Penicillin

Exp Brain Res, 1993, 96(2), 319 - 27
Phases in the development of a penicillin epileptiform focus in rat neocortex; Bashir ZI et al.; Somatosensory evoked potentials and potentials evoked by direct cortical stimulation were recorded from layer IV of the somatosensory area of the cerebral cortex in urethane anaesthetised rats . Penicillin was expelled electrophoretically from the tip of a drug-filled micropipette at constant rates into layer IV . Small fluxes of penicillin (with electrophoretic currents of -50 to -90 nA) resulted in the appearance, after a delay of 1-2 min, of an enhancement of amplitude in the voltage of both types of evoked potential, unaccompanied by any prolongation of the waveform or spontaneous focal epileptiform discharges . The amplitude of the enhanced evoked potential exhibited a strength-response curve which was a scaled-up version of the curve before penicillin, the scaling factor reflecting the enhancement of amplitude . As the interval between a pair of stimuli was increased, the magnitude of the response to the second stimulus recovered, following a time course similar to that before penicillin . With larger fluxes of penicillin (with electrophoretic currents of -250 to -1000 nA) the amplitude of evoked potentials rose more rapidly and to a higher level; as the concentration of penicillin rose, this enhancement of amplitude led into a second phase, in which there was additionally an increase in the duration of the evoked potentials and the appearance of spontaneous epileptiform discharges . The evoked potentials in this situation showed physiological properties different from those before penicillin application . The strength-response curve exhibited a discontinuity, indicating the evoked potential to be the sum of a physiological response and an epileptiform discharge, the former being graded with stimulus strength and the latter being all or none.(ABSTRACT TRUNCATED AT 250 WORDS)

Schweiz Arch Tierheilkd, 1993, 135(11-12), 345 - 55
Clinical signs, diagnosis and treatment of duodenal ileus in cattle; Braun U et al.; The clinical signs, changes in blood and rumen fluid, findings at laparotomy, therapy and course of disease of 23 cows with obstruction or compression of the duodenum are described . The duodenum was obstructed by a phytobezoar in 14 cows and by a blood clot in one cow . In eight cows, the duodenum was compressed by and adhered to a liver abscess . The most important clinical findings included moderate to severe disturbance in the general behaviour and attitude, markedly reduced gastrointestinal activity, no or greatly reduced defaecation and abomasal reflux with metabolic alkalosis . Ten cows were slaughtered after clinical examination or exploratory laparotomy . In 13 cows, the phytobezoar was compressed manually to facilitate normal elimination, and if this was not possible, the phytobezoar was removed by enterotomy . Postoperative therapy consisted of intravenous administration of a solution containing sodium chloride and glucose, potassium chloride and intramuscular administration of metoclopramide, procaine penicillin and flunixin meglumine for three to five days . Two of the treated cows were slaughtered a few days postoperatively . There was a rapid improvement in the remaining 11 cows, and general condition, appetite and defaecation returned to normal within a short time.

Glas Srp Akad Nauka {Med}, 1993, (43), 225 - 8
{Chronic encephalomyelitis caused by Borrelia burgdorferi . Case report}; Pavlovic D et al.; We present a female patient with typical third stage neuroborreliosis with progressive chronic encephalomyelitis . One month after a tick bite, in the first stage of Lyme disease, she had myalgias during ten days and after one year polyarthralgias and polyarthritis . Neurological problems occurred 15 years after the tick bite with headache, nystagmus, intentional tremor and spastic paraparesis with sphincter disturbances . Etiological diagnosis was established after three years . Cytobiochemical findings in cerebrospinal liquor were normal but oligoclonal IgG bands were found . Fluorescent antibody test was positive in serum (1:75) as well as ELISA (1:447) . The patient reacted favourably to intravenous crystal penicillin 20 x 10(6) units daily during 18 days . Till now, she is in remission and has only mild paresis of the left leg.

Glas Srp Akad Nauka {Med}, 1993, (43), 213 - 8
{Clinical picture of cardioborreliosis: from AV block to perimyocarditis}; Vasiljevic Z et al.; The third degree A-V heart block with severe Adams-Stokes attacks in nine patients with Lyme borreliosis was described . All patients had similar clinical picture: previously healthy with syncope as abrupt onset of the disease . Data on skin changes--erythema migrans--were obtained subsequently although the patients did not recall being bitten by a tick . Diagnosis was based on clinical manifestation, and on positive serologic tests to Borrelia . After the administered therapy (on admission atropine 0.5 mg i.v., and/or isoproterenol 0.02 mcg/kg/min, temporary pace-maker in two patients; and after proved diagnosis penicillin 20 mil . unit per day 10 days, and tetracyclin 2.0 gr per day 20 days A-V block returned to sinus rhythm with normal A-V conduction, and all biochemical parameters returned to normal limits . Perimyocarditis is not rare during Lyme borreliosis, but in this case infection syndrome is dominant.

Neuropsychobiology, 1993, 27(3), 171 - 5
Calcium-antagonistic effects of carbamazepine in epilepsies and affective psychoses; Walden J et al.; Carbamazepine (CBZ) is known to have beneficial effects in the treatment of epilepsies and in the prophylaxis of affective disorders . Since increased transmembrane calcium fluxes and intracellular calcium concentrations play a key role in the generation of epilepsies and possibly also in the development of these psychiatric disorders the effects of CBZ on epileptic discharges (elicited by caffeine, penicillin and low Mg2+) in CA3 neurons of hippocampal slices were compared with those of the organic calcium antagonist verapamil and found to be almost the same.

Med Dosw Mikrobiol, 1993, 45(4), 493 - 501
{Localization of penicillin G chemoreceptors in cells of Streptomyces sp . R61}; Filipek J et al.; The purpose of the present work was localization of penicillin-binding proteins (PBPs) in the cells of Streptomyces sp . R61 using immunological and autoradiographic methods and electron microscopy . The cells were treated with H3-penicillin G . PBPs of protoplasts were marked with peroxidase labelled IgG to DD-carboxypeptidase of the strain . The results indicate areas privileged in PBPs content at the cytoplasmic membrane and in vesicles located in the periplasmic space . PBPs were visualized in bulges of the protoplasts membrane . In the cells PBPs are present at hyphal tips and in centers at the periphery of cells, which are places of cross wall biosynthesis or branching of hyphae and overproduction of cell wall material.

Anesth Pain Control Dent, 1993 Fall, 2(4), 203 - 5
Acute bronchospasm following administration of lidocaine; van der Bijl P et al.; A 27-year-old woman with a history of Crohn's disease and an allergy to penicillin presented for routine restorative dental work . Xylotox E80A (3.6 mL of 2% lidocaine with 1:80,000 epinephrine) was given, and the dental work was completed uneventfully . Three months later she presented with acute pulpitis of a mandibular molar for which root canal therapy was indicated . At this time, 1.8 mL Xylotox E80A was given . Within 2 minutes, the patient experienced severe respiratory distress and the procedure was delayed for 5 days . In a fully equipped operating room, a subcutaneous test with Xylotox E80A was performed and acute bronchospasm resulted . This case report describes severe bronchospasm following the administration of lidocaine on two occasions.

Auris Nasus Larynx, 1993, 20(4), 239 - 46
Suspension organ culture of the fetal mouse ear; Tamura K et al.; To observe the development of the fetal ear, we grew the explanted ears of mouse fetuses 13 days old in suspension organ culture on a roller device for 48 hours . We used the BGJb-medium (Fitton-Jackson Modification) supplemented by 25% fetal bovine serum, and added a solution containing penicillin-streptomycin at the rate of 1% to the total volume . It was observed histologically that some explants developed ossicles that corresponded with those of mouse fetuses 15 days old in vivo . Sensory structures in the inner ear developed in organ culture as well . This method may help to resolve the question of ontogenesis of the ossicles.

J Gynecol Obstet Biol Reprod (Paris), 1993, 22(8), 843 - 7
{A difficult diagnosis: pelvic-abdominal actinomycosis abscess}; Huss M et al.; A laparotomy for hysterectomy was performed in a 46-year-old nulliparous woman who had worn an intra-uterine sterilization device for 8 years . The patient was in poor general health and had had abdominal pain and repeated episodes of fever over the preceding 3 months . An abscess of the abdominal muscle was found peroperatively . No perforations of the small or large intestine were observed . The pathology examination yielded the diagnosis of Actinomycosis . Actinomyces israeli is the most frequency observed Actinomycae in humans . It is a saprophyte organism of the intestinal flora, not usually found in the vagina and observed in 3.5% of cervical swabs of patients wearing an intra-uterine device (Gupta bodies) . The frequency increases with the duration of insertion and the pathogenicity appears when the immune responses are deficient and/or when a cofactor is involved . Treatment relies on surgical exeresis and prolonged antibiotics (penicillin G or macrolides) . Hyperbar treatment is sometimes used.

Scand J Infect Dis, 1993, 25(6), 741 - 5
Congenital syphilis: clinical manifestations in premature infants; Liu CC et al.; During the 4-year period February 1989 to January 1993, 13 premature babies aged 1-21 days and with congenital syphilis were admitted to the National Cheng Kung University Hospital . Of the 13 premature infants, 8 (62%) had unusual desquamation over palms and soles . Bone changes with periosteal reaction and/or metaphyseal dystrophy were observed in 11 cases (85%) . Three mothers were diagnosed as being infected during pregnancy; 2 were treated with penicillin . The clinical features of congenital syphilis in premature neonates are somewhat different from those previously reported . Bone changes, hepatosplenomegaly, respiratory distress, skin lesions, especially over the soles and palms, cerebrospinal fluid abnormalities, and jaundice were the major manifestations in our series . In premature infants with these symptoms and signs, congenital syphilis should be considered as one of the differential diagnoses . Once the diagnosis of congenital syphilis is made, adequate penicillin therapy should be given.

Acta Pol Pharm, 1993, 50(2-3), 159 - 63
{Influence of benzyl penicillin on cytotoxicity and level of metabolic activity of cyclophosphamide in mice}; Pakulska W et al.; The influence of benzylpenicillin on cytotoxicity of cyclophosphamide (CF) against leukaemia L 1210 was studied . The level of CF metabolites in mouse serum was traced . The benzylpenicillin appeared to enhance cytotoxic activity of CF and leads to increase of active metabolites when CF applied in high doses (300 mg/kg).

Acta Microbiol Hung, 1993, 40(4), 379 - 86
Inulin formation of penicillin producing industrial Penicillium chrysogenum strains; Olah A et al.; Conidia of certain penicillin producing Penicillium chrysogenum industrial strains produced polyfructose . Two types of polyfructoses were formed by conidia of P . chrysogenum B10 from sucrose and with less yield from raffinose . Ten percent of fructans were in water insoluble form attached to the outer wall of conidia . The other, ethanol precipitable fructan formed a colloid opalescent solution . The latter had inulin type beta (2-->1) bonds--identified by 13C NMR spectroscopy--between fructose molecules and had a molecular weight of 217,000 Daltons . The KM value of sucrose hydrolysis--the first step of inulin production--was 0.86 M . The invertase hydrolysed about 70% of sucrose on the second day . Optimal conditions for inulin formation were: pH 6.0, 25-45 degrees C, 100 mg/ml sucrose, 10(7) spore/ml . The maximum conversion rate of fructose from sucrose into precipitable inulin was about 10% after 48 h incubation . The inulin production could be inhibited by glucose.

J Chem Technol Biotechnol, 1993, 58(1), 27 - 37
Immobilization studies of an industrial penicillin acylase preparation on a silica carrier; Fonseca LP et al.; Penicillin acylase (EC 3.5.1.11) was immobilized by covalent binding on a silica gel carrier activated by silanization . High immobilization yields, operational stability, enzyme loading and support reutilization capacity were obtained . The effects of several variables on the activation of the support and on the immobilization method were studied . Other supports and immobilization methods were assessed for the immobilization of penicillin acylase and compared with the basic process used . Activity versus temperature, pH, buffer molarity and penicillin concentration profiles were determined and compared for the free, crosslinked and covalently-bound silica carrier penicillin acylase preparations . The hydrolysis performance of the latter preparation was assessed in a batch basket reactor and the time course of the hydrolysis reaction modelled by a two parameter model equation . The operational stabilities of penicillin acylase coupled covalently to the silica gel support and immobilized by a crosslinking procedure using glutaraldehyde were also compared.

J Chem Technol Biotechnol, 1993, 57(1), 79 - 85
Immobilization of penicillin acylase on copolymer of butyl acrylate and ethylene glycol dimethacrylate; Bryjak J et al.; The effects of glutaraldehyde, enzyme concentrations and reactants volumes, ionic strength, pH value and carrier particle diameter on immobilization of penicillin acylase onto acrylic carriers were studied . The activity of immobilized enzyme preparations was also studied over a range of pH values and temperatures and thermal and pH stabilities were determined . The use of the immobilized preparation for penicillin G hydrolysis in a batch reactor was investigated . The immobilized enzyme gave a significant reduction in hydrolysis time compared to hydrolysis by the native enzyme.

J Chem Technol Biotechnol, 1993, 57(1), 73 - 8
Effect of polymer matrix on penicillin acylase immobilization on copolymers of butyl acrylate and ethylene glycol dimethacrylate; Bryjak J et al.; Copolymers of butyl acrylate and ethylene glycol dimethacrylate with various degree of crosslinking and aminolysis were used for penicillin acylase immobilization . The amount and activity of the bound protein decreased with the decrease of crosslinking when copolymers having nearly constant degrees of aminolysis were compared . The increase of the carrier amino group content increased the ability to bind the protein (by glutaraldehyde method) without a proportional rise of enzyme activity . The comparative studies of immobilization effect and performance of the derivatives showed 40% crosslinked EGDMA, having an amino group content of 0.67 mmol g-3, to be the carrier of choice . This selected carrier was tested for active protein immobilization by use of crude acylase preparation . It was shown that up to a protein concentration of 9 mg cm-3 in the immobilization mixture the active protein was preferentially bound to the polymer matrix . It was indicated also that the derivative stability was mostly affected by multipoint attachment of the enzyme to the carrier surface.

Ann Trop Paediatr, 1993, 13(2), 165 - 71
Louse-borne relapsing fever in Ethiopian children: a clinical study; Borgnolo G et al.; An outbreak of louse-borne relapsing fever, caused by the return to their original recruitment areas of soldiers at the end of 30 years of fighting in northern Ethiopia, was reported in the Arsi region . We studied 103 infants and children with louse-borne relapsing fever who were admitted to Asella Hospital between 1 May 1991 and 30 April 1992 . Twenty-one per cent of the patients had a clear history of contact with sick ex-soldiers; 42% were students admitted to the hospital following the re-opening of schools after the summer vacation . The common clinical features of the disease were fever in 100%, headache in 84.5%, chills in 74%, abdominal pain in 51%, epistaxis in 20%, hepatomegaly in 26%, splenomegaly in 14%, petechial rash in 34% and jaundice in 10% . Differences in symptoms and signs according to age are described . Observed complications were pneumonia in 14% and central nervous system involvement in 10% . Four children went into deep coma, and two of them died . Severe disease was associated with a high density of spirochaetes in blood smears . Patients were treated with two low doses of penicillin or one dose of penicillin followed by, according to age, chloramphenicol or tetracycline, and with intravenous fluids . The case fatality rate was 1.9% . Jarisch-Herxheimer reactions occurred in 61% of patients . There were relapses in 2.9% of treated patients.

Mol Cell Endocrinol, 1993 Jan, 90(2), 165 - 70
The modulation of placental lactogen release by opioids: a role for extracellular calcium; Petit A et al.; We previously reported that kappa opioids stimulated the release of human placental lactogen (hPL) from trophoblastic cells and that this effect was prevented by co-incubation with naloxone . We also reported that adenylate cyclase was not directly involved in this process . In order to understand the post-receptor events mediating hPL release by opioids in the human placenta, we studied the role of extracellular calcium . Human trophoblastic cells obtained by trypsin digestion were cultured for 48 h in Ham's F-10 medium supplemented with 10% fetal bovine serum (FBS), 200 U/ml penicillin, and 200 micrograms/ml streptomycin . 45Ca2+ influx was then measured by filtration on glass-fiber filters . We observed a time- and dose-dependent stimulation of 45Ca2+ influx by ethylketocyclazocine (EKC) with an EC50 of 0.5 nM and a maximal stimulation of 196% over control . This effect was completely blocked by naloxone, a non-specific opioid antagonist, and by nor-binaltorphimine, a specific kappa antagonist . We also demonstrated that U-50,488 (kappa agonist) had the same stimulatory effect as EKC (221 +/- 25% of control) . D-Ala2,NMe-Phe4,Gly-ol5)-enkephalin (DAGO) (mu agonist) slightly stimulated Ca2+ influx (128 +/- 5% of control, p > 0.05) whereas D-Ser2,Leu,Thr6)-enkephalin (DSLET) (delta agonist) had no effect . Pre-incubation of trophoblastic cells with pertussis toxin (PTX) did not affect the EKC-induced 45Ca2+ influx, suggesting that this placental opiate effect is not coupled with PTX-sensitive G proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

J Chromatogr, 1992 Nov 27, 583(1), 105 - 10
Monitoring of benzylpenicillin decomposition in gastric contents by capillary zone electrophoresis; Arrowood S et al.; A method has been developed to follow the decay of the antibiotic penicillin, specifically penicillin G or benzylpenicillin, in the gastric contents of laboratory rats . Purification by centrifugation and DEAE cellulose treatment of the stomach contents (diluted with pH 9 phosphate-borate buffer) was sufficient to allow the quantification of penicillin by capillary zone electrophoresis . An internal standard was used to minimize the injection error . The loss of activity was greater in fasted animals, as expected from the lower pH of their gastric contents, than in fed rats . The in vivo kinetics of the decomposition of the antibiotic was compared to that obtained in water and in hydrochloric acid solutions.

FEMS Microbiol Lett, 1992 Dec 1, 78(2-3), 117 - 23
In vivo crystal formation in Escherichia coli of an over-expressed soluble form of penicillin-binding protein 5; van der Linden MP et al.; Accumulation of either native membrane-bound or soluble variants of PBP5 over-expressed in the cytoplasm was investigated by electron microscopy of ultra-thin sections . One of the soluble forms of PBP5 (PBP5s353) formed well-ordered crystals inside the cells . Cells sectioned perpendicular to their long axis showed a diamond-shaped crystal whereas cells cut parallel to their long axis contained a long, narrow crystal . In both sectioning directions an ordered ultrastructure was visible as shown by optical diffraction . Computer processing was used to enhance the crystal images . From this the unit cell parameters were calculated as a = 7.6 nm, b = 4 nm, c = 4.2 nm, gamma = 75 degrees . The calculated unit-cell volume of 120 nm3 is large enough to contain one protein molecule.

Fam Pract, 1992 Dec, 9(4), 425 - 32
Fever in general practice . II . Reasons for encounter, management and duration of fever conditions; Eskerud JR et al.; A sample of 80 direct and 36 telephone encounters for fever was established in 1988 as part of a Norwegian study on fever as a clinical problem in general practice . Reasons for encounter (ICPC) and clinical examinations were recorded along with clinical laboratory tests, treatment, management and follow up (IC-Process-PC) . The doctors assessed the diagnostic process by means of visual analogue scale . Duration of the fever conditions was estimated through a postal questionnaire . Patients with direct encounters presented a wide range of reasons for the encounters . Fever was the most frequent single presenting complaint (31%) . The general practitioners put major emphasis on the clinical examinations . They prescribed drugs in 68% of the direct encounters . Seventy per cent of the prescriptions were general systemic anti-infectives . Penicillin accounted for 58% of antibiotics . Six (8%) patients were hospitalized, and three (4%) were referred to a specialist . The mean time until complete recovery was 15 days for direct and 19 days for telephone encounters . Fever may be a sign even when it is not a presenting complaint . Major emphasis is probably put on the clinical examination of febrile patients because of the complexity of symptoms and the wide range of diagnoses associated with fever.

Eur Neuropsychopharmacol, 1992 Dec, 2(4), 455 - 62
Calcium antagonistic effects of carbamazepine as a mechanism of action in neuropsychiatric disorders: studies in calcium dependent model epilepsies; Walden J et al.; Carbamazepine (CBZ) is used in neurology for the treatment of epilepsies and trigeminal neuralgia and in psychiatry for the prophylactic treatment of affective and schizoaffective psychoses . Since a common mechanism of epilepsies and affective psychoses might be increased intracellular calcium ion levels, CBZ action was analyzed in penicillin, caffeine and low Mg2+ induced model epilepsies which have been shown to be suppressed specifically by organic calcium antagonists . In CA3 and CA1 areas of hippocampal slice preparations of guinea pigs CBZ reduced paroxysmal depolarizations and extracellular field potentials (EFP) in a typical time and concentration dependent manner as it is known from calcium antagonists . Furthermore, subthreshold concentrations of the organic calcium antagonist verapamil intensified the action of CBZ . NMDA induced increases of the discharge rate of EFP were, however, unaffected by CBZ.

Schweiz Rundsch Med Prax, 1992 Dec 1, 81(49), 1473 - 80
{Current aspects of neurosyphilis: therapy-resistant cases with high-dosage penicillin?}; Stockli HR; The occurrence of atypical and abortive cases of neurosyphilis in the last two decades has tended to make this rather infrequent, treatable condition difficult to diagnose; therefore it is advisable to perform large-scale serologic tests among neurologic and psychiatric patients . The diagnosis is confirmed by the detection of treponema antibodies in the central nervous system (TPHA index, ITpA index) . When serologic test results are positive, secondary diagnostic criteria are provided by pathologic CSF findings (elevated cell count, humoral immune reaction) . The course of the disease and the CSF parameters are favourably influenced by appropriate therapy . Over the last two decades, there has been an increase in the number of reports of cases refractory to the low-dose penicillin treatment recommended by the WHO and the CDC until two years ago . There have also been reports of treponema resistance in association with this therapeutic strategy and furthermore of failure to detect CSF concentrations of penicillin capable of eradicating the spirochetes . Counter measures have been taken worldwide in the last few years in the form of high-dose penicillin therapy (approx . 20 million IU/day for 2 to 3 weeks), in the hope that this would eliminate the resistance . We observed two patients treated with 18 and 24 million IU penicillin for 10 and 14 days respectively . The pathogens remained resistant, and the disease continued to progress . In one of these cases, immunologic processes might have been predominantly responsible for the resistance to the treatment, while in the other resistant pathogens can be assumed to be responsible . Repeated courses of treatment with higher doses of penicillin and/or with ceftriaxone finally succeeded.(ABSTRACT TRUNCATED AT 250 WORDS)

Am J Gastroenterol, 1992 Dec, 87(12), 1820 - 2
Syphilitic gastritis in an HIV-infected individual; Kasmin F et al.; We report the first known case of syphilitic gastritis in an HIV-infected person . The presentation of nonspecific abdominal pain and weight loss in a 48-yr-old former intravenous drug user previously treated for asymptomatic syphilis led to a barium swallow which demonstrated linitis plastica . Upper endoscopy reinforced a suspicion of carcinoma, but biopsy made the diagnosis of syphilis by silver staining . Further testing revealed a positive serology for syphilis as well as HIV infection with a depressed CD-4 lymphocyte count . Treatment with parenteral penicillin led to a rapid resolution of symptoms . This case represents a rare complication of late syphilis, and is another example of the unusual manifestations of syphilis seen in the HIV-infected population.

J Bacteriol, 1992 Dec, 174(23), 7572 - 8
Possible role of Escherichia coli penicillin-binding protein 6 in stabilization of stationary-phase peptidoglycan; van der Linden MP et al.; Plasmids for high-level expression of penicillin-binding protein 6 (PBP6) were constructed, giving rise to overproduction of PBP6 under the control of the lambda pR promoter in either the periplasmic or the cytoplasmic space . In contrast to penicillin-binding protein 5 (PBP5), the presence of high amounts of PBP6 in the periplasm as well as in the cytoplasm did not result in growth as spherical cells or in lysis . Deletion of the C-terminal membrane anchor of PBP6 resulted in a soluble form of the protein (PBP6s350) . Electron micrographs of thin sections of cells overexpressing both native membrane-bound and soluble PBP6 in the periplasm revealed a polar retraction of the cytoplasmic membrane . Cytoplasmic overexpression of native PBP6 gave rise to the formation of membrane vesicles, whereas the soluble PBP6 formed inclusion bodies in the cytoplasm . Both the membrane-bound and the soluble forms of PBP6 were purified to homogeneity by using the immobilized dye Procion rubine MX-B . Purified preparations of PBP6 and PBP6s350 formed a 14{C}penicillin-protein complex at a 1:1 stoichiometry . The half-lives of the complexes were 8.5 and 6 min, respectively . In contrast to PBP5, no DD-carboxypeptidase activity could be detected for PBP6 by using bisacetyl-L-Lys-D-Ala-D-Ala and several other substrates . These findings led us to conclude that PBP6 has a biological function clearly distinct from that of PBP5 and to suggest a role for PBP6 in the stabilization of the peptidoglycan during stationary phase.

Chest, 1992 Dec, 102(6), 1907 - 9
Hilar and mediastinal lymphadenopathy with hypersensitivity pneumonitis induced by penicillin; Yonemaru M et al.; A 54-year-old Japanese man demonstrated a sultamicillin-induced hilar and mediastinal lymphadenopathy with hypersensitivity pneumonitis . A positive lymphocyte stimulation test for sultamicillin and a decreased CD4/CD8 ratio of lymphocytes in BAL fluid suggested that an alteration in cell-mediated mechanisms was responsible for the patient's symptoms.

Ann N Y Acad Sci, 1992 Nov 30, 672, 643 - 8
Continuous production of 6-APA in an aqueous two-phase system; Chang HN et al.; An aqueous two-phase system of polyethylene glycol (PEG) and potassium phosphate provided a favorable environment for bioconversion of penicillin G to 6-aminopenicillanic acid (6-APA) . The recombinant E . coli cells containing penicillin acylase were partitioned in the phosphate-rich bottom phase, and the product 6-APA in the PEG-rich top phase, which protected the enzyme from deactivation for a longer period of time . The continuous production of 6-APA by recycling the bottom phase showed a slight decrease in enzyme activity from initial 80 mM of 6-APA production to 61 mM during the eight days of operation at a space velocity of 0.12 hours-1 . This work showed a possibility that the aqueous two-phase whole-cell enzyme bioconversion could serve as an alternative to immobilized cells on solid matrices.

Biochem J, 1992 Nov 15, 288 ( Pt 1), 87 - 91
Secretion by overexpression and purification of the water-soluble Streptomyces K15 DD-transpeptidase/penicillin-binding protein; Palomeque-Messia P et al.; Though synthesized with a cleavable signal peptide and devoid of membrane anchors, the 262-amino-acid-residue Streptomyces K15 DD-transpeptidase/penicillin-binding protein is membrane-bound . Overexpression in Streptomyces lividans resulted in the export of an appreciable amount of the synthesized protein (4 mg/litre of culture supernatant) . The water-soluble enzyme was purified close to protein homogeneity with a yield of 75% . It requires the presence of 0.5 M-NaCl to remain soluble . It is indistinguishable from the detergent-extract wild-type enzyme with respect to molecular mass, thermostability, transpeptidase activity and penicillin-binding capacity.

Brain Res, 1992 Nov 13, 595(2), 249 - 55
Penicillin-induced triphasic modulation of GABAA receptor-operated chloride current in frog sensory neuron; Katayama N et al.; Effects of penicillin-G (PCN) on GABA-evoked Cl- current (IGABA) were investigated in freshly dissociated frog sensory neurons by the use of the concentration-clamp technique combined with the suction-pipette method . Under conditions where the internal and external solutions allowed only Cl- permeability, PCN elicited triphasic modulation on IGABA, consisting of two modes of blockade on IGABA and a following rebound (rebound-like transient IGABA) . Simultaneously applied PCN and GABA depressed IGABA immediately (phasic blockade), with the depressed IGABA slightly recovering in amplitude to achieve a stable level of blockade (tonic blockade) . When a solution containing a mixture or PCN and GABA was quickly replaced by one containing GABA alone, a rebound-like transient Cl- current (IR) was evoked . Each component of the PCN actions on IGABA was PCN- and GABA-concentration-dependent . The reversal potential for each component of the PCN actions on IGABA was close to the chloride equilibrium potential (ECl) calculated using the Nernst equation . The current-voltage (I-V) relations for both the phasic and tonic blockade revealed inward rectification, while I-V curves for the control IGABA and the IR were outwardly rectified . The degree of IGABA-desensitization and the amplitude of the IR correlated well . The data suggest that partial removal of the GABAA receptor-desensitization may result in generation of the IR.

Neuroscience, 1992 Nov, 51(2), 439 - 44
The effect of cortical lesion on systemic penicillin epilepsy in rats; Culic M et al.; There is a certain recovery of function following brain damage, due to neuronal plasticity . The experiments were performed in order to investigate the effects of cortical lesion on seizural activity in rats induced by systemic application of penicillin . The sensorimotor cortex was unilaterally removed in the lesioned animals, while the control animals were only sham operated or non-operated (before implantation of the electrodes) . Seizural activity was recorded by means of electroencephalograms before and after penicillin treatment (1,000,000 I.U./kg, i.p) . Testing of penicillin started at least 30 days after cortical lesion . Seizural activity was characterized by spike and wave complexes accompanied by vigilance reduction and sometimes by mild myoclonic jerks in both control and lesioned animals . The early period (about 2 h after penicillin administration) with appearance of the spike-wave discharges with relative increase of the mean total electroencephalogram powers as well as the succeeding period 2.5-5.5 h after penicillin administration) with maximum number of spike-wave discharges did not differ in the electroencephalogram of the control and lesioned animals . The late period of penicillin effect (from 6-11 h after penicillin administration) with frequent spike-wave discharges and still large mean total electroencephalogram powers was observed only in lesioned animals . It is concluded that a cortical lesion destabilizes the brain function in the rat model of epilepsy induced by parenteral administration of penicillin.

J Am Vet Med Assoc, 1992 Nov 1, 201(9), 1402 - 3
Penicillin-induced immune-mediated hemolytic anemia in a horse; McConnico RS et al.; A 5-year-old female American Quarter Horse was determined to have immune-mediated hemolytic anemia after detection of a positive response to a direct Coombs' test . Penicillin-induced immune-mediated hemolytic anemia was confirmed via a direct antiglobulin test, using penicillin-coated RBC . The horse was clinically improved and the anemia resolved in response to supportive care and discontinuation of penicillin treatment . Penicillin should be considered a possible cause of immune-mediated hemolytic anemia in horses.

J Bacteriol, 1992 Nov, 174(21), 7063 - 7
Resolution of chromosomes III and VI of Aspergillus nidulans by pulsed-field gel electrophoresis shows that the penicillin biosynthetic pathway genes pcbAB, pcbC, and penDE are clustered on chromosome VI (3.0 megabases); Montenegro E et al.; An improved electrophoretic molecular karyotype of Aspergillus nidulans ATCC 28901 has been obtained by contour-clamped electric field gel electrophoresis, which separates seven chromosomal bands and allows resolution of chromosomes III and VI . The three genes of the penicillin biosynthetic pathway, pcbAB, pcbC, and penDE, encoding alpha-aminoadipyl-cysteinyl-valine synthetase, isopenicillin N synthase, and isopenicillin N acyltransferase, respectively, are clustered together on a chromosome of 3.0 Mg, corresponding to linkage group VI, whereas the argB gene was located on a chromosome of 3.4 Mb, corresponding to linkage group III . Three other strains of A . nidulans contained a modified chromosome III of about 3.1 Mb that overlaps with chromosome VI, forming a doublet . Resolution of chromosomes III and VI in strain ATCC 28901 allowed unequivocal mapping of the penicillin gene cluster on chromosome VI of A . nidulans.

J Biotechnol, 1992 Nov, 26(2-3), 143 - 54
An integrated process for the production and biotransformation of penicillin; Barenschee T et al.; The extraction of Penicillin G (PG) from the filtered cultivation medium of Penicillium chrysogenum and its conversion into 6-amino penicillanic acid (6-APA) and phenyl acetic acid (PhA) at pH 8 was performed in a 10 l kuhni extractor during the production by means of penicillin-G-amidase immobilized in a liquid membrane carrier system (LM) . 6-APA was enriched in LM, and the PhA returned to the cultivation medium . After electrocoalescence of LM, the 6-APA was converted into ampicillin with the same enzyme at pH 6, while the liquid membrane phase and enzyme were recycled and reused.

Can J Neurol Sci, 1992 Nov, 19(4), 487 - 91
Suppression of spreading depression of Leão in neocortex by an N-methyl-D-aspartate receptor antagonist; McLachlan RS; Spreading depression has been implicated in the pathophysiology of a number of diseases such as migraine, stroke and epilepsy . The characteristics of this phenomenon were explored in neocortex of anesthetized rats . Spreading depression was produced in 10 of 15 animals using mechanical, electrical and chemical stimulation . Mean amplitude of the DC shift was -9.3 mV, mean duration at any one electrode 65 sec and rate of spread 2-5 mm/min . Spreading depression was facilitated by focal interictal spike activity induced by penicillin and completely blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist, DL-2-aminophosphonovaleric acid (APV), providing further evidence that excitatory amino acid neurotransmission is a critical element in the development or propagation of the phenomenon.

Br J Pharmacol, 1992 Nov, 107(3), 732 - 7
The pharmacology of recombinant GABAA receptors containing bovine alpha 1, beta 1, gamma 2L sub-units stably transfected into mouse fibroblast L-cells; Horne AL et al.; 1 . Responses to gamma-aminobutyric acid (GABA) were evoked in mouse fibroblast L-cells stably transfected with bovine, alpha 1, beta 1, gamma 2L sub-units of the GABAA receptor . Expression was stimulated via a steroid-inducible promoter system . 2 . In near symmetrical intracellular and extracellular chloride concentrations, GABA evoked inward currents at negative holding potentials that reversed at +5 mV and displayed slight outward rectification . Concentration-response curves were fitted well by the logistic equation . GABA had a pEC50 = 5.1 +/- 0.1 and the curves had a slope of 1.9 +/- 0.1 . 3 . Responses to GABA were antagonized by bicuculline, picrotoxin and penicillin . The action of bicuculline was competitive (pA2 = 6.4) whilst the block by picrotoxin was uncompetitive and strongly agonist-dependent . 4 . Benzodiazepine receptor agonists potentiated responses to 3 microM GABA . The rank order of potency was FG 8205 > flunitrazepam > zolpidem > C1218872 . FG 8205 and C1218872 produced markedly lower maximal potentiations with efficacies 0.4 and 0.6 x that of flunitrazepam, respectively . The potencies of zolpidem and C1218872 observed are in agreement with the BZ1 type pharmacology of this sub-unit combination . The potentiation of GABA by flunitrazepam was antagonized by flumazenil with a Ki of 3.8 nM . 5 . GABA responses were potentiated in the presence of pentobarbitone and alphaxalone . The response was also noticeably broadened by these compounds due to a decrease in the response decay rate . Concentrations of pentobarbitone of 100 microM and above evoked an inward current in the absence of GABA . Alphaxalone up to 10 microM did not evoke a direct response.(ABSTRACT TRUNCATED AT 250 WORDS)

Laryngoscope, 1992 Nov, 102(11), 1255 - 9
Otosyphilis: a diagnostic and therapeutic dilemma; Gleich LL et al.; Traditional treatment of otosyphilis with penicillin and corticosteroids has achieved hearing improvement; however, selecting which patients with a positive fluorescent treponemal antibody absorption (FTA-ABS) test will benefit from treatment remains a problem . In order to study this problem, 18 patients with cochleovestibular dysfunction of unknown etiology and positive syphilis serology were treated with intravenous penicillin and corticosteroids . In addition, lumbar puncture and human immunodeficiency virus (HIV) testing were performed on all patients . Hearing improved in 5 (31%) of 16 patients, tinnitus decreased in 11 (85%) of 13, and vertigo improved in 6 (86%) of 7 . Factors associated with hearing improvement were hearing loss present less than 5 years, fluctuating hearing, and age less than 60 . Improvement was unrelated to the severity of the loss or previous therapy . All patients with cerebrospinal fluid abnormalities, including two patients with HIV disease, had subjective improvements . A diagnostic and treatment protocol is presented.

Vojnosanit Pregl, 1992 Nov-Dec, 49(6), 563 - 6
{Effects of sodium valproate in a model of penicillin epilepsy in rats}; Dragic S; Effects of sodium valproate in penicillin-induced epilepsy in rats have been described . To one group of rats penicillin was given I.P . (10(6) IU/kg) and to the another one it was given I.C . (100 IU) . After development of grand mal sodium valproate was given I.P . to all rats except the control group . In the group receiving I.C . penicillin it has come to cessation of individual discharges and grand mal after valproate application . In the group receiving I.P . penicillin, valproate prevented only grand mal while individual discharges remained . It is obvious that much higher doses of penicillin are necessary for the development of the epileptic model if penicillin is given I.P.

J Chromatogr, 1992 Oct 30, 624(1-2), 171 - 94
Chromatographic methods of analysis for penicillins in food-animal tissues and their significance in regulatory programs for residue reduction and avoidance; Boison JO; Chromatographic methods for penicillin analysis in animal tissues play a significant role in the regulation of the use of these drugs in livestock production . Regulatory agencies rely on data generated from these methods to establish withdrawal times and to determine whether presumptive positive tissue samples from slaughtered animals intended for human consumption contain violative levels of penicillins to necessitate regulatory action . The need to develop sensitive, accurate, and reliable methods to support regulatory programs is examined together with emerging techniques that could be taken advantage of to improve the sensitivity and usefulness of current chromatographic methods for tomorrow's regulatory agency.

FEBS Lett, 1992 Oct 26, 311(3), 209 - 12
Regulation of the supramolecular structure and the catalytic activity of penicillin acylase from Escherichia coli in the system of reversed micelles of Aerosol OT in octane; Kabakov VE et al.; The properties of penicillin acylase from E . coli solubilized by hydrated reversed micelles (RM) of Aerosol OT in octane were studied . The dependence of catalytic activity on the hydration degree, a parameter which determines the size of the micelle inner cavity, has a curve with three optima, each one corresponding to the enzyme functioning either in a dimer form (wo = 23) or in a form of separate subunits, a heavy one, beta, and a light one, alpha (wo = 20 and 14, respectively) . The reversible dissociation of the enzyme was confirmed by ultracentrifugation followed by electrophoresis.

Nature, 1992 Oct 22, 359(6397), 700 - 5
Molecular structure of the acyl-enzyme intermediate in beta-lactam hydrolysis at 1.7 A resolution; Strynadka NC et al.; The X-ray crystal structure of the molecular complex of penicillin G with a deacylation-defective mutant of the RTEM-1 beta-lactamase from Escherichia coli shows how these antibiotics are recognized and destroyed . Penicillin G is covalently bound to Ser 70 0 gamma as an acyl-enzyme intermediate . The deduced catalytic mechanism uses Ser 70 0 gamma as the attacking nucleophile during acylation . Lys 73 N zeta acts as a general base in abstracting a proton from Ser 70 and transferring it to the thiazolidine ring nitrogen atom via Ser 130 0 gamma . Deacylation is accomplished by nucleophilic attack on the penicilloyl carbonyl carbon by a water molecule assisted by the general base, Glu 166.

Antimicrob Agents Chemother, 1992 Oct, 36(10), 2166 - 75
Modes of action and inhibitory activities of new siderophore-beta-lactam conjugates that use specific iron uptake pathways for entry into bacteria; Brochu A et al.; We describe here the mechanism of inhibition of two new siderophore-beta-lactam conjugates against Escherichia coli X580 . One conjugate is a spermidine-based catechol siderophore-carbacephalosporin (JAM-2-263), and the other is an N5-acetyl-N5-hydroxy-L-ornithine tripeptide hydroxamate siderophore-carbacephalosporin (EKD-3-88) . In an agar diffusion test, both conjugates produced large inhibitory zones against strain X580 . Resistant strains (i.e., JAMR and EKDR) could be isolated after exposure of X580 to the conjugates JAM-2-263 and EKD-3-88, respectively . No cross-resistance was observed in these individual isolates . JAMR and EKDR were studied further to elucidate the mechanism of inhibition of each conjugated drug . The affinities of JAM-2-263 and EKD-3-88 for penicillin-binding proteins (PBPs) of isolated inner membranes were determined by a competition assay with 125I-penicillin V . JAM-2-263 targeted primarily PBPs 1A/B and 5/6, while EKD-3-88 targeted PBPs 1A/B and 3 . Strains X580, JAMR, and EKDR showed similar PBP affinities for the conjugates . However, marked changes were observed in the iron-regulated outer membrane proteins of resistant isolates grown on agar plates depleted of iron . EKDR lost the expression of FhuA (78 kDa) and its sensitivity to phages T1 and T5, whereas JAMR lost the expression of Cir (74 kDa) and its sensitivity to colicin Ia . These results revealed the requirement of FhuA and Cir for the inhibitory activities of EKD-3-88 and JAM-2-263, respectively . In an antibiotic diffusion assay, ferrichrome (1 microM) strongly antagonized the activities of both conjugates against X580 and JAMR, including the residual activity of JAM-2-263 against JAMR . However, the susceptibility of strain EKDR lacking the ferrichrome receptor (FhuA-) to the two conjugates remained the same in the presence of ferrichrome . The antagonistic effect of ferrichrome on the activity of JAM-2-263 may also indicate a role for FhuA in the activity of this beta-lactam conjugate . A FhuA- Cir- double mutant confirmed this hypothesis, since it showed a higher level of resistance to JAM-2-263 . To reproduce iron-restricted in vivo growth conditions, we grew X580 and EKDR cells in diffusion chambers implanted in the peritoneal cavities of rats . Strain EKDR showed impaired growth in such a cultivation system . This is the first report of beta-lactam drug transport into E . coli cells that involves the FhuA outer membrane protein.

Fertil Steril, 1992 Oct, 58(4), 847 - 9
Allergic reactions to penicillin during in vitro fertilization and intrauterine insemination; Smith YR et al.; Two cases are reported in which hypersensitivity reactions occurred after intrauterine placement of spermatozoa or embryos . Because the cells were processed and transferred in antibiotic-containing media, these reactions were suspected to be because of penicillin allergy . One patient had no prior penicillin allergy but was found to be penicillin allergic by skin testing . The other had a history of allergy to oral penicillin . In both cases, the allergy symptoms did not occur during subsequent cycles when antibiotics were removed from the transfer media . These reports suggest that in patients known to be penicillin sensitive, penicillin should not be used during transfer of gametes and embryos for assisted reproductive procedures . In addition, the routine use of antibiotics in these procedures should be scientifically evaluated.

J Biol Chem, 1992 Oct 5, 267(28), 20039 - 43
A murein hydrolase is the specific target of bulgecin in Escherichia coli; Templin MF et al.; A deletion in the structural gene for the soluble lytic transglycosylase, the predominant murein hydrolase in the soluble fraction of Escherichia coli, has been constructed . The mutant grows normally but exhibits increased sensitivity toward mecillinam, a beta-lactam specific for penicillin-binding protein 2 . In the presence of furazlocillin or other beta-lactams with a specificity for penicillin-binding protein 3 which normally cause filamentation, bulges were formed prior to rapid bacteriolysis . Similar morphological alterations are known to develop in wild type E . coli cells when furazlocillin is combined with bulgecin, an antibiotic of unusual glucosaminyl structure . It turned out that bulgecin specifically inhibits the Sl-transglycosylase in a noncompetitive manner . Since bulgecin shows some structural analogy to the murein subunits we postulate that the soluble lytic transglycosylase, in addition to its active site, has a recognition site for specific murein structures . The possibility of an allosteric modulation of the activity of the enzyme by changes in the structure of the murein sacculus is discussed.

Brain Res, 1992 Oct 2, 592(1-2), 298 - 304
Low concentrations of penicillin partially suppress CA3 hippocampal IPSPs in vitro; Schneiderman JH et al.; Low concentrations of penicillin (50-300 IU/ml) produce a pro-convulsant state in CA3 hippocampus characterized by low amplitude, low frequency (2-3 Hz) spontaneous field potential oscillations . Evoked field potentials were used to demonstrate that this distinct, coordinated behavior of the hippocampal neuronal network which is intermediate between normal activity and fully synchronized epileptiform bursting is the result of partial blockade of GABAA-mediated IPSPs . A new method for estimating the degree of IPSP block relative to convulsant doses of penicillin (2,000 IU/ml) indicates that the half-maximal effect occurs at 300 IU/ml . Fully synchronized bursts may require almost complete IPSP block.

Zhonghua Nei Ke Za Zhi, 1992 Oct, 30(10), 631 - 3, 659
{Borrelia burgdorferi may be the causal agent of sarcoidosis}; Hua B et al.; Serum antibody to Borrelia burgdorferi was measured in 33 patients with sarcoidosis who were confirmed clinically and pathologically . The results showed that 81.8% of the patients were positive . In addition, a strain of Borrelia burgdorferi was isolated from a patient's blood . Fourteen patients received ceftriaxone 2 g per day and/or penicillin 12 million per day and a patient received lincomycin 1.2 g per day . The antibody titer of the patients turned to normal level, their SACE turned to normal range, and chest X-ray findings were markedly improved in 3 cases after the treatment . According to the facts mentioned above, we consider that Borrelia burgdorferi may be the causal agent of sarcoidosis and sarcoidosis might be a special type of Lyme disease.

Rev Prat, 1992 Oct 1, 42(15), 1900 - 7
{Management of drepanocytic patients}; Bachir D et al.; Comprehensive supportive care includes outpatient follow up (periodic evaluation of baseline status, psychosocial support, prevention of sepsis through oral prophylactic penicillin in young children and vaccinations, early treatment of acute episodes (painful crises, other vaso-occlusive events, infection, acute anemia...); In adulthood residual organ dysfunction becomes one of the foremost problems . Further, more specific high risk situations (pregnancy, anesthesia) require adequate responses . Early diagnosis, improved strategy of care best achieved in Sickle Cell Centers can reduce mortality and morbidity in the aim of providing a better quality of life.

J Epidemiol Community Health, 1992 Oct, 46(5), 477 - 9
An epidemiological survey of rheumatic fever and rheumatic heart disease in Sahafa Town, Sudan; Ibrahim-Khalil S et al.; STUDY OBJECTIVE--The aim was to determine the prevalence of rheumatic fever and rheumatic heart disease and to initiate a programme of secondary prophylaxis in Sahafa Town, Sudan . DESIGN--The study was a prospective case finding survey, carried out by a specially trained team headed by a cardiologist . SETTING--The study involved high risk school children (5-15 years of age) from Sahafa Town in the period 1986-1989 . SUBJECTS--A total of 13,332 children on the school registers (7892 boys and 5430 girls) were examined generally and specifically for evidence of rheumatic fever or rheumatic heart disease . MAIN RESULTS--Out of the 13,322 children screened 351 were suspected cases and 146 were confirmed cases of rheumatic fever or rheumatic heart disease . The prevalence rates for all ages were 10/1000 for boys and 14/1000 for girls . The overall prevalence rate of the whole programme area was 11/1000, prevalence of rheumatic fever was 8/1000, and prevalence of rheumatic heart disease was 3/1000 . The prevalence rate was significantly increased among the inner town inhabitants (15/1000) compared to the outer town inhabitants 4/1000 (p < 0.001) . Monthly prophylactic benzathine penicillin in a dose of 1,200,000 IU was given to both suspected and confirmed cases . Penicillin coverage rate was 72% . CONCLUSIONS--Rheumatic fever continues to be a serious health problem . With economic pressures causing impending change in socioeconomic conditions in most Third World countries in the immediate future, rheumatic fever will continue to have a high prevalence rate and rheumatic fever and rheumatic heart disease prevention programmes will remain a central goal.

Epilepsy Res, 1992 Oct, 13(1), 49 - 58
Panoramic imaging of brain pHi and CBF during penicillin and metrazole induced status epilepticus; Tomlinson FH et al.; Using real-time in vivo umbelliferone fluorescent imaging, cortical intracellular brain pH (pHi) and cortical blood flow (CBF) were measured in New Zealand white rabbits during generalized seizures induced by intravenous metrazole or sodium penicillin . In the former, brain pHi declined from 7.04 +/- 0.07 to 6.78 +/- 0.07 within 15 min of generalized seizures and remained at this level for 1 h . In the penicillin group, pHi fell from 7.05 +/- 0.10 to 6.81 +/- 0.07 and also remained at this level over 60 min . This brain acidosis was uniform across the brain's surface . With the onset of status epilepticus there was a hyperemia which occurred in a heterogeneous pattern with blood flow appearing to be greater adjacent to cortical vasculature and slower in border zones between surface blood vessels . In the metrazole group, there was evidence of vasomotor paralysis with loss of autoregulation involving both cortical surface vasculature and penetrating arterioles with their capillary beds.

Can J Vet Res, 1992 Oct, 56(4), 365 - 9
Bovine platelets retain functional activity in the presence of penicillin G; Gentry PA et al.; It has been reported that antibiotics of the penicillin family impair the functional response of human, canine and lapine platelets to a broad range of agonists . In contrast, we have shown that the bovine platelet retained full functional responses to stimulation by adenosine diphosphate (ADP) or platelet activating factor (PAF) following administration of penicillin G to clinically normal cattle at 20,000 IU/kg for three days . The aggregation response to collagen was transiently reduced to approximately 50% of pretreatment values, but only while the drug was detectable in the circulation . When penicillin was added to platelet rich plasma suspensions, ADP-induced aggregation was similar to that of the control untreated platelets, while the PAF-induced aggregation response was reduced by not more than 25% . Only collagen-induced aggregation exhibited a modest dose-dependent inhibitory response in the presence of penicillin . It is postulated that the relative insensitivity of the bovine platelet to penicillin may be related to differences in postreceptor biochemical events compared to the human platelet.

Cesk Pediatr, 1992 Oct, 47(10), 592 - 5
{Long-term clinical experience with spherocytic hemolytic anemia in children}; Cap J; The author investigated during a 15-year period 27 children with spherocytic haemolytic anaemia . In 20 children the disease was familial . The initial symptoms were jaundice and anaemia . In six children the disease was manifested by severe neonatal jaundice and in four an exsanguination transfusion was made . Of five older children three were at first treated for infectious hepatitis . The anaemic syndrome was in the foreground of the clinical picture in 16 children, incl . 10 where it was present already in infant age . In 24 children splenectomy was performed, usually after the age of 6 years . For prophylaxis of bacterial infection the splenectomized children were given penicillin preparations for a period of three years . The OPSI syndrome was not recorded.

Protein Expr Purif, 1992 Oct, 3(5), 403 - 9
Rapid screening of a large number of immobilized textile dyes for the purification of proteins: use of penicillin-binding protein 4 of Escherichia coli as a model enzyme; Mottl H et al.; A rapid method for screening the affinity of proteins to dye-modified resins is described . Performing the binding and elution of the protein extracts in a batch-wise manner and eluting the bound proteins with SDS-PAGE denaturation buffer speed up the screening process and allow the analysis of large collections of dyes . Penicillin-binding protein 4 of Escherichia coli was used as a model enzyme to determine the influences of pH, metal ions, and ionic strength (0 to 500 mM NaCl) on its binding behavior using a collection of 98 dye-affinity resins.

Pharmacol Biochem Behav, 1992 Oct, 43(2), 651 - 6
Inhibitory influence of morphinans on ictal and interictal EEG changes induced by cortical application of penicillin in rabbits: a comparative study with NMDA antagonists and pentobarbitone; Zeng YC et al.; The effects of dextrorphan (DX) and dextromethorphan (DM) were tested using the electroencephalogram (EEG) and behavioral effects induced by topical cortical application of penicillin in rabbits . For comparison, the influence of the NMDA antagonists, dizocilpine (MK 801) and 3-((+-(-)2-carboxypiperazine-4-yl)propyl-1-phosphonic acid (CPP), and of pentobarbitone was investigated . Intracortical injection of 500 IU of penicillin produced an EEG spiking followed by a repeated generalization of the electrical and behavioral symptoms . Within a few minutes, DX (5-15 mg/kg, IV) or pentobarbitone (5-10 mg/kg, IV) reduced dose dependently and significantly (p less than 0.01) the interictal and ictal EEG and behavioral effects elicited by cortical injection of 500 IU of penicillin . Higher doses of pentobarbitone (20 mg/kg, IV) but not of DX (20 mg/kg, IV) completely blocked the ictal behavioral and EEG effects elicited by cortical injection of 500 IU of penicillin . Within a few minutes, MK 801 (0.1-0.2 mg/kg, IV) or CPP (10-20 mg/kg, IV) reduced dose dependently and significantly (p less than 0.01) the ictal EEG and behavioral effects elicited by cortical injection of 500 IU of penicillin, while they did not affect the penicillin-induced interictal EEG changes . Higher doses of MK 801 (0.3 mg/kg, IV) completely blocked the ictal behavioral and EEG effects elicited by cortical injection of 500 IU of penicillin . Within a few minutes, DM (10-20 mg/kg, IV) blocked the behavioral effects, but failed to affect either the interictal or the ictal EEG effects induced by cortical injection of 500 IU of penicillin.(ABSTRACT TRUNCATED AT 250 WORDS)

Genitourin Med, 1992 Oct, 68(5), 334 - 5
An unusual foreign body in the preputial sac; Jaiswal AK; A 28 year old Indian male presented with an unusual foreign body, a penicillin bottle containing tincture of iodine, in the preputial sac . The purpose of introducing the bottle was to tickle his glans penis as a form of masturbation . The bottle was so firmly impacted that it could be removed only under general anaesthesia.

J Bacteriol, 1992 Oct, 174(19), 6270 - 6
Effects of site-directed mutations on processing and activities of penicillin G acylase from Escherichia coli ATCC 11105; Choi KS et al.; Penicillin G acylase from Escherichia coli ATCC 11105 is synthesized from its precursor polypeptide into a catalytically active heterodimer via a complex posttranslational processing pathway . Substitutions in the pair of aminoacyl residues at the cleavage site for processing the small and large subunits were made . Their processing phenotypes and penicillin G acylase activities were analyzed . By the introduction of a prolyl residue at either position, the processing of the small subunit was blocked without a change in enzymatic activity . Four other substitutions had no effect . At the site for processing the large subunit, four substitutions out of the seven examined blocked processing . In general, penicillin G acylase activity seemed to be proportional to the efficiency of the large-subunit-processing step . Ser-290 is an amino acid critical for processing and also for the enzymatic activity of penicillin G acylase . In the mutant pAATC, in which Ser-290 is mutated to Cys, the precursor is processed, but there is no detectable enzymatic activity . This suggests that there is a difference in the structural requirements for the processing pathway and for enzymatic activity . Recombination analysis of several mutants demonstrated that the small subunit can be processed only when the large subunit is processed first . Some site-directed mutants from which signal peptides were removed showed partial processing phenotypes and reduced enzymatic activities . Their expression showed that the prerequisite for penicillin G acylase activity is the efficient processing of the large subunit and that the maturation of the small subunit does not affect the enzymatic activity.

Cancer Res, 1992 Oct 1, 52(19 Suppl), 5510s - 5515s
Prior medication use and health history as risk factors for non-Hodgkin's lymphoma: preliminary results from a case-control study in Los Angeles County; Bernstein L et al.; To determine whether non-Hodgkin's lymphoma (NHL) is related to prior medication use or health history, a population-based case-control study was conducted . A total of 619 male and female residents of Los Angeles County who were diagnosed with NHL between January 1, 1979, and June 30, 1982, were compared to individually age-, race-, and sex-matched neighborhood controls with regard to history of use of 49 different medications, 47 chronic and infectious diseases or other conditions, 15 types of immunizations, and 15 specific allergic reactions . Based on preliminary analyses, long-term regular use of aspirin and other pain relievers and greater than or equal to 2 mo of treatment with penicillin and other antibiotics were associated with significantly increased risk of NHL . Other drugs associated with greater risk of NHL were use of digitalis and estrogen replacement therapy by women, use of corticosteroids, and greater than or equal to 2 mo of use of tranquilizers . NHL was strongly associated with a prior history of cancer . Cases more frequently reported histories of kidney infections and anemia than did controls; a history of eczema appeared to be protective against NHL . Women who had been immunized against polio by injectable vaccine were at significantly lower risk of NHL than women who had not received this immunization . Among men, cholera immunization and allergy to nuts and berries were significantly protective . Subjects who had received a yellow fever immunization also had lower NHL risk . Further analyses of these data will attempt to establish the relative importance of these potential risk factors and to determine whether any are markers of early symptoms of NHL.

J Antimicrob Chemother, 1992 Oct, 30(4), 543 - 50
Erythema migrans: comparison of treatment with azithromycin, doxycycline and phenoxymethylpenicillin; Strle F et al.; Azithromycin, doxycycline and phenoxymethylpenicillin were compared in a prospective, randomized study of 64 patients with typical erythema migrans . Twenty patients were treated with oral azithromycin, 250 mg bd for two days followed by 250 mg od for eight days, 21 patients were given phenoxymethylpenicillin 1 million IU tds for 14 days and 23 patients received doxycycline, 100 mg bd for 14 days . All patients were followed up for 24 months . There were no significant differences between the groups with respect to the persistence of cutaneous lesions after starting treatment; the mean durations were 10.5 days in the penicillin group, 8.8 days in the doxycycline group and 8.6 days in the azithromycin group . There were statistically significant differences in terms of the resolution of associated local and/or systemic symptoms . The response time was shortest in patients treated with azithromycin . Two patients who received phenoxymethylpenicillin and two given doxycycline subsequently developed major manifestations of Lyme borreliosis; these did not occur in patients receiving azithromycin . Although azithromycin has been shown to be effective in the treatment of erythema migrans, further studies will be needed to determine the optimal dosage and duration of therapy.

Rom J Neurol Psychiatry, 1992 Oct-Dec, 30(4), 237 - 42
Effect of hypothermia on focal experimental seizures; Voiculescu V et al.; The effect of general hypothermia was investigated in 15 unanesthetized cats . The animals were immobilized with Flaxedil and maintained on mechanical respiration . An epileptogenic focus was induced by stereo-tactical injection of penicillin to the right hippocampus . Cooling of the body was followed by a marked decrease of the amplitude and frequency of the penicillin spikes . The antiepileptic effect of general hypothermia was not dependent on brain stem section as suggested by previous investigations . Seizures generated by a hippocampic penicillin focus were more resistant to hypothermia than discharges produced by penicillin applied to the visual cortex.

Biull Eksp Biol Med, 1992 Oct, 114(10), 369 - 70
{The antiepileptic effects of sodium valproate and the calcium antagonist riodipine when used jointly in a model of focal penicillin-induced epileptic activity}; Kryzhanovskii GN et al.; In experiments on 52 freely moving Wistar male rats, 200-220 g in weight, on the model of focal penicillin-induced epileptic activity (EpA) in brain cortex the efficacy of combined application of drugs influencing different mechanisms of epileptogenesis: sodium valproate enhancing GABA-ergic processes, and the calcium antagonist ryodipine (1,4-dihydropyridine) have been studied . It was shown that valproate and ryodipine when used in combination at relatively small doses (150 and 0.8 mg/kg l.p., respectively) produced a more marked antiepileptic effect than each of these drugs given alone . These and previously reported results of studies on the model of generalized pentylenetetrazol-induced EpA, suggest that complex pathogenic therapy (CPT) as a combination of the antiepileptic drugs acting on the corresponding basic pathogenic mechanisms of respective form of epilepsy is reasonable to be used . CPT allows to obtain a better curative effect with a lower dose of each drug used and to reduce the risk of side effects of the drugs applied at large doses in case of monotherapy.

Allergy, 1992 Oct, 47(5), 459 - 62
Assessment of histamine release from basophils in whole blood by benzylpenicilloyl poly-L-lysine in penicillin-sensitized patients; Koller DY et al.; Histamine release from basophil granulocytes in whole blood by benzylpenicilloyl poly-L-lysine (PPL) was investigated in 7 patients with penicillin allergy . All patients presented with systemic immediate hypersensitivity reactions after i.v . administration of penicillin G . Total histamine (of 7 patients) ranged from 27.5 ng/ml to 62.1 ng/ml (mean 43.2 ng/ml) . The spontaneous histamine release ranged from 0.15% to 5.1% (mean 1.8%) of the total content . Addition of PPL in various concentrations resulted in values between 0.8 and 9.6% . Although PPL is a reliable allergen for prick- and intradermal testing in the diagnosis of penicillin allergy--demonstrating a histamine liberation in the skin--the in vitro experiment using the same allergen showed no histamine release above 10% . Using a threshold of 5% out of 7 patients, 4 (57%) would show a positive histamine release . Therefore it might indicate that in penicillin allergy a threshold of 5% must be used . In addition, basophils in whole blood and skin mast cells may be activated differently.

Brain Res, 1992 Sep 18, 591(1), 33 - 43
Topographical analysis of epileptiform potentials in rat somatosensory cortex: the interictal to ictal transition; Barth DS et al.; Large quantities of penicillin were applied to the face and forelimb region of rat somatosensory cortex, producing an epileptic focus with both electrographic and behavioral signs of seizures that regularly repeated over a period of several minutes . Epicortical potentials were recorded simultaneously from a 64 channel micro-electrode array (8 x 8 platinum electrodes) with inter-electrode distances of 0.5 mm, covering a 3.5 x 3.5 mm2 area centered on the penicillin injection site . Cluster analysis was used to classify successive epileptiform discharges into interictal, transitional, and ictal groups . Principal components analysis (PCA) was used to extract fundamental waveforms producing the spike complex in each group, and to estimate the locations and spatial extent of neuronal populations participating in epileptiform discharge . During all states of epileptic excitability, it was possible to account for over 90% of the variance in the epicortical potential waveforms using a model with only two spatially overlapping populations of cells . The location and spatial extent of the populations remained unchanged by the transition to seizures; the interictal and ictal states were distinguished only by changes in the timing and amplitude of potentials in the two putative neuronal populations . The present model, using only two stationary neuronal populations to reproduce all spatiotemporal patterns in the neocortical epileptogenic focus, is compared to models proposed by others in which epileptic discharge is thought to propagate sequentially through adjacent cortex . It is concluded that the initiation, maintenance, and termination of seizures in neocortex relies on mechanisms that are not necessarily reflected in changes in spatiotemporal interactions among epicortically recorded cell groups within the focus . These mechanisms may be distinguished from those responsible for the spread of seizures within neocortex.

Tidsskr Nor Laegeforen, 1992 Sep 10, 112(21), 2751 - 2
{Lower respiratory tract infections among the elderly in Finnøy municipality . A retrospective study of the incidence, treatment and outcome}; Bratveit A et al.; Based on a retrospective study of the case records of the primary health care services in a small Norwegian coastal community (Finnoy), we found an incidence of 13% for lower respiratory infections in persons aged 70 years or more . Most often the initial medication was penicillin . In 23% of recorded episodes, medication was changed, owing to unsatisfactory response . Overall mortality in the group was 9% . Three out of five deaths occurred in patients terminally ill from other diseases at the time the respiratory infection started . Problems related to diagnosis, management and prevention are discussed.

J Bacteriol, 1992 Sep, 174(17), 5549 - 59
Effect of D-amino acids on structure and synthesis of peptidoglycan in Escherichia coli; Caparros M et al.; Growth of Escherichia coli in the presence of certain D-amino acids, such as D-methionine, results in the incorporation of the D-amino acid into macromolecular peptidoglycan and can be lethal at high concentrations . Previous studies suggested that incorporation was independent of the normal biosynthetic pathway . An enzymatic reaction between the D-amino acid and macromolecular peptidoglycan was proposed as the mechanism of incorporation . The application of more advanced analytical techniques, notably high-pressure liquid chromatography, revealed that the presence of a D-amino acid susceptible to incorporation induced a multiplicity of alterations in peptidoglycan metabolism . Results derived basically from the study of samples treated with D-Met, D-Trp, and D-Phe indicated that the incorporation of a D-amino acid results in the accumulation of two major new muropeptides whose general structures most likely are GlucNAc-MurNAc-L-Ala-D-Glu-m-diaminopimelic acid-D-aa and GlucNAc-MurNAc-L-Ala-D-Glu-m-diaminopimelic acid-D-Ala-GlucNAc-MurNAc-L-Ala-D-Glu-m-diaminopimelic acid-D-aa, where D-aa represents a residue of the added D-amino acid . Resting cells are proficient in the incorporation of D-amino acids and can reach peptidoglycan modification levels comparable to those in growing cells . Under our conditions, D-amino acids had no apparent effect on growth or morphology but caused a severe inhibition of peptidoglycan synthesis and cross-linking, possibly leading to a reduction in the amount of peptidoglycan per cell . The properties of the reaction support the involvement of a penicillin-insensitive LD-transpeptidase enzyme in the synthesis of modified muropeptides and a possible inhibitory action of D-amino acids on high-molecular-weight penicillin-binding proteins.

Shi Yan Sheng Wu Xue Bao, 1992 Sep, 25(3), 289 - 93
{Studies on the function of Ser579 and Arg580 in beta-subunit of penicillin G acylase with the method of site-specific mutagenesis}; Fei J et al.; According to the comparison of amino acid sequence between PGA (Penicillin G Acylase) and PBPs (Penicillin Binding Protein), We suggest that No . 565-595 peptide fragment in beta-subunit of PGA may be a substrate-binding site of enzyme . Plasmid pTZGA was constructed by cloning the 2.6 kb PGA gene of pWGA into phagemid pTZ18U The technique of site-specific mutagenesis was used to study the role of residue No . 579 (Ser) and No . 580 (Arg) of PGA . Four kinds of mutants were obtained (Ser579-->Gly579, Arg580-->Gly580, Arg580-->Glu580, Arg580-->Lys580), both Glu580 and Gly580 mutants showed no activity of enzyme and Lys580 mutant remained 30% and Gly579 mutant kept 70% activity of wilde type . The same protein expression of four mutants according to the results of ELISA indicate that mutation does not affect the expression of PGA, but Arg580 residue may be essential for substrate-binding or catalysis of PGA.

Med Hypotheses, 1992 Sep, 39(1), 35 - 40
Is syphilis an incurable disease?
Ghinsberg RC, Nitzan Y.
Structures which morphologically resemble treponemes have been found in material from patients suffering from latent or late latent syphilis, many of whom have received treatment in the past . These structures were also found in the blood or spinal fluid (SF) of asymptomatic patients with both positive and negative serological tests for syphilis . They have been found in the eye in the presence of active disease as well as in cases without inflammation ('quiet eye') . In latent syphilis, the presence of treponemes after penicillin treatment raises the question of whether the patient is completely cured of syphilis after treatment . Experimental evidence indicates that continued specific antibody production following penicillin treatment depends on the persistence of the specific antigen in the body . This raised three questions: a) Are these stimuli living treponemes? b) Are they still virulent? c) Is syphilis completely curable following penicillin treatment? Our hypothesis is that slowly dividing treponemes are not killed by penicillin . The persistence of living treponemes somewhere in the body may be the proof of this hypothesis . Cases of relapsing neurosyphilis after penicillin treatment have recently been described . We return to the old dilemma: is it a scar-tissue injury or a reactivation of the disease? Since neurosyphilis is asymptomatic, the patient is usually examined because of seroconversion . Only repeated serological analyses and clinical observations of treated cases with immediate penicillin administration can prevent relapse and damage to the central nervous system (CNS) or to other parts of the body.

J Clin Neuroophthalmol, 1992 Sep, 12(3), 171 - 2
Neuroretinitis due to seronegative syphilis associated with human immunodeficiency virus; Halperin LS; Syphilis serologic testing is felt to be extremely reliable . A case of syphilitic neuroretinitis is reported where serologic testing was negative due to human immunodeficiency virus infection . A prompt response to high-dose intravenous penicillin was achieved.

J Fam Pract, 1992 Sep, 35(3), 327 - 9
Congenital syphilis presenting as desquamative dermatitis; Wood VD et al.; During the last 5 years the incidence of congenital syphilis has increased several-fold and reached epidemic proportions . This increase is directly related to a similar increase in cases of primary and secondary syphilis in women and has been linked to the use of "crack" cocaine . Factors responsible for the increase in reported cases of congenital syphilis include poor prenatal care, implementation of new surveillance case definition, failure to perform serological tests, treatment failures with benzathine penicillin, and maternal reinfection . Clinical manifestation of congenital syphilis are multisystemic but are often absent at birth . We report a case of congenital syphilis missed at birth and later characterized by prominent desquamative dermatitis affecting most of the skin surface.

J Biotechnol, 1992 Sep, 25(3), 245 - 59
Influence of medium composition on penicillin V production in a stirred tank reactor; Moller J et al.; Penicillin production with a high-producing strain Penicillium chrysogenum was investigated under well-controlled conditions in a stirred tank reactor with complex media containing lard oil and lactose on the one hand, and lactose on the other hand . With lard oil, cell growth and product formation rates were higher, and the production time was shorter by 40 h than without lard oil . On account of the longer production time without lard oil, the amount of beta-lactam compounds was higher (29.93 g l-1), but the mole fraction of the decomposed products (penicilloic acid and penilloic acid) was larger (0.282) than the amount of penicillin V (23.25 g l-1) and the decomposed mole fraction (0.0747) with lard oil . The final product concentrations were about the same (20.86 g l-1 or 35,462 IU ml-1 with lard oil, and 20.43 g l-1 or 34510 IU ml-1 without lard oil) . The mole fractions of the by-product (p-OH-penicillin V) were 0.0365 and 0.066 . The substitution of lard oil with lactose is possible without a considerable reduction of process performance.

J Investig Allergol Clin Immunol, 1992 Sep-Oct, 2(5), 240 - 6
Diagnostic capabilities of penicillin-based structures as tools in the in vitro diagnosis of penicillin allergy; Daxun Z et al.; Various penicillin-based structures attached to paper disks were used in the radioallergosorbent test (RAST) to measure concentrations of circulating specific IgE antibodies in sera from subjects suspected of having penicillin allergy . The structures used were penicilloyl, penicillanyl, penicoyl and penicanyl groups prepared from benzylpenicillin (PG), phenoxymethylpenicillin (PV), amoxicillin (AX) and 6-amino-penicillanic acid (6-APA) . The efficacy of these structures was evaluated using serum samples from 53 subjects who, on clinical grounds, were considered to have had adverse reactions to penicillins . The results showed the presence of IgE antibodies specific to the penicillin side-chain in certain patients, whereas others had IgE antibodies specific to the penicilloyl or penicillin basic structure (penicillin nucleus), which led to clinical cross-reactions between penicillins . The results showed that the use of several penicillin-based structures in a new test system increased the positive rate observed to 54.7% from 37.7% utilizing penicilloyl G, penicilloyl V and amoxicilloyl Phadebas RAST . Thus, the prepared species improve the capabilities of the in vitro diagnosis of penicillin allergy.

Antimicrob Agents Chemother, 1992 Sep, 36(9), 1870 - 6
Effects of CO2 and pH on inhibition of TEM-1 and other beta-lactamases by penicillanic acid sulfones; Livermore DM et al.; Incubation in 5% CO2 reduced the inhibition zones of piperacillin-tazobactam (75/10 micrograms) disks for Escherichia coli strains with TEM-1, TEM-2, and SHV-1 beta-lactamases . Similarly, MICs of piperacillin-tazobactam and other penicillin-sulfone combinations for TEM producers were up to 500-fold higher at pH 6.5 than at pH 8.0 . This effect was greatest for organisms with high levels of enzyme activity . CO2 and mild acidity did not affect the susceptibility of beta-lactamase-negative strains to penicillin-sulfone combinations, and the effects of these conditions were variable for organisms with beta-lactamases other than TEM-1, TEM-2, and SHV-1 . These last observations discounted acid-mediated inactivation of piperacillin or tazobactam . MICs of amoxicillin or piperacillin alone or with clavulanate for TEM and SHV producers were affected only less than or equal to 16-fold by 5% CO2 or acidity, indicating that the greater effects seen with the penicillin-sulfone combinations depended on the behavior of the sulfones and not on that of the penicillins . This pH effect was studied in detail for TEM-1 enzyme . Inhibition of this enzyme by sulfones but not clavulanate varied grossly with pH, with 50% inhibitory concentrations of tazobactam and sulbactam up to 300-fold higher at pH 6.5 than at 8.0 . By contrast, the hydrolytic activity of TEM-1 enzyme for substrates and its level of production varied threefold or less between pH 6.5 and pH 8.0 . Increased inhibition at pH 8.0 reflected sequestration of the enzyme into a secondary noncovalent complex rather than increased irreversible inactivation.

Zhonghua Nei Ke Za Zhi, 1992 Sep, 31(9), 526 - 9, 585
{Skin tests in patients with history of anaphylactic reaction to penicillin}; Wen ZM et al.; Skin tests including immediate patch test (IPT), skin prick test (SPT), or intradermal test (IT) with penicillin G(PenG) and SPT with benzylpenicilloyl human serum albumin (BPO) were done in 54 patients with history of anaphylactic reaction to penicillin or shock of unknown cause . 26 patients with penicillin allergy were diagnosed . BPO specific IgE measured with ELISA gave a lower positive rate in detecting penicillin allergy as compared with the tests mentioned above . The results of skin tests in 26 patients showed that IPT with 500 IU/ml of PenG was not only accurate but also safe . Because no skin injury occurred and PenG residue could be washed out, the amount of PenG penetrated into skin is very small, thus, adverse reactions were very few . It is recommended that IPT with PenG in 500 IU/ml concentration is performed at the beginning of skin tests . If negative, SPT and then IT both with a solution of 500 IU/ml concentration are carried out, until a positive reaction occurs . This procedure is relatively accurate, simple and safe.

P N G Med J, 1992 Sep, 35(3), 194 - 6
Determining drug dosages by height: applying a model made for coastal children in Papua New Guinea to children from the highlands; Zind BJ; A height scale for the determination of drug dosages in children of the Madang area was applied to children from the Nipa area of the Papua New Guinea highlands . In only 13 out of 1314 children (1.0%) did the use of the height scale result in drug doses below the recommended minimum dose per kilogram of bodyweight . The scale can therefore be used safely for highlands children in areas where facilities for accurate weighing are not availablePIP: This study was designed to determine if the Madang scale would be accurate if used on children in the Nipa Basin in the Southern Highlands Province, Papua New Guinea . During July-August 1986, students from community schools in the district were weighed using a CMS beam balance and measured with a standard height stick . Heights and weights of children from the 1983 provincial nutrition survey in the Nipa Basin were used to represent a sample of children under 5 years of age . Weights for the survey were taken using a Salter's scale . Heights were taken using a height stick . Dosages of chloroquine, amodiaquine, and procaine penicillin for each child were determined for height using the measurements from the Madang study and compared with dosages determined by weight using the weight extremes from the nutrition survey and the local school survey for each height range . These dosages were then compared with a standard therapeutic dose of 7-17 mg/kg of amodiaquine and 25,000-50,000 IU/kg/day of penicillin . Of the 1314 children included, 4 (0.3%) received doses of amodiaquine that were outside the therapeutic range of 7-17 mg/kg . All of these children were 63-64 cm in height, with weights ranging from 7.2 to 8.6 kg . All of the children would have been potentially underdosed with dosages ranging from 5.8 to 6.9 mg/kg . Dosages for procaine penicillin using the height scale ranged from 22,500 IU/kg to 103,500 IU/kg . The range when dosage was determined by weight was 30,000-100,000 IU/kg . Of the 605 children measuring between 120 and 137.9 cm in height, 9 fell below the minimum recommended dose of 25,000 IU/kg/day . The lowest dose was 22,500 IU/kg/day; 7 of the others would have been dosed between 24,000 and 25,000 IU/kg/day . The height scale is a simple, accurate, and economic tool to determine drug dosages in children .

East Afr Med J, 1992 Sep, 69(9), 542 - 3
Rat bite fever: a case report of a Kenyan; Bhatt KM et al.; Rat bite fever has not been reported from Kenya previously . A case of 17 year old Kenyan male who was diagnosed to have rat bite fever after a bite of domestic rat is described . The history, clinical features and demonstration of spirillum like organisms from a thick blood film suggest infection due to spirillum minus . The patient recovered completely after a course of penicillin and gentamicin.

Ugeskr Laeger, 1992 Aug 31, 154(36), 2438 - 9
{Leptospirosis . A disease with non-specific initial symptoms}; Norgard B et al.; A case of leptospirosis in a young fish-farm worker is described . Early penicillin therapy was initiated solely on the clinical suspicion of the disease . The importance of recognition of the disease is emphasized together with early institution of penicillin therapy and effective eradication of vermin.

J Immunol Methods, 1992 Aug 30, 153(1-2), 99 - 105
Determination of IgE antibodies to the benzyl penicilloyl determinant . A comparison between poly-L-lysine and human serum albumin as carriers; Blanca M et al.; The influence of two different carriers, poly-L-lysine (PLL) and human serum albumin (HSA) in the binding of specific IgE antibodies to the benzyl penicilloyl hapten (BPO) was determined in a solid-phase assay . Serum samples from patients with a history of immediate reaction to penicillin and which had shown the presence of IgE antibodies to BPO were used . Benzyl penicilloyl derivatized cellulose discs were prepared using PLL of different molecular weight and HSA as carriers . These were treated with different molar ratios of benzyl penicillin . These reagents were compared for uptake of BPO-specific IgE using a pool of sera in a radioallergosorbent test (RAST) type assay . Two PLL systems and two HSA systems were finally compared using 26 individual sera . RAST values were compared by Kruskal-Wallis and Wilcoxon tests . The relationships between the four different assays were evaluated by determining Pearson correlation coefficients and the concordance by determining intraclass correlation coefficients (ICC) . Analysis of means by the Wilcoxon test revealed significant differences (P less than 0.01) only when the different carrier assays were compared . The correlation coefficients between all the assays were significant (P less than 0.0001), but the ICC was low when the different carrier assays were compared . These results indicate that the nature of the carriers studied (PLL and HSA) influences the capacity for binding IgE antibodies in the RAST procedure . The differences observed indicate that one conjugate cannot be substituted for the other in the determination of IgE antibodies to BPO and that BPO-PLL is preferable.

Schweiz Med Wochenschr, 1992 Aug 29, 122(35), 1271 - 4
{Palpable purpura}; Hoigne R et al.; Non-thrombocytopenic palpable purpura is a characteristic lesion of cutaneous leukocytoclastic vasculitis . In association with manifestations in the gastrointestinal tract, kidney and/or joints, it forms the clinical entity of Henoch-Schonlein purpura . Among 27,510 inpatients in the years 1974 to 1989 from the CHDM Berne/St . Gallen, 2 developed one, and a further patient as many as 4 episodes of leukocytoclastic vasculitis limited to the skin, which were probably related to drugs (most often compounds containing a sulfonamide, related structures or a penicillin) . In contrast, among 8 additional cases from the same cohort, in which Henoch-Schonlein syndrome was diagnosed on admission to hospital, a drug etiology was suspected only in one patient . In these patients an involvement in addition to that of the skin of at least two other organ systems was documented . In our experience, a drug etiology should be considered in every case of leukocytoclastic vasculitis, but will mainly be validated in cases in which the lesions are limited to the skin.

Am J Gastroenterol, 1992 Aug, 87(8), 1040 - 2
Endoscopic detection and therapy of colonic actinomycosis; Piper MH et al.; Abdominal actinomycosis is a disease that is difficult to diagnose nonoperatively . Usual manifestations are abscesses and draining sinus tracts . Treatment is typically surgical and requires prolonged intravenous antibiotics . Presented is a patient who underwent surveillance colonoscopy after resection for colon carcinoma . Diagnosis of colonic actinomycosis and subsequent resolution was demonstrated endoscopically after lengthy oral penicillin therapy (2 g/day for 1 yr) . This case documents that resection may not be necessary to effect cure of abdominal actinomycosis.

Br J Psychiatry, 1992 Aug, 161, 251 - 4
Neurosyphilis and schizophrenia; Sivakumar K et al.; Neurosyphilis continues to present in atypical forms, leading to erroneous diagnoses by physicians and psychiatrists . This patient, with a previous history of psychosis, presented in a catatonic state with rhabdomyolysis and renal failure . A subsequent breakdown was thought to be schizophrenic until unusual features led to a reassessment and discovery of neurosyphilis which was treated with penicillin and resulted in a remarkable clinical recovery.

Clin Invest Med, 1992 Aug, 15(4), 376 - 83
Newborn screening for sickle cell and other hemoglobinopathies: a Canadian pilot study; Yorke D et al.; We estimated incidence of HbS disease in Quebec . It is approximately 9 cases per 100,000 births (equivalent to the incidence of the hyperphenylalanemias) . Accordingly, we performed a voluntary pilot study in 9 self-identified ethnic groups; 3528 families were counselled about the relevance of newborn screening for hemoglobinopathies; and 2779 cord blood samples were collected (participation rate, 78.7%) and analyzed for Hemoglobin S and other hemoglobin variants by cellulose acetate electrophoresis . There were 95 (3.42%) positive tests on the initial (cord blood) samples, of which only 40 could be confirmed because of low participation in follow-up . We identified 8 false-positive tests; 7 had been classified initially as alpha-thalassemia trait and one as HbC heterozygosity on the first test . The relative frequency of hemoglobinopathy genes (confirmed) was: 52.5% HbS; 22.5% alpha-thalassemia; 22.5% other mutation; all but one patient with sickle cell disease were heterozygotes; the majority (71%) of HbS genes were accounted for by the 7% of screened newborns who were Black; a further 24% of the HbS genes were accounted for by 7% with Central American ancestry . Record linkage of the findings in heterozygotes for use later in life is an unsolved problem . Seventy five first-degree relatives of the 48 probands were screened in follow-up studies (64% of parents participated); 5 couples at risk for having a future child with a hemoglobinopathy were identified . Attitudes toward follow-up varied among the ethnic groups . The single family with an affected newborn (sickle cell anemia) was counselled effectively; the infant received penicillin prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Versicherungsmedizin, 1992 Aug 1, 44(4), 119 - 25
{Toxic polyneuropathies}; Neundorfer B; Toxic factors may have damaging effects on the peripheral nerves at different sites: on the axon, on the myelin sheath, on the cell bodies and on the vasa nervorum . The toxic neuropathies can be divided up into polyneuropathies induced by drugs, by industrial, environmental and stimulant poisons . Mostly symmetrical sensory symptoms and signs are the first disturbances, often followed by symmetrical motor pareses . Some polyneuropathies induced by amiodarone, benzene, lead, cimetidine, chloroquine, dapsone, gentamycin, gold, imipramine, hexacarbons, nialamide, penicillin, triorthocresylphosphate and vincristine are primarily dominated by motory losses . Polyneuropathies induced by amitriptyline, ethylene, oxide, lead, chlorprothixene, heroin, hydralazine, methaqualone, nialamide and penicillin show an asymmetrical distribution pattern of the neural losses . In some types of toxic polyneuropathies the cranial nerves and the autonomic nerves are particularly involved . The clinical symptomatology of the most important types of toxic neuropathies are described shortly . The best therapy is, of course, termination of exposure to the toxic substance concerned.

S Afr Med J, 1992 Aug, 82(2), 123 - 5
History of medicine . Paulesco; James T; Nicolas Constantine Paulesco achieved the unrecognised distinction of proving that an unknown but constituent factor of the pancreas controls the physiological value of the blood-sugar of a normal animal and that its absence is the cause of diabetes mellitus . His research in this particular field of medicine was carried out on dogs and his proof was the culmination of years of experimental work of precursors, colleagues and himself . This great advance, perhaps equivalent in some respect to the discovery of the therapeutic virtue of penicillin, remains unacknowledged . An exposition of the facts attendant upon this neglect follows . The reader is left to draw his or her own conclusion regarding the award of the Nobel Prize for Medicine in 1923.

Can J Microbiol, 1992 Aug, 38(8), 758 - 63
Regulation of alpha-aminoadipate reductase from Penicillium chrysogenum in relation to the flux from alpha-aminoadipate into penicillin biosynthesis; Lu Y et al.; The activity and regulation of alpha-aminoadipate reductase in three Penicillium chrysogenum strains (Q176, D6/1014/A, and P2), producing different amounts of penicillin, were studied . The enzyme exhibited decreasing affinity for alpha-aminoadipate with increasing capacity of the respective strain to produce penicillin . The enzyme from all three strains was inhibited by L-lysine, and the enzyme from the lowest producer, Q176, was least sensitive . Between pH 7.5 and 6.5, inhibition of alpha-aminoadipate reductase by L-lysine was pH dependent, being more pronounced at lower pH . The highest producer strain, P2, displayed the lowest alpha-aminoadipate reductase activity at pH 7.0 . In Q176, the addition of 0.5-1 mM of exogenous lysine stimulated penicillin formation, whereas the same concentration was ineffective or inhibitory with strains D6/1014/A and P2 . The addition of higher (up to 5 mM) lysine concentrations inhibited penicillin production in all three strains . In mutants of P . chrysogenum D6/1014/A, selected for resistance to 20 mM alpha-aminoadipate, highest penicillin production was observed in those strains whose alpha-aminoadipate reductase was most strongly inhibited by L-lysine . The results support the conclusion that the in vivo activity of alpha-aminoadipate reductase from superior penicillin producer strains of P . chrysogenum is more strongly inhibited by lysine, and that this is related to their ability to accumulate increased amounts of alpha-aminoadipate, and hence penicillin.

Respir Physiol, 1992 Aug, 89(2), 225 - 37
Neural respiratory responses to cortically induced seizures in cats; Paydarfar D et al.; Seizure activity can lead to profound respiratory stimulation in spontaneously breathing animals with intact respiratory feedback mechanisms (Paydarfar et al., Am . J . Physiol . 260, R934, 1991) . The present study was designed to test the hypothesis that peripheral respiratory feedback mechanisms are not important for the genesis of seizure-induced hyperpnea . Studies were performed in 16 anesthetized, vagotomized, glomectomized cats whose end-tidal PCO2 (PETCO2) was kept constant . Integrated phrenic nerve activity was used to represent respiration . Seizures were induced by injection of penicillin into the parietal cortex and electrocorticographic (ECoG) and biceps femoris nerve activities, arterial pressure, airway PCO2 and brain temperature were recorded continuously . Progressive seizure activity was associated with progressive increases of respiratory frequency and peak phrenic activity, despite constancy of PETCO2 and brain temperature . Patterns of entrainment were identified among ECoG spikes, biceps femoris nerve and phrenic nerve activities . Phrenic nerve activity became highly irregular during generalized ictal seizures and ceased to respond to changes of PETCO2 . Acute intercollicular decerebration in all experiments resulted in normalization of respiratory rhythm even while ictal ECoG activity continued . We conclude that stimulation of breathing during seizures occurs in the absence of respiratory feedback mechanisms . The findings suggest that an important cause of the respiratory response is a feedforward mechanism, whereby activation of subcortical structures above medulla and pons results in stimulation of breathing.

Ann Rheum Dis, 1992 Aug, 51(8), 1007 - 8
Long term treatment of chronic Lyme arthritis with benzathine penicillin; Cimmino MA et al.; The cases are reported of two patients with chronic Lyme arthritis resistant to the recommended antibiotic regimens who were cured by long term treatment with benzathine penicillin . It is suggested that the sustained therapeutic levels of penicillin were effective either by the inhibition of germ replication or by lysis of the spirochaetes when they were leaving their sanctuaries.

Thorax, 1992 Aug, 47(8), 664 - 5
Endobronchial actinomycosis mimicking pulmonary neoplasm; Lau KY; A 60 year old man had recurrent pneumonia . Bronchoscopy disclosed a necrotic mass in the left lower lobe bronchus, which histological examination showed to contain sulphur granules . The endobronchial mass had disappeared by the second bronchoscopy one week later . The patient was treated with penicillin for one year and was cured . Actinomycosis must be included in the differential diagnosis of an endobronchial mass.

Mol Microbiol, 1992 Aug, 6(15), 2175 - 82
Carbon regulation and the role in nature of the Escherichia coli penicillin acylase (pac) gene; Merino E et al.; Quantitative analysis of specific pac mRNA and a lacZ fusion to the 5'-terminal region of the pac gene demonstrated that both phenylacetic acid induction and catabolite repression by glucose are involved, at the transcriptional level, in the regulation of the pac gene . The studies presented here suggest that this regulation is also present in Escherichia coli transformed strains in which the pac gene was not originally present . Analysis of the nucleotide sequence of the 5'-terminal region of this gene, with a statistical algorithm, confirms that the putative promoter previously proposed by our group is the most feasible within this region . We demonstrate that penicillin acylase activity can confer on E . coli the ability to use penicillin G as a metabolic substrate, by detaching the phenylacetic group which can be used as a carbon source . Based on these data, the regulation properties of the pac gene studied in this work, and the specificity profile of the penicillin acylase enzyme we suggest a role for it in E . coli as a scavenger enzyme for phenylacetylated compounds.

Br J Dermatol, 1992 Aug, 127(2), 155 - 9
Roxithromycin versus penicillin in the treatment of erysipelas in adults: a comparative study; Bernard P et al.; A prospective, randomized, multicentre trial was conducted to evaluate the efficacy and safety of roxithromycin (150 mg b.i.d . orally) and penicillin (2.5 MU x 8 daily intravenously, then 6 MU daily orally) in the treatment of hospitalized adult patients with erysipelas . Seventy-two patients entered the study . Thirty-one patients in the roxithromycin group and 38 patients in the penicillin group completed the trial . The overall efficacy rates (cure without additional antibiotics) were 84% (26/31) in the roxithromycin group and 76% (29/38) in the penicillin group (P = 0.43) . No side-effects were observed in the roxithromycin-treated patients whereas rashes occurred in two cases in the penicillin group, leading to exclusion from the study . Oral roxithromycin can thus be considered an effective and well-tolerated treatment for erysipelas in adult hospitalized patients.

Br J Anaesth, 1992 Aug, 69(2), 177 - 81
Propofol anticonvulsant activity in experimental epileptic status; De Riu PL et al.; We have examined the anticonvulsant properties of propofol in high doses in two experimental models of status epilepticus: generalized pentylenetetrazol (PTZ)-induced seizures and partial, cortically applied penicillin G-induced seizures . Propofol was administered either as a single bolus injection or as a bolus injection followed by an infusion for 1 h . When administered as a single bolus injection, propofol 12 mg kg-1 suppressed electrical and clinical seizures in PTZ generalized epileptic status, and an infusion of 50 mg kg-1 h-1 prevented the reappearance of electrical and clinical signs . In focal epileptic status, the single dose stopped paroxysmal activity and the associated clonic jerks for a few seconds . When the bolus dose was followed by an infusion, the firing bursts were replaced by isolated spikes, and contralateral jerks became sporadic and feeble . The greater efficacy of propofol against PTZ convulsions may be a reflection of the opposite action of the two drugs on neural membrane conductance: PTZ induces paroxysmal neural discharge by enhancing membrane conductance while propofol appears to decrease membrane conductance, thus suppressing paroxysmal discharge . There was no close relationship between blood concentration of the anaesthetic and its clinical effects, at least after a short-term infusion, as used in the present experiments . We suggest that propofol may be a potentially useful drug in status epilepticus in patients in whom benzodiazepines, barbiturates and phenytoin have failed.

Bioorg Khim, 1992 Aug, 18(8), 1073 - 80
{Regulation of the catalytic activity and supermolecular structure of penicillin acylase from Escherichia coli in an aerosol OT reversed micelle system in octane}; Kabakov VE et al.; The properties of penicillin acylase from E . coli solubilized by hydrated reversed micelles of Aerozol OT (AOT) in octane were studied . The catalytic activity dependence on the hydration degree, a parameter which determines the size of the micelle inner cavity, represents a curve with three optima, each corresponding to the enzyme functioning either in a dimer form (omega 0 = 23) or in the form of separate subunits--heavy, beta, and light, alpha, at omega 0 = 20 and 14, respectively . Reversible dissociation of the enzyme was confirmed by ultracentrifugation followed by electrophoresis . Preparative isolation of penicillin acylase subunits, their catalytic activity being retained, was shown to be possible.

J Bacteriol, 1992 Jul, 174(14), 4689 - 700
A new mercury-penicillin V derivative as a probe for ultrastructural localization of penicillin-binding proteins in Escherichia coli; Paul TR et al.; The precise ultrastructural localization of penicillin-binding protein (PBP)-antibiotic complexes in Escherichia coli JM101, JM101 (pBS96), and JM101(pPH116) was investigated by high-resolution electron microscopy . We used mercury-penicillin V (Hg-pen V) as a heavy-metal-labeled, electron-dense probe for accurately localizing PBPs in situ in single bacterial cells grown to exponential growth phase . Biochemical data derived from susceptibility tests and bacteriolysis experiments revealed no significant differences between Hg-pen V and the parent compound, penicillin V, or between strains . Both antibiotics revealed differences in the binding affinities for PBPs of all strains . Deacylation rates for PBPs were slow despite the relatively low binding affinities of antibiotics . Cells bound most of the Hg-pen V added to cultures, and the antibiotic-PBP complex could readily be seen by electron microscopy of unstained whole mounts as distinct, randomly situated electron-dense particles . Fifty to 60% of the antibiotic was retained by cells during processing for conventional embedding so that thin sections could also be examined . These revealed similar electron-dense particles located predominantly on the plasma membrane and less frequently in the cytoplasm . Particles positioned on the plasma membranes were occasionally shown to protrude into the periplasmic space, thereby reflecting the high resolution of the Hg-pen V probe . Moreover, some particles were observed free in the periplasm, suggesting, for the first time, that a proportion of PBPs may not be restricted to the plasma membrane but may be tightly associated with the peptidoglycan for higher efficiency of peptidoglycan assembly . All controls were devoid of the electron-dense particles . The presence of electron-dense particles in cells of the wild-type JM101, demonstrated that our probe could identify PBPs in naturally occurring strains without inducing PBP overproduction.

Am J Obstet Gynecol, 1992 Jul, 167(1), 56 - 8
Nonimmune hydrops fetalis associated with maternal infection with syphilis; Barton JR et al.; Intrauterine infection with syphilis was diagnosed by reactive maternal serologic studies, ultrasonographic findings, and exclusion of other causes in three hydropic fetuses at 31, 34, and 35 weeks' gestation . With penicillin therapy and preterm delivery all infants survived through the perinatal period . Intrauterine infection that follows syphilis is a potentially treatable cause of nonimmune hydrops.

Cas Lek Cesk, 1992 Jul 10, 131(13), 402 - 4
{Actinomycosis of the ovary as a cause of cachexia in a young patient}; Jensovsky J et al.; The authors describe the case of a 40-year-old female patient treated for prolonged periods unsuccessfully with several antibiotics on account of a febrile condition of obscure aetiology and subsequently repeatedly subjected to laparotomy on account of intra-abdominal abscesses . The cause of the fever, abdominal pain and gradual cachectization was an abdominal form of actinomycosis . After establishment of the diagnosis the patient was successfully treated by long-term penicillin administration and recovered completely . The authors discuss experience reported in the literature and therapeutic possibilities in actinomycosis.

J Immunol Methods, 1992 Jul 6, 151(1-2), 269 - 75
Improved enzyme immunosorbent assay for mouse prolactin using penicillinase as label; Tomita Y et al.; Enzyme immunosorbent assay (EIA) for mouse prolactin was established by modifying a method originally developed for human prolactin by Shrivastav et al . This simple, sensitive, rapid, and reproducible assay utilizes penicillinase as the labeling enzyme, rabbit anti-mouse prolactin antibody (Ab) and goat anti-rabbit Ig Ab as the first and second antibodies . Prolactin reference preparations and enzyme-conjugated prolactin were mixed with the first Ab and incubated for 0.5 h at 4 degrees C (24-48 h for serum samples) . Then, the sample mixture was transferred to the wells of microtiter plate coated with the second Ab . After being kept at room temperature for 2 h, the plate was washed and filled with substrate solution (penicillin V) . Absorbance at 620 nm was measured with an ELISA reader to quantitate the amount of conjugated prolactin bound to the second Ab . The prolactin levels obtained by this assay exhibited good correlation with those measured by radioimmunoassay (RIA) (y = 0.95x + 9.14, r = 0.943), and the sensitivity of EIA was equivalent to that of RIA (1.7 ng/ml) . The CVs of intra-assay and inter-assay by EIA for mouse serum samples ranged comparably to those by RIA.

Eur J Biochem, 1992 Jul 1, 207(1), 97 - 102
Site-directed mutagenesis of the Streptomyces R61 DD-peptidase . Catalytic function of the conserved residues around the active site and a comparison with class-A and class-C beta-lactamases; Hadonou AM et al.; The importance of various residues in the Streptomyces R61 penicillin-sensitive DD-peptidase has been assessed by site-directed mutagenesis . The replacement of the active Ser62 by a Cys residue yielded an inactive protein which was also unable to recognize penicillin . The activity of the Lys65----Arg mutant with the peptide and thiolester substrates was decreased 100-200-fold and the rate of penicillin inactivation was decreased 20,000-fold or more . The mutant thus behaved as a poor, but penicillin-resistant, DD-peptidase . The other studied mutations, the mutations Phe58----Leu, Tyr90----Asn, Thr101----Asn, Phe164----Ala, Asp225----Glu and Asp225----Asn had little influence on the catalytic and penicillin-binding properties . The Asp225 mutants did not exhibit an increased sensitivity to cefotaxime . The Phe164----Ala mutant was significantly more unstable than the wild-type enzyme.

J Bacteriol, 1992 Jul, 174(14), 4829 - 32
Purification and partial characterization of a penicillin-binding protein from Mycobacterium smegmatis; Basu J et al.; Penicillin-binding proteins (PBPs), although characterized from several organisms, have so far not been studied in mycobacteria . The present study is the first characterization of a PBP from Mycobacterium smegmatis . The PBP was purified by solubilization of the membranes with Triton X-100 and successive chromatography of the solubilized proteins on ampicillin-linked CH Sepharose 4B and DE-52 . The purified PBP (M(r), 49,500) catalyzed a model transpeptidase reaction with the tripeptide acetyl2-L-Lys-D-Ala-D-Ala as the substrate and Gly-Gly as the acceptor . The transpeptidase activity was inhibited by 50% at a benzylpenicillin concentration of 1.8 x 10(-7) M, which was similar to the concentration (1.1 x 10(-7) M) of benzylpenicillin required to saturate to 50% this PBP . Of several antibiotics tested, the concentration of antibiotic required to inhibit {35S}penicillin binding by 90% was found to be the lowest for cefoxitin and Sch 34343.

Neurology, 1992 Jul, 42(7), 1282 - 7
Syphilitic cerebral gumma with HIV infection; Berger JR et al.; We describe two human immunodeficiency virus (HIV)-infected patients with syphilitic cerebral gummas . Both patients presented with a seizure disorder associated with an isolated, peripherally located, contrast-enhancing lesion of the brain on CT . Cranial MRI performed on one patient revealed dural thickening in the region of the lesion . A brain biopsy in that patient revealed a lymphoplasmacytic infiltrate with extensive perivascular inflammation . Clinical manifestations, radiographic resolution of the lesions, and a decline in nontreponemal serologic tests for syphilis followed high-dose aqueous penicillin therapy in both patients . These patients illustrate that (1) cerebral mass lesions occurring with HIV infection may result from syphilis; (2) seizures may be the presenting manifestation of this form of neurosyphilis; and (3) high-dose, intravenous, aqueous penicillin is effective in treating these lesions.

J Infect, 1992 Jul, 25 Suppl 1, 99 - 103
A family outbreak of Chlamydia pneumoniae infection; Ghosh K et al.; Chlamydia pneumoniae, a newly described Chlamydia species, has been shown to be a cause of acute respiratory tract infection in both adults and children, but its role in human infection is still under investigation . Here we present a family outbreak of C . pneumoniae infection where three members of a family presented with a 'flu-like illness' and acute upper respiratory tract infection which did not improve despite penicillin or septrin therapy . No history of exposure to birds, pets or animals was obtained . As C . pneumoniae isolation from respiratory secretions is not without difficulty, diagnosis usually relies currently on serum-based tests . In this study C . pneumoniae specific IgM determined by the micro-immunofluorescence test was detected in the three clinical cases . All three cases had an elevated complement-fixing antibody titre to Psittacosis-LGV antigen, which may have suggested psittacosis, if type-specific tests had not been performed . In addition, three other members of the family had C . pneumoniae-specific IgG antibody although specific IgM was absent . These three younger members of the family had been symptomatic in the month preceding symptoms in their older sibling and their parents . All the symptomatic members of the family made a complete recovery on tetracycline therapy.

Arch Ital Biol, 1992 Jul, 130(3), 167 - 77
Activity of cat cerebellar neurons in penicillin epilepsy and amphetamine treatment; Culic M et al.; The discharge pattern of cerebellar Purkinje cells and fastigial neurons was studied after acute amphetamine treatment in immobilized cats, as well as during generalized penicillin-induced epilepsy . There was a marked reversible decrease in spontaneous firing rate of Purkinje cells and an increase in spontaneous firing rate of fastigial neurons after acute d-1 amphetamine administration (5 mg/kg, s.c.) . The discharge pattern of Purkinje cells showed tendency towards inhibition, while the fastigial neurons showed less clear tendency towards disinhibition in the course of epilepsy induced by parenteral administration of penicillin (400.000-500.000 I.U./kg, i.m.) . Moreover, acute amphetamine treatment (5 mg/kg, s.c.) performed after the development of penicillin-induced epileptic episodes elicited a prominent suppression of Purkinje cell discharges associated with a parallel increase in discharges of fastigial neurons . These results suggest that the changes in discharge rate of cerebellar corticonuclear neurons induced by amphetamine contribute to suppression of seizural activity in the feline model of generalized epilepsy.

Ann Pharmacother, 1992 Jul-Aug, 26(7-8), 985 - 90
Hepatic and renal dysfunction following nafcillin administration; Lestico MR et al.; OBJECTIVE: To review four cases of combined hepatic and renal toxicity that may be associated with the administration of nafcillin in adults . This type of adverse event with the use of nafcillin has not been previously documented in the literature . DATA SOURCES: References from pertinent articles are identified throughout the text . DATA SYNTHESIS: Nafcillin is a widely used penicillinase-resistant penicillin . In four patients receiving nafcillin doses greater than 9 g/24 hours, changes in renal and hepatic function markers were noted within 72 hours of the initiation of nafcillin therapy . Laboratory values returned toward baseline when nafcillin therapy was discontinued . Elevations in blood urea nitrogen, creatinine, total bilirubin, and lactate dehydrogenase have been previously described in the literature for penicillin-like agents other than nafcillin . The exact mechanism for such toxicities as well as patient risk factors have not been clearly established . CONCLUSIONS: Caution should be taken when initiating nafcillin therapy . Evaluation of renal and liver function tests prior to initiating nafcillin therapy and within the first 72 hours appears warranted . If hepatic and/or renal toxicity is observed, discontinuation of nafcillin should be considered.

Transfusion, 1992 Jul-Aug, 32(6), 554 - 6
Detection of cell-drug (hapten)-antibody complexes by the gel test; Salama A et al.; Most drugs causing immunocytopenias do not bind firmly to the affected cells . Consequently, the drug-dependent antibodies in such cases are completely removed from their binding sites by conventional cell washing . It has recently been shown that such cell-drug-antibody complexes do survive the washing procedure, if the drug (metabolite) was included in the wash medium . The study reported here used the microtube gel test to reexamine the reactivity of different drug-dependent red cell antibodies: cefotaxime (n = 1), carbimazole (n = 1), cianidanol (n = 1), diclofenac (n = 3), penicillin (n = 3), and nomifensine (n = 10) . Whether the drug tested binds (penicillin, cianidanol, carbimazole, and diclofenac) or does not bind (cefotaxime and nomifensine) firmly to the cells, the resultant cell-drug-antibody complex could be recognized on and/or in the gel after it was separated from the mixture containing the drug by means of centrifugation alone and without washing . It is concluded that the gel test might be of value not only for the detection of drug-dependent antibodies, but also for the analysis of subtle drug--cell interactions.

Biull Eksp Biol Med, 1992 Jul, 114(8), 126 - 8
{Epileptiform activity in the somatosensory cortex of rats with trigeminal neuralgia}; Kryzhanovskii GN et al.; It was shown in experiments on rats that penicillin 1 microliter microinjection (100 U) into the caudal nucleus of the spinal tract of the trigeminal nerve, accounting for formation of a generator of pathologically enhanced excitation (GREE), brings about in rats the pain syndrome with characteristic for trigeminal neuralgia behavioural manifestations and the emergence of epileptiform activity in the somatosensory cortex, especially pronounced in the contralateral hemisphere . The emergence of this activity reflects, on the one hand, the action of the GREE in the caudal nucleus of the trigeminal nerve and, on the other hand, the involvement of the somatosensory cortex taking over stimulation from the hyperactive caudal nucleus, into formation of a pathological algic system of this form of trigeminal neuralgia.

Pediatr Med Chir, 1992 Jul-Aug, 14(4), 415 - 20
{Rheumatic fever from 1960's to 1990's . Case records in 2 hospitals of the Lombardian area}; Pugno Vanoni MC et al.; An epidemiological study of rheumatic fever (RF) has been done . Incidence and prevalence of RF observed in Monza Hospital from 1964 to 1990 and in Como Hospital from 1980 to 1990 both show a progressive reduction . An exception to this trend was observed in 1986 in Monza in 1985 in Como . The percentage of carditis in pediatric age is high (60-70%), often associated with arthritis and chorea . However carditis clinical picture seems nowadays less severe, probably because in the past the diagnosis was delayed . Sice 1980 no death were observed due to RF or related cardiac involvement . Relapses and residual valvulopathies are significantly reduced only when penicillin prophylaxis was correctly performed.

Biull Eksp Biol Med, 1992 Jul, 114(7), 56 - 8
{Prolonged action of tuftsin in penicillin epilepsy}; Popova NS et al.; The free behaviour experiments on rats showed during the first day the tuftsin-induced (0.3 mg/kg i . p.) increment of epileptic discharge in all the structures simultaneously . Open field behaviour depended on the sequence of penicillin and tuftsin injections . The rats with tuftsin used after the epileptiformic activity has been developed showed the behaviour analogical to the penicillin-injected animals . The preventive injections of tuftsin resulted in restoration of all behavioural indications by the third day . The optimal corrective effect has been obtained with tuftsin used preventively.

No To Shinkei, 1992 Jul, 44(7), 645 - 8
{A case of general paresis with marked improvement of cerebral blood flow after antiluetic therapy--case report}; Takahashi M et al.; Although the incidence of neurosyphilis has declined dramatically after the World War II because of the development of antibiotics, it is recently increasing a little bit . There has been few reports on the neuroimaging of general paresis . We studied a fresh case of general paresis by X-ray CT (XCT), MRI and PET scans, and report the changes of neuroimages before and after the therapy . A 38-year-old man was admitted with disorientation, thought disorder and personality change . He also had insomnia and megalomania . There were neither obvious neurological signs nor particular changes of the XCT scan abnormalities on admission . His clinical symptoms were gradually worsened within three months, when the XCT and MRI scans showed moderate brain atrophy especially in the frontal and temporal lobes with mild dilatation of the lateral ventricles . In the PET study, the cerebral blood flow was decreased in the entire brain, especially in the frontal lobes, although the thalamus and the basal ganglia had normal levels . By immunological procedures and the cerebrospinal fluid (CSF) studies, the diagnosis of general paresis was made . He was treated with penicillin G and other antibiotics . In one year after his first therapy, many symptoms vanished . Although the cerebral atrophy was a little advanced, the cerebral blood flow was dramatically increased . As far as we know, this is the first PET study of general paresis before and after penicillin treatments.

Ethiop Med J, 1992 Jul, 30(3), 175 - 81
Tetracycline versus penicillin in the treatment of louse-borne relapsing fever; Gebrehiwot T et al.; A prospective study of 120 louse-borne relapsing fever (LBRF) patient admitted to Mekele Regional Hospital, Tigray, Ethiopia from September to November 1991 was done . The patients were assigned systematically to a single dose of either tetracycline or procaine penicillin (sixty each) . Doses given were oral tetracycline 250 mg or intramuscular procaine penicillin 200,000 units for children ages 12 years or less, and 500 mg or 600,000 IU for adults, respectively . The aim of this study was to compare the clinical effectiveness of tetracycline to that of procaine penicillin . Both drugs induced a Jarisch-Herxheimer (JH) like reaction, which was clinically similar in the two treatment groups, but peaked later and was more prolonged in the patients treated with procaine penicillin . Spirochaetes cleared more slowly and relapses were noticed only in the procaine penicillin treated group . Thus, tetracycline is recommended as first choice therapy and a single dose is sufficient for treatment of LBRF patients.

Epilepsy Res, 1992 Jul, 12(2), 87 - 110
Chemical models of epilepsy with some reference to their applicability in the development of anticonvulsants; De Deyn PP et al.; This paper reviews chemical models of epilepsy and their relevance in the identification and characterization of anticonvulsants . For each convulsant we discuss possible modes of administration, clinical type(s) of seizures induced, proposed mechanism(s) of epileptogenesis and, where available, responsiveness of the induced seizures to anticonvulsants . The following compounds are reviewed: pentylenetetrazol, bicuculline, penicillin, picrotoxin, beta-carbolines, 3-mercaptopropionic acid, hydrazides, allylglycine; the glycine antagonist strychnine; gamma-hydroxybutyrate; excitatory amino acids (glutamate, aspartate, N-methyl-D-aspartate, quisqualate, kainate, quinolinic acid); monosubstituted guanidino compounds, metals (alumina, cobalt, zinc, iron); neuropeptides (opioid peptides, corticotropin releasing factor, somatostatin, vasopressin); cholinergic agents (acetylcholine, acetylcholinesterase inhibitors, pilocarpine); tetanus toxin; flurothyl; folates; homocysteine and colchicine . Although there are a multitude of chemical models of epilepsy, only a limited number are applied in the routine screening of potential anticonvulsants . Some chemical models have a predictive value with regard to the clinical profile of efficacy of the tested anticonvulsants . Some chemical models may contribute to a better understanding of possible mechanisms of epileptogenesis.

Hautarzt, 1992 Jul, 43(7), 409 - 16
{Current status and trends in treatment of scleroderma}; Haustein UF; Owing to the wide variety of symptoms, the long clinical course, the inadequate knowledge of the points at which therapeutic action is appropriate and the difficulty of obtaining objective measurements of the treatment results, therapy for systemic sclerosis has to be planned individually . Besides basic recommendations (avoidance of noxious substances, sensible diet, keeping warm, active exercises), physiotherapy and psychological guidance, the therapy is directed at three pathogenetic complexes . Among the vasoactive substances the prostacyclins, calcium channel blockers and angiotensin-converting-enzyme inhibitors (in the case of complicated renal involvement) are recommended . They inhibit the thrombocyte hyperaggregation and lead to vasodilatation . The anti-inflammatory substances prednisolone and azathioprine also exert immunosuppressant (and cytotoxic) effect . Their use is indicated in inflammatory, immunologically active forms of systemic sclerosis . Antifibrotic agents inhibit cross-link formation, prolylhydroxylase, extrusion of collagen from fibroblasts and, thus, collagen synthesis . In addition, they favour the degradation of collagen via the activation of collagenase . Good results have been reported with penicillamine and penicillin G . Pentoxyphyllin leads to vasodilatation and also inhibits collagen metabolism . Promising agents and procedures for future use include cyclosporin A, CD4 antibodies, photopheresis, interferon gamma and factor XIII . A critical attitude to therapy and a great deal of patience are necessary to avoid harming the patients, especially as it is often some months before any effects of the treatment are seen.

J Biotechnol, 1992 Jul, 24(3), 291 - 8
Mitotic instability of integrated plasmids in Penicillium chrysogenum transformants; Renno DV et al.; Transformation vectors based on the Streptoalloteichus hindustanus phleomycin-resistance gene placed under the control of either the Penicillium chrysogenum trpC or pcbC promoters were constructed (plasmids pGS1 and pGS7 respectively) . Up to 100 transformants per microgram of DNA were obtained with pGS7 in P . chrysogenum strain P2 . In order to follow the expression of additional penicillin biosynthetic genes introduced by transformation, a pcbC::lacZ gene fusion was introduced into pGS1, generating pGS6 . Southern analysis of three pGS6 transformants indicated that the plasmid was integrated in tandem arrays . Revertants which had lost the exogenous beta-galactosidase activity, were detected for each transformant after several cycles of subculture on non-selective medium . Southern analysis indicated that the different phenotypes obtained resulted from the loss of part or all of the integrated plasmid copies.

Drug Metab Dispos, 1992 Jul-Aug, 20(4), 578 - 84
3'-azido-3'-deoxythymidine drug interactions . Screening for inhibitors in human liver microsomes; Rajaonarison JF et al.; Zidovudine is a widely used antiretroviral drug active against human immunodeficiency virus . The drug interactions of this compound, which are primarily eliminated as a glucuronide, have not yet been extensively studied . Because zidovudine is frequently combined with other drugs, complete knowledge of interactions is essential to optimize AIDS therapy . We therefore screened the effect of 55 molecules, representative of 20 different therapeutic classes, on 3'-azido-3'-deoxythymidine (AZT) glucuronidation by human liver microsomes . We demonstrate that many drugs caused more than 15% inhibition of AZT glucuronidation in vitro, whereas major antibiotics (ceftazidine, isoniazid, aminoglycosides, macrolides, and sulfamides), antivirals (2',3'-dideoxycytidine, 2',3'-dideoxyinosine, and acyclovir), flucytosine, metronidazole, acetaminophen, and ranitidine had no effect . For compounds that appeared to inhibit AZT glucuronidation, extrapolation to the clinical situation must take into account both the in vitro apparent Ki values and the usual expected plasma level for the coadministered drug . By considering these parameters, this work indicates that clinically relevant inhibition of AZT glucuronidation may be observed with the following drugs: cefoperazone, penicillin G, amoxicilin, piperacillin, chloramphenicol, vancomycin, miconazole, rifampicin, phenobarbital, carbamazepine, phenytoin, valproic acid, quinidine, phenylbutazone, ketoprofen, probenecid, and propofol . Complementary clinical and pharmacokinetic studies should be performed to validate these assumptions.

Chin Med J (Engl), 1992 Jul, 105(7), 560 - 3
Borrelia burgdorferi infection may be the cause of sarcoidosis; Hua B et al.; Serum antibody to Borrelia burgdorferi was measured in 33 patients with sarcoidosis which was confirmed clinically and pathologically . The results showed that 81.8% of the patients were positive for anti-B . burgdorferi antibody . In addition, a strain of B . burgdorferi was isolated from a patient's blood . Fifteen patients received ceftriaxone 2g per day or penicillin 12 million U per day . The antibody titers of the patients decreased to nearly normal levels rapidly . Serum angiotensin converting enzyme (SACE) turned to normal range after the treatment . According to the findings mentioned above, we consider that B . burgdorferi infection may be the cause of sarcoidosis and sarcoidosis might be a specific type of Lyme disease.

J Biol Chem, 1992 Jun 5, 267(16), 11386 - 91
Substitution of lysine 213 with arginine in penicillin-binding protein 5 of Escherichia coli abolishes D-alanine carboxypeptidase activity without affecting penicillin binding; Malhotra KT et al.; All penicillin-binding proteins (PBPs) contain a conserved box of homology in the carboxyl-terminal half of their primary sequence that can be Lys-Thr-Gly, Lys-Ser-Gly, or His-Thr-Gly . Site-saturation mutagenesis was used to address the role of the lysine residue at this position (Lys213) in Escherichia coli PBP 5, a D-alanine carboxypeptidase enzyme . A soluble form of PBP 5 was used to replace Lys213 with 18 other amino acids, and the ability of these mutant proteins to bind {3H}penicillin G was assessed . Only the substitution of lysine with arginine resulted in a protein that was capable of forming a stable covalent complex with antibiotic . The affinity of {14C}penicillin G for the arginine mutant was 1.2-fold higher than for wild-type PBP 5 (4.4 versus 5.1 micrograms/ml for 20 min at 30 degrees C), and both proteins showed identical rates of hydrolysis of the {14C}penicilloyl-bound complex (t1/2 = 9.1 min) . Surprisingly, the arginine-substituted protein was unable to catalyze D-alanine carboxypeptidase activity in vitro, which suggests that there is a substantial difference in the geometries of the peptide substrate and penicillin G within the active site of PBP 5.

Paraplegia, 1992 Jun, 30(6), 442 - 4
Spinal cord lesion after penicillin gluteal injection; Tesio L et al.; Penicillin gluteal injection may cause sudden and irreversible paraplegia . In the literature 6 cases have been reported, and spinal infarction was conjectured, the mechanism being obscure . The actual incidence of such a complication is not known . We observed 2 more cases, 6 and 16 years respectively following such an injection . The clinical features suggested that spinal infarction had occurred, and an MRI study in the most severely impaired patient showed marked spinal atrophy, giving further support to the spinal infarction hypothesis . These findings and the pathophysiological considerations suggest that the mechanism might be the accidental injection into the superior gluteal artery, causing its distal spasm and the upstream ascent of the penicillin with ensuing embolic and/or spastic occlusion of the arterior spinal artery.

Nervenarzt, 1992 Jun, 63(6), 371 - 4
{Lack of specificity of single photon emission computerized tomography in dementia--results of a case of progressive paralysis}; Reisecker F et al.; In a 53-year old male suffering from paretic neurosyphilis, SPECT-investigations were performed before and after treatment with high doses of Penicillin G . The patient was admitted for disturbances of speech and concentration, memory disorder and tonic-clonic seizures . Mental examination showed a mild dysphoria and irritability in mood, but no disturbance of orientation, no euphoria or expansive delusions, and no paranoia . Mini-Mental-State examination was within the normal range (28 points); no abnormalities were found on neurologic examination, and CT and MRI investigations showed normal findings . The diagnosis was verified by CSF-examination (pleocytosis, elevated protein, positive Lues reactions) . SPECT investigation with Tc 99m HMPAO (20 mCi, single-head rotating camera) revealed a pronounced bilateral parieto-temporal uptake deficiency as observed in patients with dementia of Alzheimer's type . After 18 months the clinical symptoms had remitted, and laboratory findings were improved . On the other hand, the bilateral parieto-temporal uptake deficiency in SPECT remained unchanged . Possible causes of these findings are discussed in relation to neuropathologic findings . It can be concluded that bilateral parieto-temporal uptake deficiency in SPECT is a nonspecific finding and that there is no correlation between clinical improvement and SPECT pattern in paretic neurosyphilis.

Mol Microbiol, 1992 Jun, 6(11), 1457 - 65
Carbon catabolite repression can account for the temporal pattern of expression of a penicillin biosynthetic gene in Aspergillus nidulans; Espeso EA et al.; Aspergillus nidulans synthesizes penicillins as secondary metabolites when grown under certain culture conditions . Broths containing carbon (C) sources that give rise to carbon catabolite repression (CCR) support a much lower antibiotic yield than broths with non-repressing C sources . Steady-state levels of the isopenicillin N synthetase (IPNS) gene transcript are considerably reduced in mycelia grown with repressing C sources and are depressed in mycelia grown with sugars which do not cause CCR, indicating that penicillin biosynthesis is regulated by CCR through transcriptional control of structural genes . CCR is sufficient to explain the temporal window of expression of the IPNS gene during the growth cycle since (i) the transcript becomes derepressed as soon as the concentration of a repressing C source drops to non-repressing levels and (ii) derepressing C sources sustain derepressed IPNS transcription at all tested moments of the growth cycle . Several tested hypofunctional mutations in creA (the negatively acting regulatory gene which mediates CCR in A . nidulans) do not cause full derepression of IPNS transcript in the presence of a repressing C source . The slight degree of IPNS derepression caused by some creAd (derepressed) alleles parallels the strength of the mutation (as determined by the morphological effect they elicit).

J Trop Med Hyg, 1992 Jun, 95(3), 206 - 9
Louse-borne relapsing fever in children; Mekasha A; Clinical manifestations of louse-borne relapsing fever (LBRF) in children admitted to Jimma Teaching Hospital from March 1991 to September 1991 are described . The clinical manifestations were mild and the frequency of occurrence of each feature was lower than in adults . Jaundice and cardiac abnormality have not been found in children . The Jarisch-Herxheimer reaction was also mild and occurred in about 16% of the cases . The prognosis of LBRF was excellent . Initial treatment with penicillin and continued treatment with tetracycline for a couple of days was justifiable . Further detailed studies with a larger series is recommended.

J Bacteriol, 1992 Jun, 174(11), 3789 - 99
Regulation of Aspergillus nidulans penicillin biosynthesis and penicillin biosynthesis genes acvA and ipnA by glucose; Brakhage AA et al.; Expression of the Aspergillus nidulans penicillin biosynthesis genes acvA and ipnA, encoding delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase and isopenicillin N synthetase, respectively, was analyzed . The intergenic region carrying the divergently oriented promoters was fused in frame in both orientations to Escherichia coli lacZ and E . coli uidA reporter genes . Each construct permits simultaneous expression studies of both genes . Transformants of A . nidulans carrying a single copy of either plasmid integrated at the chromosomal argB locus were selected for further investigations . Expression of both genes was directed by the 872-bp intergenic region . ipnA- and acvA-derived gene fusions were expressed from this region at different levels . ipnA had significantly higher expression than did acvA . Glucose specifically reduced the production of penicillin and significantly repressed the expression of ipnA but not of acvA gene fusions . The specific activities of isopenicillin N synthetase, the gene product of ipnA, and acyl coenzyme A:6-aminopenicillanic acid acyltransferase were also reduced in glucose-grown cultures.

AJR Am J Roentgenol, 1992 Jun, 158(6), 1325 - 8
Neurosyphilis in HIV carriers: MR findings in six patients; Tien RD et al.; Neurosyphilis, a sexually transmitted disease that can cause neurologic damage, has become increasingly prevalent in the AIDS era . HIV carriers can contract neurosyphilis without the presence of other concurrent opportunistic infections . Because MR findings of neurosyphilis are seldom reported, we retrospectively reviewed and evaluated contrast-enhanced MR images of six young (average age, 33 years) HIV-positive men with high serum and CSF VDRL titers indicative of neurosyphilis . All six patients tested negative for concurrent opportunistic infections . Five patients had acute or subacute strokelike symptoms involving the basal ganglia or middle cerebral arteries; one had a parietal convexity mass mimicking meningioma with headache and ataxia . Contrast-enhanced MR images showed patchy enhancement involving the basal ganglia and middle cerebral artery territories in the first five patients and the convexity mass in the sixth patient . On the basis of brain biopsy, a convexity mass was diagnosed in the patient with syphilitic gumma . The imaging findings of the remaining five patients represented ischemic infarct caused by meningovascular syphilis . After penicillin treatment, serum and CSF VDRL titers decreased, and neurologic signs and symptoms improved in all six patients . A follow-up MR study in the patient with the gumma showed that the lesion resolved almost completely . In young HIV patients with stroke symptoms or a convexity mass, neurosyphilis should be considered . Contrast-enhanced MR can reveal the extent of involvement by neurosyphilis and should be used to facilitate diagnosis and proper treatment.

Aust Vet J, 1992 Jun, 69(6), 129 - 33
The role of procaine in adverse reactions to procaine penicillin in horses; Chapman CB et al.; Procaine penicillin is a commonly used antibiotic in equine medicine but its use is associated with a substantial incidence of adverse reactions . Soluble procaine concentrations were determined by HPLC in several commercially available procaine penicillin preparations, including some that were involved in adverse reactions . The mean (+/- SEM) soluble procaine concentrations in the veterinary preparations was 20.18 +/- 5.07 mg/ml, which was higher than the concentration in the only procaine penicillin preparation for use in humans in Australia of 7.3 mg/ml . Heating the veterinary procaine penicillin preparations to 50 degrees C for 1 day led to a significant (P less than 0.01) increase in the amount of soluble procaine . Heating to 50 degrees C for 7 days also produced a significant (P less than 0.02) increase . Soluble procaine tended to return to baseline concentrations when veterinary procaine penicillin preparations were heated to 50 degrees C for 2 days then stored for 7 days at room temperature . Administration of procaine HCl intravenously (IV) at 2, 5, and 10 mg/kg produced behavioural, locomotor and vascular reactions, which were clinically similar to those reported in adverse reactions to procaine penicillin . The more severe reactions occurred at higher doses, although different horses responded variably at the same dose . Some adverse reactions lead to recumbency but none were fatal . The blood procaine concentrations 1 min after IV administration averaged 19.0 +/- 12.6 and 25.3 +/- 16 micrograms/ml at 2.5 mg/kg and 5 mg/kg, respectively . Ten min after administration, blood procaine concentrations were significantly higher (P less than 0.001) in the 5 mg/kg group than in the 2.5 mg/kg group . Intramuscular (IM) procaine HCl at 5 mg/kg produced significantly lower (P less than 0.001) blood concentrations than similar IV doses, and, in contrast to the IV doses, the amount of procaine in the blood was significantly higher 5 and 10 min after administration than it was after 1 min . Mild excitatory reactions in 4/5 horses were noted 5 to 10 min after IM administration . Administration of diazepam 20 s before procaine HCl prevented the excitatory adverse reaction in 2/2 horses, but administration after the procaine did not influence the outcome.

Metab Brain Dis, 1992 Jun, 7(2), 101 - 13
Cortical slow potential changes during convulsions induced by maximal electroshock or penicillin focus; de Azeredo FA et al.; We have described the occurrence in freely moving gerbils of slow potential changes (SPC) in two different models of experimental epilepsy: 1) maximal electroshock and 2) bilateral epileptic foci induced by penicillin . SPC is considered a by-product of epileptiform activity in both models and correlates to the SPC which occurs during spreading depression . In the first model there develops a cortical SPC simultaneous with a depression of EEG activity, although there is no propagation of the wave . We suggest that a non-propagated multifocal depression (MD) occurs in the MES model . In the model of focal epilepsy, all requirements are fulfilled, and the SPC is characterized as the one which occurs during spreading depression propagating with an average velocity of 8 mm/min.

J Indian Med Assoc, 1992 Jun, 90(6), 155 - 6
Diphtheria in the eighties: experience in a south Indian district hospital; Havaldar PV; Epidemiological and clinical analysis of 228 cases of diphtheria treated during a 10-year period from 1980-1989 is presented . No statistically significant change in the incidence over a decade was noticed . A high percentage of cases (44.74%) were noted in the age group of 5 years and above . Bilateral tonsillar and pharyngeal membranes together were seen in 60% cases . All patients were treated with diphtheria antitoxin and benzyl penicillin . Severe myocarditis (9 cases), fulminant haemorrhagic complications (2 cases), palatal palsies (11 cases) and polyneuritis and cranial nerve paralysis (2 cases) were the significant complications . Case fatality rate was 13.21% . Statistically significant increase in the mortality (p less than 0.05) was noticed in the year 1987 and onwards . In this period, myocarditis (8 out of 16 deaths) is gradually replacing laryngeal obstruction, the major cause of death in early eighties or post-tracheostomy complications (6 out of 16 deaths) . Only 2 patients died of haemorrhagic diphtheria in this period.

Exp Eye Res, 1992 Jun, 54(6), 1005 - 10
Description of an acylpeptide hydrolase from lens; Sharma KK et al.; Acylpeptide hydrolase, which catalyses the hydrolysis of blocked N-terminal amino acids from peptide substrates, has been identified in the extracts from beef, human, rabbit and rat lens . In bovine lens sections, lower activity was observed in nuclear and inner cortical regions compared to the outer cortical region . The enzyme from bovine lens showed a high molecular weight nature, eluting between alpha and beta crystallins during Sephadex G-200 chromatography . The activity has a pH optimum around 7.8 when assayed with N-acetyl-Ala-p-NA as substrate . The enzyme was capable of hydrolyzing a variety of blocked peptides including N-acetyl-(Ala)2, Me-O-Suc-Ala-Ala-Pro-Val-p-NA, N-Acetyl-Met-Leu-Phe, Acetyl-Ser-Gln-Asn-Tyr and N-formyl-Met-p-NA . In each case the enzyme released an N-blocked amino acid and exposed a free amino group as judged by thin layer chromatography . Neither Ala-p-NA nor N-acetyl-Ala were hydrolysed by the same enzyme preparation . The enzyme activity from human and bovine lens was completely inhibited by DFP, and partially inhibited by PMSF, penicillin-G and ampicillin . These preliminary results show that lens tissue has an active acylpeptide hydrolase, however, a partially purified enzyme preparations was not able to cleave the acetyl-Met- from native alpha A-crystallin in vitro suggesting that the N-terminus of native crystallins is not accessible to the enzymes.

An Esp Pediatr, 1992 Jun, 36(6), 441 - 5
{Pneumococcal meningitis in the infantile population of Cantabria}; Alonso Palacio J et al.; A retrospective study of pneumococcal meningitis was carried out . This study included 22 cases of this illness that occurred in 17 pediatric patients in Cantabria between 1977 and 1990, inclusive . Three children suffered from recurrent meningitis . The age range of the patients was 0.3-14 years, with a mean age of 4 years . Of these cases, 77.4% occurred in the winter or spring . In 14 cases of meningitis (63.6%), corresponding to 9 patients, underlying pathology was observed: cranial fracture, occipital dermoid cyst, splenectomy, congenital cardiopathy, epilepsy and gastroduodenal "situs inversus" . The isolated pneumococci were found to be resistant to penicillin and chloramphenicol in 4 cases . One patient suffered from septic shock . The outcome was complete recovery in 19 cases (86.4%), recovery with sequelae (deafness and epilepsy, respectively) in 2 cases (9.1%) and death in another 2 cases . CSF protein levels elevated above 150 mg/dl and the absence of glucose in the CSF were found to be the most useful analytical indicators of the seriousness of the illness.

Ann Gastroenterol Hepatol (Paris), 1992 Jun-Sep, 28(4), 194 - 8
{Should subdivision of regressive ischemic colitis be envisaged?}; Mallet L et al.; The term "regressive ischemic colitis" is generally accepted and refers to acute hemorrhagic colitis which may occur at any age and recovers spontaneously in most cases, sometimes leaving colonic stenosis due to scarring . Critical analysis of the literature reveals that there is no formal diagnostic criterion for this condition and no real proof that the mechanism is ischemic, particularly in young subjects who have no vascular disorder or hemodynamic triggering factor . The number of clinical, radiological, endoscopic and even histological similarities between regressive ischemic colitis and some forms of infectious colitis, particularly due to enterohemorrhagic E . coli O157:H7 and hemorrhagic colitis due to penicillin derivatives and non-steroid anti-inflammatory drugs is also striking . These observations logically lead us to wonder whether the term "regressive ischemic colitis" does really correspond to a well-defined entity rather than to a group of acute colitis of miscellaneous etiology but with many common features.

J Vet Pharmacol Ther, 1992 Jun, 15(2), 202 - 16
Mathematical description of the concentration of oxytetracycline and penicillin-G in tissue cages in calves as related to the serum concentration; Bengtsson B et al.; A mathematical model based on Fick's laws of diffusion describing the concentration of drug in tissue cage models was elaborated . The model takes into account differences in protein binding, tissue cage geometry and serum pharmacokinetics . The validity of the model was tested against experimental data obtained from a tissue cage model in calves by simultaneous fitting to serum and tissue cage fluid (TCF) data in a non-linear least-squares regression computer program . Concentrations of penicillin-G (pen-G) in serum and TCF following intravenous (i.v.) administration of potassium pen-G were adequately described by the mathematical model . Concentrations in TCF after intramuscular (i.m.) administration of the same drug and of procaine pen-G could be predicted by the mathematical model . Concentrations of oxytetracycline (OTC) in serum and TCF following i.v . administration and continuous i.v . infusions were also adequately described by the model, and TCF concentrations after i.m . administration of the same drug could be roughly predicted . The results indicate that pen-G and OTC have the same permeability coefficient for transport from serum to TCF.

J Vet Pharmacol Ther, 1992 Jun, 15(2), 160 - 73
Bioavailability and bioequivalence of veterinary drug dosage forms, with particular reference to horses: an overview; Baggot JD; The route of administration and formulation of the dosage form affect the bioavailability (rate and extent of absorption) of a drug and may thereby influence the intensity and duration of the pharmacological effect . Location of injection site may affect the plasma concentration profile of drugs administered as aqueous suspensions or sustained release parenteral preparations (procaine penicillin G) . When absorption influences the rate of elimination ('flip-flop' phenomenon), the apparent half-life of the drug will be increased (cefazolin sodium, i.m.; meclofenamic acid, p.o.) . Absorption generally approximates a first-order process and either the absorption half-life or the mean absorption time (statistical moment term) will provide an estimate of the rate of absorption . The method of corresponding areas is the usual technique employed in estimating the extent of absorption (systemic availability) . Inherent in this technique is the assumption that clearance of the drug remains unchanged . In horses, the time of feeding relative to oral dosing has been shown to affect systemic availability (rifampin, trimethoprim) and pattern of absorption (phenylbutazone) . Oral paste formulations (trimethoprim-sulphadiazine, ivermectin) are convenient to administer, allow precision in dosage compared with powders or granules added to feed, and could provide sustained release . Assessment of bioequivalence is based on relative bioavailability, using a reference dosage form, together with a measure of the uncertainty (variance) of the estimate . Bioequivalence relies on the concept that preparations of a drug which provide essentially equivalent plasma concentration profiles should produce the same therapeutic effect.

J Vet Pharmacol Ther, 1992 Jun, 15(2), 151 - 9
Bioavailability and bioinequivalence of drug formulations in small animals; Watson AD; Differences in bioavailability of many drugs from their various dosage forms have been shown to be relatively common in human medicine . Although comparable bioavailability ('bioequivalence') is though to ensure comparable clinical effectiveness and safety ('therapeutic equivalence'), the relationship between bioinequivalence and therapeutic inequivalence is less clear . Thus the prevalence of clinically important differences in bioavailability is unknown . While similar concerns have arisen about drug products used in small animal practice, there have been few investigations and some earlier reports are incomplete . However, there are indications of bioinequivalence with enteral formulations of ampicillin, aspirin, chloramphenicol, digoxin, mitotane, oxytetracycline, penicillin V and theophylline . Other studies have suggested bioequivalence with enteral formulations of chloramphenicol, digoxin, phenytoin, oxytetracycline and thyroxine . Limited data for injectable preparations showed bioinequivalence with chloramphenicol and possibly oxytetracycline . There is no reason to expect formulation-related bioinequivalence to be less prevalent in veterinary than in human medicine . Indeed, it may be more common in veterinary practice because other potential influences on bioavailability (food, diseases, other drugs, etc.) are frequently ignored, and cheaper generic products are often favoured for economic reasons.

Enzyme Microb Technol, 1992 Jun, 14(6), 496 - 500
Penicillin amidase-catalysed transfer of low specific acyl moiety . Synthesis of 7-benzoxazolonylacetamido desacetoxycephalosporanic acid; Stambolieva N et al.; The methyl ester of 2-benzoxazolon-3-yl-acetic acid was used as an acyl donor in the penicillin amidase-catalysed transfer reaction to 7-aminodesacetoxycephalosporanic acid . The synthesis of 7-(2-benzoxazolon-3-yl-acetamido)-desacetoxycephalosporanic acid was carried out as a kinetically controlled reaction . A characteristic feature of this system is that the benzoxazolone derivatives are very low specific substrates for penicillin amidase (the kcat/Km values for their hydrolysis were shown to be 10(5)-fold lower compared to the corresponding values for phenylacetyl derivatives) . Nevertheless, penicillin amidase proved to be an effective catalyst for the synthesis of these new cephem derivatives (50% yield for 6 h) . The reason is the observed unusually high value for the transferase-hydrolase activity ratio . The determined value for (k3'/k3)app = 120,000 implies that in this case of low specific acyl moiety, penicillin amidase acts more like a transferase than a hydrolase . The maximum yield has been increased up to 70% by lowering the reaction temperature and stepwise feeding of the reaction medium with the acyl component . The results obtained extend the potential of the penicillin amidase as a catalyst for the synthesis of a new group of biologically active cephem derivatives.

Enzyme Microb Technol, 1992 Jun, 14(6), 489 - 95
Additional stabilization of penicillin G acylase-agarose derivatives by controlled chemical modification with formaldehyde; Fernandez-Lafuente R et al.; We have tested the effect of chemical modifications with formaldehyde on the activity/stability of immobilized derivatives of the enzyme penicillin G acylase (PGA) . These derivatives were previously stabilized through enzyme-support multipoint covalent attachment . We carried out very different chemical treatments of our derivatives by testing the effect of different variables which control the intensity and the nature of these amine-formaldehyde reactions . The variables tested were: formaldehyde concentration, pH, time, and temperature . We also developed a colorimetric titration of the free amine groups on immobilized PGA in order to evaluate the extension of the reaction between formaldehyde and the amine groups of the enzyme . As a consequence of these studies, we have been able to get additional stabilizations of our previously stabilized-immobilized derivatives: e.g . a factor of 24-fold was achieved in terms of stabilization against irreversible thermal inactivation . The integrated effect of additional chemical modification plus previous multipoint covalent attachment has allowed us to prepare PGA derivatives which are 50,000 more thermostable than native PGA as well as most of the commercial PGA derivatives.

Biochemistry, 1992 May 19, 31(19), 4602 - 12
Thiolate ligation of the active site Fe2+ of isopenicillin N synthase derives from substrate rather than endogenous cysteine: spectroscopic studies of site-specific Cys----Ser mutated enzymes; Orville AM et al.; Isopenicillin N synthase (IPNS) catalyzes double ring closure of the tripeptide (L-alpha-amino-delta-adipoyl)-L-cysteinyl-D-valine (ACV) to form the beta-lactam and thiazolidine rings of penicillin-type antibiotics . Our previous spectroscopic study using IPNS from Cephalosporium acremonium expressed in Escherichia coli {Chen, V . J., Orville, A . M., Harpel, M . R., Frolik, C . A., Surerus, K . K., Munck, E., & Lipscomb, J . D . (1989) J . Biol . Chem . 264, 21677-21681} indicated that a thiolate enters the coordination of the essential active site Fe2+ when ACV binds to IPNS . The presence of an Fe-S bond in the IPNS.ACV complex is confirmed by EXAFS data presented in the preceding paper {Scott, R . A., Wang, S., Eidsness, M . K., Kriauciunas, A., Frolik, C . A . & Chen, V . J . (1992) Biochemistry (preceding paper in this issue)} . However, these studies leave unclear whether the coordinating thiolate derives from ACV or an endogenous cysteine . Here, we examine the spectroscopic properties of three genetically engineered variants of IPNS in which the only two endogenous cysteines are individually and collectively replaced by serine . The EPR, Mossbauer, and optical spectra of the mutant enzymes and their complexes with ACV, NO, or both ACV and NO are found to be essentially the same as those of wild-type IPNS, showing that the endogenous cysteines are not Fe2+ ligands in any of these complexes . Spectral quantitations show that the double Cys----Ser mutation decreases the affinity of the enzyme for ACV by about 6-fold, suggesting that the endogenous cysteines influence the structure of the substrate binding pocket remote from the iron . Thiolate complexation of the Fe2+ is also examined using ACV analogues . All ACV analogues examined in which the cysteinyl thiol moiety is unaltered are found to bind to the IPNS.NO complex to give optical and EPR spectra very similar to those of the ACV complex . In contrast, analogues in which the cysteinyl moiety of ACV is replaced with serine or cysteic acid fail to elicit the characteristic EPR and optical features despite the fact that they are bound with reasonable affinity to the enzyme . These results demonstrate that the thiolate of ACV coordinates the Fe2+ . The EPR spectra of both the IPNS.NO and IPNS.ACV.NO complexes are broadened for samples prepared in 17O-enriched water, showing that water (or hydroxide) is also an iron ligand in each case . Thus, the Fe2+ coordination of the IPNS.ACV.NO complex accommodates at least three exogenous ligands.(ABSTRACT TRUNCATED AT 400 WORDS)

Arch Intern Med, 1992 May, 152(5), 1025 - 32
Results of the National Institute of Allergy and Infectious Diseases Collaborative Clinical Trial to test the predictive value of skin testing with major and minor penicillin derivatives in hospitalized adults; Sogn DD et al.; BACKGROUND--A history (or lack thereof) of penicillin allergy is known to be unreliable in predicting reactions on subsequent administration of the drug . This study tests the usefulness of four penicillin allergen skin tests in the prediction of IgE-mediated reactions subsequent to administration of penicillin . METHODS--Eight centers cooperated in the National Institute of Allergy and Infectious Diseases trial of the predictive value of skin testing with major and minor penicillin derivatives . Hospitalized adults were tested with a major determinant (octa-benzylpenicilloyl-ocytalysine) and a minor determinant mixture and its components (potassium benzylpenicillin, benzylpenicilloate, and benzylpenicilloyl-N-propylamine) . Patients then received a therapeutic course of penicillin and were observed, for 48 hours, for adverse reactions compatible with an IgE-mediated immediate or accelerated allergy . RESULTS--Among 726 history-positive patients, 566 with negative skin tests received penicillin and only seven (1.2%) had possibly IgE-mediated reactions . Among 600 history-negative patients, 568 with negative skin tests received penicillin and none had a reaction . Only nine of the 167 positive skin test reactors received a penicillin agent and then usually by cautious incremental dosing . Two (22%) of these nine patients had reactions compatible with IgE-mediated immediate or accelerated penicillin allergy; both were positive to the two determinants . CONCLUSIONS--These data corroborate previous data about the negative predictive value of negative skin tests to these materials . The reaction rate in skin test-positive patients was significantly higher than in those with negative skin tests, demonstrating the positive predictive value of positive tests to both major and minor determinants . The number of patients positive only to the major determinant or only to the minor determinant mix was too small to draw conclusions about the positive predictive value of either reagent alone.

J Chromatogr, 1992 May 8, 576(2), 315 - 20
Determination of penicillin G in bovine plasma by high-performance liquid chromatography after pre-column derivatization; Boison JO et al.; A simple, selective, and sensitive liquid chromatographic method with ultraviolet detection was developed for the analysis of penicillin G in bovine plasma . The assay utilizes a simple extraction of penicillin G from plasma (with a known amount of penicillin V added as internal standard) with water, dilute sulphuric acid and sodium tungstate solutions, followed by concentration on a conditioned C18 solid-phase extraction column . After elution with 500 microliters of elution solution, the penicillins are derivatized with 500 microliters of 1,2,4-triazole-mercuric chloride solution at 65 degrees C for 30 min . The penicillin-mercury mercaptide complexes are separated by reversed-phase liquid chromatography on a C18 column . The method, which has a detection limit of 5 ng/ml (ppb) in bovine plasma, was used to quantitatively measure the concentrations of penicillin G in plasma of steers at a series of intervals after the intramuscular administration of a commercial formulation of procaine penicillin G.

Can J Neurol Sci, 1992 May, 19(2), 201 - 3
The anticonvulsant effects of vitamin E: a further evaluation; Levy SL et al.; Vitamin E (d-alpha-tocopherol) has proven to be a useful adjunct to anticonvulsant drugs in clinical studies . Improvement has occurred even in patients with complex partial seizures, which are often resistant to drug therapy . In animals, vitamin E is effective against ferrous chloride seizures, hyperbaric oxygen seizures and penicillin-induced seizures . It has failed, however, to show anticonvulsant effects in the standard animal models used for drug screening--the maximal electroshock and threshold pentylenetetrazol tests . The present experiments were designed to further explore the anti-epileptic actions of vitamin E in animals . Three models related to complex partial epilepsy were used: 1) the development of amygdala-kindled seizures; 2) the development of electrically-induced status in kindled animals; and 3) the development of kainic-acid seizures . Vitamin E failed to produce significant effects in any of the models.

Rev Clin Esp, 1992 May, 190(8), 389 - 92
{A clinical study of human leptospirosis . Apropos 215 cases}; Roura Carrasco J et al.; 215 cases diagnosed of human leptospirosis in the Camaguey Province, Cuba, are studied, for the period between 1986 and 1990 . The clinical and epidemiological features are studied, together with the anatomopathological study of the decreased . The most frequent complications and the treatment employed, including prophylactic measures, are analyzed . It is concluded that the disease is more frequent in young males, from a rural origin and with a farming job . Acute kidney failure was the main complication, and as for the therapeutic approach, penicillin was the antibiotic of election, prophylactic measures are important, specifically vaccination.

Monatsschr Kinderheilkd, 1992 May, 140(5), 296 - 9
{Determination of hydrogen in expiratory air of premature infants in suspected necrotizing enterocolitis}; Rauter L et al.; BACKGROUND: Breath hydrogen (H2) analysis has been recommended for the differential diagnosis between necrotizing enterocolitis and transient feeding intolerance . METHODS: We performed 360 breath H2 analyses in 32 unselected premature babies by use of an electrochemical method . RESULTS: All babies on oral feedings excreted H2 . The concentration of H2 in expired air was extremely variable and often high even in well premature babies . Antibiotic medication (other than penicillin G alone) inhibited breath hydrogen excretion . CONCLUSIONS: Breath hydrogen analysis can be used as a diagnostic tool for necrotizing enterocolitis if performed in a symptomatic child on oral feedings prior to the initiation of antibiotic therapy.

J Bacteriol, 1992 May, 174(10), 3261 - 9
Deletion of an additional domain located between SXXK and SXN active-site fingerprints in penicillin-binding protein 4 from Escherichia coli; Mottl H et al.; It was suggested previously that the primary structure of penicillin-binding protein 4 (PBP4) is new and unique among proteins that interact with penicillin . Our proposal that PBP4 carries an additional domain, located between the active-site fingerprints SXXK and SXN, was investigated by mutational deletion analysis . A clustered set of internal deletions was created in this region by exonuclease treatment of the dacB coding DNA, starting from two internal restriction sites . PBP4 mutants carrying internal deletions were selected by screening for immunoreactive forms of PBP4 with reduced molecular weight that were still active with respect to penicillin binding . DNA sequencing revealed 24 distinct PBP4 mutants with internal deletions ranging from 37 to 113 amino acids . The amino- and carboxy-terminal end points of the deletions were not randomly distributed but tended to cluster in certain areas . Overproduction of the individual mutated forms of PBP4 resulted in accumulation of the major portion of the proteins in the particulate cell fraction . The yield of soluble and active mutated forms of the protein was reduced from below 1% to 79% of the level obtained for the native protein . The deletions that were introduced had minor effects on the deacylation rate of bound benzylpenicillin . Two pairs of cysteine residues (Cys-139-Cys-153 and Cys-197-Cys-214) that are located in the deletable region may form disulfide bridges.

J Pediatr, 1992 May, 120(5), 807 - 11
Therapeutic adherence to oral medication regimens by adolescents with cancer . I . Laboratory assessment; Festa RS et al.; Outpatient adherence to oral medication regimens was evaluated in 50 adolescents and young adults with cancer: 21 patients with acute lymphoblastic leukemia or Hodgkin disease who were to take prednisone as a component of their chemotherapy regimen, and 29 patients with Hodgkin disease whose chemotherapy had been discontinued and who were to take penicillin for postsplenectomy prophylaxis . Of the 21 adolescent patients with acute lymphoblastic leukemia or Hodgkin disease who were to take prednisone as outpatients, 11 patients were found to be nonadherent to treatment (52%) . Among the 29 adolescents for whom penicillin was prescribed for postsplenectomy prophylaxis, nonadherence was detected in 14 patients (48%) . If a method is available, laboratory assessment to determine adherence should be performed in adolescents and young adults receiving long-term therapy, particularly if one wishes to draw valid conclusions regarding efficacy of various treatment protocols.

Int J Immunopharmacol, 1992 May, 14(4), 673 - 9
Drug-specific immune responses induced by procainamide, hydralazine and isoniazid in guinea-pigs; Katsutani N et al.; The drug-induced graft vs host reaction (GVHR) hypothesis requires, as its first step, specific T-cell immune responses to the drug-modified self . Procainamide, isoniazid and hydralazine are known to provoke various allergic reactions including GVHR-like adverse effects in man . We now report that drug-specific immune responses can easily be induced by these drugs in guinea-pigs . Twenty-five milligrams of each of these drugs and penicillin G, which is known to make covalent bonds with proteins and to also induce drug-specific immune responses, were mixed with complete Freund's adjuvant (CFA) and subcutaneously (s.c.) injected twice at an interval of 2 weeks into female Hartley guinea-pigs . The antibodies to these drugs were assessed by means of an enzyme-linked immunosorbent assay (ELISA) . Two weeks after the last injection, all animals treated with isoniazid, hydralazine and penicillin G produced high titers of antibodies to these drugs . Antibodies to procainamide were also detected, although their antibody titers were low . The specificity of the antibodies produced were tested by the inhibition of ELISA and concentration-dependent inhibition was observed . Delayed type hypersensitivity (DTH) reactions were also observed in the animals treated with procainamide, isoniazid and hydralazine 2 weeks after the last injection . These results suggest that the allergic reactions observed in clinical use are related to the inducing potential of drug-specific immune responses in an animal system . Therefore, immunization of guinea-pigs with test drugs and CFA may give useful information for predicting the occurrence of allergic reactions in man.

Antimicrob Agents Chemother, 1992 May, 36(5), 1068 - 72
Resistance to beta-lactams in Mycobacterium fortuitum; Fattorini L et al.; It is widely assumed that the high level of intrinsic resistance to beta-lactam antibiotics exhibited by mycobacteria results from the combination of factors including permeability to the drugs, beta-lactamase production, and affinity for penicillin-binding proteins (PBPs) . We conducted an evaluation of the second and third factors by isolating nitrosoguanidine-induced mutants from the beta-lactamase-producing strain Mycobacterium fortuitum ATCC 19542 that displayed either elevated or reduced resistance to various beta-lactam antibiotics . The mutants studied included D1 (a beta-lactamase producer with high penicillin resistance), gamma 27 (a low-level beta-lactamase producer with low penicillin resistance), and D316 (a high-level beta-lactamase producer with high penicillin resistance) . In all strains examined, four major PBPs, named 1, 2a, 2b, and 3, with apparent molecular weights of 102,000, 90,000, 87,000, and 50,000, respectively, were found . The MICs of various beta-lactams toward ATCC 19542 and its mutants were considered in the context of beta-lactamase production, the quantity of PBPs synthesized, and their affinities for beta-lactam antibiotics . The data obtained show that beta-lactamase production is likely to be an important factor in the expression of resistance by clinical isolates and that PBP alterations can contribute to resistance at least in laboratory-derived mutants.

Srp Arh Celok Lek, 1992 May-Jun, 120(5-6), 206 - 8
{Penicillin allergy in children}; Abinun M; Penicillin allergy in children is overdiagnosed and paediatricians, fearing the possibility of fatal anaphylaxis, seldom question a report that a child is allergic to penicillin . Laboratory tests to predict whether a patient will react to penicillin are unhelpful in routine clinical practice and skin tests themselves carry a significant risk of anaphylaxis and even death . A few simple inquiries can often exclude the diagnosis . However, a history of penicillin therapy associated with an immediate reaction suggests penicillin allergy.

Epilepsy Res, 1992 May, 11(3), 153 - 7
An experimental study of the effect of isoflurane on epileptiform bursts; Langmoen IA et al.; The effect of isoflurane on penicillin- and picrotoxin-induced epileptiform activity was tested using hippocampal slice preparations . Isoflurane reduced both the frequency of spontaneous epileptiform bursts and the number of population spikes within each burst in a dose-dependent manner . The last population spikes in the burst were most sensitive to the anesthetic, whereas the first 4-6 spikes were quite resistant and persisted until spontaneous activity was abolished at 3% isoflurane . Isoflurane increased the stimulus current required to evoke epileptiform bursts and shifted the relationship between stimulus current and population spike amplitude to the right . At 3% isoflurane, a dose that usually causes iso-electric EEG and abolishes all spontaneous epileptiform activity, responses could still be evoked, and then invariably had an epileptiform pattern . The maximum response was reduced compared to control and 1.5% isoflurane . With isoflurane there was a reduced tendency for activity to be transmitted from one region within the hippocampus to the other . This effect was also dose-dependent . However, transmitted activity always retained a typical epileptiform character, although the number of population spikes within a train to some extent decreased with increasing concentrations of isoflurane.

Br J Pharmacol, 1992 May, 106(1), 73 - 8
Penicillin-induced potentiation of glycine receptor-operated chloride current in rat ventro-medial hypothalamic neurones; Tokutomi N et al.; 1 . Effects of penicillin G (PCN) on glycine (Gly)-evoked Cl- current (IGly) were investigated in acutely dissociated rat ventro-medial hypothalamic (VMH) neurones by the whole cell mode of patch clamp technique . 2 . When PCN was applied simultaneously with Gly, PCN depressed IGly like a Cl- channel blocker . 3 . The PCN-induced blocking action was clearly observed at a low PCN concentration (30 u), while the maximal blockade was achieved by 600 u (units per 10 ml) PCN . 4 . When tested solution containing both PCN and Gly was quickly substituted with one containing Gly only, a new rebound-like transient current (I(T)) which also passed through Cl- channel, was elicited . 5 . The peak amplitude of I(T) induced by PCN at concentrations higher than 100 u was greater than that induced by glycine alone . We termed this phenomenon PCN-induced potentiation of IGly . In all cells tested, PCN potentiated IGly . 6 . At a lower PCN concentration below 30 u, I(T) generation was not clear in the presence of 10(-5) M gamma-aminobutyric acid . With PCN a higher concentration than 300 u, I(T) amplitude was greater than that of the original peak IGly . This was observed in 18 neurones out of 21 . The maximal amplitude of the I(T) was achieved with 600 u PCN.

Appl Microbiol Biotechnol, 1992 May, 37(2), 157 - 63
The influence of preculture on the process performance of penicillin V production in a 100-l air-lift tower loop reactor; Moller J et al.; The influence of stirrer speed in the third preculture on the performance of penicillin V production by Penicillium chrysogenum in complex medium in a 100-l air-lift tower loop reactor was investigated . The process performance in the main culture was improved by increasing the stirrer speed from 500 to 750 rpm: the pellet size was reduced to half, the cell growth was influenced only slightly, but the production phase was extended considerably, and the final penicillin concentration was increased from 5.1 g l-1 to 10.4 g l-1.

Biochim Biophys Acta, 1992 Apr 22, 1116(2), 210 - 3
Involvement of microbodies in penicillin biosynthesis; Muller WH et al.; Penicillium chrysogenum strains were constructed which express a mutant acyltransferase lacking the putative targeting signal for microbody proteins . The mutated enzyme was located in vacuoles and in neighbouring cytoplasm . Although acyltransferase was expressed in vivo and was active in vitro, the mutants did not produce penicillin . The results demonstrate the involvement of microbodies in penicillin production.

Hear Res, 1992 Apr, 59(1), 75 - 84
Effects of organic acids on the edema of the stria vascularis induced by furosemide; Rybak LP et al.; Furosemide is a loop diuretic which is ototoxic . Investigations have shown the stria vascularis to be the target tissue of this ototoxic drug . The purpose of the present study was to investigate the effects of furosemide on the stria vascularis in chinchillas, in controls and in animals pretreated with the above organic acids . Control animals were injected with 0.5 ml alkalinized saline followed by furosemide IV 30 min later . Experimental animals received probenecid, penicillin or sodium salicylate IV . Thirty minutes later, furosemide was injected in the same dose as in the controls . The basal turn of the stria vascularis was rapidly removed at various times from 10 to 30 min after furosemide administration and processed for transmission electron microscopy . Control animals were found to have reversible edema of the stria vascularis . Experimental animals had variable findings . Those animals pretreated with penicillin had virtually no edema of the stria vascularis at any time . Salicylate and probenecid pretreated animals had significantly less edema from one to 10 min after furosemide injection, but more edema than controls at later times . These findings suggest a discrepancy between ultrastructural pathology and functional status of the cochlea in experimental animals pretreated with probenecid or sodium salicylate followed by furosemide . On the other hand, good structure function correlations were seen in controls and in experimental animals pretreated with penicillin.

Brain, 1992 Apr, 115 ( Pt 2), 399 - 423
The clinical and epidemiological profile of Lyme neuroborreliosis in Denmark 1985-1990 . A prospective study of 187 patients with Borrelia burgdorferi specific intrathecal antibody production; Hansen K et al.; This prospective study reports the clinical and epidemiological features of 187 consecutive patients with neuroborreliosis recognized in Denmark over the 6-yr period, 1985-1990 . Only patients with intrathecal Borrelia burgdorferi specific antibody synthesis were included . In 1990 regional incidences varied between 5.7 and 24.1 per million . Ninety-four percent of the patients had early (second stage) neuroborreliosis . The most common manifestation was a painful lymphocytic meningoradiculitis (Bannwarth's syndrome) either with paresis (61%) or as a radicular pain syndrome only (25%) . Central nervous system (CNS) involvement in early neuroborreliosis was rare; 4% had signs of myelitis and only one patient had acute encephalitis . Children showed a different course of the disease . Six percent of the patients suffered a chronic course with a disease duration between 6 mths and 6 yrs either as chronic lymphocytic meningitis (1.6%) or as third stage chronic encephalomyelitis (4.3%) . Meningeal signs were rare despite pronounced inflammatory cerebrospinal fluid (CSF) changes (median cell count 160/microliters; median protein concentration 1.13 g/l) . High dose i.v . penicillin G was administered to 91% of the patients . Based on the clinical outcome and normalization of CSF no treatment failures were recognized . The final morbidity after a median follow-up of 33 mths was low; disabling sequelae were reported in nine patients, mainly those with previous CNS involvement . We conclude that neuroborreliosis is a common and characteristic neurological disorder . The diagnosis should be based on the demonstration of inflammatory CSF changes and B . burgdorferi specific intrathecal antibody production.

P R Health Sci J, 1992 Apr, 11(1), 19 - 21
Hepatic actinomycosis presenting as liver mass: case report and review of the literature; Vargas C et al.; Primary hepatic actinomycosis is an uncommon entity . We report the case of a young man with past history of an appendectomy who presented with fever, weight loss and a liver mass that was initially suspected to be neoplastic . Percutaneous liver biopsy revealed actinomyces-like organisms . The patient was treated with intravenous and oral penicillin with good therapeutic response . Review of the literature and correlation between hepatic actinomycosis and previous appendectomy are considered.

Ann Ophthalmol, 1992 Apr, 24(4), 134 - 8
Acquired ocular syphilis: diagnosis and treatment; Deschenes J et al.; We present our findings in 14 patients with a serologically verified diagnosis of ocular syphilis . Although most patients had iridocyclitis, other ocular findings included episcleritis, scleritis, vitritis, retinitis, papillitis, panuveitis, cystoid macular edema, and retinal detachment . Most patients had only ocular manifestations of syphilis with no other definitive symptoms . Without the use of specific treponemal serologic tests, the diagnosis of ocular syphilis would have been missed in at least 20% of patients . Furthermore, 80% of patients were negative for antibody to syphilis in the cerebrospinal fluid, and therefore, this test should not be used to determine treatment for ocular syphilis . Currently, the most effective therapy for ocular syphilis is the same as that for neurosyphilis (i.e., high-dose intravenous penicillin G 12 to 24 million units/day for ten to 14 days) . Human immunodeficiency virus-positive patients should receive a full 14 days of high-dose intravenous penicillin G plus intramuscular benzathine penicillin 2.4 million units weekly for three weeks because their immune defenses are likely to be impaired.

Genitourin Med, 1992 Apr, 68(2), 120 - 2
VDRL titres in early syphilis before and after treatment; Talwar S et al.; OBJECTIVE--To observe the pretreatment VDRL titres in different stages of early syphilis and evaluate the changes in VDRL titre following treatment using different treatment schedules . DESIGN--Retrospective study was carried out by analysing the records of cases of early syphilis treated between 1976 to 1981 . SETTING--Armed Forces personnel treated at different service hospitals in India . SUBJECTS--Of 3183 cases of early syphilis treated with different regimens during this period, 1532 were fully followed-up for a period of 30 months . Records of these 1532 cases were analysed . MAIN OUTCOME MEASURES--Assessment of VDRL titres before treatment and during post treatment surveillance period of 30 months . Attainment of non-reactivity of VDRL test in various stages of early syphilis using different treatment schedules was evaluated . RESULTS--Relatively higher titres were observed in secondary syphilis . Following treatment it was observed that VDRL test was still reactive at the end of 6 months in 16.47% of primary, 27.56% of secondary and 18.95% of early latent cases; at the end of 12 months in 11.38% of primary, 17.25% of secondary and 15.79% of early latent cases while at 30 months reactivity was still observed in 6.60% of primary, 8.39% of secondary and 11.58% of early latent cases . CSF was examined in 1173 cases at 6 months, of which one case revealed VDRL reactivity while two cases showed reactivity amongst 1188 CSF examined at 30 months . There has been no significant difference with broad spectrum antibiotics and 2.4 MU benzathine penicillin . Results were better with 4.8 MU benzathine penicillin and procaine penicillin . CONCLUSION--VDRL test appears to be a reliable test for the follow-up of treated patients in early syphilis . Early treatment prevents development of seropositivity in seronegative syphilis while majority of seropositive cases attain seronegativity by 6 months . Higher doses of benzathine penicillin and procaine penicillin accelerate the speed of seroconversion.

Biochem J, 1992 Apr 1, 283 ( Pt 1), 123 - 8
Point mutations of two arginine residues in the Streptomyces R61 DD-peptidase; Bourguignon-Bellefroid C et al.; Incubation of the exocellular DD-carboxypeptidase/transpeptidase of Streptomyces R61 with phenylglyoxal resulted in a time-dependent decrease in the enzyme activity . This inactivation was demonstrated to be due to modification of the Arg-99 side chain . In consequence, the role of that residue was investigated by site-directed mutagenesis . Mutation of Arg-99 into leucine appeared to be highly detrimental to enzyme stability, reflecting a determining structural role for this residue . The conserved Arg-103 residue was also substituted by using site-directed mutagenesis . The modification to a serine residue yielded a stable enzyme, the catalytic properties of which were similar to those of the wild-type enzyme . Thus Arg-103, although strictly conserved or replaced by a lysine residue in most of the active-site penicillin-recognizing proteins, did not appear to fulfil any essential role in either the enzyme activity or structure.

EMBO J, 1992 Apr, 11(4), 1493 - 501
Penicillin binding protein 2 is dispensable in Escherichia coli when ppGpp synthesis is induced; Vinella D et al.; Mecillinam, a beta-lactam antibiotic which specifically inactivates penicillin binding protein 2 (PBP2) in Escherichia coli, prevents lateral cell wall elongation, inducing spherical morphology and cell death . Two mecillinam resistant mutants, lov-1 and lovB, both able to dispense entirely with PBP2, are shown here to be affected in the aminoacyl-tRNA synthetase genes argS and alaS, respectively . Although the argS and alaS mutants grow slowly, we show that there is no correlation between mecillinam resistance and either growth rate or translation speed . A role of the ribosomes in mecillinam sensitivity, suggested by our earlier report that the lov-1 mutation is suppressed by certain rpsL(StrR) alleles affecting ribosomal protein S12, is supported by the present observation that a pseudo-streptomycin dependent mutant is mecillinam resistant in the presence of streptomycin . The argS and alaS mutants have high pools of the nucleotide ppGpp (effector of the stringent response) and the mecillinam resistance of both mutations is suppressed by a relA mutation, inactivating the ribosome-associated ppGpp synthetase and preventing ppGpp synthesis in response to aminoacyl-tRNA starvation . Furthermore, a ptacrelA' multicopy plasmid makes a wild type strain mecillinam resistant . The effect of ppGpp is probably mediated by RNA polymerase, since sublethal doses of the polymerase inhibitor rifampicin suppress mecillinam resistance in argS, alaS and ptacrelA'-bearing strains . We conclude that ppGpp regulates the transcription of a gene whose product is involved in mecillinam sensitivity, possibly as part of a chain of interacting elements which coordinate ribosomal activity with that of the PBPs.

Ann Allergy, 1992 Apr, 68(4), 345 - 7
Toxic epidermal necrolysis due to vancomycin; Vidal C et al.; Toxic epidermal necrolysis due to vancomycin is reported in a patient with human immunodeficiency virus infection . The same patient had anaphylaxis to cloxacillin but tolerated other penicillin derivatives . These reactions were documented using in vivo and in vitro tests . The role of human immunodeficiency virus infection in the pathogenesis of these reactions is discussed.

Eur J Biochem, 1992 Apr 1, 205(1), 77 - 83
Reconstitution in vivo of penicillin G acylase activity from separately expressed subunits; Burtscher H et al.; Penicillin G acylase from Escherichia coli ATCC11105 is synthesized as a precursor polypeptide with a signal sequence for secretion into the periplasm and an endopeptide separating two subunit domains . Proteolytic processing leads to mature, heterodimeric penicillin G acylase . We have shown that the alpha- and beta-subunits of the enzyme, which have no detectable enzymatic activity on their own, can reconstitute enzyme activity when their genes are put into an E . coli host on separate plasmids . Activity is reconstituted in the cytoplasm whereas normally processing and formation of the active heterodimer occurs in the periplasm . Enzyme activity can reach levels close to wild type in the strain used . The activity recovered from a combination of alpha-subunit linked to a 54-amino-acid endopeptide and beta-subunit was lower than with the subunits alone.

J Bacteriol, 1992 Apr, 174(7), 2416 - 7
Escherichia coli mutant Y16 is a double mutant carrying thermosensitive ftsH and ftsI mutations; Begg KJ et al.; The Escherichia coli mutant Y16, which shows thermosensitive colony formation and filamentation with reduced amounts of penicillin-binding protein 3 (PBP3), has mutations in the ftsI gene encoding PBP3 and in the ftsH gene . The ftsI mutation markedly reduces the amount of PBP3 at 42 degrees C, whereas the amount of the ftsH single mutant is slightly reduced.

Clin Imaging, 1992 Apr-Jun, 16(2), 125 - 8
Solitary pulmonary nodule in secondary syphilis; Cholankeril JV et al.; A case of secondary syphilis with a solitary right upper-lobe nodule is presented . Patient presented without any pulmonary complaints or findings . This mass disappeared with residual scar after a full course of penicillin therapy . Our report is the first in the literature that reports a solitary nodule in the upper lobes in secondary syphilis . Previous reports showed nodules only in lower lobes . Our patient also presented with a rectal mass that disappeared on anti-syphilitic therapy.

Bangladesh Med Res Counc Bull, 1992 Apr, 18(1), 36 - 46
Disease profile in respect of health services of Upazila health complex; Salahuddin AK et al.; This study was carried out to identify the disease profile in relation to medical services at upazila health complex . Thirty different types of diseases were identified . Diarrhoeal diseases were found to be highest (53%), the second highest was intestinal worms (44%) . About ninety seven percent patient attended the OPD and only 2% were attended in the emergency Department . On average 172 patients were admitted per month and the highest of admission was found in the months of September and October . The average length of stay in the hospital was 11.6 days . Among the patients admitted 55% were male, and 45 were female . 5% pregnant mothers attended in U.H.C . for antenatal checkup and 2% mother were admitted into the hospital after delivery . Metronidazole was the drug of highest consumption followed by B-Complex and Penicillin.

Biull Eksp Biol Med, 1992 Apr, 113(4), 347 - 9
{Effects of magnesium and nickel ions on penicillin-induced focal epileptic activity in the cerebral cortex of rats}; Kryzhanovskii GN et al.; In experiments on freely moving male Wistar rats on the model of penicillin-induced focal epileptic activity (EA) (the application onto the sensorimotor cortex of a filter paper soaked with benzylpenicillin sodium salt solution) it was shown that addition of MgSO4 (series 1) and NiCl2 (series 2) into the solution of penicillin significantly weakened EA . The combination of Mg2+ and Ni2+ with penicillin (series 3) produced a more significant suppression of EA as compared with separate application of the above-mentioned ions: the latency period of appearance of interictal discharges (IID) increased, the frequency and amplitude of IID decreased much more, no ictal discharges appeared in any animal, the duration of epileptic foci reduced to a much greater extent . This effect can be explained by the blockade of Ca current by the above-mentioned ions . One can suppose that the amplification of antiepileptic effects of combined action of Mg2+ and Ni2+ was due to an increase in the number of blocked voltage-dependent and NMDA-operated calcium channels.

Transplantation, 1992 Apr, 53(4), 742 - 5
A new dextran 40-based solution for liver preservation; Ar'Rajab A et al.; UW solution is at present the most efficient solution for preservation of livers for transplantation . We have developed an alternative solution based on dextran instead of hydroxyethyl starch and without raffinose, allopurinol, magnesium sulfate, insulin, penicillin, or dexamethasone, which all are used in UW solution . In addition, 62.5 mM potassium in UW solution is replaced with sodium . We tested this new solution for liver preservation using the isolated perfused rabbit liver . We found that livers preserved in the UW solution for 24 or 48 hr lost 11.6 +/- 2.6% and 16.8 +/- 2.0% of the prepreservation weight, respectively, as a sign of organ shrinkage (P less than 0.001) . In contrast, no change in liver weight was observed after preservation in the new dextran-based solution . Similarly, no change in total tissue water of the rat liver slices was seen after preservation in the new solution . Furthermore, livers preserved for 24 hr in the UW solution or the new solution produced the same amount of bile as unpreserved livers . However, after preservation in the UW solution for 48 hr, bile production was reduced by 65% (P less than 0.05) . In contrast, livers preserved for 48 hr in the new solution showed no reduction in bile production . We conclude that our new solution significantly improves long-term liver preservation, and with this modified solution, 48-hr preservation may be safe.

Br J Clin Pharmacol, 1992 Apr, 33(4), 431 - 8
The effect of respiratory manoeuvres and pharmacological agents on the pharmacokinetics of nedocromil sodium after inhalation; Summers QA et al.; 1 . Eight healthy subjects inhaled nedocromil sodium from a metered-dose inhaler using a standardised inspiratory technique . Blood samples were taken for up to 270 min after inhalation for radioimmunoassay of plasma nedocromil sodium concentrations . 2 . To investigate the possibility that respiratory manoeuvres can alter the absorption of the drug from the lungs, on the first (control) study day at 70 min after dosing, subjects performed nine forced expiratory manoeuvres over a 3 min period . At 110 min after dosing, subjects took a slow, full inspiration with a 30 s breath-hold, and at 150 min after dosing the subjects performed one single forced expiration . 3 . On the second study day, subjects inhaled methoxamine, 0.15 mg kg-1 of a 20 mg ml-1 solution at 60 min after dosing, and the study continued as above . On the third day, subjects repeated the sequence of respiratory manoeuvres, after having taken phenoxymethyl penicillin and probenecid by mouth for 48 h . 4 . Both multiple forced expirations and the deep inspiration with breath-hold produced significant increases in the absorption of nedocromil sodium . Inhaled methoxamine did not alter airway calibre or the response to the respiratory manoeuvres . Probenecid, but not penicillin, was detected in the subjects' plasma, and had the effect of increasing the rise in plasma nedocromil sodium concentrations after the multiple forced expirations when compared with the control day . 5 . These data suggest that disruption of epithelial tight junctions induced by the respiratory manoeuvres leads to enhanced paracellular transport of nedocromil sodium into the draining circulation of the airways and alveoli.(ABSTRACT TRUNCATED AT 250 WORDS)

Rev Soc Bras Med Trop, 1992 Apr-Jun, 25(2), 135 - 8
{Sodoku--a case report}; Hinrichsen SL et al.; Rat-bite fever results from an infection with the organism Spirillum minus . The authors report a symptomatic patient with fever, malaise, and ulcer in forehead after a rodent exposure . The organism was identified in darkfield examination of the ulcer exudate . Penicillin was the drug used with clinical improvement of symptoms.

Scand J Prim Health Care, 1992 Mar, 10(1), 7 - 11
Amoxicillin in treatment of acute uncomplicated exacerbations of chronic bronchitis . A double-blind, placebo-controlled multicentre study in general practice; Jorgensen AF et al.; The aim of the study was to evaluate whether a broad-spectrum penicillin, amoxicillin, was superior to placebo in resolving symptoms of acute exacerbations of chronic bronchitis in patients from general practice . 131 general practitioners included 278 patients over a period of 30 months . The patients were randomly assigned to treatment with amoxicillin 750 mg b.i.d . or corresponding placebo for 7 days . Patients with pneumonia, a temperature above 38.5 degrees C or heart rate over 100 were excluded for safety reasons . The main effect parameter--the doctors' overall evaluation of the treatment--did not demonstrate any statistically significant difference between amoxicillin or placebo, 63% versus 64% of the patients . Resolution of symptoms was obtained by 19% (25/132) of the patients in the amoxicillin group compared with 10% (13/136) of the patients in the placebo group, P = 0.03 . The present findings do not favour routine use of antibiotics in an attempt to improve the course of acute exacerbations as defined in this study in patients with chronic bronchitis.

FEMS Microbiol Lett, 1992 Mar 1, 70(2), 119 - 23
Failure to trigger the autolytic enzymes in minicells of Escherichia coli; Markiewicz Z et al.; Minicells from Escherichia coli P678-54 are refractory towards procedures known to induce bacteriolysis of DNA-containing E . coli cells . Although still engaged in murein synthesis, minicells could not be lysed by penicillin G . Likewise, endogenous overproduction of the cloned soluble lytic transglycosylase, the predominant murein hydrolytic activity in E . coli, failed to lyse minicells . Furthermore, induction of the phage MS2 lysis protein, a hydrophobic protein assumed to trigger the autolytic system of the host, did not result in bacteriolysis . It is concluded that the murein hydrolases present in minicells are under a tight cellular control.

Rev Clin Esp, 1992 Mar, 190(5), 258 - 60
{An ischiorectal abscess due to Actinomyces}; Aldamiz-Echebarria San Sebastian M et al.; Actinomycosis is a chronic granulomatous inflammatory disease, with fistulization tendency, caused by Actinomyces . The clinical observation in presented of a patient with intermittent fever of three weeks duration, associated to pain and functional impotence of the right hip, observing with CT Scan an ischium-rectal abscess . After spontaneous fistulization, Actinomyces israelii was isolated in the biopsy sample by culture in anaerobic medium, confirming the diagnosis by anatomo-pathology . The patient was treated with intravenous penicillin for six weeks, followed by six months of oral treatment with which the symptoms disappeared and the radiological images normalized . Bone infection ranges between 1 and 15% of total actinomycosis.

Int J Pediatr Otorhinolaryngol, 1992 Mar, 23(2), 177 - 80
Perceptive bilateral deafness following clinical tetanus to a neonate; Skevas A et al.; A rare case of bilateral perceptive deafness following clinical tetanus is reported . The patient was a 15-day-old neonate . The clinical tetanus was treated with tetanus antitoxin (human gamma globulins) and penicillin . The exact mechanism of auditory nerve damage associated clinical tetanus and treatment with human tetanus antitoxin and penicillin is still not clearly known . We believe that the damage of the hearing organ can be attributed to the tetanus toxin and not to the human gamma globulins (tetanus antitoxin).

Clin Infect Dis, 1992 Mar, 14(3), 769 - 72
Streptobacillus moniliformis endocarditis: case report and review; Rupp ME; A 46-year-old man with rat-bite fever due to Streptobacillus moniliformis that was complicated by endocarditis is reported . Other unusual features of this case include septic arthritis with prominent involvement of the sternoclavicular joint and the absence of a rash . Sixteen cases of streptobacillary endocarditis have previously been described . This condition occurs most often in the setting of previously damaged heart valves, usually as a result of rheumatic heart disease . Echocardiography demonstrated valvular vegetations in two of the four cases in which it was performed . Embolic phenomena are rare, and therapy with adequate doses of penicillin is usually curative.

Epilepsia, 1992 Mar-Apr, 33(2), 228 - 34
Induction of epileptiform activity by temperature elevation in hippocampal slices from young rats: an in vitro model for febrile seizures?
Tancredi V, D'Arcangelo G, Zona C, Siniscalchi A, Avoli M.
Extracellular field potential recordings were performed in the CA1 subfield of hippocampal slices obtained from Wistar rats aged 2-38 days . When the brain tissue was maintained at 35 degrees-36 degrees C (values obtained in the tissue chamber well), single-shock orthodromic stimuli elicited a response in the stratum pyramidale that consisted of a single population spike . In contrast, when the temperature in the well was increased to levels greater than 38.2 degrees C for periods of 5-15 min, the same type of stimuli elicited an epileptiform response characterized by a 250- to 600-ms-long, positive-going field potential with superimposed, multiple, negative-going population spikes . This potential resembled the epileptiform response recorded in the hippocampal slice in the presence of convulsants such as penicillin or bicuculline . Once the temperature was restored to control values (i.e., 35 degrees-36 degrees C) after induction of epileptiform activity, the abnormal response could be observed for less than or equal to 2 h . In some experiments (approximately one third of the successful trials), spontaneous epileptiform discharges appeared during and persisted after the increase in temperature . The ability of the hyperthermic period to induce epileptiform changes was age dependent: Epileptiform activity outlasting the period of temperature elevation was not observed in slices obtained from rats aged less than 4 days or greater than 28 days . Our data show that epileptiform activity can be induced by a transient increase in temperature and that the age of the animals from which slices are obtained plays an important role in the appearance of this phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochem J, 1992 Mar 1, 282 ( Pt 2), 361 - 7
Importance of the two tryptophan residues in the Streptomyces R61 exocellular DD-peptidase; Bourguignon-Bellefroid C et al.; Modification of the Streptomyces R61 DD-peptidase by N-bromosuccinimide resulted in a rapid loss of enzyme activity . In consequence, the role of the enzyme's two tryptophan residues was investigated by site-directed mutagenesis . Trp271 was replaced by Leu . The modification yielded a stable enzyme whose structural and catalytic properties were similar to those of the wild-type protein . Thus the Trp271 residue, though almost invariant among the beta-lactamases of classes A and C and the low-Mr penicillin-binding proteins, did not appear to be essential for enzyme activity . Mutations of the Trp233 into Leu and Ser strongly decreased the enzymic activity, the affinity for beta-lactams and the protein stability . Surprisingly, the benzylpenicilloyl-(W233L)enzyme deacylated at least 300-fold more quickly than the corresponding acyl-enzyme formed with the wild-type protein and gave rise to benzylpenicilloate instead of phenylacetylglycine . This mutant DD-peptidase thus behaved as a weak beta-lactamase.

Southeast Asian J Trop Med Public Health, 1992 Mar, 23(1), 142 - 6
Community-acquired pulmonary infection due to Chlamydia in tropical Queensland; Ashdown LR; By using enzyme immunoassay and immunofluorescence antigen detection techniques on sputum specimens, four of 260 patients with pulmonary infection resident in tropical Queensland were found to be infected with Chlamydia . All four chlamydial infections were community-acquired and there was no history of close contact with birds by any of the four patients . One woman was deemed to be suffering with Chlamydia pneumonia, while the role of the organism in the pathogenesis of respiratory disease in the other three patients was indeterminate . At present, the incidence of pulmonary chlamydial infection in the population of tropical Queensland does not warrant routine testing, but investigations for these organisms should be undertaken in patients who present to their physicians with atypical pulmonary infection or whose clinical conditions are refractory to penicillin/ampicillin therapy.

Acta Gastroenterol Belg, 1992 Mar-Apr, 55(2), 209 - 19
Whipple's disease: the value of upper gastrointestinal endoscopy for the diagnosis and follow-up; Geboes K et al.; Due to the systemic nature of Whipple's disease the clinical presentation may be highly variable . The diagnosis may therefore be unduly delayed . If untreated, Whipple's disease is still potentially lethal . In contrast, the endoscopic findings as they are observed in the postbulbar small intestine and the light microscopic picture of small intestinal biopsies are almost pathognomonic . Out of a group of 18 patients (14 male, 4 female, mean age = 45 yrs), 12 patients were diagnosed using upper gastrointestinal endoscopy and duodenal biopsy, while six patients were diagnosed only by a small intestinal capsule biopsy . The clinical history prior to diagnosis lasted from 1 m to 22 yrs (mean = 3 yrs 6 m) in the first group and from 4 yrs to 21 yrs (mean = 12 yrs 6 m) in the second group . The endoscopic findings at the time of diagnosis were: oesophagitis (1/12), erosive gastritis (4/12), atrophic gastritis (2/12), severe erosive bulbitis (3/10), pathognomonic post-bulbar duodenal lesions (9/12) . In 20% of the patients the endoscopic lesions had disappeared 6 m after antibiotics while the lesions had disappeared in all cases 9 m after therapy, despite the fact that PAS positive macrophages remained present in the endoscopic biopsies for years . All patients were treated with antibiotics (8 tetracycline alone, 4 tetracycline, streptomycin and penicillin, 6 trimethoprim) . Five patients (27%-4 of the tetracycline group) relapsed within 2 to 20 yrs after the initial diagnosis . Three of these patients (3/5) had typical duodenal lesions on endoscopy at that time.

J Biotechnol, 1992 Mar, 23(1), 95 - 101
A geometric interpretation of the feasibility of reactive extraction/re-extraction of penicillin G; Patnaik PR; The reactive extraction (re-extraction) of penicillin G from reaction mixtures is based on complexation with a carrier and subsequent dissociation of the complex . An established mathematical model for this has been analysed to develop a feasibility domain within which the process may be designed and optimised . Geometric and physical interpretations of this domain are provided.

J Formos Med Assoc, 1992 Mar, 91(3), 342 - 5
Pelvic actinomycosis with colo-ileo-vesical fistula formation: report of a case; Chang CH et al.; Pelvic actinomycosis with multiple fistular formation is rarely reported in the literature . We herein present a case of pelvic actinomycosis with sigmoid colo-ileovesical fistulae in a 36-year-old intrauterine device (IUD) user . She was admitted to the hospital because of general malaise, weight loss and bilateral palpable adnexal masses . Sonography showed bilateral adnexal masses which contained many echolucent spots . A barium enema examination revealed sigmoid colo-ileo-vesical fistulae . A computed tomographic scan showed bilateral cystic adnexal masses, bilateral hydronephrosis and hydroureter . Preoperatively, pelvic malignancy was suspected . An exploratory laparotomy was performed . Bilateral tubo-ovarian abscesses with extensive adhesions were found . Pathologic examination of the operative specimen revealed pelvic actinomycosis . The patient was treated with penicillin for 14 weeks and had a stable clinical course.

J Chromatogr, 1992 Feb 28, 593(1-2), 15 - 20
High-performance liquid chromatographic determination of penicillin G, penicillin V and cloxacillin in beef and pork tissues; Moats WA; The objective was to develop confirmatory high-performance liquid chromatographic methods for penicillin residues in animal tissues with detection limits of less than or equal to 10 ng/g . A previously described procedure was modified by using a larger sample size and isocratic analysis . Tissues (15 g) were blended with 45 ml of water and 20 ml of homogenate were mixed with 40 ml acetonitrile and filtered . The filtrate (30 ml) was mixed with 10 ml of 0.2 M H3PO4 and extracted with methylene chloride . The combined methylene chloride layers were mixed with acetonitrile and hexane, washed with two 4-ml portions of water and then extracted with four 1-ml portions of 0.01 M phosphate buffer (pH 7) . The combined buffer extracts were concentrated to 1 ml under reduced pressure . Analysis was isocratic during 0.01 M phosphate buffer (pH 7)-acetonitrile with proportions 85:15 (penicillin G), 82:18 (penicillin V) or 78:22 (cloxacillin) . A polystyrene-divinylbenzene copolymer column, 150 x 4.6 mm I.D . (Polymer Labs . PLRP-S), was used with a flow-rate of 1 ml/min and detection at 210 nm . The presence of penicillins was confirmed by treating a duplicate sample with penicillinase . Recoveries were greater than 90% in most instances . Detection limits were 5 ng/g in muscle and higher in liver and kidney . The procedure is a simple and sensitive method for confirming the presence of penicillins in animal tissues.

Eur J Biochem, 1992 Feb 15, 204(1), 197 - 202
Cytoplasmic high-level expression of a soluble, enzymatically active form of the Escherichia coli penicillin-binding protein 5 and purification by dye chromatography; van der Linden MP et al.; High-level expression of a soluble form of penicillin-binding protein 5 (PBP5), called PBP5s, and translocation across the cytoplasmic membrane results in lysis of Escherichia coli cells . The detrimental effect of increased amounts of this D,D-carboxypeptidase on the stability of murein polymer can be avoided by accumulation of the overexpressed protein in the cytoplasm . The signal peptide of the structural gene dacAs, coding for PBP5s was deleted by creating a BamHI site at the site of processing and the truncated gene dacAsc was cloned under the control of the lambda PR promoter . Temperature induction resulted in a 200-fold overproduction of the mature PBP5s in the cytosol (PBP5sc) which is no longer harmful to the cells . PBP5sc could quantitatively be recovered in the soluble fraction after disrupting the cells . The protein retained full enzymatic activity as measured by the release of D-alanine from bisacetyl-L-Lys-D-Ala-D-Ala and formation of {14C}penicillin-protein complex at a 1:1 stoichiometry . A one-step purification procedure using the immobilized dye Procion rubine MX-B resulted in homogeneous preparations of both wild-type and mutated forms of PBP5sc.

Ugeskr Laeger, 1992 Feb 3, 154(6), 331 - 3
{Investigation for penicillin allergy among children}; Birkebaek NH et al.; During the period 1986-1991, 109 children were tested for penicillin allergy in the paediatric departments of Odense and Roskilde Hospitals . Determinations of specific IgE to penicillin (SIgEP) were performed on all of the children . Prick tests for penicillin were undertaken in the children i Odense only . All of the children who reacted negatively to SIgEP and the prick test were provoked by oral penicillin . Two children were SIgEP positive . One of these children was subsequently treated with penicillin without reaction . All of the prick tests were negative . One child reacted with an urticarial rash five hours after oral provocation . It is recommended that investigation for allergy to penicillin in children should be restricted to meticulous history taking and oral provocation with penicillin with equipment for treatment of anaphylaxis in readiness.

Am Fam Physician, 1992 Feb, 45(2), 613 - 20
Acute rheumatic fever: an update; Alto WA et al.; The incidence of acute rheumatic fever is increasing in the United States, but many physicians are now unfamiliar with the diagnosis and treatment of this disease . The revised Jones criteria provide guidance for the diagnosis of rheumatic fever; two major criteria or one major and two minor manifestations are required to make the diagnosis . Salicylates are usually the initial treatment of choice for the arthritis of rheumatic fever . Penicillin remains the recommended prophylactic agent for secondary prevention.

J Rheumatol, 1992 Feb, 19(2), 313 - 5
Chronic syphilitic polyarthritis mimicking systemic lupus erythematosus/rheumatoid arthritis as the initial presentation of human immunodeficiency virus infection; Burgoyne M et al.; Syphilitic arthritis has been well characterized but not previously described as the initial presentation of human immunodeficiency virus (HIV) infection . Our patient presented with chronic symmetric polyarthritis and autoimmune abnormalities, including positive rheumatoid factor, antinuclear antibody, dsDNA, and initially negative syphilis serologies . Subsequent investigations revealed HIV seropositivity, depletion of CD4 cells, and strongly positive syphilis serologies . Our patient's arthritis completely resolved with penicillin therapy.

Fundam Appl Toxicol, 1992 Feb, 18(2), 181 - 8
Control of the nephrotoxicity of cisplatin by clinically used sulfur-containing compounds; Jones MM et al.; Several clinically used sulfur-containing compounds were examined as potential antagonists for the nephrotoxicity of cis-platin in Sprague-Dawley rats . The compounds studied were biotin, captopril, cefoxitin, cephalexin, the sodium salt of penicillin G, sulfathiazole, and thiamine hydrochloride . Biotin, captopril, cephalexin, and sulfathiazole were found to have a significant effect in reducing the nephrotoxicity of cisplatin when administered simultaneously with cisplatin via an intravenous route in the rat . Biotin was the most effective in providing renal protection and sulfathiazole the least effective, based upon BUN, serum creatinine values, and weight changes, though all four of these compounds provided a considerable measure of protection against the typical cisplatin-induced nephrotoxicity . The effect of the simultaneous administration of cisplatin with biotin, cephalexin, and sulfathiazole was examined on the antitumor activity of cisplatin toward the L1210 murine leukemia in the DBA/2 mouse and the Walker 256 carcinosarcoma in the rat . With the L1210 murine leukemia no loss of antitumor activity was found for any of the compounds . With the Walker 256 carcinosarcoma some loss of antitumor activity was found with biotin . Both biotin and sulfathiazole are shown to be promising candidates for use in the suppression of the adverse effects of cisplatin, and other sulfur-containing compounds currently in clinical use may have equivalent or superior properties in this respect.

Allergy, 1992 Feb, 47(1), 50 - 4
PAF acether release on antigenic challenge . A method for the investigation of drug allergic reactions; Dunoyer-Geindre S et al.; This study describes an in vitro method to evaluate a PAF acether release test (PART) from white blood cells after antigenic challenge . PAF acether activity of the supernatant was tested by platelet aggregation . The aggregating power was abolished by using SRI 63-441 (Sandoz), a PAF acether inhibitor . This method was applied to 57 patients with allergic or pseudo-allergic reactions to drugs by using different drug protein conjugates . The results of PART were evaluated in relation to the clinical history (score of imputability) and to other tests (skin tests, lymphocyte transformation tests (LTT), IgE-RAST) . A good correlation was found between the release of PAF acether and a high predictability score: sensitivity 75%, specificity 83.8% . PART also correlated with skin tests (75% agreement, n = 60), with LTT (67.7% agreement, n = 74) and in 65.6% of cases with positive penicillin IgE-RAST (n = 32) . This method brings a new possibility for the investigation of drug-allergic and pseudo-allergic reactions.

Clin Infect Dis, 1992 Feb, 14(2), 592 - 3
Allergy to amoxicillin in patients who tolerated benzylpenicillin, aztreonam, and ceftazidime; Martin JA et al.; The usual battery of skin tests employed for determining penicillin allergy may fail to detect allergic reactions to side chain-specific beta-lactam agents . We report the cases of six patients who experienced anaphylactic reactions after treatment and challenge with amoxicillin but who tolerated parenteral challenges with benzylpenicillin, aztreonam, and ceftazidime . Results of skin tests for amoxicillin (10 mg/mL) were positive for four of the six patients.

J Pediatr Nurs, 1992 Feb, 7(1), 52 - 7
A successful education program for parents of infants with newly diagnosed sickle cell disease; Day S et al.; The most dramatic recent advance in the care of young children with sickle cell disease was the demonstration by a cooperative study that the use of oral penicillin prophylaxis is highly effective in decreasing the risk of pneumococcal sepsis . Subsequently, the need for more comprehensive education of the parents of these children to ensure compliance with penicillin administration has become apparent . Over the past 4 years, the Mid-South Sickle Cell Disease Program has used a seven-phase educational process for the parents of more than 200 infants with newly diagnosed sickle cell disease . This has resulted in excellent compliance and a marked decrease in the incidence of pneumococcal sepsis among sickle cell patients at our center.

J Reprod Med, 1992 Feb, 37(2), 173 - 6
Nonimmune hydrops fetalis and fetal congenital syphilis . A case report; Hallak M et al.; Nonimmune hydrops fetalis occurred secondary to a syphilitic infection . Ultrasonographic evaluation and cordocentesis were used to confirm the antenatal infection . An IgM antibody specific for Treponema pallidum wall antigen (anti-47-kDa) was used to document the fetal infection . High-dose intravenous penicillin was administered in an attempt to achieve adequate fetal levels.

Biol Reprod, 1992 Feb, 46(2), 295 - 300
Hormone secretion by preimplantation embryos in a dynamic in vitro culture system; Wilson JM et al.; Bovine embryos recovered from superovulated donors on Days 8-18 postestrus were cultured in vitro in a tissue perifusion system to quantify hormone secretion . Embryos were cultured for 24 h at 37 degrees C in Ham's F-10 medium supplemented 5% v/v with heat-treated, charcoal-stripped calf serum; 100 IU/ml penicillin; and 100 micrograms/ml streptomycin . The medium was saturated with 5% CO2 in air and perifused at 50 microliters/min (3 ml/h) . Estrone (E1) estradiol (E2), progesterone (P4), prostaglandin E2 (PGE2), and prostacyclin (PGI2) were quantified by RIA in 6-h pools of perifusate fractions . Estrone was measurable (pg/h/embryo; mean +/- SE) on Days 13 (10.80 +/- 4.56) and 15 (34.80 +/- 9.80); E2 on Days 11 (36.80), 12 (81.28 +/- 29.80), 13 (11.75 +/- 4.09), 15 (157.20 +/- 112.60), and 16 (30.26 +/- 8.76); and P4 (ng/h/embryo) on Days 13 (0.5-1.0) and 17 (approximately 1.5) . PGE2 was secreted by Day 10 bovine embryos during the last 6 h of culture (19-24 h) and throughout culture for Day 11-18 embryos . The rate of PGE2 secretion increased (p less than 0.05) over the previous days(s) at Days 13 and 17 . The mean (+/- SE) secretion rates (pg/h/embryo) for the 24-h culture by embryonic ages were as follows: Day 11 (63.39 +/- 14.61), 12 (172.10 +/- 30.90), 13 (3094.08 +/- 283.35), 14 (1633.89 +/- 49.98), 15 (3739.23 +/- 1082.79), 16 (4955.37 +/- 1381.83), 17 (11893.23 +/- 1188.48), and 18 (13827.99 +/- 3587.88).(ABSTRACT TRUNCATED AT 250 WORDS)

Enzyme Microb Technol, 1992 Feb, 14(2), 161 - 3
Immobilization of permeabilized Escherichia coli cells with penicillin acylase activity; Prabhune AA et al.; Escherichia coli cells with penicillin acylase activity were sequentially treated at pH 7.8 with aqueous solutions of N-cetyl-N,N,N-trimethylammonium bromide and glutaraldehyde and then immobilized within porous polyacrylamide beads . The immobilized whole cells showed enhanced hydrolysis rates in the conversion of benzylpenicillin to 6-aminopenicillanic acid (6-APA) compared to untreated cells immobilized and used under identical conditions . The immobilized system showed no apparent loss in enzyme activity when used repeatedly over 90 cycles for 6-APA production from 4% benzylpenicillin.

Appl Microbiol Biotechnol, 1992 Feb, 36(5), 659 - 62
Changing glycine 21 for glutamic acid in the beta-subunit of penicillin G acylase from Kluyvera citrophila prevents protein maturation; Prieto I et al.; Active penicillin acylase from Kluyvera citrophila strain ATCC 21,285 consists of two different alpha- and beta-subunits derived from a single precursor by post-translational processing . Using the chemical mutagen hydroxylamine we have treated plasmid pYKD59 containing the active penicillin acylase gene (pga) from K . citrophila and have generated different point mutant penicillin acylase genes, one producing a maturation deficient precursor . This point mutation has changed the glycine 310 residue of the precursor for a glutamic acid (residue number 21 of the mature beta-subunit) . The introduction of a charged residue in this position did not prevent translocation of the precursor to the periplasm but the resultant molecule was not able to undergo subsequent post-translational modification to yield the active protein.

Biochemistry, 1992 Jan 21, 31(2), 430 - 7
Active-site residues of the transpeptidase domain of penicillin-binding protein 2 from Escherichia coli: similarity in catalytic mechanism to class A beta-lactamases; Adachi H et al.; By means of amino acid sequence alignment with class A beta-lactamases, the residues essential for the catalytic activity of the peptidoglycan transpeptidase of penicillin-binding protein 2 (PBP2) have been predicted to be Lys333, Asp447, and Lys544, in addition to the acylation site residue for the acyl-enzyme mechanism, Ser330 . Accordingly, these residues were replaced by site-directed mutagenesis, and the resultant mutants were examined as to penicillin-binding activity and genetic complementation, which represent only the acylation step and the total reaction during transpeptidation, respectively . All the mutants at position 333 showed the complete loss of both the binding and complementation activities . Most of the mutants at position 447 retained the binding activity but lost the complementation activity, the exception being the D447E mutant, which retained both . The binding rates for various penicillins of the D447N mutant, which had lost the complementation activity, were almost identical to those of the wild type . The binding of the mutants at position 544 tended to require a higher penicillin concentration, and that of the K544H mutant required a lower pH . When the roles of the counterpart residues, Lys73, Glu166, and Lys234, in class A beta-lactamases were considered, the results suggested that Lys333 and Asp447 are essential for the acylation and acyl-transfer steps, respectively, and that Lys544 stabilizes the Michaelis complex through its side-chain positive charge.

Brain Res, 1992 Jan 13, 569(2), 287 - 94
Evoked CA3 field potentials corresponding to both EPSPs and IPSPs in hippocampal slice; Schneiderman JH et al.; Biphasic field potentials were recorded in the CA3 distal dendritic region in response to both antidromic (fornix) and orthodromic (mossy fiber) stimulation in guinea pig hippocampal slices in vitro . The positive component (P1) corresponded to intracellularly recorded excitatory postsynaptic potentials . The negative component (N1) appears to be due to GABAA-mediated inhibitory postsynaptic potentials (IPSPs) since it corresponded to the fast IPSP recorded intracellularly, was blocked by bicuculline and penicillin and augmented by barbiturates . The amplitude of N1 and the duration of P1 are sensitive and useful measures of the GABAA-mediated IPSP.

Cesk Oftalmol, 1992 Jan, 48(1), 57 - 60
{Treatment of chronic uveitis with long-term administration of penicillin}; Stibor V et al.; The authors followed up a group of 20 patients with chronic uveitis (10 men and 10 women), mean age 36.5 years . Despite treatment of the foci, they suffered on average from seven relapses of the disease, frequently several times in the course of one year . From the anamnestic aspect there was a significantly high number of spells of tonsillitis, respiratory infections and arthralgia . Half the cases of uveitis, mainly anterior, were bilateral . The patients suffered from dysimmunoglobulinaemia with low values of FW, ASLO, Latex . HLA B 27 was positive in five subjects . After one-year of Pendepon or Penclen administration (in half the patients with NORG) 18 patients did not develop a relapse for a period of 2-3 years . The method is simple, cheap, easy to use in field practice, in particular in junior patients . The clinical effect of treatment justifies the use of this method as an alternative of intermittent immunosuppression.

J Exp Zool, 1992 Jan 1, 261(1), 97 - 104
Regulation of ovarian steroidogenesis in vitro in the viviparous shark, Squalus acanthias; Tsang PC et al.; We investigated the steroid biosynthetic capabilities of ovarian granulosa and thecal elements of the viviparous dogfish, Squalus acanthias . In this report we present evidence that granulosa cells secrete quantitatively important amounts of progesterone (P), testosterone (T), and estradiol-17 beta (E), while theca has a more limited capacity to synthesize T and E . Ovarian granulosa cells were obtained from animals at each stage of gestation . After collagenase dispersion, an aliquot of 250,000 cells was incubated at 18 degrees C in basal medium, containing Eagle's salts, glutamine, penicillin, streptomycin and adjusted with 136 mM sodium chloride and 350 mM urea . After a 4 hour incubation, the content of P, T, and E in medium was determined by radioimmunoassay . P was not detectable at any time, while E was present throughout the cycle, being maximal when gestation is three quarters complete (Stage C) . T gradually increased from Stage B toward late pregnancy . In Stage C granulosa cells, E production increased in the presence of graded doses of T substrate . Also, a homologous pituitary extract (1/25 equivalents) and the calcium ionophore A23187 stimulated production of all 3 steroids . Using radioisotopes, granulosa cells showed a wide range of synthetic capacities . In Stage C thecal tissue, E production also increased in the presence of graded doses of T substrate, while pituitary extract only increased T . When granulosa and theca were recombined, in the presence of pituitary extract, P levels decreased with a corresponding increase in T, when compared to granulosa alone . These data suggest a possible interaction between granulosa and theca for steroid biosynthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Chest, 1992 Jan, 101(1), 283 - 5
Primary endobronchial actinomycosis in association with foreign body aspiration; Dicpinigaitis PV et al.; A 66-year-old diabetic man presented with a bilobar pneumonia two months after aspiration of a chicken bone . Flexible fiberoptic bronchoscopy demonstrated a mass in the bronchus intermedius . Histologic examination of endobronchial biopsy specimens revealed bone fragments, vegetable matter, and sulfur granules containing Actinomyces organisms . The patient responded to bronchoscopic removal of the foreign body and penicillin therapy . To our knowledge, the association of actinomycotic infection with an aspirated endobronchial foreign body has not previously been reported.

Dig Dis Sci, 1992 Jan, 37(1), 150 - 2
Granulomatous hepatitis due to combination of amoxicillin and clavulanic acid; Silvain C et al.; We report the case of a patient with amoxicillin-clavulanic acid-induced hepatitis with histologic multiple granulomas . This type of lesion broadens the spectrum of liver injury due to this drug combination, mainly represented by a benign cholestatic syndrome . The association of granulomas and eosinophilia favor an immunoallergic mechanism . As penicillin derivatives and amoxicillin alone are known to induce such types of lesions, the amoxicillin component, with or without a potentiating effect of clavulanic acid, might have a major role.

Eur Arch Otorhinolaryngol, 1992, 249(3), 168 - 71
Effects of organic acids on stria vascularis ultrastructure and function in the chinchilla; Rybak LP et al.; The purpose of this study was to compare the effects of several organic acids (probenecid, sodium salicylate and penicillin G) on the endocochlear potential (EP) and the ultrastructure of the stria vascularis of the chinchilla with the effects of furosemide on these parameters . Chinchillas received 50 mg/kg i.v . doses of probenecid, sodium salicylate or penicillin G, or 25 mg/kg i.v . furosemide . The EP was monitored continuously before and for 60 min afterwards . The stria vascularis was removed at 10-min intervals from animals and from 10 to 60 min after the injection of these agents . Specimens were then processed for transmission electron microscopy . Only furosemide had an effect on the EP, causing a reversible reduction . The reduction of the EP was accompanied by the appearance of edema in the intercellular spaces of the stria vascularis . No significant edema was found after probenecid, sodium salicylate or penicillin G . This was consistent with the finding that none of these latter three agents affected the endocochlear potential.

J Assoc Physicians India . 1992 Jan;40(1):44.
Factor VII inhibitor; Mehta J et al.; Acquired inhibitors of blood coagulation factors occur spontaneously or secondarily to various diseases or drug administration . A clinically significant factor VII inhibitor is very rare . We report a patient developing factor VII inhibitor possibly as a reaction to penicillin administration; it gave rise to fatal haemorrhage.

Gastrointest Radiol, 1992 Summer, 17(3), 274 - 6
Actinomycosis of the distal colon and rectum; Smith TR; Actinomycosis of the colon has rarely been reported; two such cases are presented . A predisposing factor appears to be the presence of a pre-existing intrauterine device (IUD) . This history was present in one case in which there was perisigmoid abscess, local extension, and fistulous tract or the anterior abdominal wall . A second patient had anorectal involvement which resembled Crohn's disease, and was found to be HIV positive . There was mucosal irregularity, wall thickening, reactive adenopathy, perirectal fascial thickening, and a sinus tract, which responded well to penicillin . It is unclear if there is an increased incidence of clinical actinomycosis in the HIV positive population, as it has not to our knowledge been previously reported.

Ann Pharmacother, 1992 Jan, 26(1), 26 - 9
Populations at risk for penicillin-induced seizures; Barrons RW et al.; OBJECTIVE: This article reviews principles associated with penicillin's epileptogenic activity in an effort to alert clinicians of patients at high risk for penicillin-induced seizures . The case presentation exemplifies the most prevalent factor predisposing patients to penicillin-induced seizures--renal impairment . DATA SOURCES: References are identified from pertinent articles and books . DATA SYNTHESIS: The epileptogenic properties of penicillin are explained on the basis of the beta-lactam ring's binding to gamma aminobutyric acid receptors . Several patient populations are at risk for potentially fatal neurotoxic symptoms . Most of these patients demonstrate impaired renal function, either as the primary condition or secondary to an infectious process . The other at-risk populations include infants and the elderly, patients with meningitis, patients undergoing intraventricular antibiotic therapy, and patients with a history of seizures . Treatment remains controversial; however, benzodiazepines theoretically produce a favorable response . CONCLUSIONS: Pharmacokinetic parameters explain patient populations most at risk; a guideline equation has been recommended to allow clinicians to make appropriate dose adjustments based on creatinine clearance . Physicians and pharmacists must recognize the populations most at risk for high-dose, penicillin-induced neurotoxicities; monitor these patients at least during the first 72 hours, and reduce or discontinue therapy when appropriate.

Neirofiziologiia, 1992, 24(2), 151 - 60
{Effect of penicillin on the synaptic activity of isolated spinal cord motor neurons in the lamprey}; Batueva IV et al.; Penicillin (PCN) has been studied for its effect on the membrane potential (MP) and synaptic activity of lamprey spinal cord motoneurons using intracellular recording in the in vitro spinal cord-notochord preparation . In one group of motoneurons with relative low MP (58.7 +/- 5.2 mV, n = 28) PCN induced depolarization, enhancement and prolongation (up to 80-220%) of the initial amplitude of excitatory postsynaptic potentials (EPSPs) evoked by the stimulation of dorsal roots spinal tracts . If the MPs (in the other group of motoneurons) were high (70.0 +/- 5.7 mV, n = 20) depolarization was not observed and the potentiation of EPSPs did not exceed 25-70% of the initial value . These effects of PCN can be eliminated by a preliminary addition of excitatory or inhibitory amino acid antagonists in the superfusion solution . The obtained results allow suggesting the presence of two different acceptor sites for PCN in membranes of lamprey spinal cord motoneurons.

Scand J Infect Dis, 1992, 24(1), 113 - 4
Regional differences of Chlamydia pneumoniae as causative agent of pneumonia in Sweden; Kragsbjerg P et al.; A retrospective serological study was performed on sera from 1982-83 and 1989 to investigate the incidence of Chlamydia pneumoniae infection in hospital treated patients with pneumonia in Orebro County . Paired sera from 231 patients were available and 3 cases (1.3%) of C . pneumoniae infection were documented by microimmunofluorescence . The results differ from those reported by others implying regional differences of C . pneumoniae as causative agent of pneumonia . The findings from Orebro County do not support any change in current antibiotic policy and we still regard penicillin as the first drug of choice in community-acquired pneumonia.

J Assoc Acad Minor Phys, 1992, 3(2), 50 - 6
Penicillin anaphylaxis: a review of sensitization, treatment, and prevention; Miles AM et al.; Penicillin and its derivatives are the commonest cause of drug-induced anaphylaxis, accounting for some 500 deaths per year in the United States . Penicillins are, however, sometimes withheld unnecessarily in patients who give spurious histories of penicillin allergy . A properly performed skin test will detect patients at risk of serious anaphylaxis . Many physicians do not fully appreciate the value of penicillin skin testing, however, and this has contributed to the withholding of penicillin and the use of other, often more expensive medications . Skin testing with a mixture of benzylpenicilloyl polylysine (major determinant) and a minor determinant mixture detects all patients at risk of major anaphylaxis . Of patients who test negative with these reagents, 1% to 4% will have non-life-threatening urticarial reactions . Skin testing is most useful in patients with a vague or inconsistent history of penicillin allergy for whom alternative antibiotics would not be effective or convenient . Aztreonam is the only semisynthetic penicillin that may safely be used in penicillin-allergic patients . Desensitization may be attempted in the patient with a positive skin test for whom there is no alternative to a penicillin-type drug.

Biomaterials, 1992, 13(4), 201 - 8
Comparative biophysical study of adsorbed calf serum, fetal bovine serum and mussel adhesive protein films; Olivieri MP et al.; Varying concentrations of different sera and adhesive agents are routinely used to increase cellular attachment to substrata . The surface-chemical effects of some of these surface-altering materials have been examined using ellipsometry, contact angle analysis and multiple-attenuated internal reflection infrared (MAIR-IR) spectroscopy . Specifically, 15% fetal bovine serum (FBS), Ham's F-12 (containing 10% FBS + 1% penicillin/streptomycin), 10% calf serum and mussel adhesive protein (MAP) were allowed to adsorb on to similar and different surfaces and then compared . Each of these preparations is capable of altering the surface-chemical properties of substrata with varying resultant surface energies . It is therefore important to characterize serum in the proper concentrations on the substrata under consideration in order to understand the interfacial effects.

J Neural Transm Suppl, 1992, 35, 37 - 69
Genetic absence epilepsy in rats from Strasbourg--a review; Marescaux C et al.; We have selected a strain of rats and designated it the Genetic Absence Epilepsy Rat from Strasbourg (GAERS) . In this strain, 100% of the animals present recurrent generalized non-convulsive seizures characterized by bilateral and synchronous spike-and-wave discharges accompanied with behavioural arrest, staring and sometimes twitching of the vibrissae . Spontaneous SWD (7-11 cps, 300-1,000 microV, 0.5-75 sec) start and end abruptly on a normal background EEG . They usually occur at a mean frequency of 1.5 per min when the animals are in a state of quiet wakefulness . Drugs effective against absence seizures in humans (ethosuccimide, trimethadione, valproate, benzodiazepines) suppress the SWD dose-dependently, whereas drugs specific for convulsive or focal seizures (carbamazepine, phenytoin) are ineffective . SWD are increased by epileptogenic drugs inducing petit mal-like seizures, such as pentylenetetrazol, gamma-hydroxybutyrate, THIP and penicillin . Depth EEG recordings and lesion experiments show that SWD in GAERs depend on cortical and thalamic structures with a possible rhythmic triggering by the lateral thalamus . Most neurotransmitters are involved in the control of SWD (dopamine, noradrenaline, NMDA, acetylcholine), but GABA and gamma-hydroxybutyrate (GHB) seem to play a critical role . SWD are genetically determined with an autosomal dominant inheritance . The variable expression of SWD in offsprings from GAERS x control reciprocal crosses may be due to the existence of multiple genes . Neurophysiological, behavioural, pharmacological and genetic studies demonstrate that spontaneous SWD in GAERS fulfill all the requirements for an experimental model of absence epilepsy . As the mechanisms underlying absence epilepsy in humans are still unknown, the analysis of the genetic thalamocortical dysfunction in GAERS may be fruitful in investigations of the pathogenesis of generalized non-convulsive seizures.

Zhonghua Wai Ke Za Zhi, 1992 Jan, 30(1), 48 - 9, 64
{Large dose of penicillin misinjected into the spinal subarachnoid space}; Wu ZL; Large dose of penicillin was misinjected into the spinal subarachnoid space of 3 patients . Dangerous symptoms such as epileptic status, difficult respiration and severe cerebral edema occurred . Fortunately, the patients were treated promptly without sequelae.

Padiatr Padol, 1992, 27(6), A81 - 93
{Lyme borreliosis in childhood}; Millner M; Ten years after detection of Borrelia burgdorferi as the etiologic agent of Lyme borreliosis and after introduction of serological methods an overview of the disease in children is given and compared with own observations . In view of the wide clinical spectrum and the difficulties in interpreting serological results the early diagnosis of Lyme borreliosis is still problematic at present . On the other hand, in case of late diagnosis therapeutic failure and/or partial recovery may result . Data of 138 children with clinically suspected recent Lyme borreliosis demonstrate that the early diagnosis particularly of neuroborreliosis can only be ameliorated when a careful synopsis of all specific and nonspecific laboratory parameters available is done . Additionally, the results of a prospective randomized study of the treatment of acute neuroborreliosis (penicillin G sodium versus ceftriaxone) and results of liquor patency and half-life of ceftriaxone are presented.

Clin Exp Dermatol, 1992 Jan, 17(1), 44 - 6
Bullous secondary syphilis; Lawrence P et al.; An earlier standard syphilology textbook states that 'If vesicles are an essential part of an eruption in an adult, the lesions are not due to secondary syphilis' . However, vesicular and bullous eruptions do occur in congenital syphilis and rare reports of both vesicular and pustular eruptions in adults with secondary syphilis have been published . We describe a patient with a bullous-pemphigoid-like eruption and a positive VDRL in whom treatment with a course of procaine penicillin resulted in rapid permanent resolution of the eruption.

Zentralbl Chir, 1992, 117(7), 394 - 7
{Treatment of type II B open fracture--therapeutic regimen and results}; Ostermann PA et al.; A consecutive series of 119 type III B compound fractures in 103 patients was treated at the University of Louisville from May 1983 to May 1989 . All patients had timely irrigation of their wounds, serial wound debridements, external skeletal stabilization and parenteral systemic antibiotics (penicillin, cefazolin, tobramycin) . 96 open fractures were managed with the supplemental local use of tobramycin-PMMA-beads . There were 13.5% wound infections and 10.1% osteomyelitis observed . The additional local antibiotic therapy was of significant (p less than 0.001, p less than 0.025) benefit to lower both infectious complications . The amputation rate was overall 5%, 9.7% for the lower leg . Four patients died due to multiple trauma.

Scand J Infect Dis, 1992, 24(4), 535 - 40
Rat bite fever (Streptobacillus moniliformis) with septicemia in a child; Rygg M et al.; A 5-year-old girl was admitted to hospital with fever, headache and nausea . Her C-reactive protein raised from less than 11 mg/l to 65 mg/l and she developed a maculopapular, petechial rash, especially pronounced on the soles and palms . After incubation for 3 days, Streptobacillus moniliformis was found in all blood cultures that had been taken . Some weeks before her admission, the girl had been playing with her grandmother's pet rats, which later had died from an unknown disease . There was no history of rat bite . Her condition improved rapidly after treatment with penicillin and chloramphenicol, and she was discharged from hospital after 10 days without sequelae.

Ann Trop Paediatr, 1992, 12(2), 143 - 8
A study of bacterial meningitis in Kumasi, Ghana; Mackie EJ et al.; A prospective study of acute bacterial meningitis in infants and children in Kumasi, Ghana identified 69 cases by culture or antigen detection . Of these, 50.7% (n = 35) were S . pneumoniae, 34.8% (n = 24) N . meningitidis and 14.5% (n = 10) H . influenzae . The mortality for each pathogen was 36.4%, 17.4% and 30%, respectively, showing no significant difference . In pneumococcal meningitis, the most significant clinical factor associated with an increased mortality rate or subsequent neurological sequelae was a lowered level of consciousness at admission (chi 2 = 8.66, d.f . = 1, p = 0.003) . Antibiotic susceptibilities were determined in the 40 positive isolates . Six cases of N . meningitidis and two of S . pneumoniae were penicillin-resistant, and there was a single case of chloramphenicol-resistant S . pneumoniae.

J Neural Transm Suppl, 1992, 35, 7 - 19
Pharmacological models of generalized absence seizures in rodents; Snead OC 3rd; A number of animal models of generalized absence seizures in rodents are described . These include absence seizures induced by gamma-hydroxybutyrate (GHB), low dose pentylenetetrazole, penicillin, THIP, and AY-9944 . All of these models share behavioral and EEG similarity to human absence seizures and show pharmacologic specificity for antiabsence drugs such as ethosuximide and trimethadione . Moreover, the absence seizures induced by these agents are exacerbated by GABAergic agonists, a property unique to experimental absence seizures . These models are predictable, reproducible, and easy to standardize . They are useful both in studying mechanisms of pathogenesis of absence seizures as well as in screening for antiabsence activity of potential antiepileptic drugs.

Endeavour, 1992, 16(1), 14 - 6
The possible role of gliotoxin in health and disease; Waring P et al.; Demonstration of the unique therapeutic properties of penicillin initiated an extensive investigation of other mould metabolites in the hope of finding other useful chemotherapeutic agents . While many hundreds of active substances were studied very few indeed satisfied the criteria necessary for clinical use . Among those whose toxicity ruled them out was gliotoxin . Recently, however a chance observation, in quite a different context, suggests that gliotoxin may prove valuable in human tissue transplantation.

Histochemistry, 1992, 97(2), 189 - 94
Production of monomeric antigen-enzyme conjugate to study requirements for follicular immune complex trapping; Laman JD et al.; Studies concerning the localization of immune complexes in lymphoid follicles and the involvement of these trapped immune complexes in the regulation of the immune response have thus far been performed with poorly defined complexes in terms of size and composition . For that reason, the minimum requirements for trapping in terms of number of antigen- and antibody molecules present in immune complexes could not be determined . We here describe the production and in vivo use of a monomeric HSA-HRP antigen-enzyme conjugate, readily demonstrable in cryostat sections and ELISA . This conjugate was obtained by combining the glutaraldehyde coupling-method with chromatography to fractionate monomeric and multimeric constituents . SDS-PAGE analysis showed that the conjugate consisted of a single molecular species of 109 kDa, whereas the often used periodate oxidation coupling method yielded a heterogeneous population of multimeric, oligomeric and monomeric molecules . We investigated the minimal size requirements for the composition of immune complexes to be trapped in murine spleen follicles using three different conjugates (monomeric HSA-HRP, multimeric HSA-HRP and multimeric HSA-HRP-Penicillin) and a panel of anti-HSA and anti-Penicillin monoclonal antibodies . We demonstrate that the smallest immune complexes, consisting of one antibody and two conjugate molecules, do not localize in splenic follicles . Immune complexes prepared with a single monoclonal antibody localize in follicles only if the epitope recognized occurs repeatedly on the antigen . The relevance of these results for physiological follicular trapping of protein antigens is discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Am J Perinatol, 1992 Jan, 9(1), 11 - 6
Premature rupture of the membranes: effect of penicillin prophylaxis and long-term outcome of the children; Kurki T et al.; To assess the value of prophylaxis with penicillin in women with premature rupture of membranes (PROM) and the long-term outcome of children born after prolonged PROM, we studied 221 women with this condition . Penicillin (5 mu twice, 6 hours apart) was given intravenously to 50 women and placebo to 51 women, whereas 76 comparable patients were treated without penicillin or placebo . The time interval between PROM and delivery ranged from 14 hours to 56 days . Chorioamnionitis occurred more frequently (p less than 0.05) among patients with placebo (14%) than among those treated with penicillin (2%) . One puerperal endometritis appeared in the placebo group compared with none in the penicillin group . One newborn (1.7%) born to a mother with placebo prophylaxis developed septicemia, compared with none in the penicillin group . The outcomes of pregnancies complicated with PROM treated without penicillin or placebo were comparable with those in the placebo group . In addition, we compared somatic and psychomotor development of 159 children born to mothers with prolonged PROM (more than 12 hours; mean, 5.6 days; range, 14 to 1344 hours) with those of 43 children born at similar gestational age within 5 hours after PROM . No pulmonary sequelae could be linked to the long time period between PROM and delivery, but infants born soon after PROM more often (p less than 0.05) had cerebral palsy (8 of 43, 18.6%) than did infants born after prolonged PROM (7 of 159; 4.4%) . We conclude that, in cases with PROM, penicillin prophylaxis decreases maternal and neonatal infectious morbidity and that the long interval between PROM and delivery does not impair the long-term outcome for these children.

J Chem Technol Biotechnol, 1992, 55(3), 251 - 61
Extraction of penicillin G from simulated media by an emulsion liquid membrane process; Lee SC et al.; The extraction of penicillin G from simulated media was performed by water/oil/water (w/o/w) emulsion liquid membranes (ELMs) and studied under various operational conditions in a batch system . The degree of extraction achieved was between 80% and 95% under specific conditions . A concentration of greater than nine times the initial concentration of penicillin G in the external phase was obtained in the internal phase . The pH of the internal aqueous solution, containing a basic salt, was theoretically calculated on the basis of the amount of penicillin G transported into the internal phase . The calculated results agreed with the experimental data well and were used to select a suitable type and concentration of a basic salt in the internal phase to give a pH within the range 5 to 8 where penicillin G was stable after the termination of extraction . The extraction of penicillin G was successfully performed by the ELM process with sodium carbonate in the internal phase.

J Chem Technol Biotechnol, 1992, 55(1), 79 - 84
Thermal inactivation kinetics of penicillin G acylase obtained from a mutant derivative of Escherichia coli ATCC 11105; Erarslan A et al.; Thermal inactivation kinetics of native and glutaraldehyde cross-linked forms of penicillin G acylase obtained from a mutant derivative of Escherichia coli ATCC 11105 were studied . Apparent activation energies for thermal inactivation of both native and cross-linked forms of enzyme were calculated to be {57.71 +/- 8.46} and {67.11 +/- 13.83} kcal mol-1 respectively . This slight increase in activation energy suggested that glutaraldehyde cross-linking did not markedly protect against thermal activation . Cross-linked enzyme did, however, have a significantly improved half-life at temperatures between 40 degrees C and 50 degrees C.

J Chem Technol Biotechnol, 1992, 55(1), 1 - 8
Permeation of 6-nitro-3-phenylacetamide benzoic acid (NIPAB) and hydrolysis by penicillin acylase immobilized in emulsion liquid membranes; Miesiac I et al.; The effects of various commercial and model surfactants of different structure and hydrophilicity were studied on water-in-oil (w/o) emulsion stability, potassium cation leakage and permeation of 6-nitro-3-phenylacetamide benzoic acid in a model system using Penicillin acylase (EC 3.5.1.11) immobilized in a liquid membrane . Both emulsion stability, potassium leakage and permeation of organic substances depend upon hydrophilicity of surfactants . Hydrophilic surfactants may be used to stabilize emulsions only in mixtures with hydrophobic emulsifiers . Additions of small quantities of hydrophilic surfactants to the system in which permeation occurs together within an enzymatic process may be advantageous . Both the rate of permeation and potassium transfer significantly increase when hydrophilic surfactants are present . There was no relationship observed between potassium cation transfer from the internal phase and emulsion stability in the storage test.

Appl Microbiol Biotechnol, 1992 Jan, 36(4), 499 - 502
Genetic instability of industrial strains of Penicillium chrysogenum; Kunkel W et al.; It has shown that several characteristics of high-producing industrial strains of Penicillium chrysogenum tend to segregate in the course of cultivation (slant-to-slant transfer) . Segregation includes a decrease in the yield of penicillin, mean conidial size, mean size of the nuclei, and an increase in the proportion of morphologically wild-type colonies . These lower-producing segregants also have a higher sensitivity against ultraviolet radiation and, as shown by cytofluorometric methods, a lower DNA content in the conidia, a decrease in phosphate uptake and in the activity of extracellular alkaline phosphatases compared to high-producing strains . Obviously, during mutagenesis/selection programmes ploidy mutants have been selected, which entails an increase in the number of genes coding enzymes responsible for penicillin biosynthesis . In the absence of selection pressure these high-producing strains segregate to lower-producing strains by chromosome losses in the course of slant-to-slant transfers.

J Chem Technol Biotechnol, 1992, 53(2), 205 - 14
Characterization and use of a penicillin acylase biocatalyst; Ospina SS et al.; A complete characterization of a penicillin acylase biocatalyst is presented, including the determination of physicochemical and kinetic parameters . Stability studies are detailed in terms of both storage temperature and pH as well as operational stability after 150 batch reactions of two hours duration each . An Arrhenius-type model was used to simulate the effect of pH on biocatalyst stability . A kinetic model is proposed to describe batch and continuous stirred tank reactors and to predict the long-term behavior of the process.

Synapse, 1992 Jan, 10(1), 54 - 61
Local application of bicuculline potentiates NMDA-receptor-mediated sensory responses of brain noradrenergic neurons; Shiekhattar R et al.; Direct application of bicuculline methiodide (BIC) to noradrenergic locus coeruleus (LC) neurons potently enhanced their sensory responsiveness . This increased responsiveness was due to the long-lasting expression of a new, N-methyl-D-aspartate (NMDA) receptor-mediated component of the synaptic response . This enhancement only occurred when a high stimulus intensity was used to induce the sensory response . A similar increase in responsiveness was observed with stimulation of the nucleus paragigantocellularis (PGi), one of the major direct afferents to LC . This action of BIC was neither mimicked by picrotoxin, penicillin, or the GABA-B antagonist, 2-hydroxy-baclofen, nor by agents that directly depolarize LC neurons . In addition, the inverse agonist of the benzodiazepine receptor, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), did not mimic this effect of BIC . The BIC-potentiated response component was eliminated by direct application of the neurotransmitter gamma-aminobutyric acid (GABA) . These results indicate that BIC, acting at a possibly novel site, unmasks NMDA receptors that can be activated by sensory stimuli . This may reflect a mechanism whereby interactions between two major neurotransmitter systems, excitatory amino acids (EAAs) and GABA, potently modulate signal transmission in the brain.

Trans Am Clin Climatol Assoc, 1992, 104, 15 - 23; discussion 23-5
Acute rheumatic fever; Sergent JS; A funny thing has happened on our way to the elimination of rheumatic fever from the United States . It is quite clear that, at least in some areas, rheumatic fever has made a dramatic resurgence . Although all the factors accounting for this are not clearly understood, there are several obvious conclusions that must be drawn: 1 . Rheumatic fever is no longer the province of the poor and overcrowded . 2 . Clinical manifestations, as embodied in the Jones criteria, may have changed somewhat over the years . 3 . New insights into the genetics and immunology of rheumatic fever may lead to a vaccine and/or effective therapy in the future . 4 . Rheumatic fever will continue to occur unless and until we resume an aggressive approach to the treatment and prophylaxis of pharyngitis, probably utilizing benzathine penicillin as our primary drug.

Chirurgie, 1992, 118(5), 309 - 14; discussion 315-6
{Indications and early results of splenectomy in hematologic diseases}; Fotiadis C et al.; In this retrospective study, we present 245 patients with various hematological diseases, who had undergone splenectomy for diagnostic or therapeutic purpose in our Department during the last 20-year period (1971-1991) . There were 138 men (56%) and 107 women (44%), with a mean age of 49 years . The hematological diseases, for which the splenectomy had been performed, were according to the frequency of admittance: hemolytic anemia, complicated or not by gallstone formation, Werlhoff disease (thrombocytopenic purpura), Hodgkin's disease, hairy-cell leukemia, chronic lymphatic leukemia, non-Hodgkin lymphoma . A drain was placed in the splenic bed in all patients . All patients received anticoagulant therapy and antibiotics as well . Pneumococcal vaccination had been done systematically during the preoperative period . All patients received prophylaxis with a Penicillin for two years postoperatively . During the immediate postoperative period the mortality (1.2% OPSI: 1 case) and the morbidity (3.5% OPSI: 1 case) rates were very low . In conclusion, splenectomy in patients with hematological diseases is a safe procedure, even in high risk patients, but it requires a preoperative preparation and a close cooperation between surgeon and hematologist during the peri- and postoperative periods . Additionally, we have to notice that the possibility of an acute serious infection exists for any patient during the rest of his life.

J Physiol, 1992 Jan, 445, 97 - 127
Kinetics of open channel block by penicillin of single GABAA receptor channels from mouse spinal cord neurones in culture; Twyman RE et al.; 1 . Reduction by penicillin of single gamma-aminobutyric acidA (GABAA) receptor currents from somata of mouse spinal cord neurones in culture was investigated using the excised outside-out patch-clamp recording technique . 2 . GABA (2 microM) alone or with penicillin (100-5000 microM) applied by pressure ejection from micropipettes evoked inward currents when patches were voltage-clamped at -75 mV in symmetrical chloride solutions . Averaged GABA receptor currents were decreased in the presence of penicillin . 3 . GABA receptor currents were recorded with at least two conductance states, a more frequent or main-conductance state of about 27 pS and a less frequent sub-conductance state of about 19-20 pS . The conductances of the two states were unchanged in the presence of penicillin . The kinetic properties of the main-conductance state were analysed and are summarized below . 4 . Penicillin produced a concentration-dependent reduction of GABA receptor open properties by reduction of average GABA receptor channel open duration and an increase in channel opening frequency . 5 . Penicillin shifted frequency histograms of GABA receptor channel open durations to shorter durations in a concentration-dependent manner . Three exponential functions were required to fit best the frequency histograms of open durations, suggesting that the channel had at least three open states . Penicillin produced a concentration-dependent reduction in the time constants obtained from the open duration frequency histograms . 6 . Frequency histograms of GABA receptor channel closed durations could be fitted with five to seven exponential functions, suggesting that the channel had multiple closed states . In the presence of increased concentration of penicillin, there was a reduction in the relative frequency of brief gaps and the appearance of new closed time constants . 7 . With increased penicillin concentration, GABA receptor channel burst frequency was unchanged, burst durations were increased, the number of openings per burst was increased and the per cent time open within a burst was decreased . 8 . The results suggested that penicillin produced simple open channel blockade of the GABA receptor channel . However, the experimental results also suggested that the association with and, perhaps, the dissociation of the blocker from its binding site were dependent upon the kinetic state of the open channel . Penicillin had faster association and slower dissociation rates when the channel was in unstable, brief open kinetic state than when the channel was in a more stable, longer open kinetic state . Possible models for penicillin reduction of single GABA receptor currents were simulated by computer and analysed.(ABSTRACT TRUNCATED AT 400 WORDS)

Neuroscience, 1992, 47(1), 63 - 8
GABAB receptors in various in vitro and in vivo models of epilepsy: a study with the GABAB receptor blocker CGP 35348; Karlsson G et al.; The effect of the GABAB receptor blocker CGP 35348 on epileptic processes in vitro and in vivo was studied . In hippocampal slices of the rat maintained in vitro, CGP 35348 (100 microM) induced a moderate increase in the frequency of extracellularly recorded spontaneous epileptiform burst discharges induced in CA3 by penicillin (1.2 mM), bicuculline (5 microM) and low Mg(2+) (0.1 mM) . This effect was observed in 50-75% of the slices . A similar but less consistent increase was also observed in CA1 in bicuculline and low Mg2+ . Data obtained by intracellular recordings from CA1 pyramidal cells in the presence of bicuculline (10 microM) demonstrated that CGP 35348 (100 microM) increased the duration of the paroxysmal depolarization underlying an evoked epileptiform burst and reduced the early component of the after hyperpolarization which followed the burst . In mice pretreated with isoniazid, CGP 35348 (300 mg/kg, i.p.) significantly increased the number of convulsing mice . However, convulsions induced by submaximal doses of pentylenetetrazol, picrotoxin or strychnine were not facilitated by CGP 35348 . We conclude that GABAB receptors appear to exert a suppressant effect on various kinds of epileptiform discharges of hippocampal neurons in vitro . In vivo, however, the role of GABAB receptors in regulating convulsions is less prominent since only isoniazid-induced convulsions were facilitated by GABAB receptor blockade.

Padiatr Grenzgeb, 1992, 31(1), 63 - 70
{Congenital syphilis}; Kurzke C et al.; Four infants with Lues connata, three with the early stage of the disease (patients 1-3), are reported . Diagnosis was made after exclusion of other diseases . Initially an infectious disease was expected, since anemia, leucocytosis, thrombocytopenia, hepatomegaly and/or splenomegaly and a bad condition were found . In two patients bone structure was abnormal . Elevated serum concentrations of liver enzymes (ALAT, ASAT) were the indication for liver biopsy in one patient, in whom an accompanying hepatitis was diagnosed . Treatment was performed with penicillin, no JARISCH-HERXHEIMER reaction was observed . The Lues tests were negative during pregnancy but a displacental transfer of pathogenic agents could be assumed . Patient 4 was diagnosed at 9 months of age . Infection of the mother probably occurred in the last 6 weeks of pregnancy . It can not be decided if the baby has a connatal or acquired Lues . The titer decrease of the CMT-test after the end of the penicillin therapy is a marker for a successful treatment . If treatment was started at 2 years of age a total clinical recovery can be expected . The case reports demonstrate that negative Lues test during pregnancy do not exclude Lues connata in newborns . The Lues diagnosis should be considered if an infectious disease in a newborn can not be diagnosed . A general Lues serodiagnostic test is recommended in all newborns before they leave the obstetrics department.

Rev Neurol (Paris), 1992, 148(12), 783 - 5
{Thrombosis of the upper longitudinal sinus and syphilitic cranial osteitis}; el Alaoui Faris M et al.; A 33-year old man developed progressive intracranial hypertension with papilloedema due to thrombosis of the superior sagittal sinus (SSS) by extension of a skull osteitis . Serological tests for syphilis were positive in blood, CSF and synovial fluid . Under treatment with penicillin and corticosteroids signs of intracranial hypertension and CT scan abnormalities disappeared . SSS thrombosis persisted at angiographic control.

Chin J Biotechnol, 1992, 8(2), 73 - 82
Location and trans-action of the pac regulatory gene; Jiang Q et al.; The study on the localization of the pac gene indicated that the regulatory and structural genes were located in a 3.5 kb HindIII-EcoRI fragment . In this paper we report that a series of deletion derivatives of plasmid pPA6 was constructed and the effect of deletions on the pac expression was determined . The results suggested that the pac regulatory gene was located in the SphI-PvuII fragment within the pac structural gene . Then the SphI-PvuII fragment was cloned to the plasmid pTZ18U at the SphI-SmaI sites and the resultant plasmid pPA57 was transformed into the penicillin acylase producing strain E . coli D816 to observe the effect of SphI-PvuII fragment on the chromosomal pac expression . The results demonstrated that the regulatory gene within the SphI-PvuII fragment regulated the pac expression in trans . Computer analysis indicated that there were two ORFs in the SphI-PvuII fragment as possible candidates coding for the regulatory protein . The study on precise localization of the pac regulatory gene is in progress.

Chin J Biotechnol, 1992, 8(3), 153 - 8
Regulatory mode of the pac gene expression; Jiang Q et al.; 1.65kb HindIII-BgIII DNA fragment containing pac operator was cloned from plasmid pPA4 to pBR322 at HindIII-BamHI sites, the resultant plasmid pPA41 was transformed into E . coli D816 carrying an intact pac operon on its chromosome, then the effect of operator titration was estimated . It was found that the penicillin acylase activity in E . coli D816 (pPA41) cells was higher than that of in E . coli D816 cells . The operators on high copy number plasmid pPA41 competed for the regulatory proteins with the single copy operator on the chromosomal pac operon, thus the expression of the pac gene was enhanced, because the free regulatory proteins were decreased by operator titration . The results of RNA-DNA hybridization showed that the cellular pac mRNA concentration was parallel to the penicillin acylase activity, and the pac mRNA in E . coli D816 (pPA41) cells was much higher than that of in E . coli D816 cells . These results indicated that the expression of pac gene was negatively controlled at transcriptional level.

Zhen Ci Yan Jiu, 1992, 17(2), 96 - 8
{Inhibitory effect of electro-acupuncture on penicillin-induced amygdala epileptiform discharges}; Zhang Z et al.; Epileptiform discharge induced by microinjection of penicillin in the rat's amygdala was attenuated after acupuncture of certain "acupoints", as revealed by reduction of frequency and amplitude . The effect of acupuncture was reversed by microinjection of naloxone or 3M-P into peritoneal cavity, thus suggesting the participation of endorphin and GABA in antiepileptic action of acupuncture.

J Enzyme Inhib, 1992, 6(2), 165 - 73
Novel inhibitors of enkephalin-degrading enzymes . IV: Structure-activity relationships within the penicillins as enkephalinase inhibitors; Livingston SJ et al.; A range of penicillins have been examined as competitive reversible inhibitors of enkephalinase (neutral endopeptidase; EC 3.4.24.11) . Carfecillin (Ki = 0.18 microM) was the most potent inhibitor in the series, whereas cloxacillin (27.5 microM), ampicillin (41.0 microM), nafcillin (58.7 microM) and carbenicillin (158 microM) had moderate potency and benzyl penicillin (885 microM), mezlocillin (473 microM) and azlocillin (556 microM) were weak inhibitors . Structure-activity relationships within the series have been rationalised from a consideration of molecular graphics analysis of the match between receptor binding groups with thiorphan as well as log P values.

World Health Stat Q, 1992, 45(2-3), 228 - 37
The endemic treponematoses: not yet eradicated; Meheus A et al.; The endemic treponematoses which comprise yaws, endemic syphilis (bejel) and pinta constitute a group of potentially disabling and disfiguring infections which primarily afflict children in tropical and subtropical areas . Foci where these diseases are now endemic have a patchy distribution and are typically confined to underprivileged communities living in remote rural areas, with little or no access to health services and removed from the mainstream of socioeconomic development . A drastic decline in the prevalence of these infections was brought about by the implementation of mass treatment campaigns with penicillin under the technical guidance of WHO and with material support from UNICEF in the 1950s and 1960s . These worldwide campaigns against the endemic treponematoses halted disease transmission in many areas and held the promise of complete eradication if intensive surveillance could be continued for some time with the increasing involvement of the basic health services . National campaigns were so successful that relatively low priority was given to the preparation of the rural health services for this new task . The failure of many countries to integrate active control measures into the functions of the rural health services led to the gradual build-up and extension of treponemal reservoirs and the resurgence of foci of increased disease transmission particularly in communities where standards of hygiene and health care had remained low . In a number of former endemic foci only low-level transmission persisted; in a few areas disease prevalence increased dramatically to reach pre-campaign levels . The lack of technical and financial resources limited the success of renewed national control activities in the most affected areas . Today, with waning interest in these diseases confined to remote, and thus silent, population groups, and a decreasing ability of health staff to identify cases, data collected by countries need to be supplemented by information from other sources in order to arrive at a more valid assessment of the situation concerning the endemic treponematoses . Central and West Africa are most severely affected by the resurgence of the endemic treponematoses . In recent years a number of countries (e.g . Ghana, Cote d'Ivoire and Mali) have launched renewed control efforts, often combining yaws or endemic syphilis control with other public health programmes . In Central Africa itinerant pygmy groups are still highly affected by yaws and are an important source of infection for the sedentary population with which they come into contact . In Chad, Sudan and Ethiopia, there is some evidence of persistent foci of endemic treponematoses; the epidemiological situation in Southern Africa is not well established.(ABSTRACT TRUNCATED AT 400 WORDS)

Biochem J, 1991 Dec 15, 280 ( Pt 3), 659 - 62
Chemical modification of serine at the active site of penicillin acylase from Kluyvera citrophila; Martin J et al.; The site of reaction of penicillin acylase from Kluyvera citrophila with the potent inhibitor phenylmethanesulphonyl fluoride was investigated by incubating the inactivated enzyme with thioacetic acid to convert the side chain of the putative active-site serine residue to that of cysteine . The protein product contained one thiol group, which was reactive towards 2,2'-dipyridyl disulphide and iodoacetic acid . Carboxymethylcysteine was identified as the N-terminal residue of the beta-subunit of the carboxy{3H}methylthiol-protein . No significant changes in tertiary structure were detected in the modified penicillin acylase using near-u.v . c.d . spectroscopy . However, the catalytic activity (kcat) with either an anilide or an ester substrate was decreased in the thiol-protein by a factor of more than 10(4) . A comparison of sequences of apparently related acylases shows no other extensive regions of conserved sequence containing an invariant serine residue . The side chain of this residue is proposed as a candidate nucleophile in the formation of an acyl-enzyme during catalysis.

Ugeskr Laeger, 1991 Dec 2, 153(49), 3486 - 7
{Neuroborreliosis--a diagnosis easily overlooked}; Larsen AV; Neuroborreliosis is the commonest complication of untreated erythema migrans . The case histories of two patients with well documented neuroborreliosis are presented . In these patients, the symptoms, which consisted only of pain, did not immediately raise the suspicion of a neuroinfection . Intravenous penicillin therapy proved curative . Examination of the cerebrospinal fluid for pleocytosis and Borrelia antibodies confirmed the diagnosis . In cases of suspected erythema migrans and subsequent neurological symptoms, lumbar puncture is recommended even in cases where the only symptom is pain.

Eur J Obstet Gynecol Reprod Biol, 1991 Dec, 42 Suppl, S31 - 5
Maternal mortality and its prevention; Schuitemaker NW et al.; Maternal mortality rates in developed countries have declined steeply during the last 50 years . The introduction of sulphonamides and blood transfusion techniques contributed much to lowering maternal mortality rates . The maternal mortality rate in The Netherlands in 1983-1988 was 8.8/100,000 livebirths . In 57% substandard care factors could be identified . This suggests that further improvement in preventing maternal mortality is possible . Maternal mortality rates in developing countries are still unacceptably high as a result of high fertility and a high risk of dying each time a woman becomes pregnant . Complications of illegal abortion are responsible for 25-50% of maternal deaths . Safe contraception could probably result in an important reduction in the number of maternal deaths, but also the provision of accessible maternal health services is essential to reduce maternal mortality in developing countriesPIP: Physicians analyzed 1983-88 data on 99 maternal deaths in the netherlands to examine causes of death and to what degree substandard care contributed to the deaths . 65 cases were classified as direct maternal deaths, 14 ad indirect maternal deaths, and 20 as fortuitous maternal deaths . They did not include the 20 fortuitous deaths in the maternal mortality rate which stood at 8.8/100,000 live births . The physicians knew all the details in 66 maternal deaths . They identified substandard factors in 57% of these cases . Most of the cases associated with substandard care were women with pregnancy induced hypertension (eclampsia) . The substandard care factors included patient or physician's delay, wrong diagnosis, insufficient knowledge of proper treatment, operating without knowledge of clotting disorders, interventions on patients in an unstable condition, inadequate postpartum and postoperative surveillance, and lack of organization . The leading direct cause of maternal death was eclampsia (34%) then thromboembolism (21%), and obstetric hemorrhage (19%) . 41% of the women who died from eclampsia also suffered from cerebrovascular hemorrhage . Only 2 women died from septic abortion . The major indirect cause of maternal death was cerebrovascular hemorrhage (57%) . Among the direct maternal deaths, 52% had disseminated intravascular coagulation and 25% had a cesarean section . As recently as 1935 in developed countries, puerperal sepsis was the leading cause of maternal deaths (50%) then obstetrical hemorrhage and eclampsia (25%) . Mortality rates began to fall with the introduction of sulphonamides and later penicillin . In developing countries, however, maternal mortality remains very high . High rates are due to high fertility and a high risk of death each time a woman is pregnant . Availability of safe contraception and elimination of illegal abortions would reduce maternal mortality considerably .

Reg Anaesth, 1991 Dec, 14(6), 101 - 3
{An epidural spinal abscess as a lethal complication of peridural anesthesia}; Bollensen E et al.; We present a 71-year-old male in whom an epidural abscess developed within a short temporal interval after an epidural anesthetic . Due to different locations of the abscess and the site of the epidural puncture, the diagnosis was quite problematic . The initial symptoms consisted of pain in the shoulder-neck region, elevated temperature, and leucocytosis 1 week after the puncture was performed . The further course presented a picture of high spinal paralysis with respiratory insufficiency and massive cardiovascular problems . Magnetic resonance imaging of the cervical spine confirmed the suspected diagnosis of an epidural abscess (Fig . 1) . Due to the reduced general condition of the patient, an operation was initially not possible . After the patient's condition had stabilized under antibiotic therapy with penicillin G, vancomycin, and gentamycin, exploration of the abscess area was performed . Histologic studies showed granulomatous tissue resulting from the previous inflammation . During the subsequent course of the disease, the clinical symptoms did not regress significantly . The patient required prolonged mechanical ventilation and died of recurrent bronchopulmonary infections after 5 months of intensive care treatment . The probable pathogenesis of the abscess as well as the diagnostic and therapeutic aspects are discussed in summary.

J Clin Pharm Ther, 1991 Dec, 16(6), 477 - 81
Effect of change in vehicle composition on ophthalmic bioavailability of benzylpenicillin; Zinyemba E et al.; The stability and bioavailability of benzylpenicillin ophthalmic solutions were determined at pH 5, 6, 6.5, 7 and 8 in citrate buffer . The stability of benzylpenicillin solutions stored at room temperature was greatest at pH 6.6-7 while at 2-4 degrees C stability was greatest at pH 6.5 . The uptake by corneal and aqueous humour of benzyl {14-C} penicillin into ovine eyes was greatest at a pH of 6.5, which indicates that for optimum stability and bioavailability benzylpenicillin ophthalmic solutions should be prepared in citrate buffer at pH 6.5 . Under these conditions the stability of the refrigerated preparation is acceptable for a normal treatment period.

Orv Hetil, 1991 Dec 1, 132(48), 2684, 2687 - 8
{Historical reflections on health protection and the condom}; Forrai J; PIP: The condom was first mentioned in a 1564 writing by Gabriel Fallopius as a means of protection against syphilis describing his tests on 1100 people . The name itself has been ascribed to the Latin word condere, Cum Domino, the French city of Condom, and doctor Quondom, the physician of the English King Charles II . The Marquis de Sade and Casanova used it to avoid venereal diseases (VDs) . In London condom manufacturing started in the 18th century . Later it became a symbol of prostitution and immorality . The material used consisted of fish bladder or animal intestines (calf, sheep) . The discovery of the rubber tree and the invention of vulcanization by the American technician Goodyear in 1840 made possible large-scale production . In Hungary the 1st rubber manufacturing plant EMERGE started production in 1893 along with toys and other wares . IN 1895 the HUngarian medial association warned about the spread of syphilis facilitated by the activities of 15,400 syphilitic prostitutes in the country . 30% of hospital patients had syphilis . The use of the condom was limited, and illegitimate births increased by 10.5% during the millennium celebrations of Hungary's existence in 1896 . EMERGE manufactured condoms called Nono which were mostly distributed to soldiers during World War I, yet they had little popularity . US soldiers did not use the condoms either, as 7 million active days were lost due to VDs during World War II . In the 1950's Anna Ratko was Minister of Health in Hungary who opposed promotion of condoms to increase the population . The invention of penicillin in 1942 also pushed the condom to the background, but in the 1980's the epidemic of AIDS has made its use widespread .

Laryngorhinootologie, 1991 Dec, 70(12), 695 - 7
{Clinical aspects of acute epiglottitis in adults}; Knobber D et al.; During the last three years, 79 adults suffering from acute epiglottitis have been treated in the ENT departments of the university hospital Rudolf Virchow, Berlin, 36 women (41 years of age as an average) and 43 men (average age 39 years) . Acute epiglottitis developed either all of a sudden, within hours, or gradually, within days . All patients complained of dysphagia and pain in the throat; dyspnea could be observed in 20% . During examination, we could see an inflamed, thickened epiglottis with edema of the arytenoid cartilages . 55 patients reported an infection of the upper airway prior to the onset of symptoms of acute epiglottitis, epiglottic abscess developed in 11 adults . The inflammation responded satisfactorily to conservative antibiotic management (broad spectrum penicillin) . Only one patient had to undergo intubation, none of the adults required tracheotomy.

Presse Med, 1991 Nov 27, 20(40), 2065 - 8
{Resumption of function of the liver graft . Controlled comparative study of UW solution and SLF Cochin}; Boillot O et al.; Nowadays the UW solution is usually used in liver transplantation for graft preservation . The importance of each of its components has not been fully resolved . The omission of some of the components does not result in poor hepatic function . The aim of this controlled study was to assess the early graft function (ALAT, factor V and total bilirubin at days 1, 2, 3 and 6) after use of the UW solution and SLF Cochin . SLF Cochin is a modified UW solution without hydroxyethyl starch, adenosine, penicillin, dexamethazone and allopurinol . No significant difference was observed in the early graft function between the two solutions for a cold ischemia time below 15 hours . Considering the qualities of the SLF Cochin and its three fold lower cost, it is concluded that the use of the SLF Cochin solution is justified for liver transplantation in which foreseeable cold ischemia time is less than 15 hours.

J Pharm Sci, 1991 Nov, 80(11), 1017 - 9
Penicillin-enhanced chemiluminescence of the luminol-H2O2-Co2+ system; Chen S et al.; The luminol-H2O2-Co2+ system has been widely used in chemical and biological analysis . We report here an investigation of the observation that penicillins have the ability to prolong and enhance the intensity of chemiluminescence from luminol . The basis of this phenomenon appears, as revealed by difference spectroscopy, to be the formation of a complex between the beta-lactam and the superoxide ion . The latter is the oxidizing species responsible for the oxidation of luminol in alkaline solution and has a mean lifetime, in solution, of milliseconds . The stabilization of the superoxide ion by penicillin complexation extends the effective lifetime of the superoxide ion by a few orders of magnitude and thereby allows for more efficient oxidation of the beta-lactam . Several penicillins were determined by their enhancement of luminol chemiluminescence . A detection limit of 100 ng mL was obtained for penicillin G with a less-than-ideal detection system.

Bratisl Lek Listy, 1991 Nov, 92(11), 564 - 7
Risk factors for adverse drug reactions communication of the CHDM; Hoigne R et al.; In the CHDM (Comprehensive Hospital Drug Monitoring for Adverse Drug Reactions, Bern/St . Gallen), the data of the 34,838 computer registered patient admissions 1974-1988 were available for evaluation . We summarize the results of three different studies: 1 . A multivariate analysis of the risk factors to developed an ADR during hospital stay, mainly the number of drugs, age, sex and renal function . 2 . The occurrence rate of hyperkalemia under the treatment with diurectics, mainly potassium (K+)-losing with K+ substitution compared to the combination of K(+)-sparing with K(+)-losing preparations . 3 . The occurrence-rate of exanthema in relation to amino-penicillin preparations an allopurinol . The results are presented in the communication . (Tab 7, Fig . 1, Ref . 15) . Ref . 15.).

Eur J Clin Microbiol Infect Dis, 1991 Nov, 10(11), 947 - 8
Septicaemia caused by a penicillin-resistant Moraxella-like organism in a neutropenic patient; Phillips G et al.; Invasive infections with Moraxella and related species are unusual . In this report we describe a case of septicaemia in an immunocompromised patient caused by a Moraxella-like organism . The organism was difficult to identify in the laboratory and was also unusual in that it was resistant to penicillin.

Actas Urol Esp, 1991 Nov-Dec, 15(6), 580 - 2
{Renal actinomycosis: presentation of a case}; Egido R et al.; Renal actinomycosis is rarely suspected and is difficult to diagnose, limited to a few cases in any series . A 56-year-old man with renal actinomycosis and Rendu-Osler disease is described . Long-term therapy with penicillin resulted in a clinical cures . A case report is presented.

Osaka City Med J, 1991 Nov, 37(2), 133 - 40
Preparation of a drug-induced allergic hepatic disorder model with penicillin as hapten; Mizoguchi Y et al.; A drug-induced allergic hepatic disorder model was established using a hapten and carrier . Penicillin G was bound to glycine for the preparation of N-hydroxy succinic imidylglycinyl benzylpenicillate (PG-Gly-OSu) . Using this as the hapten and liver protein as the carrier, guinea pigs were sensitized with liver protein bound to PG-Gly-OSu . After 2 weeks, the sensitized guinea pigs were directly challenged with hepatocytes bound to PG-Gly-OSu through a mesenteric vein and hepatocellular disorder was induced . When the sensitized guinea pigs were challenged with PG-Gly-OSu alone or with liver protein alone, hepatocellular disorder could not be induced . These results suggest that the combination of PG-Gly-OSu as the hapten and liver protein as the carrier elicits a hepatocellular disorder similar to drug-induced allergic hepatitis.

Acta Otorrinolaringol Esp, 1991 Nov-Dec, 42(6), 455 - 7
{A comparative study of the efficacy of josamycin versus oral penicillin in the treatment of acute tonsillitis}; Aznar E et al.; We have compared the efficacy josamycin (750 mg/12 h/orally) versus penicillin V (500 mg/8 h) for the treatment of acute tonsillitis in a prospective randomized study . Of the 82 eligible patients, 18 were diagnosed of infectious mononucleosis and excluded and the remaining 64 could be evaluated . The duration of the fever and the clinical evolution was similar away the 31 randomized to receive josamycin and the 27 treated with penicillin . In conclusion, josamycin seems to be a useful alternative to penicillin for the treatment of acute tonsillitis.

Allergy, 1991 Nov, 46(8), 632 - 8
Differences in serum IgE antibody activity to benzylpenicillin and amoxicillin measured by RAST in a group of penicillin allergic patients; Blanca M et al.; To determine the influence of the acyl side chain on the IgE antibody specificity of the two most common penicillins inducing allergic reactions in our community, benzylpenicillin (BP) and amoxicillin (AX), IgE positive sera from a group of 24 patients allergic to penicillin were studied . RAST was determined in parallel to benzyl penicilloyl-polylysine (BPO-PLL) and amoxicilloyl-polylysine (AX-PLL) in each serum, and values greater than an established coefficient of variation of 15% were considered as different for either of the haptens used (BP and AX) . 16 sera proved to be more positive to BP (Group A), six to AX (Group B) and in two IgE was positive to both haptens with a similar value (Group C) . RAST titration concentration effect curves and RAST inhibition studies with a pool of sera from each group (A, B, C) and individual sera showed that most of them were more specific for either BPO or AX, a minority being of similar value to both . These findings indicate that the side chain structure of penicillins is relevant in the constitution of the antigenic determinant, although in some instances the common chemical structure of betalactam is recognised mainly by the IgE antibodies . The clinical relevance of these data needs to be established.

Rev Infect Dis, 1991 Nov-Dec, 13(6), 1207 - 12
Pleuropulmonary infections caused by Eikenella corrodens; Joshi N et al.; A case of pleuropulmonary infection caused by Eikenella corrodens is reported, followed by a review of clinical cases reported in the English-language literature since 1970 . On the basis of this review, the predisposing factors, clinical features, and principles of diagnosis and treatment of this infection are outlined . Although infection may occur at any age, it seems to occur most often in patients less than or equal to 14 or greater than or equal to 44 years of age . Adult patients commonly have some underlying medical illness, pleuropulmonary malignancy being the most common . Patients present with a variable combination of fever, cough, and pleuritic chest pain . Four radiographic patterns may be seen: pleural effusion, pneumonia, cavitation, or a combination of these . Ampicillin and penicillin G are effective therapeutic agents; although the susceptibility of E . corrodens to penicillin G has been accepted as the rule, it may not always prevail . The need for increased awareness of this organism as a cause of pleuropulmonary disease is stressed because it is resistant to clindamycin, an agent that is increasingly used to treat anaerobic pleuropulmonary infections.

FEMS Microbiol Lett, 1991 Nov 1, 68(1), 7 - 13
Identification of a new mutation in Escherichia coli that suppresses a pbpB (Ts) phenotype in the presence of penicillin-binding protein 1B; Garcia del Portillo F et al.; Analysis of the functional role of penicillin-binding protein 1B (PBP1B) of Escherichia coli led us to find a new mutation able to suppress thermosensitive growth of the pbpB2158(Ts) mutant strain, which harbors a thermosensitive PBP3 protein only in the presence of a ponB+ background . The mutation, originally isolated in a strain with a high dosage of PBP1B, could also suppress the pbpB(Ts) phenotype when a single copy of the ponB gene was introduced . These results clearly give further support to the implication of PPB1B in the septation process in Escherichia coli.

Appl Microbiol Biotechnol, 1991 Nov, 36(2), 163 - 6
Growth and the production of penicillins in Penicillium chrysogenum with palm oil and its various fractions as carbon sources; Tan IK et al.; The utilisation of palm oil and its fractions by Penicillium chrysogenum for growth and penicillin production is strain-dependent . Strain H1107 could utilise crude palm oil, its liquid (palm olein) and solid (palm stearin) fractions and its component fatty acids (oleic, palmitic, stearic and myristic) as the main carbon source; strain M223 could not . Cell-bound lipase activity was higher in H1107 than in M223.

Ugeskr Laeger, 1991 Oct 21, 153(43), 3004 - 7
{Diagnosis and treatment of ear diseases in general practice . A controlled trial of the effect of the introduction of middle ear measurement (tympanometry)}; Lildholdt T et al.; The diagnosis and treatment of diseases of the ear in general practice could be rendered optimal by employing tympanometry (measurement of the pressure in the middle ear) which is already known from specialist practice . This was investigated by means of a controlled investigation with cooperation between general practice, otologists and the health services in the County of Vejle . Following randomizing among 20 general practitioners, ten were trained in tympanometry (the test group) while ten did not change their principles for diagnosis and treatment (control group) . The criteria for inclusion in the investigation were the findings of indications for otoscopy in children under the age of 16 years . During a period of 12 months, parallel registrations of the data were made in the two groups and 3,166 children with an average age of 3.4 years were included . The clinical course showed statistically significant differences (p less than 0.05) between the groups as regards diagnosis and treatment: acute otitis media was found in 8.4% in the control group and 2.6% in the test group . Secretory otitis media (glue ear) was found in 14.2% in the control group and in 25% in the test group . Correspondingly, penicillin was prescribed for 7.6% in the control group and 4.1% in the test group . The otologists performed tubulation of the tympanic membrane in 0.9% in the control group and 3.2% in the test group . Continued investigations are necessary to elucidate whether tympanometry should be part of the daily routine in general practice.

Brain Res, 1991 Oct 11, 561(2), 292 - 8
Threshold extracellular concentration distribution of penicillin for generation of epileptic focus measured by diffusion analysis; Lehmenkuhler A et al.; The tissue volume required to produce a penicillin-induced interictal discharge in the local EEG was estimated . A pair of microelectrodes were lowered into the motor cortex of anaesthetised and artificially ventilated rats . One double-barrelled electrode was used to release tetramethylammonium (TMA+) by iontophoresis or to pressure eject a solution containing penicillin (PEN-) and TMA+ concentration . The extracellular distribution of PEN- was defined using diffusion analysis of the TMA+ . From these data the spatial distribution of PEN- was estimated at the times of first interictal spikes in the EEG . The critical mass of active nerve cells was calculated from the threshold concentration of PEN- needed to elicit paroxysmal depolarisation shifts in neocortical slices and found to lie within a tissue sphere with a radius of ca . 150 microns.

Nature, 1991 Oct 10, 353(6344), 492 - 4
Penicillin and beyond; Chain B; The discovery of penicillin remains one of the greatest advances in medical science . From the success of the discovery the biotechnology industry became established.

Med J Aust, 1991 Oct 7, 155(7), 480 - 4
Neutropenia due to low-dose methotrexate therapy for psoriasis and rheumatoid arthritis may be fatal; Mayall B et al.; OBJECTIVE: To review experience with neutropenia related to low-dose methotrexate therapy in patients with psoriasis and rheumatoid arthritis . DESIGN: Retrospective review of medical records . SETTING: A 509-bed Melbourne teaching hospital . PATIENTS: Five patients admitted in 1987 and 1988, with neutrophil counts of less than 1 x 10(9)/L, given low doses of methotrexate for psoriasis or rheumatoid arthritis . MAIN OUTCOME MEASURES: Death, or length of hospital admission . FINDINGS: Four patients were women, and one a man; three had been treated for psoriasis, and two for rheumatoid arthritis . Ages ranged from 56 to 91 years . The eldest patients, aged 77, 81 and 91 years, died . The other two were discharged after 43 and 48 days . Prior to or shortly after admission, four patients were treated with penicillin antibiotics which may have interfered with methotrexate excretion . CONCLUSIONS: Methotrexate clearances (related to creatinine clearance rates and presumably low) were probably reduced sufficiently by concomitant therapy to result in neutropenia . Practitioners using methotrexate should be aware of drug interactions resulting in delayed methotrexate excretion . Blood counts should be monitored after changes in therapy, especially in patients with impaired renal function, such as the elderly.

J Oral Maxillofac Surg, 1991 Oct, 49(10), 1116 - 20
Facial erysipelas: report of a case and review of the literature; Ochs MW et al.; The diagnosis of erysipelas is usually made clinically . Features that help distinguish erysipelas are acute onset, erythema, warmth, edema, pain, fever, and isolated regional involvement with clearly demarcated margins . High ASO titers and response to penicillin therapy are reassuring . Simple uncomplicated erysipelas or cellulitis in adults can usually be treated on an outpatient basis . Extensive facial involvement with fever and a toxic appearance warrants hospitalization . Facial cellulitis or erysipelas in children, unless quite limited, requires hospitalization because of the high risk of Hemophilus influenzae infection and sepsis . Hospitalized patients should show visible signs of resolution and be afebrile for at least 24 hours prior to discharge . They should be maintained on oral antibiotic therapy at home for an additional 7 to 10 days.

Pharmacol Biochem Behav, 1991 Oct, 40(2), 351 - 7
Time course of interictal EEG patterns induced by a penicillin injection into the olfactory cortex; Horn E et al.; In awake rats, the time courses of behavioural and cortical interictal hyperactivity patterns were investigated following an injection of the GABA antagonist Na-penicillin (PCN) (125 IU/0.5 microliters) into the olfactory or motor cortex . The cortical EEG was recorded by means of 6 AgAgCl-electrodes, behaviour was videotaped simultaneously . Behavioural hyperactivity developed immediately after PCN injection . It lasted longer than 2.5 to 4 h in the olfactory but less than 30 min in the motor cortex group of rats . The interictal EEG pattern of the olfactory group was characterized by a slow establishing of three centers of high cortical activity . They were located in the ipsilateral central and the contralateral frontal and occipital cortex . In the motor cortex group, however, a cortical center of high activity developed immediately after the PCN injection near the injection site only, or additionally, over the homotopic area of the contralateral hemisphere . The results indicate different susceptibility properties in the underlying neuronal networks . Ongoing epileptiform activity obviously modifies this susceptibility in a site-specific manner . Moreover, the time-correlated occurrence of high activity in the frontal motor and occipital cortex evoked by a PCN injection into the olfactory cortex suggests a close coupling of these three areas . A coupling between the frontal motor, occipital and focal area could not be shown, if PCN was injected into the motor cortex.

Biull Eksp Biol Med, 1991 Oct, 112(10), 362 - 5
{Anti-epileptic effect of the new calcium channel blocker IOS-1.1212}; Karpova MN et al.; In experiments on freely moving male Wistar rats it was shown that IOS-1.1212 (1,4-dihydropyridine) in a dose 2 and 10 mg/kg (i . p.) suppressed the penicillin-induced focal epileptic activity in cerebral cortex . Similar suppressing effect of IOS-1.1212 was shown on acute generalized tonic-clonic pentylenetetrazol (PTZ) seizures (75 mg/kg i . p.) and on chronic PTZ administration (PTZ-kindling, 30 mg/kg i . p . during 30 days): when injected 30 min before each PTZ administration it delayed the development of kindling-induced seizures susceptibility in randomized animals (series 1) and attenuated the severity of seizures in PTZ-sensitive animals (series 2) . However, IOS-1.1212 had no effect on the strychnine-induced focal epileptic activity . In male Icr:Icl mice IOS-1.1212 in a dose 1.5 and 5 mg/kg also influenced the PTZ convulsions (i . v . titration of 1% solution at a rate of 0.01 ml/s) and had no effect on the strychnine convulsions (i . v . titration of 0.01% solution at a rate of 0.01 ml/s) and on maximal electroshock . In addition, IOS-1.1212 significantly increased antiepileptic effect of phenobarbital on maximal electroshock.

Biologicals, 1991 Oct, 19(4), 355 - 63
Brucella melitensis Rev . 1 living attenuated vaccine: stability of markers, residual virulence and immunogenicity in mice; Bosseray N; Five commercial Brucella melitensis Rev . 1 vaccines from different sources were compared to the original Elberg Rev . 1 strain, in vitro for classic markers and in vivo in mice, for residual virulence and immunogenicity . Because colonies of several morphology types (smooth, non-smooth) were isolated from the vaccines, representative substrains were purified to study their in vitro and in vivo activities either at once (16 strains), or after storage by subculture (12 strains) and by lyophilization (eight strains) or after passage in mice (six strains) . After purification, five strains had the characteristic pattern of resistance to penicillin and streptomycin of the original strain while 11 differed by a two-fold dilution or more . A few modifications only occurred after storage or passage . Residual virulence--the time taken by 50% of the subcutaneously vaccinated mice to eradicate the strain from their spleen--or recovery time 50%, and immunogenicity--the ability of the vaccinated mice to restrict the spleen count 15 days after a virulent intraperitoneal challenge--were compared on eight strains after purification, subculture and lyophilization . After purification, one smooth strain out of five had the same activities as the original strain and three were as immunogenic but less virulent . One smooth strain and the three non-smooth were neither immunogenic nor virulent . Some strains which were typically non-smooth after purification recovered a smooth phase aspect after subculture, concomitantly with an increase in immunogenicity but not in virulence.(ABSTRACT TRUNCATED AT 250 WORDS)

Avian Dis, 1991 Oct-Dec, 35(4), 834 - 9
Mycoplasma gallisepticum as a model to assess efficacy of inhalant therapy in budgerigars (Melopsittacus undulatus); Brown MB et al.; One hundred budgerigars (Melopsittacus undulatus) were infected in the nares (0.02 ml/naris), eye (0.02 ml/eye), and throat (0.2 ml) with Mycoplasma gallisepticum (MG) R strain (3.175 x 10(7) colony-forming units/ml) . Fifty birds were treated with sterile broth and served as the controls; 25 of those were exposed to an inhalant, and the others were not treated . Infected birds were divided into four groups; 1) no treatment, 2) penicillin in drinking water, 3) inhalant, 4) both penicillin and inhalant . At days 3, 7, 10, 14, and 21 postinfection (PI), birds were assessed for clinical signs of disease . Five birds in each group were euthanatized at each interval PI; quantitative cultures were performed on lavages from the nares and trachea and on throat swabs; tracheas and air sacs were examined histopathologically . No clinical signs, lesions, or cultural isolations occurred in any control birds . All infected birds developed clinical signs and lesions of the trachea and air sac, but none died . The most severe clinical signs were seen in birds that were infected with MG and received no other intervention or birds that received penicillin in conjunction with infection . Increased respiratory tract lesions were associated with penicillin treatment; aerosol therapy resulted in fewer lesions.

Z Lebensm Unters Forsch, 1991 Oct, 193(4), 337 - 43
{Gas chromatographic method for the analysis of residues of seven penicillins in food of animal origin}; Meetschen U et al.; A capillary gas chromatographic method is described for the determination of residues of benzylpenicillin, phenoxymethylpanicillin, methicillin, oxacillin, cloxacillin, dicloxacillin and nafcillin in bovine muscle, liver, kidney, adipose tissue and milk . The samples are extracted with acetonitrile under slightly acidic conditions, the co-extracted water is separated with the addition of sodium chloride and dichloromethane and discarded . Clean-up is performed by liquid/liquid partitioning steps and anion exchange chromatography . The penicillin residues are methylated with diazomethane . After derivatization, only the extracts from liver and kidney needed further clean-up using cartridges with a polar diol sorbent . The gas chromatographic procedure is based on split/splitless injection, programmed temperature vaporization, separation on a methyl silicone fused silica column and nitrogen-specific thermionic detection . Internal standardization is used for quantification . The limits of detection for all penicillins are well below 3 microgram/kg in milk and all tissues . Recoveries of spiked samples at 3 and 10 micrograms/kg are in the range of 65-80% for milk and 50-70% for bovine tissues.

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