Penicillin

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 Herxheimer can often mimic a peripheral vascular disorder; Fagrell B et al.; During the past few years five patients have been referred to the angiology section at Danderyd Hospital under the diagnosis of chronic venous insufficiency but who were instead suffering from acrodermatitis chronica atrophicans (ACA) . The typical case of ACA starts with a limited inflammatory lesion, which is gradually replaced by atrophy and the skin shows a bluish, red discoloration . Late changes may be subluxation of joints in hands or feet and periosteal thickening . Capillary microscopy often reveals a clear picture of atrophy and a prominent, dilated subpapillary venular plexus . If localized to the leg the blood flow of the foot and lower leg may be increased, skin temperature elevated and venous capacity and return augmented . All these variables can consequently mimic venous insufficiency of the leg . ACA is caused by a Borrelia infection and serological testing will always show a significantly elevated titer to Borrelia . The disease is most often easily cured by 2-3 g of penicillin daily for two to three weeks.

Braz J Med Biol Res, 1986, 19(1), 97 - 102
Electrocorticographic and behavioral features of turtle parenteral penicillin epilepsy; Nasi JP et al.; The epileptogenic action of parenteral penicillin was studied in turtles with electrodes chronically implanted in both cerebral hemispheres . Penicillin was administered intraperitoneally at doses of 200,000 to 1,600,000 IU/kg . Doses higher than 600,000 IU/kg caused the appearance on the electrocorticogram of bilateral sharp waves or biphasic spikes, sometimes more pronounced in one hemisphere . These events were often accompanied by clonic activity of the neck muscles and mouth movements in an epileptic automatism . Intravenous penicillin (200,000 to 1,000,000 IU/kg) also evoked changes of the basic pattern of the electrocorticogram . Doses up to 350,000 IU/kg induced bilateral sharp waves and/or spikes sometimes accompanied by the seizures described in item 2 . Doses above 400,000 IU/kg produced bilateral synchronous spike or polyspike discharges with a clonic-tonic seizure pattern . The same dose of penicillin induced more marked changes in the electrocorticogram when injected intravenously than intraperitoneally . Since larger doses of parenteral penicillin were required to evoke epileptic activity in turtles than in cats, the present results are consistent with the concept that the brain of phylogenetically lower animals is less susceptible to epileptogenic agents than the brain of higher animals.

Rev Neurol (Paris), 1986, 142(3), 228 - 32
{Surgically treated syphilitic gumma of the brain . Computerized tomography findings}; Goulon M et al.; Syphilitic gumma is now exceptional . Symptomatology is non-specific and frequently, as in the case reported here, the onset is marked by a localized or generalized convulsion . A space-occupying lesion is recognized by angiography and CT . The precise diagnosis is suggested by evidence of arteritis or of a hypodense mass outlined by contrast or slight calcifications and confirmed by positive serology in a patient with a suspected cerebral tumor . In some cases a positive diagnosis can be made only by pathological examination after surgical ablation of the gumma . An area of central necrosis is surrounded by a granulomatous layer rich in plasmocytes (the polyclonal nature of the secretion is shown by immunocytochemistry) and a peripheral fibroblastic zone . The arteries are ensheathed by a dense inflammatory infiltrate constituted almost entirely by plasmocytes and their lumens are either stenosed or filled with endarteritic debris . Surgical treatment should be combined with penicillin administration . For a patient in good general condition with a suspected gumma, medical treatment can be given initially, with follow-up by CT, neurosurgery being indicated only in case of failure of medical therapy . The rarity of gummata in relation to other tertiary syphilitic lesions remains unexplained . The patient reported here had multiple infections including one due to cytomegalovirus after ablation of the gumma, highly suggesting an immunity disorder.

Acta Paediatr Hung, 1986, 27(2), 97 - 105
Pneumococcal infections during childhood: serotyping of pneumococcal strains from forty-six children; Spencker FB et al.; The results of serotyping of forty-six strains of pneumococci isolated from children aged 3/12 to 14 9/12 years and diagnosed as having pneumonia, meningitis, primary peritonitis, otitis media, lymphadenitis, osteomyelitis, bacteraemia and conjunctivitis are presented . The results of serotyping and the frequency distribution of the detected serotypes were compared to the particular diagnoses established and the age at which the subjects involved had become ill . Questions of epidemiology and possibilities of immunoprophylaxis are discussed . Finally, the occurrence of pneumococci that are resistant to antibiotic agents are discussed since an isolated strain was found to show reduced susceptibility to penicillin G.

Arch Otorhinolaryngol, 1986, 243(3), 183 - 5
The kinetics of penicillin diffusion in serum and middle ear effusions in experimentally induced otitis media; Juhn SK et al.; The kinetics of penicillin diffusion in serum and middle ear effusions (MEE) was studied in experimentally induced serous otitis media (SOM) and purulent otitis media (POM) after systemic injection of procaine-penicillin G . A higher rate of diffusion of penicillin into the middle ear cavity was found in POM than in SOM . The time to reach peak concentrations in MEE was also shorter in POM . Elimination of penicillin from the middle ear cavity was slower in SOM than in POM.

Int J Psychiatry Med, 1986-87, 16(2), 163 - 8
Delusions induced by procaine penicillin: case report and review of the syndrome; Cummings JL et al.; A patient manifesting an acute psychosis after receiving an injection of procaine penicillin is reported . The psychosis began immediately after drug administration and gradually abated over a forty-eight-hour period . The clinical presentation was dominated by paranoid delusions and a Capgras-like syndrome . Sixty-six previously reported cases were identified and reviewed . Patients manifested combinations of fear, auditory hallucinations, somatic hallucinations, visual hallucinations, and paranoid or religious delusions . The syndrome may occur with inadvertent intravenous injection of procaine and most likely reflects the action of procaine on limbic system structures.

Acta Physiol Hung, 1986, 67(2), 223 - 32
Differential responses of synaptosomal cation movements and respiration to the convulsants penicillin, pentylenetetrazol and 3-aminopyridine; Csillag A et al.; The effect of three convulsants was tested in rat cortical synaptosomes by measuring Na+ and K+ movements and respiration . Penicillin (of its derivatives the 3-phenyl-5-methyl-4-isoxazolyl-penicillin, i.e . oxacillin was used) at 2 to 14 mM concentration prolonged the uptake phase of the K+-curve without altering final cation equilibrium . Pentylenetetrazol, at 10 to 50 mM exerted a concentration-dependent inhibitory effect on K+-uptake, while 3-aminopyridine was effective only at high concentrations (50 mM) preventing synaptosomal K+-uptake and increasing the synaptosomal Na+-content without, however, blocking respiration . The data suggest a transitional rise of K+-permeability of synaptosomal membrane in the presence of oxacillin, without lasting depolarization . Sufficient doses of 3-aminopyridine probably depolarize synaptosomes, the underlying mechanism probably being associated with the primary blocking of K+-channels and a subsequent increase in Na+ influx rather than with the inhibition of the Na+--K+-pump.

Eur Neurol, 1986, 25(4), 262 - 8
Borrelia-induced meningoradiculitis--two different forms of the disease; Kloter I et al.; The pattern of CSF cytological findings in the acute stage and after 10 days of antibiotic and steroid treatment was examined in 14 patients with meningoradiculitis due to an arthropode-transmitted infection with Borrelia duttoni (burgdorferi) . At the acute onset of neurological symptoms, 12 patients revealed lymphocytic pleocytosis (cell count 50-500 X 10(6) cells/l) with numerous plasma cells (5-12% of the total cell count) and neutrophilic granulocytes (0.2-3.4%) . 10-14 days after the onset of penicillin infusion and steroid treatment, cell count was reduced by at least 50% in 8 patients . Plasma cells then varied between 2 and 8%, whereas the neutrophilic granulocytes had disappeared . Two patients with slowly progressive neurological symptoms had a normal cell count, and inflammatory changes in CSF cytology were not observed.

J Toxicol Clin Toxicol, 1986, 24(2), 175 - 82
Acute amoxicillin nephrotoxicity following an overdose; Geller RJ et al.; A 3 year old boy developed acute renal failure following an ingestion of 574 mg/kg of amoxicillin . Accidental ingestions of oral penicillins occur commonly, and are usually considered completely nontoxic . Based on this case, however, the possibility of adverse effects following large oral doses of penicillin-type antibiotics, mediated by allergic hypersensitivity or direct toxicity, should be considered.

Adv Neurol, 1986, 44, 593 - 617
Role of electrical interactions in synchronization of epileptiform bursts; Dudek FE et al.; Four general mechanisms can hypothetically contribute to or mediate localized synchronization of neuronal activity: (a) recurrent excitatory chemical synapses, (b) electrotonic coupling via gap junctions, (c) electrical field effects (ephaptic interactions), and (d) changes in the concentration of extracellular ions (e.g., K+) . It has generally been believed that synchronization of epileptiform bursts derives primarily, if not exclusively, from recurrent excitatory chemical synapses . Dual intracellular recordings from the CA3 area of the hippocampus have been used to demonstrate the existence of recurrent synaptic excitation, and computer simulations have provided a theoretical framework for the idea that relatively sparse interactions through recurrent excitatory chemical synapses can generate synchronized bursting after inhibitory pathways are blocked with convulsant agents . Additional experimental studies have supported the hypothesis that a model for seizure discharge, the penicillin-induced paroxysmal depolarization shift (PDS), is associated with a large increase in excitatory synaptic conductance . However, recent studies have suggested that electrical interactions are also likely to play an important role in spike synchronization during epileptic discharges . Several research groups have used in vitro preparations to show that afterdischarges and spontaneous bursts of population spikes (which represent synchronized action potentials) can occur after chemical synaptic transmission has been blocked in solutions containing low {Ca2+} . Although this result was first observed in the CA1 area, it has recently been confirmed in other regions of the hippocampus . These experiments indicate that mechanisms other than chemical synaptic transmission are capable of synchronizing action potentials in the hippocampus . In this chapter, two forms of electrical interaction that could mediate synchronization will be considered: (a) electrotonic coupling through gap junctions and (b) electrical field effects through extracellular space . Changes in the concentration of extracellular ions are another mechanism not involving chemical synapses . However, it seems unlikely that ionic changes act on the rapid time scale of electrical interactions, and their contribution is discussed elsewhere in this volume . We review evidence for the existence of electrotonic coupling and electrical field effects in the hippocampus and neocortex, and discuss their possible involvement in the synchronization of epileptiform events.(ABSTRACT TRUNCATED AT 400 WORDS)

Adv Neurol, 1986, 44, 583 - 92
Cellular basis of neuronal synchrony in epilepsy; Wong RK et al.; Synchronized discharge of populations of cortical neurons are often observed to underly both the interictal spikes and tonic seizures generated in experimental epilepsy studies . Recently it has been shown that similar synchronized discharges occur in cortical brain slices treated with convulsants such as penicillin, picrotoxin, or bicuculline . The favorable experimental conditions offered by the in vitro preparation have facilitated a detailed examination on the cellular basis for the generation of the epileptic neuronal synchrony . In this chapter we shall review some experimental observations on the neuronal synchronization and describe a mechanism for its generation based on the computer simulation approach . Three factors are considered to be essential for epileptic synchronization observation in vitro . First, cortical neurons may intrinsically generate bursts of action potentials . Second, recurrent excitatory connections exist that are sufficiently powerful that bursting activity may spread between synaptically connected neurons . Third, inhibition within the local neuronal circuit must be adequately attenuated to allow excitation to spread through the recurrent excitatory connections . Computer simulation studies have been based on these assumptions, using neuronal networks where each cell is connected to more than one postsynaptic neuron . Bursting initiated in one cell excites all its follower cells, and the sequential recruitment of an increasing number of cells eventually leads to a simultaneous discharge of the population . A number of recent experimental observations lend credence to the proposed scheme for neuronal synchrony . Simultaneous paired intracellular recordings provided direct evidence that a burst of action potentials in a presynaptic cell can activate action potentials postsynaptically . Furthermore, it is shown that the rhythm of spontaneous discharge in a neuronal population can be influenced by the activity of one neuron within the population.

Adv Neurol, 1986, 44, 559 - 82
Temporal and spatial distribution of intracellular potentials during generation and spread of epileptogenic discharges; Goldensohn ES et al.; This chapter addresses the characteristics and spatial distribution of intracellular potentials, the spread of paroxysmal depolarization shifts (PDSs) through the cortex, the extracellular field potentials in three dimensions, and the concentrations of penicillin in direct contact with elements in the epileptogenic focus . Data are presented that show that there are several types or gradations of PDS intensities within each focus; PDS types are distributed in groups related to their distance from the center of the focus and to the concentration of the epileptogenic drug; the morphology and repetition rate of electroencephalogram (EEG) spikes are related to features of the intracellular potentials; a mathematical model can estimate the distribution of concentrations of penicillin within the focus over long periods; no barriers impede diffusion of penicillin either at the cortical surface or at the boundary between gray and white matter; the potential field of the EEG spike is defined in three dimensions; and PDSs spread through the focus at the rate of 0.25 m/sec.

Adv Neurol, 1986, 44, 515 - 58
Spread and arrest of seizures: the importance of layer 4 in laminar interactions during neocortical epileptogenesis; Ebersole JS et al.; Much of the past investigation of epileptogenesis has centered on characterizing the paroxysmal depolarization shift (PDS) and postulating its origin . Spatial as well as functional analyses of cortical epileptic foci have been few in number, and in nearly all of them fully evolved drug foci, which were used for their stability, probably obscured differences in the responsivity among constituent neuronal populations at earlier stages of epileptic evolution . Proportionately little attention has been directed at determining where penicillin acts within the cortex . For the past 12 years, we have addressed both issues . Specific questions have included, for both individual neurons and neuronal aggregates: what are the initial abnormalities of responsiveness in an acute epileptic focus; how do these abnormalities evolve as the focus develops; is there a differential susceptibility of various neocortical layers to epileptogenesis; how do the various cortical laminar populations interact during epileptogenesis; how do the resultant response abnormalities propagate within and between cortical columns; and what are the effects of anticonvulsants on the various spatial and temporal features of epileptogenesis? In pursuit of this information, we have recorded the evolution of discrete and temporary epileptic foci in cat striate cortex, which were induced by the microinjection or iontophoresis of penicillin into the different cortical layers . Simultaneous, multilaminar responses of individual neurons and of neuronal aggregates to selective visual stimulation have been characterized before, during, and after focus development using multibarrel micropipettes . Correlations between drug diffusion and these multilaminar recordings were made periodically by using 14C-labeled penicillin . Stages: Using these techniques, new characteristics of focal epilepsy come to light that are not apparent in the spontaneous spiking of the typical established penicillin focus . Three successive stages of penicillin-induced epileptogenic abnormality were noted in the responses of isolated neurons: (a) an initial graded enhancement of the primary latency response to field-specific stimuli into a burst discharge (the EPR burst); (b) the subsequent graded development of a longer latency burst in response to field-specific and nonspecific stimuli (the LR burst); and (c) the evolution of a single stereotyped burst discharge (IIS) as the latency separating EPR and LR bursts declined (PDS or LR discharge) . Each type of neuronal burst was accompanied by a local field potential of similar latency, but of progressively increasing amplitude, with each successive stage of epileptogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

J Steroid Biochem, 1986 Jan, 24(1), 357 - 9
Effect of estriol, estriol-3-sulfate and estriol-17-sulfate on progesterone and estrogen receptors of MCF-7 human breast cancer cells; Gelly C et al.; The levels of progesterone receptors (PR {cytosol (Cy) and nuclear (N)} and estrogen receptors (ER) {cytosol and nuclear; occupied and unoccupied specific binding sites} were evaluated in the MCF-7 cancer cell line incubated with estriol (E3), estriol-3-sulfate (E3-3-S) or estriol-17-sulfate (E3-17-S) for 7 days in culture . Cells were grown in MEM medium containing 2 mM glutamine, 10% v/v dialysed calf serum and penicillin-streptomycin (100 U/ml) in the absence (control) or in the presence of 5 X 10(-8) M E3, E3-3-S or E3-17-S . The total PR (Cy + N) concentration which was 0.47 +/- 0.10 (SE) pmol/mg DNA in the non-treated cells, increased to 1.95 +/- 0.48 in the E3 and to 1.55 +/- 0.26 in the E3-3-S treated cells . No effect (PR: 0.47 +/- 0.15 pmol/mg DNA) was observed with the E3-17-S treatment . Total ER (Cy + N, occupied + unoccupied binding sites) in pmol/mg DNA +/- SE, were as follows: control 0.79 +/- 0.17; + E3: 0.33 +/- 0.09; +E3-3-S: 0.90 +/- 0.18 and +E3-17-S: 1.82 +/- 0.58 . The measurement by radioimmunoassay of unconjugated estriol in the culture medium indicated that after incubation with E3-3-S, a fraction (0.5-1%) of the sulfate was hydrolyzed but no hydrolysis was observed in the incubations with E3-17-S . It is concluded that in the MCF-7 human mammary cancer cell line E3 and E3-3-S stimulate PR very significantly, but it is suggested that E3-3-S acts through the hydrolyzed E3 . On the other hand, E3-17-S is inactive because it is not hydrolyzed . Consequently, E3-3-S can play an important role in the biological responses of this mammary cancer cell line.

Gene, 1986, 50(1-3), 119 - 22
Characterization of the regulatory region of the Escherichia coli penicillin acylase structural gene; Valle F et al.; Penicillin acylase is utilized in the enzymatic production of semisynthetic penicillins . The enzyme is composed of two different subunits that originate from a common precursor . The partial nucleotide (nt) sequence of the structural gene has been published . This paper reports the nt sequence of the regulatory region of this gene, the identification of a functional promoter, the transcriptional start point, and the description of possible regulatory regions.

Rev Neurol (Paris), 1986, 142(4), 384 - 90
{Role of the thalamus in the physiopathology of epilepsy}; Naquet R et al.; Early hypotheses on the origin of primary generalized epilepsy suggested a determinant role for the "centrencephalon" in the triggering of discharges of generalized spike-waves (GSW) and tonic-clonic crises (TCC) . It was demonstrated in this respect that bilateral cortical spike-wave discharges at 3 c/sec were obtained by electrical stimulation of intralaminar nuclei in the rat . The role of the thalamus in the genesis of GSW and TCC was subsequently demonstrated in several experimental models . However, the thalamus is apparently not involved in the genesis of EEG manifestations of generalized epilepsy and most authors agree that the latter are of cortical origin since a) with or without cardiazol, generalized seizures may occur after ablation of cat thalamus; b) in the cat diffuse cortical application of dilute penicillin can reproduce signs of generalized epilepsy observed after systemic injection of penicillin to this animal; c) finally paroxysmal discharges which appear in subcortical structures in the photosensitive baboon are always preceded by frontal cortical spike-waves; similarly intermittent light stimulation-provoked TCC always arise from the frontal cortex and furthermore hemispheric synchronization of attacks disappears after callosotomy . These findings indicate that the origin of GSW and TCC, is not in the thalamus but that the latter nevertheless plays a role in their elaboration.

Chemotherapy, 1986, 32(4), 352 - 5
Comparative in vitro susceptibility of Treponema pallidum to ceftizoxime, ceftriaxone and penicillin G; Korting HC et al.; A procedure dating back to the early penicillin era is adapted in order to determine the activity of the new cephalosporins ceftizoxime and ceftriaxone against Treponema pallidum in vitro . While the well-known activity of penicillin G is confirmed for the virulent Nichols strain (0.002 micrograms/ml lead to 50% immobilisation) the new cephalosporins turn out to be almost as efficacious . The concentration of ceftizoxime leading to 50% inhibition amounts to 0.004 micrograms/ml . The corresponding figure for ceftriaxone is 0.01 micrograms/ml . The potential importance of these findings for the treatment of syphilis in man are discussed.

Bull Soc Pathol Exot Filiales, 1986, 79(1), 9 - 21
Lyme disease: a review; Hechemy KE; Lyme disease has protean manifestations . The causative agent is Borrelia burgdorferi, a recently discovered spirochete . The disease has been found on three continents . The initial major clinical feature is a characteristic skin eruption known as erythema chronicum migrans . Subsequent main clinical manifestations are meningopolyneuritis and arthritis . However, clinical expressions of the disease vary widely . Some patients have very mild disease and others develop severe and prolonged illness . Specific laboratory tests for the detection of antibody to the organism are now available . The sensitivity of these tests approaches 100% when the sera are collected from patients having the later clinical manifestations . Penicillin and tetracycline are the therapeutic drugs of choice.

J Infect, 1986 Jan, 12(1), 65 - 9
Primary hepatic actinomycosis; Mongiardo N et al.; A case of primary hepatic actinomycosis is reported . Multiple liver abscesses were diagnosed in a febrile 60-year-old-man by means of non-invasive techniques such as ultrasonography, CT and radioisotope scans . The aetiology was confirmed by the unusual finding of Actinomyces israelii in anaerobic blood cultures . Other sites were not involved . Early penicillin therapy enabled surgery to be avoided.

J Bacteriol, 1986 Jan, 165(1), 269 - 75
Specific location of penicillin-binding proteins within the cell envelope of Escherichia coli; Barbas JA et al.; This communication deals with the location of penicillin-binding proteins in the cell envelope of Escherichia coli . For this purpose, bacterial cells have been broken by various procedures and their envelopes have been fractioned . To do so, inner (cytoplasmic) and outer membranes were separated by isopycnic centrifugation in sucrose gradients . Some separation methods (Osborn et al., J . Biol . Chem . 247:3962-3972, 1972; J . Smit, Y . Kamio, and H . Nikaido, J . Bacteriol . 124:942-958, 1975) revealed that penicillin-binding proteins are not exclusively located in the inner membrane . They are also found in the outer membrane (A . Rodriguez-Tebar, J . A . Barbas, and D . Vasquez, J . Bacteriol . 161:243-248, 1985) . Under the milder conditions for cell rupture used in this work, an intermembrane fraction, sedimenting between the inner and outer membrane, can be recovered from the gradients . This fraction has a high content of both penicillin-binding proteins and phospholipase B activity and may correspond to the intermembrane adhesion sites (M . H . Bayer, G . P . Costello, and M . E . Bayer, J . Bacteriol . 149:758-769, 1982) . We postulate that this intermembrane fraction is a labile structure that contains a high amount of all penicillin-binding proteins which are usually found in both the inner and outer membranes when the adhesion sites are destroyed by the cell breakage and fractionation procedures.

Cancer Immunol Immunother, 1986, 23(3), 207 - 13
Inhibition of in vitro LAK generation by OK-432; Yagita M et al.; The present study was designed to investigate the in vitro effect of OK-432 on interleukin-2-(IL-2) induced lymphokine activated killer (LAK) generation, and especially to test whether OK-432 can substitute for IL-2 or act in synergism with IL-2 for activation of cytotoxic lymphocytes . Surprisingly, our results showed that the addition of OK-432 to 4-day LAK activation cultures significantly inhibited both the generation of cytotoxic effectors to the natural killer (NK) resistant Daudi cell line and the proliferative responses of lymphocytes in a dose dependent manner . The inhibition of activation was total at 0.5 KE/ml of OK-432, a dose which was still effective in augmenting NK activity against K562 . The addition of penicillin G potassium (PCGk), which is contained in OK-432 at a concentration of 134,700 units/mg of dried cocci, to the LAK culture system also inhibited LAK generation at equivalent concentrations as contained in the OK-432 preparation . This inhibition of LAK generation by OK-432 was significantly eliminated by dialysis of OK-432 . These results indicated that the inhibition of LAK generation was partly due to PCGk contained in the OK-432 preparation, and that OK-432 did not act synergistically with IL-2 in standard LAK activation systems.

Microbios, 1986, 45(184-185), 193 - 8
Protecting penicillin from penicillinase; Soufer D; A bacterial strain exposed to penicillin may produce an extracellular enzyme called penicillinase which leaves the bacterial cell and degrades the penicillin around it by hydrolysing the cyclic amide bond in the beta-lactam ring of penicillin and thus inactivates the antibiotic . Experiments were conducted to find a competitive and a non-competitive inhibitor which could irreversibly inhibit the activity of penicillinase, allowing penicillin to destroy the bacterial strain . After testing many inhibitors some had synergistic, antagonistic or even no affect on the bacterial strain . The non-competitive inhibitor which had the best result was iodine, and the best competitive inhibitor in its group was sulphoxazole.

Adv Neurol, 1986, 44, 967 - 89
Neuronal firing patterns from epileptogenic foci of monkey and human; Wyler AR et al.; The chronic, recurrent seizures induced in the monkey by cortical scarring occur spontaneously for years and share much of the phenomenology of spontaneous seizures of focal cortical onset in the human . Chronic extracellular recording in the focus of the chronic epileptic monkey reveals: A spectrum of abnormalities of unit firing ranging from grossly abnormal firing patterns to normal activity . Group I (highly epileptic) neurons fire exclusively in bursts, which are invariant during different behavioral states and during operant conditioning . Although firing within the bursts is not easily modified, the interburst interval can be modified indicating that these apparently denervated cells still have some synaptic input . All group I cells are pyramidal neurons . Group II (weakly epileptic) neurons exhibit variable burst firing, which may be intermixed with normal unit firing . The firing patterns of these cells can be modified by synaptic inputs . During operant conditioning, burst firing can decrease; during drowsiness or when inattentive, burst firing can approach that characteristic of group I cells . There is a direct relationship between the number of group I epileptic (pacemaker) neurons in the focus and the epileptogenicity of that focus as measured by frequency of spontaneous seizures in that monkey . The distribution of neurons encountered in the focus varies . On average, approximately 10% are group I (pacemaker) neurons; group II constitute 40%; and 50% of cells encountered exhibit normal firing patterns . In addition to firing in unstructured bursts, an unusual burst structure termed the long-first-interval (LFI) burst has been described that appears to be unique to the chronic focus . It is so named because the first interspike interval is longer than the remaining interspike intervals in the burst . The long first interval is extraordinarily invariant . There is little relationship between unit firing in bursts and the interictal EEG . During early parts of a spontaneous seizure, the two events become time-locked . During seizures, unit firing is synchronous with surrounding neurons and the spike portion of the EEG (as in penicillin foci) . Firing of group I neurons does not change significantly preceding a spontaneous seizure . Thus, group I neurons appear to act as pacemakers to the focus and group II cells provide the critical mass that, when synchronized to the burst firing of the pacemakers, is capable of initiating the ictal event.

J Am Dent Assoc, 1986 Jan, 112(1), 60 - 2
Management of anaphylactic shock after a single oral dose of penicillin: report of case; Kloberdanz B et al.; A report of an anaphylactic reaction to oral penicillin is presented; the relative pharmacologic reactions are reviewed; the initial signs and symptoms are analyzed; and a successful treatment method is described.

Respiration, 1986, 50(4), 301 - 3
Erythroderma and pneumonitis induced by penicillin?
Wengrower D, Tzfoni EE, Drenger B, Leitersdorf E.
Penicillin and its derivatives are known to cause several dermatologic and pulmonary hypersensitivity reactions . This report describes a patient who presented with combined generalized exfoliative dermatitis and severe pneumonitis caused by penicillin and aggravated by ampicillin, methicillin and mezlocillin . Antibiotic challenges with penicillin caused immediate reappearance of the dermatological manifestation; reactivation of the pneumonitis was probably prevented by immediate discontinuation of the drug.

Ter Arkh, 1986, 58(10), 76 - 8
{Clinico-immunological and allergological characteristics of urticaria caused by pyrazolone derivatives}; Poroshina IuA et al.; The authors describe the results of clinical, allergological and immunological examination of 35 patients with urticaria caused by pyrazolone derivatives . Clinically, the patients with pyrazolone-induced urticaria were marked by chronic diseases requiring the prolonged and frequent intake of the analgesics, pyrazolone derivatives . The allergological examination of the 35 patients with pyrazolone-induced urticaria showed that only one of the patients had pollenosis, 6 patients had IgG-mediated reactions to egg protein and one patient to penicillin . For specific diagnosis of drug allergy use was made of the natural leukocyte migration test in vivo according to A . D . Ado . The test appeared positive with analgin in all the 35 patients suffering from pyrazolone-induced urticaria . It represents a simple and accessible method for specific diagnosis of drug allergy both in inpatients and in those visiting allergological rooms at the polyclinics . The immunological examination made with the aid of the histograms demonstrated an appreciable reduction in the content of D-phagocytosing neutrophils . The latter fact might explain the presence of multiple chronic foci of infection in patients with pyrazolone-induced urticaria . Such patients manifested a decrease in C3 that might be related to immediate activation of the alternative pathway of complement by pyrazolone derivatives.

Med Cutan Ibero Lat Am, 1986, 14(3), 177 - 80
{Infectious mononucleosis and ampicillin}; Cabo HA et al.; One to 10% of the cases have cutaneous reactions caused by ampicillin . When this drug is associated to MI the percentage goes up to 90% of the cases . The physiopathogenic mechanism of the generalized exanthema in this association is unknown . The development of toxicity is postulated because these patients have no previous history of allergy to penicillin either before of after the cutaneous reaction . By a still obscure mechanism, MI predisposes or alters the patient sensibility to the drug and the cutaneous reaction appears . This picture cannot be attributed to MI because the exanthema that present is mild . Neither is this picture of allergy due to ampicillin, without relationship with the MI, because the reaction is not coincident with other descriptions of reactions by this drug . The clinic evidence, observed in patients with MI, and ampicillin, is of a strong relation between two factors and the cutaneous reaction . In our patient the eruption affected principally the sites exposed to the sun, that makes us think in a phototoxicity reaction . Despite this fact the tests done were negative . We agree with other authors that the administration of ampicillin in patients with ill-defined pharyngeal symptoms is contraindicated until infections mononucleosis is ruled out.

Allergy, 1986 Jan, 41(1), 75 - 8
Onset of penicillin rashes: relation between type of penicillin administered and type of immune reactivity; de Haan P et al.; In 90 patients with clinical symptoms of penicillin allergy, the onset of the skin reaction was related to the type of penicillin administered (small- or broad-spectrum) and to the type of immune reactivity . Early onset reactions (urticaria, Quincke's edema, Arthus-reactions) were frequently seen after the use of benzylpenicillin, while late onset reactions, mostly macular papular rashes, were mainly seen after the use of aminopenicillins . The clinical symptoms of penicillin hypersensitivity were not related to one single type of immunological (cellular or humoral) reactivity.

Exp Brain Res, 1986, 64(3), 607 - 9
Paroxysmal neuronal depolarizations in the rat motorcortex in vivo: intracellular injection of the calcium agonist BAY K 8644; Walden J et al.; Epileptic activity was elicited in the rat's motor cortex by local application of penicillin . At the neuronal level it consisted of typical paroxysmal depolarization shifts . The calcium agonist BAY K 8644 was injected into neurons showing such a discharge pattern . The application of this drug increased amplitude and after depolarization of paroxysmal neuronal depolarizations.

J Dairy Sci, 1985 Dec, 68(12), 3224 - 33
Removal of penicillin G from contaminated milk by ultrafiltration; Kosikowski FV et al.; Penicillin G purposedly added to whole raw milk at concentrations from .05 to .20 IU/ml was removed to undetectable levels by a combination of ultrafiltrations and permeate washes . After penicillin removal, whole milk 3:1 vol/vol concentrated retentates were reconstituted to milk with antibiotic-free permeate with little change in composition and with very good to excellent flavor . Washing 3:1 vol/vol concentrated retentates from penicillin-contaminated milks with water also removed penicillin to an undetectable level but changed the composition of product, which displayed a flat flavor.

Pediatrics, 1985 Dec, 76(6), 950 - 3
Recurrent bacterial meningitis: coronal thin-section cranial computed tomography to delineate anatomic defects; Steele RW et al.; Three patients with histories of recurrent bacterial meningitis were previously examined with skull and sinus radiographs, routine cranial computed tomography, intrathecal radioisotope tracer studies, and immunologic evaluation . None of these studies were diagnostic . Pneumococcal vaccine and prophylactic penicillin therapy were ineffective in preventing recurrent episodes in two cases . Thin-section (2-mm) direct coronal computed cranial tomography demonstrated anatomic defects in all three patients . The use of metrizamide cisternography was not necessary to diagnose the defects . All patients had basiethmoidal encephaloceles which were repaired surgically . Direct coronal computed tomography offers a relatively easy noninvasive method for delineating anatomic abnormalities in patients with recurrent meningitis.

Fed Proc, 1985 Dec, 44(15), 2953 - 5
Neuronal interactions during epileptic events in vitro; Traub RD et al.; Epileptic events can be produced in in vitro brain slices after perfusion with convulsant agents such as penicillin or picrotoxin . These events consist of one or more synchronized neuronal bursts . In this experimental system, epileptic events occur because of blockade of synaptic inhibition by the convulsant agent . A sparse network of excitatory synaptic interconnections in the hippocampus serves to synchronize a population of neurons, each of which is capable of bursting after appropriate stimulation.

Clin Pediatr (Phila), 1985 Dec, 24(12), 716 - 8
Acute reversible pulmonary ischemia . A cause of the acute chest syndrome in sickle cell disease; Babiker MA et al.; A 6-year-old girl with sickle cell disease was admitted to the hospital with the diagnosis of the acute chest syndrome . The laboratory findings and the radionuclear lung scan supported a diagnosis of pulmonary infarction rather than pneumonia . She improved with intravenous fluids, oxygen, penicillin, and theophylline . The most likely explanation for the rapid resolution of the clinical syndrome, the chest x-ray, and lung scan abnormalities is that masses of sickled cells caused transient pulmonary vascular occlusion leading to perfusion defects and ischemia, and that the sickled cell thrombi were dislodged before the infarction occurred . To our knowledge, this phenomenon has not been described as a cause of the acute chest syndrome in sickle cell disease in children.

Aust N Z J Med, 1985 Dec, 15(6), 727 - 30
Resurgent yaws in the Solomon Islands; Eason RJ et al.; We report a resurgence of yaws in the Solomon Islands and describe the combined clinico-serological survey and mass penicillin treatment campaign to define and curb it.

Neurol Res, 1985 Dec, 7(4), 202 - 6
Effects of anticonvulsants on K+-induced excitation and on penicillin-induced seizures; Stone WE et al.; Excitation induced in mice by intracerebral injection of KCl was antagonized by prior i.p . injection of phenytoin, chlordiazepoxide or phenobarbital, but was not significantly affected by muscimol, valproate, ethosuximide or trimethadione . In contrast, seizures induced by intracerebral injection of benzyl penicillin were antagonised by chlordiazepoxide, phenobarbital, valproate, ethosuximide and trimethadione, but not by phenytoin or muscimol . Implications with regard to mechanisms of action of the anticonvulsants and of penicillin are discussed.

Rev Infect Dis, 1985 Nov-Dec, 7 Suppl 4, S613 - 21
Cross-allergenicity and immunogenicity of aztreonam; Adkinson NF Jr et al.; The immunochemistry of aztreonam, the prototype of the new monobactam class of beta-lactam antibiotics, was studied in a series of experimental and clinical investigations . Rabbit antibodies to aztreonam and naturally occurring human antibodies that recognize aztreonam were found to have negligible cross-reactivity with benzylpenicillin, cephalothin, and cefotaxime . Aztreonam likewise displayed negligible cross-reactivity (less than or equal to 0.001%) with antibodies to penicillin (including human IgE antibodies to major and minor penicillin determinants) and to cephalothin . These studies suggest that aztreonam may be well tolerated by penicillin-allergic individuals, and this possibly is now being evaluated in clinical trials . Seven (6.25%) of 112 healthy persons tested had preexisting IgG antibodies to aztreonam in low titer, presumably as a result of exposure to naturally occurring cross-reacting moieties . Only two of seven patients with preexisting IgG antibodies to aztreonam had a rise in titer following aztreonam treatment . No IgE antibody to aztreonam was detected in serum specimens obtained on day 10 during any of the 112 courses of therapy . These clinical observations suggest but do not prove that aztreonam has only weak potential to elicit a drug-specific immunologic response.

J Neurol Neurosurg Psychiatry, 1985 Nov, 48(11), 1182 - 4
Polyneuritis cranialis associated with Borrelia burgdorferi; Schmutzhard E et al.; Three patients with classical idiopathic polyneuritis cranialis, in whom no other aetiology could be detected, were examined serologically, by means of indirect immunofluorescence test, for antibodies (IgM and IgG) against Borrelia burgdorferi, the aetiologic agent of Lyme disease . In each case polyneuritis cranialis was caused by infection with Borrelia burgdorferi . Therapy with penicillin proved to be effective.

Handchir Mikrochir Plast Chir, 1985 Nov, 17 Suppl, 37 - 43
{Therapy of severe hand infections with local penicillin-streptomycin administration}; Zifko B; The primary goal of treatment of severe hand infections (finger joint infection, tenosynovitis, infections of the palm and the dorsum of the hand) is nowadays not only a matter of bringing the infection under control, but also trying to get a good functional result . To reach good results the author regards two steps in treating severe hand infections as indispensable: a) the principle of early operation (the average interval between the first examination in the hospital and surgery was only 0,5 days) and b) the local instillation of antibiotics in high concentration (penicillin and streptomycin) . Over a period of three years 187 patients with severe hand infections were treated . 11 (5.8%) patients required a second operation and 5 (2.6%) patients a finger amputation . The functional result was in 85% of cases very good or good and in 15% poor.

Am J Hosp Pharm, 1985 Nov, 42(11), 2510 - 3
Factors affecting drug delivery from a syringe-pump infusion set; Geater RE et al.; In vitro testing of drug delivery via dual-lumen, small-volume i.v . extension tubing designed for use with a syringe pump was conducted . From a dual-lumen extension set with intraluminal diameters of 0.020 inch, effluent samples were collected at 5, 10, and 20 minutes after injection of a 1-mL volume of drug solution intended for delivery over 20 minutes by a syringe infusion pump . Variables were flow rate (5 or 25 mL/hr) of the primary infusion, tubing position (vertical or horizontal), and density of the drug solution (penicillin G potassium 250,000 units/mL and aminophylline 25 mg/mL represented high and low specific gravities, respectively) . Each drug solution was labeled with radioactive carbon and the drug content of the effluent was analyzed by liquid scintillation . For each set of variables, samples were also tested after the tubing was flushed with 5% dextrose injection 0.2-0.6 mL . Similar procedures were followed to determine delivery of the labeled penicillin G potassium solution via a dual-lumen extension set with intraluminal diameters of 0.020 inch (for drug) and 0.060 inch (for the primary infusion); a 13-mm-diameter, 0.2 micron filter was attached to the smaller-lumen tubing . A primary infusion flow rate of 5 mL/hr and flush volumes of 0.3 and 0.6 mL were used in this study . To determine the influence of intraluminal diameter on the flush volume required for delivery of a dose of aminophylline (1-mL volume), single-lumen extension tubings with different diameters were tested . The final percentage of the drug dose delivered via the dual-lumen extension set with 0.020-inch lumens was affected only by flush volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Infect Immun, 1985 Nov, 50(2), 453 - 8
Persistent infection of L cells with an ovine abortion strain of Chlamydia psittaci; Perez-Martinez JA et al.; L cells inoculated at multiplicities of infection greater than or equal to 1 inclusion-forming unit of the abortigenic chlamydial strain B577 were destroyed within 10 to 15 days . Upon continued incubation in fresh medium, a few surviving cells repopulated the flasks, and the reemerging cultures remained persistently infected . The persistent state was characterized by cycles of repopulation with a low ratio of infected cells and cycles of extensive cytopathic changes in which greater than 90% of the cells had chlamydial inclusions and which could be delayed or even terminated by penicillin treatment . Immunofluorescence and superinfection during the period of repopulation revealed that the persistently infected cells could adsorb chlamydiae but their multiplication was arrested . This nonpermissive state could be terminated by the specific action of cycloheximide . L cells spontaneously cured from a persistent infection exhibited no change in susceptibility to chlamydiae when compared with normal L cells . However, chlamydiae derived from L cells after 7.5 months of persistence destroyed L-cell monolayers more rapidly and at lower multiplicities of infection than the wild type . This state of chlamydia-host cell interaction could not be established with the arthropathogenic strain LW613 because chlamydial infectivity was lost after the first cytolytic burst of infection in the cell cultures . The persistence described for the strain B577-L-cell system appears to differ from previously described models involving other chlamydial strains.

Clin Pediatr (Phila), 1985 Nov, 24(11), 651 - 4
Actinomycosis meningitis in a girl with incontinentia pigmenti; Diamantopoulos N et al.; A 7-year-old girl with incontinentia pigmenti and a history of multiple bacterial infections developed chronic meningitis with Actinomycosis odontolyticus, which was successfully treated with long-term penicillin administration . Although all tests of immunologic function were normal in this patient, her history of recurrent and unusual infections is consistent with previous suggestions of an undefined immunodeficiency state associated with incontinentia pigmenti.

Aust Vet J, 1985 Nov, 62(11), 361 - 5
A survey of ovine dermatophilosis in Western Australia; Edwards JR et al.; A random sample of 200 Merino sheep owners was interviewed by telephone during April 1983 and asked questions relating to the prevalence of ovine dermatophilosis in their flocks, methods used for prevention and treatment of dermatophilosis, management strategies employed and the location and annual rainfall of each farm . The response rate was 99.5% . During the previous 12 months 62.3% of farmers had observed dermatophilosis in their flocks . The prevalence within flocks was highest in hoggets (mean 2.2%, range 0 to 75%) followed by lambs (mean 0.8%, range 0 to 25%), ewes (mean 0.6%, range 0 to 20%) and wethers (0.2%, range 0 to 20%) . The mean weight of wool identified as affected by dermatophilosis was 58 kg (range 0 to 882 kg) . Preventive measures were used on 57% of farms and the most common methods were changes in dipping practice (23.6%) and culling of affected sheep (21%) . An average of 13.7 sheep per farm were culled for dermatophilosis and of these, 82% were sold and the remainder (18%) were killed on the farm . Antibiotics, of which most were combinations of penicillin and streptomycin were used to treat dermatophilosis on 8.5% of farms and treatments other than antibiotics were used on 10% of farms . The prevalence of dermatophilosis and its relationship to various environmental and management factors varied with the age and sex of sheep . Discriminant analysis indicated that of the factors studied, average annual rainfall, month of lambing, average fibre diameter and the month ewes were shorn were related to the prevalence of dermatophilosis in lambs.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergol Immunopathol (Madr), 1985 Nov-Dec, 13(6), 487 - 92
Penicillin allergy: in vivo and in vitro diagnostic methods; Navarro C et al.; Hypersensitivity to beta lactams, especially that mediated by IgE or IgG4, is the most frequent complaint of adverse drug reactions . There are multiple studies dedicated at establishing a method that can permit us to arrive at an accurate diagnosis, but from these studies one deduces that the difficulty lies in the lack of a test with a 100% reliability . In the present study we evaluate the correlation between the different methods . For this we selected 16 children, composed of 8 males and 8 females, whose ages ranged between 2 years 7 months and 9 years 8 months, and who had a reaction to penicillin G via parenteral . The following tests were done on them: Skin tests with a major determinant antigen (constant composition and molecular weight), with minor determinants . Human basophil degranulation test (modified Leynadier technique) . Mathov's progressive controlled provocation test, which we considered the most reliable . Only in eight cases a diagnosis of penicillin allergy was arrived at . The correlation between the different tests were: Mathov - HBDT 93.75%; Mathov - PPL 93.75% and PPL - HBDT 87.5%.

Brain Res, 1985 Oct 28, 346(1), 89 - 107
A {14C}2-deoxyglucose analysis of the functional neural pathways of the limbic forebrain in the rat . V . The septal area; Watson RE Jr et al.; The {14C}2-deoxyglucose (2-DG) metabolic mapping technique has been used to identify the regions responding with an augmented rate of metabolism following focal electrical stimulation of various sites within the lateral septal nucleus and medial septal nucleus/diagonal band (MSN/DB) complex in the rat . Since 2-DG uptake has been correlated with rates of functional activity, it was the intention of this study to suggest the anatomical substrates underlying various physiological and behavioral responses elicited by stimulation of the septal area . The results show that stimulation of any region within the lateral septal nucleus produced a profound bilateral activation of both the lateral septal nucleus, as well as the hippocampal formation . While stimulation of a number of different fiber systems associated with the lateral septum could contribute to the observed pattern of labeling, the data suggest that, functionally, a major consequence of such stimulation is the antidromic activation of CA3----lateral septum fibers to axonal branch points, beyond which, orthodromic propagation of the impulse produces activation in CA3 target regions, including subfields CA1 and CA3, as well as the lateral septal nucleus, bilaterally . In addition, regions typically manifesting metabolic activation following stimulation of the lateral septal nucleus included the ipsilateral diagonal band of Broca, nucleus accumbens, lateral preoptic area and lateral hypothalamus, posteriorly, and the prelimbic cortex, anteriorly . Occasionally, target regions of the postcommissural fornix, including the medial mammillary nucleus and anterior thalamic nuclei were also activated following stimulation of the lateral septal nucleus . In contrast to the widespread pattern of activation resulting from stimulation of the lateral septal nucleus, stimulation of the MSN/DB complex produced activation which was largely confined to the medial forebrain bundle . In a final phase of the experiment, afterdischarge activity was elicited by sodium penicillin injection into the lateral septal nucleus . Such treatment produced more widespread 2-DG uptake, including more extensive activation within the lateral septal nucleus, hippocampal formation, amygdala, and thalamus . Additionally, the prefrontal cortex and temporal neocortex were activated.

Neurosci Lett, 1985 Oct 24, 61(1-2), 55 - 9
Striatal and septal influence on hippocampal theta and spikes in the cat; Sabatino M et al.; The experiments studied the modulation exerted by the septum and the caudate nucleus on hippocampal activity in the cat . Injections (i.v.) of sodium penicillin were performed in order to obtain a steady interictal epileptic activity . Hippocampal slow rhythmic activity showed a marked decrease either in duration or in frequency following penicillin activation . Both septal and caudate electrical stimulation inhibited spike frequency through a theta eliciting mechanism . Caudate stimulation failed to determine any sort of effect after medial septum lesions . The importance of the septum as modulation station between basal ganglia and hippocampus is emphasized.

Brain Res, 1985 Oct 21, 345(2), 306 - 14
Muscarinic mobilization of choline in rat cerebral cortex does not involve alterations of blood-brain barrier; Brehm R et al.; Efflux of choline from the rat cerebral cortex in vivo was investigated using the cup technique . After removal of the dura mater, the cup was placed on the cortex . Transmission and scanning electron microscopy revealed that the cortex was separated from the cup solution (100-300 microliter) by basal lamina, pia mater, arachnoid (with discrete defects) and remainders of the subdural neurothelium . Two kinds of experiments were carried out to determine: efflux of unlabelled choline into the cup solution; and translocation of radioactivity from the plasma into the cup solution (via blood-brain barrier and leptomeningeal layers) during i.v . infusion of {3H}choline or {14C}inulin . The former process was highly temperature-sensitive in contrast to the latter . Penicillin-G-sodium, which is known to damage the blood-brain barrier, was added to the cup solution, enhanced efflux of unlabelled choline, and caused a 5-fold increase in the rates of translocation of radioactivity during infusion of either labelled choline or inulin . In contrast, physostigmine (3 X 10(-4) M, added to cup solution) failed to enhance 3H-translocation, but markedly facilitated the efflux of unlabelled choline; this effect was highly temperature-sensitive and was blocked by atropine . It is concluded that activation of muscarinic receptors enhanced the choline efflux from cortical tissue . This effect was caused by cellular mobilization of choline presumably through an action on the metabolism of phosphatidylcholine . The effect was not due to alterations in the translocation of choline from the plasma to the cup solution, i.e . through permeability changes in the blood-brain barrier and in the leptomeningeal 'barrier'.(ABSTRACT TRUNCATED AT 250 WORDS)

FEBS Lett, 1985 Oct 21, 191(1), 39 - 44
Sequence of the OXA2 beta-lactamase: comparison with other penicillin-reactive enzymes; Dale JW et al.; The nucleotide sequence of the unusual plasmid-mediated OXA2 beta-lactamase is presented, and compared with other beta-lactamases . The OXA2 enzyme has similar features at the presumed active site, but no other significant regions of homology with other penicillin-reactive enzymes . The active site homology may therefore represent convergent evolution of otherwise dissimilar genes.

Sex Transm Dis, 1985 Oct-Dec, 12(4), 238 - 40
Solitary oral condylomata lata in a patient with secondary syphilis; de Swaan B et al.; A case report of a patient with oral condylomata lata is presented . Physical examination showed that the lesions were the only symptom of secondary syphilis . The diagnosis was based on dark-field microscopy of specimens from the lesions and serologic tests for syphilis . The condylomata lata responded well to treatment of the syphilis with procaine penicillin G.

Monatsschr Kinderheilkd, 1985 Oct, 133(10), 732 - 7
{Erythema migrans disease . 3 case examples with neurologic complications}; Christen HJ et al.; The erythema-migrans-disease is closely related to Lyme-disease as described in the USA, and represents a tickborne spirochetosis with highest incidence during summer and autumn . Besides nonspecific general symptoms in its earlier stages, it is characterized by a distinctive erythema migrans; later, additional neurological, cardiac and/or arthritic symptoms may develope . Its typical neurologic complication, the lymphocytic meningoradiculitis Garin-Bujadoux-Bannwarth, was observed in three children whose clinical features illustrate the great variability of symptoms of Erythema-migrans-disease . Serological tests for specific spirochete antibodies are valuable aids in differential diagnosis, especially for cases with late complications if a tick bite is not remembered, or as is not uncommon, the typical skin lesion has not occurred, or has not been noted . Antibiotic therapy with penicillin or tetracycline is a successful treatment of the earlier stages of the disease and can prevent, or at least ameliorate, subsequent complications.

J Appl Bacteriol, 1985 Oct, 59(4), 347 - 52
A sensitive enzymic assay for benzylpenicillin; Baker WL; A method has been developed for the determination of sodium benzylpenicillin concentrations in the range 3.3-33 micrograms/ml . 6-Aminopenicillanic acid is released from the benzylpenicillin by the action of the enzyme penicillin acylase and is estimated from its reaction with fluorescamine at pH 4 . 7-Aminocephalosporanic acid shows a similar trend to 6-aminopenicillanic acid in its reaction at pH 4 . The open beta-lactam ring form of each compound shows little fluorescence with fluorescamine at pH 4 but shows strong fluorescence in the pH range 7-9 . 6-Aminopenicillanic acid and its open beta-lactam ring form give different fluorescent responses to increasing volumes of a solution of the fluorigenic agent at pH 7.8 . This effect can be used to estimate concentrations in a mixture of the two components providing other amino material is absent.

Exp Neurol, 1985 Oct, 90(1), 278 - 80
GABA and phospholipids in penicillin-induced seizures; Loeb C et al.; The effect of a suspension of GABA and phosphatidylserine (PS), phosphatidylcholine, or phosphatidylethanolamine was studied on penicillin-induced epileptic activity in rats . GABA-PS significantly reduced the number of spikes, in comparison with either the other phospholipid compounds or normal saline . No effect was observed after GABA or PS administration alone . We suggest that the different effects probably depend on extracellular and intracellular factors.

Int J Pediatr Otorhinolaryngol, 1985 Oct, 10(1), 37 - 46
Recurrent acute otitis media--prophylactic penicillin treatment: a prospective study . Part I; Persico M et al.; Recurrent acute otitis media (RAOM) is a distressing clinical manifestation of middle ear pathology, mainly expressed in the first two years of life . In this controlled study, prophylactic treatment by phenoxymethyl penicillin reduced significantly the frequency of RAOM in 60 children, as compared to 48 children who received a short ampicillin course only on the occasion of an acute otitis media episode . The importance of breastfeeding, age at initial episode, the type of treatment given and the pertinent literature is discussed . A working hypothesis of this prophylactic treatment is suggested.

J Bacteriol, 1985 Oct, 164(1), 456 - 60
Identification of the active site in penicillin-binding protein 3 of Escherichia coli; Nicholas RA et al.; We report the sequence of the active site tryptic peptide of penicillin-binding protein 3 from Escherichia coli . Purified penicillin-binding protein 3 was labeled with {14C}penicillin G and digested with trypsin, and the resulting radioactive peptides were isolated by a combination of gel filtration and high-pressure liquid chromatography . The major radioactive peak from high-pressure liquid chromatography was sequenced, and the peptide Thr-Ile-Thr-Asp-Val-Phe-Glu-Pro-Gly-Ser-Thr-Val-Lys, which comprises residues 298 to 310 in the amino acid sequence, was identified . This sequence is compared with the active site sequences from other penicillin-binding proteins and beta-lactamases.

Biol Reprod, 1985 Oct, 33(3), 545 - 50
Regulation of baboon fetal adrenal androgen production by adrenocorticotropic hormone, prolactin, and growth hormone; Pepe GJ et al.; Factors other than adrenocorticotropic hormone (ACTH) are thought to influence fetal adrenal steroidogenesis during primate pregnancy . Therefore, we determined the effects of prolactin (Prl), growth hormone (GH), and human chorionic gonadotropin (hCG) as well as ACTH on steroid secretion by collagenase-dispersed baboon fetal adrenal cells . Adrenal glands were obtained from seven baboon (Papio anubis) fetuses following cesarean section at Day 100-107 of gestation (term = Day 184) . Tissue was minced with a fine scissors and cells were dispersed with 0.2% collagenase, then washed with Medium 199 containing penicillin/streptomycin . Cells (0.5 X 10(4)) were placed in 4 ml Medium 199 with or without 10 nmol ovine Prl, ovine GH, or ACTH, or 50 nmol hCG . After 18 h incubation (37 degrees C), cells were separated by centrifugation and the quantities of cortisol (F), dehydroepiandrosterone (DHA), and DHA-sulfate (DHAS) secreted into the medium were determined . In controls, DHA secretion {224 +/- 96 ng/(24 h X 10(5) cells} was greater (P less than 0.05) than that of DHAS (20 +/- 12) and F (14 +/- 12) . Adrenocorticotropic hormone, Prl, and GH stimulated (P less than 0.05) DHA secretion by 370% +/- 71%, 215% +/- 61%, and 292% +/- 73%, respectively; hCG was not effective . Due primarily to the relatively low secretion rates, DHAS and F secretion were not altered by hormonal treatment . Moreover, addition of 20 nmol progesterone to the medium in the presence or absence of ACTH did not influence F production . These findings indicate that the baboon fetal adrenal at midgestation does not utilize placental progesterone for F synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Ann Acad Med Singapore, 1985 Oct, 14(4), 693 - 5
Ampicillin-induced interstitial nephritis with generalised exfoliative dermatitis; Fong PH et al.; Drug induced renal failure is a serious, potentially, fatal illness that is preventable . Hypersensitivity reactions involving the kidneys can occur with any of the penicillin groups . However, there are few reports in the literature of ampicillin as a cause of acute interstitial nephritis . In the following case report, a patient developed acute interstitial nephritis with renal failure and exfoliative dermatitis following ampicillin therapy . The diagnosis was based on the rapid onset of renal failure, presence of eosinophilia, skin rash, and characteristic renal biopsy finding, following the administration of ampicillin . Renal function returned to normal eventually, but she continued to have relapses of exfoliative dermatitis up to a year later.

Electroencephalogr Clin Neurophysiol, 1985 Oct, 61(4), 314 - 22
The 'foramen ovale electrode': a new recording method for the preoperative evaluation of patients suffering from mesio-basal temporal lobe epilepsy; Wieser HG et al.; A technique to record from the mesio-basal aspect of the temporal lobe by a subdural electrode inserted through the foramen ovale (FO) is described . For this purpose a special electrode was developed that, in addition, allowed epicortical DC recording . After having tested its value experimentally in dogs with penicillin-induced hippocampal seizure foci, this 'FO electrode' was subsequently applied to 10 patients . Nine of them suffered from drug-resistant complex partial seizures suspected to be of mesio-basal limbic origin . Seven patients had in addition to the FO electrode depth electrodes stereotactically implanted within the hippocampus and nucleus amygdalae, thus allowing an evaluation of this new FO recording technique by direct comparison with stereo-EEG . Our results indicate that interictal epileptiform potentials as well as ictal discharges are reliably picked up by the FO electrode whenever nucleus amygdalae, hippocampus and parahippocampal gyrus show synchronous epileptic activity . As a rule, these events are not reflected in conventional scalp EEG records . Epileptiform activity in subcompartments of the mesio-basal limbic structures is not reliably reflected by the FO electrode . Negative epicortical DC shifts recorded by the FO electrode are a sensitive indicator of epileptic activity within the underlying deeper structures . In conclusion, in certain patients with drug-resistant epilepsy of suspected mesio-basal limbic origin the use of FO recording in the presurgical evaluation might provide sufficient information to give an indication for resective surgery, either by anterior temporal lobectomy or by selective amygdalo-hippocampectomy.

Electroencephalogr Clin Neurophysiol, 1985 Oct, 61(4), 299 - 309
Suppression of focal epileptiform discharges by intraventricular perfusion of a calcium antagonist; Walden J et al.; Calcium currents were found to participate in the generation of epileptic discharges of single cortical neurones . The present experiments tested whether a systemic administration of a calcium antagonist is able to influence epileptic activity in neuronal populations . Focal interictal epileptiform discharges (FIEDs) were elicited by application of penicillin to the motor cortex of the rat . The calcium antagonist verapamil dissolved in artificial cerebrospinal fluid was applied by intraventricular push-pull perfusion to achieve high concentrations of the drug in cerebral tissue and to avoid alterations of the systemic circulatory system . The application of the calcium antagonist reduced FIEDs in amplitude and in frequency of occurrence . In some experiments the suppression of seizure activity was preceded by a transient enhancement . After termination of the drug perfusion FIEDs were often re-established . Control experiments revealed that perfusion with drug-free cerebrospinal fluid did not change FIEDs . In experiments without epileptic activity, cortical evoked potentials elicited by stimulation of the sciatic nerve tended to increase with perfusion of the calcium antagonist . As a whole, the systemic administration of the calcium antagonist verapamil depressed FIED and exerted an inverse effect on synchronized non-epileptic neuronal activity.

Lancet, 1985 Sep 28, 2(8457), 684 - 6
Chloramphenicol alone versus chloramphenicol plus penicillin for severe pneumonia in children; Shann F et al.; 748 children with severe pneumonia in three hospitals in Papua New Guinea were randomised to receive intramuscular injections of either chloramphenicol alone or chloramphenicol plus penicillin . Sequential analysis showed no difference between the two treatments . 48 (13%) of the 377 children in the chloramphenicol alone group died, and 3 (0.8%) were changed to different treatment . 62 (17%) of the 371 children in the chloramphenicol-plus-penicillin group died, and 6 (1.6%) were changed to different treatment . The difference in failure rates (death or withdrawal for change of treatment) was 4.8% +/- 5.2% (+/- 95% confidence limits) . In children with severe pneumonia, treatment with chloramphenicol alone is as effective as treatment with chloramphenicol plus penicillin.

Lancet, 1985 Sep 28, 2(8457), 681 - 4
Chloramphenicol alone versus chloramphenicol plus penicillin for bacterial meningitis in children; Shann F et al.; 367 children with cerebrospinal-fluid findings suggestive of bacterial meningitis were randomised to receive either chloramphenicol alone by intramuscular injection, or chloramphenicol plus penicillin by intravenous injection . Sequential analysis showed no difference in mortality between the two treatments . 48 (26%) of the 183 children in the chloramphenicol alone group died, and 49 (27%) of the 184 children in the chloramphenicol plus penicillin group died . In children with bacterial meningitis chloramphenicol alone given by intramuscular injection is as effective as chloramphenicol plus penicillin given intravenously.

Neuropharmacology, 1985 Sep, 24(9), 915 - 7
Effects of phenytoin on field bursts of rat hippocampal slices in low-calcium solutions; Snow RW et al.; Recurring bursts of population spikes, a simple model of epileptiform activity, can be produced by exposing slices of rat hippocampus to saline containing 0.2 mM {Ca2+} and 4.0 mM {Mg2+}, at which concentration chemical synaptic activity is blocked . Phenytoin at 7.3-73 microM shortened the duration of these bursts . At 73 microM the bursts were slowed and often eliminated . This model appears to be more sensitive to the action of phenytoin than the penicillin model of epileptiform bursting.

J Assoc Off Anal Chem, 1985 Sep-Oct, 68(5), 968 - 71
Multiresidue method for determination of eight neutral beta-lactam penicillins in milk by fluorescence-liquid chromatography; Munns RK et al.; A method of determining total penicillins begins with an enzymatic hydrolysis of the beta-lactam ring to form their respective penicilloate product . Acetonitrile precipitates much of the casein and protein, which are then separated from the liquid by centrifugation . The lipids are removed from the aqueous fraction with methylene chloride . Mercuric chloride is added, which reacts with the penicilloate to liberate the side chain that has a terminal aldehyde . These penilloaldehyde products are extracted with methylene chloride and are subsequently reacted with dansyl hydrazine . The resulting fluorolabeled side chains are separated by liquid chromatography on a C18 column with acetonitrile-water as mobile phase . The fluorescence is measured by the mercury line at 254 nm excitation wavelength and a 500 nm filter on the emission side . The overall average recoveries from milk spiked at 25, 50, and 100 ppb are benzyl penicillin 79.4%; phenoxymethyl penicillin 59.7%; phenethicillin 75.9%; nafcillin 87.7%; methacillin 47.5%; oxacillin 57.6%; cloxicillin 37.3%; and dicloxicillin 26.4%.

Food Chem Toxicol, 1985 Sep, 23(9), 849 - 55
Susceptibilities of drugs to nitrosation under simulated gastric conditions; Gillatt PN et al.; Drugs of differing structures and pharmacological actions have been incubated at 37 degrees C and pH 2.0 under conditions simulating those within the normal fasting stomach . The nitrite concentration (25 microM) was kept as constant as possible for 3 hr in an attempt to mimic its in vivo replenishment from the saliva . The extents of N-nitrosation varied widely, but were less than those observed by Gillatt et al . (Fd Chem . Toxic . 1984, 22, 269) using the WHO Nitrosation Assay Procedure, in which the initial nitrite concentration is 40 mM, 1600 times greater, and the pH (3.0) is close to the optimum for the N-nitrosation of secondary amines . The highest yield of N-nitroso compound was obtained with the benzathine salt of penicillin G whereas some drugs, including hydrochlorothiazide and chlorthalidone, produced no detectable N-nitroso derivative . The degree of N-nitrosation was consistently reduced when the initial nitrite concentration of 25 microM was not replenished during the incubations, underlining the importance of simulating the continuous supply of nitrite from the saliva . In all instances, the reactions of the drugs with nitrous acid were inhibited and, in most cases, completely prevented by the presence of ascorbic acid (125 mg).

Am J Obstet Gynecol, 1985 Sep 1, 153(1), 96 - 9
Effect of parenteral magnesium sulfate on penicillin-induced seizure foci in anesthetized cats; Koontz WL et al.; The use of magnesium sulfate as an anticonvulsant remains controversial . The effect of parenteral magnesium sulfate on established penicillin-induced seizure foci in anesthetized cats was studied . After induction of an epileptic focus by application of penicillin to the cerebral cortex, experimental animals were infused intravenously with magnesium sulfate, whereas control animals received normal saline solution at an equivalent rate . Experimental animals achieved a mean serum magnesium level of 11.73 +/- 2.00 mg/dl . Analysis of the electroencephalogram recordings demonstrated no significant difference in epileptic spike activity between the experimental and control groups . The critical importance of adequate controls in studies of this type is stressed.

Am J Clin Pathol, 1985 Sep, 84(3), 357 - 60
The detection of penicillin-resistant pneumococci . The compliance of hospital laboratories with recommended methods; Decker MD et al.; Isolations of pneumococci with diminished susceptibility to penicillin have been reported with increasing frequency in recent years . The first reported isolations of such organisms in Tennessee occurred in December 1982, and prompted a survey of acute-care hospitals to determine the methods being used to test pneumococcal isolates for penicillin susceptibility . All 77 acute-care hospitals in Tennessee with 100 or more beds were surveyed . Eighteen (23%) did not test the penicillin susceptibility of any pneumococcal isolates obtained from blood or cerebrospinal fluid . Thirty-eight hospitals (49%) tested some or all such isolates, but did not perform the tests in accord with established standards; 21 (27%) properly tested all such isolates . There was no correlation between the proper testing of pneumococcal isolates for penicillin susceptibility and the mode of governance, numbers of beds, or medical school affiliations of the respondent hospitals . It is recommended that appropriate pneumococcal isolates be tested for penicillin susceptibility . Such testing is most reliably performed by the disk diffusion method, using a 1-microgram oxacillin disk.

Proc Natl Acad Sci U S A, 1985 Sep, 82(17), 5632 - 5
Penicillin binding proteins: role in initiation of murein synthesis in Escherichia coli; de la Rosa EJ et al.; The consequences of the specific inhibition of penicillin binding proteins (Pbps) by beta-lactam antibiotics immediately before resumption of active growth in Escherichia coli suggest that inhibition of murein biosynthesis does not prevent the earlier steps of the initiation of cell growth in mass . The activity of Pbp 2 is apparently critical for the initiation of murein biosynthesis . Provided that Pbp 2 remains active, the other Pbps (1a, 1b, 3, 4, 5, and 6) can be inhibited without any noticeable effect on the initial rate of incorporation of new precursors into macromolecular peptidoglycan . These precursors are, in addition, inserted with a high degree of cross-linkage.

Pediatrie, 1985 Sep, 40(6), 475 - 80
{Fulminating pneumococcal septicemia in children}; Floret D et al.; Three cases of fulminating pneumococcal septicemia are reported in children aged respectively 3 months, 21 months and 6 years 1 month . The third patient only have been previously splenectomized for traumatic rupture of the spleen . This patient recovered when the two others with an expected normal spleen died quickly . The fulminating pneumococcal septicemia is characterized by the association of severe infection state, collapse and hemorrhagic syndrome with often gastric bleeding . Fatal outcome is observed in 50 to 70% of cases . Most cases occur in asplenic patients that can be explained by the role of the spleen in the infectious defense . This can be prevented by vaccination or penicillin but failure has been observed with both methods . Normal spleen, as observed in two of our patients seems to be rare . Functional hyposplenism might explain such facts.

Anal Biochem, 1985 Sep, 149(2), 466 - 70
Precipitation of phenyl and phenoxypenicillin from solutions using ammonium sulfate; Luengo JM; An easy, rapid, and available method for separating 6-aminopenicillanic acid (6-APA), benzylpenicillin (penicillin G), and other related molecules from aqueous solutions or complex industrial broths is described . A high concentration of ammonium sulphate induces partially or totally the precipitation of the penicillin present in the solutions, while 6-APA, phenylacetic, and phenoxyacetic acid always remain in the supernatant . The filtration through No . 4 Pyrex glass-fiber filter or Whatman 3MM paper permits the separation of the compounds present in the supernatant from the other ones precipitated . The precipitated product was identified, in all cases, as ammonium penicillin . This method is described here for the first time.

Neurosci Lett, 1985 Aug 30, 59(2), 203 - 8
Intracortical inhibitory mechanisms are preserved in feline generalized penicillin epilepsy; Giaretta D et al.; Intracortical inhibition elicited by direct cortical stimulation or by stimulation of the cerebral peduncle, the latter inducing recurrent inhibition of cortical neurons, is not significantly affected by intramuscular injection of penicillin sufficient for inducing the syndrome of feline generalized penicillin epilepsy characterized by generalized spike and wave (SW) discharges in the EEG . This raises to four the number of paradigms of presumably postsynaptic inhibition resistant to penicillin concentrations sufficient to produce generalized SW discharges, a form of epileptic discharge which thus cannot be attributed to blockage of the forms of intracortical postsynaptic inhibition so far tested.

J Am Vet Med Assoc, 1985 Aug 15, 187(4), 405 - 7
Efficacy of ipronidazole against trichomoniasis in beef bulls; Skirrow S et al.; Preputial smegma samples from 195 beef bulls were collected repeatedly and cultured for Tritrichomonas foetus . Seventy-five (38.5%) of these bulls were positive for trichomonads on at least 1 culture . Sensitivity of the culture procedure (number of positive cultures/number of total cultures from known-positive bulls) was 81.6% . Storage of preputial smegma in lactated Ringer's solution at 5 C for 24 hours resulted in a 14% loss of sensitivity . Seventy-three of the 75 infected bulls were available for treatment and were alloted randomly to 2 groups . Bulls in both groups were treated with procaine penicillin (7,000 IU/kg, IM) for 2 days before ipronidazole treatment . Thirty grams of ipronidazole powder was dissolved in 60 ml of sterile water, and was given IM to group 1 bulls . Group 2 bulls were given a similar 30-g ipronidazole solution IM on day 1, and were given 15 g of ipronidazole dissolved in 30 ml of sterile water on days 2 and 3 . Efficacy of treatment (ie, negative cultures of preputial smegma for trichomonads for 6 consecutive weeks after treatment) was 92.8% for the 42 bulls treated once and 100% for the 31 bulls treated 3 times.

Eur J Biochem, 1985 Aug 15, 151(1), 111 - 21
Amino acid substitutions that reduce the affinity of penicillin-binding protein 3 of Escherichia coli for cephalexin; Hedge PJ et al.; The location of amino acid substitutions that allow an enzyme to discriminate between the binding of its normal substrate and a substrate analogue may be used to identify regions of the polypeptide that fold to form the substrate binding site . We have isolated a large number of cephalexin-resistant mutants of Escherichia coli in which the resistance is due to the production of altered forms of penicillin-binding protein 3 that have reduced affinity for the antibiotic . Using three mutagens, and a variety of selection procedures, we obtained only five classes of mutants which could be distinguished by their patterns of cross-resistance to other beta-lactam antibiotics . The three classes of mutants that showed the highest levels of resistance to cephalexin were cross-resistant to several other cephalosporins but not to penicillins or to the monobactam, aztreonam . The penicillin-binding protein 3 gene from 46 independent mutants was cloned and sequenced . Each member of the five classes of cephalexin-resistant mutants had the same amino acid substitution in penicillin-binding protein 3 . The mutants that showed the highest levels of resistance to cephalexin had alterations of either Thr-308 to Pro, Val-344 to Gly, or Asn-361 to Ser . The Thr-308 to Pro substitution had occurred within the beta-lactam-binding site since the adjacent residue (Ser-307) has been shown to be acylated by benzylpenicillin . The Asn-361 to Ser change occurred in a region that showed substantial similarity to regions in both penicillin-binding protein 1A and 1B and may also define a residue that is located within the beta-lactam-binding site in the three-dimensional structure of the enzyme.

Brain Res, 1985 Aug 12, 340(2), 390 - 6
Differences between strychnine and penicillin epileptogenesis suggest a laminar organization of neocortical inhibition; Ebersole JS et al.; Transient foci of epileptiform alteration in neuronal population activity were induced by microinjection of strychnine sulfate into different layers of cat striate cortex . Potentials evoked by visual field-specific photic stimulation were recorded from microelectrodes at the injection site and in adjacent laminae . Epileptogenesis, characterized by an enhancement of the normal primary response followed by the development of a large late potential, occurred only with strychnine injections into superficial pyramidal layers 2 and 3 . By contrast, stellate layer 4 has been shown to be most susceptible to epileptogenic effects of penicillin and bicuculline . Since disinhibitory convulsants should be most effective where their actions antagonize the prevalent type of inhibition, these findings suggest that there may be a laminar segregation of neocortical inhibition, possibly glycine-mediated in layers 2-3 and probably gamma aminobutyric acid (GABA)-mediated in layer 4.

Ann Allergy, 1985 Aug, 55(2), 157 - 61
Routine use of skin testing for immediate penicillin allergy to 6,764 patients in an outpatient clinic; Sarti W; A population of 6,764 individuals who had received a penicillin prescription at an outpatient clinic was tested with MDM (minor determinant mixture) and PG (penicillin G), whether or not a previous history of allergy to penicillin had been reported . Ninety-six (1.4%) patients showed positive skin tests . The 6,668 patients with negative tests were treated with penicillin and none showed any immediate allergic reaction . Because of the large size of the sample it was possible to calculate that the probability of risk of systemic reactions among patients with negative tests who were immediately treated with penicillin was 1.5/million . The method used is simple to carry out and has proved to be safe and reliable for the identification or exclusion of immediate allergic reaction to penicillin.

J Pediatr, 1985 Aug, 107(2), 201 - 6
Acute splenic sequestration in homozygous sickle cell disease: natural history and management; Emond AM et al.; Of a cohort of 308 children with homozygous sickle cell disease diagnosed at birth, 89 experienced 132 clinically significant attacks of acute splenic sequestration (ASS) over a 10-year period . The age at first attack ranged from 3 months to 6 years . Survival curve analysis of the interval until first attack indicated a cumulative probability of 0.225 by 2 years, and 0.265 by 3 years, and 0.297 by 5 years of age . Thirteen events were fatal, 11 during the first attack, and all before transfusion could be instituted . Recurrences occurred in 49% of survivors of the first attacks, and there were diminishing intervals between subsequent events . Respiratory symptoms were associated with 52 of 132 events, but bacterial isolates on blood culture were less frequent, and ASS was not prevented by pneumococcal vaccine or penicillin prophylaxis . A high fetal hemoglobin level protected against attacks of ASS . A parental education program aimed at early diagnosis of ASS was followed by an increase in the incidence rate for ASS from a mean of 4.6 per 100 patient-years to 11.3 per 100 patient-years, probably reflecting increased awareness of the complication . During the same periods, the fatality rate fell from 29.4 per 100 events to 3.1 per 100 events . The improvement in outcome is likely to have resulted from improvement in medical management and earlier detection of ASS.

Exp Neurol, 1985 Aug, 89(2), 465 - 78
Involvement of cortical, thalamic and midbrain reticular formation neurons in spike and wave discharges: extracellular study in feline generalized penicillin epilepsy; Pellegrini A et al.; Extracellular activity of single units, simultaneously recorded in cortex, thalamus, and midbrain reticular formation was investigated during feline generalized penicillin epilepsy . The firing activity of neurons recorded in the cortex was invariably and consistently enhanced in coincidence with the positive peak and the positive-negative transient of the "spike" of the spike and wave complex, and it was greatly decreased during the wave . In the nonspecific thalamic nuclei three classes of neurons were identified according to their patterns of activity during the spike and wave complex: (i) neurons behaving like cortical units, (ii) neurons with enhanced firing activity during the wave and a decreased activity during the "spike," and (iii) unmodified neurons . In the nucleus lateralis posterior neurons of the third class were not found . Most midbrain reticular neurons could be classified in the same three classes of the nonspecific thalamic nuclei; however, 11% of those units increased their activity 20 to 30 ms earlier than did the cortical units (class IV) . Investigation of the activities of all these neuronal populations immediately prior to a spike and wave discharge showed that the rhythmic cycle of excitation-inhibition commenced earlier in the cortical neurons than in any other subcortical neuron . Moreover, there were some nonspecific thalamic neurons of class II with an inhibitory phase exactly coincident with the activation of class IV midbrain reticular neurons . These data suggest (i) a leading role of cortical neurons in initiating and maintaining a spike and wave burst; (ii) the involvement of a corticothalamocortical circuit in timing the bursts, and (iii) an accessory reticulothalamic loop also involved in regulating the intraburst frequency of the spike and wave complex.

Oral Surg Oral Med Oral Pathol, 1985 Aug, 60(2), 201 - 7
Prophylactic use of penicillin V in teeth with necrotic pulps and asymptomatic periapical radiolucencies; Mata E et al.; As a result of (1) clinical experience with flare-ups occurring in teeth with necrotic pulps and asymptomatic periapical radiolucencies and (2) on apparent reduction to the incidence of such flare-ups by the administration of penicillin V at the first sign of swelling, this study on the prophylactic administration of penicillin V in similar cases was undertaken . The subjects were 100 consecutive clinic patients whose teeth had necrotic pulps and asymptomatic periapical radiolucencies . At the initial visit, all teeth were instrumented completely to the radiographic apex, with 0.5% to 2.54% sodium hypochlorite as the irrigant . Sterile, dry cotton pellets and ZOE restorations were used . Alternate patients were given 250 mg of penicillin V and an identical-appearing placebo with instructions to take two tablets every 6 hours for the first 24 hours, followed by one tablet every 6 hours until all tablets were taken . Pain and swelling were graded by the patients on five-point scales, and flare-ups were scored when either pain and/or swelling necessitated an unscheduled emergency visit . Fifteen patients developed flare-ups, with significantly more flare-ups in the placebo group (p less than 0.05) . The findings indicate that, in selected cases, prophylactic penicillin can be used to prevent flare-ups.

J Gen Microbiol, 1985 Aug, 131 ( Pt 8), 2115 - 8
Construction of a mutant of Escherichia coli that has deletions of both the penicillin-binding protein 5 and 6 genes; Broome-Smith JK; A mutant of Escherichia coli has been constructed with deletions of the genes encoding penicillin-binding protein 5 (dacA) and penicillin-binding protein 6 (dacC) . The construction of this mutant establishes that the complete loss of the two most abundant species of penicillin-binding proteins can be tolerated by E . coli . Moreover, the double deletion mutant had the same growth rate and morphology as an isogenic dacA+ dacC+ strain.

Proc Natl Acad Sci U S A, 1985 Aug, 82(15), 5107 - 11
Fusions of secreted proteins to alkaline phosphatase: an approach for studying protein secretion; Hoffman CS et al.; We have constructed a series of plasmids containing a modified form of the phoA gene of Escherichia coli K-12 that have general utility for studies of protein secretion . In these plasmids, the promoter and signal sequence-encoding region of the phoA gene have been deleted; thus, expression of the gene, giving rise to active alkaline phosphatase {orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1}, is absolutely dependent upon fusion in the correct reading frame to DNA containing a promoter, a translational start site, and a complete signal sequence-encoding region . Alkaline phosphatase, which is normally located in the periplasm of E . coli, is efficiently secreted to the periplasm when fused either to a signal sequence from another periplasmic protein, beta-lactamase (penicillin amido-beta-lactamhydrolase, EC 3.5.2.6), or to signal sequences from the outer membrane proteins LamB and OmpF . These heterologous signal sequences are processed during secretion . In the absence of a complete signal sequence, phosphatase becomes localized in the cytoplasm and is inactive . Phosphatase fusion proteins lacking up to 13 amino-terminal amino acids beyond the signal sequence show the same specific activity as that of the wild-type enzyme . However, a significant decrease in activity is seen when 39 or more amino-terminal amino acids are deleted . Addition of approximately 150 amino acids from the enzyme beta-lactamase to the amino terminus of alkaline phosphatase has little effect on the specific activity of the enzyme . The ability to change the amino terminus of phosphatase without altering its activity makes the enzyme particularly useful for construction of protein fusions . The fact that phosphatase is designed for transport across the cytoplasmic membrane makes it an ideal tool for study of protein secretion.

Antimicrob Agents Chemother, 1985 Aug, 28(2), 347 - 8
Penetration of oral doxycycline into the cerebrospinal fluid of patients with latent or neurosyphilis; Yim CW et al.; Five patients with laboratory evidence of latent or neurosyphilis were treated orally with doxycycline (200 mg) twice a day for 21 days . After the seventh dose, the mean level of doxycycline in serum was 5.8 micrograms/ml, with a mean drug level in cerebrospinal fluid of 1.3 micrograms/ml . The mean penetration into cerebrospinal fluid was 26% . These preliminary findings suggest that doxycycline, administered orally at a dose of 200 mg twice a day, reaches a sufficient concentration in cerebrospinal fluid to be worthy of further evaluation as an alternative regimen to penicillin therapy for latent or neurosyphilis.

Antimicrob Agents Chemother, 1985 Aug, 28(2), 274 - 81
In vitro interaction of aminoglycosides with beta-lactam penicillins; Wallace SM et al.; The aminoglycosides are used clinically in combination with beta-lactam antibiotics . The combined use, however, produces an interaction and inactivation of the antibiotics . A study was designed to investigate the kinetics of the interaction in vitro . Four concentrations of aminoglycosides (5 to 20 micrograms of gentamicin and tobramycin per ml) and penicillins (100 to 600 micrograms of carbenicillin and ticarcillin per ml) were incubated in plasma (3 days, 37 degrees C) . Samples taken at 12-h intervals were analyzed for both aminoglycosides (radioimmunoassay) and penicillin (high-pressure liquid chromatography) . In controls, degradation of all four antibiotics were by first-order reactions . In incubation mixtures of two antibiotics, the rate of loss of the aminoglycosides was greater than that in the controls, whereas the rate of loss of penicillins was not significantly increased . The loss of penicillins in incubation mixtures still appeared to be by first-order reactions . However, semilogarithmic plots of aminoglycoside concentrations were curvilinear, suggesting a second-order reaction . Aminoglycoside concentrations in incubation mixtures were fitted by computer to a model incorporating a second-order interaction between aminoglycosides and penicillins and the first-order loss of penicillin from the mixture . The interaction rate constant averaged 2.2 X 10(-4) (micrograms/ml h)-1 for interaction of both carbenicillin and ticarcillin with gentamicin and 1.6 X 10(-4) (micrograms/ml h)-1 for interaction of the penicillins with tobramycin . The effect of the interaction in vivo was examined by computer simulation using the kinetic parameters determined in vitro.

Pharmacol Res Commun, 1985 Aug, 17(8), 773 - 86
An investigation on the mechanism of anticonvulsant action of ketamine and phencyclidine on convulsions due to cortical application of penicillin in rabbits; Sagratella S et al.; The intracortical injection of 500 units of penicillin in rabbits elicited intermittent bilateral spikes or spike-wave complexes followed by generalization of the epileptiform activity characterized by repeated ictal high-voltage, high frequency spikes paralleled by generalized convulsions . Administration of phencyclidine (PCP) (0.7-1.0 mg/Kg i.v.), ketamine (KT) (20-40 mg/Kg i.v.), pentobarbital (PB) (10 mg/Kg i.v.) and diazepam (3 mg/Kg i.v.) inhibited the generalization of the epileptiform activity induced by penicillin (500 units) counteracting the EEG and motor patterns of the ictal events, while did not influence the interictal spike-and-wave complexes . Physostigmine (0.1 mg/Kg i.v.), clonidine (0.1 mg/Kg i.v.), haloperidol (1 mg/Kg i.v.) and naloxone (10 mg/Kg i.v.) did not affect the inhibitory influence of PCP on epileptiform activity due to cortical application of penicillin . Thus, the mechanism of this anticonvulsant action of PCP seems not to depend on the neurotransmitter system related to the reported drugs . The mechanism of action of PCP and KT is discussed in connexion with the similarities of the effects of this drugs in respect to sigma opiate agonists and pentobarbital.

Am J Obstet Gynecol, 1985 Jul 15, 152(6 Pt 1), 635 - 41
High failure rates in outpatient treatment of salpingitis with either tetracycline alone or penicillin/ampicillin combination; Thompson SE et al.; Eight hundred twenty-five ambulatory women with a clinical diagnosis of salpingitis were randomized to a 10-day course of either penicillin/ampicillin or tetracycline . Forty-four percent of women had gonococcal salpingitis and 56% nongonococcal salpingitis . Overall, both regimens cured equal proportions of women: At 30 days, 81% were cured by penicillin/ampicillin and 82% by tetracycline . However, the proportion of women with gonococcal salpingitis cured by 30 days was significantly greater than that of women with nongonococcal salpingitis . By 30 days, 14% of women with gonococcal salpingitis and 21% of women with nongonococcal salpingitis were not cured by either regimen . These data suggest that both regimens were only marginally acceptable for women with gonococcal salpingitis and that neither regimen was acceptable for nongonococcal salpingitis.

Biochemistry, 1985 Jul 2, 24(14), 3448 - 53
Purification and sequencing of the active site tryptic peptide from penicillin-binding protein 1b of Escherichia coli; Nicholas RA et al.; This paper reports the sequence of the active site peptide of penicillin-binding protein 1b from Escherichia coli . Purified penicillin-binding protein 1b was labeled with {14C}penicillin G, digested with trypsin, and partially purified by gel filtration . Upon further purification by high-pressure liquid chromatography, two radioactive peaks were observed, and the major peak, representing over 75% of the applied radioactivity, was submitted to amino acid analysis and sequencing . The sequence Ser-Ile-Gly-Ser-Leu-Ala-Lys was obtained . The active site nucleophile was identified by digesting the purified peptide with aminopeptidase M and separating the radioactive products on high-pressure liquid chromatography . Amino acid analysis confirmed that the serine residue in the middle of the sequence was covalently bonded to the {14C}penicilloyl moiety . A comparison of this sequence to active site sequences of other penicillin-binding proteins and beta-lactamases is presented.

Pathology, 1985 Jul, 17(3), 514 - 5
Gentamicin nephropathy in a neonate; Chan KW et al.; The clinical and autopsy findings in a premature baby who died of acute renal failure after therapy with gentamicin (5 mg/kg/day) and penicillin are presented . The serum gentamicin concentration had reached toxic levels when anuria developed . Numerous periodic acid Schiff (PAS) positive, diastase resistant cytoplasmic inclusion bodies which appeared as myelin figures in cytosegresomes under the electron microscope were identified in the proximal convoluted tubules . The pathological changes induced by gentamicin in the human neonatal kidneys have not been previously reported.

Neurochem Res, 1985 Jul, 10(7), 879 - 85
Effect of various drugs producing convulsive seizures on rat brain glycerolipid metabolism; Corazzi L et al.; Convulsive seizures were elicited in the rat by the injection of several different drugs (pyridoxal phosphate, bicuculline, penicillin and ouabain) . Glycerolipid metabolism was studied after the intraventricular injection of {2-3H}glycerol, which was incorporated into rat brain glycerides . The percentage of total lipid label found in each lipid class (phosphatidylethanolamine, PE; phosphatidylcholine, PC; phosphatidylserine, PS; phosphatidic acid, PA; phosphatidylinositol, PI; diacylglycerol (+ monoacylglycerol), DG and triacylglycerol, TG) depended on the time elapsed from the injection of the labeled precursor . The percent of total lipid radioactivity as PE and PC increased with time (3-60 min), whereas the opposite was true for the radioactivity of DG and PA . The radioactivity of other lipid classes did not appreciably vary between 3 and 60 min from the injection of the labeled glycerol . The intraventricular administration of pyridoxal phosphate together with labeled glycerol decreased the percent of lipid radioactivity as PE and increased that as DG . This 'lipid effect' was detected also after the administration of other convulsants, such as ouabain and penicillin . The intraperitoneal administration of bicuculline affected lipid metabolism in cerebellum.

J Assoc Off Anal Chem, 1985 Jul-Aug, 68(4), 665 - 71
Liquid chromatographic monitoring of the depletion of carbadox and its metabolite desoxycarbadox in swine tissues; MacIntosh AI et al.; A liquid chromatographic method was used to monitor a depletion study of carbadox (and its most important metabolite, desoxycarbadox) in young pigs fed carbadox-treated rations for 1 week . Carbadox was found in blood (20 ppb), blood serum (26 ppb), and muscle tissue 24 h after withdrawal from treated ration; residues were reduced to a trace (less than 2 ppb) in 48 h, and eliminated by 72 h . Desoxycarbadox, although not detected in blood, was found in muscle (17 ppb) 24 h after withdrawal; it was reduced to 9 ppb at 48 h and to a trace by 72 h . Although no carbadox was detected in liver 24 h after withdrawal, appreciable desoxycarbadox (125 ppb) was found in liver 24 h after withdrawal; it was reduced to 17 ppb at 48 h and to a trace by 72 h . Whereas only a trace of carbadox was found in kidney 24 h after withdrawal, 186 ppb desoxycarbadox was found in kidney at 24 h, 34 ppb at 48 h, and a trace at 72 h . No metabolite of carbadox other than desoxycarbadox was found in extracts of swine tissues during this medicated feed trial, and no metabolite was found in blood extracts by using the established methodology . The effect of tissue storage (aging) at -20 degrees C on levels of the drug and its metabolite was a modest alteration of residue levels . The inadvertent use of feed adulterated with furazolidone and initially medicated with chlortetracycline, sulfamethazine, and penicillin G, did not affect the uptake of carbadox in this depletion study or interfere with the analytical methodology.

Postgrad Med J, 1985 Jul, 61(717), 595 - 8
Serum creatine kinase after intramuscular injections; Konikoff F et al.; Serum creatine kinase (CK) activity was measured after intramuscular injections in 44 patients hospitalized for non-cardiac reasons . The drugs injected were: diazepam, dipyrone, metoclopramide, meperidine, pentazocine and procaine penicillin . Only 3 out of 44 patients (7%) demonstrated significant elevation of CK levels following the intramuscular injections . In these 3 patients the elevation was mainly due to a rise of the MM-isoenzyme fraction with MB levels increased in one patient . These findings do not justify the common clinical notion of regarding intramuscular injections as a frequent cause of serum CK elevation . It is concluded that high CK serum values in a patient with chest pain should always be considered with utmost suspicion, disregarding the possible effects of a previous intramuscular injection.

Anesthesiology, 1985 Jul, 63(1), 29 - 40
Anticonvulsant actions of enflurane on epilepsy models in cats; Oshima E et al.; The effects of enflurane on three epilepsy models were studied in cats . The models used were seizures in amygdaloid kindled cats and those induced by bicuculline and penicillin . The authors found that not only a subconvulsive (1.5%) but a convulsive (3.5%) dose of enflurane suppressed the seizures in all models . There was no sign of activation by enflurane of the epileptic focal activities in the dose range studied: the penicillin-induced cortical seizure was suppressed completely, and the threshold dose of bicuculline required to induce seizure in normal cats and the threshold current required to induce seizure in amygdaloid-kindled cats were both increased by both the subconvulsive and convulsive dose of enflurane . The pattern of suppression was, however, dissimilar in each model . It was dose dependent in the case of penicillin-induced seizure, while it was biphasic in several aspects in the seizures of bicuculline-induced and amygdaloid kindled models . For the subconvulsive dose the degrees of increase in the thresholds required to induce seizure in bicuculline-induced and amygdaloid-kindled models were both greater than those for the convulsive dose of enflurane . In spite of such a definite suppression of the excitability of focus, the propagation of amygdaloid after-discharge was facilitated by the convulsive dose . The intensity of convulsion induced by suprathreshold dose of bicuculline was depressed in a dose-related manner . The intensity of the convulsion in the amygdaloid-kindled model was also suppressed when it was estimated by visual inspection of behavior and the degree of activation of the brain electrical activities . The authors conclude that there is little, if any, exacerbation by enflurane of preexisting epileptic foci, the only exception possibly being the case of certain myoclonic type epilepsies such as progressive myoclonic epilepsy and photosensitive epilepsy . This anesthetic probably can be used with a considerable degree of safety for epileptic patients.

Physiologie, 1985 Jul-Sep, 22(3), 175 - 80
On the relation between the formation of antihapten and anti-carrier protein antibodies in the immune response induced by conjugates of various haptens with homologous serum proteins; Cirstea M et al.; Rabbits inoculated with conjugates of homologous serum with ortho-aminophenol (OAP), para-aminophenol (PAP), 3-hydroxy-sulfanilamide (3-HS), DOPA and alpha-methyldopa (alpha MD), 5-aminosalicylic acid (5-ASA) and 3-hydroxy-para-aminobenzoic acid (3-HPABA) give rise to both hapten specific and anti-carrier protein antibodies . By contrast, the conjugates of homologous serum with penicilloyl (P) hapten induced only antihapten antibodies . The conclusion is, therefore, drawn that the formation of anti-carrier antibodies upon inoculation with conjugates of various haptens appears to be dependent on the nature of hapten in the conjugate . The discrepancy between the behaviour of P conjugates, on the one hand, and the DOPA and alpha MD conjugates, on the other hand, is in agreement with the observation from the clinical immunology, which has signaled a high incidence of antibodies with autoantibody character in patients taking DOPA and alpha MD, but rarely, if ever, such antibodies have been found in patients treated with penicillin.

Farmakol Toksikol, 1985 Jul-Aug, 48(4), 28 - 31
{Antiepileptic action of met-enkephalin and the rapid development of tolerance to its epileptogenic action}; Gusel' VA et al.; It has been shown in chronic experiments on rabbits with electrochemoelectrodes implanted into the dorsal hippocamp that the first administration of met-enkephalin in a dose of 60 to the hippocamp induced the development of an epileptogenic focus (EF) or potentiated the action of the penicillin-induced EF . The second administration of met-enkephalin in the same dose to the hippocamp (interval in a standard scheme of experiments 5 days) did not lead to the production of the EF, which attests to rapid development of tolerance to the epileptizing action of the peptide, with this tolerance being preserved for 20 subsequent days of observation over the animals . After tolerance developed, administration of 60 micrograms met-enkephalin 5 to 10 min before penicillin produced an antiepileptic action, thereby preventing the development of the EF . Met-enkephalin (0.1 and 1 microgram) did not epileptize hippocampal neurons but lowered the action of the penicillin-induced EF after the development of tolerance to the epileptizing action of a large dose of the peptide . The animals did not develop tolerance to the antiepileptic effect of met-enkephalin . The data obtained confirm the hypothesis that different opiate receptors are responsible for the epileptizing (delta-receptors) and antiepileptic (mu-receptors) action of the enkephalin . The effect of small doses of met-enkephalin appears to mirror to a greater degree the involvement of endogenous enkephalins in the epileptogenesis.

Sex Transm Dis, 1985 Jul-Sep, 12(3), 145 - 9
Diagnostic considerations in intra-amniotic syphilis; Glover DD et al.; Amniotic fluid is rarely used in the evaluation of syphilis during pregnancy but was available from a woman with positive serologic tests in the 30th week of gestation . Nonmotile intra-amniotic spirochetes were seen by dark-field microscopy 20 hr after treatment with benzathine penicillin G . The identity of the organism in amniotic fluid was confirmed by immunofluorescent staining . Less than 0.5 units/ml of penicillin was present in the amniotic fluid at this time . The amniotic fluid was positive in the Venereal Disease Research Laboratory (VDRL; Atlanta, GA) test, and the concentration of IgM was elevated as was the ratio of lecithin to sphyngomyelin . Phosphatidyl inositol and phosphatidyl glycerol were also present in the amniotic fluid . After treatment the lecithin-sphyngomyelin ratio declined; phosphatidyl glycerol disappeared, whereas phosphatidyl inositol was still present . Despite evidence of intrauterine growth retardation at 30 weeks, the infant born at 37 weeks was of normal weight and length; however, the head circumference was below the tenth percentile . These studies suggest that analysis of amniotic fluid may provide new insights into the biology of syphilis in pregnancy, but does not constitute a recommendation for routine examination of the amniotic fluid in mothers with reactive serologic tests for syphilis.

J Am Dent Assoc, 1985 Jul, 111(1), 49 - 54
Prevention of osteoradionecrosis: a randomized prospective clinical trial of hyperbaric oxygen versus penicillin; Marx RE et al.; A prospective randomized trial comparing hyperbaric oxygen and systemic antibiotics in the prevention of osteoradionecrosis was presented . The results indicated, in a high-risk population who required tooth removal in irradiated mandibles, that up-front hyperbaric oxygen produced an incidence of osteoradionecrosis of 5.4% as compared with the antibiotic group of 29.9% (P = .005) . Hyperbaric oxygen should be considered a prophylactic measure when post-irradiation dental care involving trauma to tissue is necessary.

Pediatr Res, 1985 Jul, 19(7), 720 - 7
Morphologic and metabolic development of human fetal epiphyseal chondrocytes in primary culture; Carrascosa A et al.; Primary chondrocyte culture was carried out after enzymatic digestion of femoral and tibial epiphyseal cartilage of human fetuses, collected with informed parental consent within 12 h postmortem . Chondrocytes were cultured in HAM F-12 medium with penicillin and 15% serum . Three types of serum were used: human placental cord serum (HPS), fetal calf serum, and human male adult serum . Chondrocytes cultured with HPS grew as monolayers, formed abundant colony groups with a highly metachromatic pericellular matrix, and floating round cells were observed in the culture medium . By the 10th day of culture the great majority of proteoglycans present in the culture medium were found as aggregates . Chondrocytes cultured with fetal calf serum or human male adult serum grew as monolayers, were polygonal in shape, and the pericellular matrix was far less developed than in HPS cultures . By the confluent phase of growth, only approximately a third of the proteoglycans present in the culture medium were found as aggregates . Chondrocytes cultured with HPS proliferated significantly more rapidly than those cultured with fetal calf serum or human male adult serum . The results suggest that certain, as yet unidentified, factors are present in sufficient amount in HPS to allow chondrocytes in culture to retain phenotypic morphological and biochemical characteristics . HPS also facilitates growth of human fetal epiphyseal chondrocytes in culture . Primary human fetal epiphyseal chondrocyte culture could be a suitable experimental tool for the in vitro study of biochemical characteristics of cartilage and factors involved in fetal cartilage metabolism.

Jpn J Antibiot, 1985 Jun, 38(6), 1509 - 15
{A clinical study on the penetration of aspoxicillin into tissue and wound exudates in breast cancer}; Tsuburaya H et al.; Penetration of aspoxicillin (ASPC), a new semisynthetic penicillin of broad spectrum, into normal and cancer tissue and wound exudate were examined in breast cancer . ASPC was administered by single injection of 1 or 2 g . The concentration of ASPC in the resected skin, normal mammary gland and cancer were similar to their serum levels, when ASPC was administered before radical mastectomy . ASPC concentration in the wound exudate which was collected from the inserted drains into the resected area reached the maximum at 3 approximately 4 hours after the injection at the levels of 19.4 micrograms/ml (1 g) and 35.1 micrograms/ml (2 g) . The level decreased gradually by maintained still high at 3.7 micrograms/ml (1 g) and 11.4 micrograms/ml (2 g) even 8 hours after the injection . From these results it may be expected that ASPC is a useful penicillin in the breast surgery.

Trop Med Parasitol, 1985 Jun, 36(2), 63 - 71
Studies on a focus of yaws in Ubangi, Zaire; Ziefer A et al.; Yaws (buba, Frambosie, pian), a non-venereal treponematosis of skin and bones is a tropical disease that affects primarily children . Eradication programs launched between 1950 und 1970 reduced the incidence substantially; resurgences, however, have been reported from several countries . We have studied a geographically isolated focus of yaws in the Ubangi area of northwestern Zaire . In survey I, in 1981, of the 4.407 participants from 11 villages, 348 (7.9%) had active lesions of yaws . All patients and their contacts were treated immediately with benzathine penicillin G . In survey II, in 1982, in 6 of the previously studied villages, of 5,390 participants, 136 (2.5%) had active lesions of yaws . In 1981, the predominance of primary lesions (86%) and high numbers of patients in all age groups, with the highest prevalence (23.4%) in children 10-14 years of age, suggest that yaws recently recurred at this focus . In 1982, only 25.7% of the lesions were primary and the highest prevalence (6.5%) had shifted to the younger age group of 5-10 years-old . In survey I more males (63%) were infected in the age group 0-24 years, and more females (89%) in those over 40 years . In survey II, more males (61.3%) were infected in the age group 0-14 years, and only females (100%) in the age groups 25 years and older . Seventy-one percent (1981) and 86% (1982) of the initial lesions were on the lower limbs . Participation of the population in survey I was 41.7% and was greatest (62%) in the locality where there was a newly established dispensary . In survey II, participation rose to 73.8% . Areas adjacent to the focus of yaws with longstanding dispensaries were free of yaws.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuropharmacology, 1985 Jun, 24(6), 571 - 5
Epileptogenic action of penicillin derivatives: structure-activity relationship; Esplin B et al.; In the hippocampal slice preparation, perfusion with benzyl penicillin evokes multiple population spikes and spontaneous discharges . Doses of 0.25 to 2 mM of the drug produced this effect within 20-40 min . Cleavage products and analogues of benzyl penicillin, penicilloic acid, 6-aminopenicillanic acid, cephalexin, thioproline and penicillamine, were devoid of such action . It is concluded that the structural requirements for epileptogenic action of penicillin include not only the beta-lactam ring and side chain substitution on C-6, but also the thiazolidine ring.

Am J Hosp Pharm, 1985 Jun, 42(6), 1358 - 62
Evaluation of an extension set for intermittent intravenous drug delivery to infants; Leff RD et al.; An intravenous administration set designed for delivery of drug doses to pediatric patients was tested in vitro for the effect of fluid density and flow rate on drug delivery, and delivery of drug by this extension set was compared in vivo with delivery by other methods . Gentamicin (as the sulfate salt) and penicillin G potassium were used to represent low-density and high-density drugs, respectively; a 1-mL solution of each drug, labeled with carbon 14, was tested with each of two primary infusion solutions: 0.45% sodium chloride injection and 10% dextrose injection . The drug dose was injected via a port into a piston-containing chamber from which an equivalent amount of the primary fluid was displaced . Serial samples collected from the end of the filter-containing extension set were analyzed for drug concentration using a liquid scintillation technique . In 12 infants receiving i.v . gentamicin, this delivery method was compared in a randomized crossover trial with delivery by a syringe pump and by i.v . push . Each delivery system was used on one of three consecutive days, and serum gentamicin concentrations were measured by enzyme-multiplied immunoassay . The time required for in vitro delivery of the dose was dependent on flow rate . Density of the drug solution or the primary i.v . fluid did not significantly affect drug delivery . Serum gentamicin concentrations were not significantly different for the three delivery methods, but variability of drug delivery was greatest with the pediatric extension set . This pediatric extension set provides accurate and reliable drug delivery at primary infusion flow rates slower than 10 mL/hr when the drug dosage volume is 2-3 mL or less.

Z Hautkr, 1985 Jun 1, 60(11), 908 - 12
{Non-Hodgkin's lymphoma-like pseudolymphoma in syphilis II}; Horn U; We report on a patient suffering from early secondary syphilis associated with hepatitis and generalized papular rash which clinically and histologically appeared as non-Hodgkin lymphoma of the centrocytic-centroblastic type . The benign course and the response of the papular rash to penicillin therapy as well as repeated histological examination of many plasma cells and epithelioid cells, however, revealed pseudolymphoma.

Am J Med Sci, 1985 Jun, 289(6), 236 - 9
Drugs affecting bilirubin uptake by human erythrocyte ghosts; Karp WB et al.; Drugs known to affect the red blood cell membrane and used clinically in neonates were tested for their ability to cause increased 14C-bilirubin uptake by erythrocyte ghosts . The additional uptake of bilirubin by ghosts in the presence of penicillin G, phenobarbital, furosemide and theophylline may be explained by the effect of these drugs on free bilirubin levels as measured with a horseradish peroxidase assay . In contrast, the effect of chlorpromazine in causing increased bilirubin uptake by ghosts could not be totally explained by either ghost lysis or increased free bilirubin levels, as measured by light scattering, and was due to a direct effect of chlorpromazine on the ghost membrane . Our results demonstrate that drugs may act through different mechanisms in causing increased bilirubin uptake by erythrocytes.

Am J Hematol, 1985 Jun, 19(2), 145 - 50
Positive direct antiglobulin test associated with hyperglobulinemia in acquired immunodeficiency syndrome (AIDS); Toy PT et al.; This study determined the prevalence and clinical significance of a positive direct antiglobulin test (DAT) observed in pretransfusion tests on red cells from patients with acquired immunodeficiency syndrome (AIDS) . Transfusion service records showed that prevalence of a positive DAT on red cells was 18% (10/55) in AIDS patients compared to 0.6% in general hospital patients during a 2-year period (1981-1983) . A similar rate of 18% (8/45) was observed in other hyperglobulinemic patients . Of the 10 AIDS patients whose red cells were DAT positive, four had IgG and complement, four had IgG, and two had complement alone on their red cells . The eluates were not reactive with normal red cells nor with penicillin or cephalothin-coated red cells . Clinically, no hemolysis was observed . In this series a positive DAT in AIDS patients appeared not to be associated with autoimmune hemolytic anemia . The positive DAT in AIDS patients may be due to the hyperglobulinemic state.

Am J Dis Child, 1985 Jun, 139(6), 575 - 80
Congenital syphilis revisited; Mascola L et al.; Despite decades of experience with congenital syphilis, problems still arise in case definition, diagnostic evaluation, treatment, and follow-up . We reviewed all 50 cases of early congenital syphilis reported to the State of Texas in 1982 . A large proportion of the infants were premature (39%), of low birth weight (38%), and symptomatic at birth (62%) . Because of these findings, we believe that possible cases of asymptomatic congenital syphilis in Texas may be under-reported . Laboratory and/or roentgenographic findings were important to confirm the diagnosis of congenital syphilis . Over half of the asymptomatic infants had positive results of cerebrospinal fluid VDRLs . After diagnosis, the treatment of infants with penicillin varied considerably . While all 47 living infants were treated with penicillin, 21 different regimens were used . We urge all physicians to perform complete diagnostic evaluations on suspected infants consisting of a quantitative serum test for syphilis, serum IgM levels, a cerebrospinal fluid VDRL, roentgenographs of the long bones, and dark-field microscopy where indicated . Additionally, infants and their families need appropriate follow-up after treatment.

Antibiot Med Biotekhnol, 1985 Jun, 30(6), 423 - 8
{Physiological role of vegetable oils during penicillin biosynthesis}; Tikhonova OV et al.; Addition of liquid vegetable oils to nutrient media decreased the intensity of penicillin biosynthesis . The unfavourable effect of the oils was more pronounced at the beginning of the process while they were not completely utilized . Sunflower oil is a readily assimilated source of carbon . The rate of its consumption is higher than that of whale oil or lactose . Like the majority of readily oxidized sources of carbon, sunflower oil must be a repressor of beta-galactosidase and the enzymes of penicillin biosynthesis.

J Periodontol, 1985 Jun, 56(6), 352 - 8
A clinical trial of phenoxymethyl penicillin for adjunctive treatment of juvenile periodontitis; Kunihira DM et al.; A double-blind clinical trial of oral penicillin as an adjunct to conventional treatment of localized juvenile periodontitis (JP) was conducted . Sixteen subjects with JP were paired on the basis of general similarity of disease, and within each pair the persons were assigned randomly, one to a placebo group and one to a penicillin group . Neither patients nor therapist/examiner were aware of whether placebo or penicillin was being taken . All subjects received an initial scaling and root planing of all teeth and flap surgery of all affected sites . Every 12 weeks after surgery through Week 62 of the study, root planing and oral hygiene instructions were repeated . Phenoxymethyl penicillin (250 mg qid) or placebo was started the day of surgery and each recall visit and lasted for 10 days . Clinical measurements were made at the beginning of the study and at each recall visit . In both groups there was a significant decrease in plaque scores, gingival inflammation, gingival bleeding and probeable depths for all sites and for affected sites . Similarly there was a significant increase in attachment level and radiographic bone height, and a total elimination of suppuration . The favorable changes were apparent at the first postsurgical recall (Week 26 of the study) and remained essentially the same through Week 62 . The magnitude of change in these parameters was similar to that reported by others for treatment regimes including tetracycline therapy . However, there were no differences in any parameters between the placebo and penicillin groups . Half of the subjects (4 in each group) were continued in the study for another 9 months (Week 98).(ABSTRACT TRUNCATED AT 250 WORDS)

J Pharmacol Methods, 1985 Jun, 13(3), 275 - 80
Application of Azure C for the extractive spectrophotometric determination of microgram amounts of penicillin; Gowda AT et al.; A simple, accurate, and rapid method for the quantitative determination of penicillin is proposed . The method is based on the formation of a blue penicillin-Azure-C ion-pair that can be extracted into chloroform in phosphate-citric acid buffer . The molar absorptivities for sodium penicillin G and potassium penicillin V at 635 nm were 5.46 X 10(3) and 2.19 X 10(4) l/mol/cm, respectively . Beer's law was valid over the concentration range of 4-80 micrograms/ml for sodium penicillin G and 3-55 micrograms/ml for potassium penicillin v . Maximum absorbance was obtained almost instantaneously and was stable for several days . The method was successfully applied to pharmaceutical preparations.

Arch Neurol, 1985 Jun, 42(6), 606 - 13
Neurosyphilis; Simon RP; Syphilis and its consequent central nervous system sequelae remain clinical problems, especially when presenting in the unfamiliar acute meningeal forms of syphilitic meningitis and meningovascular syphilis . The diagnosis of neurosyphilis of all types depends on evaluation of spinal fluid reactivity as evidenced by pleocytosis and increased protein content with reactive serology . The cerebrospinal fluid is always abnormal in active disease, and only active disease responds to treatment . Penicillin remains the drug of choice for all forms of neurosyphilis, but disease progression has been frequently reported following the use of penicillin G benzathine . Documentation of cerebrospinal fluid resolution over the months following penicillin therapy is required to confirm curative treatment.

J Biol Chem, 1985 May 25, 260(10), 6394 - 7
Purification and sequencing of the active site tryptic peptide from penicillin-binding protein 5 from the dacA mutant strain of Escherichia coli (TMRL 1222); Nicholas RA et al.; The localization of the active site of penicillin-binding protein 5 from the dacA mutant of Escherichia coli strain TMRL 1222 has been determined . The protein was purified to homogeneity and labeled with {14C} penicillin G . The labeled protein was digested with trypsin, and the active site tryptic peptide was purified by a combination of gel filtration and high-pressure liquid chromatography . Sequencing of the purified {14C}penicilloyl peptide yielded the sequence Arg-Asp-Pro-Ala-Ser-Leu-Thr-Lys, which corresponds to residues 40-47 of the gene sequence (Broome-Smith, J., Edelman, A., and Spratt, B . G . (1983) in The Target of Penicillin (Hakenbeck, R., Holtje, J.-V., and Labischinski, H., eds) pp . 403-408, Walter de Gruyter, Berlin) . The catalytic amino acid residue that forms a covalent bond with penicillin was identified by treating the purified {14C}penicilloyl peptide with a mixture of proteases and then separating the radioactive products using high-pressure liquid chromatography . Analysis of the radioactive peaks by amino acid analysis confirmed that it is the serine residue that reacts with the beta-lactam ring of penicillin.

Aust Paediatr J, 1985 May, 21(2), 129 - 30
Pulmonary actinomyces in a child; Masters B et al.; Pulmonary actinomycosis is rare in Australian children . A patient with the condition is described in whom a diagnosis was made by open lung biopsy . She was treated successfully with penicillin and tetracycline.

Ann Inst Pasteur Immunol, 1985 May-Jun, 136C(3), 375 - 82
Enzyme-linked immunosorbent assay for measurement of penicilloyl groups; Lapresle C et al.; An enzyme-linked immunosorbent assay for measuring penicillin groups is described . Alkaline phosphatase conjugated to penicilloyl residue was reacted with purified anti-penicilloyl antibodies coated upon polystyrene plates . The inhibition of this reaction allowed a specific determination of penicilloyl residues at the picomole level . This assay was applied to the study of the penicilloyl groups linked to human albumin and to the measurement of some of these groups after enzymatic degradation or physical modifications of the albumin molecule.

Neurosci Behav Physiol, 1985 May-Jun, 15(3), 207 - 13
Changes in neocortical function in response to the direct action of optical radiation; Velling VA et al.; The action of optical radiation on neocortical bioelectrical activity and on a penicillin-induced epileptic focus was investigated . The direct action of ultraviolet (UV) radiation with wavelengths 280, 310, and 365 nm was shown to increase the amplitude of the spontaneous EEG and to potentiate epileptiform activity, whereas the action of subthreshold radiation with wavelengths of 580 and 630 nm caused a reduction of EEG amplitude and inhibition of epileptiform activity . On the basis of the writers' own results and data in the literature it is postulated that the mechanism of action of UV radiation on neocortical electrical activity is based on changes in permeability of neuronal membranes to Na and K ions and subsequent membrane depolarization, whereas the action of visible radiation leads to thermal injury to the neurons in the irradiated zone, inducing irreversible suppression of their activity and a decrease in amplitude of the EEG.

Contact Dermatitis, 1985 May, 12(5), 263 - 9
Allergic contact dermatitis to some medicaments; Angelini G et al.; Over the years, changes have had to be made in the list of topical drugs most frequently responsible for allergic contact dermatitis . The 4 most common sensitizers in Italy in the past have been penicillin, sulfonamide, promethazine and neomycin . Now the list is headed by neomycin, benzocaine and ethylenediamine . Antihistamines and parabens are less frequently observed as sensitizers . The increasing topical use of new drugs and additives, as well as older sensitizers, produces reactions to other substances, such as non-steroidal anti-inflammatory agents, some antimycotic drugs, propylene glycol and benzoyl peroxide.

Arch Ital Biol, 1985 May, 123(2), 141 - 54
Role of the pulvinar-lateralis posterior nucleus complex (P-LP) in the experimental epilepsy of the cat; Motles E et al.; The ability of the pulvinar-lateralis posterior nucleus complex (P-LP) to evoke epileptic activity when stimulated, was studied in 20 adult cats . Twelve animals were analyzed after they recovered from the surgical procedure (chronic model) . In seven of them a cannula with electrodes was implanted in the P-LP and one twisted bipolar electrode was placed ipsilaterally in the following structures: hippocampus, superior colliculus, caudate nucleus and cerebral cortex . Through the cannula Na penicillin was injected . The electrodes allowed both to stimulate and to record the electrical activity . In the remaining five cats, the cannula was implanted in hippocampus in order to compare its sensitivity to generate epileptic activity to that of P-LP . Another group of eight cats were surgically implanted and studied in the same day (acute model) . In four of them the cannula was placed in the P-LP through the temporal pathway, to avoid crossing the hippocampus and the ventricle . In another four, penicillin was injected in the P-LP after suctioning the cerebral cortex and the hippocampus overlying the former structure . Epileptic activity could be induced in P-LP and it spread rapidly to hippocampus and after a while to the other implanted structures . This was observed both with penicillin and electrical stimulation . The sensitivity of P-LP to generate epileptic activity was lower than that of the hippocampus . In particular, it was necessary to use two to ten times more penicillin and three times the electrical current intensity in the P-LP as compared to the values needed in the hippocampus . These results are discussed in view of the controversial problem about the ability of the thalamus to generate and spread epileptic activity.

Rev Infect Dis, 1985 May-Jun, 7 Suppl 2, S278 - 83
Mass treatment campaigns against the endemic treponematoses; Willcox RR; In pre-antibiotic times, mass campaigns against the endemic treponematoses required multiple injections of arsenicals and bismuth . The essentiality of a population census, an examination of the total population, and the treatment of clinical and latent cases were all appreciated, as was the value of a multipurpose approach . It was also recognized that, in combination with the anticipated slow correction of economic circumstances and attitudes, chemotherapy was the chief weapon against disease but that this weapon, even if successful in a particular area, could not prevent later reintroduction of infection . With the introduction of single-dose penicillin therapy and the impetus of worldwide, internationally assisted mass campaigns came a dramatic reduction in incidence . However, in some areas continued surveillance by the local health services did not materialize . Thus, there has been not just a low-level continuum of disease but a resurgence, particularly in Africa, where a return to mass therapy has once again proved necessary--this time combined with multipurpose immunization.

Rev Infect Dis, 1985 May-Jun, 7 Suppl 2, S276 - 7
Yaws in Colombia; Uribe WR; By the beginning of this century, yaws was a well-known endemic disease in Colombia . Colombian authorities estimated that by early 1930 there were 70,000 active cases of yaws, most of which were located in the Pacific coastal regions . With the advent of penicillin therapy, Colombia organized an anti-yaws campaign, which began in 1950 . The campaign relied on the use of penicillin and house-to-house case finding . From 1950 to 1953 more than 111,000 persons with active cases of yaws and 125,000 of their contacts were treated with penicillin . The reported incidence of yaws declined dramatically, and by 1973 only 573 cases were reported in the endemic areas . By 1983 this number had fallen to 31 . Because of the persistence of small foci of yaws activity, the anti-yaws campaign has been reorganized to provide a firm basis for the final eradication of the disease in Colombia.

Rev Infect Dis, 1985 May-Jun, 7 Suppl 2, S273 - 5
Yaws in Suriname; Niemel PL et al.; Frambesia tropica, or yaws, is still prevalent in the urban population of some of the districts in Suriname . In 1911 a campaign against yaws, probably the first such campaign in the world involving treatment with salvarsan, was organized . It resulted in the rapid cure of all hospitalized patients . As a consequence of this success, the disease became less important to the medical authorities in the country . After introduction of penicillin (1945) for the treatment of yaws, the disease almost disappeared in Suriname . After 1970 new cases were diagnosed, and the resurgence of yaws in Suriname became apparent . The symptoms in these cases were attenuated in comparison to those described in standard handbooks . A survey of yaws in the different districts of Suriname was undertaken to determine the prevalence of the disease and its spread through the country in order to plan a new treatment campaign.

Rev Infect Dis, 1985 May-Jun, 7 Suppl 2, S254 - 9
Yaws in Papua New Guinea: extent of the problem and status of control programs; Reid MS; Yaws was a significant health problem in Papua New Guinea until the nationwide total mass treatment campaign, which took place from 1953 to 1958 . The number of cases reported annually fell to less than 300 during the 1960s . In the early 1970s outbreaks occurred in East New Britain and Bougainville but were effectively controlled . A larger outbreak in 1977-1978 on Karkar Island was more difficult to bring under control despite the clinical appearance of the cases, which were less florid than those seen in the 1950s . The latter outbreak raised questions about decreased response to penicillin, lack of ability to develop effective immunity, and increased susceptibility to yaws . Smaller outbreaks were reported in 1983 and 1984 in remote areas, but the current extent of yaws in Papua New Guinea is not fully known . Action is being taken to rectify this situation and to ensure that reports of yaws are fully investigated and that cases are properly managed.

Rev Infect Dis, 1985 May-Jun, 7 Suppl 2, S251 - 3
Yaws in Malaysia; Lo EK; In 1954, with the assistance of the World Health Organization and the United Nations Children's Fund, a campaign against yaws was initiated in Malaysia with the formation of a yaws elimination unit in the Ministry of Health . Between 1954 and 1975, the reported annual incidence of yaws fell from 140.85 to 1.25 per 100,000 population . When rates dropped to less than two per 100,000, the program was merged with the general health services . Currently when cases are reported, contacts are traced, school and village surveys are carried out, and appropriate treatment is given . The major problems facing the control program today are a loss of interest in control activities; a smaller number of health workers experienced in the diagnosis, management, and control of the disease; and a growing reluctance to treat asymptomatic contacts with penicillin for fear of anaphylactoid reactions . Despite these problems, it is not an unreasonable expectation that, with continued stimulation from the individuals responsible for infectious disease control, yaws will eventually be eliminated.

Rev Infect Dis, 1985 May-Jun, 7 Suppl 2, S239 - 41
Endemic treponematoses in the Sudan; Abu Ahmed Mohamed H; Sudan is surrounded by eight countries and has marked movement of population across its borders . At one time yaws and syphilis were important public health problems in the Sudan . Following the wide use of penicillin, both diseases were much reduced in prevalence and were no longer public health problems . However, the extensive population movement and particularly the huge influx of refugees across the border pose important potential hazards . The rapid urbanization and the social and cultural changes that followed economic development affected family ties and community behavior and resulted in a marked increase in the prevalence of sexually transmitted diseases, including syphilis . It is difficult to know the true magnitude of the problem because of the poor health information system and coverage . Improvement of the surveillance system is urgently needed, and more attention needs to be paid to treponemal infections . This entails improvement in health services and training of health personnel.

Rev Infect Dis, 1985 May-Jun, 7 Suppl 2, S233 - 6
Yaws in Ghana; Agadzi VK et al.; The final results of a three-year campaign against yaws in the Republic of Ghana, which was introduced in an attempt to reduce an unusually high prevalence, are summarized . The campaign started in January 1981 and officially ended in December 1983 . Serious economic and technical constraints slowed the progress of work after the first year and reduced the total population covered . In spite of the shortcomings, the program provided penicillin treatment to 77,818 patients with active yaws (4.04% of those examined during the campaign) as well as chemoprophylaxis for an additional 1,556,360 contacts . The campaign staff compiled detailed information on the epidemiology of yaws in Ghana . A second attack phase using simple equipment and vehicles such as motorcycles and bicycles could be implemented with greater efficiency and could reduce costs.

Rev Infect Dis, 1985 May-Jun, 7 Suppl 2, S220 - 6
The control of endemic treponematoses; Antal GM et al.; In the 1950s and 1960s, following a decision by the Second World Health Assembly in 1949, mass treatment campaigns against the endemic treponematoses were undertaken with the support of the World Health Organization and the United Nations Children's Fund . The control policy was based on recognition of the importance of screening at least 90% of the target population; of conducting periodic resurveys and treating missed, new, and imported cases; of treating the entire treponemal reservoir (including latent cases and contacts); and of using adequate dosages of long-acting penicillin (minimal dosages were recommended) . Later, policies on the extent of contact treatment at different levels of endemicity were established . During these mass campaigns, approximately 50 million clinical and latent cases and contacts were treated; prevalence of endemic treponematoses was reduced dramatically . The major reasons for resurgence of yaws and endemic syphilis in some areas are discussed . One important factor has been the failure of many countries to integrate active control measures into local health services after the mass campaigns . Yaws and pinta are continuing to decline to very low levels in the Americas . In West Africa, especially, incidence of yaws and endemic syphilis have returned to high levels . Few significant endemic areas remain in Asia except in Indonesia and Papua New Guinea.

Exp Neurol, 1985 May, 88(2), 360 - 71
Interictal afterdischarge in focal penicillin epilepsy: thalamocortical unit activity; Albowitz B et al.; The involvement of thalamic versus cortical structures for the initiation and maintenance of brief interictal afterdischarge was evaluated by recording extracellularly units and field potentials from different subcortical and cortical sites . Afterdischarge oscillations at 16 to 22/s that followed interictal spikes with a delay of 170 to 220 ms usually appeared 10 to 30 min after the topical application of penicillin to the cat's precruciate cortex . Units in the ventrolateral nucleus of the thalamus fired in burst discharges during cortical afterdischarge and less reliably during the cortical interictal spike . In contrast, units recorded at the cortical penicillin focus and homologous contralateral site remained silent during afterdischarge but had a typical burst discharge during the interictal spike . Although these data support a thalamic basis for the rhythm, the lack of an afterdischarge-like oscillation in the thalamic field potential and the independent appearance of afterdischarge and cortical recruiting waves elicited by stimulation of the nucleus reticularis would favor its cortical origin . In accordance with its frequency characteristics and data gained from earlier cooling studies we suggest a cortical mechanism requiring thalamic triggering for the generation of afterdischarge.

Exp Neurol, 1985 May, 88(2), 349 - 59
Interictal afterdischarge in focal penicillin epilepsy: block by thalamic cooling; Gasteiger EL et al.; Interictal spikes recorded from a penicillin focus in the precruciate cortex of urethane-anesthetized cats were followed by brief afterdischarge oscillations that occurred at a delay of 170 to 220 ms from the interictal spike and consisted of as many as five cycles at 16 to 22/s . The origin of this afterdischarge was investigated by cooling different subcortical sites and thus blocking them reversibly . At none of the sites did cooling result in a block of the interictal spike whereas cooling of the ventrolateral nucleus of the thalamus resulted in block of the afterdischarge . Other subcortical sites had either no or less reliable effects on it . We conclude that afterdischarge but not the interictal spike depends on thalamic input, either as a generator of the rhythm or as a trigger for a cortically maintained oscillation.

Rev Infect Dis, 1985 May-Jun, 7 Suppl 2, S289 - 94
Research: the prerequisite for innovative strategies and technologies; Janssens PG; The search for new strategies and technologies for the control of yaws, a genuine but much neglected tropical disease problem, has been largely unsuccessful . This disease, with conspicuous early symptoms and a late crippling pathology, attracted the attention of the first generation of tropical doctors . As soon as specific therapy became available in the early part of the 20th century, mass treatment campaigns were started . The availability and efficacy of penicillin led some to anticipate yaws eradication; this expectation was not met but rather induced a false sense of security . After varying intervals resurgences occurred in several endemic regions . It is important to analyze this failure so that mistakes and underestimated or overlooked factors can be identified . On the whole, the main difficulty has been a lack of interest in a presumably disappearing disease and a consequent failure to take advantage of the benefits offered by recent advances in basic biomedical technology . Solid clinical, epidemiologic, and sociocultural data in connection with mass treatment and control are still needed . Research of high quality, with continuous assessment in the field, is a prerequisite for innovative strategies and technologies.

J Hand Surg {Am}, 1985 May, 10(3), 411 - 2
A foreign body related actinomycosis of a finger; Fayman M et al.; An extremely rare case of foreign body related actinomycosis of the finger is described . To the best of our knowledge, this condition had not been previously reported . Subtotal excisional biopsy followed by penicillin therapy eventually yielded a well functioning finger.

Contact Dermatitis, 1985 May, 12(5), 274 - 8
Skin and respiratory tract symptoms in veterinary surgeons; Falk ES et al.; Chronic or relapsing irritant eczema of the hands was the main complaint in 34 veterinary surgeons . 9 had contact allergic eczema of occupational character . In 8 cases, the allergies were probably due to antibiotics contaminating the skin during the administration of treatment . Contact allergy to penicillin was observed in 5 cases, to neomycin in 2 and to streptomycin in 1 case . Sensitivities to other work-related substances such as rubber chemicals, antiseptics and local anaesthetics were found in 6 cases . Multiple contact allergies, in particular to different penicillins, were seen frequently . Obvious work-related immediate reactions of probable allergic type were present in 10 cases, but were confirmed with positive RAST or prick test in only 2 cases.

Vet Rec, 1985 Apr 20, 116(16), 436 - 8
Persistence of detectable residues of penicillin and cloxacillin in normal and mastitic quarters following intramammary infusion; Egan J et al.; The excretion rates of sodium penicillin and sodium cloxacillin from treated and untreated quarters of normal and mastitic cows were studied . Penicillin was detected in normal and infected quarters for 72 hours after treatment . Cloxacillin was detected in normal and infected quarters for 64 and 48 hours, respectively, after treatment . Differences in the excretion rates of both antibiotics from normal and infected treated quarters were not significant . Penicillin was detected in the untreated quarters of both normal and mastitic cows but cloxacillin was only detected in the untreated quarters of mastitic cows.

N Engl J Med, 1985 Apr 4, 312(14), 869 - 74
Successful parenteral penicillin therapy of established Lyme arthritis; Steere AC et al.; In a double-blind placebo-controlled trial carried out from 1980 to 1982, 20 patients with established Lyme arthritis were assigned treatment with 2.4 million U of intramuscular benzathine penicillin weekly for three weeks (total, 7.2 million U) and 20 patients received saline . Seven of the 20 penicillin-treated patients (35 per cent) had complete resolution of arthritis soon after the injections and have remained well during a mean follow-up period of 33 months . In contrast, all 20 patients given placebo continued to have attacks of arthritis (P less than 0.02) . In 1983, of 20 patients treated with intravenous penicillin G, 20 million U a day for 10 days, 11 (55 per cent) had complete resolution of arthritis and have remained well since . As compared with nonresponders, penicillin-responsive patients in both studies were more likely to have previously received antibiotics for erythema chronicum migrans (P less than 0.02) and less likely to have been given intraarticular corticosteroids during or at the conclusion of parenteral therapy (P less than 0.1) . The Lyme spirochete was not cultured from synovium or joint fluid . We conclude that established Lyme arthritis can often be treated successfully with parenteral penicillin . However, neither of the regimens that we tested is uniformly effective, and further experience will be needed to determine the optimal course of therapy.

Jpn J Antibiot, 1985 Apr, 38(4), 1102 - 6
{Absorption, distribution, metabolism and excretion of bacmecillinam . II . The placental transfer and transition into milk of 14C-bacmecillinam}; Kobayashi S et al.; The placental transfer and transition into milk of bacmecillinam (KW-1100), a new semisynthetic penicillin, have been studied with 14C-KW-1100 administered orally in the pregnant and lactating rats, respectively . The level of 14C-KW-1100 in the umbilical cord blood was 7.2% of the peak maternal blood level and the radioactivity was eliminated slowly . At the peak fetus level (4 hours after administration), the radioactivity transferred into the fetuses was found to be 0.01% of the dose . 14C-KW-1100 was distributed into the uterus, ovary, placenta and consistently into the fetal membrane . 14C-KW-1100 was excreted into milk slightly, and the concentration of radioactivity in milk did not exceed the maternal peak blood level.

No To Shinkei, 1985 Apr, 37(4), 371 - 6
{Threshold of penicillin induced epileptiform afterdischarge in brain slices of guinea pig}; Yuasa H et al.; Investigation of the regional threshold for epilepsy in many structures in the brain would contribute to the study of epileptogenesis . So we studied the threshold for epileptiform afterdischarge in the neocortex, hippocampus and cerebellar cortex using Na-Penicillin -G (Pc) of which epileptogenesis has been intensively investigated . In order to eliminate the influence from the outside of these structures, the brain slice method was utilized . Procedures for preparation of the tissue and incubation were about the same as those described by Yamamoto . In summary, after sacrifice, brain of the guinea pig was taken out and the hippocampus, neocortex and cerebellum were cut with a razor blade under a microscope . The thickness of the section was about 0.3 mm . Slices were incubated at 37 degrees C for about 30 min in the standard medium perfused with 95% O2 and 0% CO2 . The chamber was continuously perfused with the standard medium which composed of NaCl, 124 mM, KCl, 5: KH2PO4, 1.24; MgSO4, 1.3; CaCl2, 2.4; NaHCO3, 26; and glucose, 10 . Evoked potentials were elicited by electrical stimulation in the standard medium . Mossy fibers were stimulated and responses were recorded from the CA3 area in the hippocampus by glass pipette microelectrode . Subcortical white matter was stimulated and responses were recorded from the Purkinje cell layer in the cerebellum . Pc was added in the standard medium until epileptiform afterdischarges were superimposed on the evoked potentials . The results of this experiment demonstrated that each structure in the brain has a regional own threshold for Pc induced epileptiform afterdischarge.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibiot Med Biotekhnol, 1985 Apr, 30(4), 281 - 4
{Molecular mechanism of oxacillin interaction with human serum albumin studied by microcalorimetry}; Markovich MN et al.; Interaction of oxacillin, a semisynthetic penicillin, with human serum albumin (HSA) was studied by means of reaction isothermal and differential scanning microcalorimetry . The antibiotic bound with one primary and two secondary active protein sites . The first bound molecule of the drug had a significant effect on conformation of the biopolymer, which was evident from increased enthalpy and denaturation temperature of the complex as compared to pure HSA . However, the increased thermostability of the serum albumin on its association with oxacillin did not impair the cooperative nature of the thermal denaturation of globular protein . Analysis of the thermodynamic parameters of the complex formation suggested the presence of hydrophobic and electrostatic interactions . The role of electrostatic interaction increased with a decrease in the solution ionic strength.

Mikrobiyol Bul, 1985 Apr, 19(2), 104 - 8
{A case of cervico-facial actinomycosis}; Akgun Y et al.; A 23-year old pregnant women was admitted to the hospital because of a lesion on her face simulating an ulcerated tumoral mass, The lesion had appeared after a dental extraction . Although in several anaerobic cultures actinomyces did not grow, the sulfur granules were observed under microscope and the biopsy specimen suggested actinomycosis . Penicillin therapy for 2 months provided no healing . Excision was performed.

J Pharm Sci, 1985 Apr, 74(4), 448 - 54
A liquid chromatographic study of stability of the minor determinants of penicillin allergy: a stable minor determinant mixture skin test preparation; Ressler C et al.; Various skin test reagents supplying minor determinants for detecting penicillin hypersensitivity have been examined by high-performance liquid chromatography (HPLC) for composition and stability . HPLC systems capable of separating and determining the four diastereoisomers of benzyl-D-penicilloic acid and the two benzyl-D-penicilloic acids were developed for this purpose . The "simple skin test reagent," consisting of an aged partial alkaline hydrolysate of penicillin, is possibly an adequate source of (5R,6R)-benzyl-D-penicilloate whereas the "simple skin test reagent," consisting of aged aqueous solution of penicillin, is a questionable source of this compound . A modified Levine, Voss, Redmond, and Zolov minor determinant mixture (MDM) reagent and the components (5R,6R)-benzyl-D-penicilloate and (5R)-benzyl-D-penilloate have been found to be highly labile in aqueous solution, giving rise to a mixture of diastereoisomers . The tendency to epimerize at C-5 was a prominent feature of (5R,6S)- and (5S,6R)- as well as (5R,6R)-benzyl-D-penicilloic acids . The MDM reagent has been prepared in single-dose ampules as a dried, lyophilized powder that can be stored without change and used as needed . Lyophilized MDM has served as a satisfactory substitute for freshly prepared MDM in several individuals with MDM-positive history and, in a recent clinical study, evaluating the question of penicillin skin test sensitization . This convenient, stable, single-dose form of the MDM reagent should facilitate skin testing for penicillin sensitivity.

J Clin Microbiol, 1985 Apr, 21(4), 666 - 7
Isolation of Acanthamoeba culbertsoni from a patient with meningitis; Lalitha MK et al.; A case of amoebic meningitis, presumably primary, was encountered in the Christian Medical College Hospital, Vellore, South India, in November 1983 . The patient, a 40-year-old man, had cerebrospinal fluid rhinorrhea before the meningitis developed . Acanthamoeba culbertsoni was repeatedly demonstrated in and cultured from the cerebrospinal fluid . The patient responded dramatically to a combination therapy of penicillin and chloramphenicol.

Pediatrics, 1985 Apr, 75(4), 741 - 4
Tissue damage caused by the intramuscular injection of long-acting penicillin; Schanzer H et al.; In order to elucidate whether tissue damage produced on occasion by intramuscular injection of long-acting penicillin is due to accidental intra-arterial injection or vasospasm, two types of experiments were carried out in rabbits . In the first set of experiments, six New Zealand White rabbits were given intra-arterial injections of 0.4 mL of a mixture containing 300,000 U of penicillin G benzathine and 300,000 units of penicillin procaine per milliliter (Bicillin C-R) into the left femoral artery and 0.4 mL of normal saline into the right femoral artery as autocontrol . In a second set of experiments, 0.4 mL of the same penicillin preparation was injected in the space surrounding the left femoral artery in five New Zealand rabbits, and 0.4 mL of normal saline was injected in a similar fashion around the right femoral artery as control . The legs of the rabbits that received the intra-arterial injection of penicillin invariably developed ischemic manifestations . None of the legs of rabbits given intra-arterial injections of normal saline had pathologic manifestations . None of the rabbits that received the periarterial penicillin preparation or normal saline developed abnormalities . These results strongly suggest that the tissue damage produced by penicillin is secondary to the intra-arterial administration of the drug.

Cancer Genet Cytogenet, 1985 Apr 1, 16(3), 259 - 68
Chromosomal analysis of bladder cancer: technical aspects; Smeets W et al.; Of 77 patients with bladder carcinoma, 99 tissue specimens--including tissues of patients with recurrent tumors taken after radiotherapy or cytostatics--were subjected to chromosomal analysis . In 42 specimens, recognizable metaphases could be obtained after conventional Giemsa staining and in a smaller number after C- and/or G-banding . All except one had abnormalities of the chromosomes . Short-term cultures for 24-48 hr in RPMI 1640 plus 15% fetal calf serum plus penicillin-streptomycin gave better results than a direct technique (30 min in 0.075 M KCl + 0.1 microgram colcemid/ml at 37 degrees C, followed by fixation) . In low stage/grade tumors the number of recognizable metaphases obtained after short-term cultures is lower than in higher stage/grade tissue specimens.

J Am Dent Assoc, 1985 Apr, 110(4), 505 - 6
Fatal anaphylactic reaction to oral penicillin: report of case; Roberts J et al.; A report of a fatal anaphylactic reaction to oral penicillin is presented and the unusual set of circumstances leading to its fatal outcome is reviewed . The initial signs and symptoms are analyzed and the use of the proper and immediate treatment is advised.

Proc Natl Acad Sci U S A, 1985 Apr, 82(7), 1999 - 2003
Sequences of the active-site peptides of three of the high-Mr penicillin-binding proteins of Escherichia coli K-12; Keck W et al.; The amino acid compositions of the radioactive peptides obtained from trypsin digestion of {14C}benzylpenicillin-labeled penicillin-binding proteins (PBPs) 1A, 1B, and 3 of Escherichia coli have been obtained . Complete digestion of these peptides with a combination of aminopeptidase M and carboxypeptidase Y showed that benzylpenicillin was bound to a serine residue in each of these proteins . Comparison of the compositions of the penicillin-labeled peptides with the complete amino acid sequences of PBPs 1A, 1B, and 3 showed that the acylated serine occurs near the middle of each of the proteins, within the conserved sequence Gly-Ser-Xaa-Xaa-Lys-Pro . The sequence around the acylated serine of these high Mr PBPs shows little similarity to that around the acylated serine of the low-Mr PBPs (D-alanine carboxypeptidases) or of the class A or class C beta-lactamases, except that in all of these enzymes which interact with penicillin the acylated serine residue occurs within the sequence Ser-Xaa-Xaa-Lys.

Am J Dis Child, 1985 Apr, 139(4), 335 - 7
Psychosis and seizures following the injection of penicillin G procaine . Hoigne's syndrome; Silber TJ et al.; Psychosis and/or seizures following the administration of intramuscular penicillin G procaine have not been reported in the pediatric literature to our knowledge . This omission is regrettable in light of the frequency with which this treatment is indicated as therapy for gonococcal infections . We report clinical data from four patients afflicted by this reaction known as Hoigne's syndrome . The dramatic and unexpected manifestation of this condition calls for an immediate diagnosis to proceed with the appropriate treatment.

Undersea Biomed Res, 1985 Mar, 12(1), 53 - 8
Tissue distribution of penicillin during constant rate infusion in rats at 71 ATA; Aanderud L et al.; Benzyl{14C}penicillin was infused at a constant rate of 100 mg X kg-1 X h-1 for 90 min in rats at 1 ATA air for the control group (n = 10) and at 71 ATA He-O2 for the pressure group (n = 11) . The radioactivity was measured in the arterial blood, brain, liver, kidney, muscle, and fat . The mean brain penicillin concentration after 90 min infusion was approximately 20% increased at 71 ATA (P less than 0.05), but the brain: blood concentration ratio was not significantly affected . The mean blood, liver, and muscle penicillin content was slightly higher and the mean kidney content was slightly lower at pressure, but no statistically significant changes were observed.

J Infect, 1985 Mar, 10(2), 163 - 8
Neonatal mycoplasmaemia: Mycoplasma hominis as a significant cause of disease?
Unsworth PF, Taylor-Robinson D, Shoo EE, Furr PM.
A full-term baby boy had respiratory distress, fever and pneumonia within 20 h of birth . Isolation of Mycoplasma hominis from blood taken after 20 h and 11 days was accompanied by an antibody response . Although chlamydial IgM antibody was detected, chlamydial infection probably did not cause the pneumonia . Penicillin was ineffective but treatment with gentamicin, and particularly tetracycline, was associated with slow improvement . Mycoplasma hominis should be considered as a cause of respiratory disease and fever in neonates.

Neuroscience, 1985 Mar, 14(3), 823 - 35
Changes in local cerebral glucose utilization induced by convulsants; Pazdernik TL et al.; With the six convulsants studied (Soman, intrahippocampal penicillin, bicuculline, pentylenetetrazol, picrotoxin and strychnine), the anatomical distribution of changes in local cerebral glucose utilization was related to the type of seizure observed . Strychnine induced a few very intense motor convulsions during the 2-deoxyglucose experimental period without having a major effect on brain local cerebral glucose utilization, in support of the view that its actions are predominantly in the spinal cord . Pentylenetetrazol and picrotoxin induced intermittent intense seizures and marked increases in local cerebral glucose utilization in the globus pallidus and substantia nigra . Soman, intrahippocampal penicillin and bicuculline all induced persistent status epilepticus associated with increases in local cerebral glucose utilization in many brain areas; those with striking increases in glucose use include: cortical areas, the limbic system, basal ganglia and substantia nigra . The glucose use changes produced by Soman, penicillin and bicuculline greatly exceeded those induced by pentylenetetrazol and picrotoxin . Activation of the substantia nigra and basal ganglia occurred with all centrally mediated convulsions and with status epilepticus there was also marked activation of cortical and limbic structures.

Endoscopy, 1985 Mar, 17(2), 64 - 8
Radiographic and endoscopic findings in penicillin-related non-pseudomembranous colitis; Iida M et al.; The characteristic findings of barium enema and colonofiberscopic studies and their changes over time were investigated in 10 patients with penicillin-related non-pseudomembranous colitis . Radiographic examination within 6 days of onset revealed abnormal findings such as narrowing of the lumen, loss of haustral markings, thumb-printing, transverse ridging, and saw-toothed irregularities . These findings tended to be more pronounced on the right than on the left side of the colon . Endoscopy revealed lesions characterized by mucosal reddening, edema, and hemorrhage, without definite ulceration or erosion . In 5 of the 10 patients, non-continuous distribution of the lesions was noted . In 4 patients, the rectum was unaffected . Reversion to normal occurred within an average of 15.7 days following onset of the symptoms . Thus, for an accurate diagnosis of this disease, barium enema and/or total colonoscopy should be performed within 6 days of onset.

Biull Eksp Biol Med, 1985 Mar, 99(3), 272 - 4
{Characteristics of the electrical activity in hippocampal slices in mice with Corazol kindling}; Buldakova SL et al.; It has been shown in experiments on hippocampal slices of (CBA X C57BL/6)F1 mice with corazol kindling that the threshold of the appearance of the induced seizure discharge (ISD) in the area CA1 was decreased by stimulation of Schaffer collaterals . Diazepam provoked an increase in seizure susceptibility to corazol and penicillin and reduction of the ISD . The data suggest that alterations in neuronal reactivity, which follow kindling, can be found in an individual hippocampal segment, thus making it possible to investigate this phenomenon at the synaptic and molecular levels.

Am J Hosp Pharm, 1985 Mar, 42(3), 598 - 602
pH-dependent effect of magnesium sulfate on the stability of penicillin G potassium solution; Das Gupta V et al.; The effect of magnesium sulfate on the stability of penicillin G potassium solutions (0.5 mg/mL) was investigated using a stability-indicating high-performance liquid chromatography method . The penicillin G potassium powder buffered with and without citrate was used . Twelve aqueous duplicate penicillin solutions with various concentrations of magnesium sulfate and with or without buffers were prepared and stored at room temperature . Data on clarity, pH values, and HPLC assay results were determined at intervals during the 10-day storage period . The results indicated that the presence of high concentrations of magnesium sulfate in unbuffered penicillin solutions can cause large pH changes and the degradation of penicillin . However, the effect of magnesium sulfate on the stability of penicillin G potassium was negligible in the buffered solutions . Solutions with a constant pH value of 5.6 prepared using 0.1 M acetate buffer with and without magnesium sulfate showed similar apparent first-order degradation after the 10-day storage period at 24 degrees C . During decomposition, the pH values of the unbuffered solutions decreased for three days and then started increasing in most solutions . The degradation of penicillin G potassium by magnesium sulfate in aqueous solutions resulted from decreases in pH values of the solutions.

Arch Intern Med, 1985 Mar, 145(3), 465 - 8
Lumbar puncture in asymptomatic late syphilis . An analysis of the benefits and risks; Wiesel J et al.; We evaluated the treatment of asymptomatic patients with untreated syphilis of more than one year's duration (asymptomatic late syphilis) using a decision-analysis model . Two strategies were compared: treatment with 7.2 million units of penicillin G benzathine, or performing a lumbar puncture to test for asymptomatic neurosyphilis followed by penicillin and management based on cerebrospinal fluid analysis . Estimates of probabilities of disease prevalence, test sensitivity, and cure and complication rates were derived from published studies . Both strategies resulted in a cure rate of at least 99.7% using the best estimates . Although the strategy using lumbar puncture results in a 0.2% higher cure rate, its rate of complications (0.3%) exceeds its marginal benefit . We conclude that a lumbar puncture offers little additional benefit and may increase morbidity in patients with asymptomatic late syphilis.

South Med J, 1985 Mar, 78(3), 361 - 2
Peptococcus magnus endocarditis; Cofsky RD et al.; An 18-year-old man had an eventually fatal case of Peptococcus magnus endocarditis . Multiple emboli and continued valve destruction occurred during appropriate therapy . Penicillin therapy was associated with fever and neutropenia, thought to be due to an immunologic mechanism.

J Infect, 1985 Mar, 10(2), 158 - 62
Endocarditis due to Actinobacillus actinomycetemcomitans; Chowdhury MN et al.; A case of infective endocarditis in a 38-year-old Saudi male caused by Actinobacillus actinomycetemcomitans is reported . The patient was treated successfully with a combination of benzyl penicillin and gentamicin . Previously reported cases are reviewed.

Antimicrob Agents Chemother, 1985 Mar, 27(3), 380 - 7
Isopenicillin N synthetase of Penicillium chrysogenum, an enzyme that converts delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine to isopenicillin N; Ramos FR et al.; The tripeptide delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine, an intermediate in the penicillin biosynthetic pathway, is converted to isopenicillin N by isopenicillin N synthetase (cyclase) of Penicillium chrysogenum . The cyclization required dithiothreitol and was stimulated by ferrous ions and ascorbate . Co2+ and Mn2+ completely inhibited enzyme activity . Optimal temperature and pH were 25 degrees C and 7.8, respectively . The reaction required O2 and was stimulated by increasing the dissolved oxygen concentration of the reaction mixture . Purification of the enzyme to a single major band in polyacrylamide gel electrophoresis was achieved by protamine sulfate precipitation, ammonium sulfate fractionation (50 to 80% of saturation), DEAE-Sephacel chromatography, and gel filtration on Sephacryl S-200 . The estimated molecular weight was 39,000 +/- 1,000 . The apparent Km of isopenicillin N synthetase for delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine was 0.13 mM . The enzyme activity was strongly inhibited by glutathione, which acts as a competitive inhibitor . A good correlation was observed between the isopenicillin N synthetase activity in extracts of four different strains of P . chrysogenum (with widely different penicillin-producing capability) and the amount of penicillin production by these strains.

Obstet Gynecol, 1985 Mar, 65(3), 371 - 4
Metronidazole prophylaxis in elective first trimester abortion; Heisterberg L et al.; In a double-blind controlled trial, the efficacy of prophylactic metronidazole in elective first trimester abortions was assessed . Of 119 randomized women, 100 followed the protocol . Fifty-one women received 400 mg metronidazole one hour before and again four and eight hours after abortion; 49 women received a placebo . In the placebo group 20.4% contracted postabortal genital infection compared with 3.9% in the metronidazole group (P less than .025) . Of 25 women with a positive history of pelvic inflammatory disease, six contracted postabortal infection, which was a significantly increased frequency compared with women without previous episodes of pelvic inflammatory disease (P less than .05) . The administration of prophylaxis, however, did not significantly influence the frequency . The number of hospital days was not significantly lower in the prophylaxis group (P greater than .05) . The total amount of metronidazole prescribed in the study group was significantly larger than in the placebo group (P less than .05), whereas the amount of ampicillin/pivampicillin prescribed in the placebo group was significantly larger (P less than .05) . The difference between the penicillin doses given in the treatment and placebo groups was not significant (P greater than .1).

Eur J Biochem, 1985 Mar 1, 147(2), 437 - 46
The nucleotide sequences of the ponA and ponB genes encoding penicillin-binding protein 1A and 1B of Escherichia coli K12; Broome-Smith JK et al.; Penicillin-binding proteins 1A and 1B of Escherichia coli are the major peptidoglycan transglycosylase-transpeptidases that catalyse the polymerisation and insertion of peptidoglycan precursors into the bacterial cell wall during cell elongation . The nucleotide sequence of a 2764-base-pair fragment of DNA that contained the ponA gene, encoding penicillin-binding protein 1A, was determined . The sequence predicted that penicillin-binding protein 1A had a relative molecular mass of 93 500 (850 amino acids) . The amino-terminus of the protein had the features of a signal peptide but it is not known if this peptide is removed during insertion of the protein into the cytoplasmic membrane . The nucleotide sequence of a 2758-base-pair fragment of DNA that contained the ponB gene, encoding penicillin-binding protein 1B, was also determined . Penicillin-binding protein 1B consists of two major components which were shown to result from the use of alternative sites for the initiation of translation . The large and small forms of penicillin-binding protein 1B were predicted to have relative molecular masses of 94 100 and 88 800 (844 and 799 amino acids) . The amino acid sequences of penicillin-binding proteins 1A and 1B could be aligned if two large gaps were introduced into the latter sequence and the two proteins then showed about 30% identity . The amino acid sequences of the proteins showed no extensive similarity to the sequences of penicillin-binding proteins 3 or 5, or to the class A or class C beta-lactamases . Two short regions of amino acid similarity were, however, found between penicillin-binding proteins 1A and 1B and the other penicillin-binding proteins and beta-lactamases . One of these included the predicted active-site serine residue which was located towards the middle of the sequences of penicillin-binding proteins 1A, 1B and 3, within the conserved sequence Gly-Ser-Xaa-Xaa-Lys-Pro . The other region was 19-40 residues to the amino-terminal side of the active-site serine and may be part of a conserved penicillin-binding site in these proteins.

Brain Res, 1985 Feb 11, 326(2), 273 - 80
The influence of dopamine on epileptiform burst activity in hippocampal pyramidal neurons; Suppes T et al.; Dopamine (DA) application to guinea pig hippocampal CA1 neurons in vitro causes hyperpolarization of the resting potential, increase in conductance, and increase in amplitude and duration of the afterhyperpolarization (AHP) . Since these changes could influence repetitive firing, we performed experiments to determine whether DA-induced effects would suppress epileptogenesis in the hippocampus . Epileptiform bursts were induced by adding penicillin (3.4 mM) to the perfusion medium . Focal application of DA (40-160 microns) onto CA1 cells (n = 15) produced a hyperpolarization averaging 4.5 mV beginning in 5-20 s and lasting up to 3 min . DA also caused an increase in the amplitude and duration of slow AHPs . The frequency of spontaneous epileptiform events however was not affected . CA3 neurons (n = 6) responded to DA application with an initial 1-3 mV depolarization beginning within 5-30 s and lasting 1-2 min . In 3 cases a small hyperpolarization lasting several minutes subsequently developed . AHP duration increased 70% and amplitude increased 35% (n = 4) . Along with these membrane changes the frequency of epileptiform bursting in CA3 cells slowed for 1-3 min . We added DA (10-80 microM) to the perfusion medium to see whether a significant decrease in epileptiform burst frequency might occur in the follower CA1 region if greater numbers of pacemaker CA2 and CA3 cells were exposed to DA . Spontaneous CA1 bursting was reversibly slowed, the interburst interval became variable and increased from a mean of 4 to a mean of 5-7 s (n = 6) . These results suggest that DA may play a role in decreasing the incidence or frequency of epileptogenic discharges in vivo.

Ophthalmology, 1985 Feb, 92(2), 262 - 70
Neuroretinitis in acquired syphilis; Arruga J et al.; Syphilitic disease of the retina and/or the optic nerve head, without choroidal involvement, occurred in our 4 cases and in another 19 cases . The condition almost always takes place in the secondary stage, frequently associated with meningitis, and rarely in tertiary meningovascular syphilis . Fluctuating visual loss and floating spots without ocular pain are the presenting symptoms . Retinitis, papillitis, and neuroretinitis are accompanied by an inflammatory reaction in the vitreous and, sometimes, in the aqueous . Paracentral scotomas and blind spot enlargement, related with posterior pole and papillary edema, are the most usual visual field defects . Almost complete visual recovery is the rule in the treated cases, although in some instances cystoid macular edema and retinal ischemia due to endarteritis cause permanent visual loss . Treatment with crystalline penicillin is mandatory in patients with concomitant neurosyphilis, whereas procaine penicillin is seemingly sufficient in those with a normal cerebral spinal fluid examination.

J Clin Microbiol, 1985 Feb, 21(2), 273 - 5
Actinomyces naeslundii as an agent of pelvic actinomycosis in the presence of an intrauterine device; Bonnez W et al.; PIP: This paper presents the 1st reported case of Actinomyces naeslundii isolation in pelvic actinomycosis in an IUD user . Up until this point, all such cases of infection had been linked to A . israelii . The patient was a 39-year old woman who had had a Dalkon Shield device inserted 10 years prior to her admission with sharp, progressive abdominal pain . Scanning revealed a midline, posterior, extrauterine, large, complex mass which was reduced dramatically in size after treatment with penicillin and probenecid . Direct immunofluorescence clearly identified the organism recovered from the IUD as A . naeslundii, although the clinocopathologic presentation in this case was similar to that found in A . israelii-related pelvic actinomycosis . Most infections with this agent are restricted to the oral cavity . However, these findings suggest that A . naeslundii is an occasional saprophyte of the lower genital tract as well . Orogenital sexual practices are believed to provide actinomycetes with access to the genital tract . The patient in this case had 2 risk factors for developing pelvic actinomycosis: use of the Dalkon Shield (the model associated with the highest incidence of infection) and longterm IUD use .

Invest Ophthalmol Vis Sci, 1985 Feb, 26(2), 159 - 62
Maturation of Rb+ and PAH accumulation by rabbit anterior uvea and choroid plexus; Krupin T et al.; In vitro accumulation of radioactive para-aminohippuric acid (3H-PAH) and rubidium (86Rb+) by the anterior uvea, ciliary processes, and the choroid plexus was evaluated in tissues from newborn and various aged rabbits . Accumulation of PAH was present in the anterior uvea at 1 day of age (tissue to media ratio, T/M, of 2.1 +/- 0.2) and remained at this level for the first 14 days of life . Accumulation did not rise to adult levels until 21 days of age (T/M 5.5 +/- 0.6) . Rubidium accumulation in the anterior uvea, a measure of Na+, K+-pump activity, was higher than adult values 6 hr after birth (T/M25.2 +/- 0.9) . Activity remained elevated through day 28 and did not fall to adult levels until day 60 (T/M 13.4 +/- 0.6) . Accumulation studies on isolated ciliary processes were similar to those obtained from anterior uveal tissue . Daily subcutaneous injections of penicillin (300,000 units/kg/day) for 1 week had no effect on anterior uvea PAH accumulation (penicillin T/M was 1.7 +/- 0.1 and saline control T/M was 2.0 +/- 0.2) . Accumulation of either 3H-PAH or 86Rb+ by the choroid plexus was present 1 day after birth in amounts that were similar to adult values and did not change during the 90 days of testing.

Eur J Biochem, 1985 Feb 1, 146(3), 625 - 32
Enzymes in polyelectrolyte complexes . The effect of phase transition on thermal stability; Margolin AL et al.; Penicillin amidase, alpha-chymotrypsin and urease have been immobilized in water-soluble nonstoichiometric polyelectrolyte complexes (N-PEC) . N-PEC are formed by modified poly(N-ethyl-4-vinyl-pyridinium bromide) (polycation) and excess poly(methylacrylic acid) (polyanion) . N-PEC are a new class of polymers capable, characteristically, of phase transitions solution in equilibrium precipitate induced by slight change in pH or ionic strength . Neither the chemical structure of the carrier nor the number of cross-linkages between an enzyme and a carrier change on phase transition . That gives an unique opportunity to elucidate the difference between enzymes immobilized on water-soluble and water-insoluble supports . A detailed study of the phase transition effect on thermal stability of the enzymes and protein-protein interactions has been carried out . The following effects were found . Pronounced thermal stabilization of penicillin amidase and urease may be achieved on two conditions: the enzyme is in the precipitate; (b) the enzyme is linked to the N-PEC nucleus . Then the thermal stability of N-PEC-bound penicillin amidase increases 7-fold at pH 5.7, 60 degrees C, and 300-fold at pH 3.1, 25 degrees C, compared to the native enzyme . For urease, the thermal stabilization increases 20-fold at pH 5.0, 70 degrees C . The localization of enzyme on N-PEC has been established by titration of alpha-chymotrypsin bound to a polycation or polyanion with basic pancreatic trypsin inhibitor . Both in solution (pH 6.1) and in N-PEC precipitate (pH 5.7), an alpha-chymotrypsin molecule bound to a polyanion is fully exposed to the solution . If the enzyme is bound to a polycation, only 20% of alpha-chymotrypsin molecules in the precipitate and 40% in solution retain their ability for protein-protein interactions . This means that a polycation-bound enzyme is localized in the hydrophobic nucleus of the complex, whereas the polyanion-bound enzyme sits on the hydrophilic shell of the complex . On pH-induced phase transition (pH decreases from 6.1 to 5.7), there occurs a stepwise decrease in penicillin amidase activity which is due to a 9.8-fold increase in the Km for 2-nitro-4-phenylacetamidobenzoic acid . Change of the catalytic activity and thermal stability of N-PEC-bound penicillin amidase is fully reversible and reproducible . Such soluble-insoluble immobilized enzymes with controllable thermal stability and activity may be used for simulating events in vivo and in biotechnology.

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