluble protein by dye-affinity chromatography; Mottl H et al.; The dacB gene of Escherichia coli, coding for penicillin-binding protein 4 (PBP4) was cloned under the control of the phage lambda pR promoter and cro gene translation signals . Depression of the phage lambda promoter for 2 h at 42 degrees C in E . coli led to the maximum over-production of PBP4 to 3.8% of the total soluble protein . Expression at 42 degrees C but not at 40 degrees C or 37 degrees C led to incomplete processing and aggregation of the preform of PBP4 . Cibacron navyblue 2G-E was selected from a collection of triazine dyes as having a high affinity for PBP4 . The immobilised dye was used in a two-step procedure to isolated 374 mg PBP4 from the soluble fraction of 125 g (wet mass) cells of the over-producing strain, with a recovery of 63.2% and a final purity of 99% as determined by active-site titration with radiolabelled penicillin . Saturation of PBP4 with various beta-lactam derivatives did not abolish binding to the dye material, nor was PBP4 eluted by addition of beta-lactams from the dye matrix . PBP4 behaved as a soluble protein throughout the purification, that was performed in the complete absence of detergents . Furthermore, in flotation experiments on sucrose density gradients and in Triton X-114 fractionation experiments, it showed the characteristics of a soluble protein . Cibacron navyblue 2G-E showed class specificity for all E . coli PBP except PBP3 and could be used for the isolation of these PBP from membrane extracts.

DICP, 1991 Sep, 25(9), 925 - 8
Comparative attitudes to verbal and written medication information among hospital outpatients; Harvey JL et al.; This study was undertaken to assess the comparative preference of pharmacy outpatients for verbal and written medication information and to identify factors that might influence these preferences . Two hundred forty-seven consecutive, literate outpatients presenting with a prescription for a penicillin were enrolled in the study and given standardized verbal counseling by a pharmacist and a medication information leaflet . Assessment was made at initial presentation and by a prepaid mail questionnaire completed anonymously by the patient at home . Preferences were analyzed by age, sex, and number of medications prescribed . A response rate of 63 percent (155/247) was obtained . Low recall of physician instruction (11 percent) was recorded . Respondent preferences were for pharmacist counseling (30.4 percent), leaflet (20.6 percent), both of these (44.5 percent), or neither/uncertain (4.5 percent) . The only factor having a statistically significant effect on these preferences was age (31-55 y), which influenced preference for a leaflet . Patient opinion of each leaflet section is presented . Patient preference for a leaflet or verbal counseling with a leaflet provides further evidence that leaflets should be widely used.

Prostaglandins Leukot Essent Fatty Acids, 1991 Sep, 44(1), 37 - 46
Influence of chemotherapeutic agents on prostacyclin synthesis . II . Effects of tetracycline and penicillin G on prostacyclin synthesis by the rat thoracic aorta and myometrial tissues; el Tahir KE et al.; The influence of the two antibiotics tetracycline hydrochloride (T) and penicillin G sodium (P) on PGI2 synthesis by the male rat thoracic aorta and day-20 pregnant rat myometrium was investigated in vitro using a rat platelet antiaggregatory bioassay method . Pretreatment of the tissues for 30 min at 37 degrees C with T (21-168 microM) or P (28-224 microM) significantly inhibited PGI2 synthesis in absence or presence of exogenous arachidonic acid (AA) (16.6 microM), (P less than 0.01, n = 5-6) . Furthermore, pretreatment of rats with the two drugs (T 11 and P 175 mu mole kg-1 for 30 min) significantly antagonised AA (4 n mole kg-1)-induced hypotension in urethane-anaesthetised rats . They also (T 0.5-4 and P 1-6 microM) antagonised AA-induced aggregation in rabbit citrated platelet-rich plasma . T failed to affect ADP-induced aggregation to any significant level whereas P (3-6 microM) reduced ADP-induced aggregation . The drugs seemed to interfere with the action of the PG endoperoxide synthase (or PG cyclooxygenase) enzyme resulting in decreased formation of PGG2 and PGH2 . Such an effect may have resulted from the induced formation of toxic {OH-} radicals and/or inhibition of O2 uptake by the tissues under the influence of the drugs . The demonstrated inherent property of these two antibiotics to inhibit the synthesis of the potent vasodilator, platelet antiaggregatory, anticonvulsant and inhibitor of gastric acid secretion--PGI2, may partly contribute towards better understanding of the biochemical mechanisms that underlie some of the previously known but poorly understood actions of these antibiotics . Furthermore, since good evidence exists for the involvement of excessive uterine prostaglandin synthesis in dysmenorrhoea and premature deliveries, it is suggested that the potential benefits of T or P in these two disorders be investigated.

Medicine (Baltimore), 1991 Sep, 70(5), 287 - 92
Purpura fulminans and symmetrical peripheral gangrene caused by Capnocytophaga canimorsus (formerly DF-2) septicemia--a complication of dog bite; Kullberg BJ et al.; We review the syndrome of Capnocytophaga canimorsus (DF-2) septicemia after exposure to dogs or cats . We describe a previously healthy patient who developed diffuse intravascular coagulation and symmetrical peripheral gangrene as a result of C . canimorsus septicemia after a dog bite . To our knowledge, this patient was the first to receive combined plasmapheresis and leukapheresis for C . canimorsus septicemia . Symmetrical peripheral gangrene is frequently associated with C . canimorsus septicemia and may lead to an early diagnosis in patients who become severely ill after a dog bite . Other complications include arthritis, meningitis, and endocarditis . These manifestations can also be found in previously healthy patients, although a prior splenectomy or other causes of impaired host defense clearly enhance the risk . Prompt treatment with penicillin G is required.

Hosp Pract (Off Ed), 1991 Sep, 26 Suppl 5, 20 - 3; discussion 55
Ceftriaxone in treatment of serious infections . Sexually transmitted diseases; Harrison WO; The most recent CDC guidelines for treatment of STDs list a number of syndromes for which ceftriaxone is the recommended therapy, including those caused by N . gonorrhoeae and H . ducreyi . The drug has successfully eradicated incubating syphilis . Its use in primary, secondary, and latent syphilis is promising, although adequate data regarding optimal dose and duration of therapy are not yet available . It remains to be seen whether ceftriaxone represents the sun rising on a new era of successful STD treatment or the sun setting on the old penicillin era.

Epilepsia, 1991 Sep-Oct, 32(5), 591 - 6
Aggravation of penicillin-induced epilepsy in rats with locus ceruleus lesions; Sullivan HC et al.; The rate and pattern of development of seizures induced by penicillin injected intraperitoneally were determined in rats that had been depleted of brain norepinephrine (NE) by bilateral injections of the neurotoxin 6-OH dopamine into the locus ceruleus . Behavioral observations and scalp electrographic recordings were made after injection and the efficacy of NE depletion was determined by high performance liquid chromatography measurement of cortical levels of NE and its metabolites . We found that in comparison to sham-operated control rats, NE-depleted rats had a significantly shorter latency to first observable myoclonic jerk, the first epileptic discharge, the first convulsion with sustained epileptic discharges, and a longer duration of convulsions . We observed a similar electrographic pattern of multifocal spikes with bilateral synchrony in both groups . However, more of the control rats (six of 12) had convulsions as compared to the lesioned rats (four of 12) . These findings are consistent with previous evidence that depletion of neocortical NE facilitates the development of epileptiform activity in the CNS; however, a convulsive state was not induced by NE depletion.

J Bacteriol, 1991 Sep, 173(18), 5740 - 6
Penicillin-binding protein 1B of Escherichia coli exists in dimeric forms; Zijderveld CA et al.; A high-molecular-weight band has been detected in Western immunoblots of nonboiled Escherichia coli samples incubated with polyclonal antiserum against penicillin-binding protein 1B (PBP 1B) . This band was shown to be a dimer of PBP 1B . The dimer was more strongly associated with the envelope than the monomer, and it was still able to bind penicillin G . Analysis of the binding of fusion proteins of PBP 1B and beta-lactamase showed that the part of PBP 1B necessary for complex formation lies in the amino-terminal half of the protein.

J Bacteriol, 1991 Sep, 173(18), 5668 - 76
Subcellular distribution of the soluble lytic transglycosylase in Escherichia coli; Walderich B et al.; The localization of the major autolytic enzyme, the soluble lytic transglycosylase, in the different cell compartments of Escherichia coli was investigated by immunoelectron microscopy . Ultrathin sections were labeled with a specific antiserum against purified soluble lytic transglycosylase, and the antibody-enzyme complexes were visualized with colloidal protein A-gold . A preferential localization of the lytic transglycosylase in the envelope was observed, with only 20 to 30% of the enzyme left in the cytoplasm . Most of the enzyme associated with the cell wall was tightly bound to the murein sacculus . Sacculi prepared by boiling of cells in 4% sodium dodecyl sulfate could be immunolabeled with the specific antiserum, indicating a surprisingly strong interaction of the lytic transglycosylase with murein . The enzyme-substrate complex could be reconstituted in vitro by incubating pronase-treated, protein-free murein sacculi with purified lytic transglycosylase at 0 degrees C . Titration of sacculi with increasing amounts of enzyme indicated a limiting number of binding sites for about 1,000 molecules of enzyme per sacculus . Ruptured murein sacculi obtained after penicillin treatment revealed that the enzyme is exclusively bound to the outer surface of the sacculus . This finding is discussed in the light of recent evidence suggesting that the murein of E . coli might be a structure of more than one layer expanding by inside-to-outside growth of patches of murein.

J Clin Neuroophthalmol, 1991 Sep, 11(3), 139 - 43
Meningovascular syphilis with a gumma of the midbrain; Standaert DG et al.; We report a patient with meningovascular syphilis who had a dorsal midbrain syndrome, cognitive dysfunction, and a left peripheral seventh nerve palsy . Magnetic resonance imaging (MRI) disclosed a large lesion of the midbrain and thalamus with intense enhancement of the interpeduncular cistern, both of which resolved after treatment with intravenous penicillin . The clinical features, radiographic appearance, and response to therapy suggest that this lesion was a focal syphilitic inflammatory process, or gumma . We conclude that MRI with intravenous contrast may reveal the full spectrum of pathologic involvement in neurosyphilis and, in certain situations, may obviate the need for biopsy of an associated mass lesion.

Arch Ital Biol, 1991 Sep, 129(4), 273 - 87
The contribution of diffusion to the termination of penicillin-induced convulsive activity in the awake rat; Horn E et al.; 1 . Experiments were performed to investigate the contribution of diffusion to the termination of PCN induced convulsive (epileptiform) activity in the awake rat . The basic question was whether convulsive activity terminates at the same critical concentration Ct of PCN independently of the concentration Co of PCN injected into the superficial layer of the foreleg field of the right motor cortex . Different concentrations Co were used, the lowest being 16 IU PCN/0.5 microliters saline, the largest 1000 IU PCN/0.5 microliters saline . The convulsive activity was recorded by means of the electroencephalogram (EEG) . 2 . Mathematical calculations concerning the diffusion of the substances were performed by using the diffusion equation with a PCN diffusion coefficient D = 3.52 x 10(-4) mm2/s and the tortuosity factor lambda = 1.62 . 3 . The lowest dose of PCN used was considered as a threshold dose for acute induction of convulsive activity because only 4 out of 9 rats treated with 16 IU PCN developed epileptiform activity . For the range of doses between 16 and 32 IU, the median frequency of convulsive potentials was dose-dependent, and increased from 7.9 to 13.8 pot./min, respectively . For higher doses covering the range between 63 and 1000 IU, there was only an insignificant increase from 19.2 to 22.7 pot./min, respectively . 4 . The median period of convulsive activity increased significantly (p less than 0.05 or less than 0.01) and monotonically from 19.5 min in rats treated with 16 IU PCN to 267 min after treatment with 1000 IU PCN . 5 . At the end of the convulsive activity, the median critical concentration Ct within the artificial focus ranged from 1.75 to 1.31 IU/0.5 microliters saline in rats treated with 16 to 125 IU PCN, while after induction of convulsive activity with doses of 250, 500 or 1000 IU PCN, Ct gradually increased to 2.01, 2.83, and 3.75 IU/0.5 microliters, respectively . This means that the brain became less sensitive for PCN the longer the epileptiform activity lasted . 6 . It is concluded that during long-lasting convulsive activity, the brain takes advantage of its plastic properties by eliciting counteracting mechanisms . These self-protective factors may utilize neuronal networks which needs some time to become effective in the control of the cortical activity.

Appl Biochem Biotechnol, 1991 Sep, 30(3), 297 - 302
Adsorption and expression of penicillin G acylase immobilized onto methacrylate polymers generated with varying pore generating solvent volume; Kotha A et al.; Adsorption and expression of penicillin G acylase was studied on macroporous methacrylate polymer beads of differing pore volume, generated with kerosene . The absorption and expression of the penicillin G acylase was dependent on pore volume . Maximum expression of 57% of adsorbed enzyme was obtained on beads synthesized with 40 mL of kerosene, indicating minimum pore-diffusion limitations.

Appl Biochem Biotechnol, 1991 Sep, 30(3), 265 - 72
Immobilization of penicillin acylase in porous beads of polyacrylamide gel; Prabhune A et al.; A procedure is described for the immobilization of benzylpenicillin acylase from Escherichia coli within uniformly spherical, porous polyacrylamide gel beads . Aqueous solutions of the enzyme and sodium alginate and of acrylamide monomer, N,N'-methylene-bis-acrylamide, N,N,N,N'-tetramethylethylenediamine (TEMED) and sodium alginate are cooled separately, mixed, and dropped immediately into ice-cold, buffered calcium formate solution, pH 8.5, to give calcium alginate-coated beads . The beads are left for 30-60 min in the cold calcium formate solution for polyacrylamide gel formation . The beads are then treated with a solution of glutaraldehyde and the calcium alginate subsequently leached out with a solution of potassium phosphate . Modification of the native enzyme with glutaraldehyde results in a slight enhancement in the rate of hydrolysis of benzylpenicillin at pH 7.8 and 0.05M substrate concentration . The enzyme entrapped in porous polyacrylamide gel beads shows no measurable diffusional limitation in stirred reactors, catalyzing the hydrolysis of the substrate at a rate comparable to that of the glutaraldehyde-modified native enzyme . The immobilized enzyme preparation has been used in batch mode over 90 cycles without any apparent loss in hydrolytic activity.

Kansenshogaku Zasshi, 1991 Sep, 65(9), 1116 - 22
Virulence of Escherichia coli strains with R-plasmid mediated penicillin resistance in mice infections; Obana Y et al.; Penicillinase I-, II- and III-producing R-plasmid of Escherichia coli were transferred to Escherichia coli 177, KC-14, and 444 . These strains are highly virulent in mice . This study was conducted to investigate the influence of conjugative R-plasmid on the virulence of its host strains . Escherichia coli 177 after penicillinase I- or III-producing R-plasmids transfer retained parental levels of virulence . On the other hand, penicillinase II-producing transconjugants showed reduced virulence in mice . The virulence of its revertants, in which R-plasmid was eliminated by heat, were equivalent to that of the host strain . It is suggested that the decrease in the virulence of transconjugants was not due to transferred R-plasmid . The reduced virulence of the these transconjugants may be due to alterations in their components such as the lipopolysaccharides in the cell envelope.

Biull Eksp Biol Med, 1991 Sep, 112(9), 260 - 2
{Antiepileptic effects of nifedipine}; Karpova MN et al.; In experiments on freely moving male Wistar rats it was shown that nifedipine in a dose 10 mg/kg (i.p.) suppressed the penicillin-induced focal epileptic activity in cerebral cortex . A similar suppressing effect of nifedipine was shown on acute generalized tonic-clonic pentylenetetrazol (PTZ) seizures (75 mg/kg, i.p.) . Nifedipine in the same dose was not effective on chronic PTZ administration (PTZ-kindling, 30 mg/kg i.p . during 28 days): when injected 30 min before each PTZ administration it didn't delay the development of kindling induced seizure susceptibility and had no effect on the severity of seizures . The administration of nifedipine in a dose of 10 or 30 mg/kg to control kindled animals which had not been treated with nifedipine had no influence on the severity of seizures provoked by a testing dose of PTZ (30 mg/kg i.p.): its intensity was similar to that of caused by PTZ injection along.

Epilepsy Res, 1991 Sep, 9(3), 161 - 74
Preclinical profile of the anticonvulsant remacemide and its enantiomers in the rat; Garske GE et al.; Studies conducted by Fisons Pharmaceuticals and the Antiepileptic Drug Development Program (ADD Program) of the Epilepsy Branch (NINDS, NIH) revealed that 'remacemide' (FPL 12924, formerly PR 934-423) was effective orally in the prevention of maximal electroshock seizures (MES) in rats . In this context (-)stereoisomer (FPL 14145) was of equal potency to the racemate (remacemide), while the (+)stereoisomer (FPL 14144) was 54% less potent . With respect to neurotoxicity, remacemide and its enantiomers possessed more favorable therapeutic indices than phenobarbital and valproate and less favorable indices than phenytoin and carbamazepine . The duration of protection of rats in the MES test at the ED50 or 3 x ED50 of remacemide and the (+)isomer was better or on par with the best reference compounds, phenytoin and phenobarbital . After subchronic administration of either the ED50 or the ED97 of remacemide, no tolerance developed in the hexobarbital sleep test, however, the activities of 3 hepatic microsomal enzymes were elevated . In naive rats high doses of remacemide or its (-)isomer and low doses of phenobarbital caused an increase in spontaneous motor activity . Alternatively, motor activity was depressed subsequent to high doses of phenobarbital and phenytoin . Remacemide was inactive against pentylenetetrazol and 'kindling' seizures . It was without effect in 5 electrophysiological tests (evoked responses, recurrent inhibition, long-term potentiation, penicillin-induced discharge rate and veratridine-induced depolarization) employing the in vitro hippocampal slice technique . Moreover, remacemide failed to demonstrate potent binding in vitro to neuronal L-glutamate, gamma-amino-butyrate A, adenosine A1, benzodiazepine, N-methyl-D-aspartate (strychnine-insensitive glycine and ion channel subsites) or muscarinic receptors . In conclusion, remacemide specifically prevents seizures elicited by MES, an action predicting utility in patients with generalized tonic/clonic convulsions.

Am Fam Physician, 1991 Sep, 44(3), 843 - 54
Syphilis--an STD on the increase; Kirchner JT; The number of reported cases of syphilis, including primary, secondary and congenital syphilis, has been rapidly rising since 1987 . The greatest increases have occurred in urban areas . An association between human immunodeficiency virus infection and syphilis has been established . Primary syphilis is manifested by a clean, painless ulcer called a chancre . Secondary disease often presents with constitutional symptoms and a maculopapular rash . Most infants with congenital syphilis are born without signs of infection . Serologic testing for both nontreponemal and treponemal antibodies is essential for diagnosis . Penicillin is the treatment of choice for all stages of syphilis . Case reporting and treatment of sexual contacts are two aspects of this disease that warrant greater attention from physicians.

Brain Res, 1991 Aug 23, 557(1-2), 95 - 102
The electrophysiological basis of epileptiform magnetic fields in neocortex: spontaneous ictal phenomena; Barth DS et al.; In a previous report (Barth, D.S . and Di, S., Brain Research, 530 (1990) 35-39), electrical measurements of epileptiform cellular currents produced by physiologically evoked interictal penicillin spikes in rat somatosensory cortex were directly compared to the extracranial magnetic fields these currents generate . The present study uses the same methodology to extend these observations to spontaneous interictal and ictal phenomena in rat auditory cortex, and provides a more realistic empirical foundation for physical models with which to interpret non-invasive neuromagnetic recordings of human focal seizures . These data indicate that seizure foci under 1 x 1 cm2 in cortical surface area are capable of producing magnetic fields that may be recorded at extracranial distances similar to those used in humans . Furthermore, physical models based on the dipole approximation appear to be appropriate for the interpretation of ictal magnetic field phenomena in neocortex.

FEBS Lett, 1991 Aug 5, 287(1-2), 31 - 3
Penicillin acylase-catalyzed protection and deprotection of amino groups as a promising approach in enzymatic peptide synthesis; Didziapetris R et al.; Penicillin acylase from E . coli is able to catalyze both the introduction and the removal of the phenylacetyl group . We have established that phenylacetyl derivatives of amino acids and peptides can be used in protease-catalyzed peptide synthesis . Here the synthesis of leucine-enkephalin using enzymes for N-terminal amino group protection, peptide bond formation and deprotection is described.

J Natl Med Assoc, 1991 Aug, 83(8), 724 - 6
Chancroid: a review for the family practitioner; Jordan WC; Chancroid, as the name implies, is like a chancre . Unlike the painless chancre of syphilis, it is painful, darkfield negative, and does not respond to penicillin therapy . The number of cases have continued to rise in recent years . Because it can cause irreversible anatomical destruction, making the correct diagnosis is important and can prevent chronic morbidity.

J Neurol, 1991 Aug, 238(5), 271 - 80
Acute and chronic neuroborreliosis with and without CNS involvement: a clinical, MRI, and HLA study of 27 cases; Kruger H et al.; Of the 96 serologically confirmed neuroborreliosis cases seen in our clinic between 1983 and 1988, 11 patients had mild to moderate and 4 patients had serious cerebral and/or spinal cord symptoms . Nine of these 15 patients with CNS involvement exhibited a primary chronic course of the illness . After high-dose intravenous therapy with penicillin, doxycycline or cefotaxime, given mostly in combination with cortisone, gradual recovery occurred with normalization of CSF findings characteristic of neuroborreliosis, and normalization of significantly elevated Borrelia burgdorferi IgG antibody titres in CSF and serum . Brain MRI and CT showed evidence of or were suggestive of vascular involvement which correlated with clinical symptoms in 11 of the 15 patients with CNS involvement . Brain MRI changes that were similar but much slighter in number and intensity were seen in 5 of 12 neuroborreliosis patients without clinical signs of CNS involvement (lymphocytic meningoradiculitis; Bannwarth's syndrome) . The frequencies of the HLA-DR7 (75%), HLA-B44 (50%) and HLA-A29 (33%) antigens in 12 neuroborreliosis patients with clinical symptoms of CNS involvement were significantly different from the frequencies in 12 neuroborreliosis patients without CNS involvement and in 100 control subjects . Diagnostic criteria of active neuroborreliosis are proposed.

Arch Neurol, 1991 Aug, 48(8), 832 - 6
Borrelia rhombencephalomyelopathy; Kuntzer T et al.; Three patients, in whom the diagnosis of Borrelia burgdorferi infection was unknown for several years, developed a biphasic involvement of the central nervous system: an acute brain-stem dysfunction was followed up, in two patients, by a progressive, disabling myelitis and, in one patient, by further relapsing-remitting episodes of severe multifocal rhombencephalitis . The most consistent cerebrospinal fluid abnormalities in the analysis of sequential specimens were elevated total IgM levels that normalized after penicillin therapy . The neuropathologic findings in one patient showed microgliosis and meningovascular involvement of the central nervous system, resulting in two ischemic infarcts in the myelencephalon . Few spirochetes were localized in the leptomeninges and around subependymal vessels of the fourth ventricle . The vascular element consisted of an obliterative inflammatory vasculopathy in the medullary parenchyma . This study (1) provides pathologic evidence that a vascular disease induced by B burgdorferi is a pathogenetic mechanism for cerebrovascular diseases, and (2) emphasizes the similarities between neuroborreliosis and neurosyphilis.

J Allergy Clin Immunol, 1991 Aug, 88(2), 213 - 7
Penicillin resensitization among hospitalized patients; Parker PJ et al.; The purpose of this study was to determine the frequency of resensitization to penicillin after oral or intravenous treatment with beta-lactam antibiotics in hospitalized patients with histories of penicillin allergy . Seventeen adults (aged 24 to 76 years) and one child (aged 10 years) were treated intravenously and/or orally with beta-lactam antibiotics after negative skin tests were obtained with benzylpenicilloyl polylysine, potassium penicillin G, and alkaline hydrolysis products of penicillin G as minor determinant mixture . Repeat skin testing was performed 1 to 12 months after the therapy . Three patients (16%) became skin test positive after the treatment . Two patients reacted to potassium penicillin G alone, and the other patient reacted to benzylpenicilloyl polylysine and minor determinant mixture . These three patients were among the 15 patients who were treated with intravenous antibiotics . This study reveals a high percentage of skin test conversion after intravenously administered penicillin therapy and confirms the present practice of advising patients with a history of penicillin allergy who have successfully completed penicillin treatment to have a repeat skin test before future exposure to beta-lactam antibiotics.

Exp Neurol, 1991 Aug, 113(2), 249 - 54
Effects of applied currents on epileptiform bursts in vitro; Kayyali H et al.; In this study, results show that applied electric currents can be effective to control the neuronal bursting that characterizes epileptic activity . Recordings from the CA1 region of rat hippocampus treated with penicillin show that local inhibition of epileptiform bursts is possible by short anodic current pulses (50 ms duration) applied extracellularly . Inhibition was evidenced by a large reduction (greater than 90%) in the amplitude of field potential . Data collected from 20 slices with moderate field potentials (50-80% of maximum) showed that current needed for complete inhibition was on the order of 42 +/- 3 microA . Intracellular recordings in CA1 cells (n = 13) showed that the decrease in field potential amplitude was accompanied by suppression of intracellular neuronal firing caused by somatic hyperpolarization as measured by transmembrane potentials . The resulting hyperpolarization was on the order of 13 mv below resting potential for weakly epileptiform responses (less than 50% of maximum response), and 50 mv below resting potential for strongly epileptiform activity (greater than 50% of maximum response) . These results reveal the existence of a stimulation window within which inhibition of neuronal elements can be achieved without simultaneous excitation.

J Bacteriol, 1991 Aug, 173(15), 4799 - 813
Cloning, mapping, and characterization of the Escherichia coli prc gene, which is involved in C-terminal processing of penicillin-binding protein 3; Hara H et al.; The prc gene, which is involved in cleavage of the C-terminal peptide from the precursor form of penicillin-binding protein 3 (PBP 3) of Escherichia coli, was cloned and mapped at 40.4 min on the chromosome . The gene product was identified as a protein of about 80 kDa in maxicell and in vitro systems . Fractionation of the maxicells producing the product suggested that the product was associated with the periplasmic side of the cytoplasmic membrane . This was consistent with the notion that the C-terminal processing of PBP 3 probably occurs outside the cytoplasmic membrane: the processing was found to be dependent on the secY and secA functions, indicating that the prc product or PBP 3 or both share the translocation machinery with other extracytoplasmic proteins . DNA sequencing analysis of the prc gene region identified an open reading frame, with two possible translational starts 6 bp apart from each other, that could code for a product with a calculated molecular weight of 76,667 or 76,432 . The prc mutant was sensitive to thermal and osmotic stresses . Southern analysis of the chromosomal DNA of the mutant unexpectedly revealed that the mutation was a deletion of the entire prc gene and thus that the prc gene is conditionally dispensable . The mutation resulted in greatly reduced heat shock response at low osmolarity and in leakage of periplasmic proteins.

Oral Surg Oral Med Oral Pathol, 1991 Aug, 72(2), 167 - 77
Chemoprophylaxis of prosthetic joint patients during dental treatment: a decision-utility analysis; Jacobson JJ et al.; A decision-analytic model and a cost effectiveness analysis was performed on 1 million hypothetic prosthetic joint patients undergoing dental treatment, to determine the most cost-effective strategy to prevent late prosthetic joint infections . The cost per quality-adjusted life-year saved (QALY) was determined for three preventive strategies: no prophylaxis, oral penicillin, and oral cephalexin . The UCLA Pain-Walking-Function-Activity Scale was used to obtain quality-of-life adjustments (utility assessment) for the study population . Costs were derived from 70 patients hospitalized between July 1, 1982, and June 30, 1986, at the UCLA Center for Health Sciences . The most cost-effective preventive strategy was the no prophylaxis alternative ($196,500/QALY) . However, by recommending a 1-day strategy of oral cephalexin only to those dental patients at high risk for late prosthetic joint infections rather than a 3-day regimen to all patients, the cost effectiveness improved from $1.1 million/QALY to $446,100/QALY while maintaining a low risk of death (0.38 deaths per 10(6) dental visits).

Comput Methods Programs Biomed, 1991 Aug, 35(4), 301 - 10
Distinguishing drug toxicity syndromes from medical diseases: a QMR computer-based approach; Mabry ME et al.; Drug effects can mimic a wide variety of diseases . Experts note that adverse drug reactions (ADRs) have become the 'greatest imitator' of disease in clinical medicine . Quick Medical Reference (QMR) is a decision support system providing diagnostic data about more than 600 medical diseases . Currently, QMR contains only limited drug information . Just as physicians have difficulty diagnosing ADRs, QMR has similar problems in differentiating natural disease manifestations from drug toxicity syndromes . To remedy this problem, two prototype Drug Syndromes (DS), Carbamazepine Toxicity and Penicillin Toxicity, were incorporated into the QMR Knowledge Base (KB) . Using detailed case reports, we demonstrated that a DS-augmented version of QMR was successful in discriminating these DS from the other diseases in QMR's KB . The addition of DS significantly improves QMR's diagnostic performance in cases in which some of the pathologic features are the consequence of drugs.

Enzyme Microb Technol, 1991 Aug, 13(8), 676 - 82
Studies on improved techniques for immobilizing and stabilizing penicillin amidase associated with E . coli cells; Babu PS et al.; A method for catalyst development has been suggested for immobilizing whole E . coli cells containing penicillin amidase . Conventional methods have limitations, such as permeation of substrate and product through cellular membranes, leaching of protein and other cellular components into the reaction phase, lower specific activity compared to immobilized enzyme system, etc . The whole cell immobilization technique has been optimized for different process parameters . The most suitable conditions for this process were pH, 4.25; cell concentration, 3.75%; concentration of glutaraldehyde, 1.5%; level of bovine serum albumin as additional support, 2 mg ml-1 . The reaction was continued for 2 h . The granular catalyst has good mechanical strength, low protein leachability, and high retention of penicillin amidase activity.

Fortschr Med, 1991 Jul 30, 109(22), 447 - 8
{Branhamella catarrhalis as a disease pathogen}; Simon C; Since 1980, numerous reports have been published throughout the world on the pathogenic role of Branhamella catarrhalis . Apparently, Branhamella infections have been increasing in many places . Although they can affect various organs, they are most commonly observed in the airways and eye (both in children and adults) . Not infrequently, Branhamella catarrhalis causes sepsis, in particular in immunosuppressed patients . The rapid increase in beta-lactamase-forming Branhamella strains results in frequent ineffectiveness of treatment with penicillin . In patients treated with penicillin for a primary infection by other bacteria, a secondary infection due to penicillin-resistant Branhamella organisms can subsequently occur . For treatment, therefore, beta-lactamase-stable antibiotics should be preferred.

FEMS Microbiol Lett, 1991 Jul 15, 66(1), 113 - 6
Effect of a beta-lactamase inhibitor, tazobactam, on growth and penicillin-binding proteins of Borrelia burgdorferi; Urban C et al.; The effects of tazobactam, a relatively new beta-lactamase inhibitor, were investigated on growth and penicillin-binding proteins (PBPs) of Borrellia burgdorferi . A previous communication from our group demonstrated several proteins capable of binding labelled penicillin in this organism . Of these proteins, 94-kDa and 57-kDa PBPs possessed the highest affinity for penicillin and were assumed to be essential proteins involved in cell-wall synthesis . In these experiments, tazobactam was used in competition binding experiments as well as on whole spirochetes . Only the 94-kDa and 57-kDa PBPs were affected by increasing amounts of tazobactam during competition-binding experiments and growth of B . burgdorferi was also inhibited . These results may explain the in vitro activity of beta-lactamase inhibitors in general and suggest a utility for these compounds when examining PBPs with hydrolysing activity and/or organisms with beta-lactamases.

J Biol Chem, 1991 Jul 5, 266(19), 12646 - 54
Delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase from Aspergillus nidulans . Molecular characterization of the acvA gene encoding the first enzyme of the penicillin biosynthetic pathway; MacCabe AP et al.; The Aspergillus nidulans gene (acvA) encoding the first catalytic steps of penicillin biosynthesis that result in the formation of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV), has been positively identified by matching a 15-amino acid segment of sequence obtained from an internal CNBr fragment of the purified amino-terminally blocked protein with that predicted from the DNA sequence . acvA is transcribed in the opposite orientation to ipnA (encoding isopenicillin N synthetase), with an intergenic region of 872 nucleotides . The gene has been completely sequenced at the nucleotide level and found to encode a protein of 3,770 amino acids (molecular mass, 422,486 Da) . Both fast protein liquid chromatography and native gel estimates of molecular mass are consistent with this predicted molecular weight . The enzyme was identified as a glycoprotein by means of affinity blotting with concanavalin A . No evidence for the presence of introns within the acvA gene has been found . The derived amino acid sequence of ACV synthetase (ACVS) contains three homologous regions of about 585 residues, each of which displays areas of similarity with (i) adenylate-forming enzymes such as parsley 4-coumarate-CoA ligase and firefly luciferase and (ii) several multienzyme peptide synthetases, including bacterial gramicidin S synthetase 1 and tyrocidine synthetase 1 . Despite these similarities, conserved cysteine residues found in the latter synthetases and thought to be essential for the thiotemplate mechanism of peptide biosynthesis have not been detected in the ACVS sequence . These observations, together with the occurrence of putative 4'-phosphopantetheine-attachment sites and a putative thioesterase site, are discussed with reference to the reaction sequence leading to production of the ACV tripeptide . We speculate that each of the homologous regions corresponds to a functional domain that recognizes one of the three substrate amino acids.

J Bacteriol, 1991 Jul, 173(13), 4021 - 6
Lysis of Escherichia coli by beta-lactams which bind penicillin-binding proteins 1a and 1b: inhibition by heat shock proteins; Powell JK et al.; The heat shock proteins (HSPs) of Escherichia coli were artificially induced in cells containing the wild-type rpoH+ gene under control of a tac promoter . At 30 degrees C, expression of HSPs produced cells that were resistant to lysis by cephaloridine and cefsulodin, antibiotics that bind penicillin-binding proteins (PBPs) 1a and 1b . This resistance could be reversed by the simultaneous addition of mecillinam, a beta-lactam that binds PBP 2 . However, even in the presence of mecillinam, cells induced to produce HSPs were resistant to lysis by ampicillin, which binds all the major PBPs . Lysis of cells induced to produce HSPs could also be effected by imipenem, a beta-lactam known to lyse nongrowing cells . These effects suggest the existence of at least two pathways for beta-lactam-dependent lysis, one inhibited by HSPs and one not . HSP-mediated lysis resistance was abolished by a mutation in any one of five heat shock genes (dnaK, dnaJ, grpE, GroES, or groEL) . Thus, resistance appeared to depend on the expression of the complete heat shock response rather than on any single HSP . Resistance to lysis was significant in the absence of the RelA protein, implying that resistance could not be explained by activation of the stringent response . Since many environmental stresses promote the expression of HSPs, it is possible that their presence contributes an additional mechanism toward development in bacteria of phenotypic tolerance to beta-lactam antibiotics.

J Gen Microbiol, 1991 Jul, 137 ( Pt 7), 1653 - 60
Evidence for a compartmentation of penicillin biosynthesis in a high- and a low-producing strain of Penicillium chrysogenum; Affenzeller K et al.; Pulse-chase experiments using {U14C}valine were done with P2 and Q176, high- and low-penicillin-producing strains of Penicillium chrysogenum . The metabolic flux of this amino acid into protein and penicillin was measured, and compartmentation of penicillin biosynthesis was assessed . Strain P2 took up 14C-valine more slowly than strain Q176, but their rates of incorporation into protein were comparable . Incorporation of 14C-valine into penicillin occurred immediately with the high-producer P2, but exhibited a lag with Q176 . After 14C-valine had been removed from the medium, the specific radioactivity of penicillin continued to increase in Q176 but started to decrease immediately in P2 . The specific radioactivities of 14C-valine in protein and in penicillin were significantly different in both strains: Q176 had a higher specific radioactivity of valine in penicillin than P2, whereas P2 had a higher specific radioactivity of valine in protein than Q176 . Moreover, the specific radioactivity of 14C-valine in penicillin was 20-fold higher in strain Q176 than in P2 . These results indicate that penicillin and protein biosynthesis use different pools of cellular valine, and that exchange of valine between the two compartments is slow in the low-producer, but rapid in the high-producer strain . Hence these results indicate a further control point of penicillin biosynthesis in P . chrysogenum.

J Reprod Med, 1991 Jul, 36(7), 543 - 5
Advanced actinomycotic pelvic inflammatory disease simulating gynecologic malignancy . A report of two cases; Hoffman MS et al.; Two women had large, solid, fixed pelvic masses simulating advanced ovarian cancer in one case and advanced cervical cancer in the other . Both patients had had plastic intrauterine contraceptive devices in situ for 7 and 17 years, respectively . Both patients required laparotomy to make the diagnosis . In both the surgery was markedly difficult because of the total absence of tissue planes . Both had obvious actinomycotic disease on routine histologic examination of the ovary and were treated with prolonged penicillin, with some, but not total, resolution of the pelvic fibrosis . The diagnosis of advanced actinomycotic pelvic inflammatory disease should be entertained in patients with a large, solid pelvic mass and an intrauterine device in situ or a recent history of intrauterine device use.

Fam Plann Perspect, 1991 Jul-Aug, 23(4), 173 - 7
An ounce of prevention .. . STDs and women's health; Althaus FA; PIP: Using recent data from the U.S., the argument is reiterated that sexually transmitted diseases (STDs) have serious consequences on female morbidity, mortality, pregnancy outcome and that the cost of screening and treatment can afford significant savings . Since the rosy view of the 1950s that STDs had been eliminated with penicillin, new viral, parasitic and bacterial forms have emerged, and antibiotic-resistant classical STDs have increased yearly . 13 million new cases were reported in 1989, excluding non-reportable diseases and asymptomatic infections, such as over half of chlamydia cases . Mortality is possible from STDs, most notably from AIDS, now among the top 5 causes of death of women aged 15-44 . Other fatal outcomes are cervical cancer related to human papilloma virus, accelerated by HIV, pelvic inflammatory diseases (PID) its consequences, ectopic pregnancy . Symptomatic PID affects 1 million women, resulting in 210,000 hospitalizations per year . Ectopic pregnancy accounts for 12% of maternal mortality . STDs are involved in neonatal infections with HIV, syphilis, gonorrhea, chlamydia, cytomegalovirus, and herpes . Chorioamnionitis, a finding in many miscarriages, is caused by many of the same organisms . Several studies have projected sizeable potential savings, even within the current year, by providing STD screening and treatment in family planning clinics and prenatal care, in terms of prevention of hospitalization of women, and intensive care for low birth weight, premature and infected newborns .

Antimicrob Agents Chemother, 1991 Jul, 35(7), 1517 - 9
Comparative study of various hydrogen ion buffers to assay Zn(2+)-dependent beta-lactamases; Benitez MJ et al.; The low Zn2+ complex formation constants, the capacity to degrade penicillin G in combination with Zn2+, and UV absorbance make 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, 3-{N-tris(hydroxymethyl)methylamino}-2-hydroxypropanesulfonic acid, 1,3-bis{tris(hydroxymethyl)methylamino}propane, and 1,4-piperazinediethanesulfonic acid convenient buffers to study Zn(2+)-dependent beta-lactamases.

Monatsschr Kinderheilkd, 1991 Jul, 139(7), 425 - 8
{Borrelia infections from a dermatological viewpoint}; Vocks E et al.; Erythema migrans (EM), Borrelia lymphocytoma (BL) and acrodermatitis chronica atrophicans (ACA) are the established dermatological manifestations of borrelia infection, a complex multiorganic disease . Analogous to syphilis Borrelia infection can be classified by three stages, at which stage I (localized infection) and II (disseminated infection) are manifestations of early infection and stage III (persistent infection) a symptom of late infection . At all stages skin manifestations can be present, the above mentioned as stage-marker as well as other non-specific polymorphous skin lesions which sometimes appear at stage II . Because of its frequent (60-80%) occurrence in all borrelia infections EM has a pathognomonic importance for borrelia infection . In diagnosis serology is currently the only practical laboratory aid . False negative and false positive results must be considered . Treatment of choice is ceftriaxone, penicillin G (or amoxycillin) or tetracycline . Prophylactic antibiotic therapy for tick bites is not recommended . Congenital borrelia infections seem to be unusual, but it is likely that they can occur and cause different adverse fetal outcome or abortion.

Infection, 1991 Jul-Aug, 19(4), 279 - 83
Penicillin G sodium and ceftriaxone in the treatment of neuroborreliosis in children--a prospective study; Mullegger RR et al.; A controlled clinical study was set up to examine whether penicillin G sodium (PG) or ceftriaxone (C) is superior in the treatment of acute neuroborreliosis in childhood . Within a time period of 18 months 77 children with symptoms indicative of Lyme borreliosis of the central nervous system (CNS) were seen . In 23 of these children Borrelia burgdorferi specific cerebrospinal fluid (CSF) parameters confirmed the diagnosis of a neuroborreliosis . These children were treated at random with intravenous (i.v.) PG 400,000-500,000 I.U./kg/day for 14 days (group I) or with i.v . ceftriaxone 75-93 mg/kg/day for 14 days (group II), respectively . Clinical examination and a set of diagnostic laboratory parameters were done at admission, right after therapy, three, six and partly 12 months after therapy . The general condition of all children in both groups improved dramatically during antibiotic therapy, and no relapse occurred within the observation period . Considering the clear and comparable decrease of B . burgdorferi serum titres and the clinical outcome (duration of disease and follow-up for at least six months) in children of both groups no difference between both antibiotic drugs can be demonstrated.

Vet Microbiol, 1991 Jul, 28(2), 171 - 88
Biological properties of RB51; a stable rough strain of Brucella abortus; Schurig GG et al.; A rifampin-resistant mutant of Brucella abortus, designated RB51, was derived by repeated passage of strain 2308 on Trypticase soy supplemented with 1.5% agar and varying concentrations rifampin or penicillin . The RB51 colonies absorbed crystal violet and RB51 cell suspensions autoagglutinated, indicating a rough type colonial morphology for this strain . No O-chain component was detected in lipopolysaccharide (LPS) extracted from RB51 on SDS-PAGE gels stained with silver . Western blot analysis with the monoclonal antibody BRU 38, which is specific for the perosamine homopolymer O-chain of smooth Brucella LPS, indicated that the LPS of RB51 is highly deficient in O-chain when compared with the parenteral smooth strain 2308 or rough strain 45/20 . Biochemically, RB51 resembles parental strain 2308 in its ability to utilize erythritol . Intraperitoneal inoculation of RB51 into mice results in a splenic colonization which is cleared within four weeks post infection . RB51 does not revert to smooth colony morphology upon passage in vivo (mice) or in vitro . Mice infected with RB51 produce antibodies against B . abortus antigens including class 2 and 3 outer membrane proteins but not against the O-chain . Furthermore, rabbits, goats and cattle hyperimmunized with sonicates of RB51 develop antibodies to B . abortus cellular antigens but do not develop antibodies specific for the O-chain . Immunization of mice with 1 x 10(8) viable RB51 organisms confers significant protection against challenge with virulent B . abortus strain 2308.

Transplantation, 1991 Jul, 52(1), 30 - 3
In vitro inhibition of platelet aggregation by the liver with UW solution as the preservation fluid; Himmelreich G et al.; The influence of UW preservation fluid in comparison with that of Euro-Collins and Bretschneider solutions on collagen, adenosine diphosphate and ristocetin-induced platelet aggregation was investigated in vitro using platelet-rich plasma of 4 healthy volunteers . The concentrations of the solutions tested were comparable to those that may be used in the transplant situation . 2UW solution inhibited ADP and collagen-induced platelet aggregation--an effect that could be attributed mainly to adenosine and secondarily to penicillin in UW solution--whereas ristocetin-induced aggregation was not affected . Euro-Collins and Bretschneider solutions did not alter platelet aggregation . The inhibition of platelet aggregation by UW may, on the one hand, contribute to bleeding complications after reperfusion and, on the other hand, be responsible for the observed lower incidence of hepatic artery thrombosis.

J Laryngol Otol, 1991 Jul, 105(7), 588 - 90
Pseudoaneurysm of the internal carotid artery: a forgotten complication of tonsillitis?
Watson MG, Robertson AS, Colquhoun IR.
Pseudoaneurysm of the internal carotid artery is an uncommon but potentially lethal complication of tonsillar or peritonsillar sepsis, which appears to have occurred more frequently prior to the introduction of penicillin . Management of such a case is discussed, and a literature review presented.

Epilepsia, 1991 Jul-Aug, 32(4), 446 - 53
Magnetic resonance imaging and 31P spectroscopy of an interictal cortical spike focus in the rat; Karlik SJ et al.; Magnetic resonance imaging (MRI) has proven to be an effective noninvasive technique for identifying lesions in patients with temporal lobe epilepsy . It has also been suggested that MRI may be sensitive to transient functional or metabolic changes in brain tissue . Increased brain electrical activity as monitored by electroencephalography causes changes in cerebral metabolism that may be responsible for focal or regional alterations in signal in the MRI of some patients . To test this hypotheses, experimental interictal cortical foci were produced in rats by topical application of penicillin to one hemisphere of the brain . In vivo MRI and phosphorous-31 (31P) spectroscopy of the focal and contralateral hemifield were performed in a 30-cm bore 1.89-T Bruker MSL system . 31P spectroscopy revealed no quantifiable differences in pH or in phosphocreatinine and ATP levels between the focal area and the contralateral hemisphere or between experimental and saline-treated control animals . There were also no differences in proton MRI . Similar areas of prolonged T2 were found near the cortex and in the deeper parenchyma in 55% of the experimental animals and 50% of the controls . These results suggest that the electrical activity from an interictal cortical spike focus is not severe enough to perturb cerebral metabolism sufficiently to be detectable by 31P spectroscopy or proton imaging techniques.

Arch Neurol, 1991 Jul, 48(7), 700 - 2
Neurosyphilis in human immunodeficiency virus type 1-seropositive individuals . A prospective study; Berger JR; The prevalence of neurosyphilis in human immunodeficiency virus type 1 (HIV-1)-seropositive (HIV+) persons was assessed during the course of a study of the neurological complications of HIV-1 infection . One hundred sixty-six asymptomatic HIV+ subjects, 63 neurologically symptomatic HIV+ subjects, and six at-risk HIV-1-seronegative (HIV-) control subjects underwent cerebrospinal fluid (CSF) analysis on entry into this longitudinal study . Three (1.8%) of the asymptomatic HIV+ subjects had both a reactive CSF VDRL test and a reactive CSF fluorescent treponemal antibody-absorption (FTA-ABS) test . Two of these three subjects had a history of appropriately treated early syphilis, and all had a reactive serum rapid plasma reagin test . Of the 63 neurologically symptomatic HIV+ subjects, one patient with dementia had both a reactive CSF VDRL test and a fluorescent treponemal antibody-absorption test . Subjective improvement in cognitive skills followed high-dose, intravenous penicillin therapy . Another subject had a penicillin-responsive myelopathy accompanied by a reactive CSF fluorescent treponemal antibody-absorption test result, but a nonreactive CSF VDRL . Unsuspected neurosyphilis is relatively common in our population of asymptomatic HIV+ subjects and may be responsible for neurological disease in a significant minority of neurologically symptomatic HIV+ persons . Cerebrospinal fluid examination should be performed in all HIV+ persons with a history of syphilis or serological evidence of syphilis, regardless of prior treatment . Additionally, neurosyphilis should be considered in the differential diagnosis of neurological disease in any HIV+ person.

Biull Eksp Biol Med, 1991 Jul, 112(7), 12 - 5
{Effects of activation and lesions of the superior colliculi of the lamina quadrigemina on epileptic activity in rats}; Kryzhanovskii GN et al.; In acute experiments on rats it was shown that activation of SC by bilateral microinjection of penicillin (5-15 IU) or bicuculline (25-50 ng) resulted in the increased latency and decreased severity of i.p . picrotoxin-induced seizures (2 mg/kg) . The suppression of behavioral convulsions and the decreased epileptic activity in the hippocampus and cerebral cortex were followed by occurrence of spike discharges in SC with an amplitude of 200-500 mcV and frequency of 5-12/sec which testifies to the formation of penicillin- or bicuculline-induced generator excitation in SC . The lesions of SC by kainic acid administration resulted in the decreased seizure threshold and, also, facilitated the development of seizure under conditions of picrotoxin kindling . The conclusion is made that SC activation plays an important role in the realization of functional integrative activity of the antiepileptic system.

Allergy, 1991 Jul, 46(5), 379 - 85
Imbalance of CD45R and CDw29 helper cell subsets after seven days of culture from penicillin hypersensitive patients; Perez T et al.; Specific PBMC proliferation to penicillin represents one of the in vitro diagnostic procedures to show antigenic sensitization . Nine patients with suggestive clinical history of penicillin hypersensitivity, significant stimulation index in the lymphocyte transformation test (LTT), and increased CD25 expression were selected . Their phenotypic expression of T-cell subset markers was compared with that of six normal subjects after 7 days of culture . Higher percentages of CD45R and CDw29 positive cells were found in penicillin-hypersensitive patients . This group of patients showed a significantly (P less than 0.01) higher percentage of CD45R positive cells compared with normal subjects, after 7 days of culture . The percentage of CD45R cells did not differ between patients and normal subjects at day 0, and the progressive decrease of CD45R positive cells in culture of normal subjects was not observable in our patients . These results suggest that the patients with penicillin hypersensitivity have an imbalance of CD45R/CDw29 ratio after 7 days of culture, with a higher expression of CD45R positive cells.

J Immunol Methods, 1991 Jun 24, 140(1), 85 - 92
A simple ELISA procedure for HIV-1 based on the enzyme beta-lactamase; Simon H et al.; The enzyme beta-lactamase (penicillin-amido-beta-lactam-hydrolase, EC 3.5.2.6.) has been shown to be suitable for use in ELISA procedures . The assay proposed requires a conjugate containing a beta-lactam-hydrolase as the enzymatic component, penicillin or one of its derivatives as substrate and an iodic complex (an iodine-starch or an iodine-polyvinylic alcohol complex) as the chromogenic component . Binding of conjugate molecules results in the transition of the iodic complex from dark blue to colourless . The transition is readily visualized without the aid of an EIA reader . The decolorization occurs specifically giving a clear-cut yes/no decision without a cut-off value . The rate of the colour transition strongly depends on the amount of bound conjugate . beta-lactamase-based ELISA techniques are of potential use in the immunological diagnosis of some virus diseases . The sensitivity and specificity of the assay were assessed on a panel of 670 negative and 141 positive HIV-1 sera, giving values of 100% and 99.85%, respectively.

J Clin Pathol, 1991 Jun, 44(6), 459 - 63
Patterns of mortality in sickle cell disease in the United Kingdom; Gray A et al.; Eighteen of 384 patients entered on the Brent sickle cell disease register died between 1974 and 1989, a mortality of one per 128 years of follow up . Two children died from acute splenic sequestration and a third died from fulminant pneumococcal septicaemia: none was taking prophylactic penicillin . Acute chest syndrome was the cause of death in eight young adults and one child . Three deaths occurred after surgery . Cerebrovascular accidents contributed to the cause of death in three cases and there were two sudden unexplained deaths . Ten of the deaths occurred at home or within 24 hours of admission to hospital . Post mortem examinations were made in 14 cases, but the histological appearances of acute chest syndrome were often not recognised . In most cases for whom information was available, the cause of death (chest syndrome, pneumococcal sepsis, postoperative complications) could have been prevented.

J Infect Dis, 1991 Jun, 163(6), 1201 - 6
Syphilis, neurosyphilis, penicillin, and AIDS; Musher DM; Early neurosyphilis, characterized by meningitis, cranial nerve abnormalities, and cerebrospinal accidents, was first described in patients with syphilis who received inadequate courses of arsphenamine . Although more effective, penicillin at conventional doses does not yield treponemacidal levels in the central nervous system and probably does not eradicate the infecting organisms, suggesting that it works synergistically with the host's immune response in preventing neurosyphilis . Neurosyphilis after penicillin therapy was almost unheard of in the United States until it began to appear in human immunodeficiency virus (HIV)-infected patients . Numerous cases of syphilitic meningitis, cranial nerve abnormalities, and strokes have been reported in the past decade; about one-half of reported patients had received penicillin therapy, often within the previous 6 months . Thus, more intensive diagnostic evaluation, perhaps including routine cerebrospinal fluid analysis, more intensive therapy, for example with at least three doses of benzathine penicillin, and far more rigorous follow-up are indicated in HIV-infected subjects with syphilis . Since the efficacy of conventional therapy is now uncertain, novel approaches to treatment deserve systematic evaluation.

Sangre (Barc), 1991 Jun, 36(3), 211 - 5
{Syphilis and blood transfusion}; Serrano J; Along 17 years (1973-1989), syphilis screening has been performed on 146,355 blood units in the author's blood bank . A total number of 143 positive results (confirmed by MHA-TP) was registered, which means an incidence of 0.097% . Of the total number of blood units, 31,529 came from professional donors, 51 of them (0.16%) being positive, while of the 114,826 blood units from voluntary donors 92 were positive (0.08%) . With respect to voluntary donations, the highest incidence of positive reactions was found between 1980 and 1982, but this period registered also the highest number of blood units studied . Along this 17 year period 8 patients have received blood products with positive syphilis test . They were transfused on urgent request with fresh blood or platelet concentrates, the transfusion being performed before knowing the results of the screening for syphilis . No special measures were taken in 2 such cases, who died shortly after the transfusion on account of their disease . Two other were treated with penicillin at the time of transfusion . The remaining four patients received preventive penicillin . Even taking into account that positive screening tests are uncommon amongst blood donors, and that only under special circumstances the patients receiving contaminated blood may develop the illness, it seems advisable for every blood bank to perform the screening for syphilis on every blood donation.

Hautarzt, 1991 Jun, 42(6), 356 - 65
{Borrelia infections of the skin--progress of knowledge since the discovery of Lyme disease}; Garbe C; The description of Lyme disease in 1976 and the detection of its causative agent, the spirochete Borrelia burgdorferi (B . burgdorferi), in 1982 led to an increase in our knowledge of the course of B . burgdorferi infection and its clinical manifestations . The classic tick-borne dermatoses erythema chronicum migrans (ECM), lymphadenosis benigna cutis (LABC) and acrodermatitis chronica atrophicans (ACA) were proven by isolation of the spirochete from skin lesions to be caused by B . burgdorferi infection . In early disease (less than 1 year) ECM and LABC can develop locally at the site of infection (stage I), but both these skin manifestations can also occur together with multiple lesions after dissemination of the causative organism (stage II) . ACA is typical for late infection (greater than 1 year, stage III) . High titres of B . burgdorferi antibodies have been found in patients with localized sclerodermalike lesions (circumscribed scleroderma, lichen sclerosus et atrophicus, anetoderma), and frequent simultaneous occurrence of ACA suggests an association with late B . burgdorferi infection . Similarly, we found four cases of cutaneous B-cell lymphoma possibly arising from LABC in association with the same markers of late B . burgdorferi infection . Additionally, some cases of Schonlein-Henoch purpura and of Shulman syndrome may be associated with Lyme borreliosis . The disease is endemic in central Europe, and almost exclusively ticks of the Ixodes ricinus complex seem to transmit B . burgdorferi to humans, whereas the reservoir of infection seem to be rodents, especially mice . The main diagnostic tool is serological examination for B . burgdorferi antibodies, which will become detectable 3-6 weeks after infection . Enzyme-linked immunosorbent assay (ELISA) and the indirect immunofluorescence test (IFT) revealed similar sensitivity . In early disease, sensitivity for antibody detection could be improved by immunoblot technique and by flagellum-ELISA, which is specific for this early sensitizing B . burgdorferi antigen . For treatments, penicillin is no longer recommended as the drug of first choice, because low sensitivity of B . burgdorferi has been observed in vitro and in vivo . Tetracycline, doxycycline and amoxicillin p.o . are now preferred for the treatment of Lyme borreliosis, and in neurologic and cardiac abnormalities ceftriaxone i.v . is recommended . Treatment duration should be 14 days in early disease and 30 days in late disease.

J Paediatr Child Health, 1991 Jun, 27(3), 175 - 9
Failure of intravenous infusions in neonates; Hecker JF et al.; The median life expectancy (survival) of 286 peripheral intravenous infusion sites in 105 babies in a children's intensive care unit was 36 h . Unadjusted univariate survival analysis revealed that dextrose infusions and the initial infusions received by a baby had longer survival than total parenteral nutrition (TPN) infusions and later infusions respectively . Also infusions with cloxacillin and penicillin survived for longer than average while infusions with phenytoin had reduced survival . Gestational age, weight, infusion site, other drugs, co-infusion of Intralipid with TPN solutions and neutralization of TPN did not influence survival of infusions . Multivariate survival analysis confirmed the findings for TPN and penicillin but not for cloxacillin, phenytoin or later infusions . Multivariate analysis also suggested that survival was improved with ampicillin and aminophylline and worse for leg sites, for older babies and for infusions in which the fluids were given at greater rates . It also indicated that neutralization of TPN improved survival.

Trends Biochem Sci, 1991 Jun, 16(6), 234 - 7
Semi-synthetic approaches to novel penicillins; Nayler JH; The first part of this account of the discovery of penicillin, published in last month's issue of TIBS, concluded with the detection of 6-beta-amino-penicillanic acid (6-APA), the nucleus of the penicillin structure . The exploitation of 6-APA led to the preparation of a range of clinically important semi-synthetic penicillins, which is described in this article.

Changgeng Yi Xue Za Zhi, 1991 Jun, 14(2), 101 - 5
{The clinical observation and follow-up of acute rheumatic fever}; Liang CD et al.; There were 15 patients under 15 years of age with cases of acute rheumatic fever diagnosed by revised Jones criteria admitted to pediatric department, Chang Gung Memorial Hospital of Kaohsiung from Jan . 1986 through Dec . 1989 . There were 11 boys and 4 girls . The age of onset was more commonly between 13 and 15 years old . Carditis was the most common clinical presentation, noted in 13 cases . Eleven cases had valvular involvement: mitral regurgitation (MR) and mitral valve prolapse (MVP), 5 cases; MR and aortic regurgitation (AR), 4 cases; MR, 1 case; and MVP, 1 case . One case with MR + AR also suffered transient acute glomerulonephritis, which presented with gross hematuria but improved one week later . And one case with severe MR expired due to severe congestive heart failure . Eleven of the 14 survivors had regular follow-up at our clinic with an interval of 3 months to 38 months, and received parenteral benzathine penicillin for prophylaxis . During follow-up, the murmur in 4 cases with MR + MVP and 2 cases with MR + AR disappeared within 2 months . One of the three cases who had not received secondary prophylaxis had recurrence of rheumatic fever 3 years later after the initial diagnosis.

J Trop Pediatr, 1991 Jun, 37(3), 100 - 5
A clinico-epidemiological study of sickle cell anaemia in Saudi Arabia; Mulik R et al.; Ninety-nine Saudi Arabian children aged between 3 months and 15 years attending the sickle cell anaemia (SCA) clinic were studied using a review of case notes and an interview at clinic visits . All the patients come from the southwest and west area of Saudi Arabia . Despite the lack of infant screening for SCA, 73 per cent were diagnosed before the age of 3 years, reflecting severe early symptoms of the disease . The serious complications of SCA were two times higher, the number of admissions were three times higher and the attack rate for pneumococcal meningitis was nine times higher in our study population than previously reported from the Eastern Province of the country . Hand-foot syndrome was the commonest complication affecting 58 per cent of the children . It has been stated previously that there is no need to give penicillin prophylaxis to SCA children in Saudi Arabia, based on the observations in the Eastern Province only . Our study shows that SCA in western and southwestern population of Saudi Arabia is as severe as is described in American blacks . Therefore, we recommend penicillin prophylaxis to be given to the SCA children in the southwest and west regions of the country.

Rapid Commun Mass Spectrom, 1991 Jun, 5(6), 263 - 8
Investigation of collisional-activation decomposition process and spectra in the transport region of an electrospray single-quadrupole mass spectrometer; Voyksner RD et al.; The use of collisional-activation dissociation (CAD) in the electrospray transport region was evaluated for generating structural information on several pesticides and antibiotics . The collision energy used to generate the CAD spectra could be varied easily by changing the capillary/skimmer potential difference, imparting from 0 eV to above 16 eV internal energy to the near thermal ions generated by electrospray . The internal energy distribution for low-energy collisions (capillary/skimmer potential difference of 20 V) closely matches the curves generated by a triple-quadrupole mass spectrometer . Furthermore, the CAD spectra for selected compounds generated by electrospray in the transport region at a capillary/skimmer potential difference of 30-50 V closely resembled those obtained from the {M + H}+ ion by a triple quadrupole using 30 eV collision energy . The CAD of ions in the transport region resulted in 70% to 80% daughter-ion yields and minimal loss in overall ion current compared to the ion current for protonated or cationized parent molecules . The major daughter ions for 10 pg of Aldicarb and penicillin G could be detected (signal-to-noise ratio greater than 5) under full-scan CAD conditions.

Jpn J Psychiatry Neurol, 1991 Jun, 45(2), 265 - 70
Propagation of acute seizure activities observed by local cerebral glucose metabolism; Kato M et al.; We studied the propagation of acute focal seizure activities in animals by means of the {14C}deoxyglucose method . Seizures were induced unilaterally by injecting penicillin in the neocortical area 4 and area 9 in the monkey, and by injecting kainic acid in the hippocampus of the rat and in the ventral posterolateral thalamic nucleus of the cat . The earliest and the most consistent propagation was the one to the target structures of the primary focus, mediated through the "preferential" projection pathways . At a more advanced stage, the propagation to the immediately adjoining brain regions occurred, followed by the secondary propagation to the target structures of the adjoining regions . Propagation to the contralateral homologous structure was not a major one at the early stage unless the structure of the primary focus had its own commissural connections.

P N G Med J, 1991 Jun, 34(2), 122 - 8
Management of common potentially serious paediatric illnesses by aid post orderlies at Tari, Southern Highlands Province; Rogers S et al.; Systematic observations were made of a small number of aid post orderlies (APOs) managing children with the common but potentially serious symptoms of cough, fever and diarrhoea . On-site performance was evaluated against recommended management guidelines set out in Dr Keith Edwards' Diagnosis and Treatment of Common Childhood Illnesses for APOs . History taking at the aid post was brief and usually non-exploratory; examination of patients was often neglected . Drug prescription was generally appropriate for the diagnosis made, but drug dosages were often incorrect and treatment principles were rarely explained to guardians . Preventive health issues were rarely tackled . Our study reaffirms the need for on-site assessment of the performance of paramedical workers, sets priority demands for continuing education of health workers, and provides a framework for competency-based problem-solving activities within this contextPIP: This operational study of the performance of aid post orderlies (APOs) at Taril, Southern Highlands Province, Papua New Guinea, was conducted as a follow up to prior operations research workshops and specific research which highlighted the need for adequate medical care . The assessments of the clinical performance (medical history taking, examination, diagnosis, treatment, and advice) of APOs were made by a trained Huli observer in mid-1988 . 86 consultations were recorded for children brought to the aid posts for complaints of cough (40), fever (24), or diarrhea (22) and seen by 7 Tari APOs . Data were evaluated by a medical officer who used the recommended Health Department reference . Diagnosis and Treatment of Common Childhood Illnesses for APOs . Results for each illness are provided . APOs made an adequate diagnosis based on the mild and self limiting symptoms, but the medical histories and examinations were too superficial to assess the severity of the illness . Sometimes the level of treatment was inappropriate, i.e., 70% of the children received appropriate cough mixtures and antimalarials for coughs, but over 50% received inadequate doses of procaine penicillin for their age . Several children were not properly referred to the hospital for management of severe dehydration . Treatments were qualitatively correct for the diagnosis made, but inappropriate doses were often prescribed . Information was rarely given to guardians on the need for repeat medications or the signs of treatment failure . There was ample opportunity to reinforce the importance of immunization, adequate nutrition, malaria control, or personal and food hygiene but APOs did not take advantage of the situation . The results reinforce the need for on-site assessment of paramedical workers who are entrusted with frontline care of patients . It has been found that APOs are often neglected by senior staff; there are complaints from APOs that they feel unappreciated by Health Department staff and the community served . Reference is made to a study of rural health services which found that only 585 of officers in charge of health centers had made any supervisory visit in the 2 months preceding the survey . In some provinces APOs sometimes are given a 1-week inservice training period a year . Structural changes, APO selection procedures, education, inservice training, supervision, and support must be addressed in order to overcome some of the apparent weaknesses in the delivery system . The emphasis is on a problem-based approach and education and continued training .

Lancet, 1991 Jun 1, 337(8753), 1308 - 10
Allergic reactions to long-term benzathine penicillin prophylaxis for rheumatic fever . International Rheumatic Fever Study Group.
{Fungal toxin dihydroxyaflavinine inhibits non-competitively GABAA receptor channel expressed in Xenopus oocytes}
Yao Y, Li Y.

Shanghai Institute of Physiology, Academia SinicaDihydroxyaflavinine is an indole-derived metabolite of Aspergillus flavus . Its action on GABA-induced response was quantitatively studied on the GABAA receptor expressed in Xenopus oocytes after injection of chick brain mRNA under voltage-clamp conditions . Dihydroxyaflavinine inhibits GABA-induced current non-competitively with KI = 12 mumol/L . This blockage is rapidly reversible . In comparison, the inhibitory effect of penicillin on GABAA receptor is enhanced by increasing GABA concentration . Ro 15-1788 (a benzodiazepine ligand with KD = 0.6--2 nmol/L) of concentration as high as 1 mumol/L, does not mask the action of 10 mumol/L dihydroxyaflavinine, indicating that dihydroxyaflavinine acts on a site different from benzodiazepines . Dihydroxyaflavinine appears to expedite desensitization of the receptor, which is similar to the action of picrotoxin and in contrast with that of penicillin and bicuculline.

Neuropharmacology, 1991 Jun, 30(6), 637 - 42
In vitro depressant effects of U-54494A, an anticonvulsant related to kappa opioids, in the hippocampus; Proietti ML et al.; The effects of cis-3,4 dichloro-N-2-(1-pyrrolidinyl)cyclo-hexyl-benzamide (U-54494A), an anticonvulsant related to kappa opioids, were studied in vitro on the extracellular electrical activity of the CA1 region of slices of hippocampus in the rat . The effects of U-54494A were compared to those of the kappa opioid agonist trans-3,4 dichloro-N-2-(1-pyrrolidinyl)cyclo-hexyl benzeneacetamide methane sulphonate (U-50488H) . Both U-54494A and U-50488H, in concentrations of 50 and 100 microM, respectively, reduced the magnitude of the orthodromically evoked CA1 population spikes after electrical stimulation of the stratum radiatum (100-200 microA, 70 microseconds, 0.1 Hz) . Naltrexone (25 microM), or the selective kappa opiate receptor antagonist, 1-cyclopenthyl-5-(1,2,3,4,5,6-hexahydroxy-3,6,11-trimethyl-2 -6-methano-3- benzazocin)-3-pentatone methane sulphonate (WIN 44441-3) (25 microM), prevented the depressant activity of U-54494A (200 microM) on the CA1 population spikes . High calcium (+3mM) solutions prevented the depressant activity of increasing concentrations of both U-54494A and U-50488H on the amplitude of CA1 population spikes . Up to 200 microM, both drugs were ineffective in depressing the epileptiform bursting in CA1, due to 1 mM penicillin or to perfusion of the slice in absence of magnesium ions . The results demonstrate: (1) the inability of U-54494A to show antagonistic activity in two in vitro models of interictal epilepsy; (2) a depressant effect of U-54494A on basal synaptic transmission in the CA1 region of the hippocampus, which may be related to an influence on transneuronal calcium currents and which may be involved in the reported antagonism of ictal epileptic seizures by drugs.

BMJ, 1991 May 4, 302(6784), 1051 - 2
Allergy to penicillin: fable or fact?
Surtees SJ, Stockton MG, Gietzen TW.
OBJECTIVE--To assess whether, on the basis of one blood test, penicillin allergy might be excluded sufficiently for general practitioners to give oral penicillin to patients claiming a history of penicillin allergy . DESIGN--Prospective study of patients referred by general practitioners . SETTING--Outpatient allergy clinic in a district general hospital . PATIENTS--175 referred patients who gave a history of immediate type reaction to penicillin, of whom 144 attended as requested and 132 completed the investigations . MAIN OUTCOME MEASURES--History and examination, serum radioallergosorbent test to phenoxymethylpenicillin and benzylpenicillin, and oral challenge with penicillin . RESULTS--Of 132 patients, four were confirmed to have penicillin allergy by the radioallergosorbent test and 128 had an oral penicillin challenge without ill effect . CONCLUSIONS--Most patients who gave a history of penicillin allergy are not so allergic, and their actual allergic state should be substantiated whenever feasible . For patients reporting minor or vague reactions negative findings with a radioallergosorbent test to phenoxymethylpenicillin and benzylpenicillin provide sufficient evidence to give oral penicillin safely.

J Am Acad Dermatol, 1991 May, 24(5 Pt 2), 832 - 5
Tertiary syphilis of the face; Chung G et al.; We report a case of noduloulcerative tertiary syphilis that had gone misdiagnosed as discoid lupus erythematosus for many years . This case is noteworthy for (1) a Jarisch-Herxheimer-like reaction, (2) a dramatic response to penicillin therapy despite the presence of long-standing disease, and (3) posttreatment granulomas of possible hypersensitivity origin.

Ann Allergy, 1991 May, 66(5), 385 - 92
Current status of mold immunotherapy; Dhillon M; There is evidence to suggest that molds can cause IgE-mediated upper respiratory tract disorders and immunotherapy is efficacious in a select group . The environmental sampling studies show a remarkably small numbers of molds accounting for a majority of the mold load in various diverse locations . These are Cladosporium, Basidiospores, Aspergillus, and Alternaria-Penicillin families . Basidiospores have been underreported in the older studies because of difficulties in their identification . Whether the absolute mold level is the most important factor leading to IgE formation and induction of upper respiratory tract symptoms is uncertain . Certainly, the majority of the studies are based on the assumption that the absolute level of mold in the environment is the most important factor leading to the development of symptoms, but this is not based on strong evidence . A major problem in the majority of the studies is a lack of standardization of extracts which may lead to false negatives on skin testing and thus produce variable data in population evaluations comparing the prevalence of mold to its ability to induce IgE production and symptoms . The best current trials to document the efficacy of mold immunotherapy have been with the standardized Cladosporium extract . Unfortunately, these results cannot be extrapolated to the commercially available mold extracts available in the United States either for immunotherapy or for skin testing . These extracts are highly variable in their potency, prone to high false negative rates, and at best serve as poor skin testing reagents and possibly even worse immunotherapy reagents . Adequately standardized mold reagents are urgently needed to determine whether the Cladosporium data can be extrapolated to them in any meaningful way.

Am J Physiol, 1991 May, 260(5 Pt 2), R934 - 40
Respiratory responses to focal and generalized seizures in cats; Paydarfar D et al.; We studied the effects on breathing of seizures induced by focal injection of penicillin G into the parietal cortex in 13 anesthetized cats . Electrocorticograms, ventilation, end-tidal PCO2, and intrapleural and arterial pressures were monitored; changes of these variables were related to the stages of motor seizure . The first respiratory responses, tachypnea and hyperpnea, usually occurred before any peripheral muscular contractions developed . Progression of the seizure was always accompanied by further tachypnea and hyperpnea . The hyperpnea associated with all stages of seizure activity resulted in hypocapnia, which was sustained even during prolonged tonic-clonic motor convulsions that caused a threefold increase of metabolic rate . The extreme tachypnea of tonic generalized convulsions led to increased end-expiratory lung volume because of dynamic hyperinflation associated with very short expiratory durations in the tonic phase . We suggest that the profound effects of seizures on respiration are by feedforward mechanisms from the cortical focus itself and from subcortical circuits, such as hypothalamus, that become involved during seizure propagation and generalization . Peripheral respiratory feedback mechanisms are not important for the genesis of seizure-induced hyperpnea.

Rinsho Shinkeigaku, 1991 May, 31(5), 561 - 3
{Lyme disease with the triad of neurologic manifestations}; Shiokawa T et al.; A 40-year-old man developed progressive neurologic manifestations following a tick bite with subsequent localized erythema migrans . These manifestations included bilateral sensory radiculoneuritis (T7-12), rectovesical dysfunction, paraparesis, right facial palsy and nuchal rigidity . Both serum and cerebrospinal fluid titers of IgG antibody against Borrelia burgdorferi were 1:8,192 using indirect immunofluorescence assay . No IgM antibody was detected . With high-dose intravenous penicillin and corticosteroid treatment the neurologic symptoms and signs gradually subsided, with a corresponding decrease in the IgG antibody titers . Among the cases of Lyme disease reported so far in Japan, the present case seems to be typical and serious in terms of the severity of nervous system involvement and the intensity of the antibody response.

J Assoc Off Anal Chem, 1991 May-Jun, 74(3), 497 - 501
Determination of penicillin G residues in edible animal tissues by liquid chromatography; Boison JO et al.; An improved method has been developed for the determination of benzyl penicillin in animal tissues . Tissues are fortified with a known amount of penicillin V (internal standard) and extracted with water . The extract is deproteinized with sulfuric acid and sodium tungstate, filtered, and concentrated on a conditioned C18 solid phase extraction column . Penicillin V and benzyl penicillin are then eluted from the column with 1 mL 60% acetonitrile-35% water-5% 0.2M phosphate buffer solution and derivatized with 1 mL 1,2,4-triazole-mercuric chloride solution at 65 degrees C for 30 min . An aliquot of this sample is analyzed by reverse phase liquid chromatography with UV detection at 325 nm . The limit of detection is 5 micrograms/kg (ppb) penicillin G (8.4 IU/kg) in liver, kidney, and muscle tissues).

Am J Otol, 1991 May, 12(3), 184 - 7
Endolymphatic sac surgery for refractory luetic vertigo; Huang TS et al.; The clinical symptoms of otitic syphilis, either congenital or acquired, are indistinguishable from Meniere's disease . In most cases the symptoms can be controlled by long-term and intensive medical treatment with penicillin and steroids . However, in some cases, luetic vertigo is refractory to such medical regimens, and surgical intervention may become necessary . We report on endolymphatic sac procedures performed on 37 patients with presumed luetic vertigo refractory to medical treatment, between March 1980 and December 1987, with follow-up ranging from 2 years to 9 years and 9 months . Results show that vertigo was completely and substantially controlled in 81 percent of cases, with 2 patients showing improvement in hearing, as assessed with AAO-HNS criteria . It is concluded that endolymphatic sac surgery is appropriate in treating refractory luetic vertigo when intensive medical therapy is unsuccessful, particularly in cases of late or tertiary-acquired lues, such as in this series.

Chin Med J (Engl), 1991 May, 104(5), 428 - 31
Hypothalamic encephalitis with oligodendrocytic glial nodules . Case report of a Chinese boy; Wang LN et al.; A case of hypothalamic encephalitis proved by postmortem examination is reported . The patient was a three-year-old Chinese boy who had complained of obesity for one year and fever for half a year . Three days after admission to a hospital, the patient suddenly died of allergic reaction to intramuscular penicillin, without additional complaints . Autopsy revealed severe bilateral outfall of neurons in the ventromedian hypothalamic nuclei with diffuse hyperplasia of astrocytes and some glial nodules consisting chiefly of oligodendroglias and perivascular cuffing . Similar changes were noticed in hypothalamus at the level of optic chiasm, but the posterior hypothalamic nuclei and lateral hypothalamic nuclei were intact . This article provides significant data for the study of hypothalamic function.

J Neurol Sci, 1991 May, 103(1), 48 - 50
Syphilitic meningitis causing paraparesis in an HIV-negative woman; Byrne TN et al.; Syphilitic meningitis, which can occur near the time of secondary syphilis, is frequently asymptomatic . There has been one recent report of an HIV-positive patient who developed syphilitic polyradiculopathy following a recent history of secondary syphilis . We describe an HIV-negative woman in whom paraparesis occurred secondary to syphilitic meningitis . Complete recovery followed a course of high-dose intravenous penicillin therapy, emphasizing the treatable nature of this cause of paraparesis.

Minn Med, 1991 May, 74(5), 15 - 9
Patients go home for care . But do their doctors make house calls?
Teigen T.
Caring for a patient at home no longer consists simply of a black bag and a stethoscope warmed in the physician's palm . No longer is it a quarantine sign the physician tacked up on the front door, or a thermometer and an injection of penicillin . Today, taking care of a patient at home often involves sophisticated equipment, a highly trained staff of nurses and allied professionals, and a set of skills and a body of knowledge with which many physicians are neither familiar nor comfortable.

J Heart Lung Transplant, 1991 May-Jun, 10(3), 401 - 8
Functional studies of the heart during a 24-hour preservation using a new autoperfusion preparation; Chien SF et al.; Serial cardiac function studies were carried out during a 24-hour preservation in a new autoperfusion multiorgan preparation using adult Yorkshire swine (n = 8) . The heart was removed with the lungs, liver, pancreas, duodenum, and both kidneys while they were still perfused by the heart and oxygenated by the lungs . The organs were placed in a 32 degrees C bath solution containing lactated Ringer's, heparin, and neomycin . Fresh blood and a solution containing glucose (10%) with potassium chloride (2 gm/L), calcium chloride (1 gm/L), heparin sodium (100 mg/L), mannitol (12.5 gm/L), insulin (100 U/L), metronidazole hydrochloride (500 mg/L), penicillin (1,000,000 U/L), and methylprednisolone (250 mg/L) were given slowly through the portal vein . A fat emulsion 2 ml, methylprednisolone 30 mg, and heparin sodium 20 mg were given through the portal vein every 2 hours . No inotropic drugs were used . Aortic systolic pressures ranged from 79 to 97 mm Hg; the aortic diastolic pressures ranged from 44 to 61 mm Hg . Central venous pressures ranged from 0.4 to 2.0 mm Hg, and the heart rate was 69 to 81 beats/min . Left ventricular maximum dp/dt ranged from 1405 to 1836 mm Hg/sec, and maximum dp/dt/p ranged from 17.0 to 26.2 (sec-1) . Aortic blood flow ranged from 1.2 to 1.6 L/min, and systemic resistance ranged from 33 to 53 U . Lactic acid decreased from 8.15 to 2.80 mmol/L . Myocardium wet/dry weight ratio after preservation averaged 5.13 (vs 5.09 for control) . These results suggest that the heart may be preserved up to 24 hours with minimal change in function with this new autoperfusion preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimicrob Agents Chemother, 1991 May, 35(5), 886 - 91
Characterization of a beta-lactamase found in Eikenella corrodens; Lacroix JM et al.; Eleven strains of Eikenella corrodens with beta-lactamase activity were isolated from a patient with refractory periodontitis who had previously been treated with penicillin antibiotics . These strains were relatively resistant to benzylpenicillin, amoxicillin, and ampicillin (MICs, greater than or equal to 64 micrograms/ml); susceptible to amoxicillin-clavulanate (2:1) (MICs, less than or equal to 4 micrograms/ml); and moderately susceptible to cephalothin and cephaloridine (MICs, 0.12 to 16 micrograms/ml) . The addition of 1 microgram of potassium clavulanate, a beta-lactamase inhibitor, per ml resulted in a significant increase in the susceptibilities of these strains to penicillins but not to cephalosporins . Potassium clavulanate had no effect on non-beta-lactamase-producing strains . Enzyme production was constitutive since activity was not increased when cells were cultivated in the presence of benzylpenicillin . Enzyme activity was strongly inhibited by potassium clavulanate, sulbactam, and iodine; weakly inhibited by cloxacillin, imipenem, and moxalactam; but not inhibited by aztreonam, EDTA, or p-chloromercuribenzoate . By gel infiltration, the enzyme had an estimated molecular mass of 29 kDa . Isoelectric focusing of the partially purified enzyme gave a major beta-lactamase band at pH 5.50 and a minor band at pH 5.60 . Plasmids were not detected in any of the 11 beta-lactamase-positive strains . This enzyme is considered to belong to class 2a of the Bush classification scheme.

Neuropediatrics, 1991 May, 22(2), 107 - 9
Infective acute transverse myelopathy . Report of two cases; Linssen WH et al.; Two children with acute transverse myelopathy following adenovirus and Borrelia Burgdorferi infections are presented . The diagnosis stems from the clinical presentation, the determination of specific antibodies in serum and the favorable response to penicillin treatment in the case of neuroborreliosis . Both children made a good recovery . The cerebrospinal fluid examination showed a highly increased myelin basic protein concentration, indicating demyelination.

Trends Biochem Sci, 1991 May, 16(5), 195 - 7
Early discoveries in the penicillin series; Nayler JH; It is now 50 years since the therapeutic potential of penicillin was first demonstrated . This first antibiotic and the series of compounds derived from it have been of immense importance in modern medicine . This article describes the early search for more potent penicillin derivatives, culminating with the discovery of an intermediate of penicillin biosynthesis, 6-beta-amino penicillanic acid (6-APA) . A companion article in next month's TIBS will chart the subsequent exploitation of 6-APA and the preparation of a range of clinically important semi-synthetic penicillins.

Hinyokika Kiyo, 1991 May, 37(5), 507 - 14
{Clinical analysis of male urethritis}; Nakata S et al.; We reviewed 497 patients with male urethritis diagnosed between January, 1986 and March, 1989 at the Asama General Hospital . The incidence of gonococcal urethritis (GU) was 47.7%, and that of non-gonococcal urethritis (NGU) 52.3% . There was no difference in the age distribution between GU and NGU . Prostitutes were the most common source of the infection in both GU and NGU . Incubation periods were longer in NGU than in GU, statistically . Urethral discharge was the most common symptom . Purulent urethral discharge was seen more commonly than serous urethral discharge in GU . On the contrary, serous urethral discharge was more common in NGU . Penicillin-resistant gonococcus comprised 29.4% and mixed infection of the C . trachomatis existed 25.6% in GU . C . trachomatis was detected in 71.8% in NGU . In GU, new quinolones and penicillins were administered frequently . The effective rates 1 week after the administration were 80.6% and 83.3%, respectively . In NGU, new quinolones and minocycline were administered frequently . The effective rates were 70.4% and 85.3%, respectively . Ofloxacin (OFLX) showed the highest effective rate to NGU among the four new quinolones . The relapse rate for the two-week administration group was lower than that for the one-week-administration group, but the difference was not statistically significant.

Eur J Biochem, 1991 Apr 10, 197(1), 75 - 80
Site-directed chemical conversion of serine to cysteine in penicillin acylase from Escherichia coli ATCC 11105 . Effect on conformation and catalytic activity; Slade A et al.; Penicillin acylase (EC 3.5.1.11) was completely inactivated with equimolar phenylmethane {35S}sulphonyl fluoride (PhMe35SO2F); the stability of the sulphonyl group in the modified protein was determined by measurement of the radioactivity in ultrafiltrates . In 8 M urea, the rate of loss of the sulphonyl group was similar to that observed in PhMeSO2F-inactivated chymotrypsin {Gold, A.M . & Fahrney, D . (1964) Biochemistry 3, 783-791} . Incubation of the PhMeSO2F-inactivated acylase with 0.7 M potassium thioacetate yielded an acetylthiol enzyme which was subsequently converted to a thiol-enzyme during incubation with 10 mM 6-aminopenicillanic acid . 4-Pyridyl-ethylcysteine was released by acid hydrolysis after reaction of the thiol-protein with 4-vinylpyridine . The rates of reaction of thiol-penicillin acylase with iodoacetic acid and 2,2'-dipyridyl disulphide were consistent with the presence of an incompletely accessible cysteinyl sidechain . After carboxymethylating the thiol-enzyme with iodo{2-3H}acetic acid, the label was shown by SDS/PAGE and sequencing analysis to be associated exclusively with the beta-chain NH2-terminal residue, indicating conversion of Ser290 to S-carboxymethyl-cysteine . Near-ultraviolet CD spectra showed the conformation of thiol-penicillin acylase to be indistinguishable from that of the native protein but the catalytic activity was less than 0.02% of that of the normal enzyme . The possibility that Ser290 acts as a nucleophile in catalysis is discussed.

J Pediatr Gastroenterol Nutr, 1991 Apr, 12(3), 310 - 4
Liver function in early congenital syphilis: does penicillin cause a deterioration?
Venter A, Pettifor JM, Duursma J, Pudifin DJ, Smyth A, Becker PJ.
In this prospective study, neonates with clinical congenital syphilis were investigated to determine if penicillin therapy caused a deterioration in liver function . The relationship between circulating immune complexes and liver involvement was monitored, and the efficacy of steroid therapy as an adjunct in the treatment of congenital syphilis was investigated . Thirty neonates with clinical congenital syphilis were randomly assigned into two groups: one group received penicillin therapy only, and the other group penicillin and prednisone as an adjunct . Twenty-one infants who did not have clinical or serological syphilis, born to seropositive mothers, served as a "control" group . Liver function tests, full blood counts, and immunological studies were performed at various intervals up to 3 months of age . Although the symptomatic groups differed significantly from the asymptomatic group in most of the parameters measured, there were no significant differences noted between the two symptomatic groups at any time point . No direct relationship between penicillin therapy and either deteriorating liver function or the presence of circulating immune complexes could be demonstrated . Also, prednisone therapy did not modify any of the parameters studied.

Clin Orthop, 1991 Apr, (265), 178 - 82
Infections of the clavicle in children; Rasool MN et al.; Of 23 children with infections of the clavicle, 11 had pyogenic osteomyelitis, four had tuberculosis, and eight (infants) had congenital syphilis . Acute pyogenic infections were treated by drainage . Resection of the clavicle was performed in chronic cases . Curettage and antituberculosis drugs were effective for children with tuberculous infection of the clavicle . Procaine penicillin was used for the treatment of congenital syphilis . Biopsy is generally necessary to differentiate chronic infection from neoplasm.

Farmaco, 1991 Apr, 46(4), 565 - 77
Enzymatic synthesis of ampicillin: a chemometric optimization; Boccu E et al.; Statistical methods of optimization were applied to the enzymatic semisynthesis of ampicillin catalyzed by penicillin acylase . Since the traditional approach fails in determining both the presence of interactions between the variables and their magnitude, the reaction was reconsidered by means of chemometric techniques . In this work we determined the interaction between temperature and pH for the first time.

Int J Pediatr Otorhinolaryngol, 1991 Apr, 21(2), 155 - 61
Beta-lactamase production and bacterial tolerance in recurrent acute otitis media; Roos K et al.; Different reasons for treatment failure or relapse of acute otitis media (AOM) have been suggested . In this study 38 children (8 treatment failures, 13 relapses of AOM within one month and 17 with a new AOM) were compared to 25 matching healthy children, regarding beta-lactamase producing bacteria and tolerance to penicillin V and ampicillin . Branhamella catarrhalis was the most common bacteria found in the nasopharynx and was isolated in 60% of children with AOM and in 48% of the control group . Fifty-two percent of the children classified as treatment failure or relapse of AOM had aerobic beta-lactamase producing bacteria in NPH . No bacteria tolerant to penicillin or ampicillin were found . Thus, beta-lactamase-producing bacteria seem to play a decisive role in treatment failure and relapse of AOM . On the other hand, tolerance to penicillin V or ampicillin does not seem to have any impact on healing of AOM.

Analyst, 1991 Apr, 116(4), 387 - 90
Utility of certain pi-acceptors for the spectrophotometric determination of some penicillins; Askal HF et al.; Two simple and sensitive spectrophotometric methods are described for the determination of six penicillin derivatives . The methods are based on the reaction of these drugs as n-electron donors with either 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) or 7,7,8,8-tetracyanoquinodimethane (TCNQ) as pi-acceptors, to give a highly coloured radical anion . The coloured products are quantified spectrophotometrically at 460 and 842 nm for DDQ and TCNQ, respectively . The optimization of the different experimental conditions is described . The interference from streptomycin sulphate and common degradation products was also studied . The proposed methods were applied successfully to the determination of the different penicillins investigated, either in pure or dosage forms, with good accuracy and precision . The results were compared with those given by the official United States Pharmacopeial XXI method.

Sex Transm Dis, 1991 Apr-Jun, 18(2), 102 - 6
Failure of recommended maternal therapy to prevent congenital syphilis; Rawstron SA et al.; A pregnant women with secondary syphilis received appropriate therapy with penicillin in the last trimester of pregnancy . At delivery, her titre had fallen fourfold, and the baby had a non-reactive cord blood titre at birth . However, the treatment failed to prevent infection in the infant, and the baby had developed signs of congenital syphilis at 10 weeks of age . The definition of "adequate therapy" of pregnant women is unclear, and recent guidelines are contradictory . Therefore, literature that pertains to penicillin therapy in pregnancy is reviewed, and new guidelines for therapy proposed.

Biull Eksp Biol Med, 1991 Apr, 111(4), 351 - 3
{Effects of PN 200-110 on penicillin-induced epileptic activity in the cerebral cortex of rats}; Kryzhanovskii GN et al.; In experiments on freely moving Wistar rats it was shown that an intraperitoneal administration of PN 200-110 in a dose of 2 mg/kg in the period of steady epileptic activity (EpA) with regular generation of ictal discharges in penicillin--induced focus resulted in suppression of EpA in most animals . Antiepileptic effect of the drug was manifested by decreasing frequency appearance of ictal discharges and shortening of the epileptic focus existence time . Intraperitoneal administration (5 mg/kg) and intraventricular injection (10 nmol) of PN 200-110 20 min before the epileptic focus formation resulted in an increased latency period of appearance interictal discharges and decreased number of ictal discharges, and shortening of the existence time of epileptic focus.

Pract Odontol, 1991 Apr, 12(4), 23 - 4, 28
{Report of 16 cases of Ludwig's angina: 5-year review}; Esquivel Bonilla D et al.; Ludwig's angina es a bilateral gangrenous induration of the connective tissues of the neck and floor of the mouth . It causes rapid airway obstruction and affects the submandibular, sublingual and submental spaces . The main causes of infection are usually the second and third molars . In severe or difficult cases, an early surgical procedure is often necessary . According to our experience on this entity, as gathered in five years (16 cases), the process has a dental origin . Two deaths were reported . Most cases were treated with crystalline penicillin G, metronidazole, dicloxacillin or amykacin; tracheotomy was performed on 12 patients, four other cases were treated with controlled breathing . The authors suggest antibiotic therapy, early surgery when needed, with a careful monitoring of airway symptoms to lessen the need of tracheotomy and reduce the death rate . Ludwig's angina should by no means go unnoticed in its early stages; early diagnosis should always be considered.

Immunology, 1991 Apr, 72(4), 571 - 6
Penicillamine and penicillin can generate antigenic determinants on rat peritoneal cells in vitro; O'Donnell CA et al.; Conjugation of the protein-reactive drugs D-penicillamine (PA) and benzylpenicillin (BP) to immune cells to generate drug-derived antigenic determinants has been implicated in drug-induced allergies and autoimmunity . We have therefore developed an in vitro system to demonstrate and characterize the formation of cellular antigens by these drugs . Binding of PA and BP to rat peritoneal exudate cells was detected by a cell ELISA, employing rabbit antisera specific for each drug, and an indicator system employing a second antibody coupled to biotin-streptavidin-beta-galactosidase . For both drugs, binding was detected over the concentration range 125-1000 micrograms/ml . PA bound cells rapidly (maximum binding within 10 min), whereas BP bound relatively slowly (maximum binding occurring later than 4 hr) . A possible role for intracellular processing and cellular metabolic activity in the generation of these drug-derived antigenic determinants was examined . Pretreatment of the cells with the fixative paraformaldehyde significantly enhanced binding of PA but not BP . Treatment of cells with the lysosomotropic agents ammonium chloride or chloroquine, or with the metabolic inactivator sodium azide, did not affect the binding of either drug compared with untreated control cells . However, treatment with the oxidising agent copper sulphate, or the cellular activator phorbol myristate acetate, did significantly enhance binding of both drugs to the cells . Therefore, binding of PA and BP to the cell surface appears not to require an intracellular processing event to generate a recognizable antigenic determinant, but is enhanced by treatments that stimulate oxidative processes.

Electroencephalogr Clin Neurophysiol, 1991 Apr, 78(4), 302 - 10
Relay stations and neurotransmitters between the pallidal region and the hippocampus; Sabatino M et al.; The effects of internal pallidum and lateral habenula stimulation on epileptiform activity of cat's hippocampus were studied . A steady interictal activity was induced by locally applied sodium penicillin (PCN) solution . Both pallidal and habenular electrical stimulation caused an increase in spike frequency and amplitude . Intraperitoneally injected atropine sulphate failed to modify pallidal and habenular influences . Intraperitoneal methysergide bimaleate (5-HT antagonist) suppressed the effects of habenular stimulation . In contrast to the effects of pallidal and habenular stimulation, raphe electrical stimulation inhibited hippocampal spiking and intra-raphal muscimol (a GABA receptor agonist) enhanced hippocampal-based epilepsy . After muscimol, raphe stimulation at the same threshold parameters failed to affect hippocampal activity . In cats with habenular lesions hippocampal spike frequency and amplitude were reduced and intra-raphal muscimol did not affect the hippocampus . The results are discussed in the light of a complex interrelationship between basal ganglia and hippocampus . The role of the lateral habenula and of the medial raphe as relay stations between the two regions is emphasized.

J Neurochem, 1991 Apr, 56(4), 1201 - 6
Cell damage associated with changing the medium of mesencephalic cultures in serum-free medium is mediated via N-methyl-D-aspartate receptors; Driscoll BF et al.; Dopaminergic neurons from embryonic rat mesencephalon were grown in simple serum-free media . The cells develop over a period of several weeks in vitro, particularly between day 14 and day 23 . Removing the culture medium and replacing it with fresh medium during this interval caused severe damage to the cultures; this damage is mediated by excitatory amino acids acting through glutamate receptors . Damage could be completely prevented by antagonists of the N-methyl-D-aspartate subtype of glutamate receptor . As expected, medium that contains glutamate (i.e., Ham's F-12 medium) caused damage; however, medium that contains no glutamate or aspartate (i.e., Dulbecco's modified Eagle medium) also caused severe damage, and most of the damage was dependent on the presence of glutamine in the medium . The presence of the antibiotics penicillin and streptomycin greatly enhanced damage caused by medium change.

Mol Microbiol, 1991 Apr, 5(4), 791 - 5
Cell division and peptidoglycan assembly in Escherichia coli; Nanninga N; Research on bacterial cell division has recently gained renewed impetus because of new information about peptidoglycan assembly and about specific cell-division genes and their products . This paper concerns aspects of cell division that specifically concern the peptidoglycan . It is shown that upon division, peptidoglycan assembly switches from lateral wall location to the cell centre, that assembly takes place at the leading edge of the invaginating constriction, that the mode of glycan strand insertion changes from a single-stranded mode to a multi-stranded mode, and that the initiation of division (in contrast to its continuation) requires penicillin-insensitive peptidoglycan synthesis (PIPS) . A membrane component X (possibly FtsQ) is proposed to coordinate PIPS with the cell division-initiating protein FtsZ . It is suggested that a largely proteinaceous macromolecular complex (divisome) at the leading edge of constriction encompasses three compartments (cytoplasm, membrane and periplasm) . The composition of this complex is proposed to vary depending on whether division is being initiated or completed.

J Ind Microbiol, 1991 Apr, 7(3), 209 - 14
Beijerinckia indica var . penicillanicum penicillin V acylase: enhanced enzyme production by catabolite repression-resistant mutant and effect of solvents on enzyme activity; Ambedkar SS et al.; Beijerinckia indica var . penicillanicum mutant UREMS-5, producing 168% more penicillin V acylase, was obtained by successive treatment with UV, gamma-irradiation and ethylmethane sulfonate . Penicillin V acylase production by the mutant strain was resistant to catabolite repression by glucose . Incorporation of glucose, sodium glutamate and vegetable oils in the medium enhanced enzyme production . The maximum specific production of penicillin V acylase was 244 IU/g dry weight of cells . Effect of solvents on hydrolysis of penicillin V by soluble penicillin V acylase and whole cells was studied . Methylene chloride, chloroform and carbon tetrachloride significantly stimulated the rate of penicillin V hydrolysis by whole cells.

Med Clin (Barc), 1991 Mar 23, 96(11), 419 - 21
{Paroxysmal cold hemoglobinuria: only in the textbooks?}; Escoda L et al.; Although it was common in the preantibiotic era, paroxysmal cold hemoglobinuria (PCH) is now an exceptional condition . A 34-year-old female with anemia and episodic hemoglobinuria provoked by cold is reported . The laboratory studies suggested intravascular hemolytic anemia, and the Donath-Landsteiner test showed a biphasic IgG hemolysin with anti-P specificity . This finding and the evidence of latent syphilis were diagnostic of PCH . Penicillin therapy suppressed the hemolytic episodes, although the Donath-Landsteiner test is still positive . It is concluded that PCH is still an exisiting disease which should be considered in the differential diagnosis of episodic hemoglobinuria.

Experientia, 1991 Mar 15, 47(3), 254 - 7
4-aminopyridine and barium chloride attenuate the anti-epileptic effect of carbamazepine in hippocampal slices; Olpe H et al.; The exact mode of action of the anti-epileptic agent carbamazepine is unknown . In hippocampal slices in which epileptiform discharges were induced by addition of penicillin to the perfusion medium, the depressant effect of carbamazepine was attenuated by the potassium-channel blockers barium chloride (0.1 mM) and 4-aminopyridine (200 microM), which suggested that potassium fluxes might be involved in the mechanism of action of carbamazepine.

J Biol Chem, 1991 Mar 15, 266(8), 5087 - 93
Deacetoxycephalosporin C hydroxylase of Streptomyces clavuligerus . Purification, characterization, bifunctionality, and evolutionary implication; Baker BJ et al.; Deacetoxycephalosporin C hydroxylase from cell-free extracts of Streptomyces clavuligerus was stabilized partially and purified to near homogeneity by three anion-exchange chromatographies, ammonium sulfate fractionation, and two gel filtrations . The hydroxylase was a monomer with a Mr of 35,000-38,000 . alpha-Ketoglutarate, ferrous iron, and molecular oxygen were required for the enzyme activity . The hydroxylase was optimally active between pH 7.0 and 7.4 in a 3-(N-morpholino)propanesulfonic acid buffer and at 29 degrees C . It was stimulated by a reducing agent, particularly dithiothreitol or reduced glutathione, and ATP . The requirement for ferrous ion was specific, and at least one sulfhydryl group was apparently essential for the enzymatic hydroxylation . The Km values of the hydroxylase for deacetoxycephalosporin C and alpha-ketoglutarate were 59 and 10 microM, respectively, and the Ka for ferrous ion was 20 microM . In addition to its known hydroxylation of deacetoxycephalosporin C to deacetylcephalosporin C, the hydroxylase catalyzed effectively an analogous hydroxylation of 3-exomethylenecephalosporin C to deacetoxycephalosporin C . Surprisingly, the hydroxylase also mediated slightly a novel ring-expansion of penicillin N to deacetoxycephalosporin C . The substrate specificity of the hydroxylase is overlapping with but distinguishable from that of deacetoxycephalosporin C synthase, the enzyme which normally mediates the ring-expansion reaction (Dotzlaf, J . E., and Yeh, W . K . (1989) J . Biol . Chem . 264, 10219-10227) . Furthermore, the hydroxylase exhibited an extensive sequence similarity to the synthase . Thus, the two enzymes catalyzing the consecutive reactions for cephamycin C biosynthesis in S . clavuligerus represent apparent products from a divergent evolution.

AIDS Res Hum Retroviruses, 1991 Mar, 7(3), 323 - 31
Protracted Treponema pallidum-induced cutaneous chancres in rabbits infected with human T-cell leukemia virus type I; Tseng CT et al.; In a preliminary study, two of four rabbits infected with human T-cell leukemia virus type I (HTLV-I) demonstrated prolonged primary chancres following superinfection with Treponema pallidum, the causative agent of syphilis . Two rabbits inoculated with 1 x 10(7) HTLV-I-infected human MT-2 cells and two with infected rabbit cells from a line established in this laboratory (RLT-P), developed latent HTLV-I infection as detected by seroconversion 10 weeks after infection and by detection of HTLV-I sequences in the DNA of peripheral blood lymphocytes after amplification by polymerase chair reaction (PCR) 15 weeks after infection . The rabbits remained clinically normal and had normal blood counts . Six months after infection, the four HTLV-infected rabbits and two noninfected controls were challenged by the intradermal inoculation of 1 x 10(6) Treponema pallidum into eight sites on the shaved back . The lesions of two of the HTLV-I-infected rabbits had a time course similar to non-HTLV-I-infected controls and were completely healed by 4 weeks . The lesions of one of the other two rabbits with progressive disease began to heal about 7 weeks after T . pallidum challenge . The cutaneous lesions in the other rabbit remained dark-field positive and became a confluent eschar at 8 weeks; healing only after treatment with penicillin . Four months after the primary challenge none of the six rabbits previously challenged with T . pallidum had developed lesions after rechallenge and thus expressed chancre immunity . These results demonstrate that rabbits with latent HTLV-I infections may have defective cell-mediated immunity.

Physiol Behav, 1991 Mar, 49(3), 631 - 4
Penicillin-induced paroxysmal activity in brainstem neurons; Mameli O et al.; The spontaneous electrical activity of single mesencephalic and bulbar neurons was recorded in hemispherectomized rats, following topical application of the GABA-antagonist penicillin-G on the mesencephalon or on the rhombencephalon, to investigate whether these structures could develop a specific penicillin paroxysmal activity independently of the upper structures . Twenty minutes following penicillin-G, the mesencephalic neurons developed paroxysmal activity characterized by a significant increase in the spontaneous electrical activity, the appearance of multiunit activity and, frequently, phasic activity with rhythmical outbursts . The paroxysmal activity at bulbar level appeared later than that observed in the mesencephalon and was characterized by a significant increase of the spontaneous firing rate of the neurons, single short bursts and sometimes rhythmical outbursts . The bulbar outbursts always discharged at lower frequency than those at the mesencephalic level . Following a midcollicular transection the paroxysmal bulbar activity abruptly disappeared . This phenomenon might be explained by a loss of facilitation from superior structures on the bulbar neurons which in roditors show a poor GABA-receptor distribution . In other words, penicillin alone, due to the scarcity of GABA receptors, might not be sufficient to induce paroxysmal activity in bulbar neurons but the simultaneous presence of both the superior facilitation and the drug might enhance neuronal excitability to a critical level . However, the diffusion of the drug upwards to the mesencephalon, with consequent activation of a system allowing the downward propagation of paroxysmal activity, cannot be excluded . In conclusion, while the mesencephalic neurons demonstrate a proper ability to develop penicillin paroxysmal discharge, the bulbar neurons must be sustained by intact connections with upper structures to be able to do so.

Postgrad Med J, 1991 Mar, 67(785), 297 - 8
Disseminated gonococcal infection associated with deficiency of the second component of complement; McWhinney PH et al.; A case of C2 deficiency presenting with disseminated gonococcal infection is described . The predisposition of C2-deficient individuals to infection in addition to the commoner problem of immune complex diseases is noted . Attention is drawn to the absence of documented cases of gonococcal infection associated with C2 deficiency . No other homozygous C2 deficient family members were identified . Lifelong penicillin prophylaxis was recommended for the patient.

J Med Entomol, 1991 Mar, 28(2), 266 - 9
New procedures to enhance survival of third-instar Hypoderma lineatum (Villers) (Diptera: Oestridae) in artificial media; Chamberlain WF et al.; New techniques for the maturation of late third instars of the common cattle grub, Hypoderma lineatum (Villers), in artificial media are described . Larvae were held in either 24-well culture plates with media plus penicillin, streptomycin sulfate, nystatin, and chloramphenicol or in small salve jars on Perlite and media plus the same antibiotics . Chloramphenicol was not always necessary in the jars . Survival to pupariation of young third instars increased from 5% without nystatin and chloramphenicol to 73% when the two antibiotics were present in the culture plates . The survival of mature third instats to pupariation increased from approximately 53 to 80% after addition of nystati and chloramphenicol to the culture plates . Survival to pupariation of more mature grubs was similar in the jar and culture plate techniques . The former was more convenient, but the young grubs did not survive well in the jars.

Trop Med Parasitol, 1991 Mar, 42(1), 45 - 8
Axenic in vitro cultivation of Trypanosoma vivax trypomastigote forms; Zweygarth E et al.; Cultures of Trypanosoma vivax stocks were initiated with tsetse-derived metacyclics and with organisms isolated from mouse blood . They were propagated as trypomastigote forms at 35 degrees C initially in the presence of bovine endothelial cells . All stocks were subsequently adapted to axenic culture conditions . The standard medium consisted of HEPES-buffered MEM with 1% MEM non-essential amino acids, containing 2 mM L-glutamine, 1 mM sodium pyruvate, 100 IU/ml penicillin, 100 micrograms/ml streptomycin, 0.2 mM hypoxanthine, 0.01 mM bathocuproine sulphonate, 0.1 mM L-cysteine, 0.1 mM 2-mercaptoethanol and 20% caprine or bovine serum . Cultured trypanosomes were morphologically similar to bloodstream forms found in vivo and they retained infectivity after in vitro cultivation.

J Parenter Sci Technol, 1991 Mar-Apr, 45(2), 77 - 82
The L6 muscle cell line as a tool to evaluate parenteral products for irritation; Laska DA et al.; A rat skeletal muscle cell line (L6) was evaluated for its utility in assessing cellular damage caused by parenteral administration of eight commercially available pharmaceuticals . The physical forms of the eight pharmaceuticals were diverse, including aqueous and non-aqueous suspensions and solutions . The L6 cells were exposed to therapeutic as well as diluted concentrations of methocarbamol, lorazepam, dimercaprol, phytonadione, menadiol sodium phosphate, penicillin G procaine, penicillin G benzathine, and iron dextran complex . Irritation assessment was based on the depletion of creatine phosphokinase (CK) from treated cultures versus untreated controls . The results obtained correlate well with reports of irritation and side effects noted in clinical use, and demonstrate the versatility of the model for testing suspensions and non-aqueous parenteral solutions . The L6 model is a useful tool to assist in determining the relative local irritancy of parenteral products.

Mol Microbiol, 1991 Mar, 5(3), 675 - 84
Penicillin-binding protein 4 of Escherichia coli: molecular cloning of the dacB gene, controlled overexpression, and alterations in murein composition; Korat B et al.; The penicillin-binding protein 4 (PBP4), from Escherichia coli, a DD-carboxypeptidase/DD-endopeptidase, was purified in an enzymatically active form to homogeneity by affinity chromatography on 6-aminopenicillanic acid/Sepharose and heparin/Sepharose . Polyclonal antibodies raised against the pure protein were used to identify and isolate PBP4 overproducing clones from an E . coli expression library, which was established on the basis of a temperature-inducible runaway replication plasmid . Three positive clones were isolated, one of which carried the intact structural gene dacB that codes for PBP4, on a 1.9kb SmaI-EcoRI fragment, whereas the other two carried truncated forms of this gene . The direction of transcription was determined . The PBP4 overproducing strain, when grown in rich medium, tolerated 160-fold overexpression . After disrupting cells by sonication, the majority (80%) of the overproduced PBP4 was detected in the 100,000 X g supernatant . Southern blotting analysis using the cloned dacB gene as a probe revealed that, in contrast to that described by Takeda et al . (1981), the plasmid pLC18-38 of the Clarke-Carbon collection does not code for PBP4 . The overall composition of murein, synthesized in vitro or in vivo by the PBP4 overproducing strain, as determined by high-performance liquid chromatography analysis, suggests that PBP4 is not involved in transpeptidation but exclusively catalyses a DD-carboxypeptidase and DD-endopeptidase reaction.

Fam Pract, 1991 Mar, 8(1), 32 - 6
Fever: knowledge, perception and attitudes . Results from a Norwegian population study; Eskerud JR et al.; To investigate the layman's knowledge, perception and attitudes regarding normal body temperature, fever, infections and the effect of penicillin on virus infections a representative sample of the Norwegian population (619 women and 592 men over the age of 15) was interviewed in 1988 as part of a monthly national opinion poll . One-third thought body temperatures up to 40.5 degrees C to be life-threatening, but the results do not justify the application of the term 'fever phobia' as described in other studies based on non-representative samples . More respondents were afraid of viral infections (48%) than bacterial infections (9%), which may be due to the media focus upon the HIV/AIDS epidemic . Thirty-five per cent believed penicillin to be effective against virus infections . Educational programmes on fever should also include information about virus infections and their treatment.

Rev Infect Dis, 1991 Mar-Apr, 13(2), 207 - 10
The Jarisch-Herxheimer reaction in leptospirosis: possible pathogenesis and review; Friedland JS et al.; The importance of treating leptospirosis with penicillin is emphasized by two case reports and a review documenting the occurrence of the Jarisch-Herxheimer reaction (JHR) in patients with this bacterial infection . The JHR is significant both as a cause of morbidity and mortality and as an indication of the therapeutic efficacy of penicillin . The possible etiology of the JHR is discussed, and comparisons with the changes occurring in septic shock are made; a study of either condition facilitates the understanding of the other . Tumor necrosis factor is hypothesized to play a key role in both . Current treatment of the JHR consists of general clinical support . Specific measures such as oxpentifylline therapy may play a role in the future.

FEMS Microbiol Lett, 1991 Mar 1, 62(2-3), 213 - 20
Penicillin-binding protein 4 of Escherichia coli shows a novel type of primary structure among penicillin-interacting proteins; Mottl H et al.; The nucleotide sequence of a 1884 bp DNA fragment of E . coli, carrying the gene dacB, was determined . The DNA codes for penicillin-binding protein 4 (PBP4), an enzyme of 477 amino acids, being involved as a DD-carboxypeptidase-endopeptidase in murein metabolism . The enzyme is translated with a cleavable signal peptide of 20 amino acids, which was verified by sequencing the amino-terminus of the isolated protein . The characteristic active-site fingerprints SXXK, SXN and KTG of class A beta-lactamases and penicillin-binding proteins were located in the sequence . On the basis of amino acid alignments we propose, that PBP4 and class A beta-lactamases share a common evolutionary origin but PBP4 has acquired an additional domain of 188 amino acids in the region between the SXXK and SXN elements.

Shi Yan Sheng Wu Xue Bao, 1991 Mar, 24(1), 55 - 8
{Effect of temperature on the expression of penicillin G acylase gene at the level of post-translational processing}; Wang M et al.; The expression of penicillin G acylase (PGA) gene is sensitive to temperature . Cells of E . coli DH 5 alpha harboring a plasmid pWGA carrying a gene for PGA produce active PGA at low level at 37 degrees C, but can synthesize significant amount of the enzyme below 30 degrees C . Active PGA is formed from a 94 KD precursor processed through remove of a signal peptide and a spacer peptide to yield an enzyme that contain a 23 KD (alpha) and 65 KD (beta) subunit . This paper reported the effect of temperature on transcription, translation, and post-translational processing of PGA gene expression . We detected the transcription of PGA gene by Northern blot, and found the amount of PGA mRNA at 37 degrees C much more than that 30 degrees C when the cells of DH 5 alpha (pWGA) were cultured . It is evident that the precursor processing step(s) is sensitive to temperature.

Infect Immun, 1991 Mar, 59(3), 1050 - 6
Anti-Borrelia burgdorferi antibody response over the course of Lyme neuroborreliosis; Baig S et al.; Characteristic findings on examination of cerebrospinal fluid (CSF) in Lyme neuroborreliosis include mononuclear pleocytosis, oligoclonal immunoglobulin G (IgG) bands, and evidence for local production of specific antibodies . We utilized an immunospot assay to detect cells secreting anti-Borrelia burgdorferi antibodies of different isotypes over the course of disease . Such cells were detected in CSF from 13 consecutive patients with neuroborreliosis examined before treatment . IgG antibody-secreting cells were present in high numbers (mean, 32 cells per 10(4) CSF cells), whereas IgA and IgM antibody-secreting cells were found less frequently and at lower numbers (mean, 5 and 6 cells per 10(4) CSF cells, respectively) . Clinical improvement after penicillin treatment was paralleled by a rapid decline of antibody-secreting cells in CSF, but they were still detected, although at lower numbers, in 5 of 10 patients examined more than 6 months after treatment . This specific B-cell response persisted despite clinical improvement . Whether it reflects persistence of antigen is unsettled.

Shi Yan Sheng Wu Xue Bao, 1991 Mar, 24(1), 51 - 4
{Effect of mutagenesis at Ser 177 residue in penicillin G acylase on activity of the enzyme}; Wang M et al.; The technique of cassette and site-specific mutagenesis were used to study the role of residue No . 177 in penicillin G acylase (PGA, EC 3.5.1.11) . Ser is conserved at residue No . 177 in all penicillin binding proteins . We got a series of mutants in which the amino acid at residue No . 177 was replaced by other amino acids through the site-specific and cassette mutagenesis, and we characterized the mutants by colony hybridization, NIPAB paper test and DNA sequence analysis . These mutants all show no activity of enzyme, even if the Ser residue was replaced by Thr, Gly and Ala respectively . The results show that Ser residue may be essential for substrate-binding or catalysis of PGA.

J Bacteriol, 1991 Mar, 173(6), 1879 - 85
Isolation and complementation of nitrogen fixation mutants of the cyanobacterium Anabaena sp . strain PCC 7120; Buikema WJ et al.; Approximately 140 mutants of Anabaena sp . strain PCC 7120 unable to grow aerobically on media lacking fixed nitrogen (Fix-) were isolated after mutagenesis with diethyl sulfate and penicillin enrichment . A large cosmid library of wild-type Anabaena sp . strain PCC 7120 DNA was constructed in a mini-RK-2 shuttle vector, and seven mutants representing several morphologically abnormal heterocyst phenotypes were complemented . One of these mutants, 216, failed to differentiate heterocysts . All of these mutants except 216 reduced acetylene under anaerobic conditions, indicating that they are not defective in nitrogen fixation per se . Several cosmids were isolated from each complemented mutant and in most cases showed similar restriction patterns . Comparisons of the complementing cosmids from mutant 216 and two other phenotypically distinct mutants by restriction enzyme analysis identified a common region . This region, when present in either a cosmid or a 9.5-kb NheI subclone, is capable of efficiently complementing all three mutants . A 2.4-kb subclone of this region complements mutant 216 only.

Arch Inst Cardiol Mex, 1991 Mar-Apr, 61(2), 143 - 7
{Rheumatic cardiopathy in children younger than 6 years of age}; Vazquez-Antona C et al.; Most of the published papers on Rheumatic Fever (RF) have not included the younger population . We selected 211 cases of children with RF younger than 6 years of age from 9,471 clinical files from 1944 to 1982 . These were followed retrospectively to identify the presence of rheumatic activity, subsequent attacks and penicillin profilaxis . From de 211 cases, 209 had carditis; 57% of them were girls and 43% boys . There were no previous infections of the upper respiratory tract in 36% of the patients . The number of cases with RF increased abruptly after 3 years of age and continued increasing until 5 years of age when 70.5% of the population had there first clinically recognized attack . Lesions were present in the mitral valve in 80% of the cases, in the aortic valve in 12%, in the tricuspid in 5% and in the pulmonary valve in 3% . The death rate during the first attack was 20% being refractory heart failure the main cause of death . Thirteen cases suffered rheumatic pneumonia, 9 of whom died (69.2%) . Conclusions: 1) The incidence of acute rheumatic fever in children under 6 years of age has decreased with time . 2) The death rate as well as the valvular damage decreased with the parents cooperation with the treatment . 3) The changes in the clinical picture and the severity of valve sequelea may be due to penicillin profilaxis and the better understanding of the disease.

Enzyme Microb Technol, 1991 Mar, 13(3), 210 - 4
Stabilizing effect of penicillin G sulfoxide, a competitive inhibitor of penicillin G acylase: its practical applications; Alvaro G et al.; We have found that penicillin G sulfoxide (pen G SO) behaves as a general stabilizing agent of two bacterial penicillin G acylases (PGAs) from E . coli and from K . citrophila), and this role is related to a strong inhibitory effect on the enzymes . The stabilizing effect has been observed during two different inactivation processes: (i) thermal inactivation of soluble enzymes at alkaline pH, and (ii) inactivation of immobilized enzymes as a consequence of covalent multiinteraction with highly activated agarose aldehyde gels . At the same time, pen G SO behaves as a strong competitive inhibitor of these two enzymes . The inhibition constant is more than 10-fold lower than the one corresponding to another smaller competitive inhibitor, phenylacetic acid (PAA), the structure of which is exactly the acyl donor moiety corresponding to pen G SO . In turn, PAA hardly exerts any stabilizing effect on PGAs . The stabilizing effect of pen G SO allowed the preparation of derivatives of these PGAs preserving full catalytic activity in spite of being 1,400- and 650-fold more stable than the corresponding soluble or one-point attached immobilized enzymes.

J Biol Chem, 1991 Feb 15, 266(5), 3186 - 91
Site-directed mutants, at position 166, of RTEM-1 beta-lactamase that form a stable acyl-enzyme intermediate with penicillin; Adachi H et al.; Class A beta-lactamases are known to hydrolyze substrates through a Ser70-linked acyl-enzyme intermediate, although the detailed mechanism remains unknown . On the basis of the tertiary structure of the active site, the role of Glu166 of class A enzymes was investigated by replacing the residue in RTEM-1 beta-lactamase with Ala, Asp, Gln, or Asn . All the mutants, in contrast to the wild-type, accumulated a covalent complex with benzylpenicillin which corresponds to an acyl-enzyme intermediate . For the Asp mutant, the complex decayed slowly and the hydrolytic activity was slightly retained both in vivo and in vitro . In contrast, the other mutants lost the hydrolytic activity completely and their complexes were stable . These results indicate that the side-chain carboxylate of Glu166 acts as a special catalyst for deacylation . Residues for deacylation have not been identified in other acyl enzymes, such as serine proteases and class C beta-lactamases . Furthermore, the acyl-enzyme intermediates obtained are so stable that they are considered to be ideal materials for crystallographic studies for elucidating the catalytic mechanism in more detail . In addition, the mutants can more easily form inclusion bodies than the wild-type, when they are produced in a large amount, suggesting that the residue also plays an important role in proper folding of the enzyme.

Indian Pediatr, 1991 Feb, 28(2), 157 - 9
Congenital syphilitic hepatitis; Anand NK et al.; Hepatitis is a known manifestation of congenital syphilis, however hepatitis developing during penicillin therapy is unknown . Ten patients of congenital syphilis were studied and serial liver enzymes were done before and after starting penicillin therapy . Eight of the ten patients developed hepatitis after initiating penicillin therapy . Whether hepatitis in these cases was secondary to toxic reaction to the products of treponemal lysis or an autoimmune reaction needs to be investigated.

Ann Surg, 1991 Feb, 213(2), 98 - 112
Splenic trauma . Choice of management; Lucas CE; The modern era for splenic surgery for injury began in 1892 when Riegner reported a splenectomy in a 14-year-old construction worker who fell from a height and presented with abdominal pain, distension, tachycardia, and oliguria . This report set the stage for routine splenectomy, which was performed for all splenic injury in the next two generations . Despite early reports by Pearce and by Morris and Bullock that splenectomy in animals caused impaired defenses against infection, little challenge to routine splenectomy was made until King and Schumacker in 1952 reported a syndrome of "overwhelming postsplenectomy infection" (OPSI) . Many studies have since demonstrated the importance of the spleen in preventing infections, particularly from the encapsulated organisms . Overwhelming postsplenectomy infection occurs in about 0.6% of children and 0.3% of adults . Intraoperative splenic salvage has become more popular and can be achieved safely in most patients by delivering the spleen with the pancreas to the incision, carefully repairing the spleen under direct vision, and using the many adjuncts to suture repair, including hemostatic agents and splenic wrapping . Intraoperative splenic salvage is not indicated in patients actively bleeding from other organs or in the presence of alcoholic cirrhosis . The role of splenic replantation in those patients requiring operative splenectomy needs further study but may provide significant long-term splenic function . Although nonoperative splenic salvage was first suggested more than 100 years ago by Billroth, this modality did not become popular in children until the 1960s or in adults until the latter 1980s . Patients with intrasplenic hematomas or with splenic fractures that do not extend to the hilum as judged by computed tomography usually can be observed successfully without operative intervention and without blood transfusion . Nonoperative splenic salvage is less likely with fractures that involve the splenic hilum and with the severely shattered spleen; these patients usually are treated best by early operative intervention . Following splenectomy for injury, polyvalent pneumococcal vaccine decreases the likelihood of OPSI and should be used routinely . The role of prophylactic penicillin is uncertain but the use of antibiotics for minor infectious problems is indicated after splenectomy.

Res Microbiol, 1991 Feb-Apr, 142(2-3), 345 - 50
Effect of D-amino acids on Escherichia coli strains with impaired penicillin-binding proteins; Caparros M et al.; Escherichia coli cells growing in the presence of some D-amino acids incorporate D-amino acid into the peptidoglycan layer of the cell wall by a mechanism most likely independent of the normal biosynthetic pathway . Analysis of the sensitivity of mutant strains with impaired penicillin-binding proteins (PBP) to D-amino acids indicated that ponB and DD-endopeptidase/DD-carboxypeptidase-I-defective strains are hypersensitive to D-amino acids . D-tryptophan containing peptidoglycan was found to be more susceptible to the action of lytic transglycosilases than native material, which could explain in part the harmful effects of D-amino acids . ponB strains carrying additional mutations suppressing hypersensitivity to D-amino acids have been obtained and the results of their initial characterization are reported.

Res Microbiol, 1991 Feb-Apr, 142(2-3), 333 - 44
On the role of the high molecular weight penicillin-binding proteins in the cell cycle of Escherichia coli; Wientjes FB et al.; Blocking of penicillin-binding proteins (PBP) 2 or 3 of Escherichia coli by specific antibiotics led to inhibition of peptidoglycan synthesis measured as rate of 3H-Dap incorporation . The inhibition was ca 60% by mecillinam (blocking PBP2) and ca 35% by cephalexin or furazlocillin (both specific for PBP3) . PBP3 could be inhibited primarily during constriction, whereas the inhibition of PBP2 was observed throughout the cell cycle . The ratio of PBP2 and 3 activities appeared to be correlated with cell shape, i.e . in long rods, inhibition of peptidoglycan synthesis by mecillinam was stronger than in short rods . Inhibition studies with the PBP1A/1B-specific antibiotic cefsulodin showed that, with a delay of approximately 1/2 mass-doubling time, peptidoglycan synthesis was inhibited completely with concomitant lysis . The cefsulodin-induced lysis was independent of the stage of the cell cycle . It was suggested that PBP1A/1B do not have a specific function in either elongation or constriction . Rather, they seem to have a general activity on the basis of which the other synthesizing PBP perform their special tasks . This interpretation is formulated as a "primer model of peptidoglycan synthesis".

Res Microbiol, 1991 Feb-Apr, 142(2-3), 325 - 32
Murein chemistry of cell division in Escherichia coli; Romeis T et al.; The length distribution of the glycan strands of murein has been analysed with a novel method in filamentous and spherical cells of Escherichia coli, as well as during septum formation and cell separation . A shift to the longer glycan strands was observed in the murein of furazlocillin-induced filaments . In contrast, shorter glycan strands were increased in the murein of mecillinam-induced spherical cells . During septum formation in a chain-forming envA mutant that is defective in the splitting process of the septum, a shift to the shorter glycan strands was detected that was not seen in wild type E . coli cells . It is concluded that septum-specific murein structures of rather short glycan strands are released during splitting of the septum . This intermediate material remains present in the septum of the envA mutant . The splitting process of the septum was investigated by analysing the murein during penicillin-induced bacteriolysis, which is known to take place by strictly localized murein degradation in the equatorial zone of the cell . No changes in the length distribution of the glycan strands could be detected during penicillin-induced lysis, with the exception of an increase in disaccharides, the shortest glycan strands possible . This is explained by the action of exo-muramidases progressively digesting glycan strands, leaving disaccharide units covalently linked to the remaining murein at the sites of murein cross-linkage . It is proposed that this "zipper-like" mechanism represents the normal cutting process of the septum during cell separation.

Res Microbiol, 1991 Feb-Apr, 142(2-3), 279 - 82
Structure and function of the ftsH gene in Escherichia coli; Ogura T et al.; The ftsH mutant Y16 shows thermosensitive filamentation with reduced amounts of penicillin-binding protein 3 (PBP3) (Ferreira et al., 1987) . Genetic analysis, however, showed that the lethality of the ftsH mutation was not due to a lack of PBP3 activity alone . The ftsH gene was cloned and sequenced and the FtsH protein was deduced to be a membrane protein of 70.7 kDa which has an ATP-binding domain . Highly significant homology of amino acid sequence was observed between FtsH protein and two eukaryotic proteins, yeast Saccharomyces cerevisiae Sec 18p and its mammalian homologue NSF, which are involved in protein transport pathways . This suggests that FtsH protein may act for translocation of specific proteins including PBP3 and at least one other additional protein essential for cell growth . Suppressor mutants of Y16, which were able to grow at 42 degrees C, were isolated, and the suppressor mutations (sfh) were mapped to 16 min . A wild type chromosomal fragment able to complement the sfh mutations was cloned . We also identified another gene (ftsJ) affecting cell division in the region upstream of the ftsH gene.

Allergy, 1991 Feb, 46(2), 154 - 7
Delayed allergic reactions to beta-lactams . Four cases with intolerance to amoxicillin or ampicillin and good tolerance to penicillin G and V; Vega JM et al.; We present four cases of delayed allergic skin reactions to amoxicillin or ampicillin with good tolerance to benzyl penicillin and phenoxymethyl penicillin . The clinical symptoms reported by the patients, the intradermal skin tests and the controlled challenge results suggested that the mechanism was cellular mediated . In two patients these findings were supported by histopathological studies . Although delayed-type hypersensitivity reactions to beta-lactams with positive skin test seem rare, they can occur to penicillins in allergic patients . The production of these reactions by amoxicillin or ampicillin with good tolerance to benzyl penicillin and phenoxymethyl penicillin emphasizes the role of the side chain in inducing allergic reactions to beta-lactams.

EMBO J, 1991 Feb, 10(2), 489 - 95
Localization of the pathway of the penicillin biosynthesis in Penicillium chrysogenum; Muller WH et al.; The localization of the enzymes involved in penicillin biosynthesis in Penicillium chrysogenum hyphae has been studied by immunological detection methods in combination with electron microscopy and cell fractionation . The results suggest a complicated pathway involving different intracellular locations . The enzyme delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase was found to be associated with membranes or small organelles . The next enzyme isopenicillin N-synthetase appeared to be a cytosolic enzyme . The enzyme which is involved in the last step of penicillin biosynthesis, acyltransferase, was located in organelles with a diameter of 200-800 nm . These organelles, most probably, are microbodies . A positive correlation was found between the capacity for penicillin production and the number of organelles per cell when comparing different P . chrysogenum strains.

Br Heart J, 1991 Feb, 65(2), 102 - 3
Fatal pneumococcal septicaemia associated with asplenia and isomerism of the right atrial appendages; Murdoch IA et al.; A 22 month old male infant with isomerism of the right atrial appendages (associated with a complete atrioventricular septal defect, double outlet right ventricle, and pulmonary valve stenosis) died from pneumococcal septicaemia after a 36 hour illness . He had not been given penicillin prophylaxis . Asplenia was confirmed at necropsy . In a survey of 50 paediatric cardiologists in the United Kingdom, 13 (33%) of the 40 (80%) who replied did not advise any prophylactic measures against pneumococcal infection in patients with isomerism of the right atrial appendages.

Gynecol Oncol, 1991 Jan, 40(1), 17 - 20
Chemotherapy-induced neutropenia and fever in patients receiving cisplatin-based chemotherapy for ovarian malignancy; Curtin JP et al.; Fifty-six episodes of chemotherapy-induced neutropenia and fever occurred in forty-three patients receiving cisplatin-based combination chemotherapy for ovarian cancer . All patients were treated with broad-spectrum antibiotics including gentamicin . Twelve of fifty-six episodes were associated with positive cultures; in six patients a single organism was isolated, and the other six patients had polymicrobial infection . The mean duration of antibiotic therapy was 6.5 days . One patient died of sepsis . Fifty-five episodes had a successful outcome . There was no antibiotic-related morbidity . Based on this review we recommend broad-spectrum antibiotic therapy for chemotherapy-induced neutropenia with fever . The regimen of gentamicin plus ticarcillin and clavulanic acid (ceftazidime for penicillin-allergic patients) is effective as initial therapy . Additional agents (i.e., vancomycin) may be necessary in culture-positive patients based on sensitivity testing of bacterial isolates . Gentamicin can be safely administered to patients receiving cisplatin-based chemotherapy without compromising ability to continue cisplatin therapy in subsequent treatment cycles.

Ter Arkh, 1991, 63(3), 108 - 14
{Eosinophilic lesions of the lungs (case reports and review of the literature)}; Trubnikov GV; Overall 75 references concerning the etiology, pathogenesis and the clinical picture of eosinophilic lesions of the lungs were analyzed . Sixteen patients with drug-induced disease were placed under the author's observation . Of these, 8 patients fell ill due to penicillin, 3 to tetracycline, 3 to sulfanilamide intake and alpha to intal inhalations . In 10 patients, pneumonia was characterized by high blood eosinophilia (from 20 to 53%, 37.5 +/- 2.7%) and in 6, it was of moderate nature (from 10 to 15%, 11.8 +/- 0.8%) . According to the author's data, the immunopathological response coupled with suppression of the T lymphocyte system, inhibition of the enzymatic activity of leukocytes, dysproteinemias with hypergammaglobulinemia, reductions of the concentration of IgG underlie the disease pathogenesis . In the patients with high blood eosinophilia, including 4 with polysystemic lesions, the disease ran a grave course . The therapeutic effect could only be attained owing to the monotherapy with prednisolone . In the long-term period, 9 patients developed glucocorticoid-dependent bronchial asthma . The patients with moderate blood eosinophilia showed a milder disease course and a favourable outcome.

J Immunoassay, 1991, 12(1), 47 - 64
Enzyme immunoassay of benzyl penicilloyl (BPO) groups using acetylcholinesterase as label . Application to the study of the BPO-binding sites on albumin; Wal JM et al.; Benzyl penicilloyl groups (BPO) derive from penicillin G by cleavage of the beta lactam ring; they covalently bind to proteins to give conjugates which have lost all antibiotic properties but are considered as the major allergenic determinants in penicillin allergy . A solid-phase Enzyme Immuno Assay (EIA) of BPO groups in different biological fluids is described . It is a competitive immunoassay using acetylcholinesterase as label . In all biological fluids, very low non-specific binding values are observed . The sensitivity and the precision of the assay are good since ca . 0.5 ng/ml can be measured with a coefficient of variation less than 10% . Cross reactions between BPO and penicillin or penicillin derivatives are nil or very low . This assay is more sensitive, much more rapid and easier to handle than the other methods available and is thus suitable for routine determinations . In association with reversed-phase high performance liquid chromatography this EIA has allowed an initial investigation of the location of BPO-binding sites on micro quantities of serum albumin (ca . 1 mg) from penicillin treated patients.

Ann Acad Med Singapore, 1991 Jan, 20(1), 114 - 7
Drug hypersensitivity in children; Lee BW; Drugs and their metabolites may act as haptens resulting in hypersensitivity reactions . These reactions occur less frequently in children than adults . As most pathogenetic mechanisms of drug hypersensitivity reactions (DHRs) and drug metabolic pathways are unknown, there are few diagnostic tests for DHRs . The patient's history, with particular emphasis on the type of reaction invoked by the drug is therefore, still of utmost importance in evaluation . Diagnostic tests are confined mainly to IgE-mediated DHRs, of which tests for penicillin allergy is the most established . Several factors are known to influence the occurrence of DHRs . Anaphylaxis is less common with orally administered drugs compared to those administered parenterally, and atopic persons appear to have an increased susceptibility to anaphylactic reaction . In the paediatric population, antibiotics, especially the penicillins, are common agents involved in DHRs . However, the fine erythematous macular papular rash frequently evoked by ampicillin, should not be mistaken for an allergic reaction with the associated risk of anaphylaxis . Other drugs commonly involved in DHRs in children are sulfonamides, aspirin, and vaccines, especially those against measles, mumps and rubella.

Exp Brain Res, 1991, 83(3), 683 - 6
Participation of interneurons in penicillin-induced epileptic discharges; Domann R et al.; Interneurons of rat motor cortex in vivo and of rat hippocampal slices were studied during penicillin-induced epileptic discharges . Synchronous with pyramidal cells, they showed transient depolarizations similar to paroxysmal depolarization shifts in pyramidal cells . The transient depolarizations were followed by hyperpolarizing or depolarizing afterpotentials lasting 600 to 1200 ms . During the transient depolarizations and the afterdepolarizations the interneurons discharged with increased frequency . This may contribute to the enlarged and prolonged synaptic inhibitions following interictal discharges in pyramidal cells.

Comput Med Imaging Graph, 1991 Jan-Feb, 15(1), 57 - 60
Intracranial gumma mimicking a tuber cinereum tumor; Wang AM et al.; The brain magnetic resonance (MR) and computed tomography (CT) finding in a 37-year-old patient with a history of persistent headache and secondary hypogonadism and with a strongly positive blood and cerebrospinal fluid (CSF) fluorescent treponemal antibody-absorption (FTA-ABS) test is reported . A focal enhancing mass was demonstrated involving the tuber cinereum . The mass was markedly reduced after the completion of a course of intravenous administration of penicillin G treatment . This case is interesting because of its rare incidence and unique neuroradiological findings.

Infection, 1991, 19 Suppl 1, S19 - 24
{Comparison of the adverse effect profile of different substances such as penicillins, tetracyclines, sulfonamides and quinolones}; Keller H; The penicillins, the tetracyclines and the sulfonamides have often been used in the last few decades in spite of their well-known side effects . Hypersensitivity reactions to penicillins are among the most important adverse reactions in these antibiotics; in every case a careful medical history has to be taken before a new course of penicillin treatment . The use of tetracyclines in women during the last six months of pregnancy or in children under the age of eight years is contraindicated . Patients with severe blood, kidney or liver disease should not be treated with sulfonamides . Toxic reactions to penicillin even with convulsions may occur in patients with renal insufficiency if the dosage is not adapted . The fluoroquinolones do not seem to have greater risks regarding adverse reactions than the historical compounds mentioned . Neurotoxicity is an important problem . Mild reactions are reported with incidences under 2%; severe neurotoxic side effects that require interruption of therapy are rare . Psychotic reactions, hallucinations, depressions and grand mal convulsions also belong to this category . Other side effects (skin, GI-tract) are no more frequent than with the classical antibiotics . In patients with renal insufficiency the dosage of ofloxacin has to be adapted . The cartilage lesions which are seen in juvenile rats and dogs raise the question whether or not the cases of arthralgia during therapy with older quinolones as well as under treatment with fluoroquinolones have a causal relationship . Up to date quinolones should not be prescribed in children and young adults except in cases with cystic fibrosis . The development of resistance has not been a significant problem so far.(ABSTRACT TRUNCATED AT 250 WORDS)

J Infect, 1991 Jan, 22(1), 77 - 9
Pneumococcal meningitis in a child with a ventriculo-peritoneal shunt; O'Keeffe PT et al.; A case of pneumococcal meningitis in an infant with a ventriculo-peritoneal shunt is reported . There was initial failure of treatment with penicillin and cefotaxime in full dosage . Eradication of infection without shunt removal was eventually achieved by adding rifampicin to the antibiotic regime.

Cornell Vet, 1991 Jan, 81(1), 13 - 8
Penicillin-induced hemolytic anemia and acute hepatic failure following treatment of tetanus in a horse; Step DL et al.; Acute, severe hemolytic anemia occurred in a horse being treated for tetanus with intravenous penicillin and tetanus antitoxin . During treatment, the horse developed a positive direct antiglobulin test and a high titer (maximum 1:1024) of IgG anti-penicillin antibody . The horse recovered from the tetanus and penicillin induced hemolytic anemia, but later developed acute hepatic failure, probably resulting from the administration of equine origin tetanus antitoxin.

J Bacteriol, 1991 Jan, 173(1), 94 - 100
delta-Aminolevulinic acid dehydratase deficiency can cause delta-aminolevulinate auxotrophy in Escherichia coli; O'Neill GP et al.; Ethylmethane sulfonate-induced mutants of several Escherichia coli strains that required delta-aminolevulinic acid (ALA) for growth were isolated by penicillin enrichment or by selection for respiratory-defective strains resistant to the aminoglycoside antibiotic kanamycin . Three classes of mutants were obtained . Two-thirds of the strains were mutants in hemA . Representative of a third of the mutations was the hem-201 mutation . This mutation was mapped to min 8.6 to 8.7 . Complementation of the auxotrophic phenotype by wild-type DNA from the corresponding phage 8F10 allowed the isolation of the gene . DNA sequence analysis revealed that the hem-201 gene encoded ALA dehydratase and was similar to a known hemB gene of E . coli . Complementation studies of hem-201 and hemB1 mutant strains with various hem-201 gene subfragments showed that hem-201 and the previously reported hemB1 mutation are in the same gene and that no other gene is required to complement the hem-201 mutant . ALA-forming activity from glutamate could not be detected by in vitro or in vivo assays . Extracts of hem-201 cells had drastically reduced ALA dehydratase levels, while cells transformed with the plasmid-encoded wild-type gene possessed highly elevated enzyme levels . The ALA requirement for growth, the lack of any ALA-forming enzymatic activity, and greatly reduced ALA dehydratase activity of the hem-201 strain suggest that a diffusible product of an enzyme in the heme biosynthetic pathway after ALA formation is involved in positive regulation of ALA biosynthesis . In contrast to the hem-201 mutant, previously isolated hemB mutants were not ALA auxotrophs and had no detectable ALA dehydratase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

J Bacteriol, 1991 Jan, 173(1), 1 - 5
Cell cycle-independent lysis of Escherichia coli by cefsulodin, an inhibitor of penicillin-binding proteins 1a and 1b; Jacoby GH et al.; Cefsulodin lyses actively growing Escherichia coli by binding specifically to penicillin-binding proteins (PBPs) 1a and 1b . Recent findings (F . Garcia del Portillo, M . A . de Pedro, D . Joseleau-Petit, and R . D'Ari, J . Bacteriol . 171:4217-4221, 1989) have linked cefsulodin-induced lysis to septation during the first division cycle after a nutritional shift-up or chromosome replication realignment . We synchronized cells by membrane filtration to determine whether cefsulodin-induced lysis depended on septation in normally growing cells . Populations of newly divided cells were allowed to grow for variable lengths of time . Cefsulodin was added to these synchronous cultures, which represented points in two to three rounds of the cell cycle . Since the cell numbers were small, a new lysis assay was developed that was based on the release of DNA measured by fluorometry . Lysis occurred at a constant time after addition of the antibiotic, regardless of the time in the cell cycle at which the addition was made . Thus, cefsulodin-induced lysis is not linked to septation or to any other cell cycle-related event.

J Exp Zool, 1991 Jan, 257(1), 51 - 7
Relative developmental abilities of hamster 2- and 8-cell embryos cultured in hamster embryo culture medium-1 and -2; Seshagiri PB et al.; The relative developmental abilities of hamster 2- and 8-cell embryos in culture were compared using two versions of hamster embryo culture medium (HECM) . These media differed primarily in the number of amino acids present, i.e., 20 amino acids in HECM-1 and four amino acids in HECM-2 . When 2-cell embryos were cultured for 24 h, the percentages of greater than or equal to 4-cell embryos obtained in both HECM-1 and HECM-2 were comparable (congruent to 93%); at the end of 48 h, the proportion of greater than or equal to 8-cell embryos obtained in HECM-1 (82.5%) was significantly (P less than or equal to 0.001) more than that obtained in HECM-2 (67.9%) . Interchange of media, after 24 h culture, did not enhance the ability of cultured 2-cell embryos to become blastocysts . When 8-cell embryos were cultured for 18 h in HECM-1 and -2, there was no appreciable difference in the proportion of total blastocysts formed (89-91%) . However, there were significantly (P less than or equal to 0.001) more late blastocysts in HECM-2 than in HECM-1 (68.2% vs . 38.4%) . Embryo development from 2- and 8-cell stages was compared in media that differed by the presence and absence of phenol red and penicillin-G . There was no difference in embryo development when these compounds were present or absent . Similarly, the difference in pyruvate concentration between HECM-1 and -2 (0.5 and 0.2 mM, respectively) did not affect embryo development.(ABSTRACT TRUNCATED AT 250 WORDS)

Postgrad Med, 1991 Jan, 89(1), 193 - 6, 199-202
Syphilis . A new visit from an old enemy; Wooldridge WE; Syphilis has a number of stages, including a latent one, and may be overlooked or misdiagnosed if the possibility is not kept in mind . Adequate treatment during the primary stage results in a very high cure rate . The latent stage may last for years, during which time a woman may still give birth to an infected child . Symptomatic neurosyphilis occurs more often in men than women . Penicillin G is preferred to treat all stages of the disease; other antibiotics can be used for patients sensitive to penicillin.

Am J Nephrol, 1991, 11(3), 174 - 80
Clinical characterization of drug-induced allergic nephritis; Shibasaki T et al.; To elucidate the clinical characterization of drug-induced allergic nephritis (DIAN), we analyzed the cases attending our department . We now report on the 14 cases of DIAN due to administration of penicillin in 2 cases, cephem antibiotics in 6 cases, nonsteroidal anti-inflammatory drugs in 4 cases and new quinolone anticidal drugs in 2 cases . With 1 exception, all these cases reached the stage of acute renal failure after taking these drugs for 2-13 days, followed by characteristic allergic symptoms such as fever, skin eruptions and serum IgE elevation in 5 of the 14 cases . A lymphocyte stimulation test (LST) with the suspected drugs proved to be positive in 10 of the 12 cases examined, and the uptake of 67Ga in the kidneys was extremely positive in all 6 cases examined, reflecting the natural course of this disease . Furthermore, there were some cases where 67Ga accumulated in the kidneys in spite of the negative result of LST examination . In all of these cases, a needle or open renal biopsy was performed, and acute tubulointerstitial nephritis (AIN) was diagnosed . Almost all cases were treated with glucocorticoid for AIN or dialysis for acute uremic symptoms several times . However, 4 of the 14 cases could not return to normal condition in spite of these forms of treatment . We would therefore like to suggest that LST and 67Ga scintigram are useful diagnostic tools for DIAN as an alternative to renal biopsy.

Kardiol Pol, 1991, 34(6), 367 - 70
{Unusually large vegetation on the mitral valve in a patient with bacterial endocarditis}; Wachowiak-Baszynska H et al.; We present a case history of 29-year old female with infective endocarditis, who was admitted 15 months after neurosurgical treatment of disruption of cerebral aneurysm . The diagnosis of organic heart disease had been established in her childhood . 6 months after discharge from neurosurgery she developed marked dyspnoea on exertion and became febrile (up to 39.0 C) . The presumptive diagnosis of infective endocarditis was established 6 months later, when she developed the symptoms and signs of severe anaemia with ESR 170 mm/hr although blood cultures were negative . The patient underwent treatment with Penicillin and Debecillin . On admission to our Institute echocardiography showed a very large, mobile vegetation in the left ventricle, connected to the anterior leaflet of mitral valve . Decision of mitral valve replacement was made, but rupture of the next cerebral aneurysm was the reason of unexpected, sudden death of the patient . The postmortem examination revealed 7 x 4 cm large vegetation, with the mass of 7.0 g . Histologically the vegetation consisted of mass of fibrin strands, platelets and blood cell with inflammatory cells . On its base the signs of the process of organization were marked . This vegetation was the largest one that we found in literature on this subject.

Rev Mal Respir, 1991, 8(4), 415 - 7
{Pulmonary actinomycosis . Apropos of a case}; Soyez F et al.; The authors report a case of pseudo-tumoral thoracic actinomycosis with lysis of a rib in a young man who was a heavy smoker and drinker . This observation is an opportunity to review the usual difficulties of diagnosis in patients with this rare disease occurring most often in a patient who is debilitated with important disease in the teeth and gingival margins . The standard treatment is penicillin G, which leads to a cure within one month.

Eur Urol, 1991, 19(4), 339 - 40
Actinomycosis of urachal remnants; van Wijk FJ et al.; A case of actinomycosis of the urachus is described . A 25-year-old woman presented with a midline mass below the umbilicus . The differential diagnosis included an inflammatory or a neoplastic lesion . Diagnosis was made by histologic examination, after complete excision of the tumour . Post-operative penicillin was given and the patient's recovery was uneventful . A review of the literature is presented with special reference to the pathogenesis and treatment.

Neuroscience, 1991, 41(2-3), 607 - 15
Metabolic anatomy of the focal epilepsy produced by cessation of chronic intracortical GABA infusion in the rat; Menini C et al.; Cessation of chronic (5 days), unilateral infusion of GABA into the somatomotor cortex of rats induces focal epileptic spikes which remain limited to the infused site and never evolve into generalized seizures . We have considered this finding as a new model of focal epilepsy and named it "GABA withdrawal syndrome" . In the present study, we have measured local cerebral glucose utilization in order to map the cortical and subcortical regions involved in the GABA withdrawal syndrome . Local cerebral glucose utilization increased two- to three-fold in a 1-1.5 mm diameter area, involving all the cortical layers at the GABA-infusion site . This hypermetabolic area contained a central (1-2 mm diameter) hypometabolic zone showing neuronal depopulation in some animals . Except for the epileptic focus, the hemisphere ipsilateral to the infusion site was slightly hypometabolic . However, there was a large increase (three- to five-fold) in some ipsilateral thalamic nuclei (posterior oralis, ventralis postero-lateralis, centralis lateralis, ventralis lateralis and reticularis thalami nucleus) . The local cerebral glucose utilization of the contralateral cortex and thalamus were unchanged . The present results confirm the focal nature of the epileptogenic syndrome produced by stopping chronic, intracortical GABA infusion . These results are markedly different from those described in the penicillin focal epilepsy model . Our data also show that specific ipsilateral thalamic relays may, by an as yet unknown mechanism, play a role in maintaining paroxysmal activity during the GABA withdrawal syndrome.

Auris Nasus Larynx, 1991, 18(1), 79 - 85
Actinomycosis of the larynx; Tsuji DH et al.; Actinomycosis is a disease characterized by a chronic suppurative and granulomatous process which tends to form multiple pyogenic draining sinus tracts . The most common site in which it occurs is the cervico-facial region, especially in the submandibular area . The exudates from the fistulous tracts usually contain yellow granules known as "sulfur granules," which can be considered as a hallmark of actinomycosis . We report a rare case of laryngeal actinomycosis which occurred in a 68-year-old male who had been irradiated 8 years before due to laryngeal carcinoma . During the admission, the patient was also diagnosed as being a myelodisplastic syndrome carrier . The patient was treated successfully with penicillin 10 million IU administered daily over 40 days . The etiologic agents, predisposing factors, diagnostic procedures, and available treatments are discussed, and the pertinent literature is reviewed herein.

Lijec Vjesn, 1991 Jan-Feb, 113(1-2), 16 - 20
{Mushroom poisoning with a long period of development}; Gasparovic V et al.; A group of 87 patients with the signs of poisoning with mushrooms with along period of incubation (t = 12.4 +/- 6.2 h) has been reported . Nausea, vomiting and diarrhea dominate in the clinical picture in the first phase and hepatic and/or renal insufficiency in the second phase . Forty-one patients (47.1%) had "only" clinical symptoms without severe parenchymatous impairments . Forty-six (54.9%) had evidence of a hepatic lesion and 8 patients (10.8%) had renal function impaired, 6 of which needed hemodialysis . There was a significant correlation between elevation of serum transaminases and prolongation of prothrombin complex, resulting from the decreased synthetic liver function (SGPT1/PV1r = -0.424, p = 0.00; SGOT1/PV1r = -0.448, p = 0.000) during the first days after poisoning . Hepatic and renal damage was not identical in all the cases, and there was no correlation between the elevation of serum transaminases and retention of nitrogen substances . When analysing the effect of therapy on elevation of serum transaminases and prolongation of prothrombin complex, a significant difference between elevation of serum transaminases and prolongation of prothrombin time was found in patients on competitive inhibition with penicillin or silibinin, as compared to the patients only on plasmapheresis (p = 0.004 for SGOT, p = 0.000 for SGPT) . These data unquestionably suggest the efficacy of competitive inhibition in the treatment of poisoning with mushrooms of a long period of incubation . In favour of this therapy also speaks the group of seriously ill patients who were simultaneously on plasmapheresis and competitive inhibition and who had better improvement than those "only" on plasmapheresis (p = 0.004 for SGOT).(ABSTRACT TRUNCATED AT 250 WORDS)

Exp Brain Res, 1991, 85(1), 240 - 2
A feature of caudate control of focal hippocampal epilepsy: evidence for an anterograde pathway; Vella N et al.; Previous experimental evidences showed that the caudate nucleus has a modulatory effect on hippocampal epilepsy . The caudate's regulating action might reach the hippocampus either via the septal region or, retrogradely, via the accumbens nucleus . In order to obtain new data about the pathway involved in caudate hippocampal influence the spreading of abnormal activity towards the nucleus accumbens was studied . Furthermore the effects of caudate stimulation in animals with electrolytic lesions of the nucleus accumbens were analyzed . It was observed that abnormal penicillin-induced activity spreaded from the hippocampus to the nucleus accumbens in about 30 minutes . In animals with and without lesions of nucleus accumbens, caudate stimulation brought about a significant decrease in the frequency and amplitude of hippocampal activity . The results suggest that the nucleus accumbens is reached by the spreading of hippocampal epilepsy but does not participate in the control exerted by the caudate nucleus on the hippocampus . Thus the caudate-induced inhibition takes place through an anterograde caudate-hippocampal circuit, while at the same time excluding retrograde activation by way of a caudate-accumbens-hippocampal pathway.

Hist Philos Life Sci, 1991, 13(1), 97 - 124
Streptomycin: discovery and resultant controversy; Wainwright M; The antibiotic streptomycin was discovered soon after penicillin was introduced into medicine . Selman Waksman, who was awarded the Nobel Prize for the discovery, has since generally been credited as streptomycin's sole discoverer . However, one of Waksman's graduate students, Albert Schatz, was legally recognized as streptomycin's co-discoverer and received a share of the royalties from the drug . The aim of this essay is to discuss the streptomycin story, largely using previously unquoted archival material, and in particular to provide further evidence for the important role which Schatz played in the discovery.

J Clin Pediatr Dent, 1991 Spring, 15(3), 202 - 4
Parotitis in a three-year-old; Steelman R et al.; Facial swelling cannot routinely be attributed to dento-alveolar infections until a thorough head, neck and oral examination has been completed . Facial swelling from parotitis is not commonly encountered in the pediatric patient . The purpose of this report was to document a case of unilateral parotid gland infection presumably secondary to traumatic obstruction of Stenson's duct . The parotitis resolved following a course of oral penicillin VK and lemon juice to stimulate salivary flow . Several parotid gland disorders which involve facial swelling were discussed.

Arkh Patol, 1991, 53(3), 74 - 6
{A method for storage and transportation of human and animal tissue specimens in a condition suitable for subsequent histochemical investigations}; Vishnevetskii FE et al.; A method for storage and transportation of human and animal tissue specimens suitable for subsequent histochemical investigations is described . Tissue cut into pieces of 1 X 1 cm is placed into penicillin flask containing 60-80% glycerol in a saline . The flask is hermetically closed . In such a state tissue is preserved suitable for histochemical analyses (including those for oxidative-reduction enzymes) and routine histological investigations, various fixation procedures and paraffin and celloidin embedding for 30 days at room temperature.

Rev Neurol (Paris), 1991, 147(5), 406 - 8
{Infarction of the pons, neurosyphilis and HIV infection}; Labauge R et al.; A 31-year old patient presented a right hemiparesis related to a left basis pontis infarction . Laboratory investigations revealed both neurosyphilis and HIV infection . The patient was treated with two courses of penicillin and recovered from hemiparesis . The occurrence of strokes due to syphilitic arteritis in AIDS is emphasized.

Pflugers Arch, 1991 Jan, 417(5), 469 - 78
Afterpotentials following penicillin-induced paroxysmal depolarizations in rat hippocampal CA1 pyramidal cells in vitro; Domann R et al.; Epileptic discharges were induced by superfusion of rat hippocampal slices with penicillin . Under these conditions the neurons generated paroxysmal depolarization shifts (PDS) after electrical stimulation of Schaffer collaterals . The PDS were followed by large afterhyperpolarizations lasting about 2 s . The mechanisms causing these afterhyperpolarizations were studied in CA1 pyramidal cells . A late component of the afterhyperpolarizations, which determined their overall duration, was blocked by intracellular application of EGTA and reduced by superfusion with 8-Br-cAMP . In the same neurons these drugs had a comparable effect on afterhyperpolarizations following depolarizing current injections; it was therefore concluded that the late component of the PDS afterhyperpolarizations was caused by a slow Ca2(+)-activated K+ current . An initial fast component of PDS afterhyperpolarizations, which peaked about 60 ms after PDS onset, was reduced by EGTA but not affected by 8-Br-cAMP suggesting that the fast Ca2(+)-activated K+ current also contributed to the PDS afterhyperpolarizations . Superfusion of the slice with the gamma-aminobutyric acid B receptor (GABAB) antagonists phaclofen or 5-aminovalerate reduced the amplitude of the afterhyperpolarizations during the first 1000 ms but did not affect the late Ca2(+)-dependent component, indicating that a GABAB-mediated K+ inhibitory postsynaptic potential (IPSP) contributed to the PDS afterhyperpolarization . Intracellular injection of Cl- revealed that an early part of the afterhyperpolarizations lasting about 500 ms was Cl(-)-dependent . This component was blocked by superfusion of the slices with bicuculline, suggesting that a GABAA-mediated Cl- IPSP contributed to the PDS afterhyperpolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

Shoni Shikagaku Zasshi, 1991, 29(1), 139 - 43
{Dental treatment under general anesthesia of a patient with pulmonary atresia with intact ventricular septum}; Funakoshi Y et al.; A case of pulmonary atresia with intact ventricular septum in a 4-year-4-month boy, whose dental treatment was performed under general anesthesia, was reported . For the general anesthesia, the medication Digoxin was stopped 24 hours before the treatment . For the prevention of bacterial endocarditis, medication consisting on antibiotics of the penicillin series was administered 24 hours before the treatment . The anesthesia was administered with the modified N.L.A . method with Ketamine and Diazepam . The dental treatment went smoothly, and was finished within 1-hour-15 mins from the start . Anesthesia was administered for 1-hour-45 mins . The prognosis was good, and the patient was discharged the next day . It should be noted that as for performing dental treatment under anesthesia or not using anesthesia, there are some different opinions . We think that it must be discussed from the point of view of the effect of the dental treatment on the patient versus the danger of the anesthesia . In this case, we found that, under general anesthesia, stress of the patient was reduced, and the dental treatment was able to be performed smoothly and safely.

Eur J Drug Metab Pharmacokinet, 1991, Spec No 3, 379 - 84
In vitro evaluation of the dissolution rate of crystalline suspensions destined to intramuscular administration; Cadorniga R et al.; The aqueous suspensions for intramuscular administration belong to the group of the dosage forms, that have a sustained release behaviour . These are based on the low aqueous solubility of the administered molecule whose aqueous suspensions form a depot in the muscular tissue which controls the absorption . The assays performed previously with two molecules of these characteristics have shown the inability of the habitual methods used for evaluating the dissolution rate of a drug, to determine the possible behaviour of these drugs in a definite and concrete formulation . For this reason, we have designed and developed a new method which allows us to support future processes, such as agglomeration and, possibly, cyst forming, that could be developed "in vivo" . In this way, a more reliable prediction of the efficiency of inefficiency of this kind of formulation will be possible . Tha validity of our system has been studied with three formulations . Two of them were sustained release cefazolin molecules showing agglomeration problems "in vivo" and the other one a commercial penicillin-G benzathine commercial with a great efficacy demonstrated in habitual clinical practice.

Biomed Biochim Acta, 1991, 50(10-11), S38 - 43
Stereo- and sequence specificity of serine proteases in peptide synthesis; Kasche V et al.; The sequence- and stereospecificity of the S1- and S' i-subsites (i = 1-3) of bovine alpha-chymotrypsin and trypsin, proteinase K and penicillin amidase from E . coli and A . viscosus has been determined by hydrolysis and kinetically controlled peptide synthesis using different substrates . The data are compared with results for other serine proteases and the thiol protease papain . The stereospecificities differ by orders of magnitude, decreased when the enzyme was immobilized and were influenced when organic solvent molecules were bound to the enzyme.

Biomed Biochim Acta, 1991, 50(10-11), S243 - 8
New enzymatic protecting group techniques for the construction of peptides and glycopeptides; Waldmann H et al.; The use of non-proteases for the selective removal of protecting groups from peptides and glycopeptides is described . The N-terminal deprotection of peptides can be achieved by the hydrolysis of the phenylacetyl (PhAc) amide blocking group catalyzed by penicillin G acylase . On the other hand, the lipase-mediated hydrolysis of n-heptyl (Hep) and 2-bromoethyl esters allows for the liberation of the C-terminal carboxy group . The selective C-terminal deprotection can be applied advantageously for the construction of acid- and base-sensitive polyfunctional O-glycopeptides . In all cases the enzymatic reactions are completely selective and proceed under mildest conditions (pH 7-8, r.t . to 37 degrees C) without damaging the various other functionalities present in the complex substrates.

Biomed Biochim Acta, 1991, 50(10-11), S237 - 42
Penicillin acylase-catalyzed acyl group transfer to amino acids, their esters and peptides: a kinetic study; Didziapetris RJ et al.; Kinetics of penicillin acylase-catalyzed acyl group transfer to amino acids, their esters and peptides have been analyzed . The synthesized product accumulation curves have clearly expressed a maximum . Amino acids with non-branched side chain alkyl radicals were demonstrated to be effective nucleophiles, with glycine, L-phenylalanine and L-phenylglycine being the best . D-amino acids were shown to possess much lower reactivity . Practically for all L-amino acids and peptides tested, the yield of their N-phenylacetyl derivatives in the course of penicillin acylase-catalyzed acyl group transfer reactions was found to be more than 50% . Optimization of such enzymatic synthesis required to increase its potential on the preparative scale.

J Ir Dent Assoc, 1991, 37(3-4), 75 - 7
Medical status of patients attending a primary care dental practice in Ireland; Fenlon MR et al.; Medical status of 1,500 patients attending a primary health care dental practice was examined by means of patient self-completed health questionnaire and by structured verbal interview by a dentist . Relevant medical histories and/or drug therapies affecting the practices of dentistry were found in 27.7% of patients . Problems identified included cardiovascular disease (10.4%), endocarditis risks (5.8%), hepatitis (7.9%), leukaemias (0.3%), bleeding tendencies (3%), drug allergies (7.0%), including penicillin allergy (3.6%) and intake of drugs affecting dentistry (6.0%) . For most of these categories there was a marked increase in prevalence with increasing age and many categories contained many more women than could be expected from the male/female distribution of the total patient group.

Bull Soc Pathol Exot, 1991, 84(5 Pt 5), 609 - 13
{Diverse aspects of congenital syphilis}; Maleville J et al.; Together with the new rise of recent syphilis in the adult woman, congenital syphilis reappears sporadically in our countries, where prophylactic measures (prenatal serology) are sometimes defeated . It remains much more frequent in developing countries . One should know how to interpret a positive serology in a newborn, as it may only reflect passive transplacental transfer of maternal antibodies . One should on the other hand think of syphilis again when the clinical signs are more or less suggestive, the typical picture not being, by far, the most frequent . In spite of the efficacy of Penicillin G: 50,000 U/kg/day during 10 days, neonatal death rate for congenital syphilis is in the neighbourhood of 10% . Our major effort should therefore be aimed at prevention.

Patol Fiziol Eksp Ter, 1991, (6), 34 - 6
{Change in the function of glucocorticoid receptors and translocation of glucocorticoid receptor complexes in hepatocyte nuclei exposed to nonsteroidal drugs}; Golikov PP; Experiments were conducted on male Wistar rats weighing 180-200 g to study the effect of medical agents (Tizercin 3,5.10(-4) M, 7,0.10(-4) M, Cephazolin, streptomycin and penicillin C--10(-3) M, 10(-4) M) on the function of glucocorticoid receptors of hepatic cytosol and translocation of the glucocorticoid-receptor complexes into the nuclei of hepatocytes . Synthetic labeled ligands 3H-dexamethasone and triamcinolone 3H-acetonide were used . Their specific activity was, respectively, 20 and 22 Ci/mmol The association and dissociation constants and the number of glucocorticoid-receptor complexes after their translocation into the hepatocyte nuclei were determined by Sketcher's method . It was found that streptomycin and Tizercin inhibit while Cephazolin and penicillin C activate the function of glucocorticoid receptors . Translocation of glucocorticoid-receptor complexes into the hepatocyte nuclei does not change under the effect of these agents.

J Clin Apheresis, 1991, 6(4), 230 - 3
Management of sickle cell anemia and pregnancy; Koshy M et al.; There has been significant decrease in maternal morbidity and mortality of sickle cell disease patients during pregnancy due to better understanding of the pathophysiology of the disease and physiologic changes during pregnancy . Prophylactic blood transfusion does not appear to reduce complications in patients with sickle cell anemia . Patients with sickle hemoglobin C disease and with S beta thalassemia+ have fewer complications but still need close monitoring . Blood transfusion therapy should be made available for medical and obstetrical complications to include increasing hypoxemia, progressive anemia, acute chest syndrome, twin pregnancy, splenic sequestration syndrome, preeclampsia, septicemia, or prior to general anesthesia and surgery . Blood transfusion therapy is associated with hepatitis, allergic reaction, alloimmunization, AIDS, and iron overload states . These aspects should be considered prior to using blood transfusion therapy . Excellent prenatal monitoring and aggressive intervention should be instituted when problems arise for the successful management of the pregnant patient with sickle cell disease . Prenatal diagnosis and cord blood screening should be made available for the infant . Appropriate pediatric referral and prophylactic penicillin is recommended for the infant with sickle cell disease.

J Assoc Acad Minor Phys, 1991, 2(2), 72 - 5
Hepatitis and glomerulonephritis in secondary syphilis; Balikocioglu A et al.; In early secondary syphilis, predominant features of spirochetal infection may include hepatitis and glomerulonephritis . We report a 27-year-old woman with characteristic physical, laboratory, and microscopic findings of syphilitic hepatitis and glomerulonephritis; she responded to penicillin therapy and recovered completely . The importance of clinically and pathologically recognizing this treatable disease is emphasized.

J Fr Ophtalmol, 1991, 14(11-12), 605 - 9
{Syphilitic uveitis and human immunodeficiency virus infection}; Bouisse V et al.; Ocular syphilis is rare in human immunodeficiency virus infected individuals . We think that syphilis should be considered in evaluating such patients presenting with uveitis . Most often, ocular syphilis includes retinitis associated with anterior or posterior uveitis, sometimes with optic neuritis . Concurrent neurosyphilis is frequent and may be more aggressive; it may progress more rapidly and cause more atypical signs than in patients without human immunodeficiency virus infection . This suggests the need for lumbar puncture in the evaluation of coinfected patients . The standard serological tests for syphilis (in blood and cerebrospinal fluid) may be nonreactive in human immunodeficiency virus seropositive patients . It may be because of the alteration of immunologic response of such patients . All coinfected patients with human immunodeficiency virus and syphilis should be treated with high-dose intravenous penicillin G sodium as recommended for neurosyphilis . We describe two human immunodeficiency virus infected patients with ocular syphilis and neurosyphilis.

Brain Topogr, 1991 Winter, 4(2), 85 - 93
Empirical comparison of the MEG and EEG: animal models of the direct cortical response and epileptiform activity in neocortex; Barth DS; This review directly addresses the appropriateness of the dipole model as a physical representation of neocortical sources produced by evoked and spontaneous epileptiform activity in neocortex . Three dimensional electrical measurements of cellular currents in rat sensory neocortex are compared to the extracranial magnetic fields these currents produce . Comparisons are performed for the direct cortical response (DCR) evoked by electrical stimulation of the cortical surface, and for evoked and spontaneous interictal and ictal discharge of the penicillin focus in the same animal preparation . Our data support the hypothesis that evoked and epileptiform magnetic fields result from intradendritic currents oriented perpendicular to the cortical surface . Furthermore, magnetic fields can be detected from epileptic foci smaller than 3 x 3 mm2 . This work provides an empirical foundation for physical models with which to interpret noninvasive neuromagnetic recordings of epileptic discharge in human focal seizure disorders . The dipole approximation appears to be appropriate for the interpretation of magnetic field phenomena in neocortex.

Indian J Chest Dis Allied Sci, 1991 Jan-Mar, 33(1), 25 - 9
Clindamycin in the treatment of anaerobic lung abscess; Shah A et al.; A case of anaerobic lung abscess who had treatment failure after 4 weeks of supervised parenteral penicillin and oral metronidazole is described . Anaerobic pathogens resistant to one or the other of the above drugs were isolated . The patient had a striking clinical response to subsequent therapy with oral clindamycin . Failure of therapy should alert physicians to the possibility of infection with resistant anaerobic pathogens and in such situations, clindamycin is considered as an effective alternative.

Trop Geogr Med, 1991 Jan-Apr, 43(1-2), 142 - 7
Studies on a focus of yaws in the Santiago Basin, province of Esmeraldas, Ecuador; Guderian RH et al.; A clinical and serological epidemiological study done on a yaws focus in the Santiago Basin area, province of Esmeraldas, showed a prevalence of 11.3% for active clinical lesions and a seropositivity of 94.9% . The Rio Santiago was hyperendemic for yaws (prevalence, 17.9%; seropositivity, 98.0%) while Rio Zapallito was found to be mesoendemic and the Rio Cayapas and Rio Onzoles hypoendemic . Active and latent evidence of yaws was found only in the black race . Children, ages 5-12 year, were found to have the highest incidence (55.8%) of clinical lesions, with the majority found on the legs (64.2%) . Papilloma was the most prevalent lesion (55.4%) . Mass treatment of the basin using benzathine penicillin G was done according to WHO recommendation.

Eur Arch Otorhinolaryngol, 1991, 248(7), 422 - 4
Cavernous sinus thrombosis following odontogenic and cervicofacial infection; Yun MW et al.; Cavernous sinus thrombosis (CST) is rarely seen clinically as a complication of infectious processes since the discovery of penicillin . At the present time, dental abscess is an uncommon cause of CST . We now report our experiences with a 60-year-old diabetic male, who developed CST 38 days after extraction of an infected upper third molar tooth . The importance of eradicating regional cervicofacial foci of infection is stressed.

J Hosp Infect, 1991 Jan, 17(1), 3 - 13
Penicillin-resistant pneumococci; Allen KD; Penicillin-resistant pneumococci were first reported in Australia in 1967 and appeared in the UK in 1976 . Their prevalence is increasing but varies greatly worldwide . The mechanism of resistance lies in the alteration of penicillin-binding proteins . Penicillin-resistant strains are often also resistant to a variety of non-beta-lactam antibiotics . Many different serotypes have been found to be penicillin resistant, type 23 being the most common resistant serotype in the UK . Use of oxacillin discs is recommended for penicillin sensitivity testing, otherwise resistant isolates may escape detection . Treatment of infected patients depends on several factors including the degree of resistance of the infecting strain, the sensitivity to alternative agents and the achievable concentration of antibiotic at the site of the infection . Carriage of penicillin-resistant pneumococci is more common in children, especially the recently hospitalized and those recently exposed to antibiotics . Outbreaks of infection have occurred and various control measures have been suggested in attempts to limit the spread of resistant strains.

Lung, 1991, 169(6), 311 - 23
HOCl exposure of a human airway epithelial cell line decreases its plasma membrane neutral endopeptidase; Lang ZH et al.; It has recently been demonstrated that luminal exposure of airway segments in vitro to HOCl produces airway muscle hyperresponsiveness to substance P and a decrease in neutral endopeptidase (NEP) activity of tissue segment homogenates, suggesting that HOCl may decrease airway epithelial cell NEP activity . To confirm that this effect occurs in humans and to investigate possible subcellular mechanisms for it, we assessed HOCl exposure of the human airway epithelial cell line Calu-1 . These cells, grown to confluency in Dulbecco's modified Eagle medium with 10% fetal bovine serum and penicillin-streptomycin, were exposed in situ for 5 min to 100 microM HOCl in a phosphate-buffered saline solution (PBS; pH 7.0 at 37 degrees C) or to PBS alone . Thereafter, cells were rinsed and assayed for NEP activity employing reverse-phase high-pressure liquid chromatography . This activity was characterized by the generation of phosphoramidon-inhibitable product (ANA) cleaved from the synthetic substrate succinyl-(ala)3-p-nitroaniline during a 30 min incubation at 37 degrees C . Cell viability was assessed by changes in LDH release, trypan blue exclusion, and cell volume . In some experiments, crude plasma membrane and soluble components of exposed cells were isolated and differential NEP activity was assayed . We found that a 5 min exposure to HOCl decreased whole cell NEP activity from 74.1 +/- 4.4 (mean +/- SE) to 54.3 +/- 6.0 pmoles of ANA/min/10(6) cells (p less than 0.05), while no parameter of cell viability was affected . NEP activity in the crude membrane fraction decreased 36.3 +/- 3.1% after exposure (p less than 0.01), whereas NEP activity in the soluble fraction increased 4.0 +/- 0.6% . Isolated membrane NEP exposed by itself was not affected . Subsequent experiments with reducing agents demonstrated that NEP activity of cell cultures pretreated with 100 mM of either beta-mercaptoethanol or dithiothrietol before HOCl exposure was not significantly different from control values . We conclude that whole cell HOCl exposure decreases Calu-1 plasma membrane NEP . This loss appears to occur by internalization of cell membrane NEP.

J Chem Technol Biotechnol, 1991, 51(2), 181 - 95
Kinetic investigation of penicillin G acylase from a mutant strain of Escherichia coli ATCC 11105 immobilized on oxirane-acrylic beads; Erarslan A et al.; Highly purified penicillin G acylase from a mutant derivative of Escherichia coli ATCC 11105 was immobilized on oxirane-acrylic beads by covalent binding via oxirane groups . The highest specific activity, (322 U g-1 dry matrix at 40 degrees C and at pH 8.0) was obtained by using an enzyme solution having 13.8 U mg-1 specific activity and 72.73 mg total protein . The efficiency of immobilization was 95.8% . Kinetic parameters of immobilized penicillin G acylase were determined at the same pH and temperature by a preparation having 8.1 mg bound protein . The Km value and substrate inhibition constant of the enzyme were found to be 11.36 mmol dm-3 and 680 mmol dm-3 penicillin G respectively . Phenylacetic acid and 6-aminopenicillanic acid were estimated as the competitive and non-competitive inhibitors of the enzyme and their inhibition constants were found to be 90 mmol dm-3 phenylacetic acid and 76.1 mmol dm-3 for 6-aminopenicillanic acid . The activation energy of the hydrolytic reaction was calculated to be 7.75 kcal mol-1 . The immobilized enzyme showed highest activity at pH 8.0 and at 55 degrees C . The enzyme was stable when incubated at 4 degrees C for one day at a pH range of 5.0 to 9.0 . Thermal stability (over 30 min) was observed up to 40 degrees C but decreased at higher temperatures and was almost absent at 60 degrees C . A 95% conversion rate was observed at 28 degrees C and at 40 degrees C with 60 and 30 min operation times respectively . Operational stability of the enzyme was improved further with dithiothreitol treatment . Activity loss was around 5% following 20 cycles of repeated use of the enzyme at 40 degrees C . No significant loss of activity was observed at 28 degrees C when the enzyme was used for 20 cycles . 6-Aminopenicillanic acid in the reaction mixture was observed to be stable during conversion reactions which were carried out at both temperatures.

J Biotechnol, 1991 Jan, 17(1), 81 - 90
Strain improvement of Penicillium chrysogenum by recombinant DNA techniques; Veenstra AE et al.; The penDE gene from Penicillium chrysogenum has been isolated; the gene is located in close vicinity of the pcbC gene . Amplification of the pcbC-penDE gene cluster in Penicillium chrysogenum Wis54-1255 leads to a significant increase in penicillin production . In selected transformants an increase of up to 40% is observed.

J Biotechnol, 1991 Jan, 17(1), 67 - 80
Molecular characterization and functional analysis in Aspergillus nidulans of the 5'-region of the Penicillium chrysogenum isopenicillin N synthetase gene; Kolar M et al.; The isopenicillin N synthetase gene (pcbC) was isolated from a genomic library of Penicillium chrysogenum BC39813, a penicillin production strain . The nucleotide sequence, including 555 bp upstream of the translation start site was determined . Various deletions within the pcbC 5'-region were constructed and linked to the Escherichia coli lacZ gene . An Aspergillus nidulans argB strain was transformed with DNA of these constructions . The region essential for promoter function could be localized between positions -307 and -89 by analyzing beta-galactosidase expression of transformants containing a single copy of the corresponding plasmid integrated at the homologous argB locus . A region responsible for regulatory effects concerning nitrogen metabolism was identified by determining beta-galactosidase activities in cell-lysates of transformants cultivated under varying growth conditions . Two major transcription start sites at positions -131 and -132, as well as a further upstream located site at position -397 +/- 1 could be located by primer extension studies employing RNA isolated from P . chrysogenum BC39813.

Clin Ter, 1990 Dec 31, 135(6), 469 - 73
{The determination of specific IgE in allergy diagnosis . The clinical significance of specific IgE in drug allergies}; Spinozzi F et al.; IgE-mediated allergic reactions to drugs may be diagnosed on the basis of anamnestic criteria, clinico-pathological manifestations as well as by the measurement of allergen-specific IgE . The concordance of these diagnostic procedures was investigated in 50 patients with a history of sensitivity to penicillin (12), sulphamethoxazole (9) or both (14), aspirin (2) and pyrazolones (13) . All subjects displayed chronic urticaria/angioedema syndrome . Optimal concordance values were observed for penicillin and sulphamethoxazole, while no specific IgE were detected in the ASA-sensitive group . False positive results were noted in pyrazolone-sensitive patients with high total IgE levels . Based on these results, serological methods that detect drug-specific IgE may be carefully used as complementary diagnostic procedure only in those patients in whom an adverse reaction to antibiotics is suspected.

Acta Neurol Scand, 1990 Dec, 82(6), 381 - 5
High-dose intravenous-penicillin in neurosyphilis: effect on intrathecal synthesis of IgG, IgM, IgA and IgD; Hens MJ et al.; We evaluated occurrence and levels of intrathecal synthesis of IgG, IgM, IgA and IgD by calculating corresponding index values in 8 patients with definite and 4 with suspected or possible neurosyphilis, prior to, during and after high-dose intravenous penicillin therapy . Four patients with active neurosyphilis displayed intrathecal synthesis of IgG, IgM and IgA . Only 2 of them showed elevated IgD index, and both had taboparesis, pleocytosis and positive VDRL in CSF, and simultaneous elevation of the IgG, IgA and especially of the IgM indices . This suggests that intrathecal synthesis of IgD may occur in patients with severe CNS inflammation in response to diffuse CNS treponemal damage . Penicillin therapy incited transitory elevation of one or more of the immunoglobulin index values in most patients, possibly in response to massive treponemal lysis inside the CNS . Thereafter, the values became mostly normalized but exceptions occurred, including one patient who had elevated IgG and IgM index which persisted 31 months after therapy . Our data indicate that determinations of immunoglobulin indices performed on consecutive specimens from individual patients with neurosyphilis may be helpful in the evaluation of treatment.

Epilepsy Res, 1990 Dec, 7(3), 210 - 8
Analysis of central cardioarrhythmogenic triggers in experimental epilepsy; Mameli O et al.; The cardioarrhythmogenic potential of epileptic foci induced at mesencephalic and rhombencephalic levels was analyzed in hemispherectomized rats . Topical application of penicillin-G onto the mesencephalic quadrigeminal lamina or onto the fourth ventricle induced paroxysmal activity at the mesencephalic or bulbar neurone level . At the mesencephalic levels, the paroxysmal activity was characterized by a significant increase in the spontaneous frequency of the neurones, with the appearance of multiunit activity and rhythmical outbursts . The simultaneous recording of myocardial electrical activity and blood pressure showed that the paroxysmal activity triggered short-latency sinus bradyarrhythmias with wandering of the sinus pacemaker, the appearance of biphasic or negative P waves, some premature ventricular contractions and non-significant reduction of systolic and diastolic pressures . When the paroxysmal activity stopped, the cardiac rhythm and blood pressure returned to basal values . At the bulbar level, the paroxysmal activity appeared with longer latency and usually the rhythmical outbursts were not observed . Following bulbar paroxysmal activity only short-lasting episodes of sinus bradyarrhythmias appeared . Midcollicular transection eliminated paroxysmal activity at the bulbar level, and blood pressure and cardiac rhythm resumed basal values . After transection, an additional application of convulsant drug (penicillin-G or pentylenetetrazole) onto the fourth ventricle did not induce the reappearance of paroxysmal activity and the consequent cardiovascular alterations . The results showed the existence of a cardioarrhythmogenic trigger localized at the mesencephalic level which spreads paroxysmal activity upwards . A hypothesis to explain the appearance of fetal haemodynamic modifications and life-threatening arrhythmias has been proposed.

J Bacteriol, 1990 Dec, 172(12), 6697 - 703
The balance between different peptidoglycan precursors determines whether Escherichia coli cells will elongate or divide; Begg KJ et al.; The rodA(Sui) mutation allows cell division to take place at 42 degrees C in ftsI23 mutant cells, which produce a thermolabile penicillin-binding protein 3 (PBP3, the septation-specific peptidoglycan transpeptidase) . We show here that the mutation in rodA is a single-base change from a glutamine to a chain termination (amber) codon, and that an amber suppressor (supE) present in the strain restores the ability to produce a reduced level of normal RodA protein . The reduced level of RodA is accompanied by an increase in the levels of two other proteins (PBP2 and PBP5) encoded by genes in the rodA operon . We show that an increased level of PBP5 is by itself sufficient to restore cell division to ftsI23 cells at 42 degrees C . Two other treatments were found to restore division capacity to the mutant: an increase in PBP6 (which is a D-alanine carboxypeptidase like PBP5) or suitable concentrations of D-cycloserine . All of the above treatments have the effect of reducing the number of pentapeptide side chains in peptidoglycan and increasing the number of tripeptides . We conclude that the effect of the rodA(Sui) mutation is to indirectly increase the availability of tripeptide side chains, which are used preferentially by PBP3 as acceptors in transpeptidation . A change in the proportions of different kinds of peptide side chain in the peptidoglycan can therefore determine whether cells will divide.

Am J Dis Child, 1990 Dec, 144(12), 1343 - 5
Newborn screening for sickle cell disease . When is an infant 'lost to follow-up'?
Miller ST, Stilerman TV, Rao SP, Abhyankar S, Brown AK.
Success of programs to screen newborns for sickle cell disease depends on timely follow-up . Education regarding fever and splenic palpation, and initiation of prophylactic penicillin therapy, will reduce morbidity and mortality and should occur prior to 4 months of age . However, contacting parents to permit implementation of care may be difficult, particularly in large urban populations; only nine (36%) of 25 infants recently identified as having sickle cell disease arrived at our institution for initial appointments . Medical providers must be aware of medical and legal obligations related to follow-up of newborns with sickle cell disease to prevent untoward events in "missed cases."

Ann Intern Med, 1990 Dec 1, 113(11), 872 - 81
Effect of human immunodeficiency virus (HIV) infection on the course of syphilis and on the response to treatment; Musher DM et al.; PURPOSE: To evaluate evidence that concurrent infection with human immunodeficiency virus (HIV) alters both the natural history of syphilis (by increasing the frequency of early neurosyphilis) and the response to penicillin . DATA IDENTIFICATION: Review of major works on syphilis in the English language and files maintained since 1971, supplemented by a systematic search using Index Medicus and MEDLARS . DATA EXTRACTION: The works mentioned above were critically reviewed for information on early neurosyphilis and, where relevant, HIV infection . RESULTS OF DATA ANALYSIS: The central nervous system is regularly involved in early syphilis . Standard recommended doses of benzathine penicillin provide cerebrospinal fluid levels that are probably at the borderline of efficacy, and cure relies on treatment and an adequate host immune response . Early neurosyphilis, appearing within 2 years of onset of infection with Treponema pallidum, was uncommon in the prepenicillin era and usually occurred after inadequate therapy . This complication was exceedingly rare in the first three decades of penicillin use . In contrast, in the past decade, 40 patients with HIV infection have been reported to have asymptomatic neurosyphilis, or syphilitic meningitis, cranial nerve abnormalities (predominantly in cranial nerves II and VIII), or cerebrovascular accidents, singly or together . In 40% of cases, HIV infection was first diagnosed when neurologic symptoms appeared . Of the 38 patients for whom information was available, 18 had the acquired immunodeficiency syndrome (AIDS), 7 had AIDS-related complex, and 13 had antibody to HIV . Sixteen had previously been treated for syphilis, of whom 5 (31%) had received benzathine penicillin within the previous 6 months . Preliminary data also suggest that skin lesions and VDRL (Venereal Disease Research Laboratory) antibody in HIV-infected patients with secondary syphilis respond more slowly to conventional penicillin therapy . CONCLUSION: Intensive therapy and follow-up observation is indicated for early syphilis in HIV-infected subjects . Novel approaches to treatment deserve systematic evaluation.

J Antibiot (Tokyo), 1990 Dec, 43(12), 1559 - 63
Aliphatic molecules (C-6 to C-8) containing double or triple bonds as potential penicillin side-chain precursors; Martin-Villacorta J et al.; Three different hexenoyl-CoA derivatives (trans-2-hexenoyl-CoA, trans-3-hexenoyl-CoA and trans-trans-2,4-hexadienoyl-CoA), two octenoyl-CoA (trans-2-octenoyl-CoA, trans-3-octenoyl-CoA) and 2-octynoyl-CoA were tested as substrates of the enzyme acyl-CoA: 6-Aminopenicillanic acid acyltransferase (AT) from Penicillium chrysogenum . Only trans-3-hexenoyl-CoA and trans-3-octenoyl-CoA were recognized by AT and efficiently converted into penicillin F and octenoylpenicillin, respectively . The Km values for these substrates were 0.6 and 0.5 mM, suggesting that the affinity of AT for these molecules is similar to that reported for phenyl acetyl-CoA, octanoyl-CoA and hexanoyl-CoA (0.5, 0.6, and 1 mM, respectively) . The absence of enzymatic activity shown by AT with the other acyl-CoA derivatives tested is due to the different position of the double or triple bond(s) in their aliphatic chains . The influence of the free rotation round the bond C-2-C-3 and possibility of planar conformation in such molecules and the importance in the formation of the enzyme-substrate complex is discussed.

Hell Period Stomat Gnathopathoprosopike Cheir, 1990 Dec, 5(4), 165 - 70
{Treatment of sialolithiasis and its complications with intraglandular injection of biotherapeutic solution}; Antoniadis D et al.; The creation of sialoliths in the ductal system of major salivary glands causes characteristic symptoms due to the obstruction of the flow of produced saliva . If sialolithiasis is not treated early obstructive sialadenitis will develop and its repeated relapses may lead to fibrosis and degeneration of glandular parenchyma . In this study we present the method of intraglandular injection of biotherapeutic solution (1.000.000 I.U . penicillin G in 5 cc normal saline) to achieve treatment of obstructive sialadenitis and rejection of the sialolith . Our results as shown in tables I and II and in figures 1-9 are very encouraging . From the conclusions drawn it looks like this method can be recommended as an optional solution to surgery (lithectomy-adenectomy) under the conditions mentioned in the discussion.

Enferm Infecc Microbiol Clin, 1990 Dec, 8(10), 602 - 5
{Severe leptospirosis . Description of a series of 10 cases}; Mariscal D et al.; Clinical aspects of 10 consecutive patients hospitalized for acute human leptospirosis, confirmed by serology using the microscopic agglutination test (MAT), between 1975 and 1988 in a 1000 beds Teaching Hospital are retrospectively analyzed . All of them were male, mean age of 55, presenting a suggestive epidemiological data to be at risk for Leptospira infection . Leptospira icterohaemorrhagiae was responsible for 8 cases and Leptospira canicola for 2 . 7 patients were treated, after 3-4 days of admittance, with penicillin . 5 patients died . Cause of death was gastrointestinal haemorrhage in 3 and cardiogenic shock in 2 . We discuss the clinical, biochemical, pathological and therapeutic aspects of the acute human leptospirosis.

Vrach Delo, 1990 Dec, (12), 46 - 9
{The diagnosis of drug hypersensitivity}; Badina AK; The author revealed an increase of dienic conjugates in 391 patients under the effect of drugs in patients with drug intolerance and a study is also presented in 46 patients with good tolerance to drugs . It is shown that the dienic test has an information value as to intolerance of penicillin, streptomycin, tetraolean, analgin, novocaine and vitamin B1.

Minerva Pediatr, 1990 Dec, 42(12), 543 - 6
{The follow-up in adulthood of subjects with progressive rheumatic disease in childhood . Considerations of secondary prevention}; Castagna PC et al.; We reviewed 57 patients who had previously suffered from rheumatic fever (RF) after an average period of 7.2 (+/- 2.8) years without penicillin prophylaxis . In 24 cases (42%) RF began with carditis and in 9 patients valvular damage remained after hospital discharge . Prophylaxis with retard penicillin every four week was carried out for 5.5 +/- 1.8 years . At present the patients are all asymptomatic . There was in 7 cases mild valvular damage without clinical and instrumental involvement . There was not recurrency after the end of prophylaxis, except for a doubtful case, analysed in the Discussion . Although our cases are not numerous, we believe that a regular prophylactic treatment over 5 or 6 years is sufficient to avoid any recurrency in patients with previous RF . After this period of treatment, only subjects with valvular damage should have further extensive treatment until their 20th year and always for a period not shorter than ten years.

Clin Otolaryngol, 1990 Dec, 15(6), 537 - 44
Central nervous system involvement in patients with facial palsy due to borrelial infection; Engervall K et al.; Patients with a peripheral facial palsy due to an underlying Ixodes-borne borreliosis often have cerebrospinal fluid findings indicating meningeal involvement . The aim of the present study was to identify signs of CNS involvement by means of brain-stem evoked response audiometry (BSER) in patients with a facial palsy due to borreliosis, as well as in patients with a facial palsy of unknown aetiology . Bell's palsy . Abnormalities in BSER were found to be significantly more common along the borrelial patients . Furthermore, a reversal of these abnormalities following treatment with benzyl-penicillin was found in the majority of patients with borreliosis . The results of the present study emphasize the importance of diagnosing and treating an underlying borreliosis in patients with a peripheral facial palsy.

Br J Pharmacol, 1990 Dec, 101(4), 971 - 7
Actions of acetylcholine and GABA on spontaneous contractions of the filariid, Dipetalonema viteae; Christ D et al.; 1 . Isotonic contractions were recorded from the filarial nematode, Dipetalonema viteae (Acanthocheilonema viteae), in an isolated tissue chamber . 2 . Nicotine (10(-6) M) and pilocarpine (10(-5) M) increased the spontaneous contractions in the intact filariid, but acetylcholine (ACh, 10(-4) M) and muscarine (10(-5) M) were inactive . 3 . When ACh was applied to an opened D . viteae, it was 10,000 times more potent . This indicates that the cuticle is an effective barrier to the penetration of ACh to the muscle cells . 4 . The effects of ACh on the opened D . viteae were not affected by hexamethonium (10(-3) M) or atropine (10(-5) M) and were only partially reduced by (+)-tubocurarine (10(-4) M) . 5 . gamma-Aminobutyric acid (GABA, 10(-3) M) reduced the spontaneous activity of the intact D . viteae; however, the effect of GABA had a slow onset and recovery . Muscimol (10(-5) M) was more potent than GABA and had a more rapid onset and recovery . 6 . GABA was 1,000 times more potent on the opened D . viteae than on the intact D . viteae . Baclofen (10(-3) M) was inactive on both preparations . 7 . The effect of GABA was not antagonized by bicuculline (10(-4) M), picrotoxin (10(-5) M or penicillin G (10(-3) M) . 8 . It is concluded that the filariid cuticle acts like a lipid structure and blocks the penetration of polar substances, such as ACh and GABA . Also, due to the lack of efficacy of the ACh and GABA antagonists, it was concluded that the nematode receptors are somewhat different from the mammalian ACh and GABA receptors.

J Bacteriol, 1990 Dec, 172(12), 7284 - 8
Mapping of conformational epitopes of monoclonal antibodies against Escherichia coli penicillin-binding protein 1B (PBP 1B) by means of hybrid protein analysis: implications for the tertiary structure of PBP 1B; Den Blaauwen T et al.; We have analyzed the location of the epitope areas of the four monoclonal antibody groups against penicillin-binding protein 1B (PBP 1B; T . den Blaauwen, F . B . Wientjes, A . H . J . Kolk, B . G . Spratt, and N . Nanninga, J . Bacteriol . 171:1393-1401) . They could be specified by studying monoclonal antibody binding patterns to amino- and carboxy-terminal truncated PBP 1B molecules . Monoclonal antibodies against conformational epitopes, with the exception of one epitope area, did not recognize PBP 1B molecules that had not been translocated across the membrane . Apparently, translocation is required for PBP 1B to fully obtain its native conformation.

Appl Microbiol Biotechnol, 1990 Dec, 34(3), 397 - 8
Reversion of L-lysine inhibition of penicillin G biosynthesis by 6-oxopiperidine-2-carboxylic acid in Penicillium chrysogenum PQ-96; Kurzatkowski W et al.; 6-Oxopiperidine-2-carboxylic acid (OCA; cyclic alpha-aminoadipic acid) reverses the L-lysine inhibition of penicillin G production by Penicillium chrysogenum PQ-96 . The reaction probably depends on the recovery of L-alpha-aminoadipic acid for penicillin G production from OCA.

Biochem Biophys Res Commun, 1990 Nov 30, 173(1), 317 - 22
Evidence for involvement of arginyl residue at the catalytic site of penicillin acylase from Escherichia coli; Prabhune AA et al.; Incubation of penicillin acylase from Escherichia coli with phenylglyoxal or 2,3-butanedione results in enzyme inactivation . Both benzylpenicillin and phenylacetate protect the enzyme against the inactivation, indicating the presence of arginine at or near the catalytic site . The reactions follow pseudofirst order kinetics and the inactivation kinetics indicate the presence of a single essential arginine moiety.

Brain Res, 1990 Nov 19, 533(2), 275 - 85
Different changes in spontaneous field potential oscillations precede epileptiform bursting in hippocampal slices perfused with penicillin or reduced magnesium; Schneiderman JH et al.; Power spectra were used to analyse spontaneous field potentials (SFPs) recorded in the CA3 distal apical dendritic region of guinea pig hippocampal slices perfused with either penicillin or reduced Mg2+ . High concentrations of penicillin (2000 IU/ml) progressively converted the low amplitude, irregular oscillations observed in control medium to higher amplitude, low frequency, rhythmic oscillations at approximately 2-3 Hz just prior to the onset of spontaneous, synchronized bursting . Low concentrations (50-300 IU/ml) increased the power of frequencies below 10 Hz and suppressed higher frequencies in a dose-dependent fashion . Although Mg2(+)-free medium also increased the magnitude of the SFPs prior to the onset of synchronous bursting, the changes were smaller than with penicillin and the frequency distribution was completely different . Low concentrations of Mg2+ (0.0-0.5 mM) increased the power across all frequencies, however, the maximal effect was on frequencies between 5 and 25 Hz . The transition from normal to epileptiform activity may proceed through at least 2 distinct intermediate states . When recurrent inhibition is blocked (penicillin), synchronous synaptic activity precedes the onset of bursting, whereas non-specific increases in excitability and activation of NMDA receptors (reduced Mg2+) produce an asynchronous transition state.

N Engl J Med, 1990 Nov 8, 323(19), 1299 - 302
Congenital syphilis presenting in infants after the newborn period; Dorfman DH et al.; BACKGROUND AND METHODS . There has been a recent, dramatic increase in the incidence of congenital syphilis, particularly in urban areas . We describe seven infants seen during one year who were first given a diagnosis of congenital syphilis at 3 to 14 weeks of age, when symptoms developed . We reviewed these infants' charts in order to ascertain the reasons for the failure to diagnose syphilis at birth and to identify the signs and symptoms of congenital syphilis in this group of infants . RESULTS . At delivery, four of the infants and their mothers had negative qualitative rapid-plasma-reagin tests for syphilis . The other three mothers had been seronegative during the pregnancy and were therefore not tested at delivery; two of their infants were seronegative at birth, and one was not tested . When the infants became symptomatic between 3 and 14 weeks of age and were admitted to the hospital, all seven infants and the five mothers available for testing were found to be seropositive for syphilis . Four infants presented with a characteristic diffuse rash; the other three presented with fever and were found on admission to have aseptic meningitis . All these infants had multisystem disease, as evidenced by hepatomegaly, increased aminotransferase and alkaline phosphatase levels, anemia, and monocytosis . In all the infants syphilis responded to parenteral penicillin . CONCLUSIONS . Congenital syphilis may be missed if serologic tests are not performed for both the mother and her infant at the time of delivery . Even when these tests are performed, some infants are not identified as having syphilis, probably because the infection is very recent and there has been insufficient time for an antibody response to develop . Some infants with congenital syphilis of later onset do not present with a typical rash; therefore, at least in areas where the disease is prevalent, serologic tests for syphilis should be included in the evaluation of all febrile infants, even those with negative results on serologic testing at birth.

Allergy Proc, 1990 Nov-Dec, 11(6), 299 - 304
Drug allergy; Kim K et al.; Undesirable or adverse drug effects occur with 1-15% of drug doses . The mechanisms of these reactions are not always known; however, 5-10% are immunologically mediated allergic reactions . Risk factors for allergic drug reactions include age, type of drug, degree of exposure, and route of administration . Penicillin allergy is the most common example of classical drug allergy . Skin test reagents are available which identify the patient at risk of anaphylaxis from penicillin . These patients can be given penicillin in a carefully monitored desensitization protocol . It is essential to establish first the absolute requirement for the drug in the patient sensitive to it . There are also established methods for administration to the sensitive patient: local anesthetics, measles vaccines, and sulfamethoxazole.

J Assoc Off Anal Chem, 1990 Nov-Dec, 73(6), 880 - 2
Liquid chromatographic determination of cephapirin residues in milk; MacIntosh AI; A liquid chromatographic (LC) method was developed for quantitative determination of cephapirin residues in milk that also resolved cephapirin from ampicillin, cloxacillin, and penicillin G . Diluted milk was passed through a C18 cartridge on which the cephapirin was adsorbed; then, interfering material was removed by washing with water and methylene chloride and cephapirin residues were eluted with methanol-acetonitrile (25 + 75) . After drying, residues were dissolved in the mobile phase for injection . The LC system had an ultrasphere-ODS column with RP-18 Spheri-10 guard column and a UV detector with a 254 nm filter . The mobile phase was 85% sodium acetate (0.01M) and 15% methanol-acetonitrile (25 + 75) with a flow rate of 1 mL/min . Sensitivity was 20 ppb or less with a recovery of 61-80% in the range studied . Other beta-lactam antibiotics tested did not interfere with detection of cephapirin . Analysis of 30 samples of commercial homogenized milk obtained for a survey of antibiotics in consumer milk in Canada revealed no detectable cephapirin residues.

Br J Clin Pract, 1990 Nov, 44(11), 450 - 3
Poisoning due to amatoxin-containing Lepiota species; Paydas S et al.; Twenty-seven consecutive mushroom poisoning cases were followed up over a period of 14 days . Fourteen out of 27 died of liver failure . There were no deaths from renal failure . The mushrooms were identified as the amatoxin-containing Lepiota species . Therapeutic measures included nasogastric lavage, charcoal, vitamin C, vitamin B, penicillin G, corticosteroids, oral streptomycin and, in the case of a few patients, limited amounts of thioctic acid . Of the ten haemodialysed, nine died . Unfortunately charcoal haemoperfusion was not available . It appeared that therapeutic measures were ineffective and it also seemed that the amount of mushroom ingested was the determining factor for the prognosis . An important point to make is that renal failure does not occur and liver failure is always delayed (group II) . For this reason all suspected cases of mushroom poisoning, regardless of absence of clinical signs and symptoms, must be hospitalised for a period of at least one week . The poisonous properties of wild mushrooms have been recognized since ancient times . However, despite awareness of their inherent dangers, serious poisoning continues to occur . Fatal intoxications can be attributed almost entirely to the amtoxin-containing species . Amanita phalloides have been blamed for over 90% of poisoning deaths in North America . There are reports of intoxications of other amatoxin-containing species in Europe, but fatalities due to Lepiota species are reported only rarely . It was previously acknowledged that the interval between ingestion of mushrooms and the onset of symptoms is longer than expected in serious poisonings.(ABSTRACT TRUNCATED AT 250 WORDS)

J Am Vet Med Assoc, 1990 Nov 1, 197(9), 1181 - 3
Polypoid cystitis, pyelonephritis, and obstructive uropathy in a cow; Wallace LL et al.; Polypoid cystitis, pyelonephritis, and obstructive uropathy was found in a cow with hematuria, dysuria, and colic . The cow was treated with penicillin, multiple B vitamin supplementation, and isotonic sodium chloride . Polypoid cystitis, diagnosed in this cow by use of endoscopic examination, is a common response to chronic inflammation of the bladder and can lead to obstructive uropathy . Although endoscopic confirmation of this diagnosis may not always be feasible, recognition of corresponding clinical signs can allow timely, appropriate treatment.

Arch Dis Child, 1990 Nov, 65(11), 1268 - 9
Continued need for pneumococcal prophylaxis after splenectomy; Murdoch IA et al.; Two children died from pneumococcal infection five and eight years after splenectomy . Pneumococcal vaccination had not been given to either child . When the infection developed both children were not taking prophylactic penicillin . Vaccination and daily penicillin reduce the incidence of this complication and therefore we strongly recommend that both of these measures are continued indefinitely.

Epilepsia, 1990 Nov-Dec, 31(6), 713 - 7
Triiodothyronine and brain excitability; Tauboll E et al.; We investigated mechanisms involved in thyroid hormone action on brain excitability . The effect of acute exposure of triiodothyronine (T3) to rat hippocampal slices in vitro was studied . No significant changes could be detected in prevolley, field excitatory postsynaptic potentials (fEPSP) and population spike amplitude, while there was a minor, nonsignificant trend toward shortening of the population spike latency time . T3 had no effect on penicillin-induced epileptiform activity . There was, however, an active accumulation of radioactively labeled T3 in the slices . A rat cervaux-isole preparation was used to determine focal seizure thresholds in the visual cortex, and no acute (2-4 h) effects were demonstrated . No significant acute effects of T3 on brain excitability in the hippocampus and visual cortex was observed, despite an active accumulation of T3 . Thus, the effect of T3 on brain excitability most likely is due to delayed effects.

Proc Soc Exp Biol Med, 1990 Nov, 195(2), 255 - 60
Relaxin, oxytocin, and prostaglandin effects on progesterone secretion from bovine luteal cells during different stages of gestation; Musah AI et al.; To determine the effects of relaxin, oxytocin, and prostaglandin F2 alpha on progesterone secretion, bovine luteal cells from different stages of gestation were dispersed in Medium 199 with 200 units/ml penicillin, 1.0% kanamycin, 0.5% bovine serum albumin, and 400 units/ml collagenase . Cells (10(5) were cultured in 400 microliters of Dulbecco's modified Eagle's medium and Ham's F-12 medium containing fetal bovine serum and antibiotics, in Falcon multiwell plates, in a humidified environment of 95% O2 and 5% CO2 at 37 degrees C . Cells were cultured for 24 hr without treatment and thereafter with medium-hormone replacement every 24 hr . Progesterone was quantified from unextracted media by radioimmunoassay . Basal progesterone secretion after 24 hr was 1.81 +/- 0.14, 1.76 +/- 0.17, 0.54 +/- 0.49, and 0.57 +/- 0.21 pg/ml per viable luteal cell from 145-, 165-, 185-, and 240-day-old corpora lutea, respectively . Basal progesterone secretion increased (P less than 0.05) with time in culture . Relaxin induced a dose-dependent (greater than 100 ng/ml) increase in progesterone release, compared with the controls . Oxytocin and prostaglandin F2 alpha induced greater release (P less than 0.05) of progesterone than relaxin at all stages of gestation, but progesterone release was dependent on the stage of gestation and the duration in culture . Luteinizing hormone (100 ng/ml) stimulated whereas 17 beta-estradiol (50 ng/ml) inhibited progesterone secretion by luteal cells at all stages of gestation examined . Relaxin obliterated the prostaglandin- and oxytocin-induced progesterone secretion by bovine luteal cells from 145 to 214 days of gestation . Thus, relaxin, cloprostenol, and oxytocin regulate progesterone production by cultured bovine luteal cells, but hormone secretion was dependent on the stage of gestation.

Trans R Soc Trop Med Hyg, 1990 Nov-Dec, 84(6), 852 - 6
Tick-borne relapsing fever in central Tanzania; Barclay AJ et al.; Between October 1985 and September 1986, 488 children aged less than 15 years, 45 pregnant women, 21 other women and 18 men with tick-borne relapsing fever (TBRF) were seen at Mvumi Hospital, Central Tanzania . 88% of the children were less than 5 years old and 36% were less than 1 year . Twelve children were less than 1 month old and some of the 10 infants diagnosed at between 4 and 12 days of age were cases of congenital infection . The clinical features of TBRF in the children and pregnant women were compared with 129 children with a similar age distribution and 52 pregnant women, respectively, who had blood smears positive for malaria but negative for spirochaetes . The common presenting features in children with TBRF were a high fever, splenomegaly, convulsions, and meningism . The difficulty of differentiation from malaria is described . Severe disease in both children and adults was associated with high density of spirochaetes in blood smears . Of the 45 infected pregnant women, 22 (49%) went into labour . One of the deliveries was an abortion and 10 were preterm infants, 4 of whom died . There were no maternal deaths . The estimated overall mortality for children was 1.6%, and 2.3% for those aged less than 1 years; for the 95 children admitted it was 8.4% . Penicillin was a satisfactory treatment for all ages, with a relapse rate of 4.7% . Recommendations for patient management are given.

Appl Biochem Biotechnol, 1990 Nov, 26(2), 181 - 95
Immobilization-stabilization of penicillin G acylase from Escherichia coli; Alvaro G et al.; We have developed a strategy for immobilization-stabilization of penicillin G acylase from E . coli, PGA, by multipoint covalent attachment to agarose (aldehyde) gels . We hve studied the role of three main variables that control the intensity of these enzyme-support multiinteraction processes: 1 . surface density of aldehyde groups in the activated support; 2 . temperature; and 3 . contact-time between the immobilized enzyme and the activated support prior to borohydride reduction of the derivatives . Different combinations of these three variables have been tested to prepare a number of PGA-agarose derivatives . All these derivatives preserve 100% of catalytic activity corresponding to the soluble enzyme that has been immobilized but they show very different stability . The less stable derivative has exactly the same thermal stability of soluble penicillin G acylase and the most stable one is approximately 1,400 fold more stable . A similar increase in the stability of the enzyme against the deleterious effect of organic solvents was also observed . On the other hand, the agarose aldehyde gels present a very great capacity to immobilize enzymes through multipoint covalent attachment . In this way, we have been able to prepare very active and very stable PGA derivatives containing up to 200 International Units of catalytic activity per mL . of derivative with 100% yields in the overall immobilization procedure.

G Ital Dermatol Venereol, 1990 Nov, 125(11), 533 - 5
{Cervicofacial actinomycosis . Description of a clinical case}; Apollonio M et al.; The Authors describe a clinical case of a 60 year old man with cervico-facial actinomycosis . The histology, the differential diagnosis and the successful penicillin therapy are also discussed.

J Antimicrob Chemother, 1990 Nov, 26(5), 695 - 704
Penetration of amoxycillin, ticarcillin and clavulanic acid into lymph after intravenous infusion in rabbits to simulate human serum pharmacokinetics; Woodnutt G et al.; The distribution of amoxycillin, ticarcillin and clavulanic acid into lymph collected from the right lymphatic duct of rabbits was examined after intravenous administration . The compounds were administered to simulate, in the plasma of rabbits, the concentrations of amoxycillin, ticarcillin and clavulanic acid measured in human serum after the administration of either an iv bolus dose of amoxycillin 1.0 g plus clavulanic acid 200 mg, ticarcillin 3.0 g plus clavulanic acid 200 mg, or an iv infusion of amoxycillin 2.0 g plus clavulanic acid 200 mg or ticarcillin 3.0 g plus clavulanic acid 200 mg given over 30 min . Lymph concentrations of the compounds reached a peak rapidly after the simulation of a bolus dose (0-1 h) and the concentration-versus-time profiles in plasma and lymph were generally similar after 45 min . Following simulation of an iv infusion, peak concentrations of amoxycillin and clavulanic acid in lymph were reached at approximately the same time as for the bolus simulation, but that of ticarcillin occurred slightly later . The elimination half-lives of the compounds were similar in plasma and lymph . The percentage penetration values were high (greater than 80%) irrespective of the concentration-versus-time curve simulated . The penetration of clavulanic acid was compatible with that of the coadministered penicillin agent and was similar when given with either amoxycillin or ticarcillin.

Vojnosanit Pregl, 1990 Nov-Dec, 47(6), 402 - 4
{The effect of sodium benzyl-penicillin on the mean quantal levels of released acetylcholine}; Dragic S et al.; Examined are effects of different doses of potassium (2.500 IU/ml) and sodium (5.000 IU/ml) (10.000 IU/ml) of benzylpenicillin on the mean quantum content (MQC) of the released acetylcholine in the phrenicus-hemidiaphragm specimens in rats . Very significant MQC decrease depending on the given antibiotic doses was found . Presented was hypothesis that the MQC decrease could result in the decreased Ca++ ion entering the terminal axoplasm under the benzylpenicillin molecule effect.

Mol Immunol, 1990 Nov, 27(11), 1063 - 71
Identification of penicillin allergenic determinants that bind IgE antibodies in the sera of subjects with penicillin allergy; Harle DG et al.; Much of the literature on penicillin hypersensitivity is devoted to the identification of penicillin antigens rather than allergens . Human IgE-binding determinants on different penicillins have rarely been closely investigated with the view of defining fine structural allergenic features and differences . We have developed radioimmunoassays employing ampicillin, amoxicillin and ticarcillin solid phases for the detection of penicillin-reactive IgE antibodies . Quantitative hapten inhibition studies employed to identify IgE-binding regions on the penicillin molecules revealed a heterogeneous group of allergenic determinants consisting exclusively, or in part, of the alpha-aminobenzyl and benzyl side chain groups and the beta-lactam and thiazolidine rings of the penicillin nucleus.

Ugeskr Laeger, 1990 Oct 29, 152(44), 3261 - 2
{2 fatal cases of pneumococcal septicemia after bone marrow transplantation}; Pers C et al.; Patients with bone-marrow transplants have an increased risk of developing fulminant pneumococcal infections for years after transplantation . In order to illustrate this, two cases of fetal pneumococcal septicaemia in patients with bone-marrow transplants are described . Self-medication with penicillin in case of fever is recommended.

Brain Res, 1990 Oct 15, 530(1), 35 - 9
The electrophysiological basis of epileptiform magnetic fields in neocortex; Barth DS et al.; Electrical measurements of epileptiform cellular currents in a penicillin model of focal epilepsy were directly compared to the extracranial magnetic fields these currents produce . Our data support the hypothesis that epileptiform magnetic fields result from intradendritic currents oriented perpendicular to the cortical surface . Furthermore, magnetic fields could be detected from epileptic foci smaller than 3 mm2 . This work provides an empirical foundation for physical models with which to interpret noninvasive neuromagnetic recordings of epileptic discharge in human focal seizure disorders.

FEMS Microbiol Lett, 1990 Oct, 60(1-2), 235 - 9
Initiation of growth in pbpAts and rodAts mutants of Escherichia coli; Rodriguez MC et al.; Escherichia coli strains harbouring pbpAts mutations are particularly sensitive to functional alterations of penicillin-binding protein 2 (PBP 2) at the initiation of growth . Shift-up to 42 degrees C results in the inability of cells to reach a steady rate of growth and division . Furthermore, a very high proportion of cells generate minicell-like structures which are pinched-off through a process requiring the activity of penicillin-binding protein 3 (PBP 3).

J Am Osteopath Assoc, 1990 Oct, 90(10), 926 - 8
Aerotitis: cause, prevention, and treatment; Westerman ST et al.; Aerotitis, an acute inflammation of the middle ear caused by the difference in air pressure between the airplane cabin and the middle-ear space, is becoming more common in the United States as our society becomes increasingly mobile . We describe a case in which a 33-year-old woman with a resolving upper respiratory tract infection and mildly blocked eustachian tubes flew on a business trip . During ascent, her ears became blocked . This blockage was partially alleviated by a Valsalva's maneuver . On descent, however, her ears became severely blocked, she experienced intense pain, and her tympanic membranes ruptured . She became nauseated and vomited . Her hearing became significantly diminished and she experienced vertigo . On landing, she was taken to a local emergency room and treated with penicillin and antivertiginous medication . Subsequent otologic evaluation revealed severe permanent sensorineural hearing loss . The vestibular symptoms lasted several months . She now requires hearing aids on a permanent basis . Suggestions are presented for prevention and treatment of aerotitis.

J Otolaryngol, 1990 Oct, 19(5), 343 - 4
The use of long-acting penicillin in the prophylaxis of recurrent tonsillitis; Sirimanna KS et al.; The authors report a study designed to explore the usefulness of long-acting penicillin in the management of recurrent tonsillitis . The trial, conducted in Sri Lanka, involved 179 patients aged 2 to 20 who had suffered multiple attacks of tonsillitis annually . The results showed a significant reduction in the number of attacks of tonsillitis experienced by the treated group, especially those aged 5 to 11, resulting in a drop in the number requiring tonsillectomy.

Zhonghua Liu Xing Bing Xue Za Zhi, 1990 Oct, 11(5), 291 - 4
{An investigation on injectional gluteal muscle contracture in childhood in Mianyang City}; Sun X; An investigation of 9845 healthy children with age of 3-12 years in Mianyang urban area has been made by us . One hundred and twenty-two cases of injectional gluteal muscle contracture were diagnosed . The morbidity is 1.36% and it is more common in boys than in girls (OR: 3.71) . The prevalence rate of the age group from 4 to 7 is highest and it decreases markedly with aging . This is probably due to self-recovery of some mild cases . Repeating injections of diluted penicillin by 1.5-2% Benzyl alcohol are the predominant causative factor of the disease . If Benzyl alcohol as a solvent for penicillin in children was no longer using, it would possibly reduce the morbidity . Up to now, this is a common iatrogenic disease in pediatric population and special attention should be paid to it.

Genitourin Med, 1990 Oct, 66(5), 374 - 9
Gummatous lesions in men infected with human immunodeficiency virus and syphilis; Hay PE et al.; Two HIV-infected men are reported who developed gummatous lesions more than 12 months after appropriate treatment of presumptive syphilis . In one patient the lesions developed without any change in the VDRL titre . The most likely explanation for these lesions is reactivation of syphilis in the context of HIV infection . As these lesions respond to penicillin, the possible reactivation of appropriately treated syphilis, or even yaws, should now be considered in any ulcerative lesion in HIV infected individuals at risk from treponemal infection.

Surg Gynecol Obstet, 1990 Oct, 171(4), 275 - 82
Broad spectrum penicillin as an adequate therapy for acute cholangitis; Thompson JE Jr et al.; In a previous study of patients with acute cholecystitis, we demonstrated equal efficacy with a broad spectrum penicillin (piperacillin) and a penicillin plus amino-glycoside combination . Whether a single agent broad spectrum penicillin is adequate treatment for more severe infections, such as acute cholangitis, however, is still unclear . We, therefore, conducted a three center, prospective, randomized trial to determine whether or not a broad spectrum penicillin alone is adequate therapy for patients with acute cholangitis . During a 36 month period, 96 patients with sepsis and biliary obstruction were randomly assigned to receive either piperacillin (n = 49) or ampicillin plus tobramycin (n = 47) . The two groups receiving antibiotics were similar with respect to all clinical and laboratory parameters . The incidence of blood cultures with positive results (20 versus 21 per cent) and underlying malignant lesions (51 versus 62 per cent) was also similar between the two groups . The percentage of patients with a clinical cure or significant improvement was the same in the two groups (69 versus 70 per cent) . However, there was a significant difference in the cure rate between patients with benign and malignant biliary obstructions (83 versus 59 per cent, p less than 0.01) . No significant differences were noted between the two antibiotic groups with respect to drug toxicity, but patients with malignant conditions were more prone to antibiotic related toxicities (2 versus 19 per cent, p less than 0.05) . These data suggest that outcome of treatment in patients with acute cholangitis is similar with either a broad spectrum penicillin or a penicillin plus aminoglycoside combination and is dependent upon the nature of the biliary obstruction.

Mayo Clin Proc, 1990 Oct, 65(10), 1365 - 7
Unsuspected syphilitic hepatitis in a patient with low-grade proteinuria and abnormal liver function; Blair EK et al.; A 25-year-old patient was found to have cholestatic liver enzyme abnormalities during assessment for asymptomatic low-grade proteinuria at the US Naval Hospital in Portsmouth, Virginia . These abnormalities persisted for a 6-month period, and an extensive workup, including viral serologic studies, rapid plasma reagin test, iron studies, ceruloplasmin, antimitochondrial, antinuclear, and anti-human immunodeficiency virus antibodies, endoscopic retrograde cholangiopancreatography, and liver biopsy, was unrevealing until serologic tests for syphilis were repeated to evaluate a new onset of urethral discharge . The patient had none of the more characteristic signs of secondary syphilis . The liver enzyme abnormalities rapidly resolved after treatment with penicillin . Syphilis remains the great impostor and still must be considered in the differential diagnosis of unexplained liver enzyme abnormalities, even in a patient with no symptoms or signs of early syphilis.

J Bacteriol, 1990 Oct, 172(10), 6139 - 41
Penicillin-binding proteins in Borrelia burgdorferi; Urban C et al.; Penicillin-binding proteins were identified in Borrelia burgdorferi membranes . A 94-kilodalton penicillin-binding protein was the first to be labeled with tritiated penicillin and was the first band to disappear in a competition experiment . Its binding ability was destroyed when membranes were preboiled . In addition, several of these penicillin-binding proteins comigrated with bands previously identified as surface proteins.

J Bacteriol, 1990 Oct, 172(10), 5863 - 70
Differential effect of mutational impairment of penicillin-binding proteins 1A and 1B on Escherichia coli strains harboring thermosensitive mutations in the cell division genes ftsA, ftsQ, ftsZ, and pbpB; Garcia del Portillo F et al.; To study the functional differences between penicillin-binding proteins (PBPs) 1A and 1B, as well as their recently postulated involvement in the septation process (F . Garcia del Portillo, M . A . de Pedro, D . Joseleau-Petit, and R . D'Ari, J . Bacteriol . 171:4217-4221, 1989), a series of isogenic strains with mutations in the genes coding for PBP 1A (ponA) or PBP 1B (ponB) or in the cell division-specific genes ftsA, ftsQ, pbpB, and ftsZ was constructed and used as the start point to produce double mutants combining the ponA or ponB characters with mutations in cell division genes . PBP 1A seemed to be unable to preserve cell integrity by itself, requiring the additional activities of PBP 2, PBP 3, and FtsQ . PBP 1B was apparently endowed with a more versatile biosynthetic potential that permitted a substantial enlargement of PBP 1A-deficient cells when PBP 2 or 3 was inhibited or when FtsQ was inactive . beta-Lactams binding to PBP 2 (mecillinam) or 3 (furazlocillin) caused rapid lysis in a ponB background . The lytic effect of furazlocillin to ponB cell division double mutants was suppressed at the restrictive temperature irrespective of the identity of the mutated cell division gene . These results indicate that PBPs 1A and 1B play distinct roles in cell wall synthesis and support the idea of a relevant involvement of PBP 1B in peptidoglycan synthesis at the time of septation.

Turk J Pediatr, 1990 Oct-Dec, 32(4), 249 - 58
Long-term prognosis of acute rheumatic carditis with combined aortic and mitral regurgitation; Onat T et al.; Thirty-one patients with acute rheumatic carditis associated with aortic (AR) and mitral regurgitation (MR) who received corticosteroid anti-inflammatory therapy for an average of nine weeks were followed up for 332 patient-years (mean: 10.71 years) . The age of onset was 9.34 (1 SD = +/- 1.94) years . The patients were classified according to degree of left ventricular volume overloading (LVH), duration of pre-treatment interval and regularity of penicillin prophylaxis . The probability of the yearly disappearance of MR, AR and both lesions were calculated for the total group and in relation to affecting subgroups . The mean yearly rate of disappearance of AR was 2 percent after a 10 percent probability in the first year . This rate was 6.83 percent per year for MR, and it increased to 10.15 percent per year in the patients in whom therapy was initiated in less than three weeks, and decreased to 3.14 percent in the patients in whom therapy was initiated after three weeks . The disappearance of both AR and MR was observed in only two patients (about 1% per year); MS developed in two patients (6.45%) and the mortality rate was 3.2 percent in 332 patient-years (0.0001/year).

Protein Eng, 1990 Oct, 4(1), 79 - 86
Engineering a novel beta-lactamase by a single point mutation; Jacob F et al.; beta-Lactamases are widespread and efficient bacterial enzymes which play a major role in bacterial resistance to penicillins and cephalosporins . In order to elucidate the role of the residues lying in a conserved loop of the enzymatic cavity of the active-site serine Streptomyces albus G beta-lactamase, modified proteins were produced by oligo-directed mutagenesis . Mutation of Asn116, which lies on one side of the active site cavity pointing to the substrate-binding site, into a serine residue resulted in spectacular modifications of the specificity profile of the enzyme . That replacement yielded an enzyme with a nearly unchanged activity towards good penicillin substrates . In sharp contrast its efficiency in hydrolysing cephalosporins was drastically reduced, the best substrates suffering the largest decrease in the second-order rate constant for serine acylation . In fact that single mutation generated a truly new enzyme behaving exclusively as a penicillinase, a situation which is never encountered to the same degree in any of the numerous naturally occurring variants of class A beta-lactamases.

J Bacteriol, 1990 Oct, 172(10), 5908 - 14
Molecular characterization of the acyl-coenzyme A:isopenicillin N acyltransferase gene (penDE) from Penicillium chrysogenum and Aspergillus nidulans and activity of recombinant enzyme in Escherichia coli; Tobin MB et al.; The final step in the biosynthesis of beta-lactam antibiotics in Penicillium chrysogenum and Aspergillus nidulans involves removal of the L-alpha-aminoadipyl side chain from isopenicillin N (IPN) and exchange with a nonpolar side chain . The enzyme catalyzing this reaction, acyl-coenzyme A:isopenicillin N acyltransferase (acyltransferase), was purified from P . chrysogenum and A . nidulans . Based on NH2-terminal amino acid sequence information, the acyltransferase gene (penDE) from P . chrysogenum and A . nidulans were cloned . In both organisms, penDE was located immediately downstream from the isopenicillin N synthetase gene (pcbC) and consisted of four exons encoding an enzyme of 357 amino acids (approximately 40 kilodaltons {kDa}) . The DNA coding sequences showed approximately 73% identity, while the amino acid sequences were approximately 76% identical . Noncoding DNA regions (including the region between pcbC and penDE) were not conserved . Acyltransferase activity from Escherichia coli producing the 40-kDa protein accepted either 6-aminopenicillanic acid or IPN as the substrate and made a penicillinase-sensitive antibiotic in the presence of phenylacetyl coenzyme A . Therefore, a single gene is responsible for converting IPN to penicillin G . The active form of the enzyme may result from processing of the 40-kDa monomeric precursor to a heterodimer containing subunits of 11 and 29 kDa.

J Biol Chem, 1990 Sep 25, 265(27), 16358 - 65
The cluster of penicillin biosynthetic genes . Identification and characterization of the pcbAB gene encoding the alpha-aminoadipyl-cysteinyl-valine synthetase and linkage to the pcbC and penDE genes; Diez B et al.; Penicillium chrysogenum DNA fragments cloned in EMBL3 or cosmid vectors from the upstream region of the pcbC-penDE cluster carry a gene (pcbAB) that complemented the deficiency of alpha-aminoadipyl-cysteinyl-valine synthetase of mutants npe5 and npe10, and restored penicillin production to mutant npe5 . A protein of about 250 kDa was observed in sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels of cell-free extracts of complemented strains that was absent in the npe5 and npe10 mutants but exists in the parental strain from which the mutants were obtained . Transcriptional mapping studies showed the presence of one long transcript of about 11.5 kilobases that hybridized with several probes internal to the pcbAB gene, and two small transcripts of 1.15 kilobases that hybridized with the pcbC or the penDE gene, respectively . The transcription initiation and termination regions of the pcbAB gene were mapped by hybridization with several small probes . The region has been completely sequenced . It includes an open reading frame of 11,376 nucleotides that encodes a protein with a deduced Mr of 425,971 . Three repeated dominia were found in the alpha-aminoadipyl-cysteinyl-valine synthetase which have high homology with the gramicidin synthetase I and tyrocidine synthetase I . The pcbAB is linked to the pcbC and penDE genes and is transcribed in the opposite orientation to them.

J Am Vet Med Assoc, 1990 Sep 15, 197(6), 759 - 60
Partial uterine prolapse associated with uterine foreign body in a cow; Levine HD; After correction of partial uterine prolapse in a Holstein cow, a 6-cm-long twig was found deep in the affected uterine horn . The twig was removed, and calcium-dextrose and penicillin G were administered . Recovery was unremarkable . Other reports of uterine foreign bodies in cows are scarce and do not describe uterine foreign bodies associated with uterine prolapse or invagination.

Biochem J, 1990 Sep 1, 270(2), 525 - 9
Chromogenic depsipeptide substrates for beta-lactamases and penicillin-sensitive DD-peptidases; Adam M et al.; Various ester and thioester derivatives of hippuric acid have been prepared which were substrates of both beta-lactamases and DD-peptidases . The thioesters were more rapidly hydrolysed by nearly all the enzymes . Surprisingly, the enzymes acted rather efficiently on substrates which did not contain any chiral centre.

Przegl Dermatol, 1990 Sep-Oct, 77(5), 359 - 62
{Results of the treatment of neurosyphilis with high doses of crystalline and procaine penicillins}; Starzycki Z et al.; The results of the treatment in two groups of patients with neurosyphilis are compared . In 23 cases, i.v . infusions of crystalline penicillin were given for 10 days in daily dose of 20-24 mega U., combined with probenecid . Then it was followed by i.m . procaine penicillin in daily dose of 1.2 mega U., in total dose 12-50 mega U . The mean duration of follow-up was 7,8 months . The second group (34 cases) was treated with procaine penicillin i.m . in daily dose of 1.2 mega U., the total dose was 24-60 mega U . The mean duration of follow-up was 2.5 years . The differences between the results of the treatment in both groups were not significant . In 3 reinfected patients with early asymptomatic neurosyphilis in spite of intensive treatment with penicillin sero- and cerebro-spinal fluid-resistant syphilis developed.

Ann Pediatr (Paris), 1990 Sep, 37(7), 427 - 31
{Specific serologic reactions in the cerebrospinal fluid in congenital syphilis and therapeutic implications}; Gendrel D et al.; In a study carried out in Gabon, antibodies against the treponema were looked for in the cerebrospinal fluid (CSF) in 13 children with active congenital syphilis (presence of specific IgM antibodies) and in 7 children with positive serologic reactions reflecting transplacental passage of maternal antibodies . Serologic reactions used included the VDRL test, the TPHA test, and the FTA-ABS IgG and IgM tests . Among the 13 children with syphilis, 7 had a positive FTA-ABS IgG test in the CSF; positivity of this test was not correlated with severity of clinical features, CSF protein levels or CSF cytologic findings . The TPHA test was positive in only four children and the VDRL test was consistently negative . These findings are similar to those reported in another group of patients with meningeal involvement proven by the demonstration of IgM in the CSF using recent techniques . Passage of antibodies into the CSF is possible (1 case in this study) but for safety patients with specific IgG in the CSF should be given penicillin in a dosage that provides treponema-killing levels in situ (100,000 U/kg/d) . Use of this dosage is recommended whenever sensitive techniques for CSF analysis are not available.

Clin Exp Allergy, 1990 Sep, 20(5), 475 - 81
Allergy to penicillin with good tolerance to other penicillins; study of the incidence in subjects allergic to beta-lactams; Blanca M et al.; Two hundred and eighty-eight subjects with a history of allergy to penicillin were studied for objective proof of their allergy . On the basis of skin tests, specific IgE antibody measurements and direct challenge tests . 64 patients (22%) were shown objectively to be allergic to one or more penicillins . The following tests were carried out: skin tests to benzyl-penicilloyl poly-L-lysine (BPO-PLL), minor determinant mixture (MDM), amoxycillin (AX) and ampicillin (AMP), in-vitro IgE antibody measurement to benzyl-penicilloyl (BPO) and AX and challenge with benzylpenicillin (BP), phenoxy-methyl-penicillin (PV) and amoxycillin . Forty-four cases were found to respond to benzyl or phenoxymethyl-penicillin, however, 20 were shown to be sensitive to amoxycillin and unresponsive to tests with other penicillins . The contribution that any individual test gave for establishing the diagnosis was 21.8% for skin testing with BPO-PLL, 9.3% with MDM and 12.5% with AX . Nine point three per cent were RAST positive to BPO and 1.5% to AX; 7.8% developed a positive response after challenge to BP, 7.8% to PV and 14% to AX . In 16% of the 64 positive cases more than one test was found to be positive . The challenge tests suggested that not all the penicillin-sensitive subjects had IgE-mediated reactions implying other immunological mechanisms . These results clearly demonstrate the importance of side chain-specific diagnostic reagents and challenge tests . Thirty-one per cent of the positive group or 6.9% of the total group would have been missed in this study using benzyl or phenoxymethyl-penicillin diagnostic reagents alone.

Actual Odontostomatol (Paris), 1990 Sep, 44(171), 437 - 66
{Medical treatment of epulis by local injection penicillin therapy}; Abravanel P et al.; Treatment in November 1987, of an epulis-type gingival tumor, with in situ penicillin G injections, resulted in complete eradication of this benign tumor with no recurrence more than one year later . This case-report may be added to others of the same type reported by Dr . Joseph ABRAVANEL: since 1978, date of the first presentation at the "Hospital Necker Scientific Meeting", all cases treated (approximately ten) resulted in complete cure without any recurrence; the cases reported in 1978 were all followed and there was no recurrence . Since this technique demonstrated a superior efficacy over Surgery, we decided to report this last case with a follow-up period exceeding one year . However, we are aware, in spite of the long follow-up and the constant results, of the limited number of cases in the study . We hope that, with the help of all our colleagues, we will be able to improve our results . The mechanism of action of penicillin G opens a number of prospects in the pathology of the oral mucosa, especially iatrogenic pathologies: Cyclosporine, Dihydan, etc.

Ir Med J, 1990 Sep, 83(3), 117 - 8
Seal finger in a wildlife ranger; Eadie PA et al.; We describe a case of septic arthritis of the interphalangeal joint of the thumb in a man following a seal bite . Early and continued treatment with antibiotics of the penicillin family failed to control the infection . Empirical treatment with tetracycline resolved the infection, but the patient has permanent joint damage . In apparently ordinary infective conditions, which fail to respond to therapy, the history may suggest that an unusual organism is responsible.

J Am Dent Assoc, 1990 Sep, 121(3), 436 - 7
Multiple oral and skin lesions occurring after treatment with penicillin; Staretz LR et al.; A case of erythema multiforme has been presented . Erythema multiforme may be a self-limiting or chronic disease, of varying severity . The disease is of significance to dental practitioners who may be called on to establish a diagnosis and provide appropriate referral or treatment, especially when lesions are limited to the mouth . The prognosis is generally good, although recurrence is common.

J Clin Neuroophthalmol, 1990 Sep, 10(3), 175 - 84
Syphiloma/gumma of the optic nerve and human immunodeficiency virus seropositivity; Smith JL et al.; A 68-year-old man developed the sudden onset of transient obscurations of vision in the right eye in November 1988 . Two weeks later he noted floaters, photophobia, and blurred vision in the left eye . He presented with unilateral optic disc edema in the right eye . The left eye showed anterior uveitis but a normal optic disc . He was found to be violently seroreactive for Treponema pallidum infection and was also human immunodeficiency virus (HIV) seropositive . Ultrasonography confirmed the presence of a solid thickening of the anterior optic nerve sheath in the right eye . An interesting and dramatic response to penicillin therapy occurred . This is the first instance of a gumma or solid syphiloma of the optic nerve documented by ophthalmic ultrasonography.

Bull Kanagawa Dent Coll, 1990 Sep, 18(2), 89 - 98
Biochemical study of human periodontal ligament: preparation of cell attachment materials induced by pulsed electromagnetic fields; Kim KT; The periodontium, especially the periodontal ligament and alveolar bone, are tissues constantly subjected to physical stress such as occlusion and mastication . This study was designed to explore the effect of the pulsed electromagnetic fields (PEMF) on the cell attachment and the spread of human periodontal ligament fibroblasts (HPLF) and rat osteoblasts (ROB) . PEMF are categorized as one type of mechanical stress . HPLF were obtained by the explantation method described by Saito et al . They were then subcultured in Dulbecco's modified Eagle's medium (D-MEM) and supplemented with 2 mg/ml dialyzed fetal calf serum protein (FCSP), 50 micrograms/ml ascorbic acid and penicillin/streptomycin after trypsinization . ROB were isolated from a two-day-old rat calvaria by the sequential bacterial collagenase digestion method described by Dziak and Brand and were subcultured in D-MEM supplemented with FCSP, ascorbic acid and penicillin/streptomycin . After the confluent HPLF were cultured with serum-free MCDB 107 medium, the quiescent HPLF were exposed with or without PEMF for 24 hr . This was followed by the collection of the control conditioned medium (C-CM) and PEMF exposed conditioned medium (PEMF-CM) . The cell attachment assay was performed so that the hydrophobic 24 multiwells were coated with the whole conditioned medium or fractionated conditioned medium by a PO-60K column . After coating, heat inactivated BSA blocked nonspecific sites for cell adhesion, and 3H-TdR labeled HPLF or ROB were cultured on the precoated wells . The activity of cell attachment and spreading was determined by the radioactivity of 3H-TdR using a scintillation counter . The characters of cell attachment factors derived from HPLF were hydrophobic, heat labile and proteolytic enzyme digestible . In addition, the fractionated PEMF-CM enhanced the spreading activity of ROB . PEMF induced the 10 KDa which can enhance the HPLF and ROB spreading . Therefore, the cell attachment and spreading factors secreted by HPLF exposed with PEMF may regulate HPLF and also ROB.

Neurophysiol Clin, 1990 Sep, 20(3), 189 - 201
Nigral influence on focal epilepsy; Sabatino M et al.; The substantia nigra (SN) has been proposed as a structure involved in epileptiform phenomena . Previous investigations demonstrated that SN is able to elicit hippocampal rhythmic slow activity (RSA) as well as to inhibit hippocampal interictal spikes induced by parenteral administration of penicillin . The present series of experiments was carried out in order to characterize the action of SN on a focal model of hippocampal epilepsy . Experiments were performed on encephale isole cats in which steady epileptiform activity was induced by locally applied penicillin . Electrical stimulation of SN pars reticulata (pr) caused a statistically significant decrease of hippocampal spike frequency and amplitude in 30% of the total number of stimulation sessions . Stimulation of SN pars compacta (pc) was even more effective . It induced inhibitory effects on hippocampal spikes in 91% of the cases . In 30% of the cats, RSA was noted on hippocampal recordings in correspondence to nigral activation . Experimental data support the hypothesis that the SNpc influences hippocampal excitability: a differential role may be played by SNpc and SNpr in the control of seizure processes.

Differentiation, 1990 Sep, 44(3), 232 - 8
Reconstituted skin in culture: a simple method with optimal differentiation; Basset-Seguin N et al.; Human skin is a unique organ, which can be reconstituted in vitro and represents an interesting system for studying cell proliferation and differentiation . A simple technique for producing reconstituted skin with optimal epidermal differentiation is described and characterized . A 4-mm punch biopsy of normal human skin is deposited on the epidermal side of mortified de-epidermized human dermis maintained at the air-liquid interface with a metallic support . The culture medium contains insulin, epidermal growth factor (EGF), cholera toxin, hydrocortisone, penicillin/streptomycin and fungizone . A well-differentiated epidermis develops within 15 days . Morphological and ultrastructural studies show a neoepidermis resembling normal skin . Differentiation markers such as involucrin, filaggrin, and various cytokeratins detected with pancytokeratin antibody are present and confirm this resemblance . The keratin profile is comparable to that observed in other skin culture models . A basement-membrane-like structure is reconstituted with hemidesmosomes and anchoring-filament formation . Bullous pemphigoid (BP) antigen is observed at the dermo-epidermal junction after 21 days of culture . Moreover, both dermal substrates and punch biopsies can be kept frozen for long-term storage, with little or no loss of epidermal growth kinetics and morphology . This skin culture technique is rapid, simple, economical and reproducible . Characterization has here shown high-quality epidermal differentiation . Scientists interested in epidermal in vitro studies should take interest in all these advantages.

J Chromatogr, 1990 Aug 31, 515, 245 - 55
Separation and determination of aspoxicillin in human plasma by micellar electrokinetic chromatography with direct sample injection; Nishi H et al.; Both the separation and determination of aspoxicillin in human plasma by micellar electrokinetic chromatography (MEKC) were investigated . Selectivity in the separation of seven penicillin antibiotics was improved by using MEKC in comparison with capillary zone electrophoresis . Plasma proteins, which might interfere with drug analysis in conventional chromatography, were solubilized by the micelles employed in MEKC and eluted later than the drugs . This permitted the determination of the drugs in plasma by a direct sample injection method . One analysis of a plasma sample was performed within ca . 20 min without pretreatment . Good linearity and recovery were also obtained in the range of plasma levels usually encountered in clinical analysis with a correlation coefficient r = 0.999 and 94-104% recovery . The limit of detection for aspoxicillin was 1.3 micrograms ml-1 at a signal-to-noise ratio of 3.

Eur J Biochem, 1990 Aug 28, 192(1), 133 - 41
The folding and solution conformation of penicillin G acylase; Lindsay CD et al.; The solution conformation properties of penicillin G acylase (EC 3.5.1.11) have been characterised by near- and far-ultraviolet circular dichroism, steady-state and time-resolved fluorescence spectroscopy and differential sedimentation velocity . The enzyme (86 kDa) was found to be spherical and stable unfolding over a narrow range of urea concentrations in an apparently cooperative fashion with a mid-point of 4.5 M urea . Separation of its constituent alpha and beta peptides (23.8 kDa and 62.2 kDa, respectively) was accompanied by loss of enzyme activity and unfolding, the kinetics of unfolding being highly dependent upon urea concentration . Urea gradient gel electrophoresis showed that the separated beta peptide aggregates over a wide range of urea concentrations but that the alpha peptide refolds reversibly to a compact state . Physical studies showed that the refolded alpha peptide has a compact but asymmetric structure with more alpha helix than the native enzyme, but is more sensitive to denaturant . The latter is suggested to be due to a hydrophobic patch detected by 8-anilino-1-naphthalene sulfonic acid binding and which is normally covered by the beta peptide in the native enzyme . The results of these investigations indicate that the alpha peptide constitutes a folding domain and suggest that it plays a key role in folding of the precursor for penicillin acylase.

Schweiz Med Wochenschr, 1990 Aug 25, 120(34), 1211 - 6
{Acute severe dyspnea as a side effect of drugs . Report from the CHDM (Comprehensive Hospital Drug Monitoring)}; Hoigne R et al.; This "syndrome" has been observed in 4 of 23,935 in-patients registered in the years 1974-1987 in the Comprehensive Hospital Drug Monitoring (Bern/St . Gallen), with 6 reactions . Signs of an attack of bronchial asthma, laryngeal or pulmonary edema or a (heart-)circulatory event were not observed . Each patient was cyanotic and 3 had the feeling of impending death . The eliciting drugs were penicillin-G (twice) and cefazolin (once), given i.v.; iron dextran i.m . (once); pitressin tannate i.m . (once) and dicobalt edetate (Kelocyanor) i.v.(once) . In each case the reaction started during or shortly after injection of the drug; the duration of the reaction in 5 of these events was 20-80 minutes . The pathomechanism could be a special form of anaphylactic reaction with acute pulmonary hypertension, comparable to IgE-induced anaphylaxis in the rabbit or aggregate anaphylaxis in the monkey or the dog . Further observations are needed for more detailed study.

Vet Rec, 1990 Aug 11, 127(6), 128 - 31
Use of a uterine pessary to prevent infection of the uterus of the cow after parturition; Dobson DP et al.; A uterine pessary containing penicillin, streptomycin, formosulphathiazole and ethinyloestradiol, was assessed for its efficacy in reducing the frequency and severity of uterine infections in cows after parturition . Fifteen pluriparous Holstein Friesian cows had pessaries inserted into the uterus within 24 hours after calving . Compared with 14 similar untreated cows there were significant reductions in the number infected by Actinomyces pyogenes and in the number exhibiting abnormal uterine discharges.

Ann Rheum Dis, 1990 Aug, 49(8), 641 - 2
Bone pain as the presenting manifestation of secondary syphilis; Middleton S et al.; A 31 year old fireman presented with acute pain and tenderness in both shins and forearms . Radiographs were normal but bone scintigraphy showed widespread increased isotope uptake . Serology was consistent with a diagnosis of secondary syphilis, and the patient's symptoms resolved completely six weeks after a course of penicillin.

Exp Neurol, 1990 Aug, 109(2), 237 - 42
Secondary generalization of seizures from a cortical penicillin focus following stimulation of the basal forebrain; McLachlan RS et al.; The basal forebrain has been implicated in the regulation of generalized motor convulsive activity particularly from amygdala kindling . The effect of electrical stimulation of the substantia innominata and ventral pallidal regions of the basal forebrain in rats with acute interictal penicillin foci in the frontal parietal neocortex was determined . Stimulation of this area resulted in generalized cortical EEG synchronization, an inconsistent effect on interictal spike frequency, and generalized seizures that were not prevented by atropine . The results support a role for these basal forebrain structures in the regulation of generalized seizures from a cortical focus mediated primarily through influences on thalamocortical pathways.

Biol Reprod, 1990 Aug, 43(2), 298 - 304
Suppression of lymphocyte proliferation by a greater than 30,000 molecular weight factor in horse conceptus-conditioned medium; Roth TL et al.; In this experiment we have identified and partially characterized the immunosuppressive activity of preimplantation horse conceptus-conditioned medium (HCCM) . Horse conceptuses were nonsurgically flushed from mares at Days 9-10 (n = 6), 15-16 (n = 3), and 25-26 (n = 3) . After incubating the conceptuses for 24 h in RPMI-1640 supplemented with 15% fetal calf serum (FCS) and 1% penicillin/streptomycin, HCCM was obtained from cultures and tested for immunosuppressive activity in lymphocyte proliferation assays . Peripheral blood lymphocytes obtained from randomly selected mares were stimulated with mitogens (pokeweed mitogen {PWM}, concanavalin A {Con A}, and phytohemagglutinin {PHA}) in cultures supplemented with 0%, 25%, or 50% HCCM . HCCM from all cultures suppressed lymphocyte proliferation induced by all three mitogens (p less than 0.001) . After being subjected to various treatments (heating, freeze-thawing, and nitrocellulose filtration), HCCM maintained its full biological suppressor activity . Amicon microconcentrators with 10,000 and 30,000 molecular weight (MW) exclusion filter membranes were used to fractionate HCCM by molecular weight . The suppressor factor was found to be in the greater than 30,000 MW fraction . HCCM was further tested interspecifically on donkey and goat lymphocytes stimulated with PWM . HCCM did suppress proliferation of interspecific lymphocytes (p less than 0.01); however, the suppressive capacity of HCCM in caprine lymphocyte cultures was less (p less than 0.05) than that observed in equine cultures . These data support the hypothesis that the horse conceptus produces an immunoregulatory factor . This factor is extremely stabile and appears to exhibit some degree of species-specificity . The production and immunosuppressive effectiveness of such a factor may play an important role in maintaining the fetal allograft throughout gestation.

Cent Afr J Med, 1990 Aug, 36(8), 187 - 90
Management of peritonsillar abscess (quinsy) at Harare Central Hospital; T-Buturo CG; A prospective study was done on 64 patients presenting with features suggestive of peritonsillar abscess (PTA) at Harare Central Hospital from March 1988 to March 1989 . There were 41 females and 20 makes with confirmed PTA . Needle aspiration without general anaesthesia was carried out on 60 patients and an acute tonsillectomy on one child because the child was young and uncooperative . There were no immediate recurrences . All aspirated patients were admitted to hospital for 1 to 3 days . 25 of the 60 patients were successfully aspirated by the Junior Resident Medical Officer (JRMO) covering Ear, Nose and Throat Surgery (ENT) and the rest by the author . Incision and drainage was not used . It is recommended that needle aspiration, as simple, safe, comfortable and successful treatment be the method of choice . Parental penicillin, unless contraindicated should be administered to all patients.

Epilepsy Res, 1990 Aug, 6(3), 187 - 98
Effects of pentetrazol on neuronal activity and on extracellular calcium concentration in rat hippocampal slices; Leweke FM et al.; Effects of pentetrazol (PTZ) were studied on neuronal responses in dentate granule cells and area CA1 hippocampal pyramidal cells with intra- and extracellular recording techniques . PTZ induced spontaneous epileptiform field potential transients in areas CA3 and CA1, but not in the dentate gyrus . The concentration optimum for induction of spontaneous epileptiform activity was 2 mM . The epileptiform activity compared in many respects to that induced by GABA antagonists such as picrotoxin, bicuculline and penicillin . Paired pulse stimulus induced responses were affected by concentrations of 0.5 mM . In the concentration range 0.5-2 mM mostly disinhibitory effects were noted . Stimulus induced Ca2+ concentration changes were found to be maximally augmented at concentrations of 2-5 mM . In this range, intracellular studies revealed a block of frequency habituation and an increase in input resistance . The convulsant action of PTZ decreased at concentrations above 5 mM, probably due to a decrease of inward currents . We suggest that the action of PTZ in screening studies for anticonvulsants is mostly due to a decrease of GABAA-receptor mediated IPSPs.

Antibiot Khimioter, 1990 Aug, 35(8), 25 - 8
{Natural penicillin resistance of Francisella tularensis}; Pavlovich NV et al.; Altered viable forms of F . tularensis with spheroplast specific damages of the surface structures were isolated after the culture exposure to lithium chloride (0.5 and 1%) . Study of natural penicillin resistance in the spheroplasts and bacterial forms of F . tularensis revealed their difference: the spheroplasts of the strains tested had a lower resistance to beta-lactam antibiotics than the bacterial forms while the activity of spheroplast beta-lactamase did not differ from that of the enzyme of the bacterial form and equalled 224 to 252 U/ml of the cell suspension . Therefore, on the model of the lithium-induced spheroplasts it appeared possible to show that the damages of the surface structures of the cell walls of F . tularensis changed the penicillin resistance level which was indicative of involvement of the F . tularensis cell walls in the phenomenon of the natural resistance to beta-lactams.

Nippon Ika Daigaku Zasshi, 1990 Aug, 57(4), 289 - 96
Electrical activities of pyramidal cells in the kindled hippocampus of the rabbit; Fujii N; 1) The pyramidal cell in the kindled hippocampus of the rabbit was intracellularly studied and compared with that in the normal hippocampus . 2) As previously reported, what characterized the kindled hippocampus was the appearance of a spontaneous hyperpolarization in the pyramidal cell . Practically all the pyramidal cells in the kindled hippocampus showed spontaneous hyperpolarizations . The hyperpolarization consisted of Cl-dependent and Cl-non-dependent components . The former was evidently the somatic IPSP . On the other hand, the latter was interpreted as the dendritic IPSP . This was supported by the fact that there was an interictal positivity in the apical dendrite layer . 3) There was no evidence whatsoever that indicated an increased excitability of the pyramidal cell . This showed that the kindled hippocampus was essentially different from the penicillin-treated hippocampus . It was suggested that the former was similar to the human brain in the interictal phase, whereas the latter was similar to that in status epilepticus . 4) In a few pyramidal cells there was a slow depolarization which could possibly trigger a seizure discharge and the nature of the slow depolarization was discussed . However, the slow depolarization was not peculiar to the kindled hippocampus.

Z Kardiol, 1990 Aug, 79(8), 599 - 600
{Dilated myocardial disease as sequela of chronic Lyme carditis}; Wunderlich E et al.; A report is given on a 39-year-old man, who developed, after a tick bite, erythema, progressing symptoms and, after 3 years, showed the typical clinical and echocardiographic signs of a dilative cardiomyopathy . A serological test for Lyme Borreliosis was positive . Most of the symptoms disappeared after high-dose penicillin therapy.

J Infect Dis, 1990 Aug, 162(2), 564 - 7
Limulus lysate positivity and Herxheimer-like reactions in leptospirosis: a placebo-controlled study; Watt G et al.; Jarisch-Herxheimer reactions are characteristic of some spirochetal diseases and have been reported in leptospirosis, but their pathogenesis and relationship to endotoxin remain unclear . Serial limulus amebocyte lysate assays (LAL) for endotoxin were performed on 40 patients with proven leptospirosis who were monitored for reactions after receiving either intravenous penicillin (24) or saline placebo (16) . No Herxheimer-like reactions were observed, although 78% of patients had at least one positive LAL . Serum creatinine, serum bilirubin, and white blood cell counts were significantly higher (P less than .01) in simultaneously drawn LAL-positive specimens than in negative ones . Delayed hepatic clearance of endotoxin due to liver dysfunction may explain the high LAL positivity rate, since assay results correlated with severity of disease but not with the presence or absence of spirochetes . Fear of a Herxheimer-like reaction should not dissuade clinicians from administering antibiotics to patients with leptospirosis.

Mol Gen Genet, 1990 Aug, 223(1), 114 - 20
Transcriptional analysis of the DD-peptidase/penicillin-binding protein-encoding dac gene of Streptomyces R61: use of the promoter and signal sequences in a secretion vector; Piron-Fraipont C et al.; The promoter region of the gene encoding the extracellular DD-peptidase/penicillin-binding protein of Streptomyces R61 has been identified by in vivo promoter probing and S1 mapping . A secretion vector, pDML116, was constructed by inserting into the multicopy Streptomyces plasmid pIJ702, a 247 bp DNA sequence that contained the transcriptional, translational and secretory signals and the 12 amino acid N-terminal region-encoding sequence of the mature Streptomyces DD-peptidase/penicillin-binding protein . Insertion, downstream of this 247 bp segment, of the Streptomyces R61 DD-peptidase-encoding gene or the Escherichia coli R-TEM beta-lactamase-encoding gene yielded plasmids pDML120 and pDML128, respectively, which allowed expression and secretion of the relevant enzymes by Streptomyces lividans . The maximal secretion levels obtained were 42 mg protein/ml for the autologous Streptomyces DD-peptidase and 0.9 mg protein/ml for the heterologous E . coli beta-lactamase.

Epilepsy Res, 1990 Aug, 6(3), 249 - 51
The excitatory amino acid antagonist amino-phosphono-valeric acid (APV) provides protection against penicillin-induced epileptic activity in the rat; Loeb C et al.; The effects of intraperitoneal injection of 2-amino-5-phosphono-valeric acid (APV) on EEG-monitored penicillin-induced epileptic activity in rats were evaluated . A significant decrease in the frequency of spikes occurred with low APV dosages (10 and 20 mg/kg), while an almost complete disappearance of spike activity was observed at higher APV doses (40 and 160 mg/kg) . Our data suggest that excitatory amino acids play a relevant role in penicillin-induced epileptic activity in rats.

Hindustan Antibiot Bull, 1990 Aug-Nov, 32(3-4), 84 - 7
Immobilization of penicillin G acylase onto ion exchange and hydrophobic resins; Kumar KK et al.; Penicillin G acylase was immobilized on numerous cation exchange resins and hydrophobic adsorbents . Amberlite XAD-7 was the matrix of choice among the matrices studied for the immobilization of enzyme . Binding of 96.8% and expression of 82.6% of the penicillin G acylase was achieved on XAD-7 . Penicillin G acylase immobilised on XAD-7 was used for 80 cycles for the production of 6-PA in a stirred tank reactor.

Appl Microbiol Biotechnol, 1990 Aug, 33(5), 553 - 9
Penicillin acylase mutants with altered site-directed activity from Kluyvera citrophila; Prieto I et al.; Oligonucleotide-directed mutagenesis has been used to obtain specific changes in the penicillin acylase gene from Kluyvera citrophila . Wild-type and mutant proteins were purified and the kinetic constants for different substrates were determined . Mutations in Met168 highly decreased the specificity constant of the enzyme for penicillin G, penicillin V and phenylacetyl-4-aminobenzoic acid and the catalytic constant kcat for phenylacetyl-4-aminobenzoic acid . Likewise, the phenylmethylsulphonyl-fluoride sensitivity was significantly decreased . It is concluded that the 168 residue is involved in binding by interaction with the acid moiety of the substrate . A putative penicillin-binding domain was located in penicillin acylase by sequence homology with other penicillin-recognizing enzymes . Lys374 and His481, the conserved amino acid residues that are essential for catalysis in these enzymes, can be changed in penicillin acylase with no changes to the kcat and phenylmethylsulphonyl fluoride reactivity, but change the Km . The likelihood of the existence of this proposed penicillin binding site is discussed . The reported results might be used to alter the substrate specificity of penicillin acylase in order to hydrolyse substrates of industrial significance other than penicillins.

Schweiz Med Wochenschr, 1990 Jul 21, 120(29), 1045 - 9
{Hoigné's syndrome or pseudo-anaphylactic reaction to procaine penicillin G: a still current classic}; Schmied C et al.; In this journal in 1959 R . Hoigne described the first cases of pseudo-anaphylactic reactions induced by intramuscular administration of procaine penicillin G . This complication, characterized by acute psychological and neurological manifestations, is still of current interest since recently three cases of Hoigne's syndrome were diagnosed at the University Hospital of Geneva . This entity deserves consideration because it must be differentiated from authentic anaphylactic shock due to penicillin . The distinction is important from a therapeutic viewpoint since Hoigne's syndrome allows continuation of treatment, whereas it is absolutely contraindicated in anaphylactic shock.

J Immunol Methods, 1990 Jul 20, 131(1), 55 - 64
An in vitro murine model of a penicillin specific IgE anamnestic response; Smith MC et al.; A new murine model system was developed to study hapten specific IgE anamnestic antibody forming cell (AFC) responses induced in vitro . BALB/c mice injected intraperitoneally with BPO-KLH (10 micrograms) in aluminum hydroxide gel (alum) on day 0 and 21 were killed on day 42 . Spleen cells (4 X 10(7} were cultured for 0-8 days in the presence of BPO-KLH (0.25-2500 ng/ml), after which the numbers of BPO specific IgE AFC were enumerated in an ELISPOT assay at 37 degrees C using BPO-BSA coated plates . Peak BPO specific IgE anamnestic AFC responses (approximately 40 AFC/10(7) cultured cells) occurred when cells were cultured with 100 ng/ml BPO-KLH for 5 days; peak BPO specific IgG1 and IgA responses (approximately 3000 and approximately 280 AFC/10(7) cultured cells) were detected one day earlier with the same antigen concentration . No ELISPOTs of any isotype were detected if: cells were cultured in the absence of specific antigen; cells from alum treated or unsensitized mice were used; assay wells were coated with BSA alone; isotype specific antibodies were omitted; or assays were performed in the presence of cycloheximide or at 4 degrees C . Cellular interactions in IgE anamnestic AFC responses were studied using the newly developed model system . We found that these responses were partially T cell independent, and that spleens from sensitized and unsensitized adult mice, as well as neonatal mice, contained cells which suppressed these responses.

Prikl Biokhim Mikrobiol, 1990 Jul-Aug, 26(4), 539 - 44
{Comparative characteristics of the metabolism of E . coli cells with various activity of penicillin acylase}; Shishlova OR et al.; A correlation between the synthesis and secretion of penicillin acylase (PA; EC 3.5.1.11) and the membrane phospholipid composition was observed in three E . coli strains . In cells with overproduction of PA, the phospholipid/protein ratio decreases, while the cardiolipin/phosphatidylglycerol ratio increases . The differences in the functioning of the electron transport system were revealed in cells with different levels of PA synthesis and secretion . The O2 consumption rate was 3 times lower in the cells with overproduction of PA than in those of less productive strains . On the contrary, membrane particles isolated from the cells of PA producers had no significant differences in the O2-reduction rate . The sensitivity of the strains to the inhibitor of terminal oxidases, sodium cyanide, and to the uncoupler of redox phosphorylation, chlorocarbonyl-phenylhydrazone, was different . Thus the E . coli cells with PA overproduction are characterized by significant changes in energetics and constructive metabolism . The interrelations between PA overproduction, phospholipid metabolism and the respiratory chain activity are discussed.

East Afr Med J, 1990 Jul, 67(7), 466 - 72
HIV infection surveillance in Mogadishu, Somalia; Burans JP et al.; A group of 89 prostitutes and 45 patients attending sexually transmitted disease clinics in Mogadishu, Somalia were examined for evidence of HIV infection . Both groups reported more than 1 sexual partner routinely and had sexual contacts with prostitutes . There was a significant amount of sexually transmitted diseases (STDs) in these two groups, with 11.2% and 6.7% respectively being culture positive for N . gonorrhoea . Among the prostitutes, 28.1% were positive for antibodies to T . pallidum while only 4.4% of the STD patients were positive . One isolate of N . gonorrhoea was resistant to penicillin . All study participants were negative for antibodies to HIV suggesting an extremely low prevalence of HIV in high risk behaviour groups in the capital city of SomaliaPIP: 89 prostitutes and 45 men attending the sexually transmitted disease (STD) clinic in Mogadishu, Somalia, were tested for HIV (human immunodeficiency virus) with the Abbott ELISA (enzyme-linked immuno-sorbent assay) test, cultured for gonorrhea, and screened for syphilis . There were no sera positive for HIV . 11% of the prostitutes and 7% of the men had positive gonorrhea cultures; 28% of the prostitutes and 4% of the men were positive for syphilis; 1 of the men had penicillin-resistant N . gonorrhoea with a beta-lactamase test . An epidemiological questionnaire was administered to the subjects . Most were aged 20-29; 67% were married; 80% of the men and 22.5% of the women were soldiers . 40% of the men reported use of prostitutes . Stated numbers of sexual contacts were 1.87/week for the prostitutes, and 1.51/week for the men . Data were also reported on occupations, recent injections, immunizations, intravenous drug use, surgery, blood transfusions and scarification .

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