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Arch Dermatol, 1983 Dec, 119(12), 1006 - 9 Possible drug-induced pemphigus-like antibodies with the clinical manifestation of erythema multiforme; Ansel J et al.; A patient with bullae and target lesions on the extremities and mucous membranes was seen with the clinical picture of erythema multiforme following an episode of pneumonia and a course of penicillin G potassium and tobramycin sulfate therapy . An unusually high titer of intercellular circulating (IC) antibodies was identified in the serum by indirect immunofluorescence (IF) microscopy, but direct lesional IF microscopy study results were negative . These IC antibodies were not true pemphigus antibodies and can best be termed pemphigus-like antibodies . These antibodies were characterized by their ability to fix complement, in contrast to pemphigus antibodies, which apparently fail to do so. Electroencephalogr Clin Neurophysiol, 1983 Dec, 56(6), 664 - 7 Penicillin activity in brain tissue: a method for continuous measurement; Speckmann EJ et al.; A double-barrelled microelectrode is described which permits the continuous and simultaneous measurement of penicillin concentration and of the local bioelectric activity in nervous tissue . The electrode, which is based on a chloride ligand (Corning no . 477315), has a short response time and enables reproducible measurements of penicillin concentration even below 500 IU/ml. Electroencephalogr Clin Neurophysiol, 1983 Dec, 56(6), 604 - 22 Penicillin-induced epileptic foci in the motor cortex: vertical inhibition; Elger CE et al.; Neuronal mechanisms responsible for a vertical restriction of focal seizure activity in the motor cortex were analysed . For this purpose intracellular recording from neurones in superficial (50-300 microns below cortical surface), middle (300-800 microns) and deep cortical layers (800-1300 microns) was performed . As a model of foci of various vertical extensions the spread of seizure activity from superficial to deeper cortical laminae following epicortical penicillin application was used . The appearance of characteristic epileptiform potentials in the surface record with a focus restricted to upper cortical laminae was accompanied (i) in superficial neurones by the development of paroxysmal depolarization shifts (PDS), (ii) in middle neurones by depolarization often followed by hyperpolarization, and (iii) in deep neurones by a sequence of membrane potential changes . The latter consisted of an initial depolarization, an early hyperpolarization, an intermediate depolarization, a late hyperpolarization and a final depolarization . The hyperpolarizing components led to complete suppression of action potentials (vertical inhibition) . The early hyperpolarization and the first part of the late hyperpolarization were reduced in amplitude when the intracellular chloride activity was elevated . The intermediate depolarization was replaced by PDS with the enlargement of the epileptic focus into the cortex . The actual effect of the vertical inhibition may in part be responsible for the variability in epileptic motor phenomena coinciding with epileptiform potentials in the surface EEG. Br J Vener Dis, 1983 Dec, 59(6), 404 - 5 Paul Ehrlich: pioneer of chemotherapy and cure by arsenic (1854-1915); Thorburn AL; Paul Ehrlich's experiments in staining techniques at the end of the nineteenth century resulted in many discoveries which help to form the basis of present research work . Ehrlich's chemotherapy research led to his formulating the arsenic compound, Salvarsan, which was used in the treatment of syphilis during the first half of this century until it was superseded by penicillin. Brain Res, 1983 Nov 28, 280(1), 25 - 40 Functional anatomy of limbic seizures: focal discharges from medial entorhinal cortex in rat; Collins RC et al.; Focal seizure discharges were induced in the ventral aspect of the medial entorhinal cortex of awake, freely moving rats, either with cannula injections of penicillin or picrotoxin (0.02 microliters every 10-15 min) or by repetitive tetanic electrical stimulation . {14C}Deoxyglucose autoradiography (DG) was performed when animals were in a 'steady-state' with respect to electrographic discharges and/or behavioral changes . During simple interictal spikes behavior remained normal and DG labeling was increased only in the entorhinal focus and stratum moleculare of the ventral dentate gyrus . With complex spikes and short seizures animals exhibited staring, decreased responsiveness, and occasional wet dog shakes . DG labeling was increased in all layers of the dentate gyrus, Ammon's horn (ipsilateral greater than contralateral) and, to a lesser degree, in ipsilateral amygdala, and the accumbens-ventral pallidum area . During strong seizures, rearing and forelimb clonus occurred and metabolism was strongly activated bilaterally in the hippocampal formation, amygdala, accumbens, substantia nigra, and the anterior and periventricular thalamic nuclei . These studies indicate that the dentate gyrus initially restricts the entry of seizures from entorhinal cortex into the rest of hippocampus . As this is overcome there is rapid bilateral spread through the hippocampal formation with passive interruption of normal behavior . With prolonged seizure discharges there is further capture of amygdala and subcortical extrapyramidal and thalamic nuclei associated with behavioral convulsions. Nature, 1983 Nov 24-30, 306(5941), 371 - 3 Single neurones can initiate synchronized population discharge in the hippocampus; Miles R et al.; The synchronized firing of neuronal populations is frequently observed in the mammalian central nervous system . The generation of motor activities such as locomotion and respiration requires the simultaneous activation of many neurones and synchronous firing also underlies the cortical alpha rhythm and the hippocampal theta rhythm . However the influence that single neurones may have on such neuronal population discharges is not clear . We have examined this question using small isolated segments of the CA3 region of the guinea pig hippocampus . We report here that in the presence of picrotoxin, a gamma-aminobutyric acid (GABA) antagonist, these segments spontaneously generate synchronized rhythmic bursts comparable with the interictal epileptiform discharges observed in the hippocampus and neocortex in the presence of penicillin . The activation of some individual neurones by intracellular current injection can partially entrain and reset the rhythm . The probability that a synchronized burst will follow stimulation of a single cell increases with time after a spontaneous synchronized discharge, suggesting that each population discharge is followed by a period of relative population refractoriness . A delay of 40-200 ms elapses between the activation of a single neurone and the synchronized discharge . We suggest that during this time activity elicited in one neurone spreads to other neurones through multisynaptic excitatory pathways and leads eventually to the participation of the whole population in a synchronous burst. Brain Res, 1983 Nov 14, 278(1-2), 207 - 17 Enhanced response of cortical neurons to thalamic stimuli precedes the appearance of spike and wave discharges in feline generalized penicillin epilepsy; Kostopoulos G et al.; Peristimulus time histograms of extracellularly recorded action potential discharges of cortical neurons in response to single shock and/or repetitive stimulation of 'specific' and 'non-specific' nuclei of the thalamus were studied after i.m . penicillin injection during a period corresponding to that of the development of spike and wave (SW) discharges of feline generalized penicillin epilepsy (FGPE) . After i.m . penicillin cortical neurons displayed an enhancement of both the excitatory and 'inhibitory' phases of their responses to single shock stimulation of n . centralis medialis (NCM) . This increase was even more pronounced for responses induced by repetitive stimulation of NCM at the frequencies inducing typical recruiting responses . These changes always preceded the appearance of SW discharges . Changes of the responses of cortical neurons to single shock and repetitive stimulation of 'specific' thalamic nuclei after penicillin were weak and inconsistent, although when observed were characterized by an enhancement of both excitatory and 'inhibitory' phases . The latter appeared not to decrease after i.m . penicillin . These data suggest that the appearance of SW discharges of FGPE is closely related to an increased responsiveness of cortical neurons to thalamocortical volleys arising from the so-called 'non-specific' nuclei . This facilitation of the recruiting process is accompanied by an increase of both excitatory and 'inhibitory' phases of the cortical neuronal responses induced by the volleys. J Health Econ, 1983 Dec, 2(3), 187 - 205 Costs and benefits in switching from Rx to OTC; Temin P; This paper contains an initial inquiry into the benefits and costs of switching some drugs from prescription-only (Rx) status to over-the-counter (OTC) status . It contributes to a discussion of the Food and Drug Administration (FDA) policy of making this change for selected drugs, such as chlorpheniramine (switched in 1976) and topical hydrocortisone (switched in 1979) . Costs and benefits are estimated for three representative drugs: (1) topical hydrocortisone, a medicine with limited use and side effects; (2) thiazide diuretics, drugs used on a continuing basis to treat chronic conditions; (3) and oral penicillin, a well-understood anti-infective agent . The purpose of the calculations is to suggest criteria for deciding which drugs could be switched . Reasonably potent drugs are considered to assess the limits of switching policy. Can J Microbiol, 1983 Nov, 29(11), 1526 - 31 Partial purification and characterization of isopenicillin N epimerase activity from Streptomyces clavuligerus; Jensen SE et al.; Epimerase activity, which converts isopenicillin N to penicillin N, has been partially purified from cell-free extracts of Streptomyces clavuligerus . No stimulating cofactors of this activity were found, and neither EDTA nor anaerobic incubation caused significant inhibition of activity . Although pyridoxal phosphate did not stimulate epimerase activity, the presence of this cofactor was necessary for the stabilization of enzymic activity during the purification process . Epimerase activity was purified 35.5-fold by a combination of salt precipitation, gel filtration, and ion exchange chromatography . Gel filtration indicated that the epimerase has a molecular weight of 60 000 and sodium dodecyl sulphate-polyacrylamide gel electrophoresis of the 35.5-fold purified epimerase showed a major protein band running near that location . Pyridoxal phosphate antagonists did not uniformly inhibit epimerase activity, but the inhibitory effect of hydroxylamine could be partially reversed by pyridoxal phosphate. Rev Infect Dis, 1983 Nov-Dec, 5(6), 994 - 1002 Too few and too little: barricades to the pursuit of health; Weller TH; Academic responsibilities in the field of international health are considered . Too often the instructional process neglects essential aspects of the natural history and the control of infectious diseases . Few scientists are able to teach from a background of practical experience in the field . Little emphasis is placed on the continuum of problems deriving from an ever-changing human ecology . The program of "Health for All" of the World Health Organization and the recognition by the World Bank of health as an integral component of the developmental process are salutary events . Yet, progress depends on dedicated, informed leadership . Past examples can be found in the global contributions of the International Health Division of The Rockefeller Foundation, at the national level in Costa Rica where disease preventable by immunization has disappeared, and at the community level in the successes of Drs . Warren and Gretchen Berggren in Haiti . While new "magic bullets" are to be anticipated, the resurgency of yaws, in spite of penicillin, emphasizes the need for leadership in achieving a sustained, societal effort based on sound ecologic considerations. Klin Padiatr, 1983 Nov-Dec, 195(6), 394 - 8 {Splenectomy and reimplantation of splenic tissue in children}; Holschneider AM et al.; 161 splenectomies are presented with a morbidity of 14.8% and a total mortality rate of 4.3% . The lethality rate due to severe infections (-3.9%), however, was high and mostly caused by an overwhelming postsplenectomy sepsis, pneumonia or meningitis . 61.5% of the infections were caused by pneumococcus . To drop that high lethality rate after splenectomy we replanted splenic tissue in seven patients . Scintigraphic investigations showed in all cases well vascularised splenic tissue . The immunoglobulins were in a normal range . Howell-Jolly bodies, however, did not disappear in all the patients . From our study as well as from the literature one has to conclude that replanted splenic tissue requires immunologic activity but a reduced capacity for phagocytosis . Therefore, in cases of traumatic injury to the spleen it is necessary to try to preserve as much of the organ as possible either by infrared coagulation, gluing with human fibrinogen or partial splenectomy . If these procedures are impossible a replantation of--50% of the original splenic tissue should be done and several thin homogenised particles replanted intra- or retroperitoneally . Out of that a preoperative vaccination against pneumococcal infection is necessary as well as a postoperative penicillin prophylaxis for about three years. Surg Neurol, 1983 Nov, 20(5), 422 - 6 Surgical control of semichronic epileptic foci in the cat's sensorimotor cortex; Reichenthal E et al.; The present work was undertaken in order to find out whether delicate subpial incisions can be used to stop the epileptic activity of cortical lesions induced by cobalt oxide . Epileptic foci were produced in cats by epidural application of cobalt oxide powder . The presence of epilepsy was demonstrated a week later in anesthetized cats by injections of a "trigger dose" of pentamethylenetetrazole . Performance of subpial incisions through the focus area immediately abolished all ongoing epileptic activity . Such activity could not be evoked again by subsequent injection of pentamethylenetetrazole trigger doses throughout a 2-week period . The practical implications of this result are discussed . Some theoretical consequences of the similarity between the response of penicillin foci and that of cobalt oxide foci to the application of subpial incisions were evaluated . Finally, an attempt is made to explain the differences between our results and those produced by other investigators who also attempted to inactivate cobalt lesions in the cortex. J Antibiot (Tokyo), 1983 Nov, 36(11), 1543 - 8 Induction of beta-lactamase and penicillin-binding proteins in Escherichia coli by introduction of Streptomyces DNA; Nakazawa H et al.; Introduction of hybrid plasmids, which were constructed by ligation of pCR1 or pMN1 vector plasmid and SalI restriction endonuclease cleaved segments of Streptomyces cacaoi chromosome, resulted in the production of new beta-lactamase and penicillin-binding protein in Escherichia coli . The beta-lactamase and penicillin-binding protein were not from S . cacaoi but rather induced by the plasmids . Close relationship was observed between plasmids and penicillin-binding proteins but not with beta-lactamase. Electroencephalogr Clin Neurophysiol, 1983 Nov, 56(5), 501 - 14 Measurement of small time differences between EEG channels: method and application to epileptic seizure propagation; Gotman J; Small time differences between the EEG activities of two channels were measured by a method based on the use of coherence and phase spectra over a certain frequency range . In many cases this method allowed to establish that time differences of the order of 5-50 msec were actually present between two channels which appeared synchronous on visual inspection . The method was applied to seizure activity from the penicillin and kindling models in the cat and to seizures recorded from scalp and intracerebral electrodes in epileptic patients . When the seizure activity was widespread but was known to be related to an epileptic focus, it was found that the area of the focus had a consistent time lead over the other recording sites . It was concluded that the method could frequently allow to: (1) assess the presence of an epileptic focus even when only widespread seizure activity could be recorded; (2) make inferences about the possible routes of propagation of seizure activity. Br Med J (Clin Res Ed), 1983 Oct 22, 287(6400), 1193 - 6 Prescription information leaflets: a pilot study in general practice; George CF et al.; Leaflets containing information about medicines were issued to 56 patients prescribed penicillins and 43 patients prescribed non-steroidal anti-inflammatory drugs . The patients were interviewed between four and 10 days later and their responses compared with those of 65 patients prescribed penicillin and 33 prescribed nonsteroidal anti-inflammatory drugs who did not receive a leaflet . Patients who received a leaflet were more likely to be completely satisfied with their treatment and with the information they had been given . They were also more likely to know the name of their medicine and much more aware of potential unwanted effects . Although there was no evidence that knowledge increased the incidence of adverse effects, when these did occur they were more likely to be recognised as being due to the medicine . Further studies of other leaflets are warranted, including leaflets for drugs that are taken long term. Z Hautkr, 1983 Oct 15, 58(20), 1471 - 80 {Drug-induced Quincke's edema of the mouth mucosa - an analysis of 33 cases}; Gebel K et al.; Since literature only provides us with scarce information about occurrence and etiologic conditions of oro-pharyngeal Quincke's edema, we performed a retrospective evaluation of the medical records of 4,766 in-patients between the years 1970 and 1980 with registered drug-induced cutaneous and/or mucosal side effects . Among these cases there were 187 patients (= 3.92%) showing oral side effects, 33 of them with the diagnosis of Quincke's edema on the labial, oral or pharyngeal mucosa . 30 cases revealed clinical and/or historic data about concomitant occurrence of edematous lesions also in other body sites . With all patients drug intolerance was suspected by history, yet drug testings could only prove this assumption in 24 cases . Salicylates, analgetic compounds, barbiturate, pyrazolone, and penicillin are the main etiologic factors for oral Quincke's edema. Can Med Assoc J, 1983 Oct 15, 129(8), 851 - 4 Overwhelming pneumococcal infection in a hyposplenic adult; Hatch JP et al.; In a woman with an atrophic, apparently nonfunctioning spleen pneumococcal septicemia led to death within 72 hours of admission . As in five previously described adults, the patient's presentation and subsequent clinical course were identical to those of the syndrome of overwhelming postsplenectomy infection, except that there was no history of splenectomy . Patients without spleens may be given penicillin prophylaxis for an indefinite period, vaccinated against pneumococci or both. Schweiz Med Wochenschr, 1983 Oct 8, 113(40), 1471 - 3 {Semisynthetic penicillins and cephalosporins inhibit in vitro myelopoiesis in a dose-dependent manner}; Muller M et al.; Penicillin-G degradation products have been shown to inhibit in vitro myelopoiesis in a dose-dependent manner . Similar inhibition was seen with 6 semisynthetic penicillins and 2 cephalosporins . 50% inhibitory doses in vitro well matched total and daily doses given in vivo before neutropenia developed . These findings suggest a toxic rather than an immune-mediated pathogenesis for betalactam-induced neutropenia. Am J Perinatol, 1983 Oct, 1(1), 28 - 30 Changing pattern of drug utilization in a neonatal intensive care unit; Aranda JV et al.; Drug exposures in neonates admitted to a neonatal intensive care unit in 1974 and in 1977 were compared . A significant increase in drug exposure (3.4 drugs per baby in 1974 versus 6.19 drugs in 1977) and in the total number of drugs used (71 versus 102 different drugs) were noted . The proportion of infants receiving no drugs were similar (23%) . Infants given penicillin and kanamycin decreased by about 50% with a reciprocal increase observed with ampicillin and gentamicin . Except for a few drugs (chloramphenicol, methicillin, Infantol), all drugs were used in a greater number of babies in 1977 . Data indicate increase in drugs used and a change in the pattern of drug utilization over a period of three years. J Neurophysiol, 1983 Oct, 50(4), 819 - 37 An analysis of penicillin-induced generalized spike and wave discharges using simultaneous recordings of cortical and thalamic single neurons; Avoli M et al.; To study the relationship between cortical and thalamic single-neuron activity during spike and wave (SW) discharge of feline generalized penicillin epilepsy (FGPE), extracellular single-unit and local electroencephalogram (EEG) activity were recorded simultaneously from pairs of neurons, one located in the cortex of the middle suprasylvian gyrus (MSS), the other in the dorsal thalamic nuclei (n . lateralis posterior or pulvinar) . These two areas are anatomically and functionally closely interrelated . Computer-generated EEG averages and histograms of single-unit activity triggered by either peaks of cortical or thalamic EEG transients or by cortical or thalamic action potentials (aps) showed that cortical neurons in the MSS fired at the time of the spike of the SW complex, while at the time of the wave they became silent . Two populations of thalamic neurons also fired maximally during the spike of SW discharge, but they differed in the precise timing of their firing in relation to that of the simultaneously recorded cortical neuron . The first group of thalamic neurons tended to fire 5-45 ms before the cortical neuron . Of these 28 neurons, 9 were antidromically and 2 orthodromically activated by cortical stimulation . The neurons of the second group tended to fire 0-45 ms after the cortical neuron . Cortical stimulation activated 15 of these 19 neurons orthodromically and 2 antidromically . A third and smaller population of thalamic neurons (n = 8) increased its firing probability during the wave of the SW complex and decreased it during the spike . In 74% of the pairs of neurons the cyclic alternation of excitation and "inhibition" associated with SW activity appeared in the cortex by 1-3 cycles earlier than in the thalamus . This was most common when the thalamic neuron of the pair reached its peak firing probability before the simultaneously recorded cortical neuron . In 11 pairs of neurons the same rhythmic alternation of excitation and "inhibition" of neuronal firing was seen in both the cortex and thalamus during SW discharges evoked by single-shock stimulation of nucleus centralis medialis . These data demonstrate that both cortical and thalamic neurons participate in the SW firing pattern of FGPE by undergoing periods of mutually phase-locked cyclic alternations of excitation and "inhibition" at the frequency of the EEG SW rhythm . Although the initial steps leading to generalized SW discharge in FGPE take place in the cortex, the thalamus soon becomes entrained in the SW rhythm.(ABSTRACT TRUNCATED AT 400 WORDS) J Infect Dis, 1983 Oct, 148(4), 737 - 44 Treatment of experimental brain abscess with penicillin and chloramphenicol; Haley EC Jr et al.; Recent reports have indicated that antibiotic therapy alone may be successful in resolving brain abscesses . We utilized an animal model of brain abscess to evaluate the efficacy of penicillin with and without chloramphenicol in preventing the development of brain abscess . When penicillin therapy was initiated at the time of bacterial contamination and continued for four days, the bacteria were eliminated . When therapy was delayed for 24 hr, the number of bacteria in brain tissue samples was significantly reduced, but all samples still contained bacteria . When therapy was delayed for 48 hr, there was no therapeutic benefit . Addition of chloramphenicol to each of these regimens did not significantly alter the results . Extending the duration of therapy to eight days provided no improvement over the results obtained after four days. J Pharmacol Exp Ther, 1983 Oct, 227(1), 55 - 9 Dissociation of renal organic anion transport from renal lipid metabolism . I . Endogenous nonesterified fatty acids (NEFA) as determinants of transport; Stroo WE et al.; The objective of this study was to evaluate the hypothesis that nonesterified fatty acids (NEFA) are endogenous inhibitors of renal organic anion transport and that changes in renal NEFA content could modulate renal organic anion transport capacity . The addition of 1 mM palmitate to a suspension of renal tubules produced a tissue NEFA content of 665 +/- 105 micrograms/g and a 40% decrease in the tissue-to-medium concentration ratio for p-aminohippurate . Penicillin pretreatment enhanced p-aminohippurate tissue-to-medium concentration ratio in a neonatal rabbit proximal tubule suspension but failed to alter renal NEFA content from a control of 46.4 +/- 2.6 micrograms/g . Penicillin treatment did, however, decrease renal triglyceride content and increased serum NEFA from 87.7 +/- 3.4 to 129 +/- 6.8 micrograms/ml . Fasting increased serum triglyceride and increased serum NEFA from 33.9 +/- 3.1 to 370 +/- 200 micrograms/ml . Fasting decreased p-aminohippurate transport capacity 42% from a control tissue-to-medium concentration ratio of 6.78 +/- 1.2 but did not alter renal NEFA from a control value of 65 +/- 15 micrograms/g . The data support the suggestion that penicillin treatment can alter lipid metabolism in vivo but fail to support the suggestion that altered renal organic anion transport is due to altered renal NEFA content and further suggest that NEFA can alter renal organic anion transport only at a supraphysiological concentration. Oral Surg Oral Med Oral Pathol, 1983 Oct, 56(4), 361 - 4 Penicillin-induced anaphylaxis in a patient under hypotensive anesthesia; Gallagher DM et al.; Elective use of penicillin during hypotensive anesthesia for orthognathic surgery induced a nearly fatal anaphylactic reaction . The first symptom of anaphylaxis was increased inspiratory resistance to mechanical ventilation, followed by severe hypotension . The therapeutic management of anaphylaxis is discussed . Patients susceptible to reactions from the administration of B-lactam antibiotics can be identified through skin tests . Patients reactive to such antibiotics should be treated with alternate antibiotics or they should be desensitized prior to receiving penicillin. J Gen Microbiol, 1983 Oct, 129 (Pt 10), 3027 - 33 The genetic location of three mutations impairing penicillin production in Aspergillus nidulans; Makins JF et al.; Three mutations impairing penicillin production in Aspergillus nidulans, npeB, npeC and npeD, have been located on linkage groups III, IV and II, respectively, and positioned relative to other loci on these chromosomes. Z Hautkr, 1983 Oct 1, 58(19), 1391 - 6 {Single-dose penicillin therapy of acute gonorrhea}; Bardach H et al.; A new penicillin preparation (sodium-penicillin G3.5 mill . I.U., clemizolpenicillin G 1.0 mill . I.U.) has been tested with regard to the treatment of uncomplicated gonococcal infections during a multicenter trial in Vienna . 101 out of 102 patients could be sufficiently cured by one single injection of the preparation. J Trauma, 1983 Oct, 23(10), 924 - 6 Human skin storage techniques: a study utilizing a nude mouse recipient; Cram AE et al.; The nude mouse model is an excellent technique for studying the viability of stored human skin . In this study Roswell Park Memorial Institute (RPMI) tissue culture medium provided reliable storage of viable human skin for 20 days . Antibiotic concentration plays a role in stored skin viability with low concentrations of penicillin and streptomycin providing adequate bacterial control and improved viability when compared to identical media with high concentrations of the same antibiotics . Addition of fetal calf serum to the storage medium did not improve human skin viability in this experiment. J Trauma, 1983 Oct, 23(10), 872 - 3 Short-term preservation of human autografts; Cram AE et al.; Short-term storage of a patient's harvested skin is clinically desirable for numerous reasons . Previous experience in our center using a skin storage solution of saline with a high concentration of antibiotics resulted in poor graft viability and an unsatisfactory clinical outcome . This report defines an improved method of storage which allows longer storage time, yielding viable skin and results in subsequent graft acceptance on the patient . Split-thickness autografts from patients were stored in: 1) saline + 10(4) units/ml penicillin and 0.005 gm/ml streptomycin, or 2) RPMI-1640 + 25 units/ml penicillin and 25 mcg/ml streptomycin, at 4 degrees C . The pH range of the saline solution was 5.90-6.20, compared to 7.20-7.32 for the RPMI-1640 solution . The medium was changed every 3 to 4 days during the storage period . Before graft reapplication the autografts were rinsed with sterile saline . Previous clinical results using the saline-antibiotic storage solution resulted in poor graft viability and no graft survival was noted on patients after 5 days of skin storage . In contrast 11/16 autografts which had been stored in the RPMI-1640 solution for 5 to 22 days (median, 11 days) were successful takes when regrafted to patients . Graft loss was observed in five cases due to the following reasons: inability to immobilize graft (one); poor vascular bed (two); and bacterial infections (two) . These data are in agreement with results reported in a separate paper, demonstrating the effectiveness of RPMI-1640 as a storage medium for maintaining viable human skin grafts which were subsequently transplanted to athymic nude mice.(ABSTRACT TRUNCATED AT 250 WORDS) J Biol Chem, 1983 Sep 25, 258(18), 10824 - 6 Direct measurement of peptidoglycan cross-linking in bacteria by 15N nuclear magnetic resonance; Jacob GS et al.; Cross-polarization magic angle spinning 9.12-MHz 15N nuclear magnetic resonance was used to measure the extent of peptidoglycan cross-linking within intact bacterial cells and isolated cell walls of Aerococcus viridans ATCC 10400 grown in the presence of L-{epsilon-15N}lysine . A value of 49% for the cross-linking index was found for normal cells, while for those grown in the presence of low levels of penicillin G (0.1 micrograms/ml), the cross-linking index was reduced to 35%. Fed Regist . 1983 Sep 30;48(191):44931. Pharmaceutical Reimbursement Board; suspension of maximum allowable cost limits on specific drug products--HCFA. {Immunoallergic intravascular hemolysis and tubulointerstitial nephritis due to penicillin G} Jaeger A, Rihn B, Rodier L, Walti M, Sauder P, Kopferschmitt J, Mantz JM. A 51-year old woman treated with high doses of penicillin G developed acute intravascular haemolysis and tubulointerstitial nephritis . Immunological investigations showed circulating immune complexes, decreased C3 and C4 components of complement, IgG deposits in the renal interstitium, positive direct Coombs test with anti-IgG sera and complement and circulating anti-penicillin antibodies demonstrated by indirect antiglobulin tests and IgG RAST . Plasma haemoglobin and anti-penicillin antibodies could be removed by an early exsanguino-transfusion . These findings suggest that the nephritis was due to immune complexes and the haemolysis, to a combined hapten-type and immune complex mechanism. Br J Haematol, 1983 Sep, 55(1), 155 - 60 Demonstration of an immune-mediated mechanism of penicillin-induced neutropenia and thrombocytopenia; Murphy MF et al.; Severe neutropenia may be a more common complication of high-dose penicillin therapy than previously recognized . This report describes five such patients, one of whom also had thrombocytopenia . The neutrophil and platelet counts rapidly increased on stopping penicillin, and the bone-marrow, which was hypocellular in some cases, became normal . Further studies on one of these patients, using a fluorescent antiglobulin technique with paraformaldehyde-fixed cells, demonstrated a complement-fixing IgG penicillin antibody reacting with the patient's granulocytes and platelets in the presence of the drug . This suggested an immune mechanism similar to the well-recognized penicillin-induced immune haemolytic anaemia . The associated bone-marrow hypoplasia may also be due to antibody-mediated suppression of penicillin-coated precursor cells. Antimicrob Agents Chemother, 1983 Sep, 24(3), 307 - 12 Analysis of penicillin N ring expansion activity from Streptomyces clavuligerus by ion-pair high-pressure liquid chromatography; Jensen SE et al.; An ion-pair, reversed-phase, high-pressure liquid chromatographic method for the analysis of penicillin N ring expansion activity has been developed which allows simultaneous measurement of both substrate and product . The high-pressure liquid chromatography conditions were as follows: stationary phase, C18; flow rate, 2 ml/min; detection, 220 nm . The stationary phase was preconditioned with 4.5 mM tetrabutylammonium bromide in 0.05 M KH2PO4 (pH 4.0)-methanol (85:15, vol/vol) and then equilibrated with 0.06 mM tetrabutylammonium bromide in 0.05 M KH2PO4 (pH 4.0)-methanol (95:5, vol/vol) for analysis of reaction mixtures . These conditions separated authentic samples of penicillin N and desacetoxycephalosporin C and allowed cell-free studies of the ring expansion of penicillin N to desacetoxycephalosporin C by a partially purified enzyme from Streptomyces clavuligerus to be followed conveniently. Biull Eksp Biol Med, 1983 Sep, 96(9), 29 - 31 {Combined effect of a magnetic field and anti-hypoxic agents on epileptogenic foci in the rabbit hippocampus}; Tyvin LI et al.; Magnetic field (MF) intensifies the activity of penicillin-induced epileptogenic foci (EF) in the rabbit hippocamp . The same effect was obtained with gutimin . Injections of sodium hydroxybutyrate produced but little changes in hypersynchronous activity as compared to the data of control experiments . Combined influence of MF and gutimin on the rabbits somewhat reduced the quantity of the electrographic correlates of the seizures as compared with the results obtained with MF or gutimin alone . Meanwhile the use of MF coupled with sodium hydroxybutyrate reduced the number of the correlates and the amount of interictal epileptiform discharges as compared with these parameters in experiments where MF alone was applied or in control . It is assumed that MF induces slight hypoxia in the tissues thereby provoking an increase in the epileptogenic foci, whereas sodium hydroxybutyrate but not gutimin compensates for pathological action of MF. Br Heart J, 1983 Sep, 50(3), 290 - 2 Pulmonary valve gonococcal endocarditis . A forgotten disease; Rosoff MH et al.; Although gonococcal infections of the pulmonary valve were common before the introduction of antibiotics, such infections have rarely been reported since penicillin became available . In an elderly man with gonococcal endocarditis of the pulmonary valve the non-specific signs and symptoms, the late appearance of a pulmonary murmur, and the sterility of early blood cultures made the diagnosis unclear until three weeks after admission . Endocarditis was localised to the pulmonary valve by M-mode and cross-sectional echocardiography . Echocardiography may be useful for diagnosing endocarditis in patients with fever of unknown origin . Gonococcal infection should be suspected in patients with pulmonary vegetations and sterile blood cultures. Mol Biol (Mosk), 1983 Sep-Oct, 17(5), 1001 - 8 {Enzymes incorporated in polyelectrolyte complexes . Effect of matrix conformational changes and phase transitions in solutions on catalytic properties}; Margolin AL et al.; Immobilization of enzymes (penicillin amidase and alpha-chymotrypsin) in water-soluble nonstoichiometric polyeloctrolyte complexes (PEC) formed by poly(4-vinyl-N-ethylpyridinium bromide) (polycation) and polymethacrylic acid (polyanion) was carried out . Particles of these PEC consist of a nucleus formed by sequences of salt bonds between the units of oppositely charged polyelectrolytes and the hydrophylic shell formed by ionized groups of polyanions which is in excess in PEC . Such a structure of PEC particles results in a cooperative phase transitions of these systems at slight variations of pH and ionic strength . The work demonstrates phase diagrams of PEC solutions . The values of pH and ionic strength at which phase transitions in solutions of different PEC occur were elucidated . The decrease of pH value from 6.1 to 5.7 leads to reversible phase transition followed by a saltatory increase of Km for immobilized penicillin amidase by 5-10 fold depending on substrate used . The phase transition induced by ionic strength increase up to 0,27 M NaCl doesn't change significantly the Km-value of enzymic reaction . The phenomenon observed can be accounted for by the different structure of PEC particles . The catalytic properties of immobilized chymotrypsin were shown to depend on the loci of enzyme attachment . If the enzyme is bound to polyanion, neither conformational changes of the matrix nor phase transition in solution influence its accessibility for the protein inhibitor, but rather change the binding constant . If the enzyme is attached to polycation, i.e . included in the polycomplex nucleus, two fractions of enzymes accessible and inaccessible for protein inhibitor appear.(ABSTRACT TRUNCATED AT 250 WORDS) J Clin Neuroophthalmol, 1983 Sep, 3(3), 197 - 203 Ocular syphilis . Acute and chronic; Spoor TC et al.; We describe our experience over the past 2 years with the ocular manifestations in 32 patients with acute and chronic syphilis . We urge that syphilis be considered in evaluating those patients with recurrent iritis, chorioretinitis, papillitis, optic atrophy, or abnormal pupillary findings . Specific serologic testing (FTA-ABS) must be obtained . Screening serologies (VDRL) are inadequate . We suggest that patients with evidence for CSF involvement or active ocular disease be treated by continuous intravenous infusion of 24 million units penicillin G daily for 10 days. Scand J Haematol, 1983 Sep, 31(3), 283 - 6 The effects of cisplatin on normal human erythrocytes in vitro; Dawson M et al.; Therapeutic administration of cisplatin is often followed by anaemia which may not be due entirely or even largely to myelosuppression but rather to drug-induced haemolysis . Similar experience with other cytotoxic agents prompted earlier investigations which yielded evidence of drug-induced changes in RBC shape in vitro . Current studies of cisplatin and bleomycin, which have been used together in clinical practice, revealed a significant alteration in the profile of RBC morphology; specifically a reduction in the number of 'bowl' shaped cells . However, this finding is in contrast to the increase in 'bowls' which was observed previously with other drugs . So it appears that direct erythrocytotoxicity cannot explain the occurrence of anaemia in patients who receive cisplatin . An alternative mechanism, similar to that of penicillin induced haemolysis, is suggested by immunoradiometric assays of surface IgG on red cells. Am J Med, 1983 Aug 29, 75(2A), 119 - 24 Efficacy, pharmacology, and safety of amdinocillin in treatment of neonates; de Louvois J et al.; One hundred and nine neonates with complications conducive to lethal infections were investigated to determine the efficacy, pharmacokinetics, and safety of amdinocillin . Of these 109 neonates, 70 were participants in the clinical study and 39 in the pharmacokinetic study . Amdinocillin (40 mg/kg per day) and penicillin (60,000 units/kg per day) were administered separately in divided doses by intramuscular injection at six-hourly intervals for five days . Amdinocillin/penicillin proved to be a safe and effective alternative to gentamicin/penicillin; no adverse reactions were noted nor did the regimen adversely affect renal or hepatic function . Throughout the treatment period, amdinocillin maintained high therapeutic serum levels . Resistance to amdinocillin did not develop during treatment. Biull Eksp Biol Med, 1983 Aug, 96(8), 24 - 8 {Effect of "blue spot" hyperactivation on the rhythm of the intact heart and the heart with altered reactivity}; Pivovarov IuI et al.; Experiments on rats were made to study the character of rhythmical activity of intact heart and heart with abnormal reactivity under electrical stimulation of the blue spot (BS) and formation in it of the generator of pathologically enhanced excitation (GPEE) by penicillin microinjections . Hyperactivation of the BS by electrostimulation or formation of the GPEE led to the same disorders of rhythmical activity . Provoking changes in intact heart rhythm according to the tachycardia type, hyperactivation of the BS was accompanied by various arrhythmias under abnormalities of the heart regulatory mechanisms proper . It is assumed that hyperactivation of the BS may initiate cardiac rhythm disturbances . The dependence of the realization of pathological process on the changes in control apparatus function and target organ reactivity is stressed. Ann Emerg Med, 1983 Aug, 12(8), 507 - 9 Psychotic-like reaction to procaine penicillin G; Lankin DL et al.; A patient developed a psychotic-like reaction immediately after receiving an intramuscular injection of procaine penicillin G . The patient complained of a metallic taste, dizziness, ringing of the ears, and the fear of imminent death . No cardiovascular or pulmonary disturbances were noted . The reaction and all symptoms resolved within 15 minutes, and the patient has reported no further episodes . The case and a review of the literature are presented. Epilepsia, 1983 Aug, 24(4), 431 - 9 Epileptogenic activity of cephalosporins in rats and their structure-activity relationship; Kamei C et al.; The epileptogenic properties of 10 cephalosporins and penicillin G were compared by intraventricular application to rats . At doses greater than 32 micrograms per head, cefazolin provoked tremendous seizure signs, a spike-and-wave complex appeared in close succession for more than 30 min, and severe convulsions were observed repeatedly . Reactions to cefotiam, ceftezole, and cephaloridine were almost equal to reactions to penicillin . No epileptogenic signs were observed on EEGs, and no behavioral symptoms were observed after administration of 1,000 micrograms of cephalexin and cephradine per head . Reactions to cephapirin, cefmetazole, cephalothin, and ceftizoxime exhibited less marked epileptogenic features; activity was diminished in that order on EEGs and in behavioral signs . Compounds substituted with two different heterocyclic rings at position 7 (R1) and position 3 (R2) of 7-aminocephalosporanic acid were potent in producing epileptogenic signs both on EEGs and in behaviors . Compounds substituted with a heterocyclic ring at either position of 7-aminocephalosporanic acid were less potent . Compounds such as ceftizoxime, cephalexin, and cephradine, substituted at R2 with small groups, were almost incapable of producing epileptogenic activity . This may indicate that the substitution of a heterocyclic ring at position 3 will provoke the convulsive actions. Br J Vener Dis, 1983 Aug, 59(4), 225 - 7 Treatment of neurosyphilis with chloramphenicol . A case report; Romanowski B et al.; Although penicillin is the drug of choice in syphilis, treatment failures with benzathine and procaine penicillin have occurred in neurosyphilis . Patients allergic to penicillin have traditionally been treated with tetracycline but, since this drug diffuses poorly into the cerebrospinal fluid, its use in neurosyphilis is uncertain . In the case reported here, a penicillin allergic patient with general paresis of the insane was successfully treated with chloramphenicol . This drug has been used in the treatment of syphilis and achieves high concentrations in the cerebrospinal fluid . Thus chloramphenicol may be a more appropriate agent than tetracycline in treating patients with neurosyphilis who are allergic to penicillin. Radiology . 1983 Aug;148(2):388. Pelvic actinomycosis; Maloney JJ et al.; PIP: In the past Actinomycosis has been associated with diverticular disease of the colon, abdominal surgery, cholecystitis, and penetrating trauma . Recent reports have demonstrated an increased incidence in women using IUDs . Such a case is presented . a 40-year-old woman experienced lower abdominal pain and a 20 pound weight loss over a 2 month period . The patient had had an IUD (a Dalkon shield) placed 7 years previously and had not sought medical attention since then . Pelvic examination revealed an IUD in place and an 8 cm mass fixed to the left side wall and displacing the rectum . The IUD was removed after the pelvic examination . Laboratory studies were all within normal limits except for mild anemia . A computed tomographic scan of the pelvis showed a left hydroureter, an 8 cm pelvic mass with left side wall extension, and displacement of the rectum to the right . A barium enema examination showed fixed narrowing of the rectum and mucosal irregularity . A fine needle aspiration biopsy showed endometritis and frank pus with the presence of Actinomyces . Surgery confirmed these findings . The patient responded to antibiotic therapy after surgery and did well . The colonization of the vagina, cervix, and uterus by Actinomyces and complications such as tubo-ovarian and pelvic abscesses have been reported in IUD users . 1 study reported Actinomyces in as many as 25% of IUD users, although all patients in that study were asymptomatic . In addition, this group had an increased incidence of abnormal pap smears, which may add a confusing note in the event of a pelvic mass . The association if IUD use and abscess appears increased in those patients who have had the same iud in place for more that 2 years, although the complication has been reported only 2 1/2 months following IUD insertion . Actinomycosis is a diagnosis seldom made before biopsy or surgery . Culture of the organism is essential and the diagnosis is best made using immunofluorescent staining of formaldehyde-fixed, paraffin-embedded tissue . This needle biopsy can provide a quick diagnosis . Therapy includes high dose penicillin, to which the disease responds quickly, and incision and drainage if necessary . Prompt diagnosis and adequate treatment reduce the morbidity of dissemination and of chronic infection . Radiology, 1983 Aug, 148(2), 357 - 62 Adult-onset pulmonary tuberculosis; Choyke PL et al.; Medical records and radiographs of 103 adults with primary tuberculosis were reviewed . The shift toward delayed presentation appears to be related to decreasing childhood exposure and an increasing number of compromised hosts . Compared with classic "childhood" tuberculosis, there is a higher incidence of lower-lobe disease, but infiltrates also commonly involve the upper lobe or upper segments of the lower lobe . Adenopathy, cavitation, and tuberculoma are rare . If a pleural effusion is present and tuberculosis is suspected, pleural biopsy is mandatory . Adult respiratory distress syndrome can be a complication, particularly in miliary tuberculosis, and disseminated intravascular coagulopathy usually follows . A normal chest radiograph or clinical improvement of the patient with bed rest and penicillin does not exclude tuberculosis . Increased awareness of adult-onset tuberculosis on the part of radiologists could lead to a more rapid diagnosis and successful management. Lab Anim Sci, 1983 Aug, 33(4), 388 - 9 Methods for transport and long-term maintenance of spiny dogfish sharks; Jones RT et al.; Spiny dogfish shark (Squalus acanthias) embryos were transported from Maine to the Maryland laboratory where they were maintained for 20 months . During this maintenance period, these sharks progressed from a yolk-sac stage to feeding stage . Animals were maintained at 10 degrees C in artificial seawater containing penicillin and streptomycin and were fed frozen brine shrimp and krill . The ease with which these animals could be maintained in the laboratory for an extended period of time greatly enhanced their usefulness as an experimental animal in a variety of studies. J Clin Invest, 1983 Aug, 72(2), 504 - 15 Antibodies of patients with Lyme disease to components of the Ixodes dammini spirochete; Barbour AG et al.; Lyme disease is an inflammatory disorder of skin, joints, nervous system, and heart . The disease is associated with a preceding tick bite and is ameliorated by penicillin treatment . A spirochete (IDS) isolated from Ixodes dammini ticks has been implicated as the etiologic agent of Lyme disease . We examined the antibody responses of Lyme disease patients to IDS lysate components in order to further understand the pathogenesis of this disease . The components were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose, reacted with patients' sera, and the bound IgG was detected with 125I-labeled protein A (western blot) . We found that (a) Lyme disease patients had antibodies to IDS components (b) most patients studied had antibodies to two components with apparent subunit molecular weights of 41,000 and 60,000, and (c) the patients' antibody responses during illness and remission were specific, for the most part, for the IDS . In contrast to the findings with Lyme disease sera, sera from controls showed little reactivity with IDS components in either the western blots or a derivative solid-phase radioimmunoassay. Infect Immun, 1983 Aug, 41(2), 636 - 43 Inhibition of macromolecular synthesis in cultured rabbit cells by Treponema pallidum (Nichols); Wong GH et al.; Treponema pallidum partially inhibited the synthesis of DNA, RNA, and protein by rabbit cells in vitro . The inhibition of DNA synthesis was proportional to treponemal concentration and persisted during the period of exposure to T . pallidum . The toxic effect was not dependent on treponemal metabolism or on whole treponemes, since heat- and penicillin-killed treponemes and a cell-free sonicate of treponemes had similar toxicities . The toxic factor(s) was also detected in extracts of syphilitic rabbit testes but not in extracts of normal rabbit testes or testes inflamed by chemical means . The T . pallidum-derived toxic material had a molecular weight greater than 20,000 as determined by dialysis . Protein and DNA synthesis were most rapidly inhibited; RNA synthesis continued at normal rates for up to 2 h after exposure to treponemes . Protein synthesis or a necessary precursor of protein synthesis appeared to be the primary target of the T . pallidum toxin(s). Neurosci Lett, 1983 Jul 15, 38(1), 29 - 33 Topographical distribution of propagation of seizure activity in the basal ganglia during focal motor seizures in the monkey; Hosokawa S et al.; Topographical distribution of the propagation of seizure activity in the basal ganglia was studied during focal motor seizures from the focus in the face-hand area of Area 4 in the monkey, using the {14C}deoxyglucose autoradiography method . The focal seizures were induced by injecting potassium penicillin G into the face-hand area in the right motor cortex . The propagation of seizure activity in the basal ganglia was localized in the ventral and caudal parts of the ipsilateral putamen and globus pallidus lateral and medial segments, and in part of the reticular portion of substantia nigra . These areas in the basal ganglia seem to be functionally linked to the face-hand area of the motor cortex. Ann Allergy, 1983 Jul, 51(1 Pt 1), 30 - 2 Dermographia caused by IgE mediated penicillin allergy; Smith JA et al.; A patient developed symptomatic dermographia while taking penicillin . The dermographia disappeared when the penicillin was stopped . The patient usually was negative for dermographia testing up to 400 g pressure . While taking penicillin a dermographic response occurred at 50 g pressure . Passive transfer skin testing established that the reaction was mediated by an IgE antibody to penicillin breakdown products . Interestingly, in both the subject and the passive transfer recipient skin testing to Pen G, M.D.M . and B.P.L . was negative . We concluded that the dermographia in our patient resulted from specific IgE penicillin interactions not recognized by the usual testing reagents. Brain Res Bull, 1983 Jul, 11(1), 103 - 10 A short duration GABAergic inhibition in identified neostriatal medium spiny neurons: in vitro slice study; Lighthall JW et al.; Inhibition in the neostriatum was investigated in rat in vitro slice preparation using intracellular recording and labeling technique . The initial response recorded following local stimulation is a monosynaptically activated EPSP . In 17% of the neurons tested, IPSPs were observed following EPSPs evoked by local stimulation . In paired shock experiments reduction of test EPSP amplitude or action potentials occurred over interstimulus intervals (ISIs) of 3-38 msec . In some neurons, a pulse injection of depolarizing current was used to trigger an action potential which was in a paired shock, used to condition a test monosynaptically induced EPSP . Test EPSPs were shunted over ISIs less than 45 msec . Paired shock performed on the slices perfused with the medium containing GABA antagonists (e.g., bicuculline methiodide, picrotoxin, or penicillin-G) resulted invariably in potentiation of test EPSPs . Inhibition in the neostriatum in vitro is demonstrated as reduction in test amplitude in paired shock tests, by the presence of IPSPs and by the shunting of EPSPs conditioned by an action potential triggered by direct depolarization . Neurons exhibiting these forms of inhibition were intracellularly labelled with HRP and identified as medium spiny neurons . These results indicate that striatal GABAergic medium spiny neurons which are known to have an extensive axon collateral plexus play in a role in a short lasting inhibition observed in the striatum. Neuropharmacology, 1983 Jul, 22(7), 903 - 6 Central cardiovascular action of penicillin in anaesthetized dogs and rats; Tsoucaris-Kupfer D et al.; Penicillin (2-3 mg X kg-1) administered into the cisterna magna (i.c.) of dogs anaesthetized with alpha-chloralose induced a significant increase in mean blood pressure (MBP) and bradycardia, whereas intravenous injections of the same doses had negligible effects . Moreover, dogs receiving central injections of penicillin showed seizures abolished by administration of decamethonium bromide (100 micrograms X kg-1, i.v.) . In urethane anaesthetized rats, intracerebroventricular (i.c.v.) injections of penicillin (0.3-3 mg X kg-1) caused dose-dependent increases in mean blood pressure while the intravenous route led to opposite effects . gamma-aminobutyric acid (GABA) (1 mg X kg-1), its agonist muscimol (2 micrograms X kg-1) and the alpha 2-adrenoceptor agonist clonidine (1 micrograms X kg-1) injected intracisternally induced hypotension and bradycardia in dogs . These effects were abolished in animals pretreated with penicillin . In rats, the same agents injected intraventricularly respectively at 0.5 mg X kg-1, 0.5 micrograms X kg-1 induced also hypotension . The effect of clonidine only, was antagonized by pretreatment with penicillin, while penicillin administered at the peak of the hypotensive effect caused by GABA or muscimol reversed it . It is suggested that penicillin acts centrally as a GABA-antagonist, and that the cardiovascular effects of clonidine seem to be mediated, at least in part, by the stimulation of a GABAergic pathway controlling the autonomic nervous system. Brain Res Bull, 1983 Jul, 11(1), 91 - 101 Focal penicillin seizures--motor activity and cellular physiology and morphology; Greenwood RS et al.; Two types of intracellular activity have been found in neurons in the cortical penicillin seizure focus during an interictal spike; a prolonged depolarization (PDS) followed by hyperpolarization or predominantly hyperpolarization . In the present study of a penicillin focus we have correlated the penicillin focus location with motor behavior and the cellular physiology with cellular morphology and location . Penicillin injection at the same location in the anterior sigmoid gyrus invariably resulted in focal seizures involving the contralateral shoulder . From the locations of the myoclonus and the focus, the character of the movements and the route of seizure spread we conclude that the same pathways mediate movement produced by penicillin seizures or by electrically stimulating the same motor cortex . Intracellular recordings and dye-marking of cells in and around the seizure focus revealed that PDS neurons were located within a 3 mm radius from the site of penicillin injection . All PDS neurons either lacked well filled processes or had abnormal dendrites . Inhibited neurons were all pyramidal neurons with normal dendrites . The dendritic abnormalities observed could be important in the genesis of the PDS. Brain Res Bull, 1983 Jul, 11(1), 11 - 3 Substantia nigra single unit activity during penicillin-induced focal cortical epileptiform discharge in the rat; Kaniff TE et al.; In urethane anesthetized rats single unit activity was recorded in the substantia nigra (SN) during focal cortical epileptiform discharges induced by topical application of penicillin to the cortical surface . Eighty percent of SN units responded during the cortical interictal spike discharge, 50% with an initial burst or increase in firing rate and 30% with an initial inhibition or decrease in firing rate . In view of the SN's widespread projections to thalamus and brainstem, these results suggest the SN may be a prominent element of the pathway involved in the spread and generalization of cortical epileptiform activity. No To Shinkei, 1983 Jul, 35(7), 711 - 8 {Surface negative waves in penicillin-induced epileptogenesis in cats}; Iwayama K et al.; The "surface negative (SN) wave" produced by pyramidal tract stimulation and recorded at the cortical surface has been identified as a reflection of postsynaptic potentials generated through recurrent inhibitory pathways (Humphrey, et al.) . We studied changes in SN wave in an attempt to examine inhibitory mechanisms underlying epileptogenesis in immobilized cats . 1) A single shock applied to the cerebral peduncle evoked alpha and beta wave at the surface of ipsilateral anterior sigmoid gyrus (Fig.1 A) . A train of 4 shocks with 4 msec shock-interval elicited SN wave which had a peak latency of 20 msec and decayed in 60-80 msec (Fig . 1 B,C,D) . 2) The spindle-like after-discharges elicited by direct cortical shock were markedly suppressed with conditioning stimulation of the ipsilateral pyramidal tract (Fig . 2) . Spike-and-wave complexes and other ECoG paroxysms produced by intramuscular administration of penicillin (Pc) were also depressed by repeated stimulation of the cerebral peduncle (Fig . 3) . These facts revealed that the inhibitory effects of pyramidal tract stimulation caused to suppress the occurrence of epileptic discharges . 3) SN wave gradually diminished in amplitude after topical application of Pc at the anterior sigmoid gyrus (Fig . 4 A-D) . It disappeared completely when tonic-clonic sustained paroxysms occurred at the focus (Fig . 4 E) . These effects are due presumably to depression of recurrent postsynaptic inhibition caused by topical penicillin . 4) SN wave observed at the contralateral secondary focus was almost unchanged during interictal and ictal stage (Fig . 5).(ABSTRACT TRUNCATED AT 250 WORDS) Allergy, 1983 Jul, 38(5), 319 - 24 Humoral immune response to some benzylpenicillin preparations; de Haan P et al.; In this study the humoral immune responses to long-term administration of benzylpenicillin preparations with and without adjuvants were compared . In 44.4% of the patients on long-term treatment with a benzylpenicillin preparation containing oil and alum monostearate, an induction of benzylpenicilloyl (BPO)-specific IgG, IgM and IgE was demonstrated during and after the course . Patients treated with a benzylpenicillin preparation containing no oil and alum monostearate showed only a very weak BPO-specific IgM and IgG response during the course . In patients in whom long-term treatment with a benzylpenicillin preparation without adjuvants was initiated by a benzylpenicillin preparation containing oil and alum monostearate, not only BPO-specific IgM and/or IgG but also IgE were demonstrated in 13.0% . The differences in immune response in the various long-term courses were significant (P less than 0.05) . The data suggest that the presence of such adjuvants as oil and alum monostearate has an influence on the synthesis of BPO-specific antibodies . However, it can not be excluded that the difference in immunogenicity had some unknown connection with the differences in penicillin/blood levels. Acta Otolaryngol, 1983 Jul-Aug, 96(1-2), 99 - 104 Two versus seven days penicillin treatment for acute otitis media . A placebo controlled trial in children; Meistrup-Larsen KI et al.; 103 children between 1 and 10 years of age participated in a double-blind placebo-controlled trial testing the effect of penicillin-V, 55 mg/kg/day, for two days versus seven days in acute otitis media . No significant differences could be demonstrated with regard to earache, healing of the tympanic membrane, tympanometry, fever or common cold symptoms . 76% in the group treated for seven days had a satisfactory course of the disease, compared to 71% in the group treated for two days (p greater than 0.1) . In spite of the relatively small number of patients, it is concluded that the effect of penicillin for additional five days in acute otitis media after the initial treatment for two days, can at most be marginal . The advantages of a shortened treatment period are several; the authors have outlined a new treatment modality, consisting of masterful inactivity for 8-12 hours, penicillin-V for two days, and myringotomy in refractory cases, after a new evaluation by the otologist . We believe hereby to be able to reduce penicillin consumption in children with acute otitis media to about 15% of the previous level, without increasing the risk of serious complications. Sex Transm Dis, 1983 Jul-Sep, 10(3), 148 - 50 Treponemicidal levels of amoxicillin in cerebrospinal fluid after oral administration; Faber WR et al.; Seven patients in various stages of syphilis were treated by oral administration of amoxicillin (6 g daily) and probenecid (2 g daily) for 15 days . The treponemicidal level of amoxicillin was studied by a Treponema pallidum immobilization assay and found to be 0.070 micrograms/ml, as compared with 0.003 micrograms of penicillin/ml . Taking into account the WHO-recommended level of 0.018 micrograms/ml of penicillin, the minimal level of amoxicillin was estimated as 0.42 micrograms/ml . This level was obtained in serum and cerebrospinal fluid (CSF) of all patients treated with the above mentioned oral combination . It is concluded that treponemicidal levels of amoxicillin can be obtained in CSF after oral administration . The amoxicillin regimen described may be a valuable alternative to single-dose parenteral penicillin in the treatment of syphilitic patients with suspected CNS involvement, provided that reasonable compliance can be obtained. Clin Pharmacokinet, 1983 Jul-Aug, 8(4), 286 - 96 Influence of food intake on presystemic clearance of drugs; Melander A et al.; Many drugs have a low degree of oral bioavailability even though their gastrointestinal absorption is complete . This is because they undergo extensive presystemic metabolic transformation during the first passage of the drug through the gastrointestinal mucosa and the liver . In addition to effects on the absorption of some drugs, food intake has been found to influence the bioavailability of drugs with extensive presystemic metabolic clearance . Extensive presystemic clearance occurs commonly with compounds that are lipophilic bases, e.g . propranolol and amitriptyline, but rarely if ever with lipophilic acids, e.g . salicylic acid and penicillin, except for esters of such acids, e.g . acetylsalicylic acid (aspirin) and pivampicillin . While presystemic clearance of (esterified) acidic drugs is unaffected by food, concurrent food intake markedly reduces presystemic clearance, and thus enhances bioavailability, of several lipophilic bases . Among these are propranolol, metoprolol, labetalol, dixyrazine and hydralazine, which are presystemically metabolised by hydroxylation, glucuronidation and acetylation enzymes systems . In contrast, the bioavailability of lipophilic bases which undergo presystemic dealkylation (amitriptyline, codeine, dextropropoxyphene, prazosin, zimelidine) is unaffected by concurrent food intake . Food intake reduces presystemic clearance of hydralazine and propranolol when these drugs are administered in conventional rapid-release tablets but not when they are given in slow-release formulations . Likewise, coadministration of hydralazine reduces presystemic clearance of rapid-release but not slow-release propranolol . These and other observations favour the view that food may reduce presystemic clearance of (certain) lipophilic basic drugs via transient, complex effects on splanchnic-hepatic blood flow and/or shunt processes, and that the extent of this effect is influenced by the rate of drug delivery to the liver . In addition, these findings refute the notion that the reduced presystemic clearance results from (long-lasting) hepatic enzyme inhibition by some nutrient . On the other hand, repeated intake of specific nutrients (protein) and food contaminants (benzpyrene) can enhance presystemic drug clearance by enzyme induction . Thus, food may exert a dual effect on presystemic drug clearance . A complete evaluation of the influence of food on presystemic drug clearance necessitates bioavailability studies carried out following both single and repeated meals, including different kinds of food prepared by various cooking methods . The influence of food on the presystemic clearance of drugs is most likely to be clinically relevant with drugs having narrow therapeutic margins and/or steep dose-response curves. South Med J, 1983 Jul, 76(7), 921 - 2 Medical management of visceral actinomycosis; Schlech WF 3rd et al.; A patient had extensive retroperitoneal actinomycosis with renal and vertebral involvement . Abdominal computed tomography was invaluable in defining the extent of the disease and in assessing the effects of therapy . A cure was accomplished with a prolonged course of oral penicillin and probenecid, and surgical exploration was avoided. Am J Med, 1983 Jul, 75(1), 166 - 70 Unusual manifestations of secondary syphilis occurring after orthotopic liver transplantation; Petersen LR et al.; A 48-year-old actively homosexual man who had undergone liver transplantation for cirrhosis secondary to hepatitis B infection six years previously presented with a syndrome of diffuse pain, cholestasis, and low-grade fever . The development of thrombocytopenia and persistent hypoprothrombinemia precluded liver biopsy . Subsequently, a skin eruption and VDRL result of 1:128 indicated that most of the findings could be explained by a diagnosis of secondary syphilis with luetic hepatitis and periostitis . This impression was confirmed by a complete response to penicillin therapy . The relation of thrombocytopenia to lues in this case remains uncertain. Acta Chir Belg, 1983 Jul-Aug, 83(4), 266 - 8 {Gas gangrene of the abdominal wall following appendectomy}; Milani H et al.; Gas gangrene of the abdominal wall after appendicectomy is reported . Discussion evokes etiology and literature review . Penicillin, large excision of necrotic tissues and hyperbaric oxygenotherapy are the basis of the treatment. Lymphology, 1983 Jun, 16(2), 107 - 14 Overwhelming postsplenectomy infection (OPSI): the clinical syndrome; Van Wyck DB; Critical examination of the infectious risk following splenectomy raises questions about several widely held notions . True hazard of OPSI is difficult to quantify and probably underestimated, susceptibility is life-long, questionably altered by splenosis, and persists despite penicillin prophylaxis and vaccination against common pneumococcal serotypes. J Pharm Sci, 1983 Jun, 72(6), 668 - 73 Nonisothermal kinetics using a microcomputer: a derivative approach to the prediction of the stability of penicillin formulations; Hempenstall JM et al.; A procedure is described for the determination of the shelf-life of pharmaceutical preparations using nonisothermal kinetics . A BASIC computer program, which enables the data analysis to be undertaken rapidly and automatically on a microcomputer, is presented. J Antibiot (Tokyo), 1983 Jun, 36(6), 709 - 14 The preparation and determination of structure of benzylpenicilloyl compounds used in skin-testing for penicillin allergy; Goldschmidt BM et al.; The preparation of alpha-D-benzylpenicilloyl-n-propylamine and octa-epsilon-(alpha-D-benzylpenicilloyl)-octa-alpha-L-lysine are described . Their structures were established by chemical and spectroscopic evidence . Proton and carbon-13 nuclear magnetic resonance spectra of these two penicillin derivatives and some related compounds are provided . These compounds are useful in skin testing for penicillin allergy. South Med J, 1983 Jun, 76(6), 740 - 2 Lyme disease in North Carolina; Pegram PS Jr et al.; We report two cases of Lyme disease in North Carolina, further expanding the distribution of known sporadic cases of this predominantly northeastern problem in southern states . Physicians in areas where Lyme disease has traditionally not been recognized should be alerted to its characteristic rash (erythema chronicum migrans), tick vector (Ixodes species), possible severe manifestations (neurologic, arthritic, and cardiac), and response to appropriate antibiotic therapy (penicillin or tetracycline). J Neurosurg, 1983 Jun, 58(6), 959 - 61 Multiple cerebral gummata . Case report; Punt J; The case of a patient with multiple small cerebral gummata presenting with severely raised intracranial pressure is reported . The diagnosis, which was quite unexpected, was based on positive serological tests for syphilis . Computerized tomography (CT) showed small enhancing lesions with intense cerebral edema . The patient was treated successfully with penicillin, and resolution of the lesions was observed on CT scanning over a 1-year period . The importance of "routine" serological testing is noted. Br J Haematol, 1983 Jun, 54(2), 255 - 60 Penicillin-G degradation products inhibit in vitro granulopoiesis; Neftel KA et al.; 38% of penicillin-G in solution decays at 20 degrees C within 24 h, 50% at 37 degrees C and 66% within 3 h at 56 degrees C . These degraded penicillin-G solutions strongly inhibit growth and maturation of granulocytic stem cells in vitro . Inhibitory concentrations are in the range obtainable with high dose penicillin therapy in vivo . No cytotoxicity of degraded penicillin solutions on bone marrow cells was seen over 24 h . It is suggested that penicillin-G degradation products are responsible for severe granulocytopenia observed after high dose penicillin-G therapy. Arch Otolaryngol, 1983 Jun, 109(6), 410 - 2 Arachnia propionica (Actinomyces propionicus) as an unusual agent in tympanomastoiditis; Miglets AW et al.; The actinomycetes are extremely uncommon causative agents in chronic tympanomastoiditis . Few cases have been reported in the literature, and, before the use of penicillin, the majority of patients died of intracranial extension of their disease . Two patients described in the recent literature could have had their conditions diagnosed preoperatively as cholesterol granuloma . They had intact but immobile or bulging tympanic membranes and histories of intermittent perforations with drainage . The diagnosis was suggested during surgery because of the presence of yellow-green amorphous "sulfur granules" scattered throughout the mastoid . Both patients were well following mastoidectomy and long-term penicillin therapy . The clinical history of a patient with tympanomastoiditis due to Arachnia propionica (Actinomyces propionicus) is discussed . To our knowledge, this is the first case reported of a patient with otic disease due to this strain of the organism. Acta Psiquiatr Psicol Am Lat, 1983 Jun, 29(2), 111 - 5 {Profession and origin of patients with neurosyphilitic diseases in a psychiatric hospital over a 50-year period}; Fonseca Costa G; Through informations obtained at the statistical and medical register service, it was done a descriptive study of some epidemiological aspects of neurosyphilis and general progressive paralysis at the Juliano Moreira Hospital, Bahia, Brasil, in a period of 50 years (1930-1979) . For this purpose medical dossiers, obituaries, ingoing and outgoing register books, the census and nosocomial bulletin were referred . The distribution of disease was analysed comparing profession and origin according to sex, diagnosis, decade and time before and after penicillin therapy . The results allowed us to conclude that: a) The professions that we found more frequently were: formers, merchants, housewives, stoneworkers, public officials, tailors, soldiers, shoemakers, laborer workers; b) During the periods of war, we observed an increase in the number of ill soldiers; c) Patients coming from the urban zone were more frequently affected by the disease. An Esp Pediatr, 1983 Jun, 18(6), 467 - 73 {Clinical evolution of rheumatic carditis treated with aspirin}; Maroto Alvaro E et al.; We have analyzed the clinical, laboratory, electrocardiographic and echocardiographic findings of six patients with rheumatic carditis whose antiinflammatory treatment was aspirin . We include one case who was initially treated with steroids . She relapsed when the steroid treatment was discontinued and she was then treated with aspirin . There were 2 males and four females . The age range was 9 to 14 years . This was the first rheumatic attack for all the patients . They were also treated with penicillin G during ten days . The prophylaxis was accomplished with benzatine penicillin 1.200.000 IU at 28 days intervals . The aspirin was given at doses ranging from 60 to 100 mg/Kg/day for eight to twelve weeks . All the patients had auscultatory findings consistent with mitral insufficiency accompanied in two cases with findings of aortic regurgitation . In three cases, there was a transient mild diastolic murmur during the first five days . In one case the rheumatic carditis was complicated with acute renal failure due to acute rheumatic nephritis that required peritoneal dialysis . The follow-up period ranged from nine to twenty six months . There have been no relapses . All the patients remain asymptomatic and leading a normal life . At the last visit three patients had mild mitral insufficiency and in three patients the clinical findings, electrocardiogram and echocardiogram were normal . If we accept that most of the cases of rheumatic carditis are mild or moderate, is our believe that the aspirin is the antiinflammatory treatment of choice at the present time. Am J Dermatopathol, 1983 Jun, 5(3), 267 - 76 Fatal, penicillin-induced, generalized, postinflammatory elastolysis (cutis laxa); Kerl H et al.; A 13-year-old boy received penicillin for influenza and otitis media . Within days of taking this medication, he developed recurrent edema of the face and a generalized urticarial eruption which waxed and waned . The salient and unusual features of this person's disease were: 1) A senile appearance of his face with flaccid folds and sagging of the skin . Histopathologic findings were dense dermal inflammatory-cell infiltrates with numerous eosinophils and destruction of elastic fibers . Findings by electron microscopy were fragmentation and clumping of elastic fibers and accumulation of granular material in the dermis . 2) Dermatitis herpetiformis-like cutaneous lesions and gluten-sensitive enteropathy . 3) Elastolysis increased in time and led to further deterioration of the patient's physical appearance . Six years later, the patient developed severe internal manifestations and died . We assume that the inflammatory-cell infiltrates and prolonged edema following therapy with penicillin caused the dissolution of elastic tissue and resultant systemic elastolysis. Nippon Seikeigeka Gakkai Zasshi, 1983 Jun, 57(6), 629 - 41 {Tissue reconstitution by isolated articular chondrocytes in vitro}; Yoshihashi Y; It is well known that isolated chondrocytes can form a tissue resembling hyaline cartilage when reaggregated in vitro . Recently, this tissue has been experimentally transplanted as an allograft into the defect of articular cartilage . This phenomenon, however, has not been investigated in detail up to this time . The present study was designed to examine the tissue reformed by isolated articular chondrocytes in comparison with normal articular cartilage . Chondrocytes were released by enzymatic digestion from slices of articular cartilage taken from 8 week old white rabbits . The cells were suspended in culture medium (Ham's F12/10% fetal calf serum, 1% penicillin-streptomycin, 80 micrograms/ml ascorbic acid), and were inoculated in a large number into a 0.28 cm2 stainless cylinder on the Millipore filter . After 12 hours these chondrocytes were layered by gravity onto the Millipore filter and were cultured in the same medium during 7 days . Subsequently the cell aggregate was transferred to organ culture system and then was fed every other day . Aggregates of cells were sampled at 1, 2, 4, 8, 12 weeks in culture for morphological and biochemical studies . The results were obtained as follows: One week in culture, deposition of metachromatic matrix was observed under a light microscope only at the periphery of the aggregate of cells . Matrix formation in the whole aggregate occurred after 2 weeks in culture . The tissue reformed in this culture consisted of metachromatic hyaline cartilage like matrix and chondrocytes within lacunae but for cells at the surface arranged in a tangential flattened layer . The collagen in this tissue was of type II mixed with a very small amount of type I . In view of the above facts, it seemed most reasonable to conclude that the tissue reconstituted in vitro by freshly isolated chondrocytes had characteristics of hyaline cartilage except over the surface . Compared with normal articular cartilage, the cells in this tissue were distributed randomly and the intercellular hyaline matrix was poor under a light microscope, and collagen fibrils in the matrix observed under an electron microscope were much thinner than those of normal articular cartilage . The number of collagen fibrils in the intercellular matrix gradually increased under an electron microscope . Similarly, hydroxyproline content of the tissue increased until 8 weeks in culture . But the maximum value was only approximately a quarter of that of normal articular cartilage of an 8 week-old rabbit . Freshly isolated chondrocytes were thus shown to form hyaline cartilage in this culture method . This method thus provides a tissue culture model of cartilage organization . On the other hand, there were several points of difference between the tissue formed in vitro and normal articular cartilage . Consequently, more investigations are required to use cartilage reformed in vitro as an autologous or allogeneic graft into the defect of articular cartilage. J Trauma, 1983 Jun, 23(6), 478 - 82 Eikenella corrodens in human bite infections of the hand; Schmidt DR et al.; Over a 51/2-year period 30 patients were found with Eikenella corrodens infections of the hand following closed fist injury . Twenty-four had mixed infections; six grew pure cultures of Eikenella . Twenty-one of the 30 patients had positive cultures from an injured metacarpophalangeal joint . A delay in presentation or an inaccurate initial diagnosis appeared to be the most significant factors leading to the complications of osteomyelitis (in five patients) and significant loss of joint function (in eight other patients) . Clinicians must have a high index of suspicion when evaluating any hand injury and clenched fist injuries of the hand should be treated by early adequate surgical debridement followed by IV penicillin given until operative cultures confirm or deny contamination with Eikenella corrodens. Prostaglandins Leukot Med, 1983 Jun, 11(2), 199 - 211 Penicillin induced human platelet dysfunction and its reversal by epinephrine; Rao GH et al.; Antibiotics administered orally can impair platelet function and cause a bleeding diathesis . Platelet function impairment induced by antibiotics such as penicillin, carbenicillin and tetracycline could be corrected by exposing the refractory platelets to epinephrine first and then challenging with other agonists . Penicillin used in this study inhibited the platelet aggregation response and release reaction without blocking the ability of these platelets to convert arachidonic acid to thromboxane . The thromboxane generated in the presence of penicillin could not activate the platelets when threshold concentrations of arachidonate was used as stimulus . Epinephrine stimulation restored the platelet membrane sensitivity and normalized the platelet response to the action of agonists . These studies demonstrate that both by in vitro as well as in vivo routes penicillin induced temporary impairment of platelet function . The refractoriness was not due to the interference of membrane receptors for various agonists or due to the depletion of serotonin, adenine nucleotides or inhibition of cyclooxygenase activity . Penicillin inhibits some essential mechanism involved in platelet activation by agonists and this process may be calcium dependent . Epinephrine through alpha adrenergic stimulation restores the mechanism by which agonists initiate platelet activation. Boll Soc Ital Biol Sper, 1983 May 30, 59(5), 697 - 703 The effects of penicillin on the ECoG of rabbit; Musolino R et al.; The effects of non-convulsive doses of i.v . penicillin (1.100.000/1.300.000 I.U./Kg) on the ECoG of rabbits was studied . A tendency to an increase in spindling activity together with the presence of characteristic penicillin spikes, polyspikes and spike and wave complexes often preceding or intermixed to the spindling activity, was the most prominent finding . These data indicate that spindles and penicillin induced spikes show a straight correlation and seem consistent with the hypothesis that spindles have a facilitant effect on epileptic discharges. Minerva Med, 1983 May 12, 74(20), 1179 - 86 {Current clinical aspects of leptospirosis}; Suter F et al.; Leptospirosis is still endemic in the Po valley . It has an extremely protean clinical picture . In a series of 79 cases diagnosed at Pavia in the period 1970-79 hepatonephritic forms were the most common (29.1%), followed by febrile or pseudo-influenza forms (25.3%), hepatitis (20.2%), nephritis (17.8%), and meningitis (7.6%) . Febrile hepatonephritis was always accompanied by the most severe pictures . Timely antibiotic management with penicillin or ampicillin, and above all the early use of peritoneal dialysis (carried in 10 subjects) enable a final cure to be obtained even in these cases . The only death in that series did not appear to be ascribable to the disease itself. Fortschr Med, 1983 May 12, 101(18), 824 - 7 {Increase in phagocytosis by nonspecific antigens}; Meyer-Rohn J; By determination of Wright's opsonic index (modified method) in man after application of penicillin simultaneously with and without an "unspecific vaccine" (Omnadin) as an immunostimulant, it was shown that Omnadin stimulates the phagocytosis of peripheral leucocytes while penicillin inhibits phagocytosis (compared with untreated control persons). Brain Res, 1983 May 9, 267(1), 101 - 12 Participation of cortical recurrent inhibition in the genesis of spike and wave discharges in feline generalized penicillin epilepsy; Kostopoulos G et al.; Cortical recurrent inhibition (RI) evoked in pericruciate cortex by antidromic stimulation of the cerebral peduncle (CP) was studied in normal cats and in cats exhibiting the signs of feline generalized penicillin epilepsy (FGPE) following the i.m . injection of penicillin . Two measures of RI evoked by antidromic CP stimulation were used: (i) the averaged focal potential in the pericruciate gyrus; and (ii) the duration of the suppression or diminution of extracellularly recorded action potential (ap) discharge of antidromically activated pericruciate neurons measured in peristimulus time histograms (PSTHs) . After i.m . injection of 350,000 IU/kg of penicillin RI remained preserved as long as only generalized spike and wave (SW) discharges appeared in the EEG, although in 5/17 neurons a modest to moderate reduction in the duration of RI occurred once SW discharges had appeared in the EEG . This inconstant reduction was probably not caused by a direct anti-inhibitory action of penicillin, but is a consequence of the increased number of ap discharges curtailing RI . At the small concentrations of penicillin existing in brain in FGPE its anti-inhibitory action evident with larger concentrations cannot be demonstrated . When focal or generalized tonic-clonic (T-C) seizures occurred, RI was reduced in slightly more than half of the instances for a few minutes before the onset of these seizures . This suggests that the transition from SW discharge to T-C seizure may be caused by a breakdown of RI. J Dairy Res, 1983 May, 50(2), 185 - 91 An evaluation of the Charm test--a rapid method for the detection of penicillin in milk; Thorogood SA et al.; Using the Charm radioactive assay technique as a rapid test for the determination of penicillin in milk in experiments with milks containing known concentrations of penicillin, the coefficient of variation was found to be 15 and 11% for raw whole and reconstituted skim-milks respectively . Storage of reagents for up to 4 d increased the variance of the test by more than 20% and the estimated penicillin concentration 0.4%/d of storage up to 25 d . In comparison with the Bromocresol Purple Test, which was capable of 100% accuracy in defining a threshold of 0.02 i.u . penicillin/ml milk, the Charm Test falsely classified 15.6% of the samples. Drug Intell Clin Pharm, 1983 May, 17(5), 351 - 6 Interaction of penicillins with the components of plasma expanders; Koshiro A et al.; The interaction of penicillin with high molecular components of plasma expander such as dextran, 6-hydroxyethylstarch, and polygeline were studied . The formation of penicilloyl polysaccharides and smaller amounts of penicilloyl polygeline during incubation were confirmed by ultrafiltration and gelfiltration . The ultrafiltration through Collodion-Bags SM 13 200 was found to be a rapid and convenient method for the determination of macromolecular penicilloates . The accelerated degradation by the formation of penicilloyl esters with glucose and lactic acid was also suggested. Can J Neurol Sci, 1983 May, 10(2), 114 - 6 Sensorineural deafness in early acquired syphilis; Saltiel P et al.; A 36 year old male developed bilateral sensorineural deafness as the chief manifestation of secondary syphilis . Cerebrospinal fluid showed pleocytosis . Treatment with penicillin and prednisone resulted in good recovery of hearing . Initial recovery seemed dependent on corticosteroids . Deafness can complicate acquired syphilis in both early and late stages of the disease and may be its sole manifestation . Early acquired syphilitic deafness is usually the result of a meningitis affecting the eighth nerve and responds well to treatment . These features are contrasted with those of late acquired syphilitic deafness. Cutis, 1983 May, 31(5), 537 - 40 Syphilis: a cause of fever of unknown origin; Chung WM et al.; A homosexual man presented with a persistent high fever and a pruritic maculopapular eruption . All symptoms abated following penicillin treatment . Physicians should be aware that syphilis may present as a fever of unknown origin. J Infect Dis, 1983 May, 147(5), 898 - 909 Pathophysiology and immunology of the Jarisch-Herxheimer-like reaction in louse-borne relapsing fever: comparison of tetracycline and slow-release penicillin; Warrell DA et al.; Twelve men with louse-borne relapsing fever were treated with single doses of procaine penicillin plus aluminum monostearate (PAM) intramuscularly or of tetracycline intravenously . All patients experienced a definite Jarisch-Herxheimer-like reaction . Fever and spirochetemia were significantly prolonged and peak temperature was lower and occurred later in the PAM-treated group . Peak pulmonary ventilation, metabolic rate, and arterial PO2 were significantly higher in the tetracycline-treated group . Circulatory changes were similar in the two groups but were prolonged in the PAM-treated patients . Thus, tetracycline is recommended for treatment because it is more rapidly effective in eliminating Borrelia spirochetes and produces a reaction no more stressful physiologically than the one after PAM . There was no evidence of complement activation, and there was no change in immunoglobulin levels throughout the reaction . Immune complexes were detected in serum of five patients before treatment, but in fewer patients at the peak of the reaction and subsequently. Infect Immun, 1983 May, 40(2), 741 - 51 Chlamydia psittaci elementary body envelopes: ingestion and inhibition of phagolysosome fusion; Eissenberg LG et al.; The cell surface of Chlamydia psittaci seems important for establishing infection since (i) UV-treated elementary bodies (EB) attach to and are ingested by L cells and (ii) heat or antibody treatment decreases attachment to L cells and promotes the fusion of chlamydiae-containing phagosomes with lysosomes in macrophages . In the studies reported here, {3H}uridine-labeled UV-treated EB also persisted in mouse resident peritoneal macrophages and L cells, suggesting that phagosome-lysosome fusion is inhibited . We therefore chose to investigate the ingestion and internal fate of isolated purified EB envelopes in both nonprofessional and professional phagocytic cells . EB envelopes are internalized by target host cells as efficiently as are whole EB . Transmission electron microscopy of macrophages whose lysosomes were marked with ferritin revealed the persistence of individual envelopes in phagosomes devoid of ferritin for the 3-h observation period . In contrast, EB envelopes heated to 56 degrees C for 15 min were consistently found in ferritin-labeled phagolysosomes as early as 30 min . As another index of persistence, isolated EB envelopes were radioisotopically labeled with a Bolton-Hunter analog, {3H}N-succinimidyl propionate, and their fate as trichloroacetic acid-precipitable material was followed . A third probe, employed to detect the persistence of non-biodegradable antigen, was indirect immunofluorescence . Fluorescein-positive antigens were brightly visible for 7 days in both macrophages and L cells when they were inoculated with untreated EB or EB maintained in penicillin . But L cells inoculated with EB envelopes or EB treated with UV or chloramphenicol, all of which prevent the conversion of infectious EB into the metabolically active reticulate bodies, displayed reduced internal fluorescence by 2 days and the appearance of fluorescent material on the cell surface . This release of EB envelope material occurred in the absence of phagolysosome fusion . The data add credence to the belief that the spontaneous breakdown or autolytic enzyme release of EB envelope components must occur preparatory to the conversion of EB to reticulate bodies. Zh Vyssh Nerv Deiat Im I P Pavlova, 1983 May-Jun, 33(3), 407 - 15 {Shifts in the steady potential in the dynamics of stationary excitation of the cerebral cortex}; Koroleva VI; Shifts of steady potentials (SP) in the cerebral cortex of rats were studied during formation of stationary excitation foci by low-frequency electric stimulation and application of penicillin . The dynamics of SP shifts reflects summary effect of depolarization and hyperpolarization processes, actively involved in each cycle of excitation . As a result of functional heterogeneity of different cortical areas, a spontaneously appearing wave of spreading depression (SD) may be transformed into a spiral wave, actively influencing the dynamics of excitation resulting from direct stimulation of the cortex . The cause of long-term inhibition of paroxysmal activity foci may be repeated generation of slow negative waves of SD persisting in conditions of rapid restoration of cortical ability to conduct SD. Rev Electroencephalogr Neurophysiol Clin, 1983 May, 13(1), 3 - 19 {Various aspects of the physiology and pathophysiology of spindles in the cat}; Gloor P; Spindles are a thalamocortical rhythm entirely dependent upon a thalamic mechanism . Generators of cortical spindle waves are the pyramidal neurons of the cortex . A positive statistical relationship exists between postsynaptic excitatory events of these neurons and spindle waves, but there is no significant association with inhibitory postsynaptic events . The excitatory synaptic coupling between thalamocortical fibers and cortical neurons implicated in the genesis of spindles is weak, but increases considerably after i.m . injection of penicillin which induces a transformation of spindles into generalized spike and wave discharges (feline generalized penicillin epilepsy) . The bursts of increased discharges of pyramidal neurons after penicillin recruit the recurrent intracortical inhibitory pathway . There results from this an oscillation between phases of increased excitability and phases of diminished excitability which correspond respectively to the spike and to the slow wave component of the spike and wave complex . In its turn the cortex imposes this pattern of discharge upon the thalamus which brings about a close coupling of cortical and thalamic neuronal discharges during spike and wave activity. J Pharm Sci, 1983 May, 72(5), 508 - 13 In-beam electron ionization mass spectra of penicillins; Ohashi M et al.; The characteristics of in-beam electron ionization mass spectra of 6-aminopenicillanic acid and several penicillins, which yield no detectable molecular ion peaks using a conventional direct-insertion probe, have been established . The spectra of all compounds studied, with the exception of amoxicillin, exhibited molecular ion or (M+1) peaks with spectral features similar to the reported methyl ester or amide derivatives of the compounds . The fragmentation of penicillin G on electron impact under in-beam conditions can be described on the basis of data from mass analyzed ion kinetic energy spectrometry . A desorption technique utilizing polyethylene glycol 4000 was used as a means of obtaining satisfactory spectra of ampicillin and amoxicillin. Antimicrob Agents Chemother, 1983 May, 23(5), 653 - 7 Tobramycin inactivation by carbenicillin, ticarcillin, and piperacillin; Konishi H et al.; The in vitro and in vivo inactivation of tobramycin by carbenicillin, ticarcillin, or piperacillin was investigated by the enzyme immunoassay method in clinically employed dosages . After the addition of an 80-mg dose of tobramycin to 4- to 5-g doses of a penicillin in 100 ml of 0.9% saline or distilled water, the degradation profile of tobramycin appeared to follow a biexponential pattern of decay . Remarkable losses (30 to 40%) of tobramycin combined with carbenicillin or ticarcillin were observed within 1 h, as compared with the later decline . The combination of tobramycin with piperacillin was least inactivating . When the admixture of tobramycin with carbenicillin or piperacillin used in the in vitro study was infused to six volunteers over 1 h, the observed maximum concentrations of tobramycin were on the average 66 and 74% for carbenicillin and piperacillin, respectively, of that observed after tobramycin alone was given . In contrast, the value obtained for tobramycin in combination with piperacillin was close to 90% of the control value . The elimination half-lives of tobramycin combined with the penicillins were slightly shorter than those of tobramycin alone, indicating that the interaction occurs even in patients with normal renal function. J Immunol, 1983 May, 130(5), 2330 - 6 Studies of antigen binding on human basophils . I . Antigen binding and functional consequences; MacGlashan D Jr et al.; We developed an assay to study simultaneously antigen binding and its functional consequences on human basophils . Using a 125iodine-labeled penicillin-human serum albumin conjugate, we were able to detect as few as 100 molecules of antigen bound to purified basophils . We found that histamine release could be initiated with fewer than 100 molecules of antigen and that the optimum for histamine release occurred at a concentration at which 10 to 15% of the available antibody-binding sites were occupied . Analysis of the binding kinetics in the presence of monovalent hapten allowed a calculation of the affinity constant for the antibody:hapten association; the value of 2 to 3 X 10(6)/Msec confirmed an earlier independent calculation . Binding data also suggested a 25% fraction of the bound antigen was binding in monogamous bivalent form . It is anticipated that studies of this kind will delineate the nature of the antibody-antigen reaction on cell surfaces. Biull Eksp Biol Med, 1983 May, 95(5), 23 - 5 {Effect of N- and M- cholinoblockaders on experimental epileptogenesis}; Tkachenko EI et al.; It has been shown in chronic experiments on rabbits with epileptogenic foci provoked by microinjections of penicillin into the dorsal hippocamp that the N-cholinoblockers gangleron (3 mg/k, intravenously) and etherophen (5-10mg/kg, intravenously) possess marked anticonvulsant activity . Diphenin (50 mg/kg, intraperitoneally) was less potent . The M-cholinoblocker methamizil (1 mg/kg, intravenously), on the contrary, potentiated the epileptiform seizures . Emphasis is laid on the necessity of the goal-oriented synthesis and search for agents that would exhibit a "purely" central N-cholinoblocking action with a purpose of applying such agents as antiepileptic drugs . It is not recommended using the M-cholinoblockers for such purposes. Brain Res, 1983 Apr 25, 266(1), 137 - 42 Cholinergic enhancement of penicillin-induced epileptiform discharges in pyramidal neurons of the guinea pig hippocampus; Kriegstein AR et al.; Acetylcholine (1-20 mM) was applied to guinea pig hippocampal slices bathed in normal and penicillin-containing media . Recordings in the CA 1 pyramidal cell layer in the presence of penicillin showed that acetylcholine caused a prolonged enhancement of the extracellular field potential . Intracellular recordings documented an increase in duration of cell bursting, a decrease in burst afterhyperpolarization, and a membrane depolarization lasting 1-5 min . These results suggest that the actions of acetylcholine to increase membrane excitability interact with penicillin-induced disinhibition to enhance hippocampal epileptogenesis. Wien Klin Wochenschr, 1983 Apr 1, 95(7), 240 - 3 {Treatment of Amanita phalloides poisoning with silybin in combination with penicillin and cortisone}; Hofer JF et al.; A report is presented of Amanita phalloides poisoning in a family of 3 members admitted with acute gastrointestinal symptoms after eating a meal of various self-picked mushrooms . A latent period of 11 hours preceded the onset of symptoms, a typical feature of this form of poisoning . There was an enormous increase in liver-specific enzymes in two of the cases . The clinical picture was markedly mitigated by the early initiation of silybin therapy, in combination with penicillin and cortisone . The patients made a rapid symptomatic recovery and the liver parameters were sufficiently improved by the 12th day so that the patients could be discharged. Hum Toxicol, 1983 Apr, 2(2), 183 - 95 Chemotherapy of Amanita phalloides poisoning with intravenous silibinin; Hruby K et al.; 1 A total of 18 cases of Amanita phalloides intoxication was treated by combined chemotherapy during 1980 and 1981 . After attempted primary elimination of the toxin all patients received silibinin as basic therapy mainly by infusion and in two instances orally . 2 In order to evaluate the effect of silibinin therapy a retrospective study of the followed-up case records was made . The cases were arbitrarily classified into three groups according to the severity of liver damage (light, medium and severe) . 3 There was found a close relationship between the severity of liver injury and the delay between mushroom ingestion and the onset of silibinin therapy . With the exception of one fatality in a particularly high dosage suicidal intoxication, all patients survived . 4 Administration of silibrinin even up to 48 h after mushroom ingestion appears to be an effective measure to prevent severe liver damage in Amanita phalloides poisoning . Contrarily, the onset of general supportive treatment together with penicillin therapy which was throughout several hours before silibinin administration did not correlate with the severity of liver damage. Ann Intern Med, 1983 Apr, 98(4), 466 - 71 Clindamycin compared with penicillin for the treatment of anaerobic lung abscess; Levison ME et al.; The clinical efficacy of clindamycin was compared with that of penicillin in a randomized study of the treatment of community-acquired putrid lung abscess . After starting therapy, patients treated with clindamycin had a shorter febrile period and fewer days of fetid sputum than patients treated with penicillin (mean 4.4 versus 7.6 days and 4.2 versus 8.0 days, respectively, p less than 0.05) . Four of 20 patients treated with penicillin had clinically significant pulmonary or pleural extension of their infection within 10 days after starting therapy; this was not found in any of 19 patients treated with clindamycin (p less than 0.05) . Penicillin treatment failed in two additional patients after 20 days of therapy . Within 1 month after treatment, 1 of 4 patients given penicillin for 3 weeks had relapse, but none of the 13 patients given clindamycin for 3 or 6 weeks, and none of the 5 patients given penicillin for 6 weeks had relapse . Overall, only 8 of 15 patients treated with penicillin who could be followed to the end of the study were cured, whereas all 13 patients treated with clindamycin who could be followed were cured (p less than 0.01) . These results suggest that penicillin may not be optimal therapy for anaerobic lung abscess. Am J Ophthalmol, 1983 Apr, 95(4), 480 - 6 Syphilitic neuroretinitis; Folk JC et al.; Four patients (three men, 32, 43, and 53 years old, and one 37-year-old woman) with syphilitic neuroretinitis had cerebrospinal fluid evidence of neurosyphilis . Therapy failed in one patient given penicillin G benzathine intramuscularly and it may have failed in a second patient . Another treatment failure occurred in a patient given tetracycline orally . Intramuscular penicillin G benzathine or intramuscular penicillin G procaine in doses of less than 2.4 million units/day does not produce spirocheticidal drug levels in the cerebrospinal fluid . All four patients improved after high-dose treatment with aqueous penicillin G. Epilepsia, 1983 Apr, 24(2), 200 - 13 Feline generalized penicillin epilepsy: changes of glutamic acid and taurine parallel the progressive increase in excitability of the cortex; van Gelder NM et al.; A coinciding temporal sequence of electrophysiological and biochemical correlates of developing generalized penicillin epilepsy in cats may indicate a "cause and effect" relationship between the two phenomena . After intramuscular injection of penicillin, in the pre-epileptic state prior to the onset of spike-and-wave discharge, the cortical content of glutamic acid decreases . This change occurs when an increased amplitude of visual evoked potentials in association cortex heralds the approach of spike-and-wave activity . The decrease of glutamic acid and that of aspartic acid occur in parallel with an almost stoichiometric increase of glutamine, gamma-aminobutyric acid (GABA), or both, while taurine levels in the pre-epileptic state remain near normal . As the pre-epileptic progresses to the epileptic state, characterized by generalized 4-5 cycles/s spike-and-wave discharges, a failure of the glial capture mechanisms for taurine and glutamate appears to occur, since both amino acids are lost from the tissue and glutamine levels fall while GABA levels are maintained or become elevated but increasingly at the expense of aspartic acid . A presumed increase in interstitial glutamic acid concentration possibly in combination with subsequent failure of GABA inhibition appears the most plausible explanation for the increasing hyperexcitability during the development of feline generalized penicillin epilepsy. Sex Transm Dis, 1983 Apr-Jun, 10(2), 53 - 5 Cefoxitin vs . penicillin in the treatment of uncomplicated gonorrhea; Greaves WL et al.; Four hundred six men and women with gonorrhea were randomly assigned to receive either 2 g of cefoxitin or 4.8 X 10(6) units of aqueous procaine penicillin G intramuscularly . All patients also received 1 g of probenecid orally . There was no statistically significant difference in the failure rate between patients treated with penicillin (4.3%) and those treated with cefoxitin (5.1%) . Twelve (92%) of 13 homosexual men with gonococcal proctitis who received penicillin and 19 (95%) of 20 who received cefoxitin were cured . Adverse reactions were infrequent and mild in the cefoxitin-treated group . Three patients who received penicillin developed reactions consistent with procaine toxicity . It is concluded that cefoxitin is a safe and effective alternative to penicillin for treating uncomplicated anogenital gonorrhea in men and women. J Neurosurg Sci, 1983 Apr-Jun, 27(2), 73 - 6 Observations on the "dependent stage" of the "mirror focus"; Turano C et al.; The present communication was part of a larger study in which penicillin induced epileptogenic activity in the hippocampus of the "cerveau isole cat" was investigated . The discharge contralateral to the side of the PCN focus, i.e., the mirror focus, was dependent upon the integrity of the commissural pathways . Interhippocampal latencies of bisynchronous epileptogenic discharge varied between 0 and 50 msec (mean 20) . Interestingly the discharges could occur absolutely simultaneously and even more surprising, the mirror focus discharge occasionally led that in the primary focus! An interpretation as to how this might occur is given. J Neurosurg Sci, 1983 Apr-Jun, 27(2), 69 - 71 Metabolic changes in the hippocampus after prolonged epileptic discharge; Galella G et al.; Sustained epileptic seizures were induced in cats by means of penicillin (PCN) . After a three hour period tissue from the archicortex was removed, frozen, and extracted for metabolic studies . The concentration of ATP, ADP, AMP, phosphocreatine, glucose, glucose-6-phosphate, pyruvate, lactate, glutamate and aspartate were determined . There was a 50% decrease in phosphocreatine concentration, a slight decrease in the level of ATP and a slight increase in the levels of ADP and AMP . There was a decrease in the total adenine nucleotide and the ATP/ADP and ATP/AMP ratios . The absence of a significant change in adenylate energy charge potential reflects the |