Arch Intern Med, 1986 Sep, 146(9), 1739 - 40 Disseminated gonococcal infection in elderly patients; Geelhoed-Duyvestijn PH et al.; Four elderly patients (71, 53, 57, and 62 years old) had disseminated gonococcal infection . Three patients presented with suppurative arthritis and the fourth with fever, skin lesions, and malaise . Although the signs and symptoms did not differ from those in the younger age group, the diagnosis was not considered clinically . All gonococci were susceptible to penicillin. Trop Geogr Med, 1986 Sep, 38(3), 299 - 300 A fatal pneumococcal infection in a vaccinated 9-year-old child with sickle cell disease; Babiker MA et al.; A fatal case of pneumococcal septicaemia and meningitis is described in a vaccinated nine-year-old Saudi child with sickle cell disease . Non-compliance to prophylactic penicillin might have been the cause of its fatal illness. Trop Geogr Med, 1986 Sep, 38(3), 277 - 82 Experience on follow-up of registered rheumatic fever patients in the Zimbabwean Midlands; Lutalo SK et al.; A total of 75 patients with rheumatic fever, 49 acute (ARF) and 26 acute-on-chronic (A-C-RF), registered in the Zimbabwean Midlands during a 7 year period {1973-1980}, followed up for 1-12 years where each one had a potential of follow-up of at least 5 years, were reviewed . Their mean age at diagnosis was 13.2 +/- 7.9 (range 3-39) years and 5 of them were over thirty years old . Thirty five percent were followed up regularly although only 20% realised the full potential . 12% of ARF who initially had no carditis, developed it on a recurrence . The disease was more florid among defaulters than among regulars; chronic valvular lesions being clinically established in 2.8 +/- 1.8 (range 1-6) years; chronic heart failure developing in 5.2 years and death occurring in relatively young patients aged 10.9 +/- 3.0 years old . There were more recurrences among defaulters than among regulars (p less than 0.001) . The follow-up was better in those with clinically established valvular lesions, worse in the asymptomatic ones and it was unrelated to age or residence . In addition to improving social-economic conditions, parenteral penicillin prophylaxis should be continued until one is at least 40 years old. J Lab Clin Med, 1986 Sep, 108(3), 217 - 23 In vitro comparison of antiplatelet effects of beta-lactam penicillins; Fletcher C et al.; beta-Lactam antibiotics have been shown to cause platelet dysfunction and bleeding in some patients . However, relative antiplatelet activity of various beta-lactams has remained controversial . Results of clinical studies have been variable because of the presence of underlying disease in the study patients, in addition to inherent difficulties of in vivo experimentation such as individual variations of drug metabolism and drug kinetics . Thus, we designed in vitro experiments to study the direct effect of penicillin G, carbenicillin, ticarcillin, mezlocillin, piperacillin, nafcillin, and azlocillin on platelets . Platelets obtained from normal volunteers were exposed in vitro for 15 minutes to increasing concentrations of the test penicillins (10.0, 12.5, 15.0, and 20.0 mmol/L), and the platelet aggregation response determined after the additional of adenosine diphosphate (2.5 to 5.0 mumol/L), epinephrine (0.1 X 10(-3) mol/L), thrombin (0.01 to 0.02 U/ml), and collagen (11.62 micrograms/ml) . All tested penicillins inhibited platelet aggregation in a saturable dose-dependent manner that was reversible by platelet washing . Biostatistical comparison of inhibition of platelet aggregation demonstrated nafcillin to cause significantly more inhibition, followed by azlocillin, mezlocillin, and piperacillin as a group . Penicillin G, carbenicillin, and ticarcillin were the least inhibitory . The mean percent inhibition (epinephrine) at 20 mmol/L concentration was nafcillin 86.4%, mezlocillin 83.2%, piperacillin 80.3%, azlocillin 76.4%, ticarcillin 73.2%, carbenicillin 66.4%, and penicillin G 58.4% (overall P less than 0.001) . We conclude that all penicillins tested in vitro inhibit platelet aggregation in normal individuals, but to varying degrees . The inhibitory response, which is most likely a membrane-related phenomenon, is dose dependent and reversible. J Bone Joint Surg Am, 1986 Sep, 68(7), 1057 - 61 Chronic arthritis of the knee in Lyme disease . Review of the literature and report of two cases treated by synovectomy; McLaughlin TP et al.; The arthritis that may be a part of Lyme disease, a spirochetal infection transmitted by ticks, has not been widely reported in the orthopaedic literature . Established chronic arthritis in patients who have Lyme disease most commonly affects the knee and may cause erosive joint disease . Antibiotics given early in the course of the disease can prevent chronic arthritis . When the arthritis is established, penicillin administered intravenously is curative in as many as 55 per cent of patients, but medical therapy alone may be insufficient to successfully treat the chronic stage of arthritis. J Neurochem, 1986 Sep, 47(3), 966 - 71 Pantothenic acid transport through the blood-brain barrier; Spector R et al.; The unidirectional influx of D-pantothenic acid (PA) across cerebral capillaries, the anatomical locus of the blood-brain barrier, was measured with an in situ rat brain perfusion technique using {3H}D-PA (1.1 Ci/mmol) . PA was transported across the blood-brain barrier by a saturable system that could be described by a Michaelis-Menten transport model with a half-saturation concentration and maximal influx rate of 19 microM and 0.21 nmol/g of brain/min, respectively . PA (0.3 microM) transport through the blood-brain barrier was significantly inhibited by probenecid, nonanoic acid, and biotin (all less than or equal to 0.25 mM), but not by penicillin G, pyruvate, beta-hydroxybutyrate, L-leucine (all 1 mM), or poly-L-lysine HBr (1 mg/ml) . Probenecid (0.25 mM), nonanoic acid (0.5 mM), and PA (1.0 mM) did not inhibit {3H}L-leucine transport through the blood-brain barrier, whereas 30 microM-L-leucine inhibited {3H}leucine transport to 23% of control values . Thus, PA is transported through the blood-brain barrier by a low-capacity, saturable transport system with a half-saturation concentration approximately 10 times the plasma PA concentration . Although involved in the transfer of PA from blood into brain, this system does not play an important regulatory role in the synthesis of CoA from PA in brain. EMBO J, 1986 Sep, 5(9), 2399 - 405 The C terminus of penicillin-binding protein 5 is essential for localisation to the E . coli inner membrane; Pratt JM et al.; Penicillin-binding protein 5 (PBP5) has been previously identified as a component of the inner membrane of Escherichia coli and we present here further evidence that PBP5 is tightly bound to the membrane . To investigate the regions of PBP5 involved in membrane binding we have constructed a series of C-terminal deletions and shown that the removal of as few as 10 amino acids results in the release of the truncated protein into the periplasm . The C terminus, therefore, appears to be important for interaction with the membrane; however, inspection of the amino acid sequence does not reveal extended runs of hydrophobicity typical of a membrane anchor . Thus we conclude that PBP5 is anchored to the inner membrane by a mechanism not previously described. Antibiot Med Biotekhnol, 1986 Sep, 31(9), 655 - 8 {Induced mutagenesis in Escherichia coli--a producer of penicillin acylase}; Kochetkova EF et al.; The action of certain chemical mutagens such as N-nitroso methyl urea, N-nitroso ethyl urea, N-nitroso dimethyl urea and N-nitroso methyl biuret, as well as physical ones such as UV light on Escherichia coli producing penicillin acylase was studied . High mutagenic activity of N-nitroso methyl biuret with respect to this culture was shown. Biol Reprod, 1986 Sep, 35(2), 372 - 6 Testosterone production by collagenase-dispersed cells from baboon fetal testis; Redmond AF et al.; We determined whether dehydroepiandrosterone (DHA) and androstenedione (A) were converted to testosterone (T) by the midgestation primate fetal testis in the absence of gonadotropins . Testes from six baboon (Papio anubis) fetuses, obtained by cesarean section at Day 100-107 of gestation (term = Day 184) were dispersed with 0.2% collagenase . Cells (1.1 X 10(6)) were suspended in 4 ml Eagle's Minimum Essential Medium containing penicillin/streptomycin (MEM) and incubated for 20 h (37 degrees C) with or without DHA, A, pregnenolone (P5), 17 alpha-hydroxypregnenolone (17OH-P5), progesterone (P4) or 17 alpha-hydroxyprogesterone (17OH-P4) . Concentrations of T, A, P4, and 17OH-P4 in the medium and cells were measured by radioimmunoassay . Mean secretions of T and A, in the absence of exogenous substrates, were 0.5 +/- 0.2 and 0.8 +/- 0.3 ng/mg testis, respectively, and were not elevated by human chorionic gonadotropin (hCG) . Addition of DHA at 100, 500, or 1000 ng/4 ml increased (p less than 0.05) the production of T to 6 +/- 0.6, 33 +/- 10, and 64 +/- 26 ng/mg testis and the production of A to 13 +/- 5.5, 54 +/- 10, and 67 +/- 22 ng/mg testis, respectively . Similarly, addition of A at 100, 500, or 1000 ng/4 ml increased (p less than 0.05) production of T to 27 +/- 5.3, 155 +/- 29, and 254 +/- 79 ng/mg testis, respectively . In contrast, production of T and A remained near baseline concentrations when cells were incubated with 1000 ng/4 ml of P5, P4, 17OH-P5, or 17OH-P4.(ABSTRACT TRUNCATED AT 250 WORDS) J Clin Neuroophthalmol, 1986 Sep, 6(3), 157 - 9 Ophthalmoplegia due to actinomycosis; Leigh RJ et al.; A patient with actinomycosis, involving the meninges and right cavernous sinus, presented with diplopia due to a total right external ophthalmoplegia and left abduction weakness . These was partial right ptosis but the pupils were spared . The diagnosis was made by biopsy of a neck mass . A complete recovery was made in response to intravenous penicillin. Farmakol Toksikol, 1986 Sep-Oct, 49(5), 109 - 11 {Manifestation of the sensitization to penicillin preparations in rheumatism patients with a history of adverse reactions to them}; Smirnova RV et al.; Observation over 56 out-patients with rheumatism who had previously developed side responses to penicillin preparations indicated a longer preservation of the condition of sensitization to prolonged preparations of penicillin (bicillin-3) and a direct dependence of its preservation degree on the extent of aggravation of allergologic history. Neurosci Lett, 1986 Aug 29, 69(2), 143 - 9 Ketamine selectively suppresses synchronized afterdischarges in immature hippocampus; Brady RJ et al.; The role of excitatory amino acid neurotransmission in epileptogenesis was investigated in the developing hippocampus . Bath application of ketamine blocked penicillin-induced, synchronized afterdischarges in immature rat CA3 hippocampal neurons . Ketamine also decreased the duration of the preceding intracellularly recorded depolarization shift but had no measurable effect on the resting membrane potential or input impedance of pyramidal cells . Concentrations of ketamine that blocked afterdischarge generation dramatically depressed intracellular depolarizations produced by iontophoretic application of N-methyl-D-aspartate (NMDA) but not quisqualate . The effects of the NMDA antagonist 2-amino-7-phosphonoheptanoic acid on epileptiform discharges were identical to those of ketamine . These results suggest that an endogenous excitatory amino acid acting on an NMDA receptor plays a key role in the pronounced capacity of immature hippocampus for seizures. Z Kinderchir, 1986 Aug, 41(4), 239 - 40 Abdominal actinomycosis; Hadary A et al.; Abdominal actinomycosis seldom occurs before puberty . The symptomatology of abdominal actinomycosis is non-specific and the diagnosis is difficult to make . Previously, this condition was associated with a high mortality rate . The following patient had a flank abscess due to actinomycosis as a late complication of perforated appendix which was diagnosed by biopsy and culture . The patient responded to a prolonged course of chemotherapy with intravenous penicillin and metronidazole . This case illustrates the problems encountered in the diagnosis and management of childhood actinomycosis. J Dairy Sci, 1986 Aug, 69(8), 2214 - 8 Determining animal drug combinations based on efficacy and safety; Kratzer DD et al.; A procedure for deriving drug combinations for animal health is used to derive an optimal combination of 200 mg of novobiocin and 650,000 IU of penicillin for nonlactating cow mastitis treatment . The procedure starts with an estimated second order polynomial response surface equation . That surface is translated into a probability surface with contours called isoprobs . The isoprobs show drug amounts that have equal probability to produce maximal efficacy . Safety factors are incorporated into the probability surface via a noncentrality parameter that causes the isoprobs to expand as safety decreases, resulting in lower amounts of drug being used. Hautarzt, 1986 Aug, 37(8), 463 - 6 {Acquired cutis laxa (elastolysis generalisata)}; Hunziker T et al.; Following glomerulonephritis with subsequent anasarca and repeated penicillin treatments, generalized cutis laxa developed in a forty-year-old patient . Progressive signs of pulmonary emphysema appeared in the same period . Additionally, a monoclonal gammopathy was detected during extensive examination. Ital J Neurol Sci, 1986 Aug, 7(4), 413 - 20 Interictal EEG pattern in rabbit penicillin epilepsy; Gallitto G et al.; The effects of Na-penicillin G (1,000,000 I.U./kg i.v.) were studied in 28 rabbits implanted with surface and deep electrodes in the medial (mT) and lateral (lT) nuclei of the thalamus and in the cornu Ammonis dorsalis (CAd) . Attention was focused on interictal spike activity, cortical spindle activity and spikes-spindles relationship . A multifocal interictal EEG pattern, represented by cortical and thalamic spikes, was observed in 20 animals . A clear association between cortical spikes and spindles occurred almost constantly . Moreover a statistically significant increase in the average duration of spindles without changes in the average frequency was noticed . Seizure discharges had always a focal start and secondary generalization . The EEG features of parenteral penicillin epilepsy in the rabbit appeared to be more similar to those of the rat than to those of the cat . The spindle activity changes and the paroxysmal spike activity can be interpreted as two independent penicillin induced features appearing during raised cortical excitability periods. Methods Find Exp Clin Pharmacol, 1986 Aug, 8(8), 491 - 6 Parenteral penicillin model of epilepsy in the rat: a reappraisal; Bo GP et al.; A parenteral penicillin model of epilepsy in the rat was investigated with the aim of evaluating its reliability . Behavioral and EEG patterns were strongly variable in a group of 100 rats injected with 1,000,000 IU/kg of penicillin i.p . Gross counts of spikes were Fourier transformed and grouped into two time windows in 24 out of the 100 rats . Analysis of variance applied to compare the two time windows showed a sufficient suitability of the phenomenon for antiepileptic drug testing purposes . Five subsequent injections of penicillin performed in 8 rats showed that a spontaneous decrease of the response takes place, preventing a crossover design in pharmacological analyses . Evans Blue studies demonstrated that there was not a breakdown of the blood-brain barrier; this model can be used for testing anticonvulsants unable to penetrate the blood-brain barrier. Clin Pharm, 1986 Aug, 5(8), 682 - 9 Management of Stevens-Johnson syndrome; Crosby SS et al.; A patient with Stevens-Johnson syndrome is described, and the literature concerning the etiology, pathophysiology, clinical manifestations, and management of Stevens-Johnson syndrome is reviewed . A 2 1/2-year-old girl was treated with phenobarbital and i.v . ampicillin, followed by oral amoxicillin, for an upper-airway infection, otitis media, and febrile seizures . The fever returned, and she was treated unsuccessfully with penicillin and cefaclor . She was admitted to the hospital and treated with i.v . ampicillin . Within 24 hours an erythematous maculopapular rash developed . Phenobarbital was discontinued and phenytoin was begun . Four days later bullous lesions developed; ampicillin and phenytoin were discontinued, and cefazolin and phenobarbital were given . By the eighth day severe sloughing of the skin occurred over 75% of her body, and mucosal sloughing was apparent . The patient's condition was diagnosed as Stevens-Johnson syndrome . Porcine xenografts were immediately grafted to 75% of her total body surface . Severe lesions of the mouth and pharynx made parenteral nutrient therapy necessary, and ocular complications required the care of an ophthalmologist . Although the skin had healed by 14 days after grafting, another 14 days of treatment for respiratory complications was required . Stevens-Johnson syndrome is a severe exfoliative dermatitis accompanied by fever, inflammation of the gastrointestinal mucosa, and severe purulent conjunctivitis . It is associated with high morbidity and mortality . The etiologic factors may be iatrogenic (e.g., various antibiotics and anticonvulsants), infectious, or idiopathic . Respiratory complications, leukopenia, infections, erosion of the gastrointestinal mucosa, fluid and electrolyte disturbances, and chronic ocular complications may occur.(ABSTRACT TRUNCATED AT 250 WORDS) Neurology, 1986 Aug, 36(8), 1104 - 7 Resolution of gumma with steroid therapy; Fleet WS et al.; Antibiotic usage has rendered neurosyphilis uncommon, and cerebral gummas are rare . Reduced awareness of cerebral gummas and abolition of serologic screening can delay diagnosis of this treatable disease . Diagnostic confusion between syphilitic and nonsyphilitic cerebral mass lesions can be increased by apparent resolution of a gumma during steroid therapy . Such an occurrence in a young woman emphasizes the need for serologic testing for syphilis in diagnosing cerebral mass lesions . A trial of conservative therapy using penicillin (with or without prednisone) should be considered for patients with intracerebral mass lesions and positive serologic findings. Anal Biochem, 1986 Aug 1, 156(2), 413 - 6 A method for screening penicillin G acylase-producing bacteria by means of 2-nitro-5-phenylacetaminobenzoic acid test paper; Zhang QJ et al.; A simple, rapid assay for screening penicillin G acylase-producing bacteria is presented . The method is based on the formation of yellow 2-nitro-5-aminobenzoic acid by penicillin G acylase acting on 2-nitro-5-phenylacetaminobenzoic acid (NIPAB) . NIPAB test paper is briefly applied to bacterial colonies on the agar surface, which are subsequently scored individually on the paper by color; bright yellow indicates the presence of penicillin G acylase, natural color its absence . The present method is suitable not only for screening penicillin G acylase-production by a variety of bacteria but also for detection from a large number of transformant colonies of clones containing a gene encoding for the enzyme. Vet Hum Toxicol, 1986 Aug, 28(4), 318 - 22 Treatment of Amanita mushroom poisoning: a review; Parish RC et al.; Poisoning with mushrooms of the genus Amanita, members of which occur frequently in both North America and Europe, accounts for a significant number of deaths annually . Liver damage is the main clinical feature and death rates are variously reported to be from 11.3% to 51.3% of patients . The amount of mushroom ingested appears to be the main prognostic indicator and a fatal outcome appears inevitable if a large amount is eaten . In sublethal exposures, supportive therapy seems effective; when definitive treatment is considered, hyperbaric oxygen, penicillin and silymarin are indicated in conjunction with careful management of blood glucose concentration . Charcoal hemoperfusion, forced diuresis, hyperbaric oxygen, and thioctic acid may also be considered, although these treatment modalities are not clearly associated with increased survival. J Bacteriol, 1986 Aug, 167(2), 492 - 5 Penicillin-binding site on the Escherichia coli cell envelope; Amaral L et al.; The binding of 35S-labeled penicillin to distinct penicillin-binding proteins (PBPs) of the "cell envelope" obtained from the sonication of Escherichia coli was studied at different pHs ranging from 4 to 11 . At low pH, PBPs 1b, 1c, 2, and 3 demonstrated the greatest amount of binding . At high pH, these PBPs bound the least amount of penicillin . PBPs 1a and 5/6 exhibited the greatest amount of binding at pH 10 and the least amount at pH 4 . With the exception of PBP 5/6, the effect of pH on the binding of penicillin was direct . Experiments distinguishing the effect of pH on penicillin binding by PBP 5/6 from its effect on beta-lactamase activity indicated that although substantial binding occurred at the lowest pH, the amount of binding increased with pH, reaching a maximum at pH 10 . Based on earlier studies, it is proposed that the binding at high pH involves the formation of a covalent bond between the C-7 of penicillin and free epsilon amino groups of the PBPs . At pHs ranging from 4 to 8, position 1 of penicillin, occupied by sulfur, is considered to be the site that establishes a covalent bond with the sulfhydryl groups of PBP 5 . The use of specific blockers of free epsilon amino groups or sulfhydryl groups indicated that wherever the presence of each had little or no effect on the binding of penicillin by PBP 5, the presence of both completely prevented binding . The specific blocker of the hydroxyl group of serine did not affect the binding of penicillin . These observations suggest that a molecule of penicillin forms simultaneous bonds between its S at position 1 and sulfhydryl groups of PBP 5 and between its C-7 and free epsilon amino groups of PBP 5. Nucleic Acids Res, 1986 Jul 25, 14(14), 5713 - 27 Penicillin acylase from E . coli: unique gene-protein relation; Schumacher G et al.; The nucleotide sequence of the gene (pac) coding for penicillin G acylase from E . coli ATCC 11105 was determined and correlated with the primary structure of the two constituent subunits of this enzyme . The pac gene open reading frame consists of four structural domains: Nucleotide positions 1-78 coding for a signal peptide, positions 79-705 coding for the alpha subunit, positions 706-867 coding for a spacer peptide, and positions 868-2538 coding for the beta subunit . Plasmids were constructed which direct the synthesis of a pac gene product lacking the signal peptide, and the synthesis of the alpha subunit or the beta subunit . The following results were obtained: The two dissimilar subunits are processing products of a single precursor polypeptide; the spacer peptide is removed during processing; the precursor polypeptide lacking the signal sequence is accumulated in the cytoplasm; it is not processed proteolytically in the cytoplasm and it does not display enzyme activity . Processing, therefore, requires translocation through the cytoplasmic membrane; processing follows a distinct sequential pathway in vitro. JAMA, 1986 Jul 18, 256(3), 388 - 90 Evaluation for endotoxemia in patients receiving penicillin therapy for secondary syphilis; Shenep JL et al.; To determine if endotoxin liberation occurs after antibiotic administration to patients with syphilis, serial plasma samples were obtained from 15 patients receiving intramuscular penicillin G benzathine for secondary syphilis . The endotoxin content of these plasma samples was determined using a Limulus lysate assay (detection limit, 0.025 ng of reference Escherichia coli endotoxin per milliliter of patient plasma) . Although secondary syphilis is the stage of syphilis having the greatest burden of spirochetes and the highest incidence of Jarisch-Herxheimer reactions, no endotoxin was detected in plasma either before or after antibiotic therapy . Despite the absence of detectable endotoxemia, five patients experienced mild Jarisch-Herxheimer-like reactions . These results suggest that endotoxin is not an important factor in either secondary syphilis or the reactions associated with antibiotic therapy of this disease. Sex Transm Dis, 1986 Jul-Sep, 13(3 Suppl), 185 - 8 Ceftriaxone therapy for asymptomatic neurosyphilis . Case report and Western blot analysis of serum and cerebrospinal fluid IgG response to therapy; Hook EW 3rd et al.; A 27-year-old man with documented hypersensitivity to penicillin was treated intramuscularly for asymptomatic neurosyphilis with ceftriaxone (1 g daily for 14 days) . After treatment the serum titer in the VDRL (Venereal Disease Research Laboratory) test declined from 32 to four dilutions . Lumbar punctures at months 3, 6, 9, and 28 after treatment revealed normalization of the cell count in cerebrospinal fluid and a decline in the VDRL titer in cerebrospinal fluid from four to one dilution(s) . Western blot analysis revealed the presence in serum of IgG antibodies to at least 17 treponemal antigens and in cerebrospinal fluid of antibodies to at least ten treponemal antigens . Following ceftriaxone therapy serum and cerebrospinal fluid IgG reactivity to all antigens steadily decreased in intensity . These results indicate that ceftriaxone may provide a useful alternative therapy for penicillin-allergic patients with neurosyphilis. Klin Padiatr, 1986 Jul-Aug, 198(4), 299 - 305 {Guidelines for therapy of idiopathic thrombocytopenic purpura (ITP) in childhood}; Gadner H et al.; The term "idiopathic thrombocytopenic purpura (ITP)" comprises a rather heterogeneous group of diseases with different etiology and pathogenesis . 80% of the cases are acute forms following viral infections . Within the first 6 months the spontaneous remission rate is higher than 80% . The remaining patients develop an intermittent or chronic form of the disease . Lethal complications, commonly cerebral hemorrhage, are rare (less than 2%) . Following a review of the established and the recent experimental therapeutic approaches, the authors try to give comprehensive therapeutical guide-lines for the management of the various clinical forms of the disease . If there is only a minor bleeding diathesis, it is recommended to withhold therapy for 2 to 3 weeks, irrespective of the platelet count . If no spontaneous remission occurs, we suggest therapy with corticosteroids . In case of failure of this therapy, infusions of high-dose immunoglobulins are advisable . Short-lasting successes may even be prolonged with further infusions (once a week or at longer intervals)--thus postponing splenectomy . In addition, a combination of high-dose immunoglobulins and corticosteroids may be effective . Following pneumococcal vaccination and penicillin prophylaxis, splenectomy should be performed not earlier than one year after diagnosis of ITP and only in children older than 5 years . If splenectomy does not lead to recovery of the platelet count, immunoglobulin infusions--possibly combined with corticosteroids--may be repeated . Finally, if all the above proposed therapeutic actions have failed, immunosuppressive drugs (azathioprime or vincristine) may be necessary.(ABSTRACT TRUNCATED AT 250 WORDS) Farmakol Toksikol, 1986 Jul-Aug, 49(4), 22 - 5 {Effect of Cavinton on convulsions caused by chemical substances}; Dutov AA et al.; Cavinton was shown to protect mice against convulsions induced by corazol, strychnine and thiosemicarbazide . In addition, cavinton exhibited a definite antagonism to convulsive reactions produced by systemic administration of penicillin to cats and a combined administration of penicillin (intramuscularly) with tryptophan metabolite, quinolinic acid (intracerebroventricularly) . The anticonvulsant action of cavinton is suggested to be due to the involvement of the brain GABA- and serotonergic mechanisms . It is reasonable to test cavinton as a drug for treating some forms of epilepsy. J Forensic Sci, 1986 Jul, 31(3), 1150 - 3 Fatal intravenous drug abuse secondary to streptomycin overdose; Rance F et al.; A fatal case of chronic intravenous drug abuse involving the injection of a nonpsychoactive veterinary combination of penicillin G and streptomycin is reported . The circumstances surrounding the death indicate that the decedent died as a result of streptomycin induced paralytic neuromuscular blockade. Clin Exp Immunol, 1986 Jul, 65(1), 10 - 8 Expression of the B cell repertoire and autoantibodies in human African trypanosomiasis; Kazyumba G et al.; The relative importance of polyclonal B cell activation has been studied in relation to the development of autoantibodies in human African trypanosomiasis . In 34 patients investigated before specific treatment a broad expression of the B cell repertoire was observed including the production of anti-hapten (FITC, Penicillin, Phosphorylcholin) antibodies, of high levels of antibodies against some heterologous protein antigens (ovalbumin and tetanus toxoid) and of autoantibodies . Anti-ssDNA antibodies were detected in 84% of the patients and anti-IgG rheumatoid factors in 88% . Anti-striated muscle and anti-smooth muscle antibodies were also observed in 57 and 63% of the patients . Correlation analysis indicated that the formation of anti-DNA antibodies is associated with polyclonal B cell activation but probably depends on an additional B cell stimulation by released DNA or cross-reacting antigens . Anti-immunoglobulin antibodies are closely correlated with polyclonal B cell activation and their production is likely to reflect the high frequency of anti-IgG B cell precursors in the normal human B cell repertoire . The significance of these observations in relation to the pathological expression of trypanosomiasis should be particularly considered in the generation of immune complexes either in circulating blood or locally at the sites of parasite destruction. Antibiot Med Biotekhnol, 1986 Jul, 31(7), 514 - 9 {Oil and fat metabolism and the biosynthesis of penicillin}; Tikhonova OV et al.; When grown on media with vegetable oils the producer of penicillin was more sensitive to changes in the conditions of mass transfer . Their worsening resulted in a more significant decrease in the level of the mycelium productivity than that of media containing animal fats . The observed differences were associated with the fact that the rate of consumption of readily assimilated fat substrates, for instance sunflower oil, by the cells was sufficiently high even at defective aeration and agitation . Their further oxidation in the mycelium was retarded which resulted in increasing lipid levels in the cells, irreversible destruction of the mitochondria, followed by further lowering of the oxidation processes in the cells, and inhibition of basic and secondary metabolism . On media containing whale oil there were also changes in the structure of the hyphae and first of all mitochondria of Penicillium chrysogenum and inhibited oxidation of fats evident from fractional composition of the mycelium lipids . However, all these changes were less pronounced because of the low rate of the whale oil assimilation by the cells. Epilepsia, 1986 Jul-Aug, 27(4), 347 - 53 Effects of anticonvulsants on penicillin-induced bursting in guinea pig hippocampal slices; Schneiderman JH et al.; The effects of gamma-aminobutyric acid (GABA) and six anticonvulsants on penicillin-induced bursting were compared in guinea pig hippocampal slices . GABA, phenobarbital, pentobarbital, phenytoin, and diazepam slowed and eventually blocked spontaneous bursts . Low-intensity stimulation at concentrations that blocked spontaneous activity still evoked synchronous all-or-none burst responses, although the threshold increased and the bursts were briefer . Sodium valproate had similar effects, but very high concentrations (approximately 10 mM) were required . Ethosuximide paradoxically increased spontaneous burst rate . This model appears to be differentially susceptible to the actions of GABA and the anticonvulsants commonly used to treat tonic-clonic and partial seizures but not to the antiabsence drugs. Epilepsia, 1986 Jul-Aug, 27(4), 341 - 6 Effects of antiepileptic drugs on pentylenetetrazole-induced epileptiform activity in the in vitro hippocampus; Piredda S et al.; We studied the effects of four antiepileptic drugs on pentylenetetrazole-induced burst discharges in the CA3 region of the in vitro hippocampus . Diazepam and carbamazepine abolished the bursting activity in a gradual and dose-dependent manner . Phenobarbital only decreased the burst frequency . Valproic acid was either ineffective or actually caused an increase in both burst frequency and amplitude . The findings in this model were compared with results obtained by other investigators in a penicillin-induced model of epileptiform activity in the hippocampal slice . Diazepam had a similar effect on both pentylenetetrazole- and penicillin-induced burst discharges, but phenobarbital was ineffective in the pentylenetetrazole model, indicating that these chemically induced hippocampal epileptiform activities may be differentially sensitive to antiepileptic drugs. Rev Electroencephalogr Neurophysiol Clin, 1986 Jul, 16(2), 179 - 90 Relations between basal ganglia and hippocampus: action of substantia nigra and pallidum; Sabatino M et al.; Several interrelationships exist between basal ganglia and hippocampus . The ventral striatum appears to be involved in the control of the dopaminergic nigro-striatal pathway . The caudate, in turn, seems to influence the hippocampal theta rhythm and to inhibit hippocampal spikes . In the present work the role played by globus pallidus pars interna and substantia nigra pars compacta on hippocampal bioelectrical activity is studied . Injection of sodium penicillin i.v . produces steady interictal spikes in the hippocampus . Substantia nigra stimulation induces regular theta rhythm and inhibits the spikes . Pallidal stimulation, on the contrary, appears to strongly enhance epileptiform activity, proceeding to generalised seizure activity . The results are discussed in the light of a putative feedback loop from basal ganglia to hippocampus, probably underlying co-participation of the two subcortical structures in the control of motor behaviour. Epilepsia, 1986 Jul-Aug, 27(4), 359 - 66 Suppression of penicillin-induced focal epileptiform activity by locus ceruleus stimulation: mediation by an alpha 1-adrenoceptor; Neuman RS; Application of penicillin to the cerebral cortex of anesthetized rats by pressure ejection from a micropipette resulted in the appearance of focal epileptiform activity with low rates of penicillin release and focal penicillin spikes with higher rates . Electrical stimulation of the locus ceruleus (LC), a major norepinephrine-containing nucleus in the brainstem, or of its axons projecting to the forebrain, the dorsal noradrenergic bundle, suppressed penicillin-induced focal epileptiform activity but was less effective in suppressing focal penicillin spikes . Depletion of monoamines with reserpine blocked the suppressant effect of LC stimulation . Neither the selective depletion of 5-hydroxytryptamine with p-chlorophenylalanine nor administration of methysergide reduced the effectiveness of LC stimulation, suggesting that 5-hydroxytryptamine probably does not mediate the suppression . Pimozide partially antagonized the suppression of focal epileptiform activity induced by LC stimulation, which is consistent with antagonism of alpha-adrenoceptors but not dopamine receptors . beta-Receptor antagonists did not block the suppression of focal epileptiform activity by LC stimulation, suggesting that beta-receptors are not important in the observed suppression . Prazosin, a selective alpha 1-antagonist, at low doses blocked the suppression of focal epileptiform activity by LC stimulation whereas yohimbine, an alpha 2-antagonist enhanced the stimulation-induced suppression . Taken together, the data are consistent with LC and dorsal bundle stimulation releasing norepinephrine, which in turn suppresses focal epileptiform activity by an action mediated by an alpha 1-adrenoceptor. Br J Pharmacol, 1986 Jul, 88(3), 541 - 7 Convulsant doses of penicillin shorten the lifetime of GABA-induced channels in cultured central neurones; Chow P et al.; The influence of sodium benzylpenicillin (PCN) on membrane channels activated by gamma-aminobutyric acid (GABA) was studied in cultured spinal neurones of the mouse by the extracellular patch clamp technique . In whole-cell, current clamp recordings, concentrations of PCN above 0.2 mM significantly reduced the amplitude of the GABA response . Single channel currents activated by GABA were studied in outside-out patches of neuronal membrane . In both the absence and presence of PCN, cumulative open time distributions for GABA-activated channels were well fitted by the sum of two exponential terms, characterized by fast (tau f) and slow time constants (tau s) . PCN (2mM) reduced the mean value of tau s from 4.29 +/- 0.56 ms (mean +/- s.e . mean) to 1.12 +/- 0.09 ms but had no significant effect on tau f . The mean open time of GABA-activated channels, calculated from the double exponential fits, decreased from 1.39 +/- 0.35 ms to 0.53 +/- 0.02 ms in the presence of 2 mM PCN . The reduced mean open time of GABA-sensitive channels seen in the presence of PCN may contribute to the convulsant action of the drug in vivo. CMAJ, 1986 Jun 15, 134(12), 1353 - 6 Penicillin allergy: a practical approach to management; Sussman GL et al.; Although penicillin is nontoxic, it is highly immunogenic and is the most common drug that causes allergic reactions . A previous reaction to penicillin has been shown to be unreliable in predicting sensitivity in 75% to 90% of patients . To more accurately test for penicillin allergy, diagnostic skin test reagents have been developed; these include the major determinant (benzylpenicilloyl-polylysine) and the minor determinant mixture (penicillin G potassium, benzylpenicilloate sodium and benzylpenicilloyl-N-propylamine) . Penicillin skin testing has been shown to be safe and useful in predicting immediate IgE-mediated reactions (overall predictive value 99%) . Reactions that occur when patients are challenged with penicillin are mild or accelerated urticarial reactions . We outline a practical and rational therapeutic approach based on the current understanding of penicillin allergy. Exp Neurol, 1986 Jun, 92(3), 533 - 40 Systemic penicillin as an experimental model of epilepsy; Chen RC et al.; Systemic use of high-dose penicillin was studied in rats and cats to establish an experimental model of epilepsy . In rats, intraperitoneal injection of 2.5 to 5.0 million units/kg (MU/kg) penicillin was effective to induce spikes in 45.7 +/- 31.0 min (means +/- SD) and seizure in 71.5 +/- 38.4 min . In cats, intravenous administration of penicillin at 0.5 to 1.0 MU/kg induced spikes in 10.4 +/- 7.8 min and seizure in 32.2 +/- 19.8 min . Intraperitoneal use of penicillin at 1.0 to 2.0 MU/kg caused spikes in 24.0 +/- 18.4 min and seizure in 71.2 +/- 38.3 min . Pretreatment with intravenous isoniazid at 16.3 +/- 10.3 mg/kg significantly delayed the appearance of intravenous penicillin-induced spikes to 63.1 +/- 49.8 min or prevented the appearance of spikes and abolished the occurrence of seizures . Acupuncture at various points increased the penicillin-induced spikes and seizures. J S Afr Vet Assoc, 1986 Jun, 57(2), 91 - 3 A field trial comparing the efficacy of sulphamonomethoxine, penicillin, and tarantula poison in the treatment of pododermatitis circumspecta of cattle; Stampa S; Nearly 80% of 87 cattle suffering for the first time from pododermatitis circumspecta were cured by each of the three drugs under test . Sixty and 73% of those cured by sulphamonomethoxine and penicillin, respectively, and 29% of those cured by the tarantula poison (Theranekron), showed relapses within 6 months . Of the 92 cattle with previous records of pododermatitis circumspecta, sulphamonomethoxine cured 44%, penicillin 73% and Theranekron 32% . Of the latter three groups 72-80% showed relapses within the subsequent 6 months . The results of surgical treatments were, possibly, improved by the prior administration of Theranekron . In addition, in a pilot trial, the demarcation of a gangreneous udder half of a goat suffering from blue-bag, appeared to be accelerated by the parenteral administration of Theranekron. Ann Intern Med, 1986 Jun, 104(6), 798 - 800 Borrelia burgdorferi in joint fluid in chronic Lyme arthritis; Snydman DR et al.; Although indirect evidence suggests that chronic Lyme arthritis is caused by persistent infection with Borrelia burgdorferi, direct visualization has been lacking . We report the demonstration of B . burgdorferi from synovial fluid aspirated from the right knee of a 31-year-old man with Lyme arthritis for more than 1 year . After 6 days, culture medium inoculated with synovial fluid showed one motile and several nonmotile spirochetes . Direct immunofluorescence staining showed reactivity with anti-B . burgdorferi serum . Spirochetes were not seen in subcultured material . The patient's arthritis improved with high-dose intravenous penicillin . Identification of B . burgdorferi from the joint fluid of a patient with long-standing arthritis supports the concept that the arthritis is due to persistent infection. Can J Microbiol, 1986 Jun, 32(6), 473 - 80 alpha-Aminoadipate pool concentration and penicillin biosynthesis in strains of Penicillium chrysogenum; Jaklitsch WM et al.; Intracellular amino acid pools in four Penicillium chrysogenum strains, which differed in their ability to produce penicillin, were determined under conditions supporting growth without penicillin production and under conditions supporting penicillin production . A significant correlation between the rate of penicillin production and the intracellular concentration of alpha-aminoadipate was observed, which was not shown with any other amino acid in the pool . In replacement cultivation, penicillin production was stimulated by alpha-aminoadipate, but not by valine or cysteine . Exogenously added alpha-aminoadipate (2 or 3 mM) maximally stimulated penicillin synthesis in two strains of different productivity . Under these conditions intracellular concentrations of alpha-aminoadipate were comparable in the two strains in spite of the higher rate of penicillin production in the more productive strain . Results suggest that the lower penicillin titre of strain Q 176 is due to at least two factors: (i) the intracellular concentration of alpha-aminoadipate is insufficient to allow saturation of any enzyme which is rate limiting in the conversion of alpha-aminoadipate to penicillin and (ii) the level of an enzyme, which is rate limiting in the conversion of alpha-aminoadipate to penicillin, is lower in Q 176 (relative to strain D6/1014/A) . Results suggest that the intracellular concentration of alpha-aminoadipate in strain D6/1014/A is sufficiently high to allow saturation of the rate-limiting penicillin biosynthetic enzyme in that strain . The basis of further correlation of intracellular alpha-aminoadipate concentration and penicillin titre among strains D6/1014/A, P2, and 389/3, the three highest penicillin producers studied here, remains to be established.(ABSTRACT TRUNCATED AT 250 WORDS) J Bacteriol, 1986 Jun, 166(3), 985 - 92 Interaction of FtsA and PBP3 proteins in the Escherichia coli septum; Tormo A et al.; Mutations in the ftsA gene of Escherichia coli conferred a higher resistance to lysis induced by penicillin or by a combination of cefsulodin and furazlocillin . The ftsA2 allele codes for an FtsA protein which is inactive at 42 degrees C but is able to regain its activity once it is transferred back to 30 degrees C; ftsA2 filaments formed at 42 degrees C in the presence of penicillin divided once the penicillin was removed and the temperature was lowered to 30 degrees C . Potential septation sites in the filaments of wild-type cells treated in the same way remained inactive . The binding of a radioactively labeled derivative of ampicillin to penicillin-binding protein 3 (PBP3) was significantly decreased in strain D-3, containing the mutant allele ftsA3, when the binding assay was performed at the restrictive temperature . A molecular species able to cross-react with an anti-PBP3 serum was nevertheless found to be present in the envelope of D-3 cells . These observations suggested that the FtsA protein, a protein with a structural and regulatory role in septation, and PBP3, a protein enzymatically active in the synthesis of murein for septation, interact with each other. Z Hautkr, 1986 Jun 1, 61(11), 805 - 10 {Decreased incidence of postgonococcal urethritis following minocycline treatment compared to penicillin/spectinomycin}; Krause W et al.; Two groups of 30 patients each suffering from gonococcal urethritis were treated either with minocyclin for 7 days or with a single administration of penicillin or spectinomycin, respectively . 30% of them revealed an additional infection with C . trachomatis or U . urealyticum . On the 8th day, we observed remaining symptoms in only 20% of the patients treated with minocyclin, but in 40% of the group treated with penicillin/spectinomycin. Dtsch Med Wochenschr, 1986 May 30, 111(22), 861 - 4 {Double infection with early summer meningoencephalitis virus and Borrelia burgdorferi}; Kristoferitsch W et al.; A 68-year-old woman developed a meningoencephalitis 18 days after a tick bite . IgG and IgM antibodies against tick-encephalitis virus were demonstrated, by enzyme-linked immunoabsorbent assay, in both serum and cerebrospinal fluid (csf) . Lymphoplasmocytic pleocytosis was present in csf for over six weeks, as was an increased IgM level . Three weeks after the onset of neurological symptoms and clearing of the encephalitis there occurred multiple peripheral pareses in the left leg which were slow to regress . Retrospectively, IgM and IgG antibodies against Borrelia burgdorferi were demonstrated in deep-frozen serum and csf . Since IgG antibodies against Borrelia burgdorferi, locally synthesised in csf, could also be demonstrated, it must be assumed that the patient had a double infection . It is suggested that in confirmed cases of tick-encephalitis with an atypical course an additional infection with Borrelia should be considered, because if present the latter can be successfully treated with high doses of penicillin. J Biol Chem, 1986 May 25, 261(15), 7024 - 31 Peptidoglycan synthetic activities in membranes of Escherichia coli caused by overproduction of penicillin-binding protein 2 and rodA protein; Ishino F et al.; Penicillin-binding protein (PBP)-2 and the RodA protein are known to function in determining the rod shape of Escherichia coli cells . Peptidoglycan biosynthetic reactions that required these two proteins were demonstrated in the membrane fraction prepared from an E . coli strain that overproduced both of these two proteins and which lacked PBP-1B activity (the major peptidoglycan synthetase activity in the normal E . coli membranes) . The cross-linked peptidoglycan was synthesized from UDP-N-acetylmuramylpentapeptide and UDP-N-acetylglucosamine in the presence of a high concentration of cefmetazole that inhibited all of PBPs except PBP-2 . The peptidoglycan was synthesized via a lipid intermediate and showed up to 30% cross-linking . The cross-linking reaction was strongly inhibited by the amidinopenicillin, mecillinam, and by other beta-lactam antibiotics that have a high affinity for PBP-2, but not by beta-lactams that had very low affinity for PBP-2 . The formation of peptidoglycan required the presence of high levels of both PBP-2 and the RodA protein in the membranes, but it is unclear which of the two proteins was primarily responsible for the extension of the glycan chains (transglycosylation) . However, the sensitivity of the cross-linking reaction to specific beta-lactam antibiotics strongly suggested that it was catalyzed by PBP-2 . The transglycosylase activity of the membranes was sensitive to enramycin and vancomycin and was unusual in being stimulated greatly by a high concentration of a chelating agent. Eur J Biochem, 1986 May 15, 157(1), 101 - 6 Antibodies against the benzylpenicilloyl moiety as a probe for penicillin-binding proteins; Hakenbeck R et al.; Antibodies against the benzylpenicilloyl determinant were used to identify complexes of benzylpenicilloyl and penicillin binding protein (PBP) of several bacterial species on immunoblots . Since radioactive penicillin was not needed, this technique readily allowed in vivo labeling studies even in Escherichia coli, where the saturating concentration was around 0.6 mg/ml . The antibodies showed no substantial cross-reactivity to other beta-lactam-PBP complexes with the exception of 6-aminopenicillanic acid . Surprisingly, some penicilloyl-PBP were hardly recognized by the antiserum, whereas the others could be stained according to the amount of penicillin bound. Aust N Z J Ophthalmol, 1986 May, 14(2), 127 - 32 Interstitial keratitis in untreated latent (late) syphilis; Brooks AM et al.; Untreated latent syphilis with interstitial keratitis is not uncommon in the older age group who may present with refractive problems . It is important to investigate these patients with a full range of serological tests for syphilis to determine whether they have been treated adequately in the past . If there is evidence of untreated latent syphilis, examination of the cerebrospinal fluid is important to exclude asymptomatic neurosyphilis for which intensive systemic therapy in hospital is indicated . If there is no evidence of central nervous system involvement a course of penicillin is still indicated, but may be given on an outpatient basis . This is illustrated by the histories of six patients who presented to The Royal Victorian Eye and Ear Hospital between 1962 and 1979. Allergol Immunopathol (Madr), 1986 May-Jun, 14(3), 221 - 8 Human basophil degranulation test in drug allergy; Sastre Dominguez J et al.; We have evaluated the usefulness of HBDT as an in vitro method for the diagnosis of drug allergy . Two hundred and thirty six patients with suspected drug sensitization to penicillin, streptomycin, sulfamides, pyrazolones and A.S.A . were analyzed . Seventy-nine of them were allergic; in 43 cases it was confirmed by in vivo methods . Other patients were diagnosed by clinical history only if they had more than two reactions to the same drug . In order to be included in this group patients with reactions to pyrazolones and A.S.A . had to have tolerated other NSAI, therefore these patients were allergic to one compound only . All patients were considered non-allergic were determined by a negative provocation test . In the group of allergic patients we obtained 63 (79%) positive degranulations and 16 (21%) negative . One hundred and thirty two (84%) negative degranulations and 25 (16%) positive were obtained in the group of non-allergic patients . Once having analyzed 10 statistical parameters with each drug, the HBOT appears to be a useful method for these drugs except for streptomycin . In 16 (80%) out of 20 aspirin sensitive asthmatic patients we found that their basophils were degranulated . In 7 patients with urticaria and/or angioedema by A.S.A . and other NSAI the degranulation was negative, confirming the absence of the involvement of basophils in this reactions. Aust Paediatr J, 1986 May, 22(2), 127 - 30 Stosstherapy: a fresh look at some principles of therapy--especially chemotherapy; Keipert JA; Stosstherapy is the treatment of disease by a single or short-term, large and sometimes massive, dose of a therapeutic agent . It was most commonly used after the discovery of sulphonamides and penicillin, but has been revived with the recent use of single-dose chemotherapy . It is effective in many disorders, and these are documented, together with the dosage ranges which can be used . Stosstherapy has a rational basis, is safe, effective, has many advantages compared with long-term therapy, and could be used much more frequently . Reasons are given why stosstherapy conforms with accepted principles of chemotherapy, but it is given for a much shorter period because the time for an infection to be overcome may be much shorter than has been assumed . It is postulated that the duration of chemotherapy could be shortened in many diseases. Infection, 1986 May-Jun, 14(3), 134 - 5 Wound infection following dog bite despite prophylactic penicillin; Skurka J et al.; Dog bite wounds of 39 children (ages one to 16 years) were cultured and irrigated . Cultures showed various organisms but were of no predictive value for development of infection . By using a table of random numbers, patients were assigned to either oral penicillin V-K (100,000 U/kg/day every 6 h) or placebo for two days . All patients were seen in follow-up in three to four days and again at seven to 10 days or earlier if signs of inflammation occurred . The mean patient age, location and type of wound, and initial wound care were similar in the two treatment groups . Three of 39 (7.7%) children enrolled in the study developed infection at the bite site, including two of 19 in the penicillin group and one of 20 in the placebo group . In our study, prophylactic penicillin failed to prevent infection in dog bite wounds . Good local care on presentation seems to be the most important factor in determining future infection. Am J Emerg Med, 1986 May, 4(3), 241 - 7 Penicillin anaphylaxis; O'Leary MR et al.; A case of oral penicillin anaphylaxis is described, and the terminology, occurrence, clinical manifestations, pathogenesis, prevention, and treatment of anaphylaxis are reviewed . Emergency physicians should be aware of oral penicillin anaphylaxis in order to prevent its occurrence by prescribing the antibiotic judiciously and knowledgeably and to offer optimal medical therapy once this life-threatening reaction has begun. Pharmacol Biochem Behav, 1986 May, 24(5), 1241 - 6 Inhibition of penicillin-induced EEG discharges by low doses of morphine or naloxone in the rabbit . Evidence for a possible non-opioid receptor-mediated mechanism at the sensorimotor cortex; Spillantini MG et al.; In rabbits, pretreatment by intravenous (IV) and intracortical (IC) routes with low doses of morphine (250 micrograms/kg IV or 60 pmoles/rabbit IC) and naloxone (1-50 micrograms/kg IV or 0.3 pmoles/rabbit IC) antagonizes the EEG and behavioural seizures due to the IC injection of penicillin (150 Units) at the level of the sensorimotor cortex . Pretreatment with naloxone (20 micrograms/kg IV) did not alter the anticonvulsant effect of morphine (250 micrograms/kg IV) . The similar anticonvulsant effect of the two drugs together with the absence of any antagonism by naloxone on the effect of morphine seem to suggest that both drugs act through a non-opioid receptor-mediated mechanism . Further, in light of the low effective doses of the drugs and of the absence of any additive effect after their combined administration, one might speculate that morphine and naloxone do not act through different pharmacological receptors . However, the presence of distinct EEG patterns with either morphine or naloxone, injected IC and IV, in animals fully protected against penicillin-induced seizures, does not seem to be in favour of the latter possibility. Contact Dermatitis, 1986 May, 14(5), 307 - 11 Contact dermatitis to semisynthetic penicillins in factory workers; Moller NE et al.; 45 workers developed dermatitis after handling semi-synthetic penicillins in a factory . All reacted on patch test, but several agents had to be used . Only 7 reacted to benzyl penicillin . 1/3 reacted to only one allergen, while 2/3 reacted to several . The duration of exposure before symptoms was short, often less than 2 months . 19 had hay fever or asthma, and they developed their symptoms after a shorter exposure time . A survey for airborne antibiotics was performed. Ann Intern Med, 1986 May, 104(5), 655 - 8 Epidemiology and treatment of oropharyngeal gonorrhea; Hutt DM et al.; The natural history, transmissibility, and treatment of oropharyngeal gonorrhea have been incompletely examined in previous studies . We repeated cultures on 60 patients with untreated pharyngeal gonorrhea, before treatment . The probability that the culture would remain positive decreased progressively as the interval between cultures increased, suggesting self-limited colonization . Gonococci were easily grown from expectorated saliva in 34 of 51 cultures from patients with oropharyngeal gonorrhea, suggesting transmissibility and providing another reason for ensuring effective treatment . Five treatment regimens were evaluated in 292 cases of oropharyngeal gonorrhea . Compared with aqueous procaine penicillin G, single-dose ampicillin and spectinomycin had unacceptably higher failure rates, and oral tetracycline given for 5 or 7 days was shown to be effective . A simple oral regimen providing a second dose of ampicillin plus probenecid 8 to 14 hours after the first dose was also effective. Farmakol Toksikol, 1986 May-Jun, 49(3), 96 - 100 {Effect of GABA-positive substances on the primary and mirror epileptogenic foci in the hippocampus of rats}; Gusel' VA et al.; The effects of beta-alanine, phenibut and muscimol on the activity of the "mirror" (MEF) and primary (PEF) epileptogenic foci were studied in rats on the model of penicillin-induced epilepsy using the direct administration of the drugs into the foci (muscimol only into MEF) . All the drugs suppressed the development of electrographic correlates of seizures both in PEF and MEF . The varied characters of the drugs' effects on interseizure epileptiform bursts depending on administration into PEF (provocation) or MEF (no effect) were revealed . Possible dose-dependent mechanisms of the drugs' actions on GABA-A and GABA-B receptors involved in inhibitory control of the activity of epileptogenic foci in the rat hippocamp are discussed. Clin Pharmacokinet, 1986 May-Jun, 11(3), 223 - 35 Pharmacokinetic drug interactions of commonly used anticancer drugs; Balis FM; With the use of combination chemotherapy as well as a wide range of symptomatic therapies (e.g . analgesics and antiemetics) for the treatment of patients with cancer, the field of oncology practises polypharmacy to an extreme degree . The risk for a drug interaction under these conditions is high, and the pharmacological characteristics of the anti-cancer drugs, such as steep dose-response curves, low therapeutic indices and severe toxicities, suggest that even small changes in the pharmacokinetic profile of the affected drug could significantly alter its toxicity or efficacy . In this review, drug interactions which quantitatively affect the absorption, distribution, biotransformation or excretion of the commonly used anticancer drugs are described . Most of the significant drug interactions involving this class of drugs occur at the level of biotransformation and excretion . For example, the renal excretion of methotrexate by glomerular filtration and tubular secretion is affected by a number of weak organic acids, such as probenecid, salicylates and penicillin, which compete for tubular secretion, resulting in delayed clearance of methotrexate . The best described example of an interaction at the level of biotransformation is the effect of allopurinol on the catabolism of 6-mercaptopurine . By inhibiting xanthine oxidase, allopurinol blocks the first-pass metabolism of 6-mercaptopurine following its oral administration, leading to a 4- to 5-fold increase in plasma concentrations . Known drug interactions may potentially be used to enhance the antitumour activity of a drug--for instance, the administration of tetrahydrouridine (a cytidine deaminase inhibitor) with cytarabine in an attempt to block its rapid inactivation to uridine arabinoside . Overall, little information is available concerning the pharmacokinetic interactions of anticancer drugs with each other and with other classes of drugs in man, in part because the high incidence of toxicity and treatment failure, and empirical dosing methods, obscure the recognition of possible interactions . Awareness on the part of the clinician and more extensive pharmacokinetic investigation will be needed to recognise, document and avoid potentially harmful pharmacokinetic drug interactions involving this class of drugs. J Immunol Methods, 1986 Apr 17, 88(2), 265 - 75 Large scale production of human lymphokine activated killer cells for use in adoptive immunotherapy; Muul LM et al.; Immunotherapy utilizing the adoptive transfer of lymphokine activated killer (LAK) cells in conjunction with recombinant interleukin 2 (RIL-2) is capable of reducing established metastatic cancer in a variety of animal tumor models . A major difficulty in the application of these efforts to the treatment of human cancer has been the activation in vitro of up to 2 X 10(11) human peripheral blood lymphocytes obtained by repeated leukaphereses . We have thus developed optimal and simplified techniques for the generation of human LAK cells for use in clinical trials . We have found that 1.5 X 10(9) lymphocytes separated on Ficoll-Hypaque gradients and incubated in 1000 ml of culture medium in a 2.3 liter roller bottle with 1000-1500 U of RIL-2 per ml, generated LAK cells capable of killing fresh human tumor cells in a 4 h chromium release assay . The culture medium used was RPMI 1640 with 2 mM glutamine, 2% heat-inactivated human AB serum, 50 micrograms/ml streptomycin and gentamicin and 50 U/ml penicillin . This technique allows activation of sufficient numbers of cells in a research laboratory setting to conduct human clinical trials . The administration of LAK cells generated in this fashion can mediate the regression of human tumors when administered in conjunction with IL-2. Brain Res, 1986 Apr 16, 371(1), 1 - 8 Penicillin-induced epileptiform activity does not prevent ocular dominance shifts in monocularly deprived kittens; Videen TO et al.; Epileptiform activity was induced in the visual cortex with penicillin to test whether it would prevent the ocular dominance shift that normally occurs in monocularly deprived kittens . The eyelids of one eye of 5-week-old kittens were sutured shut for several days . During this period, whenever the kittens were in the light, aqueous penicillin in artificial cerebrospinal fluid (CSF) or just CSF was applied in a cylinder mounted over the visual cortex . Electroencephalograms monitored during the period of deprivation indicated nearly continuous interictal spiking in the visual cortex . Extracellular recordings were made of cells in the region directly under the position of the cylinder . 14C-labeled 2-deoxyglucose autoradiography in a control kitten showed that this area had considerably increased metabolism during epileptiform activity . The majority of cortical cells were dominated by the non-deprived eye in both epileptic and control kittens, with no noticeable difference between them . These preliminary observations indicate that the disruption of cortical activity that occurs during interictal epileptiform activity does not prevent the ocular dominance shift in monocularly deprived kittens. Z Hautkr, 1986 Apr 15, 61(8), 549 - 55 {Lymphomatoid papulosis--pseudolymphoma with uncertain prognosis}; Hagedorn M et al.; On account of its distinct clinical and histological picture, lymphomatoid papulosis (l.p.) is mostly considered an entity . A 70-year-old patient with l.p . is described . Histologically, there were similarities to the granulomatous type of pseudolymphoma . The oral treatment with penicillin for 4 weeks was successful, but we cannot exclude a spontaneous remission. Am J Vet Res, 1986 Apr, 47(4), 804 - 7 Concentrations of penicillin, streptomycin, and spiramycin in bovine udder tissue liquids; Franklin A et al.; Concentrations of benzylpenicillin and spiramycin adipate were determined in bovine plasma and milk and in lymph draining the udder tissue after IM or IV administration . Combined benzylpenicillin and dihydrostreptomycin sulfate concentrations were also determined in the same fluids after intramammary injection . A superficial parenchymal lymph vessel, afferent to the supramammary lymph gland of the left quarters, was cannulated with a polythene catheter from which the lymph was allowed to drain freely . After injections of 9.5 mg of benzylpenicillin/kg of body weight IM, a mean peak concentration (PC) in lymph (3.7 micrograms/ml), constituting 77% of the PC in plasma (4.8 micrograms/ml), was obtained 0.5 to 1 hour after PC in the plasma . The benzylpenicillin lymph concentration was close to that in plasma for about 7 hours after injection . Thereafter, the benzylpenicillin lymph concentration continued to exceed that in plasma, but not that in milk . After IV administration of spiramycin adipate, the lymph concentration was almost identical to that in plasma . After intramammary injection of procaine benzylpenicillin (400 mg), in combination with the same amount of dihydrostreptomycin sulfate, into 2 udder quarters each, mean PC in the lymph of 3.5 micrograms/ml and 8.4 micrograms/ml, respectively, were obtained 6 hours after injection . In plasma, the mean PC of benzylpenicillin (0.07 micrograms/ml) and of dihydrostreptomycin sulfate (0.85 micrograms/ml) were obtained after 4 and 6 hours, respectively . In milk from the nontreated quarters, a mean concentration of 5 ng of benzylpenicillin/ml was obtained, whereas dihydrostreptomycin sulfate (greater than or equal to 0.3 microgram/ml) was not detected.(ABSTRACT TRUNCATED AT 250 WORDS) Anesthesiology, 1986 Apr, 64(4), 501 - 3 Lidocaine depresses synaptic activity in the rat hippocampal slice; Schurr A et al.; The direct effect of the local anesthetic lidocaine was studied using the hippocampal slice preparation in order to assess the involvement of this structure in lidocaine-induced seizure activity . Changes in the evoked field potential amplitude and latency were used to measure the effect of the drug . A dose-dependent depression of the evoked field potentials was observed at lidocaine concentration of 10(-4)M and greater . No synchronized population bursting (seizures) was observed at any of the concentrations tested (10(-6)M to 10(-3)M) . However, the hippocampal slice preparation is capable of producing seizure activity, as was demonstrated following application of penicillin G . The results suggest that the hippocampus is not the site of lidocaine-induced seizure activity. Exp Neurol, 1986 Apr, 92(1), 134 - 46 Penicillin epileptogenic focus in the rat: requisites for transcortical reflex triggering; Gioanni Y et al.; Epileptiform discharges elicited by natural or electrical stimulations, proprioceptive or cutaneous, were studied in the rat with an experimental acute focus induced by penicillin application in the motor area . EEG paroxystic spikes were easily triggered with restricted foci (0.5 to 1 mm2) located in the representation area of the stimulated region . However, despite the large overlap of sensory and motor cortical limb areas in the rat, EEG spikes, either spontaneous or triggered, were followed by muscular jerks only with much larger foci: at least 2 and 4 mm2, respectively, for anterior and posterior limb areas . Cutaneous stimulations were the most efficient in discharge production; however, discharges were triggered indifferently by muscular or cutaneous afferent fibers in about three-fourths of the cases . The temporal relation between EEG spike and myoclonic jerk were very close . A latency analysis (delay between triggered EEG spike and EMG response, parallel latency fluctuation of both phenomena, delay between spontaneous EEG spike and jerk) supported the hypothesis that a transcortical reflex mechanism, rather than a spinal excitability rebound, was involved in the jerk genesis . Iontophoretic ejection of penicillin within layers III-IV resulted in the development of electroclinical paroxysms . However, similar penicillin ejection within layer V, did not allow efferent discharge production . It is concluded that the involvement of a large surface or volume of cortical tissue is required to produce efferent discharges following EEG paroxysms . This observation is likely related to the unexpectedly wide representation of individual muscles at the motor cortical level. Cent Afr J Med, 1986 Apr, 32(4), 89 - 91 Neonatal tetanus--a simplified treatment and preventive measures; Topley JM et al.; PIP: The conservative management of neonatal tetanus usually involves use of intravenous Iv sedative drugs and is hazardous unless monitored with a high level of nursing observation . This is often not available in hospitals where this condition is most commonly seen and many iatrogenic deaths occur . A simplified oral regime for the treatment of neonatal tetanus in 22 patients admitted to Mutare General Hospital in Zimbabwe is described and a mortality of 36.4% was recorded . The traditional birth attendant training scheme which commenced in Mainicaland in 1982 is described . The oral treatment regime involves the passing of a naso-gastric tube after sedation if necessary, and administration of tetanus antiserum (1 intramuscular dose of 10,000 units), procaine penicillin for 7 days and kanamycin it necessary . Expressed breast milk was given by naso-gastric tube until the baby was able to nurse . Cooperation with traditional birth attendants has been demonstrated elsewhere to dramatically reduce neonatal mortality rates, and to a lesser degree, neonatal tetanus deaths . In combination with antenatal tetanus prophylaxis it would be expected that neonatal tetanus could be eradicated even in a population where a large proportion of birth take place at home . author's modified Mutat Res, 1986 Apr, 164(2), 91 - 9 Murine bone marrow culture system for cytogenetic analysis; Krishna G et al.; A mouse bone marrow culture system for examining genotoxicity of agents by first exposing animals in vivo then growing cells in vitro is presented . This assay can also be used for in vitro and/or for the in vivo and in vitro comparative cytogenetic studies . The protocol involves culturing of approximately 1,000,000 nucleated cells obtained from mice tibia and femora in 5 ml of Ham's F-12 medium containing 20% fetal bovine serum, 10% whole uterus extract from pregnant mice and 1% penicillin-streptomycin . The use of flasks and mouse uterus extract for culturing are important steps for higher mitotic yield . The addition of 20 microM BrdU for 24 h helps in the differentiation of sister chromatids for sister-chromatid exchange (SCE) analysis . Cyclophosphamide, given to mice through intraperitoneal injection, induced significant dose-related SCEs in culture . Trinitrofluorenone, a direct-acting mutagen, caused dose-related SCEs in in vitro bone marrow cell culture. Biochem J, 1986 Apr 1, 235(1), 159 - 65 Active-site-serine D-alanyl-D-alanine-cleaving-peptidase-catalysed acyl-transfer reactions . Procedures for studying the penicillin-binding proteins of bacterial plasma membranes; Ghuysen JM et al.; Under certain conditions, the values of the parameters that govern the interactions between the active-site-serine D-alanyl-D-alanine-cleaving peptidases and both carbonyl-donor substrates and beta-lactam suicide substrates can be determined on the basis of the amounts of (serine ester-linked) acyl-protein formed during the reactions . Expressing the 'affinity' of a beta-lactam compound for a DD-peptidase in terms of second-order rate constant of enzyme acylation and first-order rate constant of acyl-enzyme breakdown rests upon specific features of the interaction (at a given temperature) and permits study of structure-activity relationships, analysis of the mechanism of intrinsic resistance and use of a 'specificity index' to define the capacity of a beta-lactam compound of discriminating between various sensitive enzymes . From knowledge of the first-order rate constant of acyl-enzyme breakdown and the given time of incubation, the beta-lactam compound concentrations that are necessary to achieve given extents of DD-peptidase inactivation can be converted into the second-order rate constant of enzyme acylation . The principles thus developed can be applied to the study of the multiple penicillin-binding proteins that occur in the plasma membranes of bacteria. An Esp Pediatr, 1986 Apr, 24(4), 257 - 9 {Ischemia after intramuscular injection of benzathine penicillin}; del Peral Aguilar C et al.; Two cases of ischemia produced by arterial spasms following an intragluteal injection of benzathine-penicillin which have been solved successfully are reported . Authors review literature on this subject and warn of the serious problems that may happen with this procedure. Genitourin Med, 1986 Apr, 62(2), 75 - 7 Epidemiology of infectious syphilis in Singapore; Thirumoorthy T et al.; The incidence of early infectious syphilis in Singapore rose from 8.7 per 100,000 in 1980 to 25 per 100,000 in 1984 . In this epidemiological study of 100 patients with early syphilis, 70 were men, the mean age was 31.7 (range 17 to 68) years, 25 patients had primary syphilis, 47 secondary syphilis, and the remaining 28 had early latent syphilis . Female prostitutes were cited as sources of infection by 46 and homosexual contacts by 11 . Reduced herd immunity, decreased use of penicillin, greater population movement, and decreased surveillance and awareness have contributed to this rise in infectious syphilis. Genitourin Med, 1986 Apr, 62(2), 129 - 31 Neurosyphilis after treatment of latent syphilis with benzathine penicillin; Jorgensen J et al.; Two patients developed neurosyphilis after treatment of latent syphilis with intramuscular benzathine penicillin . The cases confirm recent investigations that show that neither benzathine penicillin nor procaine penicillin in the standard doses results in treponemicidal concentrations of penicillin in cerebrospinal fluid . Neurosyphilis can be treated effectively by intravenous benzylpenicillin infusions of 18 to 21.6 g daily for 15 days. HNO, 1986 Apr, 34(4), 149 - 50 {Differential diagnosis of idiopathic facial paralysis: Bannwarth meningopolyradiculitis}; Roloff A et al.; Lymphocytic meningopolyradiculitis (Bannwarths' syndrome) is a tick-borne Borrelia infection of man . About 60 per cent of such patients exhibit a peripheral facial paresis whose characteristics are clinically not distinguishable from Bell's paresis . Of major importance for the diagnosis, besides the radicular pain that nearly always prevails, are particularly further motoric deficits, a previous erythema migrans and remembered thick bites . A tentative diagnosis can be verified by liquor examination which reveals a characteristic pattern of protein distribution and lymphocytic pleocytosis . Penicillin in high doses is the therapy of choice. Ann Acad Med Singapore, 1986 Apr, 15(2), 258 - 61 Clinical experience in the use of clavulanic acid/penicillin regimens in the treatment of uncomplicated gonorrhoea; Lim KB et al.; In an attempt to investigate the possibility of re-establishing the use of penicillins in the treatment of gonorrhoea in Singapore, a series of studies were conducted between 1981 and 1984, to evaluate the efficacy of a variety of penicillin-clavulanic acid combinations . A total of 6 different regimens were evaluated, and we concluded that 3 regimens consisting of 2 doses of Augmentin 3.25 g P.O., 4 hours apart (regimen C), aqueous procaine penicillin G (APPG) 4.5 mega units I.M . + Augmentin 375 mg + probenecid 1g P.O . (regimen E), and APPG 4.5 mega units I.M . + Augmentin 750 mg + probenecid 1g P.O . (regimen F) were very efficacious against infection due to PPNG and non PPNG . The cure rates obtained were 96.6% (regimens C and E), and 95% (regimen F) for infection due to PPNG and 95.6% (regimen C), and 100% (regimens E and F) for those due to non PPNG . Regimen E consisting of aqueous procaine penicillin G 4.5 meg units I.M . + Augmentin 375 mg + probenecid 1g P.O . was felt to be economical as well as effective against PPNG and non PPNG, and had the potential advantage of being effective against incubating syphillis . Regimen consisting 2 oral doses of Augmentin 3.25 g, 4 hours apart was an effective therapy for patients who preferred oral medication alone . However, this therapy was most costly . No serious side effects of treatment were observed with any of the regimens used. J Neurol, 1986 Apr, 233(2), 69 - 72 Neuropathy of vasculitic origin in a case of Garin-Boujadoux-Bannwarth syndrome with positive borrelia antibody response; Camponovo F et al.; A 42-year-old man suffered from erythema chronicum migrans on different parts of the body after repeated tick bites . A few months after the last tick bite he developed a painful neuropathy in both legs with patchy disturbance of sensibility, mild weakness of the feet and loss of the right ankle jerk . Repeated determinations of antibodies against borrelia spirochetes revealed increasing IgG titres . Biopsy of the left sural nerve, which was clinically and electrophysiologically affected, showed a vasculitis of epineurial vasa nervorum and severe angiopathic lesions of the perineurium and the neural parenchyma . Parenteral high-dose penicillin treatment resolved the clinical symptoms. Biull Eksp Biol Med, 1986 Apr, 101(4), 436 - 8 {Effect of N- and M-cholinergic-potentiating and cholinergic-blocking agents on the epileptogenesis of a penicillin focus in the dorsal hippocampus}; Losev NA et al.; Chronic experiments on rabbits with penicillin epilepsy have shown that intravenous injections of the ACHE inhibitor galanthamine (1 mg/kg), and N-cholinergic-blockers, ganglerone (3 mg/kg) and eterofen (8 mg/kg), decreased or suppressed completely epileptogenesis manifestations . Combination of galanthamine with one of the N-cholinergic-blockers markedly increased their anticonvulsive actions . On the contrary, combination of galanthamine with the M-cholinergic-blocker metamizil (0.5 mg/kg) enhanced epileptogenesis activity . It is postulated that both M- and N-cholinergic mechanisms take part in the genesis of penicillin epilepsy . The use of N-cholinergic-blockers and their combinations with M-cholinomimetics as anticonvulsants seems expedient. Exp Neurol, 1986 Apr, 92(1), 20 - 36 Neuronal sensitivity to GABA and glutamate in generalized epilepsy with spike and wave discharges; Kostopoulos G; In awake but painlessly immobilized cats the extracellular activity of the same cortical neurons was recorded before and for 2 to 5 h after the injection of penicillin G (350,000 IU/kg, i.m.) during the development of generalized epilepsy with bilaterally synchronous spike and wave discharges . Possible changes in their sensitivity to microiontophoretically applied glutamate and GABA during this period were searched for using computer-generated periejection histograms at intervals of about 30 min . In contrast to reported studies in other models of epilepsy, glutamate excited and GABA depressed virtually all neurons tested during fully developed spike and wave epilepsy . Spike height was not apparently affected either by the amino acids or by the development of epilepsy . Comparison of relative thresholds for the above effects on rhythmical neuronal activity associated with spike and wave discharge versus effects on random neuronal activity during the interburst periods, supported the idea that spikes and waves result from strong excitatory and inhibitory synaptic drives of the neurons . In all neurons until the appearance of spike and wave discharges, changes in the effect of amino acids, if observed, were small and statistically nonsignificant . This suggests that the hyperexcitability of cortical neurons which reportedly leads to the appearance of spike and wave discharges depends on mechanisms other than an increase in sensitivity to glutamate or a desensitization to GABA . Sometimes the sensitivity to GABA decreased later in this experimental model when the very frequent appearance of spike and wave discharges eventually led to EEG tonic-clonic seizures. J Immunol, 1986 Mar 15, 136(6), 2231 - 9 Characteristics of human basophil sulfidopeptide leukotriene release: releasability defined as the ability of the basophil to respond to dimeric cross-links; MacGlashan DW Jr et al.; Human basophils release approximately 90 pmol of LTC4/micrograms histamine when challenged with anti-IgE antibody, but donor to donor variation produces a 1000-fold range of response . There is little conversion to LTC4 to LTE4 in purified preparations of basophils, but conversion to LTE4 does occur if cell densities are high during incubation . Like histamine release, leukotriene release is calcium and temperature dependent and is complete in 20 min, with a t1/2 of approximately 8 min . The process of desensitization also ablates leukotriene release, but there is a distinct two phase process where leukotriene release is enhanced after 5 min of desensitization, whereas histamine release is inhibited and total ablation of leukotriene release occurs only after 45 min of desensitization . Human basophils respond well to stimulation with covalently cross-linked trimeric IgE myeloma but respond poorly to dimeric IgE . This differential sensitivity to the two forms of cross-linked IgE is most exaggerated in the context of leukotriene release, where dimer is 30-fold less efficacious and 100- to 1000-fold less potent than trimer on some donors' basophils . This dichotomy of response is also observed in antigen-challenged cells, where the bivalent hapten, BPO2, also poorly induces leukotriene release in accord with the fact that it predominantly induces dimeric cross-links of penicillin-specific IgE . Anti-IgE dose-response curves reveal a region of dimeric cross-link dominance that may explain the peculiar differences observed in pharmacologic studies of basophil release induced with antigen vs anti-IgE . In addition, there is a continuum of "releasability," where some donors' basophils display no response (histamine or leukotriene release) to dimeric IgE, and others' basophils are essentially equally responsive to both dimeric and trimeric IgE . This releasability difference manifests itself by conferring increased sensitivity to antigenic challenge in those donors' basophils capable of responding to dimeric cross-links such that these donors' basophils are capable of releasing histamine upon antigen challenge while possessing only 50 molecules of cell surface antigen-specific IgE; other dimer-insensitive donors' basophils require 6 to 10-fold greater IgE densities for equal histamine release. Neurosci Lett, 1986 Mar 14, 64(3), 293 - 8 Effects of substantia nigra and pallidum stimulation on hippocampal interictal activity in the cat; Sabatino M et al.; In the present work the role played by substantia nigra pars compacta and globus pallidus pars interna on hippocampal bioelectrical activity is studied . Injections of sodium penicillin (i.v.) produce steady interictal spikes in the hippocampus . Substantia nigra stimulation induces regular theta rhythm and inhibits the spikes . Pallidal stimulation, on the contrary, appears to strongly enhance epileptiform activity, proceeding to generalized seizure activity . The results are discussed in the light of the interrelationships between basal ganglia and hippocampus, hypothesizing a putative feedback loop from striatal to limbic centers. Brain Res, 1986 Mar 12, 368(1), 36 - 48 Intracellular currents of interictal penicillin spikes: evidence from neuromagnetic mapping; Barth DS et al.; To analyze the net intracellular current produced by interictal spikes, we mapped the extracranial magnetic fields of the rat brain following application of penicillin to the right or left medial cingulate cortex . Averaged interictal spikes in both the magnetoencephalogram (MEG) and in the electrocorticogram (ECoG) were composed of 4 temporal components, a biphasic spike and slow wave . Magnetic field maps for each of these components indicated a source at the location of penicillin application, with intracellular currents oriented perpendicular to the surface of the cingulate cortex, along the axis of the major pyramidal cells . The polarity of the magnetic fields for each of the components was reversed between the two cingulate groups, reflecting the respective orientation of pyramidal cells between the juxtaposed faces of the medial cingulate cortex . This neuromagnetic study of net intracellular current complements and extends the analysis of extracellular currents within the penicillin focus obtained using laminar electrodes . These data also demonstrate how animal neuromagnetometry may provide an empirical foundation for the neurogenesis of the MEG and a new unique method for the non-invasive study of population cell physiology. Klin Wochenschr, 1986 Mar 3, 64(5), 206 - 15 Lyme arthritis: clinical features, serological, and radiographic findings of cases in Germany; Herzer P et al.; The clinical manifestations, serological data, and radiographic findings of ten cases of Lyme arthritis in Germany are summarized . Qualitative assessment shows that the characteristics of the disease in Germany do not differ fundamentally from those reported in the USA . However, since a serological test for antibodies to the causative spirochete is now available, the great variety of the clinical features of Lyme arthritis can be described more precisely . The cases of chronic Lyme arthritis without prior erythema chronicum migrans, hitherto the most important diagnostic hallmark of the disease, may have been underestimated . One of the cases reported provides evidence that the disease was transmitted via a fly bite . Radiographic abnormalities consisting of marked juxta-articular osteoporosis and osseous erosions were found in two patients with chronic arthritis . Three patients were treated with high-dose intravenous penicillin, two did not respond to the therapy. J Am Acad Dermatol, 1986 Mar, 14(3), 487 - 91 Treatment of primary and secondary syphilis: serologic response; Fiumara NJ; Eighty-eight patients with their first attack of primary syphilis and 101 patients with secondary syphilis were treated with penicillin G benzathine, 2.4 million units intramuscularly each week for 2 consecutive weeks, for a total of 4.8 million units . The serum of all patients with primary syphilis became negative within 1 year and of those in the secondary stage, within 2 years . This report confirms three previously published articles on the serologic response to treatment in a grand total of 588 patients with primary syphilis and 623 patients in the secondary stage. Antimicrob Agents Chemother, 1986 Mar, 29(3), 432 - 9 In vivo target of benzylpenicillin in Gaffkya homari; Wrezel PW et al.; It has been established that the DD-carboxypeptidase is the primary in vitro target of benzylpenicillin in Gaffkya homari (W . P . Hammes, Eur . J . Biochem . 70:107-113, 1976) . To determine whether this enzyme is also the primary target of benzylpenicillin in vivo, we compared the effects of this beta-lactam, cefmenoxime, cephalothin, and cefoxitin on growth with their acylation of penicillin-binding protein (PBP) 9, the DD-carboxypeptidase . Results of three types of experiments with membrane-walls indicated that PBP 9 is this enzyme and that it is the primary in vitro target of these beta-lactams in the synthesis of sodium dodecyl sulfate (SDS)-insoluble peptidoglycan . First, the acylation of PBP 9 by these beta-lactams paralleled the inhibition of DD-carboxypeptidase and the inhibition of SDS-insoluble peptidoglycan synthesis . Second, the rate of benzylpenicillin release from PBP 9 correlated with the recovery of DD-carboxypeptidase . Third, DD-carboxypeptidase activity was detected in a protein with the same apparent molecular weight as PBP 9 after elution from an SDS-polyacrylamide gel . When intact cells were treated with benzylpenicillin, the minimum growth inhibitory concentration (MGIC) correlated with the concentration of {35S}benzylpenicillin required to acylate PBPs 6 and 9 by 50% . When intact cells were treated with cefmenoxime, cephalothin, or cefoxitin, the MGICs correlated with the concentration of unlabeled beta-lactam required to reduce the subsequent binding of {35S}benzylpenicillin by 50% (ED50) for PBP 6 . In contrast, the MGICs of these beta-lactams did not correlate with the ED50s for PBP 9 . PBP 9 was not acylated by cefmenoxime or cephalothin at their MGICs, whereas this PBP was fully acylated by cefoxitin at one-tenth of its MGIC . It is suggested that PBP 6 may be a primary target of growth inhibition by benzylpenicillin, cefmenoxime, cephalothin, and cefoxitin; PBP 9, the DD-carboxypeptidase, is dispensable for growth under laboratory conditions; and PBP 9 does not appear to be a primary in vivo target of these beta-lactams, even though this PBP is their primary target in vitro. Antibiot Med Biotekhnol, 1986 Mar, 31(3), 178 - 81 {Metastable and steady-state solubility of the salt forms of semisynthetic penicillins at 4 degrees C}; Savel'ev EA et al.; Steady-state and metastable solubility of penicillin salts in water, aqueous organic solutions and the same systems with addition of an inorganic electrolyte at a temperature of 4.0 +/- 1.0 degree C was studied . The leveling effect of the temperature decrease on the difference in solubility of modifications I and II of sodium salts of methicillin, oxacillin and dicloxacillin in isopropanol, acetone and respective aqueous organic solutions with insignificant water content was observed . An increase in the salting-out effect of sodium chloride on solubility of sodium salts of carbenicillin, methicillin, oxacillin and dicloxacillin at lowered temperatures was revealed. Ann Gastroenterol Hepatol (Paris), 1986 Mar-Apr, 22(2), 77 - 81 {Liver involvement in syphilis}; Rampal P et al.; The authors report two cases of syphilitic hepatitis . In the first case, acute hepatitis occurred during the secondary stage of syphilis . The diagnosis was made without waiting for the hepatitis to respond to penicillin treatment, on the basis of the following signs: icterus involving inflammatory syndrome, moderate cytolysis, clear retention, eruption of papular syphilids and a strongly positive test for syphilis . The second case involved a female patient who had been treated 15 years earlier for bone syphilis with ulcerous gummas . The signs were sclerotic, gummatous, hepatic lesions revealed by a syndrome of calcified hepatic lesions . The serologic test for syphilis was negative in this patient . Laparotomy and biopsy were necessary before a firm diagnosis could be made . The authors examine literature data concerning this pathology. Fiziol Zh SSSR Im I M Sechenova, 1986 Mar, 72(3), 306 - 10 {Interaction of adrenergic and serotoninergic mechanisms in modulation of seizure activity of the brain}; Khanbabian MV et al.; Electrical stimulation of the raphe nuclei and locus coeruleus induces inhibition of the penicillin-induced seizure activity . Adrenoblocking agents facilitate the effects of raphe nuclei on the seizure activity. Scand J Immunol, 1986 Mar, 23(3), 383 - 8 Expression of HLA-DQ antigens on keratinocytes in Borrelia spirochete-induced skin lesions; Tjernlund U et al.; Skin biopsies were investigated with two different immunohistochemical techniques, thus revealing HLA-DQ antigens on HLA-DR-expressing keratinocytes in the late skin manifestations of a Borrelia spirochete infection . In the early skin lesions only HLA-DR antigens were present on the keratinocytes . The invariant gamma chain of class II transplantation antigens was observed on keratinocytes in 1:5 of the late cases . Upon penicillin treatment detectable HLA-DR and HLA-DQ antigens disappeared completely from the keratinocytes . Furthermore, the mononuclear cell infiltrates dominated by anti-Leu 1 and anti-Leu 3a-reactive cells and containing many cells with markers for activation (HLA-DR, HLA-DQ, transferrin, and interleukin 2 receptors) diminished markedly . The possibility that the expression of different class II transplantation antigens on keratinocytes might reflect separate functional demands of these cells or an altered immunological reactivity in the host, is discussed . The precise functional role of the temporary expression of the class II antigens on non-lymphoid cells, however, remains an enigma. Schweiz Med Wochenschr, 1986 Feb 1, 116(5), 135 - 42 {Neurologic manifestations of Borrelia burgdorferi infections}; Uldry PA et al.; Lyme disease, first recognized in 1975, typically begins in summer with erythema chronicum migrans (ECM) followed some months later by neurological symptoms (meningoencephalitis, cranial neuropathy), associated with carditis and arthritis . Bannwarth's syndrome is characterized by an ECM followed by radicular pain and radicular sensory and motor disturbances, accompanied by aseptic meningitis . In both cases the cerebrospinal fluid typically shows marked lymphocytic pleocytosis accompanied by an oligoclonal reaction . Despite differences in the clinical symptoms, a borrelia isolated from ticks has been implicated as the etiologic agent of both diseases, and specific antibody titers usually reach a peak between the third and sixth week after onset of the disease . Investigations in 5 patients who developed neurologic symptoms after tick-borne borrelia infection revealed specific antibodies (IgM, IgG) against Borrelia burgdorferi in all sera, and all the patients recovered, one of them without treatment and the others under penicillin or tetracyclines . None developed major complications (carditis, arthritis). Arch Neurol, 1986 Feb, 43(2), 137 - 8 Acute syphilitic meningitis . Its occurrence after clinical and serologic cure of secondary syphilis with penicillin G; Bayne LL et al.; Acute syphilitic meningitis developed in a 36-year-old man three months after apparently successful treatment of secondary syphilis with doses of penicillin G benzathine recommended by the current Centers for Disease Control guidelines . He was then treated with high-dose intravenous penicillin G sodium, with resolution of symptoms and cerebrospinal fluid abnormalities . Although other instances of neurosyphilis following adequate therapy for early syphilis have been reported, in most cases reinfection cannot be convincingly excluded . We believe this patient represents a particularly well-documented example of progression to neurosyphilis, despite recommended therapy with penicillin . A review of recently reported cases suggests that progression of syphilis, despite "appropriate" therapy, is not an isolated event. Acta Pathol Microbiol Immunol Scand {B}, 1986 Feb, 94(1), 33 - 7 The pneumococcus and the mouse protection test: inoculum, dosage and timing; Frimodt-Moller N et al.; Intraperitoneal inoculation in mice of a S . pneumoniae type 3 in beef broth resulted in immediate growth in vivo as evidenced by bacterial counts in peritoneal washings and in blood . Treatment with penicillin 1 hour after inoculation reduced the bacterial counts in vivo; however, different doses of penicillin-G showed a similar effect as measured by bacterial counts, in spite of differences in their effect upon survival of the mice . Therefore, the effect of antibiotics in vivo in this model was better correlated with death/survival of the animals . For comparative purposes the ED50, i.e . the 50% effective dose, should be determined . The effect of cephalosporins, i.e . cefuroxime and cefotaxime, in this model highly depended upon timing of the antibiotic administration as related to inoculation. J Antimicrob Chemother, 1986 Feb, 17(2), 251 - 3 Benzylpenicillin-induced neutropenia; Al-Hadramy MS et al.; Neutropenia is a potentially serious complication of parenteral benzylpenicillin administration . It is thought to occur more frequently in patients receiving infusions of stored penicillin solutions . We report three cases of neutropenia produced after bolus injections of freshly prepared benzylpenicillin . Twenty-five other cases were reviewed from the literature and the data summarized. Prostaglandins, 1986 Feb, 31(2), 239 - 51 Identification of the major endogenous leukotriene metabolite in the bile of rats as N-acetyl leukotriene E4; Hagmann W et al.; Mercapturic acid formation, an established pathway in the detoxication of xenobiotics, is demonstrated for cysteinyl leukotrienes generated in rats in vivo after endotoxin treatment . The mercapturate N-acetyl-leukotriene E4 (N-acetyl-LTE4) represented a major metabolite eliminated into bile after injection of {3H}LTC4 as shown by cochromatography with synthetic N-acetyl-LTE4 in four different HPLC solvent systems . The identity of endogenous N-acetyl-LTE4 elicited by endotoxin in vivo was additionally verified by enzymatic deacetylation followed by chemical N-acetylation . The deacetylation was catalyzed by penicillin amidase . Endogenous cysteinyl leukotrienes were quantified by radioimmunoassay after HPLC separation . A N-acetyl-LTE4 concentration of 80 nmol/l was determined in bile collected between 30 and 60 min after endotoxin injection . Under this condition, other cysteinyl leukotrienes detected in bile by radioimmunoassay amounted to less than 5% of N-acetyl-LTE4 . The mercapturic acid pathway, leading from the glutathione conjugate LTC4 to N-acetyl-LTE4, thus plays an important role in the deactivation and elimination of these potent endogenous mediators. Int J Oral Maxillofac Surg, 1986 Feb, 15(1), 25 - 9 Postoperative complications after surgical removal of mandibular third molars . Effects of penicillin V and chlorhexidine; Krekmanov L et al.; A random material of 112 patients, was investigated after surgical removal of impacted lower third molars . 2 experimental groups and 1 control group were studied . Prophylactic medication with penicillin V combined with preoperative rinsing using 0.2% chlorhexidine gluconate (Hibitane) was found to reduce postoperative symptoms, when compared with preoperative rinsing alone . In both cases, patients were compared with the control group. J Pharmacol Exp Ther, 1986 Feb, 236(2), 380 - 3 Ceftriaxone pharmacokinetics in the central nervous system; Spector R; The transport and metabolism of ceftriaxone was studied in vitro in the isolated choroid plexus and in vivo in New Zealand White rabbits . In vitro, {14C}ceftriaxone was accumulated by a saturable, probenecid-sensitive system in choroid plexus, although much less readily than {14C}penicillin G . Ceftriaxone was also a much less potent inhibitor of {14C}penicillin G accumulation by the isolated choroid plexus than penicillin G itself (IC50 = 1.6 vs . 0.07 mM, respectively) . In vivo, 2 hr after intraventricular injection, {14C}ceftriaxone was not metabolized or cleared from the cerebrospinal fluid more rapidly than {3H}mannitol, a molecule transported in the central nervous system by simple diffusion . These in vitro and in vivo results show that ceftriaxone, unlike penicillin G, has minimal affinity for the choroid plexus active transport system that transfers most penicillins and cephalosporins from cerebrospinal fluid to blood. Klin Wochenschr, 1986 Jan 2, 64(1), 38 - 43 Clinical findings and follow-up evaluation of an outbreak of mushroom poisoning--survey of Amanita phalloides poisoning; Fantozzi R et al.; One hundred and sixty cases of mushroom poisoning during the period July-November 1981 are reported . The survey details 116 observations of short incubation syndromes and 44 cases of delayed syndrome, identified as Amanita Phalloides poisoning . Of the latter, 40 patients were adult (mean age 46 years, range 20-77; 18 females and 22 males) and 4 were children (less than or equal to 12 years old; 3 females and 1 male) . All the patients with Amanita Phalloides poisoning were treated according to a therapeutic protocol, based on the infusion of high doses of penicillin G, administration of dexamethasone and thioctic acid, careful correction of water and electrolyte unbalance . The severity of the disease varied in the population of 44 patients: 4 patients died (2 females, 10 and 77 years old; 2 males, 56 and 64 years old); 26 patients were discharged from the hospital as clinically cured; 14 were discharged with persistently abnormal levels of transaminases and they were advised of a follow-up evaluation . The average length of stay in hospital was 2 weeks . Of the patients followed-up, 6 were symptom-free after 6 months, with normal transaminase values and a normal histopathological picture of liver biopsy specimens . In the remaining patients, there was no normalization of transaminase values and liver biopsy specimens showed a picture of chronic active hepatitis . These patients displayed abnormal immunological tests, with presence of immune complexes and of anti-smooth muscle autoantibodies . The results indicate that Amanita Phalloides poisoning represents a threat not only in the high mortality acute phase, but also in the development of chronic active hepatitis in some survivors. Jpn J Pharmacol, 1986 Jan, 40(1), 178 - 81 Cephalothin and penicillin G polymers as elicitors of rat PCA mediated by mouse IgE antibodies; Harada M et al.; PCA-eliciting activities of cephalothin- and penicillin G-polymers were examined in rats sensitized with homologous IgE antibodies of mouse origin . Cephalothin-polymers elicited PCA regardless of the source of antibodies and the methods to raise them, the minimal effective dose being 2 to 20 micrograms/animal . Penicillin G-polymers provoked PCA only when anti-benzylpenicilloyl IgE antibody of C57BL/6J mouse raised early after immunization was used . The minimal effective dose in this case was 5 micrograms/animal, being comparable to that of cephalothin polymers. Infection, 1986 Jan-Feb, 14(1), 32 - 5 Reinfection in erythema migrans disease; Weber K et al.; Two patients received oral penicillin for erythema migrans disease (EMD) in 1973 and 1977 . Five and seven years later, respectively, they developed EMD for a second time after being bitten by ticks . The first and second erythema migrans lesions appeared in different places . Tests of sera evaluated for antibodies to Borrelia burgdorferi before (in one case), during and after the second episode of EMD remained negative (patient 1) or yielded an at least four-fold rise of IgG antibody titers, but did not become positive (patient 2) . These cases provide evidence that reinfection in EMD may occur without a significant elevation of specific antibody titers. Naunyn Schmiedebergs Arch Pharmacol, 1986 Jan, 332(1), 89 - 92 Testing of prototype antiepileptics in hippocampal slices; Rose GM et al.; The effects of six prototype anticonvulsant drugs, phenytoin, carbamazepine, midazolam, phenobarbital, ethosuximide and sodium valproate, were evaluated in two different experimental models of epileptiform activity using the in vitro slice preparation from the rat hippocampus . The relative potencies of the agents were determined: a) in the complete absence of synaptic transmission by recording spontaneous burst firing from the CA 1 pyramidal cell layer in a low calcium high magnesium solution and b) during blocked synaptic inhibition by observing the activity of each drug upon orthodromically evoked population spikes in penicillin containing medium . The rank order of potencies was a) in low Ca2+: carbamazepine, phenytoin, midazolam, phenobarbital, valproate, ethosuximide; b) in penicillin containing medium: midazolam, phenobarbital, carbamazepine, phenytoin, valproate, ethosuximide . These observations illustrate that the use of multiple paradigms is warranted when examining the mechanisms of action of new anticonvulsants. J Antimicrob Chemother, 1986 Jan, 17(1), 83 - 9 In-vitro interaction between dibekacin and penicillins; Navarro AS et al.; The in-vitro inactivation kinetics of dibekacin by three semi-synthetic penicillins (carbenicillin, ampicillin and ticarcillin) were studied taking into account the influence of certain factors such as time, the concentration of the semi-synthetic penicillin in the sample and the reaction medium used in the inactivation process . For a dibekacin/beta lactam concentration ratio of 1/100, the maximum percentage of inactivation of dibekacin was obtained for ticarcillin (99%), followed by carbenicillin (90%) and finally by ampicillin (65%) over a period of 45 h . For carbenicillin and ampicillin a linear relationship was established between the inactivation constant (Ki) and the concentration of these penicillins in the sample . It was also found that under the same experimental conditions the inactivation percentage in human serum was smaller than that observed in buffered solution, pH = 7.4 . It was observed that the degree of inactivation of dibekacin and gentamicin was similar under the experimental conditions employed in this study. Epilepsia, 1986 Jan-Feb, 27(1), 3 - 9 Differences in penicillin-induced synchronous bursts in the CA1 and CA3 regions of the hippocampus; Schneiderman JH; Epileptiform field potentials were compared in the CA3 and CA1 regions of penicillin-treated hippocampal slices . The CA3 field bursts usually began with decrementing spike patterns similar to reported single-unit bursts, whereas spike amplitude gradually increased in spontaneous and long-latency CA1 bursts . Stimuli close to CA1 recording sites also evoked short-latency, decrementing CA1 responses . We postulate that these patterns reflect a more rapid recruitment of CA3 neurons into synchronous bursts and a gradual sequential activation of the CA1 neurons by Schaffer collateral input from CA3 . Stimulation of stratum radiatum close to CA1 also produced long-latency "all-or-none" bursts in CA3 and then CA1, identical to spontaneous bursts and those produced by stimulation remote from CA1 . At threshold, 76% of the latency to the CA1 burst occurred between the stimulus and the onset of the CA3 burst . The latency to the CA3 burst decreased with increasing stimulus intensity but the intervals from CA3 to CA1 bursts remained constant . Thus, long-latency CA1 bursts appear to be due to antidromic activation of CA3 followed by reexcitation of CA1. Med Toxicol, 1986, 1 Suppl 1, 99 - 104 Adverse drug reaction reporting . Philippine experience; Ines Cuyegkeng E; For almost 20 years, the Philippine Medical Association, and specifically its Committee on Foods, Drugs and Cosmetics, has not been able to successfully gather information on adverse drug reactions (ADRs) . The reporting of ADRs began in 1967, using a very comprehensive reporting form, at a time when news items of anaphylactic shock and deaths allegedly from intramuscular injections of penicillin, and subsequent litigation, were appearing . Up until 1973, when there were new initiatives, a few ADR reports were obtained mainly from hospitals who employed Philippine Medical Association committee members . Despite the issuing of directives for co-operation from hospitals, reports were not forthcoming . Involvement of hospital pharmacists and officers of specialist societies subsequent to the arrival of a World Health Organization (WHO) consultant in 1981 resulted in a simplified reporting form . Initial enthusiasm generated some ADR reports, but information was often inadequate and requests for further details were ignored . A new form entitled 'Drug Experience Reporting'--based on the USA FDA example--was introduced in 1984, when the Philippine Pediatric Society on ADR reporting also designed a project for use in hospitals . A change in doctor and patient attitudes is necessary before progress can be made, and a new strategy based on the education of doctors and medical students has been implemented . An important requirement is a mechanism to review and assess ADRs that will satisfy health authorities and maintain confidentiality. Nauchnye Doki Vyss Shkoly Biol Nauki, 1986, (12), 50 - 3 {Effect of exogenous DNA on convulsive activity}; Khanbabian MV et al.; On the corazole model of the experimental epilepsy and epileptiform activity evoked by penicillin application to the cerebral cortex with electroencephalographic registration, it has been shown that exogenous DNAs in the most cases completely or partially inhibit convulsive activity . DNA inhibited also the pacemaker activity of the Helix RPa-1 neurons. Acta Med Scand, 1986, 220(5), 485 - 8 Acrodermatitis chronica atrophicans He