J Antimicrob Chemother, 1977 Jul, 3 Suppl B, 83 - 8 Mecillinam serum levels following intravenous injection: a comparison with pivmecillinam; Mitchard M et al.; Serum mecillinam concentrations have been obtained in 6 volunteers after intravenous injection of 200 mg mecillinam and two 200 mg tablets containing pivmecillinam hydrochloride . Initial concentrations were between 6 and 9 mg/1 and peak concentrations of about 2-0 mg/1 occurred at 1 to 1-5 h after the tablets . Analysis of the intravenous data shows the concentration/time curve to be biphasic and similar to that previously reported for penicillin G . The biexponential curves describing the data have been calculated using nonlin . Comparison of the areas under the serum mecillinam concentration/time curves suggests a bioavailability of 65 to 70% for the tablets . However, the two preparations contain therapeutically equivalent amounts of antibiotic, as two 200 mg tablets of pivmecillinam contain 30% more mecillinam than the 200 mg injection. Poult Sci, 1977 Jul, 56(4), 1153 - 7 Apparent inadequacy of sodium requirement in broiler chickens; Ross E; Wheat-soy and corn-soy basal diets designed to be complete in all known nutrients failed to support normal growth and feed efficiency of male broiler chicks to two weeks of age . Highly significant growth responses to these diets were obtained from the addition of faba meal (Vicia faba L.) or of 0.2% Na2SO4 . Subsequent studies showed these diets to be deficient in sodium even though they contained, by analysis, 0.13 or 0.14% of sodium . A very low sodium content of the drinking water (3 p.p.m.) is believed to be contributory to this deficient state . A significant growth response was obtained from the addition of 0.2% sodium (0.33% total sodium) whether from NaCl or a combination of NaCl and Na2SO4 . These data suggest that it may be important to consider the sodium content of the drinking water when determining the sodium requirement of the chick . A further response was obtained from 5.0 p.p.m . procaine penicillin G suggesting the presence of some toxic substance in the feed ingredients or that a subclinical infection may also have contributed to the poor growth supported by the basal diets. Proc Natl Acad Sci U S A, 1977 Jul, 74(7), 2980 - 4 Simultaneous deletion of D-alanine carboxypeptidase IB-C and penicillin-binding component IV in a mutant of Escherichia coli K12; Iwaya M et al.; Mutants of Escherichia coli with much decreased activity of D-alanine carboxypeptidase (peptidyl-D alanine hydrolase, EC 3.4.12.11) were found among E . coli K12 extensively mutagenized with nitrosoguanidine treatment by assaying individual colonies for the enzyme activity . One such mutant with only 10-12% residual activity was characterized extensively . The soluble carboxypeptidase activity (corresponding to D-alanine carboxypeptidase IC of Tamura T., Imae, Y . & Strominger, J.L . {(1976) J . Biol . Chem . 251, 414-423} was deleted . This enzyme activity in the particulate fraction was markedly reduced but transpeptidase activity was normal . However, penicillin-binding component IV was deleted from the particulate fraction . Both the physiology and penicillin sensitivity of the organism were relatively normal, except that mutant cells were markedly more stable to penicillin-induced lysis, suggesting the possibility that carboxypeptidase IC really functions as an endopeptidase . The possible relationship of the deleted carboxypeptidase activity and the deleted penicillin binding component are discussed. Proc Natl Acad Sci U S A, 1977 Jul, 74(7), 2976 - 9 Mutants of Escherichia coli lacking in highly penicillin-sensitive D-alanine carboxypeptidase activity; Matsuhashi M et al.; Mutants of Escherichia coli lacking in the highly penicillin-sensitive enzyme activities of D-carboxy-peptidase, transpeptidase, and endopeptidase, and with the concomitant absence of penicillin-binding protein 4 of B.G . Spratt and A.B . Pardee {(1975) Nature 254, 516-517} were isolated . The defect of these mutants is ascribed to the lack of an enzyme, D-alanine carboxypeptidase Ib . Genetic mapping studies show the mutation (dacB) to be located at 68 min on the E . coli chromosome map . The dacB mutation results in the simultaneous loss of D-alanine carboxypeptidase and penicillin-binding protein 4 . The mutants grew normally under a wide range of growth conditions . We conclude that the enzyme is not a necessary component for normal peptidoglycan biosynthesis in E . coli. Zh Mikrobiol Epidemiol Immunobiol, 1977 Jul, (7), 81 - 5 {Obtaining spheroplasts from the agents of glanders and melioidosis and separation of membrane structures from them}; Farber SM et al.; Spheroplasts were obtained from the causative agents of glanders and melioidosis under the effect of lysozyme and antibiotics . In the capacity of an inducing agent lysozyme was effective in high concentration only (0.4%); preliminary washing and incubation in sucrose were necessary to obtain glanders spheroplasts . Of the antibiotics studied penicillin was more useful for obtaining melioidosis spheroplasts and ampicillin--for glanders spheroplasts . Membrane preparations were derived from the spheroplasts of glanders and melioidosis causative agents. Arch Intern Med, 1977 Jul, 137(7), 858 - 62 Acute venereal arthritis . Comparative study of acute Reiter syndrome and acute gonococcal arthritis; McCord WC et al.; Acute venereal arthritis, a syndrome of fever and inflammatory arthritis following recent sexual intercourse, is a frequently misdiagnosed arthritic presentation . Nearly half of 39 patients admitted with a diagnosis of acute gonococcal arthritis were subsequently recognized as having acute Reiter syndrome . A retrospective study of both diseases revealed differentiating features that, when prospectively applied to 21 consecutive patients, permitted a correct and prompt bedside diagnosis . Acute Reiter syndrome could be differentiated by characteristic mucucutaneous lesions, arthritis/tenosynovitis confined to lower extremities, massive recurrent knee effusions, low back pain, conjunctivitis, and genitourinary inflammation . Gonococcal arthritis could be differentiated by migratory arthralgias, high fevers, arthritis/tenosynovitis initially confined to upper extremities, typical cutaneous lesions, and dramatic defervescence to penicillin therapy . Laboratory data provided support for each diagnosis. Isr J Med Sci, 1977 Jun, 13(6), 604 - 8 Renal failure and interstitial nephritis due to trichloroethylene anesthesia and high-dose penicillin; Brautbar N et al.; An unusual case of acute renal failure is described . The patient, who had no previous history or signs of renal impairment, underwent lumbar laminectomy under general anesthesia with trichloroethylene (Trilene) and nitrous oxide . On the fifth postoperative day i.v . administration of 12 million units of penicillin was started . Within 16 h the patient developed oliguria and a clinical picture of acute renal failure . The course of the disease was prolonged and necessitated four hemadialysis treatments . The patient recovered only about 50% of his renal function . A biopsy performed two months after the onset of the acute renal failure was interpreted as indicating tubulo-interstitial nephritis . The role of trichloroethylene in the etiology of acute renal failure is discussed. Can J Physiol Pharmacol, 1977 Jun, 55(3), 670 - 80 Bicuculline, benzyl penicillin, and inhibitory amino acids in the spinal cord of the cat; Krnjevic K et al.; Bicuculline methochloride (BMC), applied by microiontophoresis, tends to depolarize spinal motoneurons and lower their input resistance . With approximately equal iontophoretic currents of gamma-aminobutyric acid (GABA) and BMC, there is an almost equal chance of observing no change, a potentiation, or a depression of the GABA-evoked conductance increase . A block of the GABA action is seen consistently only when the iontophoretic current of BMC is at least double that of GABA . Under these conditions BMC can selectively antagonize GABA without blocking the effects of glycine, though the latter can also be blocked by larger amounts of BMC . BMC also regularly eliminates the usual apparent desensitization to GABA . This may be due to depression of GABA uptake by BMC, which would also account for its potentiating action at lower relative doses . Comparable effects are observed with iontophoretic applications of benzyl penicillin (BP); but even large doses of BP produce no definite change in membrane properties or in conductance increase evoked by GABA or glycine. Biull Eksp Biol Med, 1977 Jun, 83(6), 646 - 9 {Effect of micropolarization of focal and extrafocal brain structures on experimental epilepsy}; Tkachenko EI; The influence of micropolarization (MCP, 0.05-0.75 muA) was studied in chronic experiments on rabbits with epileptogenic foci provoked by penicillin (doses of 500 and 1000 U) injection into the motor cortex . A single MCP of extrafocal structure (the corpus calossum, nucleus caudatus) and the site of the focus inhibited the development of seizure reactions . Numerous MCP of the focus facilitated the seizure reactions . These effects may be explained not only by the specific role of the structures studied in the processes of the formation and propagation of the excitation, their initial functional state, but also by the dependence of the activity of these structures on the MCP regimen. Tijdschr Diergeneeskd, 1977 Jun 1, 102(11), 665 - 9 {The use of a dry cow preparation for the prevention of summer mastitis in maiden heifers (author's transl)}; van Os JL et al.; An investigation was made of the preventive value of topical application to juvenile udders of a dry cow preparation containing 300,000 IU of procaine penicillin G (Penzal N 300) . Penicillin concentrations in udder secretions of 30 young cows were examined . In calves up to 10 weeks and in maiden heifers up to 7 weeks after application an average concentration of 0.05 ml IU per ml of secretion was found . In the same groups, 12 and 9 weeks respectively after application, the concentration was 0.01 IU per ml of secretion . Experiences in practice in an area with a high infection rate have shown an obvious protection in 700 maiden heifers . Some cases of infection did occur both shortly (1.0%) and from 5 weeks after application (1.9%) . The clinical character of the latter was much milder than is usual for summer mastitis . When administered in time and in the correct manner the dry cow preparation examined showed reasonable protection against summer mastitis. J Pharmacol Exp Ther, 1977 Jun, 201(3), 778 - 85 Nephrotoxicity of cephaloridine in newborn rabbits: role of the renal anionic transport system; Wold JS et al.; The nephrotoxicity of cephaloridine, cefazolin and mercuric chloride was studied in rabbits of various ages . Cephaloridine produced dose-related elevations in serum urea nitrogen, creatinine and renal tubular necrosis in adult and 30-day-old rabbits, only slight changes at 15 days of age and no effect in 5-day-old rabbits . Cefazolin also produced dose-related nephrotoxicity in adult rabbits but no effect in 15-day-old rabbits . Mercuric chloride administration resulted in similar nephrotoxicity in 5-, 15- and 30-day-old rabbits and adults . The development of susceptibility to cephaloridine nephrotoxicity paralleled the maturation of the renal anionic transport system as determined by the accumulation of p-aminohippurate by renal cortical slices in vitro . Substrate stimulation of the anionic transport system by p-aminohippurate or penicillin increased the nephrotoxicity of cephaloridine in between rabbits . The authors concluded that the lack of cephaloridine nephrotoxicity in newborn rabbits is due to the incomplete development of the renal anionic transport system. Eur J Biochem, 1977 May 2, 75(1), 133 - 47 The stereochemistry of beta-lactam formation in penicillin biosynthesis; Young DW et al.; 1 . (2R,3S)-{U-14C,3-3H1}- and (2R,3R)-{U-14C,2,3-3H2} Cysteine hydrochlorides have been separately synthesised . The latter compound has been shown to have uniform distributions of tritium between C-2 and C-3 . 2 . The abvoe cysteines and (2R)-{U-14C,3,3,3',3'-3H4}cystine have been converted to samples of penicillin G by Penicillium chrysogenum . 3 . Incorporation results indicate that all but 14% of the tritium is lost from the (2R,3S)-{3-3H1}isomer; that 42% of tritium is retained by the non-stereospecifically C-3 tritiated cystine; and that 58% of tritium is retained by the (2R,3R)-{2,3-3H2}isomer on conversion to penicillin G . 4 . Degradation of the penicillin G derived from (2R,3R)-{U-14C,2,3-3H2}cysteine hydrochloride has indicated that in fact about 87% of the original C-3 tritium of cysteine is retained at C-5 of penicillin G . 5 . The results indicate stereospecificity in the cyclisation giving rise to the beta-lactam ring in penicillin G in nature with loss of the 3-pro-S-hydrogen and rentention of the 3-pro-R-hydrogen of cysteine . Thus there is net retention of stereochemistry in the cyclisation. Zh Vyssh Nerv Deiat Im I P Pavlova, 1977 May-Jun, 27(3), 582 - 90 {Changes in the functional characteristic of motor cortex neurons following their rhythmic polarization}; Chepkova AN et al.; The study was devoted to the effect of rhythmical extracellular activating polarization on spontaneous and evoked (by stimulation of the ventroposterolateral nucleus of the thalamus) unit activity of the motor cortex, preliminarily sensitized by application of an epileptigen (penicillin or strychnine solution) . The experiments were carried out on alert unrestrained rabbits . A 3-5 minutes rhythmical polarization of the neurons (0,12, 0, 10 c/s, 200-600 msec pulse duration) resulted in following aftereffects: 1) changes in the mean spike frequency in 58% of neurons; 2) increase of grouping of firing in units with an initial group-type spontaneous activity (21%); 3) assimilation of the polarizing rhythm (10%); 4) facilitation of excitatory phases of thalamically evoked unit responses that occured simultaneously with an increase of mean discharge frequency (18%) . The results are discussed from the point of view of the hypothesis of excitatory reverberation in the microsystem of interconnected neurons. Am J Surg, 1977 May, 133(5), 582 - 3 Staging laparotomy for Hodgkin's disease in children; Bell MJ et al.; Experience with staging laparotomy in twenty-one children has produced minimal immediate postoperative morbidity . Sepsis in two patients after discharge has prompted the long-term use of penicillin . Confirmation or revision of clinical staging by laparotomy has proved to be an accurate means of determining therapy and prognosis in children. Ann Neurol, 1977 May, 1(5), 463 - 9 Penicillin-induced epileptiform activity in the hippocampal in vitro prepatation; Schwartzkroin PA et al.; An in vitro preparation has been developed in which epileptogenesis in mammalian central nervous system tissue may be studied . Addition of sodium penicillin to the medium bathing slices of guinea pig hippocampus induced epileptiform activity similar to that seen in hippocampal penicillin foci in vivo . Epileptiform events were recorded as synchronous field potentials and correlated cellular bursts that occurred spontaneously and could be triggered by orthodromic stimulation . Intracellular recordings revealed that bursts were generated from large depolarization shifts in some neurons, while in others, burst discharges had little underlying baseline depolarization . This finding, and the presence of fast prepotentials in penicillin-treated preparations, suggested the involvement of dendritic activity in generation of epileptiform discharges. Genetics, 1977 May, 86(1), 25 - 32 Isolation of spontaneously derived mutants of Caulobacter crescentus; Johnson RC et al.; Caulobacter crescentus has a penicillinase which precludes the use of penicillin for mutant enrichment . However, two other antibiotics, fosfomycin and D-cycloserine, can be enrich for C . crescentus mutants . In enrichment procedures for C . crescentus auxotrophs, spontaneously derived mutants occur at a frequency of 5-10% among the survivors of an enrichment procedure . Consequently, large numbers of mutants are readily obtained without any need for mutagenesis . These mutants are heterogeneous both with regard to the type of mutation and to the nutritional requirement . A similar procedure has been used to isolate temperature-sensitive mutants. Am J Hosp Pharm, 1977 May, 34(5), 528 - 31 Hypokalemic, metabolic alkalosis induced by high-dose ampicillin sodium; Gill MA et al.; A case of hypokalemic metabolic alkalosis precipitated by high-dose intravenous ampicillin sodium is discussed . Cases of hypokalemic metabolic alkalosis attributable to ampicillin sodium have not been reported previously . There have been reports of this phenomenon associated with high doses of penicillin sodium and carbenicillin disodium . The possible mechanism of antibiotic-induced hypokalemic metabolic alkalosis is discussed . It is suggested that most cases of antibiotic-induced hypokalemia respond to oral or intravenous potassium chloride. Community Dent Oral Epidemiol, 1977 May, 5(3), 103 - 7 Medical history of children undergoing dental treatment in Ireland; LeMasney JF; A simple medical history questionnaire suitable for filling in at home by the parents of children about to undergo a school dental inspection is described . Information on the medical status of 2,542 primary schoolchildren between the ages of 4 and 14 years as obtained by the use of this questionnaire is presented . The number of children giving one or more positive replies to the 10 questions on the list was 401 . This was 15.8% of the total number investigated . The question on heart defects was answered positively for 2.8% of the children, while nearly 1% were said to be allergic to penicillin. J Oral Surg, 1977 May, 35(5), 416 - 7 Erysipelas: facial lymphangitis; Slade E et al.; Two cases of facial lymphangitis have been described, and the pathophysiology of erysipelas has been discussed . Now rarely observed by hospital residents, this potentially serious infection can create considerable diagnostic confusion in medical as well as dental services . Rapid response of erysipelas to penicillin therapy is the modern expectation. Electroencephalogr Clin Neurophysiol, 1977 May, 42(5), 640 - 55 Pathophysiology of generalized penicillin epilepsy in the cat: the role of cortical and subcortical structures . I . Systemic application of penicillin; Quesney LF et al.; The mechanism of precipitation of generalized epileptiform discharges in feline generalized penicillin epilepsy, a model of human generalized corticoreticular ('centrencephalic') epilepsy, was studied in acute and chronic experiments in cats with implanted skull and intracerebral electrodes . Single shock and low frequency repetitive stimulation of subcortical sites from which prior to penicillin administration spindle activity and recruiting responses could be elicited, readily triggered epileptiform discharges in the same animals after penicillin . These structures comprised the intralaminar and midline thalamic nuclei, the neostriatum, and some posterior thalamic association nuclei (Pulvinar and nucleus lateralis posterior) . Subcortical and cortical structures which prior to penicillin elicited neither spindle activity nor recruiting responses were significantly less effective in triggering generalized epileptic bursts after penicillin injection . The probability with which such bursts were elicited from these structures was still, however, in many instances above chance level . It is concluded that the generalized epileptiform discharges in feline generalized penicillin epilepsy can be triggered from a large number of brain sites, but most reliably so from subcortical nuclei involved in spindle generation and recruiting responses . The experimental evidence presented still does not allow one to determine whether epileptic alteration of neuronal function in this form of epilepsy primarily resides in cortical or subcortical nerve cells or in both. Electroencephalogr Clin Neurophysiol, 1977 May, 42(5), 625 - 39 Spike-wave rhythms in cat cortex induced by parenteral penicillin . II . Cellular features; Fisher RS et al.; Epileptiform potentials, consisting of spontaneous, generalized bursts frequently assuming a 3/sec spike-wave form and tonic clonic electrographic seizures were produced in 32 lightly anesthetized cats by parenteral injections of penicillin . The activity of 83 identified pyramidal tract cells and 207 cortical non-pyramidal tract cells was correlated with the surface EEG . The majority of both cell types generated depolarizations and action potentials with the EEG spike . Hyperpolarizations, during which cells were inhibited, followed the depolarizations . The depolarizations responded to injected current as if they were generated by excitatory synapses; and hyperpolarizations to injected current and chloride ions as if generated by proximal inhibitory synapses . Attempts to identify a class of neurons firing during the surface-negative wave (presumed inhibitory interneurons) were unsuccessful . Forty-two units were recorded during tonic-clonic seizures . Intracellular records disclosed tonic oscillations of membrane potential, phased bursting with "depolarization shifts", abortive action potentials and post-ictal hyperpolarizations . Cell somata often depolarized to the point of inactivation, but axons continued to fire at high rates . These results emphasize the role of EPSP-IPSP sequences in the generation of spike-wave rhythms. Electroencephalogr Clin Neurophysiol, 1977 May, 42(5), 608 - 24 Spike-wave rhythms in cat cortex induced by parenteral penicillin . I . Electroencephalographic features; Fisher RS et al.; Surface and depth recordings were made in 21 cats with generalized, parenteral penicillin induced epileptiform activity often assuming spike-wave forms, to obtain information on the structural substrate of "spontaneous" spike-wave rhythms . Recordings were made from neocortex, medial and lateral thalamus, hippocampus and brainstem reticular formation . Epileptiform activity first appeared in cortex and subsequently projected to depth structures . Occasionally, focal discharges could be seen in subcortical structures, but these generally did not spread to cortex . No consistent "pacemaker" was identified in cortex or depth . Bilateral applications of penicillin to cortex produced synchronous spike-wave bursts . In contrast, ventriculocisternal perfusion of penicillin solutions yielded synchronous cortical potentials which differed clearly in morphology and frequency from parenterally induced spike-wave bursts . During generalized activity, transcortical, intrahemispheric lesions interfered with ipsilateral synchrony . After transcortical section, projection of localized cortical bursts to thalamus did not necessarily result in "recruitment" of diffuse cortical regions into epileptiform activity . These results emphasize the importance of cortical circuitry and corticocortical connections in the genesis and synchronization of spike-wave rhythms. N Engl J Med, 1977 Apr 21, 296(16), 889 - 94 Spectinomycin versus tetracycline for the treatment of gonorrhea; Karney WW et al.; Spectinomycin and tetracycline are alternative drugs to penicillin in the treatment of gonorrhea . To compare the efficacy of these agents and their propensity to select resistant gonococci, we treated 4043 patients randomly with either 2 or 4 g of spectinomycin once or 9 g of oral tetracycline for four days . Minimum cure rate for anogenital gonorrhea was 94 per cent with either drug . Oropharyngeal infection responded poorly to spectinomycin in men, with failure of therapy in six of 11 . Postgonococcal urethritis in men was less common after tetracycline than after spectinomycin (P less than 0.005) . Spectinomycin failure was not related to drug resistance . Tetracycline failure correlated with resistance (P less than 0.0002); one fifth of the isolates resistant to 1.0 mug per milliter of tetracycline were not eradicated . For several reasons, including the appearance of beta-lactamase-producing gonococci, it is no longer clear that penicillin G is the "drug of choice" for gonorrhea . Spectinomycin and tetracycline are equally acceptable alternatives, each with distinct advantages and disadvantages. Med J Aust, 1977 Apr 16, 1(16), 586 - 8 Human infection caused by penicillin-insensitive pneumococci; Devitt L et al.; Three cases of infection, including two fatal ones, caused by pneumococci relatively resistant to penicillin are reported . The patients were a 19-year-old New Guinean with fatal multisegmental pneumonia, a 10-week-old Caucasian infant who died suddenly from purulent meningitis, and an Australian Aboriginal child aged two years with bronchiectasis complicated by pneumococcal bacteraemia . The pneumococci isolated (serotypes 6, 16 and 19) showed minimal inhibitory concentrations of penicillin G ranging from 0-1 microgram/ml to 1-0 microgram/ml (resistance ratios five to 50) and were also relatively resistant to penicillin V, methicillin, cloxacillin and cephalosporins. Brain Res, 1977 Apr 15, 125(2), 293 - 303 Anatomic localization of topically applied {14C}penicillin during experimental focal epilepsy in cat neocortex; Noebels JL et al.; 14C-labeled penicillin was topically applied to the suprasylvian gyri of adult cats in order to study the distribution of the convulsant agent at the onset of focal epileptogenesis . Using radioassay and autoradiographic techniques, a steep gradient of penicillin was found . At the time interictal EEG spike discharges appeared, 95% of the labeled drug was in the uppermost cortical layers (laminae I-III) . Analysis of the concentration profiles obtained by scintillation counting showed that penetration of penicillin into brain occurs primarily by passive diffusion . An apparent diffusion coefficient for penicillin in neocortex of 1.5 sq . mm/h was calculated using modifications of standard diffusion equations . It is apparent that with a rapidly acting topical convulsant such as penicillin, the dimensions of the neuronal pool actually in contact with the drug will change significantly over time . The changing boundaries of the epileptic neuronal aggregate must be taken into account when interpreting observations made within and around such experimentally produced epileptic foci. In Vitro, 1977 Apr, 13(4), 218 - 22 Earthworm coelomocytes in vitro; Toupin J et al.; Contamination and low viability of earthworm coelemocytes in tissue culture have delayed in vitro studies . Using penicillin, streptomycin, tetracycline and Amphotericin B, Lumbricus terrestis coelomocytes were maintained viable and uncontaminated for 10 days at 15degreesC in medium L-15 supplemented with 5 to 10% fetal bovine serum . The coelomocytes survived for at least 10 days with 85% viability as assessed by trypan blue exclusion assays and phagocytosis of heat-killed yeast . Studies on the thymidine uptake, however, were negative . With the involvement of coelomocytes in tissue graft rejection, in vitro techniques can now be applied to study their capacity in the immune response. Br J Vener Dis, 1977 Apr, 53(2), 113 - 4 Oral talampicillin in the treatment of gonorrhoea; Price JD et al.; Talampicillin was effective in eradicating the causitive organism in uncomplicated gonorrhoea, with only four treatment failures (1-6%) in 245 patients seen at least once after treatment . Symptoms, such as discharge, were seen in 61 patients at some stage after treatment but 31 of these cases were clear after one or two follow-up visits . The anitbiotic was well tolerated . One patient developed a maculopapular rash, penicillin allergy was reported in two patients, and a generalised itch (possibly penicillin allergy) in one further patient . A total of 241 out of 245 (98%) cases had the urethral gonococcus successfully eradicated with talampicillin . Talampicillin given in single doses appears to be an extremely good choice of antibiotic in the treatment of uncomplicated gonorrhoea in men. Br J Surg, 1977 Apr, 64(4), 277 - 80 Some surgical aspects of homozygous beta-thalassaemia; Craig RP et al.; The surgical aspects of the management of patients with homozygous beta-thalassaemia are reviewed, and the operative findings in 10 patients with the disease who underwent splenectomy are described . Postoperatively, blood consumption was reduced and there was a longer time interval between transfusions needed to maintain the haemoglobin level . Hyperplastic lymph nodes containing erythropoietic elements are always present, and the first reported case of extrabiliary obstructive jaundice caused by this tissue is included . All the patients survived for 2-3 years after treatment and there were no serious infections . All received prophylactic oral penicillin after surgery . Cholelithiasis was not found . Two malleolar ulcers were successfully grafted with split skin after preparation of the craters with silver sulphadiazine cream. Am J Vet Res, 1977 Apr, 38(4), 437 - 42 Pharmacology of procaine in the horse: evidence against the existence of a "procaine - penicillin" complex; Tobin T et al.; It has recently been suggested that procaine penicillin existed in solution in vitro and in vivo as a "procaine - penicillin" complex rather than as dissociated ions . In vivo, this complexed procaine was considered unavailable for hydrolysis by plasma esterases or for interaction with pharmacologic receptors for procaine . When procaine penicillin was intramuscularly given to horses, about 90% of the procaine in blood drawn from these horses was split at the same rate as authentic procaine or procaine penicillin added to equine blood in vitro . In vitro, procaine and procaine penicillin partitioned similarly from aqueous medium at physiologic pH into several organic solvents and were split at the same rate by blood or plasma esterases . Experiments on the time course of the partitioning of procaine from procaine penicillin into benzene showed no evidence for the existence of a "procaine - penicillin" complex within seconds after procaine penicillin was added to aqueous medium . Thin layer chromatography in 2 dimensions also yielded no evidence for the existence of this postulated complex . These results show no evidence in support of the "procaine - penicillin" hypothesis and argue against the physical and pharmacologic and forensic implications of this hypothesis. Trop Doct, 1977 Apr, 7(2), 51 - 6 Sexually transmitted diseases in the tropics . Epidemiological, diagnostic, therapeutic, and control aspects; Arya OP et al.; PIP: Sexually transmitted diseases, especially syphilis, gonorrhea, granuloma inguinale, and lymphogranuloma, are on the increase in the tropics . Several environmental factors contribute to disease transmission, including polygamy, high bride price, prostitution, civil war, urbanization, and economic development . Diagnosis is generally made on clinical grounds due to inadequate laboratoary facilities, and it is not possible to differentiate syphilis from yaws . This diagnostic inaccuracy has meant that there are no reliable data with which to assess epidemiologic trends, institute control measures, and evaluate their effects . Inadequate treatment, caused by a lack of drugs and poorly trained medical attendants, is also a major problem . Inappropriate treatment has caused over 80% of gonococcal strains in some areas to be penicillin-resistant . Late complications of gonorrhea, epididymitis, and salpingitis are frequently seen and lead to sterility in many cases . These complications are as prevalent in some areas today as they were in pre-sulfonamide days . A determined effort is needed to control the spread of these diseases . A central unit with modern facilities for diagnosis and treatment should be established . Diagnostic tests, such as culture and serology, should be introduced at the district and provincial levels . Rural health centers should employ a polyvalent microscopist who is trained to recognize gonococcus in stained smears . Given the high default rates, treatment should be simplified, using a single dose schedule where possible . The impracticality of follow-up requires epidemiologic treatment of contacts in many cases . If mass screening of pregnant women is not possible, Crede's silver nitrate eyedrops are recommended to prevent ophthalmia neonatorum . High risk populations, including bar girls, migrant workers, soldiers, and sailors, should be targeted for health education campaigns . Such education should focus on regulation of sexual behavior, condom use, and, when infection is present, the importance of avoiding self-medication, early treatment, and cooperation in contact tracing . J Laryngol Otol, 1977 Apr, 91(4), 331 - 40 Treatment of acute suppurative otitis media; Lorentzen P et al.; The effect of myringotomy versus Penicillin therapy in the treatment of patients with acute suppurative otitis media was compared . A third group of patients treated with both myringotomy and Penicillin was included in the investigation . Ten days after institution of the treatment there were significantly more days with secretion/bulging drum in the myringotomy group than in the two other groups . At this time Penicillin therapy was started also in those patients belonging to the myringotomy group . With this reservation the occurrence of such late complications as secretory otitis media and relapses was the same, independent of treatment . No cases of mastoiditis were observed. Electroencephalogr Clin Neurophysiol, 1977 Apr, 42(4), 518 - 27 The results of penicillin G Administration of chronic unrestrained cats: electrographic and behavioral observations; Rodin E et al.; Intramuscular administration of penicillin G was carried out in a series of 27 chronic cat preparations . In addition to the EEG, the high frequency components of cerebral electrical activity were also recorded from cortical and deep structures . Videotape recordings using split-screen technique allowed correlations of the animal's clinical state with the EEG . The results showed that 'spike-wave' type activity occurred earliest in the cortex . The discharges were also best formed in cortical and thalamic structures . The other deep structures showed characteristic bursting, but not of the 'spikewave' type variety . The cerebellum showed also early participation . Clinical expressivity of the bursts depended upon the state of alertness of the animal, the height of the spike components and the extent of depth participation . The high frequency recordings revealed characteristic alternation of decrease and increase in activity mostly in cortical structures and to a lesser extent in thalamus . Pontine and medullary reticular formation areas showed usually no changes in the high frequency records during the bursts . When major seizures were induced, they were always of focal onset rather than of the primary generalized type as one sees with pentylenetetrazol . Different cortical or deep structures served as the initiating site in different animals . It was concluded that systemic penicillin adminstration does not lead to a truly primary generalized form of epilepsy, but produces its effects by multifocal activation of various cerebral structures, with cortex and cerebullum usually showing earliest involvement. Electroencephalogr Clin Neurophysiol, 1977 Apr, 42(4), 480 - 92 The penicillin focus . I . Distribution of potential at the cortical surface; Goldensohn ES et al.; The potential field of a penicillin focus of controlled size was recorded from a rectangular array of 12 electrodes occupying a 4 X 6 mm area on the exposed anterior sigmoid gyrus of the cat . The array was made with 2 mm interelectrode spacing of 0.4 mm I.D . glass capillary tubes filled with Ringer's in agar, excepting one containing penicillin to create the focus . Early in the development of the focus a negative spike appears at the penicillin electrode reaching amplitudes of as high as 3,000 muV while all of the other electrodes showed no synchronous activity of more than 100 muV . Within the first 15 min spike activity becomes visible at about 100 muV at all the electrodes and after 30 min, waveforms of all activity become quite stable . At the penicillin-containing electrode, at intervals of 2--10 sec each, a negative sharp wave of up to 4 mV occurs, having a shorter rise time than fall time . A smaller positive spike of about 30 msec duration which showed marked variations in amplitude often preceded the stable negative sharp wave . During the rise of the negativity at the penicillin electrode, practically all the surrounding electrodes showed a predominantly positive spike . This was occasionally followed by negativity during the falling phase at the penicillin electrode . Displays of potential surfaces interpolating the average values at the 12 recording points on the cortex at 4 msec intervals demonstrate a relationship between the field of the sharp wave at the penicillin focus which is less than 2 mm in diameter and that of the surrounding electrode which indicates that symmetrically located synaptic inhibitory processes are strongly activated in areas adjacent to the small simultaneous excitation at the penicillin electrode . Degrees of attenuation of interictal spikes that take place between cortex and scalp are estimated from the measured potential distributions . Explanation is offered for the reported apparent discrepancies between the findings at the cortex and the scalp EEG. Exp Brain Res, 1977 Mar 30, 27(3-4), 237 - 43 Extracellular free calcium and potassium during paroxsmal activity in the cerebral cortex of the cat; Heinemann U et al.; Extracellular calcium and potassium activities (aCa and aK) as well as neuronal activity were simultaneously recorded with ion-sensitive electrodes in the somatosensory cortex of cats . Baseline aCa was 1.2-1.5 mM/l, baseline aK 2.7-3.2 mM/l . Transient decreases in aCa and simultaneous increases in aK were evoked by repetitive stimulation of the contralateral forepaw, the nucleus ventroposterolateralis thalami and the cortical surface . Considerable decreases in aCa (by up to 0.7 mM/l) were found during seizure activity . A fall in aCa preceded the onset of paroxysmal discharges and the rise in aK after injection of pentylene tetrazol . The decrease in aCa led also the rise in aK during cyclical spike driving in a penicillin focus . It is concluded that alterations of Ca++ dependent mechanisms participate in the generation of epileptic activity. Wien Klin Wochenschr, 1977 Mar 18, 89(6), 199 - 200 {Spectinomycin (Trobicin) in Male Gonorrhoea (author's transl)}; Honigsmann H et al.; 28 male patient with uncomplicated acute gonorrhoea were treated with a single intramuscular injection of 2.0 g spectinomycin . All of them were cured . The suitable alternative to penicillin in the treatment of uncomplicated gonorrhoea, but it will not cure simultaneously-acquired syphilis . Its use should, therefore, be restricted to specific indications. Acta Med Iran, 1977 Mar, 19(2), 104 - 12 Cervicofacial actinomycosis in man; Tabibi V et al.; Two cases of advanced jaw destruction due to Actinomyces is reported; one with diabetic diathesis and a history of tooth extraction the other had a trauma of the mandible with the fracture; good results were obtained with penicillin therapy. Z Gesamte Inn Med, 1977 Mar 1, 32(5), 123 - 5 {Proof of drug hypersensitivity using an in vivo leukocyte migration inhibition test}; Ruffert K et al.; 22 chloramphenicol allergics, 10 penicillin allergics and 6 patients with a chromate eczema as well as altogether 34 non-allergic control persons with healthy skin were examined according to the skin chamber method . After addition of the adequate antigen (chloramphenicol, penicillin, ammonium bichromate) into one of the two simultaneously applied skin chambers in sensitized persons an inhibition of the leucocyte migration in the antigen chamber develops . The polymorphonuclear neutrophilic granulocytes mobilised into the inflammation field were regarded as indicator cells . 5 chloramphenicol allergics with eczematous skin abnormalities and all control persons were negative . The investigation method is simply to be performed and therefore it is particularly suitable for clinical routine work. Z Gesamte Inn Med, 1977 Mar 1, 32(5), SUPPL 73 - 8 {Current problems in the pathology of the thyroid gland}; Dhom G; 22 chloramphenicol allergics, 10 penicillin allergics and 6 patients with a chromate eczema as well as altogether 34 non-allergic control persons with healthy skin were examined according to the skin chamber method . After addition of the adequate antigen (chloramphenicol, penicillin, ammonium bichromate) into one of the two simultaneously applied skin chambers in sensitized persons an inhibition of the leucocyte migration in the antigen chamber develops . The polymorphonuclear neutrophilic granulocytes mobilised into the inflammation field were regarded as indicator cells . 5 chloramphenicol allergics with eczematous skin abnormalities and all control persons were negative . The investigation method is simply to be performed and therefore it is particularly suitable for clinical routine work. Neurol Neurochir Pol, 1977 Mar-Apr, 11(2), 211 - 4 {Nervous system changes in patients treated with penicillin during the period of symptomatic and early asymptomatic syphilis}; Zielinski T et al.; The results of cerebrospinal fluid examination of 451 patients treated for syphilis were analysed . In 34 patients abnormalities were found in the protein level, cell number and serological investigations . Thus, there is an absolute indication to cerebrospinal fluid examination in each case in which serological tests remain positive despite adequate specific therapy. Blood, 1977 Mar, 49(3), 477 - 82 Techniques for demonstration of the specificity of circulating anticoagulants against antihemophilic factor (factor VIII), with studies of two cases possibly related to diphenylhydantoin therapy; Poon MC et al.; Circulating anticoagulants against antihemophilic factor (AHF, factor VIII) sometimes seem to inactivate other clotting factors as well . Measurements of the concentration of clotting factors in highly diluted plasma, or after neutralization of the anticoagulant with purified AHF, have demonstrated the specific nature of the anticoagulant in a patient under treatment with diphenylhydantoin . A second case in a patient treated with this agent, and with penicillin, an agent previously associated with the evolution of circulating anticoagulants, is also described. EEG EMG Z Elektroenzephalogr Elektromyogr Verwandte Geb, 1977 Mar, 8(1), 1 - 17 {The phenomenon of synchronization in the status epilepticus produced by penicillin and its changes after Clonazepam (author's transl)}; Petsche H et al.; The purpose of this series of experiments was to understand how Clonazepam changes the mechanisms of synchronization in seizures . Penicillin was applied to the rabbits cortex . Interictal spikes and seizures were recorded with multiple electrodes from both the cortical surface and intracortically . The spatio-temporal relationships during these electrical events were studied by topographical methods . Moreover, power spectrum and coherence estimates were performed . A most characteristic feature seen with low doses of Clonazepam is a regularization of the spatio-temporal behaviour of both spikes and seizures . The number of tonic phases considerably increases at the cost of clonic phases . The seizures take more time to become generalized . The generator-zones become larger . This is explained by a decrease of the number of neurones--by Clonazepam--which are still left to produce "paroxysmal depolarization shifts" . The findings confirm the increase of postsynaptic cortical inhibition under Clonazepam, as demonstrated by various authors. J Bacteriol, 1977 Mar, 129(3), 1239 - 44 Activity of murein hydrolases in synchronized cultures of Escherichia coli; Hakenbeck R et al.; Murein hydrolase activities were analyzed in synchronized cultures of Escherichia coli B/r . Cell wall-bound murein hydrolase activities, including the penicillin-sensitive endopeptidase, increased discontinuously during the cell cycle and showed maximum activity at a cell age of 30 to 35 min (generation time, 43 min) . Maximum activity was observed at the same time that the rate of cell wall synthesis reached its maximum . These oscillations depended on the termination of replication: no increase in hydrolase activity was found if deoxyribonucleic acid synthesis was inhibited at an early time in the life cycle . In contrast, the activity of another murein hydrolase that was not tightly bound to the membrane (transglycosylase) increased exponentially with time, even when deoxyribonucleic acid synthesis was inhibited. Arch Dermatol, 1977 Mar, 113(3), 325 - 7 Bullous disease of childhood: report of a case demonstrating antibasal cell antibody; Shmunes E et al.; This report describes a child with protracted bullous disease responsive only to high doses of steroids, who on immunofluorescent testing, consistently displays antibasal cell antibody . The child had been treated with penicillin a week prior to the development of the bullous disease . The etiologic possibility of this drug history in the evolution of the bullous disease is raised, with particular respect to recent reports of similar circulating antibody in drug reactions. Arch Microbiol, 1977 Mar 1, 112(2), 219 - 23 Penicillinase (beta-lactamase) formation by blue-green algae; Kushner DJ et al.; Beta-Lactamase (penicillinase) activity was found in a number of strains of blue-green algea . In some cases, this enzyme permitted algae to overcome the inhibitory effects of penicillin . Production and localization of beta-lactamase were studied in a unicellular species, Coccochloris elabens (strain 7003), and in a filamentous, nitrogen-fixing Anabaena species (strain 7120) . When cells were grown in a neutral medium with NaNO3 as N source, the pH rose during growth; at a pH of about 10, most of the enzyme was expressed equally well in intact or disrupted cells . If the pH was kept near neutrality during growth by gassing with CO2 in N2 or by growth under conditions of N2 fixation, the enzyme remained cell-bound and cryptic for most of the growth phase, being measurable only after cells were disrupted . The enzymes from strains 7003 and 7120 had greater activity on benzyl penicillin and other penicillins than on cephalosporins . Some differences were observed in the "substrate proliles" of penicillinases from the two strains against different penicillins. Antibiotiki, 1977 Mar, 22(3), 211 - 6 {Penicillin amidase from E . coli . A direct spectrophotometric method of determining the enzyme's activity}; Nys PS et al.; A method for determination of the enzymatic activity of penicillinamidas (PA) based on spectrophotometric estimation of the stained product amount produced in hydrolysis of 4-phenylacetamido-2-nitrobenzoic acid (PANBA) catalyzed by the enzyme is proposed . Some physico-chemical properties of the substrate and the stained product were studied . The kinetic parameters of the PANABA enzymatic hydrolysis were determined . Catalytic activity of some enzyme products of PA of different purity levels was studied comparatively in reactions of PANBA and benzylpenicillin hydrolysis. Brain Res, 1977 Feb 25, 122(3), 513 - 21 Longitudinal changes of brain amino acid content occurring before, during and after epileptic activity; Mutani R et al.; In cats affected with cortical epileptogenic foci induced by penicillin application to and cobalt implantation into the pericruciate area, the brain amino acids contents were determined in the focus as well as in extrafocal areas . In different groups of animals, brain removal for biochemical determinations was performed at different times before, during and after epilepsy and the values compared to controls . The only amino acid to show a significant change before appearance of spikes in both types of epilepsy was taurine, which decreased . Cobalt epilepsy was accompanied by changes in a larger number of amino acids than penicillin epilepsy: in the former the brain content of taurine, GABA, aspartate, glutamate, serine, threonine, glycine and alanine was altered . The changes were proportional to the severity of epilepsy and more prominent in the focus area . After disappearance of spikes the levels of most amino acids returned to normal except for some amino acids, previously unaffected by penicillin epilepsy, which were decreased . It is proposed that the decrease in brain taurine, occurring before the appearance of penicillin and cobalt epilepsy, could increase the excitability of a certain neuronal population and thus, by potentiating the effects on neurons of penicillin and cobalt, contribute to the initiation of epilepsy. Appl Environ Microbiol, 1977 Feb, 33(2), 249 - 53 Study of conditions of production of roquefortine and other metabolites of Penicillin roqueforti; Scott PM et al.; Experiments to determine optimum yields of roquefortine, isofumigaclavine A, and PR toxin, metabolites from Penicillum roqueforti Thom, were performed . Four strains, isolated from blue cheese, and five liquid media were evaluated, although not all permutations were studied . Sucrose (15%)-yeast extract (2%) was the medium chosen for time-course studies at 25 and 15 degrees C using one favorable strain . At 25 degrees C, maximum estimated yields of roquefortine were about 100 mg/liter in the mycelium by 16 days, and no subsequent degradation of this alkaloid was observed . On the other hand, production of PR toxin in the medium peaked at 770 mg/liter at 21 days . At 15 degrees C, yields of roquefortine and PR toxin after 49 days were 60 to 70% of the maximum yields obtained at 25 degrees C . However, about three times more isofumigaclavine A (up to 11 mg/liter) was formed in the mycelium at 15 degrees C than at 25 degrees C . All four strains of P . roqueforti procedure both roquefortine and PR toxin on the sucrose-yeast extract medium at 25 degrees C; isofumigaclavine A was detected in all but one strain grown on this medium. Transplantation, 1977 Feb, 23(2), 136 - 41 Maintenance of the functional state of isolated rat liver by hypothermic perfusion with an erythrocyte-free medium; Lee D et al.; Isolated rat liver was studied before, during, and after hypothermic perfusion at 5 C for 24, 48, or 72 hr with an acellular perfusate consisting of 7% bovine serum albumin in Kreb-Ringer buffer containing glucose, penicillin, and streptomycin . Bile production ceased at 5 C but resumed when the temperature was raised to 35 C . The rate of flow and the total amount produced was unaffected by 24 hr of hypothermia but decreased when the cooling period was extended to 48 and 72 hr . The data of other workers was used to show a correlation between bile flow and oxygen consumption by the liver . Cooling also caused the release of potassium into the perfusate but it was quickly reaccumulated after rewarming; however, the extent and rate of reaccumulation decreased as the cooling period increased, as did the ability of the livers to retain the ion . Urea synthesis did not cease after cooling and after rewarming, the rate of synthesis increased as the period of hypothermia was lengthened . The maximum concentration of urea in the perfusate was found when rewarmed livers had produced 200 mumol of urea but at this point, control livers had produced 280 mumol . The concentration of glucose in the perfusate of livers maintained at 35 C showed peaks at 2 and 9 to 10 hr after the start of perfusion . After cooling for 24 hr these peaks arose at 2 and 7 hr after rewarming, but with 48 hr of hypothermia, these peaks were higher and appeared at 2 and 4 hr . When the cooling period was extended to 72 hr, only a single peak was seen 2 hr after rewarming . These results suggest that rat liver can be cooled to 5 C for 24 hr with little effect on its functional characteristics but a marked decline becomes apparent when the cooling period is extended beyond 24 hr . None of the livers studied was transplanted after perfusion and it remains to be seen how the functional tests conducted in vitro correlate with the ability of the livers to support life. Acta Allergol, 1977 Feb, 32(1), 8 - 14 Cellular immunity to penicillin in newborns; Herve M et al.; A leukocyte migration micromethod has been used to study the cellular immunity to penicillin (CIP) in newborns . No detectable CIP has been found in newborns who had not been treated with penicillin . Fifteen per cent of the newborns treated with pencillin were found to have a CIP as early as the 12th day of life. Arch Intern Med, 1977 Feb, 137(2), 156 - 60 Infectious syphilis mimicking neoplastic disease; Drusin LM et al.; Five patients who were initially evaluated for malignant neoplasm actually had infectious syphillis (one primary, two secondaries, two secondaries with persistence of primary) . Two patients were considered for radical surgery and one for extensive radiation and/or chemotherapy . In four patients an elevated routine admission VDRL was the first indication of the correct diagnosis . Dark-field examination is the most important laboratory test in the diagnosis of primary syphillis; VDRL and FTA-ABS are most important in confirming secondary syphillis . Penicillin remains the drug of choice for therapy . At a time when the incidence of sexually transmitted diseases is increasing, it is extremely important to develop adequate educational programs for medical students and physicians. Am J Ophthalmol, 1977 Feb, 83(2), 206 - 12 Corneal endothelium under various storage conditions; Geeraets R et al.; Three rabbit corneas each were stored in McCarey-Kaufman (M-K) medium, rabbit serum, and in a moist chamber at 4 degrees C refrigeration for various lengths of observation . The endothelial cells appeared normal under all conditions for the first 24 hours as compared with control corneas processed concurrently with each experimental group . After 48 hours of storage the specimens in the moist chamber showed isolated endothelial cell damage . The endothelia in M-K medium or rabbit serum appeared viable up to six days without significant differences although those stored in rabbit serum showed a better preservation of microvilli on individual endothelial cells . Under all conditions a mild shrinkage of the cells seemed to have taken place as indicated by the more pronounced cell boundaries . We incubated an equal number of control rabbit corneas at 37 degrees C with 5% CO2 and moist air in M-K medium, serum, and minimal essential medium (MEM) with 10% fetal calf serum and 100 units/ml of a penicillin and streptomycin mixture . In serum, the endothelia showed rapid destruction with swelling of the entire cornea . Those stored in M-K medium maintained a normal endothelial covering of the cornea up to six days . At nine days of storage, marked cellular changes were observed with dehiscence of the cellular layer . When stored in the MEM mixture, the endothelial cells showed a normal layer without obvious cell damage when compared with those stored in M-K medium up to four days . However, after six and nine days of storage, cellular destruction was greater in these specimens than in those stored in M-K medium . In addition, there was considerable swelling of the whole cornea under this storage condition. Arch Invest Med (Mex), 1977, 8(2), 85 - 90 Surface fixation as a rapid test for detection of penicillin antibodies; Ruiz-Castaneda M et al.; Surface fixation has been used to detect antigen antibody-reactions with bacteria, protozooa and in some instances with drugs considered responsible of adverse reactions attributed to allergy . The application of this method to penicillin is reported . The test has been positive with serum from well-proven cases of hypersensitivity but also in subjects that had undergone penicillin treatment . So far, no comparative observations with conventional tests have been made; however, if the presence of circulating antibody is considered the cause of adverse reactions to penicillin, this simple test may have clinical usefulness. Monogr Allergy, 1977, 11, 116 - 23 Evaluation of genetic control of the immune response to penicillin in man; Spengler H et al.; HLA typing of 46 patients with demonstrated penicillin allergy did not show significant correlation of hypersensitivity to the penicilloyl group with any HLA antigens . On the other hand, lymphocytes from penicillin-sensitive patients generated nonspecific cytotoxic cells (e.g., cytotoxic for P 815 mastocytoma mouse cells or chicken red blood cells) when cultured in vitro together with penicillin . Under similar conditions, only some lymphocyte populations from nonpenicillin-sensitive normal individuals showed cytotoxicity . Although family studies are required to demonstrate that differences in the generation of cytotoxic cells by penicillin in nonsensitive populations are due to genetic factors, it is obvious that attempts to achieve primary sensitization in vitro is the most rational approach to a study of Ir genes in man. Trans R Soc Trop Med Hyg, 1977, 71(1), 49 - 51 Louse-borne relapsing fever: II . Combined penicillin and tetracycline therapy in 160 Sudanese patients; Salih SY et al.; One hundred and sixty patients with louse-borne relapsing fever were treated with a combination therapy of procaine penicillin and tetracycline . Fortified procaine penicillin B.P . was given as 400,000 units in the first day . This was followed the next day by 2 g tetracycline orally in divided doses for seven days . A mild rise in temperature was observed in 22 (13-7%) patients within four hours of administering penicillin . Rigors and hypotension occurred in one patient . Relapse occurred in two patients, of whom one had concomitant typhoid and one visceral leishmaniasis . The combined therapy has been found to be effective and safe . It lacks the disadvantages of penicillin (relapses) and tetracycline (severe reaction), when each drug is used alone. Br J Haematol, 1977 Jan, 35(1), 135 - 52 Effects of cephalothin and penicillin G on platelet function in vitro; Cazenave J-P et al.; High concentrations of cephalothin or penicillin G inhibit a number of the functions of human or rabbit platelets in citrated platelet-rich plasma (PRP) and in suspensions of washed platelets . The reactions shown to be inhibited are: ADP-induced shape change and the primary and secondary phases of aggregation and release induced by ADP or adrenaline in human cirtated PRP; release and aggregation of washed human platelets exposed to collagen, thrombin, vasopressin, or the ionophore A 23,187; aggregation of washed human platelets exposed to phytohaemagglutinin from Phaseolus vulgaris (PHA) or polylysine; release induced by concanavalin A or PHA in suspensions of washed platelets from rabbits; platelet adherence to a collagen-coated surface or to the damaged intimal surface of the rabbit aorta; platelet factor 3 availability; lysis of rabbit platelets by an antiserum directed against them; and clot retraction . Neither antibiotic affected serotonin-induced aggregation; a high concentration of cephalothin slightly inhibited the initial rate of serotonin uptake . Penicilloic acid showed about half the inhibitory effect of penicillin G on ADP-induced aggregation . In citrated human platelet-rich plasma, ampicillin and oxacillin inhibited ADP-induced aggregation to the same extent as similar concentrations of penicillin G; in suspensions of washed platelets, however, ampicillin was less inhibitory than penicillin G or oxacillin . Platelet ultrastructure, assessed by transmission electron microscopy, was not visibly altered . Evidence that the antibiotics become bound to platelets is the finding that platelets incubated with the antibiotics ans resuspended in fresh media showed less response to aggregating agents compared with control platelets . Penicillin G and related antibiotics may be inhibitory because they coat the platelet surface . Their effects on platelet functions are probably responsible for excessive bleeding and increased bleeding times observed in patients and volunteers receiving high doses of these antibiotics. Jpn J Antibiot, 1977 Jan, 30(1), 121 - 3 {Clinical studies with amoxicillin in patients with biliary tract infections (author's transl)}; Hoshino H et al.; Six patients with biliary tract infections who came to our hospital were administered 1.5 g (potency) per day of amoxicillin, a synthetic penicillin for oral use, to examine its clinical effects . The results were as follows . 1) Out of six patients with biliary tract infections, amoxicillin proved to be effective in four patients, ineffective in one patient, and unknown in one patient . 2) Oral administration of amoxicillin gave the same success in treatment as injection of other synthetic penicillin preparations in mild cases with the exception of acute deterioration of chronic with subjective symptoms such as nausea and vomiting . 3) No noteworthy side effects were observed in any cases examined this time. Forensic Sci, 1977 Jan-Feb, 9(1), 33 - 6 Fatal poisoning by potassium in human and rabbit; Bhatkhande CY et al.; An unusual case of suicidal poisoning by intra venous injection of K+ is presented to demonstrate the limitations of toxicological analysis of post-mortem examination in such a case . Its potential for a "clean undetectable murder" in a homicidal situation is indicated, the parallel being intra muscular insulin/penicillin poisoning which on the other hand are detectable . The intra venous lethal dose is approximately 30-35 mg K+/kg (Human/Rabbits). J Pharmacol Exp Ther, 1977 Jan, 200(1), 65 - 74 Glutathione S-transferases: an evaluation of their role in renal organic anion transport; Pegg DG et al.; Organic anion transport capacity measured as accumulation of p-aminohippurate by renal cortical slices was less in kidneys from newborn rats and rabbits than adults and increased with age . Glutathione (GSH) S-aryltransferase activity in 100,000 X g supernatant of renal homogenates, an estimate of GSH-S-transferase concentration in the tissue, was also less in newborn of both species . Enzyme activity increased to adult values by 1 week of age in rats, prior to maturation of transport capacity . Enzyme activity in rabbit kidney was not different at 1 day and 2 weeks but was increased by 4 weeks coincident with transport maturation . In rats, 25 mg/kg of 3-methylcholanthrene administered once a day for 3 days significantly increased enzyme activity but had no effect on transport capacity . Chronic ammonium chloride acidosis increased enzyme activity 8-fold but decreased transport capacity . Forty-eight hours after unilateral nephrectomy in rats transport capacity was significantly increased with little effect on enzyme activity . L-Methionine-SR-sulfoximine (1.85 mmol/kg) significantly reduced glutathione concentration in renal cortex but had no effect on transport capacity . Organic anion transport was greater in male than in in female mice yet there was no difference in enzyme activity between sexes . 3-Methylcholanthrene (10,20, 30 and 40 mg/kg) administered to 2-week-old rabbits twice daily for 3 days increased transport in a dose-dependent manner . GSH S-transferase activity was also increased . Penicillin (90,000 I.U . twice daily for 2 days) similarly increased transport but had no stimulating effect on enzyme activity . The apparent lack of correlation between transport capacity and GSH S-transferase in several instances suggests that GSH S-transferase concentration is probably not the rate-limiting step in renal organic anion transport. J Neurophysiol, 1977 Jan, 40(1), 9 - 15 Antidromic activity in visual radiation during evoked cortical responses; Rosen AD et al.; 1 . Antidromic stimulation of the visual radiation of cats has been used to investigate the possibility that some of the activity in principal geniculate cells following an optic tract stimulus is antidromic . Single spikes were selected from two classes of poststimulus activity to condition the antidromic test spike--the undoubted orthodromic postsynaptic spike and the later spikes, occurring up to 100 ms after the optic tract stimulus . 2 . In 15 of 39 cells the minimum antidromic activation times and the minimum spike-spike intervals were found to be shorter and latencies for antidromic stimulation were longer when the conditioning spikes belonged the class of late poststimulus activity . The differences are in accord with the assumption that some of the conditioning spikes were antidromic . 3 . Test spikes were frequently found to have long and variable latency when the conditioning spike occurred more than 45 ms after the optic tract stimulus . Possible reasons are briefly discussed . 4 . It is suggested that antidromic activity may occur in conditions of the cortex that are more physiological than those associated with a penicillin-induced seizure focus . Some possible mechanisms and functional significance are briefly discussed. Ann Rech Vet, 1977, 8(3), 327 - 31 {Treatment of mastitis in dry cows: treatment of all cows vs treatment of infected cows only (author's transl)}; Roguinsky M et al.; Within a herd, three groups have been randomly constituted . --Control group: No dry cow therapy . -- Total Treatment group: all cows were submitted to dry cow therapy, in their four quarters . -- Limited Treatment group: cows were submitted to dry cow therapy in their four quarters, only if at least one quarter had given a CMT larger than or equal to +++, in the month before drying-off . --The cows were treated either with cloxacillin or with penicillin-streptomycin in 3% monostearate . The number of cows and quarters examinated and treated are given in table 1; the results of treatments are indicated in table 2 . No significant differences can be found between Total and Limited Treatment groups; a slight improvement was observed when compared to Control group . Cloxacillin and penicillin-steptomycin gave similar results . The pathogenic and practical signification of these results is discussed. Bilt Hematol Transfuz, 1977, 5(2), 23 - 9 {Immune hemolytic anemia and thrombocytopenia after peroral therapy with a penicillin derivative (phenoxymethylpenicillin)}; Jelic S et al.; A previously apparently healthy male patient developed Coombs-positive haemolytic anaemia and thrombocytopenia during phenoxymethylpenicilline intake . A drug dependent IgG red cell antibody was demonstrated in patient's serum . In vitro tests with patient's serum suggested formation of complexes involving penicilline which by complement mediated mechanisms were able to agglutinate red cells in saline medium . Platelet agglutinins were demonstrated in patient's serum but their drug dependence has not been fully elucidated . The mechanism of drug mediated autoantibody synthesis might have been involved in the pathogenesis of thrombocytopenia. Clin Allergy, 1977 Jan, 7(1), 21 - 8 Specific and total serum IgE measurements in the diagnosis of penicillin allergy . A long term follow-up study; Kraft D et al.; Sera from 204 patients with acute or former reactions following penicillin treatment were investigated by RAST with specificity for benzylpenicilloyl and phenoxymethyl-penicilloyl . The IgE antibody levels were followed up for of more than 2 years . Positive results could be observed at the time of the acute reactions and the weeks following; later months or years in many cases . Occasionally negative RAST results occurred within 30 days; on the other hand high levels of specific IgE persisted for years in some patients . Total serum IgE measured by RIST and the RAST results showed similar patterns, with mean levels of 568 u/ml between 0 and 30 days after the penicillin allergic reaction, 286 u/ml between 30 days and 1 year, and 195 u/ml in cases after 1 year corresponded well with the observed decline in specific IgE . Skin tests performed with penicilloyl-polylysine in 118 patients showed an overall correlation of 91-5% with the RAST results . Differences between the two test systems were observed in patients with a long interval between the test and the last allergic attack . None of the patients with proved penicillin allergy had atopic diseases or a history of atopy . On the basis of these findings it is suggested that the determination of both circulating specific IgE and total IgE should be of great value for diagnostic purposes during acute drug reactions and in the months immediately afterwards. Int Arch Allergy Appl Immunol, 1977, 54(1), 19 - 28 Antibody reactivity in penicillin-sensitive patients determinated with different penicillin derivatives; Juhlin L et al.; 35 individuals showing reactions to penicillin of anaphylactic shock, angioedema or urticaria were investigated . Their skin sensitivity was analysed using 16 different penicillin derivatives . In addition, the content of circulating reagins against the penicilloyl structure in the patient's sera were analysed using RAST . 17 of the patients had negative skin reactions and RAST results to all substances tested . The other 18 were skin test-positive to at least one derivative but showed markedly heterogeneous patterns of skin reactivity . 14 had positive reactions against penicilloyl structures accompanied by anti-penicilloyl reagins . Four patients showed doubtful reactions only to penicillin or penicilloate and/or penilloate . These patients also had very low levels of reagins against penicilloyl in their sera . Positive skin test results using monovalent penicillin derivatives such as penicillin, penicilloate, penilloate, penicilloyl amide, penicilloyl-formyl-lysine, penicillamine, which cannot form a multivalent antigen with penicillyol specificity, indicated formation of other derivatives of importance in penicillin allergy, e.g., penicillamine protein conjugates . Three patients showed skin reactions to ampicillin polymer and two to benzyl-penicillin polymer . The skin tests performed with the penicillin derivatives used do not seem to give more information on the sensitivity of the patients than does the RAST using penicilloyl structures. Zh Mikrobiol Epidemiol Immunobiol, 1977, (1), 90 - 3 {Biological properties and ultrastructure of brucellae during L-transformation and reversion}; Tolmacheva TA et al.; There was shown a difference in the biological properties and the ultrastructure of two strains of brucellae, spheroplasts obtained from them under the action of penicillin, L-form and revertants obtained from the L-form . Spheroplasts formation was characterized by a change of brucellae into R-form and some virulence reduction . The cells had an outer and a cytoplasmic membranes, and usually lost their capacity to binary division . L-forms were obtained during the 9th and the 35th passage on a medium with penicillin; their formation was accompanied by the change in serological properties of the culture and significant reduction of the virulence; the cells were characterized by a marked polymorphism and the capacity to budding; they had 2 membranes on the cell surface and an intensively developed system of intracytoplasmic membranes . The revertants formed on the medium without penicillin during the 16th-30th passage or spontaneously on the medium with penicillin . They differed from the initial strains of brucella culture by a marked increase in penicillin-resistance, by the changes in serological properties, and also by polymorphism of cells, capable, however, of binary division. Am J Hematol, 1977, 2(2), 193 - 201 Overwhelming postsplenectomy infection; Krivit W; One of the more intriguing aspects of the spleen is the protection against certain bacterial infections afforded by its unique vascular and immune function . There have been extensive clinical surveys which indicate an incidence of overwhelming postsplenectomy infection (OPSI) above that of the disease for which the splenectomy was done . In the absence of the spleen, either congenital or subsequent to surgical removal, this overwhelming sepsis has a 50% case fatality rate . The most common infective organism has been Diplococcus (tstreptococcus) pneumoniae (D . pneumoniae) . Intensive investigations indicated loss of phagocytic function of the spleen, depression of serum IgM levels, a possible suppression of the lymphocyte responsiveness, and changes in opsonin-alternative complement system as potential causes of OPSI . Preventive measures against OPSI include trials of prophylactic Phenoxymethyl Penicillin (penicillin) and pneumococcal vaccine. Arch Immunol Ther Exp (Warsz), 1977, 25(1), 25 - 34 Cell-mediated immunity in experimental syphilis in rabbits; Metzger M et al.; The development of cell-mediated immunity was studied in rabbits: a) experimentally injected with T . pallidum, and b) artificially immunized with nonviable T . pallidum . The macrophage migration inhibition test (MMI test) using ultrasonicate of T . pallidum as antigen was employed to demonstrate this type of immunologic response . Lymphocytes of syphilitic rabbits were found to exert a pronounced inhibitory effect upon macrophage migration as early as one month after infection; between the fourth and sixth month, a transient decrease of this capacity occurred, followed by a slow but steady increase during the next two years, i.e . until the end of the observation period . In rabbits in which the infection had been controlled by penicillin treatment in the fifth month, no increase but gradual diminution of this capacity was observed . In the group of rabbits artificially immunized with nonviable T . pallidum, the MMI response appeared very shortly after commencement of the immunization and persisted for about nine months after completion of the immunization procedure . Only a crude correlation could be established between levels of the MMI response of the immunized animals and their resistance to infection with T . pallidum. Antibiotiki, 1977, 22(2), 130 - 6 {Penicillin amidase from E . coli . A comparative study of the stability of penicillin amidase immobilized by various means}; Nys PS et al.; The properties of immobilized penicillinamidases prepared by different methods were studied . Immobilization of penicillinamidase was achieved by using the covalend binding ion exchange sorption, incorporation into gel and other procedures . The effect of the carrier type, purification level of the native enzyme and other factors on stability of the immobilized preparations was studied . In 4 cases significant stabilization of the enzyme in the immobilized state was observed, while in 3 cases destabilization was registered. Eur J Biochem, 1977 Jan, 72(2), 341 - 52 Properties of the penicillin-binding proteins of Escherichia coli K12,; Spratt BG; Benzyl{14C}penicillin binds to six proteins with molecular weights between 40000 and 91000 in the inner membrane of Escherichia coli . Two additional binding proteins with molecular weights of 29000 and 32000 were sometimes detected . All proteins were accessible to benzyl{14C}penicillin in whole cells . Proteins 5 and 6 released bound benzyl{14C}penicillin with half times of 5 and 19 min at 30 degrees C but the other binding proteins showed less than 50% release during a 60-min period at 30 degrees C . The rate of release of bound penicillin from some of the proteins was greatly stimulated by 2-mercaptoethanol and neutral hydroxylamine . Release of benzyl{14C}penicillin did not occur if the binding proteins were denatured in anionic detergent and so was probably enzymic . No additional binding proteins were detected with two {14C}cephalosporins . These beta-lactams bound to either all or some of those proteins to which benzyl{14C}penicillin bound . No binding proteins have been detected in the outer membrane of E coli with any beta-{14C}lactam . The binding of a range of unlabelled penicillins and cephalosporins were studied by measuring their competition for the binding of benzyl{14C}penicillin to the six penicillin-binding proteins . These results, together with those obtained by direct binding experiments with beta-{14C}lactams, showed that penicillins bind to all six proteins but that at least some cephalosporins fail to bind, or bind very slowly, to proteins 2, 5 and 6, although they bind to the other proteins . Since these cephalosporins inhibited cell division and caused cell lysis at concentrations where we could detect no binding to proteins 2, 5 and 6, we believe that these latter proteins are not the target at which beta-lactams bind to elicit the above physiological responses . The binding properties of proteins 1, 3, and 4 correlate reasonably well with those expected for the above killing targets. Curr Probl Clin Biochem, 1977, 7, 59 - 74 Cytochrome C as antidote in mice poisoned with the mushroom toxin alpha-amanitin; Floersheim GL; The curative potencies of cytochrome c applied 8 hours after lethal doses of alpha-amanitin in mice are confirmed . In a comprehensive series of experiments, various dosage schedules were explored . Optimal effects with cure rates approaching 100% were obtained either with repeated doses of cytochrome c or by combining it with penicillin . Male mice are more sensitive to alpha-amanitin than female mice but it was established that the antidote is effective in both sexes . Substantial cure rates are seen even when the treatment after supralethal doses of alpha-amanitin is withheld for 12 hours after the poisoning. Am J Hematol, 1977, 3, 219 - 23 Penicillin-induced immunohemolytic anemia associated with circulating immune complexes; Funicella T et al.; Eleven days after administration of multiple penicillin analogs, a 55-year-old female developed a Coombs-positive hemolytic anemia . The patient's erythrocytes were coated with IgG, complement components (C4/C3) and her serum contained elevated 125I-Clq binding activity (a measure of the presence of immune complexes) . Her serum, in the presence of fresh complement and penicillin, induced complement sensitization of normal erythrocytes . Immune complex-mediated complement activation and the haptene type of erythrocyte sensitization accounted for accelerated red blood cell destruction in this patient. Physiol Bohemoslov, 1977, (2), 143 - 8 The effect of dexphenmetrazine and acetyldexphenmetrazine upon epileptic electrographic activities in the brain of the turtle; Servit Z et al.; The effect of acetyldexphenmetrazine (ADP) and dexphenmetrazine (DP) on normal and epileptic electrographic activities in the cortical and thalamic structures of the turtle brain were studied in curarized and artificially ventilated animals . Both drugs almost exclusively influenced cortical activities . The effect of low doses of ADP and DP was similar--they desynchronized cortical activity and suppressed the activity of a cortical penicillin focus . They also elevated the cortical response to optic stimuli . Higher doses of ADP continued to suppress both normal and epileptic cortical activities . Higher doses of DP had a two phase effect with enhancement of epileptic activity in the first phase . Continuous trains of theta activity appeared after low doses of ADP and very often after both low and high doses of DP . The findings are discussed in terms of comparative physiology of the brain. Psychiatr Neurol Med Psychol Beih, 1977, 22-23, 24 - 7 {Complications and emergency conditions in acute inflammatory brain and spinal cord diseases}; Sayk J; A therapy comprising large doses of combined antibiotics and sulphonamides is the best way to prevent complications . Allowances are made for side-effects . OTC or similar widespectrum antibiotics, if there are no penicillin G or new better agents available, are to be used in conjunction with hydantoins because of the increase in excitability and the convulsivant effect, and cerebral decompensation as a result of the edematous effect should be prevented through early osmoregulation . In emergencies concerning central respiratory and circulatory disorders the best choice is artificial respiration with infusion therapy and osmoregulation . Success is gained by the use of discernment, both great and small amounts of effort, but most of all by the exercise of patience. Int Arch Allergy Appl Immunol, 1977, 55(1-6), 23 - 8 Antigens in penicillin allergy . II . The influence of the number of penicilloyl residues on the antigenicity of macromolecules as determined by radioimmunoassay (RIA), passive cutaneous anaphylaxis (PCA) and antibody induction; Kristofferson A et al.; The present communication reveals a relationship between the epitope density of penicilloylated protein antigens and their antigenic activities in a radioimmunoassay (RIA), in passive cutaneous anaphylaxis (PCA) and in inducing antibody formation in mice . In the RIA and PCA a critical number of 2-4 penicilloyl residues per protein molecule was noted . At this level small changes in the number of substituents considerably influenced the antigenic activities . The molecular weight and the nature of the carrier proteins, myoglobin, bovine serum albumin (BSA) and dimeric BSA also affected the threshold concentration for efficient antigenic activity . The results with the RIA and PCA were significantly correlated to each other . Using penicilloylated BSA as immunizing antigen in mice it was found that an epitope number higher than 11 penicilloyl residues per protein molecule induced significant antibody formation after a single injection . Antigens with a lower degree of penicilloyl substitution were less immunogenic . An antigen carrying 0.6 penicilloyl residues per BSA molecule did not induce penicilloyl-specific antibodies even after three injections . The capacity of heavily penicilloylated proteins to induce and elicit penicillin allergy as revealed by the present results stresses the importance of limiting their presence in penicillin preparations. Int Arch Allergy Appl Immunol, 1977, 55(1-6), 13 - 22 Antigens in penicillin allergy . I . A radioimmunoassay for detection of penicilloylated protein contaminants in penicillin preparations; Kristofferson A et al.; This communication presents a sensitive and discriminative method for detection of protein impurities in penicillin preparations . Antibodies against various penicilloyl derivatives of high avidities and specificities raised in rabbits were coupled to microcrystalline cellulose . The amount of penicilloyl antigen present in a sample was calculated from the relative uptake of a radioiodinated penicilloylated albumin competing with the sample for binding to the antipenicilloyl immunosorbent . As little as 0.048 pmol/ml of penicilloylated human serum albumin could be detected . The accuracy of the determination was within +/- 23% (p less than 0.05) . The pronounced specificities against the penicillin side chains demonstrated by the various immunosorbents were not displayed by the antibodies in passive cutaneous anaphylaxis experiments in guinea pigs . Furthermore, the immunosorbents showed the same pattern of specificity against monomeric penicillins as for penicilloylated proteins, but the former were considerably less efficiently recorded . The relatively small quantities of protein impurities in penicillin preparations, however, necessitated a separation from penicillin prior to analyses with the RIA . This was accomplished by fractionation on Sephadex G-50 fine, ginving a recovery of 80-90% of 0.1-2.5 ppm of penicilloylated protein. Antibiotiki, 1977, 22(2), 125 - 30 {Penicillin amidase from E . coli . Some physicochemical properties of the enzyme incorporated into polyacrylamide gel}; Shellenberg NN et al.; The physico-chemical properties of penicillinamidase (PA) immobilized in polyacrylamide gel (IPA) were investigated . It was shown that simple incorporation of PA into polyacrylamide gel was not effective because of gradual washing out of the enzyme . The use of a complex method for the immobilization (immobilization in the presence of a linking agent) resulted in higher stability of IPA, the choice of the optimal ratio of the reagents being of paramount importance . The mechanical strength of IPA was studied in model experiments. Antibiotiki, 1977, 22(2), 121 - 5 {Penicillin amidase from E . coli . Some physicochemical properties of the soluble enzyme}; Savitskaia EM et al.; Homogeneity of the enzyme was shown with the methods of gel filtration and disc electrophoresis . The molecular mass of penicillinamidase (PA) was determined . Sorption of PA by a carboxylic ion exchanger within a wide range of pH was studied . The values of pH in the ion exchanger phase under the conditions of the enzyme sorption were estimated . The ion exchange technique for determination of the isoelectric points of the proteins is described and the isoelectric point of PA is determined . It is proposed to use the method for estimation of close ionization constants of amphoteric an weak electrolites for interpretation of the bell-like pH dependence of kinetic and equilibrium parameters of the enzymatic reaction . The ionization constants of Michaelis complex of PA were evaluated . The activation energy of benzylpenicillin hydrolysis catalized by PA was determined. JAMA, 1976 Dec 6, 236(23), 2646 - 8 Destructive bone disease in early syphilis; Dismukes WE et al.; Although destructive bone disease is a well-known complication of tertiary syphilis, osteitis or osteomyelitis are not commonly recognized as complications of early (primary or secondary) syphillis . A patient with secondary syphilis characterized by generalized lymphadenopathy, perianal condyloma lata, and positive rapid plasma reagin (RPR) and fluorescent treponemal antibody-absorption (FTA-ABS) tests also complained of headache, right should pain, and right anterior chest pain and swelling . Roentgenograms showed mottled osteolytic lesions consistent with previously described luetic bone disease . Biopsy confirmed the diagnosis of syphilitic osteomyelitis, and treatment with penicillin resulted in prompt resolution of symptoms. MMW Munch Med Wochenschr, 1976 Dec 3, 118(49), 1597 - 1600 {Importance of intensive therapy in the treatment of purulent meningitis (author's transl)}; Kunst H; In recent years the lethality of purulent meningitis has not fallen significantly in spite of antibiotic therapy . Aspects are indicated which complicate the successful treatment of purulent meningitis, and in addition the problems of artificial respiration, the provocation of cerebro-organic paroxysms by high dose penicillin therapy, the not uncommonly observed hemorrhagic diatheses, disturbances of acid-base balance and the results of neuropathologic and echoencephalographic investigations are discussed . In addition to beginning treatment early and selective antibiotic therapy, intensive medical measures can contribute to an improvement in the prognosis of purulent meningitis. Biull Eksp Biol Med, 1976 Dec, 82(12), 1413 - 6 {Effect of damage to the zone of the medial forebrain bundle and preoptic area on the activiy of a penicillin-induced epileptiform focus (phenomenon of the hyperactive determinant dispatch station)}; Kryzhanovskii GN et al.; It was shown in experiments on cats under nembutal anesthesia that a lesion of the medial forebrain bundle (MFB) and partly of the preoptic region at the side of local penicillin application on the cerebral cortex (g . suprasylvius medius) results in depression of the epileptiform activity in the penicillin-induced focus, as well as in the secondary "mirror" focus, which appeared in the symmetrical cortex area of the other hemisphere . The MFB lesion at the "mirror" focus side led to depression of the seizure spike potentials in this focus only and did not change the activity in the primary epileptiform one . The described effects are considered from the aspect of the conception on the role of the determinant dispatch station (DDS) in the central nervous system: the primary epileptiform focus plays the role of the hyperactive DDS which induces the secondary focus and determines the character of its activity . The results of the study substantiate a suggestion that the MFB can take part in the modulation of the cortical epileptiform activity. West Afr J Pharmacol Drug Res, 1976 Dec, 3(2), 161 - 7 Peripheral nerve injuries from intramuscular injection of drugs; Ohaegbulam SC; 17 patients who were treated at the University of Nigeria Teaching Hospital for peripheral nerve paralysis resulting from intramuscular injection of drugs are analyzed . Ten of them were below the age of 5 years . Sciatic nerve was affected in 16 patients and only one patient had median nerve paralysis . Penicillin, ampicillin, tetracycline, paraldehyde and optalgin were some of the offending drugs . The prognosis was poor as only three patients achieved a partial recovery of function in the paralyzed nerves . With determination and public education, this iatrogenic tragedy could be eradicated. J Rheumatol, 1976 Dec, 3(4), 409 - 19 Pneumococcal arthritis; Kauffman CA et al.; Twelve patients with pneumococcal arthritis are described . Seven of the 12 patients had underlying diseases which predisposed them to pneumococcal infections; five were alcoholics and two had hypogammaglobulinemia . Five patients had pre-existing joint disease prior to the onset of septic arthritis . Seven patients had co-existent pneumococcal infection, including meningitis and/or endocarditis in five . The other five patients had pneumococcal arthritis without evidence of other foci of pneumococcal infection . With penicillin therapy and drainage of the purulent joint fluid (by needle aspiration in four and surgical drainage in seven), the function of the involved joint returned to normal or to the previous baseline level in all but one patient. J Am Vener Dis Assoc, 1976 Dec, 3(2 Pt 2), 172 - 6 Adverse reactions in syphilis therapy; Brown ST; Reactions related to treatment of syphilis may be due to treponemal infection, therapy, or to the interaction of these . In this review I discuss the Jarisch-Herxheimer (J-H) reaction and the therapeutic paradox . Antibiotic side effects are not unique among patients treated for syphilis; therefore, readers are referred elsewhere for reviews of major antibiotic side effects . J-H reactions are acute, transient episodes with manifestations occurring both systemically and at local sites of treponemal concentration . These reactions are related to the rapid destruction of treponemes by various therapeutic agents . In this review, I suggest that J-H reactions may be significant only in syphilitic paresis, pregnancy complicated by syphilis, and when local inflammation can cause serious functional compromise, as with second or eighth cranial nerve involvement . Many workers use prednisone in conjunction with penicillin in some or all of these situations . However, the efficacy of corticosteroids has not been evaluated for such problems in clinical trials . Therefore, the use of prednisone can be supported only in very selected situations and for short duration (ie, 2 days) . Therapeutic paradox, which is clinical worsening despite cure of infection, is said to result from scar formation after rapid treponemal destruction by therapeutic agents . The therapeutic paradox does not appear of great significance . Futhermore, no methods to prevent such reactions are generally advocated. J Am Vener Dis Assoc, 1976 Dec, 3(2 Pt 2), 168 - 71 Treatment of congenital syphilis; Budell JW; Although penicillin remains the drug of choice for congenital syphilis, the optimal regimen has not been established . The published clinical trials were completed before the development of repository preparations such as benzathine penicillin . Consequently, current therapy must be derived from available clinical and pharmacologic data. J Am Vener Dis Assoc, 1976 Dec, 3(2 Pt 2), 153 - 8 Treatment of neurosyphilis; Rothenberg R; Penicillin has some ameliorative effect in every stage of neurosyphilis . Meningovascular disease responds most dramatically . Once anatomic damage has occurred, penicillin is not effective in restoring lost function . In addition, blindness secondary to primary optic atrophy or 8th nerve deafness responds poorly to any type of treatment . Penicillin schedules employing more than 5 million units appear more effective than lower dose regimens . Reports of alternative antibiotic regimens are too fragmentary to allow recommendations to be made. J Am Vener Dis Assoc, 1976 Dec, 3(2 Pt 2), 148 - 52 Treatment of cardiovascular syphilis; St John RK; The English literature on the treatment of cardiovascular syphilis with penicillin was reviewed . To date there have been no controlled randomized clinical trials to demonstrate that penicillin therapy prolongs life expectancy, alleviates symptoms, or arrests the disease process . In spite of many shortcomings in the published data, penicillin is safe and free of severe reactions . Most authors agree that significant subjective improvement in the patient's status occurs following penicillin treatment . Once the patient has become symptomatic penicillin may have little efficacy . The optimal dosage and duration of therapy have never been established . Because of its low cost, ease of administration, and lack of toxicity, it should be given to all patients with cardiovascular syphilis in hope of arresting the effects of the disease on the heart and great vessels. J Am Vener Dis Assoc, 1976 Dec, 3(2 Pt 2), 146 - 7 Treatment of late benign syphilis: review of the literature; St John RK; The English literature on the treatment of late benign syphilis with penicillin was reviewed . To date there have been no controlled randomized therapeutic trials to support the efficacy of this therapy . This disease responds rapidly to all antisyphilitic drugs including arsphenamine and heavy metals . There are ample case reports and 2 major therapy studies which demonstrate the safety and beneficial effects of penicillin in individual patients . Although the exact dosage and duration of therapy are open to speculation, it is wise to treat patients with late benign syphilis with doses of penicillin judged to be effective for concomitant neuro-or cardiovascular syphilis. J Am Vener Dis Assoc, 1976 Dec, 3(2 Pt 2), 136 - 42 Treatment of secondary syphilis; Brown ST; There are few studies of therapy for secondary syphilis which are adequate by modern standards of scientific design . Penicillin has been the best documented, effective antibiotic, although not all forms and regimens are equally effective . Although both aqueous penicillin G and procaine penicillin G in oil with aluminum monostearate (PAM) appear effective, these are not practical penicillin forms . The first requires injections every 2 to 4 hours for 7 to 10 days and the latter is no longer available in the United Sates . Aqueous procaine penicillin G (APPG) regimes have been evaluated in limited trials, but do appear effective . However, APPG requires daily injections and is impractical for widespread use in the treatment of secondary syphilis . The injection of 2.4 million units of benzathine penicillin G appears to be an effective single session regimen . Although tetracycline is widely accepted as the drug of choice for patients allergic to penicillin, this drug has been less rigorously evaluated for treatment of secondary syphilis . Other antibiotics have been even less well evaluated and none has been clearly shown to be highly effective. J Am Vener Dis Assoc, 1976 Dec, 3(2 Pt 2), 128 - 35 Treatment of primary syphilis; Elliott WC; Reports in the English language of the treatment of primary syphilis are reviewed . Except for benzathine penicillin, the efficacy of the currently recommended dosage schedules are documented only by Schroeter et al . Although these investigators reported generally acceptable failure rates, further study is necessary to determine: (1) if differences in efficacy exist among regimes; (2) if the current schedules are equally effective in both primary and secondary syphilis; and (3) if increased dosages reduce failure rates. Epilepsia, 1976 Dec, 17(4), 449 - 59 Experimental bilateral deep temporal epilepsy . Effects of ablation of one focus and of different brain lesions; Meglio M et al.; In acute experiments in the rabbit, the amygdaloid nuclear complexes of the two sides were made epileptogenic through electrical stimulation or local injection of penicillin in gel . The effects on the epileptic pattern produced by surgical removal of one of the two epileptogenic amygdalae and the effects of sterotactic lesioning of the region of anterior commissure, head of caudate nucleus, and occipital cortex were analyzed . The occurrence of phenomena of both inhibitory and facilitatory interaction between the two epileptogenic amydalae was confirmed . In some experimental conditions, the restraining influence of an amygdaloid penicillin focus on the contralateral one was quite relevant, and its effect could persist even after surgical removal of the focus from which it originated . The mediation of the interamygdadoid epileptic interaction could not be ascribed to a single cerebral structure or anatomofunctionally homogenous group of structures . The phenomenon appears to involve several structures at different encephalic levels. Epilepsia, 1976 Dec, 17(4), 437 - 48 Interaction of epileptic activities of bilateral deep temporal origin . An experimental study; Meglio M et al.; The interaction of epileptic activities obtained with electrical or chemical (penicillin) stimulation of the amygdaloid nuclear complexes of the two sides was studied in acute experiments on the rabbit . Several findings indicate that reciprocal influences between the two epileptogenic amygdalae can occur . Inhibitory as well as facilitatory interactive phenomena were observed . The occurrence of interaction and its sign seem related to the level of epileptic activity. Hoppe Seylers Z Physiol Chem, 1976 Dec, 357(10), 1365 - 77 {Synthesis of conjugates of heptalysine and penicillins (author's transl)}; Schnabel E; Heptalysine was synthesized as a non-immunogenic carrier for artificial antigens with penicilloyl-group specificity . The synthesis was carried out by conventional techniques via different routes by condensation of appropriately protected intermediates . Best results were obtained with the use of the benzyloxycarbonyl group for intermediate protection of the alpha-amino-groups and the tert.-butyloxycarbonyl-group together with the tert.-butylester for permanent blockage of the terminal alpha-amino group, the epsilon-amino groups and the terminal carboxyl group . Heptalysine and also lysine were reacted with benzylpenicillin, alpha-aminobenzylpenicillin and tert.-butyloxycarbonyl-alpha aminobenzylpenicillin--to prevent the alpha-amino groups of penicillin from reacting--in aqueous solutions at pH 10.6-11.6 according to Levine and Redmond . The products were isolated after precipitation with acid or dialysation against water by lyophilisation . The penicilloyl group content of the conjugates as estimated from elemental analysis, penamaldate tests and the NMR spectra proved to be rather high: 5-7 residues/mol. J Med Chem, 1976 Dec, 19(12), 1385 - 91 Preparation, hydrolysis, and oral absorption of lactonyl esters of penicillins; Clayton JP et al.; Lactonyl esters of ampicillin and other penicillins have been synthesized as prodrugs designed to improve the oral absorption of the parent penicillins . In general, the esters hydrolyzed rapidly in the presence of tissues including blood and certain of the esters were better absorbed than the parent penicillin . The phthalidyl ester of ampicillin {talampicillin (British Pharmacopoeia approved name), BRL 8988} was selected for extended studies . The compound was found to be well absorbed in various animal species and gave ampicillin serum concentrations in fasting human volunteers 2.5-3 times those obtained for ampicillin itself. J Am Vener Dis Assoc, 1976 Dec, 3(2 Pt 2), 109 - 27 Biopharmacology of syphilotherapy; Rein MF; Data collected from experimental rabbit syphilis and from in vitro studies with nonpathogenic treponemes can be extended only with great caution to human syphilis . The following tentative conclusions may be drawn: penicillin acts on Treponema pallidum by interfering with cell wall synthesis . Concentrations of penicillin greater than 0.1 mug/ml do not have increased treponemicidal effect . Regimens producing penicillinemia for at least 8 days are considerably more efficient than treatment yielding high peak serum levels of brief duration . Treponemal residence in antibiotic-protected sites increases the need for long duration therapy . Other antibiotics are less effective than penicillin, and patterns of antibiotic interaction against treponemes do not match those seen with other bacteria. Acta Allergol, 1976 Dec, 31(6), 478 - 86 In vitro histamine release from leukocytes in penicillin allergies; Saraclar Y et al.; The definite diagnosis of Type I allergy against penicillin is very important . The in vivo tests used for this purpose may have some disadvantages for the patient . Among the in vitro tests used for the evidence and differential diagnosis of Type I allergy against penicillin, the determination of histamine release from leukocytes and the detection of IgE by the RAST test are the most promising . We have used the test of histamine release from leukocyte in this study of 18 cases, nine of whom had Type I hypersensitivity reactions to penicillin and comprised the study group, the rest were control cases . The per cent of histamine release in the control group was "zero" while in the study group it ranged from 3.9 to 51.7 per cent . The results indicate that the method used in this study is a sensitive and reliable method for the diagnosis of Type I penicillin allergies. Electroencephalogr Clin Neurophysiol, 1976 Dec, 41(6), 571 - 9 Influence of association cortex on penicillin discharges in the primary visual cortex; Rosen AD; The influence of visual association cortex on the pattern of neuronal activity in the lateral geniculate body, during penicillin-induced discharges in visula cortex, was studied . In a majority of those geniculate cells which exhibited a pre-penicillin discharge increment in activity, that increment was abolished or significantly reduced during focal hypothermia of the visual association cortex . The frequency of penicillin discharges in visual cortex was, in most cases, reduced during cooling of association cortex . These findings are briefly discussed in terms of corticothalamic interactions. Arch Dermatol Res, 1976 Nov 26, 257(1), 1 - 15 Treponema pallidum in early syphilitic lesions in humans during high-dosage penicillin therapy . An electron microscopical study; Wecke J et al.; The alterations of early syphilitic infection occuring in the course of high dosage penicillin (120 mega IU, 36 h) as clinical experimental trial has been studied both from the clinical and the electron microscopical views . By electron microscopical studies, findings revealing the localization and the status of treponemes before and during penicillin treatment could be established . Before treatment started, the majority of treponemes was of intercellular localization . In the course of treatment various forms of destruction could be differentiated . The most striking change in the host tissue after 7-8 h of penicillin therapy was an elimination of treponemes by penetrating phagocytes . 24 h after the beginning of treatment, treponemes could not be demonstrated any more . The clinical and serological findings after the high dosage penicilline will produce results comparable to those of conventional therapie. JAMA, 1976 Nov 22, 236(21), 2410 - 2 Low dose penicillin for gonococcal arthritis . A comparative therapy trial; Trentham DE et al.; Sixty-three patients with gonococcal arthritis completed a double-blind randomized penicillin therapy trial comparing a low dose regimen (procaine penicillin G, 600,000 units intramuscularly, given every 12 hours for up to ten days) with a high dose (the same procaine penicillin regimen and intravenous aqueous penicillin G, 10 million units daily, for the first three days) . Pretherapy features were similar in the 36 patients allocated to low-dose vs the 27 to high-dose therapy . All patients had definite improvement within 48 hours of the initiation of either regimen . No therapeutic response variable studied differed significantly between the groups . Thus, no additional therapeutic benefit accrued from the high doses of penicillin . The absence of complications or failures in either treatment group indicate that gonococcal arthritis is ordinarily quite responsive to low doses of penicillin given intramuscularly, and that massive intravenous therapy is unnecessary. Lancet, 1976 Nov 13, 2(7994), 1039 - 41 Penicillin-induced coagulation disorder; Andrassy K et al.; A coagulation disorder was seen after penicillin-G administration (10 million units/day) in uraemic patients and after high-dose penicillin G (40 million units/day) in patients with a normal glomerular filtration-rate (5 patients after cardiac surgery) . This disorder was characterised by: prolongation of bleeding-time, appearing immediately after penicillin-G administration and persisting until 4 days after withdrawal of therapy; disturbance of collagen-induced and ristocetin-induced platelet aggregation; increase of antithrombin-III activity; and inhibition of factor-xa activity . The inhibition of factor-xa activity corresponded to that seen after low-dose-heparin prophylaxis . The clinically latent coagulation disorder, when super-imposed upon pre-existing coagulation abnormalities (uraemia, treatment with anti-coagulants) may cause severe bleeding, as observed in 1 patient with acute renal failure on haemodialysis. Biochim Biophys Acta, 1976 Nov 8, 452(1), 177 - 85 Purification and properties of penicillin acylase of Bovista plumbea; Schneider WJ et al.; 1 . A penicillin acylase (penicillin amidohydrolase, EC 3.5.1.11) formed constitutively in the basidiomycete Bovista plumbea was purifed 220-fold by a combination of two gel filtration runs, ion-exchange chromatography on DEAE-cellulose, ultrafiltration and final chromatography on hydroxyapatite . Recovery was 40% . 2 . The enzyme was clearly distinguished from penicillin acylases previously characterized: the molecular weight of the purified enzyme was evaluated by gel filtration to be 88 000 . Km for the best substrate phenoxymethylpenicillin was 1.67 mM . The maximum of activity occurred at 52 degrees C and pH 7.5 . The activation energy calculated by Arr