Penicillin

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 course of penicillin, and his condition continued to deteriorate after reinstitution of this treatment . Intravenous chloramphenicol was used successfully and resulted in a substantial improvement.

J Am Vet Med Assoc, 1987 Jun 1, 190(11), 1435 - 6
Endocardial fibroelastosis and tricuspid valve insufficiency in a calf; Scarratt WK et al.; A 5-month-old Holstein heifer had clinical signs of tricuspid valve insufficiency and histopathologic evidence of endocardial fibroelastosis . The calf had a 3-week history of weight loss, abdominal distention, dyspnea, and decreased appetite . Physical examination revealed signs of right-sided heart failure, and a systolic murmur (II/VI) was heard best over the right heart base . Results of cardiac catheterization and echocardiography indicated tricuspid valve insufficiency and right-sided heart failure . The calf was euthanatized after not responding to treatment with penicillin, furosemide, and removal of fluid from the thorax and abdomen . Necropsy findings included multifocal areas of thickening and opacification of the endocardium of the left and right ventricles . Excessive elastic fibers, consistent with fibroelastosis, were seen by use of special stains applied to sections of endocardium.

Br J Surg, 1987 Jun, 74(6), 466 - 8
Mammillary fistula; Bundred NJ et al.; Forty women presenting with mammillary fistulas over a 6 year period have been reviewed . The events preceding the fistula were incision of a periareolar breast abscess (n = 24), breast biopsy (n = 13) and spontaneous discharge of an inflammatory mass (n = 3) . Only two of the women with abscesses were lactating . Two patients had granulomatous mastitis . The remaining 36 patients were all considered to have periductal mastitis/mammary duct ectasia as the cause of their fistulas . The two mammillary fistulas associated with lactation healed spontaneously . Nine patients had the fistula excised and the wound packed; this resulted in satisfactory healing in all but one patient . Twenty-one patients had excision of the fistula and primary closure, without antibiotic cover, but only ten healed without complications and six patients required further surgical procedures for a recurrent fistula . Six patients had primary excision and closure under antibiotic cover with a penicillin and metronidazole; all healed . Mammillary fistulas are complications of the periductal mastitis/duct ectasia syndrome . They should be treated by excision and primary closure under appropriate antibiotic cover or alternatively excised and left open to granulate.

Neurology, 1987 Jun, 37(6), 1031 - 4
Chronic forms of Borrelia burgdorferi infection of the nervous system; Wokke JH et al.; Three European patients had chronic active forms of Borrelia burgdorferi infection of the nervous system, with high titers of antibodies to this spirochete in serum and CSF . Two patients had meningitis for 3 to 4 years, with remissions in one and slowly progressive symptoms in the other . Both had CT lucencies in the basal ganglia . The third patient had lumbosacral plexus neuropathy for 1 year . All three patients responded to intravenous penicillin treatment.

Jpn J Psychiatry Neurol, 1987 Jun, 41(2), 269 - 71
Syphilitic myelitis with its magnetic resonance imaging (MRI) verification and successful treatment; Tashiro K et al.; A 31-year-old man with a 10-day duration of a progressive paraparesis and sensory disturbance was found to have a syphilitic infection which was confirmed by the blood and cerebrospinal fluid (CSF) syphilitic reaction . A discrete and wedge-shaped Gadolinium-DTPA-enhanced lesion on magnetic resonance imaging (MRI) was identified at the level of Th 3/4 . The neurologic states and MRI findings improved noticeably after a 16-day course of penicillin with a high dose of prednisolone . Therefore, we want to emphasize the importance and usefulness of MRI in syphilitic myelitis.

Arq Neuropsiquiatr, 1987 Jun, 45(2), 99 - 108
{Intravenous penicillin therapy in high doses in neurosyphilis: study of 62 cases . I . Clinical evaluation}; 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 . Thirteen patients developed new neurological signs after the treatment . Their diagnosis were: general paresis (9), taboparesis (2), tabes dorsalis (1) and meningovascular neurosyphilis (1) . After the treatment, thirty-six patients (58.1%) improved, 22 patients (35.5%) were unchanged and 4 patients (6.4%) deteriorated on clinical grounds . In two patients there was a progression to other forms of neurosyphilis . The results of the treatment of these patients with high doses of intravenous penicillin G were not different from the results verified with classical intramuscular penicillin that were reported in the literature, from the clinical standpoint.

Appl Biochem Biotechnol, 1987 Jun, 15(1), 1 - 10
Radiation-induced polymerization for the immobilization of penicillin acylase; Boccu E et al.; The immobilization of Escherichia coli penicillin acylase (EC 3.5.1.11) was investigated by radiation-induced polymerization of 2-hydroxyethyl methacrylate at low temperature . A leak-proof composite that does not swell in water was obtained by adding the cross-linking agent trimethylolpropane trimethacrylate to the monomer-aqueous enzyme mixture . Penicillin acylase, which was immobilized with greater than 70% yield, possessed a higher Km value toward the substrate 6-nitro-3-phenylacetamidobenzoic acid than the free enzyme form (Km = 1.7 X 10(-5) and 1 X 10(-5) M, respectively) . The structural stability of immobilized penicillin acylase, as assessed by heat, guanidinium chloride, and pH denaturation profiles, was very similar to that of the free-enzyme form, thus suggesting that penicillin acylase was entrapped in its native state into aqueous free spaces of the polymer matrix.

Pathol Biol (Paris), 1987 Jun, 35(5 Pt 2), 843 - 6
{Penicillin G in the treatment of pneumococcal meningitis . Its real importance at the present time}; Do Carmo G et al.; The authors carried out this work with the purpose both of verifying the present importance of penicillin G for the treatment of pneumococcal meningitis and of comparing it with the clinical effectiveness of other medicines presently available for the same purpose . They have studied 27 patients with clinical and laboratory diagnosis of pneumococcal meningitis and which were admitted in the "Servico de Infecto-Contagiosos" of Santa Maria Hospital, Lisbon, for the period from 1.1.81 until 31.05.86 . Of these patients 18 were males and 9 females, ranging from 8 to 80 years old . All of them were treated exclusively with penicillin G, the medium dose being 400,000 IU/kg per day and for a medium period of 15 days . The final results accounted for: 23 patients healed (85.2%), 2 decreased (7.4%) and the remaining 2 (7.4%) with neurological sequels by the time of discharge from the hospital . These, in our opinion, are values for the minimum equivalent to those in other series of the same pathology and under treatment by the different medicines presently available in alternative . Bearing in mind these results and considering it is more expensive to use these new antibiotics, the authors think they may state that penicillin G keeps ahead for the treatment of pneumococcal meningitis, except for cases of hypersensitivity to this medicine or penicillin-resistance.

J Bacteriol, 1987 Jun, 169(6), 2410 - 6
Modulation of cell wall synthesis by DNA replication in Escherichia coli during initiation of cell growth; Garcia-del Portillo F et al.; Resting cells of Escherichia coli are able to initiate growth and murein biosynthesis in the presence of beta-lactam antibiotics binding to penicillin-binding proteins (PBPs) 1a and 1b (E . J . de la Rosa, M . A . de Pedro, and D . Vazquez, Proc . Natl . Acad . Sci . USA 82:5632-5635, 1985) . Under these conditions, cells elongate normally until they approach the first doubling in mass, the time at which cell lysis starts . Assuming that coupling between DNA replication and cell division both in cells starting growth and in growing cells is essentially similar, triggering of the lytic response in the beta-lactam-treated cells coincides with the termination of the first round of DNA replication . This coincidence suggests that both events are interrelated . We investigated this possibility by studying the initiation of growth in cultures of wild-type strains and in cell division mutants treated with beta-lactams inhibiting PBPs 1a and 1b and with the DNA replication inhibitor nalidixic acid . Addition of nalidixic acid, even late in the first cell cycle, prevented the lytic response of the cells to the blockade of PBPs 1a and 1b . The effect of nalidixic acid is more likely due to its action on DNA replication itself than to its indirect inhibitory effect on cell division or to its ability to induce the SOS system of the cell . These observations favor the idea that the cell wall biosynthetic machinery might be modulated by DNA replication at precise periods during cell growth.

Infect Dis Clin North Am, 1987 Jun, 1(2), 383 - 423
Human interferon in viral diseases; Greenberg SB; Interferons have been studied in animals and man for local and systemic viral infections that are either rare or common . Recent clinical studies in humans with purified or recombinantly derived interferons have demonstrated significant clinical response in rhinovirus common colds, herpetic keratitis, condyloma acuminata, and laryngeal papillomatosis . However, only 40 per cent of published papers with IFN have been appropriately controlled . The toxicity of these newer preparations when administered either topically or parenterally prevents their immediate licensing for general use . The toxic to therapeutic ratio for HuIFN and rIFN appears to be close to one in most clinical situations in which it has been tested . Although interferons have not proved to be the "penicillin" for viruses many thought they would become, basic in vitro work and clinical studies have contributed greatly to our understanding of host defense and immunopathology . Future studies must focus on increasing our understanding of the mechanisms of toxicity, in addition to devising controlled clinical trials with interferon alone or in combination with other antiviral agents . Thus, after 30 years of research on interferons, it would appear our work has just begun.

Z Gesamte Inn Med, 1987 May 15, 42(10), 280 - 2
{Headache in early syphilis--a case report}; Risse A et al.; A 16-year-old girl fell ill with headache of uncertain etiology . Some weeks later an exanthem led to the diagnosis of lues . Characteristic changes in serum and liquor parameters were found . Hearing disorder and choked disc improved during the therapy with penicillin . The rare picture of early luetic meningitis remains important for the differential diagnosis of headache.

Cancer Res, 1987 May 15, 47(10), 2737 - 40
Detection of small cell lung cancer bone marrow involvement by discontinuous gradient sedimentation; Hunter RF et al.; Marrow involvement by small cell lung cancer (SCLC) is detected in 10-23% of patients at initial diagnosis by marrow aspirate and biopsy techniques . To improve the detection and potentially monitor marrow involvement by SCLC we have attempted to concentrate malignant cells with clonogenic potential on a discontinuous density gradient (DDG) . The bone marrow from 43 patients with SCLC (36 with histologically negative marrow aspirates and biopsies) were separated on a Ficoll-based DDG . Samples were also separated by conventional Ficoll-diatrizoate (FD) (density, 1.077) gradient sedimentation . The cellular interphase from three fractions (F X) corresponding to specific densities 1.050 (F X 1), 1.055 (F X 2), and 1.060 (F X 3) as well as cells separated by Ficoll-diatrizoate (F X FD) centrifugation were isolated and 2.5 X 10(5) cells from each fraction were cultured in 2 ml of 0.3% agar in McCoy's media with 10% fetal calf serum, 2.5 micrograms transferrin, 1 microgram insulin, and 1% penicillin-streptomycin . Colony growth was assessed after 14 days of culture at 37 degrees C and 6% CO2 . Tumor colony growth was seen in eight of 36 (22%) patients with histologically negative marrows as well as in four of seven (57%) patients with known involvement . Mean colony growth per 2.5 X 10(5) cells for all 12 patients was 4.3 colonies for F X 1; 8.8 for F X 2; and 2.7 for F X 3 . In contrast mean growth from the F X FD was 1.0 colonies . Cells with clonogenic potential could be demonstrated from F X 2 and F X 3 in seven of 12 and eight of 12 patients, respectively; in F X FD four of 12 patients had tumor growth . We conclude that separation of marrow samples by DDG concentrates malignant cells with clonogenic potential at least 8-fold compared to FD separation and that the sensitivity of the clonogenic assay in detecting marrow involvement by SCLC is enhanced by DDG sedimentation.

Clin Exp Immunol, 1987 May, 68(2), 427 - 36
Mouse anti-benzylpenicilloyl IgE monoclonal antibody: preparation, characterization and cross-reactivity; Fukushima H et al.; Anti-benzylpenicilloyl (BPO-) monoclonal antibody of the IgE class was prepared from spleens of immune C57BL/6 mice whose sera reacted with BPO-hapten, penicillin G(PCG) polymer, cephalothin (CET)-hapten and CET polymer . Affinity chromatography experiments showed that the haptenic specificity of the IgE monoclonal antibody (designated BIE-13CE) was directed mainly to phenylacetyl portion of BPO group . BIE-13CE antibody reacted on passive cutaneous anaphylaxis (PCA) assay with BPO-hapten, CET-hapten, cephaloridine-hapten and CET polymer, but did not react with PCG polymer, ampicillin-hapten, or cefazolin-hapten . These results indicated that the sera of the immune C57BL/6 mice contained IgE antibodies capable of cross-reacting at the monoclonal antibody level with various forms of eliciting antigens and that the cross-reactivity of the antibody could be ascribed essentially to the structural similarity of acyl side chains of the antibiotics . The structure of the CET polymer is also discussed in terms of its PCA reactivity with the monoclonal antibody and analytical and spectral data of the polymer.

Antibiot Med Biotekhnol, 1987 May, 32(5), 385 - 8
{Pharmacokinetics of benzylpenicillin and ampicillin in patients after combined administration with sulfalen and sulfadimethoxine}; Bobrov VI et al.; Combined use of the penicillins and sulfanylamides in patients resulted in increased antibiotic blood levels and circulation . Retarded elimination of the penicillins was mainly due to the depositing effect of the sulfanylamides on the antibiotics at the account of increasing levels of the latter in peripheral tissues which was realized through increasing the drug distribution volume . It is not excluded that the primary mechanism of changing the penicillin kinetics in patients is lowered antibiotic binding to plasma proteins.

Br J Surg, 1987 May, 74(5), 353 - 7
Splenectomy in the management of haematological disease; Dawson AA et al.; Patients, both adults and children, with various haematological disorders who had splenectomy electively in the diagnosis, staging or treatment of their condition during a 15-year period in the Aberdeen hospitals were reviewed . The outcome regarding the disease and the immediate and long-term complications of splenectomy in this group of 185 patients are presented . Splenectomy has an acceptably low morbidity, even in patients with serious haematological disease, in the hands of an experienced surgical team, where there is close co-operation between surgeon and haematologist . Occasionally, late overwhelming infections may occur, despite prophylaxis with penicillin and pneumococcal vaccination . It seems likely that, in their zeal to report such hazards, authors may allow the pendulum against splenectomy to swing too far, in the direction of leaving patients, especially adults, with considerable symptoms and poor health, rather than risk the occasional consequences of the asplenic state.

J Allergy Clin Immunol, 1987 May, 79(5), 726 - 33
Vocal cord dysfunction: the importance of psychologic factors and provocation challenge testing; Selner JC et al.; We present three case reports involving patients with vocal cord dysfunction . The onset of symptoms in one case was coincident with a generalized cutaneous reaction to penicillin with laryngeal involvement . The other cases had been misdiagnosed as food allergy and chemical sensitivity . We describe the psychologic factors in these cases in terms of the primary and secondary gain operative in the somatoform disorder of conversion reaction and emphasize the importance of belief and learned sensitivity in the induction of symptoms . The necessity of considering psychologic factors and the use of blinded, controlled, provocation challenges to evaluate subjective symptomatology is underscored . This study emphasizes the heterogenicity of clinical presentations involving vocal cord dysfunction and illustrates the value of fiberoptic-assisted examination of laryngeal function in conjunction with provocation challenge testing in establishing causal relationships for specific clinical symptoms.

J Bacteriol, 1987 May, 169(5), 2310 - 2
Temperature sensitivity of the penicillin-induced autolysis mechanism in nongrowing cultures of Escherichia coli; Kusser W et al.; The effect of incubation temperature on the ampicillin-induced autolysis of nongrowing Escherichia coli was determined . The autolysis mechanisms in amino acid-deprived relA mutant cells treated with chloramphenicol were temperature sensitive . This temperature-sensitive autolysis was demonstrated in three independent ways: turbidimetric determinations, viable cell counts, and solubilization of radiolabeled peptidoglycan.

Vet Surg, 1987 May-Jun, 16(3), 245 - 50
Cardiovascular effects of intravenous sodium penicillin, sodium cefazolin, and sodium citrate in awake and anesthetized horses; Hubbell JA et al.; Sodium penicillin, sodium cefazolin, and sodium citrate were administered to six adult horses on separate occasions, when awake and during anesthesia . The order of administration was randomized and studies were separated by a minimum of 7 days . Arterial blood pressure decreased significantly (less than 0.05) from control 5 minutes after intravenous (IV) sodium penicillin in awake and anesthetized horses . Systolic arterial blood pressure remained significantly (less than 0.05) decreased 10 minutes after IV sodium penicillin in anesthetized horses . Sodium cefazolin and sodium citrate did not significantly affect any of the measured cardiovascular variables . Although the changes in arterial blood pressure were small (8-15 mm Hg), monitoring of arterial blood pressure is advised when sodium penicillin is administered IV to anesthetized horses.

Epilepsy Res, 1987 May, 1(3), 173 - 7
Distribution of diphenylhydantoin in the brain during experimental status epilepticus of the cat; Sechi GP et al.; The distribution of diphenylhydantoin (PHT) (40 mg/kg i.p.) in the brain was investigated in cats with convulsive generalized (group 1) and focal penicillin-induced status epilepticus (group 2), and in controls . A significant increase in the amount of PHT entering the brain during the convulsive status was found, with peak brain levels at 45 min (12 +/- 3.2 micrograms/g vs . 6.0 +/- 0.8 in normal cats, P less than 0.05) . In the focal status brain concentrations of PHT reached levels intermediate between controls and group 1 cats . At 15 min, elevated blood levels of the drug were paralleled by increased concentrations in the brain, whereas at 30 and 45 min other factors, such as changes in cerebral blood flow, cerebral pH, vascular resistance, metabolic derangement and blood-brain barrier disruption were presumably responsible for the altered brain PHT uptake . The relevance of these data to clinical practice is discussed, in relation to the treatment of human status epilepticus and the potentially neurotoxic effects of the drug.

Am J Emerg Med, 1987 May, 5(3), 220 - 3
Carotid hemorrhage: a complication of peritonsillar abscess; Garino JP et al.; Carotid hemorrhage secondary to peritonsillar abscess occurs infrequently today because of the effectiveness of antibiotic therapy . When it does occur, however, emergency physicians unfamiliar with such a complication may have difficulty making its diagnosis and instituting appropriate therapy . Prevention is the easiest way to treat septic erosion . Abscesses are treated best with penicillin or, in the allergic patient, clindamycin followed by incision and drainage . Once the abscess has eroded into the carotid artery, it usually must be tied off to control the subsequent massive bleeding.

Microbiol Sci, 1987 May, 4(5), 147 - 8
Beta-lactamases: a new twist to an old problem; Nichols WW; Beta-lactamases have been known for as long as penicillin has been used for chemotherapy . Their importance to man is that they are overwhelmingly responsible for bacterial resistance to beta-lactam antibiotics, i.e . those similar to penicillin and the cephalosporins.

Neuroscience, 1987 May, 21(2), 441 - 55
The initiation and spread of epileptiform bursts in the in vitro hippocampal slice; Knowles WD et al.; We recorded spontaneous synchronized epileptiform bursts from hippocampal slices from guinea pig using an array of 16 extracellular electrodes placed over the stratum pyramidale of CA2 and CA3 . The slices were made epileptogenic with the GABA antagonist picrotoxin (or occasionally penicillin) . We found that spontaneous bursts always originate at a discrete focus at or near CA2 . These bursts spread smoothly and uniformly across CA3 at an average velocity of 0.13 m/s . This velocity is slower than the conduction velocity of the Schaffer collaterals or mossy fibers . Picrotoxin produced afterdischarges following the initial primary burst, and these afterdischarges were found to originate and spread in a fashion nearly identical to the primary burst . These results indicate that CA2 is a unique region which must possess unusual cellular and/or synaptic connectivity properties which result in a decreased threshold for initiation of epileptiform activity . We consider several hypothetical patterns of local synaptic connectivity in the light of these results, and we discuss the possible role of residual inhibition in limiting the spread of synchronized discharges.

Clin Allergy, 1987 May, 17(3), 229 - 34
Penicillin in milk--its importance in urticaria; Ormerod AD et al.; Fifty patients with recurrent urticaria were tested by means of the RAST test for penicillin allergy . Fifteen patients had positive reactions and of these, thirteen received provocation tests with 0.1 U/ml of penicillin in milk . Four had definite positive reactions, three doubtful reactions and six had no reaction . Although there has been improvement in the purity of milk, penicillin residues remain a potential cause of urticaria even in very low amounts and could have contributed to the urticaria in at least 8% of our patients . Veterinary use of antibiotics and food quality should be strictly regulated to prevent contamination of our diet.

Farmakol Toksikol, 1987 May-Jun, 50(3), 33 - 6
{Behavioral and EEG signs of the convulsive action of kynurenine and quinolinic acid in cats}; Dutov AA et al.; Administration of quinolinic acid but not L-kynurenine into the cat caudate nucleus was found to produce the appearance of epileptiform charges in the EEG with concomitant behavioral convulsions . A combination of quinolinic acid injections with systemic administration of penicillin resulted in the development of the status of myoclonic convulsions alternating with generalized tonicoclonic seizures . These states were eliminated by diazepam . The right caudate nucleus was revealed to be more sensitive as compared to the left one to the convulsant action of combined administration of quinolinic acid with penicillin.

Biochim Biophys Acta, 1987 Apr 30, 912(3), 325 - 8
Enzyme action in polymer and salt solutions . II . Activity of penicillin acylase in poly(ethylene glycol) and potassium phosphate solutions in relation to water activity; Andersson E et al.; Increasing concentrations of poly(ethylene glycol) and potassium phosphate solutions decreased the enzymatic activity of penicillin acylase (penicillin aminohydrolase, EC 3.5.1.11) . Low molecular weight poly(ethylene glycol) reduced the penicillin acylase activity more than high molecular weight poly(ethylene glycol) . The decrease in enzymatic activity seemed to be related to the decrease in water activity in solutions containing poly(ethylene glycol), irrespective of the molecular weight of the polymer . The decrease in enzymatic activity in potassium phosphate solutions was lower than in poly(ethylene glycol) solutions and did not fit the water activity relationship . The decreased enzymatic activity is discussed in relation to the enzyme stability in these solutions.

Biochim Biophys Acta, 1987 Apr 30, 912(3), 317 - 24
Enzyme action in polymer and salt solutions . I . Stability of penicillin acylase in poly(ethylene glycol) and potassium phosphate solutions in relation to water activity; Andersson E et al.; The stability of penicillin acylase (penicillin aminohydrolase, EC 3.5.1.11) was studied in poly(ethylene glycol) and potassium phosphate solutions . Enzyme stability measured as the half-life of the enzymatic activity and the transition temperature determined by differential scanning calorimetry, correlated well . The enzyme stability could not be related to the water activity as a measure of solute-solvent interaction . It seems to be related more to the concentration of the solutes and much less to the molecular weight of poly(ethylene glycol) . The stabilizing effect of poly(ethylene glycol) is also discussed in terms of poly(ethylene glycol)-protein interactions.

FEBS Lett, 1987 Apr 20, 214(2), 357 - 61
A spectrophotometric assay for deacetoxycephalosporin C synthase; Baldwin JE et al.; A continuous direct spectrophotometric assay for deacetoxycephalosporin C synthase was developed, based on the absorption at 260 nm characteristic of the dihydrothiazine moiety of cephalosporins . Km values of 0.18 mM for penicillin N and 0.16 mM for alpha-ketoglutarate were determined . A coupled assay using succinate thiokinase, pyruvate kinase and lactate dehydrogenase showed that succinate was a product of both deacetoxycephalosporin C synthase and hydroxylase reactions . The expandase reaction exhibited a 1:1.06 stoichiometry for deacetoxycephalosporin C and succinate.

Sex Transm Dis, 1987 Apr-Jun, 14(2), 116 - 8
Ceftriaxone for treatment of primary syphilis in men: a preliminary study; Moorthy TT et al.; Eighteen male patients with primary syphilis were randomly assigned to one of the following treatment schedules: ceftriaxone (3 g in a single intramuscular {im} injection), ceftriaxone (2 g im daily for two days), ceftriaxone (2 g im daily for five days), and benzathine penicillin (2.4 X 10(6) units in a single im injection) . The single 3-g dose of ceftriaxone cured three men, one had a sustained response, and one failed to be cured . Of the patients given 2 g of ceftriaxone im daily for two days, three were cured and two had a sustained response . All three men treated with 2 g of ceftriaxone daily for five days had a sustained response . In the group given penicillin, three men were cured, one had a sustained response, and one was lost to follow-up.

No To Shinkei, 1987 Apr, 39(4), 375 - 9
{Three cases of syphilitic optic atrophy--its clinical features and significance}; Moriwaka F et al.; Three cases of syphilitic optic atrophy were reported . All 3 cases showed progressive deteriorations of visual acuity, and visual field defects associated with central scotoma . Following optic nerve atrophy, two of them developed the signs and symptoms related to spinal cord involvements, which were considered to be early development of tabes dorsalis clinically . After the introduction of penicillin into the therapy of syphilis, especially neurosyphilis, it has been said that this disease is markedly decreased in incidence, and its clinical features are changed . However, there are some reports stating that neurosyphilis might be still prevalent and more atypical forms of neurosyphilis has been encountered . The incidence of syphilitic optic atrophy is still rare, and there is no difference between its' incidence in old and recent reports . From our recent experience and review of the literatures, it is proposed that we should never forget the existence of syphilis in differential diagnosis of optic nerve atrophy.

Z Hautkr, 1987 Apr 1, 62(7), 547 - 9
{Treatment of circumscribed scleroderma in childhood}; Nagy E et al.; 17 children suffering from morphea were treated with penicillin and antimalaria drugs . The best effects were observed after the combination of penicillin and antimalaria drugs.

Microbiologica, 1987 Apr, 10(2), 229 - 34
Changes in penicillin-binding proteins during the life cycle of Micromonospora; Cheng YR et al.; The penicillin-binding proteins (PBPs) of Micromonospora were studied . Only one PBP (48,000 mol weight) was found in membranes isolated from primary mycelia, whereas three PBPs were observed in secondary mycelia and designated PBP 1 (89,000 mol weight), PBP2 (69,000) and PBP3 (48,000) . Both the unique PBP produced by primary mycelia and PBP3 of secondary mycelia had the same affinity for penicillin which was higher than that of PBP2 and 3 . The role of these proteins in the cell life cycle of Micromonospora is discussed.

Genitourin Med, 1987 Apr, 63(2), 92 - 4
Response of pharyngeal gonorrhoea to single dose penicillin treatment; Sulaiman MZ et al.; The prevalence of gonococcal infection of the pharynx in 205 women, 331 heterosexual men, and 11 homosexual men with gonorrhoea was 6.8%, 4.2%, and 27.3% respectively . In only one patient, a heterosexual man, was the pharynx the sole site of infection . Throat symptoms were found in 7% of women, 21% of heterosexual men, and none of the homosexual men . Orogenital contact was reported by 29% of women, 36% of heterosexual men, and all the homosexual men . A single intramuscular dose of 1.8 g Bicillin (procaine penicillin 1.5 g plus benzyl penicillin 300 mg) cured 90% of patients.

Am Rev Respir Dis, 1987 Apr, 135(4), 869 - 74
Induction of pulmonary inflammation by components of the pneumococcal cell surface; Tuomanen E et al.; Using a rabbit model of experimental pneumonitis, the components on the surface of the pneumococcus that incite pulmonary inflammation were identified . Rabbits were challenged intratracheally with live pneumococci, capsular polysaccharide, purified cell walls, or cell wall subcomponents . Leukocytosis and elevation of protein concentration was quantitated in bronchial lavage fluid during the first 24 h after challenge . Of the pneumococcal surface components tested, cell wall preparations had the highest specific activity in inducing inflammation; abnormalities in bronchial lavage fluid cytochemistry appeared rapidly and in a dose-dependent manner . Cell wall building blocks and the products of penicillin-induced hydrolysis of the cell wall were also highly inflammatory, indicating that inflammation can be generated by disruption of the cell wall during lysis of bacteria by beta-lactam antibiotics . Administration of inhibitors of arachidonic acid metabolism suggested that inhibition of the lipoxygenase pathway reduced inflammation associated with cell walls . We propose that pulmonary inflammation during pneumococcal pneumonia arises in large part from the interaction of the bacterial cell wall with complement and noncomplement-mediated host defenses.

South Med J, 1987 Apr, 80(4), 534 - 5
Pneumococcal vertebral osteomyelitis in an adult; Gelfand MS et al.; We have presented the case of an adult with a chronic and indolent pneumococcal vertebral osteomyelitis, mimicking a malignancy and making diagnosis difficult . The increased frequency of relatively penicillin-resistant strains of pneumococci necessitates susceptibility testing and complicates the selection of antibiotic therapy for serious pneumococcal infections.

J Bacteriol, 1987 Apr, 169(4), 1611 - 8
Copurification and characterization of deacetoxycephalosporin C synthetase/hydroxylase from Cephalosporium acremonium; Dotzlaf JE et al.; Deacetoxycephalosporin C synthetase (expandase), which catalyzes ring expansion of penicillin N to deacetoxycephalosporin C (DAOC), has been stabilized in vitro and purified to near homogeneity from the industrially important fungus Cephalosporium acremonium . Throughout the purification, the expandase activity remained physically associated with and in a constant ratio of 7:1 to DAOC hydroxylase activity . The latter activity mediates hydroxylation of DAOC to deacetylcephalosporin C (DAC) . The copurified expandase/hydroxylase appeared to be monomeric, with a molecular weight of 41,000 +/- 2,000 and an isoelectric point of 6.3 +/- 0.3 . Both catalytic activities required alpha-ketoglutarate, Fe2+, and O2 and were stimulated by ascorbate, dithiothreitol, and ATP . The Fe2+ requirement was specific, and sulfhydryl groups in the purified protein were apparently essential for both ring expansion and hydroxylation . The kinetics and stoichiometry of DAOC/DAC formation from the expandase/hydroxylase-catalyzed reactions suggested that ring expansion of penicillin N preceded hydroxylation of DAOC.

Eur J Clin Microbiol, 1987 Apr, 6(2), 194 - 5
Treatment of abdominothoracic actinomycosis with imipenem; Edelmann M et al.; The probably successful treatment of a 42 year old diabetic patient suffering from relapsing abdominothoracic actinomycosis with imipenem is reported . Several earlier attempts to cure the patient by combination of surgical procedures (including cysto-jejunostomy and pancreatic tail resection) in combination with four or six week courses of intravenously administered penicillin G had failed.

Aust N Z J Med, 1987 Apr, 17(2), 241 - 2
Meningitis due to Branhamella catarrhalis; O'Neill JH et al.; We report a case of Branhamella catarrhalis meningitis which was unusual in that the patient was a healthy immunocompetent adult, the onset was subacute, and the cerebrospinal fluid pleocytosis was predominantly lymphocytic . Following treatment with intravenous penicillin, recovery was complete apart from residual cortical dysarthria.

Ital J Neurol Sci, 1987 Apr, 8(2), 143 - 50
Pentylenetetrazol-induced spike wave discharges in rats: a polygraphic study; Gallitto G et al.; 14 male Wistar rats were studied, before and after pentylenetetrazol (PTZ) 20 mg/kg i.p., since a petit mal-like electroclinical pattern, either spontaneous or PTZ-induced was recently described in a breeding station where this strain is raised . In particular, surface EEG, muscular, respiratory and cardiac activities were recorded in order to detect possible clinical-electroencephalographic correlations . Spontaneous epileptic phenomena were never observed . In all the animals PTZ-induced short, usually generalized and synchronous spike wave discharges often concomitant with rhythmic twitches of the vibrissae . Epileptic bursts were related to arousal level, disappearing during motor behavior and arousing stimuli . Moreover individual discharges could be interrupted by a sudden noise . Photosensitivity was not present . Muscular tone and autonomic functions were not affected . The features of PTZ-induced generalized nonconvulsive seizures in rats are compared to those of cat penicillin epilepsy and human petit mal.

Biull Eksp Biol Med, 1987 Apr, 103(4), 396 - 8
{Anticonvulsive effect of superoxide dismutase}; Kryzhanovskii GN et al.; The influence of superoxide dismutase (SOD) on the development of focal epileptic activity (EpA) in the rat brain cortex has been investigated . Intraperitoneal administration of SOD to rats (1 mg/kg) 30 minutes before penicillin application to the sensorimotor cortex led to marked relaxation of EpA and a decrease in the concentration of lipid peroxidation (LPO) products in EpA focus . The results corroborate our earlier assumption on an important pathogenetic role of LPO disturbances in epileptogenesis and make reasonable the combination of the traditional anticonvulsive therapy with the agents activating the oxidative system.

J Bacteriol, 1987 Apr, 169(4), 1772 - 6
Structural inhibition and reactivation of Escherichia coli septation by elements of the SOS and TER pathways; Dopazo A et al.; The inhibition of cell division caused by induction of the SOS pathway in Escherichia coli structurally blocks septation, as deduced from two sets of results . Potential septation sites active at the time of SOS induction became inactivated, while those initiated during the following doubling time were active . Penicillin resistance increased in wild-type UV light-irradiated cells, a behavior similar to that observed in mutants in which structural blocks were introduced by inactivation of FtsA . Potential septation sites that have been structurally blocked by either the SOS division inhibitor, furazlocillin inhibition of PBP3, or inactivation of a TER pathway component, FtsA3, could be reactivated one doubling time after removal of the inhibitory agent in the presence of an active lon gene product . Reactivation of potential septation sites blocked by the presence of an inactivated FtsA3 was significantly lower when the lon protease was not active, suggesting that Lon plays a role in the removal of inactivated TER pathway products from the blocked potential septation sites.

Endocrinology, 1987 Apr, 120(4), 1576 - 80
gamma-Aminobutyric acid antagonists stimulate vasopressin release from organ-cultured hypothalamo-neurohypophyseal explants; Sladek CD et al.; gamma-Aminobutyric acid (GABA) has been identified in axon terminals innervating neurons of the supraoptic nucleus and has been shown to inhibit the electrical activity of supraoptic neurons when applied iontophoretically . This study examines the effects of GABA and GABA antagonists on vasopressin (VP) release from organ-cultured explants of the hypothalamo-neurohypophyseal system (HNS) . The GABA antagonists bicuculline and picrotoxin stimulated VP release in a concentration-dependent manner . These observations suggest that VP release by HNS explants is tonically inhibited by GABA . Exposure of HNS explants to GABA (10(-8)-10(-3) M) did not consistently alter basal VP release . This was true even when penicillin, which can block GABA-activated chloride channels, was omitted from the medium . Similarly, nipecotic acid, an agent that potentiates GABA activity by inhibiting GABA uptake, did not alter basal VP release; stimulation of VP release by acetylcholine and increases in osmolality was not diminished by the addition of 10(-5) M GABA . The failure of exogenous GABA to modify basal and stimulated VP release suggests that GABAergic inhibition of VP release is maximally activated by endogenously released GABA in cultured HNS explants . This is consistent with evidence for a local source of GABA in the supraoptic nucleus and suggests that one role of GABA in the regulation of VP release is that of a potent local inhibitory neurotransmitter.

Brain Res, 1987 Mar 3, 405(1), 68 - 79
Intracellular recordings in pericruciate neurons during spike and wave discharges of feline generalized penicillin epilepsy; Giaretta D et al.; Concurrent EEG and intracellular recordings from pericruciate neurons of cats obtained before and after i.m . injection of penicillin inducing the syndrome of feline generalized penicillin epilepsy (FGPE) characterized by spike and wave (SW) discharge in the EEG, display large excitatory postsynaptic potentials (EPSPs) at the time of the EEG 'spike' which alternate with hyperpolarizing potentials occurring in coincidence with the EEG 'wave' component of the SW complex . The large EPSPs trigger discharges of single or multiple high-frequency action potentials which do not show a progressive decrement in amplitude nor an appreciable increase in duration . These bursts thus differ in some respects from typical paroxysmal depolarization shifts . The hyperpolarizing potentials show an early phase which is reversed by intracellular Cl- injection or diffusion and thus behaves like a classical inhibitory postsynaptic potential (IPSP) . The late phase is unaffected by Cl- . Hyperpolarizing potentials of pericruciate neurons induced by antidromic activation of the cerebral peduncle (CP) or by direct cortical stimulation are not altered after i.m . injections of penicillin at doses sufficient to induce generalized SW discharge . The early phase of hyperpolarization both before and after i.m . penicillin is reversed by intracellular Cl- injection or diffusion, the late phase remains unchanged . The early phase thus represents a classical IPSP, which does not appear to be affected by the low brain penicillin concentrations sufficient to induce generalized SW discharge . It is concluded that this form of epileptic discharge cannot be attributed to blockage of phasic (presumably somatic) postsynaptic inhibition by penicillin . These results indicate that to regard all forms of epileptic discharge as the consequence of a blockage of gamma-aminobutyric acid-mediated phasic postsynaptic inhibition acting on the soma represents an unduly restrictive view of epileptogenesis.

Biochem Pharmacol, 1987 Mar 1, 36(5), 601 - 8
Drug-protein conjugates--XII . A study of the disposition, irreversible binding and immunogenicity of penicillin in the rat; Kitteringham NR et al.; The disposition, irreversible binding and immunogenicity of benzylpenicillin (BP) were studied in male Wistar rats . {3H}BP, administered i.v . to anaesthetized rats at two doses (27 mumol/kg, 2.7 mmol/kg), showed dose-dependent kinetics: plasma and tissue concentrations of total BP were disproportionately increased at the higher dose . BP was rapidly cleared from the plasma at both doses (less than 0.05% of administered dose/ml plasma after 3 hr) . In spite of the disproportionately elevated levels of total BP after the higher dose, covalent binding to plasma proteins was quantitatively similar as a percentage of the dose at both doses . Three hours after i.v . injection of 27 mumol/kg and 2.7 mmol/kg of the drug, 5.6% +/- 1.7% and 3.3% +/- 1.1% respectively of circulating BP was covalently bound, representing less than 0.004% of the administered dose bound per ml of plasma in each case . Covalent binding of BP to rat plasma proteins in vitro was of a similar magnitude to that observed in vivo: 1.6% +/- 0.4% of BP was bound to 25% rat plasma after 3 hr incubation at 37 degrees . In a separate series of experiments the immunogenicity of BP was studied by chronic administration of the drug to rats . Following daily i.v . or i.m . administration of BP (27 mumol/kg, 270 mumol/kg, 2.7 mmol/kg) for 4 consecutive days at 4-week intervals (three series of injections) neither IgG nor IgM anti-benzylpenicilloyl (BPO) antibodies were detected by enzyme-linked immunosorbent assay (ELISA) . Intravenous administration of the high dose of BP was discontinued after the first series of injections due to local necrosis . In contrast to free BP, BPO-keyhole limpet haemocyanin (BPO-KLH, 42 nmol BP bound/mg KLH) administered by single i.v . injection at 4-week intervals at two doses (20 and 200 micrograms conjugate/kg, corresponding to 0.84 and 8.4 nmol BPO/kg) readily induced IgG and IgM anti-BPO antibody responses (median IgG titres were 872 and 5470 one week after the third injection of the low and high dose of conjugate respectively; corresponding IgM titres were 4513 and 22,866) . The specificity of the IgG and IgM antibodies for the BPO determinant was confirmed by ELISA inhibition with BPO-aminocaproate . These experiments show that BP binds irreversibly, but to a limited extent, to plasma proteins in vivo, and that such a degree of conjugation appears to be insufficient to elicit a detectable anti-BPO antibody response.

J Allergy Clin Immunol, 1987 Mar, 79(3), 523 - 32
Acute and chronic desensitization of penicillin-allergic patients using oral penicillin; Stark BJ et al.; The efficacy, safety and mechanisms of penicillin desensitization were studied in 24 adults and two children with serious infections that required therapy with a beta-lactam drug . Indications for desensitization included debilitating as well as life-endangering infections . Increasing oral doses of phenoxymethyl penicillin were administered at 15-minute intervals to a cumulative dose of 1.3 million units . Parenteral therapy with the beta-lactam drug of choice was instituted at that point . Immunologic complications of desensitization or therapy, ranging from pruritus to serum sickness, occurred in 12 patients . The appearance of gradually worsening wheezing led to abandonment of the procedure in one subject with cystic fibrosis and severe pulmonary disease . The remaining 25 patients were successfully desensitized and received full-dose parenteral therapy . Chronic desensitization was maintained in seven individuals with twice daily oral penicillins for 3 weeks to more than 2 years . No allergic complications of chronic desensitization or recurrent full-dose parenteral therapy were detected . Skin test reactions to one or all penicillin determinants became negative in 11 of 15 patients retested after acute desensitization . Two desensitized patients became skin test negative, remained skin test negative after cessation of desensitization, and tolerated subsequent beta-lactam therapy without allergic reactions or resensitization . The results of this study provide new evidence that acute and chronic penicillin desensitization is useful and an acceptably safe approach and suggest that antigen-specific mast cell desensitization contributes to the protection against anaphylaxis.

Cell Mol Neurobiol, 1987 Mar, 7(1), 97 - 103
Multiple mechanisms of antagonism of gamma-aminobutyric acid (GABA) responses; Akaike N et al.; Gamma-aminobutyric acid (GABA) is one of the most important neurotransmitters in the brain . In an effort to understand the operation of the GABA receptor-ionophore complex, the antagonism of GABA responses by four substances was studied in bullfrog dorsal root ganglion cells by concentration-clamp and internal-perfusion techniques . Two antagonists (bicuculline and Zn2+) were competitive; two (picrotoxin and penicillin) were noncompetitive . However, significant changes in the kinetics of activation and inactivation were produced by the antagonists, including those that were competitive . The causes of these changes may be important clues to the structure and operation of the GABA receptor-ionophore complex.

Acta Paediatr Scand, 1987 Mar, 76(2), 228 - 33
Tick-borne Borrelia-meningitis in children . An outbreak in the Kalmar area during the summer of 1984; Jorbeck HJ et al.; Nine children, aged 5 to 11 years, with subacute or chronic meningitis were studied . Symptoms started during the summer season in all patients and in eight of the patients the disease began with a localized erythematous lesion (ECM), mostly in the face . In one patient only there was a history of an insect bite at the site of the erythema . The neurological abnormalities included aseptic meningitis, peripheral facial nerve palsy (5/9) and oculomotor nerve palsy (1/9) . Most children complained of headache, fatigue, loss of appetite and had a low grade fever . High antibody titers to Borrelia spirochetes in serum and/or cerebrospinal fluid (CSF) were demonstrated by ELISA in eight of the nine patients and by indirect immunofluorescence assay (IFA) in three patients . All patients had a dramatic improvement in their general condition and became afebrile within three days of institution of i.v . penicillin G treatment (i.v . cefuroxime in one patient).

J Pharmacol Exp Ther, 1987 Mar, 240(3), 712 - 6
Drug inhibition of penicillin tubular secretion: concordance between in vitro and clinical findings; Nierenberg DW; Using the rabbit kidney slice model of active tubular secretion, I studied the active accumulation of penicillin (PEN) in the absence and presence of competing drugs to evaluate the feasibility of using in vitro uptake to predict in vivo secretion . Active accumulation of PEN by these slices was saturable at high PEN concentrations and was inhibited by incubation conditions which decreased ATP production . PEN uptake in the presence of 1 mM concentrations of mannitol, tolazoline and tetraethylammonium was unchanged . However, PEN uptake in the presence of eight weak organic acid drugs (probenecid, phenylbutazone, sulfinpyrazone, salicylate, sulfamethizole, chlorothiazide, sulfamethoxypyridazine and indomethacin) was inhibited significantly . This inhibition appeared to be competitive in nature and the inhibitor-transport carrier protein dissociation constant (Ki) for each inhibitory drug was calculated (range, 0.38-74.8 X 10(-5) M) . When these values for Ki obtained with PEN were compared to values obtained with methotrexate and p- aminohippurate, the values of Ki were similar, implying the presence of a similar transport carrier protein for PEN, methotrexate and p-aminohippurate . The effects of these eight drugs upon PEN clearance in vivo were extrapolated from the medical literature . The relative inhibitory strengths of these drugs based upon in vitro findings (drug plasma concentration/Ki ratios) and clinical findings (inhibition of PEN clearance) were concordant . This in vitro model for assessing inhibition of renal tubular secretion may be of general utility in predicting clinically important drug interactions between weak organic acid drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Fertil Steril, 1987 Mar, 47(3), 527 - 30
Importance of semen preparation in avoidance of reduced in vitro fertilization results attributable to bacteria; Forman R et al.; Although the physical treatment of semen for IVF and related procedures is sufficient to remove most organisms present in semen, the pathogenic varieties tend to be more resistant . The supplementation of oocyte culture medium with both penicillin and streptomycin was associated with the eradication of 100% of organisms in the current study . In these circumstances, the presence of pathogenic organisms in the untreated semen is not associated with reduced oocyte fertilization in vitro.

Act Nerv Super (Praha), 1987 Mar, 29(1), 36 - 44
Influence of clonazepam on cortical epileptogenic foci in the rat; Mares P et al.; The antiepileptic action of clonazepam was studied on epileptogenic foci induced by penicillin in sensorimotor cortex in acute experiments in rats . Clonazepam (1 mg/kg intraperitoneally) only moderately decreased the frequency of interictal discharges of single cortical focus and delayed the propagation of discharges into the ipsilateral occipital region . On the contrary, clonazepam failed to influence the callosal projection of interictal discharges in single unilateral as well as in two symmetrical foci . Spontaneous transition of interictal discharges into ictal phases regularly seen when two symmetrical foci were formed was only delayed but not blocked by clonazepam . It may be concluded that clonazepam exhibits only a weak anticonvulsant action against cortical foci and against secondary generalization of epileptic activity.

J Clin Neuroophthalmol, 1987 Mar, 7(1), 11 - 9
Syphilis in 1986; Poitevin M et al.; Symptoms of syphilis have evolved over the ages . In the 16th century, they were essentially cutaneomucous ones . While the intensity of the symptoms decreased localization of the infection in the various organs--mainly those of the cardiovascular and nervous system--gradually appeared . Over a period of years following the introduction of penicillin therapy, the cutaneous and visceral stages became less common . Reminder of the chief serological reactions and of some aspects of the experimental syphilis in the rabbit, similar to certain forms of human syphilis--a strong but late penicillin therapy has been proven ineffective in humans as well as in animals . It is to be regretted that numerous methods of using penicillin (all over the world), had been, from the beginning--except in a few cases--of a purely empirical nature . The authors emphasize--with proof to support their opinion--the failure of antibiotic therapy, which can explain the recent reappearance of hepatic and nervous localizations that had disappeared for 30 years . Despite views to the contrary the authors conclude that penicillin has in no way resolved all the problems raised by the treatment of syphilis.

Ann Trop Paediatr, 1987 Mar, 7(1), 54 - 8
Rheumatic heart disease in Nigerian children: clinical and preventive aspects; Fadahunsi HO et al.; Ninety-two children with rheumatic heart disease were studied clinically, and through a post-diagnosis surveillance period of varying duration over a 10-year period . The logistics and effectiveness of secondary penicillin prophylaxis, administered monthly, were assessed during the surveillance period . Eighty-one (88%) of the 92 children were seen for the first time with already established rheumatic heart disease . Mitral insufficiency was the major functional defect in these children whose mean age was 8.6 years . There was a high default rate of just under 50% among children referred to the surveillance clinic . Socio-economic inadequacies were found to be major factors in the high default rate . Regular monthly parenteral penicillin was found to be effective in reducing recurrence of rheumatic fever and maintaining good health in these children.

Brain Res, 1987 Feb 10, 403(1), 162 - 6
'Slow' field potentials in penicillin-perfused hippocampal slices; Schneiderman JH; Slow field potentials (SFP) lasting up to 5 s followed penicillin-induced bursts in CA3 of guinea pig hippocampal slices and accounted for most of the interburst interval . The longest lasting component of the SFP which was maximal in the distal apical dendritic region was usually absent in s . pyramidale . Potassium flux underlies the entire potential, however, chloride-mediated components also contribute to the initial portion (approximately 1 s) . The SFP was associated with neuronal afterhyperpolarization and glial cell depolarization, however, no unique cellular events could be identified with the 3 peaks of the SFP . The complex waveform of the SFP is probably the result of summation of neuronal and glial components.

Eur J Biochem, 1987 Feb 2, 162(3), 509 - 18
Primary structure of the Streptomyces R61 extracellular DD-peptidase . 1 . Cloning into Streptomyces lividans and nucleotide sequence of the gene; Duez C et al.; An 11,450-base DNA fragment containing the gene for the extracellular active-site serine DD-peptidase of Streptomyces R61 was cloned in Streptomyces lividans using the high-copy-number plasmid pIJ702 as vector . Amplified expression of the excreted enzyme was observed . Producing clones were identified with the help of a specific antiserum directed against the pure DD-peptidase . The coding sequence of the gene was then located by hybridization with a specific nucleotide probe and sub-fragments were obtained from which the nucleotide sequence of the structural gene and the putative promoter and terminator regions were determined . The sequence suggests that the gene codes for a 406-amino-acid protein precursor . When compared with the excreted, mature DD-peptidase, this precursor possesses a cleavable 31-amino-acid N-terminal extension which has the characteristics of a signal peptide, and a cleavable 26-amino-acid C-terminal extension . On the basis of the data of Joris et al . (following paper in this journal), the open reading frame coding for the synthesis of the DD-peptidase was established . Comparison of the primary structure of the Streptomyces R61 DD-peptidase with those of several active-site serine beta-lactamases and penicillin-binding proteins of Escherichia coli shows homology in those sequences that comprise the active-site serine residue . When the comparison is broadened to the complete amino acid sequences, significant homology is observed only for the pair Streptomyces R61 DD-peptidase/Escherichia coli ampC beta-lactamase (class C) . Since the Streptomyces R61 DD-peptidase and beta-lactamases of class A have very similar three-dimensional structures {Kelly et al . (1986) Science (Wash . DC) 231, 1429-1431; Samraoui et al . (1986) Nature (Lond.) 320, 378-380}, it is concluded that these tertiary features are probably also shared by the beta-lactamases of class C, i.e . that the Streptomyces R61 DD-peptidase and the beta-lactamases of classes A and C are related in an evolutionary sense.

Am J Kidney Dis, 1987 Feb, 9(2), 176 - 9
Renal disease and syphilis: a report of nephrotic syndrome with minimal change disease; Krane NK et al.; A case of nephrotic syndrome and acute renal failure in a 74-year-old man with latent syphilis is described . A renal biopsy demonstrated focal global sclerosis in three of nine glomeruli, however, the remaining glomeruli revealed typical lesions of minimal change disease . Previous reports of renal involvement in syphilis have described membranous glomerulonephritis, mesangial and endothelial cell proliferative glomerulonephritis, and, recently, rapidly progressive glomerulonephritis . The proteinuria and renal failure resolved after penicillin therapy alone . This response strongly suggested that there was a causal relationship between the syphilis and the nephrotic syndrome . This is the first report of such a relationship.

J Pediatr, 1987 Feb, 110(2), 299 - 302
Serum concentrations of penicillin after intramuscular administration of procaine, benzyl, and benethamine penicillin in children with pneumonia; Shann F et al.; Serum concentrations of penicillin were measured in 37 children with pneumonia . The mean serum concentration of penicillin was greater than 1.0 microgram/mL for 11 hours after intramuscular administration of 48,000 U/kg benethamine penicillin compound (nine children), for 26 hours after 48,000 U/kg aqueous procaine penicillin (10 children), and for 40 hours after 79,000 U/kg aqueous procaine penicillin (seven children) . After intramuscular administration of 35,000 U/kg benzyl penicillin in 11 children, the serum concentration was 13.3 +/- 7.4 micrograms/mL (mean +/- SD) 30 minutes after the injection, and 4.9 +/- 3.2 micrograms/mL after 3 hours . Our findings lend support to the World Health Organization recommendation that children with mild pneumonia in developing countries be given daily intramuscular injections of 50,000 U/kg aqueous procaine penicillin.

Clin Immunol Immunopathol, 1987 Feb, 42(2), 211 - 7
Effect of Fluosol DA 20% on antibody response to type 3 pneumococcal polysaccharide in rats; Molina NC et al.; Exchange transfusion with the oxygen-carrying resuscitation fluid, Fluosol DA 20% (FDA), interferes with the efficacy of penicillin therapy of pneumococcal infection in rats . Because this effect could not be attributed to an interaction between FDA and penicillin, the effect of FDA on the ability of rats to mount an antibody response to type 3 pneumococcal polysaccharide was tested . FDA (25 ml) was administered by isovolumetric exchange transfusion . Rats were immunized intravenously with 0.2 microgram of type 3 pneumococcal polysaccharide 3 days before, 1 day before, 1 day after, or 3 days after transfusion with FDA . IgM and IgG antibody responses were determined by ELISA 0, 3, 7, 10, 14, 21, and 28 days after immunization . When rats were immunized 3 days before or 1 day before transfusion with FDA, antibody levels were increased above control levels and remained relatively high through Day 28 . When the animals were immunized 1 day after transfusion, antibody levels were approximately the same as in the control group . When the rats were immunized 3 days after transfusion, antibody levels were suppressed . These data suggest that FDA does not inhibit the humoral immune response when administered after or within 1 day before immunization, but does inhibit the response when immunization is given 3 days after transfusion.

Biochem J, 1987 Feb 1, 241(3), 893 - 7
Effects of thiol reagents on Streptomyces K15 DD-peptidase-catalysed reactions; Leyh-Bouille M et al.; The 26,000-Mr DD-peptidase of Streptomyces K15 binds one equivalent of thiol reagents as 5,5'-dithiobis-(2-nitrobenzoate) or p-chloromercuribenzoate (pCMB) . Derivatization of the DD-peptidase by pCMB decreases the efficacy of the initial binding of the ester carbonyl donor Ac2-L-Lys-D-Ala-D-lactate to the enzyme (K), the rate of enzyme acylation by the donor (K+2) and the rate of enzyme deacylation (k+3) . However, the value of the k+2/k+3 ratio, and therefore the percentage of total enzyme which, at saturating concentrations of the donor, is present as acyl-enzyme at the steady state of the reaction, are not modified . The enzyme's binding sites for pCMB and benzylpenicillin are not mutually exclusive . But, when compared with the native enzyme, the pCMB-derivatized enzyme undergoes acylation by benzylpenicillin with a decreased second-order-rate constant (k+2/K) value and gives rise to a penicilloyl adduct of increased stability . Since the acyl-enzyme mechanism is not annihilated by pCMB derivatization, it is proposed that basically, and like all the other DD-peptidases/penicillin-binding proteins so far characterized, the Streptomyces K15 DD-peptidase is an active-site-serine enzyme.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1987 Feb, 263(3), 365 - 71
Acute and chronic illness after tick-bite Borrelia burgdorferi-infections: results of treatment; Kohlhepp W et al.; We report on clinical and laboratory findings of 28 patients with tick-bite Borrelia burgdorferi-infection . In 5 cases chronic tertiary metaluetic manifestations were recognized . All were treated either with high-dose penicillin intravenously or tetracycline . Results of treatment and recommendations are given.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1987 Feb, 263(3), 357 - 64
High-dose penicillin therapy in meningopolyneuritis Garin-Bujadoux-Bannwarth . Clinical and cerebrospinal fluid data; Kristoferitsch W et al.; Clinical data of 19 patients with meningopolyneuritis Garin-Bujadoux-Bannwarth (MPN-GBB), treated with 2 X 10 million units intravenous sodium penicillin for 10 days, were evaluated at the beginning of therapy, 3 weeks thereafter, and 6 months after onset of the neurological disease . Cerebrospinal fluid (CSF) was analysed in 14 patients at the onset of therapy and 3 1/2 weeks thereafter . At the same interval antibodies against B . burgdorferi were measured by enzyme-linked immunosorbent assay (ELISA) in the CSF and sera of 12 patients . Clinical data and all CSF results, with exception of specific antibody titers, were compared with those of patients who had suffered from MPN-GBB between 1979 and 1983, and who had not received antibiotic or corticosteroid therapy . Comparing the clinical data of all treated patients with those of all non-treated controls, no significant difference could be observed . A significant improvement could however be detected in those patients who had their treatment begun 5 weeks within onset of the neurological disease . Changes in CSF 3 1/2 weeks after onset of treatment showed slight differences when compared with controls.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1987 Feb, 263(3), 348 - 50
Borrelia meningitis in Denmark; Hansen K et al.; We studied 23 patients with borrelia meningitis, a tick-borne spirochetosis increasingly recognized in Denmark . The disease showed a seasonal incidence from June to December . Twenty one patients experienced a painful sensory radiculitis, in 17 cases followed by a predominantly cranial mononeuritis multiplex mainly affecting the facial nerve (Bannwarth's syndrome) . Three patients had focal CNS involvement in the form of a transverse myelitis, a focal encephalitis and a disseminated leucoencephalopathy, respectively . The CSF showed invariably lymphocytic pleocytosis and elevated spinal protein concentration . Measuring borrelia antibodies in the CSF seemed of higher diagnostic sensitivity than in serum . Penicillin therapy was effective even in cases with focal CNS lesions.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1987 Feb, 263(3), 328 - 33
Involvement of Borrelia burgdorferi in cranial nerve affection; Schmutzhard E et al.; From January 1984 to August 1985 54 patients presented with cranial nerve lesions at the neurological department of the University hospital Innsbruck . Median age was 42 years, range 5-81 years . Female male ratio was 49/15 . In 17 patients cranial neuritis was consistent with meningopolyneuritis Bannwarth (MPN) in 37 cases mere facial palsy was present . Cranial neuritis in MPN-patients affected N . facilis in 10, N . opticus and N . oculo-motorius in one case each . Five patients had polyneuritis cranialis with affection of the cranial nerves II, V, VI, VII, VIII, and IX (Table 1) . IgG-antibodies to B . burgdorferi were found in the sera of all MPN patients and in 15 of cases with mere facial palsy . Patients with antibodies to B . burgdorferi were treated with intravenous penicillin and latamoxef dinatrium . The remaining 22 patients were treated with vitamin B compound and corticosteroids . The time for full recovery was 4 weeks on the average in each treatment group.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1987 Feb, 263(3), 289 - 96
Clinical manifestations of Borrelia infections of the nervous system; Stiernstedt G et al.; Clinical, treatment and laboratory parameters were analyzed in 46 consecutive Swedish patients with Borrelia infections of the nervous system . The importance of age in the clinical symptoms, the wide spectrum of disease, and the chronic behaviour of the Borrelia infection of the nervous system was stressed, as well as the benefit of high-dose intravenous antibiotics, especially penicillin G . Borrelia infection of the nervous system can imitate other diseases . When associated with meningitis it can mimic psychosomatic disorders, when associated with radiculoneuritis it may imitate herniated discs and when central nervous involvement of the Borrelia infection occurs, it can mimic a non-infectious, thrombotic or haemorrhagic cerebro-vascular disease.

Rev Rhum Mal Osteoartic, 1987 Feb, 54(2), 97 - 103
{Lyme arthritis}; Caroit M; Infection by spirochete Borrelia burgdorferi is mainly observed in the United States where it has taken the name of Lyme's disease, and in Europe . Its evolution may be very extended, in several phases . A few weeks after a tick-bite, the primary lesion appears, which is a chronic migrating erythema . In the following weeks or months, in the secondary phase, nerve lesions may appear, quite similar in Europe and in the United States, and cardiac lesions, mostly seen in the United States . In the following weeks, months, or years, during the tertiary phase, articular lesions may appear, frequent in the United States, much more unusual in Europe . Several years later, chronic lesions of the central nervous system may appear, described in the United States, and chronic skin lesions such as chronic atrophying acrodermatitis sometimes associated with destructive lesions of the joints underlying the skin lesion, which are only recognized in Europe . The discovery of the spirochete in a small number of these lesions, including the latest in the evolution, permits to think that, throughout this evolution, this disease is secondary to the persistence of the germ within the body; this explains the efficacy of the penicillin treatment, including in the oldest forms of the disease . Serology is quite reliable; but it becomes positive only 2 to 4 weeks after the onset of the chronic migrating erythema: needless to say the importance of this single cutaneous lesion which enables to make the diagnosis and requires the use of a tetracycline or penicillin treatment.

Antimicrob Agents Chemother, 1987 Feb, 31(2), 187 - 90
Roxithromycin (RU 965): effective therapy for experimental syphilis infection in rabbits; Lukehart SA et al.; Roxithromycin (RU 965), a new macrolide antibiotic, was shown to be effective for therapy of active syphilis in rabbits . Dark-field-positive lesions were produced in adult male rabbits by intradermal inoculation of approximately 10(6) Treponema pallidum organisms at each of 11 sites . Beginning 7 days after infection, six animals per group were treated with benzathine penicillin G (200,000 U, intramuscularly, weekly for 2 weeks) or roxithromycin (15 mg/kg of body weight, orally, twice daily for 15 days); six animals were not treated . Chancres in untreated animals were dark-field positive throughout the 16-day observation period; all benzathine penicillin-treated rabbits were dark-field negative 1 day after the initiation of therapy . Five of six animals treated with roxithromycin were dark-field negative on day 3 following the initiation of therapy; the sixth animal was dark-field negative by day 6 . Lesions in untreated animals reached a mean (+/- standard deviation) maximum diameter of 14.7 +/- 1.91 mm compared with 8.4 +/- 3.6 mm for benzathine penicillin-treated (P less than 0.005) and 10.4 +/- 1.2 mm for roxithromycin-treated (P less than 0.001) animals . Ulceration occurred at 62 of 66 lesions in untreated animals compared with 0 of 66 lesions in each treated group . At 3, 6, and 12 weeks postinfection, Venereal Disease Research Laboratory antibody titers were significantly higher (P less than 0.05) in untreated than in treated animals . Titers in penicillin-treated versus roxithromycin-treated animals were significantly different at 6 weeks postinfection but not at 3 and 12 weeks postinfection . Transfer of tissue from treated rabbits to seronegative recipient animals did not reveal any evidence of persistent infection in the benzathine penicillin- or roxithromycin-treated animals . These findings indicate that benzathine penicillin and roxithromycin, at the doses indicated above, are effective in treating active syphilis in rabbit model.

Obstet Gynecol, 1987 Feb, 69(2), 251 - 4
Prophylactic mezlocillin in radical hysterectomy; Micha JP et al.; The role of prophylactic antibiotics in radical hysterectomy patients was studied in a double-blind randomized prospective study of mezlocillin (Mezlin, Miles Pharmaceuticals), a broad-spectrum semisynthetic penicillin, compared to placebo . Thirty evaluable patients received 4 g mezlocillin or saline placebo intravenously one-half hour before surgery, a second dose four to six hours later, and a final dose six hours after that . The rate of wound infection, postoperative use of additional antibiotics, fever index, and the incidence of standard febrile morbidity were all significantly lower in the mezlocillin group . Short-term perioperative prophylactic antibiotics are indicated in patients undergoing radical hysterectomy.

J Bacteriol, 1987 Feb, 169(2), 891 - 3
Conversion of the alpha component of penicillin-binding protein 1b to the beta component in Escherichia coli; Suzuki H et al.; Among components alpha, beta, and gamma of penicillin-binding protein 1b, the alpha and gamma components were confirmed to represent the primary gene products by agreement of their N-terminal amino acid sequences with those predicted from the nucleotide sequence of the ponB (penicillin-binding protein 1b) gene with exclusion of the first methionine in each component . The generation of beta occurred primarily after cell disruption, and the simultaneous loss of alpha suggested the conversion of alpha to beta . The N-terminal amino acid sequence analyzed for beta showed that the conversion was due to the removal of 24 amino acids from the N terminus of alpha.

Clin Otolaryngol, 1987 Feb, 12(1), 1 - 5
Peritonsillar abscess with parapharyngeal involvement: incidence and treatment; Stage J et al.; In 2.3% of 217 patients with peritonsillar abscess, the clinical picture was atypical, with inflammatory swelling of the pharyngeal wall below and behind the tonsil, oedema of the epiglottis and a diffuse swelling on the side of the neck . The typical signs of peritonsillar abscess, i.e . trismus, a medially displaced tonsil and displacement of the uvula toward the opposite side, were either completely lacking or less pronounced than usual . The abscesses were all located in the peritonsillar space at the lower pole or behind the tonsil . To ensure rapid, uncomplicated recovery in such cases with parapharyngeal involvement, it is essential that abscess tonsillectomy under antibiotic cover with penicillin is not postponed.

J Gen Microbiol, 1987 Feb, 133 ( Pt 2), 361 - 7
Glucose and penicillin concentrations in agar medium below fungal colonies; Robson GD et al.; The growth of colonies of Rhizoctonia cerealis and Penicillium chrysogenum on solid media in plate cultures was studied . When grown on defined media containing 10-50 mM-glucose, R . cerealis did not cause a significant reduction in the glucose concentration of the medium in advance of colonization, but did cause the formation of a steep glucose concentration gradient in the substrate below the colony; the medium directly below the centre of a 7 cm diameter colony of R . cerealis was exhausted of glucose even when the fungus was grown on medium containing 50 mM-glucose . Penicillin produced by colonies of P . chrysogenum accumulated in the medium in advance of fungal colonization . For a period up to about 18 d after inoculation, the concentration of penicillin in the medium throughout the plate increased with colony development and thereafter, except at the margins of the plate, decreased.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1987 Feb, 263(3), 372 - 6
Treatment and course of erythema chronicum migrans; Neumann R et al.; 72 patients with Erythema chronicum migrans were treated with phenoxymethyl penicillin, 1,5 mill . IU p.o . three times a day for 14 days . Two children got the same therapy, but in a dosage of 400,000 IU three times a day for 10 days . In three of 15 skin samples, taken from the periphery of ECM lesions, spirochetal organisms were isolated . Of the 72 patients 16 had raised IgG (greater than or equal to 128) and 9 had raised IgM (greater than or equal to 64) titers to Borrelia burgdorferi . Under treatment with phenoxymethyl penicillin (penicillin V) all ECM lesions resolved within 6 to 10 days . After an observation period of 9 to 14 months no major or minor late manifestations of Lyme disease have developed in any of the 72 patients.

J Chromatogr, 1987 Jan 16, 386, 79 - 86
Comparison of bonded, polymeric and silica columns for chromatography of some penicillins; Moats WA et al.; The retention of ampicillin, amoxicillin, and penicillin G was determined on ODS and cyanopropyl (CN)-bonded to silica, on an all-organic polymeric reversed-phase column (styrene-divinylbenzene) and on bare silica . Solvents tested were 0.01 M H3PO4 (pH 1.6)-acetonitrile and 0.002 M KH2PO4 (pH 4.6)-acetonitrile in the proportions 100:0 to 10:90 . Retention with 0.002 M KH2PO4 was weaker than with 0.01 M H3PO4 at all proportions of acetonitrile on all packings . With 0.01 M H3PO4, retention of penicillins on the polymeric column decreased rapidly from 100 to 50% aqueous phase and remained low to 10% aqueous phase . On the ODS bonded column, retention was similar, except that retention of the aminopenicillins, amoxicillin and ampicillin increased at less than 30% aqueous phase . On the CN-bonded column, results were similar to those on the ODS column, except that the aminopenicillins were less strongly retained when using 100% 0.01 M H3PO4 . On the bare silica, penicillin G was poorly retained at all proportions of acetonitrile, while retention of aminopenicillins increased rapidly at less than 50% 0.01 M H3PO4 . Retention of aminopenicillins at less than 50% 0.01 M H3PO4 was parallel on bonded and bare silica but weaker on the bonded silica . A bonded organic layer weakened but did not prevent binding of amines to silica.

Brain Res, 1987 Jan 6, 400(2), 371 - 6
Carbamazepine suppresses synchronized afterdischarging in disinhibited immature rat hippocampus in vitro; Smith KL et al.; Bath application of therapeutic concentrations of the anticonvulsant carbamazepine suppressed penicillin-induced synchronized afterdischarging in immature rat CA3 hippocampal pyramidal cells . Afterdischarging was completely abolished in all preparations at a concentration of 30 microM (IC50 = 8.5 +/- 1.4 microM; mean +/- S.E.M.) . The duration of the preceding epileptiform burst was not altered at this concentration and was diminished by only 24.4 +/- 1.2% at a supratherapeutic concentration of 100 microM . These results suggest that a carbamazepine-sensitive neurophysiological mechanism distinct from those responsible for epileptiform burst generation plays a key role in the generation of afterdischarges in developing hippocampus.

J Neurol, 1987 Jan, 234(1), 40 - 3
Chronic progressive neurological involvement in Borrelia burgdorferi infection; Weder B et al.; Five patients with chronic meningitis were hospitalized several times for progressive neurological symptoms . The clinical manifestations included cranial neuritis, radiculoneuritis, myelitis and encephalitis . In two cases cerebral infarction occurred . The course was commonly characterized by a tendency to deteriorate . From the clinical point of view, it was repeatedly difficult to exclude multiple sclerosis or tuberculous meningitis . Finally, specific antibodies against Borrelia burgdorferi were detected by indirect immunofluorescence assay . The diagnosis of a borreliosis was not considered initially because there was no history of tick-bite or erythema chronicum migrans, and the neurological involvement of the central nervous system seemed unusual . The latency between the first symptoms and diagnosis varied from 3 months to 5 years . After a parenteral, high-dose therapy with penicillin, there was a significant improvement in all patients . In two cases, there was evidence of intrathecally produced antibodies to myelin basic protein.

Clin Cardiol, 1987 Jan, 10(1), 44 - 7
Acute myocardial infarction during streptokinase therapy; Horn EM et al.; A 45-year-old man developed sequential inferolateral and anterior myocardial infarctions within 10 hours of a possible allergic reaction to oral penicillin . The anterior myocardial infarction occurred during apparently successful streptokinase therapy for the initial inferolateral infarction . Subsequent coronary arteriography confirmed a subtotal stenosis of the left circumflex coronary artery and a complete thrombotic occlusion of the left anterior descending artery . This case documents the occurrence of three rare clinical phenomena; first, the occurrence of sequential acute myocardial infarctions in close temporal proximity; second, the occurrence of myocardial infarction during thrombolytic therapy; and third, the association of myocardial infarction with a possible allergic reaction.

J Bone Joint Surg Am, 1987 Jan, 69(1), 96 - 9
Lyme arthritis in children . An orthopaedic perspective; Culp RW et al.; The cases of forty-three children with clinical and serological evidence of Lyme arthritis that was diagnosed between August 1983 and July 1985 were evaluated . The mean length of follow-up was twenty months, with a range of five to thirty months . All of the children lived in or had visited an area where the disease was known to be endemic . Arthritis was the presenting feature in more than half of the children, and half of the children had initially consulted an orthopaedic surgeon, none of whom made the correct diagnosis . Only twenty patients had a history of erythema chronicum migrans, the characteristic rash that precedes the arthritis, and for only nineteen children was there any recollection of having been bitten by a tick . Three patients had Bell palsy and one had a popliteal cyst in conjunction with the arthritis . All of the patients had oligoarticular involvement . The knee was involved in all but two patients . Recurrent attacks of synovitis were common . Effusion was the only radiographic abnormality that was observed, and it was found in thirty-two patients . The sedimentation rate was elevated in thirty of thirty-six patients . Immunofluorescent serology for Lyme disease, which is sensitive and specific, was uniformly positive . Of thirty-three patients who were treated with oral administration of penicillin or tetracycline alone, thirty-one responded, while two patients who had recurrent attacks of the disease responded to parenteral administration of antibiotics . The remaining ten patients responded to combinations of orally and parenterally administered antibiotics . Longer follow-up is needed to further document the apparently low rate of relapse after antibiotic therapy in this young population.

Pharmacotherapy, 1987, 7(4), 125 - 9
Increased frequency of doxycycline side effects; Bryant SG et al.; As part of a study investigating new methods of detecting adverse drug reactions, adult outpatients receiving new prescriptions for 1 of 4 antibiotics (doxycycline, penicillin VK, ampicillin, or tetracycline) were assigned to 1 of 2 methods of monitoring adverse drug reactions . Data were collected from a total of 457 staff-initiated interviews and from 1467 patients who were asked to telephone to report possible adverse effects . Doxycycline is considered by authoritative sources to be generally comparable in side effects to other tetracyclines and penicillins, with the exception that it increases photosensitivity . Results from both monitoring methods consistently indicated at least a 3-fold higher frequency of nausea or vomiting with doxycycline relative to the other antibiotics . Complaints of skin rash also were at least 4 times more frequent with doxycycline, depending on the particular sample.

Urol Int, 1987, 42(4), 313 - 5
Severe thrombocytopenia due to apalcillin; Lee M et al.; Whereas impaired platelet aggregation is a well-known complication of penicillin usage, thrombocytopenia rarely occurs . We present the first case of apalcillin-induced thrombocytopenia and review the literature about this uncommon adverse effect of penicillins.

Physiol Behav, 1987, 40(5), 617 - 24
Epileptogenesis is associated with heightened arousal responses in fish; Laming PR et al.; Intramuscular injection of sodium penicillin in roach (Rutilus rutilus) caused delayed habituation of arousal responses to repeated presentation of the onset of illumination or of a 'tap' stimulus . Topical application of aluminum hydroxide to the telencephalon of roach had a similar effect but was shown, also, to induce electroencephalographic seizures, in which the EEG amplitude was elevated from 4-20 times its normal level . Both treatments caused intermittent, abnormal 'weaving' behaviour and sporadic, violent, uncoordinated motor activity . In goldfish, Carassius auratus, topical application of aluminum hydroxide also caused delayed habituation of quantitatively measured, cardiac arousal responses to a moving shadow stimulus, compared to controls . This delayed habituation was, however, largely a result of the elevated magnitude of these arousal responses . The results are discussed in relation to brain mechanisms normally operative during arousal which may be hyperactive in epilepsy.

Chemotherapy, 1987, 33(5), 376 - 80
Ceftriaxone given repeatedly cures manifest syphilis in the rabbit; Korting HC et al.; Repeated intramuscular injection of ceftriaxone to rabbits with manifest syphilitic orchitis leads to clinical cure as does penicillin, given the serum levels reached are similar to the ones obtained clinically in man . Totally different to untreated controls the Treponema pallidum hemagglutination (TPHA) titers remain relatively low and later even tend to decrease further . Thus, it seems justified to start clinical trials on the definite role of ceftriaxone in the treatment of clinical syphilis.

Scand J Infect Dis, 1987, 19(2), 257 - 60
The effect of heat upon the interaction between aminoglycosides and semi-synthetic penicillins in human serum: a consideration for HIV infectious serum; Pohlod DJ et al.; We conducted 2 experiments to study the effect of heat on the interaction between aminoglycosides and semi-synthetic penicillins in human serum . In one experiment, human serum spiked with either gentamicin or tobramycin at a concentration of 4.7 mg/l plus carbenicillin, ticarcillin, piperacillin, mezlocillin, or azlocillin at concentrations of either 50 mg/l or 150 mg/l was subjected to a 30-min, 56 degrees C waterbath incubation . In the second experiment, randomly selected sera from patients receiving either gentamicin or tobramycin were also heat-treated . Two methods, the Abbott TDx and the Syva Emit, were used for each aminoglycoside assay . The difference between pre- and post-heat treatment aminoglycoside concentration was less than 10% in approximately 92% of the patient sera and in 93% of the spiked sera containing an aminoglycoside plus a semi-synthetic penicillin at 50 mg/l . For sera spiked with an aminoglycoside plus a semi-synthetic penicillin at 150 mg/l, post-heat treatment concentrations were 5-19% lower than pre-heat treatment concentrations . In most instances, heat treatment of sera does not alter aminoglycoside concentrations to any clinically significant degree.

Nephron, 1987, 46(3), 263 - 7
Infection-resistant continuous peritoneal dialysis catheters; Trooskin SZ et al.; The techniques of bonding of anionic antibiotics by treatment with cationic surfactants were applied to continuous ambulatory peritoneal dialysis (CAPD) catheters . The elution of 14C-penicillin from tridodecylmethylammonium chloride (TDMAC) treated silicone elastomer catheters in dialysis solution was biphasic, with 95% dissociated from the catheter by 48 h . Forty percent of the TDMAC left the catheter surface during the initial 2 days . The ability of the surfactant TDMAC to bind antibiotics after incubation in dialysis solution correlated directly with the amount of surfactant remaining . Rats with intraperitoneal dialysis catheters were inoculated with exit site and intraluminal bacterial challenges . Intraperitoneal catheter tips treated with TDMAC-penicillin were rendered more resistant to colonization after exit site and intraluminal bacterial challenges.

Allergol Immunopathol (Madr), 1987 Jan-Feb, 15(1), 1 - 5
Status of patch and other skin tests in diagnosis of systemic penicillin allergy; Patriarca G et al.; It is generally accepted that cell-mediated immunity is responsible for contact dermatitis, but controversy still exists about the involvement of Type IV immune-reactions in other clinical manifestations following inhalant, oral and parenteral administration of penicillin and semi-synthetic penicillin or cephalosporins . The aim of the present study was to contribute to a better understanding of the pathogenetic mechanism responsible for these reactions . Detailed history taking, clinical and immuno-allergological investigation on 161 patients with a history of an allergic reaction to penicillin and/or semisynthetic penicillins and/or cephalosporins was carried out with the following tests: skin tests, patch tests, RAST, PRIST and lymphocyte transformation test . The statistical evaluation of data was performed by X2 test . Comparative studies were focused on groups of patients who presented a positive reaction to patch test (37) skin test (scratch and intradermal) (42), simultaneous skin and patch test (5) and negative skin test (87) . No significant difference was observed among the groups studied, although in positive and skin test, a higher frequency is observed to be associated with anaphylactic shock and eczematous type of reaction . It is not possible however not only, to establish whether this is due to a combined immune-reaction (Type I and IV), orto a causal coexistence of the two mechanisms but even to determine either of allergic or pseudoallergic phenomenon without any accurate immunoallergological test . It is suggested that patch tests be carried out as routine investigations on patients with a systematic reaction to penicillins and/or cephalosporins, regardless of the route of administration.

Trop Geogr Med, 1987 Jan, 39(1), 92 - 3
Fatal-Jarisch Herxheimer reaction in a case of relapsing fever misdiagnosed as lobar pneumonia; Melkert PW; A fatal Jarisch-Herxheimer reaction developed after treatment with high doses of penicillin in a case of lobar pneumonia caused by Borrelia duttoni . Penicillin given on the first day and tetracycline on subsequent days to avoid severe Jarisch-Herxheimer reactions, has the disadvantage of a longer period of spirochetemia and hypotension as compared with tetracycline on the first day . Treatment may have contributed to the death of this patient.

Dev Biol Stand, 1987, 66, 23 - 8
The use of doxycycline, mezlocillin and clotrimazole in cell culture media as contamination prophylaxis; Hovel H et al.; The antibiotics Doxycycline (Vibramycin) and Mezlocillin (Baypen) have been compared with the commonly used bacteriostatic substance Neomycin, Streptomycin and Penicillin (NSP), and the broad-spectrum antifungal agent Clotrimazole (Canesten) has been tested in relation to the antimycotic Nystatin (Moronal) in different mammalian cell cultures for cytotoxicity and its influence of increasing concentration in the media on the growth of diploid and heteroploid cell population over several subcultures . Numerous experiments over the last years showed that small amounts of the tested substances were effective against contamination without noteworthy inhibition of cell growth . As suitable levels for the tested antibiotics we would recommend: Doxycycline at 1-2 micrograms/ml (2-5 micrograms/ml), Mezlocillin at 100-200 micrograms/ml (200-1000 micrograms/ml) and Clotrimazole at 0.5-1 microgram/ml (1-2 micrograms/ml) medium for diploid, fibroblastlike cell strains (for continuous epithelial-like cells.

Pharmacol Res Commun, 1987 Jan, 19(1), 59 - 68
Comparison of the effect of althesin with diazepam and thiopental sodium on cortical and subcortical epileptic activity in the rat; De Riu PL et al.; Althesin antiparoxysmal effect was comparatively studied with diazepam and thiopental sodium on penicillin induced cortical epileptic focus and on mesencephalic reticular unitary activity triggered by cortical spikes . Althesin was shown to abolish both cortical and subcortical epileptic activity, while diazepam was able to suppress the paroxysmal unitary activity evoked from the cortical spikes at the level of the reticular mesencephalic formation, but was ineffective on focal paroxysm . Thiopental sodium exhibited behaviour similar to Althesin, but its action was weak and short lasting at both levels . A comparative study showed that Althesin had, at cortical and subcortical level, a more drastic and longer antiparoxysmal effect than the other two drugs tested . Althesin would seem to exert a potent antiepileptic effect through a double action: i) it suppresses abnormal activity at cortical focus level ii) it depresses the multineural mechanism involved in the seizure spread at subcortical level.

Pharmacotherapy, 1987 Jan-Feb, 7(1), 25 - 7
Risks and indications of phenylbutazone: another look; Faich GA; In 1984 an extensive review of phenylbutazone risks was undertaken by the Food and Drug Administration (FDA) . Since that review, new recommendations for the drug's use have been published . Marketed in 1952, phenylbutazone has long been recognized as capable of inducing aplastic anemia . The risk of marrow depression is greatest in elderly females treated for over a month . Overall, the risk does not exceed that of many commonly used drugs (e.g., penicillin, which induces anaphylaxis) . Nonetheless, phenylbutazone should not be a drug of first choice and should not be used for minor, self-limited conditions.

Klin Monatsbl Augenheilkd, 1987 Jan, 190(1), 53 - 5
{A case of syphilitic uveitis simulating Harada disease}; Fiala W et al.; On the basis of clinical findings and fluorescein angiography the authors diagnosed Harada's disease in a 30-year-old Caucasian woman . A drastic deterioration occurred under treatment with corticosteroids and immunosuppressive agents . Another cause of the uveitis was looked for and a reactive serology for lues was found in the blood and the cerebrospinal fluid . The severe inflammation was then treated successfully with high doses of penicillin, intravenously administered; visual acuity also improved as a result this treatment . The differential diagnosis of the two conditions is discussed.

Int Arch Allergy Appl Immunol, 1987, 82(3-4), 461 - 4
Side-chain-specific lymphocyte responses in workers with occupational allergy induced by penicillins; Stejskal VD et al.; Eight workers with clinically diagnosed or suspected occupational allergy caused by penicillins were studied by the lymphocyte transformation test (LTT) and by skin test . The majority of the workers handled bacampicillin, some of them had been in contact with benzylpenicillin and one worked with azidocillin only . Six workers had eczema and 2 workers suffered from rhinitis only . Lymphocytes from workers with bacampicillin-induced symptoms responded to this drug in vitro by an increased 3H-thymidine incorporation and by lymphoblastogenesis . Bacampicillin-specific allergy had been confirmed by positive patch test in 5 workers . Lymphocytes from bacampicillin-allergic workers did not respond to other penicillins such as benzylpenicillin or azidocillin in vitro . However, such penicillins were antigenic in vitro since lymphocytes from an azidocillin patch test positive worker proliferated on exposure to azidocillin in vitro . The findings at the cellular level were further supported by the specificity of the skin test . Thus, bacampicillin patch test positive workers had a negative skin reaction to benzylpenicillin . In conclusion, these data suggest the role of penicillin side chains in the sensitization process underlying occupational allergy to penicillins . LTT can be used as a tool for studying antigenic specificities involved in a sensitization process leading to penicillin allergy.

Arch Orthop Trauma Surg, 1987, 106(2), 108 - 12
Total hip replacement ad modum Lubinus: five- to seven-year follow-up; Soballe K et al.; A study of 141 total hip replacements with the Lubinus prosthesis is presented . The complications in the total patient group and the results in 129 hips with follow-up times from 5 to 7 years are described . Three prostheses (2.1%) have been reoperated because of loosening . There were radiographic signs of definitive loosening in 2.3% . Varus positioning was associated with an increased loosening rate . No infections have been encountered, and none of the hips have undergone excision arthroplasty . Ninety-two percent of the hips were free from significant pain and 78% had a total range of motion exceeding 160 degrees . THR was performed, without subsequent infections, in a conventional operating room using prophylactic penicillin and gentamicin cement . We propose that the surgical technique of exposure and the cement injection technique with a partial vacuum in the medullary canal may be responsible for the low incidence of femoral prosthesis loosening (0.7%).

Antibiot Med Biotekhnol, 1987 Jan, 32(1), 24 - 6
{Intensification of the penicillin drying process based on the theory of short-term contact of material with a heat-exchange surface}; Sadykov RA et al.; The process of potassium benzylpenicillin vacuum drying was investigated . The kinetics of the process showed that a larger period of the drying process was needed for eliminating bound moisture . The influence of the angular velocity of the drier drum rotation on drying duration was studied in a short-term contact model . It was shown that intensity of drying increased with increasing velocity of the drum rotation . Experimental trials confirmed the conclusion and revealed adequacy of the relationship between the drying time and dispersion intensity in the short-term contact model . A qualitative dependence of the coefficient of convective heat exchange between the heating surface and the product on the angular velocity of the drier drum rotation was constructed.

J Immunoassay, 1987, 8(1), 73 - 96
Methodological considerations for penicillin radioimmunoassay; Elsasser TH et al.; The objective of this study was to identify and define factors that compromise the utility of radioimmunoassay for quantitation of beta-lactam antibiotics in biological aqueous fluids . Serum containing antibodies to benzylpenicillin coupled as a hapten to keyhole limpet hemocyanin was used as the assay primary antibody . Two significant factors that limited the utility of the assay were the tendency for penicillin to hydrolyze in aqueous solutions, resulting in a mixture of immunorecognizable forms; and in the hydrolyzed state, to bind covalently with matrix proteins . Assay sensitivity, crossreactivity, and assay binding parameters varied with the state of hydrolysis of penicillin in tracer, standards, and unknowns and with the composition of the assay buffer . Hydrolysis of the beta-lactam ring of penicillin immediately before assay by addition of 0.1 N NaOH or penicillinase resulted in improvements in assay repeatability and uniformity by forming predominantly the penicilloate form of the compound, which was immunologically well recognized by the antibody . Nonspecific binding of penicillin (and derivatives) to proteins in biological fluids such as milk or assay buffers was shown to be a possible cause of error in the immunoassay of penicillins.

Gastroenterol Clin Biol, 1987 Jan, 11(1), 93 - 5
{Hepatic involvement in secondary syphilis}; Archambeaud-Mouveroux F et al.; A case of secondary syphilitic hepatitis is reported . A 49-year old woman was admitted for weight-loss, fever, hepatomegaly and splenomegaly . Diagnosis of syphilitic hepatitis was based on cholestasis associated with positive serologic tests for syphilis without other immunological disturbances . Biopsy of the liver showed a moderate infiltration in and around the portal tracts . Immunofluorescence study for treponema was negative . Rapid improvement was obtained with penicillin initially associated with steroid therapy . Liver involvement in secondary syphilis is characterized by anicteric cholestasis, an inflammatory syndrome, and periportal infiltrate inconstantly associated with centrilobular necrosis, granulomatous reaction and presence of treponemas in the lesions . Due to the increasing frequency of sexually transmitted diseases, this diagnosis could become more frequent.

Biochem Cell Biol, 1987 Jan, 65(1), 62 - 7
Variability in the posttranslational processing of penicillin-binding protein 1b among different strains of Escherichia coli; Rojo F et al.; Screening of a number of unrelated strains of Escherichia coli confirms the existence of at least two patterns of molecular forms for penicillin-binding protein 1b in E . coli cell envelopes . Our data support that the beta-form of this protein is produced by posttranslational modification of the alpha-form and suggest that the absence of the beta-form in some strains is due to a strain-dependent variability in the alpha-form processing mechanism.

Eur Neurol, 1987, 26(1), 23 - 8
Neurosyphilis: a changing diagnostic problem?
Wolters EC.
In the recent literature about neurosyphilis, several publications have mentioned more atypical presentations of neurosyphilis . Inadequate penicillin therapy and improved serological methods are supposed to be responsible for these findings . In contrast with this proposition the present retrospective study of two groups of neurosyphilitic patients (518 patients during the period 1930-1940 and 121 during 1970-1984) reveals no marked differences in clinical data of these groups . Besides the fall in incidence of syphilis and neurosyphilis and the shift in the male/female ratio, conforming to modern literature, there is an increase in the cases of asymptomatic neurosyphilis, due to development of the immunological techniques to detect the diagnosis 'neurosyphilis' earlier.

Ann Med Interne (Paris), 1987, 138(8), 601 - 3
{Pericardial manifestations of Lyme disease}; Lorcerie B et al.; Among cardiac manifestations of Lyme disease, pericardic involvement, as the main symptom, seems to be exceptional . We report two cases of pericarditis with typical clinical features . In both cases, pericarditis was the only clinical sign of the disease . Diagnosis was based on significant high serological antibodies levels with no evidence of any other etiological factor . Penicillin was administered and lead in one case to negativation of the serology . As cardiac involvement can occur without any preexisting cutaneous lesion, the frequency of pericardic involvement in Lyme disease is certainly underestimated.

J Fr Ophtalmol, 1987, 10(10), 547 - 9, 551-5
{Preservation of human corneas in an enriched culture medium at +37 degrees Centigrade: histological and biochemical analyses}; Delbosc B et al.; Using the methods of Doughman, Sperling and Pels 66 human corneas were preserved up to five weeks in a modified tissue culture medium at +37 degrees C . The organ culture medium consisted of the following ingredients: Dulbecco Iscov's medium, 2% fetal calf serum, penicillin 100 IU/ml, Streptomycin 0.5 mg/ml, and fungizone 5 mg/ml . After culture the corneal endothelium was examined by light microscopy after staining with trypan blue 0.3% and alizarin red 1% . The number of dead cells was counted and the morphological alterations were described at 7, 14, 21 and 35 days . Biochemical analysis of the medium (pH, lactate, glucose) during storage has allowed the comparison of three kinds of storage: 50 ml, 20 ml, and 20 ml with 10 ml substitution weekly . After culture the number of dead cells did not exceed 1% at each period indicating that no dead cell was present at that time . Alteration of the cell shape and formation of rosette and joint meetings of 5 to 8 cells were the dominating morphological changes of the endothelial cells . The endothelial layer was intact and coherent on to 35 days culture . Endothelial cells loses during culture were not determined . The biochemical studies have shown the better quality (pH stability, anaerobic ratio) of storage in 50 ml medium or 20 ml 50% weekly substitution medium . This last kind of storage has given the best metabolic conditions for the preserved corneas . However for long period of storage up to 3-4 weeks, renewing 50% of the medium is found appropriate . At the end of this study a clinical trial is proposed.

Acta Gastroenterol Latinoam, 1987, 17(2), 105 - 11
{Hepatic lesions induced by drugs . Report of 26 cases}; Olmos M et al.; Two thousand six hundred and seventy one liver biopsies were reviewed from 1972 to 1985 at the Hospital A . Posadas . There were 26 patients with drug-induced liver injury; those who fulfilled the following criteria were included: contact with a drug known to produce hepatotoxicity; clinic, biologic and histologic picture corresponding to the drug studied, complete recovery after the drug was stopped and no other hepatic toxics . Fourteen patients showed estrogen-induced intrahepatic cholestasis, 5 had hepatitis-like lesions due to: alphamethyldopa (3), ketoconazole (1) and indomethacin (1) . Carbon tetrachloride caused fatty degeneration in two patients and phenylbutazone a granulomatous hepatitis in one patient and cholestatic hepatitis in other . The last three cases were cholestatic lesions after the administration of chlorpromazine allopurinol and penicillin respectively . The evolution in 24 patients was excellent after the drug was withdrawn . Two patients died because of surgical complications since they were operated on with the wrong diagnosis of extrahepatic cholestasis.

Z Hautkr, 1987, 62 Suppl 1, 79 - 87
{Skin reactions to food and food constituents--allergic and pseudoallergic reactions}; Paul E; Which skin reactions, with allergic or pseudo-allergic mechanism, are actuated by food? Contact urticaria or "forme-fruste-anaphylaxis" is the most common . Tests, using purchasable allergen extracts, mostly produce negative results, due to inadequate natural identity . Therefore, scratchtests with the natural antigens are necessary . Apart from the acute and chronic urticaria, classic other reaction types (Coombs and Gell) within the scope of real food allergy are also present (allergic vasculitis from meat containing penicillin, thrombocyopenic purpura after taking aspirin or quinine); cellular immune reactions to food and its components are also not uncommon . The importance of natural salicylate for the aetiopathogenesis of chronic urticaria has not yet been ascertained; nevertheless, a suitable diet is recommended on the understanding that degranulation of the mast cells, possibly due to subclinical stimuli, is triggered off.

Vutr Boles, 1987, 26(5), 40 - 5
{Current status of the Q-rickettsial endocarditis problem and the 1st case reported in Bulgaria}; Shishmanov D et al.; A vast literary review on Q-rickettsial endocarditis is presented--spread, frequency, predilection, clinical course, laboratory findings, diagnosis, treatment, prognosis . The first case of Q-rickettsial endocarditis in Bulgaria is reported . The case was proved by the high titre of the specific antibodies while the patient was still alive and post mortem by visualizing the causative agent in the aortic valve and by its isolation through inoculation of material from the aortic valve . The infection was not influenced by high doses of penicillin, gentamycin and brulamycin but was suppressed by vibramycin in combination with lincomycin and biseptol . The lethal outcome was due to severe heart failure . It is suggested that other cases of Q-rickettsial endocarditis should be expected since Q-fever is widely spread in Bulgaria and the characteristics of the disease, its diagnosis and treatment ought to be well known.

Drugs, 1987, 34 Suppl 2, 164 - 79
Role of cephalosporins in gonorrhoea and other sexually transmitted diseases; Phillips I; Cephalosporins have a role in the treatment of gonorrhoea, and especially infections caused by strains that are penicillin-resistant, either because they produce plasmid-mediated beta-lactamase or they have chromosomally mediated diminished permeability or modified penicillin-binding proteins . Although none of the oral or Group I agents are useful, most of the Group II, III and IV agents are, and especially cefuroxime, cefotaxime, ceftriaxone and cefoxitin . In addition to uncomplicated urethral, cervical or rectal infections, appropriate regimens are also effective for the treatment of pharyngeal infections, disseminated infections and gonococcal ophthalmia . The cephalosporins have no clear role in the treatment of syphilis, granuloma inguinale, Mycoplasma or chlamydial infections or bacterial vaginosis, but ceftriaxone may be effective in chancroid, and cefoxitin in combination with an antichlamydial agent (such as a tetracycline) might be used for the treatment of pelvic inflammatory disease.

Med Cutan Ibero Lat Am, 1987, 15(3), 239 - 42
{Histopathological aspects of tertiary pinta}; Pecher SA et al.; A study was made of twenty-two biopsies of achromic lesions of Tikuna Indians, carriers of tertiary pinta, inhabitants of the Umariuassu island, on the Peruvian border, ten of the subjects had been treated two years previously with a single dose of penicillin . The histopathological picture was similar for both groups . In most cases (86.36%) slight hyperkeratosis was found on the epidermis, as well as acanthosis (18.18%), with atrophy in only two cases (9.09%) . In all cases there was a reduction of the melanin of the basal layer . The inflammatory lymphocyte infiltrate was predominantly perivascular (88.18%) . There wasn't any endothelial swelling.

Arch Immunol Ther Exp (Warsz), 1987, 35(1), 57 - 62
Enzyme-linked immunosorbent assay (ELISA) of penicillin amidases; Prusak E et al.; Non-competitive, sandwich enzyme immunoassay for both penicillin amidases from Escherichia coli is described . The assay involves the use of monospecific antibodies and their conjugates . The amidases inactivated by heating and by acid- or alkali-treatment cannot be assayed . Reproducible results for each amidase were achieved within 5-6 hours in the range of 3-500 ng/ml (0.25-40 mU/ml) and coefficient of variation was 13%.

Crit Rev Oncol Hematol, 1987, 7(1), 53 - 69
Inhibitors of coagulation in children; Desposito F et al.; Acquired inhibitors of coagulation factor interaction in nonhemophilic children are usually nonspecific, transient, and unassociated with clinical bleeding . They occur with some frequency and are the most common cause for a prolonged APTT found by routine testing . In children, some association with viral infections and treatment with penicillin has been noted, but their interrelationship with the development of antibodies remains unclear . The exact nature of these antibodies, usually directed against coagulant factor phospholipid, is not clear and multiple antibodies both specific as well as nonspecific may occur . No therapy is generally required . Rarely has the acute development of antibodies directed against specific coagulation factors occurred . The laboratory evaluation of the type of inhibitor is, therefore, most important as specific inhibitors may be associated with life-threatening bleeding situations . Their therapy should probably include attempts at eradication of the inhibitor by immunosuppressive agents or other newer modalities . Unfortunately, little information is available regarding the nature and outcome of specific inhibitors in children . Acquired inhibitors in hemophilic patients occur in about 6 to 10% of patients . Newer approaches to their therapy include activated PCC which have generally improved the outlook for such patients . Treatment regimens involve a knowledge of inhibitor response and the concomitant use of plasmapheresis, high-dose or continuous i.v . Factor VIII, and porcine Factor VIII, followed by activated PCC . The role of immunosuppressive agents and other newer modalities appears promising, however, prospective controlled studies are necessary to evaluate their role in the overall management of such patients.

Crit Rev Oncol Hematol, 1987, 7(1), 1 - 36
Splenic function: physiology and splenic hypofunction; Sills RH; A wide variety of disorders can result in diminished splenic function . The pathophysiology appears to be clearly defined in some instances, such as congenital asplenia and disorders of splenic vascular obstruction or congestion . In others, such as the autoimmune and GI disorders, the mechanism remains poorly defined . Further research is needed . The hyposplenia which occurs in many of these disorders has been associated with an increased risk of life-threatening, overwhelming bacterial sepsis . In other instances, this complication has not been reported . This certainly should not be interpreted to mean that it cannot occur . The risk of septicemia in hyposplenic disorders is rarely above 10 to 15% . In disorders with minimal inhibition of splenic function, the incidence of sepsis would presumably be less than the 1.5% incidence following surgical splenectomy for trauma . Considering these data, a very large number of patients would have to become asplenic before it would be likely that one would develop sepsis . Furthermore, the lack of awareness of the possibility of hyposplenia-related sepsis in many of these disorders may cause such occurrences to go unrecognized . Finally, since the risk of sepsis is probably less in hyposplenic adults as compared to children, studies on adults may underestimate the incidence of this complication in children . Many of the disorders reported to cause hyposplenia in adults have not been noted to do so in children . In instances such as celiac disease, it may take many years for the complication to manifest so that it would be unlikely for a child to manifest hyposplenia during childhood . However, in other instances, not enough children have been studied to be confident that the hyposplenia and its associated risk of sepsis are not complications that occur in children . Hyposplenia-related bacterial septicemia is a catastrophic complication . If a patient develops a disorder that is potentially associated with hyposplenia, the patient should be observed for signs of asplenia in the peripheral blood . If the technique is available, quantitation of red cell pits should be performed . If not, other studies of splenic function such as radionuclide scans should be considered, depending on the incidence of hyposplenia in that particular disorder . If evidence of asplenia develops, pneumococcal vaccine should be administered, penicillin prophylaxis should be considered, significant febrile episodes should be managed aggressively, and probably most importantly, the patient and family should be carefully educated about this complication . Most deaths from hyposplenia-related septicemia are preventable.

Dev Pharmacol Ther, 1987, 10(3), 174 - 98
Clinical pharmacokinetics in pregnancy and perinatology . II . Penicillins; Nau H; Ampicillin has been most thoroughly studied in regard to placental transfer . Both during the first/second trimester and at term, fetal drug levels rose slowly to reach values similar to those in the maternal circulation 1-3 h after maternal drug administration; thereafter, fetal drug levels exceeded corresponding maternal values . Amniotic fluid levels were low during early gestational periods; during late gestation these levels were significant and even exceeded corresponding maternal values 6-8 h after drug administration . Slow exchange rates and fetal micturation may be responsible for the elevated ampicillin levels during late gestation . Administration via the intramuscular (recommended with 0.5 g every 4-6 h) or intravenous routes, but not by the oral route, resulted in adequate drug levels . Because of increased plasma clearance of ampicillin during pregnancy, a dose increase in pregnant patients may be necessary to obtain adequate drug levels . Amoxillin and azidocillin have been suggested to give effective drug levels even after oral administration, except during labor . The fetal levels of epicillin and benzylpenicillin (Penicillin G) were lower than the corresponding maternal values; amniotic fluid concentrations of these two drugs were elevated during late, but very low during early gestation, similar to the situation with ampicillin . Methicillin and sulbenicillin were effectively transferred across the placenta (similar to ampicillin), while dicloxacillin was not . The low concentrations of dicloxacillin in the fetus and amniotic fluid may be the results of extensive protein binding (greater than 90%) of this drug in maternal blood . Other highly bound penicillins such as cloxacillin and flucloxacillin have not yet been investigated in regard to placental transfer . Excretion of penicillins in human milk was usually very limited . Following therapeutic doses, the mean milk concentrations were 0.1-0.6 microgram/ml for amoxicillin, 0.1-0.2 microgram/ml for epicillin, about 0.5 microgram/ml for sulbactam, 2-2.5 micrograms/ml for ticarcillin, and 0.1-0.4 microgram/ml for aztreonam.

Proc Natl Sci Counc Repub China B, 1987 Jan, 11(1), 54 - 8
Multiple loop purification method for selective cultivation of Pentatrichomonas hominis; Chao D et al.; It is always troublesome having protozoan cultures contaminated with other organisms in the laboratory . The method described here produces high efficiencies of purification for fast moving flagellate protozoa . A human strain Pentatrichomonas hominis was employed in the study to examine the effects of multiple loop tubes on the purification of flagellates . Trichomonads were harvested from a trypticase yeast extract iron-serum-33 (TYI-S-33) medium, adjusted to 2 X 10(5) organisms/ml, and mixed with an equal volume of 2 X 10(6) organisms/ml of bacteria . The isolation was performed at 37 degrees C in TYI-S-33 medium containing a suitable amount of antibiotics (1000 U/ml of penicillin, 1000 micrograms/ml of streptomycin, and 4 micrograms/ml of fungizone) . Four days later, 10(6) organisms/ml of protozoa, free of bacteria, were observed at the other end of the single loop and the double loop tubes . About the same amount of flagellates could be found at the other end of the triple loop tube six days after incubation . The traditional U-shaped tubes were used as controls and 10(5) cells/ml of flagellates were recovered in the presence of bacteria two days after incubation . An axenic culture of P . hominis was successfully isolated from the feces of a Formosan rock-monkey, Macaca cyclopsis, by this method . Purified trichomonads were recovered from a double loop purification tube five days after incubation.

J Assoc Off Anal Chem, 1987 Jan-Feb, 70(1), 39 - 41
Liquid chromatographic determination of penicillin V potassium in tablets and powders for oral solution; Mopper B; A reverse-phase liquid chromatographic method is described for the assay of penicillin V potassium in tablets and powders for oral solution . Under isocratic conditions, the combined use of an octadecylsilane column, with a mobile phase composed of acetonitrile-methanol-0.01M monobasic potassium phosphate (21 + 4 + 75, v/v), and photometric detection at 225 nm, separated penicillin V potassium from excipients, related compounds, and degradation products . Sulfadimethoxine was used as an internal standard . Detector responses were linearly related to concentrations of penicillin V over the range 25-225 micrograms/mL (r = 0.99997) . Standard addition recoveries ranged from 98.8 to 99.9% (mean 99.5%, n = 8) for tablets and from 97.9 to 101.6% (mean 99.8%, n = 8) for powders for oral solution . The liquid chromatographic assay results were compared with those obtained by the official iodometric titration method . The proposed method is simple, selective, stability-indicating, and free from interference by excipients and degradation products.

Physiol Bohemoslov, 1987, 36(5), 453 - 62
Electrocorticographic development of epileptogenic foci in the occipital region of the rat cerebral cortex; Mares P et al.; The development of cortical penicillin foci in the occipital region was studied in rats whose ages ranged from five days up to the adult age . The local application of penicillin induced the formation of an epileptogenic focus for the first time at the age of seven days . With advancing age, the amplitude of focal discharges increased, the duration of the individual components of the discharge shortened, its originally negative-positive configuration changed to a triphasic form and in the third week of life initial positivity, for a time, become the dominant component of the discharge . Projection of the discharges to the contralateral hemisphere was found to be inconstant in the second postnatal week, but appeared regularly from the age of 14 days . Synchronization of the discharges of two symmetrical foci was very poor in 7-day-old young, but improved noticeably by the 14th day; it was never complete, however, even in adulthood . The activity of symmetrical foci changed spontaneously to ECoG seizures, which were most common in 7-day-old young (in which ictal activity was usually not generalized, however) and were least frequent in 14-day-old animals . Focal discharges could not be reliably triggered by electrical stimulation of the contralateral cortex until the age of 18 days and later . The occipital part of the cortex develops somewhat later than the sensorimotor, frontal region, and during its development there also appeared phenomena which are not present in the frontal cortex.

Hear Res, 1987, 26(1), 89 - 93
Some organic acids attenuate the effects of furosemide on the endocochlear potential; Rybak LP et al.; A series of organic acid transport inhibitors significantly reduced the endocochlear potential (EP) decline produced by furosemide in the chinchilla . Probenecid, sodium salicylate and penicillin G were much more effective than novobiocin, meclofenamate or diatrizoate . Inhibitors of organic base transport, choline and N-methyl nicotinamide, had no effect on the furosemide-induced drop of the EP . These findings suggest that at least part of furosemide ototoxicity may be mediated by organic acid transport.

Synapse, 1987, 1(1), 96 - 101
The GABAA receptor: new insights from single-channel recording; Mathers DA; The GABAA receptor of mammalian neurons exists as a macromolecular complex incorporating several interacting components . These include a chloride-permeable ion channel and a recognition site for GABA . The binding of GABA molecules at the latter site triggers the transient opening of the chloride ion channel, resulting in a flow of charge which inhibits the generation of action potentials in the cell . The precise amount of charge passed during this event is modulated by ligand binding at at least three regulatory sites . These sites act as receptors for barbiturates, benzodiazepines, and certain convulsants . The extracellular patch clamp method has now been used to study the gating of chloride channels by GABA and the modulation of this process by drugs . Even in the absence of drugs, GABAA channels exhibit complex gating behavior, indicating the presence of multiple open and closed states and of substate conductance levels . GABAA channels from different preparations show considerable diversity in their detailed gating characteristics . In the presence of the barbiturate pentobarbital, GABAA channels open in prolonged bursts, consistent with the potentiating effect of this drug on macroscopic GABA responses . In contrast, the convulsant penicillin decreases charge transfer through open GABAA channels by shortening the average duration of the open state . Benzodiazepine receptor ligands exert complex effects on the GABAA channel . A general model of barbiturate and benzodiazepine potentiation of GABAA receptor responses is proposed.

Biomed Biochim Acta, 1987, 46(5), 429 - 32
Influence of beta adrenergic blockers and their combinations with anticholinergic drugs on epileptiform activity in rabbit hippocampus; Tkatchenko EI et al.; The influence of alpha- and beta-receptor antagonists combined with drugs which act as antagonists at muscarinic and nicotinic receptor sites on epileptic focus produced by topic penicillin application was investigated . The beta-receptor blocking agent caused a faster and more intense activity of epileptogenic focus in comparison with activity in control animals, but the number of seizures decreased relatively for 25% . N-receptor antagonists diminished the facilitating effect of the beta-receptor antagonist on focal activity . Combination of m- and beta-receptor antagonists did not influence the spike activity of the focus . Treatment with alpha-receptor antagonists enhanced spikes and number of seizures only insignificantly . The combination of alpha- and n-receptor blocking substances does not influence the development of the epileptic process . The alpha-receptor antagonist together with the m-receptor blocking drug induces a facilitation of spike activity.

Comp Biochem Physiol C, 1987, 86(2), 405 - 9
The effects of procaine, strychnine and penicillin on nociceptive neurons in leech segmental ganglia; Johansen J et al.; Procaine, strychnine and penicillin selectively depolarized the membrane potential and prolonged the action potential recorded in the lateral but not the medial nociceptive (N) cell in the hirudinid leech Macrobdella decora . In contrast, procaine did not differentiate between medial and lateral N cells in two other hirudinid leeches Hirudo medicinalis and Haemopis marmorata . In these species, the drug equally decreased the amplitude of action potentials in both types of N cells without effecting their resting membrane properties . In the nociceptive neurons of the glossiphoniid leech Haementeria ghilianii which possesses only one type of N cell, procaine produced a depolarization and prolonged the action potential . This finding indicates that the single pair of N cells in Haementeria is of the lateral type . The results suggest that the lateral type N cell in Macrobdella and Haementeria share a unique Na+-dependent conductance which is selectively opened by the local anesthetics procaine and strychnine as well as by penicillin . This conductance is either not present or insensitive to the drugs in the homologous N cells in the two other leech species examined.

Comp Biochem Physiol C, 1987, 86(2), 305 - 11
Pharmacology of GABA receptors on skeletal muscle fibres of the locust (Schistocerca gregaria); Scott RH et al.; GABA and the trans isomer of 4-aminocrotonic acid are equally potent at inducing increases in Cl- conductance when applied to distal extensor tibia muscle fibres of the locust (Schistocerca gregaria) . beta-Alanine, norvaline, glycine and norleucine induced conductance increases of less than 5% of GABA responses . C9 and meso-di-GABA did not alter input conductance in a manner consistent with actions on a GABA receptor Cl- channel complex . Picrotoxin and anisatin were equally potent GABA antagonists, however bicuculline and penicillin G did not reduce GABA-induced changes in input conductance . Pentobarbitone, in addition to inducing an increase in K+ conductance, potentiated GABA-induced increases in Cl- permeability.

Folia Haematol Int Mag Klin Morphol Blutforsch, 1987, 114(4), 482 - 3
Antioxidants increase the cryoresistance of GM-CFC; Matthes G et al.; The influence of antioxidative drugs on the cryopreservation of human bone marrow cells was studied . The viability of bone marrow cells was tested after freezing and thawing from--196 degrees C by the growth of GM-CFC in agar culture . The results suggest the ability of antioxidants to protect stem cells against damage caused by freezing and thawing . Addition of tocopherol or penicillin to a cryoprotective medium increases the number of surviving GM-CFC . From the colony-to-cluster ratio can be concluded that antioxidants especially protect more immature haematopoietic (colony forming) cells.

Acta Derm Venereol, 1987, 67(3), 225 - 31
Evidence for spirochetal origin of circumscribed scleroderma (morphea); Aberer E et al.; Acrodermatitis chronica atrophicans (ACA) and morphea are clinically distinct skin diseases with some common features and possible coexistence . We found antibodies to Borrelia burgdorferi in eight of fifteen patients with morphea . Six of them had IgG antibodies and two both IgG and IgM antibodies . Four of the eight seropositive and five of the seven seronegative patients had been treated with high dose penicillin previously . Spirochetal organisms could be cultured in Barbour-Stoenner-Kelly's medium from a skin biopsy of one seropositive untreated patient . Spirochetes were recovered from histological sections in three of eight, two seropositive and one seronegative morphea and in one of three erythema chronicum migrans patients by an avidin-biotin immunoperoxidase method . The similar clinical picture of ACA and morphea, the response to penicillin therapy in both entities, the presence of antispirochetal antibodies, the isolation of spirochetes in culture and the detection of spirochetal organisms on histological sections suggest a close relationship among these diseases . We conclude that morphea may represent a Borrelia infection . The correlation to ACA is discussed.

Int Arch Allergy Appl Immunol, 1987, 82(2), 221 - 4
Antigen-induced formation of a lymphokine with a possible role as a mediator of the late component of dual allergic reaction; Ezeamuzie IC et al.; In a penicillin-allergic patient who showed a strong dual skin reaction (immediate and late components) to an intradermal injection of the antigen, we investigated the possibility that the lymphokine, histamine-releasing factor (HRF), which has been shown to release histamine from human basophils and mast cells, might play a part in the elicitation of the late phase of the 'dual reaction' . In vitro stimulation of this patient's lymphocytes, but not those of a patient with a monophasic (immediate) reaction with the antigen, caused the production of a large amount of HRF, while a moderate lymphoproliferation occurred in both patients . The purified HRF released histamine from the patient's own leucocytes and also caused immediate wheal and flare reaction on intradermal injection.

Electroencephalogr Clin Neurophysiol, 1987 Jan, 66(1), 43 - 55
Motor cortical epileptic foci in vivo: actions of a calcium channel blocker on paroxysmal neuronal depolarizations; Witte OW et al.; Focal epileptiform activity was induced by local application of penicillin to the surface of the rat motor cortex . Neurons located within the epileptic focus displayed typical paroxysmal depolarization shifts (PDS) . The participation of membrane calcium currents in the generation of PDS was examined by injecting the quaternized calcium entry blocker D890 into single neurons by iontophoresis or by pressure pulses . After intracellular injections of D890, PDS were depressed in amplitude by up to 55% . In a few cases the depression of PDS following intracellular application of D890 was preceded by a transient increase . Similar increases of PDS amplitude were obtained by injections of the calcium chelator EGTA . Control experiments in preparations without epileptic activity revealed that excitatory potentials elicited by thalamic stimulation and Cl(-)-dependent inhibitory postsynaptic potentials evoked by epicortical stimulation were not affected by intracellular D890 . In these experiments successful intracellular drug application was verified by monitoring the transient shift of the Cl(-)-equilibrium potential induced by injection of KCl together with D890 . It is concluded that in the penicillin-induced epileptic focus of the motor cortex Ca2+ inward currents participate in the generation of neuronal PDS.

Doc Ophthalmol, 1986 Dec 30, 64(1), 23 - 9
Neuroretinitis in secondary syphilis; Veldman E et al.; A 30-year-old man with bilateral neuroretinitis and uveitis associated with secondary syphilis is described . Characteristic lesions on the palms of the hands and the soles of the feet gave us the clue to the diagnosis . Treatment with penicillin resulted in a rapid cure . Syphilic neuroretinitis is often associated with secondary meningitis . Early diagnosis and adequate therapy are important in this serious but treatable condition.

Brain Res, 1986 Dec 3, 399(1), 194 - 9
Long-term effects of sinusoidal extracellular electric fields in penicillin-treated rat hippocampal slices; Bawin SM et al.; Rat hippocampal slices in 0, 0.25, 1.5 or 3 mM penicillin were exposed briefly to extracellular sinusoidal electric fields (20 s, 5 and 60 Hz, 20-40 mV/cm in tissue) . Fields induced long-term (min) changes in population spike amplitudes in the CA1 cell layer . Post-field effects included both depression of strongly epileptiform responses and potentiation of weakly epileptiform and normal responses . Endogenous extracellular fields may participate in the dynamic regulation of the course of seizures.

Rev Rhum Mal Osteoartic, 1986 Dec, 53(12), 677 - 80
{Bone and joint Actinomyces meyeri infections . Cervicofacial localizations excluded . Apropos of 3 cases}; Bussiere JL et al.; The authors report three observations of osseous and/or articular actinomycosis . Osseous localizations, always in contact with abscessed foci of the soft tissues, included the spine and one or several limbs . In one case there was an arthritis of the knee . Culture and typing of the responsible germ: Actinomyces meyeri, were obtained from infectious foci in the three cases . The authors insist on the rare occurrence, at the moment, of osteo-articular actinomycoses outside the maxillo-facial area . Actinomyces meyeri has exceptionally been implicated . The prognosis of osteo-arthritis is similar to that of other localizations . It is usually favorable due to the great sensitivity of the germs to antibiotics, especially penicillin.

J Antibiot (Tokyo), 1986 Dec, 39(12), 1754 - 9
Direct enzymatic synthesis of natural penicillins using phenylacetyl-CoA: 6-APA phenylacetyl transferase of Penicillium chrysogenum: minimal and maximal side chain length requirements; Luengo JM et al.; In vitro synthesis of different natural penicillins (hexanoyl, heptanoyl and octanoyl-penicillin) have been carried out by direct acylation of 6-aminopenicillanic acid (6-APA) with several fatty acid-CoA derivatives (hexanoyl-CoA, heptanoyl-CoA and octanoyl-CoA) . The reactions were catalyzed by the enzyme Acyl-CoA: 6-aminopenicillanic acid acyltransferase from Penicillium chrysogenum AS-P-78 . This enzyme only accepts as substrate, aliphatic side chain precursors whose carbon length is between 6 and 8 atoms . Although the enzymatic synthesis of octanoylpenicillin has been previously reported the in vitro synthesis of hexanoyl and heptanoyl penicillins is described here for the first time.

Exp Neurol, 1986 Dec, 94(3), 455 - 68
Laminar field potentials and unit activity in the cortex during visual evoked potentials in feline generalized penicillin epilepsy; Pellegrini A et al.; Modifications of the visual evoked potential during generalized epilepsy were investigated in feline generalized penicillin epilepsy . Visual evoked potentials and their intracortical profiles were averaged during intraburst periods and during the wave of the spike and wave complex to a fixed latency from the preceding spike . During interburst periods, the evoked potentials showed an increase in the amplitude of the early positive peak and the appearance after a variable latency period of a second consistent peak during the late phase of the evoked potential . Laminar profiles of visual evoked potentials and their current source density analysis compared with the activity of single cortical units suggested an early excitation of neuronal populations at layers II, III and IV, as seen before penicillin, followed by a variable inhibitory period and by a subsequent rebounded excitation at those same levels . In evoked potentials recorded during the wave of the spike and wave complex, the early phase was unchanged and the late positive peak and the corresponding deep sink were greatly reduced or nonexistent, although the rebounded activation of cortical units was still evident . These data support the conclusion that during feline generalized penicillin epilepsy a larger number of cortical neurons are activated and a sequence of excitation-inhibition-excitation, probably involving also subcortical structures, is brought about . Moreover, the inhibitory phase of the spike and wave complex is soon disrupted whenever a consistent sensory stimulus arrives at the cortex.

Brain Res, 1986 Dec, 395(2), 243 - 55
Extracellular K+ accumulation during penicillin-induced epileptogenesis in the CA3 region of immature rat hippocampus; Swann JW et al.; Ion-selective microelectrode techniques were used to study extracellular K+ changes associated with penicillin-induced epileptogenesis in the CA3 region of hippocampal slices . Recordings were made in slices taken from rats 9-16 days of age, which have a pronounced capacity to undergo prolonged synchronized afterdischarges . Direct comparisons were made to slices from hippocampus from more mature rats, 30-35 days old, which are much less prone to seizure-like events . The amplitude and time course of the K+ transients varied across the CA3 laminae . K+ signals were largest close to stratum pyramidale in stratum oriens (the infrapyramidal zone) . Recordings from this site showed extracellular K+ accumulation to be unusually large in immature hippocampus . The ceiling {K+}o level recorded during seizure-like events ranged from 14.4 to 20.2 mM and averaged 16.9 mM . The peak amplitude of extracellular K+ transients following an epileptiform burst in slices from immature rats averaged 4.31 mM while the mean of similar recordings from mature rats was 0.97 mM . Detailed laminar distribution studies in developing hippocampus revealed that the K+ signals were large in the proximal two-thirds of the basilar dendrites and proximal half of the apical dendrites . K+ accumulation in stratum pyramidale was comparatively small even though at its very edge in stratum oriens large K+ transients were always recorded . The latter was also true in recordings from mature hippocampus . Other dendritic signals in mature tissue were comparatively small . Laminar analysis was performed of the field potentials recorded by the reference barrel of the K+ electrodes . Negative field potential for the epileptiform burst and subsequent slow potential correlated in space with sites of K+ accumulation in both immature and mature hippocampal slices . Interictal and prolonged ictal-like discharges, recorded in developing hippocampus, arose from the same baseline {K+}o . However, since {K+}o is excessively high during the course of these epileptiform events it most likely has a role in the unusual propensity of immature hippocampus for seizures.

Ann Emerg Med, 1986 Dec, 15(12), 1451 - 5
Ballistic injury; Fackler ML; Wound profiles made under controlled conditions in the wound ballistics laboratory at the Letterman Army Institute of Research showed the location along their tissue path at which projectiles cause tissue disruption and the type of disruption (crush from direct contact with the projectile or stretch from temporary cavitation) . Comparison of wound profiles showed the fallacy in attempting to judge wound severity using velocity alone, and laid to rest the common belief that in treating a wound caused by a high-velocity missile, one needs to excise tissue far in excess of that which appears damaged . All penetrating projectile wounds, whether civilian or military, therefore should be treated the same regardless of projectile velocity . Diagnosis of the approximate amount and location of tissue disruption is made by physical examination and appropriate radiographic studies . These wounds are contaminated, and coverage with a penicillin-type antibiotic should be provided.

Antibiot Med Biotekhnol, 1986 Dec, 31(12), 921 - 4
{Possibility of using the etiological factor and the function of the immune system in assessing the pathogenetic treatment of chronic suppurative sinusitis}; Gorshtein RM et al.; The etiologic profile and state of the immune system of the patients with different forms of sinusitis treated at the Moscow Research Institute of the Ear, Throat and Nose in 1983-1985 were studied . The treatment of the patients with a combination of penicillin and dimexide was shown to be efficient . Differences between the humoral factors of the nonspecific defence and between the indices of the cell reactivity of the patients before and after the treatment were revealed.

Monatsschr Kinderheilkd, 1986 Dec, 134(12), 878 - 80
{Pasini and Pierini idiopathic and progressive atrophoderma in childhood}; Lohrer R et al.; In an eleven year old girl Atrophodermia idiopathica et progressiva Pasini et Pierini, a rare variety of localised scleroderma developed within six months as well outlined, reddish-brown, patchy lesions without induration on her right side . The histological examination revealed perivascular inflammatory infiltrations in all corium layers, and discrete sclerosis radiating into fat tissue cells . The levels of antinuclear antibodies and C-reactive protein were both elevated . During intravenous therapy with penicillin G the skin alterations faded but did not disappear.

Burns Incl Therm Inj, 1986 Dec, 12(8), 578 - 85
Ecthyma gangrenosum in a burned child; Eldridge JP et al.; The history of ecthyma gangrenosum has been presented, as well as its pathological diagnosis, prognosis and natural history . The history of forms of treatment has been outlined and the grave prognosis is emphasized . A case presentation introduces the experience at the Cincinnati Shriners Burns Institute . From a review of the literature and the experience at the Shriners Burns Institute, a suggestion for optimal treatment has been proposed . The particulars of this treatment include: early recognition, general nutritional and metabolic support, as well as high-dose aminoglycoside and semi-synthetic penicillin therapy, administered parentally and by sub-eschar clysis . Despite the grave prognosis, attention to these factors should result in optimal survival of patients with ecthyma gangrenosum.

Biull Eksp Biol Med, 1986 Dec, 102(12), 683 - 5
{Effect of adaptation to hypoxia on the resistance of rats to the epileptogenic action of penicillin}; Agadzhanian NA et al.; The influence of adaptation to moderate hypoxia on anticonvulsive resistance of low tolerant rats has been investigated . Focal epilepsy was induced by penicillin application to sensorimotor cortex of the rat brain . Adaptation to hypoxia has been shown to increase the resistance of rats to epileptogenic penicillin effect which is manifested in the prolongation of the latent period of epileptiform discharges and less frequent epileptic fits . The mechanisms of the resistance increase remains to be investigated.

J Neurophysiol, 1986 Dec, 56(6), 1718 - 38
The dendritic origins of penicillin-induced epileptogenesis in CA3 hippocampal pyramidal cells; Swann JW et al.; Experiments were performed in order to identify the sites of epileptiform burst generation in rat hippocampal CA3 pyramidal cells . A subsequent slow field potential was studied, which is associated with afterdischarge generation . Laminar field potential and current source-density (CSD) methods were employed in hippocampal slices exposed to penicillin . Simultaneous intracellular and extracellular field recordings from the CA3 pyramidal cell body layer showed that whenever an epileptiform burst was recorded extracellularly, individual CA3 neurons underwent an intense depolarization shift . In extracellular records a slow negative field potential invariably followed epileptiform burst generation . In approximately 10% of slices, synchronous afterdischarges rode on the envelope of this negative field potential . Intracellularly a depolarizing afterpotential followed the depolarization shift and was coincident with the extracellular slow negative field potential . A one-dimensional CSD analysis performed perpendicular to the CA3 cell body layer showed that during epileptiform burst generation large current sinks occur simultaneously in the central portions of both the apical and basilar dendrites . The average distance of the peak amplitude for these sinks from the center of the cell body layer was 175 +/- 46.8 microns and 158 +/- 25.0 microns, respectively . A large current source was recorded in the cell body layer . Smaller current sources were observed in the distal portions of the dendritic layers . During the postburst slow field potential a current sink was recorded at the edge of the cell body layer in stratum oriens--a region referred to as the infrapyramidal zone . Simultaneous with the current sink recorded there, smaller sinks were often observed in the dendritic layers that appeared to be "tails" or prolongations of the currents underlying burst generation . Two-dimensional analyses of these field potentials were performed on planes parallel and perpendicular to the exposed surface of the slice . Isopotential contours showed that the direction of extracellular current is mainly orthogonal to the CA3 laminae . Correction of CSD estimates made perpendicular to the cell body layer for current flowing in the other direction did not alter the location of computed current sources and sinks . In order to show that the dendritic currents associated with epileptiform burst generation were active sinks, tetrodotoxin (TTX) was applied locally to the dendrites where the current sinks were recorded.(ABSTRACT TRUNCATED AT 400 WORDS)

Arch Int Physiol Biochim, 1986 Dec, 94(5), 295 - 303
Negative occurrence between hippocampal rhythmic slow activity and epileptiform spikes: influence of the striatum; La Grutta V et al.; The effects of caudate and septal stimulation on hippocampal activity were studied . Sodium penicillin was intravenously injected in order to induce a steady rate of interictal epileptic activity . Penicillin injection caused significant reduction of the rate of occurrence and duration of hippocampal rhythmic slow activity (RSA) . Spontaneous RSA as well as RSA-eliciting caudate and septal stimulation induced a marked inhibition on frequency of epileptiform complexes . Lesions of the medial septal nucleus made it impossible to record RSA or to observe any sort of influence on hippocampal epileptiform activity by caudate stimulation . This result suggests that the septum is important for RSA genesis in the striato-hippocampal pathway or in the reciprocal septo-hippocampal connections.

Clin Exp Immunol, 1986 Dec, 66(3), 633 - 9
Total and allergen-specific IgE in relation to allergic response pattern following bone marrow transplantation; Walker SA et al.; Total and allergen-specific serum IgE were measured in relation to allergic response pattern before and after bone marrow transplant (BMT) in seven sibling donor/recipient pairs . Two non-atopic recipients developed persistently raised total serum IgE levels but no apparent allergic response after BMT from non-atopic donors; three non-atopic recipients showed raised total serum IgE after BMT, with allergen-specific IgE to the same allergens as their respective atopic donors . A penicillin-tolerant recipient showed clinical sensitivity and specific IgE to penicillin after BMT from a penicillin-sensitive donor, but with this case both donor and recipient showed raised serum IgE levels . One atopic recipient showed decreased total IgE after BMT from a mildly atopic donor . These allergic response patterns could occur as a result of repopulation in the recipient with IgE-specific T lymphocytes having similar regulatory influences as in the donor . The pattern of acquired responses would also be consistent with reconstitution by primed B lymphocytes of donor origin.

Electroencephalogr Clin Neurophysiol, 1986 Dec, 64(6), 546 - 55
Suppression of penicillin-induced epileptiform activity by noxious stimulation: mediation by 5-hydroxytryptamine; Neuman RS; Noxious stimulation has a well known suppressant effect on epileptiform activity in both laboratory animals and man . To study this phenomenon in an animal model, focal epileptiform activity was induced in anaesthetized rats by applying penicillin from one barrel of a micropipette while recording intracortical electrical activity from another barrel . Penicillin produced either focal epileptiform activity or focal penicillin spikes, depending somewhat on the rate of penicillin release . Focal epileptiform activity was suppressed by noxious stimulation, both somatic and olfactory, whereas non-noxious stimulation was ineffective in this regard . Focal penicillin spikes were only rarely suppressed by noxious stimulation . Reserpine blocked the suppressant effect of noxious stimulation as did p-chlorophenylalanine, a more selective depletor of 5-hydroxytryptamine . L-5-Hydroxytryptophan, a 5-hydroxytryptamine precursor, restored the suppressant effect of noxious stimulation blocked by reserpine and p-chlorophenylalanine . These results suggest that the suppression of SW by noxious stimulation is mediated by 5-hydroxytryptamine . Data from experiments employing pharmacological antagonists suggest the suppression of spike and wave activity by noxious stimulation not to be mediated by activation of dopamine receptors, alpha 2 or beta adrenoceptors, or muscarinic cholinoceptors . Prazosin, a selective alpha 1 adrenoceptor antagonist, did block the suppressant effect of noxious stimulation but only at a very high dose (2.4 mumols/kg) . This likely reflects a known analgesic action of prazosin or weak binding to the 5-HT receptor . Methysergide, a 5-hydroxytryptamine antagonist, failed to antagonize the suppressant effect of noxious stimulation, however, many inhibitory actions of 5-hydroxytryptamine are not blocked by methysergide . It is concluded that suppression of focal epileptiform activity by noxious stimulation is mediated, at least in part, by 5-hydroxytryptamine.

Brain Res, 1986 Nov 29, 398(2), 231 - 41
Low concentrations of penicillin reveal rhythmic, synchronous synaptic potentials in hippocampal slice; Schneiderman JH; Field and intracellular recordings were used to examine the effects of varying concentrations of penicillin on synchronous CA3 activity in guinea pig hippocampal slices . In addition to the high-amplitude bursts, extracellular recordings in the distal apical dendrites (700-1200 microns from the soma) revealed biphasic mini field potentials (MFPs) which were not evident at the soma in 2000 IU/ml . A long-lasting (76 ms) field potential (A potential) with a waveform similar to the positive component of the MFP initiated the bursts . The cellular correlate of the positive component of the MFP and of the A potential appeared to be an EPSP and that of the negative component of the MFP and IPSP . Reductions of penicillin concentration below 2000 IU/ml (3.4 mM) decreased the burst rate and amplitude and increased burst threshold . At concentrations below 250 IU/ml the bursts were blocked and the MFPs increased in amplitude and occurred rhythmically at a mean frequency of 2.6 Hz . At intermediate concentrations the bursts arose from the rhythmic background . This activity more closely resembles that recorded with electroencephalography in human epileptic foci than does the high-dose penicillin preparation and may provide a better model of epileptiform discharge.

Klin Wochenschr, 1986 Nov 17, 64(22), 1204 - 8
Meningopolyneuritis Bannwarth with focal nodular myositis . A new aspect in Lyme borreliosis; Schmutzhard E et al.; A patient with serologically confirmed infection by Borrelia burgdorferi presenting with painful paresis and atrophy of the proximal muscles of both upper extremities and bilateral facial paresis is described . Electromyography showed a neurogenic and myopathic pattern, and creatine kinase was raised . Muscle biopsy revealed the typical signs of focal myositis . Treatment with i.v . penicillin led to dramatic clinical and serological improvement . Muscle biopsy was repeated 2 months later; neurogenic changes were still present, but no inflammatory signs could be seen anymore . Thus, the presented case may be the first reported of meningopolyneuritis accompanied by focal nodular myositis, in the second stage of Lyme borreliosis.

JAMA, 1986 Nov 14, 256(18), 2561 - 2
Intravenous penicillin desensitization and treatment during pregnancy; Ziaya PR et al.; Untreated syphilis during pregnancy may result in stillbirth in one fourth of cases, while in infants who survive, there may be serious immediate and delayed manifestations . Penicillin is the drug of choice for treating both mother and fetus . We describe a woman with an allergy against both major and minor determinants of penicillin in whom syphilis was diagnosed on routine obstetric screening . Her obstetric history included one vaginal delivery at term and four subsequent spontaneous abortions at 12 to 16 weeks . The patient underwent desensitization utilizing graduated intravenous doses of penicillin followed by treatment with a constant infusion for eight days . She experienced no serious allergic reactions requiring alteration of therapy . We conclude that antibiotic desensitization may be a safe alternative during pregnancy if performed with careful monitoring . In this case, it allowed use of penicillin rather than less desirable alternatives.

Arch Fr Pediatr, 1986 Nov, 43(9), 705 - 7
{Lyme disease . Apropos of a case in children}; Moutard ML et al.; A case of Lyme disease with purely neurological manifestations is reported in an 11 year-old girl . Positive blood and cerebrospinal fluid serology allowed for diagnosis . Treatment with Penicillin led to favourable outcome . Atypical manifestations and treatment of Lyme disease are reviewed.

Antimicrob Agents Chemother, 1986 Nov, 30(5), 798 - 801
Survey of anaerobic susceptibility patterns in Canada; Bourgault AM et al.; The in vitro activity of penicillin, cefoxitin, moxalactam, ticarcillin, clindamycin, chloramphenicol, and metronidazole against 590 anaerobic isolates collected from five Canadian hospitals during 1984 was determined by an agar dilution technique . Cefoxitin, clindamycin, chloramphenicol, and metronidazole were very active against most of the isolates . No major regional differences in the susceptibility patterns were observed.

Int J Clin Pharmacol Ther Toxicol, 1986 Nov, 24(11), 622 - 4
Plasma penicillin-G parameters in man after intraduodenal or intramuscular administration; Gonciarz Z et al.; Concentrations of penicillin-G produced in serum by either direct intraduodenal (i.d.) or intramuscular (i.m.) administration were compared in 9 healthy volunteers . Serum specimens were assayed by the Sarcina lutea cup plate method . The peak serum levels achieved by i.d . application were similar to those observed after intramuscular dose . However, higher concentrations were better sustained after i.m . penicillin . We concluded that intraduodenal administration of penicillin-G could be considered as an alternative for i.m . injection.

South Med J, 1986 Nov, 79(11), 1461 - 2
Cardiobacterium hominis causing late prosthetic valve endocarditis; Jolie A et al.; We have described a patient with a prosthetic mitral valve who had endocarditis due to Cardiobacterium hominis 14 years after valve placement . She was cured with a six-week course of antibiotics, and valve replacement was not required . A four- to six-week course of ampicillin or penicillin G appears to be the therapy of choice.

Acta Paediatr Scand, 1986 Nov, 75(6), 964 - 9
Serum-sickness-like disease is a common cause of acute arthritis in children; Kunnamo I et al.; Among 283 children in a prospective study of arthritis we found 15 patients with a self-limited serum-sickness-like disease consisting of urticaria or joint erythema and mostly polyarticular arthritis . The mean duration of joint symptoms was 5.9 days . A preceding infection was reported in 12 patients and 12 had received drugs, the therapy starting on average 12.8 days before the onset of joint symptoms . In 9 cases the drug was penicillin . Four patients had recurrent attacks . Circulating immune complexes were detected in the serum of 12 patients, but specific IgE antibodies to penicillin only in 3 patients . The estimated annual incidence of the condition was 4.7/100,000 children under age 16.

Hautarzt, 1986 Nov, 37(11), 583 - 6
{Lyme borreliosis}; Weber K; Lyme borreliosis has in common features with another spirochetosis, syphilis, e.g . the development in three stages and the occurrence of reinfection and congenital infection . The European variant (erythema migrans disease in the broader sense) initially more often seems to have a mild course than in the United States, but lymphocytoma, Bannwarth syndrome and acrodermatitis chronica atrophicans seem to be more common in Europe . Administration of tetracycline for stage 1 and of parenteral penicillin G in high doses for stages 2 and 3 and during pregnancy is recommended.

J Bacteriol, 1986 Nov, 168(2), 947 - 52
Glucose represses formation of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine and isopenicillin N synthase but not penicillin acyltransferase in Penicillium chrysogenum; Revilla G et al.; The content of alpha-aminoadipyl-cysteinyl-valine, the first intermediate of the penicillin biosynthetic pathway, decreased when Penicillium chrysogenum was grown in a high concentration of glucose . Glucose repressed the incorporation of {14C}valine into alpha-aminoadipyl-cysteinyl-{14C}valine in vivo . The pool of alpha-aminoadipic acid increased sevenfold in control (lactose-grown) penicillin-producing cultures, coinciding with the phase of rapid penicillin biosynthesis, but this increase was very small in glucose-grown cultures . Glucose stimulated homocitrate synthase and saccharopine dehydrogenase activities in vivo and increased the incorporation of lysine into proteins . These results suggest that glucose stimulates the flux through the lysine biosynthetic pathway, thus preventing alpha-aminoadipic acid accumulation . The repression of alpha-aminoadipyl-cysteinyl-valine synthesis by glucose was not reversed by the addition of alpha-aminoadipic acid, cysteine, or valine . Glucose also repressed isopenicillin N synthase, which converts alpha-aminoadipyl-cysteinyl-valine into isopenicillin N, but did not affect penicillin acyltransferase, the last enzyme of the penicillin biosynthetic pathway.

J Clin Microbiol, 1986 Nov, 24(5), 749 - 52
Screening pneumococci for penicillin resistance; Swenson JM et al.; Eighty-four pneumococci with various MICs of penicillin (38 with MICs of less than or equal to 0.06 micrograms/ml {susceptible}, 35 with MICs of 0.12 to 1.0 micrograms/ml {relatively resistant}, and 11 with MICs of greater than 1.0 micrograms/ml {resistant} ) were screened by a disk diffusion test using oxacillin and methicillin to see how well they distinguished penicillin-susceptible strains from those with decreased susceptibility to penicillin . The effects of Mueller-Hinton agar plus 5% sheep blood and Trypticase soy agar plus 5% sheep blood and two atmospheres, ambient air and a candle extinction jar (increased CO2), were compared . There were no obvious differences between the effects of the two media, but zones were generally larger in ambient air than in increased CO2 . Although the oxacillin test can separate penicillin-susceptible and -resistant strains, it cannot separate penicillin-resistant from relatively penicillin-resistant strains by using the breakpoint of less than 20 mm recommended by the National Committee for Clinical Laboratory Standards . When the 20-mm breakpoint was applied to methicillin, 12% of the relatively resistant strains tested were erroneously classified as susceptible . When different breakpoints were used for methicillin, there was better separation of the two classes of penicillin-resistant isolates, but a few relatively resistant strains were still classified as susceptible . We recommend that oxacillin, not methicillin, be used as the screening agent with Mueller-Hinton sheep blood agar and ambient air incubation and that the breakpoint be less than 20 mm to indicate resistance or relative resistance.

Epilepsia, 1986 Nov-Dec, 27(6), 678 - 84
Dicarboxylic amino acids block epileptiform activity in hippocampal slice; ffrench-Mullen JM et al.; Effects of prolonged (5-10 min) continuous perfusion of excitatory amino acids on penicillin (PEN)-evoked epileptiform activity in hippocampal slices were examined with extracellular and intracellular recordings . L-glutamate (GLU), L-aspartate (ASP), quisqualate (QUIS), and N-methyl-D,L-aspartate reversibly depressed multiple (epileptiform) population spikes elicited by PEN (1.7 mM) . Intracellularly recorded, PEN-evoked paroxysmal depolarization shifts (PDS) were partially blocked by 1 mM GLU and largely eliminated by 2 mM GLU or ASP . In the presence of PEN, perfusion with both GLU and ASP induced a transient 4 to 6-mV depolarization, usually followed by spontaneous return of membrane potential to control levels . During the amino acid (AA)-induced block of epileptiform activity, there was no significant change in resting membrane potential, input resistance, or the ability to fire action potentials in response to depolarization, indicating that the decreased responsiveness is not a consequence of nonspecific pyramidal cell overdepolarization . The observed depression of epileptiform activity by continued exposure to GLU and its analogues may reflect desensitization or another regulatory mechanism to limit overexcitation.

Schweiz Med Wochenschr, 1986 Oct 18, 116(42), 1426 - 30
{Disease (Lyme disease) in pediatric patients in Switzerland caused by spirochetes (Borrelia burgdorferi) of Ixodes ricinus}; Schaad UB et al.; Lyme disease in children is studied in the light of questionnaires sent out twice to departments and divisions of pediatrics in Switzerland . Thirty-six serologically proven cases were collected . The 48 clinical signs attributed to Lyme disease involved the skin in 40%, the nervous system in 40%, and the joints in 20% . They were erythema chronicum migrans (13), lymphocytoma (4), acrodermatitis chronica atrophicans (2), peripheral facial palsy (14), sensomotor radiculoneuritis (2), meningoencephalitis (3) and arthritis (10, 7 of which were monoarthritic) . Only half the patients had a history of tick-bite . Antibiotic therapy, usually with penicillin, reduced both the duration of symptoms and frequency of secondary disease . Cardiac involvement and chronic stages with residua were not observed in this series.

Eur J Biochem, 1986 Oct 15, 160(2), 231 - 8
Nucleotide sequence of the pbpA gene and characteristics of the deduced amino acid sequence of penicillin-binding protein 2 of Escherichia coli K12; Asoh S et al.; We have determined the nucleotide sequence of the pbpA gene encoding penicillin-binding protein (PBP) 2 of Escherichia coli . The coding region for PBP 2 was 1899 base pairs in length and was preceded by a possible promoter sequence and two open reading frames . The primary structure of PBP 2, deduced from the nucleotide sequence, comprised 633 amino acid residues . The relative molecular mass was calculated to be 70867 . The deduced sequence agreed with the NH2-terminal sequence of PBP 2 purified from membranes, suggesting that PBP 2 has no signal peptide . The hydropathy profile suggested that the NH2-terminal hydrophobic region (a stretch of 25 non-ionic amino acids) may anchor PBP 2 in the cytoplasmic membrane as an ectoprotein . There were nine homologous segments in the amino acid sequence of PBP 2 when compared with PBP 3 of E . coli . The active-site serine residue of PBP 2 was predicted to be Ser-330 . Around this putative active-site serine residue was found the conserved sequence of Ser-Xaa-Xaa-Lys, which has been identified in all of the other E . coli PBPs so far studied (PBPs 1A, 1B, 3, 5 and 6) and class A and class C beta-lactamases . In the higher-molecular-mass PBPs 1A, 1B, 2 and 3, Ser-Xaa-Xaa-Lys-Pro was conserved . In the putative peptidoglycan transpeptidase domain there were six amino acid residues, which are common only in the PBPs of higher molecular mass.

Br Med J (Clin Res Ed), 1986 Oct 4, 293(6551), 857 - 9
Effect on prescribing of the limited list in a computerised group practice; Irwin WG et al.; The prescribing of drugs in the therapeutic classes that are affected by the government's limited list was investigated in a computerised group practice of just over 3,000 patients . Prescribable drugs in categories that are affected by the list were identified for two consecutive six month periods before and one six month period after the introduction of the list . A significant decrease in the prescribing of cough and cold remedies, vitamins, and antacids occurred after the list was introduced, whereas no change occurred in the prescribing of laxatives, benzodiazepines, or analgesics . The prescribing of iron and penicillin increased significantly after the list was introduced, whereas the use of H2 antagonists and non-steroidal anti-inflammatory drugs showed no significant change.

Sex Transm Dis, 1986 Oct-Dec, 13(4), 245 - 50
The effect of C3 depletion on resistance of hamsters to infection with the yaws spirochete; Steiner BM et al.; The role of complement in humoral-mediated resistance to frambesial infection (yaws) needs to be defined . The level of serum C3 was reduced shortly after infection of hamsters with Treponema pallidum subspecies pertenue . Five weeks after frambesial infection, the serum C3 level began to increase and by week 7 no difference was detected between infected and uninfected hamsters . When C3 was depleted in hamsters by injection of 20 units of cobra venom factor (CoVF), two alterations in host resistance to frambesial infection occurred . Depletion of C3 abrogated the ability of immune serum to confer complete protection on normal hamsters against infection with the yaws spirochete . In all hamsters receiving immune serum but not CoVF, lesions failed to develop and lymph nodes weighed significantly less (P less than or equal to 0.1) than those of controls . Furthermore, no treponemes were detected in the lymph nodes of passively immunized animals . Second, depletion of C3 increased the susceptibility of hamsters to frambesial infection . The onset and progression of frambesial lesions were enhanced as compared with frambesial-infected hamsters not treated with CoVF . Finally, CoVF treatment did not reduce the ability of frambesia-immune hamsters cured of disease with penicillin to resist reinfection . These results demonstrate that complement influences the pathogenesis of yaws.

J Reconstr Microsurg, 1986 Oct, 3(1), 33 - 7
Peripheral nerve injection injury: an experimental pilot study of treatment modalities; Yaffe B et al.; The accidental injection of various drugs into peripheral nerves has serious medical complications and medicolegal implications . The most neurotoxic substances of II agents tested in a previous study were penicillin G, diazepam, and chlorpromazine . The appropriate management of such an injury has not been well-established . In an attempt to define the proper treatment in accidental peripheral nerve injection, an experimental study was carried out, in which 70 sciatic nerves of rats were injected intrafascicularly with penicillin G and treated by neurolysis, neurolysis and Celestone irrigation (betamethasone, a synthetic glucocorticoid), and neurolysis and saline irrigation . The degree of damage was evaluated histologically after two weeks . Statistical analysis of the results showed that neurolysis performed at 24 hours after the injury lessened the damage to the peripheral nerve . No additional improvement was found when, in addition to neurolysis, the nerves were irrigated with Celestone or saline solutions.

J Antimicrob Chemother, 1986 Oct, 18(4), 537 - 45
Rapid high performance liquid chromatographic assay of cephalosporins in biological fluids; Chan CY et al.; A simple isocratic HPLC method is described for the rapid analysis of cephalosporins in body fluids . Sample preparation by protein precipitation takes only five minutes; HPLC analysis is completed within two to ten minutes, using one of two simple solvent mixtures eluted on a single C18 reversed phase column . Nine cephalosporins and nine types of body fluid were formally analysed, but the system was also found to be suitable for the assay of benzyl penicillin, ampicillin, cloxacillin, carbenicillin and chloramphenicol . It is likely that this method, with only minor modifications, would be suitable for the analysis of most beta-lactam antibiotics in most clinical specimens . The method is therefore particularly recommended for use in clinical laboratories.

South Med J, 1986 Oct, 79(10), 1301 - 3
Retroperitoneal actinomycosis; Palmer TE et al.; A 44-year-old man had an abscess involving the left psoas muscle and inferior pole of the left kidney associated with characteristic sulfur granules of actinomycosis . The patient was treated with surgical drainage and debridement and with intensive and prolonged penicillin therapy, resulting in a clinical cure and resolution of both the hydronephrosis and the retroperitoneal mass.

Antimicrob Agents Chemother, 1986 Oct, 30(4), 553 - 8
Penicillin-binding proteins of penicillin-susceptible and -resistant pneumococci: immunological relatedness of altered proteins and changes in peptides carrying the beta-lactam binding site; Hakenbeck R et al.; There are several major differences between the penicillin-binding proteins (PBPs) of highly penicillin-resistant and -susceptible strains of pneumococci . The highest-molecular-size PBP 1a (98 kilodaltons {kDa}) of susceptible pneumococci is not detectable in resistant bacteria . Instead, resistant strains contain a PBP of smaller size: 92 and 94 kDa in South African strains 8249 and A95210, respectively, and 96 kDa in New Guinea strain 2955 (S . Zighelboim and A . Tomasz, Antimicrob . Agents Chemother . 17:434-442, 1980) . Using antibodies prepared against PBP 1a of penicillin-susceptible pneumococci, we demonstrated that these anomalous-sized proteins in the resistant strains are immunologically related to PBP 1a of penicillin-susceptible bacteria . A second difference between the PBP patterns of strain 8249 and the susceptible pneumococci is that the 78-kDa PBP 2b is not detectable by the radioactive penicillin binding assay in the resistant strain . Using antibodies prepared against PBP 2b of susceptible cells, we demonstrated the presence of PBP 2b in membrane preparations from strain 8249 cells . Thus, the poor detection of this PBP appears to be related to its greatly decreased affinity for the antibiotic molecule . We also compared the patterns of penicillin-labeled peptides derived from PBPs of resistant and susceptible cells during partial proteolysis by V8 protease . Several changes were observable in small peptides carrying the beta-lactam binding site generated from the high Mr (PBP 1a-related) binding proteins . In contrast, no differences in the pattern of penicillin-labeled peptides were seen when the pattern of PBP 2a of susceptible pneumococci was compared with the peptide pattern of PBP 2a from resistant strains . One of the resistant isolates (strain 2955) also had a PBP 3 with a higher-than-normal molecular weight . This protein gave strong positive reaction with antibodies against PBP 3 of susceptible cells . Examination of the pattern of penicilloyl peptides generated from the susceptible and resistant PBP 3s during partial proteolysis revealed only differences which seem to reside distant from the beta-lactam binding site.

J Bacteriol, 1986 Oct, 168(1), 199 - 206
Activity of penicillin-binding protein 3 from Escherichia coli; Pisabarro AG et al.; The activity of penicillin-binding protein 3 of Escherichia coli has been studied both in vivo and in ether-permeabilized cells . The peptidoglycan transpeptidase activity of penicillin-binding protein 3 appears to use either nascent or exogenously added UDP-N-acetylmuramyl tripeptide-derived substrates as acceptors . By means of a defilamentation system which elicited the activity of penicillin-binding protein 3 in vivo, the structure of peptidoglycan made by this enzyme has been elucidated . This peptidoglycan, very probably of septal location, contained increased amounts of cross-linked peptidoglycan as well as a higher ratio of tripeptide-containing cross-linked subunits.

Acta Ophthalmol (Copenh), 1986 Oct, 64(5), 553 - 6
Visual evoked response in syphilitic optic atrophy . A case report; Kerty E et al.; A case of neurosyphilis is described . The presenting symptoms were reduced visual acuity and impaired colour vision . The examination revealed bilateral optic atrophy and acquired red-green colour defect . A syphilitic aetiology was based on positive serological tests in blood and CSF, pleocytosis and increased total protein in the CSF . The abrupt decline in visual acuity was arrested by treatment with penicillin and systemic steroids, but normalization of vision was not obtained . All VER-records, of P2 latencies and morphologies were surprisingly normal, but the amplitudes were reduced.

J Allergy Clin Immunol, 1986 Oct, 78(4 Pt 1), 645 - 52
T cell reactivity to penicillin: phenotypic analysis of in vitro activated cell subsets; Koponen M et al.; Patients with penicillin allergy demonstrate a T cell proliferative response after in vitro stimulation with penicillin G (Pen G) and other beta-lactam antibiotics . To understand better penicillin-allergic reactions, T cell subset stimulation with Pen G was studied and compared with other soluble (tetanus toxoid and purified protein derivative {PPD}) and membrane-bound viral (influenza A and Epstein-Barr viruses) antigens . A double fluorescence method for flow cytometry was used to evaluate the activated cells simultaneously by pyronin Y staining of RNA and by indirect immunofluorescence of cell surface T4, T8, or Leu 8 antigens . The antigens used stimulated mainly the T4+ subset (greater than 90%), whereas the number of activated T8 cells was slightly increased only in Pen G- and influenza A-triggered cultures (5% to 15%) . Leu 8 antigen was used to analyze more precisely the activated T4+ cells . Pen G and influenza A and Epstein-Barr viruses stimulated both T4+, Leu 8+ (greater than 50% of activated cells, inducers for suppressor cells), and T4+, Leu 8- (helpers for B cells) subsets, whereas PPD activated mainly T4+, Leu 8- subpopulations . These results indicate that penicillin-allergic patients with skin symptoms demonstrate a T cell subset stimulation that resembles more the reaction versus viral antigens (membrane incorporated) than to soluble antigens like PPD . These results suggest that Pen G is presented to T cells like viral proteins and might thus cause allergic reactions resembling skin symptoms observed in viral diseases.

Physiologie, 1986 Oct-Dec, 23(4), 237 - 43
The diagnostic value of intradermal tests with penicilloyl-dextran and aspiryl-polylysine; Cirstea M et al.; Intradermal tests (i.d.t.) with penicillin (P) and penicilloyl-dextran (P-Dex) were performed in 32 penicillin allergic patients and in 37 controls with allergy to other drugs . The incidence of the positive i.d.t . was much higher in the group of penicillin allergy of immediate type (17 of 18 patients) than in the group of penicillin allergy of half-late or late type (4 of 14 cases) . I.d.t . with P and P-Dex were concordant in 75% of cases . Among 28 patients with penicillin allergy tested with both reagents, i.d.t . positive only to P-Dex were found in two cases . The utilisation of i.d.t . with P-Dex or penicilloyl-polylysine (PPL) in penicillin allergy furnishes, therefore, only very modest additional information besides that furnished by i.d.t . performed with plain penicillin . I.d.t . with aspiryl-polylysine (APL) were performed in 23 patients with aspirin allergy/intolerance and in 60 controls with allergy to other drugs . 70% of the individuals with aspirin allergy and 27% of the patients with allergy to other drugs showed positive i.d.t . to APL . Although the specificity of i.d.t . with APL in aspirin allergy seems lower than that of i.d.t . with P-Dex and PPL in penicillin allergy, a positive cutaneous test with APL may constitute an important argument for the allergic nature of an aspirin adverse reaction evoking an allergic mechanism.

J Biol Chem, 1986 Sep 25, 261(27), 12562 - 7
alpha-Amanitin uptake into hepatocytes . Identification of hepatic membrane transport systems used by amatoxins; Kroncke KD et al.; Hepatic transport studies with amatoxins, toxic bicyclic octapeptides from poisonous mushrooms of the genus Amanita were performed, using {(6'-O,1'-N-di{3H}methyl)trp4}-alpha-amanitin and {(6'-O,1'-N-di-methyl)trp4}-{4-{3H}desmethyl)hyi3}-gamma-ama nitin . Uptake into hepatocytes from rat liver was inhibited by taurocholate and antamanide . Photoaffinity labeling studies with isolated hepatocytes and basolateral plasma membranes, using the sodium salt of (7,7-azo-3 alpha, 12 alpha-dihydroxy-5 beta-{3 beta-3H}cholan-24-oyl)-2- aminoethanesulfonic acid demonstrated that the presence of alpha-amanitin decreased the labeling of the two sinusoidal bile salt-binding membrane polypeptides with the apparent molecular weights of 54,000 and 48,000 . In basolateral plasma membrane vesicles amanitin uptake was temperature-dependent and could be stimulated 1.5 to 2-fold by an out to in Na+ gradient as compared to a K+ gradient or sucrose and 2 to 2.5-fold as compared to amanitin equilibration (overshoot) . Kinetic studies proved saturability of amanitin uptake in the presence and absence of a Na+ gradient . Membrane transport could be inhibited by taurocholate, antamanide, phalloidin, prednisolone, and silybin, but not by penicillin G or thioctic acid . Hepatic uptake of amatoxins is mediated by the sinusoidal bile salt-transport systems which are also involved in the uptake of antamanide and phalloidin . This supports the concept of a multispecificity of hepatic transport systems for a wide variety of amphipathic molecules.

Brain Res, 1986 Sep 10, 382(1), 139 - 44
Electrical stimulation can inhibit synchronized neuronal activity; Durand D; The effect of electrical stimulation on abnormal neuronal activity was studied in the hippocampus in vitro . Epileptiform electrical activity was induced by adding penicillin or picrotoxin to the perfusing medium . Orthodromic stimulation generated large repetitive field potentials measured extracellularly . Electrical stimulation was then applied to the neurons with a 50 micron electrode located in the somatic layer . Large decreases in the amplitude of the population spikes were generated when stimulation was synchronized with the electrical activity . The inhibitory effect was charge-dependent and could be obtained with applied electrical charges similar to those used to stimulate nerves in the central nervous system . It is suggested that this method could be useful to prevent the synchronization and propagation of epileptic seizures.

Ukr Biokhim Zh, 1986 Sep-Oct, 58(5), 12 - 22
{Thiol-disulfide metabolism as a mechanism in the formation of albumin minor fractions with pI 5.2-7.4 in various pathologic states}; Troitskii GV et al.; The mechanism of formation of minor isoelectric fractions of albumin with pI 5.2-7.4 which arise in the blood channel with pathologies is studied . This phenomenon is nonspecific for any definite type of the disease and is possibly a result of the disease gravity . The mechanism of thiol-disulphide metabolism is shown to underlie the appearance of isoelectric fractions of albumin with pI 5.2-7.4 . The fractions possess a lower ability to bind the bromo-phenol blue dye and a higher ability to bind penicillin.

Ann Ophthalmol, 1986 Sep, 18(9), 260 - 1
Neurosyphilis and retrobulbar neuritis in a patient with AIDS; Zaidman GW; A 33-year-old homosexual patient with acquired immune deficiency syndrome (AIDS) developed sudden unilateral loss of vision . Slit-lamp and funduscopic examination of the affected eye was completely within normal limits . The patient, however, had a Marcus Gunn pupil, decreased color vision, and a large central scotoma on visual field examination . This was consistent with retrobulbar optic neuritis . Laboratory investigation revealed a highly positive serum and cerebrospinal fluid venereal disease reaction level (VDRL) . A diagnosis of neurosyphilis was made, and the patient was treated with ten days of intravenous penicillin therapy . Ophthalmologists should be aware that many patients with AIDS have also been exposed to syphilis . Regardless of their clinical presentation, all AIDS patients should be examined and tested for syphilis and treated as is necessary.

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