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Neurology, 1994 Jul, 44(7), 1203 - 7
Comparison of intravenous penicillin G and oral doxycycline for treatment of Lyme neuroborreliosis; Karlsson M et al.; To compare the efficacy of oral doxycycline and IV penicillin G for the treatment of neuroborreliosis, we randomized consecutive patients with Lyme neuroborreliosis to receive either IV penicillin G (3 g q 6 h) or oral deoxycycline (200 mg q 24 h) for 14 days . All patients had antibodies against Borrelia burgdorferi in serum, CSF, or both, or had a positive CSF culture . Twenty-three patients randomized to penicillin G and 31 patients to doxycycline were included in the study . All patients improved during treatment, and there were no significant differences between the two treatment groups in patient scoring, CSF analysis, or serologic and clinical follow-up during 1 year . There were no treatment failures, although one patient in each treatment group was re-treated because of residual symptoms . In conclusion, oral doxycycline is an adequate and cost-effective alternative to IV penicillin for the treatment of Lyme neuroborreliosis.

J Neurol Neurosurg Psychiatry, 1994 Jul, 57(7), 865 - 7
Jarisch-Herxheimer reaction in a patient with neurosyphilis; Zifko U et al.; A 40 year old man presented with progressive personality changes in the previous six months . Specific serological tests for syphilis in blood and CSF were highly positive and CSF sedimentation showed signs of an inflammatory process . Ten hours after the start of penicillin treatment a severe symptomatic Jarisch-Herxheimer reaction with alteration of level of consciousness, pupillary changes, and focal neurological signs developed . Jarisch-Herxheimer reaction may occur in various settings, particularly in the treatment of syphilis . Investigation of CSF before the treatment may predict a potential risk . Corticosteroid treatment has been suggested for prevention.

Pediatrics, 1994 Jul, 94(1), 24 - 8
The incidence of prenatal syphilis at the Boston City Hospital: a comparison across four decades; Klass PE et al.; OBJECTIVE . To examine the incidence and epidemiologic correlates of congenital syphilis at an inner-city Boston hospital, and draw comparisons with the situation at the same hospital 40 years ago . DESIGN . Chart review and comparison with data collected in 1951 . SETTING . Maternity and pediatric services at Boston City Hospital . METHODS . A study conducted in 1951 on the maternity service of Boston City Hospital in which demographic data were collected on all women admitted in labor over a 5-month period was replicated . Serologic testing for syphilis was carried out on these women, and the demographic and medical correlates of positive maternal syphilis serology were examined . This study was repeated exactly 40 years later, using the cord blood screening for syphilis done routinely at delivery and a review of prenatal records . RESULTS . From a group made up largely of married white women in 1951, the study population shifted in 1991 to a group made up mostly of minority women, with 75% unmarried . In 1951, 24 patients were diagnosed with syphilis either before or during the pregnancy, giving a prevalence rate of 2.4% . In 1991, 25 of 647 women were diagnosed with syphilis, for a prevalence rate of 3.9% . The women with positive cord blood serologies had a higher rate of other sexually transmitted diseases and substance abuse . No symptomatic cases of congenital syphilis were seen in 1951 or in 1991, although at least 11 of the 26 infants born to mothers with positive serologies in 1991 received intravenous penicillin therapy . CONCLUSIONS . The continued prevalence of diagnosed syphilis in women at delivery reflects an inner-city epidemic of congenital syphilis that is tied to substance abuse, human immunodeficiency virus, and changing social patterns, as well to older problems of serologic screening, prenatal care, treatment failures, and maternal reinfection . It is essential that screening programs be maintained and improved in this high-risk population, and that infants born to mothers with positive serologies receive full and adequate treatment if there is any doubt at all about their infection status.

J Neurol Sci, 1994 Jul, 124(2), 188 - 97
Dynamic changes of focal hypometabolism in relation to epileptic activity; Witte OW et al.; The interictal hypometabolism in patients with focal epilepsy is usually regarded as stationary . In this study we investigated to which extent the hypometabolism may depend on the activity of the epileptic focus . In focal penicillin-induced epilepsy in rats the epileptic focus is hypermetabolic . This focus is accompanied by hypometabolism in widespread areas of adjacent cerebral cortex . The experiments revealed that these metabolic alterations are transient . Data from a patient experiencing a focal seizure during PET scanning gave similar results . They showed that the transition from interictal to ictal activity was accompanied by the development of hypermetabolic epileptic focus and the dynamic enlargement of the surrounding hypometabolism . Both, the experimental and clinical data provide evidence that the cerebral hypometabolism may vary in size depending on the activity of the epileptic focus . It is hypothesized that in human PET studies the large interictal hypometabolism may prevent the identification of hyperactive interictal epileptic foci due to the partial volume effects resulting from the limited spatial resolution of PET cameras.

Intensive Care Med, 1994 Jul, 20 Suppl 3, S14 - 20
Pharmacokinetic characteristics of piperacillin/tazobactam; Sorgel F et al.; Piperacillin/tazobactam is a new combination of a broad-spectrum penicillin and a beta-lactamase inhibitor . In studies in healthy volunteers, the pharmacokinetics of piperacillin combined with tazobactam were similar to those of piperacillin alone . In contrast, tazobactam administered with piperacillin achieved higher plasma concentrations and had a longer half-life than tazobactam administered alone . Intravenous infusion of 4.0 g piperacillin with 0.5 g tazobactam over 5 min resulted in mean maximum plasma concentrations of 380 micrograms piperacillin/ml and 35.3 micrograms tazobactam/ml; half-lives were 1.14 h for piperacillin and 0.92 h for tazobactam . Within 30 min of infusion, piperacillin/tazobactam achieves 16-85% of plasma concentrations in skin, muscle, lung, gallbladder, and intestinal mucosa . Plasma and tissue levels remain above the MIC90s of major pathogens for 2 h post administration . These findings show that piperacillin/tazobactam is truly synergistic combination which can be expected to be effective in treating a wide variety of infections in the clinical setting.

Clin Exp Dermatol, 1994 Jul, 19(4), 321 - 3
Pre-septal cellulitis and facial erysipelas due to Moraxella species; Cox NH et al.; We describe a patient with an acute ulcerated pre-septal cellulitis with subsequent spread across the face, in whom conjunctival swabs demonstrated the presence of Moraxella species . Unusually, this organism was resistant to penicillin . Clinical improvement was only achieved when treatment with co-amoxiclav was commenced on the basis of the antibiotic sensitivities demonstrated by culture of this organism . Moraxella species are rare skin pathogens but may be underestimated as they usually respond to a wide range of antibiotics; they should be considered as a cause of facial cellulitis or erysipelas which responds poorly to conventional therapy.

In Vitro Cell Dev Biol Anim, 1994 Jul, 30A(7), 420 - 4
Altered free calcium transients in pig kidney cells (LLC-PK1) cultured with penicillin/streptomycin; Bird SD et al.; The effect of a conventional antibiotic (penicillin/streptomycin) mixture on the widely used kidney epithelial cell line, LLC-PK1, was investigated by measuring growth and intracellular free calcium . Free calcium concentration was the same in cells cultured for 3 to 7 wk with ("plus") and without ("minus") antibiotics both at rest and when challenged with high (14 mM) external calcium . When exposed to vasopressin, minus cells exhibited significantly smaller calcium transients than plus cells . A similar difference existed for transients elicited by a calcium ionophore, 4-br-A23187 . After longer periods of culture (> 20 wk), minus cells grew slower than plus cells but on reaching confluence (minus cells took 1 day longer) the morphologies and viabilities were indistinguishable . The finding that culture with penicillin/streptomycin reversibly modified some properties of LLC-PK1 cells, at least partly through altered calcium homeostasis, is of importance for workers using this cell model to study drug effects and raises the general possibility of similar effects on other cultured cells.

Clin Infect Dis, 1994 Jul, 19(1), 143 - 5
Bilateral pulmonary infiltrates in association with disseminated actinomycosis; Dontfraid F et al.; The most common infectious cause of bilateral upper-lobe pulmonary disease is tuberculosis . However, we recently encountered a patient with bilateral apical infiltrates and multiple soft-tissue abscesses caused by Actinomyces odontolyticus . Other findings included fever, weight loss, and leukocytosis, and the patient's only known source of immunosuppression was a long history of alcoholism . There was no history of diabetes, steroid use, or other chronic underlying disease . The diagnosis was made by culture of drainage fluid from one abscess . Therapy with intravenous penicillin G led to rapid clinical improvement and reduction in the infiltrates . To our knowledge, the presentation of pulmonary infection, with bilateral apical infiltrates due to A . odontolyticus has not been previously reported in the medical literature.

Pharm Res, 1994 Jul, 11(7), 984 - 9
Drug binding by reservoirs in elastomeric infusion devices; Jenke DR; Drug binding by an elastomeric infusion device reservoir was assessed by measuring its ability to bind fifteen model solutes . Octanol/water (o/w) and hexane/water (h/w) partition coefficients were regressed against the reservoir's solute equilibrium binding constant to generate a binding model . The reservoir's drug binding ability was calculated with the model and drug partition coefficients, which were determined for seventeen commonly infused drugs including tobramycin, gentamicin, penicillin G, piperacillin, lidocaine, morphine, ceftriaxone, imipenem-cilastatin, amphotericin B, ticarcillin and clavulanate, pentamidine, vancomycin, foscarnet, desferoxamine, acyclovir, fluconazole and vinblastine . Formulations studied included 0.9% Saline and 5% Dextrose . With the exception of lidocaine, imipenem, vinblastine and fluconazole, octanol/formulation and hexane/formulation partition coefficients were too low to be measured for these drugs . Thus, the majority of the drugs, when reconstituted in 0.9% Saline or 5% Dextrose, will not be bound by the reservoirs . The magnitude of drug loss for the most highly bound species, fluconazole, is less than 2% . Therefore the reservoirs used in this study are essentially inert with respect to binding of the drugs evaluated in this study.

Leber Magen Darm, 1994 Jul, 24(4), 171 - 3
{Acute segmental hemorrhagic penicillin-associated colitis in a 32-year-old patient}; Benz C et al.; We report on a 32-year old patient who developed acute abdominal cramps and bloody diarrhea two days after taking phenoxymethyl penicillin . After excluding other causes, we diagnosed an acute segmental hemorrhagic penicillin associated colitis . In this case report we discuss the literature on this diagnosis and present the etiology, course, prognosis, and differential diagnosis of this entity.

Eur Respir J, 1994 Jul, 7(7), 1379 - 80
Skin lesions and an intrathoracic mass; Vasmel WL et al.; We describe a case of thoracic actinomycosis in a previously healthy man . The clinical features were a paramediastinal mass with skin lesions due to haematogenic dissemination . After parasternal mediastomy, the diagnosis was made . After treatment with penicillin, there was complete recovery.

Rev Med Chil, 1994 Jul, 122(7), 795 - 802
{Mushroom poisoning in the IX region . Role of Amanita gemmata}; Sierralta A et al.; We report four episodes of mushroom poisoning that occurred between 1986 and 1990 in the province of Malleco . Twenty five of 36 individuals who ingested the mushroom became ill; they had an acute gastroenteritis that was followed in 7 by an acute hepatitis and in one by a massive upper gastrointestinal bleeding . Three subjects with fulminant hepatic failure and the subject with the massive bleeding died . Amanita gemmate (strain described as toxic in Chile since 1967) was found in two episodes and Amanita sp in one . The clinical picture is similar to that described for Amanita phaloides . The treatment is symptomatic but penicillin and silymarin may have an antitoxic action . The importance of warning the population about the existence of toxic mushrooms in Chile is emphasized.

J Pediatr, 1994 Jun, 124(6), 859 - 62
Fatal pneumococcal septicemia in hemoglobin SC disease; Lane PA et al.; We retrospectively examined the medical and autopsy records of seven previously unpublished cases of fatal pneumococcal septicemia in children with hemoglobin SC disease . The earliest death occurred in a 1-year-old child who had congenital heart disease with cyanosis; the other children were aged 3 1/2 to 15 years . Only one child had received pneumococcal vaccine or prophylactic penicillin therapy . All seven children had an acute febrile illness and rapid clinical deterioration despite parenterally administered antibiotic therapy and intensive medical support . Erythrocyte pit counts in two patients were 40.3% and 41.7%, respectively (normal, < or = 3.6%) . Autopsy data from five cases showed marked splenic congestion without infarction in five, splenomegaly in four, and bilateral adrenal hemorrhage in three . These cases illustrate that functional asplenia predisposes some children with hemoglobin SC disease to the development of fatal septicemia after the age of 3 years . We conclude that pneumococcal vaccine should be administered to all children with hemoglobin SC disease and that acute febrile illnesses should be investigated promptly for the possibility of septicemia . The routine use of prophylactic penicillin therapy in infants and children with hemoglobin SC disease remains controversial.

Clin Infect Dis, 1994 Jun, 18(6), 1004 - 6
Leptospirosis complicated by a Jarisch-Herxheimer reaction and adult respiratory distress syndrome: case report; Emmanouilides CE et al.; Leptospirosis, severe infection due to Leptospira interrogans, is a potentially lethal disease that causes multiple organ failure . In addition to hepatic, renal, and CNS involvement, which are classic complications of leptospirosis, the disease may also be complicated by adult respiratory distress syndrome . Treatment with penicillin may precipitate a severe Jarisch-Herxheimer reaction . The mechanisms of Leptospira-induced toxicity remain obscure . We report a near-fatal case of leptospirosis in a patient who developed a JHR and respiratory failure immediately after initiation of therapy.

Lakartidningen, 1994 Jun 1, 91(22), 2255 - 6
{HIV spreads fast in Africa . Women and children especially, are at high risk}; Christenson B et al.; PIP: The HIV situation in Africa was very dismal in 1994, with about 10 million people infected . The causes of the rapid spread were the high incidence of sexually transmitted diseases (STDs), urbanization, and breakup of families because of migrations, since men often seek work at other places . In the age group of 15-19 years in Malawi, Uganda, and Zimbabwe, there were 5 HIV-infected women for 1 infected man, but in the 30-39 year age group, there 3 infected men for every 1 woman . A report from Kenya showed that 69% of boys and 25% of girls were sexually active, while 50% had more than 4 partners . Among 15-24 year old pregnant women, 36% had STDs . A study from the Ivory Coast indicated that HIV prevalence increased from 27% in 1987 to 53% in 1992 among patients who were seeking care for an STD in Abidjan . Among tuberculosis (TB) patients this increased from 16% to 35%, and among pregnant women from 7% in 1987 to 14% in 1992 . Another group, 745 prostitutes, were also studied in Abidjan . 48% were infected with HIV and 34% were infected both with HIV-1 and HIV-2 . It is estimated that 50-75% of HIV-infected people in Africa also had STDs, compared to 20% of the HIV-infected in Thailand and India and 5% in Brazil . It has been proven in a US cohort study that the treatment of STDs reduces the spread of HIV . In Gambia, Rwanda, Zaire, and Kenya, 50-100% of gonococcal isolates were resistant to penicillin and tetracycline, and 40% of women with symptoms of STD infection did not receive adequate treatment . A study from England indicated that both HIV and TB follow the same epidemiological patterns among men 30-39 and among women 20-29 years old . In developing countries HIV is the main risk factor for developing TB . About 4-5 million people have TB as a cofactor for HIV infection, of whom 80% are in Africa . In 1994 about 3% of TB cases were associated with HIV, which will increase to 10% by the year 2000 .

Genitourin Med, 1994 Jun, 70(3), 196 - 9
An outbreak of a penicillin-sensitive strain of gonorrhoea in Sydney men; Rowbottom JH et al.; OBJECTIVE--To describe an outbreak of gonorrhoea caused by penicillin sensitive Wild type 1B2-Wt/1B2(FS), in homosexual men in Sydney . DESIGN AND SETTING--The study sample comprised all gonococcal isolates referred to the Gonococcal Reference Laboratory (GRL), New South Wales, Australia between 1 January 1990 and 30 June 1992 . Demographic data on Wt/1B2(FS) were sought by review of all request forms accompanying specimens to the GRL . Detailed review was undertaken of the clinical records of all men with gonorrhoea which had been differentiated by auxotype and serotype (A/S) from two large STD clinics in Sydney . MEASUREMENTS AND MAIN RESULTS--The first isolation of Wt/1B2(FS) was made in April 1990 and by the end of July 1992, 140 such isolates were identified in 131 patients . The male:female ratio was 130:1 suggesting male homosexual transmission, which was confirmed in 55 of 57 evaluable cases . There was a higher proportion of pharyngeal and anal infections among Wt/1B2(FS) isolates compared with all other male gonorrhoea . Demographic information showed that 60% of men with Wt/1B2(FS) were under the age of 30, and 80% lived in Central or Eastern Sydney . CONCLUSIONS--An outbreak of a penicillin sensitive strain of gonorrhoea has occurred in Sydney, primarily among gay men living in the inner city . The extent to which the outbreak represents an increase in the risk of HIV transmission is unclear.

Appl Environ Microbiol, 1994 Jun, 60(6), 1705 - 10
Catabolism of lysine in Penicillium chrysogenum leads to formation of 2-aminoadipic acid, a precursor of penicillin biosynthesis; Esmahan C et al.; Penicillium chrysogenum L2, a lysine auxotroph blocked in the early steps of the lysine pathway before 2-aminoadipic acid, was able to synthesize penicillin when supplemented with lysine . The amount of penicillin produced increased as the level of lysine in the media was increased . The same results were observed in resting-cell systems . Catabolism of {U-14C}lysine by resting cells and batch cultures of P . chrysogenum L2 resulted in the formation of labeled saccharopine and 2-aminoadipic acid . Formation of {14C}saccharopine was also observed in vitro when cell extracts of P . chrysogenum L2 and Wis 54-1255 were used . Saccharopine dehydrogenase and saccharopine reductase activities were found in cell extracts of P . chrysogenum, which indicates that lysine catabolism may proceed by reversal of the two last steps of the lysine biosynthetic pathway . In addition, a high lysine:2-ketoglutarate-6-aminotransferase activity, which converts lysine into piperideine-6-carboxylic acid, was found in cell extracts of P . chrysogenum . These results suggest that lysine is catabolized to 2-aminoadipic acid in P . chrysogenum by two different pathways . The relative contribution of lysine catabolism in providing 2-aminoadipic acid for penicillin production is discussed.

Arthritis Rheum, 1994 Jun, 37(6), 878 - 88
Treatment of Lyme arthritis; Steere AC et al.; OBJECTIVE . To test treatment regimens for Lyme arthritis . METHODS . Patients were randomly assigned to treatment with doxycycline or amoxicillin plus probenecid for 30 days . Patients who had persistent arthritis for at least 3 months after treatment with oral antibiotics or parenteral penicillin were given intravenous ceftriaxone for 2 weeks . RESULTS . Eighteen of the 20 patients treated with doxycycline and 16 of the 18 patients who completed the amoxicillin regimen had resolution of the arthritis within 1-3 months after study entry . However, neuroborreliosis later developed in 5 patients, 4 of whom had received the amoxicillin regimen . Of 16 patients (2 from the oral antibiotic study and 14 additional patients) who had persistent arthritis despite previous oral antibiotics or parenteral penicillin, none had resolution of the arthritis within 3 months after ceftriaxone therapy . The HLA-DR4 specificity and OspA reactivity were associated with a lack of response . CONCLUSION . Lyme arthritis can usually be treated successfully with oral antibiotics, but patients may still develop neuroborreliosis . Patients with certain genetic and immune markers may have persistent arthritis despite treatment with oral or intravenous antibiotics.

Biol Chem Hoppe Seyler, 1994 Jun, 375(6), 373 - 8
Semisynthetic insulin analogues modified in positions B24, B25 and B29; Svoboda I et al.; New semisynthetic analogues of human insulin, modified in the C-terminal region of the B-chain, were prepared to refine our understanding of the importance of particular amino acid residues in the expression of hormone biological properties . The following insulin analogues were synthesized by trypsin-catalyzed peptide-bond formation between the C-terminal arginineB22 of des-octapeptide(B23-B30)-insulin and synthetic octapeptides with the epsilon-amino group of lysineB29 protected by a phenylacetyl group: {L-Lys(Pac)B29}insulin, {D-PheB24,B25,L-Lys(Pac)B29}insulin and {D-Phe(p-Et)B24, L-Lys(Pac)B29}insulin . Enzymatic deprotection using immobilized penicillin amidohydrolase yielded: human insulin, {D-PheB24,B25}insulin and {DPhe(p-Et)B24}-insulin . Biological in vitro potencies (specific binding to cultured human lymphocytes IM-9 and lipogenic potency in isolated rat adipocytes) of the semisynthetic analogues were estimated, ranging from 0.2 to 100% relative to porcine insulin.

Ital J Neurol Sci, 1994 Jun, 15(5), 229 - 37
General paresis: neuropsychological and SPECT study of five cases; Farina E et al.; Although much less common than before the advent of the antibiotics, cognitive impairment due to general paresis can still be found in clinical practice . Five patients with general paresis underwent longitudinal neuropsychological assessment; on the occasion of the final evaluation, Single Photon Emission Tomography (SPECT) was also performed in four cases . The most frequent cognitive deficit at admission was long term spatial memory impairment, which was present in four patients . Only the two patients who received the highest dosage of intravenous penicillin therapy showed significant improvement at neuropsychological tests after treatment . SPECT findings included areas of cortical hypoperfusion and/or perfusion asymmetry in three out of four patients.

Am J Vet Res, 1994 Jun, 55(6), 825 - 30
Disposition of penicillin G after administration of benzathine penicillin G, or a combination of benzathine penicillin G and procaine penicillin G in cattle; Papich MG et al.; Plasma concentration of penicillin G was evaluated in beef steers after administration of either a combination of benzathine penicillin G and procaine penicillin G in a 1:1 mixture at a dosage of 9,000 U/kg of body weight, IM (n = 5), 24,000 U/kg, IM (n = 5), or 8,800 U/kg, SC (n = 5), or benzathine penicillin G alone at a dosage of 12,000 U/kg, IM (n = 7) . Plasma concentration of penicillin G was measured by use of a high-performance liquid chromatography assay that had a limit of determination of 0.005 microgram/ml . At a dosage for this combination of 9,000 U/kg IM, and 8,800 U/kg, SC, which are approved label recommendations in Canada, and the United States, respectively, mean (+/- SEM) peak plasma concentration was 0.58 (+/- 0.15) and 0.44 (+/- 0.02) microgram/ml, respectively . Although plasma penicillin concentration was quantifiable for 7 days in the steers that received 9,000 U/kg, IM, and for 4 days in the steers that received 8,800 U/kg, SC, the concentration was < 0.1 microgram/ml in both groups after the first 12 hours . After administration of the combination at dosage of 24,000 U/kg, IM, there was an initial peak plasma concentration at approximately 2 hours; thereafter, plasma concentration decreased slowly, with half-life of 58 hours . Although plasma penicillin G concentration was quantifiable for 12 days at this dosage, concentration was < 0.1 microgram/ml after the first 48 hours . After the initial 48 hours, plasma concentration of penicillin was of similar magnitude and decreased at similar rate for the combination at dosage of 24,000 U/kg and for 12,000 U/kg of benzathine penicillin G alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Acupunct Electrother Res, 1994 Jun-Sep, 19(2-3), 129 - 40
Effect of electroacupuncture on the level of preproenkephalin mRNA in rat during penicillin-induced epilepsy; Wang BE et al.; Our previous studies have shown that seizure induced by injecting penicillin (0.24 mg/2 microliters) into hippocampus could be inhibited by electroacupuncture (EA) probably via decreasing enkephalin content in hippocampus . To determine whether this change reflected the peptide synthesis, preproenkephalin (PPE) mRNA was detected in hippocampus and some other limbic structures during seizure and after EA treatment by in situ hybridization . Four hours after injecting penicillin into hippocampus, PPE mRNA levels were significantly increased by 10 folds in entorhinal cortex, subiculum, CA1 area of hippocampus, amygdaloid nucleus and piriform cortex, whereas EA treatment apparently attenuated the seizure-induced increase of PPE mRNA in the areas mentioned above . The results indicated that EA may regulate the biosynthesis of PPE in hippocampus during seizure by an alteration in gene transcription.

Biochem Med Metab Biol, 1994 Jun, 52(1), 27 - 35
Application of molecular genetics in public health: improved follow-up in a neonatal hemoglobinopathy screening program; Zhang YH et al.; Newborn screening for the hemoglobinopathies has been shown to reduce morbidity and mortality, particularly for sickle cell anemia, by facilitating initiation of penicillin prophylaxis by 4 months of age . The purpose of the current investigation was to determine whether molecular genetic follow-up testing could be introduced into a neonatal hemoglobinopathy screening program and, if successfully introduced, whether it would reduce time to diagnostic confirmation . Between July 1, 1991, and October 7, 1992, 518 original dried blood specimens were referred from the Texas Department of Health Neonatal Hemoglobinopathy Screening Program for molecular genetic follow-up testing . Allele-specific cleavage (ASC) after amplification with matched and mismatched polymerase chain reaction primers was compared to allele-specific oligonucleotide (ASO) hybridization . By November 2, 1992, molecular genetic analyses were definitive in 506, and agreement was observed between ASC and ASO hybridization in all specimens analyzed . Approximately 13% of those initially screened FS were considered probable S/beta-thal by DNA and RNA testing . Rapid molecular genetic analysis contributed to a substantial reduction of the mean age at confirmation by approximately 50%, to about 2 months of age . ASC is a reliable method for molecular genetic analysis of dried blood specimens, providing methodology which can be readily automated . An automated method is demonstrated that is based on microtiter plate technology and will significantly reduce labor intensity and costs, while increasing sample throughput . Even with current manual testing methods, DNA and RNA analysis of initial newborn screening specimens will reduce the age at confirmation well under 4 months, the age cut-off for effective initiation of penicillin prophylaxis.

Aten Primaria, 1994 May 31, 13(9), 487 - 90
{Mycoplasma pneumoniae pneumonia: serologic study of a family outbreak in primary care}; Santos Lozano JM et al.; OBJECTIVE . To describe the clinical-radiological, epidemiological, therapeutic and evolutive characteristics of an outbreak of atypical Pneumonia in a family, which was serologically diagnosed by means of the technique of complement fixation of Pneumonia caused by Mycoplasma . DESIGN . A descriptive study . SETTING . An urban Health Centre . PATIENTS AND OTHER PARTICIPANTS . A family of 7 members, consisting of father, mother and five children . MEASUREMENTS AND MAIN RESULTS . Three presented Pneumonia caused by Mycoplasma pneumoniae, with the other family members remaining asymptomatic and serologically negative . The three cases evolved until cure . Treatment was with Macrolides in two of the cases and Penicillin in the other . Clinical-radiological dissociation existed in two of the patients . 33% had a secondary attack . CONCLUSION . The accessibility of Primary Care to microserological methods, together with the greater ease with which this level of Care can reach the family environment, allows for more precise knowledge of infectious epidemic outbreaks which occur in the community.

J Biotechnol, 1994 May 31, 34(3), 259 - 68
High density cultivation of hybridoma in charged porous carriers; Ong CP et al.; A porous carrier whose surface is charged with polyethyleneimine (PEI) was evaluated for high-density cultivation of immobilized hybridoma cells . The carrier was used either in suspension or in fixed bed . For suspended carriers, the effect of carrier pore size, ion-exchange capacity (IEC), mixing intensity and inoculum concentration on the attachment and growth of HBs MAb-producing hybridoma cells in carrier CELLSNOW EX were studied . The carrier with 100 microns pore size was more efficient than that with 500 microns in supporting cell attachment . In addition, the amount of antibody which was detected by PHA (passive hemagglutination assay) was 4-times higher in 100 microns compared with 500 microns pore size . At low initial cell concentration, 2.8 x 10(5) ml-1, the attached cells did not grow in the first 7 d as indicated by a negligible glucose consumption . However, cell proliferation was observed at high inoculum, 9 x 10(5) ml-1 . Hybridoma cells were expected to attach faster to EX with high IEC than with low IEC but results showed no significant difference . A different hybridoma cell line producing monoclonal antibody (MAb) against penicillin-G-amidase was successfully cultivated in an axial-flow fixed bed containing CELLSNOW carriers . The specific glucose uptake rate as an indicator for cell activity was 24-times higher compared with conventional chemostat cultures . The CELLSNOW carriers offers many advantages over other carriers.

Gene, 1994 May 27, 143(1), 79 - 83
The penicillin amidase of Arthrobacter viscosus (ATCC 15294); Konstantinovic M et al.; The nucleotide (nt) sequence of the gene encoding penicillin G amidase (PA) of Arthrobacter viscosus strain ATCC 15,294 was determined . The sequence contained an open reading frame of 2406 nt with a G+C content of 37% . The deduced amino-acid sequence shows significant homology with other so far identified beta-lactam amidases of Gram- bacteria.

Pol Tyg Lek, 1994 May 16-30, 49(20-22), 472 - 4
{Treatment outcome of purulent meningitis in adults from material of the Clinic of Infectious Diseases AM in Lodz in the years 1990-1991}; Wrodycki W et al.; 81 patients (pts) with bacterial meningitis hospitalised in the Clinic for Infectious Diseases in the years 1990-1991 were treated according to two therapeutic schedules . First: young pts (under 40 years), without coexisting diseases obtained Penicillin G and aminoglycoside and/or synthetic penicillin . Second: pts over 40 years old with coexisting diseases or cases of recurrent meningitis were treated with third-generation cephalosporins and aminoglycoside and/or synthetic penicillin . The mortality was 16% in the study group . 11 of 13 pts with coexisting diseases died . Neurologic sequelae were found in 23% of pts . The complete recovery was obtained in 34% of pts, more often (35.9%) in a group treated with third--generation cephalosporins comparing to 29.4% with other antibiotic therapy.

J Biotechnol, 1994 May 15, 34(2), 119 - 31
Segregated mathematical model for the fed-batch cultivation of a high-producing strain of Penicillium chrysogenum; Tiller V et al.; A new segregated mathematical model for the penicillin fed-batch process is presented and applied to the growth of the pellet-forming, industrially used high-producing strain Penicillium chrysogenum S2 . The model comprises two kinds of biomass (growing and producing, nongrowing and still producing), cell lysis, and complex medium as an important substrate for primary growth . In accordance with our experimental observation, product formation is not inhibited by glucose, but related to the growth rate . Maintenance metabolism is cell age-dependent . The model was verified with two sets of experimental data including exhaust gas measurements while keeping the estimated parameters almost constant . The presented model derived from that of Bajpai and Reuss (1980, 1981) does not describe our data properly . The particular influence of the pellet structure on the model is discussed . The necessity of new model assumptions (e.g., different kinds of biomass, non-constant maintenance coefficient) is explained by cell damage by lysis and shear forces, and the succeeding repair processes.

Ann N Y Acad Sci, 1994 May 2, 721, 178 - 93
Improved expression of a hybrid Streptomyces clavuligerus cefE gene in Penicillium chrysogenum; Queener SW et al.; A hybrid cefE gene, encoding penicillin N expandase, was constructed by fusing the promoter sequences, Pcp, and terminator sequences, Pct from the Penicillium chrysogenum pcbC gene to the open reading frame (orf), cefEorf, from the Streptomyces clavuligerus cefE gene . The resulting hybrid gene, Pcp/cefE'orf/Pct, differed from a previously reported hybrid cefE gene contained on plasmid pPS65 . The latter gene, Pcp/cefE'orf/Sct, contained the Pcp sequences fused to the S . clavuligerus cefE orf still attached to the S . clavuligerus terminator sequences, Sct . The new hybrid gene was transformed into P . chrysogenum on plasmid vector pRH6 . Transformants were selected by phleomycin resistance conferred by a hybrid ble gene present on plasmid pRH6 . The hybrid ble gene was formed by attaching Pcp sequences to the ble orf . Among transformants obtained with pRH6, one exhibited a 70-fold higher level of activity of penicillin N expandase than the best transformant previously obtained from a 10-fold larger population of pPS65 transformants . The penicillin N expandase activity in pRH6 transformant, 9EN-5-1, was fourfold higher than the activity in the S . clavuligerus strain used as the source of the cefE orf and 75% of the activity observed in an industrial strain of Cephalosporium acremonium . Sequencing of the junctions of the heterologous DNA in Pcp/cefEorf/Pct uncovered a modification of the cefE open reading frame introduced during construction of the hybrid gene; the modified open reading frame is designated cefE'orf.

Lab Invest, 1994 May, 70(5), 656 - 66
Defect of nephrogenesis induced by gentamicin in rat metanephric organ culture; Gilbert T et al.; BACKGROUND: In the rat, in utero exposure to gentamicin during early renal differentiation leads to a permanent nephron deficit . The aim of the present study was to analyze, in vitro, the potential direct effect of gentamicin on early nephrogenesis . EXPERIMENTAL DESIGN: We used paired rat metanephric organ cultures from 14 (F14) or 15-day-old (F15) fetuses . We measured gentamicin accumulation into explanted metanephroi and then assessed in vitro growth in the absence or presence of the drug . Glomerular labeling and counting were performed on the whole explant to analyze the effect of antibiotics on early nephrogenesis . RESULTS: Growth of F14 metanephric explants in the presence of 50 micrograms of gentamicin/ml was significantly reduced from 4 days onwards as compared to controls, whereas F15 explants grown with gentamicin displayed a normal in vitro development . After 6 days of culture, F14 and F15 explants had the same accumulation of gentamicin (1 microgram/mg protein) but the gentamicin content was 4 times larger in F15 explants . At both ages, gentamicin-exposed metanephric explants exhibited a significant reduction in their number of nephrons . However, the effects of 50 micrograms of gentamicin/ml on nephrogenesis were significantly more drastic on F14 than F15 explants (35% versus 18%) . When grown with 0.5 microgram of gentamicin/ml, F14 explants still exhibited a 16% defect in nephrogenesis as compared with controls, and about the same reduction was observed for cultures in the presence of 100 micrograms/ml of streptomycin and 100 IU/ml of penicillin . Incubation of F14 explants with streptomycin alone for 6 days had no effect on nephrogenesis . CONCLUSIONS: These results indicate that gentamicin induces a significant reduction in the number of nephrons in metanephric explants and that this effect is more important on less differentiated metanephroi . Metanephric organ culture combined with glomerular labeling represents a useful model to test the effect of various growth factors and other drugs on early nephrogenesis.

Allergy, 1994 May, 49(5), 317 - 22
Immediate allergic reactions to amoxicillin; Vega JM et al.; A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated . A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives . Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX . RAST for BPO-PLL and AX-PLL was done . When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX . A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics . We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG . Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema . All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG . Skin tests with AX were positive in 34 (63%) patients . RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%) . None of the sera with negative RAST for AX were positive to BPO . Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative . PG was well tolerated by all 54 patients . We describe the largest group of AX-allergic patients who have tolerated PG reported so far . Diagnosis of these patients can be achieved only if specific AX-related reagents are employed . Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.

Epilepsy Res, 1994 May, 18(1), 43 - 55
Afterpotentials of penicillin-induced epileptiform neuronal discharges in the motor cortex of the rat in vivo; Witte OW; Interictal spikes and sharp waves in the EEG are followed by intervals in which the excitability of the brain seems to be normal or decreased . Often interictal spikes even appear in rhythmical patterns with intervals in the order of 0.5-2 s . These observations suggest that intrinsic and synaptic inhibitory and excitatory processes are activated which outlast the duration of the interictal discharge . In the present study such afterpotentials were analyzed in penicillin foci of the rat motor cortex in vivo using intracellular recording techniques . Paroxysmal depolarizations (PDS) of neurons within the focus were followed by afterpotentials comprising several components . Fast afterpotentials with a duration of 640 ms were associated with a sevenfold increase in membrane conductance . The fast afterpotentials were depolarizing in the majority of recordings and had an average equilibrium potential of -62 mV . This equilibrium potential was Cl(-)-dependent and was not affected by intracellular EGTA or Cs+ . It is suggested that these afterpotentials represent GABAA responses . In 38% of the neurons slow afterhyperpolarizations with a twofold increase in membrane conductance and a duration of 2 s were observed . These afterhyperpolarizations had a reversal potential of -79 mV, were blocked by intracellular Cs+, were reduced in duration and amplitude by intracellular EGTA, and are suggested to present a combination of a GABAB response and a calcium-dependent potassium current . In addition, slow afterdepolarizations with a duration of about 1900 ms were registered in 16% of the recordings . It is concluded that afterpotentials with several intrinsic and synaptic components follow penicillin-induced PDS . Among these are giant Cl(-)-dependent potentials which probably represent GABAA responses, GABAB responses and a slow calcium-dependent potassium current . It is suggested that the depolarizing equilibrium potential of the Cl(-)-dependent component is due to intracellular Cl- accumulation which might favor transition to ictal discharges.

Antimicrob Agents Chemother, 1994 May, 38(5), 1203 - 4
Penicillin concentrations after increased doses of benzathine penicillin G for prevention of secondary rheumatic fever; Currie BJ et al.; Plasma penicillin levels were studied 2, 3, and 4 weeks after intramuscular benzathine penicillin G (BPG) doses of 1,200,000, 1,800,000, and 2,400,000 U . Proportions of patients with penicillin levels above 25 ng/ml at each week increased with increasing BPG dose . Further studies of higher-dose BPG for rheumatic fever prophylaxis are required.

J AOAC Int, 1994 May-Jun, 77(3), 565 - 70
Analysis of penicillin G in milk by liquid chromatography; Boison JO et al.; A liquid chromatographic (LC) method that was previously developed for penicillin G residues in animal tissues has been adapted to milk and milk products . After protein precipitation with sodium tungstate, samples are applied to a C18 solid-phase extraction cartridge, from which penicillin is eluted, derivatized with 1,2,4-triazole-mercuric chloride solution, and analyzed by isocratic liquid chromatography (LC) on a C18 column with UV detection at 325 nm . Quantitation is done with reference to penicillin V as an internal standard . Penicillin G recoveries were determined to be > 70% on standards fortified at 3-60 ppb . Accuracy approached 100% using the penicillin V internal standard . The detection limit for penicillin G residues was 3 ppb in fluid milk . Samples may be confirmed by thermospray/LC at concentrations approaching the detection limit of the UV method.

J Exp Biol, 1994 May, 190, 141 - 53
Mobilization of shell calcium by the chick chorioallantoic membrane in vitro; Packard MJ; Two explants of shell were removed from each of several fertile eggs of domestic fowl at different times during incubation . The chorioallantoic membrane (CAM) was removed from one of the explants (SHELL ONLY) and was left in situ on the other (SHELL+CAM) . Explants were cultured for 24, 48 or 96 h at 37 degrees C and 5% CO2 in air in individual Petri dishes containing Dulbecco's modified Eagle's medium, bovine serum albumin, penicillin and streptomycin . Both SHELL+CAM and SHELL ONLY explants released calcium into the culture medium, but the former released considerably more calcium than the latter . More calcium was released by SHELL+CAM explants taken from older eggs than from younger ones, but the age of the donor eggs did not affect release of calcium by SHELL ONLY explants . In addition, release of calcium by SHELL+CAM explants exceeded that shown by SHELL ONLY explants for multiple 24 h intervals . However, the capacity for sustained release of calcium by SHELL+CAM explants declined with age and maturity of the CAM . Manipulations that lead to the death of the CAM abolish the capacity for SHELL+CAM explants to release more calcium than SHELL ONLY explants . Differential release of calcium by SHELL+CAM explants was not attributable to calcium present in the CAM at the onset of culture or to non-specific degradation of the shell by intracellular constituents released as a result of the death of the CAM . Taken in concert, these results indicate that the CAM mobilizes calcium from the eggshell during in vitro culture.

Int J Gynaecol Obstet, 1994 May, 45(2), 169 - 74
Gonorrhea and chlamydial infections . ACOG Technical Bulletin Number 190-March 1994 (replaces No . 89, November 1985).
{Whole embryo culture for detecting teratogen}
He WG, Li HL, Zheng GY.

Department of Obstetric and Gynecology, Second Teaching Hospital, N . Bethune University of Sciences, Medical ChangchunWhole embryo culture technique was used to study direct effects of Penicillin G, Thiadiazole, Actinomycin D and glucose solution of high concentration on the development and growth of rat embryos, without maternal and placental influence . Nine-and-a-half-day rat embryos were transplanted to culture flasks from the animal's wombs for in vitro culture, and the four chemicals were added to culture medium, respectively . Results showed all those chemicals could cause death and malformation of the embryos and retardation in embryonic development and growth cultured in vitro, with an apparent dose-effect relationship . The embryonic malformations caused by the chemicals were the same both in vitro culture and in vivo . Possible teratogenesis of the chemicals and survival of the malformed embryos were speculated based on the above dose-effect relationship.

J Ind Microbiol, 1994 May, 13(3), 144 - 6
Inhibition of penicillin biosynthetic enzymes by halogen derivatives of phenylacetic acid; Martinez-Blanco H et al.; The effect of phenylacetic acid (PAA) and several analogs on the activity of isopenicillin N synthase (IPNS) and acyl-CoA: 6-APA acyltransferase (AT) from Penicillium chrysogenum Wis 54-1255 has been tested . Whereas the substitution on the ring of a hydrogen atom by hydroxy-, methyl- or methoxy- groups did not cause any effect, the presence of halogens (Cl or Br) at positions 3 and/or 4 of PAA strongly inhibited these two enzymes . The replacement of hydrogen atoms by fluorine in certain positions also caused inhibition, but to a lesser extent.

Allerg Immunol (Paris), 1994 May, 26(5), 181 - 3
{Alimentary anaphylactic shock: implication of penicillin residues}; Kanny G et al.; The case of a 64 y.o . female is reported . She experienced formerly four anaphylactic shocks . Two shocks occurred after ingestion of pork and beef meat . Any food allergy to animal proteins was discarded . A high degree of sensitivity to penicillin G was proved by a positive prick test to penicillin G 1 Ul/ml, which induced a systemic reaction . RAST to penicillin G was class 4 . The leucocyte histamine release test showed a high level of spontaneous histamine release . A double blind, placebo controlled, oral challenge with penicillin mixed to milk induced wheezing and a fall of blood pressure at the cumulative dose of 20 Ul . The hypothesis of food induced anaphylaxis, linked to penicillin residues in meats, is highly plausible . The significance of the phenomenon of spontaneous histamine release is discussed . It might point to frequent ingestions of hidden penicillin residues in the diet.

Biochim Biophys Acta, 1994 Apr 13, 1205(2), 199 - 206
The reaction of cephalosporins with penicillin-binding protein 1b gamma from Escherichia coli; Page MG; The kinetics of the reaction of purified penicillin-binding protein 1b gamma from Escherichia coli with cephalosporins suggest that the enzyme exists in two kinetically distinct conformations that are in slow equilibrium . One of these forms can effect rapid hydrolysis of some beta-lactams and it is only through its deactivation by conversion to the slower reacting form that complete inhibition can be achieved . With some cephalosporins and with penicillins having simple aromatic side-chains the reaction was slower and did not exhibit the same kinetic behaviour . This could be attributed to the rate of reaction being similar to the rate of conformation change and thus sets an upper limit on the isomerization rate.

Ugeskr Laeger, 1994 Apr 11, 156(15), 2211 - 3
{Prevention of duodenal ulcer recurrence with penicillin}; Rune SJ et al.; The aim of this study was to test the hypothesis that infection with Helicobacter pylori is essential for recurrence of duodenal ulcer . We performed a randomized controlled trial of the relapse rate of duodenal ulcer during 12 weeks treatment with penicillin V or placebo in 170 out-patients from five centres . The relapse rate was 9% during treatment with penicillin and 50% with placebo, P < 0.0001 . It is concluded that infection with penicillin-sensitive bacteria, i.e . H . pylori, plays an important role for recurrence of duodenal ulcer disease . Penicillin V suppresses this infection but does not eradicate it.

Genitourin Med, 1994 Apr, 70(2), 138 - 45
Sexually transmitted diseases in the history of Uganda; Lyons M; First noticed in Uganda in 1863 by a European explorer, sexually transmitted diseases (STDs) were cited as a major cause of morbidity and mortality throughout this century . In 1908 the venereal diseases campaign was launched marking the real introduction of western medicine . By the mid-1920s, the campaign was combined with the medical service but throughout the colonial period (1901-1962) venereal diseases were considered intractable . A 1991 survey revealed alarming incidence rates and in light of the importance of STDs as a co-factor in the transmission of HIV, it is of paramount importance to implement more effective control measuresPIP: Sexually transmitted diseases (STDs) were first noticed in Uganda in 1863 and have been a major cause of morbidity and mortality throughout this century . By the mid-1920s, the venereal diseases campaign introducing Western medicine was combined with the medical service, but throughout the colonial period (1901-1962) venereal diseases were considered intractable . A 1991 survey revealed alarming incidence rates . A recent retrospective study of sexually transmitted diseases over the period 1986-1990 at 9 sentinel sites (hospitals located along the major east-west trade axis) revealed that in some hospitals they accounted for 16% of all admissions . Testing for syphilis antibody during the National Serosurvey for HIV in 1988 revealed that 17.5% of random specimens were antibody positive . The Serosurvey also discovered that in some areas of Uganda 15-30% of those infected with HIV had a history of genital ulcer disease within the past 5 years; for example, 30% of the outpatients at Mulago's sexually transmitted diseases clinic present with genital ulcers . A most disturbing discovery is the fact that well over 90% of gonorrhea in Uganda is resistant to penicillin . AIDS had first been noticed by many practitioners during 1981-1982, and by 1985 it was declared to be epidemic . Many epidemiologists believe that AIDS was perhaps introduced by 45,000 Tanzanian soldiers during their occupation of the country in 1979 and 1980 . However, the long history of high incidence of other STDs combined with the fact that treatment never eliminated venereal diseases, better explain the wildfire spread of HIV . By June 1991, it was estimated that nearly 1.5 million Ugandans were infected with HIV, and that in some urban hospitals, like Mulago, about 40% of beds were occupied by patients with AIDS or AIDS-related illnesses . In light of the importance of STDs as a cofactor in the transmission of HIV, it is of paramount importance to implement more effective control measures .

J Pediatr, 1994 Apr, 124(4), 649 - 53
Concentrations of procaine and aqueous penicillin in the cerebrospinal fluid of infants treated for congenital syphilis; Azimi PH et al.; Penicillin concentrations in cerebrospinal fluid (CSF) were measured at various hours and days of treatment in 163 infants undergoing therapy for congenital syphilis . The CSF levels were compared for three treatment regimens . Aqueous penicillin G (A-PEN), 100,000 U/kg per day, was used in 23 infant, and a dosage of 200,000 U/kg per day was used in 40 patients; procaine penicillin G (P-PEN), 50,000 U/kg per day, was used in 100 children . Mean CSF penicillin levels were 0.416, 0.493, and 0.077 microgram/ml, respectively, in the three treatment groups . The mean CSF penicillin concentration among the 63 infants treated with either of the A-PEN regimens (0.465 microgram/ml) was significantly greater than the mean concentration (0.077 microgram/ml) among those treated with P-PEN (p < 0.001) . Among those who received A-PEN, the difference in dosage was not associated with a significant difference in mean CSF penicillin concentration (p = 0.68) . All the specimens obtained from patients who received A-PEN, but only 82% of those from patients who received P-PEN, had treponemicidal concentrations (> or = 0.018 microgram/ml) . However, 33.3% (9/27) of specimens from infants who received P-PEN, tested between 18 and 24 hours after a dose, had CSF penicillin concentrations < 0.018 microgram/ml . These data suggest that administration of A-PEN may be the preferred therapy if CSF levels > 0.018 microgram/ml are desired, especially for infants with severe disease or congenital neurosyphilis.

Med Hypotheses, 1994 Apr, 42(4), 261 - 4
Hoigné's syndrome: a procaine-induced limbic kindling; Araskiewicz A et al.; Procaine-induced limbic kindling may be a principal pathogenetic factor for the psychiatric symptoms of the acute non-allergic reaction to procaine penicillin (Hoigne's syndrome) . The syndrome develops with repeated injections of the drug and runs a rapidly spasmodic course . Its acute symptoms (anxiety, perceptual disturbances, sympathetic hyperactivity) are similar to those in temporal lobe and limbic system seizures and are also reminiscent of psychiatric complications following the repeated use of other local anesthetics (lidocaine, cocaine) . Compatible with the mechanisms of kindling are also possible predispositions to the occurrence of this reaction as well as the recurrent after-effects during follow-up . Penicillin, a second component of the injection may contribute to the development of kindling by its properties of antagonizing GABA neurotransmission.

Antimicrob Agents Chemother, 1994 Apr, 38(4), 898 - 900
Susceptibilities of 177 penicillin-susceptible and -resistant pneumococci to FK 037, cefpirome, cefepime, ceftriaxone, cefotaxime, ceftazidime, imipenem, biapenem, meropenem, and vancomycin; Spangler SK et al.; MICs of six extended-spectrum cephalosporins (cefotaxime, ceftriaxone, ceftazidime, FK 037, cefpirome, cefepime), three carbapenems (imipenem, meropenem, biapenem), and vancomycin for 49 penicillin-susceptible (S), 77 penicillin intermediate-resistant (I), and 51 penicillin-resistant (R) pneumococci were determined by agar dilution . Compared with ceftazidime (MICs for 90% of strains tested {MIC90s} of 2.0, 16.0, and 16.0 micrograms/ml for S, I, and R strains, respectively), all other cephalosporins yielded lower MICs (MIC90s of 0.06 to 0.125, 0.5 to 1.0, and 1.0 to 2.0 micrograms/ml against S, I, and R strains, respectively) . All three carbapenems were very active, with MIC90s, even for R strains, of < or = 1.0 micrograms/ml . All strains were susceptible to vancomycin (MIC90 of 0.5 micrograms/ml).

Wiad Lek, 1994 Apr, 47(7-8), 280 - 3
{Prophylactic use of ampicillin and sulbactam in colonic surgery}; Andziak P et al.; The purpose of the work was an evaluation of the effectiveness of ampicillin and sulbactam administered parenterally in the prophylaxis of infections in patients after colonic surgery . The group of patients treated with ampicillin and sulbactam was compared with the control group in which penicillin, gentamicin and metronidazole were given prophylactically . Surgical wound infections were found in the group receiving ampicillin and sulbactam in 20% of cases, and in the control group in 13.3% of patients . This difference was not statistically significant (p > 0.05) . In both groups infections of all perineal wounds were observed after abdominoperineal operations . No allergic reactions nor side effects were found in the group treated with ampicillin and sulbactam . Conclusion: Prophylactic administration of ampicillin and sulbactam in colonic surgery is similar in its effectiveness to prophylactic administration of penicillin, gentamicin and metronidazole.

Bol Asoc Med P R, 1994 Apr-Jun, 86(4-6), 24 - 7
{Gastric syphilis . Report on first 2 cases in Cuba}; Castano Hernandez S et al.; Two 28 and 25 year old female patients were studied . Endoscopic analysis of their stomachs showed an hyperemic mammillation picture, neoplasia compatible, in the first patient, and an ulcerous lesion in the second one . Both findings were the result of a positive serological test to discard syphilis . All this, together with a cutaneous and epidemiological history, represented an assumed diagnosis of a secondary stage syphilis with gastric disorders . Although it was not necessary, one case was submitted to a specific spirochaeta stain, but results were negative . The true diagnosis resulted from a penicillin treatment, which provoked a cutaneous-visceral history regression as well as a diminishing in V.D.R.L . titles.

J Chem Technol Biotechnol, 1994 Apr, 59(4), 371 - 6
Penicillin G extraction from model media using an emulsion liquid membrane: determination of optimum extraction conditions; Lee KH et al.; Penicillin G extraction by an emulsion liquid membrane (ELM) was investigated . The effects of surfactants, diluents, and carrier mixtures, together with their combined effects on the initial extraction rate and the emulsion stability were examined . Surfactants, diluents, and carriers used were Span80 (sorbitan monooleate)/ECA4360J (nonionic polyamine), n-butyl acetate/kerosene, and DOA (dioctylamine)/Amberlite LA-2 (secondary amine), respectively . The optimum extraction conditions were found to be 20% (v/v) of Span80 in ECA4360J as a surfactant, kerosene as a diluent and Amberlite LA-2 as a carrier.

J Chem Technol Biotechnol, 1994 Apr, 59(4), 365 - 70
Penicillin G extraction from model media using an emulsion liquid membrane: a theoretical model of product decomposition; Lee KH et al.; To confirm the applicability for the extraction of penicillin G by an emulsion liquid membrane (ELM), the degree of decomposition of penicillin G during extraction was theoretically calculated . Decomposition was less than 1% provided that the initial sodium carbonate concentration in the internal phase was correctly determined, which proved the applicability of the ELM process . The procedure to determine the initial carbonate concentration in the internal phase was also described in order that the pH in the internal phase should be within the relatively stable range for penicillin G at the end of the extraction.

J Biotechnol, 1994 Mar 15, 33(1), 71 - 85
Suboptimal control of fed-batch bioprocesses using phase properties; Diener A et al.; A new method for the evaluation of suboptimal feeding strategies for fed-batch bioprocesses is introduced . This method is based on a time-local optimization of the process dynamics . To include global effects into the optimization, the process has to be partitioned into several phases with different local extremality conditions . The penicillin bioprocess is used to illustrate the method . One advantage of the proposed method is that the evaluated control function appears as a feedback law . Simultaneously, the new method allows the inclusion of constraints on the process states and the use of very complex models . Due to the simplicity and stability of the numerical procedure the method is robust against external perturbation . Therefore, it is suited for use in on-line controls.

Neurosci Lett, 1994 Mar 14, 169(1-2), 93 - 6
Anticonvulsant activity of the noradrenergic locus coeruleus system: role of beta mediation; Ferraro G et al.; Many experimental observations have demonstrated the modulatory role exerted by several neural structures and neurotransmitters on spontaneous and paroxysmal bioelectric activity of the hippocampus . Recently, the control exerted by locus coeruleus (LC) and its noradrenergic (NA) efferent pathway on different experimental models of epilepsy (e.g . cortical cobalt chronic epilepsy, amygdaloid and hippocampal kindling) was emphasised . On this basis, a series of experiments was performed to elucidate the functional role of LC-NA system on the hippocampal penicillin (PCN) focus and the type of adrenergic receptor involved . The experiments were carried out on 25 rats in which an epileptiform hippocampal focus was obtained through intrahippocampal PCN administration (100-200 I.U.) . In these conditions, LC, ipsilateral to PCN hippocampal focus, was stimulated before and after intraperitoneal (i.p.) administration of a beta-adrenergic receptor antagonist propranolol (2 mg/kg) . Results showed a significant reduction of hippocampal spiking frequency during LC stimulation; after i.p . propranolol injection, LC stimulation, at the same parameters, failed to induce any sort of modification of PCN hippocampal spiking frequency . Furthermore, intrahippocampal application of a beta-selective agonist 2-fluoro-noradrenaline (2-FNA) mimics the inhibitory effects of LC stimulation . All data suggest that the LC-NA system is able to induce a net reduction of hippocampal epileptiform focus and the inhibitory NA control involves the activation of adrenergic beta receptors.

Sex Transm Dis, 1994 Mar-Apr, 21(2), 124 - 6
Treatment regimens of STD patients in Cameroon: a need for intervention; Trebucq A et al.; BACKGROUND AND OBJECTIVES: The management of patients with STDs is an important element in the fight against AIDS . To define effective STD control strategies a survey was carried out to understand the attitudes of STD patients and the treatment regimens they follow . STUDY DESIGN: The study was based on interviews with male patients with typical symptoms of urethritis leaving private pharmacies in Douala and Yaounde . Each case was asked to answer a questionnaire comprising the origin of the therapeutic choice, the nature and cost of the treatment and any advice received . RESULTS: Fifty-six men in Douala and 86 in Yaounde were recruited . The sources of prescription were dispensary (38%, 54%) private MD (9%, 15%) pharmacist (7%, 9%), diverse (46%, 21%) in Douala and Yaounde respectively . At least two medicines were recommended in three-quarters of the patients . The most frequently used antibiotics were aminoglycosides and penicillin . The cost of the treatment ranged from $3.50 to $110 . The more "medical" the initial visit, the higher was the cost of the prescribed treatment . In Douala only 49% of the prescribers advised the patients to treat their partners and condom promotion was done by 21% of the prescribers . CONCLUSION: This survey provides useful data on the care of patients with urethritis . Such surveys are simple, rapid, reasonable inexpensive (about $10,000) and contribute to the efficient design of STD control strategies . In addition, repeat survey to monitor the impact of the strategies are simple to carry out.

Ear Nose Throat J, 1994 Mar, 73(3), 169 - 75
Surgical treatment and rehabilitation of prelingually and perilingually deafened children and adults with the nucleus multichannel cochlear implant; Garcia JM et al.; We began our program in September 1992, using the Nucleus 22 Channel Cochlear Implant . To date, we have operated on four patients, one child with congenital hearing loss, two prelinguistically deaf adults and one perilingually deaf adult . Our results have shown a significant increase in auditory and speech reception and perception skills in the child . The perilingually deaf adult is able to understand speech in open set speech discrimination testing and, although we do not expect open set speech discrimination in the prelinguistically deaf adults, to date their results have been satisfactory . The two prelingually deaf adults are in an audiological rehabilitation program . Their response in prosodic aspects of speech and lipreading ability with sound have improved significantly . The only surgical complication was an infection of the flap in the child, but it was treated satisfactorily with i.v . penicillin.

Br Poult Sci, 1994 Mar, 35(1), 157 - 60
Inhibitory effect of penicillin on caecal urease activity in chickens fed on a low protein diet plus urea; Karasawa Y et al.; 1 . The effects of dietary penicillin on the urease activities of small intestine, large intestine, caecum and their contents, liver and kidney in chickens fed a diet containing 5 g/kg protein plus urea were examined . 2 . About 0.88 of the total urease activity determined was observed in intestinal contents, of which 0.95 of the activity was accounted for by caecal contents, 0.05 by colo-rectal contents and none by small intestinal contents . Intestinal tissues (caecum included), liver and kidney accounted for 0.03, 0.06 and 0.02, respectively, of the total urease activity . 3 . Dietary penicillin decreased urease activity to 0.17 in caecal contents and to 0.05 in colo-rectal contents of the corresponding control values (P < 0.01) . The urease activity of caecal tissue was lowered by penicillin to half that of control activity (P < 0.05) but none of the activities of other tissues were affected . 4 . It is concluded that, even when the urease activity is stimulated by dietary urea, 20 mg/kg dietary penicillin can strikingly lower it in the caecum, where most of the urease activity in the chicken body is to be found.

Nippon Kyobu Geka Gakkai Zasshi, 1994 Mar, 42(3), 442 - 5
{A case of infantile thoracic actinomycosis involving the bronchocutaneus fistula}; Kobayashi K et al.; Pulmonary actinomycosis is rare at present . A 11-year-old girl complained of left anterior chest pain and chest wall swelling . A radiograph of the chest revealed a consolidation in the left upper lobe . Sputum cultures showed normal flora and sputum cytology was negative for malignant disease . On 16 days after admission, the infection involved the bronchocutaneous fistula . Surgery was necessary to curettage . Histopathological specimen of resected necrotic tissue showed typical "sulfur granule" of actinomycosis . We administered penicillin for 3 months and the consolidation disappeared.

Dig Dis Sci, 1994 Mar, 39(3), 555 - 60
Childhood infections and the risk of inflammatory bowel disease; Wurzelmann JI et al.; Adults with inflammatory bowel disease from North Carolina were questioned during 1986 and 1987 to assess risk due to a variety of childhood infections and treatments with antibiotics . Responses were compared with those of neighbor controls . Persons with Crohn's disease were more likely to report an increased frequency of childhood infections in general (odds ratio 4.67, 95% CI 2.65-8.23) and pharyngitis specifically (odds ratio 2.14, 95% CI 1.30-3.51) . This was validated by an increased frequency of tonsillectomy (odds ratio 1.53, 95% CI 1.07-2.20) . Crohn's cases were more likely to report frequent treatment with antibiotics for both otitis (odds ratio 2.07, 95% CI 1.03-4.14) and pharyngitis (odds ratio 2.14, 95% CI 1.20-3.84) . Although Crohn's cases were more likely to report frequent exposure to penicillin (odds ratio 1.81, 95% CI 0.98-3.31), there did not appear to be excess risk conferred by penicillin after controlling for frequency of infections . Persons with ulcerative colitis also reported an excess of infections generally (odds ratio 2.37, 95% CI 1.19-4.71), but not an excess of specific infections or treatments with antibiotics . Persons who reported an increased frequency of infections tended to have an earlier onset of Crohn's disease (P < 0.0001) and ulcerative colitis (P = 0.04) . Finally, it was noted that urban living in childhood increased the risk for Crohn's disease . We conclude that childhood infections may be a risk factor for Crohn's disease and may presage the early onset of disease.

Am J Respir Crit Care Med, 1994 Mar, 149(3 Pt 1), 815 - 7
Oral desensitization to rifampin and ethambutol in mycobacterial disease; Matz J et al.; The incidence of disease caused by Mycobacterium tuberculosis (including drug-resistant strains) and M . avium complex (MAC) is increasing . Hypersensitivity reactions to antimycobacterial agents are relatively uncommon, but when they occur they may result in cessation of therapeutic medications . We report our experience with rapid oral desensitization to ethambutol and rifampin in a group of 10 patients with mycobacterial disease who had experienced cutaneous hypersensitivity reactions to these drugs . An adaptation of the rapid oral desensitization protocol for penicillin was used, with the dosing intervals increased to account for the different kinetics of these drugs . Adverse reactions were few and easily treated without necessitating cessation of therapy . We conclude that oral desensitization to rifampin and ethambutol by our protocol is safe and effective, allowing these patients to proceed with an optimal antimycobacterial regimen.

J Vet Intern Med, 1994 Mar-Apr, 8(2), 128 - 32
Tetanus in the horse: a review of 20 cases (1970 to 1990); Green SL et al.; The case records of 20 horses with tetanus referred to the Ontario Veterinary College-Veterinary Teaching Hospital between 1970 and 1990 were reviewed . The fatality rate was 75% . There was a strong association with previous vaccination and survival (P = .03) . Most of the animals had been injured an average of 9 days (range 2 to 21 days) prior to development of clinical signs . Hyperesthesia and prolapse of the third eyelid were the most common clinical signs . Treatment regimens varied during hospitalization; however, all horses received parenteral penicillin, tranquilizers, tetanus toxoid, and antitoxin . Five of the nonsurviving animals were given intrathecal tetanus antitoxin . One animal had seizures as a complication of intrathecal treatment . The prognosis was best for horses that (1) had been vaccinated prior to the injury, (2) responded to the phenothiazine tranquilizers, and (3) did not rapidly (over 24 to 48 hours) become recumbent . Considering the species susceptibility, potential for contaminated wounds, and the increased survival of vaccinated horses, yearly revaccination is recommended.

Zhongguo Yao Li Xue Bao, 1994 Mar, 15(2), 155 - 7
{Alteration of dynorphin1-8 and leu-enkephalin in rat hippocampus during seizure and electroacupuncture}; Wang BE et al.; Immunocytochemical technics were used to evaluate the influence of penicillin-induced seizure and electroacupuncture treatment on dynorphin1-8 and leu-enkephalin immunoreactivity in hippocampus . It was found that 3 h after beginning of seizure there started a dramatic decrease in dynorphin1-8 in hilus, mossy fiber of hippocampus but an increase in hilus, mossy fiber of hippocampus but an increase in leu-enkephalin in subiculum, CA1 area of hippocampus and some other limbic structures . Electroacupuncture treatment decreased the leu-enkephalin immunoreactivity in the nuclei mentioned above and increased dynorphin1-8 immunoreactivity in hippocampus . The results show that epileptiform activity and electroacupuncture inhibitory effect on seizure may be related to the alteration of dynorphin1-8 and leu-enkephalin in the brain.

Neuroscience, 1994 Mar, 59(2), 259 - 73
Hippocampal plasticity following epileptiform bursting produced by GABAA antagonists; Schneiderman JH et al.; The effects of epileptiform bursts on hippocampal excitability were examined in the CA3 region of guinea-pig hippocampal slices . Partial blockade of gamma-aminobutyric acidA (GABAA)-mediated inhibition by 500 IU/ml penicillin produced low frequency (2-4 Hz) "pro-convulsant" field potential oscillations . Normal spontaneous activity recovered less than 30 min after the penicillin was rinsed out providing bursting was prevented . Synchronized bursting rarely began on its own even after 1 h in penicillin 500 IU/ml, but could be initiated in most slices after one to eight all-or-none bursts were evoked by low-intensity, low-frequency (0.2-0.25 Hz) stimuli . Spontaneous bursting, once initiated, persisted for at least 1 h without further stimulation suggesting that a small number of bursts produced a long-lasting increase in excitability . Bursts disappeared more slowly than anticipated after convulsants were rinsed out and were followed by "post-burst" oscillations with different frequency characteristics than proconvulsant oscillations which persisted for at least 4 h . Selective augmentation of evoked N-methyl-D-aspartate excitatory postsynaptic potentials appeared to be the critical first step in the initiation of bursting . The specific N-methyl-D-aspartate antagonist, 2-amino-5-phosphonovaleric acid (50-100 microM), only partially suppressed pro-convulsant oscillations in partially disinhibited slices but completely prevented stimulus-triggered spontaneous bursting and prolonged hyperexcitability . Although N-methyl-D-aspartate receptors were necessary for the induction of bursting in partially disinhibited slices, they were not required to initiate bursting after more complete disinhibition . However, when 2-amino-5-phosphonovaleric acid was applied prior to and during perfusion with 2000 IU/ml penicillin, spontaneous bursts occurred at long, irregular intervals and lacked afterdischarges . These bursts rapidly disappeared upon penicillin washout and were not followed by persistent post-burst oscillations . N-methyl-D-aspartate antagonists applied only after bursts already established in penicillin blocked the afterdischarges but did not reduce the burst frequency . These observations indicate that epileptiform bursts can produce long-lasting, hippocampal hyperexcitability . The induction of these plastic changes requires N-methyl-D-aspartate receptor activation which then enhances both N-methyl-D-aspartate and non-N-methyl-D-aspartate receptor mechanisms . Furthermore, N-methyl-D-aspartate excitatory postsynaptic potentials can participate in triggering spontaneous bursts but this role is masked once plasticity has occurred . Partial disinhibition produces a pro-convulsant state which does not induce long-lasting changes in hippocampal excitability but renders the neuronal network vulnerable to develop persistent epileptiform bursting with small additional excitatory inputs.(ABSTRACT TRUNCATED AT 400 WORDS)

No To Hattatsu, 1994 Mar, 26(2), 101 - 10
{Neurochemical approach to epilepsy}; Ito M; To elucidate the neurochemical mechanism of epilepsy, we investigated the role of neurotransmitter systems in the animal models of epilepsy, the mechanism of anticonvulsants and proconvulsants, the neurotransmitters in the CSF of children with epilepsy, and the new therapy for epilepsy . The main results are as follows . 1) In El mice, the increased activity of excitatory amino acids system in cortex and decreased activity of noradrenergic system in striatum and hippocampus were related to the increased seizure susceptibility . 2) GABA sensitivity was reduced in young DBA 2 J mice which are susceptible to audiogenic seizures . 3) Lower benzodiazepine receptor densities were found in hippocampus of 4 and 16 weeks-old tremor rats . GABA concentrations in the cerebral cortex and hippocampus of the tremor rats increased at 5 weeks-old and decreased at 15 weeks-old . These changes may be related to the absence-like seizures in tremor rats . 4) Anticonvulsant mechanism of ACTH may be due to antagonizing glutamate binding . Proconvulsant mechanism of thyroid hormone may be related to the decrease in number of cerebral cortical neuronal benzodiazepine receptors . Penicillin acts its proconvulsant effect through inhibiting GABA-gated chloride ion influx . 5) CSF GABA level in children with infantile spasms was lower than in controls . The combination of vitamin B6 and valproic acid is effective and safe therapy in the treatment of infantile spasms . Further investigations by the neurochemical approaches are necessary to understand the mechanisms of epilepsy and develop the new therapy.

Southeast Asian J Trop Med Public Health, 1994 Mar, 25(1), 152 - 6
Recurrence of yaws outbreak in Thailand, 1990; Tharmaphornpilas P et al.; In November 1990, an outbreak of yaws was reported in a rural village of southern Thailand . A survey consisting of history taking, physical examination and blood tests for VDRL and TPHA was undertaken in the whole village and in the primary school of the village . A yaws case was defined as a person who had a positive VDRL confirmed by TPHA without history of other treponemal infection or post-treatment of yaws . Fifty-four cases, an attack rate of 23%, were found in the age range from 2 to 79 years old . The epidemic curve started with a few cases in 1989 and early 1990 with an increasing number of cases from June, and reached its peak in November . Half of the cases (53.7%) were children under 15 years . Male cases were higher than female (1.5:1) . A survey of 105 primary school students found an attack rate of 32% (34/105) and the prevalence was higher in younger classes . Benzathine penicillin injection was given to cases for treatment . From this investigation, the Ministry of Public Health was alerted about the recurrence of yaws . Strengthening health education and surveillance activities was recommended in adjacent districts and provinces . The extent of the problem was assessed through surveys among school children and expanded to their family members if cases of yaws were found.

Nature, 1994 Feb 24, 367(6465), 750 - 3
Doughnut-shaped structure of a bacterial muramidase revealed by X-ray crystallography; Thunnissen AM et al.; The integrity of the bacterial cell wall depends on the balanced action of several peptidoglycan (murein) synthesizing and degrading enzymes . Penicillin inhibits the enzymes responsible for peptide crosslinks in the peptidoglycan polymer . Enzymes that act solely on the glycosidic bonds are insensitive to this antibiotic, thus offering a target for the design of antibiotics distinct from the beta-lactams . Here we report the X-ray structure of the periplasmic soluble lytic transglycosylase (SLT; M(r) 70,000) from Escherichia coli . This unique bacterial exomuramidase cleaves the beta-1,4-glycosidic bonds of peptidoglycan to produce small 1,6-anhydromuropeptides . The structure of SLT reveals a 'superhelical' ring of alpha-helices with a separate domain on top which resembles the fold of lysozyme . Site-directed mutagenesis and a crystallographic inhibitor-binding study confirmed that the lysozyme-like domain contains the active site of SLT.

Brain Res Dev Brain Res, 1994 Feb 18, 77(2), 251 - 5
The effects of epileptic cortical activity on the development of callosal projections; Grigonis AM et al.; The effect of epileptic neural activity on the postnatal development of the corpus callosum was studied . Epileptiform activity was induced in the visual cortex of postnatal rabbits by continuous infusion of penicillin . Callosal projections of the occipital cortex were studied in rabbits aged at least 4 weeks . In these penicillin-exposed rabbits, the visual callosal projections extended through most of area 17 in a projection pattern characteristic of neonatal rabbits, rather than being restricted to a narrow callosal zone at the lateral border of area 17, as they usually are by this age . The results indicate that epileptic cortical activity stabilizes immature callosal projections which are normally eliminated during development . The maintenance of such immature and non-specific projections in the mature CNS may interfere with normal cortical functions and could underlie the cognitive deficits which have been observed following childhood epilepsy.

Biochem J, 1994 Feb 15, 298 ( Pt 1), 189 - 95
Engineering and overexpression of periplasmic forms of the penicillin-binding protein 3 of Escherichia coli; Fraipont C et al.; Replacement of the 36 and 56 N-terminal amino acid residues of the 588-amino-acid-residue membrane-bound penicillin-binding protein 3 (PBP3) of Escherichia coli by the OmpA signal peptide allows export of F37-V577 PBP3 and G57-V577 PBP3 respectively into the periplasm . The modified ftsI genes were placed under the control of the fused lpp promoter and lac promoter/operator; expression of the truncated PBP3s was optimized by varying the copy number of the recombinant plasmids and the amount of LacI repressor, and export was facilitated by increasing the SecB content of the producing strain . The periplasmic PBP3s (yield 8 mg/l of culture) were purified to 70% protein homogeneity . They require the presence of 0.25 M NaCl to remain soluble . Like the membrane-bound PBP3, they undergo processing by elimination of the C-terminal decapeptide I578-S588, they bind penicillin in a 1:1 molar ratio and they catalyse hydrolysis and aminolysis of acyclic thioesters that are analogues of penicillin . The membrane-anchor-free PBP3s have ragged N-termini . The G57-V577 PBP3, however, is less prone to proteolytic degradation than the F37-V577 PBP3.

J Chromatogr A, 1994 Feb 4, 660(1-2), 137 - 45
Perfusible and non-perfusible supports with monoclonal antibodies for bioaffinity chromatography of Escherichia coli penicillin amidase within its pH stability range; Kasche V et al.; Several monoclonal antibodies (mABs) have been prepared and immobilized for the biospecific isolation of penicillin amidase (PA) from Escherichia coli (EC 3.5.1.11), an enzyme without S-S bridges and a pH stability range of 4-9 . During the immobilization the fluorescence emission maxima of the mABs were found to change from 336 nm to ca . 350 nm . Only one of these mABs was found to be suitable for preparative bioaffinity chromatography of PA within the pH stability range . This mAB was immobilized on different spherical supports (Eupergit C 250 L and Sepharose) and one perfusible support (Knauer Quick Disc) and used for analytical and preparative bioaffinity chromatography . Under isocratic conditions the plate height for the perfusible biospecific adsorbent was found to be an order of magnitude lower than for the other supports . The different forms of this proteolytically processed bacterial enzyme could not be separated, however, by the biospecific adsorbents . At the mAB density used in the adsorbents (10-30 microM), less than 30% of the theoretical binding capacity of the immobilized mABs could be used to adsorb the enzyme.

Genitourin Med, 1994 Feb, 70(1), 35 - 9
Gonococcal infection in Edinburgh and Newcastle: serovar prevalence in relation to clinical features and sexual orientation; Ross JD et al.; AIMS--The variable distribution of gonococcal serovars in different areas is well recognised but the factors that are important determinants of serovar prevalence are less clear . The aim of this study was to identify relevant clinical variables by comparing serovar prevalence in two cities over the same time period . METHODS--A prospective analysis of serovar prevalence was made between January and December 1992 in Edinburgh and Newcastle with respect to age, sex, sexual orientation, antibiotic sensitivity and presence of symptoms . RESULTS--224 infective episodes of gonorrhoea were studied . The serovar distribution varied between the two cities with serovar 1B-1 being more common in Edinburgh (20/91 cf . 4/133, p < 0.01) and serovar 1B-6 more common in Newcastle (26/133 cf . 2/91, p < 0.01) . Serovar 1A-2 was associated with heterosexual infection (35/114 in heterosexuals cf . 0/85 in homosexuals, p < 0.01) and was more sensitive to penicillin than average (39/39 1A-2 strains highly penicillin sensitive cf . 98/184 for all other strains, p < 0.01) whilst 1B-6 was mostly acquired through homosexual contact (22/26 cf . 63/142 for all other strains, p < 0.01) and tended to show reduced penicillin susceptibility (13/28 1B-6 strains less penicillin sensitive cf . 45/195 for all other strains, p < 0.01) . Infection with serovar 1A-2 was significantly less often symptomatic in heterosexuals than average (15/33 asymptomatic 1A-2 infections cf . 17/59 for all other serovars, p = 0.015) . Subgroup analysis of male heterosexual infections confirms an association between asymptomatic infection and serovar 1A-2 (2/14 asymptomatic 1A-2 infections cf . 1/72 for all other serovars, p = 0.02) . The distribution of infections over the year differed between the cities . CONCLUSIONS--A variety of factors including penicillin sensitivity and virulence may be important in determining the prevalence of gonococcal serovars within a given area.

Antimicrob Agents Chemother, 1994 Feb, 38(2), 205 - 10
Penicillin-binding proteins are regulated by rpoS during transitions in growth states of Escherichia coli; Dougherty TJ et al.; Attention has been recently focused on the role of the rpoS (formerly katF) gene product as a regulator during the transition from the exponential growth phase to the stationary phase as well as during nutritional starvation . It has been demonstrated that RpoS is an alternate sigma factor which would bind to promoters of genes induced at these times . It was previously noted that rpoS mutants do not undergo a transition to short rods during entry into the stationary phase . Because of their well-established role in morphogenesis, we investigated the status of the penicillin-binding proteins (PBPs) in Escherichia coli wild-type and isogenic rpoS mutants . Samples from cultures of E . coli ZK126 and ZK1000 (rpoS::kan) were taken in the midlogarithmic, early stationary, and late (24 h) stationary phases . The increase in PBP 6 seen upon entry of the wild-type strain into the stationary phase was not observed with the rpoS::kan cells, even after 24 h . There was also a marked decrease of PBP 3 in wild-type stationary-phase cells; PBP 3 has a known influence on morphogenesis . This decrease in PBP 3 was found to be markedly affected by the disruption of rpoS . Similar observations were made after prolonged starvation of the two strains for either glucose or a required amino acid . Inasmuch as PBPs are involved in peptidoglycan synthesis, we also examined two properties of peptidoglycan, autolysis and cross-linkage, that might be altered by the PBP differences . However, neither of these properties, which are known to undergo changes in the stationary phase, appeared to be influenced by the status of RpoS.

Ann Pharmacother, 1994 Feb, 28(2), 236 - 41
Prevention of anaphylactoid reactions in high-risk patients receiving radiographic contrast media; Wittbrodt ET et al.; OBJECTIVE: To review various pretreatment regimens for the prophylaxis of anaphylactoid reactions to radiographic contrast media (RCM) in high-risk patients . The proposed etiologies and risk factors for such reactions are also reviewed . DATA SOURCES: A MEDLINE search of the English-language literature was used to identify pertinent human studies and reviews . STUDY SELECTION: All studies comparing pretreatment regimens for anaphylactoid reactions to RCM were reviewed as well as studies comparing the incidence of anaphylactoid reactions between lower and higher osmolar RCM . DATA SYNTHESIS: The two types of reactions to RCM are dose-independent, unpredictable anaphylactoid (pseudoallergic or idiosyncratic) reactions and the dose-dependent, predictable physicochemical (intrinsic, nonidiosyncratic) reactions . Prophylaxis of the former type is targeted at stemming the effects of certain chemical mediators, primarily histamine . The use of lower osmolar RCM is associated with a lower incidence of anaphylactoid reactions compared with higher osmolar RCM, but is significantly more expensive . Risk factors for such reactions are a history of previous anaphylactoid reaction to RCM, asthma, and reaction to skin allergens or penicillin . Discontinuation of any beta-blockers before the procedure is suggested . Pretesting patients with a small amount of RCM has little predictive value for an anaphylactoid reaction . Various pretreatment prophylactic regimens have been studied . Almost all included a corticosteroid to target the inflammatory response and a histamine1 (H1)-antagonist to blunt the effects of histamine . In some clinical trials, ephedrine was added for bronchodilation and cimetidine for its antagonism at the histamine2-receptor . The few controlled clinical trials that have been performed show the combination of prednisone and diphenhydramine to be most beneficial in preventing anaphylactoid reactions to RCM . The addition of ephedrine or cimetidine to a pretreatment regimen remains controversial . CONCLUSIONS: More controlled clinical studies comparing various pretreatment regimens for high-risk patients need to be performed, especially in patients receiving lower osmolar RCM . Recommendations for high-risk patients who must receive RCM include use of a lower osmolar agent, pretreatment with a corticosteroid and an H1-antagonist, discontinuation of beta-blockers if the patient is taking any, and bedside availability of appropriate medications and equipment to treat anaphylaxis.

Clin Infect Dis, 1994 Feb, 18(2), 250 - 2
Syphilitic osteitis in a patient with secondary syphilis and concurrent human immunodeficiency virus infection; Kastner RJ et al.; Destructive bone disease is a well-recognized complication of congenital and tertiary syphilis . Clinically significant osteitis and osteomyelitis are rare complications of primary or secondary syphilis in patients who are not infected with human immunodeficiency virus (HIV) . We report a case of an HIV-infected man who presented with symptomatic, left ulnar osteitis as the initial manifestation of secondary syphilis . The patient's clinical course was complicated by a pathological fracture, but he responded to high-dose intravenous penicillin G therapy and surgical intervention . Results of physical examination on follow-up at 15 months were normal, and a serofast (rapid plasma reagin {RPR}) titer of 1:4 and a markedly decreased uptake on bone scintigraphy were observed . Our case report suggests that bone disease can represent an atypical manifestation of early acquired syphilis and that HIV-positive patients who present with orthopedic complaints or bone lesions should be evaluated for the presence of syphilitic bone disease.

Nippon Kyobu Geka Gakkai Zasshi, 1994 Feb, 42(2), 302 - 5
{A case of ruptured left ventricular aneurysm due to syphilitic myocarditis}; Minami T et al.; This case involved a 20-year-old male who on May, 14, 1992, lost consciousness while working and went into a state of shock . He was taken to a hospital, where cardiac tamponade was diagnosed . He was later transferred to this hospital . Based on the results of echocardiography, coronary arteriography and left ventriculography, a ruptured ventricular aneurysm was diagnosed . The patient underwent emergency surgery . Serologic tests for syphilis performed at admission were definitely positive . Histopathological examination of the wall of the ventricular aneurysm disclosed fibrous myocarditis and peripheral coronary endarteritis accompanied by infiltration of plasma cells and lymphocytes . Immunohistological study revealed treponeme in the histiocytes of the aneurysmal wall . The diagnosis was a ruptured ventricular aneurysm caused by syphilitic myocarditis . Since the advent of penicillin therapy, cardiovascular syphilis, particularly syphilitic myocarditis, has become a rare disease . The chief interest of this case is that treponeme was detected in the lesion of myocarditis.

Am J Obstet Gynecol, 1994 Feb, 170(2), 516 - 21
A prospective, randomized, placebo-controlled trial of penicillin in preterm premature rupture of membranes; Ernest JM et al.; OBJECTIVE: Preterm premature rupture of the fetal membranes is common and frequently results in infectious complications . A prospective, randomized, controlled trial of penicillin versus placebo in preterm premature rupture of membranes is reported . The aim of the study was to determine if prophylactic antibiotics after preterm premature rupture of membranes would reduce infectious complications in the mother or neonate . STUDY DESIGN: Patients with preterm premature rupture of membranes between 21 and 37 weeks' gestation were randomized into a penicillin group that received 1 million units of benzylpenicillin intravenously every 4 hours followed by 250 mg of potassium phenoxymethyl penicillin (Pen-Vee K, Wyeth-Ayerst) orally twice daily or a placebo group before delivery . Latency period, infectious complications, and neonatal outcomes were studied . RESULTS: Patients with preterm premature rupture of membranes who received prophylactic penicillin had fewer infectious complications, including intraamniotic infection and postpartum endometritis (4 vs 11, p < 0.03), without adverse effects on the mother or fetus . CONCLUSION: Prophylactic penicillin in patients with preterm premature rupture of membranes reduces maternal infectious complications without adversely affecting the mother or newborn.

J Bacteriol, 1994 Feb, 176(4), 973 - 84
The thioredoxin system of Penicillium chrysogenum and its possible role in penicillin biosynthesis; Cohen G et al.; Penicillium chrysogenum is an important producer of penicillin antibiotics . A key step in their biosynthesis is the oxidative cyclization of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) to isopenicillin N by the enzyme isopenicillin N synthase (IPNS) . bis-ACV, the oxidized disulfide form of ACV is, however, not a substrate for IPNS . We report here the characterization of a broad-range disulfide reductase from P . chrysogenum that efficiently reduces bis-ACV to the thiol monomer . When coupled in vitro with IPNS, it converts bis-ACV to isopenicillin N and may therefore play a role in penicillin biosynthesis . The disulfide reductase consists of two protein components, a 72-kDa NADPH-dependent reductase, containing two identical subunits, and a 12-kDa general disulfide reductant . The latter reduces disulfide bonds in low-molecular-weight compounds and in proteins . The genes coding for the reductase system were cloned and sequenced . Both possess introns . A comparative analysis of their predicted amino acid sequences showed that the 12-kDa protein shares 26 to 60% sequence identity with thioredoxins and that the 36-kDa protein subunit shares 44 to 49% sequence identity with the two known bacterial thioredoxin reductases . In addition, the P . chrysogenum NADPH-dependent reductase is able to accept thioredoxin as a substrate . These results establish that the P . chrysogenum broad-range disulfide reductase is a member of the thioredoxin family of oxidoreductases . This is the first example of the cloning of a eucaryotic thioredoxin reductase gene.

J Bacteriol, 1994 Feb, 176(4), 966 - 72
Thermoinducible filamentation in Escherichia coli due to an altered RNA polymerase beta subunit is suppressed by high levels of ppGpp; Vinella D et al.; The Escherichia coli strain known as GC2553, FB8, UTH1038, or K12S (Luria), considered an F- lambda- wild-type strain, is shown here to carry a cryptic mutation, ftsR1, causing nonlethal filamentation during exponential growth in Luria-Bertani (LB) broth at 42 degrees C and the inability to grow in salt-free LB broth at 42 degrees C . The ftsR1 mutation is completely suppressed in genetic backgrounds which increase RelA-dependent synthesis of the nucleotide ppGpp, i.e., argS201 (Mecr) and alaS21 (Mecr) mutations, affecting aminoacyl-tRNA synthetases, or the presence of a plac-relA' plasmid . These backgrounds also confer resistance in LB broth to the beta-lactam mecillinam, an antibiotic which specifically inhibits penicillin-binding protein 2 and, in wild-type cells, causes an indirect block in cell division . Furthermore, the ftsR1 mutant (but not an isogenic ftsR+ strain) is sensitive to mecillinam in minimal glucose medium at 37 degrees C . Since the division block caused by mecillinam can be overcome by overproduction of the cell division protein FtsZ, we tested the effect of plasmid pZAQ (carrying the ftsZ, ftsA, and ftsQ genes) on the ftsR1 mutant; it suppressed the filamentation in LB broth and the mecillinam sensitivity on minimal glucose medium at 37 degrees C but not the growth defect in salt-free LB broth at 42 degrees C . Genetic analysis indicated that the full phenotype of the ftsR1 mutant is due to a single mutation in the rpoB gene (90 min), coding for the beta subunit of RNA polymerase; we call this allele rpoB369(Fts) . We propose that the rpoB369(Fts) mutation alters the specificity of the polymerase and that the mutant enzyme can recover normal activity in the presence of high salt concentrations or via interaction with the nucleotide ppGpp.

Zhonghua Liu Xing Bing Xue Za Zhi, 1994 Feb, 15(1), 10 - 3
{Discovery and clinical investigation of Lyme disease in Beijing area}; Feng FP et al.; The investigation of Lyme disease in Beijing area is reported for the first time . The sera of 1314 local residents were examined by indirect immunofluorescent assay . 11.9% of them were seropositive to Borrelia burgdorferi . The principal vector was Haemapsysalis longicornis . Six strains of B . burgdorferi were isolated from ticks or patients using modified BSK medium . Spirochetes were found in 5 of 30 patients' skin biopsy samples . Penicillin or ceftriaxone was used to treat the patients, and the effective rates were 64% and 88%, respectively.

Zhonghua Yi Xue Za Zhi, 1994 Feb, 74(2), 92 - 3, 127
{Relationship between Melkersson-Rosenthal syndrome and spirochetes infection}; Liu HG et al.; By using Warthin-Starry spirochete special stain method and a transmission electron microscope for the first time, we detected spirochetes separately in lesions of 23 cases of MRS and 5 cases of MRS . Their shapes and distributive places were described . 11 cases were treated by high dose of penicillin, and 10 were responsive . This result provided further basis for a conjecture that the attack of MRS may be related to the infection of spirochetes.

Zhongguo Zhong Yao Za Zhi, 1994 Feb, 19(2), 76 - 7, 126
{Preliminary study on spraying penicillin on Ligusticum chuanxiong Hort.}; Xie DM; It has been proved that penicillin spray on Ligusticum chuanxiong can contribute to the growth of the plant in the following ways: cutting down the tissue water potential, strengthening the capability of sucking moisture, increasing the contents of chlorophyll and restraining its degradation to facilitate the formation of photosynthetic compounds, enriching the nutrition root and increasing the root-shoot ratio . All these help to keep the stem tuber rot under 5% so as to guarantee higher economic yield of the plant.

Appl Microbiol Biotechnol, 1994 Feb, 40(6), 883 - 7
Utilization of side-chain precursors for penicillin biosynthesis in a high-producing strain of Penicillium chrysogenum; Eriksen SH et al.; Utilization of the side-chain precursors phenoxyacetic acid (POA) and phenylacetic acid (PA) for penicillin biosynthesis by Penicillium chrysogenum was studied in shake flasks . Precursor uptake and penicillin production were followed by HPLC analysis of precursors and products in the medium and in the cells . P . chrysogenum used both POA and PA as precursors, producing phenoxymethylpenicillin (penicillin V) and benzylpenicillin (penicillin G), respectively . If both precursors were present simultaneously, the formation of penicillin V was blocked and only penicillin G was produced . When PA was added at different times to cells that were induced initially for POA utilization and were producing penicillin V, the POA utilization and penicillin V formation were blocked, whereas the cells started utilizing PA and produced penicillin G . The blocking of the POA turnover lasted for as long as PA was present in the medium . If POA was added to cultures induced initially for PA utilization and producing penicillin G, this continued irrespective of the presence of POA . Utilization of POA increased concomitant with depletion of PA from the medium . Analysis of cellular pools from a growing cell system with POA as precursor to which PA was added after 48 h showed that the cellular concentration of POA was kept high without production of penicillin V and at a concentration comparable to the concentration in the medium . The cellular concentration of POA was higher than the concentration of PA that was utilized for penicillin G production.

Brain Res, 1994 Jan 7, 633(1-2), 105 - 11
The role of excitatory amino acids in the generation of spontaneous hippocampal oscillations; Schneiderman JH et al.; We examined the role of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in generating spontaneous CA3 field potential oscillations in the hippocampal slice . Non-NMDA EPSPs are responsible for a portion of the spontaneous activity recorded in standard perfusion medium . NMDA receptors are not activated when inhibition is intact, however, recurrent excitation via NMDA receptors accounts for an increasing proportion of the low frequency (2-4 Hz) rhythms produced as inhibition is progressively blocked by low concentrations of the GABAA antagonist, penicillin . Production of these rhythms involves complex interactions among NMDA, non-NMDA and GABAA receptors . NMDA EPSPs can drive the rhythm in the absence of non-NMDA receptors only when inhibition is suppressed by more than 50% . Otherwise non-NMDA EPSPs appear to be necessary to depolarize neurons before NMDA EPSPs can be activated.

J Bacteriol, 1994 Jan, 176(1), 256 - 9
Artifactual processing of penicillin-binding proteins 7 and 1b by the OmpT protease of Escherichia coli; Henderson TA et al.; Penicillin-binding proteins (PBPs) were visualized in strains of Escherichia coli that carried mutations in one or more of the following protease genes: tsp, degP, ptr, and ompT . In the absence of a functional ompT gene, PBPs 1b alpha and 7 were not processed to the shortened forms 1b beta and 8, respectively . Cleavage of PBPs 1b alpha and 7 could be restored by introduction of a plasmid carrying the wild-type ompT gene . These PBPs were processed only after cell lysis or after membrane perturbation of whole cells by freeze-thaw, suggesting that the cleavage was a nonspecific artifact due to contact with OmpT, an outer membrane protease, and that such processing was not biologically significant in vivo . The degradation of other PBPs during purification or storage may also be effected by OmpT.

CMAJ, 1994 Jan 1, 150(1), 37 - 41
Radioallergosorbent testing for penicillin allergy in family practice; Worrall GJ et al.; OBJECTIVES: To determine (a) the prevalence of patients supposedly allergic to penicillin who have a positive radioallergosorbent test (RAST) result for penicillin G or V and (b) the predictive power of family physicians' clinical judgement that a patient who is supposedly allergic to penicillin will have a positive RAST result . DESIGN: Prospective multicentre cross-sectional observational study . SETTING: Eleven primary care practices in Newfoundland; 10 were in a rural setting . PATIENTS: Of 110 consecutive adult patients with a supposed allergy to penicillin 97 agreed to participate in the study; 92 underwent RAST . INTERVENTIONS: Patients helped physicians complete a questionnaire and had a venous blood sample taken for the RAST . Physicians examined the clinical history and judged whether the patient was likely to have a positive RAST result . MEAN OUTCOME MEASURES: Rates of positive and negative RAST results for penicillin V and G . RESULTS: Of the 92 patients 8 had a positive RAST result and 84 a negative one . The positive predictive power of a "good" clinical history (e.g., urticaria, swollen eyes, tongue or lips, or an anaphylactic reaction witnessed by a physician) was low (10%); the negative predictive power of a "poor" clinical history (e.g., nausea, vomiting, diarrhea, fever, nonspecific rash or fainting) was 92% . CONCLUSIONS: Less than 10% of primary care patients with a supposed allergy to penicillin will have a positive RAST result . In addition, physicians' predictions of allergy in such patients are imprecise.

Womens Health Issues, 1994 Spring, 4(1), 16 - 9
The political history of syphilis and its application to the AIDS epidemic; Amstey MS; The history of syphilis control from the mid-19th century through the present time is a strong argument for the need to enhance the public health efforts to find cases of human immunodeficiency virus (HIV) infection and to notify the partners of infected individuals . To do this, public policy must be changed to allow better case-finding (mandatory testing) and partner notification (mandatory reporting) . The history of syphilis is such that one person in 22 was infected in this country in 1918 . If we are to use this history to control the current HIV epidemic, control measures used for syphilis (before penicillin) are needed; these are equal attention to education, available health care, case-finding, and partner notification.

Food Addit Contam, 1994 Jan-Feb, 11(1), 1 - 6
Depletion of penicillin G residues in tissues and injection sites of yearling beef steers dosed with benzathine penicillin G alone or in combination with procaine penicillin G; Korsrud GO et al.; The contribution of benzathine penicillin G to residues in tissues and injection sites of yearling beef steers was assessed by treating seven groups of five to seven steers with either benzathine and procaine penicillin G together or benzathine penicillin G alone . Steers were injected with a commercial combination of benzathine and procaine penicillin G according to the Canadian (intramuscular) or United States (subcutaneous) label dosages of 8600 and 8800 IU penicillin G/kg body weight, respectively . They were killed 14 or 30 days after the intramuscular injections, and 30 days after the subcutaneous injections . At the label withdrawal times, Canadian 14 days and United States 30 days, the levels in the injection sites for all of the treatments were 30-60 times above the Canadian and United States' Maximum Residue Limit of 50 micrograms/kg, while liver, kidney and gluteal muscle levels were below the Maximum Residue Limit . Other steers were injected intramuscularly with 24,000 IU benzathine/procaine penicillin G/kg body weight and slaughtered 8, 14 or 50 days after injection . Fifty-day injection site residues were 24 times the Maximum Residue Limit . Another group of steers was injected intramuscularly with benzathine penicillin G alone at 12,000 IU/kg body weight and slaughtered 14 days later . Penicillin G levels in the injection sites were 156 times the Maximum Residue Limit . The persistence of penicillin G residues at the injection sites in all the treatment groups appears to be attributable primarily to benzathine penicillin G . Visual inspection of muscle surfaces did not reliably reveal all injection site lesions in the underlying musculature.

Microbiology, 1994 Jan, 140 ( Pt 1), 79 - 87
Alterations of murein structure and of penicillin-binding proteins in minicells from Escherichia coli; Obermann W et al.; Minicells, as compared with a whole cell preparation of a minA/B mutant of Escherichia coli, showed a number of changes in the structure of the murein sacculus . Minicell murein was enriched in LD-A2pm-A2pm crossbridges by about 66% and reduced in the amount of L-Ala-D-Glu dipeptide moieties by about 55% . In addition, the length distribution of the glycan strands in the murein was shifted to shorter lengths . In particular, the relative amount of the shortest possible strand, the size of a disaccharide, was more than doubled . Minicells were also found to have an altered penicillin-binding protein (PBP) pattern . Whereas PBP4 and PBP6 were greatly diminished, PBP8 was significantly increased . We consider it unlikely that the sort of changes observed in murein structure reflect the fact that minicells are composed of two hemispherical polar caps.

Microbiology, 1994 Jan, 140 ( Pt 1), 73 - 7
Analysis of the membrane-anchoring properties of the putative amphiphilic alpha-helical anchor at the C-terminus of Escherichia coli PBP 6; Phoenix DA et al.; Penicillin-binding protein (PBP) 6 is anchored to the periplasmic face of the Escherichia coli inner membrane . Analysis of the C-terminal 20 amino acids of PBP 6 implies the presence of a C-terminal amphiphilic alpha-helical anchor comparable to that of PBP 5 . A C-terminal deletion of PBP 6 was constructed; it resulted in the release of the protein from the inner membrane into the periplasm, thus confirming that this region is essential for anchoring . Treatment of E . coli K12 membrane vesicles with various reagents was used to probe the membrane-binding characteristics of both PBP 5 and PBP 6 . The results indicate that, although the strength of membrane anchoring of PBP 6 is weaker than that of PBP 5, both modes of anchoring involve a large hydrophobic element and have similar membrane-binding characteristics . This is in agreement with the hypothesis that both proteins exhibit the same novel method of anchoring.

Epilepsia, 1994, 35 Suppl 3, S5 - 9
Oxcarbazepine: mechanisms of action; McLean MJ et al.; The antiepileptic drug (AED) oxcarbazepine (OCBZ) and its rapidly formed 10-monohydroxy metabolite (MHD) protect against electroshock-induced tonic hindlimb extension in rodents (ED50 14-21 mg/kg p.o.) . Both stereoisomers of MHD also protect . As with carbamazepine (CBZ), these findings suggest clinical efficacy against generalized tonic-clonic and, to some extent, partial seizures . OCBZ (IC50 5 x 10(-8) M), MHD (IC50 2 x 10 (-8) M), and CBZ (IC50 6 x 10(-7) M) limit the frequency of firing of sodium-dependent action potentials by cultured mouse central neurons and reduce Vmax progressively in a use-dependent manner at concentrations below therapeutic plasma concentrations in OCBZ-treated patients . This suggests that blockade of voltage-sensitive sodium channels could contribute to the antiepileptic efficacy of OCBZ . Blockade of penicillin-induced epileptiform discharges in hippocampal slices by MHD and its stereoisomers was diminished when the potassium channel blocker 4-aminopyridine was added to the bath fluid . This indicates that additional mechanisms of action, e.g., an effect on potassium channels, might be clinically important . In addition, both stereoisomers are equally responsible for the antiepileptic activity of the racemate, i.e., MHD, and are therefore likely to play a therapeutic role . Such actions could confer broad clinical utility on OCBZ.

Neurochem Res, 1994 Jan, 19(1), 1 - 4
Effect of penicillin on GABA-gated chloride ion influx; Tsuda A et al.; To investigate the mechanism of penicillin-induced convulsions, we have studied the effects of penicillin G (PC-G) on GABA-gated chloride ion influx in brain 'microsac' preparations of mice . In the presence of 10(-4) M GABA, PC-G inhibited GABA-gated chloride ion influx in a dose-dependent manner . The dose-response curve for GABA in the presence of 10(-3) M PC-G was shifted rightward and there was a decrease in maximum response . The inhibitory effects of PC-G were not reversed by RO 15-1788, an antagonist of benzodiazepine (BZ) receptors, but were reversed by washing the 'microsac' membranes . Therefore, PC-G probably exerts its proconvulsant effect by inhibiting GABA-gated chloride ion influx . However, it appears not to act through the BZ receptor of the GABA/BZ receptor complex.

Anal Biochem, 1994 Jan, 216(1), 89 - 96
Discovery and analysis of a series of C2-symmetric HIV-1 proteinase inhibitors derived from penicillin; Gray NM et al.; In order to identify a suitable peptide substrate for human immunodeficiency virus-1 (HIV-1) proteinase, a range of peptides from various cleavage sites within the gag-pol polyprotein were assayed by HPLC for specific cleavage . The peptide with the optimal combination of favorable kinetics and good solubility was based on the N-terminus cleavage site of HIV-1 proteinase (KQGTVSFNF*PQIT) . The HPLC assay, using the above peptide, was developed into a rapid isocratic method in order to analyze inhibition kinetics . An assay suitable for high-throughput screening was developed using a radioactively labeled peptide with the same sequence, coupled to a solid phase . Using this assay, a C2-symmetric HIV-1 proteinase inhibitor derived from penicillin was discovered during random screening of a compound library . A chemical synthesis program developed this structure into a series of potent inhibitors . The lead structures were highly selective for HIV-1 proteinase with good antiviral activity in vitro against HIV and no cytotoxicity . The HPLC assay was used to demonstrate that these compounds are competitive tight-binding inhibitors of HIV-1 proteinase.

Hokkaido Igaku Zasshi, 1994 Jan, 69(1), 84 - 94
{Regional differences in seizure threshold following systemic and topical administration of penicillin in cats}; Kataoka N; The regional differences of epileptic seizure susceptibilities in various brain structures were investigated by using the feline model of systemic and local applications of penicillin (PC) . After PC application, "repetitive isolated discharges" (RIDs) were observed and thereafter, it developed to "sustained high-frequency discharge" (SHD) . The following results were obtained . 1 . After the intraperitoneal application of PC, the areas involved by RIDs in order of frequency were cerebral cortex, hippocampus, mesencephalic reticular formation, centro-median nucleus of thalamus, amygdaloid nucleus, dorsal median nucleus of thalamus and globus pallidus . SHD was firstly arising from cerebral cortex (100%), especially from suprasylvian gyrus of 13 out of 16 cats (18.2%) . SHD immediately propagated to either the other cortical areas or subcortical structures . Hippocampus, centro-median nucleus and dorsal median nucleus of thalamus were rapidly involved by SHD from cerebral cortex in comparison with the other subcortical structures . 2 . PC was applied topically on the surface of several different cortical areas . RIDs tended to appear in posterior suprasylvian gyrus . On the other hand, SHD arose from posterior ectosylvian gyrus in most cases . The mechanisms of initiation and propagation of epileptic discharge were discussed in conjunction with epileptic seizure susceptibility in various neuronal structures.

FEMS Microbiol Rev, 1994 Jan, 13(1), 1 - 12
Multiple mechanisms of membrane anchoring of Escherichia coli penicillin-binding proteins; Gittins JR et al.; The major penicillin-binding proteins (PBPs) of Escherichia coli play vital roles in cell wall biosynthesis and are located in the inner membrane . The high M(r) PBPs 1A, 1B, 2 and 3 are essential bifunctional transglycosylases/transpeptidases which are thought to be type II integral inner membrane proteins with their C-terminal enzymatic domains projecting into the periplasm . The low M(r) PBP4 is a DD-carboxypeptidase/endopeptidase, whereas PBPs 5 and 6 are DD-carboxypeptidases . All three low M(r) PBPs act in the modification of peptidoglycan to allow expansion of the sacculus and are thought to be periplasmic proteins attached with varying affinities to the inner membrane via C-terminal amphiphilic alpha-helices . It is possible that the PBPs and other inner membrane proteins form a peptidoglycan synthesizing complex to coordinate their activities.

Ann Dermatol Venereol, 1994, 121(1), 34 - 6
{Cutaneous tertiary syphilis with neurological symptoms}; Drobacheff C et al.; INTRODUCTION . The tertiary cutaneous syphilis is now extremely rare . We report a case of tubercular cutaneous syphilis associated with neurological dysfunction . We emphasize the difficulties to interpret serologic and CSF tests for the diagnosis of neurosyphilis . CASE REPORT . A 63 year-old-woman had nodular, purplish and painless cutaneous lesions on forehead and forearm for 6 months . The biopsy showed a dermohypodermic lymphoplasmocytic granuloma, without necrosis, with endothelitis . Syphilis serologic tests were positive: VDRL = 512 U; TPHA = 40,960 U; FTA abs: IgG = 72,000 U; IgM = 1,350 U; Nelson test = 100 p . 100 (1,200 U) . HIV test was negative . There was a past history of a positive syphilis serologic test when the patient was 20-year-old . The patient complained of shaking and her family spoke of gradual mental deterioration and behaviour troubles . The neurological examination showed a major frontal syndrome, cerebellar dysfunction with dysarthria and a major labial and lingual tremor . There is no lymphocytosis nor increased protein in the CSF; VDRL test was negative, TPHA test was positive, FTA abs = 4,000 U (IgG), and TPHA was increased . Penicillin G 16 millions units/day was given intravenously for 20 days; a slow increase was made in association with steroids at the beginning . The cutaneous lesions regressed in 14 days, but the neurologic state did not change . Six months later, there was still no IgM, TPHA decreased and VDRL was unchanged . DISCUSSION . While the diagnosis of tertiary cutaneous syphilis was correct, the neurological abnormalities are difficult to classify . The symptoms were those of general paresis, but there is no argument favouring biological CSF activity (no increase in protein or lymphocytosis, negative VDRL) . Nevertheless, in the context of very positive serologic tests and tertiary cutaneous syphilis, we treated this case as a neurological syphilis . The treatment regimen and the need of current cures are still under discussion.

Rev Alerg Mex, 1994 Jan-Feb, 41(1), 19 - 24
{Insulin allergy in type II diabetes: rapid desensitization}; Ruiz Barrera E et al.; Eight patients (7 female, 1 male) diagnosed as being allergic to insulin, between the ages of 49 and 68, were evaluated . In seven patients there was a previous history of allergies to other drugs: 4 to penicillin, two to sulfurs and one to nalidixic acid . The clinical manifestations were predominantly systemic: ras, six patients; angioedema, 3 patients; hypotension, three patients; bronchial spasm, 2 patients; generalized eruption, one patient . All 8 patients were subjected to skin tests which were positive, one patient showed a positive local skin reaction and the other seven proved to be positive . All reactions were favorable in all cases which allowed for the continuation of the administration of insulin without adverse reactions.

J Fr Ophtalmol, 1994, 17(6-7), 394 - 8
{Syphilitic uveitis}; Harada T et al.; Three cases of syphilitic uveitis were described in which penicillin therapy combined with oral steroid regimen afforded rash disappearance of retinal edema in all cases . However, remarkable recuperation of vision was obtained in 2 cases.

Yi Chuan Xue Bao, 1994, 21(2), 155 - 60
{Site-directed mutagenesis at Ser177 of penicillin G acylase gene}; Peng T et al.; Site-directed mutagenesis was performed at Ser177 of Penicillin G Acylase (PGA) gene of E . coli by gap duplex method . Screened by 2-nitro-5-phenylacetaminobenzoic acid (NIPAB) test paper assay and confirmed by DNA sequencing, the mutants Cys177, Gly177, Arg177 and Asn177 were obtained . They have no activity of PGA . The mutant enzyme was expressed and detected by PAGE . It is suggested that Ser177 is at the substrate binding center of PGA and can not be replaced.

Acta Otolaryngol Suppl, 1994, 515, 57 - 64
The efficacy of oxymetazoline administered with a nasal bellows container and combined with oral phenoxymethyl-penicillin in the treatment of acute maxillary sinusitis; Wiklund L et al.; The efficacy of a new administration form of oxymetazoline, a nasal bellows container, was investigated in two separate studies by means of a combined treatment with phenoxymethyl-penicillin for acute maxillary sinusitis . In the first study (study 1), oxymetazoline administered with a bellows (OXBE) was compared both with a placebo belows (PLBE) as well as with oxymetazoline and placebo administered with a conventional nasal spray (OXSP respective PLSP) in 73 patients . In the second study (study 2), OXBE was compared only with PLBE in 48 patients . Objective evaluation was made by comparing the radiographical improvement in conventional plain sinus X-ray images . A scoring system corresponding to the outcome of antral irrigation was used for evaluating the X-ray pictures . Subjective symptoms; nasal stuffiness and pain, were assessed by registrations on visual analogue scales . Neither with regard to radiographical improvement nor to decrease in subjective symptoms could any significant differences be found between the different treatment modes . Oxymetazoline administered with a nasal bellows thus did not accelerate the rate of healing of acute maxillary sinusitis in these two studies . It is inferred from these results that decongestion of the sinus ostia is not of primary importance for the course of healing of a manifest acute sinusitis.

Biosens Bioelectron, 1994, 9(3), 179 - 88
The bilayer lipid membrane as a generic electrochemical transducer of hydrolytic enzyme reactions; Nikolelis DP et al.; Bilayer lipid membranes (BLMs) can be used as generic transducers to monitor hydrolytic enzyme reactions occurring at the membrane surface . The representative enzymatic reactions presented herein were between membrane associated urease and penicillinase with urea and penicillin, respectively . Transient electrochemical signals from BLMs which contained enzyme were obtained by proper selection of the lipid composition of membranes . Negatively charged lipid membranes composed of egg phosphatidylcholine (PC) and 35% dipalmitoylphosphatidic acid were used for this purpose . The results were consistent with an electrostatic mechanism of perturbation of the surface structure of the BLMs, where changes of local hydronium ion activity associated with the enzymatic reaction altered the extent of ionization of the headgroups of the acidic constituent of the membranes, thereby providing a transient charging current which lasted for a period on the order of seconds . The delay time for observation of the transient was directly and reproducibly related to the concentration of the substrate which could be determined over a range of microM to mM levels . The results indicate that BLMs can be used as generic selective electrochemical transducers and as switchable biosensors to monitor rapid enzymatic reactions which alter pH.

Physiol Res, 1994, 43(1), 45 - 9
Effect of phenytoin on cortical epileptic foci in cerveau isolé rats; Mares P; The action of phenytoin was studied in acute experiments in rats with brainstem transection at the midcollicular level . Symmetrical epileptogenic foci were elicited in sensorimotor cortical areas of both hemispheres by local application of penicillin . Seven rats formed a control group, ten animals were pretreated with phenytoin (60 mg/kg i.p., 10 min before penicillin application) . Synchronization of interictal discharges in control rats was delayed in comparison to animals with an intact brainstem; phenytoin did not influence this synchronization . Spontaneous transition of interictal into ictal activity was not abolished by phenytoin, i.e . in cerveau isole preparations phenytoin lost this activity . The loss of anticonvulsant activity was not complete . Ictal episodes were modified; they started as very short ones and their duration progressively increased . Structures localized below the level of transection represent a site of at least one of the mechanisms of phenytoin anticonvulsant action.

Exp Brain Res, 1994, 98(1), 97 - 100
Decrease of extracellular catecholamine content in the vicinity of cortical penicillin-induced epileptogenic focus: voltammetric study in the rat; Pavlasek J et al.; Differential pulse voltammetry with carbon-fibre microelectrodes was used in chloralhydrate-anaesthetized rats to test the influence of the penicillin-G-Na (PNC)-induced (topical application, approximately 2000 IU) epileptic activity on the catecholamine content (catechol-oxidative current, CA.OC) in the parietal cortex . In the experimental group (n = 4) after PNC a nonlinear CA.OC lowering was observed; this decrease during the first 10 min was faster than in the control group (n = 4) . Significantly different values were observed from the 4th min after application . The best fit for this experimental curve gave the logarithmic function (f(t) = a+b.ln(t), a = 105.8, b = -10.6) with regression coefficient r = 0.98 . From the 12th min after PNC application until the end of the experiments (54th min) CA.OC values ranged from 78% to 84% of the control group.

Zhongguo Yao Li Xue Bao, 1994 Jan, 15(1), 73 - 5
{C-fos expression in rat brain during seizure and electroacupuncture}; Wang BE et al.; C-fos proteins were visualized immunohistochemically in the brain of rats after seizures induced by injecting penicillin into hippocampus and by penicillin+electroacupuncture treatment . Three hours following seizures there was an evident expression of c-fos proteins in the hippocampus (CA1 area), dentate gyrus, piriform cortex, dorsal part of entorhinal cortex, and amygdaloid nucleus, and there was a dramatic increase of c-fos proteins in CA3 area and the areas mentioned above except the CA1 area where c-fos proteins apparently decreased after electroacupuncture treatment . The results showed that seizures can induce c-fos proteins in some nuclei related with seizure and that electroacupuncture can also regulates the c-fos expression after seizure.

Cathet Cardiovasc Diagn, 1994, Suppl 2, 61 - 8
Acute and chronic efficacy of percutaneous transvenous mitral commissurotomy: implications for patient selection; Herrmann HC; Despite the introduction of penicillin and improvements in the standard of living and delivery of primary health care, rheumatic mitral stenosis remains an important medical problem in the United States as well as abroad . In the past decade, percutaneous transvenous mitral commissurotomy (PTMC) with the Inoue balloon catheter has emerged as a safe and efficient treatment for symptomatic patients and has supplanted surgical commissurotomy as the initial treatment approach in the majority of patients with mitral stenosis . Acutely, balloon valvuloplasty can achieve an approximately 100% increase in mitral valve area and markedly improve symptoms, including dyspnea and NYHA functional class . However, peak oxygen consumption during exercise may not increase acutely, and the subjective improvement in dyspnea is likely related to a diminished work of breathing . Chronically, the hemodynamic improvements achieved with PTMC are maintained (up to 5 yr) with a low rate of recurrent symptoms due to restenosis, production, or progression of mitral regurgitation or inadequate initial dilation . Freedom from death, mitral valve replacement, and repeat valvuloplasty range between 51% and 84% at 4-5 yr postprocedure, depending on various selection criteria . Functional improvement, as measured by exercise capacity with respiratory gas analysis, occurs over several months suggesting that chronic peripheral alterations in the skeletal muscle and vasculature of patients with long-standing mitral stenosis may limit the initial benefit of successful PTMC until vascular remodeling or aerobic training can allow the skeletal musculature to use the greater cardiac output afforded by successful PTMC . Careful patient selection is essential to obtain the best hemodynamic improvement with the lowest rate of complications.(ABSTRACT TRUNCATED AT 250 WORDS)

J Toxicol Clin Toxicol, 1994, 32(6), 715 - 21
Poisoning by amatoxin-containing mushrooms in suburban New York--report of four cases; Feinfeld DA et al.; We report four cases of poisoning with amatoxin-producing mushrooms in suburban Long Island . All occurred when amateur mushroom hunters picked mushrooms from neighboring lawns . Two patients presented 30 hours post ingestion with evidence of acute hepatic dysfunction . One survived, after treatment with charcoal and penicillin; the other, a 90-year-old woman with prior cardiac disease soon developed shock and subsequently died . The other two patients were admitted 18 hours after ingestion of Lepiota chlorophyllum and received prompt charcoal hemoperfusion . Both did well, although one had a mild elevation of transaminases . Although most reports of amatoxin poisoning originate in Europe, these cases confirm that amatoxin-producing mushrooms, including Lepiota chlorophyllum, may be found in northeastern American suburbs . Such patients who present prior to 24 hours after ingestion should receive charcoal hemoperfusion if a lethal dose (> 50 g of mushroom) has been eaten.

Pneumonol Alergol Pol, 1994, 62(7-8), 397 - 404
{Clinical characterization of "asthma-prurigo" syndrome with emphasis on risk factors}; Rudzki E et al.; In a group of 228 patients with Asthma-Prurigo syndrome in 82.5% of patients the onset of skin lesions was earlier than the onset of asthma . It was found that the early onset of atopic dermatitis suggests the greater probability of subsequent asthma . In 88.6% of patients also other allergic diseases were diagnosed, and rhinitis allergica was observed most frequently . In the investigated group of patients urticaria chronica idiopathica or physical urticarias were not observed . Among 228 patients with Asthma-Prurigo syndrome, 74.6% of patients pointed to house dust as one of the most frequent causative factors . The house dust similarly to other inhalant allergens, somewhat more frequently had influence on the course of atopic dermatitis than on the course of asthma . Contrary to this observation according to patients food allergens (milk, eggs, fish, chocolate) aggravated or induced the relapses of skin lesions much more frequently than asthma . It was shown how often patients noticed adverse reactions due to penicillin and sulphonamides.

Rev Med Interne, 1994, 15(7), 452 - 9
{Epidemiological, clinical, biological and developmental aspects of leptospirosis: apropos of 30 cases in Aquitaine}; Ragnaud JM et al.; We have studied retrospectively 30 cases of leptospirosis observed in Aquitaine (South West France) from 1980 till 1992 . This review was made in three internal and a nephrology department in Bordeaux hospital . Most cases occurred by indirect contact with infected animals or by occupational exposures . Onset was brutal with fever often associated with painful syndrome and sometimes conjunctival suffusion . Jaundice (70%), acute renal failure (67%), meningitis (50%) and hemorrhagic signs (50%) were among the major visceral manifestations . Diagnosis was always confirmed by micro-agglutination test . Leptospira ictero-hemorrhage was the predominant serogroup found . The outcome was favorable in 22 patients; reversible complications were seen in six cases (five acute renal failure with hemodialysis myocarditis and pulmonary edema in two hemodialysed patients, polyradiculoneuritis) . Two patients died (acute respiratory failure and meningo-encephalitis with diffuse hemorrhagic syndrome) . The characteristic of our series is the high frequency of hepatorenal syndrome due to the importance of our nephrologist recruitment . Furthermore our study confirm the vital prognostic characters of the pulmonary, renal, hemorrhagic and neurologic complications . No absolute relationship was found between the clinical and laboratory findings and the serotype of leptospira . Penicillin remains the treatment of choice and should be started as soon as possible the avoid the life threatening visceral complications.

Ter Arkh, 1994, 66(10), 70 - 3
{The Extencillin treatment of patients with early forms of syphilis}; Mashkilleison AL et al.; Outpatient treatment of syphilis was given to 250 patients . All of them received extencilline (benzathine penicillin G) in intramuscular injections . One injection of the drug (2400000 U) was administered for primary seronegative syphilis (15 cases) and for prevention (65 subjects) . Two injections with 7-day interval were carried out in the dose 2400000 U for primary seropositive (58 cases), secondary early (14 cases) and recurrent syphilis (36 cases) . Patients with secondary recurrent syphilis whose body mass exceeded 85 kg (55 cases) and subjects with latent disease (72 cases) received 3 injections in 7-day intervals . Extencilline proved a potent antisyphilis tool able to rapidly eliminate clinical symptoms of the disease and to promote making serological reactions negative . Extencilline activity is superior to that of bicillin and water-soluble penicillin . Treponema pallidum escape from syphilid surface within 7 treatment hours, on the average . Extencilline is worthy of being used among most effective drugs in outpatient treatment of early syphilis.

Rev Mal Respir, 1994, 11(6), 601 - 3
{Diffuse alveolar hemorrhage and myositis in icterohemorrhagic leptospirosis . Rapid control by a single bolus of corticoids}; Courtin JP et al.; Leptospirosis is one of the commonest causes of diffuse alveolar haemorrhage . Despite good sensitivity to penicillin and current techniques of ventilation, there remains a considerable mortality which is particularly linked to the initial pulmonary disease at presentation . The authors describe a new case of a gravely ill patient with leptospirosis and sever hypoxaemia . There was diffuse alveolar haemorrhage and myositis thus a bolus of corticosteroids was used over the first 24 hours complementary to the traditional treatment.

Drugs Exp Clin Res, 1994, 20(6), 247 - 55
Biliary elimination and hepatic disposition of an association of piperacillin and tazobactam: experimental evaluation; Brogard JM et al.; Biliary elimination and hepatic disposition of tazocillin, an association of a highly bile-excreted ureido-penicillin, piperacillin, with a beta-lactamase inhibitor, tazobactam, have been assessed applying an isolated perfused rabbit liver experimental model . Six investigations were performed, each during a 3 h period, using reconstituted blood circulating in a closed circuit . Piperacillin and tazobactam concentration in all specimens were determined by high performance liquid chromatography . Blood samples and cumulative bile secretion were collected every 30 min, and liver fragments were isolated at the end of each experiment for dosage purposes . Following the simultaneous administration of piperacillin 80 mg and tazobactam 10 mg (dose ratio 8/1) in the perfusion device, theoretical initial serum concentrations were respectively 414 micrograms/ml and 32.1 micrograms/ml . Maximal biliary concentrations of 4431 +/- 1541 (s.d.) of piperacillin and 21.3 +/- 7.8 micrograms/ml of tazobactam were reached between 0.5-1 h and 2.5-3 h, respectively . Cumulative biliary excretion (0-3 h) amounted to 37.6 +/- 17.7% of the administered dose for piperacillin and 1.5% for tazobactam . At the end of the perfusion, respectively 22.1% and 50.7% of piperacillin and tazobactam doses remained in the circulating blood, while 1.1% and 5.6% were found in the liver . On the basis of these data, the calculated percentages of piperacillin and tazobactam doses having undergone hepatic biotransformation, were 6.5% and 1.2%, respectively . Under such experimental conditions, concentrations and excretion of piperacillin in bile prove to be substantial . Of note, tazobactam concentrations turn out to be stable both in serum and in bile whereas they stay at a relatively constant level of 20 micrograms/ml during nearly all the perfusion time.(ABSTRACT TRUNCATED AT 250 WORDS)

Acta Biomed Ateneo Parmense, 1994, 65(3-4), 213 - 24
Evaluation of a cardiopulmonary preservation method for heart-lung transplantation; Le Gal YM et al.; This study was designed to examine whether concomitant administration of anti-free radicals with donorcore cooling on cardiopulmonary bypass (CPB) and hypothermic storage of the heart and lung, could provide successful extended cardiopulmonary preservation . Fourteen sheep heart-lung blocks harvested after core-cooling and cardioplegic arrest were preserved at 4 degrees C for 8.5 hr . Before and during CPB, the animals were perfused with Prostaglandin E1 (PGE1), superoxide dismutase (SOD), catalase (CAT) and deferoxamine (DEF) . Cardioplegic arrest was induced with St . Thomas' Hospital solution (Plegisol) to which SOD, CAT and DEF had been added . The preservation solution consisted of Plegisol modified by the addition of K-lactobionate, raffinose, mannitol, SOD, CAT, DEF, a phosphate buffer and penicillin . Histological examination performed on 3 donor heart-lung blocks before and after CPB and cardioplegia, then immediately following cold storage, produced no clear evidence of structural damage in cardiac myocytes and lung parenchyma . Eleven donor organs were therefore transplanted in size-matched recipients with a total mean ischemic time of 12 hr . The combined administration of SOD, CAT, DEF, insulin and glucose during the initial period of reperfusion had no beneficial effect on cardiopulmonary performance . A progressive fall in Pa O2 and mean aortic pressure was observed post-operatively in the 7 animals that were weaned from CPB . Five of them died within 3 to 5 hr after CPB weaning, the remaining 2 animals died of cardiac arrest within the fourth hour . The results of this experiment seem to indicate that: 1 . better organ function and improved survival could have been obtained if the duration of anti-radical treatment had been prolonged after reperfusion and, 2 . physical manipulation of the donor grafts during harvesting and transplantation may have been partly responsible for the poor post-transplantation cardiopulmonary performance.

Acta Biomed Ateneo Parmense, 1994, 65(3-4), 181 - 98
Heart-lung protection from ischemic injury during 8 hour hypothermic preservation; Le Gal YM et al.; Optimal techniques of heart-lung preservation are yet to be defined . The aim of this study was to develop, in a canine model, a method of heart-lung preservation which would permit distant procurement of the organs . The animals were divided into 2 groups . In the experimental group (N = 6) the method of preservation consisted of cold cardioplegic arrest of the heart with St . Thomas' Hospital solution containing superoxide dismutase, catalase and deferoxamine, followed by cold pulmonary artery flush with modified Euro-Collins solution to which prostaglandin E1, superoxide dismutase, catalase, deferoxamine and Dextran 40 were added . Following harvesting, the heart-lung block was stored for 8 hours in cold (4 degrees C) Euro-Collins solution containing superoxide dismutase, catalase, deferoxamine, lactobionic acid, raffinose, mannitol, Dextran 40, magnesium sulfate, insulin and penicillin . In the control group (n = 6), the heart-lung block underwent the same treatment as the experimental group except that lactobionic acid, raffinose and insulin were omitted from the storage solution, and that oxygen radical scavengers were excluded from the cardioplegic, pneumoplegic and storage solutions . Histologic and electron microscopic examinations of heart-lung specimens taken before and after 8 hours cold storage of the organs suggested that our preservation technique may be effective in preventing ischemia-induced injury.

Schweiz Arch Neurol Psychiatr, 1994, 145(5), 25 - 30
Single photon emission computed tomography with 99mTc hexamethyl propylene amine oxime (HMPAO) and focal motor seizures; Weder B et al.; The proper localization of regions of interest (ROIs) in Single Photon Emission Computed Tomography (SPECT) is an essential task . The limited spatial resolution makes it difficult to define regions by their structure . The particular problems are: 1) the difficulty to find the appropriate slice and its orientation in space; 2) the individual variation of the brain in dimension and shape . Referring to the basic work of Talairach and Szikla (1967), research is conducted to overcome these methodical problems in interpreting cranial computed tomography by using a proportional localization system . We analyzed four cases with focal motor seizures of different aetiology (tumour, hemorrhagic infarction, intracerebral hematoma, multifocal leukencephalopathy) by 99mTc HMPAO SPECT . The accumulation of the radiopharmacon was measured in ROIs which were delineated with the aid of the above mentioned system . The regions were selected in accordance to the autoradiographic study of penicillin induced epileptic seizures in animal experiments . Dependent on the severity of the clinical manifestation we were able to document the involvement of the supposed primary focus and of several related zones . We suggest that this approach should prove some usefulness in the examination of the interdependency of different brain areas.

Eur J Surg Suppl, 1994, (573), 39 - 44
Pharmacokinetics and tissue penetration of piperacillin/tazobactam with particular reference to its potential in abdominal and soft tissue infections; Sorgel F et al.; Piperacillin/tazobactam is a new drug consisting of a highly active penicillin and a beta-lactamase inhibitor . Pharmacokinetic variables of both components after they have been given together have been studied in healthy volunteers and in patients . Drug analysis in all studies was done by specific high pressure liquid chromatography (HPLC) . In this review we summarise the pharmacokinetic properties of piperacillin/tazobactam . Most importantly, data on the piperacillin show that its behaviour is not changed when it is given with tazobactam . The pharmacokinetics of tazobactam are typical of beta-lactams, including the tissue penetration . It is distributed mainly into the extra-cellular space . Tissue concentrations of piperacillin/tazobactam and the concentrations of the two agents and their time course in plasma and tissue indicate that this combination is well formulated and truly synergistic pharmacokinetically . Clinical trials will show how these characteristics influence treatment outcomes.

Pediatr Infect Dis J, 1993 Dec, 12(12 Suppl 3), S142 - 7
Overview of the safety profile of clarithromycin suspension in pediatric patients; Craft JC et al.; Results of preclinical studies conducted to characterize the safety of clarithromycin oral suspension in juvenile mice, rats and dogs as compared with that in adult animals indicate that there is no enhanced risk in younger animals . Adverse events in these preclinical studies mainly involved decreased body and increased liver and kidney weights . The safety profile of clarithromycin suspension also has been evaluated in Phase II (pharmacokinetic) and III (clinical) United States and international clinical trials conducted in pediatric patients . The most frequently reported adverse events occurring among the 1676 patients studied who received clarithromycin suspension in Phase III trials included diarrhea (7%), vomiting (6%), abdominal pain (2%), headache (2%) and nausea (1%) . Adverse events were not serious and were usually rapidly reversible . Adverse event rates did not vary with sex or race . Overall adverse event rates were generally similar to those of comparator beta-lactam suspensions (i.e . amoxicillin, amoxicillin/clavulanate, penicillin VK, cefaclor, cefadroxil) . With regard to specific gastrointestinal events, however, clarithromycin was better tolerated than amoxicillin/clavulanate whereas penicillin VK showed a lower incidence of gastrointestinal events . Overall clarithromycin oral suspension appears to be safe and well-tolerated, making it suitable for use in the pediatric population.

Mol Gen Genet, 1993 Dec, 241(5-6), 573 - 8
Resolution of four large chromosomes in penicillin-producing filamentous fungi: the penicillin gene cluster is located on chromosome II (9.6 Mb) in Penicillium notatum and chromosome I (10.4 Mb) in Penicillium chrysogenum; Fierro F et al.; Four chromosomes were resolved by pulsed field gel electrophoresis in Penicillium notatum (10.8, 9.6, 6.3 and 5.4 Mb in size) and in five different strains of Penicillium chrysogenum (10.4, 9.6, 7.3 and 6.8 Mb in the wild type) . Small differences in size were found between the four chromosomes of the five P . chrysogenum strains . The penicillin gene cluster was localized by hybridization with a pcbAB probe to chromosome II of P . notatum and to chromosome I of all P . chrysogenum strains except the deletion mutant P . chrysogenum npe10, which lacks this DNA region . The pyrG gene was localized to chromosome I in P . notatum and to chromosome II in all P . chrysogenum strains except in the mutant AS-P-78 where the probe hybridized to chromosome III . A major chromosomal rearrangement seems to have occurred in this high penicillin producing strain . A fast moving DNA band observed in all gels corresponds to mitochondrial DNA . The total genome size has been calculated as 32.1 Mb in P . notatum and 34.1 Mb for the P . chrysogenum strains.

J Otolaryngol, 1993 Dec, 22(6), 401 - 8
Otosyphilis: diagnostic and therapeutic update; Linstrom CJ et al.; The thorough investigation of patients presenting with sudden or fluctuating hearing loss, ringing or vertigo includes serology to exclude otosyphilis . Treatment of otosyphilis with penicillin and corticosteroids has achieved improvement in hearing, tinnitus and vertigo, but not in all patients . Selecting which patient with positive serology will benefit from treatment remains a difficult clinical problem . All patients presenting to The New York Eye and Ear Infirmary with cochleovestibular dysfunction of unknown aetiology and positive syphilis serology were assumed to have otosyphilis and were treated with intravenous penicillin, if non-allergic, and steroids . Lumbar puncture and HIV testing were performed . Eighteen patients were treated . Hearing (SRT and/or discrimination) improved in 4 of 16 patients with hearing loss (25%), tinnitus decreased in 10 of 14 (71%) and dysequilibrium improved in 6 of 9 (66%) . Factors associated with a good response included fluctuating symptoms, especially hearing, hearing loss less than five years, and age less than 60 . Improvement was unrelated to the severity of the loss or previous therapy . Patients with CSF abnormalities, including two patients with HIV disease, had subjective improvement . A summary of our results and a treatment protocol are presented.

Toxicon, 1993 Dec, 31(12), 1513 - 40
Clinical symptomatology and management of mushroom poisoning; Koppel C; Among poisonous mushrooms, a small number may cause serious intoxication and even fatalities in man . Humans may become symptomatic after a mushroom meal for rather different reasons: (1) ingestion of mushrooms containing toxins, (2) large amounts of mushrooms may be hard to digest, (3) immunological reactions to mushroom-derived antigens, (4) ingestion of mushrooms causing ethanol intolerance, and (5) vegetative symptoms may occur whenever a patient realizes that there might be a possibility of ingestion of a toxic mushroom after a mushroom meal . Based on the classes of toxins and their clinical symptoms, seven different types of mushroom poisoning can be distinguished: (1) phalloides, (2) orellanus, (3) gyromitra, (4) muscarine, (5) pantherina, (6) psilocybin, and (7) gastrointestinal mushroom syndrome . Two other entities of adverse reactions to mushrooms are (8) coprinus and (9) paxillus syndrome . Phalloides, orellanus, gyromitra and paxillus syndrome may lead to serious poisoning, which generally requires treatment of the patient in an intensive care unit . Diagnosis of mushroom poisoning is primarily based on anamnestic data, identification of mushrooms from leftovers of the mushroom meal, spore analysis, and/or chemical analysis . Therapeutic strategies include primary detoxification by induced emesis, gastric lavage and activated charcoal, secondary detoxification, symptomatic treatment and rarely specific antidotes . Owing to progressing fulminant hepatic failure, lethality associated with phalloides syndrome is still high (5-20%) . Basic treatment includes administration of silibinin and penicillin G, although controlled studies on its therapeutic efficacy are still lacking . In serious phalloides syndrome, orthotopic liver transplantation has to be considered . Fortunately, the prognosis in most other mushroom poisonings is excellent.

West J Med, 1993 Dec, 159(6), 690 - 1
Rothia dentocariosa endocarditis; Ruben SJ; Despite its presence normally in the mouth, R dentocariosa appears rarely to cause infection outside the oral cavity . There is no doubt, however, as additional reports accumulate, that this organism should be recognized as having the ability to cause a serious illness in humans . In addition, in vivo experience seems to suggest that a penicillin regimen should remain first-line therapy for this infection, with the efficacy of other agents remaining unproved.

Seizure, 1993 Dec, 2(4), 309 - 10
The antiepileptic effect of low-dose amino-phosphono-valeric acid (APV) is not enhanced by phosphatidylserine association; Loeb C et al.; We investigated the effects of the NMDA antagonist amino-phosphono-valeric acid (APV), alone or in combination with phosphatidylserine (PS) in the penicillin model of epilepsy . After penicillin injection, rats were treated i.p . with either APV alone (5 mg/Kg) or APV (5 mg/Kg) + PS (740 mg/Kg) . EEG epileptic activity decreased significantly in the group treated with APV alone, even at the very low dose used . This effect was not further enhanced by PS, suggesting that the previously reported effects of PS on GABA activity may be related to a specific interaction between these compounds.

J Biotechnol, 1993 Dec, 31(3), 345 - 56
Two FIA-based biosensor systems studied for bioprocess monitoring; Scheper T et al.; In this paper, two different FIA-based biosensor systems are described for application to different biotechnologically relevant purposes . In the first system, single fiber optodes were used to determine the pH, urea and penicillin V concentrations . A two-channel system was developed for the simultaneous monitoring of different variables to increase the analysis accuracy . This system was used for monitoring the penicillin V concentration during a cultivation of Penicillium chrysogenum . The second system described is a calorimetric immunoassay based on the use of an enzyme thermistor . A sandwich assay with protein A immobilized on a solid support for the determination of various IgGs was established . A fusion protein of protein A and beta-galactosidase obtained from a recombinant E . coli strain was used in the labelling and detection reaction . This system is designed for future application in bioprocess monitoring.

J Biotechnol, 1993 Dec, 31(3), 327 - 43
Software FIACRE: bioprocess monitoring on the basis of flow injection analysis using simultaneously a urea optode and a glucose luminescence sensor; Busch M et al.; Various computer programs for large-scale bioprocess control and optimization have been developed as well as software for simple laboratory routine analysis . In comparison, software can hardly be found that works on laboratory scale and provides the control of complex flow injection analysis (FIA) systems, multisubstrate determination, data evaluation as well as minimal process control abilities . The sensors applied can be of different type (luminometric or other optical as well as electrochemical biosensors) . The development of such a software may be very helpful for the transfer of FIA/biosensor systems from the state of development to industrial processes . Hence, each analysing system--even a well established biosensor--has to be individually adapted to the process, a task which is best done under laboratory conditions . Such a flexible, computer-controlled FIA system for research level based on the software FIACRE is presented . Five FIA/(bio)sensor system can be controlled simultaneously . Additionally, common temperature and pH recordings are possible . Determinations of substrate concentrations are performed by means of calibration curves which can be recorded at different times . This allows supervising the activities of the sensors during a cell cultivation and controlling the bioprocess, e.g . by adding substrate to a cell culture . The automated monitoring of the degradation of glucose and urea by two different optical sensing principles during a cell cultivation under the control of one microcomputer is presented for the first time . For this purpose, already well examined biosensors (a urease optode and a luminometric glucose sensor) were employed and their properties discussed under the aspect of working in real cultivation media . It will also be shown that substrates being of interest for bioprocess control can be detected by slight modifications of known reactions . For example, substrates of NADH-dependent enzymatic reactions can be detected by the luminol chemiluminescence system, and optodes can be employed for pH, penicillin and glucose determination.

Enzyme Microb Technol, 1993 Dec, 15(12), 1070 - 3
Studies of operational variables in batch mode for genetically engineered Escherichia coli cells containing penicillin acylase; Bhattacharya S et al.; A recombinant Escherichia coli was constructed by cloning the penicillin acylase gene from E . coli ATCC 11105 . The cloning was carried out using a recombinant plasmid pUSAD2 harboring the pac gene . The recombinant E . coli DH 5 cells were used as a biocatalyst and were studied in a batch reactor for determination of optimum value for some of the process parameters, such as effect of pH, temperature, substrate concentration, kLa and effect of carbon and nitrogen source on penicillin acylase production . These values were then compared with the values obtained with the standard parent strain . Whereas the cloned pac gene was found to produce higher levels of penicillin acylase constitutively, the process parameters remained about the same for both the parent and the recombinant.

Ugeskr Laeger . 1993 Nov 29;155(48):3932.
{Severe consequences of delayed diagnosis and treatment of neurosyphilis}; Larsen EB et al.; A case of full-blown neurosyphilis in a 40 year old university man is demonstrated . The disease was initially misdiagnosed as Creutzfeldt-Jakob disease . Nuclear magnetic resonance scanning supported this diagnosis . One year later the patient was hospitalized owing to increasing neurological deficits . For the first time he was examined for syphilis, and the disease was confirmed by a WR test . Despite lege artis penicillin treatment the patient was left with severe deficits, particularly of the intellect . The old phrase that syphilis can mimic any form of psychopathology is still true, and WR is still the test of choice whenever a neuropsychiatric diagnosis is unclear.

JAMA, 1993 Nov 24, 270(20), 2456 - 63
Clinical experience with penicillin skin testing in a large inner-city STD clinic; Gadde J et al.; OBJECTIVE--To establish (1) the prevalence of positive penicillin skin tests among outpatients with well-defined but variable history of penicillin allergy and (2) the reproducibility, safety, and negative predictive value of skin testing with benzylpenicilloyl polylysine (PPL) and a minor-determinant mixture (MDM) . DESIGN--Serial consenting outpatients with current indications for penicillin therapy were skin-tested in duplicate with PPL and MDM . Subjects with negative skin tests (93% of those positive by history and 95% of those negative by history) received therapeutic courses of benzylpenicillin (81%) or ampicillin (19%) . Negative predictive value of skin testing was established by 72-hour follow-up for adverse reactions to drug . SETTING/PATIENTS--A total of 5063 consecutive, qualifying outpatients in a Baltimore, Md, sexually transmitted disease (STD) clinic . The study group was young (73% between 20 and 40 years old), 66% male, and 90% black; 25% had history of atopy . Follow-up was 94% complete . RESULTS--Positive skin tests were observed in 7.1% of 776 individuals with previous history of penicillin allergy and in 1.7% of 4287 subjects negative by history (P << .001) . Previous history of anaphylaxis or urticaria was associated with significantly higher rates of positive skin tests of 17.3% and 12.4%, respectively (P<<.001) . Only 4% with history of exanthem had positive skin tests (P = .03) . The coefficient of variation for duplicate skin tests was 11% . Time intervals since last penicillin treatment did not influence the rate of positive skin tests . Adverse reactions to skin tests occurred in 13 (1.2% of patients positive by history; 9.4% of those with positive skin tests) . A mild anaphylactic reaction occurred in one individual whose preliminary scratch testing was inadvertently omitted; systemic pruritus or urticaria occurred in 11 subjects; one had a large local reaction . After penicillin administration to individuals with negative skin tests, acute allergic reactions occurred in 0.5% of subjects negative by history compared with 2.9% of subjects positive by history (chi 2 = 33.3; P = .0001) . Reactions were generally mild and self-limited; only two cases of mild anaphylactic reaction occurred, both in patients with history of severe IgE-mediated reaction . CONCLUSIONS--Skin testing with both major and minor penicillin determinants is safe using current recommendations, and both reagents are necessary for maximizing the identification of sensitized subjects . Routine penicillin skin testing can facilitate the safe use of penicillin in 90% of individuals with a previous history of penicillin allergy.

Neurosci Behav Physiol, 1993 Nov-Dec, 23(6), 562 - 7
The influence of activation of the superior colliculi on convulsive activity during picrotoxin kindling; Shandra AA et al.; It has been demonstrated in experiments in rats in which kindling was induced by repeated subconvulsive doses of picrotoxin (1.0 mg/kg) that the bilateral microinjection of picrotoxin, bicuculline, and penicillin into the deep layers of the superior colliculi of the corpora quadrigemina leads to the appearance of a generator of pathologically intensified excitation . An increase in the latent period of the initial convulsive manifestations, the suppression of clonic-tonic convulsive attacks, as well as the prevention of generalized epileptic activity induced by the systemic utilization of picrotoxin were observed under the conditions of the appearance of a generator of pathologically intensified excitation . An inference was drawn regarding the role of the superior colliculi in the mechanisms of the suppression of convulsive activity and regarding their inclusion in the antiepileptic system.

AJNR Am J Neuroradiol, 1993 Nov-Dec, 14(6), 1329 - 31
Third cranial nerve palsy caused by gummatous neurosyphilis: MR findings; Vogl T et al.; The clinical and MR findings in an unusual case of gummatous neurosyphilis are reported . A 44-year-old woman suffering from diplopia and right-sided headaches was admitted . Physical examination and routine laboratory parameters were normal except for a third-nerve palsy . MR images revealed a contrast-enhancing lesion of the upper brain stem and third cranial nerve . Differential diagnosis included neuroma of the third cranial nerve, as well as neurosarcoidosis and other inflammatory processes . Serologic tests and lumbar puncture revealed the presence of active syphilis . After intravenous treatment with penicillin G, follow-up MR examinations showed diminishing size of the lesion with its complete resolution within 3 months.

FEMS Microbiol Lett, 1993 Nov 1, 113(3), 247 - 51
Site-directed mutagenesis of dicarboxylic acid residues of the penicillin-binding module of the Escherichia coli penicillin-binding protein 3; Goffin C et al.; The glutamic acid E396, aspartic acid D409 and glutamic acid E411 residues of the Escherichia coli penicillin-binding protein 3 were each converted into an alanine residue . As deduced from penicillin-binding and complementation experiments, none of these dicarboxylic acid residues is involved in the mechanism of acylation by penicillin and none of them is essential for the in vivo functioning of the PBP . The mutation E396, however, causes an increased thermolability of the protein.

J Fam Pract, 1993 Nov, 37(5), 499 - 502
Association of penicillin allergy with idiopathic anaphylaxis; Antony SJ et al.; Idiopathic urticaria is a common and usually self-limited illness that is occasionally associated with life-threatening idiopathic anaphylaxis . A case is presented in which urticaria existed for 30 years before tests that revealed penicillin allergy as the probable cause . Our findings suggest that evaluation for penicillin allergy may be useful in some cases of urticaria.

Infection, 1993 Nov-Dec, 21(6), 367 - 72
Azithromycin versus penicillin V for the treatment of early Lyme borreliosis; Weber K et al.; In a randomized multicenter therapeutic trial, 32 patients with erythema migrans received oral azithromycin 500 mg once daily and 33 patients received phenoxymethylpenicillin (penicillin V) 1 million U three times daily for 10 days . Follow-up was for a median of 17 (range 3-32) months . Four weeks after initiation of therapy, 20 (62%) patients given azithromycin and 17 (51%) patients given penicillin V were completely free of all signs and symptoms and did not develop new ones subsequently (no significant difference) . Three months after initiation of therapy, the corresponding figures were 25 (78%) azithromycin and 28 (85%) penicillin V recipients (no significant difference) . There were only minor sequelae such as arthralgia, headache, fatigue, stiff neck and dysesthesia . Azithromycin led to a significantly faster resolution of the erythema migrans than penicillin V (p < 0.001) . Significantly more patients with more severe compared with mild initial disease had an elevated IgM antibody titer prior to therapy (p < 0.001) . Usually mild to moderate side effects occurred in 12 patients given azithromycin and five patients given penicillin V (p < 0.05) . Azithromycin appears to be as effective as penicillin V for the treatment of early Lyme borreliosis and it seems to clear the erythema migrans more promptly.

Sex Transm Dis, 1993 Nov-Dec, 20(6), 346 - 7
Asymptomatic neurosyphilis after doxycycline therapy for early latent syphilis; Zenilman JM et al.; A 50-year-old woman allergic to penicillin with early latent syphilis was treated with two courses of doxycycline . Ten months after diagnosis, she had no evidence of serologic response . A lumbar puncture demonstrated asymptomatic neurosyphilis . Penicillin desensitization was performed and she was successfully treated . This case re-emphasizes the need for close serologic follow-up in patients with latent syphilis.

Ukr Biokhim Zh, 1993 Nov-Dec, 65(6), 42 - 50
{Phosphorus-containing inhibitors of penicillin acylase . 3 . Inhibition of Escherichia coli penicillin acylase by phosphonate analogs of substrates}; Solodenko VA et al.; Phosphonic analogues of penicillin acylase substrates are found to be selective reversible competitive inhibitors of the enzyme from E . coli (EC 3.5.1.11) . The mode of binding of the inhibitors to the enzyme and the influence of the stereoelectronic parameters of the phosphonic inhibitors on their affinity to the enzyme are discussed.

Ukr Biokhim Zh, 1993 Nov-Dec, 65(6), 33 - 42
{Phosphorus-containing inhibitors of penicillin acylase . 2 . Design, synthesis and study of the hydrolytic stability of phosphonic acid derivatives as potential inhibitors of penicillin acylase}; Solodenko VA et al.; Phosphonate and phosphonoamidate derivatives of benzylphosphonic acids were synthesized as potential inhibitors of penicillin acylase (EC 3.5.1.11) proceeding from the concept of transition-state analogues . The compounds obtained are not the substrates of the enzyme and they are stable under conditions of enzyme activity testing.

Brain Res, 1993 Oct 29, 626(1-2), 149 - 55
Superfusion of verapamil on the cerebral cortex does not suppress epileptic discharges due to restricted diffusion (rats, in vivo); Kohling R et al.; The organic calcium channel blocker verapamil has been demonstrated to block epileptic activity in various experimental models both in vitro and in vivo . The drug, however, does not pass the blood-brain barrier, so that both the oral route and intravenous administration of the drug are ruled out for antiepileptic treatment . The present investigations analyzed the effects of verapamil applied epicortically in experimental models of interictal penicillin-induced and ictal pentylenetetrazol-induced epileptic activity in rats . Such epicortical application of verapamil was ineffective in suppressing either interictal or ictal epileptic activity . To test whether this lack of effect was due to poor penetration of the substance into the cortical tissue, the diffusion characteristics of verapamil were studied in agar and in gray matter by pressure microejection and an appropriate verapamil-selective microelectrode . The diffusion could be described fully by a diffusion coefficient D (5.08 x 10(-6) cm2 x s-1), tortuosity lambda (1.51) and concentration-dependent uptake, k' (2.23 x 10(-3) s-1) . Using these values, the depth-dependent concentration gradient resulting from superfusion of the substance was calculated for agar and brain . In concentration measurements done in brain tissue, however, verapamil could not be detected in cortical layers deeper than 150 microns, which did not agree with the theoretical prediction . This observation may indicate a diffusion barrier at the interface between superfusing fluid and tissue . The results indicate that epicortical administration of verapamil is not efficacious in treatment of epilepsy.

Ugeskr Laeger, 1993 Oct 18, 155(42), 3394 - 6
{Whipple disease}; Gaist D et al.; A case of Whipple's disease (WD) initially presenting with migrating arthralgia and later with weight loss, malaise, fever and abdominal discomfort is reported . On examination the patient showed signs of malnutrition, was anaemic and pyrexial (37.6-38.8) and had mild abdominal distention . Retroperitoneal lymph node enlargement was demonstrated by CT-scanning . Gastroduodenoscopy demonstrated white plaques and erosions in the 2nd and 3rd part of the duodenum . Repeated small bowed biopsies revealed pathological changes typical of WD . The patient was treated with parenteral penicillin 2 MIE t.i.d . for 14 days followed by sulfamethoxazole 800 mg and trimethoprim 160 mg b.i.d for a year . Response to treatment was satisfactory . Serum alkaline phosphatase levels were raised: 324-649 U/l (80-275) on admission and remained so following treatment.

J Med Chem, 1993 Oct 15, 36(21), 3129 - 36
Synthesis and structure-activity relationships of a series of penicillin-derived HIV proteinase inhibitors containing a stereochemically unique peptide isostere; Holmes DS et al.; A series of HIV-1 proteinase inhibitors was synthesized based upon a single penicillin derived thiazolidine moiety . Reaction of the C-4 carboxyl group with (R)-phenylalaninol gave amide 10 which was a moderately potent inhibitor of HIV-1 proteinase (IC50 = 0.15 microM) . Further modifications based on molecular modeling studies led to compound 48 which contained a stereochemically unique statine-based isostere . This was a potent competitive inhibitor (Ki = 0.25 nM) with antiviral activity against HIV-1 in vitro (5 microM) . Neither modification to the benzyl group in an attempt to improve interaction with the S2' pocket, nor introduction of a hydrogen bond donating group to interact with residue Gly48' resulted in improved inhibitory or antiviral activity.

J Med Chem, 1993 Oct 15, 36(21), 3120 - 8
A series of penicillin derived C2-symmetric inhibitors of HIV-1 proteinase: synthesis, mode of interaction, and structure-activity relationships; Humber DC et al.; The C2-symmetric diester 1 was identified by random screening as a novel inhibitor of HIV-1 proteinase . This led to the preparation of a series of related more potent amides from readily accessible penicillins . Many of the compounds showed potent antiviral activity in HIV-1-infected MT-4 cells and an ability to inhibit syncytia formation in infected C8166 cells, with no evidence of cytotoxicity . The compounds showed no activity against other aspartyl proteinases (renin, pepsin, and cathepsin D) . Structure-activity relationships support a symmetrical interaction with the enzyme . Pharmacokinetic evaluation of the ethylamide 3 revealed it was subject to rapid plasma clearance and had low oral bioavailability.

J Med Chem, 1993 Oct 15, 36(21), 3113 - 9
A series of penicillin-derived C2-symmetric inhibitors of HIV-1 proteinase: structural and modeling studies; Wonacott A et al.; The binding modes of a series of penicillin-derived C2 symmetric dimer inhibitors of HIV-1 proteinase were investigated by NMR, protein crystallography, and molecular modeling . The compounds were found to bind in a symmetrical fashion, tracing and S-shaped course through the active site, with good hydrophobic interactions in the S1/S1' and S2/S2' pockets and hydrogen bonding of inhibitor amide groups . Interactions with the catalytic aspartates appeared poor and the protein conformation was very similar to that seen in complexes with peptidomimetics, in spite of the major differences in ligand structure.

Ned Tijdschr Geneeskd, 1993 Oct 9, 137(41), 2098 - 100
{Lyme psychosis}; van den Bergen HA et al.; A woman aged 64 was admitted to the psychiatric department because of a psychotic decompensation with visual hallucinations, disorientation in time and space and associative thinking . On psychotropic drugs the condition failed to improve; subsequently neurological symptoms developed . EEG abnormalities prompted a lumbar puncture . In the CSF a strong plasma cell reaction with atypical cells was observed . The enzyme immunoassay for Borrelia burgdorferi was positive and after treatment with penicillin the psychiatric and neurological signs and symptoms disappeared . From the history which could then be taken it appeared that the patient had been bitten by ticks . Her husband aged 66 years passed through a similar episode of disease.

Dtsch Med Wochenschr, 1993 Oct 8, 118(40), 1437 - 41
{A severe course of leptospirosis with acute kidney failure and extensive icterus (Weil disease)}; Notheis WF et al.; A 77-year-old man developed a fever up to 38.4 degrees C, with diarrhoea, acute renal failure (creatinine up to 8.7 mg/dl; urea up to 308 mg/dl) and marked jaundice (total bilirubin up to 24.3 mg/dl) . In addition there was thrombocytopenia, conjunctivitis and epistaxis, as well as cerebral symptoms with somnolence and general slowing up . At first he was thought to have cholangitis resulting from previously diagnosed gall-stones, and he was therefore treated with ampicillin, 2 g two times daily, and metronidazole, 0.5 g two times daily . The fewer regressed, but the renal failure required haemodialysis and haemofiltration under strict fluid control . Endoscopy excluded obstructive jaundice, but a suspicion of inflammatory liver disease or possibly cirrhosis was raised in the differential diagnosis . Serology revealed an increased titre for Leptospira interrogans var . sejroe (1:200, later 1:1600) . Liver biopsy finding was compatible with the diagnosis of leptospirosis . Because of the high inflammatory activity in the liver, 2 mega units of penicillin G were administered three times daily for six days . Gradually the renal functions and jaundice improved and, on discharge on the 36th day, the patient was again in generally good health, although creatinine and bilirubin values were still slightly elevated (1.7 mg/dl each).

J Bacteriol, 1993 Oct, 175(20), 6704 - 10
Penicillin-binding protein 2 inactivation in Escherichia coli results in cell division inhibition, which is relieved by FtsZ overexpression; Vinella D et al.; Aminoacyl-tRNA synthetase mutants of Escherichia coli are resistant to amdinocillin (mecillinam), a beta-lactam antibiotic which specifically binds penicillin-binding protein 2 (PBP2) and prevents cell wall elongation with concomitant cell death . The leuS(Ts) strain, in which leucyl-tRNA synthetase is temperature sensitive, was resistant to amdinocillin at 37 degrees C because of an increased guanosine 5'-diphosphate 3'-diphosphate (ppGpp) pool resulting from partial induction of the stringent response, but it was sensitive to amdinocillin at 25 degrees C . We constructed a leuS(Ts) delta (rodA-pbpA)::Kmr strain, in which the PBP2 structural gene is deleted . This strain grew as spherical cells at 37 degrees C but was not viable at 25 degrees C . After a shift from 37 to 25 degrees C, the ppGpp pool decreased and cell division was inhibited; the cells slowly carried out a single division, increased considerably in volume, and gradually lost viability . The cell division inhibition was reversible when the ppGpp pool increased at high temperature, but reversion required de novo protein synthesis, possibly of septation proteins . The multicopy plasmid pZAQ, overproducing the septation proteins FtsZ, FtsA, and FtsQ, conferred amdinocillin resistance on a wild-type strain and suppressed the cell division inhibition in the leuS(Ts) delta (rodA-pbpA)::Kmr strain at 25 degrees C . The plasmid pAQ, in which the ftsZ gene is inactivated, did not confer amdinocillin resistance . These results lead us to hypothesize that the nucleotide ppGpp activates ftsZ expression and thus couples cell division to protein synthesis.

J R Army Med Corps, 1993 Oct, 139(3), 132 - 4
Rheumatic fever: atypical presentation in an adult; Sahi SP; A 38 year old Caucasian lady presented with a history of vague ill health, raised ESR and prolonged P-R interval on ECG . These features became normal within a week . Contrary to the usual presentation, this patient developed fleeting arthritis, one of the major diagnostic features of rheumatic fever, towards the end of her illness . It is important to recognise such variants of rheumatic fever, even in retrospect, for the sake of giving penicillin prophylaxis to prevent cardiac morbidity.

Can J Vet Res, 1993 Oct, 57(4), 223 - 30
Depletion of intramuscularly and subcutaneously injected procaine penicillin G from tissues and plasma of yearling beef steers; Korsrud GO et al.; Withdrawal periods required when doses of 24,000 IU and 66,000 IU of procaine penicillin G/kg body weight were administered to yearling beef steers by intramuscular injection daily for five consecutive days were investigated . These dosages are in excess of product label recommendations, but are in the range of procaine penicillin G dosages that have been administered for the treatment of some feedlot bacterial diseases . The approved dose in Canada is 7,500 IU/kg body weight intramuscularly, once daily, with a withdrawal period of five days . Based on the tissue residue data from this study, the appropriate withdrawal period is ten days for the 24,000 IU/kg body weight dose and 21 days for the 66,000 IU/kg body weight dose when administered intramuscularly to yearling beef steers . In a related study, 18 yearling beef steers received 66,000 IU of procaine penicillin G/kg body weight administered by subcutaneous injection, an extra-label treatment in terms of both dose and route of administration, typical of current practice in some circumstances . Deposits of the drug were visible at subcutaneous injection sites up to ten days after injection, with more inflammation and hemorrhage observed than for intramuscular injections of the same dose . These results suggest that procaine penicillin G should not be administered subcutaneously at high doses; and therefore a withdrawal period was not established for subcutaneous injection.

Enferm Infecc Microbiol Clin, 1993 Oct, 11(8), 433 - 6
{Thoracic actinomycosis}; Ibanez-Nolla J et al.; BACKGROUND: Thoracic actinomycosis is an rare disease in our medium . This fact, together with the variability of its forms of presentation and the difficulty in isolating its etiologic agent, make its diagnosis, particularly difficult . METHODS: A series of 8 cases diagnosed in the years 1988, 1989 and 1990 in two centers (Hospital de Bellvitge-Princeps d'Espanya and Hospital de l'Esperanca) is described with evaluation of the clinical and analytical data and the therapy applied . RESULTS: Species were only identified in 3 cases with Actinomyces israelii in two and Actinomyces odontolyticus in the third . The proven association with Mycobacterium tuberculosis, the presence of distant septic metastasis and eosinophilic pleuritis as forms of presentation are of note . Medical treatment was penicillin or derivatives in all the cases except one which was treated with diagnostic/therapeutic segmentectomy . CONCLUSIONS: It is concluded that when any subacute involvement of the thoracic and/or pleuropulmonary wall specific cultures should be carried out to discard eventual thoracic actinomycosis.

Transfus Med Rev, 1993 Oct, 7(4), 230 - 41
Specificity of drug-induced immune cytopenias; Christie DJ; What conclusions can be drawn concerning specificity of drug-induced immune reactions? We have seen that specificity of these reactions depends on several molecular features including the chemical nature of the drug, specific domains of particular membrane components, and as yet unidentified characteristics that determine selectivity for one or more cell types . This latter property does not seem to be related to shared membrane components because, for example, Rh antigens on RBCs, the peptide tail region of GPIb alpha on platelets, and the 85-kd GP on neutrophils are clearly not part of the same molecules . From multiple studies of quinine/quinidine-dependent and nomifensine-dependent antibody interactions with platelets and RBCs, respectively, we can conclude that these particular reactions are a function of specific features of the drug molecules and specific domains of various membrane glycoproteins . These characteristics strongly argue that the hypervariable regions of drug-dependent, platelet and RBC antibodies recognize simultaneously a specific domain of the membrane GP and a specific configuration of the drug molecule . If this is true, then it follows that together a specific domain of the cell membrane component plus the drug define an antigenic determinant or epitope for attachment of certain drug-dependent antibodies . We have also seen that some drug-dependent antibodies preferentially react with the drug alone when it is attached to cell membranes (eg, penicillin-dependent antibodies reacting with penicillin-coated RBCs or platelets) . Some drugs elicit antibodies that react at specific sites on the cell membrane independently of drug (eg, nomifensine and the Rh antigens (E) or quinidine and platelet GPV) . These three concepts of antibody specificity induced by drugs are presented in Fig 6, using RBCs as an example . Despite major advances in understanding drug-induced immune reactions during the past four decades, several important questions remain to be answered . For example, why are platelets involved more frequently than other cells of the circulation in these types of reactions? Why do some individuals develop drug-induced immune cytopenias that are specific for a single cell type, whereas others develop reactions involving multiple cell types with distinct antibodies? What mechanism directs the reaction toward platelets, RBCs, or neutrophils? How are drug-dependent antigens presented to the immune system? This latter question is particularly intriguing considering that most drugs known to induce immune cytopenias bind only weakly to target tissues.(ABSTRACT TRUNCATED AT 400 WORDS)

Cesk Gynekol, 1993 Oct, 58(5), 229 - 32
{Early-stage lyme borreliosis during pregnancy: treatment in 15 women with erythema migrans}; Hercogova J et al.; The authors treated and followed-up since July 1987 9 women with non-complicated erythema migrans and 4 women with erythema migrans associated with general signs and symptoms during pregnancy; two patients were treated only after delivery . For treatment antibiotics of the penicillin series were used . The course of gestation in 14 patients was without complications, one patient was followed-up on account of oedema of the lower extremities . The infants of 14 women were born in term, one infant was born during the 37th week of gestation . All infants were eutrophic . Umbilical blood for serological examination was collected from 8 infants, elevated IgG antibody levels against Borrelia burgdorferi were detected in one . The post-partum development of all infants was normal . During the subsequent follow-up for 6-26 months elevated antibodies against Borrelia burgdorferi were not found in any of the 4 infants subjected to serological examination . One child was operated at the age of one year on account of a patent ductus arteriosus, another child was treated at the age of two years on account of cryptorchism, two children were treated on account of hypoplastic enamel, in one infant at the age of 10 months the psychomotor development was retarded by two months . Transplacental transmission of Borrelia burgdorferi was not proved . With regard to the variety of the observed deviations and the small number of data the problem of a possible teratogenic action of this spirochete remains open.

South Med J, 1993 Oct, 86(10), 1147 - 50
Pediatric cervicofacial actinomycosis; Foster SV et al.; It is well recognized that cervicofacial actinomycosis is rare in children . We have summarized the cases in the English language literature and reported a recent case from our hospital . In only 10% of clinical situations is actinomycosis the primary diagnosis . Failure to consider actinomycosis in the differential diagnosis of a cervical mass may compromise the ability to make the diagnosis, given the fastidious nature of the most common pathogen, Actinomyces israelii . Indeed, the recovery rate of only 30% in some of the earlier studies of actinomycosis may have been in part due to this oversight . The correct diagnosis, however, is imperative because the treatment of actinomycosis is different from that of routine cervical adenitis in that actinomycosis requires high doses of penicillin over a prolonged time, since it is subject to relapse . Our case serves as a reminder to consider actinomycosis as the possible cause of a cervical mass, not only in adults, but in children as well.

Biull Eksp Biol Med, 1993 Oct, 116(10), 357 - 60
{The effect of the new amino acid-containing 1,4-dihydropyridine glutapyrone on penicillin-induced focal epileptic activity and convulsions induced by bicuculline and thiosemicarbazide}; Karpova MN et al.; The experiments on focal penicillin-induced epileptic activity in the brain cortex (Wistar rats) and bicuculline- and thiosemicarbazide-induced seizures (Icr:Icl mice) showed that the glutapyrone possessed a significant antiepileptic activity . As previously shown, that glutapyrone has an influence on 45Ca2+ uptake by rat cortical synaptosomes (evoked by K+ depolarization) as compared with nifedipine and nimodipine, and it was effective in pentylenetetrazol-induced seizures in rats and mice . The mechanism of action of convulsants is associated with the disturbance of different links of GABAergic inhibition . It is suggested that the antiepileptic effects of glutapyrone are realized at least in part by the participation of GABAergic system.

J Chromatogr, 1993 Sep 10, 647(1), 167 - 81
Determination of penicillin G, ampicillin, amoxicillin, cloxacillin and cephapirin by high-performance liquid chromatography-electrospray mass spectrometry; Straub RF et al.; This report contributes to a preliminary investigation of high-performance liquid chromatographic (HPLC)-mass spectrometric (MS) methods for confirming beta-lactam antibiotic residues in bovine milk . Initial work for each antibiotic evaluated the collisional activated dissociation (CAD) spectra that could be generated between the capillary and skimmer in the electrospray (ESP) interface . The drugs show various characteristic fragmentation, mostly within the beta-lactam ring and the amide group . Response for a particular compound in a given solvent can vary drastically . Usually, the more organic component in the solvent, the higher the ESP response . In many cases use of acetonitrile also results in slightly better ion currents than for methanol when comparing equal percentages of either organic solvent in water . The ESP response of most of the tested antibiotics can be enhanced by the addition of formic acid or acetic acid to the mobile phase methanol-water (1:1) . In general, the negative ion spectra are lower in intensity, exhibiting an {M-H}- ion and producing less fragmentation at higher CAD voltages as compared to positive ion spectra . An isocratic reversed-phase HPLC method for the separation of a mixture of five common beta-lactam antibiotics was developed using acetic acid as a mobile phase additive and optimized for detection with a new ESP HPLC-MS interface . A post-column split ratio of 70:1 for the eluent from a 150 x 2 mm I.D . column was chosen to provide the required lower flow-rate (approximately 4 microliters/min) . The limit of detection for the simultaneous determination of these antibiotics was estimated to be 100 ppb . Electrospray HPLC-MS could be used to confirm these antibiotics for quantities down to about 100 pg entering the mass spectrometer . Multiresidue analysis with microbore HPLC-ESP-MS has the advantage that no post-column splitting of the eluent is required and all of the analyte (on-column injected) will be transferred into the ESP interface . Preliminary work showed good mass spectrometric sensitivity down to the level of regulatory interest, but chromatographic separation efficiency must be improved.

Schweiz Med Wochenschr, 1993 Sep 4, 123(35), 1645 - 9
{A trial of modified triple therapy for the eradication of H . pylori in recurrent duodenal ulcer}; Wirth HP et al.; In a prospective trial we examined the efficacy and acceptability of a modified triple therapy in H . pylori (HP)-positive patients with recurrent duodenal ulcer disease . Oral administration of amoxicillin for two weeks was substituted for one single injection of intramuscular depot penicillin (benzathine penicillin G) . Additionally, patients were given ornidazole 500 mg tid for 14 days and 120 mg colloidal bismuth sub-citrate qid for 28 days . The patients were investigated for H . pylori colonization using a rapid urease test (CLO), histology (H&E-, Giemsa stain), culture (including determination of the minimal inhibitory concentrations for metronidazole, penicillin G and amoxicillin) and H . pylori serology (Cobas Core Anti-H . pylori EIA, F . Hoffmann-La Roche) . Control endoscopies using the same methods were performed 1 and 6 months after eradication therapy . The eradication rate was 50% and the ulcer healing rate 90% 1 month after therapy . Ulcers recurred in 2/3 of patients with persistent infection vs 0/5 of HP-eradicated patients after 6 months . Both successfully HP-eradicated patients and patients with treatment failure exhibited comparable decreases in mean serum IgG anti-HP concentration within 2 months . Discrimination between the two groups and hence identification of the eradication success by serology was not possible within a time period of 2 months . After 6 months, serum IgG anti-HP concentrations in non-HP-eradicated patients returned to pre-therapy values, in HP-eradicated patients the concentrations further decreased . The above-described modified triple therapy against HP cannot be recommended as a standard therapy, mainly because of the insufficient eradication effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Epilepsia, 1993 Sep-Oct, 34(5), 918 - 23
Suppression of interictal spikes and seizures by stimulation of the vagus nerve; McLachlan RS; The effects of electrical stimulation of the vagus nerve, a proposed treatment for patients with intractable epilepsy, on focal interictal spikes produced by penicillin and EEG secondarily generalized seizures induced by pentylenetetrazol were assessed in rats . Interictal spike frequency was reduced by 33% during 20 s of stimulation (p < 0.001) and remained low for < or = 3 min . Amplitude of residual spikes was also decreased . Cardiac and respiratory rates were suppressed . Cooling the nerve proximal to the point of stimulation abolished the EEG and respiratory effects . A similar reduction in spike frequency of 39% was obtained by heating the animals' tail (p < 0.01) . Vagal stimulation at onset of seizures reduced mean seizure duration from 30.2 +/- 15.7 s without stimulation to 5.0 +/- 1.8 s (p < 0.01) . Only the EEG equivalent of the clonic phase of the seizure was affected . These findings suggest that vagus nerve stimulation can be a potent but nonspecific method to reduce cortical epileptiform activity, probably through an indirect effect mediated by the reticular activating system.

Eur J Biochem, 1993 Sep 1, 216(2), 631 - 7
Bovine lens acylpeptide hydrolase . Purification and characterization of a tetrameric enzyme resistant to urea denaturation and proteolytic inactivation; Sharma KK et al.; An acylpeptide hydrolase has been purified from bovine lens tissue by anion-exchange and hydrophobic-interaction chromatography . The enzyme, purified over 27000-fold with 44% recovery, has a molecular mass of 300 kDa under native conditions . Under denaturing conditions it shows a subunit molecular mass of 75 kDa . The enzyme is inhibited by diisopropylfluorophosphate (iPr2P-F), phenylmethylsulfonyl fluoride and N-ethylmaleimide, indicating the presence of an essential serine residue and -SH group . Each subunit of the enzyme has one active serine residue which can be labelled with {3H}iPr2P-F . N alpha-blocked amino acids in L form act as competitive inhibitors of the enzyme . The antibiotics penicillin-G and ampicillin partially inhibit the enzyme . Exposure of the purified enzyme to the proteases trypsin, chymotrypsin or elastase do not result in any loss of activity . Digestion of the native enzyme with bovine trypsin generates a 55-kDa protein containing the active-site serine and a 22-kDa polypeptide, indicating the presence of a unique trypsin site . N-terminal amino acid sequencing of the 55-kDa polypeptide shows that the bovine lens enzyme has a sequence at the trypsin cleavage site identical to the porcine liver acylpeptide hydrolase sequence 196-215 . The data show that the split enzyme is as active as the native enzyme towards the synthetic substrate Ac-Ala-p-nitroanilide . The enzyme activity decreases with increasing urea, but 15% of the activity remains even in the presence of 6.0 M urea . On removal of urea, complete recovery of the enzyme activity is observed . However, treatment with 1 M guanidine/HCl completely inactivates the enzyme.

Arq Neuropsiquiatr, 1993 Sep, 51(3), 358 - 62
{Actinomycosis of the central nervous system: a rare complication of cervicofacial actinomycosis}; Ferraz AC et al.; Central nervous system actinomycosis is a rare but treatable chronic suppurative bacterial infection . The case of a young immunocompetent male with actinomycosis of the CNS is presented . The abscess originated from a primary cervico-facial infection and was located in the left parasellar region . After excision of the mass, that showed Actinomyces colonies, the patient was treated with intravenous Penicillin for 42 days followed by oral administration of the drug for 30 days . After surgery the patient was left with mild sequelae that had improved by the last follow-up, 7 months later . A new CT scan at that time revealed no residual disease or recurrence . The early diagnosis of cerebral actinomycosis relies essentially on a clinical suspicion . Hence it is imperative to be aware of the natural history of this infection and its various modes of presentation.

Brain Dev, 1993 Sep-Oct, 15(5), 356 - 61
High doses of penicillin decreases {3H}flunitrazepam binding sites in rat neuron primary culture; Shiraishi H et al.; Penicillin (PC) neurotoxicity (convulsions and encephalopathy) is considered to be due to GABAergic inhibition . The effects of penicillin G(PCG) on {3H}flunitrazepam (FNZ) binding in rat neuron-enriched primary cultures was examined to assess the role of the benzodiazepine (BDZ) receptor in the neurotoxicity . PCG application for 24 h induced a significant decrease in {3H}FNZ binding activity at 10(-3) M, and a decrease in available receptor number (Bmax) at 10(-2) M, without obvious cell damage . Pre-application of the BDZ receptor antagonist, Ro-15-1788, prevented the PC-induced decrease in {3H}FNZ binding activity . Therefore, PC seems to reduce the number of BDZ receptors through a direct effect on this receptor, which is a part of the major inhibitory system in mammalian brain; the GABAergic macromolecular receptor complex . This decrease in BDZ receptors may play a role in PC-induced neurotoxicity, especially encephalopathy.

Bioconjug Chem, 1993 Sep-Oct, 4(5), 309 - 13
Synthesis and characterization of a penicillin-poly(L-lysine) which recognizes human IgE anti-penicillin antibodies; Caneva E et al.; Conjugates of poly(L-lysine) containing a penicillin or a penicilloyl residue were prepared and characterized by 1H NMR and by size-exclusion HPLC . These conjugates and conjugates with human serum albumin were used in radioallergosorbent tests (RAST) for the determination of allergy toward penicillins.

J Endod, 1993 Sep, 19(9), 466 - 70
Prophylactic penicillin: effect on posttreatment symptoms following root canal treatment of asymptomatic periapical pathosis; Walton RE et al.; It has been reported that administration of prophylactic penicillin may prevent flare-ups or other undesirable posttreatment sequelae following root canal treatment . To test this hypothesis in a prospective study, 80 patients with a diagnosis of pulp necrosis and chronic apical periodontitis were divided into three groups: group A (prophylactic penicillin, AHA recommendation), group B (placebo, same regimen), and group C (no medication) . Medications and evaluations were double-blinded . Patients reported their posttreatment events including incidence of flare-ups, incidence and severity of pain/swelling, and occurrence of adverse side effects . Differences in the three groups were determined statistically using chi-square tests . The outcome showed no significant difference (p = 0.68) among the three groups . That is, administration/nonadministration of penicillin prophylactically was unrelated to posttreatment signs and symptoms following canal preparation . Incidence of flare-ups was very low (1 of 80) . Occurrence of pain in the mild-moderate levels was fairly high (approximately 70% overall), but was primarily in the mild category . Overall incidence of side effects was also very low (2 of 80) . Severe levels of pain/swelling and flare-up incidence were low with no difference between administration or nonadministration of antibiotics . Based on our data, using penicillin (a potentially dangerous drug) prophylactically to control posttreatment symptoms is not recommended in cases of pulp necrosis and asymptomatic periapical pathosis.

J Pharm Sci, 1993 Sep, 82(9), 897 - 900
Characterization of the oral absorption of some beta-lactams: effect of the alpha-amino side chain group; Oh DM et al.; The intestinal absorption mechanisms of cefixime, 7-aminocephalosporanic acid (7-ACA) and 6-aminopenicillanic acid (6-APA) were determined from the results of single-pass perfusion experiments in rats by modified boundary layer analysis . The estimated absorption parameters (SEM) were as follows: for cefixime, J*max = 0.016 (0.008) mM, Km = 0.031 (0.015) mM, P*m = 0.184 (0.037), P*c = 0.523 (0.051); for 7-ACA, J*max = 6.39 (1.57) mM, Km = 19.33 (5.64) mM, P*c = 0.33 (0.03) mM; and for 6-APA, P*m = 0.41 (0.11), where J*max is the maximal flux of peptide transport system, Km is the intrinsic Michaelis constant, P*m is the dimensionless membrane permeability, and P*c is the dimensionless carrier permeability . Cefixime was absorbed by a carrier-mediated mechanism because its wall permeability (P*w) was concentration dependent and significantly inhibited by cephradine . A concentration-dependent permeability of 7-ACA was observed, but an inhibition study failed to show significant inhibition by cephradine . The absorptions of 6-APA and penicillin V were not inhibited by cephradine or cefixime . The fractions of dose absorbed of several beta-lactam antibiotics correlated well with their absorption numbers obtained from P*w values in rats . These results further demonstrate that an alpha-amino group is not necessary for transport by the intestinal peptide transporter.

J Clin Pharmacol, 1993 Sep, 33(9), 837 - 44
The effect of phenobarbital on autonomic function and epileptogenic activity induced by the hippocampal injection of penicillin in cats; Lathers CM et al.; This study addressed whether penicillin-induced epileptiform discharges in the right hippocampus produced associated autonomic dysfunction . The study also examined the effect of phenobarbital on the heart rate and blood pressure changes that were induced by the epileptiform discharges . The delay in onset of epileptiform activity at the site of injection ranged from 1 second to 16 minutes, and consisted of interictal discharges or ictal discharges . With the onset of epileptiform activity, blood pressure and heart rate increased significantly from control (P < .05) . Electrocardiogram alterations included: P-R interval changes; increased P-wave amplitude; QRS complex changes; T-wave inversion; and ST elevation . Phenobarbital 20 mg/kg intravenously suppressed the epileptogenic activity and depressed the blood pressure and heart rate below control (P < .05) . In an additional series of experiments, penicillin G injected into the right hippocampus in five cats produced epileptiform activity and increased the blood pressure and the heart rate significantly from the control (P < .05) . Phenobarbital (20 mg/kg, intravenously, and 40 mg/kg, intravenously) also prevented the penicillin-induced epileptiform activity . Phenobarbital (40 mg/kg, intravenously) reversed the effect of penicillin on the blood pressure and heart rate, to levels significantly below that of control (P < .05) . Phenobarbital diminished both epileptiform activity and autonomic dysfunction . The autonomic dysfunction related to epileptiform activity induced by focal hippocampal administration of penicillin was similar to that induced by the intravenous administration of pentylenetetrazol.

Southeast Asian J Trop Med Public Health, 1993 Sep, 24(3), 595 - 600
Congenital syphilitic nephrosis; Niemsiri S; Analysis of congenital syphilis in 455 infants and neonates between 1977-1991 in Children's Hospital, Bangkok, Thailand revealed 11 cases (2.4%) with evidence of congenital syphilitic nephrotic syndrome which were confirmed by clinical, serologic and laboratory findings, long bone x-rays and renal biopsy . Ages of all 11 cases were between 1 day to 2 months (mean 24 days); 6 were boys and 5 girls . Two of them died because of necrotizing enterocolitis and sepsis respectively; the mortality rate was 18% . The other nine had complete recovery following penicillin therapy.

Biull Eksp Biol Med, 1993 Sep, 116(9), 288 - 90
{The effect of calcium-regulating pharmacological preparations on the formation of a generator of pathologically enhanced excitation in the system of the dorsal horns of the spinal cord}; Danilov EI et al.; A model of spinal pain syndrome induced by a generator of abnormally increased excitation in the system of dorsal horns of the spinal cord with penicillin was used to test the calcium channel blockers OF5015 and nimotop, as well as calcium gluconate for their effects . The drugs were administered orally, intraperitoneally, intracisternally and applied to the spinal cord in combination with penicillin which was used to induce the pain syndrome . The action of the agents were compared with that of analgin . OF5015 given in a dose orally was shown to attenuate the pain syndrome to a greater extent than analgin . Nimotop and calcium gluconate given orally or intrasystematically failed to affect the pain syndrome . When applied to the spinal cord, all the drugs substantially attenuated the pain syndrome or prevented its development.

Curr Microbiol, 1993 Sep, 27(3), 153 - 6
Low temperature protocol for efficient transformation of Mycobacterium smegmatis spheroplasts; Naser SA et al.; Spheroplasts of Mycobacterium smegmatis LM15, strain 607, were prepared by a combined treatment with glycine and lysozyme . The spheroplasts were tested for ability to take up and express purified mycobacteriophage DNA . Exposure of 1.0 x 10(8) to 1.0 x 10(9) spheroplasts to saturating DNA (1 microgram) for 15 min at 5 degrees C resulted in a transfection efficiency of approximately 0.009% . The transfer of the beta-lactamase marker with DNA purified from strain LM15 to spheroplasts of a beta-lactamase-negative mutant, strain LM144, was achieved . The DNA-treated cultures, after reversion to the bacillary form, contained 20-fold more penicillin-resistant cells than the nontreated control culture . Approximately 80% of the penicillin-resistant colonies from the DNA-treated cells were positive for beta-lactamase Cell-free extracts of penicillin-resistant transformants contained beta-lactamase activity that ranged from 0.046 to 0.134 micromol of benzylpenicillin hydrolyzed/min per mg protein . This low temperature procedure is recommended for high efficiency transformation of M . smegmatis.

Gene, 1993 Aug 25, 130(2), 265 - 70
Characterisation of the gene encoding acetyl-CoA synthetase in Penicillium chrysogenum: conservation of intron position in plectomycetes; Martinez-Blanco H et al.; Acetyl-coenzyme A synthetase (ACS; EC 6.2.1.1) from some plectomycete fungi is possibly involved in an accessory step of penicillin biosynthesis, in addition to its role in primary metabolism . We present the characterisation of the gene encoding this enzyme in Penicillium chrysogenum, which we designated acuA . Sequencing of genomic and cDNA clones showed that the coding region was interrupted by five introns, located at the same positions as those present in the Aspergillus nidulans homologue . This supports the possibility that the gene acquired its definitive mosaic organisation before the Penicillium/Aspergillus divergence . The mature transcript encodes a polypeptide with an M(r) of 74,287 which is 89.4% identical to its A . nidulans counterpart.

Pharm World Sci, 1993 Aug 20, 15(4), 156 - 60
Pharmacy personnel and fever: a study on perception, self-care and information to customers; Eskerud JR et al.; To study the fever perception and self-care of pharmacy personnel as well as the information given to customers about the management of fever problems, a random sample of 152 Norwegian pharmacists and 150 pharmacy technicians were interviewed, in 1989, by a national opinion poll company . One-third thought that body temperatures between 39.0 degrees C and 40.5 degrees C could be life-threatening . Of all respondents 24% (33% of technicians, 16% of pharmacists) assumed body temperatures to be rising when sweating accompanied fever . In cases of common cold or influenza accompanied by fever 56% of the personnel would use antipyretics . 7% Of the staff (14% of technicians, 1% of pharmacists) believed penicillin to be effective against viral infections . Antipyretic drug preferences were consistent, but a wide range of perceptions was revealed, in particular with respect to start of antipyretic therapy and seeking medical care for children . Undergraduate and postgraduate education of pharmacy personnel should aim more at satisfying the demand for information of the general public and focus more on the symptomatic treatment of fever and minor illness in general . Pharmacists in charge have a special responsibility in counselling their assistants.

Pharmacol Biochem Behav, 1993 Aug, 45(4), 857 - 63
Arrest of seizure series induced by an intracortical injection of penicillin in the awake rat; Horn E et al.; Experiments were performed to answer the question, whether series of generalized tonic-clonic seizures, induced in the awake rat by a local injection of Na-penicillin (PCN) solution into the motor cortex, terminates at the same critical concentration Ct of PCN within the focal area independently of the concentration C0 of PCN injected . Using the PCN diffusion coefficient D = 3.52 x 10(-4) mm2/s and the tortuosity factor lambda = 1.62, the concentration Ct at the onset of the last generalized seizure was calculated . The median duration of seizure series increased from 32 to 190 min, when the dose of injected PCN was raised from 32 to 1000 IU . At the onset of the last seizure, the median concentration Ct within the artificial focus ranged from 2.1 to 4.0 IU/0.5 microliter saline in rats treated with 32 to 125 IU PCN . After induction of convulsive behaviour with C0 = 250, 500, or 1000 IU PCN/0.5 microliter saline, however, Ct was at a higher level between 6.1 and 7.4 IU PCN/0.5 microliter saline . The difference between the cumulated data from the low-dose vs . the high-dose range was significant (p < 0.01) . It is concluded that during long-lasting series of generalized seizures, the brain takes advantage of its plastic properties . By forming a counteracting mechanism, it protects itself from extreme epileptiform activity . This autoprotection may be due to the activation of neuronal networks which probably needs a certain frequency of seizures to become operatively.

Gastroenterol Nurs, 1993 Aug, 16(1), 36 - 8
Unasyn (ampicillin sodium/sulbactam sodium); Claussen DW; Unasyn is a combination drug used for the treatment of infections as well as a prophylactic intervention prior to surgical or endoscopic interventions . Unasyn is a broad spectrum antibiotic of the penicillin family that inhibits beta-lactamases, ensuring activity of the ampicillin against resistant organisms . Peak serum levels of Unasyn are reached in 15 min to 1 hr after an IV infusion of 15 min.

Transfusion, 1993 Aug, 33(8), 689 - 92
Hemolytic anemia associated with injection of fluorescein; Munizza M et al.; A 49-year-old woman presented with a hemoglobin level of 9.5 g per dL (95 g/L), reticulocyte count of 6.7 percent (0.067), and hemoglobinuria . The next day, the hemoglobin had dropped to 5.8 g per dL (58 g/L), and total bilirubin was 8.8 mg per dL (150 mumol/L) . The serum reacted 2+ with all red cells (RBCs) . The direct antiglobulin test (DAT) was 3+ with anti-IgG and 1+ with anti-C3, but eluates prepared by two different methods did not react with untreated RBCs . The eluate reacted 2+ with amoxicillin-coated RBCs; amoxicillin had been listed in the patient's record as a previous medication . The patient denied recent ingestion of amoxicillin . Further investigation documented the injection of a dye, fluorescein sodium (AK-FLUOR-25%), for a ophthalmologic fluorescein angiographic study 2 days before admission . RBCs coated with AK-FLUOR reacted with the eluate . Controls consisting of normal serum, an eluate prepared from DAT-negative RBCs, and a serum known to contain anti-penicillin did not react with AK-FLUOR-coated RBCs . Nine days later, the DAT was negative and the serum did not react with untreated RBCs . In the presence of AK-FLUOR (1-in-125) or amoxicillin (1 mg/mL), the serum reacted 2+ in the antiglobulin test . Antibodies to AK-FLUOR and amoxicillin appeared to react by two mechanisms, which is similar to results in recent reports of other drugs associated with hemolytic anemia . AK-FLUOR has not previously been reported to be associated with hemolytic anemia.

Mol Microbiol, 1993 Aug, 9(4), 881 - 95
Molecular characterization of a fungal secondary metabolism promoter: transcription of the Aspergillus nidulans isopenicillin N synthetase gene is modulated by upstream negative elements; Perez-Esteban B et al.; The Aspergillus nidulans IPNS gene, encoding isopenicillin N synthetase, is a secondary metabolism gene . It is contiguous to, but divergently transcribed from, the ACVS gene at the penicillin gene cluster . The untranslated region between both ORFs is 872bp long . Here we present the physical and functional characterization of the IPNS transcriptional unit . Transcriptional start point (tsp) mapping reveals heterogeneity at the 5'-end of the mRNA, with a major start at -106 relative to the initiation codon . This indicates that the actual length of the non-transcribed intergenic region is 525bp . Functional elements in the IPNS upstream region have been defined by assaying beta-galactosidase activity in extracts from recombinant strains carrying deletion derivatives of the IPNS promoter fused to lacZ, integrated in single copy at the argB locus . Strains were grown in penicillin production broth under carbon catabolite repressing or derepressing conditions . The results of deletion analysis indicate that: (i) the IPNS promoter is mostly regulated by negative controls that act upon a high basal activity; (ii) sequential deletion of three of the negative cis-acting elements results in a mutated promoter that is 40 times (sucrose broth) or 12 times (lactose broth) more active than the wild type; (iii) one of these negative cis-acting elements is involved in sucrose repression . Strikingly, it is located outside the non-transcribed 525bp intergenic region and maps to the coding region of the divergently transcribed ACVS gene; (iv) a 5'-deletion up to -56 (relative to the major tsp) contains information to provide almost half of the maximal promoter activity and allows initiation of transcription at the correct site . By using total-protein extracts from mycelia grown under penicillin producing conditions we have detected a DNA-binding activity that specifically shifts a promoter fragment located between -654 and -455 (relative to IPNS tsp) . Deletions covering this region partially abolish IPNS promoter activity . The fragment in question overlaps the ACVS tsp.

Eur J Surg, 1993 Aug, 159(8), 387 - 92
Modulation of inflammatory reactions by previous contact with Escherichia coli in rats; Kinnaert P et al.; OBJECTIVE: To find out if contact with Escherichia coli had any effect on a subsequent inflammatory reaction induced by the same micro-organism . DESIGN: Controlled laboratory study . SETTING: University laboratory . MATERIAL: Male white Wistar rats divided into groups of 6 to 10 . INTERVENTIONS: Pretreatment with sponges soaked in 1 x 10(9) heat killed E . coli inserted either subcutaneously into the back or intraperitoneally into the right hypochondrium, and 14 days later repeat challenge . Controls received sponges soaked either in saline with penicillin and streptomycin or with carrageenan lambda . Pretreatment with live or heat killed E . coli or E . coli endotoxin injected intradermally or intraperitoneally (controls were given saline) . MAIN OUTCOME MEASURES: Number of white cells present in the inflammatory infiltrate and the peritoneal cavity, and titres of anti-E . coli antibody . RESULTS: Pretreatment of Wistar rats with heat-killed or live E . coli (ATCC 25922) was followed by increase in the cellular infiltrates at the site of subsequent challenge with the same micro-organism . The effect was not related to the synthesis of anti-E . coli antibodies . CONCLUSION: Surgical patients have commonly been in previous contact with E . coli; this might affect their inflammatory reactions if they came into contact with the organism after operation . Further studies are needed to clarify the precise mechanisms and clinical relevance of these findings.

Zentralbl Mikrobiol, 1993 Aug, 148(5), 343 - 50
Effects of potassium sorbate on growth and penicillic acid production by Aspergillus ochraceus and Penicillium aurantiogriseum; Garza S et al.; The effect of potassium sorbate on the growth and penicillin acid production of Aspergillus ochraceus and Penicillium aurantiogriseum was studied . Yeast extract sucrose (YES) broth at initial pH values of 5.5 or 7.0, and containing different concentrations of potassium sorbate was inoculated with fungal spores and incubated for 35 days at 28 degrees C . In all cases, although the pH changes in sorbate-containing media were delayed, patterns were similar to those of the cultures without sorbate . This was most evident when the highest concentration of potassium sorbate was used . Potassium sorbate also inhibited mycelial growth . Penicillic acid production was initially delayed by the presence of potassium sorbate but this inhibition was eventually overcome (30-35 days) and penicillic acid levels at the end of the experiment were similar or higher then the controls . Generally cultures growing in culture media at an initial pH of 5.5 produced less toxin than those growing at pH 7.0.

J Med Primatol, 1993 Aug, 22(6), 355 - 9
Cryopreservation of vervet monkey semen and recovery of progressively motile spermatozoa; Seier JV et al.; A method to cryopreserve semen from the Vervet monkey (Cercopithecus aethiops) has been developed, yielding a mean post thaw recovery of 63.60% of pre-freeze progressive motility . The extender contained a TES-TRIS buffer, egg yolk, dextrose, streptomycin, penicillin, and glycerol as cryoprotectant . The pH ranged from 7.10-7.18 and the osmolality was 330-345 mOsmol/L.

Eur J Biochem, 1993 Jul 15, 215(2), 323 - 32
The isopenicillin-N acyltransferase of Penicillium chrysogenum has isopenicillin-N amidohydrolase, 6-aminopenicillanic acid acyltransferase and penicillin amidase activities, all of which are encoded by the single penDE gene; Alvarez E et al.; The isopenicillin-N acyltransferase of Penicillium chrysogenum catalyzes the conversion of the biosynthetic intermediate isopenicillin N to the hydrophobic penicillins . The isopenicillin-N acyltransferase copurified with the acyl-CoA:6-aminopenicillanic acid (6-APA) acyltransferase activity which transfers an acyl residue from acyl-CoA derivatives (e.g . phenylacetyl-CoA, phenoxyacetyl-CoA) to 6-APA . Other thioesters of phenylacetic acid were also used as substrates . An amino acid sequence similar to that of the active site of thioesterases was found in the isopenicillin-N acyltransferase, suggesting that this site is involved in the transfer of phenylacetyl residues from phenylacetyl thioesters . Purified isopenicillin-N acyltransferase also showed isopenicillin-N amidohydrolase, penicillin transacylase and penicillin amidase activities . The isopenicillin-N amidohydrolase (releasing 6-APA) showed a much lower specific activity than the isopenicillin-N acyltransferase of the same enzyme preparation, suggesting that in the isopenicillin-N acyltransferase reaction the 6-APA is not released and is directly converted into benzylpenicillin . Penicillin transacylase exchanged side chains between two hydrophobic penicillin molecules; or between one penicillin molecule and 6-APA . The penicillin amidase activity is probably the reverse of the biosynthetic acyl-CoA:6-APA acyltransferase . Four P . chrysogenum mutants deficient in acyl-CoA:6-APA acyltransferase lacked the other four related activities . Transformation of these mutants with the penDE gene restored all five enzyme activities.

Brain Res, 1993 Jul 9, 616(1-2), 303 - 6
Separation of different interictal discharge patterns in acute experimentally induced epileptic foci of the rat in vivo; Dorn T et al.; Epileptic discharge patterns in an acute experimental model of epilepsy were analyzed . Epileptic foci were induced by epicortical application of penicillin on the rat motor cortex in vivo . Patterns with regular 1/s discharges, patterns with irregular discharges of about 0.5/s as well as compound patterns comprising discharges with intervals of about 300 ms could be differentiated by means of interval histograms and autocorrelation functions . These patterns occurred in an ordered sequence indicating that the different rhythms are activated by a progressive enlargement of the focus and duration of focal activity . The experiments suggest that different interictal discharge patterns can occur within the same brain regions and are not specific for a certain etiology; instead they seem to represent 'resonance' frequencies characteristic for the brain tissue which are disclosed under pathophysiological conditions.

Ugeskr Laeger, 1993 Jul 5, 155(27), 2147 - 50
{Serious arrhythmias in Borrelia infections}; Midttun M et al.; Carditis is seen in about 4-10% of cases of Lyme's disease . It is usually dominated by varying degrees of atrioventricular block, and implantation of a temporary pacemaker may be necessary . Ventricular and supraventricular tachycardias seem to be less frequent than block, and as far as we know ventricular tachycardia provoked by bradycardia has not been reported previously . Third degree AV-block after oral penicillin treatment of erythema migrans is unusual in Europe . When an atrioventricular block of unknown origin is diagnosed, Lyme carditis must be considered, especially among young patients.

J Dermatol, 1993 Jul, 20(7), 436 - 40
Relapsing syphilis; Yoon J et al.; Although penicillin still remains highly effective for syphilis, concerns have been raised that current regimens may be inadequate for the treatment of early syphilis . We report the failure of benzathine penicillin in the treatment of secondary syphilis . Extensive tracing of sexual contact history failed to identify sources of possible reinfection; therefore, we believe that this case represents a treatment failure and an ensuing relapse of secondary syphilis.

Bol Med Hosp Infant Mex, 1993 Jul, 50(7), 520 - 5
{Drug allergy}; del Rio-Navarro BE et al.; Adverse reaction to drugs are classified as immunological and non-immunological . It is consider that one to five percent of the general population reactions to drugs . Allergic reactions are the most intense and dangerous, but they represent only five to ten per cent of all of them . Immunological adverse reactions may be induced by the drug or by their metabolites . There are risk factors to induced allergic reactions such as doses, administration time and way of administration . The four mechanism of damage from Gell and Coombs are discussed regarding to drugs, stressing the penicillin issue . Other common drugs reactions in the diary practice are cutaneous reactions with unknown immunological mechanism as it happens in febrile mucocutaneous syndrome and the phototoxic and photoallergic reactions . Pseudoallergic or "anaphylactoid" reactions have signs and symptoms like those of anaphylaxis, but the mechanism of damage is not immunological, as with local and general anesthetics and radiopaque media . Treatment for any adverse events is to stop the administration as soon as possible . The drug of choice is 1:1000 subcutaneous adrenaline besides colloid solutions, steroids and antihistaminics.

Antimicrob Agents Chemother, 1993 Jul, 37(7), 1463 - 7
Facilitation of penicillin haptenation to serum proteins; DiPiro JT et al.; Traditionally, penicillin binding to serum proteins was believed to be a passive chemical process; however, it appears to be facilitated by serum factors . The objectives of this in vitro investigation were to examine facilitated penicillin haptenation, to study the kinetics of haptenation, and to determine the nature of haptenation-facilitating factors . The model involved addition of {3H}benzylpenicillin to serum or albumin solutions (at pH 7.3 to 7.4) and incubation at 37 degrees C for up to 72 h . The extent of penicillin binding to proteins in serum was found to be four- to fivefold higher than with solutions having comparable concentrations of purified albumin, total protein, or total immunoglobulin . Ultrafiltration of serum reduced penicillin binding to serum proteins substantially . An ultrafiltrable haptenation-facilitating factor(s) was found to be less than 0.5 kDa but was not calcium or magnesium . Finally, the extent of penicillin binding was related to albumin purity, as binding substantially increased with albumin purity . These findings suggest that there is a factor(s) in serum that facilitates covalent binding of penicillin to serum proteins . The factor(s) can be removed and then restored to increase penicillin binding to albumin . It appears that at least one component of the facilitation factor is less than 0.5 kDa, which suggests that it is not a peptide and that it is some simple serum component other than calcium or magnesium.

No Shinkei Geka, 1993 Jul, 21(7), 623 - 7
{Actinomycotic granuloma of the optic chiasma: a case report}; Toyoda O et al.; A case of actinomycotic granuloma of the optic chiasma and the optic nerve is reported . A 53-year-old man was admitted to our hospital with headache and vomiting on September 25, 1989 . General physical and neurological examination on admission revealed no remarkable findings . CT-scan demonstrated almost normal pictures . On the 17th hospital day, his temperature was 38 degrees C and white blood cell (WBC) count was 12000 cumm . And he presented right abducens palsy . MRI demonstrated no abnormal findings then . After antibiotic therapy of penicillin intravenously for 4 days, his temperature returned to normal and abducens palsy disappeared for two weeks . He was discharged 43 days after admission . But one year after discharge he developed progressive impairment of right visual acuity . He was admitted to our hospital again on January 19, 1991 . His neurological examination revealed severe impairment of right visual acuity and bitemporal hemianopsia . WBC count was 5400 and CRP was negative and temperature was 36.2 degrees C . CT-scan and MRI demonstrated a suprasellar enhancing mass lesion . Serum prolactin was 38 ng/ml . A diagnosis of pituitary adenoma was considered and a right frontotemporal craniotomy was performed . At operation, abnormally swelled right optic nerve and chiasma were found and the swelled chiasma only was resected . Histological examination showed an abscess containing necrotic tissues and actinomycotic granules with radiating filaments . The patient was given penicillin intravenously for 37 days and orally for two months . At that time, MRI revealed no abnormal enhancing lesion, and his visual acuity improved gradually . Actinomycosis of the optic nerve and chiasma is very rare.(ABSTRACT TRUNCATED AT 250 WORDS)

J Pediatr, 1993 Jul, 123(1), 156 - 8
Evaluation of secondary prophylactic schemes, based on benzathine penicillin G, for rheumatic fever in children; Meira ZM et al.; Serum concentrations of penicillin were measured in children with rheumatic fever . The adequacy of the values after administration of 1.2 million units of benzathine penicillin G every 2 or 3 weeks was confirmed; the adequacy of a 4-week regimen was questionable . The administration of 0.6 million units every 3 weeks was found to be inadequate to maintain serum levels high enough for the secondary prophylaxis of rheumatic fever.

Epilepsy Res, 1993 Jul, 15(3), 171 - 8
The brainstem cardioarrhythmogenic triggers and their possible role in sudden epileptic death; Mameli O et al.; The cardiovascular effects of simultaneous activation of hypothalamic and mesencephalic cardioarrhythmogenic triggers were studied in hemispherectomized rats . Paroxysmal activity of hypothalamic neurons (HEF), elicited by topical application of penicillin G on the thalamus, triggered short-lasting bradyarrhythmic episodes, up to a maximum of 6 s, and alterations in repolarization . In the hypothalamic neurons, an additional penicillin G epileptic focus at mesencephalic level (MEF) induced the enhancement of paroxysmal activity by a recruitment of new units and potentiation of their background activity . HEF+MEF triggered second-degree 2:1-8:1 atrioventricular (A-V) blocks, impairment of the A-V conduction, alterations in the recovery phase and bundle branch blocks . After HEF, the arterial blood pressure decreased by 4-6% . HEF+MEF induced a further reduction of 17% in systolic pressure only . It is possible that the enhancement of the HEF following MEF could depend on MEF spreading upward . The HEF, in turn, by spreading downward could influence the MEF and so activate, between HEF and MEF, a circuitry with reciprocal co-excitation that could explain the more serious cardiovascular alterations observed during HEF+MEF compared with those observed during HEF only or during MEF only . However, this cardiovascular impairment, which must be neurogenic in origin as it was observed in animals with normal acid-base and blood parameter values, did not induce heart death . Thus, additional concomitances must be considered, such as metabolic derangement which can occur during seizures, to explain sudden death in epileptic patients . Some aspects of metabolic complications in cardiac activity during epilepsy are also discussed.

Biomed Chromatogr, 1993 Jul-Aug, 7(4), 217 - 9
High performance liquid chromatography of penicillins with penicillin-enhanced luminol chemiluminescence detection; Nakashima K et al.; A high performance liquid chromatographic method with chemiluminescence detection for the determination of penicillin G and ampicillin is reported . The method is based on the enhancement of the luminol chemiluminescence with beta-lactam antibiotics . The linear relationship was obtained between the peak height and the concentration of penicillin G or ampicillin up to 15 nmol per 20 microL injection . Detection limits were 1 nmol for penicillin G and 0.5 nmol for ampicillin with a signal-to-noise ratio of 2 . Relative standard deviations for five replicate measurements of 4 nmol/injection each of penicillin G and ampicillin were 2.1 and 2.3%, respectively.

Br Heart J, 1993 Jul, 70(1), 88 - 90
Complete heart block in a 9 year old girl caused by borreliosis; Gildein HP et al.; A complete atrioventricular block was seen in a nine year old girl in whom an infection with Borrelia burgdorferi was confirmed by serological testing . There were no other symptoms or cutaneous manifestations of the disease . Though a rash on the right ear was later recalled by her parents . The patient was treated with high dose penicillin and orciprenaline was given intermittently . The complete heart block disappeared within four days.

Br Dent J, 1993 Jun 19, 174(12), 443 - 9
The effect of amoxycillin versus penicillin V in the treatment of acutely abscessed primary teeth; Paterson SA et al.; A clinical study was carried out to compare the efficacy of a short course, high dose amoxycillin versus a conventional penicillin regimen in the treatment of acute abscessed primary teeth . In a blind way children were assigned to either group A (amoxycillin) or group B (penicillin) . The efficacy of the antibiotics was assessed using the clinical parameters of pain, swelling, tenderness, mobility and lymphadenitis . The results showed a general trend of less swelling in patients in group A as compared with patients in group B . This was significant at days 1 and 7 for the operators assessment (Mann Whitney U test; z = 2.48 and z = 2.12) . More teeth in group A were considered suitable for first stage pulpectomy by day 7 (c2 test; P 0.037 pounds) . A short course, high dose amoxycillin regimen proved as efficacious as a conventional penicillin regimen.

Chest, 1993 Jun, 103(6), 1886 - 7
Pulmonary actinomycosis . A cause of endobronchial disease in a patient with AIDS; Cendan I et al.; We report a case of a 47-year-old man with AIDS who presented with fever, cough and a lingular infiltrate . Flexible fiberoptic bronchoscopy revealed an endobronchial exophytic mass with extensive purulent exudate which on Gram stain and cytology from bronchial washings revealed Actinomyces infection . There was a clinical response to penicillin therapy, and on repeat bronchoscopic examination, there was a partial resolution of the endobronchial infection . To our knowledge, this is the first known case of endobronchial pulmonary actinomycosis in a patient with AIDS.

Cephalalgia, 1993 Jun, 13(3), 207 - 9
Headache resembling tension-type headache as the single manifestation of Lyme neuroborreliosis; Brinck T et al.; We present two patients with monosymptomatic headache resembling chronic tension-type headache as the first manifestation of Lyme neuroborreliosis . The headache developed over a few days in both cases and lasted for three months in the first case and for two and a half years in the second case before the diagnosis of Lyme neuroborreliosis was made . Neuroimaging and many laboratory investigations did not lead to the diagnosis, which was only established after lumbar puncture . The CSF in both cases showed high protein, lymphocytic pleocytosis and Borrelia burgdorferi-specific intrathecal antibody synthesis . The headache disappeared completely after treatment with penicillin G . In patients suffering from daily headaches which have developed subacutely, Lyme neuroborreliosis should be considered even in the absence of signs of meningeal irritation . A lumbar puncture should be performed more often than is presently customary and the CSF should be examined for pleocytosis as well as Borrelia burgdorferi-specific intrathecal antibody synthesis.

Cesk Pediatr, 1993 Jun, 48(6), 332 - 3
{Severe Amanita phalloides poisoning in a 7-year-old girl}; Rambousek V et al.; Authors describe a case of a very severe poisoning, the prothrombin-time was less than 10% of the normal value and the child developed hepatic coma . We suppose, the favourable outcome may have been influenced by the treatment with Silymarin in combination with high doses of G-Penicillin.

Neuroreport, 1993 Jun, 4(6), 715 - 8
GABA-responses of CA3 neurones at epileptogenic threshold concentrations of convulsants; Bonnet U et al.; Epileptogenic actions of convulsants are often attributed to weakened inhibitory synaptic mechanisms . This assumption was tested by studying GABA-induced postsynaptic membrane potential (MP) changes of CA3 neurones (guinea-pig) before and during exposure to bicuculline methoiodide (BMI), pentylenetetrazol (PTZ), penicillin (PEN) and caffeine (CAF) . Under control conditions GABA ejections elicited polyphasic MP fluctuations (components I-III) . After adding BMI, PTZ, PEN or CAF, early hyperpolarizations (component I) did not change at epileptogenic threshold concentrations . These convulsants, however, exerted differential effects on the depolarizing component II, but only threshold concentrations of penicillin strongly reduced the amplitude of this component . Simultaneously, component III was slightly accentuated . These findings indicate that changes of GABA responses are not an essential prerequisite for the generation of paroxysmal depolarizations.

J Clin Pharm Ther, 1993 Jun, 18(3), 187 - 90
The use of evaporative cooling to extend the shelf life of reconstituted oral penicillin solutions; Dzuda C et al.; The relationship between temperature and the degradation of reconstituted penicillin solutions was evaluated . In all cases storage at temperatures of 25 degrees C or less was sufficient to maintain penicillin stability within acceptable pharmacopoeial limits for 5 days . In addition, the relationship between humidity and dry bulb temperature was examined in order to assess the use of evaporative cooling in lowering the temperature of penicillin solutions in those areas of the country where temperatures commonly exceed 25 degrees C . The results of this study suggest that, with the use of evaporative cooling, penicillin solutions can be maintained in a stable state for a 5-day period without the need for refrigeration.

Biotechnol Appl Biochem, 1993 Jun, 17 ( Pt 3), 311 - 25
pH studies to elucidate the chemical mechanism of penicillin acylase from Kluyvera citrophila; Martin J et al.; The variation with pH of the kinetic parameters of penicillin acylase from Kluyvera citrophila has been used to gain information about the chemical mechanism of the reaction catalysed by the enzyme . The pH-dependence of log (V/Km) for penicillin G showed that a group with a pK value over 4.7 must be deprotonated and that a group with a pK value over 9.7 must be protonated in the free enzyme for activity . The solvent perturbation and temperature studies indicated that these groups are respectively of cationic and neutral acid type with ionization enthalpies of 29.7 and 111 kJ/mol . It was proved that penicillin G sulphoxide is a reversible linear competitive inhibitor with respect to the hydrolysis of penicillin G . The similarity of the pH profile and the magnitude of the pK values derived from the dissociation constant, Ki, suggest that both groups are concerned with the binding of penicillin G and its analogues to the enzyme . It is proposed that binding of substrate involves the formation of hydrogen bonds between the substrate and the essential ionizable groups in the enzyme which lie within the hydrophobic environment of the active site of penicillin acylase . This suggestion is supported by the finding that the profile of V (Vmax.) is similar to the V/Km profile, except that the low and high pK values are respectively shifted downward and upward due to the entry of substrate . Moreover, the bell shape of the V profile indicated that they are also essential in the catalytic steps subsequent to binding.

Asian Pac J Allergy Immunol, 1993 Jun, 11(1), 13 - 8
Skin testing in patients with high risk of anaphylactic reactions to penicillin; Wen ZM et al.; Sequential skin testing including immediate patch test (IPT), skin prick test (SPT), and intradermal test (IT) with sodium benzylpenicillin G (Pen G), and SPT with benzylpenicilloyl human serum albumin (BPO-HSA) was done in 58 subjects with a history of probable anaphylactic reaction or shock of unknown cause . Based on positive skin tests, the diagnosis of penicillin anaphylaxis was confirmed in 30 patients . The average age of onset of penicillin allergy was 42 years ranging from 20-70 years . The sex ratio was 2:28 with marked female predominance . Anaphylactic shock, wheezing and urticaria occurred in 21, 20, 19 patients, respectively . Most symptoms were induced by skin tests and inhalation . The results of skin tests in these patients showed that IPT with 500 U/ml of Pen G was not only reliable but also safe . It is suggested that patients suspected of penicillin anaphylaxis should received IPT with 500 U/ml of Pen G as the initial diagnostic step; if a negative reaction occurred, then SPT and IT should be applied with the same concentration of Pen G, until a positive reaction developed or all the skin testing showed negative results . SPT to BPO-HSA was safe, but its positive rate was only 47.8% in our study; it seems to be less important than skin test to Pen G . As a whole, the skin testing procedure we recommend is relatively reliable, safe and practical even in individuals extremely sensitive to penicillin . In addition, once the patient develops a positive IPT, Pen G residue on the testing site should be wiped away rapidly and washed out with cool water thoroughly to disrupt further violent reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

J Chromatogr, 1993 May 19, 615(1), 180 - 5
Determination of aspoxicillin in broncho-alveolar lavage fluid by high-performance liquid chromatography with photolysis and electrochemical detection; Yamazaki T et al.; A determination method for the penicillin antibiotic aspoxicillin in broncho-alveolar lavage fluid has been developed, involving high-performance liquid chromatography and post-column photolysis . The method enabled the determination of aspoxicillin at concentrations below 100 ng/ml, with a linear calibration curve at concentrations of 1-1000 ng/ml for 100 microliters of lavage fluid . The detection limit was 1 ng/ml at a signal-to-noise ratio of 3:1.

FEBS Lett, 1993 May 17, 322(3), 215 - 8
Membrane interaction of Escherichia coli penicillin binding protein 5 is modulated by the ectomembranous domain; Phoenix DA et al.; E . coli penicillin binding protein (PBP) 5 is anchored to the periplasmic face of the inner membrane by a C-terminal domain which is predicted to form an amphiphilic alpha-helix . Here we show that the presence of a substrate analogue, benzyl penicillin, causes the protein to be converted from a membrane bound urea inaccessible form to a urea extractable form . If the anchor region is fused to the periplasmic protein, beta-lactamase, the fusion protein becomes membrane bound but is unable to exhibit the changes in urea extractability which are observed with PBP5 . We therefore conclude that although the C-terminus of PBP5 is sufficient to anchor the protein to the membrane surface the ectomembranous domain can affect the state of the anchor and in vivo changes in the state of anchoring may be related to enzyme activity.

Ugeskr Laeger, 1993 May 10, 155(19), 1475 - 6
{Rat-bite--an infant bitten by a rat}; Mathiasen T et al.; Three days after a rat-bite a two-month-old girl developed clinical symptoms of Streptobacillus moniliformis infection, called rat-bite fever . She became seriously ill, but responded well to treatment with benzylpencillin . In the light of our case and previous publications, we recommend prophylactic penicillin to be given to infants after rat-bites.

Scand J Gastroenterol, 1993 May, 28(5), 438 - 42
Prevention of duodenal ulcer recurrence with penicillin . A double-blind, placebo-controlled trial; Rune SJ et al.; Eradication of Helicobacter pylori is associated with a reduced recurrence of duodenal ulcer (DU) . The relationship between H . pylori and DU has been interpreted as causal, but the evidence has been criticized for methodologic reasons . To ascertain whether an antibiotic with no effect on epithelial-cell integrity prevents DU recurrence, we conducted a randomized double-blind trial of phenoxymethylpenicillin (PEN), 2.4 twice daily, and placebo (PLA) . Patients with an active DU and positive H . pylori culture from antral biopsy specimens were treated with 40 mg omeprazole daily for 4 weeks, but at week 2 they were allocated at random to PEN (85 patients) or PLA (85 patients) for up to 14 weeks . Those without recurrence during this treatment were followed up for another 6 months . Endoscopy and H . pylori culture were performed at the end of the treatment period and at the end of follow-up, and in between if ulcer symptoms recurred . During the treatment period the ulcer relapse rate was 5 of 58 (9%) in the PEN group and 34 of 68 (50%) in the PLA group (P < 0.0001, log-rank test), with 53% and 14%, respectively, of the patients in the two groups being H . pylori-negative . The relapse rate in the PEN group did not differ between H . pylori-negative and H . pylori-positive patients . The recurrence rate in the PEN group remained low for another 5 months but then approached the rate in the PLA group . The prevalence of H . pylori-negative patients at the end of follow-up was 20% in the PEN group and 10% in the PLA group . These data provide strong evidence that DU has a bacterial cause, with H . pylori as the likely agent.

Ann Allergy, 1993 May, 70(5), 386 - 8
Successful oral acyclovir desensitization; Henry RE et al.; A 65-year-old woman with the acquired immunodeficiency syndrome (AIDS) complicated by recurrent mucocutaneous herpes simplex virus (HSV) infection developed angioedema on the initiation of her second course of oral acyclovir therapy . Oral rechallenge in hospital three days later confirmed acyclovir hypersensitivity . Vidarabine and foscarnet therapies were abandoned after treatment failure and unacceptable toxicity . Acyclovir desensitization was accomplished using a protocol derived from oral penicillin desensitization regimens . Mucocutaneous HSV infection responded to intravenous acyclovir followed by chronic oral suppression without recurrences of HSV or hypersensitivity . This report is an example of acyclovir hypersensitivity and successful oral desensitization.

Biochem J, 1993 May 1, 291 ( Pt 3), 907 - 14
Inactivation of penicillin acylase from Kluyvera citrophila by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline: a case of time-dependent non-covalent enzyme inhibition; Martin J et al.; Penicillin acylase (PA) from Kluyvera citrophila was inhibited by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), a specific carboxy-group-reactive reagent . Enzyme activity progressively decreased to a residual value depending on EEDQ concentration . Neither enzymic nor non-enzymic decomposition of EEDQ is concomitant with PA inactivation . Moreover, enzyme re-activation is achieved by chromatographic removal of EEDQ, pH increase or displacement of the reagent with penicillin G . It was then concluded that PA inactivation is due to an equilibrium reaction . The kinetics of enzyme inactivation was analysed by fitting data to theoretical equations derived in accordance with this mechanism . Corrections for re-activation during the enzyme assay were a necessary introduction . The pH-dependence of the rate constant for EEDQ hydrolysis either alone or in the presence of enzyme was studied by u.v . spectroscopy . It turned out to be coincident with the pH-dependence of the forward and reverse rate constants for the inactivation process . It is suggested that previous protonation of the EEDQ molecule is required for these reactions to occur . The thermodynamic values associated with the overall reaction showed little change . Finally it is proposed that the inactivation of PA by EEDQ proceeds through a two-step reaction . The initial and rapid reversible binding is followed by a slow, time-dependent, non-covalent, reversible inactivating step . The expected behaviour in the case of enzyme modification by covalent activation of carboxy residues is also reviewed.

Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi, 1993 May-Jun, 34(3), 191 - 7
Congenital syphilis: report of twelve cases; Wang YJ et al.; Between 1983 and 1992 at the Taichung Veterans General Hospital, twelve congenital syphilis patients were diagnosed, according to the Centers for Disease Control (CDC) criteria . For the five boys and seven girls, ages at diagnosis ranged from 1 day to 8 months, with an average of 23 days . Among these 12 patients, four (33%) were premature . Seven patients (58%) were diagnosed in the past three years . These 12 patients were divided into inborn and outborn patient groups . Serological tests for syphilis were done in all inborn patients, but none in the outborns . All five outborn patients were symptomatic . In comparison, only one of seven inborn infants showed clinical evidence of congenital syphilis . The mean age at diagnosis was obviously older in the outborn patient group (53 days vs . 1 day) . Six of ten patients (60%) had cerebrospinal fluid (CSF) abnormalities, while four of nine (44%) showed radiological abnormalities of bones . The hematologic and biochemical abnormalities compatible with congenital syphilis were also described . Penicillin was the drug of choice in ten patients . Despite adequate treatment, one patient died of respiratory failure . There has been no evidence of any signs of late congenital syphilis in those patients who survive . Congenital syphilis, a serious but preventable disease, is best treated adequately and early for minimal sequelae.

Exp Toxicol Pathol, 1993 May, 45(2-3), 113 - 20
Adriamycin alters the alkaline phosphatase activity in hamster molars during development in vitro; Karim AC et al.; The effect of a 2 hour exposure to adriamycin (1 mg/litre) on alkaline phosphatase (ALPase) activity of the golden hamster 4-5 day old second maxillary molars (M2) was investigated in vitro . The molars were grown in BGJb medium containing 15% fetal bovine serum, glutamine (200 micrograms/ml), vitamin C (250 micrograms/ml), penicillin G (50 micrograms/ml), and streptomycin sulphate (30 micrograms/ml) . The gas phase contained 50% O2 + 5% CO2 + 45% N2 . The molars were supported on cellulosic membrane filters and grown for 3, 5, and 7 days at the medium-gas interface in a closed humidified chamber . Biochemical analysis indicated a steady increase in ALPase activity throughout this study in the control samples . However, after adriamycin treatment no increase in ALPase activity could be observed . The histochemical data showed that the increased activity in the control was confined to the peripheral pulp, sub-odontoblastic layer, stratum intermedium, ameloblasts and odontoblasts . Although these layers showed a decreased activity after adriamycin treatment, the ameloblasts showed an increase in activity over the control . The data has shown that adriamycin caused a reduction in total ALPase activity in developing molars in vitro; osteodentin production by pulp cells; and appeared to produce an acceleration in the differentiation of ameloblasts.

Orv Hetil, 1993 Apr 25, 134(17), 907 - 10
{Amanita phalloides poisoning in a 15-year case load of a pediatric intensive care unit}; Mikos B et al.; The clinical course of eight patients with Amanita phalloides poisoning is reviewed . Early diagnosis was based on the history, characteristic clinical features and non-specific laboratory data . A complex supportive therapy with gastric lavage, bowel irrigation, correction of volume and electrolyte abnormalities, and penicillin-G (Penicillin, Biogal), silibinin (Legalon SIL, Madaus), thioctacid (Thioctacid, Asta), corticosteroid (Di-Adreson-F aquosum, Organon) administration was commenced in every cases before identification of the mushroom . Haemoperfusion was performed in six cases, and in one patient plasmapheresis was applied as well . Seven children recovered completely . Unfortunately, a girl of 12 years died . According to the authors' experience, the use of non-invasive and invasive methods of the non-specific detoxication is proposed in case of severe Amanita phalloides poisoning.

Tidsskr Nor Laegeforen, 1993 Apr 20, 113(10), 1230 - 1
{Pleuropulmonary actinomycosis}; Dahl PE et al.; A previously healthy 42 years old male was admitted to hospital with chest pain . Chest radiograms revealed a solid mass in the left thoracic cavity . A lung biopsy showed findings consistent with probable actinomycosis . It was feared that the specimen was not representative and a left upper lobe lobectomy was performed . This confirmed the diagnosis of actinomycosis . The patient was postoperatively treated with penicillin and tetracycline and has remained well during a follow-up period of two years.

Biochem J, 1993 Apr 15, 291 ( Pt 2), 537 - 44
The mechanism of action of DD-peptidases: the role of tyrosine-159 in the Streptomyces R61 DD-peptidase; Wilkin JM et al.; Tyrosine-159 of the Streptomyces R61 penicillin-sensitive DD-peptidase was replaced by serine or phenylalanine . The second mutation yielded a very poorly active protein whose rate of penicillin binding was also drastically decreased, except for the reactions with nitrocefin and methicillin . The consequences of the first mutation were more surprising, since a large proportion of the thiolesterase activity was retained, together with the penicillin-binding capacity . Conversely, the peptidase properties was severely affected . In both cases, a drastic decrease in the transferase activity was observed . The results are compared with those obtained by mutation of the corresponding residue in the class A beta-lactamase of Streptomyces albus G.

J Med Chem, 1993 Apr 2, 36(7), 919 - 23
Prodrugs of doxorubicin and melphalan and their activation by a monoclonal antibody-penicillin-G amidase conjugate; Vrudhula VM et al.; The syntheses and cytotoxic activities of substituted N-phenylacetamido derivatives of doxorubicin and melphalan are described . The derivatives were designed as prodrugs which could be activated in a site-specific manner by monoclonal antibody-penicillin-G amidase (mAb-PGA) conjugates . N-(Phenylacetamido)doxorubicin (2) and N-(phenylacetyl)melphalan (6) were found to be 10- and 20-fold less cytotoxic against H2981 lung adenocarcinoma cells than doxorubicin and melphalan, respectively . When incubated with PGA, the cytotoxicity of 2 and 6 increased and became equivalent to that of the corresponding drugs from which they were made . The poor solubility characteristics of 2 in aqueous solutions provided the basis for the development of the more soluble doxorubicin derivatives, N-(4-aminophenylacetyl)doxorubicin (3) and N-(4-phosphonooxy)phenylacetyl)-doxorubicin (4) . In vitro cytotoxicity assays indicated that 3 and 4 were at least 1000-fold less toxic than doxorubicin against H2981 cells . PGA and the mAb conjugate L6-PGA were able to effect the activation of 3 and 6 on H2981 cells (L6-antigen positive) . Hydrolysis of the phosphate group of 4 was required prior to activation with PGA or L6-PGA . This was achieved using alkaline phosphatase, or by exposing 4 to phosphatases present in cell culture medium . The activation of 3, 4, and 6 on H2981 cells by L6-PGA occurred in an immunologically specific manner, since activation could be blocked by saturating cell surface antigens with L6 prior to treatment with L6-PGA . These results demonstrate that 3, 4, and 6 are prodrugs that can be specifically activated to release clinically approved anticancer agents by a mAb-PGA conjugate.

J Chemother, 1993 Apr, 5(2), 133 - 4
Risk/benefit in the treatment of children with imipenem-cilastatin for meningitis caused by penicillin-resistant pneumococcus; Asensi F et al.; A new case of pneumococcal meningitis in a child successfully treated with imipenem-cilastatin after failure of standard antibiotics is presented . Seizures, as the major adverse effect, were easily treated and no sequelae were later observed . The difficulty in distinguishing between seizures due to meningitis and those due to imipenem is discussed . We conclude that imipenem-cilastatin is a good alternative therapy in children's meningitis caused by pneumococcus resistant to standard antibiotics.

Clin Infect Dis, 1993 Apr, 16(4), 472 - 5
Tularemia from a cat bite: case report and review of feline-associated tularemia; Capellan J et al.; We report the case of a 63-year-old man who developed ulceroglandular tularemia complicated by pneumonia following a cat bite . A review of the literature revealed 51 cases of cat-related tularemia reported since 1928 . Details of 15 cases (including the present case) were available and analyzed . If, following feline contact, patients develop pneumonia or if patients with skin and soft-tissue infection fail to respond to therapy with penicillin, physicians should be alerted to the possibility of tularemia . A greater awareness of this complication following a cat bite or cat scratch is important for recognizing this uncommon infection.

J Vet Diagn Invest, 1993 Apr, 5(2), 198 - 201
Erysipelas in caged laying chickens and suspected erysipeloid in animal caretakers; Mutalib AA et al.; Erysipelas was diagnosed in 2 succeeding caged layer flocks housed in the same building and was characterized clinically by sudden death . At necropsy, lesions comprised generalized congestion, hemorrhages in the skeletal muscles and visceral organs, and swelling of liver, spleen, and kidney with or without large irregular zones of necrosis . Focal to massive hepatic necrosis was seen histologically with minimal or no inflammatory reaction . Erysipelothrix rhusiopathiae was cultured from internal organs of affected birds in both outbreaks . Medication with penicillin in the feed controlled the mortality, but relapse occurred after cessation of medication . Two attendants who handled the dead birds in this building developed a painful localized infection of the fingers that later spread to the regional lymph node . The infection responded when antibiotic therapy for erysipeloid was initiated.

Allergy, 1993 Apr, 48(3), 151 - 7
Enzyme-linked immunosorbent assay for detection of antibodies to the unmodified beta-lactam ring; Klein GF et al.; Dose- and pH- dependent carbodiimide-mediated coupling of Penicillin-G to polystyrene microtiter-plates that leaves the beta-lactam ring unchanged is described . A new ELISA method was developed using Penicillin-G coated plates . The binding of 3 different monoclonal antibodies as well as human IgG antibodies of the IgG1 and IgG3 subclasses is demonstrated, whereas IgG2, IgG4 and IgE antibodies did not bind . Thus, covalently coupled Penicillin-G can be used to study the immune-response to the unchanged beta-lactam ring in patients receiving penicillin therapy . The new method is complementary to hitherto described techniques, which generally only allow detection of antibodies binding to penicilloyl-groups.

Nervenarzt, 1993 Apr, 64(4), 273 - 7
{Myasthenia gravis in AIDS and neurosyphilis}; Wullenweber M et al.; The co-occurrence of myasthenia gravis and AIDS in a 38 year old drug addict with HIV-infection is reported . The diagnosis "myasthenia gravis" is based on clinical features with muscle weakness worsening with exercise and depending on the time of day, and secondly on the result of electrophysiological tests, with a typical decrement in repetitive nerve conduction study, and on the presence of antibodies to acetylcholine receptors . A co-existing neurosyphilis was treated intravenously with penicillin G, resulting in good improvement of the associated myopathy . The remaining muscle weakness responded well to treatment with pyridostigmine bromide started after the end of the antibiotic therapy . A tumor in the anterior mediastinum measuring 3 by 2 cm was diagnosed by CT scan and removed, histology showed normal thymus tissue . After operation the patient became asymptomatic on treatment with low dosage pyridostigmine (3 x 30 mg) . The association of myasthenia gravis with AIDS may derive from an alteration of the immune system based on changes in the thymus gland . Differential diagnosis in AIDS patients with generalized weakness should include a myasthenic reaction.

Antimicrob Agents Chemother, 1993 Apr, 37(4), 864 - 7
Clarithromycin therapy of experimental Treponema pallidum infections in hamsters; Alder J et al.; Clarithromycin was shown to be effective therapy for Treponema pallidum infections in hamsters . Clarithromycin therapy was effective when initiated either 1 or 8 days after infection . The delay in initiation of therapy allowed an active infection to develop . The treponemal burden in lymph tissue of treated hamsters was eradicated, as determined by dark-field microscopy and by inoculation of lymph material into susceptible hamsters . Treatments with clarithromycin and the 14-hydroxy metabolite of clarithromycin were equally effective . Therapy with clarithromycin and penicillin was not antagonistic and did not appear to be synergistic when the two drugs were given concurrently . Pharmacokinetic evaluation of clarithromycin in hamsters showed that the doses which produced effective therapy yielded concentrations in serum similar to those routinely achieved in human sera . These findings demonstrate that clarithromycin is effective in treating active or incubating syphilis in the hamster model and could be useful in treating humans.

Surgery, 1993 Apr, 113(4), 462 - 5
Fivefold enlargement of implants in a splenic autotransplant recipient; Moore FA et al.; A 30-year-old patient underwent splenectomy for trauma with splenic autotransplantation . Four years later he survived a bout of pneumococcal sepsis with only oral penicillin therapy . Seven years after splenectomy, he underwent another laparotomy with the finding of fivefold enlargement of the splenic implants . Splenic autotransplants enlarge and probably function in human beings.

J Lab Clin Med, 1993 Apr, 121(4), 546 - 54
Penicillin-induced dysfunction of platelet membrane glycoproteins; Pastakia KB et al.; We examined the effects of the beta-lactam antibiotic penicillin G on platelet function and on specific membrane glycoproteins in vitro . Platelet concentrates exposed to 3 to 10 mmol/L penicillin for 48 hours showed irreversible inhibition of aggregation by thrombin in washed platelets after removal of the antibiotic . Although a brief 15-minute exposure to similar doses of penicillin also inhibited thrombin aggregation, the inhibition was reversed on removal of the penicillin by washing . Aggregation activity was also restored to normal levels by stimulation with high thrombin concentrations (> 0.4 U/ml) . Results of the aggregation studies led us to examine how penicillin affects platelet membrane proteins . Membranes isolated after 48 hours of exposure of platelet concentrates to penicillin showed no differences from the control in total protein profiles on sodium dodecylsulfate--polyacrylamide gel electrophoresis or in the glycoprotein Ib or IIb content on immunoblotting . However, flow cytometric analysis with fluorescently labeled monoclonal antibodies revealed that exposure of platelets to penicillin for 15 minutes inhibited thrombin-induced modulations in the glycoproteins Ib, Ib-IX, IIb-IIIa, and P-selectin . These effects were observed with washed platelets and platelets in plasma . Penicillin also inhibited the regulation of expression of glycoproteins Ib-IX and IIb-IIIa in adenosine diphosphate--activated platelets . The inhibitory effects were partially reversed at high agonist concentrations.

Dtsch Tierarztl Wochenschr, 1993 Apr, 100(4), 147 - 8
Characterization of serum lysosomal enzymatic activities . III . Effect of infectious influenza in Egyptian equines; Abdalla MA et al.; An outbreak of infectious influenza was recognized in Menofeia governorate in October 1989 . Eight naturally influenza infected as well as 8 healthy control horses, mules and donkeys were selected for collection of blood and sera separation to estimate four lysosomal enzymatic activities and to describe the clinical findings, which were fever, congested nasal, conjunctival membranes and cough . Bronchopneumonia followed later with bilateral purulent nasal discharge as a complication in 2 donkeys . Thereafter laboured breathing occurred . Therefore a therapeutic penicillin-streptomycin dose was injected to safeguard against the secondary bacterial invasion . All lysosomal enzyme levels in serum of diseased equines were subjected to consistent regression except N-acetyl-beta-glucosaminidase -beta-NAG) that behaved very highly significant activity, probably due to the acid pH resulting from bronchopneumonia and respiratory acidosis which override the inhibitory action of the antibiotics . Influenza virus may inhibit the synthesis of the pulmonary surfactant in alveolar and bronchial epithelium, thereafter, the animals suffered from respiratory distress and bronchospasm with resultant decreased acid phosphatase (ACP) value which was histochemically located in both sites . The disappearance of alpha- and beta-galactosidases (alpha-GAL & beta-GAL) from the serum of diseased animals can be attributed to the antibiotic dose.

Biochem J, 1993 Apr 1, 291 ( Pt 1), 19 - 21
A new, highly sensitive method for the detection and quantification of penicillin-binding proteins; Galleni M et al.; A new method for the identification and quantification of penicillin-binding proteins is described which uses fluorescein-coupled penicillins . It allows the rapid detection of 0.2 pmol with the naked eye and 2 fmol with the help of an A.L.F . automatic DNA sequencer . Direct labelling can also be performed on whole bacterial cells.

Pharmacol Toxicol, 1993 Apr-May, 72(4-5), 205 - 7
Electroencephalographic effects of flucloxacillin in rats; Contreras S et al.; The neurotoxicity of flucloxacillin, an isoxazolyl derivative of beta-lactamic antibiotics, was studied in rats by electroencephalographic recordings . The results show that intravenous flucloxacillin, (200 mg/kg) produced cortical activity modifications . The changes in electroencephalogram consist of irritative activity patterns and bursts of high voltage waves with spikes and polyspikes . The effects of other beta-lactamic drugs (cloxacillin, ampicillin-sulbactam and penicillin G) on electroencephalography activity were also investigated after intravenous administration of equivalent doses . These drugs did not change the normal bioelectric cerebral activity of the rats.

J Am Optom Assoc, 1993 Apr, 64(4), 245 - 9
Neurosyphilis with associated retinitis; Ruder AJ et al.; A 59-year-old black male presented with an acute unilateral central scotoma and decreased visual acuity in each eye . Ocular examination revealed bilateral vitritis, nerve fiber layer hemorrhages and infarcts, arteritis, serous macular edema and optic nerve head edema with telangiectasia . Vascular work-up was remarkable for a reactive FTA-ABS, VDRL and RPR . Lymphocytes, monocytes, basophils and platelet count were elevated . HIV tests were nonreactive . Ocular, serologic and cerebrospinal fluid findings along with past sexual history were consistent with a diagnosis of early neurosyphilis . Prompt referral to an infectious disease physician and subsequent treatment with parenteral penicillin resulted in complete resolution of the vitreoretinitis.

Boll Soc Ital Biol Sper, 1993 Apr, 69(4), 209 - 14
{Quantitative variations of osteocalcin in the culture media of bones subjected to intermittent mechanical loads in vitro}; Lozupone E et al.; A study has been carried out on the dynamics of the osteogenesis induced in vitro by an intermittent mechanical load applied on intact metatarsals isolated from 12 day-old rats . The metatarsals, as soon as isolated, were deprived of both the ends and placed in culture medium (BGJb enriched with 10% FCS, 65 micrograms of ascorbic acid, penicillin, strepto) without a mechanical load . After 4-5 hours, half the bones were placed in our device, described in our previous paper (2), and submitted to a daily cycle of an intermittent mechanical load (11.6 g/mm2) 1/2 h long, at 1 Hz frequency . The remaining bones, used as control, were cultured in the same medium, without any mechanical load . 24, 48 and 72 hours from the first application of the load the bones were fixed, embedded (decalcified or undecalcified) and serially sectioned . The sections were stained with toluidin blu and trichromic Masson-Goldner . On the perimeter of 5 non-consecutive sections of each bone the number of the osteoblasts at 250x, and the nuclear volume of the same cells at 1000x were evaluated . In the culture media the alcaline phosphatase activity (p-nitrophenol as substrate) and the concentration of osteocalcin (RIA) were measured . The number and nuclear volume of the osteoblasts are higher in the loaded than in the control bones (tab . 1) . The alcaline phosphatase activity does not vary in the control bones between 24 and 72 h, while it increases in the loaded bones . The concentration of the osteocalcin shows a slight increase at 48 h in the control bones, and a significant decrease int he loaded bones (fig . 1).(ABSTRACT TRUNCATED AT 250 WORDS)

J Med Assoc Thai, 1993 Apr, 76(4), 222 - 9
Impetigo:an assessment of etiology and appropriate therapy in infants and children; Pruksachatkunakorn C et al.; We found that mixed organisms of S.aureus and GABHS were the most common cause of impetigo in children in our study; that, of the two regimens evaluated, cloxacillin is the most effective treatment; that penicillin is equally effective in cases of mild to moderate forms and may be preferred on the basis of cost-effectiveness.

Antibiot Khimioter, 1993 Apr-May, 38(4-5), 37 - 9
{Diagnosis of penicillin side effects}; Badina AK; A procedure for diagnosing drug allergy is described . It includes collection of the blood specimens, isolation of the lymphocytes, their incubation with an allergen and determination of the quantity of the diene conjugates in the lymphocytes before and after the incubation . When the quantity of the diene conjugates after the incubation with an allergen is 2 times as lower, the drug allergy is stated . The time course of the diene conjugate contents is followed up . A decrease in the initial level of the diene conjugates at least by 55 per cent in 7 patients with penicillin intolerance, in 4 patients with novocaine intolerance and in 1 patient with streptomycin intolerance could be indicative of the allergy atopic mechanism.

Ugeskr Laeger, 1993 Mar 29, 155(13), 955 - 7
{WR in patients with secondary syphilis and HIV infection}; Weismann K et al.; In recent years, there have been sporadic reports of aberrant manifestations of syphilis and a changed syphilis serology in AIDS patients, which might indicate difficulties in diagnosing the infection and monitoring the response to penicillin treatment . Six male patients aged 25 to 42 years with asymptomatic HIV infection and secondary syphilis were retrospectively compared with a control group of seven HIV-negative males aged 26 to 52 years with secondary syphilis . All patients presented with macular-papular exanthema of secondary syphilis; in all cases it was also their first episode of the disease . The median WR titre was 13 (range 11 to 20) in syphilis patients with HIV and nine (8 to 14) in the control group (p = 0.1) . The median time until WR was found non-reactive after penicillin was four months (3 to 16) and five months (3 to 9), respectively (p = 0.8) . Thus, in this small series there was no statistically significant difference in the WR-titres of asymptomatic HIV positive and HIV negative patients with secondary syphilis, although there was a tendency towards initially higher WR titre in the HIV group, as reported by others.

Presse Med, 1993 Mar 20, 22(10), 472 - 4, 479
{Acquired autoantibodies directed against human factor VIIIc . Treatment of 2 hemorrhagic accidents with porcine factor VIIIc}; Moreau P et al.; The emergence of an autoantibody directed against factor VIII may be responsible for severe, life-threatening haemorrhages . This rare disease is usually idiopathic, but it may be consecutive to an autoimmune disease or to the absorption of certain drugs such as penicillin . The diagnosis rests on the finding of a prolonged activated thromboplastin time with presence of a circulating anticoagulant and deep fall in factor VIII level . Two cases of severe haemorrhage successfully treated with porcine factor VIIIc are reported . The first case concerned an 80-year old woman presenting with a large haematoma of the thigh uncontrolled by injections of human factor VIIIc . The second case was that of a 24-year old woman in a state of shock due to a pleural blood effusion that occurred during heparin treatment of cerebral thrombophlebitis, combined with penicillin treatment of bronchial superinfection . In both cases the high-titer autoantibody to the human factor VIIIc did not, or little, cross with porcine factor VIIIc . Factor VIII rose after the first injection of the porcine factor, and the haemorrhage was rapidly controlled . In both cases, the autoantibody disappeared within a few months, either spontaneously or after treatment with immunosuppressants.

J Biol Chem, 1993 Mar 15, 268(8), 5632 - 41
Penicillin-binding protein 1B from Escherichia coli contains a membrane association site in addition to its transmembrane anchor; Nicholas RA et al.; A working structural model of penicillin-binding protein 1B (PBP 1B) from Escherichia coli derived from previous data consists of a highly charged aminoterminal cytoplasmic tail, a 23-amino-acid hydrophobic transmembrane anchor, and a 758-amino-acid periplasmic domain . Using an engineered thrombin cleavage site, we have investigated the solubility properties of the periplasmic domain of PBP 1B . Twelve amino acids, comprised of the consensus thrombin cleavage site (LVPR decreases GS) and flanking glycine residues, were inserted into PBP 1B just past its putative transmembrane segment . To aid in purification, a hexa-histidine tag was also inserted at its amino terminus, and the engineered protein (PBP 1B-GT/H6) was purified and characterized . Inclusion of the thrombin cleavage site had no effect on the protein's intrinsic tryptophan fluorescence and affinity for {14C}penicillin G, indicating that the protein structure was not significantly perturbed . PBP 1B-GT/H6 was readily cleaved by thrombin at low thrombin/protein ratios to a protein with properties consistent with the removal of its cytoplasmic tail and transmembrane regions . Cleavage of the protein was dependent upon the presence of the thrombin cleavage site, and the thrombin-cleaved protein (PBP 1Bper) displayed an identical affinity for {14C} penicillin G binding as wild-type PBP 1B and uncleaved PBP 1B-GT/H6 . {14C}Penicillin G-labeled PBP 1Bper eluted from a gel filtration column in the presence but not in the absence of 0.7% 3-{(3-cholamidopropyl)dimethylammonio}-1- propanesulfonic acid, and PBP 1Bper was found entirely in the membrane fraction of a thrombin digest of membranes containing overproduced PBP 1B-GT/H6 . To further characterize this unusual solubility behavior, purified PBP 1Bper was reconstituted into lipid vesicles, which were then floated on a sucrose gradient . Floated vesicles contained > 95% of total 125I-penicillin V binding, indicating that PBP 1Bper directly associates with lipid membranes . These results strongly suggest that the periplasmic domain of PBP 1B associates with membranes independent of its amino terminal transmembrane region.

J Dermatol, 1993 Mar, 20(3), 171 - 4
Sexually transmitted diseases in a HIV infected patient; Ishii N et al.; We report a case of HIV infection with herpes simplex, syphilis, and condyloma acuminatum in a 66-year-old heterosexual man . The patient was an asymptomatic carrier (group II) of HIV infection . Herpes simplex on his penis was controlled by aciclovir . Secondary syphilis was treated with penicillin G, after which skin lesions disappeared . These four diseases were all sexually transmitted diseases (STD) . One should consider the possible existence of other STD in similar cases.

Anal Biochem, 1993 Mar, 209(2), 332 - 4
A colorimetric assay for penicillin-V amidase; Kerr DE; The hydrolysis of penicillin-V to phenoxyacetic acid and 6-aminopenicillanic acid by the fungal enzyme penicillin-V amidase is of industrial importance since the 6-aminopenicillanic acid produced is an intermediate for semisynthetic penicillins . A rapid colorimetric assay of penicillin-V amidase was developed which uses 2-nitro-5-(phenoxyacetamido)-benzoic acid as a substrate . The released chromophore, 2-amino-5-nitrobenzoic acid, was detected at 405 nm . Using penicillin-V amidase from the fungus Fusarium oxysporum, the KM and Vmax for this substrate were 0.89 mM and 2.6 mumol/min/mg enzyme, respectively . Hydrolysis could be competitively inhibited by penicillin-V with a Ki of 4 mM . The change in the initial velocity of hydrolysis of 2-nitro-5-(phenoxyacetamido)-benzoic acid at 500 microM was linear over the range of 0.5 to 10 micrograms/ml enzyme . These results show that this new compound is useful in determining the presence and levels of penicillin-V amidase.

Pharm Res, 1993 Mar, 10(3), 449 - 53
Three approaches to the analysis of trace formaldehyde in bulk and dosage from pharmaceuticals; Manius GJ et al.; Trace-level determinations for the presence of formaldehyde in both bulk and dosage form pharmaceuticals were developed using three innovative strategies . One system adapted the chromotropic acid spot test for formaldehyde . This was accomplished spectrophotometrically over a linear detection range against authentic control samples . The other two chromatographic approaches necessitated rapid derivatization . One derivative was its corresponding oxime, formaldoxime, which was resolved on a gas chromatographic porous polymer column and sensed by a nitrogen-specific detector . The other derivative, sodium formate, was detected and quantified on an ion chromatograph using an anion-exchange column and a conductivity detector . The chromotropic acid technique was sensitive but not specific for formaldehyde . The chromatographic techniques required a high degree of water solubility . All were subject to interferences that could preclude their use for a particular application . None of the tested samples, which included a penicillin analogue, a pharmaceutical dosage from additive, a vitamin, and biological proteins, showed the presence of formaldehyde at trace levels.

J R Soc Med, 1993 Mar, 86(3), 156 - 8
Management of service personnel with a history of penicillin allergy: discussion paper; Williams MD et al.; A false label of penicillin allergy may have important consequences for wartime medical evacuation . This article outlines the antibiotic protocol for war wounds, the current status of tests to diagnose true penicillin allergy and suggests a strategy for the management of personnel with a history of such allergy.

J Allergy Clin Immunol, 1993 Mar, 91(3), 694 - 701
The frequency of skin test reactions to side-chain penicillin determinants; Silviu-Dan F et al.; BACKGROUND: Skin testing for immediate hypersensitivity to penicillins is usually carried out with reagents prepared from benzylpenicillin, and it is believed that side-chain-specific reactions to semisynthetic derivatives are rare . Because some experimental and clinical data suggest that antibodies can be induced to immunogenic epitopes on the side chains of penicillins, we looked for side-chain-specific reactions to skin testing in patients with a history of allergy to penicillins or semisynthetic penicillins . METHODS: One hundred twelve patients with a clinical history of allergic reactions to penicillins and other semisynthetic penicillins were skin tested an average of 4.9 +/- 0.7 years after their reactions with the major and minor determinants of benzylpenicillin and minor determinant mixtures of ampicillin, amoxicillin, or cloxacillin . RESULTS: In these patients the most common clinical reactions were urticaria and angioedema (36.6%) and exanthema (48.8%) . It was found that 21 cases (18.8%) still exhibited immediate hypersensitivity reactions on skin testing . But of these 21 patients, skin test reactivity was limited in 47.6% to the semisynthetic penicillin reagents derived from ampicillin, amoxicillin, or cloxacillin; that is, skin tests were negative with the benzylpenicillin derivatives . Ampicillin and amoxicillin were the semisynthetic beta-lactams causing most clinical reactions (24.1% and 33.9%, respectively), and ampicillin was the most common penicillin derivative to which skin test reactivity occurred (38.1%), other than the benzylpenicillin derivatives (52.3%) . CONCLUSIONS: IgE antibodies appear therefore to discriminate between benzylpenicillin and ampicillin or other semisynthetic penicillins in a significant proportion of patients allergic to penicillin . Although it has not been proved that side-chain-specific skin reactivity implies the presence of clinically significant immediate hypersensitivity to semisynthetic penicillins, it is possible that side-chain-specific reagents may be required to exclude possible immediate hypersensitivity to the penicillins in patients who reacted to these antibiotics clinically.

Pharmacol Biochem Behav, 1993 Mar, 44(3), 709 - 15
Protective sensitivity changes of the motor cortex due to epileptiform experience of the visual cortex; Horn E et al.; In awake rats, experiments were performed to study early epileptiform events (interictal spike, myoclonic jerk) in relation to a) the strength of the convulsive stimulus, b) the site of the focus, and c) epileptiform experience . For this reason, Na-penicillin G (PCN) was injected either into the motor or visual cortex and, in a second test 2 weeks thereafter, into the motor cortex in all these rats . The median latencies of both the first interictal potential and jerk were independent of the applied PCN concentration in the range between 16-1,000 IU/0.5 microliter (90.5-113 s, and from 106-196 s, respectively), as well as from the injection site in the visual or motor cortex (potential: 80 vs . 69 s; jerk: 124 vs . 129 s, respectively) . After epileptiform experience in the visual cortex, the latencies of the first potential and jerk were significantly (p < 0.05) increased compared to animals with an experience in the motor cortex (first potential: 100 vs . 66 s; first jerk: 159 vs . 116 s, respectively) . The results show that a PCN focus in the visual cortex decreases the susceptibility of the motor cortex for the convulsant action of PCN . This means that an autoprotective mechanism is activated whose efficiency depends upon a close linkage between the visual and motor cortex.

Ann Intern Med, 1993 Mar 1, 118(5), 350 - 5
Effects of HIV infection on the serologic manifestations and response to treatment of syphilis in intravenous drug users; Gourevitch MN et al.; OBJECTIVE: To describe the effects of human immunodeficiency virus (HIV) infection on the serologic manifestations and response to treatment of syphilis in intravenous drug users . DESIGN: Cohort study of intravenous drug users . SETTING: Medical clinic in a hospital-based methadone maintenance treatment program in New York City . PATIENTS: Fifty patients with syphilis, of whom 31 were HIV seropositive and 19 HIV seronegative . MEASUREMENTS: Serologic tests for syphilis and clinical manifestations . RESULTS: Stage of syphilis at presentation was not associated with HIV serologic status . No unusual or fulminant manifestations of early syphilis or neurosyphilis were noted among HIV-seropositive cases . Maximum nontreponemal titers were higher among HIV-seropositive (median, 1:128) than among HIV-seronegative (median, 1:32) patients with syphilis (P = 0.05); this difference was present only among patients with first-episode syphilis . All 26 evaluable, HIV-seropositive patients treated for syphilis responded appropriately, including 13 patients given standard or less-than-standard doses of penicillin . Seven of 43 patients (16%) showed reversion to negative treponemal antibody assay results after treatment for syphilis; this finding was not associated with HIV infection, CD4 count, or stage of syphilis . Low nontreponemal titer was weakly associated with treponemal test reversion . CONCLUSIONS: Infection with HIV did not alter the stage at presentation, clinical course, serologic manifestations, or response to treatment of syphilis in this cohort of intravenous drug users.

Tidsskr Nor Laegeforen, 1993 Feb 28, 113(6), 704 - 6
{Sinusitis in general practice--treatment and referral}; Lindbaek M et al.; Sinusitis is usually diagnosed and treated in general practice . A questionnaire was sent to Norwegian general practitioners and to ear, nose and throat specialists to assess which treatment was preferred when treating patients with sinusitis . Penicillin is the drug chosen by both groups of doctors, with tetracycline in second place . A majority of the general practitioners state that they would prescribe 4 mill . IU per day, compared with the recommended 6-8 mill . IU . General practitioners with long clinical experience tend to prescribe tetracycline more often than the sample group of doctors as a whole . Various alternative treatments are used, but the majority of the general practitioners recommend only topical nasal decongestants and paracetamol . Systemic nasal decongestants are still considered relevant in the treatment of sinusitis . Less than half the general practitioners had treated children younger than 12 years of age for sinusitis . 63% state that they periodically treat patients with sinusitis after a consultation by telephone . While Norwegian general practitioners seldom refer patients with acute sinusitis to ear, nose and throat specialists, the majority of patients with recurrent sinusitis are referred.

Dtsch Med Wochenschr, 1993 Feb 19, 118(7), 213 - 20
{The tryptophan-associated eosinophilia-myalgia syndrome . A clinical follow-up of 8 patients}; Szeimies RM et al.; Seven women and one man aged from 51 to 70 years suffered from eosinophilia-myalgia syndrome after taking medicines containing tryptophan for depression or sleep disorders; the total duration of intake ranged from three to 106 months and the average daily dose was 1312 mg . All the patients had muscle pains and skin lesions resembling scleroderma together with impairment of general well being; six of them had high eosinophil counts of up to 2,600 cells/microliters (mean 1,629); other symptoms were weight loss, pruritus, fever, dyspnoea and sensory abnormalities . Discontinuation of tryptophan combined with systemic treatment with prednisone in doses of 32 or 20 mg/d for 4 to 16 weeks soon brought the eosinophil counts down, but the skin lesions, muscle pains and other symptoms showed little improvement over a follow-up period averaging 17.1 months . Treatment with penicillin G (20 mega-units daily for 14 days), azathioprine (100 mg daily for 2 months) or cyclosporin (2.5 mg/kg.day) was tried in some cases but had no significant effect.

JAMA, 1993 Feb 3, 269(5), 598 - 602
The epidemiology of intravenous vancomycin usage in a university hospital . A 10-year study; Ena J et al.; OBJECTIVES--To examine the trends of intravenous vancomycin usage during a 10-year period, to classify the indications for which physicians prescribed the antibiotic, and to identify the independent predictors for empirical use of vancomycin . DESIGN--A descriptive epidemiological study, a cross-sectional study, and a case-control study were performed . SETTING--A 900-bed university-teaching hospital . MAIN OUTCOME MEASURES--The annual crude usage (grams) and incidence density (grams/1000 patient-days) of vancomycin were measured for 10 years (July 1981 to July 1991) . In 109 randomly selected patient medical records, we evaluated the proportion of usage of vancomycin classified as prophylaxis, empirical therapy, or specifically directed therapy . Univariate and multivariate analyses were performed to identify determinants of empirical administration of vancomycin vs a penicillase-resistant penicillin to 64 case patients and 64 control patients . RESULTS--The rate of vancomycin usage increased 20-fold from 5.72 g/1000 patient-days in 1981 to 121.25 g/1000 patient-days in 1991 . The use of vancomycin was significantly higher (P < .0001) in hematology-oncology areas compared with that in other hospital areas . The rates for each indication for vancomycin were 35.0% for prophylaxis 31.8% for empirical therapy, and 33.2% for therapy specifically directed by culture results . In a multivariate analysis, the presence of "plastic" medical devices was the best independent predictor for patients receiving vancomycin: intravenous lines (odds ratio {OR}, 6.23; 95% confidence interval {CI}, 2.28 to 17.06; P < .001), Hickman catheters (OR, 76.12; 95% CI, 15.06 to 384.73; P < .001), and other medical devices (OR, 10.50; 95% CI, 2.54 to 43.38; P = .001) . CONCLUSIONS--Vancomycin use has increased linearly in the last decade primarily related to the presence of indwelling vascular devices in hematology-oncology patients . Use of vancomycin is equally divided among empirical therapy, prophylaxis, and specific therapy for a documented infection.

Aust N Z J Obstet Gynaecol, 1993 Feb, 33(1), 96 - 8
Pelvic actinomycosis in association with an intrauterine device; Garland SM et al.; A case of pelvic actinomycosis is described which occurred in association with the use of an intrauterine device (IUD) . Initially medical management alone was used, but surgical intervention was necessitated for multiple pelvic abscesses . We would strongly recommend that any IUD be removed should it be associated with actinomyces on genital smears and/or culture . If sepsis is also apparent, IUD removal with use of long-term antibiotics is requiredPIP: In Australia, a 31-year old IUD user with 3 children came to the Royal Women's Hospital in Melbourne, Victoria, for elective laparoscopic sterilization . Cytological examination of a Pap smear revealed actinomyces-like organisms (ALO), yet she had no symptoms . Her physician removed the IUD during tubal occlusion 2 months later, at which time she was febrile . She received 2 g intravenous (IV) cefoxitin . The physician applied a clip to the right tube, but not to the left tube due to dense adhesions around a small ruptured tubo-ovarian abscess . Aspirate culture indicated Actinomyces israelii and Fusobacterium rusii . No . A israelii grew from the removed cultures IUD, however . Histological examination of the curettings revealed proliferative endometrium with IUD effect and ALO-like microcolonies . After the operation, she received IV amoxycillin and rectal metronidazole . Upon a positive Actinomyces culture, she received IV crystalline penicillin and metronidazole . This treatment did not resolve her anorexia, fever, and pelvic infection signs . She received 4 units of blood . Ultrasound showed 4 complex masses near the ovaries and too the right of the fundus . Her physician did a laparotomy to drain the abscesses . Extensive adhesions made the bowel dilate and mat together and to the abdominal wall . The physician removed the left xanthomatous salpinigitic tube . Postoperatively, she underwent nasogastric suction, administration of IV fluids via a central line, a blood/plasma transfusion, and gentamicin . After developing a chest infection, she received IV cefotaxime . 7 days later she no longer had a fever, took oral fluids, and was ambulatory . She took oral penicillin and probenecid . 2 months later, she suffered lower abdominal and adnexal tenderness . Ultrasound revealed a mass near the left tubal stump and a mass near the right ovary . Over the next few weeks the left mass disappeared, but the other mass grew . The physician aspirated hemoserous fluid . They switched to doxycycline over 4 months . 12 months after the initial operation, she had no symptoms and no pelvic abnormalities .

Curr Opin Pediatr, 1993 Feb, 5(1), 74 - 9
Sickle hemoglobinopathies; Lane PA; Neonatal screening for hemoglobinopathies, coupled with comprehensive medical care that includes parental education, prophylactic penicillin, and immunizations, has markedly reduced mortality from sickle hemoglobinopathies during infancy and early childhood . However, despite an increased knowledge of pathophysiology, current therapy does little to prevent acute, noninfectious complications such as anemic crises, pain events, or strokes; nor does it reliably prevent or delay the development of chronic organ damage . Recent publications have increased our understanding of factors that contribute to the clinical heterogeneity of sickle hemoglobinopathies, improved modestly our ability to identify and treat acute complications, and provided real hope for the development of potentially curative therapies . Prospective therapeutic trials of hydroxyurea and of bone marrow transplantation have recently begun.

Biochem J, 1993 Jan 15, 289 ( Pt 2), 593 - 8
Domain organization of penicillin-binding protein 5 from Escherichia coli analysed by C-terminal truncation; van der Linden MP et al.; The structural organization of penicillin-binding protein (PBP) 5 was investigated by C-terminal truncation . Compared with other low-M(r) penicillin-interacting proteins, PBP5 carries a C-terminal extension of about 100 amino acids . The sites for introduction of stop codons were chosen on the basis of the established three-dimensional structure of the Streptomyces albus G beta-lactamase {Dideberg, Charlier, Wery, Dehottay, Dusart, Erpicum, Frere and Ghuysen (1987) Biochem . J . 245, 911-913} and comparative hydrophobic cluster analysis {Gaboriaud, Bissery, Bencheritt and Mornon (1987) FEBS Lett . 224, 149-155} . Two stop codons were introduced at positions Ile-354 or Val-348 to construct an optimized soluble form of PBP5 for crystallization purposes . The newly constructed soluble and enzymically active form (PBP5s353) was isolated by dye-affinity chromatography and gave rise to small crystals . Another two stop codons were introduced at positions Arg-261 or Ala-276 to determine the minimal enzymically active 'core protein' . The truncated form (PBP5s275), missing the entire C-terminal extension, showed unaltered penicillin-binding characteristics and a catalytic-centre activity 40% that of PBP5s353 + 9 using bisacetyl-L-Lys-D-Ala-D-Ala as substrate . This protein, however was more susceptible to proteolytic degradation, which might indicate a role of the C-terminal portion in stabilizing the protein.

J Biol Chem, 1993 Jan 5, 268(1), 737 - 44
Biochemical characterization and molecular genetics of nine mutants of Penicillium chrysogenum impaired in penicillin biosynthesis; Cantoral JM et al.; Nine mutants of Penicillium chrysogenum (npe1 to npe8 and npe10) impaired in penicillin biosynthesis were screened after nitrosoguanidine mutation . Mutants npe1, npe4, npe5, npe6, npe7, npe8, and npe10 failed to synthesize significant levels of penicillin, whereas strains npe2 and npe3 synthesized about 20% of the penicillin level produced by the parental strain . Mutants npe5 and npe10 did not show alpha-aminoadipylcysteinyl-valine (ACV) synthetase activity in vitro and did not form ACV in vivo . Immunoblotting analysis of the different mutants using antibodies raised against Aspergillus nidulans ACV-synthetase showed that mutants npe5 and npe10 lacked this multienzyme protein, which in the parental strain had a molecular mass of about 420 kDa, and mutants npe2 and npe3 formed reduced level of this protein . All mutants showed normal levels of isopenicillin N synthase, as shown by Western blot analysis and enzyme assays (except npe10 that lacked this enzyme and npe2 and npe3 that formed reduced levels); npe1, npe4, npe6, npe7, npe8, and npe10 lacked isopenicillin N acyltransferase . Southern hybridizations of total DNA of the parental strain and mutants npe5, npe6, npe8, and npe10 with probes internal to the pcbAB, pcbC, and penDE genes showed that mutants npe5, npe6, and npe8 had the same arrangement of the penicillin gene cluster carrying probably point mutations, but mutant npe10 lacked the three penicillin biosynthetic genes, suggesting that it had suffered a deletion of the entire penicillin cluster . Southern hybridization with a pyrG probe as control and fingerprinting analysis of total DNA of npe10 as compared to several P.chrysogenum strains and other Penicillium and Aspergillus species, confirmed that npe10 is a deletion mutant of P . chrysogenum that had lost the penicillin biosynthetic genes.

J Biol Chem, 1993 Jan 5, 268(1), 665 - 71
Subcellular compartmentation of penicillin biosynthesis in Penicillium chrysogenum . The amino acid precursors are derived from the vacuole; Lendenfeld T et al.; The cellular localization of the origin of alpha-aminoadipate used in penicillin biosynthesis and the first enzymic step in Penicillium chrysogenum involved, delta-(alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS), has been studied . Subcellular fractions were obtained from protoplasts of a high penicillin-producing strain upon lysis by Triton X-100, and vacuoles purified from them . They were identified by the aid of alpha-mannosidase as a marker enzyme, by the presence of polyphosphate, and their ability to sequester {14C}lysin, added to the protoplasts prior to subcellular fractionation . 15.6 and 26.5%, respectively, of 6-{14C}alpha-aminoadipate, and 8.5 and 10.3%, respectively, of {14C}valine added accordingly were also found in the vacuole, and the higher proportion was found in vacuoles isolated from penicillin-producing mycelia . ACVS protein was detected in the membrane as well as the soluble fraction of the purified vacuoles . We propose therefore that ACVS is located either within or bound to the vacuolar membrane, and that the precursor amino acids for penicillin biosynthesis are withdrawn from the vacuolar amino acid pool.

Ugeskr Laeger, 1993 Jan 4, 155(1), 22 - 5
{Juvenile recurrent parotitis}; Paaske PB; Juvenile recurring parotitis is a relatively rare condition . The clinical picture as illustrated by a characteristic case history is reviewed . The condition shows a tendency to remission around puberty . Sialographic examination is characterised by the configuration of the parotid gland said to resemble a bunch of grapes . Biochemical tests do not contribute to the diagnosis which is established by the clinical picture and the typical sialographic findings . No systemic disease can be demonstrated in the patients who are healthy in other respects . The cause of the condition appears to be congenital sialectic changes localised to the parotid gland with resultant secondary ascending bacterial infection . In treatment during the acute stages, attempts should be made to stimulate secretion of saliva with sour foodstuffs and chewing gum . Treatment with penicillin for one week is recommended . On account of the benign character of the condition and the good long-term prognosis, operative intervention should not prove necessary.

Vet Med (Praha), 1993, 38(4), 215 - 22
{Effectiveness of the BR-Test and the Intest in the determination of chemotherapeutic residues in raw and preserved milk}; Rysanek D et al.; Negative detection of residues of inhibitory substances has become one of the standard quality traits of raw milk also in the Czech Republic . Hence a requirement appeared in 1991 to evaluate the usability of two commercially produced microtitration tests for this purpose . The tests of BR-TEST (Enterotox) and INTEST (Mlekarensky prumysl) were performed in weekly intervals for the time longer by a week than is the declared expiration, that means seven replications in BR-TEST and five replications in INTEST . Compact and stripped microplates (STRIPS) designated BR-TEST "AS", BR-TEST 12x8 "AS" and INTEST C-96 type and INTEST 0-96/6x16 were used for the tests . The principle of inhibition demonstration in the concentration series of selected drugs was applied . The drugs were chosen with respect to the frequency of their use for clinical treatments in the CR . Tab . II shows the used drugs and concentration series . The following parameters were tested: detection limits, reproducibility, effect of milk preservation, and the declared expiration . Tab . III shows detection limits . It is apparent the BR-TEST detection responses to streptomycin and chloramphenicol were lower in BR-TEST than in INTEST in our experiments . The responses to penicillin, oxacillin and oxytetracycline were lower in some cases, and equal in other ones . On the other hand, the INTEST detection response to sulfadimidin was markedly lower in comparison with BR-TEST . Tab . IV summarizes the range of detection limits in milk with Heeschen's reagent . In our experiments the detection response of BR-TEST to the tested chemotherapeutics was lower in some cases, in other cases it was the same as in INTEST.(ABSTRACT TRUNCATED AT 250 WORDS)

Trop Geogr Med, 1993, 45(2), 66 - 9
Louse-borne relapsing fever . A clinical and an epidemiological study of 389 patients in Asella Hospital, Ethiopia; Borgnolo G et al.; An outbreak of louse-borne relapsing fever, due to the return of soldiers to their original recruitment areas, after the end of thirty years of fighting in northern Ethiopia, was reported in Arsi region, southern Ethiopia . The epidemic spread to different members of the community and eventually the schools . We studied 389 patients affected by the epidemic and who were admitted to Asella Hospital between June 1991 and May 1992 . Twenty-seven per cent of the patients were ex-soldiers; 28% were students, who were admitted to the hospital since the schools were opened after the summer vacations . The common clinical features of the disease were fever (99%), headache (92%), hepatosplenomegaly (66%), myalgia (55%), arthralgia (51%), petechial rash (43%), epistaxis (24%) and jaundice (23%) . Observed complications were pneumonia (10%), pulmonary edema (6%), myocarditis (3%) and 6 abortions in 15 pregnancies . Patients were treated with low dose penicillin and i.v . fluids . The in-hospital case fatality rate was 3.6% . Jarisch-Herxheimer reaction occurred in 43% of the patients . 1.8% of the patients had relapses after treatment.

Lung, 1993, 171(3), 161 - 72
Dexamethasone increases airway epithelial cell neutral endopeptidase by enhancing transcription and new protein synthesis; Lang Z et al.; Neutral endopeptidase (NEP; also known as EC 3.4.24.11, CALLA) is a widely distributed membrane-bound enzyme that hydrolyzes many biologically important endogenous peptides . To evaluate the influence of glucocorticoids on airway epithelial cell NEP expression, we used the human airway epithelial cell line Calu-1 . Cells, grown to confluency in Dulbecco's modified Eagle medium with 10% fetal bovine serum and penicillin-streptomycin, were incubated with different concentrations of dexamethasone or vehicle alone in the presence or absence of actinomycin D or cycloheximide for planned times . NEP activity was assayed at the end of treatment employing reverse-phase, high-pressure liquid chromatography . In some experiments, changes in NEP-specific mRNAs in the presence or absence of dexamethasone and/or the inhibitors were also evaluated by Northern blot analysis . We found that dexamethasone increased Calu-1 NEP activity in a dose- and time-dependent manner . Northern blot analysis indicated that NEP-specific mRNAs were also increased by dexamethasone . Furthermore, neither actinomycin D nor cycloheximide inhibited the increases in NEP activity and NEP-specific mRNAs caused by dexamethasone stimulation . We speculate, therefore, that dexamethasone increases NEP expression of these airway epithelial cells by enhancing transcription and new protein synthesis.

Ann Acad Med Singapore, 1993 Jan, 22(1), 86 - 9
Adverse drug reactions--tales of a forensic pathologist; Chao TC; Drugs can produce adverse reactions in susceptible patients . This can range from minor discomfort to major morbidity or even death . The pharmacological properties of certain drugs have a high potential in producing these adverse reactions, especially if large doses are given or given simultaneously with interacting drugs or given in the presence of renal or liver dysfunction of the patient . Clinicians should be aware of the potential toxicity of the drugs they prescribe and their interacting drugs . In Singapore, deaths due to adverse drug reaction are regarded as unnatural deaths and they should be reported to the Coroner . These cases are usually subjected to a post-mortem examination . Clinicians are not allowed to sign up cases of death due to adverse drug reactions and those who do so will be subjected to queries from the Registrar of Death and the Coroner . Every year doctors have been called up to explain their misdeeds and warned . Fortunately there are not many such cases . Some cases of deaths due to adverse reactions to tetracyclines, sulphur, phenylbutazone, penicillin, paracetamol, etc will be discussed.

Arch Ital Biol, 1993 Jan, 131(1), 47 - 60
Transient epileptiform experience affects the duration of penicillin-induced convulsive activity in the awake rat; Horn E et al.; 1 . Experiments were performed to investigate whether the sensitivity of the cerebral cortex to produce convulsive activity was modified by a transient epileptic focus . For this reason, 30 awake rats received two intracerebral penicillin (PCN) injections (125 IU/0.5 microliter solvent), the first one into the motor or visual cortex, the second one two weeks later into the motor cortex . Convulsive activity was recorded by means of EEG . 2 . After the first PCN injection, interictal activity lasted 143.4 +/- 19.3, S.E . min (n = 17) in the motor cortex group, but 426 min (n = 13) in the visual group (p < 0.05) . The median frequency of interictal potentials (np/min) was significantly lower in the motor cortex group than in the visual cortex group (18.4 and 25.5 np/min, respectively, p < 0.05) . The period between the onset of the first and last seizure was 110.6 +/- 10.2 min for the motor cortex group, and 119.8 +/- 31.2 min for the visual cortex group . The seizures lasted longer and were less frequent in the motor than in the visual group (length: 12.5 +/- 1.1 vs 7.5 +/- 2.8 s; number: 43 +/- 11 vs 131 +/- 40, respectively, 0.05 < p < 0.1) . 3 . After the second PCN injection which was performed in all rats into the motor cortex, the duration but not the frequency of the interictal activity depended on the site of the first injection . The duration after this treatment was 96.8 +/- 43.3, S.E . min in the visual and 173.2 +/- 30.5 min in the motor cortex group (p < 0.05), while the frequency values of both groups were at a similar level (20.5 +/- 2.1 vs 18.9 +/- 1.7 np/min, respectively) . Also the period with generalized activity after the second PCN injection was shorter in the visual than in the motor cortex group (43.9 +/- 32.3 vs 114.3 +/- 31.8 min, respectively, p < 0.05), and the number of seizures slightly lower (8 +/- 210 vs 54 +/- 30, respectively, p < 0.1) . The length of the seizures was rather equal 11.6 +/- 2.5 vs 12.0 +/- 3.5 s, respectively, p > 0.1) . 4 . It is postulated that a transient epileptiform focus can induce, in a site-specific manner, long-lasting anticonvulsant effects . Therefore, epileptogenic experience may not only sensitize the brain, but also desensitize it with respect to the induction and duration of epileptiform activity.

Br J Clin Pract, 1993 Jan-Feb, 47(1), 14 - 6
Sydenham's chorea: a new look at an old disease; al-Eissa A; Eight children with Sydenham's chorea were studied to illustrate the clinical characteristics and the outcome of the disease . Their ages ranged from 8 to 13 years and the male to female ratio was 1.7:1 . Most of them had hemichorea, which frequently affected the right side of the body . The common presenting manifestations were involuntary movements, facial grimacing, clumsiness, and emotional instability . The duration of chorea ranged from one week to three years, with a median of 11 weeks . One half of the patients had associated mild carditis . Recurrences of chorea occurred only among patients who were not maintained on continuous penicillin prophylaxis . Haloperidol seemed to be an effective and tolerable agent in controlling the motor manifestations of the disease.

J Clin Neurophysiol, 1993 Jan, 10(1), 99 - 107
The neurophysiological basis of epileptiform magnetic fields and localization of neocortical sources; Barth DS; In this review, we present animal studies that evaluate the appropriateness of the dipole model as a physical representation of neocortical sources produced by evoked and spontaneous epileptiform activity in neocortex . Three-dimensional electrical measurements of cellular currents in rat sensory neocortex are compared to associated extracranial magnetic fields . Comparisons are performed for the direct cortical response evoked by electrical stimulation of the cortical surface, and for evoked and spontaneous interictal and ictal discharge of the penicillin focus in the same animal preparation . These data support the hypothesis that evoked and epileptiform magnetic fields result from intradendritic currents oriented perpendicular to the cortical surface . Furthermore, magnetic fields can be detected from epileptic foci smaller than 3 x 3 mm2 . Results from animal studies are then used as an empirical foundation for physical models with which to interpret noninvasive neuromagnetic recordings of epileptic discharge in human focal seizure disorders . Examples are presented in which the spatial and temporal distribution of extracranial magnetic fields produced by interictal events in humans may be adequately represented by multiple dipolar sources.

Int Orthop, 1993, 17(1), 43 - 7
Persistent bony lesions in congenital syphilis . A report of three cases; Gadea A et al.; We report three cases of congenital syphilis with bony lesions which were unusual because they were unilateral and asymmetrical . They did not heal with conventional penicillin treatment and they resulted in angular deformities, shortening of the limb and pseudarthrosis following pathological fractures.

Hautarzt, 1993 Jan, 44(1), 23 - 9
{Analysis of 1983-1991 Leipzig University Dermatology Clinic observed cases of syphilis}; Haustein UF et al.; A total of 1380 patients with syphilis were diagnosed and treated from January 1983 to December 1991 at the Department of Dermatology and Venereology at Leipzig University in West Saxon, Federal Republic of Germany where the population is 1.4 million . The incidence of syphilis increased gradually from 1983 to 1989 and then decreased again . The number of recent cases of syphilis was almost twice as high as latent syphilis cases (63:37%) . The vast majority of cases suffered from early syphilis . In almost half the source of infection was casual contacts (44%); in one-third it was a stable partners (30%); about 6% were homosexuals and about 4% were prostitutes . Among the primary syphilis cases multiple chancres were seen in 16% . In 31% of cases, the ulcus durum was extragenital . Among the secondary syphilis cases macular and maculopapular exanthema were the commonest features (51%), followed by palmoplantar syphilis (5%), condylomata lata (5%), angina specifica (3%) and papular exanthema (3%) . However, in 30% of the cases multiple skin features were observed . Secondary syphilis with persistent chancres were seen in 12% . Five percent of the patients were suffering from the second to the fifth reinfection in their life, and again 5% of the syphilis cases were detected during pregnancy . Only two patients had an HIV infection, 10% suffered from gonorrhea and 10% from trichomoniasis, 12% from chlamydial infection, 4% from genital warts and 8% from herpes simplex genitalis at the same time . The therapy of choice was penicillin . In 0.3% an allergy to penicillin was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

S Afr Med J, 1993 Jan, 83(1), 34 - 5
The antenatal prevention of congenital syphilis in a peri-urban settlement; Swingler GH et al.; The obstetric records of patients from Khayelitsha were examined to assess the efficiency of a system for the antenatal prevention of congenital syphilis, and to identify points of breakdown in the process . Seventy-seven (12.7%) of 607 mothers had serological evidence of syphilis, including 10 (32.3%) of 31 mothers who had received no antenatal care . Of 70 patients who required routine management, only 36 (51.4%) received 3 or more of the recommended 4 penicillin injections . Two main weaknesses in the system were identified . One was the centralisation of serological testing . This delayed results reaching the relevant unit, and was responsible for a high cumulative attrition of patients during the many stages necessitated by the centralised testing . The other was a 24.5% attrition of patients referred from the antenatal clinic to a separate sexually transmitted diseases clinic.

Biol Reprod, 1993 Jan, 48(1), 68 - 76
Comparison of functional response of rat, macaque, and human ovarian cells in hormonally defined medium; Woodruff TK et al.; A serum-free medium has been developed which supports in vitro function by ovarian cells derived from rat, monkey, and human tissue . This granulosa cell medium (GCM) consists of Dulbecco's Modified Eagle's Medium: Ham's F-12 medium (1:1, v:v) supplemented with insulin, transferrin, aprotinin, selenium, fibronectin, penicillin, and streptomycin . Ovarian cells from three species were compared: rat, macaque, and human . Four types of ovarian cultures were examined: 1) purified granulosa cell cultures and 2) co-cultures containing granulosa-theca-stroma cells, 3) luteal cells, and 4) granulosa-lutein (harvested from in vitro fertilization cultures) cells . Each cell type was characterized by its response to FSH or hCG when cultured in GCM . Morphologic responses to FSH were observed in GCM in rat granulosa and granulosa-theca-stroma cell cultures, macaque and human granulosa-lutein cells, and human granulosa-theca-stroma cell cultures . The FSH-stimulated cells retracted and became rounded, leaving long intercellular connections . Luteal cells did not retract in response to FSH, and the cells remained firmly attached to the fibronectin matrix . Steroidogenic regulation of the GCM-cultured ovarian cells was monitored following stimulation of the cultures with FSH . The ability of the cells to aromatize testosterone was first examined . Rat granulosa cell cultures and granulosa-theca-stroma cell cultures, macaque granulosa-lutein cell cultures, and human granulosa-theca-stroma cell cultures all accumulated estradiol when given FSH and testosterone for 48 h . Moreover, these cell types as well as human luteal cells were able to metabolize 25-hydroxy {1,2-3H}cholesterol to various steroid metabolites . The data indicate that GCM supports normal granulosa cell morphologic response to FSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Chest, 1993 Jan, 103(1), 303 - 4
Hypersensitivity pneumonitis and airways hyperreactivity induced by occupational exposure to penicillin; de Hoyos A et al.; A patient with penicillin-induced hyperreactive airways in association with hypersensitivity pneumonitis is described . Patch tests and intradermal tests to penicillin were positive . Bronchoalveolar lavage demonstrated a relative lymphocytosis and mild neutrophilia . Symptoms and physiologic abnormalities of pulmonary function and gas exchange resolved on cessation of exposure to penicillin.

Pediatrics, 1993 Jan, 91(1), 88 - 91
Comparison of maternal sera, cord blood, and neonatal sera for detecting presumptive congenital syphilis: relationship with maternal treatment; Chhabra RS et al.; The incidence of congenital syphilis has increased rapidly over the past few years . Most infected mothers and their newborns are asymptomatic at birth and diagnosis depends on serologic testing during pregnancy and at delivery . This study was initiated to compare maternal sera, cord blood, and neonatal sera for detecting presumptive congenital syphilis and to assess the role of maternal treatment (administration of penicillin to the mother at least 1 month before delivery) on the serologic results at the time of delivery . The serologic results from all live deliveries complicated by a positive maternal and/or neonatal test for syphilis during a 12-month period were compared using chi 2 analysis and multiple comparisons for proportions . Of 3306 livebirths, 73 (2.2%) were complicated by a positive maternal or neonatal serology . At delivery, the serologic test was positive in 68 (94%) of 72 maternal sera, 30 (50%) of 60 cord sera, and 43 (63%) of 68 neonatal sera . In the absence of maternal treatment, 95% of the maternal sera, 66% of the cord blood samples, and 86% of the neonatal sera were positive . If the mother had been treated, 94% of maternal sera, 36% of cord sera, and 39% of neonatal sera were positive . Cord blood and neonatal sera appear to be inferior to maternal sera for detecting prenatal exposure to syphilis . Cord serology is also inferior to neonatal serology at 2 to 3 days of age . The most effective way to identify newborns at risk for congenital syphilis is to obtain a maternal serologic diagnosis during pregnancy and to test maternal and neonatal sera at delivery.

Pediatrie, 1993, 48(3), 241 - 7
{Mycoplasma pneumoniae pneumopathies in children: clinical, biological and radiological study}; Gambert C et al.; Clinical, radiological and biological features of 19 cases of serologically proven Mycoplasma pneumoniae pneumonia were compared with those of 21 cases of other types of pneumonia . Some clinical features were more frequent in M pneumoniae: patients older than 5 years, association with upper respiratory tract infection, skin rashes, acute course, unsuccessful treatment with penicillin . There were no specific radiological features . When compared with the complement fixation method, the serological diagnosis using agglutination technique appears to be more sensitive.

J Basic Microbiol, 1993, 33(1), 27 - 34
Fructose-2,6-bisphosphate level and beta-lactam formation in Penicillium chrysogenum; Kozma J et al.; The rate of penicillin formation in the medium containing lactose as sole carbon source markedly decreased after addition of glucose but at the same time the growth rate of fungal mycelium increased . Significant correlation was found between the formation of penicillin and the intracellular concentration of fructose-2,6-bisphosphate . It appears that penicillin production is influenced by the level of fructose-2,6-bisphosphate.

J Clin Microbiol, 1993 Jan, 31(1), 89 - 96
Characterization of ehrlichial organisms isolated from a wild mouse; Kawahara M et al.; An infectious agent was isolated from the enlarged spleen of a wild mouse, Eothenomys kageus, by intraperitoneal inoculation of the spleen homogenate into laboratory mice . The laboratory mice developed splenomegaly, and the agent was maintained by serial passage of spleen homogenates in laboratory mice . The agent in the spleen homogenate was inactivated after incubation at 37 or 50 degrees C . Tetracyclines were effective in preventing infection of mice with this agent, but penicillin and sulfonamides were ineffective . Cytoplasmic inclusion bodies were observed in the peritoneal macrophages of infected mice . Electron microscopy revealed numerous small pleomorphic cocci within membrane-lined vacuoles in the cytoplasm of splenic macrophages . Morphologically similar to the ehrlichial organisms, each organism was surrounded by a distinct plasma membrane and rippled outer cell membrane without a distinct peptidoglycan layer . The agent did not grow in chicken embryos, and the Weil-Felix test result was negative . In the indirect fluorescent-antibody test, the agent reciprocally cross-reacted with Ehrlichia canis and cross-reacted somewhat with Ehrlichia sennetsu but did not cross-react with Ehrlichia risticii, Neorickettsia helminthoeca, Rickettsia tsutsugamushi, or Chlamydia spp . The mouse antiserum against this agent reacted with 64-, 47-, 46-, 44-, and 40-kDa proteins of E . canis by Western blotting (immunoblotting) . Since E . canis and closely related Ehrlichia chaffeensis and Ehrlichia ewingii are not known to proliferate or cause splenomegaly in mice, these results suggest that the agent is a new species within the tribe Ehrlichieae of the family Rickettsiaceae . The finding suggests that wild rodents may serve as reservoirs for pathogenic ehrlichiae.

Wien Klin Wochenschr, 1993, 105(15), 437 - 9
{Unilateral blindness in neurosyphilis}; Dobos GJ et al.; A 55 year-old patient developed loss of vision in his right eye over a period of a few weeks with the clinical finding of uveitis and papillaedema . Subsequently, also the left eye was affected by a marked deterioration of vision . The neurological findings were normal . The laboratory findings showed a marked elevation of the ESR (> 100 mm within the first hour) and protein electrophoreses showed changes suggestive of chronic inflammation . Analysis of the cerebrospinal fluid revealed a lymphocytic meningitis with 180/3 cells; the positive serological and liquor findings for TPHA and FTA led to the definite diagnosis of neurosyphilis . Treatment intravenously with 3 x 4 million units penicillin G daily for a fortnight proved curative . Vision of the left eye recovered fully, but the ophthalmological changes in the right eye were irreversible . This case shows that even today the differential diagnosis of syphilis must be considered with loss of vision of doubtful aetiology and uveitis.

Appl Biochem Biotechnol, 1993 Spring, 39-40, 445 - 53
Gene manipulation by protoplast fusion and penicillin production by Penicillium chrysogenum; Tahoun MK; Hybrids have been obtained by protoplast fusion of nitrate-nonutilizing cnx- and acetate-nonutilizing fac- mutants of Penicillium chrysogenum strains 4/95 and 26/818, respectively . Induced haplodization of the hybrids allowed the recovery of stable segregants, which were screened for penicillin production . The penicillin-producing segregants showed a wide range of titers that reached for a certain mutant to 290-390% increase above the parent strains.

Bull World Health Organ, 1993, 71(6), 773 - 80
Syphilis-associated perinatal and infant mortality in rural Malawi; McDermott J et al.; In Mangochi District, a rural area of Malawi, the prevalence of active syphilis was 3.6% among 3591 women who had singleton births and who were negative for human immunodeficiency virus (HIV) . Compared with non-syphilitic women, those with active syphilis (positive Venereal Disease Research Laboratory/rapid plasmin reagin tests (titre > or = 1:8) and a reactive microhaemagglutination assay) were more likely to experience stillbirths as well as the early and late neonatal deaths and even postneonatal deaths of their children . Characteristics associated with active syphilis were not very useful in targeting women at high risk of having the condition, which makes universal screening in antenatal programmes the most efficacious way to prevent syphilis-associated morbidity and mortality . The potential for a programme to prevent congenital syphilis in the perinatal, neonatal, and post-neonatal periods is evident . In considering resource allocation to child survival programmes in areas where the prevalence of syphilis is high, officials need to include antenatal syphilis screening, using rapid tests and treatment at the first contact of the mother with the health care systemPIP: Syphilis infection in pregnancy causes high rates of fetal and early infant death and adversely affects women's health . Despite the existence of a simple screening test for syphilis and the continued effectiveness of penicillin in treating the disease, syphilis remains a largely ignored maternal and perinatal health problem in most sub-Saharan African countries . The prevalence of reactive syphilis serology among pregnant women in Africa is in the range 6-16% . In Malawi, despite national policy, routine antenatal syphilis screening programs were discontinued in many rural district hospitals when they could not sustain the programmatic requirements . In this context, the authors explored the prevalence of and risk factors for acquiring syphilis and its outcomes in 1991-92 among 3591 women in Mangochi District, Malawi, who had singleton births and were negative for HIV . 3.6% of the subjects had active syphilis . Women with syphilis were more likely than nonsyphilitic women to experience stillbirths, early and late neonatal deaths, and even postneonatal deaths of their children . Characteristics associated with active syphilis were not, however, very useful in targeting women at high risk of having the condition . Universal screening in antenatal programs is therefore the best way to prevent syphilis-associated morbidity and mortality . Syphilis prevention programs in areas with a high prevalence of syphilis should include antenatal syphilis screening with rapid tests and treatment when the mother first contacts the health care system .

Rev Neurol (Paris), 1993, 149(5), 320 - 5
{Demyelinating involvement in Borrelian neuropathies}; Clavelou P et al.; Five patients (4 men, 1 woman, aged 51-67), were hospitalized for peripheral painful neuropathies . The serological survey and the dramatic responses to penicillin confirmed the responsibility of Borrelia burgdorferi in all 5 cases . Electromyographical studies showed evidence of demyelination: prolonged distal latency, slowing down of nerve conduction velocity . In 3 patients this pattern was related to axonal degeneration as shown by fibrillation potentials and reduced voluntary motor unit potentials recorded on needle examination . The other two showed no axonal degeneration . One also had motor conduction blocks . Such a demyelination could be due to vasculitis of the vasa nervorum described in tick-bone meningoradiculitis.






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