Br J Clin Pharmacol, 1988 Jan, 25(1), 33 - 40 Milk transfer of phenoxymethylpenicillin during puerperal mastitis; Matheson I et al.; 1 The milk excretion of phenoxymethylpenicillin (PMP) was studied from both breasts in patients with mastitis (n = 12) and healthy volunteers (controls, n = 4) to investigate the hypothesis that milk transfer of PMP is higher in mastitic than in non-mastitic breasts . 2 Patients were included according to clinical symptoms of mastitis . Milk (and serum from controls) were sampled 0, 1, 2, 3, 4, 6 and 8 h after a single oral dose of 1320 mg PMP . Penicillin concentrations in milk and serum were measured by an agar diffusion technique . 3 Maximum milk concentrations (Cmax) of PMP in patients were higher (P less than 0.05) in mastitic than in non-mastitic breasts . The latter concentrations were higher (P less than 0.05) than those in breast milk from healthy controls . In milk from the mastitis patients (both breasts) the Cmax was reached after 2 h with a subsequent rapid decline in concentration . In milk from the healthy controls the PMP concentration reached a plateau after 4 h . The area under the milk concentration vs time curve (AUC0-8h) was not different for mastitic vs non-mastitic breast milk in patients nor for mastitic vs control breast milk . This can be explained by higher rates of appearance and disappearance of PMP in the breast milk of mastitis patients compared with healthy controls . In mastitic breast milk there was a moderate (P less than 0.01) increase in sodium and albumin compared with non-mastitic milk . However, milk potassium, glucose and lactose values were within normal limits.(ABSTRACT TRUNCATED AT 250 WORDS) Epilepsia, 1988 Jan-Feb, 29(1), 74 - 82 Neurogenic myocardial arrhythmias in experimental focal epilepsy; Mameli P et al.; The potential for cardiac arrhythmia was studied in an experimental focal epilepsy induced in hemispherectomized rats by topical application of buffered penicillin G onto the thalamus . The epileptic burst triggered cardiac and hemodynamic responses, as simultaneously monitored by arterial pressure, and hypothalamic and heart activity . During interictal epileptic activity, the single burst triggered a short-latency cardiac arrhythmia, characterized by sinus bradyarrhythmia and junctional rhythm, and lengthening of intervals between sphygmic waves with significant reduction of diastolic pressure . When the epileptic burst stopped, the cardiac activity resumed normal rhythm, and diastolic pressure returned to basal value . During ictal epileptic activity, the sinus and junctional bradyarrhythmic episodes lasted longer, and supraventricular extrasystoles, sinus arrest, and bigeminal ventricular extrasystoles were observed . Both systolic and diastolic pressures decreased from 120/85 to 100/65 mm Hg . The end of the ictal episode always marked resumption of normal cardiac rhythm and systemic pressure . Considering the absence of metabolic complications (blood-gas analytic parameters and acid-base balance being controlled) and the short latency of the cardiac and hemodynamic responses, it is suggested that during paroxysmal hypothalamic activity the observed cardiac arrhythmias and the hemodynamic modifications were neurogenic in origin . A role for cardiovascular alterations in sudden unexplained epileptic death is postulated. Exp Neurol, 1988 Jan, 99(1), 38 - 49 Focal hippocampal epilepsy: effect of caudate stimulation; La Grutta V et al.; The basal ganglia seem to be involved in the control of abnormal hippocampal activity . The caudate nucleus has been reported to elicit hippocampal theta rhythm and to inhibit epileptiform spikes . Experiments were conducted to test the action of caudate stimulation on focal penicillin epilepsy of the hippocampus in the cat prior to and after septal coagulation and parenteral atropine administration . Results showed that the caudate is able to reduce both hippocampal spike frequency and amplitude . The effects are abolished by septal lesions and either decreased or totally suppressed by atropine administration . The findings are discussed in terms of caudate influence on septum; the importance of cholinergic pathways is also emphasized. Rev Neurol (Paris), 1988, 144(12), 765 - 75 {Multiple neurologic manifestations of Borrelia burgdorferi infection}; Dupuis MJ; The neurological spectrum of Borrelia burgdorferi infections is still enlarging . We review epidemiological, pathological and serological data of Lyme disease . The course of the disease is divided in three stages: stage 1 during the first month is characterised by erythema chronicum migrans and associated manifestations; stage 2 includes not only the classical European meningoradiculitis but also less specific neurological symptoms: isolated lymphocytic meningitis with an acute or even relapsing course, apparently idiopathic facial palsy, neuritis of other cranial nerves, polyneuritis cranialis, Argyll-Robertson sign, peripheral nerve involvement, acute transverse myelitis, severe encephalitis, myositis . During stage 3, three to five months or longer after the onset of the disease, chronic arthritis, acrodermatitis chronica atrophicans and various neurological symptoms can be observed: chronic neuropathy with mainly sensory or motor signs, recurrent strokes due to cerebral angiopathy and progressive encephalomyelitis; this third stage the central nervous system involvement is characterised by slowly progressive or fluctuating course during months or years, ataxic or spastic gait disorder, bladder disturbances, cranial nerve dysfunction including optic atrophy and hypoacusia, dysarthria, focal and diffuse encephalopathy . This chronic central nervous system disease can mimic multiple sclerosis, anorexia nervosa, psychic disorders or subacute presenile dementia . It is often associated with pleiocytosis, abnormal EEG and evoked potentials, sometimes multifocal and mainly periventricular white matter lesions visualised by CT or MRI, and as a rule high antibody titers against Borrelia burgdorferi . High doses of penicillin can halt the disease, sometimes induce spectacular regression of symptoms or sometimes be inefficient; ceftriaxone could be a more powerful therapy . Similarities between syphilis and Borreliosis are multiple: both of these spirochetes contain plasmids, can be transmitted through the placenta and progress for many years through successive stages, with multiorgan symptoms, including parenchymatous and vascular lesions of the central nervous system . Borrelia burgdorferi is the new great imitator. Ann N Y Acad Sci, 1988, 539, 317 - 23 Treatment of Lyme borreliosis with emphasis on neurological disease; Skoldenberg B et al.; We have studied 113 patients with neurologic Lyme borreliosis and meningitis who were treated with intravenous high-dose antibiotics (penicillin G, 12 g, mostly for 14 days in 47 patients; penicillin G, 9 g, mostly for 10 days in 58 patients; doxycycline, 200 mg, in 5 patients; and cefuroxime, 4.5-9 g, in 3 patients) . Seventy percent of the patients had peripheral nerve symptoms and 13% had central nervous symptoms . Almost half of the patients were treated more than 4 weeks after the onset of symptoms and 15% of the patients had persisting or progressive symptoms between 4 and 11 months . There seemed to be clinical benefit as well as a decrease of spinal fluid pleocytosis and spinal proteins . No significant symptoms of Herxheimer reaction were demonstrated. Med Cutan Ibero Lat Am, 1988, 16(2), 111 - 4 {Immunology of tertiary pinta}; Pecher SA et al.; We've studied the immunological performed of twenty two natives Tikunas suffering from tertiary pinta . Among those, patients had been treated previously (two years earlier) which 2,400,000 IU of G benzathine penicillin, and twelve had no treatment . Both groups demonstrated an increment in the IgM synthesis (72.72%), IgG (50%), indicating the presence of strong antigenic stimuli . The great majority presenting a negative response revealed also a reduction in the cellular immune competence to at least two of the tests performed (92.3%), when were realized the PPD, DNCB and skin grafts tests. Ann Parasitol Hum Comp, 1988, 63(1), 5 - 15 {The rabbit, experimental host of Pneumocystis carinii}; Soulez B et al.; Pneumocystis carinii can be collected from experimentally immunodepressed rats . However, development of experimental pneumocystosis in this host requires corticoid-treatment during 8 to 12 weeks while P . carinii can be obtained from immunodepressed rabbits after 2 to 4 weeks . In 400 to 650 g body weight-white rabbits normally fed, two immunodepression protocols were used: (a) daily subcutaneous injections of hydrocortisone acetate (10 mg/kg body weight) and G penicillin (25,000 IU)-streptomycin (3 mg); (b) continuous oral administration of prednisolone (20 mg/l/day) and amoxicillin (25 mg/l/day) both diluted in drinking water . Between 55 and 78% of rabbits treated by any immunodepression protocol died within 5-20 days after a terminal important diarrhoea . Seventy and seventy-seven per cent of the young rabbits respectively treated by protocols (a) or (b), showed the presence of Pneumocystis by the direct microscopic examination, but all of them were found positive after lung concentration . Fifty-five per cent of the older rabbits (950-1,400 g) were positive by pulmonary smear examination when treated with protocol (a) . Pneumocystis obtained were good antigens for indirect immunofluorescence and immunoblot assays using human and rabbit sera. Acta Morphol Neerl Scand, 1988-89, 26(2-3), 69 - 80 Issues involved in the transmission of chemical signals through the brain extracellular space; Nicholson C; Two classes of substances exist within the extracellular space: energetic and informational . Examples of the former are glucose, dissolved oxygen and CO2 while the latter include excitatory amino acids, cathecholamines and opiates . The simple ions Na+ and Cl- are generally associated with energetic processes while extracellular K+ and Ca2+ tend to be informational in function . Local release of an informational substance brings about a concentration gradient that causes the substance to be dispersed in the extracellular space by diffusion . This process is modified relative to a free aqueous medium by the constraints of volume fraction, tortuosity and uptake . Volume fraction is defined simply as the fraction of a brain region that is extracellular . If a given quantity of substance is released into a region with a reduced volume fraction then the substance will reach a higher concentration than it would in a free medium . Tortuosity is related to the increase in the path length of the random walk of a diffusing particle due to the necessity to navigate around cellular obstructions . Tortuosity manifests itself as a decrease in the diffusion coefficient . Uptake represents the movement of a substance from the extracellular space to the intracellular . Since initially a concentration gradient exists in this direction and all membranes have some permeability some concentration-dependent uptake always occurs . In addition there exist specific carrier-mediated uptake processes for some substances such as amino acids or catecholamines . In some regions the dispersal process can be dominated by uptake rather than diffusion . While volume fraction, tortuosity and uptake have all been demonstrated by a technique based on the use of radiolabels and other methods, these classical techniques have limited spatial and temporal resolution . The advent of methods based on micro-injection of substances by iontophoresis or pressure and subsequent detection with ion-selective microelectrodes (ISMs) or voltammetric microsensors (VMs) has opened a new window onto the dynamic local behavior of the extracellular space . In the last decade our laboratory and others have studied the migration of the test substances tetramethylammonium, tetraethylammonium, AsF6- and alpha naphthalene sulfonate, the endogenous ions K+ and Ca2+, the epileptogenic agent penicillin and the neurotransmitter dopamine . These studies have been carried out on the cerebellum and some other regions in a variety of species that include rat, turtle, skate and an intervertebrate, the cuttlefish.(ABSTRACT TRUNCATED AT 400 WORDS) FEBS Lett, 1987 Dec 21, 226(1), 150 - 4 A water-soluble form of penicillin-binding protein 2 of Escherichia coli constructed by site-directed mutagenesis; Adachi H et al.; Penicillin-binding protein (PBP) 2 of Escherichia coli is located in the cytoplasmic membrane . The N-terminal hydrophobic segment (31 amino acids, residues 15-45) of PBP2 was removed by a deletion in the PBP2 gene by site-directed mutagenesis, resulting in the production of a water-soluble form of PBP2 (called PBP2*) . PBP2* retained the penicillin-binding activity, was localized in the cytoplasm and was overproduced under the control of the lpp-lac promoter . this indicates that the removed hydrophobic segment is an uncleaved signal sequence required for translocation of PBP2 across the cytoplasmic membrane, and also suggests that the segment anchors the protein to the membrane. Am J Ophthalmol, 1987 Dec 15, 104(6), 595 - 7 Syphilitic episcleritis and scleritis; Wilhelmus KR et al.; We screened patients with episcleritis or scleritis to detect syphilis by using either fluorescent treponemal antibody absorption testing or microhemagglutination assay for antibodies to Treponema pallidum . Four patients, two with nodular episcleritis and two with scleritis, had ocular involvement as the initial manifestation of late syphilis . Topical or oral corticosteroid therapy provided minimal initial clinical benefit, but ocular inflammation resolved within one to three weeks after administration of systemic penicillin. S Afr Med J, 1987 Dec 5, 72(11), 781 - 3 The problem of compliance in rheumatic fever; Walker KG et al.; During a 12-month period 115 patients defaulted from a rheumatic fever clinic, so a study was undertaken to identify factors related to non-compliance by comparing defaulters with a group of 50 regular attenders . Those defaulting were significantly more likely to be coloured, male, and over 12 years old . They lived 10-99 km from the hospital, were on several drugs and despite more frequent appointments, usually had a record of poor attendance . The severity of the underlying heart disease and use of parenteral penicillin did not affect compliance . Since the use of regular penicillin prophylaxis for the secondary prevention of rheumatic fever is an essential step in reducing the prevalence of rheumatic heart disease, rheumatic fever clinics should be structured to address the needs of adolescents . Furthermore, the use of neighbourhood clinics for routine therapy between visits to a rheumatic fever clinic is essential to improve compliance. J Immunol Methods, 1987 Dec 4, 105(1), 107 - 10 A rapid Percoll technique for the purification of human basophils; Warner JA et al.; We have refined a rapid single-step Percoll technique to obtain a basophil-enriched mononuclear cell fraction suitable for further purification . Greater than 75% of the total blood basophils were recovered from a blood-Percoll interface at a purity of between 5 and 23% . The contaminating cells were principally lymphocytes with a smaller (20-25%) percentage of monocytes . Further purification using the penicillin affinity column led to the recovery of between 28 and 64% of the total blood basophils at purities ranging from 52 to 92%, a substantial improvement over our earlier protocol . There was also a marked increase in the recovery of basophils from the affinity column over our previous technique, which lead to a moderate (5-10%) increase in overall recovery. Am J Dis Child, 1987 Dec, 141(12), 1285 - 90 Human bites in children . A six-year experience; Baker MD et al.; Three hundred twenty-two human bites in children, occurring during a six-year period, were reviewed . The majority occurred during warm-weather months between 2 PM and 11 PM . The upper extremities (42%), face and neck (33%), and trunk (22%) were most commonly bitten . At the time of injury, children were most often engaged in fights (61%) or play (26%) . Seventy-five percent of wounds were superficial abrasions, 13% were punctures, and 11% were lacerations . None of the 242 abrasions became infected as opposed to 38% of the punctures and 37% of the lacerations . Other factors associated with increased risk of infection were delay in initial physician assessment beyond 18 hours after injury, location of the bite on the upper extremities, and occurrence of injury during sports activities . Prophylactic use of penicillin was probably not effective in reducing infection rates in these children; however, prospective data are needed to properly address this issue. Antibiot Med Biotekhnol, 1987 Dec, 32(12), 894 - 8 {Penicillin-selective electrode based on a cellulose membrane with immobilized enzyme}; Dobroliubov AG et al.; Modified cellulose films are recommended to be used as carriers in preparing enzymatic membranes for penicillin-selective electrodes . The results of laboratory testing of the enzymatic penicillin-selective electrode based on the cellulose membrane with immobilized penicillinase are presented . In principle it was shown possible to use the enzymatic electrode in determining penicillin concentration in solutions . Dependence of the electrode reading on the buffer capacity was revealed . Optimal characteristics of the enzymatic membranes and the life-expectancy of the enzymatic electrode were determined. Chemioterapia, 1987 Dec, 6(6), 434 - 6 Azlocillin and the immune response in intensive care; Santamaria LB et al.; The authors have followed the course of the immunological cellular and humoral parameters in 12 patients in the Intensive Care Unit at the University Polyclinic of Messina having grave infections of the respiratory apparatus, for which an antibiotic therapy with azlocillin, semisynthetic penicillin was carried out; all this with the aim of pointing out any possible interferences with the already precarious immune system in such patients . The results obtained seem to exclude any immunodepressing activity by the molecule. J Infect Dis, 1987 Dec, 156(6), 959 - 66 Beta-lactam resistance in Nocardia brasiliensis is mediated by beta-lactamase and reversed in the presence of clavulanic acid; Wallace RJ Jr et al.; Forty clinical isolates and the type strain of Nocardia brasiliensis were screened for susceptibility to 20 beta-lactams . Isolates exhibited a single pattern of resistance, with large zones of inhibition by disk diffusion and low MICs by broth and agar dilutions only to cefotaxime, ceftriaxone, ceftizoxime, Augmentin, and Timentin . All strains produced beta-lactamase, with five different enzyme patterns by isoelectric focusing . Despite the differences in their isoelectric points, the enzymes had the same substrate profiles, with equivalent activity against penicillin, ampicillin, cefamandole, cephalothin, and cephalordine . In an in vitro assay, the enzymes were highly susceptible to clavulanic acid . The MIC50 and MIC90 for the combination of amoxicillin and clavulanic acid (Augmentin) was 2 and 4 micrograms/ml, respectively, compared with 16 micrograms/ml for both values for amoxicillin alone . These studies suggest that beta-lactamase is the major mechanism of beta-lactam resistance in this species and that Augmentin is the first oral beta-lactam with good potential for treating infections due to N . brasiliensis. Antimicrob Agents Chemother, 1987 Dec, 31(12), 1994 - 6 Outer membrane penetration by (2,3)-methylenepenams; Chapman JS et al.; The penetration of the Escherichia coli outer membrane by two sterically restricted analogs of penicillin G was determined . The analog corresponding to the "open" conformation of penicillin G penetrated faster than the "closed"-form analog did, and both analogs penetrated faster than penicillin G did . The results suggest that the conformation of the beta-lactam nucleus may affect penetrability via the porin-mediated pathway. Hematol Oncol Clin North Am, 1987 Dec, 1(4), 603 - 20 Hodgkin's disease in children; Sullivan MP; Hodgkin's disease may now be managed with several different regimens with the expectation of curing approximately 90 per cent of patients . Radiotherapy alone achieves this cure rate only in unilateral high cervical or inguinal stage 1 presentations . With all other presentations, radiotherapy requires the addition of chemotherapy to sustain the 90 per cent cure level . Combined modality regimens offer the patient the advantage of reduced doses of each modality in terms of number of Gy and courses of chemotherapy . The contribution of the staging laparotomy to combination therapy is now being questioned . This issue becomes pressing as imaging of the lymphatic system and commonly involved extranodal sites of disease is improved by computed tomography, magnetic resonance, and ultrasound technology . Only the spleen escapes adequate examination . The failure of imaging techniques to adequately determine the status of the spleen is compensated by the chemotherapy sensitivity of splenic disease, as often demonstrated in the treatment of patients with stage IV disease . Staging laparotomy for preadolescent children should be done on special indications, because splenectomy confers a life-long (50 years or more) threat of overwhelming infection despite administration of pneumococcal vaccine and the use of oral penicillin prophylaxis . The use of radiotherapy in a dose range that inhibits bone and dental development in immature, preadolescent children can no longer be condoned . Treatment with chemotherapy alone must be considered as the option for preadolescent and younger adolescent children . Radiotherapy in a low dose range (2000 to 2200 cGy) in combination with chemotherapy constitutes a possible alternative treatment . In combined therapy regimens, it appears unnecessary to deliver six full courses of chemotherapy because regimens using three or four courses have demonstrated effectiveness in adults with early stage disease . The selection of the chemotherapy regimen should be made with care so as to eliminate drugs causing sterility in the young male, ovarian dysfunction in females, and second malignant tumors including acute myeloid leukemia (AML) . In addition, doxorubicin should be used only in noncardiotoxic cumulative doses . Pretreatment determinations of the cardiac ejection fraction provide some assurance of safety during doxorubicin therapy.(ABSTRACT TRUNCATED AT 400 WORDS) Dig Dis Sci, 1987 Dec, 32(12), 1435 - 7 Actinomycotic liver abscess . Case report and literature review; Jonas RB et al.; A 28-year-old male with hepatic actinomycosis presented with several months of anorexia, weight loss, fever, night sweats, and mild right upper quadrant abdominal tenderness . Despite normal liver function tests, hepatic involvement was demonstrated by imaging studies . A liver biopsy and ultrasound-guided aspirate were, however, unrewarding . Laparotomy was, therefore, necessary to establish a definitive diagnosis . The patients was then successfully treated with intravenous penicillin followed by oral clindamycin . This case is presented to illustrate the diagnostic difficulties that may be encountered in such patients with hepatic actinomycosis. JAMA, 1987 Nov 27, 258(20), 2891 - 9 Allergic reactions to drugs and biologic agents; Anderson JA et al.; In summary, the term adverse drug reaction is used to designate any type of undesirable and unintended response to a drug and can be broadly classified on the basis of either the presence or absence of an immune mechanism . Allergic reactions (immune) constitute only 5% to 10% of adverse drug reactions . Drug intolerance (nonimmune) constitutes the rest of these reactions . Many of these latter reactions are mild and self-limited, and many drug intolerances cannot be exactly characterized . Of those reactions in which an immune mechanism has been indicated or reactions that clinically appear to be "allergiclike," a limited number of in vivo (eg, skin tests) or in vitro (eg, RAST, IgE-ELISA, other antibody, or cell-mediated assays) tests have proved helpful in the diagnosis . Best studied are adverse reactions to aspirin, penicillin, insulin, and RCM . The principal treatment of all adverse drug reactions is to avoid the drug that has been specifically identified as being responsible for the previous reaction . In cases where avoidance is not possible, desensitization is an alternative (eg, penicillin and insulin) . Prophylactic treatment of patients who had previously demonstrated a drug intolerance reaction (eg, systemic RCM reaction) with medication--particularly type I activation--may be helpful in some patients. Brain Res, 1987 Nov 3, 425(1), 198 - 203 Thalamocortical mechanisms of state-dependent seizures during amygdala kindling and systemic penicillin epilepsy in cats; Shouse MN; Somatomotor system-evoked potential data suggested that thalamus and cortex provide a final common pathway for the timing of generalized seizures in the sleep-wake cycle . Results indicated thalamic mediation of sleep-activated seizures in the amygdala kindling model of secondary generalized epilepsy; in contrast, cortical hyperexcitability was implicated in the timing of seizures with the systemic penicillin model of primary generalized, petit mal epilepsy . Even though thalamic or cortical hyperexcitability peaked during seizure prone sleep or awakening states in the two models, increased, 'subclinical' levels of hyperexcitability persisted during seizure resistant states, notably rapid-eye-movement (REM) sleep . This finding suggested a chronic, if often latent neuropathology for both epilepsy models and upon which the sleep-wake state modulation of seizures is superimposed. J Am Acad Dermatol, 1987 Nov, 17(5 Pt 2), 918 - 20 Penicillin-induced generalized pustular psoriasis; Katz M et al.; We describe a case of penicillin and penicillin-related drugs that induced severe generalized pustular psoriasis on several different occasions in a young patient known to have suffered from recalcitrant psoriasis since childhood. Biull Eksp Biol Med, 1987 Nov, 104(11), 582 - 5 {Effect of the delta sleep peptide on epileptic activity in the cerebral cortex of rats and cats}; Kryzhanovskii GN et al.; In free behaviour experiments on rats it has been shown that the intraperitoneal injection of delta sleep-inducing peptide (DSIP) (100 micrograms/kg) suppressed penicillin-induced relatively moderate epileptic foci which generated spike potentials as well as severe foci with ictal epileptic discharges . In the experiments on cats it was shown that intravenous DSIP injection (100 micrograms/kg) suppressed strychnine-induced epileptic focus and complexes of epileptic foci. Antimicrob Agents Chemother, 1987 Nov, 31(11), 1826 - 30 Pharmacokinetics and distribution of ticarcillin-clavulanic acid (Timentin) in experimental animals; Woodnutt G et al.; The pharmacokinetics and distribution of ticarcillin and clavulanic acid were studied in rats and rabbits after intravenous coadministration of the compounds . The elimination half-lives for ticarcillin and clavulanic acid were similar in both rats (ticarcillin, 0.22 h; clavulanic acid, 0.24 h) and rabbits (ticarcillin, 0.38 h; clavulanic acid, 0.31 h) . Both compounds distributed widely throughout rat tissues, and the patterns of distribution were similar to those observed for other beta-lactams . Values for penetration into rat pleural, peritoneal, and subcutaneous fluids calculated from the equation (AUCfluid/AUCserum) X 100, where AUC is the area under the concentration-time curve, were between 83 and 93% for ticarcillin and 86 and 103% for clavulanic acid . Values for penetration into tissue cages in rabbits were 139% +/- 45% for ticarcillin and 109% +/- 22% for clavulanic acid . The penetration of clavulanic acid into rabbit cerebrospinal fluid was higher (P less than 0.05) (4.0% +/- 0.61%) than that of ticarcillin (1.3% +/- 0.53%) . Overall, the results show that ticarcillin and clavulanic acid distribute readily throughout body tissues and fluids and predict that the penicillin and beta-lactamase inhibitor would be present together at sites of infection. Biull Eksp Biol Med, 1987 Nov, 104(11), 586 - 8 {Effect of strophanthin and digoxin on the activity of an experimental epileptogenic focus in the frog hippocampus}; Mikhailov IB; It has been shown on frogs with epileptogenic focus induced by the injection of penicillin (1000 U in 0.4 ml) into the hippocamp that preinjection (or injection on the background of the functioning epileptogenic focus) of strophanthin (1.8 and 0.18 microgram/g) or digoxin (1.2 micrograms/g) into spinal lymphaticus sac led to a sharp increase in interparoxysmal epileptiform discharges and electrographic correlates of fits on the ECG . The influence of cardiac glycosides upon the epileptized cerebral neurons is thought to be associated with the capacity of these drugs to inhibit Na+, K+-ATPase of neurons and their axons resulting in the disturbance of cerebral mediator activity. J Gen Microbiol, 1987 Nov, 133 ( Pt 11), 3165 - 74 Purification and characterization of a 2-oxoglutarate-linked ATP-independent deacetoxycephalosporin C synthase of Streptomyces lactamdurans; Cortes J et al.; The deacetoxycephalosporin C (DAOC) synthase (expandase) of Streptomyces lactamdurans was highly purified, as shown by SDS-PAGE and isoelectric focusing . The enzyme catalysed the oxidative ring expansion that converts penicillin N into DAOC . The enzyme was very unstable but could be partially stabilized in 25 mM-Tris/HCl, pH 9.0, in the presence of DTT (0.1 mM) . The enzyme required 2-oxoglutarate, oxygen and Fe2+, but did not need ATP, ascorbic acid, Mg2+ or K+ . The optimum temperature was between 25 and 30 degrees C . The DAOC synthase showed a high specificity for the penicillin substrate . Only penicillin N but not isopenicillin N, penicillin G or 6-aminopenicillanic acid served as substrates . 2-Oxoglutarate analogues were not used as substrates although 2-oxobutyrate and 3-oxoadipate inhibited the enzyme by 100% and 56% respectively . The enzyme was strongly inhibited by Cu2+, Co2+ and Zn2+ . The apparent Km values for penicillin N, 2-oxoglutarate and Fe2+ were 52 microM, 3 microM and 71 microM respectively . The enzyme was a monomer with a molecular mass of 27,000 Da +/- 1,000. Scand J Prim Health Care, 1987 Nov, 5(4), 241 - 3 An acceptability study of two pivampicillin mixtures in children in general practice; Jahnsen T et al.; In order to evaluate the paediatric patient compliance to treatment with penicillin mixture, 84 children with respiratory system infections were randomized to treatment with pivampicillin (Pondocillin) mixture with two different flavour additives, cocoa-peppermint and banana . Using a scoring system, the taste acceptability and the easiness of administration were evaluated at the beginning and the end of treatment . While taste acceptability and easiness of administration decreased significantly during the treatment (p = 0.046 for taste and p = 0.049 for easiness) with Pondocillin cocoa-peppermint mixture, only small non-significant differences were noticed during treatment with Pondocillin banana mixture. Med Clin North Am, 1987 Nov, 71(6), 1093 - 112 The penicillins; Parry MF; Penicillin derivatives have an extraordinary track record of safety and efficacy since their introduction in the late 1940s . The in vitro activity, pharmacokinetics, adverse reactions, and clinical use of these agents are reviewed. J Bacteriol, 1987 Nov, 169(11), 5308 - 10 Changes in peptidoglycan composition and penicillin-binding proteins in slowly growing Escherichia coli; Tuomanen E et al.; The composition of peptidoglycan of chemostat-grown cultures of Escherichia coli was investigated as a function of growth rate . As the generation time was lengthened from 0.8 to 13.8 h, there was a decrease in the major monomer (disaccharide tetrapeptide) and dimer (bis-disaccharide tetrapeptide), while disaccharide tripeptide moieties increased to greater than 50% of the total wall . The average chain length became much shorter; lipoprotein density tripled, and the number of unusual diaminopimelyl-diaminopimelic acid crossbridges increased fivefold . As cells grew more slowly, amounts of penicillin-binding proteins (PBPs) 1a-1b complex and 4 decreased, while amounts of PBPs 3 and the 5-6 complex increased . We propose that the chemical composition of E . coli cell walls changes with growth rate in a manner consistent with alterations in the activities of PBPs and cell shape. J Bacteriol, 1987 Nov, 169(11), 5298 - 300 Identification of Treponema pallidum penicillin-binding proteins; Cunningham TM et al.; Penicillin-binding proteins of 180, 89, 80, 68, 61, 41, and 38 kilodaltons were identified in Treponema pallidum (Nichols) by their covalent binding of {35S}benzylpenicillin . Penicillin-binding proteins are localized in the plasma membranes of many bacterial species and may serve as useful markers for determining plasma membrane intactness in T . pallidum fractionation studies. J Bacteriol, 1987 Nov, 169(11), 4912 - 5 Penicillin-binding protein 7 and its relationship to lysis of nongrowing Escherichia coli; Tuomanen E et al.; The characteristics and possible physiological role(s) of a 30-kilodalton low-molecular-size penicillin-binding protein (PBP), PBP 7, in Escherichia coli were investigated . The amount of penicillin required to half saturate PBP 7 was approximately 5 micrograms/ml, and this PBP bound 15% of the total penicillin bound to all PBPs with a deacylation rate of greater than 120 min . This PBP was distinguishable from E . coli PBPs 1 to 6 by the pattern of {3H}penicillin-labeled peptides generated by partial proteolysis . A unique feature of PBP 7 was its capacity to bind numerous members of penem class antibiotics at relatively low concentrations . A striking correlation existed in drugs between capability of lysing amino acid-starved (nongrowing) E . coli and binding to PBP 7 . The findings suggest that PBP 7 is a new, physiologically significant target for beta-lactam antibiotics. J Bacteriol, 1987 Nov, 169(11), 4935 - 40 Mutant isolation and molecular cloning of mre genes, which determine cell shape, sensitivity to mecillinam, and amount of penicillin-binding proteins in Escherichia coli; Wachi M et al.; A chromosomal region of Escherichia coli contiguous to the fabE gene at 71 min on the chromosomal map contains multiple genes that are responsible for determination of the rod shape and sensitivity to the amidinopenicillin mecillinam . The so-called mre region was cloned and analyzed by complementation of two closely related but distinct E . coli mutants characterized, respectively, by the mutations mre-129 and mre-678, that showed a rounded to irregular cell shape and altered sensitivities to mecillinam; the mre-129 mutant was supersensitive to mecillinam at 30 degrees C, but the mre-678 mutant was resistant . The mre-678 mutation also caused simultaneous overproduction of penicillin-binding proteins 1Bs and 3 . A chromosomal region of the wild-type DNA containing the total mre region and the fabE gene was first cloned on a lambda phage; a 7-kilobase (kb) fragment containing the whole mre region, but not the fabE gene, was then recloned on a mini F plasmid, pLG339; and finally, a 2.8-kb fragment complementing only mre-129 was also cloned on this low-copy-number plasmid . The whole 7-kb fragment was required for complementing the mre-678 mutant phenotypes . Fragments containing fabE but not the mre-129 region could be cloned on a high-copy-number plasmid . Southern blot hybridization indicated that the mre-678 mutant had a large deletion of 5.25 kb in its DNA, covering at least part of the mre-129 gene. Acta Otolaryngol, 1987 Nov-Dec, 104(5-6), 468 - 71 Presence of interferon in the middle ear during secretory otitis media; Birch L et al.; In connection with grommet insertion due to secretory otitis media (SOM), the middle ear effusion was collected and studied for content of interferon and bacteria . The study material comprised a total of 47 ears in 29 children, but from 10 ears the effusion was too viscous for interferon titration, so only 24 children were ultimately included . Interferon was present in 5 ears of 3 children . A child having a low titre in both ears had recently been treated with penicillin . From the other 2 children, pneumococci were cultured . Twelve of the included children had a common cold, but of them only 2 had interferon in the middle ear . The production of interferon was presumably induced by the pneumococci, not by virus. Presse Med, 1987 Oct 24, 16(35), 1733 - 6 {Borrelian meningoencephalomyelitis . A case}; Benoit P et al.; A 22-year old man had spastic paraparesis and cerebellar syndrome of 5 months duration . CSF showed lymphocytosis, elevated protein content, hypoglycorachia, hypochlorurachia and oligoclonal banding . CT scan and MRI were normal . Extensive laboratory procedures disclosed no bacterial, viral, fungic, parasitic or inflammatory disease . Anti-Borrelia burgdorferi antibodies were present in blood (1/4000) and in CSF (1/1024) . With antibiotics (penicillin G 20 millions units per day for 10 days, followed by latamoxef 1.5 g per day for 3 months) and prednisone (50 mg per day for 2 months), the cerebellar signs disappeared, the paraparesis improved and the CSF abnormalities disappeared; blood and CSF anti-Borrelia antibody levels decreased . This case is an example of a severe form of CNS impairment by Borrelia burgdorferi . In Europe, most reports show progressive para- or tetraparesis with, sometimes, intellectual, cerebellar or cranial nerve impairment . In some cases, the signs are less diffuse or more acute . Lymphocytic meningitis is present with hyperalbuminorachia and oligoclonal banding; hypoglycorachia is mentioned in only one other report . Diagnosis is made by high blood and CSF antibody titers and demonstration of local synthesis . As in syphilis, borrelian meningoencephalomyelitis could be the third stage of the disease . Its treatment, often disappointing, consists of antibiotics (penicillin G or latamoxef) and in some cases corticosteroids. Microbiologica, 1987 Oct, 10(4), 385 - 92 Adherence of S . bovis to adult buccal epithelial cells; von Hunolstein C et al.; The ability of S . bovis 83/5364, glucan-positive (biotype I) and S . bovis R 81/536 glucan-negative (biotype II) to adhere to buccal epithelial cells (BEC) by lipoteichoic acid (LTA) was examined . LTA from both biotypes was prepared by cold phenol extraction from supernatants of penicillin supplemented cultures and partially purified by Sepharose CL-6B chromatography . Both glucan-positive and glucan-negative S . bovis strains adhered to BEC, but biotype I seemed to be more adhesive . For both biotypes the adhesion was not significantly inhibited by treatment of the bacteria with anti-LTA serum, while the preincubation of BEC with LTA, extracted from S . agalactiae, or cardiolipin strongly decreased the S . bovis binding. Genitourin Med, 1987 Oct, 63(5), 312 - 5 Aetiology of genital ulceration in the Gambia; Mabey DC et al.; The aetiology of genital ulceration was studied in 104 unselected patients (94 men, 10 women) attending a sexually transmitted disease (STD) clinic in the Gambia . Chancroid was diagnosed in 54 (52%), syphilis in 23 (22%), lymphogranuloma venereum (LGV) in seven (7%), and herpes in six (6%) . In 28 (27%) patients no diagnosis was reached . Ten (10%) patients were found to have both chancroid and syphilis, three (3%) had both LGV and syphilis, and one (1%) had both herpes and syphilis . Trimethoprim 160 mg and sulphamethoxazole 800 mg twice daily for one week was found to be effective in the treatment of chancroid . This regimen with a single intramuscular injection of benzathine penicillin 2.4 MIU is recommended for the treatment of genital ulcers in Gambian health centres without laboratory facilities. Biull Eksp Biol Med, 1987 Oct, 104(10), 405 - 8 {Modelling psychosis in cats by creating a generator of pathologically enhanced excitation in one of the septal nuclei}; Kryzhanovskii GN et al.; The experiments on adult freely behaving cats have shown that the injection of penicillin into the internal part (TI) of bed nucleus of stria terminalis (BST) caused the formation of the generator of pathologically enhanced excitation (GPEE) . This part of BST became hyperactive and played the role of a pathologic determinant which caused the formation of a complex pathologic system and behavioural disorders with catatonia, stereotypy, food rejection, eating of uneatable things, hypoalgesia, zoosocial behavioural changes, depression of different emotions, etc . The development of these disorders was progressing and was accompanied by corresponding electrophysiological activity in TI and other brain structures studied . Coagulation of GPEE zone at the early stages of the process prevented the development of the above disorders. Arch Neurol, 1987 Oct, 44(10), 1062 - 5 Pure motor hemiplegia due to meningovascular neurosyphilis; Johns DR et al.; Two young male homosexuals developed prodromal syndrome followed by penicillin-responsive meningitis and the acute onset of pure motor hemiplegia . The clinical and laboratory features are consistent with meningovascular neurosyphilis . Basis pontis infarctions were subsequently demonstrated on magnetic resonance imaging scans . To our knowledge, this is the first description of syphilitic arteritis as a pathophysiologic basis for pure motor hemiplegia. Allerg Immunol (Paris) . 1987 Oct;19(8):330, 332. {Value of cellular immunity tests (lymphocyte transformation test and leukocyte migration test) in the detection of sensitivity to drugs}; Harrabi S et al.; We studied degranulation of human basophils (HBDT), lymphoblast transformation and leucocyte migration in 8 cases of patients who were sensitive to penicillin (type 1 hypersensitization of the Gell and Coombes classification) . The HBDT was negative in 7 of the cases, whilst the lymphoblast transformation and leucocyte migration tests were positive in 6 cases and negative in 2 . These latter tests are more efficient than HBDT in the detection of human sensitization to penicillin. Br J Psychiatry . 1987 Oct;151:556. Neurosyphilis--a treatable psychosis; Brooke D et al.; A patient presenting with mixed affective symptoms was found to have active neurosyphilis after intermittent cognitive impairment suggested an organic cause . Most of these symptoms resolved after treatment with penicillin. Aust Vet J, 1987 Oct, 64(10), 301 - 4 Treatment of ovine virulent footrot with zinc sulphate/sodium lauryl sulphate footbathing; Malecki JC et al.; Trials were conducted on 2 commercial sheep flocks in the Gippsland region of Victoria to determine the efficacy of treating ovine virulent footrot by footbathing in aqueous zinc sulphate solution (20% w/v) . The effects of foot paring, parenteral penicillin, vaccination and addition of sodium lauryl sulphate (SLS) to the footbaths were assessed . Trial 1 comprised 297 sheep with an initial prevalence of footrot of 33% and most lesions were severe and chronic . Treatment of sheep with unpared feet by zinc sulphate footbathing for 1h did not result in a significant reduction in footrot prevalence (n = 120, cure rate 33%) whereas a significant (P less than 0.01) response was obtained by footbathing for 1h with zinc sulphate/SLS (n = 120, cure rate 55%) . Trial 2 comprised 1,042 sheep with a pretreatment footrot prevalence of 71% and predominantly severe lesions . In this flock all treated sheep were footbathed in zinc sulphate/SLS for 1h on 2 occasions, 5 days apart and the effects of additional surgical and parenteral treatments were assessed . Foot paring had a significant detrimental effect on cure rate (P less than 0.01) . The administration of procaine penicillin at the time of the first footbathing with zinc sulphate/SLS made no significant improvement to the rate of cure . Footrot vaccine given 8 and 2 weeks prior to footbathing did not cure significantly more sheep than footbathing alone, but the results were significantly better than from foot paring plus footbathing, and from combined foot paring, footbathing and parenteral penincillin treatment (P less than 0.01) . The cure rate was 84% for sheep that were only footbathed, 72% for those foot pared and footbathed, 72% for those foot pared, footbathed and given penicillin, and 88% for those vaccinated and footbathed. Antibiot Med Biotekhnol, 1987 Oct, 32(10), 747 - 9 {Photometric control of the presence of potassium benzylpenicillin crystals after centrifugation}; Zosimov EV et al.; A photometric (turbidimetric) method was proposed for automatic control of the content of potassium benzylpenicillin crystals after centrifugation . The optical properties of the technological media were studied . It was found that along with intensive absorption in the UV spectrum due to the presence of the penicillin and its degradation products the solutions absorbed the light of the visible spectrum (400-700 nm) . Therefore, determination of the penicillin crystal concentration by light dispersion in the UV and visible spectra was possible only with a differential procedure . For the near IR region there were defined areas at 930-950, 1020-1080 and 1200-1260 nm without self-absorption of the solutions providing the use of the one-canal measurement scheme . Procedures for determining the presence of penicillin crystals by light dispersion were developed: differential procedures in the visible spectrum (490 nm) and the near IR region (940-980 nm) . The use of market photometers for realization of the procedures was recommended. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1987 Oct, 266(3-4), 506 - 21 The role of cell population kinetics in the efficacy of penicillin--an experimental analysis and stochastic modeling of the tumour tetanus and wound tetanus of the mouse; Schneeweiss U et al.; When investigating tetanus lethality summation curves of mice under comparable quantitative conditions following a temporarily limited administration of penicillin, the curves obtained can be calculated by the kinetics of tumour cells or wound fibroblasts . In particular, it has been shown that the optimal efficacy of penicillin, after short-time usage as compared with a long-time administration schedule, is determined by the generation time of the tetanus rods as a function of the mitotic cycle of the "pace-making" tumour cells or wound fibroblasts . Further variables of the mathematical model imply the pharmacokinetics of penicillin and the recovery process of the "hit" tetanus rods . From these results some basic experimental and clinical tetanus issues can be elucidated; thus, the mitosis theory of tetanus is being verified for the stage of incubation and of clinical manifestation, while the classical necrosis theory of the pathogenesis of tetanus infection should be valid only for the final stage. J Am Vet Med Assoc, 1987 Oct 1, 191(7), 829 - 30 Blue-green algae toxicosis in five dairy cows; Kerr LA et al.; Five Holstein cows developed a sudden clinical syndrome of ataxia, muscle tremors, recumbency, and bloody diarrhea . The pond where these cows obtained water contained a near pure culture of Microcystis aeruginosa, a toxic blue-green algae . All cows affected were treated with activated charcoal, procaine penicillin, glucose, and calcium and magnesium gluconate . All 5 cows were clinically normal ten days later . Many practicing veterinarians regard blue-green algae toxicosis as a rare syndrome that results in rapid death for consuming animals; however, this toxicosis may be common and not lethal . Because no diagnostic test is available for blue-green algae toxicosis, this condition rarely is diagnosed. Exp Neurol, 1987 Oct, 98(1), 152 - 60 Attenuation of penicillin models of epilepsy by nonsteroidal anti-inflammatory drugs; Wallenstein MC; Prostaglandin and thromboxane levels increase in mammalian brain during seizures, but whether a metabolite of arachidonic acid has a role in induction, or is merely a by-product, of seizures is still not clear . It has been shown that nonsteroidal anti-inflammatory drugs block arachidonic acid metabolism through inhibition of the enzyme, cyclooxygenase . In the present study, the antiepileptic action of nonsteroidal antiinflammatory drugs was investigated utilizing penicillin-induced focal (250 IU) and primary generalized (2.5 million IU kg-1) models of epilepsy . The effects of the drugs on the electrocortical and motor manifestations of both models were examined . As a group, the nonsteroidal anti-inflammatory drugs significantly affected the central nervous system excitation produced by penicillin . However, individual drugs affected different parameters of the excitation . Paracetamol, the most effective, delayed and/or blocked spikes and seizures in both models . Ibuprofen was more effective against the primary generalized model . Mefenamic acid decreased the number of seizures and indomethacin decreased the voltage output in both models . The present study, together with earlier papers, suggests that an arachidonic acid metabolite plays a role in induction of several animal models of epilepsy. Q J Exp Physiol, 1987 Oct, 72(4), 439 - 52 Comparison of penicillin epileptogenesis in rat somatosensory and motor cortex; Holmes O et al.; The relative sensitivities of somatosensory and motor areas of the cerebral cortex in penicillin epileptogenesis were compared in urethane-anaesthetized rats . Penicillin was applied electrophoretically from a fluid-filled micro-electrode . Spontaneous focal interictal epileptiform discharges were detected by a nearby recording electrode . In motor cortex, every cortical layer was less sensitive in penicillin epileptogenesis than the corresponding layer in somatosensory cortex; epileptic spikes occurred later, were of lower amplitude and were less frequent . In motor cortex, the sensitive depth extended from the deep part of layer III to the upper part of layer V . It seemed possible that penicillin applied to motor cortex might be producing its effects by diffusing back to the sensitive somatosensory area . This was excluded by applying penicillin to motor cortex whilst recording from both somatosensory and motor areas and demonstrating that the spikes were found in motor but not in somatosensory cortex. Life Sci, 1987 Sep 7, 41(10), 1277 - 87 Characterization of GABAA receptor-mediated 36chloride uptake in rat brain synaptoneurosomes; Luu MD et al.; gamma-Aminobutyric acid (GABA) receptor-mediated 36chloride (36Cl-) uptake was measured in synaptoneurosomes from rat brain . GABA and GABA agonists stimulated 36Cl- uptake in a concentration-dependent manner with the following order of potency: Muscimol greater than GABA greater than piperidine-4-sulfonic acid (P4S)greater than 4,5,6,7-tetrahydroisoxazolo-{5,4-c}pyridin-3-ol (THIP) = 3-aminopropanesulfonic acid (3APS) much greater than taurine . Both P4S and 3APS behaved as partial agonists, while the GABAB agonist, baclofen, was ineffective . The response to muscimol was inhibited by bicuculline and picrotoxin in a mixed competitive/non-competitive manner . Other inhibitors of GABA receptor-opened channels or non-neuronal anion channels such as penicillin, picrate, furosemide and disulfonic acid stilbenes also inhibited the response to muscimol . A regional variation in muscimol-stimulated 36Cl- uptake was observed; the largest responses were observed in the cerebral cortex, cerebellum and hippocampus, moderate responses were obtained in the striatum and hypothalamus and the smallest response was observed in the pons-medulla . GABA receptor-mediated 36Cl- uptake was also dependent on the anion present in the media . The muscimol response varied in media containing the following anions: Br- greater than Cl- greater than or equal to NO3- greater than I- greater than or equal to SCN- much greater than C3H5OO- greater than or equal to ClO4- greater than F-, consistent with the relative anion permeability through GABA receptor-gated anion channels and the enhancement of convulsant binding to the GABA receptor-gated Cl- channel. Rev Electroencephalogr Neurophysiol Clin, 1987 Sep, 17(3), 329 - 41 Study of spindle-spike interactions: features of basal ganglia control; Sabatino M et al.; Changes in cortical spindle distribution following penicillin (PCN) injections were studied in feline generalized PCN epilepsy . PCN activation caused no substantial changes in spindle duration, frequency and intraburst frequency, while significant reductions in the amplitude of the negative waves were noted . At the same time combinations of spindle waves and epileptic complexes were recorded with one or more spikes randomly occurring at the beginning, in the middle, or at the end of a spindle envelope . Low frequency stimulation of the caudate nucleus induced a certain degree of enhancement in cortical precruciate spike frequency while high frequency activation of the entopeduncular nucleus caused significant inhibition of cortical spike frequency . The results are discussed in the light of the reciprocal interrelationship between spindles and spikes . Furthermore, the role played by the caudate and the entopeduncular nucleus in the control of the cortico-thalamo-cortical circuit is also emphasized. Arch Dis Child, 1987 Sep, 62(9), 964 - 5 Penicillin resistant pneumococcal peritonitis in nephrotic syndrome; Milner LS et al.; Two infants with nephrotic syndrome who developed penicillin resistant pneumococcal peritonitis while receiving penicillin chemoprophylaxis are reported and the problems associated with prophylaxis against pneumococcal infection discussed . It is suggested that penicillin prophylaxis may be hazardous in an environment in which penicillin resistant pneumococci are prevalent. Ann Neurol, 1987 Sep, 22(3), 389 - 92 Chronic muscle weakness caused by Borrelia burgdorferi meningoradiculitis; Wokke JH et al.; A 19-year-old man developed chronic weakness of the lower limbs as the predominant manifestation of Borrelia burgdorferi infection of the nervous system . Spirochetes were demonstrated in the cerebrospinal fluid . The condition resolved following intravenous penicillin treatment. Acta Physiol Scand, 1987 Sep, 131(1), 33 - 42 The effect of progesterone and its metabolites on the interictal epileptiform discharge in the cat's cerebral cortex; Landgren S et al.; The antiepileptic effect of progesterone, 5-alpha-pregnane-3,20-dione, 3-alpha-hydroxy-5-alpha-pregnane-20-one, and 3-alpha-hydroxy-5-beta-pregnane-20-one were tested in an experimental animal model, and compared with the effect of clonazepam . The steroids were dissolved in serum from ovariectomized cats . Ovariectomized adult cats were used and spontaneous epileptic discharges were generated by placing small pieces of penicillin-soaked filter papers on the ipsi and contralateral cerebral cortex . The frequency and amplitude of the interictal epileptiform spikes were recorded, and analysed in a computer . The changes in frequency and amplitudes were calculated . The drugs were infused during 20-s periods into one cerebral hemisphere via the ipsilateral lingual artery with speeds of 1.1, 3.4 and 6.3 ml min-1 . A penicillin focus on the contralateral hemisphere served as a simultaneous control . Progesterone and clonazepam showed similar inhibitory effects on epileptiform interictal spiking (median reduction of spike frequency 21%, cf . Table I) . The 5-alpha-pregnane-3, 20-dione was generally less potent than progesterone (median reduction 9%) and the 5-alpha- and 5-beta-pregnanolones were two to three times more potent than progesterone (54-66% reduction) . The latency of the inhibitory effect was 4-10 s measured from the entrance of the infusion into the lingual artery . The depression lasted 10-20 min . It is concluded that the pregnanolones have strong antiepileptic properties . The rapid onset of effect indicates that the steroids may interact with the neuronal function at the membrane or synaptic levels. Nervenarzt, 1987 Sep, 58(9), 564 - 7 {Chronic Borrelia disease of the central nervous system}; Behringer A et al.; A few years ago meningoradiculitis Garin-Bujadoux-Bannwarth (Bannwarth's syndrome) was discovered to be a neurological manifestation of Lyme disease transmitted by tick-bites and caused by Ixodes-ricinus-spirochaete (borrelia burgdorferi) . Not enough attention is given to the fact that more serious and chronic disease of the central nervous system may be entailed . Two cases are reported in which detection of the borrelian-antibodies corroborated the diagnosis . After parenteral treatment with penicillin there was a drastic improvement in both patients. Nervenarzt, 1987 Sep, 58(9), 557 - 63 {Acute and chronic diseases in transmitted borreliosis by tick bite}; Kohlhepp W et al.; We report on clinical and laboratory findings of 58 study patients with tick-bite burrelia burgdorferi-infection . In seven cases, chronic borreliosis like a tertiary metaluetic illness was recognized . All were treated either with high-dose penicillin intravenously or tetracycline . Results of treatment and recommendations are given. Ann Intern Med, 1987 Sep, 107(3), 305 - 9 Aminophylline for acute exacerbations of chronic obstructive pulmonary disease . A controlled trial; Rice KL et al.; Study Objective: To determine the efficacy of intravenous aminophylline in the treatment of patients hospitalized for exacerbation of chronic obstructive pulmonary disease . Design: Randomized, double-blind, placebo-controlled trial during the first 72 hours of hospitalization . Patients: Thirty patients admitted from the emergency room or walk-in clinic with the primary diagnosis of an exacerbation of chronic obstructive pulmonary disease . Twenty-eight patients completed the study; 2 patients, 1 receiving placebo and 1 receiving aminophylline, were removed from the study because of respiratory failure requiring mechanical ventilation . Interventions: Patients received either intravenous aminophylline or placebo, in addition to nebulized, inhaled 0.3 mL of a 5% solution every 6 hours; methylprednisolone, 0.5 mg/kg body weight every 6 hours intravenously; ampicillin, 500 mg orally every 6 hours (tetracycline or trimethoprim-sulfamethoxazole were substituted in penicillin-allergic patients); and supplemental oxygen as needed . Aminophylline infusion rates were adjusted by an unblinded investigator to achieve theophylline levels of 72 to 83 mumol/L . Changes were also made in placebo infusion rates to maintain the double-blind design . Measurements and Main Results: The forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) before and after metaproterenol inhalation were measured twice daily by a blinded investigator, who also administered a verbal dyspnea index with a scale of 1 to 10 and questioned patients regarding possible side effects of treatment (tremor, palpitations, nausea, or vomiting) . Arterial blood gas measurements at 72 hours were compared with those obtained on admission . Significant improvements in FEV1 and FVC measured before and after metaproterenol treatment and in dyspnea occurred over time in both treatment groups (p less than 0.05 for all measurements) . However, there were no significant differences between the placebo and aminophylline groups in any of the spirometric measurements or the dyspnea indices (p greater than 0.5 in all five analyses) . The mean increases (+/- SE) in Po2 of 1.9 (+/- 0.5) kPa with placebo and 1.7 (+/- 0.7) kPa with aminophylline and the mean decreases in PCO2 of 0.5 (+/- 0.4) kPa with placebo and 1.2 (+/- 0.4) kPa with aminophylline were not significantly different (p greater than 0.6 for PO2, p greater than 0.2 for PCO2).(ABSTRACT TRUNCATED AT 400 WORDS) J Biol Buccale, 1987 Sep, 15(3), 163 - 70 {The respective roles of occlusal abrasion and bacterial plaque in the etiology of alveolar lysis in periodontitis in hamsters}; Saffar JL et al.; This study was designed to determine the respective roles of occlusal attrition and subsequent tooth egression, and bacterial plaque accumulation on bone loss (or radicular denudation) during hamster periodontitis . Seventy young male animals were separated into 7 groups . Occlusal attrition was compared on 3 different diets (standard in pellet form, standard in powder form, and Keyes 2000 in powder form), thought to have different abrasiveness . The role of bacterial plaque wad evidenced by inhibiting it with Penicillin V in animals fed the same 3 diets . Compared to animals killed at the beginning of the experimental period (absolute controls), 3 months later bacterial plaque was slightly increased in hamsters fed the standard diet, very markedly increased in 2000 diet-fed animals and, decreased in the 3 antibiotic treated groups . Occlusal attrition was increased in the 2 groups fed the standard diets but not in the 2000 diet-fed animals . Radicular denudation was slightly increased in the standard diet groups, very markedly increased in the 2000 diet group, and unchanged in the antibiotic treated animals . Thus, the less abrasive diet was associated with the greatest plaque accumulation and bone loss; conversely, with the most abrasive diets, radicular denudation had slightly progressed with only small amounts of plaque . This suggests that in hamster periodontitis, bone loss is not influenced by occlusal attrition but is completely dependent on the direct action of bacterial plaque. J Colo Dent Assoc, 1987 Sep-Oct, 66(2), 5 - 6 Oral contraceptive failure secondary to dentally prescribed drugs: fact or fiction? Kleier DJ, Tucker JE. PIP: Drug interactions likely to occur with dentally prescribed drugs and oral contraceptives include 2 broad mechanisms: reduced reabsorption of contraceptive steroids and stimulation of liver metabolism of the steroids . The antibiotics ampicillin and tetracycline are often reported to cause failure of oral contraceptives, now that pills contain such low doses . These medications destroy bacteria in the gut that normally hydrolyze conjugated steroids, re-releasing them into the circulation . Thus reduced entero-hepatic recirculation lowers active levels of the contraceptive steroids . Drugs that induce hepatic enzymes such as barbiturates and sedatives, enhance elimination of steroids . Other drugs, such as rifampin the anti-tubercular antibiotic, and barbiturates, phenobarbital meperidine, penicillin V, phenylbutazone, phenytoin sodium, sulfonamides and chloramphenicol have also been implicated in failures of the pill . Dentists should take a detailed history of drug intake, specifically mentioning oral contraceptives, and counsel patients accordingly . They are ultimately responsible for unintended pregnancy in the event of pill failure when writing prescriptions for their patients . Mikrobiologiia, 1987 Sep-Oct, 56(5), 824 - 30 {Structural and ultrastructural changes in Mycobacterium rubrum cells exposed to penicillin}; Poglazova MN et al.; The action of penicillin taken at subbacterioscopic doses on Mycobacterium rubrum cells causes changes in the size and shape of the cells, in the structure of the cell wall, in the intracellular membrane systems and in functions associated with them, and in the structure of nucleoids whose DNA packing becomes more loose . If the antibiotic is added at bacteriostatic doses, the size and shape of the cells do not change, but peptidoglycan precursors being synthesized are not incorporated into the polymer and accumulate in the periplasm . DNA overspiralization in nucleoids is a non-specific reaction, which indicates that DNA is physiologically passive . DNA is isolated with a membrane from the cytoplasm in certain cells . It is possible that the resistance of cells against penicillin is associated with the capability of DNA to become inactive in physiological terms. Rev Med Interne, 1987 Sep-Oct, 8(4), 350 - 6 {Tick bite meningoradiculitis and other neurological aspects of Lyme disease}; Poullot B et al.; In the majority of cases, meningoradiculitis consecutive to tick bite most probably belongs to Lyme disease caused by Borrelia burgdorferi . The disease may be limited to the primary, though inconstant, stage of cutaneous migratory erythema, or it may develop into cardiac and, mostly, neurological disorders . The nervous system involvement, which we observed in 7 patients, mainly consists of peripheral motor neuropathy of moderate severity and sometimes limited to the cranial nerves, associated with very severe radicular pain regularly heralding radicular deficit . Lyme disease predominates in a rural environment, and most patients live near wooded areas where ticks parasitize numerous mammals . The diagnosis, suggested by the socio-environmental context, the clinical features and the results of CSF examination, is confirmed by serology at a 1/256 dilution . Tetracyclines are effective in the initial stage, but intravenous penicillin is necessary in the secondary stage and to reduce the risk of arthritis and also perhaps neuropsychiatric disorders at a late stage. Infect Dis Clin North Am, 1987 Sep, 1(3), 511 - 27 Lyme disease; Duffy J; Lyme disease is a complex multisystem disorder recognized on three continents, which is epidemic in some regions during spring, summer, and fall seasons . It primarily affects skin, nervous system, heart, and joints . It is an infectious disease caused by a spirochete Borellia burgdorferi, which is transmitted chiefly by Ixodes dammini and pacificus ticks in the United States and Ixodes ricinus in Europe . Diagnosis is based on patient contact with an endemic area, one or more characteristic clinical features, particularly erythema migrans rash, and a positive serologic test for B . burgdorferi infection in the majority of cases . Although infection is the primary cause of the disease, immune mechanisms may play a synergistic role in some manifestations . Prompt diagnosis and treatment are important for full recovery . Treatment with oral tetracycline or penicillin is effective in the earliest stages but late complications require high doses of intravenous penicillin and sometimes corticosteroids . Some late complications are refractory to antibiotic therapy . Antibody appears to be protective in human and experimental studies. Ann Inst Pasteur Microbiol, 1987 Sep-Oct, 138(5), 537 - 47 Effects of temperature inactivation of penicillin-binding protein 2 on envelope growth in Escherichia coli; Buchnik D et al.; The transition from rod-shaped to spheroidal cells was studied in a temperature-sensitive strain (SP45) of Escherichia coli K12, carrying a mutation (pbpA) in the gene coding for penicillin-binding protein 2 (PBP-2) . This transition imposed by the restrictive temperature was associated with reduction of peptidoglycan/surface area and of cellular osmotic stability . Addition of nalidixic acid (20 micrograms/ml) at the temperature shift from 30 to 42 degrees C resulted in lysis of some cells and appearance of spheroidal bulges along the cylinders in other cells, consistent with the hypothesis of envelope weakening due to inactivation of PBP-2. Arq Neuropsiquiatr, 1987 Sep, 45(3), 242 - 7 {High-dose intravenous penicillin therapy in neurosyphilis . III . Evaluation of antitreponemal antibodies of the IgM class in cerebrospinal fluid and serum}; Nitrini R et al.; IgM antibodies against Treponema pallidum were investigated in the serum and in the CSF of 9 patients with symptomatic neurosyphilis, before the treatment and in several occasions after the treatment . Tests used were the FTA-Abs test, the IgM-solid phase hemadsorption test and an IgM-Elisa test . Titers of reactions decreased after treatment but they were still reactive in the blood and in the CSF during the second year after the treatment. Arzneimittelforschung, 1987 Sep, 37(9), 1048 - 51 Lack of effectiveness of ofloxacin against experimental syphilis in rabbits; Une T et al.; Ofloxacin, a new pyridone-carboxylic acid derivative, was evaluated in experimental syphilis in rabbits in comparison with penicillin G . Experimental syphilis was established by intradermal injection of Treponema pallidum subsp . pallidum Nichols . Ten days after infection, the dermal lesions were characterized by syphilitic papula accompanied with central necrosis . These animals were subsequently treated either with ofloxacin twice a day at an oral dose of 10 mg/kg or with penicillin G once a day at an intramuscular dose of 10,000 U/kg for 21 consecutive days . In penicillin G-treated animals, the dermal lesions became smaller as early as day 3 of treatment and almost disappeared during the therapy . In marked contrast to remarkable efficacy of penicillin G was further development of the lesions in ofloxacin-treated animals, showing no difference in pathological manifestations as compared to untreated animals . The results of nontreponemal serologic test correlated well with the response of animals to treatment. Surv Ophthalmol, 1987 Sep-Oct, 32(2), 111 - 22 Tobramycin in ophthalmology; Wilhelmus KR et al.; Selman Waksman's laboratory at Rutgers University discovered the first aminoglycoside antibiotic, streptomycin, in 1943 . Other aminoglycoside antibiotics, such as gentamicin and tobramycin, soon followed . Tobramycin is compatible with most intravenous fluids and tear substitutes, but it is incompatible with heparin and some beta-lactam antibiotics such as penicillin and cephalosporins . Due to tobramycin's broad spectrum of activity, it has proven useful in controlling both superficial and deep infections of the eye and ocular adnexa (i.e., blepharitis, conjunctivitis, keratitis, and endophthalmitis) . However, since tobramycin has been associated with neuromuscular blockade, as well as possessing ototoxic and nephrotoxic effects, care must be taken to minimize toxicity by monitoring patients undergoing systemic tobramycin therapy. Neuroscience, 1987 Sep, 22(3), 1123 - 33 Antagonists of GABA responses, studied using internally perfused frog dorsal root ganglion neurons; Yakushiji T et al.; Responses of frog dorsal root ganglion neurons to GABA were studied under conditions of internal perfusion . Conductances to Na, Ca and K were pharmacologically blocked, C1 concentrations were maintained equal on both sides of the membrane and a small holding potential was used . Under these conditions GABA-induced C1 currents could be studied in isolation without shifts in EC1 occurring after GABA application . GABA currents were blocked by a variety of agents . The blockade by bicuculline and Zn was competitive, while that to penicillin was competitive at low concentrations (6 x 10(-5) M) and non-competitive at high concentrations (3 x 10(-4) M) . Picrotoxin was non-competitive at all concentrations studied . The time course of the GABA-induced currents was changed in the presence of antagonists, including those that were competitive . These actions appear to be due to a change in the rates of receptor desensitization rather than shifts in EC1 . Pretreatment with antagonists increased the degree of inhibition only for picrotoxin as compared to simultaneous application of GABA plus antagonist . The voltage dependence of the GABA response was altered by penicillin but not by other antagonists . GABA responses on frog dorsal root ganglion cell were also depressed by a variety of other metal ions (Cd, Ni, Cu, Co, Mn) and other drugs (strychnine, curare, 4-acetamide, 4'-isothiocyano-stilbene-2,2'-dilsulfonic acid disodium salt, 4,4'-diisothiocyano-stilbene-2,2'-dilsulfonic acid disodium salt trihydrate, bemegride and folic acid) . In this preparation bicuculline and the heavy metal ions appear to block at or very near to the agonist binding site, while penicillin probably blocks the ion channel . The non-competitive action of picrotoxin appears not to be channel blockade, but to be due to a slowly equilibrating action at a site different from either the agonist binding site or the channel. Appl Environ Microbiol, 1987 Sep, 53(9), 1987 - 95 Mixed fungal populations and lignocellulosic tissue degradation in the bovine rumen; Akin DE et al.; Anaerobic fungi in ruminal fluid from cows eating Bermuda grass hay plus a grain and minerals supplement were evaluated for diversity in sporangial morphotypes and colony growth patterns and for the degradation of various lignocelluloses . In selective cultures containing streptomycin and penicillin, an active population of ruminal fungi colonized leaf blades and degraded fiber at rates and extents almost equal to that of the total ruminal population . Three major sporangial morphotypes were consistently observed on leaf blades: oval, globose, and fusiform . Fungal colonies representing three distinct growth types consistently developed in anaerobic roll tubes inoculated with strained ruminal fluid . Sporangial morphotypes could not be matched to colony types due to multiple sporangial forms within a colony . Under identical growth conditions, one type exhibited a monocentric growth pattern, while two types exhibited polycentric growth patterns previously unreported in ruminal fungi . Mixed ruminal fungi in selective cultures or in digesta taken directly from the rumen produced a massive clearing of the sclerenchyma . Quantitation of tissue areas in cross sections by light microscopic techniques showed that fungal incubations resulted in significant (P = 0.05) increases in sclerenchyma degradation compared to whole ruminal fluid incubations . The mestome cell wall was at times penetrated and partially degraded by fungi; the colonization was less frequent and to a lesser degree than with the sclerenchyma . Conversely, ruminal bacteria were not observed to degrade the mestome sheath . Phenolic monomers at 1 mM concentrations did not stimulate to a significant (P = 0.05) extent the dry weight loss or fungal colonization of leaf blades; at 10 mM concentrations cinnamic and benzoic acids were toxic to ruminal fungi. Arq Neuropsiquiatr, 1987 Sep, 45(3), 231 - 41 {High-dose intravenous penicillin therapy in neurosyphilis: study of 62 cases . II . Evaluation of cerebrospinal fluid}; Nitrini R et al.; Sixty-two patients with symptomatic neurosyphilis were treated with 20 or 24 megaunits of intravenous penicillin G daily for 15 to 30 days . The mean follow-up time after the treatment was 30 months . Forty-one patients had pleocytosis in the CSF before treatment . Six months and twelve or more months later, abnormal cell count was observed in 4 (9.8%) and in 3 patients (7.3%), respectively . The CSF protein level and the titers of Wassermann reaction in the CSF decreased slowly after treatment . The gammaglobulin concentration of the CSF and the immunoglobulin production inside the blood-brain barrier were still increased beyond the first year after treatment . The results of the treatment of these patients with high doses of intravenous penicillin G were not different from the results verified with lesser doses of intramuscular penicillin that were reported in the literature. Clin Chest Med, 1987 Sep, 8(3), 481 - 94 Bronchiectasis--new therapeutic approaches based on pathogenesis; Stockley RA; This article has highlighted several new concepts in the pathogenesis of bronchiectasis and proposed a hypothesis that could explain the deterioration seen in some of the patients . Modification of our current antibiotic policy has been shown to be beneficial in both the short and long term . The results of recent studies would suggest that patients with purulent sputum benefit from antibiotic therapy whether this represents an acute exacerbation or the usual clinical state . Exacerbations respond well to broad-spectrum antibiotics effective against H . influenzae and S . pneumoniae in conventional doses . However failure to respond, particularly when the usual secretions are purulent, often indicates that dosage is inadequate and a trial of a higher dosage of an agent such as amoxicillin may well prove effective . Treatment of patients who are also penicillin sensitive needs to be clarified, although no orally effective alternative has yet been identified . Relapse is rapid in patients whose usual secretions are purulent, and long-term therapy improves well-being and several biochemical indices of important pathogenic mechanisms . However, as we understand the reasons for bacterial colonization and persistence better, it should prove possible to modify other mechanisms therapeutically, thus negating the need for long-term antibiotic therapy and the associated potential risks of resistance. Ann Allergy, 1987 Sep, 59(3), 167 - 70 Skin test for diagnosis of penicillin allergy--current status; Ressler C et al.; The skin test for evaluating allergy to penicillin is reviewed . The reagents, penicillin, penicilloylpolylysine, benzyl penicilloate, and benzyl penilloate provide a safe and effective skin test for screening out the likelihood of severe allergic reactions to penicillin . The skin test gives much more accurate information than the patient's history and will enable many patients to receive penicillin despite a past history of allergy to the drug . Recent developments in the standardization and stabilization of the minor determinant mixture should result in making this reagent more available. J Chromatogr, 1987 Aug 28, 404(1), 195 - 214 Standardized high-performance liquid chromatography of 182 mycotoxins and other fungal metabolites based on alkylphenone retention indices and UV-VIS spectra (diode array detection); Frisvad JC et al.; A general standardized method for the analysis of mycotoxins and other fungal secondary metabolites has been developed, based on high-performance liquid chromatography (HPLC) with an alkylphenone retention index and photodiode-array detection combined with thin-layer chromatography (TLC) in two different eluents . Each fungal secondary metabolite is characterized by its bracketed alkylphenone retention time index, its UV-VIS absorption maxima and its retardation factors relative to griseofulvin in two TLC eluents . This system is effective for the comparison of chemotaxonomic data in different laboratories and for a precise identification of fungi based on organic solvent extracts of fungal cultures . All important groups of mycotoxins and other fungal secondary metabolites could be detected in the HPLC system described and data are listed for 182 metabolites . The fungal secondary metabolites separated and characterized include aflatoxin B1, B2, G1 and G2, ochratoxin A, citrinin, penicillin acid, viomellein, penitrem A, patulin, sterigmatocystin, alternariol, tenuazonic acid, trichothecenes, roquefortines, fusarin C, zearalenone, PR-toxin, citreoviridin, viridicatumtoxin, verruculogen, rugulosin, cyclopiazonic acid, penicillin G and many other alkaloids, polyketides and terpenes. FEBS Lett, 1987 Aug 10, 220(1), 206 - 8 Location of penicilloyl groups on CNBr fragments of the albumin from penicillin-treated patients; Lafaye P et al.; Two fixation sites for penicilloyl groups on human albumin were demonstrated . Using CNBr cleavage the first site was located between methionine 123 and methionine 297 and the second one between methionine 297 and the C-terminal residue . In both cases, penicilloyl groups were unmasked by pronase degradation or disulfide bond reduction. Br J Obstet Gynaecol, 1987 Aug, 94(8), 788 - 90 Recurrent acute leg cellulitis after hysterectomy with pelvic lymphadenectomy; Dankert J et al.; Recurrent acute leg cellulitis known to occur in patients with impaired venous or lymphatic circulation was surveyed prospectively in 270 patients after radical hysterectomy with pelvic lymphadenectomy and in 66 patients after hysterectomy with pelvic lymphadenectomy from 1977 to 1985 . Among them, six (2%) and three (4%) patients experienced a total of 17 episodes of acute leg cellulitis, respectively . Analysis showed that postoperative percutaneous radiation therapy of the pelvic area was a highly significant risk factor . Penicillin prophylaxis is recommended for patients experiencing recurrent attacks. Biochem J, 1987 Aug 1, 245(3), 831 - 41 Purification and initial characterization of an enzyme with deacetoxycephalosporin C synthetase and hydroxylase activities; Baldwin JE et al.; Deacetoxycephalosporin C synthetase (expandase) from Cephalosporium acremonium (Acremonium chrysogenum) was purified to near homogeneity as judged by SDS/polyacrylamide-gel electrophoresis . The enzyme (Mr about 40,000) exhibited a pH optimum around 7.5 . It required 2-oxoglutarate (Km 0.04 mM), Fe2+ and O2 as cofactors, and ascorbate and dithiothreitol were necessary for maximum activity . It was stable for over 4 weeks at -70 degrees C in the presence of 1 mM-dithiothreitol . Activity was inhibited by the thiol-quenching reagent N-ethylmaleimide, the metal-ion-chelating reagent bathophenanthroline, and NH4HCO3 . The highly purified enzyme also showed deacetoxycephalosporin C hydroxylase (deacetylcephalosporin C synthetase) activity, indicating that both expandase and hydroxylase activities are properties of a single protein . These activities could not be separated by ion-exchange, dye-ligand, gel-filtration or hydrophobic chromatography . A beta-sulphoxide and a 3 beta-methylene hydroxy analogue of penicillin N were synthesized to test as potential intermediates in the ring-expansion reaction, Neither compound was a substrate for the enzyme . A synthetic analogue in which the 3 beta-methyl group and the 2-hydrogen atom of penicillin N were replaced by a cyclopropane ring was not a substrate but was a reversible inhibitor of the enzyme. Appl Environ Microbiol, 1987 Aug, 53(8), 1955 - 8 Use of chitinase to assess ruminal fungi associated with plant residues in vitro; Akin DE; Treatment of fibrous residue from in vitro digestion trials with chitinase was evaluated gravimetrically and microscopically to determine the associated fungal biomass . The percent dry weight removed by chitinase with time paralleled changes in the number of sporangia associated with leaves . The fungal biomass contributed about 12% dry matter to the residue of leaves incubated with ruminal fluid plus streptomycin and penicillin. Neuroscience, 1987 Aug, 22(2), 553 - 61 Synaptic control of pyramidal cell activation in the hippocampal slice preparation in the rat; Dingledine R et al.; Recordings were made from CA1 pyramidal neurons in a rat hippocampal slice preparation to compare the effectiveness of orthodromic stimuli when delivered at different distances from the cells under study . A stimulating electrode placed in stratum radiatum was less effective in driving nearby pyramidal cells (within 200 micron) than those farther away (greater than 800 micron) . Thus for a given field excitatory postsynaptic potential both the intracellular excitatory postsynaptic potential and the evoked population spike were smaller when evoked from a local stimulating electrode than from one more distant . Laminar mapping experiments indicated that the spatial distribution of activated excitatory synapses over the pyramidal cell dendrites was similar for local and distant stimuli . The firing threshold, and the amplitude of hyperpolarizing inhibitory postsynaptic potentials, were also similar for the two stimuli . Responses evoked by the local stimulating electrode were more sensitive to morphine, penicillin and pentobarbital than responses elicited by the distant stimulus, suggesting that some form of GABAergic inhibition limited the efficacy of the local stimulus . The data suggest that in the CA1 region a vertically oriented synaptic inhibitory system exists that powerfully regulates the ability of an orthodromic stimulus to activate pyramidal cells . These results also illustrate the practical importance of controlling the distance between stimulating and recording electrodes, when performing quantitative pharmacological studies of synaptic transmission in the hippocampus. Brain Res, 1987 Aug, 431(2), 161 - 71 Cellular and synaptic physiology and epileptogenesis of developing rat neocortical neurons in vitro; Kriegstein AR et al.; The cellular and synaptic physiology of developing rat neocortical neurons was studied using the in vitro slice method . Rats aged 1-28 days were used for analysis . During the first two postnatal weeks several sequential changes occur in membrane properties and evoked synaptic potentials . Immature neurons had higher input resistances, more linear I-V characteristics, longer membrane time constants, and slower rising and falling phases of action potentials . The developmental increase in rate of rise of the action potential suggests an increasing density of voltage-dependent Na+-channels are inserted in neuronal membranes during postnatal development . The higher input resistance of young cells might be due to their small size and differences in membrane properties . The long time constant indicates a higher specific membrane resistivity of immature neurons . Postsynaptic potentials (PSPs) recorded in young neurons were longer in latency, longer in duration, and more fragile during repetitive activation than their mature counterparts . In addition, PSPs evoked in neurons of animals less than 1 week old did not contain inhibitory postsynaptic components . These physiological features of immature neocortical neurons help explain the pattern of epileptogenesis in young animals . When neonatal cortical slices were exposed to the gamma-aminobutyric acid (GABA) antagonists penicillin or bicuculline, the frequency of occurrence of discharges resembling epileptiform depolarization shifts approached that found in mature slices only during the second postnatal week . Depolarization shifts at younger ages were less stereotyped and more sensitive to stimulus parameters than those in mature neurons. Neuropharmacology, 1987 Aug, 26(8), 1181 - 4 Effects of ketamine and (+)cyclazocine on 4-aminopyridine and "magnesium free" epileptogenic activity in hippocampal slices of rats; Sagratella S et al.; The effects of ketamine and (+)cyclazocine on three in vitro models of epilepsy: the "Mg2+ free", the 4-aminopyridine (4-AP) and, for comparison, the penicillin model were studied . These data indicate that the two compounds had an inhibitory effect in hippocampal slices of rats, bathed in "Mg2+ free" solution at a concentration that did not influence the basal field potential . They also had an inhibitory effect on the penicillin model, but at concentrations ten times greater than those effective against "Mg2+ free" model . On the other hand, (+)cyclazocine was equally active against epileptogenic activity produced by 4-AP and "Mg2+ free" solution, while ketamine failed to produce an effect on epileptiform activity induced by 4-AP. S Afr Med J, 1987 Jul 18, 72(2), 110 - 3 Treatment of neurosyphilis . A comparison of penicillin regimens; Philcox DV et al.; Recommendations for treatment of neurosyphilis and reasons for renewed debate are briefly reviewed and discussed . Experience with 11 patients with neurosyphilis who were treated with different preparations of penicillin by different routes of administration is recorded . The concentration of penicillin was measured in the serum and cerebrospinal fluid in each case . Very high levels were attained by the intravenous administration of penicillin G, but in the follow-up period of 1 year this has not been shown to confer any advantage . The administration of procaine penicillin 1.2 million U intramuscularly daily for 20 days is as effective as a dosage schedule which requires admission to hospital for intravenous administration. Biochem Pharmacol, 1987 Jul 15, 36(14), 2393 - 403 Automated analysis of enzyme inactivation phenomena . Application to beta-lactamases and DD-peptidases; De Meester F et al.; In the presence of a reporter substrate, the progressive inactivation of an enzyme was easily studied by directly transmitting absorbance readings to a microcomputer . Pseudo-first order rate constants as high as 0.3 sec-1 were rapidly and accurately measured . When utilization of the reporter substrate did not exceed 10%, the rate of the reaction (vt) could be considered as proportional to the active enzyme concentration at any time during the analysis and the decrease of vt was first order with time . This simple method was used to follow the inactivation of beta-lactamases (EC 3.5.2.6) by various physical and chemical agents . When a large proportion (30-80%) of reporter substrate was destroyed, a correction was introduced to account for the corresponding decrease of its rate of utilization . This enabled experiments to be performed with a DD-peptidase and a substrate exhibiting a low delta epsilon upon hydrolysis . For the first time, the inactivation of a penicillin-sensitive enzyme by a beta-lactam could be continuously and directly observed . Finally, the method was extended to the study of hysteresis phenomena. J Immunol, 1987 Jul 15, 139(2), 506 - 12 Studies of IgE-dependent histamine releasing factors: heterogeneity of IgE; MacDonald SM et al.; Nasal lavage fluids from unstimulated individuals contain a histamine-releasing factor (HRF) similar to those which we have previously described from macrophages, platelets, and from blister fluids obtained during the late cutaneous reaction . The nasal HRF was partially purified by ion-exchange chromatography and gel filtration . Although some m.w . heterogeneity was observed, the majority of the HRF eluted at an apparent m.w . range of 15,000 to 30,000 . This partially purified HRF induced histamine release from basophils of certain individuals . Histamine release occurred via a mechanism which is IgE-dependent in that: basophils desensitized by exposure to anti-IgE in the absence of calcium no longer respond to HRF, and desensitization with HRF reduces responsiveness to anti-IgE; and removal of IgE from the basophil surface by using lactic acid renders cells unresponsive to HRF . We have further defined this IgE dependence and have shown that the reason that only selected basophil donors respond to HRF is due to a previously unrecognized, functional heterogeneity of IgE . Thus, passive sensitization using sera from responders restored the responsiveness of acid-stripped basophils and conferred responsiveness to basophils of a nonresponder with naturally unoccupied IgE receptors . Sera from nonresponders failed to do this even though similar numbers of IgE molecules were put onto the basophil surface in each case . This property of responder sera was due to IgE because both heating sera at 56 degrees C for 2 hr and passage of sera over anti-IgE-Sepharose (which removes greater than 90% of the IgE) markedly reduced the ability of sera to induce responsiveness, and because an excess of either purified IgE myeloma or purified penicillin-specific IgE antibody from a nonresponder competitively inhibited the ability of IgE from responder sera to induce responsiveness to HRF . We conclude that nasal lavage fluids contain an HRF which induces basophil histamine release in a specific, IgE-dependent fashion but only from individuals with the appropriate type of IgE . Because we have shown that basophils are recruited into the nose during the late-phase reaction, we suggest that nasal HRF may induce these cells to release histamine and other mediators which could contribute to the symptomatology of the late-phase reaction. Neurosci Lett, 1987 Jul 9, 78(1), 75 - 9 An electrophysiological study of habenular influence on hippocampus; Sabatino M et al.; The action of lateral habenula (LH) stimulation on focal epileptiform activity in the hippocampus was studied . Local microinjection of sodium penicillin induced a steady interictal activity in the dorsal hippocampus . Low frequency electrical stimulation of the habenula caused a marked enhancement of spike activity in both frequency and amplitude . The effect was blocked by intraperitoneally injected methysergide . The facilitatory influence of the habenula on hippocampal activity might be due to a disinhibitory mechanism . The results are regarded as suggesting that the habenula may be a relay station between the basal ganglia and the hippocampal formation . LH as well as basal ganglia might modulate hippocampal excitability, exerting a control on the genesis and diffusion of abnormal activities. Cornell Vet, 1987 Jul, 77(3), 263 - 76 Immune-mediated hemolytic anemia induced by penicillin in horses; Blue JT et al.; Three horses developed severe, immune-mediated hemolytic anemia after treatment with penicillin . The horses had positive direct antiglobulin (Coombs) tests and high titers of IgG antibody that agglutinated penicillin-coated equine red cells . Two of the horses were tested for antibodies to autologous red cell antigens; autoantibodies were not present . Titers of antipenicillin antibody decreased after penicillin was discontinued but IgG antibody was detectable months after recovery . One of the horses was challenged with penicillin; antibody titer increased slightly, but anemia did not develop . Antipenicillin antibody of the IgM class was present in low titer in 23 (77%) of 30 non-anemic horses tested . Apparently, the horse is similar to man in that penicillin-induced anemia is rare but the percentage of individuals with antipenicillin antibody is high. In Vitro Cell Dev Biol, 1987 Jul, 23(7), 465 - 73 Growth of exocrine acinar cells on a reconstituted basement membrane gel; Oliver C et al.; Methods have been developed for culturing a dividing population of morphologically differentiated rat parotid, lacrimal, and pancreatic acinar cells in vitro . Isolated acinar cells were plated onto tissue culture dishes coated with a three-dimensional, reconstituted basement membrane gel . After attachment in Ham's nutrient mixture F12, the cells were cultured at 35 degrees C in F12 supplemented with 10% heat inactivated rat serum, epidermal growth factor, dexamethasone, insulin, transferrin, selenium, putrescine, reduced glutathione, ascorbate, penicillin, streptomycin, and the appropriate secretagogue . Under these conditions, the cells attached rapidly and DNA synthesis was initiated within 2 to 3 d . Although the cells flattened on the substratum, they continued to maintain their differentiated morphology . The cells contained secretory granules, and the secretory enzymes peroxidase and amylase could be detected . The use of a reconstituted basement membrane gel proved critical for the attachment and growth of exocrine acinar cells. J Thorac Cardiovasc Surg, 1987 Jul, 94(1), 44 - 56 Valvuloplasty for rheumatic mitral valve disease . A surgical challenge; Antunes MJ et al.; From January 1981 through February 1985, 241 patients with rheumatic mitral valve disease (mean age 21.5 +/- 11.8 years) were subjected to comprehensive mitral valvuloplasty . One hundred seven patients (44.4%) were 15 years or younger and 63 (26.1%) were 12 years or younger . One hundred seventy five patients had pure or predominant regurgitation (mean age 19.3 +/- 10.7 years) and 40 (16.6%) had active rheumatic carditis at the time of the operation . Almost all patients (229) were in New York Heart Association Functional Class III or IV . The techniques used included shortening of anterior leaflet chordae tendineae (136 patients), resection of secondary, tertiary, and basal posterior leaflet chordae (156 patients), commissurotomy (113 patients), and implantation of a Carpentier ring (164 patients) . Current operative mortality is 1.9% . The survivors were followed up for 576 patient-years (mean 2.64 +/- 1.32 years) . Late mortality was 2.60% per patient-year and was valve related in 1.04% per patient-year . Reoperation was required in 25 patients (4.34% per patient-year), mostly (72%) in the first year . There were only two cases (0.35% per patient-year) of thromboembolism and three cases (0.52% per patient-year) of infective endocarditis . Hence valve failure occurred at a linearized rate of 6.08% per patient-year but was fatal in only 22% of the patients . There was no relationship between valve failure and the type of lesion or procedure performed, but reoperation was required more frequently in patients aged 12 years or less (7.33% per patient-year) than in those older than 12 years (3.29% per patient-year) (p less than 0.05) . Actuarial survival rate at 41/2 years was 90%, and 82% of the patients were free from valve-related complications . Valve function after valvuloplasty was assessed clinically . Eighty-four percent of the patients had a good immediate result, but this figure dropped to 69% at the end of the follow-up period (p less than 0.05) . The remainder had moderate valve dysfunction . However, 85% of the patients remain in New York Heart Association Functional Class I . Mitral valvuloplasty is an excellent alternative to valve replacement in young patients with rheumatic mitral valve disease . Persistent or reactivated rheumatic carditis may be a significant factor of valve failure, and penicillin prophylaxis is mandatory after operation. Cancer, 1987 Jul 1, 60(1), 14 - 7 Azlocillin, cephalothin, and tobramycin therapy in febrile solid tumor patients with chemotherapy-induced leukopenia; Lowenbraun S et al.; Although the semisynthetic broad-spectrum acylureido-penicillin, azlocillin has been demonstrated to have significant antibiotic activity in leukemic patients, its role in combination therapy of febrile granulocytopenic patients with chemotherapy-treated solid tumors has not been clearly delineated . Thirty-five solid tumor patients with chemotherapy-induced absolute granulocytopenia (less than 1000 granulocytes/ml) associated with fever (greater than 38.3 degrees C) were treated on a prospective study with a combination of azlocillin 4 g intravenously (IV) every 6 hours, cephalothin 2 g IV every 6 hours, and tobramycin 80 to 100 mg IV every 8 to 12 hours . Prior chemotherapy included doxorubicin combinations in 18 patients and other combinations in 17 patients . Granulocyte counts preantibiotic therapy were greater than 100 granulocyte/ml in 14 patients, 100 to 499 in nine patients, and 500 to 1000 in 12 patients . Granulocyte nadirs were less than 100 in 20 patients, 100 to 499 in nine patients, and 500 to 1000 in six patients . Times for granulocytes to rise towards normal were 1 to 3 days in eight patients, 4 to 6 days in 18 patients, and 7 or more days in nine patients . Tobramycin levels were primarily in the peak range of 3 to 6 micrograms/ml and trough range of 0 to 1.9 micrograms/ml . The site and pathogen were identified in nine patients, the infection site clinically documented without isolated pathogen in three patients, and no site or pathogen identified in 23 patients . Of the 35 patients, 34 had good responses to the antibiotic combination (complete disappearance of fever and other evidence of infection) . Serum creatinine rose 0.4 to 0.6 mg/dl in nine patients, 0.7 to 1.5 in four patients, and 1.5 in one patient (obstructive uropathy) . The only other noted antibiotic-related side effect was hypokalemia . This antibiotic combination had little toxicity with marked efficacy. Mol Microbiol, 1987 Jul, 1(1), 23 - 8 An 18 amino acid amphiphilic helix forms the membrane-anchoring domain of the Escherichia coli penicillin-binding protein 5; Jackson ME et al.; Small (10 residue) C-terminal deletions of PBP5 cause release of this inner membrane protein into the periplasm, indicating disruption of the membrane binding domain . To define the extent of the membrane anchoring domain, oligonucleotide-directed mutagenesis was used to introduce both single amino acid changes and novel restriction sites into the DNA, allowing subsequent construction of precise internal deletions . The 10 C-terminal amino acid residues possess very weak membrane anchoring potential . By extending the sequence to 18 residues membrane binding equivalent to that of authentic PBP5 was achieved . A proline substitution in this region, breaking a potential alpha-helix, also disrupts the membrane binding domain . These results are discussed with respect to the amphiphilicity of the C-terminal sequence when arranged in an alpha-helix. Mol Microbiol, 1987 Jul, 1(1), 101 - 6 Use of a beta-lactamase fusion vector to investigate the organization of penicillin-binding protein 1B in the cytoplasmic membrane of Escherichia coli; Edelman A et al.; The coding region for the mature form of TEM beta-lactamase was fused to random positions within the coding region of the penicillin-binding protein 1B (PBP 1B) gene and the nucleotide sequences across the fusion junctions of 100 in-frame fusions were determined . All fusion proteins that contained at least the NH2-terminal 94 residues of PBP 1B provided individual cells of E . coli with substantial levels of ampicillin resistance, suggesting that the beta-lactamase moiety had been translocated to the periplasm . Fusion proteins that contained less than or equal to 63 residues of PBP 1B possessed beta-lactamase activity, but could not protect single cells of E . coli from ampicillin, indicating that the beta-lactamase moiety of these fusion proteins remained in the cytoplasm . The beta-lactamase fusion approach suggested a model for the organization of PBP 1B in which the protein is embedded in the cytoplasmic membrane by a single hydrophobic transmembrane segment (residues 64-87), with a short NH2-terminal domain (residues 1-63), and the remainder of the polypeptide (residues 88-844) exposed on the periplasmic side of the cytoplasmic membrane . The proposed model for the organization of PBP 1B was supported by experiments which showed that the protein was completely digested by proteinase K added from the periplasmic side of the cytoplasmic membrane but was only slightly reduced in size by protease attack from the cytoplasmic side of the membrane. J Bacteriol, 1987 Jul, 169(7), 3099 - 103 Two distinct transpeptidation reactions during murein synthesis in Escherichia coli; Kraus W et al.; Murein synthesized in ether-permeabilized cells of Escherichia coli deficient in individual penicillin-binding proteins (PBPs) and in the presence of certain beta-lactam antibiotics was analyzed by high-pressure liquid chromatography separation of the muramidase split products . PBP 1b was found to to be the major murein synthesizing activity that was poorly compensated for by PBP 1a . A PBP 2 mutant as well as mecillinam-inhibited cells showed increased activity in the formation of oligomeric muropeptides as well as UDP-muramylpeptidyl-linked muropeptides, the reaction products of transpeptidation, bypassing the lipid intermediate . In contrast, penicillin G and furazlocillin severely inhibited these reactions but stimulated normal dimer production . It is concluded that two distinct transpeptidases exist in E . coli: one, highly sensitive to penicillin G and furazlocillin, catalyzes the formation of hyper-cross-linked muropeptides, and a second one, quite resistant to these antibiotics, synthesizes muropeptide dimers. Epilepsia, 1987 Jul-Aug, 28(4), 399 - 408 Differences between two feline epilepsy models in sleep and waking state disorders, state dependency of seizures and seizure susceptibility: amygdala kindling interferes with systemic penicillin epilepsy; Shouse MN; The objective of the study was to determine whether contemporary feline models of petit mal (systemic penicillin epilepsy) or temporal lobe epilepsy (amygdala kindling) resemble human seizure disorders with respect to disturbances of sleep and waking states, the state dependency of seizures, and transference of seizure susceptibility . These variables were examined in 6-h polygraphic recordings before and during exposure to both seizure models in 24 cats; 12 cats had intramuscular (i.m.) injections of 300,000 or 400,000 IU/kg of penicillin prior to kindling, and 12 were kindled before penicillin challenge . Results were as follows . First, penicillin increased light slow wave sleep (SWS) and drowsiness, during which spike-wave (SW) activity was maximal . Generalized tonic-clonic convulsions (GTCs) occurred predominantly in drowsiness after awakening from SWS . Second, kindling produced more deep SWS than did penicillin; susceptibility to kindled GTCs peaked during deep SWS, especially in transition to rapid eye movement sleep (REM) . Third, penicillin did not influence subsequent sleep disorders or seizure susceptibility during kindling; kindling interfered with penicillin-induced GTCs, SW activity, and sleep disorders . Collectively, the findings suggest distinct state disorders and state-dependent seizure profiles in the two models . These differences parallel human analogues and may have contributed to the transference results . Kindling is a chronic model with persistent sleep and seizure abnormalities that differ from and may have discouraged penicillin epilepsy . Penicillin is an acute model with transient state and seizure disorders, a fact that may account for the absence of penicillin transference to kindling. J Bacteriol, 1987 Jul, 169(7), 3358 - 61 Primary structure of colicin M, an inhibitor of murein biosynthesis; Kock J et al.; The DNA sequence of the colicin M activity gene cma was determined . A polypeptide consisting of 271 amino acids was deduced from the nucleotide sequence . The amino acid sequence agreed with the peptide sequences determined from the isolated colicin . The molecular weight of active colicin M was 29,453 . The primary translation product was not processed . In the domain required for uptake into cells, colicin M contained the pentapeptide Glu-Thr-Leu-Thr-Val . A similar sequence was found in all colicins which are taken up by a TonB-dependent mechanism and in outer membrane receptor proteins which are constituents of TonB-dependent transport systems . The structure of colicin M in the carboxy-terminal activity domain had no resemblance to the pore-forming colicins or colicins with endonuclease activity . Instead, the activity domain contained a sequence which exhibited homology to the sequence around the serine residue in the active site of penicillin-binding proteins of Escherichia coli . The colicin M activity gene was regulated from an SOS box upstream of the adjacent colicin B activity gene on the natural plasmid pColBM-Cl139. N Engl J Med, 1987 Jun 25, 316(26), 1622 - 6 Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis; Schwartz LB et al.; Better methods are needed to assess mast-cell activation in vivo and to distinguish the activation of mast cells from that of basophils . Tryptase, a neutral protease selectively concentrated in the secretory granules of human mast cells (but not basophils), is released by mast cells together with histamine and serves as a marker of mast-cell activation . In 17 patients with systemic mastocytosis, concentrations of tryptase in plasma were linearly related to those of histamine (P less than 0.01) . Eleven of the 17 patients had tryptase levels of 4 to 88 ng per milliliter, indicating ongoing mast-cell activation . In each of six patients who experienced corresponding anaphylactic reactions after penicillin, aspirin, or melon ingestion, a wasp sting, exercise, or antilymphocyte globulin injection, tryptase levels in serum ranged from 9 to 75 ng per milliliter, indicating mast-cell activation during each of these events . In contrast, serum tryptase levels were less than 5 ng per milliliter in all patients presenting with myocardial disease (n = 8, 6 with hypotension) or sepsis (n = 6, 3 with hypotension) and in the controls (n = 20) . One patient had a myocardial infarction after anaphylaxis in response to a wasp sting and an elevated tryptase level of 25 ng per milliliter . Thus, the plasma or serum tryptase level is a diagnostic correlate of mast-cell-related events. N Engl J Med, 1987 Jun 18, 316(25), 1569 - 72 Alteration in the natural history of neurosyphilis by concurrent infection with the human immunodeficiency virus; Johns DR et al.; Within the past 18 months, we have seen four cases of neurosyphilis at our institution (two of meningovascular syphilis, one of acute syphilitic meningitis, and one of asymptomatic neurosyphilis) in young homosexual men with serologic evidence of exposure to human immunodeficiency virus (HIV) . Two of the four patients had neurosyphilis despite previous adequate therapy for early syphilis with benzathine penicillin . Meningovascular syphilis developed in one patient within four months after a primary infection, in a manner consistent with an accelerated course of syphilitic infection . These findings suggest the possibility that HIV infection may alter the natural course of syphilis because of the profound defects in cell-mediated immunity it causes . The possible potentiating effects of HIV on Treponema pallidum infection suggest the need for lumbar puncture in the evaluation of HIV-seropositive patients with syphilis, as well as modifications of the currently recommended treatment regimens for primary, secondary, and latent syphilis and neurosyphilis in this patient population . Neurosyphilis should probably be added to the growing list of infectious complications of the acquired immunodeficiency syndrome (AIDS) and may be the first such complication to appear. Arthritis Rheum, 1987 Jun, 30(6), 705 - 8 Lyme meningoencephalitis: report of a severe, penicillin-resistant case; Diringer MN et al.; Although Lyme disease frequently attacks the central nervous system, this involvement is rarely severe, and high-dose intravenous penicillin usually is adequate treatment . The patient we describe developed severe Lyme meningoencephalitis despite receiving a full cours