Penicillin

Eur J Biochem, 2001 Mar, 268(5), 1298 - 303
Expression of penicillin G acylase from the cloned pac gene of Escherichia coli ATCC11105 . Effects of pacR and temperature; Dai M et al.; The structural gene pac in Eschericia coli ATCC11105 encodes penicillin G acylase (PGA) . Within the pac gene, there is a regulatory gene pacR, which is transcribed in the opposite direction . Site-directed mutagenesis was performed at base 1045 of pac by replacing a T with a C . This substitution did not alter the amino-acid sequence of PGA, but changed the translation start codon of pacR from AUG to GUG . The expression of the mutant pacR decreased dramatically and the lacZ transcriptional fusion analysis showed that GUG was an extremely poor initiation codon for pacR . The pacR mutation caused PGA expression to be constitutive rather than inductive in two strains (E . coli A56, DH10B) . The pac inducer phenylacetic acid (PAA) gave significant induction of PGA production at a concentration of 0.2% in wild type, but PAA at this concentration inhibited both cell growth and PGA production in the pacR mutated strains . The temperature-dependent expression character of pac is preserved in the pacR translation-initiation mutant and the optimum temperature of PGA production was 22 degrees C in both wild type and mutant . At a higher temperature of 37 degrees C, the PGA precursor polypeptide could not be matured into subunits and formed inclusion bodies, as revealed by western blot analysis . Our investigations confirmed the hypothesis of pacR-mediated PAA induction for PGA expression and clarified the inhibitory effect of high temperature upon the post-translational processing of the PGA precursor polypeptide.

Fresenius J Anal Chem, 2000 Nov, 368(6), 624 - 6
Rapid liquid chromatographic determination of residual penicillin G in milk; Furusawa N; A simple and rapid high-performance liquid chromatographic (HPLC) method for determination of residual penicillin G (benzylpenicillin, PCG) in milk was developed . The sample preparation was performed by stirring with ethanol and reacting with 5 M 1,2,4-triazole-mercury (II) chloride solution at 65 degrees C for 10 min followed by an ultra centrifugation step . The HPLC separation was carried out using a Mightysil RP-4GP column, a mobile phase of acetonitrile and 0.1 M phosphate buffer (pH 6.5) (35:65, v/v) and a photo-diode array detector . The average recoveries from spiked PCG (0.004, 0.01, 0.05 and 0.1 microgram/mL) were above 86% with coefficients of variation between 1.2 and 4.5% . The limit of detection was 0.004 microgram/mL . This value corresponds to the maximum residue limit (MRL) in milk (0.004 microgram/mL, EU and Japan) . The total time required for the analysis of one sample was below 40 min.

Biomol Eng, 2001 Mar, 17(3), 113 - 7
DNA architecture and transcriptional regulation of the Escherichia coli penicillin amidase (pac) gene; Stojcevic N et al.; The transcriptional regulation of Escherichia coli ATCC11105 penicillin amidase (pac) gene was studied by modifying DNA sequences responsible for promoter activation by cyclic AMP receptor protein (CRP) . The nucleotide sequence of the 5'-flanking region of the pac gene contains putative tandem CRP binding sites positioned at -69/-70 and at -111/-112 with respect to the transcriptional start site . Our results obtained with either point mutations or insertion or deletion mutants (each of which rotated the helix structure at the CRP binding site one-half turn) showed significant decrease of penicillin amidase (PA) activity, suggesting the CRP as a major activator . In this study, the evidence for the importance of spacing between tandem binding sites for CRP as well as for their location related to the promoter core sequence has been provided . Involvement of integration host factor (IHF) as an additional regulatory protein in the pac gene transcription regulation was also analyzed . It is shown that activation of the pac gene transcription is elevated by IHF.

Nippon Rinsho, 2001 Feb, 59(2), 367 - 73
{Mechanism of drug resistance in Helicobacter pylori}; Maeda S et al.; Clarithromycin is one of the most important antibiotics for H . pylori eradication . However, 5-10% was reported to be resistant . It has been shown that one point mutation in the 23S rRNA gene is associated with resistance to clarithromycin . To detect H . pylori infection and the mutation simultaneously, we have designed PCR primers specific for H . pylori, and established assays of PCR-RFLP and PCR-preferential homo-duplex formation (PHFA) . Using this assay, we can detect mixed infections with wild and mutant-strains . The prevalence of mutant infection increased through clarithromycin-based eradication . However, the existence of mutant strains had been confirmed before therapy in most cases who 'converted' to mutant after therapy . Metronidazole is also one of the most important antibiotics for eradication . However, 5-50% was reported to be resistant . It has been shown that rdx gene mutation is associated with resistance . It is reported that inactivation of the rdx gene is frequently, but not always, associated with resistance to metronidazole . Amoxicillin resistant strains were rare (1.2% in Japanese strains) . It is reported that penicillin-binding protein might play a role in the resistance . By detecting of the resistance based on the molecular mechanism, patients can be treated with adequate antibiotics with information about resistance.

Rev Mal Respir, 2000 Dec, 17(6), 1089 - 93
{Prognosis of asthmatic adolescents in adulthood}; Rance F et al.; Little is known about the long-term outcome of asthmatic adolescents . According to the literature, 20 to 50% of asthmatic adolescents become symptom-free when they become adults . We report 50 cases of asthmatic adolescents, 25 girls and 25 boys, with a mean follow of 4.4 years (range 1-12 years) . Only 4 patients (8%) became symptom-free, all 4 were stage I and II patients . One death occurred subsequent to penicillin allergy, but was not related to status asthmaticus . Nor remission was observed in stage III and IV patients, whereas 5.8% and 12% of stage II and II patients respectively grew out of their asthma . The factors predictive of persistent asthma in adulthood were severe asthma at the age of 13 years, female gender, onset of asthma before the age of 7 years, no periodic rhinitis, and exercise induced asthma.

J Pediatr Hematol Oncol, 2001 Feb, 23(2), 112 - 6
Parental health beliefs and compliance with prophylactic penicillin administration in children with sickle cell disease; Elliott V et al.; PURPOSE: Prophylactic penicillin is effective in preventing severe invasive pneumococcal infection in children with sickle cell disease . In some families, compliance has been problematic . The aims of this study were to monitor compliance and to assess the efficacy of the Health Belief Model (HBM) in predicting compliance . METHODS: Fifty mothers of children with sickle cell disease, ages 6 to 60 months, participated in the study . On enrollment, mothers completed surveys assessing their health beliefs regarding sickle cell disease and infections . Compliance was assessed through self-reporting by the mothers and through review of local pharmacy records of penicillin refills . RESULTS: Sixty percent of the mothers reported that they were highly compliant with obtaining the prescribed 14-day refills . Pharmacy records indicated that only 12% actually adhered to this schedule . The self-reports were significantly related to compliance ratings; mothers who admitted less than optimal compliance averaged 42 days between refills, compared with 19 days for mothers who reported good compliance . Varying perceptions identified through the HBM accounted for approximately 30% of the variance in compliance rates . The perceived burdens of picking up the refills and remembering to administer the medication were the most significant factors . CONCLUSIONS: Educational efforts alone are not sufficient to ensure compliance with penicillin prophylaxis . Routinely monitoring compliance through pharmacy records, reviewing parental beliefs about sickle cell disease and infections, and exploring barriers to treatment will promote dialogue about the importance of strict compliance with this relatively simple yet life-saving prophylaxis.

J Neurosurg, 2001 Feb, 94(2), 270 - 80
Anticonvulsant effects of gamma surgery in a model of chronic spontaneous limbic epilepsy in rats; Chen ZF et al.; OBJECT: The management of intractable epilepsy remains a challenge, despite advances in its surgical and nonsurgical treatment . The identification of low-risk, low-cost therapeutic strategies that lead to improved outcome is therefore an important ongoing goal of basic and clinical research . Single-dose focal ionizing beam radiation delivered at necrosis-inducing and subnecrotic levels was investigated for its effects on seizure activity by using an established model of chronic recurrent spontaneous limbic seizures in rats . METHODS: A single 90-minute period of repetitive electrical stimulation (inducing stimulus) of the hippocampus in rats elicited a single episode of status epilepticus, followed by a 2- to 4-week seizure-free period . Spontaneous recurrent seizures developed subsequently and persisted for the duration of monitoring (2-10 months) . Simultaneous computerized electroencephalography and video recording were used to monitor the animals . After the establishment of spontaneous recurrent seizures, bilateral radiation centered in the ventral hippocampal formation was administered with the Leksell gamma knife, aided by a stereotactic device custom made for small animals . A center dose of 10, 20, or 40 Gy was administered using a 4-mm collimator . Control animals were subjected to the same seizure-inducing stimulus but underwent a sham treatment instead of gamma irradiation . In a second experiment, the authors examined the effects of gamma irradiation on the proclivity of hippocampal neurons to display epileptiform discharges . Naive animals were irradiated with a single 40-Gy dose, as already described . Slices of the hippocampus were prepared from animals killed between 1 and 178 days postirradiation . Sensitivity to penicillin-induced epileptiform spiking was examined in vitro in slices prepared from control and irradiated rat brains . CONCLUSIONS: In the first experiment, single doses of 20 or 40 Gy (but not 10 Gy) reduced substantially, and in some cases eliminated, behaviorally and electrographically recognized seizures . Significant reductions in both the frequency and duration of spontaneous seizures were observed during a follow-up period of up to 10 months postradiation . Histological examination of the targeted region did not reveal signs of necrosis . These findings indicate that single-dose focal ionizing beam irradiation at subnecrotic dosages reduces or eliminates repetitive spontaneous seizures in a rat model of temporal lobe epilepsy . In the second experiment, synaptically driven neuronal firing was shown to be intact in hippocampal neurons subjected to 40-Gy doses . However, the susceptibility to penicillin-induced epileptiform activity was reduced in the brain slices of animals receiving 40-Gy doses, compared with those from control rats that were not irradiated . The results provide rational support for the utility of subnecrotic gamma irradiation as a therapeutic strategy for treating epilepsy . These findings also provide evidence that a functional increase in the seizure threshold of hippocampal neurons contributes to the anticonvulsant influence of subnecrotic gamma irradiation.

Afr J Med Med Sci, 1999 Sep-Dec, 28(3-4), 185 - 7
Routine antenatal syphilis screening--a case against; Obisesan KA et al.; To highlight the deficiencies associated with the routine antenatal syphilis screening as it is done now in the University College Hospital, Ibadan, and determine the cost effectiveness or otherwise of syphilis screening using as parameters the specificity of the method of screening as well as the gravity of the disease . The results of VDRL tests performed on pregnant women attending the antenatal clinic of the University College Hospital, Ibadan, in a 10-year period, January 1988 to December 1997 were analysed for seropositivity as well as congenital syphilis . The case notes of 110 sero-reactive patients were retrieved and analysed for pregnancy outcome . The prevalence rate of seropositive patients was 1.1% . Only 3 of the seropositive had repeated tests and were treated empirically with high doses of penicillin . There was no case of congenital syphilis . This study has shown that the syphilis screening as it is done now is not cost-effective . If VDRL test is to be continued, efforts must be made to reintroduce TPHA-test, which is more specific-specificity; it wastes a lot of time and money of the patients . Hence it is not cost effective . If VDRL test is to be continued efforts must be made to reintroduce TPHA-test, which is more specific.

Acta Derm Venereol, 2000 Sep-Oct, 80(5), 378 - 80
A two-step schedule for the treatment of actinomycotic mycetomas; Ramam M et al.; Actinomycotic mycetomas usually respond slowly to treatment with antibiotics . In an attempt to hasten clinical resolution, we used a 2-step regimen consisting of an intensive phase of therapy with penicillin, gentamycin and co-trimoxazole for 5-7 weeks, followed by maintenance therapy with amoxicillin and co-trimoxazole . Seven patients were treated, all of whom showed significant reduction in discharge and swelling after the intensive phase . Maintenance therapy was continued for 2-5 months after the lesions became completely inactive . Five patients completed maintenance therapy, which was given for 6-16 months (mean 10.7 months), and remained free of disease during a mean post-treatment follow-up period of 6.4 months . The other 2 patients also responded satisfactorily and continue to receive maintenance therapy . Side-effects necessitating a modification of the treatment schedule occurred in 2 patients but reversed on discontinuation of the drugs responsible . This treatment schedule produces a rapid clinical response during the initial, intensive phase and promotes compliance with the longer maintenance phase of treatment necessary to achieve a complete cure.

Intensive Care Med, 2000 Nov, 26(11), 1698 - 700
Critical illness onychomadesis; Wester JP et al.; OBJECTIVE: To present our observation of the development of a rare nail deformity in the prolonged course of disease of a critically ill patient with a pulmonary abscess . DESIGN: Case report . SETTING: Tertiary referral, 16-bed, level I surgical ICU in an academic hospital . PATIENT: A 48-year-old Caucasian male was treated with penicillin for a pneumococcal meningitis and pneumonia . He developed a large pulmonary abscess of the right upper lobe and needed prolonged mechanical ventilation . Extensive surgical treatment was successful eventually . A remarkable feature concerned the occurrence of onycholysis of all finger nails and toe nails resulting in complete shedding of the nails (onychomadesis) . This phenomenon can be regarded as an extreme manifestation of Beau's lines precipitated by a severe systemic insult . CONCLUSION: We observed the development of onychomadesis in a critically ill patient with a large pulmonary abscess . This association has not been described before.

Crit Rev Microbiol, 2000, 26(4), 205 - 20
Penicillin binding proteins, beta-lactams, and lactamases: offensives, attacks, and defensive countermeasures; Koch AL; A strong outer covering of peptidoglycan (the sacculus) is essential for most bacteria . Beta-lactams have evolved billions of years ago and can block saccular growth of the organism . This led to the evolution of beta-lactamases and resistant penicillin binding proteins (PBPs) . With the introduction of lactam antibiotics by the pharmaceutical industry, resistance genes in nature were laterally transferred to antibiotic-treated disease-causing organisms and additional modification of beta-lactamase genes and of the regulatory genes of the mecA region took place . However, it can be concluded that very little of either type of resistance mechanisms represents new basic evolution against the penicillin type antibiotics . In the last 60 years the resistant bacteria in the main arose by movement of genes from other organisms, from minor genetic changes, and from alteration of the regulation of synthesis.

Biologist (London), 2000 Jun, 47(3), 115 - 9
The discovery of penicillin: so many get it wrong; Diggins FW; Alexander Fleming discovered penicillin in September 1928, the most likely date being Monday 3 September on his return from holiday in Suffolk . This discovery has attracted more myths and misinformation than probably any other in the history of medicine.

Rev Fac Cien Med Univ Nac Cordoba, 2000, 57(1), 51 - 7
{Collagenase production increases in rheumatoid arthritis and osteoarthritis synoviocytes incubated}; Montrull HL et al.; Cartilage is a specialized connective tissue . It contains few cells into an extracell matrix . The matrix mainly constituents are collagen and proteoglycans . Its degradation depends on synoviocytes activity, that secrete metalloproteases, agents to proteoglycans catabolism . There are two types of synoviocytes: macrophagics (type "A:') and fibroblastics (type "B") . The proteoglycan destruction can be LT-dependent or LT-independent . The aim of this work is synoviocytes function ex vivo study, free immune system influence . In order to do it, heparinized synovial fluid samples were obtained from 6 osteoarthritic (OA) and 6 arthritic (RA) both sex untreated patients, diagnosed according ACR criteria, which disease duration was longer than 6 months . Patients average age was 70 +/- 2 years . Control samples were synovial fluid from traumatic arthritis or non inflammatory bone-muscle pathology . Synovial fluid was centifugated at 1500 g for 30 minutes to isolate synoviocytes . Sediment containing cells was 6 hs incubed with Dulbecco-Eagles media, that has HEPES Gibco (26 mM); NaHCO3 (0.5 g/I); glutamine (2 mM), streptomicine (100 mg/l), G-penicillin (1 U/ml); anphotericine B (2.5 mg/l) . Cells calification and viability were cytopathologically determined . Before and after incubation, collagenase activity was measured by ELISA-double-sandwich, using 10 micrograms/ml monoclonal anti-MMPs in phosphate-buffer-saline . The antigen-antibody complex production with inespecific proteins was blocked by bovine seric albumine . Streptavidin peroxidase was added and washed with 2,2,azin,di(3-ethyl-benztazoilinsuiphonic) acid to develop color . The link of labeled antibody by absorbance at 410 nm was determined in ELISA-spectrophothometer . RA patients earlier MMPs synoviocytes production was 1373 +/- 115 ng/ml . Then 6 hs incubation 2143 +/- 132 ng/ml was reached . The increase (56%) had high significance (p < 0.0001) . OA earlier MMPs cells production was 276 +/- 23 ng/ml, but after incubation it reached 542 +/- 47 ng/ml . (96% increased with highly significativa difference too: p < 0.0001) . Microscopic study was carried out before and after incubation, and shows a lot of synoviocytes with plenty of cytopiasme when the collagenase leveis were highest . On the contrary, when low MMPs production by synovial fluid, as no incubated osteoarthritic material, a few cells containing picnotics nucleous were observed . Significant quantitative differences in AR and OA enzymatic secretion were observed . Although in rheumatoid arthritic MMPs leveis synoviocytes production were 4.6 times than OA levels, after 6 hs incubation percentage of increase in OA cells secretion was highest . Described results confirm MMP-1 synthesis by synoviocytes, and these levels correlate with inflammation, more pronounced in acute (RA) than chronic pathology (OA) . Synoviocyte incubation let us to test disease changes in synovial fluid according to cells number and phagocytic activity . Authors agree to assert that synovial fluid may reflect what is happening in an articular cartilago, because SF provides markers of joint disease . MMPs are giving information about pathways involved in OA and RA cartilage degradation.

Antimicrob Agents Chemother, 2001 Mar, 45(3), 870 - 7
Penicillin-binding proteins in Leptospira interrogans; Brenot A et al.; The Leptospira interrogans ponA and pbpB genes were isolated and characterized . ponA and pbpB encode the penicillin-binding proteins (PBPs) 1 and 3, respectively . There is little sequence variation between the PBP genes from two L . interrogans strains (serovar icterohaemorrhagiae strain Verdun and serovar pomona strain RZ11) . The deduced L . interrogans PBP 1 and PBP 3 protein sequences from the two strains shared over 50% similarity to homologous proteins from Escherichia coli . It was demonstrated for strain Verdun that ponA and pbpB are transcribed individually from their own promoter . The ponA and pbpB genes from both strains are separated by 8 to 10 kb and oriented such that their transcription is convergent . The L . interrogans PBP 1 and PBP 3 proteins were synthesized in E . coli and were modified with ampicillin using a digoxigenin-ampicillin conjugate . These data show that both genes encode functional PBPs.

Biotechnol Bioeng, 2001 Feb 20, 72(4), 379 - 88
Quantitative analysis of Penicillium chrysogenum Wis54-1255 transformants overexpressing the penicillin biosynthetic genes; Theilgaard H et al.; The low penicillin-producing, single gene copy strain Wis54-1255 was used to study the effect of overexpressing the penicillin biosynthetic genes in Penicillium chrysogenum . Transformants of Wis54-1255 were obtained with the amdS expression-cassette using the four combinations: pcbAB, pcbC, pcbC-penDE, and pcbAB-pcbC-penDE of the three penicillin biosynthetic genes . Transformants showing an increased penicillin production were investigated during steady-state continuous cultivations with glucose as the growth-limiting substrate . The transformants were characterized with respect to specific penicillin productivity, the activity of the two pathway enzymes delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS) and isopenicillin N synthetase (IPNS) and the intracellular concentration of the metabolites: delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV), bis-delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (bisACV), isopenicillin N (IPN), glutathione (GSH), and glutathione disulphide (GSSG) . Transformants with the whole gene cluster amplified showed the largest increase in specific penicillin productivity (r(p))-124% and 176%, respectively, whereas transformation with the pcbC-penDE gene fragment resulted in a decrease in r(p) of 9% relative to Wis54-1255 . A marked increase in r(p) is clearly correlated with a balanced amplification of both the ACVS and IPNS activity or a large amplification of either enzyme activity . The increased capacity of a single enzyme occurs surprisingly only in the transformants where all the three biosynthetic genes are overexpressed but is not found within the group of pcbAB or pcbC transformants . The indication of the pcbAB and pcbC genes being closely regulated in fungi might explain why high-yielding strains of P . chrysogenum have been found to contain amplifications of a large region including the whole penicillin gene cluster and not single gene amplifications . Measurements of the total ACV concentration showed a large span of variability, which reflected the individual status of enzyme overexpression and activity found in each strain . The ratio ACV:bisACV remained constant, also at high ACV concentrations, indicating no limitation in the capacity of the thioredoxin-thioredoxin reductase (TR) system, which is assumed to keep the pathway intermediate LLD-ACV in its reduced state . The total GSH pool was at a constant level of approx . 5.7 mM in all cultivations .

Biochemistry (Mosc), 2000 Dec, 65(12), 1367 - 75
Kinetics of ampicillin synthesis catalyzed by penicillin acylase from E . coli in homogeneous and heterogeneous systems . Quantitative characterization of nucleophile reactivity and mathematical modeling of the process; Youshko MI et al.; Kinetic regularities of the enzymatic acyl group transfer reactions have been studied using ampicillin synthesis catalyzed by E . coli penicillin acylase as an example . It was shown that ampicillin synthesis proceeds through the formation of an acylenzyme-nucleophile complex capable of undergoing hydrolysis . The relative nucleophile reactivity of 6-aminopenicillanic acid (6-APA) is a complex parameter dependent on the nucleophile concentration . The kinetic analysis showed that the maximum yield of antibiotic being synthesized depended only on the nucleophile reactivity of 6-APA, the ratio between the enzyme reactivities with respect to the target product and acyl donor, and the initial concentrations of reagents . The parameters characterizing the nucleophile reactivity of 6-APA have been determined . The algorithm of modeling the enzymatic synthesis has been elaborated . The proposed algorithm allows the kinetics of the process not only in homogeneous, but also in heterogeneous ("aqueous solution-precipitate") systems to be quantitatively predicted and described based on experimental values of parameters of the reaction . It was shown that in heterogeneous "aqueous solution-precipitate" systems PA-catalyzed ampicillin synthesis proceeds much more efficiently compared to the homogeneous solution.

Catheter Cardiovasc Interv, 2001 Feb, 52(2), 237 - 9
Syphilitic aortitis; Cohen MG et al.; A case of syphilitic aortitis, complicated by bilateral coronary ostial stenosis, in a 40-year-old man is described . Treatment included coronary artery bypass grafting and a drug regimen of penicillin . At 3-month follow-up, an exercise stress test revealed no signs of ischemia.

Enzyme Microb Technol, 2001 Feb 1, 28(2-3), 218 - 224
Production of immobilized penicillin acylase using aqueous polymer systems for enzyme purification and in situ immobilization; Guan YH et al.; A novel approach for the isolation and purification of penicillin acylase (PA), which couples aqueous two-phase partitioning and enzyme immobilization has been investigated.A PA yield of 90% was achieved by treating E . coli cells with 4% butyl acetate, freeze-thawing step, and pressure homogenization . PA purification (93% recovery) was achieved by (1) removing cell debris via precipitation with polyethylene glycol (PEG 2000); (2) aqueous two-phase partitioning using a PEG 2000 + phosphate system (87% recovery).An in situ enzyme immobilization approach, using oxirane acrylic or aldehyde-agarose beads dispersed in the PEG-rich phase, was explored for the conversion of penicillin G to 6-aminopenicillanic acid . An appropriate immobilization reaction time was found . The catalytic performance of the enzyme, when immobilized, was found not to be affected by recycling of the phase-forming components.

J Nutr, 2001 Feb, 131(2), 255 - 61
Vitamin A supplementation at birth delays pneumococcal colonization in South Indian infants; Coles CL et al.; Nasopharyngeal colonization is a risk factor for pneumococcal disease, a leading cause of complications and death in infants . We assessed the impact of vitamin A supplementation in reducing pneumococcal colonization in infants from an area with endemic vitamin A deficiency . We recruited 464 2-mo-old infants from a rural area in South India . Infants were randomly assigned to receive two 7000-microg retinol equivalent doses of vitamin A (n = 239) or placebo (n = 225) orally at birth, and nasopharyngeal specimens were collected at ages 2, 4 and 6 mo . We studied the effect of vitamin A on culture-confirmed pneumococcal colonization and on the distribution of pneumococcal serotypes . Analyses were conducted by intention-to-treat . The risk of colonization among infants aged 4 mo who were not colonized by age 2 mo was significantly reduced in the vitamin A group compared with the placebo group {odds ratio 0.51 (0.28, 0.92), P = 0.02) . The odds of colonization were 27% lower in the treatment group than in the placebo group {odds ratio 0.73 (0.48, 1.1), P = 0.13} . No differences were detected in the prevalence of invasive serotypes . The risk of colonization with penicillin-resistant isolates was 74% lower in the vitamin A group than in the placebo group at 2 mo of age . However, the prevalence of penicillin-resistant isolates was only 4% . Neonatal vitamin A supplementation may play a role in lowering morbidity rates associated with pneumococcal disease by delaying the age at which colonization occurs.

Antimicrob Agents Chemother, 2001 Feb, 45(2), 616 - 20
Nucleotide sequence and characterization of a novel cefotaxime-hydrolyzing beta-lactamase (CTX-M-10) isolated in Spain; Oliver A et al.; A cefotaxime-resistant, ceftazidime-susceptible Escherichia coli isolate was obtained from a patient with sepsis in 1997, from which a beta-lactamase with a pI of 8.1 was cloned . Cephaloridine and cefotaxime relative hydrolysis rates were 167 and 81, respectively (penicillin G rate = 100), whereas ceftazidime hydrolysis was not detected . The nucleotide sequence revealed a bla gene related to that coding for CTX-M-3 . Despite 21 nucleotide substitutions, only 2 determined amino acid changes (Ala27Val and Arg38Gln) . The amino acid sequence identity between this enzyme, designated CTX-M-10, and the chromosomal beta-lactamase of Kluyvera ascorbata was 81%.

Microbiology, 2001 Feb, 147(Pt 2), 325 - 35
Construction and analysis of ss-lactamase-inhibitory protein (BLIP) non-producer mutants of Streptomyces clavuligerus; Thai W et al.; The gene encoding BLIP, a beta-lactamase-inhibitory protein, was disrupted in wild-type Streptomyces clavuligerus and in a clavulanic acid non-producing mutant . The resulting BLIP mutant and BLIP/clavulanic acid double mutant showed no residual proteinaceous beta-lactamase-inhibitory activity, indicating that only a single beta-lactamase-inhibitory protein exists in S . clavuligerus . The lack of any proteinaceous beta-lactamase-inhibitory activity in the bli and bli/claR mutants also indicates that BLP, the BLIP-like protein, encoded by S . clavuligerus does not possess beta-lactamase-inhibitory activity despite its similarity to BLIP . The bli mutant and the bli/claR double mutant did not show any aberrant growth morphology, sporulation defects, or alterations in cephamycin C production or penicillin G resistance when compared to wild-type S . clavuligerus or to the claR single mutant . Mutants bearing the bli gene disruption did show an elevated level of production of clavam-2-carboxylate and hydroxymethyl clavam as well as clavulanic acid . This phenomenon was observed in the middle stages of production of these clavams but was not detected during maximum production . The production of BLIP was also determined to be down-regulated in a ccaR mutant, lacking the pathway-specific transcriptional regulator required for production of cephamycin C and clavulanic acid . Sequencing of the regions flanking the bli gene showed the presence of a partial open reading frame that encodes a DNA-binding protein, and several open reading frames apparently involved in the production of an ABC transporter.

Usp Fiziol Nauk, 2000 Jan-Mar, 31(1), 71 - 80
{The experimental development of the concept of O . S . Adrianov on the correlation of functional and neurochemical processes: regulatory peptides in mediator system dysfunction}; Popova NS et al.; The article is devoted to commemoration of full member of Russian Academy of Medical Sciences, Oleg Andreevich Adrianov, who would have celebrated his 75-th anniversary in 1998 . O . S . Adrianov, author of numerous works on physiology and morphology of central nervous system, in the recent years of his was studying the problem of the processes relationship at macro and micro levels of brain organization . Further to the concept created by O.S . Adrianov, data on action of two peptides: delta-sleep and tafcine, on behavior, neurophysiological and neurochemical processes have been consolidated . Experimental data were obtained for rabbits, cats, and dogs, both intact and in the state of pathology (psychomotoric excitement, bradykinesia, penicillin epilepsy) . Impact of peptides on convergation processes is discussed: peptide of delta-sleep depresses reactions of brain structures to photo- and phono-stimulation, and activates the serotoninergic system in general; tafcine enforces the convergation processes and activates the dopaminergic system.

Arch Intern Med, 2001 Jan 8, 161(1), 15 - 21
Anaphylaxis in the United States: an investigation into its epidemiology; Neugut AI et al.; BACKGROUND: Anaphylaxis is a severe, life-threatening allergic reaction that affects both children and adults in the United States . However, data regarding the incidence and prevalence of anaphylaxis and the number of deaths caused by it are limited . OBJECTIVE: To provide a better understanding of the magnitude of the problem of anaphylaxis in the United States . METHODS: A thorough review of the current medical literature was conducted to obtain prevalence estimates on each of the 4 major subtypes of anaphylaxis (food, drugs, latex, and insect stings) . We calculated an overall estimate of the risk of anaphylaxis by using only estimates that are specifically derived from epidemiologic studies measuring anaphylaxis in the general population . RESULTS: Known rates or cases of anaphylaxis were 0.0004% for food, 0.7% to 10% for penicillin, 0 . 22% to 1% for radiocontrast media, and 0.5% to 5% after insect stings . There were 220 cases after latex exposure . Considering the 1999 US population of 272 million, the population at risk for anaphylaxis from food is 1099, from penicillin is 1.9 million to 27 . 2 million, from radiocontrast media is 22 000 to 100 000, from latex is 220, and from insect stings is 1.36 million to 13.6 million . These calculations yield a total of 3.29 million to 40.9 million individuals at risk of anaphylaxis . CONCLUSION: The occurrence of anaphylaxis in the US is not as rare as is generally believed . On the basis of our figures, the problem of anaphylaxis may, in fact, affect 1.21% to 15.04% of the US population.

Am J Surg, 2000 Nov, 180(5), 345 - 52
The last fifty years of neonatal surgical management; Rowe MI et al.; Neonatal surgical mortality has steadily fallen over the last five decades . Improved survival does not appear to be related to the introduction of new operative procedures . Most of the basic procedures were developed by 1960 . Eight developments appear to be responsible: (1) The growth of pediatric surgery resulted in widespread availability of neonatal surgeons and dissemination of knowledge about newborn surgical emergencies . (2) The parallel growth of pediatric anesthesia, beginning in 1946, provided specialized intraoperative management of the neonate . (3) Understanding neonatal physiology is the key to successful management; major advances occurred between 1950 and 1970 . (4) New inventions revolutionized patient care; the transistor (1947) made it possible for medical devices to sense, amplify and control physiologic responses and opened the communication and computer age . (5) Neonatal mechanical ventilation had a prohibitive mortality and was seldom utilized; the development of CPAP and a continuous flow ventilator in the 1970s allowed safe ventilatory support . (6) Total parenteral nutrition (1968) prevented starvation that frequently affected infants with major anomalies . (7) The effective treatment of infection began with the clinical use of penicillin (1941); antibiotics have reduced mortality but infants suffering from the septic syndrome have a prohibitive mortality; cytokine, proinflammatory agent research, and the development of anti-inflammatory and blocking agents in the 1980s have not affected mortality . (8) The establishment of newborn intensive care units (1960) provided an environment, equipment, and staff for effective physiologic management.

Microsc Res Tech, 2001 Jan 1, 52(1), 137 - 52
Porcine Choroid plexus epithelial cells in culture: regulation of barrier properties and transport processes; Haselbach M et al.; The epithelial cells of the choroid plexus are the structural basis of the blood-cerebrospinal fluid (CSF)-barrier . Here we summarise our recent efforts to culture those cells mainly on permeable supports in vitro . Isolated from porcine brains, we report a simple protocol for the primary culture using cytosine arabinoside as an additive that is cytotoxic for other cells except the plexus epithelial cells . Enhanced barrier properties are obtained by withdrawal of serum from the culture medium after confluency is reached . Cells improve their polarity, permeability for hydrophilic substrates is lowered, electrical resistance is increased tenfold, and a pH-gradient is built up across the cell monolayer . Polarised secretion of proteins and most importantly fluid secretion into the apical filter compartment was attained and proven to be dependent on the Na(+),K(+)-ATPase activity . Active transport processes (penicillin G, riboflavin, myo-inositol, ascorbic acid) were studied and clearly showed the involvement of the organic anion transporter . The permeability of the barrier was found to be regulated by cyclic adenosine monophosphate (cAMP) . Moreover, we report that cell proliferation and differentiation is controlled by components of the extracellular matrix . The present culture model could now be used as an in vitro system to quantify drug transport across the blood-CSF-barrier .

J Bacteriol, 2001 Jan, 183(2), 628 - 36
pbpB, a gene coding for a putative penicillin-binding protein, is required for aerobic nitrogen fixation in the cyanobacterium Anabaena sp . strain PCC7120; Lazaro S et al.; Transposon mutagenesis of Anabaena sp . strain PCC7120 led to the isolation of a mutant strain, SNa1, which is unable to fix nitrogen aerobically but is perfectly able to grow with combined nitrogen (i . e., nitrate) . Reconstruction of the transposon mutation of SNa1 in the wild-type strain reproduced the phenotype of the original mutant . The transposon had inserted within an open reading frame whose translation product shows significant homology with a family of proteins known as high-molecular-weight penicillin-binding proteins (PBPs), which are involved in the synthesis of the peptidoglycan layer of the cell wall . A sequence similarity search allowed us to identify at least 12 putative PBPs in the recently sequenced Anabaena sp . strain PCC7120 genome, which we have named and organized according to predicted molecular size and the Escherichia coli nomenclature for PBPs; based on this nomenclature, we have denoted the gene interrupted in SNal as pbpB and its product as PBP2 . The wild-type form of pbpB on a shuttle vector successfully complemented the mutation in SNa1 . In vivo expression studies indicated that PBP2 is probably present when both sources of nitrogen, nitrate and N(2), are used . When nitrate is used, the function of PBP2 either is dispensable or may be substituted by other PBPs; however, under nitrogen deprivation, where the differentiation of the heterocyst takes place, the role of PBP2 in the formation and/or maintenance of the peptidoglycan layer is essential.

Rev Mal Respir, 2000 Nov, 17(5), 969 - 72
{Acute pleuro-pneumonitis resulting from leptospirosis}; Mennecier B et al.; We report a case of acute pneumonitis with pleural effusion and respiratory distress syndrome that was the inaugural sign of leptospirosis in a 37-year-old patient exposed to rat dejections at home . The patient was given penicillin and oxygen therapy with evacuation of the pleural effusion . Lung manifestations in leptospirosis usually occur as non-specific cough and hemoptysis . Pleural effusion is uncommon . Adult respiratory distress syndrome and profuse hemoptysis can also occur, requiring special care.

Vet Res, 2000 Nov-Dec, 31(6), 623 - 34
Inflammatory response to intramuscular implantation of polyacrylonitrile ultrafiltration probes in sheep; Imsilp K et al.; Polyacrylonitrile is used in the manufacture of dialysis membranes . These membranes are fundamental to the functioning of implantable probes for microdialysis and ultrafiltration sampling of tissue fluids . Although in vivo experimentation using polyacrylonitrile has been reported to cause little inflammatory response when implanted subcutaneously, such information is not available for intramuscular implantation in sheep . The procaine and benzathine salts of penicillin are formulated for intramuscular injection . These salts of penicillin or the formulation excipients may cause inflammatory reactions . Use of polyacrylonitrile probes to draw samples from sites at which these formulations have been injected may be compromised by inflammation or direct interaction between formulation excipients and the dialysis membrane . The aim of this project was to describe tissue responses to intramuscular implantation of polyacrylonitrile in the presence and absence of either procaine or procaine plus benzathine salts of penicillin G . Each of 20 normal sheep was implanted with two ultrafiltration probes, one at the site of an injection of procaine or benzathine plus procaine penicillin G . Similar injections were also made at remote intramuscular sites . After 8, 9, and 11 days of the experiment, sheep were killed and the injection and implantation site muscle were excised and prepared for histopathological examination . The implantation of the probe alone caused greater inflammatory response than the injection of procaine or procaine plus benzathine penicillin G at remote intramuscular sites . The histopathological lesions were greatest where the implantation site was coupled with the injection of either formulation of penicillin G . Polyacrylonitrile may not be a suitable dialysis membrane material for intramuscular implantation in sheep.

Bioelectrochemistry, 2000 Dec, 52(2), 229 - 38
Agents facilitating the electric field-induced fusion of intact rabbit erythrocytes; Haritou M et al.; In the recent years, the role of specific membrane active agents in the electrofusion process has started to draw attention, and it has been found that the presence of various substances in the cell medium can affect the fusion process either in a positive or negative way . In this work, the effect of several proteins, bivalent cations and antibiotics was tested with respect to their ability to protect intact erythrocytes from hemolysis and facilitate the fusion process . The effect of different sugars was also studied . Among the different proteins, pronase and proteinase were found to be the most effective . With respect to bivalent cations, Ca2+ and Mn2+ were more effective while Mg2+ was less important . From the antibiotics, penicillin caused a negative effect while streptomycin acted positively . Finally, glucose medium was found to be the most effective compared to all sugars tested . The results indicated that there are strong differentiations of the induced effects caused by each substance, and some possible mechanisms of action of these agents on the erythrocyte membrane were discussed.

Eur J Dermatol, 2000 Dec, 10(8), 611 - 3
Linear atrophoderma of Moulin; Rompel R et al.; We report a typical case of linear atrophoderma of Moulin that represents a distinct clinical entity . A 17-year-old woman presented with hyperpigmented and atrophic band-like skin lesions measuring 3-5 cm in breadth on the right side of her trunk and on the right buttock, in an arrangement following the system of Blaschko's lines . The skin lesions had a normal texture and showed no signs of inflammation, lilac ring, erythema, induration, sclerosis or depigmentation . Routine laboratory data were normal . Antinuclear antibodies and anti-Scl70-antibodies were negative . Histopathologically, a moderate diffuse hyperpigmentation within the lower epidermis, a focal vacuolar degeneration of the basal layer, and a few dermal perivascular lymphocytes accompanied by signs of pigment incontinence were noted . Intravenous penicillin G was administered for 14 days in a dosage of 10 x 10(6) IU twice daily . This treatment was repeated after 3 and 9 months . No effect was noted . Linear atrophoderma of Moulin takes a chronic course without progression or regression . The disease leads to significant cosmetic impairment and this may cause emotional stress . Due to its relationship to idiopathic atrophoderma of Pierini-Pasini and linear scleroderma, treatment with intravenous penicillin was tried . In our case it had no effect.

Trop Med Int Health, 2000 Nov, 5(11), 800 - 4
Impact on perinatal mortality of missed opportunities to treat maternal syphilis in rural South Africa: baseline results from a clinic randomized controlled trial; Rotchford K et al.; OBJECTIVE: To demonstrate the impact on perinatal mortality of inadequate treatment for maternal syphilis despite adequate screening . METHOD: In 12 clinics providing antenatal care in Hlabisa, South Africa 1783 pregnant women were screened for syphilis at their first antenatal visit between June and October 1998 . Pregnancy outcome was determined among those with syphilis . RESULTS: A total of 158 women were diagnosed with syphilis: prevalence 9% (95% CI 8-10%) . Mean gestation at first antenatal visit was 24 weeks . Thirty women (19%) received no treatment and 96 (61%) received all three recommended doses of penicillin . Among those receiving at least one dose, mean delay to the first dose was 20 days . Among those fully treated mean delay to treatment completion was 34 days . Pregnancy outcome was known for 142 women (90%) and there were 17 perinatal deaths among 15 women (11%) . Eleven of 43 women (26%) who received one or fewer doses of penicillin experienced a perinatal death whilst only four of 99 women (4%) who received two or more doses of penicillin did so (P = 0.0001) . Protection from perinatal death increased with the number of doses of penicillin: linear modelling suggests that one dose reduced the risk by 41%, two doses by 65% and three doses by 79%, compared with no doses . A dose-specific, categorical model confirmed reduction in risk by 79% for all three doses . CONCLUSION: Despite effective screening, many pregnant women with syphilis remain inadequately treated, resulting in avoidable perinatal mortality . Delays in starting and finishing treatment, as well as incomplete treatment occur . Near-patient syphilis testing in the antenatal clinic with early treatment could improve treatment of syphilis and reduce perinatal mortality, and a randomized trial to test this is underway.

Enzyme Microb Technol, 2000 Dec, 27(10), 766 - 773
Genetic strategies to enhance penicillin acylase production in Escherichia coli; Chou CP et al.; We demonstrated the improvement of penicillin acylase (PAC) production by optimization of the host/vector system using genetic engineering strategies . Several expression plasmids with improved efficiency for the transcription of the pac gene and/or translation of the pac mRNA were constructed . Mutant strains, isolated by a novel screening method, were effective for use as the expression host to produce PAC . The feasibility of using the mutant strains harboring a selection of expression plasmids for the production of PAC was evaluated . The effect of the mutation(s) resulting in the improved PAC producing ability was characterized . While the production of PAC was significantly enhanced using the optimized host/vector system, the formation of PAC inclusion bodies was shown to be another step limiting the production of recombinant PAC.

Hautarzt, 2000 Nov, 51(11), 869 - 71
{Recurrent mitigated erysipelas in severe combined immunodeficiency}; Stark R et al.; A patient with congenital severe combined swiss-type immune deficiency suffered from recurrent cellulitis and at least 26 documented cases of bacterial pneumonia . Parenteral immunoglobins prevented the recurrence of the bacterial pneumonias but not of the cellulitis . This was successfully halted by benzathine penicillin injections every four weeks.

Hautarzt, 2000 Nov, 51(11), 838 - 45
{Penicillin allergy as a diagnostic problem . Overview and personal studies}; Walker T et al.; BACKGROUND AND OBJECTIVE: Penicillin allergy is a common clinical problem . The distinction between penicillin and para-infectious exanthems is difficult . We investigated the reliability of the history, as well as the sensitivity and specificity of skin tests and specific IgE levels . PATIENTS/METHODS: 160 patients with a history of penicillin allergy were retrospectively evaluated in the outpatient department of a dermatological clinic . RESULTS: Nearly 50% were diagnosed as allergic to penicillin by detection of specific IgE or skin test . About 60% of the patients with immediate type reactions, and 72% with maculo-papular erythema showed positive reactions in skin tests . Significantly more patients were diagnosed as allergic to penicillin by intradermal testing than by prick testing (p < 0.05) . The sensitivity of the specific IgE RAST was 17.9%; the specifity, 89.5% . For the prick test the sensitivity was 8.2%; the specificity 90.8% . For the intradermal test the sensitivity was 26%; the specifity 69.7% . CONCLUSIONS: We suggest a step by step procedure to detect penicillin allergy making the diagnostic results as valid as possible.

Biotechnol Appl Biochem, 2000 Dec, 32 ( Pt 3), 173 - 7
Optimization of 6-aminopenicillanic acid (6-APA) production by using a new immobilized penicillin acylase; Torres-Bacete J et al.; A new immobilized penicillin acylase (ECPVA) was obtained by covalent binding of penicillin acylase from Streptomyces lavendulae on Eupergit C . Enzymic hydrolysis of penicillin V catalysed by ECPVA was optimized using a 2(3) factorial design of experiments, and the selected parameters for this study were pH, temperature and substrate concentration . The immobilized enzyme showed an optimal pH value of 9.5-10.5, and an optimal temperature of 60 degrees C, whereas its soluble counterpart showed the same optimal pH value and a lower optimal temperature of 50 degrees C.

J Bacteriol, 2001 Jan, 183(1), 200 - 6
Differential responses of Escherichia coli cells expressing cytoplasmic domain mutants of penicillin-binding protein 1b after impairment of penicillin-binding proteins 1a and 3; Chalut C et al.; Penicillin-binding protein 1b (PBP1b) is the major high-molecular-weight PBP in Escherichia coli . Although it is coded by a single gene, it is usually found as a mixture of three isoforms which vary with regard to the length of their N-terminal cytoplasmic tail . We show here that although the cytoplasmic tail seems to play no role in the dimerization of PBP1b, as was originally suspected, only the full-length protein is able to protect the cells against lysis when both PBP1a and PBP3 are inhibited by antibiotics . This suggests a specific role for the full-length PBP1b in the multienzyme peptidoglycan-synthesizing complex that cannot be fulfilled by either PBP1a or the shorter PBP1b proteins . Moreover, we have shown by alanine-stretch-scanning mutagenesis that (i) residues R(11) to G(13) are major determinants for correct translocation and folding of PBP1b and that (ii) the specific interactions involving the full-length PBP1b can be ascribed to the first six residues at the N-terminal end of the cytoplasmic domain . These results are discussed in terms of the interactions with other components of the murein-synthesizing complex.

Biotechnol Bioeng, 2001 Jan 20, 72(2), 185 - 93
Energetics of growth and penicillin production in a high-producing strain of Penicillium chrysogenum; vanGulik WM et al.; The results of a large number of carbon-limited chemostat cultures of Penicillium chrysogenum carried out on glucose, ethanol, and acetate as the growth limiting substrate have been used to obtain an estimation of the adenosine triphosphate (ATP) costs for mycelium growth, penicillin production, and maintenance and the overall stoichiometry of oxidative phosphorylation of the fungus . It was found that penicillin production was accompanied by a significant additional energy drain (73 mol of ATP per mole of penicillin-G) from primary metabolism . This finding has been confirmed in independent experiments and has been shown to result in a significantly lower estimate for the maximum theoretical yield of penicillin-G on the carbon source.

Anal Biochem, 2000 Dec 15, 287(2), 196 - 202
Fluorescent coupled enzyme assays for D-alanine: application to penicillin-binding protein and vancomycin activity assays; Gutheil WG et al.; D-Alanine (D-Ala) is a ubiquitous constituent of bacterial cell walls . Assays for D-Ala can be used to investigate several aspects of cell wall biosynthesis and the effects of antibiotics on this process . High-sensitivity fluorescent assays for D-Ala were developed in a microtiter plate format based on d-aminoacid oxidase/horseradish peroxidase (DAO/HRP)-coupled reactions . For comparative purposes the classic chromogenic (UV-vis) assay using o-phenylenediamine (OPD) was also adapted to microtiter plates . OPD gave a lower limit of sensitivity of 2 nmol and was linear up to 60 nmol . Two commercially available fluorogenic HRP substrates were then tested in this assay . Amplex Red (AR) gave a lower limit of sensitivity of 2 pmol and was linear up to 400 pmol d-Ala . QuantaBlu (QB) based assays exhibited a lag in their response to D-Ala corresponding to 50 pmol D-Ala . This lag complicated calibration, but could be eliminated by addition of 150 pmol D-Ala to all assays . The QB assays were linear up to 3000 pmol D-Ala and gave a lower limit of sensitivity of 10 pmol . These assays are demonstrated for the characterization of the dd-carboxypeptidase activity of a soluble form of Escherichia coli penicillin-binding protein 5 (PBP 5) against the classic PBP substrate diacetyl-L-Lys-D-Ala-D-Ala . AR and QB based assays gave identical v/E(T) profiles, whereas OPD based assays gave slightly (10%) higher activity . This is consistent with the loss of a small amount of E . coli PBP 5 activity during the dilution necessary prior to its use in the highly sensitive fluorescent assays . These assays were then demonstrated for characterization of vancomycin binding to a D-Ala-D-Ala-based substrate .

Tidsskr Nor Laegeforen, 2000 Oct 30, 120(26), 3128 - 32
{Legionella pneumonia--important differential diagnosis in pneumonia after travelling abroad}; Berdal JE; BACKGROUND: Legionella pneumophila is a rare cause of pneumonia in Norway . From 1992 to 1999, only 27 cases were reported to the Norwegian Surveillance System for Communicable Diseases . MATERIAL AND METHODS: Five cases diagnosed at the Akershus Central Hospital over the last three years are presented . RESULTS: All patients acquired their infection while travelling abroad, mainly in the Mediterranean area, and all fell ill within fourteen days of returning home . The course was serious with marked hypoxaemia in three of the patients, and one patient died . Confusion and altered mental state were prominent features of the clinical presentation . INTERPRETATION: Patients returning from visits abroad and presenting with a pneumonia within to weeks after arriving in Norway, should be investigated for Legionella as a causative agent unless there is a prompt response to empiric penicillin therapy.

J Neuroradiol, 2000 Sep, 27(3), 207 - 10
{Syphilitic spinal cord gumma}; El Quessar A et al.; Syphilitic spinal cord gumma Syphilitic gummas of the central nervous system are exceptional and are in general described in the brain . We report the case of a Brown-Sequard syndrome in a 25-year-old patient . The cervical myelography and the brain CT as well as the vertebro-occipital junction were normal . The diagnosis of multiple sclerosis was evoked and corticosteroid therapy was initiated . The patient experienced clinical improvement . Two years later, the patient was readmitted . Immunological reactions for syphilis were positive, in serum and CSF . Tests for HIV were negative . The MRI showed a cervical spinal cord process at the C3 level with adhesive spinal associated arachnoiditis . Penicillin therapy was started prior to surgery for the spinal process . The syphilitic nature was confirmed by pathology . To our knowledge, the MR appearance of a syphilitic gumma of the spinal cord has not been described previously in the scientific literature.

Genetics, 2000 Dec, 156(4), 1483 - 92
Selected amplification of the cell division genes ftsQ-ftsA-ftsZ in Escherichia coli; Vinella D et al.; Rapidly growing Escherichia coli is unable to divide in the presence of the antibiotic mecillinam, whose direct target is penicillin-binding protein 2 (PBP2), responsible for the elongation of the cylindrical portion of the cell wall . Division can be restored in the absence of PBP2 activity by increasing the concentration of the cell division proteins FtsQ, FtsA, and FtsZ . We tried to identify regulators of the ftsQ-ftsA-ftsZ operon among mecillinam-resistant mutants, which include strains overexpressing these genes . By insertional mutagenesis with mini-Tn10 elements, we selected for insertions that conferred mecillinam resistance . Among 15 such mutants, 7 suppressed the thermosensitivity of the ftsZ84(Ts) mutant, strongly suggesting that they had increased FtsZ activity . In all 7 cases, however, the mutants resulted from a duplication of the ftsQAZ region . These duplications seemed to result from multiple events, suggesting that no simple insertional inactivation can result in a mutant with sufficiently amplified ftsQAZ expression to confer mecillinam resistance . The structure of the duplications suggests a general method for constructing directed duplications of precise sequences.

Ann Allergy Asthma Immunol, 2000 Nov, 85(5), 363 - 5
Frequency of systematic reactions to penicillin skin tests; Valyasevi MA et al.; BACKGROUND: Penicillin skin testing is generally considered to be safe when performed sequentially with puncture and intradermal testing although fatalities have been reported . OBJECTIVE: We analyzed the rate of systemic reactions to penicillin skin tests for a period of seven and two-thirds years . METHOD: This retrospective study used a computerized database at the Mayo Clinic . Altogether 1710 patients were skin-tested to penicillin from January 1992 to September 1999 . All patients tested had a history of penicillin allergy . Patients were tested with benzylpenicilloyl polylysine (Pre-Pen) (6.0 X 10(-5) M), freshly prepared penicillin G (10,000 units/ml), and penicilloate (0.01 M) . Prick tests were done first and if negative then intradermal tests . Systemic reactions were evaluated and treated by physicians . RESULTS: Eighty-six patients had positive penicillin skin tests of which two had systemic reactions . Our systemic reaction rate for all patients tested was 0.12%; and 2.3% for the penicillin skin test-positive group, with no fatalities . CONCLUSION: The incidence of systemic reaction to penicillin skin tests is low . Skin prick tests should always be done first . If there is a history of a previous serious reaction, the skin tests-if done-should be diluted to start with . Those doing penicillin skin tests should be prepared to treat a systemic reaction.

Folia Microbiol (Praha), 1999, 44(6), 625 - 8
Escherichia coli strain with a deletion of the chromosomal ampC gene marked with TcR, suitable for production of penicillin G acylase; Vizvaryova M et al.; Escherichia coli strain which contains a marker of tetracycline resistance gene (TcR) placed by P1 transduction beside the chromosomal deletion of ampC gene (delta ampC) coding for beta-lactamase was constructed . Such introduction of TcR marker permits a fast and simple selection for the transfer of delta ampC by P1 transduction into industrial E . coli strains . This approach was used for constructing an E . coli strain suitable for penicillin acylase production.

Clin Infect Dis, 2000 Dec, 31(6), 1512 - 4
Incidence of imipenem hypersensitivity reactions in febrile neutropenic bone marrow transplant patients with a history of penicillin allergy; McConnell SA et al.; The purpose of this retrospective study was to assess cross-hypersensitivity between imipenem/cilastatin and penicillin in patients with reported penicillin allergies . Medical records of febrile neutropenic, penicillin-allergic bone marrow transplant recipients who received imipenem/cilastatin treatment were retrospectively reviewed . The findings of this study indicate the incidence of cross-reactivity between imipenem/cilastatin and penicillin among patients with a history of penicillin allergy may be lower than previously reported.

FEBS Lett, 2000 Nov 24, 485(2-3), 142 - 6
Studies of isopenicillin N synthase enzymatic properties using a continuous spectrophotometric assay; Dubus A et al.; Isopenicillin N synthase (IPNS) from Aspergillus nidulans is a no-heme iron(II)-dependent oxygenase which catalyses, in a single reaction, the bicyclisation of delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine into isopenicillin N, the precursor of all other penicillins, cephalosporins and cephamycins . The IPNS reaction can be followed directly and continuously by a new assay which monitors the absorbance increase at 235 nm characteristic of penicillin nucleus formation . Using this assay, the effects of influential factors affecting the in vitro IPNS enzymatic reaction were investigated . Even under optimal conditions, enzyme inactivation occurred during catalysis . Iron(II) depletion and product inhibition were not the cause of this phenomenon, the addition of antioxidants or reducing agents failed to slow down inactivation or reactivate the enzyme . Therefore, this phenomenon appears to be irreversible and is attributed to oxidative damage caused to the enzyme by reactive oxygen species generated in solution during catalysis . Nevertheless, the steady-state kinetic parameters for the IPNS reaction were determined.

Curr Treat Options Neurol, 2000 Jul, 2(4), 375 - 387
Chronic Meningitis; Coyle PK; Treatment of chronic meningitis depends on the underlying cause . Once a specific cause has been established, appropriate targeted therapy is initiated . When the cause is unknown, a decision must be made whether to employ empiric therapy while the diagnostic evaluation is ongoing . This decision is based on three factors: 1) the clinical status of the patient; 2) the most likely cause based on demographic, historical, examination, and initial laboratory data; and 3) the risk-to-benefit ratio of the proposed treatment regimen . Initial efforts focus on deciding whether the meningitis is infectious or noninfectious . When a decision is made to start empiric therapy, antituberculous treatment is generally given for several weeks to judge therapeutic response . Patients who do not respond to antituberculous therapy are next treated with broad-spectrum antibiotics for unusual bacterial pathogens such as Actinomyces (penicillin), the Lyme disease spirochete Borrelia burgdorferi (ceftriaxone), Brucella (doxycycline plus rifampin), or Francisella tularensis (streptomycin plus gentamicin) . Antifungal therapy is generally reserved for patients who are at particular risk for mycotic infection (owing to underlying immunosuppression or an extraneural infection site) . Finally, empiric glucocorticoids are generally reserved for patients with consistently negative culture results and a probable noninfectious cause.

Curr Treat Options Neurol, 1999 May, 1(2), 139 - 146
Neuroborreliosis (Nervous System Lyme Disease); Halperin JJ; Treatment of nervous system Lyme disease depends on the severity and site of involvement . Although some data indicate that uncomplicated Lyme meningitis can be treated effectively with oral doxycycline, central nervous system infection (meningitis, radiculitis, encephalomyelitis, and cranial neuritis) is usually treated with parenteral antibiotics for 14 to 30 days, depending on disease severity, as is severe and progressive peripheral nervous system involvement . Ceftriaxone, 2 g/d, is the most commonly used regimen; cefotaxime, 2 g every 8 hours, appears to be equally effective . Penicillin in meningeal doses is also effective, perhaps slightly less so than the third-generation cephalosporins, but it is less convenient to administer . For patients with prohibitive drug allergies, treatment with oral doxycycline in doses of 300 to 400 mg/d may be effective . In patients with facial palsy or with indolent peripheral neuropathies, a trial of oral medication (doxycycline, 100 mg two or three times a day, or amoxicillin, 500 to 1000 mg three times a day for 21 to 30 days) is reasonable . Patients for whom this fails are treated with parenteral medications.

Curr Treat Options Cardiovasc Med, 1999 Oct, 1(3), 253 - 258
Rheumatic Fever; Visvanathan K et al.; There have been numerous reports stating that treatment of acute rheumatic fever with either aspirin or corticosteroids does not alter the long-term outcome of rheumatic heart disease . Yet, it should be emphasized that most of these studies were carried out with the first generic corticosteroids before the advent of the more active and more potent corticosteroid agents . In spite of this caveat, there is no question that all the clinical and laboratory parameters of inflammation (erythrocyte sedimentation rate, C-reactive protein) return to normal much more rapidly with corticosteroids than with aspirin alone . It is therefore our belief that steroids should be used when clinical and laboratory evidence of carditis exists, and aspirin should be reserved for cases of acute rheumatic arthritis with no evidence of carditis . The incidence of long-term valvular disease in active carditis may be decreased with steroid therapy . For example, the number of valve replacements differs markedly in centers that do use steroids and in those that do not . In Capetown, South Africa, where steroids are routinely used for carditis, valve replacement is quite rare . In contrast, in Johannesburg, where steroids are rarely used, the rate of valve replacement is quite high . The racial backgrounds of both groups of patients are similar, thus eliminating the question of racial differences . Concerning secondary prophylaxis, there is also controversy concerning the best second-line therapy . It is now well known that monthly intramuscular injections of benzathine penicillin are really effective for only 20 days . Thus, there is a window in which penicillin coverage is not adequate . To circumvent this problem, some investigators give benzathine penicillin every 3 weeks . These injections are quite painful, however, and it has been our "rule" that compliance with this treatment is inversely proportional to the ratio of the size of the child to the mother . In our own experience over 30 years with the follow-up of more than 300 patients with acute rheumatic fever, careful discussion of the consequences of missing oral doses has been adequate to insure proper compliance . An analysis of our patients on oral penicillin prophylaxis compared with other groups using benzathine penicillin revealed that there was very little difference in recurrence rate.

Curr Infect Dis Rep, 1999 Apr, 1(1), 39 - 46
Deep Neck Infections; Nicklaus PJ; Deep neck infections are less common in the antibiotic era, but when they do occur they remain serious infections . Historically, these infections carried significant morbidity and mortality due to the proximity of the airway, mediastinum, and other vital structures . Deep neck infections were once routinely treated with penicillin, and if infection progressed to abscess, surgical drainage was performed . In recent years the standard medical, surgical, and diagnostic approaches to deep neck infection have changed, and they continue to evolve . Physicians must be aware of these changes to optimally manage patients with deep neck infections.

Proc Natl Sci Counc Repub China B, 2000 Oct, 24(4), 156 - 60
Cultivation of recombinant Escherichia coli to achieve high cell density with a high level of penicillin G acylase activity; Liu YC et al.; A mutant strain of E . coli EP1 harbouring pGL-5 was employed to develop a process for producing penicillin G acylase (PGA) . In comparison with different carbon sources in the medium, it was found that the specific levels of PGA activity obtained in the glucose medium were the lowest . which was likely due to catabolic repression . Phenylacetic acid (PAA) was previously reported to be an regulatory inducer for PGA production, whereas in this study, the addition of PAA repressed both cell growth and enzyme expression . In a fed-batch culture, the increase of specific PGA activity followed the pattern of the cell concentration during the early to middle cell growth phase . With application of pure oxygen aeration and an appropriate medium design, the cell concentration reached 162 (g wet weight/l), which was 2.4 times higher compared to that of the original operation, and a specific PGA activity of 37 (IU/g wet weight) was achieved after 12 h of cultivation.

J Biol Chem, 2001 Mar 2, 276(9), 6093 - 7 Epub 2000 Nov 14.
The lysis protein E of phi X174 is a specific inhibitor of the MraY-catalyzed step in peptidoglycan synthesis; Bernhardt TG et al.; Coliphage phi X174 encodes a single lysis protein, E, a 91-amino acid membrane protein . Dominant mutations have been isolated in the host gene mraY that confer E resistance . mraY encodes translocase I, which catalyzes the formation of the first lipid intermediate in bacterial cell wall synthesis, suggesting a model in which E inhibits MraY and promotes cell lysis in a manner analogous to cell wall synthesis inhibitors like penicillin . To test this model biochemically, we monitored the effect of E on cell wall synthesis in vivo and in vitro . We find that expression of Emyc, encoding an epitope-tagged E protein, from a multicopy plasmid inhibits the incorporation of {(3)H}diaminopimelic acid into cell wall and leads to a profile of labeled precursors consistent with MraY inhibition . Moreover, we find that membranes isolated after Emyc expression are drastically reduced in MraY activity, whereas the activity of Rfe, an enzyme in the same superfamily, was unaffected . We therefore conclude that E is indeed a cell wall synthesis inhibitor and that this inhibition results from a specific block at the MraY-catalyzed step in the pathway.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2000 Nov, 90(5), 636 - 40
Effect of systemic penicillin on pain in untreated irreversible pulpitis; Nagle D et al.; OBJECTIVE: The purpose of this prospective, randomized, double-blind study was to determine the effect of penicillin on pain in untreated teeth diagnosed with irreversible pulpitis.Study Design: Forty emergency patients participated, and each had a clinical diagnosis of an irreversible pulpitis . Patients randomly received a 7-day oral dose (28 capsules, 500 mg each, to be taken every 6 hours) of either penicillin or a placebo control in a double-blind manner . No endodontic treatment was performed . Each patient also received ibuprofen; acetaminophen with codeine (30 mg); and a 7-day diary to record pain, percussion pain, and number and type of pain medication taken . RESULTS: The administration of penicillin did not significantly (P >.05) reduce pain, percussion pain, or the number of analgesic medications taken by patients with untreated irreversible pulpitis . The majority of patients with untreated irreversible pulpitis had significant pain and required analgesics to manage this pain . CONCLUSION: Penicillin should not be prescribed for untreated irreversible pulpitis because penicillin is ineffective for pain relief.

Mol Microbiol, 2000 Nov, 38(3), 658 - 65
G-protein signalling mediates differential production of toxic secondary metabolites; Tag A et al.; Filamentous fungi elaborate a complex array of secondary metabolites, including antibiotics and mycotoxins . As many of these compounds pose significant economic and health concerns, elucidation of the underlying cellular mechanisms that control their production is essential . Previous work revealed that synthesis of the carcinogenic mycotoxins sterigmatocystin (ST) and aflatoxin (AF) in Aspergillus species is negatively controlled by FadA, the alpha-subunit of a heterotrimeric G-protein . In sharp contrast, we show here that the dominant activating fadA allele, fadAG42R, stimulates transcription of a gene from the A . nidulans penicillin (PN) gene cluster and elevates penicillin production . Thus, FadA has opposite roles in regulating the biosynthesis of a potent antibiotic (PN) and a lethal mycotoxin (ST) in A . nidulans . Furthermore, expression of fadAG42R in Fusarium sporotrichioides increases trichothecene (TR) mycotoxin production and alters TR gene expression . Our findings reveal that a G-protein defines an important control point for differential expression of fungal secondary metabolites within and across fungal genera . These data provide critical evidence suggesting that targeting G-protein signal transduction pathways as a means of controlling or preventing the production of a single mycotoxin could have serious undesirable consequences with regard to the production of other secondary metabolites.

Prescrire Int, 2000 Aug, 9(48), 106 - 9
Pneumococcal vaccination for elderly subjects: license extension . Still no proof of clinical efficacy; Homeostatic role of the active transport in elimination of {3H}benzylpenicillin out of the cerebrospinal fluid system; Department of Pharmacology, University of Zagreb School of Medicine, CroatiaCerebral acidic metabolites and penicillin are organic anions which can be carried by active transport into capillaries of the central nervous system (CNS) . However, it is generally believed that these metabolites are mainly delivered from CNS to cerebrospinal fluid (CSF) and eliminated by CSF circulation over cortex and its absorption into dural venous sinuses . To test this hypothesis we studied fate of penicillin ({3H}benzylpenicillin) in the CSF under control conditions and when its active transport was blocked by probenecid . After application of penicillin into cisterna magna of control dogs, it is distributed only in traces to lumbar, ventricular and cortical CSF . However, when active transport of penicillin across capillary wall is blocked by probenecid, its disappearance from cisterna is slowed down and its distribution is greatly enhanced so that at 300 min penicillin concentrations in cisternal, lumbar and cortical CSF approach or equal each other . Disappearance of penicillin from cisternal CSF shows a single exponential course (half-time 30 min) in control, while in probenecid pretreated dogs this is a slow multiexponential process . The results indicate that the active transport across capillary wall in CNS, but not generally postulated unidirectional CSF circulation over cortex and its absorption into dural venous sinuses, is instrumental in elimination of cerebral acidic metabolites and in such a way homeostasis in brain and cerebrospinal fluid is maintained.

Prog Urol, 2000 Sep, 10(4), 587 - 9
{Renal actinomycosis with fistulized lumbar abscess}; Mallick S et al.; The authors report a case of renal actinomycosis in an adolescent presenting with two fistulized lumbar abscesses . This rare disease, which generally has a good prognosis, is difficult to diagnose, both clinically and radiologically . The positive diagnosis is based on histological examination, more frequently of the nephrectomy operative specimen, than ultrasound-guided fine needle aspiration biopsy of an atypical renal tumour . Conservative treatment with high-dose penicillin gives excellent results.

Allergy Asthma Proc, 2000 Sep-Oct, 21(5), 297 - 9
The value of skin testing for penicillin allergy in an inpatient population: analysis of the subsequent patient management; Warrington RJ et al.; It was decided to assess the value of skin testing in a group of inpatients with a remote history of penicillin allergy, in terms of whether or not beta-lactams were subsequently given, if any adverse reactions occurred as a result of this therapy, and if labeling of the patient record was changed subsequent to skin testing and/or challenge . All patients seen in consultation with a history of penicillin allergy were assessed . When done, skin tests were performed with the major and minor determinants of penicillin and semisynthetic penicillins . Charts were reviewed after discharge in terms of the antibiotics given during admission, adverse events, and the medical record and hospital database labeling for drug allergy at discharge . Skin testing was carried out in 79% of 67 patients assessed and in all, the tests were negative . Beta-lactam therapy was recommended in 51/53 patients but was given in only 57% of these cases . At discharge, 49% of patients' records still carried the penicillin allergy label, despite negative skin testing and/or successful completion of a course of beta-lactam therapy . So, in approximately half of the patients reviewed, beta-lactams were not given despite negative skin tests and a recommendation to do so, if indicated, and 49% of patients were still inappropriately labeled as being penicillin-allergic on discharge.

Bratisl Lek Listy, 2000, 101(7), 402 - 8
{Tularemia--an old and a new problem in the South Moravia Region}; Cerny Z; BACKGROUND: The first epidemic of ulceroglandular forms of tularemia acquired in coincidence with the manipulation with tularaemic hares took place in 1936 in the surroundings of Breclav and Valtice . The largest epidemic took place in the 1960's when hundreds of agricultural workers in the initial phases of the production of sugar within sugar refineries were afflicted by pulmonary forms of this disease . In the subsequent period which was interrupted only by smaller local epidemics, the number of new cases were gradually decreasing to the minimum at the beginning of 1990's . However, since 1994, the number of cases has began to increase again, namely those afflicted by ulceroglandular and oroglandular forms . SUBJECTIVES: In consequence of the long absence of this disease in clinical practice, the diagnostic awareness has decreased, and therefore the author has decided to indicate and review the current basic data on epidemiology and clinical manifestations of tularaemia . GROUP OF PATIENTS AND METHODS: The author has analysed the documentation of 577 of adults afflicted by tularemia and medically treated at the clinic of the Faculty Hospital in Brno in the period form 1959 to 1999 . The study reviews the onset of the disease and the pathway of transmission of infection and its clinical manifestation . MAIN RESULTS: Following the long-termed sporadic occurrence of tularaemia after major epidemics of pulmonary forms of this disease in 1960's, interrupted only by smaller local epidemics, the incidence has began to increase again in 1994 . The number of pulmonary forms has decreased whereas the occurrence of ulcerulceroglandular and oroglandular forms has increased . Hares have become the source of infection again . CONCLUSIONS: The fact that tularemia has repeatedly become a threat in Southern Moravia should be taken into account in the assessment of diagnosis in cases with unclear lymphadenitis and febrile states which defy the penicillin treatment especially in winter . (Tab . 3, Fig . 3, Ref . 23.)

Rev Inst Med Trop Sao Paulo, 2000 Sep-Oct, 42(5), 287 - 9
Massive ocular hemorrhage resulting in blindness in a patient with the sickle cell trait who developed leptospirosis . Case report; Costa E et al.; This case report describes the findings of a 18 year-old black male from Bahia, a Northeastern state in Brazil, with the sickle cell trait, who developed bilateral hyphema and vitreous hemorrhage with blindness in the course of leptospirosis . The patient started to complain of blurred vision four days after the start of fever and muscular pain and approximately twelve hours after the introduction of penicillin . The severity of the leptospirosis in conjunction with sickle cell trait was considered to be the most likely explanation for this ocular complication.

Ophthalmology, 2000 Nov, 107(11), 2015 - 23
Posterior segment manifestations of active ocular syphilis, their response to a neurosyphilis regimen of penicillin therapy, and the influence of human immunodeficiency virus status on response; Browning DJ; OBJECTIVE: To determine the relative frequencies of signs in posterior segment ocular syphilis, the response to a neurosyphilis regimen of penicillin, and differences in findings between human immunodeficiency virus (HIV)-coinfected and -noncoinfected patients in a community setting . DESIGN: Retrospective, noncomparative, consecutive case series . PARTICIPANTS: Fourteen consecutive patients with posterior segment ocular syphilis over a 14-year period within or during the acquired immune deficiency syndrome era . INTERVENTION: Neurosyphilis intravenous penicillin regimen . MAIN OUTCOME MEASURES: Initial and final visual acuity; treponemal and nontreponemal serologic analyses; cerebrospinal fluid cell count, protein, and Venereal Disease Research Laboratory analyses; posterior segment signs; and relapses and recurrences . RESULTS: Blacks and males were predominantly affected . Five (36%) of patients were HIV coinfected, and ocular syphilis led to the HIV infection diagnosis in three . Four (29%) patients had received previous antibiotic therapy for primary or secondary syphilis, raising the suspicion of relapse . Two patients had negative nontreponemal serologic results . All patients responded rapidly to neurosyphilis therapy . One patient subsequently relapsed after neurosyphilis therapy, and a second was reinfected with recurrence of ocular involvement . One previously undescribed retinal manifestation was discovered: a sectorial retinochoroiditis with delayed retinal circulation in the involved area . CONCLUSIONS: Ocular syphilis is a form of neurosyphilis and requires neurosyphilis therapy regardless of when it develops after primary infection . Conventional syphilis staging is of little use in understanding ocular syphilis . A high suspicion for this diagnosis is appropriate, especially in poorer black males with posterior segment inflammatory disease . Human immunodeficiency virus coinfection with ocular syphilis is common, but does not affect response to a neurosyphilis regimen of penicillin in the short term . Awareness of the multiple presentations of posterior segment ocular syphilis will aid ophthalmologists in averting misdiagnosis or delayed diagnosis.

Pediatr Dent, 2000 Sep-Oct, 22(5), 401 - 4
Adverse reaction to amoxicillin: a case report; da Fonseca MA; Penicillin is the drug that most often leads to allergic reactions and anaphylaxis . The incidence of adverse events triggered by penicillins is believed to be between 1% and 10% . Up to one-tenth of these episodes are life-threatening, with the most serious reactions occurring in patients with no history of allergy . The case of a 5 year, 3 month-old female who had a severe allergic reaction to amoxicillin prior to a dental appointment is described . The literature on penicillin hypersensitivity is reviewed and recommendations for management of an allergic reaction in the pediatric dental office are discussed.

Ugeskr Laeger, 2000 Oct 2, 162(40), 5351 - 3
{Penicillin treatment of acute maxillary sinusitis in adults . A randomized, double-blind, placebo-controlled trial from general practice}; Hansen JG et al.; INTRODUCTION: The aim of the study was to compare the effectiveness of penicillin V with placebo in the treatment of adult patients with acute maxillary sinusitis (in general practice) . MATERIAL AND METHODS: The study was designed as a randomised, double-blind, placebo-controlled trial in 26 Danish general practices . The participants were 133 adult patients with acute maxillary sinusitis clinically diagnosed on maxillary pain and raised values of either C-reactive protein (CRP) or the erythrocyte sedimentation (ESR) rate . Main outcome measures were pain score and illness score, and CRP and ESR values after initiation of treatment . RESULTS: Penicillin V led to a better recovery than placebo . The difference in pain reduction was statistically significant three days after initiation of treatment, whereas no significant difference was found in the reduction in the sense of illness . At the end of the study, significantly more patients in the penicillin group were completely free of pain than in the placebo group . This difference was found only in patients with an initial pain score of more than three . The cure rate was 71% in the penicillin group and 37% in the placebo group . Significantly more patients treated with penicillin achieved normal CRP values than those receiving placebo, respectively 88% and 75% . CONCLUSION: Penicillin V is more effective than placebo in the treatment of acute maxillary sinusitis in adults in general practice, but only in patients with pronounced pain.

Chest, 2000 Oct, 118(4), 1106 - 8
A pilot study of penicillin skin testing in patients with a history of penicillin allergy admitted to a medical ICU; Arroliga ME et al.; BACKGROUND: Penicillin skin testing is an accurate method to determine whether a person with a history of penicillin allergy is at risk of having an immediate reaction to penicillin . A patient with a negative reaction to a skin test may be able to use a penicillin compound safely, which could reduce the use of broad-spectrum antibiotics in this patient population . METHODS: We prospectively studied all patients with histories of penicillin allergy who were admitted to a medical ICU during a 3-month period and who received antibiotics . Skin testing was performed with benzylpenicilloyl polylysine and penicillin G . We determined the incidence of true allergy, the percentage of patients in whom antibiotic coverage was modified, and the safety of the test . RESULTS: Two hundred fifty-seven patients were admitted to the medical ICU of The Cleveland Clinic Foundation during the study period . Twenty-four patients (9%), labeled as penicillin allergic and receiving antibiotics, were enrolled . Three patients (13%, 3 of 21) gave histories of type I reaction to penicillin and were not skin tested . Twenty patients (95%, 20 of 21) had negative skin test reactions to penicillin and positive skin test reactions to histamine control . One patient (4%, 1 of 21) with negative skin test reactions to both penicillin and histamine control had a test dose challenge with piperacillin that was well tolerated . There were no adverse events . Antibiotic coverage was changed in 10 patients (48%) as a result of skin testing . CONCLUSION: Most patients with histories of allergy to penicillin have negative reactions to skin tests and may receive penicillin safely . Penicillin skin testing can be utilized as a safe and effective strategy to reduce the use of broad-spectrum antibiotics.

Int J Pediatr Otorhinolaryngol, 2000 Oct 16, 55(3), 197 - 201
Alteration of clinical picture and treatment of pediatric acute otitis media over the past two decades; Joki-Erkkila VP et al.; The clinical picture of acute otitis media (AOM) has changed greatly over the last few decades: serious complications have almost disappeared but more and more children suffer from recurrent middle ear infections and prolonged silent effusion . In this retrospective study we registered all AOM attacks among children under 10 in two rural municipal areas of Finland during 12-month-periods in 1978-79 and 1994-95 . In addition to epidemiological data, the clinical picture and given treatments were recorded . Between study periods the number of children with recurrent AOM attacks increased heavily . The percentage of spontaneous otorrhea decreased from 6.0 to 3.3% (P=0.01) and the proportion of afebrile patients increased from 64.0 to 73.4% (P=0.002) . In 1978-79 there were significantly more cases of diagnostic symptoms lasting over 24 h . Prescribing penicillin-V as a primary treatment decreased from 80.2 to 10.5% in favor of broad-spectrum antibiotics . The primary treatment with penicillin-V was associated with a decreased risk of recurrences . Acute tympanocentesis was performed less often and the incidence of surgical treatments (adenoidectomy and/or tympanostomy tube insertion) doubled from 6.2 to 12.4% of the acute cases . Although the clinical picture of AOM has become milder, children are treated with wider spectrum antibiotics . Nevertheless, a large number of children suffer from sequelae and there is a greater need for surgical treatments than 20 years ago.

Ann Allergy Asthma Immunol, 2000 Sep, 85(3), 195 - 9
Penicillin allergy: prevalence of vague history in skin test-positive patients; Solensky R et al.; OBJECTIVE: Penicillin (PCN) skin testing is a reliable tool for predicting which patients can safely receive the antibiotic . Depending on the study, 7% to 76% of patients who have a history of PCN allergy have positive PCN skin tests . Many physicians approach patients who have a vague history of PCN allergy less cautiously than they approach those who have a convincing history suggestive of an IgE-mediated reaction . We reviewed the published literature to determine how many patients who had a history of PCN allergy and who were skin test-positive had a vague history of allergy . DATA SOURCES: By cross-referencing the keywords "penicillin" and "skin test," an Ovid MEDLINE search for English language studies published from 1966 to 1998 was performed . STUDY SELECTION: Studies in which history positive/skin test-positive patients were identified, and which contained documentation of the type of previous reaction in these patients, were included in the analysis . The MEDLINE search revealed 295 English language articles, of which 27 fulfilled the inclusion criteria . Three additional studies published prior to 1966 (and therefore not available through MEDLINE) also were found, bringing the total to 30 . A "convincing" history was defined to be one likely to be IgE-mediated (such as anaphylaxis, urticaria, angioedema or pruritic rash) . A "vague" history was one unlikely to be IgE-mediated (such as maculopapular rash, GI symptoms, or an unknown reaction) . RESULTS: Overall, 347/1063, or 33%, of history positive/skin test-positive patients had a vague PCN allergy history, with a range of 0% to 70% among the 30 studies . CONCLUSION: A large proportion of patients who have PCN-specific IgE antibodies, as determined by skin testing, have vague PCN allergy histories . These results therefore, indicate that, like patients with convincing histories, patients with vague allergic histories should undergo PCN skin testing prior to PCN administration.

Prim, Care Update Ob Gyns . 2000 Sep 1, 7(5), 186 - 191
Syphilis in women; Edwards RK; Infection with the spirochete Treponema pallidum causes syphilis . Transmission of syphilis occurs through sexual contact with persons who have infectious mucocutaneous lesions . Before the advent of penicillin, this infection was responsible for a large portion of the debilitated patients residing in mental institutions . Later during this century, the disease became somewhat uncommon, only to see a resurgence during the early part of this decade . Syphilis progresses through stages defined as primary, secondary, latent, and tertiary . Diagnosis of this infection is by clinical examination, dark-field microscopy, and serology . Penicillin is the treatment of choice for all stages of syphilis . Doxycycline and tetracycline are acceptable alternatives in some penicillin-allergic patients . If patients are pregnant or have central nervous system involvement, alternative regimens should not be used because of lack of efficacy and/or fetal toxicity . Therefore, these patients must be desensitized and treated with penicillin . No effective vaccine for this infection is currently available.

Appl Environ Microbiol, 2000 Oct, 66(10), 4536 - 8
Sulfur regulation of the sulfate transporter genes sutA and sutB in Penicillium chrysogenum; van de Kamp M et al.; Penicillium chrysogenum uses sulfate as a source of sulfur for the biosynthesis of penicillin . Sulfate uptake and the mRNA levels of the sulfate transporter-encoding sutB and sutA genes are all reduced by high sulfate concentrations and are elevated by sulfate starvation . In a high-penicillin-yielding strain, sutB is effectively transcribed even in the presence of excess sulfate . This deregulation may facilitate the efficient incorporation of sulfur into cysteine and penicillin.

Korean J Parasitol, 2000 Sep, 38(3), 173 - 5
Postmetacercarial changes in Echinostoma caproni maintained in a defined medium plus calf serum; Fried B et al.; The present study examined postmetacercarial changes in the excysted metacercariae of Echinostoma caproni maintained in the defined medium Mixture 199 plus 20% calf serum for 7 days at 41 degrees C . The gas phase was atmospheric air . Each culture was inoculated with 25 excysted metacerariae . Cultures were maintained upright in closed 15 ml plastic centrifuge tubes each containing 10 ml of medium plus 200 units of penicillin/ml and 200 micrograms of streptomycin/ml . By 4 days in culture, most metacercariae had voided their excretory concretions . Organisms were clumped or solitary at the bottom of the cultures . Many organisms showed flaring of the oral collar and extension of both the collar and tegumentary spines . By 4 days in culture, posterior protuberances or bumps were noted on many of the organisms and some organisms showed abnormal vesicular growths or blebs at their posterior ends . Some mortality was noted in culture by day 5, but most organisms were still alive when the cultures were terminated on day 7.

J Neuropsychiatry Clin Neurosci, 2000 Spring, 12(2), 246 - 50
Relationship between MRI findings and prognosis for patients with general paresis; Kodama K et al.; MRI was performed in 7 patients with general paresis before or at a very early stage of treatment . A large dose of antibiotics, mainly penicillin, was given to all patients, and the effects of treatment, the patients' outcome, and MRI findings were investigated . Three of the 7 patients had MRI findings of atrophy of the medial temporal lobe including the hippocampus . In the medial temporal lobe atrophy group, a personality change or general dementia remained even after the treatment was completed, and outcome in social functioning was poor . Medial temporal lobe atrophy may be a poor prognostic sign in general paresis.

Clin Exp Allergy, 2000 Oct, 30(10), 1450 - 9
Characterization of primary recall in vitro lymphocyte responses to bacampicillin in allergic subjects; Cederbrant K et al.; BACKGROUND: Antigen-specific cell lines or clones are often used as models of drug-specific allergy . However, cloning procedures are time consuming, and the repeated antigen stimulation cycles as well as the addition of various growth enhancers may affect the in vivo relevance of these systems . OBJECTIVE: Using bacampicillin-allergic subjects, we wanted to investigate the applicability of primary recall in vitro lymphocyte responses to characterize type I and type IV allergy . The sensitivity and specificity of LTT (Lymphocyte transformation test), when used as an in vitro diagnostic tool, were also assessed . METHODS: A total of 39 patients with symptoms of type I (rhinitis) or type IV (allergic contact dermatitis, ACD) allergy following occupational exposure to bacampicillin, were included . Ten individuals without penicillin allergy or occupational exposure to bacampicillin served as controls . All subjects were LTT tested . Four patients with rhinitis and two patients with ACD were available for studying the immunophenotype and the TCR-Vbeta repertoire of bacampicillin induced lymphoblasts as well as the cytokine profiles and expression of the activation markers CD23 and CD134 in primary PBMC cultures . RESULTS: LTT was positive in 87% and at least one of the skin tests was positive in 85% of the patients with allergic symptoms . 69% of the patients with type I allergies were patch test-positive . Results from LTT and skin test correlated in 87% of the cases . The combined sensitivity of LTT and skin tests was 92% . The specificity of LTT was 90% in healthy controls . Bacampicillin induced lymphoblasts were mainly CD4 + in both ACD and rhinitis patients . The TCR-Vbeta profiles of the predominant CD4 + lymphoblasts were heterogeneous with individual skewing towards Vbeta2, Vbeta3, Vbeta5.1 and/or Vbeta14 . An increased expression of IFNgamma was detected in bacampicillin treated PBMC cultures from the ACD but not from rhinitis patients . IL-5 was detected in bacampicillin exposed PBMC cultures from all patients but not from healthy controls . This Th2 environment could also be verified by CD23 and CD134 expression . CONCLUSION: LTT and skin tests are equally sensitive in identifying bacampicillin allergic subjects . When the two tests are combined, the sensitivity increases . The patch test is useful not only for detection of type IV but also for the identification of type I allergies . When using primary PBMC cultures, IFNgamma is the most suitable cytokine to discriminate between type I and type IV allergy . IL-5 can possibly be used as a general marker for bacampicillin induced allergy . Thus, primary cell cultures may be considered as an alternative to T-cell lines or clones for the study of drug induced allergy.

Clin Neurophysiol, 2000 Sep, 111 Suppl 2, S27 - 38
Spike-and-wave discharges of absence seizures as a transformation of sleep spindles: the continuing development of a hypothesis; Kostopoulos GK; OBJECTIVES: This review aims to offer a critical account of recent scientific developments relevant to the hypothesis which Pierre Gloor proposed in the 1970s for the generation of spike and wave discharges (SWDs) of primary generalized absence seizures . RESULTS: According to this hypothesis SWDs develop in the same circuits, which normally generate sleep spindles, by an initially cortical transformation of one every two or more spindle waves to a 'spike' component of SWDs, while the next one or more spindle waves are eliminated and replaced by a slow negative wave . This hypothesis was based on experiments in feline generalized penicillin epilepsy showing the possibility of transition from spindles to SWDs, when cortical neurons become hyper-responsive to thalamocortical volleys, which normally induce spindles, and thus engage feedback cortical inhibition, rebound excitation, recurrent intracortical dissemination of excitation during the 'spike' and strong excitation of thalamus for further augmentation of a brain wide synchronous oscillation . In the 1980s, electrophysiological studies in vitro and in vivo revealed the basic features of spindle rhythm generation by neurons in nucleus reticularis thalami and thalamocortical-corticothalamic oscillatory reverberations . CONCLUSIONS: In the light of this knowledge, experimental studies in several genetic and pharmacological animal models of absence seizures, clinical observations and theoretical studies in computer models have considered, tested, modified and challenged this hypothesis . It may still be found useful in the era of dynamic digital EEG analysis of SWDs and its current sources.

Clin Neurophysiol, 2000 Sep, 111 Suppl 2, S9 - S18
Physiological basis: how NREM sleep components can promote and REM sleep components can suppress seizure discharge propagation; Shouse MN et al.; OBJECTIVES: To describe how the neural generators of different sleep components can provoke seizure discharge propagation during NREM sleep and can suppress it during REM sleep . METHODS: Experimental manipulations of discrete physiological components were conducted in feline epilepsy models (n=64), mostly in the systemic penicillin epilepsy model of primary generalized epilepsy and the amygdala kindling model of the localization-related seizure disorder, temporal lobe epilepsy . Procedures included seizure induction as well as quantifying norepinephrine concentrations (microdialysis) and the sleep-waking state distribution of seizures before and after lesions, systemic and localized drug administration and/or photic stimulation . RESULTS: (1) Neural generators of synchronous EEG oscillations, including tonic background slow waves and phasic 'arousal' events (sleep EEG transients such as sleep spindles, k-complexes), can combine to promote electrographic seizure propagation during NREM and drowsiness; anti-gravity muscle tone permits seizure-related movement . (2) Neural generators of asynchronous neuronal discharge patterns can reduce electrographic seizures during alert waking and REM sleep; skeletal motor paralysis blocks seizure-related movement during REM . (3) Etiology of the seizure disorder can interact with sleep and arousal mechanisms to determine sleep-waking state distribution of interictal and ictal events . CONCLUSIONS: Differential effects of NREM versus REM sleep components on seizure discharge propagation are to some extent non-specific and in other ways specific to seizure etiology.

J Mol Biol, 2000 Sep 29, 302(4), 917 - 26
A fast method to predict protein interaction sites from sequences; Gallet X et al.; A simple method for predicting residues involved in protein interaction sites is proposed . In the absence of any structural report, the procedure identifies linear stretches of sequences as "receptor-binding domains" (RBDs) by analysing hydrophobicity distribution . The sequences of two databases of non-homologous interaction sites eliciting various biological activities were tested; 59-80 % were detected as RBDs . A statistical analysis of amino acid frequencies was carried out in known interaction sites and in predicted RBDs . RBDs were predicted from the 80,000 sequences of the Swissprot database . In both cases, arginine is the most frequently occurring residue . The RBD procedure can also detect residues involved in specific interaction sites such as the DNA-binding (95 % detected) and Ca-binding domains (83 % detected) . We report two recent analyses; from the prediction of RBDs in sequences to the experimental demonstration of the functional activities . The examples concern a retroviral Gag protein and a penicillin-binding protein . We support that this method is a quick way to predict protein interaction sites from sequences and is helpful for guiding experiments such as site-specific mutageneses, two-hybrid systems or the synthesis of inhibitors .

J Mol Biol, 2000 Sep 29, 302(4), 887 - 98
Structure of a slow processing precursor penicillin acylase from Escherichia coli reveals the linker peptide blocking the active-site cleft; Hewitt L et al.; Penicillin G acylase is a periplasmic protein, cytoplasmically expressed as a precursor polypeptide comprising a signal sequence, the A and B chains of the mature enzyme (209 and 557 residues respectively) joined by a spacer peptide of 54 amino acid residues . The wild-type AB heterodimer is produced by proteolytic removal of this spacer in the periplasm . The first step in processing is believed to be autocatalytic hydrolysis of the peptide bond between the C-terminal residue of the spacer and the active-site serine residue at the N terminus of the B chain . We have determined the crystal structure of a slowly processing precursor mutant (Thr263Gly) of penicillin G acylase from Escherichia coli, which reveals that the spacer peptide blocks the entrance to the active-site cleft consistent with an autocatalytic mechanism of maturation . In this mutant precursor there is, however, an unexpected cleavage at a site four residues from the active-site serine residue . Analyses of the stereochemistry of the 260-261 bond seen to be cleaved in this precursor structure and of the 263-264 peptide bond have suggested factors that may govern the autocatalytic mechanism .

Pediatr Dermatol, 2000 Jul-Aug, 17(4), 302 - 3
Partial lipoatrophy in a child; Kuperman-Beade M et al.; A 2-year-old boy was referred to the pediatric dermatology clinic for evaluation of an idiopathic, hypopigmented, atrophic patch on the right gluteal area . After extensive questioning the patient's parents recalled a penicillin injection several months prior to the appearance of lipoatrophy . There were no associated abnormalities.

Structure Fold Des, 2000 Sep 15, 8(9), 971 - 80
Crystal structure of a D-aminopeptidase from Ochrobactrum anthropi, a new member of the 'penicillin-recognizing enzyme' family; Bompard-Gilles C et al.; BACKGROUND: beta-Lactam compounds are the most widely used antibiotics . They inactivate bacterial DD-transpeptidases, also called penicillin-binding proteins (PBPs), involved in cell-wall biosynthesis . The most common bacterial resistance mechanism against beta-lactam compounds is the synthesis of beta-lactamases that hydrolyse beta-lactam rings . These enzymes are believed to have evolved from cell-wall DD-peptidases . Understanding the biochemical and mechanistic features of the beta-lactam targets is crucial because of the increasing number of resistant bacteria . DAP is a D-aminopeptidase produced by Ochrobactrum anthropi . It is inhibited by various beta-lactam compounds and shares approximately 25% sequence identity with the R61 DD-carboxypeptidase and the class C beta-lactamases . RESULTS: The crystal structure of DAP has been determined to 1.9 A resolution using the multiple isomorphous replacement (MIR) method . The enzyme folds into three domains, A, B and C . Domain A, which contains conserved catalytic residues, has the classical fold of serine beta-lactamases, whereas domains B and C are both antiparallel eight-stranded beta barrels . A loop of domain C protrudes into the substrate-binding site of the enzyme . CONCLUSIONS: Comparison of the biochemical properties and the structure of DAP with PBPs and serine beta-lactamases shows that although the catalytic site of the enzyme is very similar to that of beta-lactamases, its substrate and inhibitor specificity rests on residues of domain C . DAP is a new member of the family of penicillin-recognizing proteins (PRPs) and, at the present time, its enzymatic specificity is clearly unique.

J Immunol Methods, 2000 Aug 28, 242(1-2), 43 - 51
In vitro reactivity of penicilloyl and penicillanyl albumin and polylysine conjugates with IgE-antibody; Zhao Z et al.; Penicilloylated (BPO) and penicillanylated (BPA) poly-L-lysine (PLL) and human serum albumin (HSA) were prepared and characterized by penamaldate assay and proton NMR spectroscopy . The conjugates were coupled to nitrocellulose (NC) discs and cyanogen bromide activated paper discs and their in vitro reactivities with serum IgE antibodies were examined . Results showed that on paper discs, 55.3 and 83% of the sera reacted with PLL conjugates of BPO and BPA, respectively, while 41.5 and 58.1% reacted with HSA conjugates . On NC discs, HSA conjugates gave better results, 75.6 and 70.7%, respectively for BPO and BPA, compared with 38.6 and 50%, respectively for the PLL conjugates . Overall, the BPA-PLL conjugate on paper discs proved to be the most reactive preparation . Addition of the BPO-PLL paper disc preparation detected more positive sera (85.1%) and we believe that the combined use of these two specificities offers the best test for the detection of penicillin-reactive IgE antibodies.

Indian J Biochem Biophys, 2000 Feb, 37(1), 6 - 12
Penicillin acylase catalyzed synthesis of penicillin-G from substrates anchored in cyclodextrins; Prabhu KS et al.; Penicillin acylase (EC 3.5.1.11) catalyses the condensation of phenylacetic acid (PAA) and 6-aminopenicillanic acid (6-APA) to form benzylpenicillin (BP) . Both PAA and 6-APA were found to form host-guest complexes with beta-methylcyclodextrin (beta m-CD) and gamma-cyclodextrin (gamma-CD) respectively . The rate of the reaction catalyzed by the enzyme remained unaffected if one of the substrates used was in the cyclodextrin complexed form . However, in this case, the reaction lasted longer and yielded about 20 per cent more products compared to the condensation reaction involving only uncomplexed substrates . There was distinct increase in the rate of formation of the antibiotic, if both substrates used are in CD-complexed form.

Forensic Sci Int, 2000 Sep 11, 113(1-3), 497 - 9
An historical review of criminal abortion; Williams DJ et al.; Criminal abortion is rarely seen in modern Australia . This historical review examine cases seen in Brisbane during the period 1939 and 1947 . Instrumentation or introduction of fluid into the uterus were the common causes of fatalities in this pre-penicillin era.

Bull Exp Biol Med, 2000 May, 129(5), 420 - 2
Effect of akatinol (memantine) in central spinal pain syndrome; Zinkevich VA et al.; On the model of central spinal pain syndrome in rats induced by application of penicillin to the dorsal surface of the lumbar spinal cord, akatinol injected intraperitoneally at the peak of syndrome or applied locally simultaneously with penicillin produced a dose-dependent analgesic effect . Intraperitoneal injection of akatinol at the peak of pain syndrome inhibited neuronal activity in spinal dorsal horn: the amplitude of total evoked neuronal response significantly decreased and the duration of action potentials returned to normal . It is concluded that activation of NDMA receptors plays a significant role in the development of central spinal pain syndrome, in particular spontaneous pain attacks, hyperalgesia, and tactile allodynia . Akatinol can be an essential component of the complex pathogenetic therapy of central pains.

Ther Apher, 2000 Aug, 4(4), 303 - 7
Treatment of Amanita phalloides poisoning: I . Retrospective evaluation of plasmapheresis in 21 patients; Jander S et al.; Amanita phalloides poisoning is the most common cause of lethal mushroom poisoning (lethality >20% in adults) . A specific antidote against the amanitin toxins is not available . This retrospective study reports results in 21 patients (12 males, 9 females; ages 9-59 years) treated for amanita phalloides poisoning between 1984 and 1993 . Plasmapheresis was carried out using a commercial plasma protein solution (Biseko, Biotest, Dreieich, Germany) in 17 patients, fresh plasma in 2 patients, and human albumin/Ringer's solution in 2 patients . Ancillary drugs, including penicillin and silibinin, also were used for detoxification, correction of blood-clotting deficiencies, and hepatic protection . One patient died of acute hepatic failure . The results, assessed using mortality (4.8% overall) and frequency of complications, indicate that plasmapheresis is a safe and effective treatment for amanita phalloides poisoning but that further investigations are needed, especially involving measurements of efficacy and the efficiency of toxin removal.

Microbiology, 2000 Sep, 146 ( Pt 9), 2209 - 17
Mutants of Mycobacterium smegmatis impaired in stationary-phase survival; Keer J et al.; A bank of 600 insertional mutants of Mycobacterium smegmatis was screened for mutants defective in stationary-phase survival . Of 74 mutants picked by the initial screen, 21 had stationary-phase survival defects and 7 of these were studied in more detail . In general, mutants survived stationary phase significantly less well in rich medium than under carbon-starvation conditions . In all cases the loss of viability in stationary phase was not complete even after prolonged incubation . All mutants showed an initial decrease in viability, during the first 40 d in stationary phase, followed by an increase in viable counts that returned viability close to the levels of the wild-type . Southern hybridization experiments showed that recovery of viability was not a consequence of precise excision or movement of the transposon . Two of the survival mutants differed from the wild-type in their colony morphology, and recovery of their viability in stationary phase was coincident with the return of wild-type colony morphology . It is possible that second-site suppressor mutations accumulate that alleviate the effects of the original mutation . For five of the mutants the DNA flanking the site of transposition was amplified by ligation-mediated PCR and sequenced to identify the disrupted locus . In each case, homologous genes were identified in the Mycobacterium tuberculosis genome, three of which have clearly predicted functions in M . tuberculosis as a penicillin-binding protein, in biotin biosynthesis and as a polyketide synthase . This is the first identification of genes implicated in the stationary-phase survival of mycobacteria.

Appl Microbiol Biotechnol, 2000 Aug, 54(2), 238 - 42
Isolation of Penicillium chrysogenum PEX1 and PEX6 encoding AAA proteins involved in peroxisome biogenesis; Kiel JA et al.; In Penicillium chrysogenum, key enzymes involved in the production of penicillin reside in peroxisomes . As a first step to understand the role of these organelles in penicillin biosynthesis, we set out to isolate the genes involved in peroxisome biogenesis . Here we report the cloning and characterization of P . chrysogenum PEX1 and PEX6, which encode proteins of the AAA family of ATPases . The second AAA module, which is essential for the function of Pex1p and Pex6p in peroxisome biogenesis, is highly conserved in both PcPexlp and PcPex6p . PcPEX1 and PcPEX6 contain three and two introns, respectively.

Appl Microbiol Biotechnol, 2000 Aug, 54(2), 212 - 7
Metabolic characterization of high- and low-yielding strains of Penicillium chrysogenum; Christensen B et al.; A recently developed method for analyzing metabolic networks using 13C-labels was employed for investigating the metabolism of a high- and a low-yielding strain of Penicillium chrysogenum . Under penicillin-producing conditions, the flux through the pentose phosphate (PP) pathway in the high- and the low-yielding strains was estimated to 70 and 66, respectively . When the high-yielding strain was cultivated in a medium without the penicillin side chain precursor, phenoxyacetic acid, the PP pathway flux was estimated as 71 . Thus, in all three experiments, the flux through the PP pathway was almost constant with an average value of 69+/-3, and the method therefore allows for a very reproducible estimation of the PP pathway flux . Phenoxyacetic acid was found to be a source of cytosolic acetyl-CoA and thereby a source of precursors for the biosynthesis of 2-aminoadipic acid, which is a central amino acid in penicillin biosynthesis . However, the labeling patterns also indicated the presence of an unrecognized pathway to cytosolic acetyl-CoA.

Anim Reprod Sci, 2000 Oct 2, 63(1-2), 27 - 39
In vitro culture of bovine preantral follicles; Saha S et al.; Bovine preantral follicles (40-100 microm diameter at collection) were collected from ovaries of slaughtered cows and cultured in vitro with one of the four treatments: follicle stimulating hormone (FSH; 100 ng/ml) alone; FSH plus epidermal growth factor (EGF; 100 ng/ml); FSH plus insulin-transferrin-selenium (ITS; +1%) or FSH plus hypoxanthine (4 mM) in tissue culture medium (TCM 199) supplemented with 10% fetal calf serum (FCS), 0.1 mg/ml sodium pyruvate, 100 IU/ml of penicillin and 100 microg/ml streptomycin . The control culture medium was TCM 199 with supplements without any treatments . Follicles of each size were cultured separately in groups of one to three in 24-well multidishes each containing 500 microl of the appropriate culture medium . Culture commenced at follicle recovery (day 1) and continued for 10 days (harvested on day 11) . In each case, half the medium was removed and replaced by fresh medium every third day . Follicle diameters were recorded on days 1, 5 and 11 of the experiment . At the end of the 10-day culture period, half of the follicles were stained with trypan blue to assess their potential viability and half were stained with bisbenzimide plus propidium iodine to estimate various morphological features of the follicles . Follicles of all initial sizes, on all culture treatments, increased in diameter during in vitro cultures with the greatest increases, both in absolute and proportional size, occurring between days 1 and 5 of culture . All of the culture medium supplements caused greater increases in follicle diameters than control medium at both days 5 and 11 of culture for all initial sizes of follicles (p<0.01) . The most effective culture supplements for follicles of 40-, 60- and 80-microm initial diameter were FSH alone and FSH+EGF . The size of these follicles at both days 5 and 11 of culture on both the treatments was significantly larger (p<0.01) than follicles cultured in the presence of the other two supplementary treatments . The growth of follicles of 100-microm initial diameter did not differ between culture medium supplements . None of the culture media caused follicle size to increase to the initial diameters of the next larger size category during the 10 days of culture although follicles of 100-microm diameter achieved a diameter of 120 microm, after 4 days of culture.The overall follicular viability and morphology were better with treatments than the controls in all cases; however, there was no significant difference (p>0.05) among them.From this experiment, FSH and FSH plus EGF may be recommended for in vitro culture of smaller (40, 60 and 80 microm) follicles.

J Biol Chem, 2001 Jan 5, 276(1), 616 - 23
Crystal structure of a deacylation-defective mutant of penicillin-binding protein 5 at 2.3-A resolution; Davies C et al.; Penicillin-binding protein 5 (PBP 5) of Escherichia coli functions as a d-alanine carboxypeptidase, cleaving the C-terminal d-alanine residue from cell wall peptides . Like all PBPs, PBP 5 forms a covalent acyl-enzyme complex with beta-lactam antibiotics; however, PBP 5 is distinguished by its high rate of deacylation of the acyl-enzyme complex (t(12) approximately 9 min) . A Gly-105 --> Asp mutation in PBP 5 markedly impairs this beta-lactamase activity (deacylation), with only minor effects on acylation, and promotes accumulation of a covalent complex with peptide substrates . To gain further insight into the catalytic mechanism of PBP 5, we determined the three-dimensional structure of the G105D mutant form of soluble PBP 5 (termed sPBP 5') at 2.3 A resolution . The structure is composed of two domains, a penicillin binding domain with a striking similarity to Class A beta-lactamases (TEM-1-like) and a domain of unknown function . In addition, the penicillin-binding domain contains an active site loop spatially equivalent to the Omega loop of beta-lactamases . In beta-lactamases, the Omega loop contains two amino acids involved in catalyzing deacylation . This similarity may explain the high beta-lactamase activity of wild-type PBP 5 . Because of the low rate of deacylation of the G105D mutant, visualization of peptide substrates bound to the active site may be possible.

Ugeskr Laeger, 2000 Jul 31, 162(31), 4154 - 5
{Borreliosis associated with Lofgren's syndrome}; Klint H et al.; A man with positive Borrelia-titres, joint pain, erythema nodosum and fever was treated with penicillin . After finding hilar adenitis Lofgren's syndrome was thought to be more likely and penicillin was discontinued . Later the patient developed symptoms of neuroborreliosis and S-Borrelia IgG was 10 units . After treatment with doxycycline symptoms disappeared and IgG levels fell.

Transfusion, 2000 Aug, 40(8), 943 - 8
Description of serologic features in autoimmune lymphoproliferative syndrome; Carter LB et al.; BACKGROUND: Autoimmune lymphoproliferative syndrome (ALPS) is a recently recognized and rare disorder associated with inherited defects in the FAS: gene or other regulators of lymphocyte apoptosis . It is characterized by massive lymphadenopathy; splenomegaly; autoimmunity including episodes of immune hemolytic anemia, thrombocytopenia, and neutropenia.(1) The serologic basis for immune cytopenias associated with ALPS has not been previously characterized . STUDY DESIGN AND METHODS: RBC, granulocyte, and platelet serologies for ALPS patients and hepatitis C patients were assessed . Medical records were reviewed for clinical, immunologic, serologic, and transfusion history . Testing included: DAT; serum screening for antibodies to RBCs, granulocytes, platelets, cardiolipin, penicillin-coated RBCs, and human leukocyte antigens; antibody identification and IgG subclass; RBC phenotype . RESULTS: In a cohort of 11 patients with apoptosis defects (eight with heterozygous FAS: gene mutations); many had histories of hemolytic anemia (7), thrombocytopenia (4), and/or leukopenia (11); nine received steroid therapy, seven underwent splenectomy; five had been remotely transfused . On the basis of serologic testing even when they were clinically stable, nine had positive DATs; two had alloantibodies; 6 had IgG and/or IgM antibodies to cardiolipin; seven had platelet-directed antibodies; three had granulocyte-directed antibodies; none had HLA antibodies . CONCLUSIONS: Nearly all ALPS patients have antibodies directed against one or more hematopoietic cell lineages . Serologic testing is critical in the evaluation of these individuals and when transfusion is indicated, red cells that are matched for clinically significant C, E, and K antigens should be considered.

Harefuah, 1999 Nov 15, 137(10), 457 - 9, 510
{Congenital syphilis: need for adequate antenatal care}; Friedberg M; Congenital syphilis is well-known and treatable with penicillin . Diagnosis in the neonate and young child may be difficult and consequently morbidity and mortality can be high . Prevention in children is of utmost importance and can be achieved by proper antenatal care and adequate follow-up of pregnant women . This includes identification of pregnant women at risk for contracting syphilis . The case presented demonstrates this need.

Biochemistry, 2000 Aug 29, 39(34), 10557 - 65
Interaction of the antitumor drug 9-aminoacridine with guanidinobenzoatase studied by spectroscopic methods: a possible tumor marker probe based on the fluorescence exciplex emission; Murza A et al.; Fluorescence spectroscopy, surface-enhanced Raman spectroscopy (SERS), and analytical centrifugation are applied in this work to study the interaction of the antitumor drug 9-aminoacridine (9AA) with a trypsin-like protease, guanidinobenzoatase (GB), extracted from an Erlich tumor . As a consequence of this interaction, a strong 9AA exciplex emission can be detected at a certain drug and enzyme concentration . The 9AA exciplex emission was also studied for 9AA interacting with others serin proteases: alpha-chymotrypsin, trypsin, and penicillin G-acylase (PGA), as well as with bovine serum albumin (BSA) in order to obtain information about the active center of GB . We have found that the exciplex 9AA emission may be induced by a ring-stacking interaction between the monomeric drug, under the amino form, and an aromatic residue placed in the catalytic site of the protein . The results derived from Raman spectroscopy corroborate this interaction mechanism, as demonstrated by the existence of typical protonated amino 9AA marker bands as well as an important modification of the ring vibrations, thus indicating the existence of an interaction through ring stacking . The analytical centrifugation technique was applied to study the GB association in aqueous solution, demonstrating that the 9AA/GB interaction depends on the enzyme quaternary structure . An interaction of 9AA with an associate form of GB, which may be the actual enzyme active form, is suggested.

Rev Invest Clin, 2000 May-Jun, 52(3), 229 - 33
{Effectiveness of partial splenectomy in the treatment of hereditary spherocytosis}; Pavon Moran V et al.; OBJECTIVES: To evaluate the hematological and clinical response to partial splenectomy in a group of children with hereditary spherocytosis . MATERIAL AND METHODS: We analyzed the main hematological and clinical features in 13 patients with hereditary spherocytosis submitted to partial splenectomy . The diagnosis of the disease and the hematological studies was made according to standard methods . To establish the inheritance pattern we also studied both parents . During the surgical procedure the upper two thirds of the spleen were removed and the lower pole was preserved . We use prophylactic penicillin (250 mg twice a day) during 3 years . RESULTS: The diagnosis of the disease was made during the first year of life in 11 patients, 76.9% had neonatal hyperbilirrubinemia, 53.8% showed hepatomegaly and in 69.2% we observed splenomegaly . 84.6% received blood transfusion . The hemoglobin level was significantly increased (p = 0.04) and the reticulocytes significantly diminished (p = 0.01) after splenectomy . No hemolytic crises, blood cell transfusion requirement neither infection was observed after surgery . CONCLUSIONS: Although the number of patients and the post-surgical follow-up is reduced, the hematological recovery observed in our cases suggest that partial splenectomy is a beneficial surgical procedure for the treatment of the typical and severe form of hereditary spherocytosis.

Appl Microbiol Biotechnol, 2000 Jul, 54(1), 69 - 77
Overexpression of the lys1 gene in Penicillium chrysogenum: homocitrate synthase levels, alpha-aminoadipic acid pool and penicillin production; Banuelos O et al.; Homocitrate synthase activity (encoded by the lys1 gene) catalyzes the first step of the lysine and penicillin pathway and is highly sensitive to feedback regulation by L-lysine . The transcript levels of the lys1 gene and the homocitrate synthase activity are high during the growth phase and decrease during the antibiotic production phase, except in the high penicillin producer strain AS-P-99 which maintained high levels of homocitrate synthase activity in cultures at 96 h and 120 h . The lys1 gene was overexpressed in Penicillium chrysogenum using additional copies of lys1 with its own promoter or under the control of the pcbC promoter in either autonomously replicating or integrative vectors . Transformants containing 3 to 32 additional copies of the lys1 gene were selected . Some of these transformants, particularly Ti-C4 (integrative) and TAR-L9 (with autonomously replicating plasmids) showed very high levels of lys1 transcript and, in the case of TAR-L9, high levels of homocitrate synthase activity in cultures of 120 h . However, these transformants did not show increased alpha-aminoadipate or lysine pools . A mutant P . chrysogenum L-G- disrupted in the lys2 gene (therefore lacking the lysine branch of the pathway) showed increased alpha-aminoadipate levels and produced higher levels of penicillin than non-disrupted control strains . Overexpression of the lys1 gene in the L-G- mutant resulted in high homocitrate synthase levels but no additional increase of the alpha-aminoadipate pool or penicillin production levels . These results suggest that after amplification of the homocitrate synthase levels there are other limiting steps in the common stem of the lysine and penicillin pathways.

Appl Biochem Biotechnol, 2000 May, 87(2), 135 - 40
Immobilized Streptomyces clavuligerus NP1 cells for biotransformation of penicillin G into deacetoxycephalosporin G; Demain AL et al.; An investigation was conducted to determine whether immobilized resting cells of Streptomyces clavuligerus NP1, entrapped on a polymeric matrix, are able to perform oxidative ring expansion of benzylpenicillin into deacetoxycephalosporin G by virtue of their deacetoxycephalosporin C synthase ("expandase") activity . Cells entrapped in polyethyleneimine-barium alginate (1.5%) were able to sustain activity for at least four 2-h cycles, whereas free resting cells were inactive after the second cycle . Although entrapped cells exhibited lower oxidative ring expansion activity than free resting cells, immobilization may offer storage stability, recyclability, and operational stability for biotransformation of penicillins to cephalosporins, thus contributing to the development of a biological means for the production of the important industrial intermediate 7-aminodeacetoxycephalosporanic acid.

Public Health Nutr, 2000 Jun, 3(2), 113 - 24
Hepatotoxicity of botanicals; Stickel F et al.; OBJECTIVE: Hepatic impairment resulting from the use of conventional drugs is widely acknowledged, but there is less awareness of the potential hepatotoxicity of herbal preparations and other botanicals, many of which are believed to be harmless and are commonly used for self-medication without supervision . The aim of this paper is to examine the evidence for hepatotoxicity of botanicals and draw conclusions regarding their pathology, safety and applications . DESIGN: Current literature on the hepatotoxicity of herbal drugs and other botanicals is reviewed . The aetiology, clinical picture and treatment of mushroom (Amanita) poisoning are described . RESULTS: Hepatotoxic effects have been reported for some Chinese herbal medicines (such as Jin Bu Huan, Ma-Huang and Sho-saiko-to), pyrrolizidine alkaloid-containing plants, germander (Teucrium chamaedrys), chaparral (Larrea tridentata), Atractylis gummifera, Callilepsis laureola, and others . The frequency with which botanicals cause hepatic damage is unclear . There is a lack of controlled treatment trials and the few studies published to date do not clarify the incidence of adverse effects . Many plant products do not seem to lead to toxic effects in everyone taking them, and they commonly lack a strict dose-dependency . For some products, such as Sho-saiko-to, the picture is confused further by demonstrations of hepatoprotective properties for some components . Mushroom poisoning is mostly due to the accidental consumption of Amanita species . Treatment with silymarin, thioctic acid, penicillin and liver transplantation have been shown to be effective but require early diagnosis . CONCLUSIONS: Severe liver injury, including acute and chronic abnormalities and even cirrhotic transformation and liver failure, has been described after the ingestion of a wide range of herbal products and other botanical ingredients, such as mushrooms . It is concluded that in certain situations herbal products may be just as harmful as conventional drugs.

Doc Ophthalmol, 1999, 98(3), 273 - 83
Human amniotic membrane in the reconstruction of the ocular surface; Gabric N et al.; We sought to determine the efficacy of amniotic membrane transplantation (AMT) in the reconstruction of ocular surface . AMT was performed on 40 eyes with following indications: I, persistent corneal ulceration (n = 12); II, impending perforation (n = 6); III, persistent epithelial defect on the corneal graft (n = 6); IV, recurrent pterygia (n = 10), and V, risk of conjunctival scarring (n = 6) . Amniotic membrane was prepared from a fresh placenta under sterile conditions, washed with BSS containing penicillin, streptomycin, neomycin and amphotericin B and stored at -80 degrees C in 1:1 InoSol:Glycerol solution . Donor serological test for HIV, HBV and HCV were all negative . Associated surgical procedures according to indication were performed . Healing of the corneal ulcer in Group I was obtained in 67% of eyes at 1-3 weeks after surgery, Group II: AMT was followed by 'a chaud' keratoplasty in 33% and by planned keratoplasty in 67% patients, Group III: healing of the defect in 33% of eyes in 2-5 postoperative weeks, Group IV: no recurrence of pterygium ingrowth in 70% in the follow up period of 6-14 months, and V: 84% of patients had good eye motility without any synechia formation . We concluded that AMT have shown to be effective in enhancing healing of the corneal defects, in prevention of symblepharon formation and recurrent pterygium ingrowth . In case of impending perforation, AMT alone was not a method of treatment but is useful as a first step procedure in preparing the eye for the corneal transplantation.

FEMS Microbiol Lett, 2000 Aug 15, 189(2), 201 - 4
Two-step procedure for purification and separation of the essential penicillin-binding proteins PBP 1A and 1Bs of Escherichia coli; von Rechenberg M et al.; The penicillin-binding proteins PBP 1A and 1Bs are the essential murein polymerases of Escherichia coli . Purification of these membrane-bound bifunctional transglycosylase-transpeptidases was a major obstacle in studying the details of both enzymatic reactions . Here we describe a simple, highly specific affinity chromatography method that takes advantage of the availability of the specific inhibitor of the transglycosylase site moenomycin A in order to enrich PBP 1A and 1Bs in one step from crude membrane preparations . Separation of PBP 1A from PBP 1Bs is achieved in a second step employing cation exchange chromatography yielding enzymatically active native murein polymerases.

Biochem J, 2000 Aug 15, 350 Pt 1, 75 - 80
Characterization of derivatives of the high-molecular-mass penicillin-binding protein (PBP) 1 of Mycobacterium leprae; Mahapatra S et al.; Mycobacterium leprae has two high-molecular-mass multimodular penicillin-binding proteins (PBPs) of class A, termed PBP1 and PBP1* {Lepage, Dubois, Ghosh, Joris, Mahapatra, Kundu, Basu, Chakrabarti, Cole, Nguyen-Disteche and Ghuysen (1997) J . Bacteriol . 179, 4627-4630} . PBP1-Xaa-beta-lactamase fusions generated periplasmic beta-lactamase activity when Xaa (the amino acid of PBP1 at the fusion junction) was residue 314, 363, 407, 450 or 480 . Truncation of the N-terminal part of the protein up to residue Leu-147 generated a penicillin-binding polypeptide which could still associate with the plasma membrane, whereas {DeltaM1-R314}PBP1 (PBP1 lacking residues Met-1 to Arg-314) failed to associate with the membrane, suggesting that the region between residues Leu-147 and Arg-314 harbours an additional plasma membrane association site for PBP1 . Truncation of the C-terminus up to 42 residues downstream of the KTG (Lys-Thr-Gly) motif also generated a polypeptide that retained penicillin-binding activity . {DeltaM1-R314}PBP1 could be extracted from inclusion bodies and refolded under appropriate conditions to give a form capable of binding penicillin with the same efficiency as full-length PBP1 . This is, to the best of our knowledge, the first report of a soluble derivative of a penicillin-resistant high-molecular-mass PBP of class A that is capable of binding penicillin . A chimaeric PBP in which the penicillin-binding (PB) module of PBP1 was fused at its N-terminal end with the non-penicillin-binding (n-PB) module of PBP1* retained pencillin-binding activity similar to that of PBP1, corroborating the finding that the n-PB module of PBP1 is dispensable for its penicillin-binding activity.

Arq Neuropsiquiatr, 2000 Jun, 58(2B), 578 - 82
{Dementia caused by neurosyphilis: clinical and neuropsychological follow-up of a patient}; Vargas AP et al.; Dementia is one of the manifestations of late syphilis and it is characterized by cognitive deterioration and behaviour disturbances . We report on a male patient with cognitive decline, behaviour disorder, hyperactivity, hallucinations, short-term memory and Argyll Robertson pupils due to neurosyphilis . Minimental state test (MST) was 16 . Cerebrospinal fluid (CSF) protein concentration was 82 mg/dl, CSF-leucocyte count 128 cells/mm3 (98% mononuclear cells), CSF-VDRL 1:4, and CSF-T.pallidum haemaglutination assay 1:2560 . MRI showed no cerebral alteration, but SPECT revealed left fronto-temporal hypocaptation . He received intravenous penicillin . MST done 3 months after the treatment scored 22 . A new spinal tap showed normal CSF . Neurosyphilis should be part of the differential diagnosis of every patient showing cognitive deterioration and behaviour disturbances . During follow-up, MMS is an useful instrument to ++measure cognitive decline and response to treatment.

Clin Infect Dis, 2000 Jul, 31(1), 58 - 64 Epub 2000 Jul 24.
Invasive pneumococcal infections in Canadian children, 1991-1998: implications for new vaccination strategies . Canadian Paediatric Society/Laboratory Centre for Disease Control Immunization Monitoring Program, Active (IMPACT); Scheifele D et al.; We reviewed 2040 consecutive cases of invasive pneumococcal infection that were seen at 11 pediatric centers across Canada during 1991-1998 to determine if such infections could be prevented by new conjugate vaccines . Isolates from 1528 cases were serotyped . Most cases (61.5%) occurred in patients aged >2 years . Underlying medical conditions were present in 23.2% of case patients . Serotypes in the 7-valent conjugate vaccine matched isolates as follows: 85.8% of tested isolates from children aged 6 months to 5 years, but significantly fewer isolates in younger and older children; 72.9% of isolates from non-healthy children, but 83.9% of isolates from previously healthy children; and 95.4% of isolates with high-level penicillin resistance, but only 72.7% of those with intermediate-level resistance . Significant natural variation in the proportion of isolates matching 7-valent vaccines occurred from year to year and among centers . New conjugate vaccines have great potential but their effectiveness and limitations require ongoing study.

Neurology, 2000 Jul 25, 55(2), 312 - 5
Optical intrinsic signal imaging in a rodent seizure model; Chen JW et al.; ARTICLE ABSTRACT: The authors studied seizure activity with optical intrinsic signal (OIS) imaging in a rat seizure model . OIS, which measures vascular and metabolic effects associated with neuronal activity, showed significant cortical reflectance changes from penicillin-induced seizures, and correlated well with EEG epileptiform discharges . Furthermore, OIS changes often preceded initial EEG spikes . These observations suggest that OIS is well coupled with seizure activity, and may provide sensitive cues for seizure detection.

Contraception, 2000 May, 61(5), 347 - 50
Uterine perforation with Lippes loop intrauterine device-associated actinomycosis: a case report and review of the literature; Phupong V et al.; A case of a 67-year-old postmenopausal woman, gravida 2, para 2, with an uterine perforation from actinomycotic infection with Lippes loop IUD is reported . She had the Lippes loop IUD inserted for 35 years, and had never had any pelvic examination nor Papanicolaou smear . She presented with acute abdominal pain . The clinical picture mimicked peptic ulcer perforation . The woman underwent laparotomy and exudative fluid was discovered in the abdominal cavity with the tip of the Lippes loop IUD at one of the two small holes of the uterine fundus . Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed . The postoperative microscopic pathological report demonstrated characteristics of actinomycosis . She was treated with parenteral high-dose penicillin for 4 weeks followed by oral penicillin for 6 months . The woman had an uneventful recovery . To our knowledge, this is the first case report of uterine perforation due to Lippes loop IUD-associated actinomycotic infection.

Diagn Microbiol Infect Dis, 2000 Jul, 37(3), 213 - 4
Splenic abscesses caused by Actinomyces meyeri in a patient with autoimmune hepatitis; Garduno E et al.; We report a case of actinomycosis with uncommon localizations that was due to Actinomyces meyeri . Although penicillin is the standard treatment for this condition, our patient was treated successfully with imipenem . Actinomyces organisms are important constituents of the normal flora of mucous membranes and are considered opportunistic pathogens; these organisms may produce infection after local trauma, surgery, or aspiration . The mains forms of actinomycosis are cervicofacial, thoracic, and abdominal; most cases are due to Actinomyces israelii, whereas other Actinomyces species are occasionally implicated . Actinomycosis usually occurs in immunocompetent persons, but may occur in persons with diminished host defenses.

Neurosci Lett, 2000 Aug 4, 289(2), 103 - 6
Relations between early prespike magnetic field changes, interictal discharges, and return to basal activity in the neocortex of rabbits; Zwiener U et al.; To evaluate possible prespike field synchronizations, its relation to both interictal discharges and postspike return to baseline, penicillin-induced cortical interictal discharges were recorded in anaesthetized rabbits by magnetoencephalography (MEG) and electrocorticography (EcoG) . Statistical parameters of spatial (global field power (GFP)) and temporal properties (Z-parameter) of field synchronization were calculated . In our previous report, three types of prespike field synchronization were found before the onset of interictal spike . We report here that the continuous and fluctuating, but not the abrupt prespike increases, were more often associated with a spike and wave pattern of interictal discharge than with a spike alone . Furthermore, the postspike return of these statistical parameters shows the same three patterns as the prespike field synchronizations, but in the inverse time sequence . More often than not pre- and postspike pattern were of the same type . The results suggest an influence of prespike field synchronization upon interictal discharge and subsequent field return dynamics.

J Neurophysiol, 2000 Jul, 84(1), 274 - 80
Effects of applied electric fields on low-calcium epileptiform activity in the CA1 region of rat hippocampal slices; Ghai RS et al.; It is well established that exogenous electric fields can suppress activity obtained in different models of epileptiform discharge such as penicillin and high potassium . In the low-calcium model of epilepsy, spontaneous epileptiform bursting is generated in the absence of synaptic transmission . It has been suggested that ephaptic interactions play a critical role in neuronal synchronization and burst propagation in this nonsynaptic model . We, therefore, tested the hypothesis that low-calcium bursting induced in the CA1 region of transverse and longitudinal hippocampal slices should be highly sensitive to exogenous electric fields . Uniform, low amplitude DC electric fields were applied during spontaneous low-calcium epileptiform activity . Modulation and full suppression of epileptiform activity was observed at field strengths between 1 and 5 mV/mm, a value significantly lower than in other in vitro models of epilepsy . We further investigated the hypothesis that the efficacy of electrical fields was related to changes in the extracellular space . Our results suggest that the osmolality of the perfusate can modulate the efficacy of electric fields . It was also observed that the ability of a field to suppress or modulate low-calcium activity was highly dependent on its orientation, polarity, as well as magnitude . Finally, it was observed that the extracellular potassium "waves" that normally accompany individual epileptiform events was abolished when the individual events were suppressed . These results suggest that DC fields modulate and suppress low-calcium activity by directly polarizing CA1 pyramidal cells.

Int J Food Microbiol, 2000 Jun 30, 58(1-2), 59 - 63
Karyotype of Penicillium nalgiovense and assignment of the penicillin biosynthetic genes to chromosome IV; Farber P et al.; The karyotype of Penicillium nalgiovense was determined by pulsed-field gel electrophoresis and compared to the karyotype of P . chrysogenum . Both species have four chromosomes, but they differ in the size of the chromosomes and in the overall size of the genome . The sizes of the P . nalgiovense chromosomes as determined by pulsed-field gel electrophoresis are: 9.1 Mb, 7.9 Mb, 5.4 Mb and 4.1 Mb which gives in summary a genome size of 26.5 Mb . This compares to 34.1 Mb for P . chrysogenum . The penicillin gene cluster was located by Southern hybridization on chromosome IV, the smallest chromosome of P . nalgiovense compared to chromosome 1, the largest chromosome of P . chrysogenum.

Arch Pharm Res, 2000 Jun, 23(3), 197 - 201
Electrochemical behavior and differential pulse polarographic determination of piperacillin sodium; Hahn Y et al.; In an aqueous piperacillin sodium solution, a well-defined single wave or single peak was observed by direct current (DC) polarography or differential pulse polarography (DPP) . The peak potential change per pH unit was -54 mV in the phosphate buffer at 18 degrees C, which indicated that protons were involved in the electrochemical reduction of the 2,3-dioxopiperazine moiety of piperacillin sodium with a H+/e- ratio of one . Using a phosphate buffer of pH 4.3, the 1.0 x 10(-7) M piperacillin sodium single peak could be determined by DPP with relative standard deviation of 1.6% (n=3) . Piperacillin sodium could be analyzed without interference from penicillin G-potassium, which enabled the employment of DPP as a fast and simple technique for monitoring the synthetic process of the antibiotic.

Acta Med Port, 1999 Dec, 12(12), 331 - 40
{Human leptospirosis . A short review concerning a caseload}; Vieira A et al.; Leptospirosis, a zoonosis with worldwide distribution, may have a broad spectrum of clinical manifestations that can delay the diagnosis, especially in wet climates where other conditions may dissimulate the main aspects . The authors describe 42 cases of patients with leptospirosis admitted to the Infectious Diseases Unit of a general hospital since 1990 . The goal was to analyse epidemiological features, clinical manifestations, laboratory findings, treatment and evolution . There were 23 males (54.7%) and 19 females (45.2%), with ages ranging from 17 to 82 years . Most cases occurred in occupational settings, especially in those in contact with animals or stagnant water . All the cases had serological confirmation (by MAT or ELISA methods) . Anicteric forms represented 42.9% of the total, which implies that in many cases a diagnosis is not immediately evident . The main symptoms, other than fever (97.6%) and jaundice (57.1%), were myalgia (71.4%), headache (42.8%) and nausea (33.3%) . Renal involvement was common (52%), but the most severe forms occurred in 3 patients who required hemodialysis; followed by D.I.C . in 9.5%; meningitis in 4.7% and pulmonary involvement in 2.3% of the cases . The serovars most commonly identified were L . icterohaemorraghiae (28.5%), L . australis (14.3%), L . grippothyphosa (11.9%) and L . canicola (9.5%) . The patients were treated with penicillin G (83.3%) or doxycyclin (9.5%) . Two of them deceased (4.7%) and the remainder had a good evolution . The diagnosis of leptospirosis may be delayed if physicians fail to include this infection in the initial differential diagnosis . In view of this, the authors emphasize that when nonspecific clinical manifestations occur, a good epidemiological history is useful in proposing this diagnosis.

Surg Endosc, 2000 Jun, 14(6), 527 - 31
Pediatric laparoscopic splenectomy; Park A et al.; BACKGROUND: Lateral laparoscopic splenectomy in adults, first reported in 1991, was begun with children in 1993 . METHODS: The authors reviewed records of 59 patients 2 to 17 years old who underwent laparoscopic splenectomy by the lateral approach between 1994 and 1998 at four medical centers . Patients received prophylactic penicillin or vaccinations preoperatively . RESULTS: Of the 59 patients, 51 required splenectomy for one of the following conditions: idiopathic thrombocytopenic purpura, hereditary spherocytosis, or sickle-cell disease . Splenomegaly was found in 86% of the patients, and ten accessory spleens were resected . No deaths or infection occurred, and only three patients had perioperative complications: acute chest crisis, small diaphragmatic injury, and intraoperative hemorrhage . One operation was converted to a minilaparatomy because of difficulty with specimen extraction . CONCLUSIONS: Pediatric laparoscopic splenectomy is safe and effective, resulting in little blood loss, rapid recovery, and a good cosmetic outcome.

J Chromatogr A, 2000 Jun 2, 880(1-2), 85 - 91
Application of ion-exchange cartridge clean-up in food analysis III . Determination of benzylpenicillin, phenoxymethyl-penicillin, oxacillin, cloxacillin, nafcillin and dicloxacillin in bovine liver and kidney by liquid chromatography with ultraviolet detection; Ito Y et al.; A multiresidue analytical method was developed for the simultaneous determination of benzylpenicillin (PCG), phenoxymethylpenicillin (PCV), oxacillin (MPIPC), cloxacillin (MCIPC), nafcillin (NFPC) and dicloxacillin (MDIPC) in bovine liver and kidney . The method involves the use of an ion-exchange cartridge for sample clean-up followed by ion-pair high-performance liquid chromatography with ultraviolet detection . The recoveries of PCG, PCV, MPIPC, MCIPC, NFPC and MDIPC from bovine liver spiked at levels of 0.5 mg/kg and 0.1 mg/kg were in the range of 73-91% and 83-96% with coefficients of variation of 1.4-4.2% and 3.4-8.7%, respectively . For bovine kidney spiked at levels of 0.5 mg/kg and 0.1 mg/kg, the recoveries of these compounds were 79-92% and 82-92% with RSDs of 1.8-5.9% and 2.7-7.8%, respectively . The detection limits for the six penicillins were 0.02-0.05 mg/kg in bovine liver and kidney.

Biochemistry (Mosc), 2000 Jun, 65(6), 672 - 6
Reactivation of heterodimer and individual subunits of penicillin acylase from E . coli after inactivation in urea; Shamolina TA et al.; Individual subunits of penicillin acylase from E . coli were isolated by gel-filtration under denaturing conditions (8 M urea) . Recovery of the catalytic activity of the penicillin acylase heterodimer was studied after removal of urea . In the case of the heterodimer, 40-60% of the initial activity was recovered, whereas the activity of individual subunits was not recovered . Combination of native enzyme subunits with subunits isolated from the enzyme pre-inactivated with the irreversible inhibitor phenylmethylsulfonyl fluoride resulted in heterodimers which were active only in the case of involvement of the beta-subunit of the active enzyme.

Biologicals, 2000 Jun, 28(2), 119 - 27
In vitro markers and biological activity in mice of seed lot strains and commercial Brucella melitensis Rev 1 and Brucella abortus B19 vaccines; Grillo MJ et al.; Four seed lots and fourteen batches of Brucella melitensis Rev 1 and B . abortus B19 living anti-Brucella commercial vaccines obtained from six Spanish laboratories were tested in vitro and in vivo in the reference mouse model for quality control . All the strains tested showed the characteristic morphology of their respective Rev 1 or B19 reference strains with the exception of three Rev 1 strains: seed lot SL2 and commercial vaccine R3, in which giant colonies were predominant, and commercial vaccine R5, in which 5% rough colonies were detected . Strains SL2 and R5 (but not the R3) had a deficient activity when tested in the mouse model . All strains but two (Rev 1 strain R1 and B19 strain B2) had standard resistance/ sensitivity patterns to streptomycin and penicillin G . Strains R1 and B2 had an increased resistance to penicillin when incubated in a 10% CO2 atmosphere and both strains showed an increased residual virulence in mice . As residual virulence and immunogenicity in mice were not always correlated one another nor with the in vitro tests, all tests should be performed to control properly the anti-Brucella live vaccines . A computerized statistical procedure to calculate the residual virulence of vaccines is proposed as an alternative to that used in the current method.

Ross Fiziol Zh Im I M Sechenova, 2000 May, 86(5), 532 - 40
{Structural basis of the intracortical synchronization of epileptic potentials in the sensomotor region of the rat neocortex}; Pasikova NV et al.; In control rats, penicillin-induced epileptiform discharges were completely synchronous in the neocortex sites at a distance of up to 4 mm from each other . Number of the cells decreased by 45.5% during 90 days in isolated cortical slabs and the synchronisation disappeared . The data obtained show that the loss of large pyramidal neurones of the layer V entailed a loss of the spatial synchronisation . The main axonal collaterals of large pyramidal neurones of the layer V could be followed horizontally for a distance of up to 2 mm in the somatosensory cortex . The neuronal network formed by the large pyramidal neurones of the layer V seems to provide a spatial synchronisation in the neocortex.

Protein Expr Purif, 2000 Jul, 19(2), 235 - 45
Overexpression and biosynthetic deuterium enrichment of TEM-1 beta-lactamase for structural characterization by magnetic resonance methods; Sosa-Peinado A et al.; An expression system has been developed that allows high levels of production of TEM-1 beta-lactamase with ease of biosynthetic incorporation of nuclear isotopes . The gene for mature TEM-1 beta-lactamase fused to the leader sequence of the ompA protein was subcloned into the pET-24a(+) vector by introduction of an NdeI restriction site at the first codon of the fused genes and transformed into Escherichia coli BL21 (DE3) cells . With protein induction at 25 degrees C supported by LB medium supplemented with osmolytes (300 mM sucrose and 2.5 mM betaine), the extracellular, mature form of wild-type TEM-1 beta-lactamase was recovered at a level of 140 mg/L . The production level of E166N, E240C, E104C, and M272C mutants depended on the mutation but was invariably higher than reported by others for expression systems of the wild-type enzyme . Comparison of different carbon sources on the efficiency of biosynthetic incorporation of covalent deuterium showed maximal (90%) incorporation with minimal medium containing 99% (2)H(2)O and sodium d(3)-acetate (99 atom% (2)H) . The yield of deuterium-enriched wild-type enzyme was 80 mg/L with yields for mutants proportionally reduced . The high level of protein deuteration achieved with this system allowed detection of the hyperfine coupling between the paramagnetic nitroxyl group of a spin-labeled penicillin substrate and hydrogens on the penicillin moiety in a cryokinetically isolated acylenzyme reaction intermediate because of the decrease in overlapping resonances of active site residues . The overexpression system is readily adaptable for other target proteins and facilitates studies requiring large quantities of protein in isotopically enriched forms .

J Periodontol, 2000 May, 71(5), 825 - 9
Case report of regional alveolar bone actinomycosis: a juvenile periodontitis-like lesion; Nagler RM et al.; BACKGROUND: Cervicofacial actinomycosis infection most often involves the mandibular bone and rarely the alveolar crest . METHODS: We describe a 14-year-old patient who had actinomycosis involving the alveolar bone at the left lower dental quadrant region . Resembling juvenile periodontitis, it was difficult to diagnose properly and resulted in devastating dental and periodontal consequences: loss of one tooth with most of its adjacent regional alveolar bone, severely compromising the support of two other teeth . RESULTS: With the diagnosis came successful treatment, including surgical removal of the soft and hard tissues with concomitant prolonged penicillin administration . CONCLUSIONS: We feel that this case should raise the interest and concern of both the periodontist and the general practitioner so that early diagnosis can be obtained, significantly improving the clinical outcome.

Biochem Biophys Res Commun, 2000 May 27, 272(1), 199 - 204
Identification of a new active site for autocatalytic processing of penicillin acylase precursor in Escherichia coli ATCC11105; Lee H et al.; Penicillin acylase (PA) from Escherichia coli ATCC11105 is a periplasmic heterodimer consisting of a 24 kDa small subunit and a 65 kDa large subunit . It is synthesized as a single 96 kDa precursor and then matures to functional PA via a posttranslational processing pathway . The GST-PA fusion protein expression system was established for monitoring the precursor PA processing in vitro . The purified PA precursor was processed into mature PA the same way as in vivo, but pH dependently . From the primary sequence analysis, we identified a putative conserved lysine residue (K299) responsible for the pH dependent processing . The substitution of K299 residue by site-directed mutagenesis affected both the enzyme activity and the precursor PA processing in vivo . Furthermore, it was shown that the processing rates of wild-type and mutant precursor PAs depended on the pKa values of their side chain R group . These results demonstrated that the lysine residue (K299) was involved in the precursor processing of PA together with N-terminal serine residue (S290) of the large subunit.

Enzyme Microb Technol, 2000 Jul 1, 27(1-2), 122 - 126
Prediction of penicillin V acylase stability in water-organic co-solvent monophasic systems as a function of solvent composition; Arroyo M et al.; Hydrolytic activity of penicillin V acylase (EC 3.5.1.11) can be improved by using organic cosolvents in monophasic systems . However, the addition of these solvents may result in loss of stability of the enzyme . The thermal stability of penicillin V acylase from Streptomyces lavendulae in water-organic cosolvent monophasic systems depends on the nature of the organic solvent and its concentration in the media . The threshold solvent concentration (at which half enzymatic activity is displayed) is related to the denaturing capacity of the solvent . We found out linear correlations between the free energy of denaturation at 40 degrees C and the concentration of the solvent in the media . On one hand, those solvents with logP values lower than -1.8 have a protective effect that is enhanced when its concentration is increased in the medium . On the other hand, those solvents with logP values higher than -1.8 have a denaturing effect: the higher this value and concentration, the more deleterious . Deactivation constants of PVA at 40 degrees C can be predicted in any monophasic system containing a water-miscible solvent.

Sex Transm Infect, 2000 Apr, 76(2), 73 - 9
Syphilis in pregnancy; Genc M et al.; Syphilis can seriously complicate pregnancy and result in spontaneous abortion, stillbirth, non-immune hydrops, intrauterine growth restriction, and perinatal death, as well as serious sequelae in liveborn infected children . While appropriate treatment of pregnant women often prevents such complications, the major deterrent has been inability to identify the infected women and get them to undergo treatment . Screening in the first trimester with non-treponemal tests such as rapid plasma reagin (RPR) or venereal disease research laboratory (VDRL) test combined with confirmation of reactive individuals with treponemal tests such as the fluorescent treponemal antibody absorption (FTA-ABS) assay is a cost effective strategy . Those at risk should be retested in the third trimester . Treatment during pregnancy should be with penicillin . In determining a penicillin regimen, the clinician must consider the stage of the maternal infection and the HIV status of the mother . Patients who are allergic to penicillin should be desensitized before treatment . Despite appropriate treatment, as many as 14% will have a fetal death or deliver infected infants . Treatment may further be complicated by the Jarich-Herxheimer reaction, a complex allergic response to antigens released from dead micro-organisms, which can cause fetal distress and uterine contractions . Thanks to effective intervention strategies and inexpensive penicillin, syphilis rarely complicates pregnancy in the Western world today . In parts of the world where the traditional sexually transmitted diseases have not been controlled, the magnitude of problems associated with syphilis during pregnancy is reminiscent of that faced by the West during the early 1900's.

Appl Biochem Biotechnol, 2000 Spring, 84-86, 931 - 45
A kinetic study of synthesis of amoxicillin using penicillin G acylase immobilized on agarose; Goncalves LR et al.; We present a kinetic model for the synthesis of amoxicillin from p-hydroxyphenylglycine methyl ester and 6-aminopenicillanic acid, catalyzed by penicillin G acylase immobilized on agarose, at 25 degrees C . Michaelis-Menten kinetic parameters (with and without inhibition) were obtained from initial velocity data (pH 7.5 and 6.5) . Amoxicillin synthesis reactions were used to validate the kinetic model after checking mass transport effects . A reasonable representation of this system was achieved under some operational conditions, but the model failed under others . Nevertheless, it will be useful whenever a simplified model is required, e.g., in model-based control algorithms for the enzymatic reactor.

Trop Doct, 2000 Apr, 30(2), 97 - 9
A survey to gather sexually transmitted disease epidemiological and management data in the Solomon Islands; Lucas RE; A survey of 15 clinics and hospitals in the Solomon Islands (a South Pacific nation with a 45% rate of penicillin-resistant gonorrhoea) was undertaken to audit the quality of sexually transmitted diseases data collection, adherence to public health fundamentals and knowledge of the national gonorrhoea management guidelines . With the exception of one town clinic, data collection was limited, syphilis serological testing was low (28%) and correct knowledge of the national gonorrhoea treatment guidelines was also limited to 4/8 clinics (50%) . Contact tracing was definitely undertaken in 2/8 (25%) of clinics . A high male/female notification ratio (3.6:1) for gonorrhoea was detected . Solomon Island clinics may be typical of other South Pacific Island communities in their inadequate attention to public health fundamentals . Every effort should be made to identify these shortcomings and provide feedback to clinic health workers to improve this service, particularly in the context of the more recent arrival of the HIV epidemic in the region.

Trop Gastroenterol, 2000 Jan-Mar, 21(1), 22 - 7
Bio-artificial liver from cultured human foetal hepatocytes: feasibility and prospects; Anand AC et al.; BACKGROUND: Conventional therapy for acute liver failure has not been able to improve survival beyond 40% . Apart from liver transplantation, the most promising development in this field is the utilization of cultured hepatocytes to make 'bio-artificial liver support systems' as a 'bridge to transplantation' or ideally as a 'bridge to total recovery' . This study examines the feasibility of culturing foetal hepatocytes without the use of growth factors and formulating a bio-artificial liver support device in our set-up . METHODS: Foetal hepatocytes were harvested from the liver obtained from mid trimester abortions at Armed Forces Medical College and Command Hospital (SC), Pune . The liver was perfused with Phosphate Buffered Saline (PBS) and collagenase type IV and was cut with a pair of sterile scissors into tiny pieces . Cells so separated, were washed with PBS plus foetal calf serum and stirred to disperse the cell aggregates . Filtered cell suspensions were inoculated in polystyrene flasks containing hepatocyte culture medium (MEM E: 75%, M199: 25%, BSA: 0.1%, Bovine Insulin 5 micrograms/ml, FCS: 10%, Penicillin: 10 i.u., Streptomycin 50 micrograms/ml, Hydrocortisone 5 micrograms/ml and incubated at 37 degrees C . The functional capabilities of the cultured hepatocytes were analyzed by studying production of albumin and a foetoprotein . Structural integrity of hepatocytes was assessed by light and electron microscopy . RESULTS: The hepatocyte yield varied from 2 to 60 x 10(6) cells/L with an average of 38 x 10(6) cells/L in the eight consecutive experiments . Initial hepatocyte viability varied from 25% to 90% with an average of 61% . The yield and the viability of hepatocytes were adversely affected by the condition of foetus at birth and use of intra-amniotic injections for inducing abortions . Hepatocyte monolayers and colonies formed in 75% experiments . The cultures could be maintained in incubation without the use of epidermal or hepatocyte growth factors for 2-25 days with a mean survival of 8.9 days . The cells in culture were found to be structurally normal and functionally active and could be cryo-preserved . These hepatocytes were inoculated into a hollow fiber module to formulate bio-artificial liver support device . The cultures ultimately developed either cellular disintegration or bacterial infections despite use of antibiotics in the culture medium . CONCLUSIONS: We conclude that it is feasible to maintain foetal hepatocyte cultures without the use of expensive growth factors for over 8 days . Bio-artificial liver formulated with cultured foetal hepatocytes is now a step closer to clinical trials.

Biotechnol Prog, 2000 May-Jun, 16(3), 368 - 71
Activation and stabilization of penicillin V acylase from streptomyces lavendulae in the presence of glycerol and glycols; Arroyo M et al.; Penicillin V acylase (EC 3.5.1.11) from Streptomyces lavendulae showed both enhanced activity and stability in mixed water/glycerol and water/glycols solvents . The catalytic activity was increased up to a critical concentration of these cosolvents, but further addition of the latter led to a gradual protein deactivation . The highest stabilizing effect was achieved in the presence of glycerol . Thermal stability was increased proportionally to the concentration of glycerol and glycols in the reaction mixture only if the amount added is below the threshold concentration . Reaction conditions that allow simultaneously enhanced activity and stability in the hydrolysis of penicillin V catalyzed by penicillin V acylase from S . lavendulae could be established.

Arch Gynecol Obstet, 2000 Apr, 263(4), 178 - 81
Oral phenoxymethylpenicillin treatment during pregnancy . Results of a population-based Hungarian case-control study; Czeizel AE et al.; The objective of the study was to examine the human teratogenic potential of oral penicillin V: phenoxymethylpenicillin treatment during pregnancy in the large population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996 . The dataset included 22,865 pregnant women who had fetuses or newborns with congenital abnormalities and 38,151 matched pregnant women who had newborn infants without any congenital abnormality (population control group) . Of 22,865 case pregnant women, 173 (0.8%) had phenoxymethylpenicillin treatments, while of 38,151 population controls, 218 (0.6) were treated by this penicillin V (crude OR 1.3 with 95% CI: 1.1-1.6) . This difference was explained mainly by recall bias and confounders because adjusted OR for medically documented phenoxymethylpenicillin treatments did not show difference during the second-third months of gestation, i.e . in the critical period for most major congenital abnormalities in case-matched control pairs . Thus, treatment with oral phenoxymethylpenicillin during pregnancy presents very little if any teratogenic risk to the fetus.

Biomed Sci Instrum, 2000, 36, 343 - 8
Long-term sustained delivery of 3'-azido-2',3'-dideoxythymidine in vivo by means of HA and TCP delivery devices; Benghuzzi H; This study will attempt to determine the amount of circulating drug, when provided at sustained levels over an extended period of time, which provides efficacy and reduces the toxic side effects seen with the use of AZT in vivo . Two ceramic delivery systems were selected for this investigation namely tricalcium-phosphate (TCP) and hydroxyapatite (HA) ceramic implants . Three different dosages were selected (60, 90, 180 mg AZT) . A total of 105 rats were used in this study and they were further divided into seven equal groups (n = 15 per group, 250-300 gm BW) . Rats in groups I, II and III were implanted with TCP ceramic capsules containing 30, 60, and 90 mg AZT powder, respectively . Each rat in groups IV, V, and VI were implanted with HA capsules containing 30, 60, and 90 mg AZT powder, respectively . Rats in group VII were unimplanted and served as controls . The standard aseptic surgical techniques were performed in this investigation . Rats were anesthetized with a mixture of Zylazine/Ketamine, and their hind limbs shaved and scrubbed with providone iodine . The sterilized ceramics (gas/24 hours) were inserted under the skin using standard surgical techniques . After implantation, the site was sealed with wound clips, and the animals were injected with 0.1 ml of 200,000 units of Penicillin . At the end of 2, 4, and 6 weeks after implantation, five rats from each group were euthanized and the ceramic capsules, reproductive, and vital organs were removed and examined by following standard laboratory protocols . Results obtained from this study revealed that the rates of AZT released from TCP ceramic implants (30 mg = 2.38 +/- 0.23 ng/ml, 60 = 4.64 +/- 1.03 ng/ml, and 90 mg = 11.92 +/- 2.36 ng/ml serum AZT) were significantly higher than the rates of AZT released from HA ceramic implants (30 mg = 0.84 +/- 0.05 ng/ml, 60 = 2.40 +/- 0.83 ng/ml, and 90 mg = 6.41 +/- 1.24 ng/ml serum AZT) . Data obtained from this investigation suggest that: (I) TCP and HA ceramic implants can be used effectively to deliver AZT in amounts capable of eliciting physiological responses in vivo, and (II) large fluctuations of AZT concentrations in the blood stream and tissues due to the conventional routes of administration could be eliminated by using ceramic sustained delivery system.

Indian J Pediatr, 1996 Jul-Aug, 63(4), 433 - 6
Do we need to treat otitis media?
Chaudhary S.
Otitis media is a common pediatric problem . It is well established that over half of infants and children with acute otitis media may have spontaneous recovery . Since it is difficult to predict the course (self-limited versus serious disease) all the children with acute suppurative otitis media need to be treated with antibiotics . Amoxicillin is still the initial antibiotic of choice . There are several alternate antibiotics available with activity against beta-lactamase positive bacteria . These agents have no advantage over amoxicillin in infections due to penicillin resistant pneumococci . Recent use of beta-lactam antibiotics and/or attendance in a day care where there is frequent use of antibiotics are predisposing factors for penicillin resistant pneumococcal infection . In such cases after tympanocentesis, higher dose of amoxicillin, clindamycin or intramuscular ceftriaxone should be considered . Secretory otitis media does not need to be treated with antibiotics unless the patient is in high risk group . Prophylactic use of antibiotics should be actively discouraged . Influenza and pneumococcal vaccination (2 years or older) should be encouraged in children with recurrent episodes of acute otitis media . Breast feeding should be encouraged.

Indian J Pediatr, 1995 Nov-Dec, 62(6), 717 - 23
Reversibility of mitral regurgitation following rheumatic fever: clinical profile and echocardiographic evaluation; Kassem AS et al.; The clinical disappearance of the murmur of rheumatic mitral regurgitation after period of time has been documented by many researchers . However no studies have related the disappearance of the murmur with the functional or anatomical state of the mitral valve . This study was done to elucidate the mitral valve status using doppler and color coded echocardiography among those children who have lost their apical pansystolic murmur on auscultation following a documented attack of rheumatic fever . The study sample consisted of 51 patients including 31 patients in whom the murmur has disappeared (group I), and 20 patients with persistent isolated mitral regurgitation (group II) . Patients of group I had significantly lower grades of murmur intensity, lower incidence of cardiomegaly, and had no heart failure in the initial attack . They were more compliant with prophylaxis and had less recurrences than patients of group II . The murmur disappeared in patients of group I from 1/2 to 14 years after the initial attack . Echocardiography revealed that such patients had a normal mitral valve apparatus, and a normal heart size and function . Only 5 patients of this group had a significant regurgitant jet demonstrated by colour doppler . We concluded that recovery of the mitral valve and return of cardiac functions to normal is possible in patients who had mitral regurgitation following rheumatic fever . Some of them may still have an inaudible mild regurgitation . Patients who have lost their murmur may be allowed to exercise freely, yet penicillin prophylaxis should not be discontinued.

Tidsskr Nor Laegeforen, 1999 Dec 10, 119(30), 4507 - 13
{Welfare and health in the century of social security}; Westin S; Great achievements for public health in this century include penicillin, oral contraception, vaccination and transplantation, but the greatest contribution to the health of Norwegians may have been made by social security and the welfare state policies . The beneficial effects of social security include: less social inequality, a factor which in itself makes for better health, some degree of financial security for people who are ill and unable to support themselves or their families, universal availability of medical and health services . This paper explores the ideas and sources from which present-day social security legislation stems . The emergence of state based welfare legislation was inspired by developments in Germany under Bismarck; accident insurance for industrial workers was the first to be introduced in 1894 . Several periods of active social security legislation followed at times when labour unions and socialist ideas were strong, supported, to some degree, by radical clergy and public health doctors . Social democratic governments, inspired by the British Beveridge plan towards the end of World War II, took the lead during the long post-war period until the mid 1970s . The Scandinavian model of social security is based on universal coverage and a single payer system . However, since the 1980s, as in other countries of Northern Europe, the social security system has come under pressure from market liberalism . Now at the turn of the century, increasing social inequalities cause some concern for the future of the welfare state.

Biochemistry, 2000 May 9, 39(18), 5312 - 21
Structure-based design guides the improved efficacy of deacylation transition state analogue inhibitors of TEM-1 beta-Lactamase(,); Ness S et al.; Transition state analogue boronic acid inhibitors mimicking the structures and interactions of good penicillin substrates for the TEM-1 beta-lactamase of Escherchia coli were designed using graphic analyses based on the enzyme's 1.7 A crystallographic structure . The synthesis of two of these transition state analogues, (1R)-1-phenylacetamido-2-(3-carboxyphenyl)ethylboronic acid (1) and (1R)-1-acetamido-2-(3-carboxy-2-hydroxyphenyl)ethylboronic acid (2), is reported . Kinetic measurements show that, as designed, compounds 1 and 2 are highly effective deacylation transition state analogue inhibitors of TEM-1 beta-lactamase, with inhibition constants of 5.9 and 13 nM, respectively . These values identify them as among the most potent competitive inhibitors yet reported for a beta-lactamase . The best inhibitor of the current series was (1R)-1-phenylacetamido-2-(3-carboxyphenyl)ethylboronic acid (1, K(I) = 5.9 nM), which resembles most closely the best known substrate of TEM-1, benzylpenicillin (penicillin G) . The high-resolution crystallographic structures of these two inhibitors covalently bound to TEM-1 are also described . In addition to verifying the design features, these two structures show interesting and unanticipated changes in the active site area, including strong hydrogen bond formation, water displacement, and rearrangement of side chains . The structures provide new insights into the further design of this potent class of beta-lactamase inhibitors.

Sex Transm Infect, 2000 Feb, 76(1), 18 - 24
Investigation of the increased incidence of gonorrhoea diagnosed in genitourinary medicine clinics in England, 1994-6; Hughes G et al.; OBJECTIVES: To determine important risk factors associated with cases of gonorrhoea in England, and whether any particular risk groups were associated with the substantial rise in numbers of cases seen between 1994 and 1996 . DESIGN: Two retrospective cross sectional surveys . SETTING: 70 randomly selected genitourinary medicine (GUM) clinics in England . SUBJECTS: 10% of all gonorrhoea patients attending GUM clinics in England in 1994 (847 patients) and 1996 (1146 patients) . MAIN OUTCOME MEASURES: For risk factors in 1996 (study 1), unadjusted rates per 100,000 population aged 14-70 and relative rates (RR) with 95% confidence intervals (CIs) . For the change in risk factors between 1994 and 1996 (study 2), adjusted odds ratios (ORs) with 95% CIs, derived from logistic regression analyses of data on patients in 1996, with patients in 1994 as the comparison group . RESULTS: The incidence of gonorrhoea in 1996 was higher in homosexual males (812 per 100,000; RR = 30.2, CI = 25.2 to 36.0) compared with heterosexual males (27 per 100,000); in black Caribbeans (467 per 100,000; 21.4, 17.9 to 25.5) and black Africans (235 per 100,000; 10.8, 7.5 to 15.5) compared with white people (22 per 100,000); and in previous GUM clinic attenders (433 per 100,000; 37.93, 35.46 to 40.56) compared with those who had not attended previously (11 per 100,000) . However, most patients were either white or heterosexual . Heterosexual patients in 1996 were significantly more likely to have reduced sensitivity to penicillin (2.55, 1.20 to 5.41) than those in 1994 . Male homo/bisexual patients in 1996 were significantly more likely to be from the north west (3.77, 1.45 to 9.80) and to have either reduced sensitivity (2.63, 1.03 to 6.73) or complete resistance (1.98, 1.03 to 3.78) to penicillin, compared with those in 1994 . CONCLUSIONS: Homo/bisexual men and the black Caribbean population in England experience a disproportionate burden of gonococcal infections, however, the bulk of diagnoses are in white heterosexuals . No single risk group was associated with the rise in numbers of cases between 1994 and 1996 . Resistance to penicillin is widespread and has increased in homo/bisexual men, and it is possible that a rise in treatment failures has, to some extent, enhanced transmission of gonorrhoea and contributed to the rise in numbers of diagnoses in this group.

Org Lett, 2000 May 18, 2(10), 1361 - 4
Cross-linked enzyme aggregates: a simple and effective method for the immobilization of penicillin acylase; Cao L et al.; {reaction--see text} Penicillin G acylase (penicillin amidohydrolase, E.C . 3.5.1.11) was immobilized in a simple and effective way by physical aggregation of the enzyme, using a precipitant, followed by chemical cross-linking to form insoluble cross-linked enzyme aggregates (CLEAs) . These had the same activity in the synthesis of ampicillin as cross-linked crystals of the same enzyme, but the accompanying hydrolysis of the side-chain donor was much less . Penicillin G acylase CLEAs also catalyzed the synthesis of ampicillin in a broad range of organic solvents.

Scand J Prim Health Care, 2000 Mar, 18(1), 44 - 7
Randomised, double blind, placebo controlled trial of penicillin V in the treatment of acute maxillary sinusitis in adults in general practice; Hansen JG et al.; OBJECTIVE: To compare the effectiveness of penicillin V with placebo in the treatment of adult patients with acute maxillary sinusitis in general practice . DESIGN: Randomised, double blind, placebo controlled trial . SETTING: 26 Danish general practices . PATIENTS: 133 adult patients with a clinical diagnosis of acute maxillary sinusitis based on maxillary pain and raised values of either C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) . MAIN OUTCOME MEASURES: Pain score and illness score as well as measurement of CRP and ESR values after initiation of treatment . RESULTS: Penicillin V led to a better recovery than did placebo . The difference was statistically significant 3 days after the initiation of treatment with regard to pain reduction, whereas no significant difference was found with regard to the reduction in the sense of illness . At the end of the study, significantly more patients in the penicillin group were completely free of pain compared to the placebo group . This difference was only found in patients with an initial pain score of more than three . The cure rate was 71% in the penicillin group and 37% in the placebo group . Significantly more patients achieved normal CRP values when treated with penicillin (88%) as opposed to placebo (75%) . CONCLUSION: Penicillin V is more effective than placebo in the treatment of acute maxillary sinusitis in adults in general practice, but only in patients with pronounced pain.

Eur J Neurol, 2000 Mar, 7(2), 231 - 6
Syringomyelia complicating syphilitic spinal meningitis: a case report; Bulundwe KK et al.; An association between syringomyelia and spinal syphilis was described in the early literature but has not been the subject of reports subsequently . We give details of a contemporary case, affirmed by magnetic resonance imaging . The patient showed significant clinical recovery following penicillin treatment, while the imaging appearances became less pronounced.

N Engl J Med, 2000 May 11, 342(19), 1399 - 407
Mortality from pneumonia in children in the United States, 1939 through 1996; Dowell SF et al.; BACKGROUND AND METHODS: Pneumonia remains an important cause of childhood deaths throughout the world, but in developed countries, the mortality rate is decreasing . We reviewed death records for children in the United States from 1939 through 1996 . A plot of the annual rates of change in the number of deaths from pneumonia was used to generate hypotheses about the influence of various events and interventions . We used data from the National Hospital Discharge Survey, the Medicaid program, and published reports to test these hypotheses . RESULTS: During the 58-year study period, the number of children who died from pneumonia declined by 97 percent, from 24,637 in 1939 to 800 in 1996 . During the same period, the rate of mortality from other causes declined by 82 percent . There were steep declines in the mortality rates for pneumonia from 1944 to 1950, although the rate increased among older children in 1957, and there were sustained declines in all age groups from 1966 to 1982 . From 1966 to 1982, the mortality declined by an average of 13.0 percent annually, and these decreases coincided with increases in the proportion of poor children covered by Medicaid, increases in rates of hospitalization for pneumonia, a narrowing of the gap between the mortality rate for black children and the rate for white children, and a convergence between the mortality rate in the South and the rates in the other three census regions . CONCLUSIONS: Since 1939, the rate of mortality from pneumonia in children in the United States has declined markedly . We hypothesize that the steep declines in the late 1940s are attributable to the use of penicillin, that the peak in 1957 was due to the influenza A pandemic, and that the sustained decline from 1966 through 1982 may be attributable in part to improved access to medical care for poor children.

Epilepsia, 2000 May, 41(5), 493 - 501
Distribution and initiation of seizure activity in a rat brain with subcortical band heterotopia; Chen ZF et al.; PURPOSE: Misplaced (heterotopic) cortical neurons are a common feature of developmental epilepsies . To better understand seizure disorders associated with cortical heterotopia, the sites of aberrant discharge activity were investigated in vivo and in vitro in a seizure-prone mutant rat (tish) exhibiting subcortical band heterotopia . METHODS: Depth electrode recordings and postmortem assessment of regional c-fos mRNA levels were used to characterize the distribution of aberrant discharge activity during spontaneous seizures in vivo . Electrophysiologic recordings of spontaneous and evoked activity also were performed by using in vitro brain slices from the tish rat treated with proconvulsant drugs (penicillin and 4-aminopyridine) . RESULTS: Depth electrode recordings demonstrate that seizure activity begins almost simultaneously in the normotopic and heterotopic areas of the tish neocortex . Spontaneous seizures induce c-fos mRNA in normotopic and heterotopic neocortical areas, and limbic regions . The threshold concentrations of proconvulsant drugs for inducing epileptiform spiking were similar in the normotopic and heterotopic areas of tish brain slices . Manipulations that blocked communication between the normotopic and heterotopic areas of the cortex inhibited spiking in the heterotopic, but not the normotopic, area of the cortex . CONCLUSIONS: These findings indicate that aberrant discharge activity occurs in normotopic and heterotopic areas of the neocortex, and in certain limbic regions during spontaneous seizures in the tish rat . Normotopic neurons are more prone to exhibit epileptiform activity than are heterotopic neurons in the tish cortex, and heterotopic neurons are recruited into spiking by activity initiated in normotopic neurons . The findings indicate that seizures in the tish brain primarily involve telencephalic structures, and suggest that normotopic neurons are responsible for initiating seizures in the dysplastic neocortex.

Prog Neuropsychopharmacol Biol Psychiatry, 2000 Feb, 24(2), 327 - 36
Effects of some GABA and NMDA antagonists on a model of presynaptic hippocampal paired pulse inhibition; Sagratella S et al.; 1 . The effects of some NMDA antagonists (7-chlorokynurenic acid and CGS 19755) and of the GABA antagonist penicillin were tested in a model of presynaptic short-term paired-pulse inhibition elicited in rat hippocampal slice with high (+ 2 mM) calcium solutions subjected to paired (15 ms)-pulse stimulation paradigm . 2 . In control condition a 15 ms paired-pulse stimulation delivered at the level of stratum radiatum, as revealed by the ratio between amplitudes of the conditioned and unconditioned CA1 population spikes (R2/R1), ranging from 1.27 to 2.57, a clear paired-pulse facilitation occurred . Slice perfusion with high (+ 2 mM) calcium shifted, within 30 min, as revealed by a significant (P<0.01) decrease in R2/R1 ratio, paired-pulse facilitation into inhibition . Further perfusion together to high (+ 2 mM) calcium with 0.5 mM penicillin or with 50 microM CGS 19755, but not with 50 microM 7-chlorokynurenic acid significantly decreases the degree of paired-pulse inhibition as revealed by a significative increase in the R2/R1 ratio . 3 . The data, demonstrating an inhibitory influence of specific NMDA antagonists in a model a presynaptic paired-pulse inhibition, were discussed in relation with the specific psychodysleptic effects elicited by the drugs in animals and humans.

Hawaii Med J, 2000 Feb, 59(2), 44 - 7, 56
Angioimmunoblastic T-cell lymphoma (AIL-TCL) following macrolide administration; Sasaki TY et al.; Angioimmunoblastic Lymphadenopathy with Dysproteinemia (AILD) is a rare benign reactive process which often follows exposure to certain drugs such as penicillin . Treatment with corticosteroids usually reverses the process, however there have been reports of 18% of cases evolving into non-Hodgkins lymphoma . In our case report, we present a relatively healthy woman with history of various drug hypersensitivities who developed AILD and resultant lymphoma after treatment with azithromycin . A review of the literature has failed to find reports of AILD following macrolide exposure . Clonality, not present in other forms of hyperplasia, is present in AILD and immunosuppression may account for this difference . It is difficult to say whether the drugs are simply coincidently associated or actually cause, maintain, or exacerbate clonality in AILD and facilitate malignant transformation.

Biotechnol Bioeng, 2000 Jun 20, 68(6), 652 - 9
Metabolic network analysis of Penicillium chrysogenum using (13)C-labeled glucose; Christensen B et al.; Using (13)C-labeled glucose fed to a penicillin-overproducing strain of Penicillium chrysogenum, the intracellular fluxes were quantified, and the presence of two new pathways, not previously described in this organism, is suggested . Thus, glycine was synthesized not only by serine hydroxymethyltransferase, but also by threonine aldolase . The formation of cytosolic acetyl-CoA was found to be synthesized both via the citrate lyase-catalyzed reaction and by degradation of the penicillin side-chain precursor, phenoxyacetic acid . Furthermore, the experimental data indicate that the main activities of homocitrate synthase and alpha-isopropylmalate synthase are located in the cytosol . All experimental data on the labeling patterns were obtained using gas chromatography-mass spectrometry, which is faster and more sensitive than the nuclear magnetic resonance methods usually applied for analysis of labeling patterns .

J Antimicrob Chemother, 2000 May, 45(5), 591 - 8
Use of digoxigenin-labelled ampicillin in the identification of penicillin-binding proteins in Helicobacter pylori; Harris AG et al.; Amoxycillin is used in current therapeutic regimens to treat the infection caused by the human gastric pathogen, Helicobacter pylori . The penicillin-binding proteins (PBPs) are the primary targets for the beta-lactam antibiotics, such as amoxycillin, and are involved in the terminal stages of peptidoglycan synthesis . They also play active roles in the determination and maintenance of cellular morphology . It was believed that an organism with a complex morphology, such as H . pylori, would have more than the three PBPs previously suggested . Using digoxigenin-labelled ampicillin (DIG-ampicillin), we report the identification of eight PBPs in H . pylori with masses of 72, 62, 54, 50, 44, 33.5, 30.5 and 28 kDa . A smaller (21 kDa) ninth band was also detected, which may represent another PBP . However, the relatively small size of this apparent PBP raises questions as to whether this is a true PBP . In an attempt to identify the PBPs to which amoxycillin preferentially binds, amoxycillin was used in competition assays with DIG-ampicillin . It appeared that amoxycillin inhibited the binding of DIG-ampicillin to only the 72 kDa PBP . The experimental data were also compared with the seven putative PBPs identified in the two published H . pylori genomes, most of which correlate with the experimental data . To investigate further the properties of these PBPs, the seven putative PBP genes identified in the H . pylori genomes were examined . The derived amino acid sequences of the putative PBPs were examined for the three characteristic motifs found in all conventional PBPs, SXXK, SXN and KTG . We were able to determine that all of the putative PBPs had at least one of these motifs, but none possessed all three motifs with the characteristics of conventional PBPs . These findings suggest that the PBPs of H . pylori are unique.

Cochrane Database Syst Rev . 2000;(2):CD001913.
Neonatal screening for sickle cell disease; Lees CM et al.; BACKGROUND: Sickle cell disease is an inherited disorder that occurs throughout the world with its highest incidence in areas of Africa where malaria is endemic . It affects up to one in 60 infants born in some areas of Africa . There are a number of potentially serious complications associated with the condition, and it is suggested that early treatment (before symptoms develop) can improve both morbidity and mortality . Screening for the condition in the neonatal period would enable early diagnosis and therefore early treatment . OBJECTIVES: To assess whether there is evidence that neonatal screening for sickle cell disease rather than symptomatic diagnosis reduces adverse short and long term outcomes for those in whom the disease is detected, without adverse outcomes in the population screened . SEARCH STRATEGY: We searched the Controlled Trials Register of the Cochrane Cystic Fibrosis and Genetic Disorders Group (See Group search strategy) . Contact was made with experts in the field for any work as yet unpublished and reference lists of published studies were also searched . Date of the most recent search of the Group's specialised register: November 1999 . SELECTION CRITERIA: Any randomised or pseudorandomised trial, published or unpublished comparing diagnosis by screening to clinical diagnosis would have been considered eligible for inclusion . DATA COLLECTION AND ANALYSIS: No trials of neonatal screening for sickle cell disease were found . MAIN RESULTS: No trials of neonatal screening for sickle cell disease were found . REVIEWER'S CONCLUSIONS: There is a lack of evidence from trials of neonatal screening for sickle cell disease . There is evidence of benefit from early treatment which is made possible by screening and there are a number of reviews and economic analyses of non-trial literature suggesting that screening is appropriate . Health care providers must therefore assess whether the information provided by these documents is relevant to their practice and situation when making decisions regarding neonatal screening for sickle cell disease . Systematic reviews of early treatments/interventions, including penicillin prophylaxis, pneumococcal vaccine and parental education should be considered.

Cochrane Database Syst Rev . 2000;(2):CD001084.
Pharmacotherapy for Behcet's syndrome; Saenz A et al.; OBJECTIVES: To determine the effects of available pharmacological interventions in treating the different clinical features of Behcet's syndrome . SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register, and Medline up to January 1998 . The computer search was complemented by a hand search of all bibliographic references from the reference lists of included trials . Principal investigators were contacted to seek unpublished literature . All languages were included . SELECTION CRITERIA: Studies were eligible if they fulfilled all of the four following criteria: 1 . Randomized controlled trials, single or double-blind; 2 . Participants were patients with Behcet's Syndrome as defined by the International Study Group, 1990 (Int Study Group, 1990); 3 . Interventions included any pharmacological therapy compared to placebo or some other pharmacological intervention for the treatment of Behcet's syndrome . 4 . Outcome measures included active ocular inflammatory processes, arthritis, mucocutaneous manifestations (oral ulcer, genital ulcer, erythema nodosum), laboratory changes and major events such as adverse effects and death . DATA COLLECTION AND ANALYSIS: The 32 potentially relevant references were assessed by two independent reviewers (MA, AS) according to the inclusion criteria . Ten trials fit the inclusion criteria and were included in this review . From the 10 included trials, data were independently extracted by the same two observers and crosschecked . The quality of the included trials was assessed independently by two observers (MA, AS) using a validated scale (Jadad 1996) . For dichotomous measures, the treatment effect for each trial was calculated using a fixed effect model {Peto model (Petitti 1994)} . The weighted mean differences were based, if available, on end-of-trial results . The analysis was conducted separately for each different intervention . Since the trials could not be pooled it was not possible to carry out a sensitivity analysis by quality scores or a subgroup analysis by drug dosages . Because of this lack of comparability across trials and the small number of trials, we could not conduct a heterogeneity test or a funnel plot . MAIN RESULTS: Ten trials and 679 patients were included . The main results were the lack of efficacy of some of the classic treatments for Behcet's syndrome, including colchicine, cyclophosphamide and steroids for eye involvement, azapropazone and colchicine for arthritis and acyclovir, colchicine and topical interpheron for aphthas . The results confirm the protective effects of cyclosporine and azathioprine for eye involvement and benzathine-penicillin for arthritis . REVIEWER'S CONCLUSIONS: We conclude that further randomized, placebo-controlled, double-blind trials should be carried out to compare cyclosporine, azathioprine and benzathine-penicillin versus placebo in order to make the results generalizable and comparable.

Am J Epidemiol, 2000 May 1, 151(9), 839 - 45
Sickle hemoglobin (HbS) allele and sickle cell disease: a HuGE review; Ashley-Koch A et al.; Sickle cell disease is caused by a variant of the beta-globin gene called sickle hemoglobin (Hb S) . Inherited autosomal recessively, either two copies of Hb S or one copy of Hb S plus another beta-globin variant (such as Hb C) are required for disease expression . Hb S carriers are protected from malaria infection, and this protection probably led to the high frequency of Hb S in individuals of African and Mediterranean ancestry . Despite this advantage, individuals with sickle cell disease exhibit significant morbidity and mortality . Symptoms include chronic anemia, acute chest syndrome, stroke, splenic and renal dysfunction, pain crises, and susceptibility to bacterial infections . Pediatric mortality is primarily due to bacterial infection and stroke . In adults, specific causes of mortality are more varied, but individuals with more symptomatic disease may exhibit early mortality . Disease expression is variable and is modified by several factors, the most influential being genotype . Other factors include beta-globin cluster haplotypes, alpha-globin gene number, and fetal hemoglobin expression . In recent years, newborn screening, better medical care, parent education, and penicillin prophylaxis have successfully reduced morbidity and mortality due to Hb S.

Retina, 2000, 20(2), 190 - 4
Exudative retinal detachment and retinitis associated with acquired syphilitic uveitis; Jumper JM et al.; PURPOSE: To describe three cases of exudative retinal detachment and focal retinitis associated with acquired syphilitic uveitis . METHODS: Three patients who were referred for evaluation of uveitis were examined . Slit-lamp examination, ophthalmoscopy, B-scan ultrasonography, fundus photography, and fluorescein angiography were performed before and after therapy . RESULTS: Each patient had uveitis with exudative retinal detachment, periphlebitis, and focal retinitis . Laboratory testing (fluorescent treponemal antibody absorption) revealed positive serology for active syphilis in all cases . Human immunodeficiency virus antibody testing was negative in all patients . Retinal detachment resolved in all cases after treatment with intravenous penicillin . Despite resolution of subretinal fluid, visual acuity remained poor in eyes in which the macula was detached . CONCLUSION: Syphilis is a cause of exudative retinal detachment . Antibiotic therapy can lead to retinal reattachment . Early recognition and treatment may prevent severe vision loss.

Chem Pharm Bull (Tokyo), 2000 Apr, 48(4), 447 - 53
Catalytic mechanism of class A beta-lactamase . I . The role of Glu166 and Serl30 in the deacylation reaction; Hata M et al.; The tetrahedral intermediate formation process, which is the first step in the deacylation reaction by class A beta-lactamase, was investigated by the ab initio molecular orbital method . In this study, benzyl penicillin was used as the substrate . From the results of our molecular dynamics study of the structure of beta-lactam antibiotics-beta-lactamase complex, the substrate, Ser70, Lys73, Ser130, Glu166 and a water molecule for the deacylation reaction were considered for construction of a model for calculation . The calculation results indicated that Glu166 plays a role in holding a water molecule, which is necessary for the deacylation reaction, and that the hydrogen bond network among Lys73Nzeta, Ser130Ogamma, and the carboxyl group of the beta-lactam antibiotics was formed by the uptake of beta-lactam antibiotics by beta-lactamase . The activation energy for this reaction was 33.3 kcal/mol, and it is very likely that the reaction occurred at body temperature . Subsequent calculation results obtained by using the model excluding Ser130 and the carboxyl group of the substrate indicated that the activation energy for this reaction was 40.8 kcal/mol, which is 7.5 kcal/mol higher than that of the previous reaction . It was found that the hydrogen bond network plays an important role in decreasing the activation energy for the tetrahedral intermediate formation reaction . Lys73Nzeta, which is located at the edge of the hydrogen bond network, played a role in forming a hydrogen bond with Glu166Oepsilon in order to help the deacylation reaction . The role of amino acid residues around the active site of class A beta-lactamase was also discussed.

Hosp Pract (Off Ed), 2000 Apr 15, 35(4), 89 - 95; quiz 96
Treatment of latent and tertiary syphilis; Augenbraun M; Although the efficacy of penicillin treatment for syphilis has been amply demonstrated, the optimal, curative dosage is still undefined . Some patients experience a third stage of the disease long after secondary-stage symptoms have resolved . Treatment differs in early and late latency and with the specific manifestations of tertiary-stage disease.

Pediatr Nephrol, 2000 Apr, 14(4), 322 - 4
Spontaneous clinical improvement in dense deposit disease; Marks SD et al.; The clinical course and 3-year follow-up of a female patient aged 11 years who presented with nephrotic syndrome and renal failure is described . The renal biopsy revealed type II membranoproliferative glomerulonephritis or dense deposit disease . She was treated with penicillin prophylaxis, frusemide and captopril, and was not given immunosuppression, anticoagulation or antiplatelet therapy . Despite poor prognostic clinical and pathological features, she had spontaneous resolution of her renal failure and proteinuria, although her proteinuria recurred 17 months post presentation . Her unusual progress, with improvement in her disease activity and normalisation of her glomerular filtration rate, is described.

Dermatology, 2000, 200(2), 111 - 4
Penicillin G does not alter collagen type I metabolism of dermal fibroblasts in culture; Anderegg U et al.; BACKGROUND: Penicillin G (PenG) has successfully been used for therapy of dermal fibrosis in patients suffering from systemic sclerosis (SSc) . However, there is little knowledge on the mechanism of the antifibrotic action of PenG . OBJECTIVE: We studied the effects of PenG on dermal fibroblasts by analysing the influence of various amounts of PenG on the proliferation, synthesis and degradation of collagen by human dermal fibroblasts from healthy donors and 1 SSc patient (collagen high producer) . METHODS: Collagen metabolism of cultured dermal fibroblasts was studied by Northern hybridisation for mRNA of collagen I, proline-4-hydroxylase, lysyl hydroxylase, matrix metalloproteinase I and determination of collagen content in culture supernatants . RESULTS: PenG did not alter the expression of the investigated mRNA, independently of the dosage and the incubation times used . The amount of collagen I protein was not influenced . CONCLUSION: There is no evidence of a direct antifibrotic effect of PenG on dermal fibroblasts; therefore, other mechanisms might be responsible for its effect in the treatment of SSc patients .

Indian J Pediatr, 1997 Jan-Feb, 64(1), 73 - 7
Clinical profile of sickle cell disease in Orissa; Kar BC et al.; Children comprised 52% of patients with Sickle Cell Disease (SCD) . Types of Sickle Cell Disease encountered were SS (92.7%) . SB thalassaemia (6.7%) and SD disease (0.7%) . The disease was widespread in almost all castes and communities in the society; largest number of patients (20%) belonging to scheduled castes and only 1.4% were from scheduled tribes . Maximum number of cases were in the age group 2-4 and 4-6 years, many of whom died around this age . Besides attacks of pain, jaundice and anemia, frequent attacks of fever with anemia or only anemia in childhood were a predominant presenting feature . Splenic sequestration was frequent (10.1%) . The patients usually had a steady state hemoglobin level of 6-10 g/dl, with which they thrived well . Fetal hemoglobin was 5-30% . Blood transfusion was not a frequent requirement, but prophylactic long acting penicillin was helpful in preventing frequency of crisis.

Antimicrob Agents Chemother, 2000 May, 44(5), 1181 - 5
A simple screen for murein transglycosylase inhibitors; Vollmer W et al.; A simple assay for detection of compounds that bind to the active site in the transglycosylation domain of the essential bifunctional transglycosylase and transpeptidase penicillin-binding proteins (PBPs) is reported . The method is based on a competition with the specific transglycosylase inhibitor moenomycin . With moenomycin coupled to Affi-Gel beads, a simple filtration procedure allows the amount of labeled PBPs that bind to moenomycin beads in the presence of test substances to be determined . The PBPs can easily be labeled by the covalent binding of penicillin derivatives . Crude membrane extracts can be used as a source for the PBPs, and different kinds of labels for the penicillin-PBP complexes can be used . The assay can be adapted to high-throughput screens.

Acupunct Electrother Res, 1999, 24(3-4), 161 - 7
Anticonvulsion effect of acupuncture might be related to the decrease of neuronal and inducible nitric oxide synthases; Yang R et al.; To measure the levels of hippocampal nitric oxide synthase isoforms in penicillin induced epilepsy and to test the effect of electroacupuncture (EA) on changes of these levels during epilepsy, we injected penicillin into rat hippocampus to make an epilepsy model and performed electroacupuncture treatment on "Feng Fu" (DU 16) and "Jin Suo" (DU 8) points in Wistar rats . Nitric oxide synthase (NOS) mRNA levels of rat hippocampus were determined by reverse transcription-polymerase chain reaction (RT-PCR) . The neuronal nitric oxide synthase (nNOS) mRNA markedly increased (p<0.01) and inducible nitric oxide synthase (iNOS) mRNA significantly emerged during epilepsy, whereas no significant change in epithelial nitric oxide synthase (eNOS) mRNA was observed . EA inhibited the epilepsy and decreased nNOS (p<0.01) and iNOS (p<0.01) correspondingly but had no effect on the amount of eNOS mRNA . The data suggest that penicillin-induced epilepsy caused an increase in nNOS and iNOS, and the EA anticonvulsant effect might be related to the decrease of these nitric oxide synthases.

J Vet Med B Infect Dis Vet Public Health, 2000 Mar, 47(2), 155 - 7
Isolation of Dermatophilus congolensis from a cat; Kaya O et al.; Dermatophilus congolensis was isolated from a cat with dermatitis . The isolate was sensitive to oxytetracyclin, streptomycin and penicillin but resistant to ampicillin, amoxicillin, gentamycin and cefoperazone.

Rev Med Chir Soc Med Nat Iasi, 1998 Jul-Dec, 102(3-4), 134 - 7
{A retrospective clinical study on pneumococcal meningitis in 0- to 1-year-old infants hospitalized in 1987-1996 in the Infectious Disease Clinic, Iaşi}; Rudnic E; During a period of ten years (1987-1996) in Iasi Infections Diseases Hospital, were observed 19 children, 0-1 year, with pneumococcal meningitis . This disease represented one important cause of morbidity and mortality in children in developing countries . Clinical symptoms in these cases were very serious, including: fever, headache, vomiting, altered sensorium, seizures etc . Cerebrospinal fluid analysis confirmed the diagnosis, after showing purulent, turbid fluid . The germ was isolated in 100% of the cases through direct examination and culture of cerebrospinal fluid . They were treated with penicillin and chloramphenicol (55%) and ampicillin and chloramphenicol . The mortality was 52% . This study concludes that delay in diagnosis, virulence of germ, prematurity and hypertrophy were elements of a bad prognosis.

Vet Hum Toxicol, 2000 Apr, 42(2), 90 - 1
The futility of hemoperfusion and hemodialysis in Amanita phalloides poisoning; Mullins ME et al.; Amanita phalloides mushrooms are extremely toxic . A variety of treatments have been proposed based as often on anecdotal experience as on firm evidence . General consensus exists regarding some treatments, such as the use of silibinin, penicillin, and activated charcoal . The most polarized debate concerns the value of extracorporeal elimination . We describe a case of 2 adults with confirmed Amanita phalloides poisoning treated with hemodialysis (HD) immediately after arrival at our tertiary care hospital (23 h after ingestion) and later with hemoperfusion (HP); a series blood samples were taken to determine the clearance of the toxin by each method . No amatoxin was detected before treatment, after treatment, or in the HD/HP circuits . Neither HD nor HP contributed to the clearance of amatoxin.

J Biol Chem, 2000 May 19, 275(20), 14964 - 8
Design of potent beta-lactamase inhibitors by phage display of beta-lactamase inhibitory protein; Huang W et al.; Beta-lactamase inhibitory protein (BLIP) binds tightly to several beta-lactamases including TEM-1 beta-lactamase (K(i) 0.1 nm) . The TEM-1 beta-lactamase/BLIP co-crystal structure indicates that two turn regions in BLIP insert into the active site of beta-lactamase to block the binding of beta-lactam antibiotics . Residues from each turn, Asp(49) and Phe(142), mimic interactions made by penicillin G when bound in the beta-lactamase active site . Phage display was used to determine which residues within the turn regions of BLIP are critical for binding TEM-1 beta-lactamase . The sequences of a set of functional mutants from each library indicated that a few sequence types were predominant . These BLIP mutants exhibited K(i) values for beta-lactamase inhibition ranging from 0.01 to 0.2 nm . The results indicate that even though BLIP is a potent inhibitor of TEM-1 beta-lactamase, the wild-type sequence of the active site binding region is not optimal and that derivatives of BLIP that bind beta-lactamase extremely tightly can be obtained . Importantly, all of the tight binding BLIP mutants have sequences that would be predicted theoretically to form turn structures.

Analyst, 1999 Nov, 124(11), 1605 - 10
Automated stand-alone flow injection immunoanalysis system for the determination of cephalexin in milk; Meyer UJ et al.; A fully automated stand-alone flow injection immunoanalysis (FIIA) device for the determination of cephalexin in milk is developed with a main focus on the investigation of the influence of the sample matrix . The system is based on principles of flow-through immunoassays and on sequential addition of the assay components to an immunoreactor . Protein G is immobilised on the surface of the immunoreactor serving as affinity matrix for the polyclonal anti-cephalexin antibodies . A cephalexin-alkaline phosphatase conjugate is mixed with the analyte-containing sample and binds in a competitve manner to the corresponding antibodies in the immunoreactor . After substrate addition enzymatically generated p-aminophenol is detected at a carbon electrode at +150 mV vs . Ag/AgCl . One assay cycle takes 16 min including regeneration of the immunoreactor . The large excess of protein G allows for more than 150 regenerations without significant loss of signal height . Due to the high specificity of the anti-cephalexin antibodies, other beta-lactam antibiotics like penicillin, amoxicillin and cloxacillin do not interfere in the measurements, even when added at 10 mg l-1 . To deactivate alkaline phosphatase present in milk, samples are heat-treated for 3 min prior to measurements . Cephalexin recoveries from two milk samples are 90 and 110% . The detection limit in milk is 1 microgram l-1 (mean relative standard deviation of 3%), less than the maximum residue level of 4 micrograms per kg milk fixed for some beta-lactam antibiotics in the European Union . The device is suitable for fast quantitative data generation from consecutively measured samples and thus adds to analytical screening methods.

Biotechnol Bioeng, 2000 May 5, 68(3), 245 - 51
Growth-rate-independent production of recombinant glucoamylase by Fusarium venenatum JeRS 325; Wiebe MG et al.; Most recombinant proteins generated in filamentous fungi are produced in fed-batch cultures, in which specific growth rate normally decreases progressively with time . Because of this, such cultures are more suited to the production of products that are produced efficiently at low-growth rates (e.g., penicillin) than to products which are produced more efficiently at high-growth rates (e . g., glucoamylase) . Fusarium venenatum A3/5 has been transformed (JeRS 325) to produce Aspergillus niger glucoamylase (GAM) under the control of the Fusarium oxysporum trypsin-like protease promoter . No glucoamylase was detected in the culture supernatant during exponential growth of F . venenatum JeRS 325 in batch culture . In glucose-limited chemostat cultures, GAM concentration increased with decrease in dilution rate, but the specific production rate of GAM (g GAM {g biomass}(-1) h(-1)) remained approximately constant over the dilution-rate range 0.05 h to 0.19 h(-1), i.e., the recombinant protein was produced in a growth-rate-independent manner . The specific production rate decreased at dilution rates of 0.04 h(-1) and below . Specific production rates of 5.8 mg and 4.0 mg GAM {g biomass}(-1) h(-1) were observed in glucose-limited chemostat cultures in the presence and absence of 1 g mycological peptone L(-1) . Compared to production in batch culture, and for the same final volume of medium, there was no increase in glucoamylase production when cultures were grown in fed-batch culture . The results suggested that a chemostat operated at a slow dilution rate would be the most productive culture system for enzyme production under this trypsin-like promoter .

J Chromatogr B Biomed Sci Appl, 2000 Feb 28, 739(1), 63 - 72
Preparation, evaluation and application of new pseudo-affinity chromatographic supports for penicillin acylase purification; Santarelli X et al.; New pseudo-affinity chromatographic supports for penicillin acylase were prepared and evaluated with three different samples: pure penicillin acylase, industrial clarified feedstock and crude extract . The different gels were studied for their purification fold (three to six) and their recovery power (80-100%) . The best support was characterized by its dynamic capacity, (20 mg/ml) and its recovery power was tested at five flow-rates (30, 150, 300 and 750 cm/h) to determine the optimal flow-rate (300 cm/h) . In addition we used cleaning in place to test the resistance to hard conditions of sanitization by 1 M NaOH (90% of recovery for 12 h of contact) . These gels may therefore be used on an industrial scale.

Cutis, 2000 Mar, 65(3), 163 - 6
Azithromycin eruption in infectious mononucleosis: a proposed mechanism of interaction; Schissel DJ et al.; The penicillin family of antibiotics may induce drug eruptions when prescribed to patients with infectious mononucleosis . Very similar phenomena have also been cited with other antibiotic families . We report the first case of a cutaneous reaction in a patient with infectious mononucleosis treated with azithromycin . We propose an immune-based hypothesis to explain the transient sensitivity resulting in this secondary cutaneous eruption.

Int J Infect Dis, 2000, 4(2), 70 - 4
Amoxicillin for fever and sore throat due to non-exudative pharyngotonsillitis: beneficial or harmful?
Leelarasamee A, Leowattana W, Tobunluepop P, Chub-upakarn S, Artavetakun W, Jarupoonphol V, Varangphongsri K, Leelarasamee I.
OBJECTIVES: To determine duration of signs and symptoms and adverse reactions after treatment with amoxicillin of patients with fever and sore throat due to non-exudative pharyngotonsillitis . DESIGN: This was a randomized, double-blinded, placebo-controlled trial . Outpatients at four medical centers were enrolled . Patients over 5 years of age presented with fever and sore throat for less than 10 days due to non-exudative pharyngotonsillitis . Cases with any of the following symptoms or illness were excluded: earache, nasal discharge with foul smell, rheumatic fever, valvular heart disease, renal disease, and penicillin hypersensitivity . Amoxicillin or identical placebo at the dosage of 50 mg/ kg per day was given three or four times daily for 7 days . RESULTS: There were 1217 patients enrolled in this study . Some were lost to follow-up, which is the reason for the variability in number of cases in these analyses . After therapy, duration of fever was 2.46 and 2.48 days (P = 0.78) and of sore throat 3.01 and 3.04 days (P = 0.80) in amoxicillin (n = 431) and placebo (n = 436) groups, respectively . Complications were clinically documented in 13 (2.5%) and 16 (3.0%) cases in amoxicillin (n = 527) and placebo (n = 524) groups (P = 0.56) . Two cases (0.46% and 0.46%) from each group (n= 433 and 431) were positive by antistreptolysin O antibody determination . The history of carditis and abnormal urinalysis after treatment were not obtained . CONCLUSIONS: Amoxicillin therapy for non-exudative pharyngotonsillitis conferred no beneficial or harmful effect.

J Postgrad Med, 1999 Apr-Jun, 45(2), 58 - 9
Benzathine penicillin induced immune haemolytic anaemia; Tullu MS et al.; Penicillin-induced immune haemolytic anaemia is very rare . A ten year-old-female with rheumatic mitral stenosis on benzathine penicillin prophylaxis presented with features of haemolytic anaemia and investigations supported the diagnosis of immune haemolytic anaemia . Patient responded to discontinuation of the drug and therapy with oral prednisolone . This is first such case reported from India.

J Clin Gastroenterol, 2000 Mar, 30(2), 144 - 54
Gastrointestinal manifestations of Behcet's disease; Bayraktar Y et al.; Behcet's disease (BD) is a multisystem, chronic, relapsing vasculitis of unknown origin that affects nearly all organs and systems . While recurrent oral ulcerations are a "sine qua non" of BD, the frequency of extra-oral parts of the gastrointestinal involvement varies widely in different countries . The most frequent extra-oral sites of gastrointestinal involvement are the ileocecal region and the colon . The liver (except with Budd-Chiari syndrome), pancreas, and spleen are rarely involved . The symptoms associated with these extra-oral manifestations of BD are abdominal pain, nausea, vomiting, diarrhea with or without blood, and constipation . The lesions typically are resistant to medical treatment and frequently recur with surgical treatment . We review the literature regarding the gastrointestinal and hepatobiliary systems in BD . Also, we present a patient who had BD complicated with radiologically-proven hepatic veins involvement (Budd-Chiari syndrome) and complete occlusion of hepatic portion of inferior vena cava and who had a good response to colchicine and penicillin treatment.

Clin Infect Dis, 2000 Mar, 30(3), 540 - 4
A pilot study evaluating ceftriaxone and penicillin G as treatment agents for neurosyphilis in human immunodeficiency virus-infected individuals; Marra CM et al.; To compare intravenous (iv) ceftriaxone and penicillin G as therapy for neurosyphilis, blood and CSF were collected before and 14-26 weeks after therapy from 30 subjects infected with human immunodeficiency virus (HIV)-1 who had (1) rapid plasma reagin (RPR) test titers >/=1&rcolon;16, (2) reactive serum treponemal tests, and (3) either reactive CSF-Venereal Disease Research Laboratory (VDRL) tests or CSF abnormalities: (a) CSF WBC values >/=20/microL or (b) CSF protein values >/=50 mg/dL . At baseline, more ceftriaxone recipients had skin symptoms and signs (6 {43%} of 14 vs . 1 {6%} of 16; P=.03), and more penicillin recipients had a history of neurosyphilis (7 {44%} of 16 vs . 1 {7%} of 14; P=.04) . There was no difference in the proportion of subjects in each group whose CSF measures improved . Significantly more ceftriaxone recipients had a decline in serum RPR titers (8 {80%} of 10 vs . 2 {13%} of 15; P= . 003), even after controlling for baseline RPR titer, skin symptoms and signs, or prior neurosyphilis were controlled for . Differences in the 2 groups limit comparisons between them . However, iv ceftriaxone may be an alternative to penicillin for treatment of HIV-infected patients with neurosyphilis and concomitant early syphilis.

Clin Infect Dis, 2000 Mar, 30(3), 520 - 8
Impact of penicillin susceptibility on medical outcomes for adult patients with bacteremic pneumococcal pneumonia; Metlay JP et al.; The impact of penicillin susceptibility on medical outcomes for adult patients with bacteremic pneumococcal pneumonia was evaluated in a retrospective cohort study conducted during population-based surveillance for invasive pneumococcal disease in the greater Atlanta region during 1994 . Of the 192 study patients, 44 (23%) were infected with pneumococcal strains that demonstrated some degree of penicillin nonsusceptibility . Compared with patients infected with penicillin-susceptible pneumococcal strains, patients whose isolates were nonsusceptible had a significantly greater risk of in-hospital death due to pneumonia (relative risk {RR}, 2.1; 95% confidence interval {CI}, 1-4.3) and suppurative complications of infection (RR, 4.5; 95% CI, 1-19.3), although only risk of suppurative complications remained statistically significant after adjustment for baseline differences in severity of illness . Among adults with bacteremic pneumococcal pneumonia, infection with penicillin-nonsusceptible pneumococci is associated with an increased risk of adverse outcome.

Clin Infect Dis, 2000 Mar, 30(3), 479 - 85
Posterior uveitis in patients with positive serology for syphilis; Villanueva AV et al.; The clinical features and ophthalmologic findings of 20 patients with syphilitic posterior uveitis seen at the Detroit Medical Center from November 1993 through February 1996 were reviewed . The mean age was 58 years; 8 patients were male and 12 were female; and all patients were black . Three of 9 patients tested were HIV positive . Patients were divided into 2 groups: those with acute (8) and those with chronic (12) syphilitic posterior uveitis . Chorioretinitis was the predominant uveitic pattern (15/20) . Eighteen patients presented with blurred vision . All patients had reactive serum fluorescent treponemal antibody, absorbed (FTA-ABS); 3 had nonreactive rapid plasma reagin (RPR) . Mean RPR titer in the chronic uveitis group and in the acute uveitis group was 1:27.3 and 1:209.8, respectively . Seven patients had abnormal cerebrospinal fluid (CSF); CSF VDRL was reactive in 2 patients . All patients were treated with intravenous penicillin G . Eight of 14 patients seen at follow-up showed improvement of ophthalmologic findings . Syphilis should be considered in the differential diagnosis of posterior uveitis.

Clin Exp Allergy, 2000 Apr, 30(4), 590 - 5
Skin and laboratory tests in amoxicillin- and penicillin-induced morbilliform skin eruption; Schnyder B et al.; BACKGROUND: Cutaneous amoxicillin- and penicillin-mediated reactions can be classified as immediate and delayed-type reactions . Immediate reactions are thought to involve IgE antibodies and have been studied extensively . In contrast only few data exist about delayed reactions such as morbilliform or maculopapular rash . OBJECTIVE: To assess the predictive value of immediate skin tests, skin-patch tests, specific IgE and lymphocyte transformation tests with regard to the diagnosis of delayed skin eruptions . METHODS: Skin and in vitro tests were performed in 18 subjects . Twelve subjects had penicillin- or amoxicillin-induced morbilliform exanthema and six were controls without hypersensitivity reaction, tested before and after exposure . RESULTS: Specific IgE to penicillin and immediate penicillin skin tests were negative in amoxicillin- or penicillin-induced delayed skin eruptions . In contrast, skin-patch testing and LTT were positive in 9/12 or 10/12, respectively, but negative in all six controls . CONCLUSION: These findings substantiate a T-cell-mediated immune pathomechanism in the majority of penicillin-induced delayed skin reaction . Moreover, they underline the necessity to adapt the test procedures to underlying pathomechanisms and support the diagnostic value of skin-patch testing and LTT in delayed cutaneous reactions to penicillins.

J Mol Biol, 2000 Mar 24, 297(2), 395 - 408
Thioesterase domain of delta-(l-alpha-Aminoadipyl)-l-cysteinyl-d-valine synthetase: alteration of stereospecificity by site-directed mutagenesis; Kallow W et al.; The carboxy-terminal thioesterase domain of delta-(l-alpha-aminoadipyl)-l-cysteinyl-d-valine synthetase catalyzes the hydrolytic release of the tripeptide product (LLD-ACV) . By site-directed mutagenesis an S3599A change was introduced into the highly conserved GXSXG motif, resulting in a more than 95 % decrease of penicillin production . Purification of the modified multienzyme showed surprisingly only a 50 % reduction of the peptide formation rate, with the stereoisomer delta-(l-alpha-aminoadipyl)-l-cysteinyl-l-valine (LLL-ACV) as the dominating product . Thioesterases of ACV synthetases differ from other thioesterases integrated in non-ribosomal peptide synthetases in their direct association with an epimerase domain, and their respective GXSXG-seryl residue is apparently not essential in acyl transfer leading to peptide release . Instead, this motif may be involved in the control of tripeptide epimerization by selection of the isomer to be released, and the construct supports the presence of LLL-ACV as an intermediate in penicillin biosynthesis .

Am J Gastroenterol, 2000 Mar, 95(3), 641 - 5
A single drug for Helicobacter pylori infection: first results with a new bismuth triple monocapsule; de Boer WA et al.; OBJECTIVE: In this pilot study we investigated the efficacy and tolerability of a new monocapsule that contains a bismuth compound, tetracycline, and metronidazole . If proven to be effective, this monotherapy would turn the well-accepted multidrug regimen of standard bismuth-based triple therapy into an easy and more patient-friendly regimen . It can be used in patients allergic to penicillin . METHODS: A total of 53 consecutive H . pylori-infected patients (30 with proven ulcer disease, 23 with gastritis only) from a single center were prescribed two monocapsules q.i.d . after the three meals and after an evening snack during 10 days . Each capsule contained 60 mg colloidal bismuth subcitrate (as Bi2O3 equivalent), 125 mg tetracycline, and 125 mg metronidazole . Repeat endoscopy with biopsies for urease test, Giemsa stain, and culture was carried out > or =5 wk later . Side effect data were collected . RESULTS: One patient was lost to follow-up, two failed to respond, and 50 were cured . The intention-to-treat cure rate was 50 of 53 (94.4%, 95% CI 88.1-100%) . Antibiotic sensitivity was available from 51 isolates . The cure rate in the metronidazole sensitive strains was 44 of 45 (97.8%, 95% CI: 93.5-100%), whereas it was four of five in the resistant strains . The regimen was well tolerated, with only two drop-outs (4%) because of side effects . CONCLUSIONS: The new monocapsule is an inexpensive, well tolerated, and patient-friendly formulation of a bismuth based triple therapy . A 10-day course with this multidrug capsule reached a very high cure rate in metronidazole-sensitive strains . The number of cases with resistant strains was insufficient to allow firm conclusions about its efficacy in case of resistance . The results are in agreement with previous data with bismuth triple therapy using separate drugs . From the high cure rate, we can conclude that the new capsule dissolves adequately, with proper delivery of its ingredients at the site of action.

J Pharm Biomed Anal, 1999 Mar, 19(3-4), 633 - 8
Enzymatically modified ion-selective electrodes for flow injection analysis; Koncki R et al.; The application of potentiometric biosensors based on membrane ion-selective electrodes for flow injection analysis (FIA) is presented . The biosensors have been obtained by covalent binding of enzyme molecules directly to surface of ion-selective membranes . The biosensor/FIA systems enable the determination of urea and penicillin in the millimolar ranges of concentration . About 30 samples per hour can be analysed in the performed FIA systems . The operational stability of the bioanalytical systems exceeds 1 month.

Pediatr Int, 2000 Feb, 42(1), 71 - 5
Acute rheumatic fever in Konya, Turkey; Karaaslan S et al.; BACKGROUND: Patients with acute rheumatic fever (ARF), who were admitted to Pediatric Cardiology Unit of Selcuk University Faculty of Medicine from July 1993 to 1998, were studied retrospectively to verify the clinical profile of the disease and to compare the results with those from other countries . METHODS: All patients were examined by one of the two pediatric cardiologists in our study group . Every patient had a chest X-ray, electrocardiogram and an echocardiographic investigation . Throat culture, antistreptolysin O test, C-reactive protein and sedimentation rates were investigated for each patient . RESULTS: During the study period, 274 cases with ARF were identified among patients admitted to the present institution . There were 8032 visits during the study period, giving an occurrence rate of 3.4% . Arthritis was the most common major manifestation (81.4%) . It was followed by carditis (60.9%) and chorea (17.9%) . Subcutaneous nodules (0.7%) and erythema marginatum (0.4%) were both seen in patients with carditis . The mitral valve was the most commonly affected valve (95.8%), followed by the aortic valve (40.1%) . Two patients died and regurgitation disappeared in 21% of patients with mitral regurgitation . Fifteen patients (14%) with isolated arthritis and pure chorea had mitral regurgitation demonstrated by echocardiographic investigation but without any significant murmur . CONCLUSION: The present study indicates that ARF is still a significant problem in Konya and that recurrences can be prevented by administering a 3-week benzathine penicillin G regimen.

Lancet, 2000 Feb 19, 355(9204), 605 - 9
Interferon alfa-2b, colchicine, and benzathine penicillin versus colchicine and benzathine penicillin in Behçet's disease: a randomised trial; Demiroglu H et al.; BACKGROUND: Sight-threatening eye involvement is a serious complication of Behcet's disease . Extraocular complications such as arthritis, vascular occlusive disorders, mucocutaneous lesions, and central-nervous-system disease may lead to morbidity and even death . We designed a prospective study in newly diagnosed patients without previous eye disease to assess whether prevention of eye involvement and extraocular manifestations, and preservation of visual acuity are possible with combination treatments with and without interferon alfa-2b . METHODS: Patients were randomly assigned 3 million units interferon alfa-2b subcutaneously every other day for the first 6 months plus 1.5 mg colchicine orally daily and 1.2 million units benzathine penicillin intramuscularly every 3 weeks (n=67), or colchicine and benzathine penicillin alone (n=68) . The primary endpoint was visual-acuity loss . Analysis was by intention to treat . FINDINGS: Significantly fewer patients who were treated with interferon had eye involvement than did patients who did not receive interferon (eight vs 27, relative risk 0.21 {95% CI 0.09-0.50}, p<0.001) . Ocular attack rate was 0.2 (SD 0.62) per year with interferon therapy and 1.02 (1.13) without interferon therapy (p=0.0001) . Visual-acuity loss was significantly lower among patients treated with interferon than in those without interferon (two vs 13, relative risk 0.13 {95% CI 0.03-0.60}, p=0.003) . Arthritis episodes, vascular events, and mucocutaneous lesions were also less frequent in patients treated with interferon than in those not receiving interferon . No serious side-effects were reported . INTERPRETATION: Therapy with interferon alfa-2b, colchicine, and benzathine penicillin seems to be an effective regimen in Behcet's disease for the prevention of recurrent eye attacks and extraocular complications, and for the protection of vision.

Asian Pac J Allergy Immunol, 1999 Sep, 17(3), 137 - 41
The epidemiology of atopic dermatitis at a tertiary referral skin center in Singapore; Tay YK et al.; Atopic dermatitis is a common chronic, relapsing, pruritic ecematous skin condition with a predilection for the flexural areas and occurs in patients with a personal or family history of atopy . The aim of this study is to describe the profile of atopic dermatitis seen at the National Skin Centre in Singapore . A retrospective chart review was conducted of all the patients with atopic dermatitis seen during the first six months of 1994 . There were 492 patients whose ages ranged from one month to 74 years with an equal sex ratio . The prevalence was 2% . The onset of the disease occurred before the age of 10 years in 61.2% of patients . In 13.6% of the patients, the onset was after the age of 21 years . Two hundred and fifty-four patients (52%) had "pure" atopic dermatitis without concomitant respiratory allergies . Two hundred and thirty-eight patients (48%) suffered from a "mixed" type, with 23% having allergic rhinitis, 12% having asthma and 13% having both asthma and allergic rhinitis . Two hundred and thirty-one patients (47%) had at least one first-degree family member with atropy: atopic dermatitis (17%), asthma (15%) and allergic rhinitis (15%) . Most of the patients, 416 (84.5%), had subacute eczema at presentation . Ichthyosis vulgaris was present in 38 patients (8%) and pityriasis alba in 13 patients (3%) . The most common infective complication was bacterial infection (impetiginized eczema, folliculitis, cellullitis) present in 95 patients (19%) followed by viral infections (eczema herpeticum, viral warts and molluscum contagiosum) in 17 patients (3%) . Allergies were noted in 43 patients (9%) based on the history given . The most common was drug allergies (penicillin and co-trimoxazole) in 28 patients followed by food allergies in 11 patients . Common aggravating factors reported include heat, sweating, stress, thick clothing and grass intolerance . Most patients could be controlled with a fairly simple regimen of moisturizers, topical steroids and antibiotics for acute flares . Short courses of systemic steroids were used in 78 patients (16%) . Three patients were treated with phototherapy, Two on UVAB and one on PUVA . The pattern of atopic dermatitis in Singapore is similar to that reported in the Western literature except for a lower prevalence and a significant proportion of adult onset atopic dermatitis.

Southeast Asian J Trop Med Public Health, 1999 Mar, 30(1), 157 - 60
Fatal mushroom poisoning caused by Amanita virosa in Thailand; Chaiear K et al.; Consumption of toxic mushrooms belonging to the genus Amanita frequently leads to severe gastrointestinal distress followed by acute hepatic failure with a fatal outcome . In Thailand, valuable information as to the locally prevalent poisonous species, the preferred habitat and the management of suspected victims of intoxication is basically non-existent . We report here 5 cases of fatal poisoning with Amanita virosa having occurred in a family residing in the northeast of Thailand who as countless others had enjoyed mushroom gathering as a pasttime . Within 4 to 6 days after ingestion of the mushrooms, all had succumbed to acute hepatic failure with subsequent hepatoencephalopathy . Treatment modalities exist in the form of penicillin and silibinin, or thioctic acid administration followed by plasmapheresis . In cases taking a lethal course apparent from the results of liver biochemistry, liver transplantation is clearly indicated . In order to prevent mushroom poisoning altogether, educating the general population to that end certainly presents the method of choice.

Przegl Lek, 1999, 56(9), 566 - 7
{Modifications in treatment of tetanus and prognosis--observations from the Cracow Department of Infectious Diseases}; Garlicki A et al.; The assessment of modifications in the tetanus treatment, which included using metronidazol and midazolam instead penicillin and diazepam, was presented . According to our own observations and previous investigations, mentioned above changes in the tetanus therapy improve survival rate, reduce psychiatric disturbances and shorten hospitalisation time.

Br J Pharmacol, 2000 Jan, 129(2), 402 - 8
Modulation by bicuculline and penicillin of the block by t-butyl-bicyclo-phosphorothionate (TBPS) of GABA(A)-receptor mediated Cl(-)-current responses in rat striatal neurones; Behrends JC; 1 . T-butyl-bicyclo-phosphorothionate (TBPS) is a prototypical representative of the cage-convulsants which act through a use-dependent block of the GABA(A)-receptor-ionophore complex . Using current recordings from cultured neurones of rat striatum the manner was investigated in which two antagonists, bicuculline and penicillin, presumably acting at the agonist binding site and in the ionic channel, respectively, modify the rate of block by TBPS . 2 . Penicillin (5 or 10 mM) did not slow the rate of block by TBPS, but produced a significant enhancement of block rate, which, however, was inversely related to the degree of antagonism by penicillin of the GABA-induced current . 3 . Bicuculline (10 microM) reduced the rate of block by TBPS . However, this effect was 3 fold weaker than its GABA-antagonistic action . The slowing of block rate and the current antagonism exhibited a biphasic, positive-negative relationship . Co-application of bicuculline (100 microM) in a concentration that produced nearly complete antagonism and TBPS (10 microM) resulted in a marked ( approximately 40%) reduction of subsequent GABA response amplitudes compatible with a direct, bicuculline-induced conformational change in the receptor required for the binding of and block by TBPS . 4 . The lack of protection afforded by the channel blocker penicillin as well as the lack of correlation between bicuculline antagonism of the Cl(-)-current and its efficiency in protecting against TBPS block is evidence against an open channel blocking mechanism for TBPS . TBPS does, therefore, not appear to gain access to its binding site via the open pore but through alternative routes regulated from the agonist binding site.

J Bacteriol, 2000 Mar, 182(6), 1714 - 21
Penicillin binding protein 5 affects cell diameter, contour, and morphology of Escherichia coli; Nelson DE et al.; Although general physiological functions have been ascribed to the high-molecular-weight penicillin binding proteins (PBPs) of Escherichia coli, the low-molecular-weight PBPs have no well-defined biological roles . When we examined the morphology of a set of E . coli mutants lacking multiple PBPs, we observed that strains expressing active PBP 5 produced cells of normal shape, while mutants lacking PBP 5 produced cells with altered diameters, contours, and topological features . These morphological effects were visible in untreated cells, but the defects were exacerbated in cells forced to filament by inactivation of PBP 3 or FtsZ . After filamentation, cellular diameter varied erratically along the length of individual filaments and many filaments exhibited extensive branching . Also, in general, the mean diameter of cells lacking PBP 5 was significantly increased compared to that of cells from isogenic strains expressing active PBP 5 . Expression of cloned PBP 5 reversed the effects observed in DeltadacA mutants . Although deletion of PBP 5 was required for these phenotypes, the absence of additional PBPs magnified the effects . The greatest morphological alterations required that at least three PBPs in addition to PBP 5 be deleted from a single strain . In the extreme cases in which six or seven PBPs were deleted from a single mutant, cells and cell filaments expressing PBP 5 retained a normal morphology but cells and filaments lacking PBP 5 were aberrant . In no case did mutation of another PBP produce the same drastic morphological effects . We conclude that among the low-molecular-weight PBPs, PBP 5 plays a principle role in determining cell diameter, surface uniformity, and overall topology of the peptidoglycan sacculus.

Ann Trop Paediatr, 1999 Jun, 19(2), 161 - 5
Sydenham's chorea: risk factors and the role of prophylactic benzathine penicillin G in preventing recurrence; Gebremariam A; To determine the effect of prophylactic long-acting penicillin G in preventing recurrence of Sydenham's chorea and to discover the risk factors associated with occurrence of symptoms, 18 children with symptoms over a 5-year period were prospectively identified . Of these, ten were boys and eight were girls . The majority occurred between the ages of 8 and 10 years {mean (SD) 9.10 (2.62) years} . Sydenham's chorea was generalized in 14 children and one-sided in four . There was no difference in the incidence of right- and left-sided hemichorea . Among the risk factors examined, only a history of chorea in relatives had a significant association with the occurrence of Sydenham's chorea (OR = 6.39; 95% CI 1.30-31.3) . A comparison of recurrence between those given prophylactic long-acting penicillin G and those who had none showed a statistically significant difference in the recurrence experience between the two groups (p < 0.02).

Postgrad Med, 2000 Feb, 107(2), 181 - 4, 189-90, 193-7
Sexually transmitted diseases in women . Gonorrhea and syphilis; Emmert DH et al.; Gonorrhea has been declining since its 1975 peak . Risk factors include age 15 to 19 years, multiple or casual sexual contacts, sexual activity related to drug use, and low socioeconomic status . Infection is usually mild but may be asymptomatic . While no physical signs are specific to the gonococcus, pelvic inflammatory disease is a common complication and cause of infertility and should be treated if it is suspected . Diagnosis of gonorrhea is typically by culture . Newer, more accurate tests are available but are more expensive . For treatment, the CDC recommends only highly effective regimens . Patients need to refer recent sexual partners for treatment and abstain from sexual intercourse until completion of therapy and resolution of symptoms . The incidence of syphilis appears to be declining in the United States, but it should be considered if an ulcer is found in the genital region . If untreated, the disease progresses through primary, secondary, latent, and tertiary phases, and systemic symptoms can mimic other conditions . Positive standard screening tests should be confirmed by fluorescent treponemal antibody absorption testing . Darkfield microscopy is appropriate for diagnosis of an ulcer . The treatment of choice for all phases of syphilis is a single dose of intramuscular benzathine penicillin . Other components of therapy include partner notification and patient follow-up . The spread of HIV is closely linked to STD transmission . Therefore, testing for HIV is strongly encouraged when another STD has been diagnosed.

Enzyme Microb Technol, 2000 Feb 1, 26(2-4), 165 - 170
The relative importance of intracellular proteolysis and transport on the yield of the periplasmic enzyme penicillin amidase in Escherichia coli*
Ignatova Z, Enfors S, Hobbie M, Taruttis S, Vogt C, Kasche V V.
Intracellular proteolysis is an important mechanism for regulating the level of the periplasmic enzyme penicillin amidase in Escherichia coli . Evidence is presented that the active enzyme is localized in the periplasmic space and maturation of pro-enzyme occurs during transport through the cytoplasmic membrane or rapidly after its entrance in the periplasm . The rate constants of the transport through cytoplasmic membrane and of the intracellular proteolysis were estimated to be 0.01 h and 0.5 h, respectively . This indicates that more than 90% of the synthesized pre-pro-enzyme is lost by intracellular proteolysis occurring in the cytoplasm.

Enzyme Microb Technol, 2000 Feb 1, 26(2-4), 142 - 151
Enzymatic synthesis of cephalothin by penicillin G acylase*
Shaw S, Shyu J, Hsieh Y, Yeh H.
Enzymatic synthesis of cephalothin from 7-aminocephalosporanic acid (7-ACA) and amide derivatives of 2-thienylacetic acid (2-TA) using penicillin G acylase (pen G acylase) was studied . Two amide derivatives of 2-TA namely 2-thienylacetamide (2-TAA) and 2-thienylacetohydroxamic acid (2-TAH) were used in this study . The main reason for choosing amide but not the methyl ester derivative of 2-TA for the enzymatic synthesis was to increase their solubilities in water . The solubility of 2-TA methyl ester (2-TAM), 2-TAA, and 2-TAH in aqueous solution is 8 +/- 0.05 mM, 87 +/- 0.75 mM and 120 +/- 1.65 mM, respectively . Enzymatic conversion of 2-TAH to cephalothin yielded side products but they were not found in the conversion of 2-TAA to cephalothin . The side products were derived from reactions between hydroxyamine and 7-ACA . The effects of pH, temperature, initial substrate concentrations and reaction time on the conversion of 2-TAA and 7-ACA to cephalothin were examined . The optimum reaction condition was determined at pH 6.5 and 10 approximately 15 degrees C . The best conversion yield of 72% was obtained when the initial concentration of 2-TAA and 7-ACA was at 0.4 M and 0.1 M, respectively . Furthermore, a one-step method was developed to purify cephalothin from the enzymatic reaction mixture with the purity of 91% and the recovery yield of 96%.

J Am Vet Med Assoc, 2000 Feb 15, 216(4), 510 - 5
Types and doses of injectable medications given to periparturient sows; Straw BE et al.; OBJECTIVE: To determine types and doses of injectable medications given to periparturient sows and reasons for administering those medications, and to compare medication practices among farms of different sizes . DESIGN: Survey . SAMPLE POPULATION: 301 farms; 231,016 periparturient sows . PROCEDURE: A survey was used to obtain information regarding medications given to sows during the farrowing period . State and federal veterinary medical officers completed surveys during their final interview with producers who had participated in the National Animal Health Monitoring System's (NAHMS) Swine 95 study . Data were summarized and treatment regimens compared among farms of different sizes . RESULTS: More than a third of the sows received medications during the farrowing period . The most common reasons for administering medications were routine preventive treatment and treatment of dystocia, uterine discharge, and poor appetite . The most commonly used medications for treatment of sick sows were oxytocin, procaine penicillin G, and B vitamins . A high percentage of medications were either not indicated for the specific condition or used at greater or less than the approved dose . In general, treatment rates and medications used did not differ among farms of different sizes . CONCLUSIONS AND CLINICAL RELEVANCE: Better treatment protocols are needed to provide more appropriate treatment of sick sows.

Hua Xi Yi Ke Da Xue Xue Bao, 1997 Dec, 28(4), 383 - 7
{Antiepileptic effects of nimodipine on penicillin-induced seizures in rats}; Zou X et al.; Injecting penicillin (PNC) intraperitoneally in Wistar rats, we observed their epileptic behaviour and electroencephalographys . The results showed that nimodipine (NIM), a calcium antagonist, could inhibit the seizures and epileptic discharges significantly . No epileptic action was noted while NIM was injected before PNC . It supports our consideration of NIM as a new sort of nonsedative anticonvulsant in clinical practice.

Hua Xi Yi Ke Da Xue Xue Bao, 1997 Jun, 28(2), 136 - 9
{Alterations of substance P-immune reaction positive neurons of cerebral tissues in epileptic rats}; Zou X et al.; Employing the immunocytochemical analysis, we observed the alterations of Substance P-Immune Reaction (SP-IR) positive neurons of the cerebral cortex, hippocampus and amygdala in rats suffering from epilepsy induced by Penicillin (PEN) . The result showed that the number of neurons of epileptic group was higher than that of the control group and no significant change in the rumber of neurons was observed in the group in which PEN was given after injection of Nimodine . It indicates that SP and Ca2+ participate in the process of epileptogenesis.

Rapid Commun Mass Spectrom, 2000, 14(4), 195 - 202
Electrospray multistep ion trap mass spectrometry for the structural characterisation of poly
Adamus G, Kowalczuk M.
Electrospray 'soft' ionisation (ESI) and multistep mass spectrometry (MS(n)) techniques enable characterisation of a bioactive polymer, poly{(R,S)-3-hydroxybutanoic acid} (a-PHB), containing covalently bonded benzylpenicillin . The chemical structures of individual mass-selected bioactive macromolecules have been determined, and their fragmentation mechanisms have been compared with those of pure penicillin G .

Rev Fac Cien Med Univ Nac Cordoba, 1999, 56(1), 73 - 83
{Importance of the benzylpenicillin nucleus and the side chain of the beta-lactams . Demonstration by skin tests and RAST in penicillin allergic patients}; Muino JC et al.; We studied 30 patients with beta-Lactams allergy demonstrated by clinical findings . The aim of this work was to determine the capacity of the beta-Lactams nucleus and the side chain in the induction of specific IgE to BPO, Ax, Amp, performed by intradermal skin test and RAST . The patients were divided by clinical manifestations in: 1-Accelerated reactions (n:19); and 2-Immediate reactions (n:11) . The Prick tests were performed with BPO-PL, Ax-PL, Amp-PL, MDM-BP, MDM-Ax, MDM-Amp . The accelerated group presented BPO-PL (+) in 2 cases, Ax-PL & Amp-PL (+) in 4 cases, and all of the reactives were (+) in 13 out of 19 cases . The immediate group presented MDM-BP (+) in 10 out of 11 cases and MDM-Amp was (+) in 1 out of 11 cases . The RAST's were performed in all patients(n:30) . In accelerated group were (+) to BPO-PL in 13 out of 19 cases, to Ax-PL in 3 out of 19 cases, to Amp-PL in 1 out 19 cases, to BPO-PL and Ax-PL on overlap in 1 out of 19 cases, and 1 case was negative to all reactives . The immediate group presented RAST's negatives in 11 out of 11 cases . The control group(n:20) presented Prick (+) to Ax-PL in 1 out of 20 cases, and the others reactives were negatives in all cases . The RAST's to all reactives were (-) in 20 out of 20 subjects . These results indicate that BPO was the most important determinant, and the side chain of the Ax or Amp were others determinants of the beta-Lactams drugs . These determinants induced specific IgE, and in rare occasions appears specific IgE for two different determinants on overlap in the same patient . The intradermal skin testing is the method of choice to study the penicillin allergies, because non satisfactory RAST's have yet been developed for minor determinant-specific IgE antibodies.

Wien Klin Wochenschr, 1999 Dec 10, 111(22-23), 933 - 40
Erythema migrans in pregnancy; Maraspin V et al.; From 1990 through to 1997, 105 pregnant women with typical EM were investigated at the Lyme Borreliosis Outpatients' Clinic of the Department of Infectious Diseases at the University Medical Centre in Ljubljana, Slovenia . Twenty-five (23.8%) patients acquired borrelial infection during the first trimester of pregnancy; eight (7.6%) of them had noticed the skin lesion before they became pregnant . In 43 (40.6%) patients the EM appeared in the second trimester, and in 37 (35%) patients in the third trimester of pregnancy . Two (1.9%) patients received phenoxymethyl penicillin (1 million IU t.i.d.), three (2.9%) benzyl penicillin (10 million IU b.i.d.), and 100 (95.2%) ceftriaxone (2 g daily) . All patients were treated for 14 days except three (2.9%) in whom the treatment with ceftriaxone was discontinued because of mild side effects . The outcome of disease was good in all 105 patients . Ninety-three (88.6%) out of 105 patients had normal pregnancies; the infants were delivered at term, were clinically healthy, and subsequently had a normal psychomotor development . In the remaining 12 (11.4%) patients an adverse outcome was observed . Two (1.9%) pregnancies ended with an abortion (one missed abortion at 9 weeks, one spontaneous abortion at 10 weeks), and six (5.7%) with preterm birth . One of the preterm babies had cardiac abnormalities and two died shortly after birth . Four (3.8%) babies born at term were found to have congenital anomalies; one had syndactyly at birth and three had urologic abnormalities which were registered at the age of 5, 7, and 10 months, respectively . A causal association with borrelial infection was not proven in any infant . For at least some unfavourable outcomes a plausible explanation not associated with Lyme borreliosis was found.

Folia Microbiol (Praha), 1999, 44(3), 263 - 6
Indigenous plasmids in a production line of strains for penicillin G acylase derived from Escherichia coli W; Sobotkova L et al.; Three indigenous plasmids designated pRK1, pRK2 and pRK3 were identified among producers of penicillin G acylase (PGA) derived from the strain Escherichia coli W ATCC 9637 . Their size and copy number (CN) in E . coli W were determined (kb; CN): pRK1 (80; 3.4), pRK2 (5.1; 71), and pRK3 (4.8; 13.7) . Strain E . coli RE2 harboring these plasmids was used for selection of strains with reduced number of plasmids: the strain RE3 without plasmid pRK1 and the plasmid-less strain cERE3 were isolated . Indigenous plasmids did not code for the resistance determinants against 23 antibiotics and 10 heavy metals.

J Biol Chem, 2000 Feb 11, 275(6), 4507 - 12
Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta; Cha SH et al.; A cDNA encoding a novel multispecific organic anion transporter, OAT4, was isolated from a human kidney cDNA library . The OAT4 cDNA consisted of 2210 base pairs that encoded a 550-amino acid residue protein with 12 putative membrane-spanning domains . The amino acid sequence of OAT4 showed 38 to 44% identity to those of other members of the OAT family . Northern blot analysis revealed that OAT4 mRNA is abundantly expressed in the placenta as well as in the kidney . When expressed in Xenopus oocytes, OAT4 mediated the high affinity transport of estrone sulfate (K(m) = 1.01 microM) and dehydroepiandrosterone sulfate (K(m) = 0.63 microM) in a sodium-independent manner . OAT4 also mediated the transport of ochratoxin A . OAT4-mediated transport of estrone sulfate was inhibited by several sulfate conjugates, such as p-nitrophenyl sulfate, alpha-naphthyl sulfate, beta-estradiol sulfate, and 4-methylumbelliferyl sulfate . By contrast, glucuronide conjugates showed little or no inhibitory effect on the OAT4-mediated transport of estrone sulfate . OAT4 interacted with chemically heterogeneous anionic compounds, such as nonsteroidal anti-inflammatory drugs, diuretics, sulfobromophthalein, penicillin G, and bile salts, whereas tetraethylammonium, an organic cation, did not . OAT4 is the first member of the multispecific organic anion transporter family, which is expressed abundantly in the placenta . OAT4 might be responsible for the elimination and detoxification of harmful anionic substances from the fetus.

Ann Trop Med Parasitol, 1999 Jun, 93(4), 367 - 77
A double-blind, placebo-controlled study of the efficacy of oral penicillin, diethylcarbamazine or local treatment of the affected limb in preventing acute adenolymphangitis in lymphoedema caused by brugian filariasis; Shenoy RK et al.; Acute attacks of adenolymphangitis (ADL) contribute significantly to the morbidity seen in cases of filarial lymphoedema . Such cases are now being treated with multiple courses of the antifilarial drug diethylcarbamazine (DEC), either alone or in combination with antibiotics or anti-inflammatory drugs, based on anecdotal experience . In this, the first double-blind, placebo-controlled study, 150 patients with lymphoedema caused by brugian filariasis, each of whom recalled two or more ADL attacks in the previous year, were enrolled on a comprehensive foot-care programme . Each was also randomly allocated to one of the following five daily regimens (30 patients/regimen) for 1 year: 800 mg oral penicillin; 1 mg DEC/kg; 800 mg oral penicillin plus 1 mg DEC/kg; local antibiotics; or placebo . Each patient was followed up for another year . For each regimen group (including the placebo group), the number of ADL attacks in the treatment year was significantly less than that in the year prior to treatment (P < 0.001) . Although, in all but the placebo group, there was a slight increase in the number of episodes in the follow-up year compared with the treatment year, the increase was only significant in the two groups given penicillin . Of all the treatments tested therefore, foot care seems to play the most important role in the prevention of ADL attacks . Additional benefit may accrue from local or systemic antibiotic use in those with high grades of oedema, but antifilarials have no place in the prevention of ADL attacks in an individual patient . These observations should help in the rational management and prevention of ADL attacks in filarial lymphoedema, so that the progression of the disease may be halted and morbidity reduced.

Appl Biochem Biotechnol, 1999 Sep, 81(3), 145 - 52
Further studies on the bioconversion of penicillin G into deacetoxycephalosporin G by resting cells of Streptomyces clavuligerus NP-1; Baez-Vasquez MA et al.; Resting cells of Streptomyces clavuligerus NP-1, which possess deacetoxycephalosporin C synthase activity, have been shown previously to perform oxidative ring expansion of penicillin G in the presence of iron, ascorbic acid, and alpha-ketoglutaric acid to form deacetoxycephalosporin G . Further studies on this bioconversion indicated that use of MOPS or HEPES buffer at pH 6.5 more than doubled the extent of the reaction observed with the previously used Tris-HCl at pH 7.4 . Levels of bioconversion as high as 16.5% were achieved at low penicillin G concentrations . Previously, conversion yields were < 1%.

Rheumatol Int, 1999, 19(1-2), 51 - 7
Musculoskeletal manifestations with panniculitis--a hospital based study on 62 patients in Kuwait; Malaviya AN et al.; The study describes 62 patients seen over a period of 4 years mainly presenting with an acute inflammatory ankle arthritis/periarthritis associated with panniculitis . Based upon the clinical characteristics of panniculitis two distinct categories could be defined . These included patients with characteristic lesions of erythema nodosum, seen in 51 (82%), the idiopathic form in 29 (57%), and secondary EN in 22 (43%) . Associated conditions included Behcet's disease, oral contraceptive pills, pregnancy and penicillin treatment . Patients clinically not having typical EN was seen in 11 (18%) . In this group the histopathology showed erythema induratum in 4, cutaneous-polyarteritis nodosa with minimal panniculitis in 3, Weber-Christian disease, cytophagic histiocytic panniculitis, and 'mixed' lobular and septal variety of panniculitis in 1 each . (In 1 patient the disease was not panniculitis but cutaneous variant of granuloma annulare) . It is concluded that in a hospital setting EN associated with acute musculoskeletal symptoms, mainly ankle arthritis/periarthritis or an acute peripheral polyarthritis, was a common rheumatological problem in Kuwait . However, other forms of panniculitides also presented with musculoskeletal manifestations requiring accurate histopathological diagnosis for appropriate treatment.

J Biol Chem, 2000 Jan 28, 275(4), 2423 - 30
A novel heptameric sequence (TTAGTAA) is the binding site for a protein required for high level expression of pcbAB, the first gene of the penicillin biosynthesis in Penicillium chrysogenum; Kosalkova K et al.; The first two genes pcbAB and pcbC of the penicillin biosynthesis pathway are expressed from a 1.01-kilobase bidirectional promoter region . A series of sequential deletions were made in the pcbAB promoter region, and the constructions with the modified promoters coupled to the lacZ reporter gene were introduced as single copies at the pyrG locus in Penicillium chrysogenum npe10 . Three regions, boxes A, B, and C, produced a significant decrease in expression of the reporter gene when deleted . Protein-DNA complexes were observed by using the electrophoretic mobility shift assay with boxes A and B (complexes AG1, BG1, BG2, and BL1) but not with box C . Uracil interference assay showed that a protein in P . chrysogenum cell extracts interacts with the thymines in a palindromic heptanucleotide TTAGTAA . Point mutations and deletion of the entire TTAGTAA sequence supported the involvement of this sequence in the binding of a transcriptional activator named penicillin transcriptional activator 1 (PTA1) . In vivo studies using constructions carrying point mutations in the TTAGTAA sequence (or a deletion of the complete heptanucleotide) confirmed that this intact sequence is required for high level expression of the pcbAB gene . The TTAGTAA sequence resembles the target sequence of BAS2 (PHO2), a factor required for expression of several genes in yeasts.

Appl Microbiol Biotechnol, 1999 Dec, 53(1), 81 - 4
Enhanced production of penicillin V acylase from Streptomyces lavendulae; Torres R et al.; A 28 degrees C, Streptomyces lavendulae produced high levels of penicillin V acylase (178 IU/l of culture) when grown on skim milk as the sole nutrient source for 275 h . The enzyme showed catabolite repression by glucose and was produced in the stationary phase of growth . Penicillin V was a good inducer of penicillin V acylase formation, while phenoxyacetic acid, the side-chain moiety of penicillin V, did not alter enzyme production significantly . The enzyme was stable between pH 6 and 11 and at temperatures from 20 degrees C to 55 degrees C . This extracellular enzyme was able to hydrolyse natural penicillins and unable to hydrolyse penicillin G.

Epilepsy Res, 2000 Feb, 38(2-3), 217 - 29
Early magnetic field changes preceding the intracortical penicillin induced spikes; Zwiener U et al.; Events preceding interictal activity were studied using a combination of magnetoencephalography (MEG), electrocorticography (ECoG), and intracortical field potential recordings in rabbits . We measured MEG signals simultaneously with ECoG before and during interictal discharges induced by penicillin injected in the cortex (group 1: n = 12, medial cortex, regio retrosplenialis granularis; group 2: n = 4, cortical convexity, regio retrosplenialis agranularis; control group: n = 5); in group 3 (n = 12) a 16-channel depth electrode array was used to calculate the current source density in the cortical area exhibiting interictal epileptiform discharges . The modified Z-parameter as a lumped measure of magnetic field pattern changes and the global field power as a lumped measure of changes of field amplitude differences were calculated . In almost all recordings of both group 1 and 2, the Z-parameter of intra-individual MEG data became significantly larger than the control condition before the earliest change of the interictal spike recorded at the penicillin injection site (20-310 ms earlier, median: 91 ms, n = 151) . The increase in Z-parameter in averaged MEG data of group 1 was significantly correlated with time as early as 790 ms before the spike (Pearson correlation coefficient, P < 0.05) . After the start of the early increase of the Z-parameter, the global field power also began to increase before the ECoG spike . These results suggest a prespike field recruitment nearly 1 s before an interictal spike.

West Indian Med J, 1999 Dec, 48(4), 242 - 3
The prophylaxis of acute rheumatic fever in a pair of monozygotic twins . The public health implications; Denbow CE et al.; Recurrent acute rheumatic fever and rheumatic heart disease can be prevented by antibiotic intervention . We report the case of genetically identical twins, one of whom had overt rheumatic fever, received penicillin prophylaxis and did not have rheumatic heart disease . The other must have had inapparent rheumatic fever, received no chemotherapy prophylaxis and proceeded to develop rheumatic heart disease . A greater clinical and laboratory vigilance is required for the diagnosis of acute rheumatic fever in the asymptomatic identical twin of a patient with rheumatic fever . This case provides further evidence of a genetic predisposition to rheumatic fever and demonstrates the continued value of penicillin in the prophylaxis of acute rheumatic fever . It emphasises the need to maintain the integrity of preventive programmes against rheumatic fever worldwide . Studies which explore the HLA and other genetic linkages with rheumatic fever should be encouraged.

J Indian Med Assoc, 1999 Dec, 97(12), 489 - 92
Rheumatic fever in children; Bavdekar SB et al.; Rheumatic fever (RF) and rheumatic heart disease (RHD) are major public health problems in developing countries . A prospective study carried out in a large general hospital showed that carditis was the predominant feature in first attack and also the recurrence of RF but that recurrence was associated with more severe manifestations . Echocardiography picked up cases of subclinical carditis . Presence of congestive cardiac failure in association with carditis always led to chronic RHD . Recurrence occurred only when patient defaulted penicillin prophylaxis . The overall recurrence rate was 0.026 per patient.

Am J Hematol, 2000 Feb, 63(2), 68 - 73
Splenic function in sickle cell anemia patients in Qatif, Saudi Arabia; Al-Jam'a AH et al.; A prospective study was conducted to study the splenic function among sickle cell anemia (SCA) patients in Qatif (Eastern Province of Saudi Arabia) . Seventy-seven patients (30 children and 47 adults aged 2-57 years) were included . (99m)Tc stannous colloid liver-spleen scan was done for each patient during steady state . The splenic function was graded from 0 to 4 in relation to liver uptake . Seventy percent of our patients showed evidence of splenic hypofunction, and most of them (83%) had severe hyposplenism . Up to the age of 4 years, only 17% of the children showed evidence of functional hyposplenism, but by the age of 10 years >50% were hyposplenic . Most of the hyposplenic children had functional hyposplenism, whereas only one-third of hyposplenic adults had autosplenectomy . There was no effect of level of HbF on the frequency of hyposplenism, but on the other hand low MCV seems to be protective against hyposplenism . A significant number of adult SCA patients have clinically enlarged spleens, and almost a third have normally functioning spleens . Because of the low prevalence of hyposplenism in children younger than 4 years of age, routine penicillin prophylaxis is probably not indicated in this population, an issue which needs further evaluation .

J Mol Biol, 2000 Jan 21, 295(3), 527 - 40
Selection of beta-lactamases and penicillin binding mutants from a library of phage displayed TEM-1 beta-lactamase randomly mutated in the active site omega-loop; Vanwetswinkel S et al.; A combinatorial library of mutants of the phage displayed TEM-1 lactamase was generated in the region encompassing residues 163 to 171 of the active site Omega-loop . Two in vitro selection protocols were designed to extract from the library phage-enzymes characterised by a fast acylation by benzyl-penicillin (PenG) to yield either stable or very unstable acyl-enzymes . The critical step of the selections was the kinetically controlled labelling of the phages by reaction with either a biotinylated penicillin derivative or a biotinylated penicillin sulfone, i.e . a beta-lactamase suicide substrate; the biotinylated phages were recovered by panning on immobilised streptavidin . As labelling with biotinylated suicide substrates tends to select enzymes that do not turnover, a counter-selection against penicillin binding mutants was introduced to extract the beta-lactamases . The selected phage-enzymes were characterised by sequencing to identify conserved residues and by kinetic analysis of the reaction with benzyl-penicillin . Several penicillin binding mutants, in which the essential Glu166 is replaced by Asn, were shown to be acylated very fast by PenG, the acylation being characterised by biphasic kinetics . These data are interpreted by a kinetic scheme in which the enzymes exist in two interconvertible conformations . The rate constant of the conformational change suggests that it involves an isomerisation of the peptide bond between residues 166 and 167 and controls a conformation of the Omega-loop compatible with fast acylation of the active site serine residue .

Anesth Analg, 2000 Jan, 90(1), 142 - 7
The anticonvulsant effects of volatile anesthetics on penicillin-induced status epilepticus in cats; Murao K et al.; Volatile anesthetics may be used to treat status epilepticus when conventional drugs are ineffective . We studied 30 cats to compare the inhibitory effects of sevoflurane, isoflurane, and halothane on penicillin-induced status epilepticus . Anesthesia was induced and maintained with one of the three volatile anesthetics in oxygen . Penicillin G was injected into the cisterna magna, and the volatile anesthetic discontinued . Once status epilepticus was induced (convulsive period), the animal was reanesthetized with 0.6 minimum alveolar anesthetic concentration (MAC) of the volatile anesthetic for 30 min, then with 1.5 MAC for the next 30 min . Electroencephalogram and multiunit activity in the midbrain reticular formation were recorded . At 0.6 MAC, all anesthetics showed anticonvulsant effects . Isoflurane and halothane each abolished the repetitive spike phase in one cat; isoflurane reduced the occupancy of the repetitive spike phase (to 27%+/-22% of the convulsive period (mean +/- SD) significantly more than sevoflurane (60%+/-29%; P < 0.05) and halothane (61%+/-24%; P < 0.05), and the increase of midbrain reticular formation with repetitive spikes was reduced by all volatile anesthetics . The repetitive spikes were abolished by 1.5 MAC of the anesthetics: in 9 of 10 cats by sevoflurane, in 9 of 9 cats by isoflurane, and in 9 of 11 cats by halothane . In conclusion, isoflurane, sevoflurane, and halothane inhibited penicillin-induced status epilepticus, but isoflurane was the most potent . IMPLICATIONS: Convulsive status epilepticus is an emergency state and requires immediate suppression of clinical and electrical seizures, but conventional drugs may be ineffective . In such cases, general anesthesia may be effective . In the present study, we suggest that isoflurane is preferable to halothane and sevoflurane to suppress sustained seizure.

Srp Arh Celok Lek, 1999 Jul-Aug, 127(7-8), 236 - 40
{Clinical characteristics and therapy of neurosyphilis in patients who are negative for human immunodeficiency virus}; Pavlovic DM et al.; INTRODUCTION: Neurosyphilis is still a significant medical problem in developing countries and its occurrence in HIV infection is the reason for a growing number of new cases in developed countries {1-4} . Personality changes are the commonest symptom of late neurosyphilis {5} . Neurologic deficits are usually due to syphilitic vasculitis with lacunar infarctions {6} . The laboratory confirmation of neurosyphilis must depend on a cluster of tests (Venereal Disease Research Laboratories--VDRL; Fluorescent Treponemal Antibody-Absorption--FTA-ABS; Treponema Pallidum Immobilization--TPI or Nelson-Mayer) . The diagnosis of active neurosyphilis also requires an inflammatory cerebrospinal fluid (CSF) test {4} . METHODS: A retrospective study of hospitalized neurosyphilitic patients at the Institute of Neurology, Belgrade, Serbia, was carried out . Between 1990 and 1996 seven cases were found: five males and two females, aged from 22 to 66 years, mean 56 years . All were in tertiary stage and HIV negative . None of them reported previous veneral disease and only one reported meningitis . In all patients neurological examination, VDRL and TPI in blood and CSF, CT or MRI of the brain, Mini Mental State (MMS) test {11} and psychiatric evaluation were performed . To patients with active disease 24 million units of crystalline penicillin were administered, in divided daily doses in continuous intravenous infusions for three weeks . RESULTS: Symptoms . Five patients (71%) had gait disturbances, four (57%) headache, three (43%) hearing loss, speech complaints, forgetfulness, mood changes, and two (29%) seizures and stroke-like episodes . Malaise, diplopia, visual loss, vertigo, loss of sphincter control and paresthesia were noticed in one patient (14%) . Neurologic findings . Five patients (71%) had pupillary changes . In four (57%) of them we found hemiparesis, gait disturbances and signs of cerebellar involvement, in three (43%) hearing loss, dysarthria, paraparesis, hypesthesia for light touch, mood disorders (depression in two, hypomania in one), mild cognitive decline and tremor of the tongue and hands . Lesion of the second and the sixth cranial nerve, position sense and positive release signs were recorded in one patient (14%) . Gonarthrotic changes were observed in two (29%) patients . Cerebrospinal fluid . Elevated cell count and high protein level were detected in four (57%) patients . Three had also positive oligoclonal bands . Serological tests . In six patients (86%) serological tests for syphilis were positive (VDRL and/or Nelson-Mayer Test) in serum and in three (43%) in CSF . Results in one patient were negative both regarding serum and CSF, as he was treated for secondary syphilis in his twenties (now 65 years old) presumably as a "burnt out" case with neurologic sequelae . Neuroimaging . CT and MRI of the brain showed cortical and subcortical reduction in the brain parenchyma in four (57%) and multiischaemic changes in two (29%) patients . Therapy . Crystalline penicillin was administered to five patients with no side effects . Improvement of mood and cognitive status were noted in three patients, improvement of neurologic status in two subjects and arrest of progression in two patients . DISCUSSION: None of our patients reported previous venereal disease . They complained of impaired gait, headache, hearing loss, speech difficulties, forgetfulness, and mood changes . Pupillary changes, hemiparesis, gait disturbances and cerebellar signs, hearing loss, dysarthria, paraparesis, hypesthesia, mood disorders, mild cognitive decline and tremor of the tongue and hands were found during the examination . Pupillary signs are the most important symptoms because they can point to neurosyphilis . A two-step approach is recommended for establishing the diagnosis of syphilis with simple nontreponemal tests for screening purpose, and specific treponemal tests for its confirmation {21} . In our patients all but one were positive for syphilis in serum-tests and/or CSF . (ABS

Biochem Biophys Res Commun, 2000 Jan 7, 267(1), 445 - 8
The effect of cysteine mutations on recombinant deacetoxycephalosporin C synthase from S . clavuligerus; Lee HJ et al.; Cysteines 100, 155, and 197 of recombinant deacetoxycephalosporin C synthase were mutated to alanine residues . The C100A mutant had properties similar to those of the wild-type enzyme, but mutation of Cys-155 and Cys-197 reduced enzyme activity with penicillin N and penicillin G to different extents .

Pharmacoeconomics, 1999 Oct, 16(4), 355 - 65
Decision analysis of histamine H2-receptor antagonist maintenance therapy versus Helicobacter pylori eradication therapy: a randomised controlled trial in patients with continuing pain after duodenal ulcer; Tavakoli M et al.; BACKGROUND: Much has been published on the efficacy and cost effectiveness of Helicobacter pylori eradication treatment as an alternative to histamine H2-receptor antagonist maintenance treatment in peptic ulcer disease . However, most studies have analysed and emphasised H . pylori eradication rates rather than management/control of symptoms and the associated cost savings . Although H . pylori eradication therapy is very successful in clearing the infection, dyspeptic symptoms may persist and management of these can be expensive . OBJECTIVE: The aim of this study was to assess the cost implications in controlling symptoms using either H2-receptor antagonist maintenance therapy or H . pylori eradication therapy in patients with duodenal ulcer disease . DESIGN: This was a non-blind, prospective, randomised, parallel-group study comparing maintenance H2-receptor antagonist treatment using ranitidine with H . pylori eradication therapy, with a 1-year follow-up . SETTING: This was a study of outpatients from general practices in Dundee, Scotland, or the Ninewells Hospital, Dundee, gastroenterology clinic . PATIENTS AND PARTICIPANTS: 119 patients with confirmed duodenal ulcer, free from active ulceration at study entry but positive for H . pylori infection, who were receiving maintenance H2-receptor antagonist therapy . INTERVENTIONS: Patients were randomised to receive either continuing maintenance therapy with ranitidine (initially 150 mg daily; 58 patients) or H . pylori eradication therapy using an omeprazole/amoxicillin/metronidazole regimen (or omeprazole/clarithromycin if allergic to penicillin) . MAIN OUTCOME MEASURES AND RESULTS: Overall, H . pylori eradication rates were 100% per protocol and 95.1% intention-to-treat . At completion of 1 year of follow-up, 12 of the 61 (19.7%) patients successfully eradicated of H . pylori were still dependent on acid suppression for symptom relief . H . pylori eradication treatment was the least-cost strategy in managing/controlling symptoms at 1 year (168 Pounds vs 210 Pounds per patient; 1996 values) . However, over time, post-eradication treatment costs were greater than H2-receptor antagonist therapy costs . Any potential savings were directly related to the proportion of patients needing further treatment post-eradication, the cost of endoscopy and the urea breath test . CONCLUSIONS: If dyspepsia persists long term, H . pylori eradication treatment may not be the least-cost option for patients with duodenal ulcer.

Ann Allergy Asthma Immunol, 1999 Dec, 83(6 Pt 1), 543 - 6
Effective acute desensitization for immediate-type hypersensitivity to human granulocyte-monocyte colony stimulating factor; Shahar E et al.; BACKGROUND: Granulocyte-monocyte colony stimulating factor (GM-CSF) is the treatment of choice for patients with life threatening neutropenias . Hypersensitivity to GM-CSF may lead to cessation of treatment . Acute desensitization is an alternative mode of managing drug hypersensitivity, especially when other common modes like substitution of offending drug or premedication with antihistamines and/or corticosteroids are not available or fail . CASE REPORT: A 42-year-old woman with a 17-year history of severe chronic mucocutaneous candidal infections became resistant to all common antifungal drugs . As her disorder was associated with defective functions of monocytes and granulocytes, GM-CSF treatment was started yielding a very good clinical effect . After a short period of treatment, however, the patient developed anaphylactic reactions which could not be abolished by preadministration of antihistamines and/or corticosteroids . Replacement of therapy by G-CSF caused identical hypersensitivity phenomena . METHODS: Prick skin tests with 100, 200, or 400 microg/mL of GM-CSF or G-CSF, using also negative and positive controls, were performed on the patient and three healthy control subjects . A positive local reaction was observed only in patient at the prick point of 200 microg/mL GM-CSF or 400 microg/mL G-CSF . Acute desensitization to GM-CSF was initiated adopting a protocol used for parenteral desensitization to penicillin . RESULTS: The patient tolerated the desensitization procedure very well and we could resume the administration of GM-CSF . For the past 30 months the patient has been treated uneventfully by subcutaneous administration of GM-CSF, 500 microg twice weekly, and is free of candidal infections . Skin prick tests were repeated 1 month postdesensitization and resulted in a very weak response to GM-CSF compared with the predesensitization response . CONCLUSIONS: Acute desensitization can be utilized in patients who develop drug hypersensitivity reactions to GM-CSF . As GM-CSF is a very unique agent and in most cases cannot be replaced by another one, acute desensitization may play a very important role in managing failure of GM-CSF treatment due to hypersensitivity reactions.

J Drug Target, 1999, 7(1), 43 - 53
Folate-targeted enzyme prodrug cancer therapy utilizing penicillin-V amidase and a doxorubicin prodrug; Lu JY et al.; In antibody-targeted enzyme prodrug therapy, a monoclonal antibody (mAb) covalently linked to an enzyme is commonly exploited to concentrate the enzyme on the tumor cell surface prior to administration of a relatively nontoxic prodrug . The tumor-localized enzyme then converts the prodrug into a cytotoxic agent, which in turn diffuses into the tumor causing localized cell death . In this paper, we have substituted folic acid for the mAb as a mean of delivering an attached enzyme, penicillin-V amidase (PVA), to folate receptor (FR)-positive tumor cells . The enzyme PVA is capable of converting a doxorubicin-N-p-hydroxyphenoxyacetamide prodrug (DPO) into its potent parent drug, doxorubicin . For PVA targeting, each PVA molecule was covalently labeled with three molecules of folic acid via the formation of amide bonds . In vitro binding assays showed that folate-PVA-125I conjugates bind specifically to KB cells (FR-positive tumor cells) but not to A549 cells (FR-negative tumor cells) . Moreover, in a series of in vitro cytotoxicity tests, folate-PVA conjugates were found to kill folate receptor positive but not receptor negative cells, and when bound to FR-positive cells, folate-PVA conjugates rendered the DPO prodrug as toxic as free doxorubicin (IC50, approximately 0.6 microM) . Finally, preliminary in vivo plasma clearance studies in normal mice revealed that i.v . administered folate-PVA-125I and PVA-125I are both cleared from the blood within a 24 h time period, removing concern that nonspecifically trapped folate-PVA might activate prodrug in nontargeted tissues . In view of the fact that only a small number of folate-PVA molecules are required to mediate killing of target cells in vitro, these data argue that folate-targeted enzyme prodrug therapy should be considered for tumor eradication in vivo.

Rinsho Shinkeigaku, 1999 Sep, 39(9), 953 - 7
{Therapeutic case of general paresis manifested by bradykinesia and recent memory loss}; Iwasaki Y et al.; We reported a 32-year-old man with general paresis . He showed slowly progressive bradykinesia and recent memory loss . Argyll Robertson pupils were not present . Muscle strength and sensations were normal except for slight vibratory disturbance . Tendon reflexes were slightly exaggerated . MMSE, HDS-R and WAIS-R scores showed the intellectual impairment . His laboratory investigations revealed elevated both TPHA and FTA-ABS titers in the serum and the CSF . The CSF contained leukocytosis (25/mm3) and protein 80 mg/dl . Cranial CT and MRI demonstrated diffuse cortical atrophy . SPECT revealed marked reduction of the blood flow in bilateral cerebral hemisphere . Cerebral angiography revealed moderate stenosis of the major vessels . The diagnosis of neurosyphilis (general paresis) was made and the treatment of intravenous benzyl penicillin potassium 24 million units per day was started . After 6 weeks of the treatment, the clinical signs (includes MMSE, HDS-R and WAIS-R scores) and the findings of SPECT and cerebral angiography showed improvement . Although the cell count and protein in the CSF became decreased, the titers of TPHA and FTA-ABS in the serum and the CSF were not decreased . Neurosyphilis should always be considered in a etiologically unknown case with bradykinesia and dementia.

Presse Med, 1999 Dec 4, 28(38), 2098 - 9
{Pelvic actinomycosis: a case with secondary localization in the liver}; Reyal F et al.; BACKGROUND: Actinomycosis is uncommonly observed in a pelvic localization . The presence of an intrauterine device is an important risk factor . CASE REPORT: A 50-year-old woman presented a tumoral mass in the pelvis with secondary liver involvement . Pathology examination corrected the initial diagnosis of advanced stage pelvic neoplasia to actinomycosis . Rapid improvement was achieved with penicillin . DISCUSSION: Differential diagnosis is difficult but essential in case of pelvic actinomycosis as misdiagnosis can have disastrous surgical consequences . Medical treatment is indicated . Actinomycosis should be entertained as a possible diagnosis in all cases associating a pelvic tumor and inflammation in women wearing an intrauterine device.

Genet Anal, 1999 Dec 15, 15(6), 235 - 8
DNA region responsible for transcriptional regulation of the Escherichia coli penicillin amidase (pac) gene by CRP and PAA; Radoja S et al.; Transcriptional regulation of Escherichia coli ATCC11105 penicillin amidase gene (pac) by cAMP receptor protein (CRP) and phenylacetic acid (PAA) was studied by using operon fusions with divergent reporter gene (lacZ, and phoA) constructs . A 150 bp DNA segment essential for the regulation of pac gene transcription by CRP and PAA was defined.

Epilepsy Res, 2000 Jan, 38(1), 33 - 44
Seizures induced by penicillin microinjections in the mesencephalic tegmentum; Jimenez F et al.; The location and extension of a convulsive area in the brain stem in cats was determined through penicillin microinjections (0.5-1.0 microl) of a concentrated sodium penicillin solution (500 IU/microl), stereotactically oriented to multiple structures, in fully awake animals, partially restrained through a rod fixation system that avoided pain, allowed the observation of clinical seizures and simultaneous recording of EEG, EMG and multiple unit activity (MUA) from the injected site and the motor cortex (Cx) . Clinical and EEG seizure patterns in relation to the injected sites and penicillin doses were studied in another group of animals using doses from 12.5 IU/0.1 microl to 125 IU/1.0 microl . The time relationship between muscular clonus, EEG spikes and MUA at the injected site and Cx were analyzed . The only area in which penicillin induced seizures was the mesencephalic tegmentum (MT) . The amount of penicillin but not the stereotactic coordinates determined the seizure type . MT EEG and MUA paroxysms anticipated clinical seizure and Cx EEG spikes . When Cx EEG appeared, they were accompanied by an increase in MUA beginning in the Cx and EMG, followed by significant increase in MT MUA . The sequence of events suggest that MT seizure activity propagates via alternative pathways not involving direct reticulospinal or pyramidal tract pathways.

Eur Radiol, 1999, 9(9), 1869 - 72
Misleading diagnosis of retroperitoneal actinomycosis; Berchtenbreiter C et al.; A 34-year-old woman presented with a left-sided suprarenal space-occupying lesion on sonography . Culture of material obtained during sonographic-guided puncture of the retroperitoneal lesion yielded a mixed flora of Actinomyces and Peptostreptococcus . Initially, a misleading diagnosis of an adrenal pheochromocytoma was initiated by highly positive metaiodobenzylguanidine scintigraphy after chemical chemistry vanillylmandelic acid (VMA) test showed elevated values for adrenaline and its derivatives . Retroperitoneal actinomycosis with yet unproven spread into thoracic and cervical compartments is a particular unusual presentation of an infection with these organisms . Because it may mimic subacute infections or malignant masses in terms of clinical and laboratory findings, radiological diagnosis of this entity may be difficult . The diagnosis was based on results of culture and the response of the patient to long-term penicillin-derivate therapy after surgical drainage of the suprarenal abscess formation.

Rev Esp Enferm Dig, 1999 Nov, 91(11), 777 - 84
{Helicobacter pylori infection . The Spanish consensus report . The Spanish Consensus Conference Group}; Sainz R et al.; OBJECTIVES: taking into account the small amount of infection eradication treatments carried out in our country and some characteristics arising from the resistances to some antibiotics, the Spanish Club for the Study of Helicobacter pylori decided to organize a Spanish Consensus Conference to clarify the use of the different infection diagnostic tests, to establish the exact indications of its diagnosis and treatment, to recommend the best treatment guidelines for our country and to promote the use of eradication treatments in adequate indications . DESIGN: on April 23, 1999 in Madrid, physicians who were experts in infection by Helicobacter pylori representing the different Scientific Societies of our country were gathered . Prior to this, three work areas, diagnosis, indications and treatments, were created and the participants freely joined them . One month before the conference, all of the participants were sent the questions which would be debated . An 80% consensus level, always based on scientific evidence, was required for a recommendation . In the first session, a meeting by work areas was held and in a second session, all of the recommendations were voted on in the meeting of the representatives . CONCLUSIONS: the conference recommends the eradication of the infection in all the gastric or duodenal ulcers, in the erosive duodenitis, in the MALT lymphomas and in gastrectomized patients due to gastric cancer with residual stomach . In the de novo diagnoses of gastroduodenal ulcer, the rapid test of urease is recommended, and a histological study is recommended only if it is negative . In the case of a history of ulcers and also to know the eradication treatment result, the C13 urea breath test is recommended . The culture is reserved for primary treatment and rescue treatment failures so as to select the adequate antibiotic . The primary treatment regimes recommended for our country mean the combination of amoxicillin, clarithromycin and any proton pump inhibitor or with Ranitidine bismuth citrate . If there is allergy to penicillin, amoxycillin will be substituted by metronidazol.

Pol Merkuriusz Lek, 1999 Sep, 7(39), 124 - 5
{Hypersensitivity to penicillin therapy in the course of treatment: a case report}; Zdziarski P; Adverse reactions to benzylpenicillin are well known . Full allergy testing is time-consuming, expensive and doesn't exclude anaphylaxis to penicillin . It is accepted that penicillin allergy is overdiagnosed . Therefore clinical observations are not useful for pathogenesis research without follow up examination . 100 patients with negative skin test before and with symptoms of penicillin hypersensitivity during treatment was diagnosed . We report only 4 cases of patients, whose allergy to penicillin was confirmed by the same skin test . They had received penicillin during serious bacterial infections and had experienced allergic symptoms . Skin rush, asthma or hypotension have been observed during treatment with penicillin . Immediate hypersensitivity was confirmed by positive skin test after treatment . This study reinforce findings of our experimental study, when intraperitoneal injections of penicillin and Freunds adjuvant or bacterial lysate lead to anaphylactic shock and death of guinea pigs . Eastaway et all published similar case report of gas gangrene complicated by penicillin allergy . These observations indicate that pathogenesis of penicillin allergy may be associated with bacterial infection and nonspecific inflammation.

J Chromatogr B Biomed Sci Appl, 1999 Nov 12, 734(2), 307 - 18
Simultaneous determination of seven penicillins in muscle, liver and kidney tissues from cattle and pigs by a multiresidue high-performance liquid chromatographic method; Sorensen LK et al.; A high-performance liquid chromatographic (HPLC) method based on solid-phase extraction (SPE) was developed for determination of amoxicillin, penicillin G (benzylpenicillin), ampicillin, oxacillin, cloxacillin, nafcillin and dicloxacillin in muscle, liver and kidney tissues of pigs and cattle . The compounds were extracted in aqueous solution by precipitation of organic materials with a mixture of sulphuric acid and sodium tungstate . The extract was cleaned up by SPE on a divinylbenzene-co-N-vinylpyrrolidone polymeric sorbent . Further clean-up was performed by liquid-liquid partition with diethyl ether . The extract was derivatised with benzoic anhydride and 1,2,4-triazole mercury (II) reagent . Chromatography was performed by reversed-phase gradient HPLC on a C18 column with ultraviolet detection at 323 nm . The limits of detection estimated by a conservative model were in the range 8.9-11.1 microg/kg for amoxicillin, penicillin G, ampicillin, oxacillin, cloxacillin and nafcillin and 18.3-20.9 microg/kg for dicloxacillin . The mean recovery range was 66-77% for amoxicillin, 73-75% for penicillin G, 81-82% for ampicillin, 73-76% for oxacillin, 74-75% for cloxacillin, 66-72% for nafcillin and 58-65% for dicloxacillin.

Curr Pharm Des, 1999 Nov, 5(11), 929 - 37
Structural and mechanistic aspects of evolution of beta-lactamases and penicillin-binding proteins; Massova I et al.; Penicillin-binding proteins (PBPs) and b-lactamases are related enzymes, the former are the targets for b-lactam antibiotics and the latter are resistance enzyme to these antibiotics . The two families of enzymes share structural topologies and certain mechanistic features . However, these classes of enzymes have diversified substantially and have broadened the reaction repertoire for their catalytic properties . This report addresses the issues of the evolution of function of these proteins.

Laryngoscope, 1999 Dec, 109(12), 1978 - 81
Penicillin reduces new bone formation in acute otitis media; Caye-Thomasen P et al.; OBJECTIVE: Previous studies have shown that acute otitis media alters modeling dynamics in bone tissue structures surrounding the middle ear cavity . Initial resorption is followed by formative activity, which is seen as massive osteoneogenesis . However, neither resorptive nor formative activity occurs in the otic capsule, supporting the theory on existence of a perilymphatic barrier of specialized bone . STUDY DESIGN: To investigate the effect of penicillin administration on the pathological bone modeling in acute otitis media, we employed a rat model of acute pneumococcal otitis media . METHODS: Five rats were sacrificed on postinoculation days 4, 8, 16, 90, and 180, preceded by oral administration of penicillin V 100 mg/kg per day, initiated on day 2 and lasting 5 (2) days . Using a light microscope, bone histomorphology was registered and the thickness measured in four well-defined localities, followed by comparison with a previous study of untreated animals . RESULTS: Measured bone thickness was unaffected by treatment on day 4, but significantly reduced in two localities on day 8 and in all localities on following days of sacrifice . Bone cytomorphology and histomorphology were otherwise unaffected by penicillin administration . CONCLUSION: Penicillin reduces new bone formation in acute otitis media, leaving other features of histomorphology unchanged.

Am J Hematol, 1999 Dec, 62(4), 201 - 7
Acid-base and electrolyte abnormalities in patients with acute leukemia; Milionis HJ et al.; Disturbances of acid-base balance and electrolyte abnormalities are commonly seen in patients with acute leukemia . Our study aimed at illuminating the probable pathogenetic mechanisms responsible for these disturbances in patients with acute leukemia admitted to our hospital . We studied 66 patients (24 men and 44 women) aged between 17 and 87 years old on their admission and prior to any therapeutic intervention . Patients with diabetes mellitus, acute or chronic renal failure, hepatic failure, patients receiving drugs that influence acid-base status and electrolyte parameters during the last month, such as corticosteroids, cisplatin, diuretics, antacids, aminoglycosides, amphotericin, penicillin, and K(+), PO(4)(3-), or Mg(2+) supplements were excluded . Forty-one patients had at least one acid-base or electrolyte disturbance . There were no significant differences in the incidence of acid-base balance and electrolyte abnormalities between patients with acute myeloid leukemia (AML) and patients with acute lymphoblastic leukemia (ALL) . The most frequent electrolyte abnormality was hypokalemia, observed in 41 patients (63%), namely in 34 patients with AML, and 7 with ALL; the main underlying pathophysiologic mechanism was inappropriate kaliuresis . Furthermore, hypokalemic patients more frequently experienced concurrent electrolyte disturbances (i.e., hyponatremia, hypocalcemia, hypophosphatemia, and hypomagnesemia), as well as various acid-base abnormalities compared to normokalemic patients . Hypokalemia in patients with acute leukemia may serve as an indicator of multiple concurrent, interrelated electrolyte disturbances, especially in patients with AML .

Surv Ophthalmol, 1999 Nov-Dec, 44(3), 247 - 52
Not so slowly progressive visual loss; Danesh-Meyer H et al.; A 51-year-old man presented with bilateral progressive visual loss during a 2-month period . Visual acuity was 20/60 in both eyes with bilateral constricted visual fields . Funduscopy revealed bilateral disk pallor and arteriolar attenuation . His vision declined rapidly during the next 2 weeks . Investigations showed a positive cerebrospinal fluid Venereal Disease Research Laboratory test (1:8) . A diagnosis of neurosyphilis was made, and treatment was started with high-dose intravenous and intramuscular penicillin.

Eur J Clin Microbiol Infect Dis, 1999 Oct, 18(10), 729 - 32
Response to standard syphilis treatment in patients infected with the human immunodeficiency virus; Bordon J et al.; In a study designed to evaluate the efficacy of penicillin in HIV-infected patients with syphilis and to determine the clinical and laboratory responses after treatment, 13 patients with HIV infection and syphilis were assessed at enrollment and at the last follow-up examination (median time of 21 months) . The Venereal Diseases Research Laboratory (VDRL) test, the Treponema pallidum hemaglutination test, and leukocyte counts in cerebrospinal fluid were evaluated both at enrollment and at the last follow-up visit, and the polymerase chain reaction for Treponema pallidum DNA and the rabbit infectivity test were performed on cerebrospinal fluid samples at the last follow-up visit . Primary syphilis was confirmed in four patients, latent syphilis in five, and neurosyphilis in four . After penicillin treatment, all patients were asymptomatic . The serum rapid plasma reagin test became negative in five patients, and titers declined in eight . The VDRL test, Treponema pallidum DNA, and the rabbit infectivity test were negative in all 13 patients . Except for one patient whose serological titer was slow to decline, all patients had good clinical and serological responses to penicillin . In certain settings, factors other than penicillin treatment failure should be considered in HIV-infected patients with suspected relapse of syphilis.

Appl Environ Microbiol, 1999 Dec, 65(12), 5222 - 8
Cloning and characterization of an Aspergillus nidulans gene involved in the regulation of penicillin biosynthesis; Van Den Brulle J et al.; To identify regulators of penicillin biosynthesis, a previously isolated mutant of Aspergillus nidulans (Prg-1) which carried the trans-acting prgA1 mutation was used . This mutant also contained fusions of the penicillin biosynthesis genes acvA and ipnA with reporter genes (acvA-uidA and ipnA-lacZ) integrated in a double-copy arrangement at the chromosomal argB gene . The prgA1 mutant strain exhibited only 20 to 50% of the ipnA-lacZ and acvA-uidA expression exhibited by the wild-type strain and had only 20 to 30% of the penicillin produced by the wild-type strain . Here, using complementation with a genomic cosmid library, we isolated a gene (suAprgA1) which complemented the prgA1 phenotype to the wild-type phenotype; i.e., the levels of expression of both gene fusions and penicillin production were nearly wild-type levels . Analysis of the suAprgA1 gene in the prgA1 mutant did not reveal any mutation in the suAprgA1 gene or unusual transcription of the gene . This suggested that the suAprgA1 gene is a suppressor of the prgA1 mutation . The suAprgA1 gene is 1,245 bp long . Its five exons encode a deduced protein that is 303 amino acids long . The putative SUAPRGA1 protein was similar to both the human p32 protein and Mam33p of Saccharomyces cerevisiae . Analysis of the ordered gene library of A . nidulans indicated that suAprgA1 is located on chromosome VI . Deletion of the suAprgA1 gene resulted in an approximately 50% reduction in ipnA-lacZ expression and in a slight reduction in acvA-uidA expression . The DeltasuAprgA1 strain produced about 60% of the amount of penicillin produced by the wild-type strain.

Antimicrob Agents Chemother, 1999 Dec, 43(12), 3011 - 3
Characterization of a Mycobacterium smegmatis mutant lacking penicillin binding protein 1; Billman-Jacobe H et al.; The ponA gene of Mycobacterium smegmatis encodes a 95-kDa penicillin binding protein, PBP1, that is similar to PBP1s of Mycobacterium tuberculosis and Mycobacterium leprae . Transposon disruption of ponA in M . smegmatis resulted in a PBP1-deficient mutant that was sensitive to beta-lactam antibiotics, was more permeable to glycine, and grew slowly in liquid culture.

S Afr Med J, 1999 Oct, 89(10), 1088 - 91
Nephrotic syndrome in Namibian children; van Buuren AJ et al.; BACKGROUND AND OBJECTIVES: Patterns of nephrotic syndrome vary between regions and countries, and influence approaches to management . In the mid-1970s the University of Stellenbosch became involved in providing tertiary care to Namibia, including a paediatric nephrology service . The aim of this study was to document the clinical, pathological and outcome features of nephrotic syndrome in Namibian children . SUBJECTS: Seventy black Namibian children with nephrotic syndrome were managed from 1975 to 1988 . Sixty-eight renal specimens (67 biopsies and 1 autopsy specimen) were evaluated . RESULTS: Twenty-nine of the 70 children (41.4%) were hepatitis B virus (HBV) carriers, of whom 25 (86.2%) were male . Of the 29, 26 had predominantly membranous glomerulonephritis (MGN), 1 mesangiocapillary glomerulonephritis (MCGN), and 1 focal segmental glomerulosclerosis (FSGS); 1 child in advanced renal failure was not biopsied . Five children (7.4%) showed minimal change disease (MCD), 11 (16.2%) FSGS and 15 (22.1%) diffuse mesangial proliferative glomerulonephritis (DMP) . The remaining 10 children showed diffuse glomerulosclerosis (6), MCGN (3) and endocapillary proliferative GN (1) . Four of the 5 children with MCD went into remission on immunosuppressive treatment . Of the 15 with DMP, 4 improved spontaneously and only 1 of those treated did not improve . Only 2 of those with FSGS improved on treatment . The children with HBV-associated MGN and MCGN were offered symptomatic rather than specific treatment . Thirteen children presented with degrees of chronic renal failure . Eight are known to have died, 3 of relentless nephrotic syndrome and 4 (of whom 3 were HBV carriers) of end-stage renal failure . One child died of penicillin anaphylaxis . CONCLUSIONS: The pattern of nephrotic syndrome in black Namibian children differed greatly from the non-African pattern elsewhere in that MCD was uncommon and HBV-associated GN was the most common single group . The most frequent pattern of HBV-associated GN was MGN with some mesangiocapillary features showing marked male predominance . MCD and DMP were potentially treatable and could only be identified by biopsy . HBV carrier rates exert a major influence on the proportions of morphological subgroups of nephrotic syndrome in children . As these HBV carrier rates alter in future due to the influence of vaccination and urbanisation, the relative size of nephrotic subgroups seems likely to alter.

Bioorg Med Chem, 1999 Oct, 7(10), 2221 - 9
Use of enzyme penicillin acylase in selective amidation/amide hydrolysis to resolve ethyl 3-amino-4-pentynoate isomers; Topgi RS et al.; The beta-amino acid, (S)-ethyl-3-amino-4-pentynoate, is a chiral synthon used in the synthesis of xemilofiban hydrochloride, an anti-platelet agent . A biocatalytic approach was developed to resolve (R)- and (S)-enantiomers of ethyl 3-amino-4-pentynoate in enantiomerically pure form employing the enzyme Penicillin acylase . In the acylation, phenylacetic acid was used as an acylating agent . We have shown that both the acylation and deacylation can be employed and that the activity of the enzyme Penicillin acylase can be controlled by maintaining an appropriate pH of the reaction medium.

J Chromatogr B Biomed Sci Appl, 1999 Oct 29, 734(1), 15 - 22
Partial purification of penicillin acylase from Escherichia coli in poly(ethylene glycol)-sodium citrate aqueous two-phase systems; Marcos JC et al.; Studies on the partition and purification of penicillin acylase from Escherichia coli osmotic shock extract were performed in poly(ethylene glycol)-sodium citrate systems . Partition coefficient behavior of the enzyme and total protein are similar to those described in other reports, increasing with pH and tie line length and decreasing with PEG molecular weight . However, some selectivity could be attained with PEG 1000 systems and long tie line at pH 6.9 . Under these conditions 2.6-fold purification with 83% yield were achieved . Influence of pH on partition shows that is the composition of the system and not the net charge of the enzyme that determines the behaviour in these conditions . Addition of NaCl to PEG 3350 systems significantly increases the partition of the enzyme . Although protein partition also increased, purification conditions were possible with 1.5 M NaCl where 5.7-fold purification and 85% yield was obtained . This was possible due to the higher hydrophobicity of the enzyme compared to that of most contaminants proteins.

Nippon Hinyokika Gakkai Zasshi, 1999 Oct, 90(10), 843 - 6
{A case of renal actinomycosis}; Fujita Y et al.; A case of renal actinomycosis is reported . A 63-year-old man was admitted to our hospital for further examinations of a right renal mass, complaining of dull pain in his right loin and progressive weight loss . Laboratory findings showed an anemia with a grossly raised ESR, CT, MRI and ultrasonography revealed a solid mass of the right kidney . Chest CT films revealed several infiltrates in the bilateral lobes . A diagnosis of neoplasm or inflammatory mass of the right kidney was considered, and the right nephrectomy was performed . Microscopically, characteristic colonies of actinomyces were seen, and histological diagnosis was renal actinomycosis . The patient made good progress after operation and was subsequently treated with penicillin.

Biochemistry (Mosc), 1999 Oct, 64(10), 1196 - 9
Stability and catalytic properties of penicillin acylase in systems with low water content; Youshko MI et al.; Stability and catalytic properties of native and immobilized penicillin acylase were studied in systems with low water content . Preparations of both native and immobilized penicillin acylase demonstrated the catalytic activity even in solid-phase systems which contained 3-5 wt . % of water . The stability and catalytic activity of penicillin acylase at low water content depended on the thermodynamic water activity (aw) in the system.

Biochemistry (Mosc), 1999 Oct, 64(10), 1186 - 95
Activity of penicillin acylase from E . coli in the reversed-micelle system AOT--H2O--octane; Shamolina TA et al.; The behavior of a penicillin acylase from E . coli was studied in the reversed-micelle system AOT--H2O--octane . Kinetic studies of the enzymatic hydrolysis of the m-carboxy-p-nitroanilide of phenylacetic acid, titration of the penicillin acylase active site with an irreversible specific inhibitor (phenylmethylsulfonyl fluoride), sedimentation analysis at different hydration degrees, and chemical modification showed that the enzyme loses no more than 20% of its initial activity during 3-4 h in the reversed-micelle systems of different hydration degrees and retains its catalytically active structure.

Mol Microbiol, 1999 Oct, 34(2), 350 - 64
The catalytic, glycosyl transferase and acyl transferase modules of the cell wall peptidoglycan-polymerizing penicillin-binding protein 1b of Escherichia coli; Terrak M et al.; The penicillin-binding protein (PBP) 1b of Escherichia coli catalyses the assembly of lipid-transported N-acetyl glucosaminyl-beta-1, 4-N-acetylmuramoyl-L-alanyl-gamma-D-glutamyl-(L)-meso-diaminopimelyl+ ++- (L)-D-alanyl-D-alanine disaccharide pentapeptide units into polymeric peptidoglycan . These units are phosphodiester linked, at C1 of muramic acid, to a C55 undecaprenyl carrier . PBP1b has been purified in the form of His tag (M46-N844) PBP1bgamma . This derivative provides the host cell in which it is produced with a functional wall peptidoglycan . His tag (M46-N844) PBP1bgamma possesses an amino-terminal hydrophobic segment, which serves as transmembrane spanner of the native PBP . This segment is linked, via an congruent with 100-amino-acid insert, to a D198-G435 glycosyl transferase module that possesses the five motifs characteristic of the PBPs of class A . In in vitro assays, the glycosyl transferase of the PBP catalyses the synthesis of linear glycan chains from the lipid carrier with an efficiency of congruent with 39 000 M-1 s-1 . Glu-233, of motif 1, is central to the catalysed reaction . It is proposed that the Glu-233 gamma-COOH donates its proton to the oxygen atom of the scissile phosphoester bond of the lipid carrier, leading to the formation of an oxocarbonium cation, which then undergoes attack by the 4-OH group of a nucleophile N-acetylglucosamine . Asp-234 of motif 1 or Glu-290 of motif 3 could be involved in the stabilization of the oxocarbonium cation and the activation of the 4-OH group of the N-acetylglucosamine . In turn, Tyr-310 of motif 4 is an important component of the amino acid sequence-folding information . The glycosyl transferase module of PBP1b, the lysozymes and the lytic transglycosylase Slt70 have much the same catalytic machinery . They might be members of the same superfamily . The glycosyl transferase module is linked, via a short junction site, to the amino end of a Q447-N844 acyl transferase module, which possesses the catalytic centre-defining motifs of the penicilloyl serine transferases superfamily . In in vitro assays with the lipid precursor and in the presence of penicillin at concentrations sufficient to derivatize the active-site serine 510 of the acyl transferase, the rate of glycan chain synthesis is unmodified, showing that the functioning of the glycosyl transferase is acyl transferase independent . In the absence of penicillin, the products of the Ser-510-assisted double-proton shuttle are glycan strands substituted by cross-linked tetrapeptide-pentapeptide and tetrapeptide-tetrapeptide dimers and uncross-linked pentapeptide and tetrapeptide monomers . The acyl transferase of the PBP also catalyses aminolysis and hydrolysis of properly structured thiolesters, but it lacks activity on D-alanyl-D-alanine-terminated peptides . This substrate specificity suggests that carbonyl donor activity requires the attachment of the pentapeptides to the glycan chains made by the glycosyl transferase, and it implies that one and the same PBP molecule catalyses transglycosylation and peptide cross-linking in a sequential manner . Attempts to produce truncated forms of the PBP lead to the conclusion that the multimodular polypeptide chain behaves as an integrated folding entity during PBP1b biogenesis.

Obstet Gynecol, 1999 Nov, 94(5 Pt 2), 810 - 2
Herpes simplex virus encephalitis in pregnancy; Dupuis O et al.; BACKGROUND: Although polymerase chain reaction (PCR) can detect herpes simplex virus (HSV) in the cerebrospinal fluid (CSF), HSV encephalitis remains a significant cause of neurologic impairment in pregnant women . Assessment of fetal contamination also remains a problem . CASES: We report two cases in which HSV encephalitis initially was not suspected and led to significant maternal neurologic impairment . In both cases, HSV PCR of CSF confirmed the diagnosis . In one case, fetal serum HSV PCR excluded fetal contamination . CONCLUSION: As soon as encephalitis in pregnancy is suspected, a combination of acyclovir and penicillin is recommended because the potential benefits far outweigh the risks . Using the HSV PCR, HSV infection in the fetus can be diagnosed.

J Biol Chem, 1999 Nov 5, 274(45), 32031 - 9
Cloning and characterization of PBP 1C, a third member of the multimodular class A penicillin-binding proteins of Escherichia coli; Schiffer G et al.; All proteins of Escherichia coli that covalently bind penicillin have been cloned except for the penicillin-binding protein (PBP) 1C . For a detailed understanding of the mode of action of beta-lactam antibiotics, cloning of the gene encoding PBP1C was of major importance . Therefore, the structural gene was identified in the E . coli genomic lambda library of Kohara and subcloned, and PBP1C was characterized biochemically . PBP1C is a close homologue to the bifunctional transpeptidases/transglycosylases PBP1A and PBP1B and likewise shows murein polymerizing activity, which can be blocked by the transglycosylase inhibitor moenomycin . Covalently linked to activated Sepharose, PBP1C specifically retained PBP1B and the transpeptidases PBP2 and -3 in addition to the murein hydrolase MltA . The specific interaction with these proteins suggests that PBP1C is assembled into a multienzyme complex consisting of both murein polymerases and hydrolases . Overexpression of PBP1C does not support growth of a PBP1A(ts)/PBP1B double mutant at the restrictive temperature, and PBP1C does not bind to the same variety of penicillin derivatives as PBPs 1A and 1B . Deletion of PBP1C resulted in an altered mode of murein synthesis . It is suggested that PBP1C functions in vivo as a transglycosylase only.

J Bacteriol, 1999 Nov, 181(21), 6607 - 14
On the origin of branches in Escherichia coli; Gullbrand B et al.; Some Escherichia coli strains with impaired cell division form branched cells at high frequencies during certain growth conditions . Here, we show that neither FtsI nor FtsZ activity is required for the development of branches . Buds did not form at specific positions along the cell surface during high-branching conditions . Antibiotics affecting cell wall synthesis had a positive effect on branch formation in the case of ampicillin, cephalexin, and penicillin G, whereas mecillinam and D-cycloserine had no substantial effect . Altering the cell morphology by nutritional shifts showed that changes in morphology preceded branching, indicating that the cell's physiological state rather than specific medium components induced branching . Finally, there was no increased probability for bud formation in the daughters of a cell with a bud or branch, showing that bud formation is a random event . We suggest that branch formation is caused by abnormalities in cell wall elongation rather than by aberrant cell division events.

Nature, 1999 Oct 14, 401(6754), 721 - 4
The reaction cycle of isopenicillin N synthase observed by X-ray diffraction; Burzlaff NI et al.; Isopenicillin N synthase (IPNS), a non-haem iron-dependent oxidase, catalyses the biosynthesis of isopenicillin N (IPN), the precursor of all penicillins and cephalosporins . The key steps in this reaction are the two iron-dioxygen-mediated ring closures of the tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV) . It has been proposed that the four-membered beta-lactam ring forms initially, associated with a highly oxidized iron(iv)-oxo (ferryl) moiety, which subsequently mediates closure of the five-membered thiazolidine ring . Here we describe observation of the IPNS reaction in crystals by X-ray crystallography . IPNS Fe2+ substrate crystals were grown anaerobically, exposed to high pressures of oxygen to promote reaction and frozen, and their structures were elucidated by X-ray diffraction . Using the natural substrate ACV, this resulted in the IPNS x Fe2+ x IPN product complex . With the substrate analogue, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-L-S-methylcysteine (ACmC) in the crystal, the reaction cycle was interrupted at the monocyclic stage . These mono- and bicyclic structures support our hypothesis of a two-stage reaction sequence leading to penicillin . Furthermore, the formation of a monocyclic sulphoxide product from ACmC is most simply explained by the interception of a high-valency iron-oxo species.

Ceska Slov Farm, 1998 Nov, 47(6), 279 - 83
{Development of the scientific basis of Czech pharmacy 1939-1945}; Novacek L; The German occupation of the Czechoslovak Republic in 1938-1945 and the worldwide war conflict which limited the import of drugs and medicines into the Czech Lands were a stimulus for the development of Czech pharmaceutical industry and research, which incorporated experts-lecturers and students from the closed Czech universities . Important roles in obtaining and disseminating scientific knowledge in pharmaceutical sciences were played by the Institute for Drug Research in Prague, Central Union of Pharmacists, and a number of pharmacies . In drug research, several new preparations were devised; the greatest achievement was the method of manufacture of "Czech" penicillin, which was used already during the war . The inland basis of raw materials was enlarged by cultivation and collection of medicinal plants . Scientific knowledge gained during the war in pharmaceutical chemistry, pharmacognosy and galenical pharmacy contributed after the liberation in 1945 to the establishment of pharmaceutical sciences, which had not had a sufficient basis before.

Drug Des Discov, 1999 Aug, 16(2), 131 - 43
The role of water molecules in the deacylation of acylated structures of class A beta-lactamase; Ishiguro M et al.; Molecular dynamics simulation of the penicillin- and penem-acylated enzymes reveals that the conformational flexibility of the acyl moieties in the binding cleft and the conformational change of the acyl moieties are crucial for deacylation . The water molecule adjacent to the Glu 166 residue is not the nucleophile for deacylation, but construction of a model of the oxyanion tetrahedral intermediate suggested a plausible role of the water molecule as a proton donor for the oxyanion to facilitate the deacylation.

Pediatr Emerg Care, 1999 Oct, 15(5), 332 - 4
Tubulointerstitial renal failure in childhood leptospirosis; Vachvanichsanong P et al.; We report three children with tubulointerstitial renal failure following leptospirosis . All had acute nonoliguric renal failure with mild hypocalemia and mild metabolic acidosis . Maximum blood urea nitrogen (BUN) and creatinine were 217 and 7.1 mg/dl, respectively, on the 6th day of disease, and no patient required dialysis . They presented with acute febrile illness and dehydration, and required intravenous fluid supplements . Myalgia, vomiting, and bleeding were found in two children . Abdominal pain, arthralgia, diarrhea, and conjunctival suffusion were found in one child . Only one child, who had an underlying disease of beta-thalassemia/Hb E, had jaundice, hepatosplenomegaly, anemia, and thrombocytopenia . Penicillin treatment was given in one case . All recovered, with normal renal function . The leptospirosis complement fixation test was used to confirm diagnosis . L . batavia was considered the etiologic agent in two of the children.

Int J Antimicrob Agents, 1999 Aug, 12 Suppl 1, S3 - 7; discussion S26-7
Beta-lactamases and beta-lactamase inhibitors; Williams JD; Penicillin, the first of the beta-lactam antibiotics, was introduced into medical practice in the 1940s . Since then, a large number of different beta-lactams, including penicillins, cephalosporins, monobactams, and carbapenems, have been developed, all of which are structurally related through the presence of a core beta-lactam ring . Resistance to beta-lactam antibiotics among target pathogens developed early in the history of their use . Of the mechanisms of resistance, the most widespread and most important is the destruction of the beta-lactam ring, which is mediated by beta-lactamases . The fact that these resistance enzymes may be coded on plasmids means that they are mobile within a bacterial community, and that they have spread widely . Resistance to beta-lactams mediated by beta-lactamases can be overcome successfully with the use of beta-lactamase inhibitors . The combination of beta-lactams with beta-lactamase inhibitors restores the activity of the beta-lactams, allowing their continued clinical use . The development of beta-lactamase inhibitors allows clinicians to rely on the well-tolerated, clinically effective beta-lactam antibiotics to treat a variety of bacterial infections.

Int J Dermatol, 1999 Sep, 38(9), 689 - 92
The profile of atopic dermatitis in a tertiary dermatology outpatient clinic in Singapore; Tay YK et al.; BACKGROUND: Atopic dermatitis is a common, chronic, relapsing, pruritic, eczematous skin condition occurring in patients with a personal or family history of atopy . The aim of this study is to describe the profile of atopic dermatitis seen at a tertiary referral skin center in a tropical multiracial country . METHODS: A retrospective chart review was conducted of all the patients with atopic dermatitis seen during the first six months of 1994 . RESULTS: There were 492 patients, age range from 1 month to 74 years, with an equal sex ratio . The prevalence was 2% . The onset of the disease occurred before the age of 10 years in 61.2% of patients . In 13.6% of patients, the onset was after the age of 21 years . Two hundred and fifty four patients (52%) had "pure" atopic dermatitis without concomitant respiratory allergies; 238 patients (48%) suffered from a "mixed" type, with 23% having allergic rhinitis, 12% having asthma, and 13% having both asthma and allergic rhinitis; 231 patients (47%) had at least one first-degree family member with atopy: atopic dermatitis (17%), asthma (15%), and allergic rhinitis (15%) . Most of the patients, 416 (84.5%), had subacute dermatitis at presentation . Ichthyosis vulgaris was present in 38 patients (8%) and pityriasis alba in 13 patients (3%) . The most common infective complication was bacterial infection (impetiginized dermatitis, folliculitis, cellulitis) present in 95 patients (19%), followed by viral infections (dermatitis herpeticum, viral warts, and molluscum contagiosum) in 17 patients (3%) . Allergies were noted in 43 patients (9%) . The most common was drug allergy (penicillin and cotrimoxazole) in 28 patients, followed by food allergy in 11 patients . Common aggravating factors reported included heat, sweating, stress, thick clothing, and grass intolerance . Most patients could be controlled with a fairly simple regimen of moisturizers, topical steroids, and antibiotics for acute flares . Short courses of systemic steroids were used in 78 patients (16%) . Three patients were treated with phototherapy: two on combined UVA and UVB (UVAB) and one on oral psoralen photochemotherapy (PUVA) . CONCLUSIONS: The pattern of atopic dermatitis in Singapore is similar to that reported in the Western literature, except for a lower prevalence and a significant proportion of adult-onset atopic dermatitis.

J Chromatogr A, 1999 Sep 3, 855(1), 247 - 53
Application of ion-exchange cartridge clean-up in food analysis . II . Determination of benzylpenicillin, phenoxymethylpenicillin, oxacillin, cloxacillin, nafcillin and dicloxacillin in meat using liquid chromatography with ultraviolet detection; Ito Y et al.; A multiresidue analytical method was developed for the simultaneous determination of benzylpenicillin (PCG), phenoxymethylpenicillin (PCV), oxacillin (MPIPC), cloxacillin (MCIPC), nafcillin (NFPC) and dicloxacillin (MDIPC) in meat . The method involves the use of an ion-exchange cartridge for sample clean-up followed by ion-pair high-performance liquid chromatography with ultraviolet detection . The recoveries of PCG, PCV, MPIPC, MCIPC, NFPC and MDIPC from pork muscle spiked at levels of 0.5, 0.1 and 0.05 mg/kg were in the range of 77-90, 73-95 and 80-93% with coefficients of variation of 0.5-1.7, 1.6-4.4 and 3.2-6.6%, respectively . For beef muscle spiked at levels of 0.5, 0.1 and 0.05 mg/kg, the recoveries of these compounds were 83-92, 71-86 and 77-90% with coefficients of variation of 1.7-4.4, 2.6-7.0 and 3.9-6.4%, respectively . The detection limits for each penicillin were 0.02 mg/kg in meat.

J Biochem Biophys Methods, 1999 Aug 30, 41(1), 1 - 11
Evaluation of data produced by optode arrays under flow injection analysis (FIA) conditions using a partial least squares method (PLS2); Wollenweber M et al.; Transient diffuse reflectance spectra in the visible wavelength region from an enzyme optode were evaluated to determine artificial mixtures consisting of penicillin and ampicillin simultaneously . In order to achieve a discrimination of the samples the optode operated at two different working pH values . Using an appropriate FIA modus a linear range in the increase and decrease of the time-dependent signal was registered which could be easily fitted by means of ordinary linear regression . In this way characteristic static and dynamic features of the enzyme catalyzed reaction could be extracted for the evaluation by partial least-squares (PLS) . The pre-processed raw data were differently weighted and the optimal number of primary factors was each selected by full cross validation . The interpretation of the spectral loadings and the correlation matrix identifies redundant variables resulting in a model with an optimal number of variables . The results obtained with this model show that the straightforward linear regression can be a sufficient approach to avoid the introduction of systematic errors in on-line pre-processing of data.

Prog Neuropsychopharmacol Biol Psychiatry, 1999 Jul, 23(5), 951 - 61
The influence of nimodipine, nicardipine and amlodipine on the brain free fatty acid level in rats with penicillin-induced seizures; Zupan G et al.; 1 . The aim of this study was to investigate the effects of the calcium channel blockers, nimodipine, nicardipine and amlodipine, on the brain free fatty acid (FFA) level in rats with chemically-induced seizures . 2 . The study was carried out on Hannover-Wistar rats . Animals were anesthetized and placed in a stereotaxic apparatus . Each of them received an injection of penicillin (5000 IU/5 microliters) into the left lateral ventricle (i.c.v.) . Various doses (1, 3, 10 or 30 mg/kg) of nimodipine, nicardipine or amlodipine had been injected i.p . 30 min before the penicillin application . The rats were decapitated 5 min after the occurrence of epileptic seizures . FFAs were quantified by gas chromatography using the internal standard method . 3 . The results demonstrate that i.c.v . injection of penicillin was associated with significant increase in the brain FFA concentration . Tested doses of nicardipine and amlodipine did not influence the increase of the brain free palmitic, stearic, oleic and arachidonic acid level while nimodipine prevented the accumulation of free palmitic, oleic and arachidonic acid in rats with penicillin-induced seizures . Statistically insignificant decrease of steric acid was observed in animals pretreated with nimodipine . 4 . It maybe assumed that the brain FFA accumulation caused by i.c.v . penicillin administration is not predominantly associated with a disturbance in calcium homeostasis via L-type voltage-sensitive calcium channels, but by some other membrane and/or intracellular mechanisms.

FEBS Lett, 1999 Oct 1, 459(1), 111 - 4
Escherichia coli TEM1 beta-lactamase in CTAB reverse micelles: exchange/diffusion-limited catalysis; Moreno-Hagelsieb G et al.; We report kinetic data of penicillin hydrolysis catalyzed by beta-lactamase entrapped in reverse micelles formed with cetyl trimethylammonium bromide (CTAB), n-octane, hexanol and aqueous buffer . The K(cat) of this diffusion-limited reaction can be improved in aqueous buffer by a factor of 1.1-1.2 just by increasing the phosphate buffer concentration from 50 to 100 mM . In reverse micelles, increasing the buffer concentration has little effect on K(cat) when the size of the empty micelle is below the size of the protein . However, in larger micelles, the effect is enhanced and the K(cat) improves several fold, changing the form of the curve of K(cat) versus Wo from bell-shaped to almost hyperbolic . The results indicate that micellar exchange and internal diffusion may limit the reaction in reverse micelles and provide further evidence that the form of the curve depends on other factors besides the relationship between the size of the enzyme and that of the empty reverse micelle.

Ann Allergy Asthma Immunol, 1999 Sep, 83(3), 257 - 66
Clinical usefulness of patch and challenge tests in the diagnosis of cell-mediated allergy to betalactams; Patriarca G et al.; BACKGROUND: Literature reports dealing with cell-mediated allergy to betalactams have appeared with increasing frequency in the last years . OBJECTIVE: To evaluate patients with such reactions and to identify cross-reactivities among betalactams in order to provide safe guidelines for their further clinical management . METHODS: Thirty consecutive subjects with cell-mediated allergy to betalactams (history of adverse reactions to these antibiotics; serum total IgE within the normal range; absence of serum specific IgE antibodies to penicillin G and V, amoxicillin, and ampicillin; negative skin tests with a wide pattern of betalactam preparations; and positive patch-test to at least one betalactam antigenic determinant) were investigated . The subjects admitted to the study were patch tested with a wide variety of betalactam preparations in order to identify alternative molecules tolerated by the patient . To better evaluate the cross-reactivity pattern, tolerance challenges with patch-negative betalactams were also performed in each subject . RESULTS: Both specific IgE and skin tests were negative in all patients . The skin biopsies performed on the positive patch-tested area in four patients showed a clear T-lymphocyte, CD4+-type infiltrate, thus definitely proving the occurrence of a cell-mediated response . A total of 44 adverse reactions (mean: 1.47 episodes for each patient) were reported in history, with a mean interval of 15 hours after betalactam administration . The reported symptoms were mainly cutaneous (maculo-papular rash and urticaria) and the responsible drugs were chiefly aminopenicillins (86.4% of cases) and penicillin G (9.1%) . We were able to identify three separate groups of patients on the basis of clinical history, patch-test, and tolerance challenge pattern: allergy to the side chain of aminopenicillins in 16 patients (53.3%); allergy to the thiazolidine ring in 3 patients (10.0%); undetermined specificity in the remainder 11 patients (36.7%) . Cross-reactivity among different betalactam molecules (revealed by positive tolerance tests performed with patch-negative betalactams) was found in 4.8% of cases only (23.3% of all investigated patients) . This fact demonstrates a very high (95.2%) predictive value of a negative patch-test in excluding the occurrence of a cross-reactivity . The mis-match between patch and tolerance tests was observed in 3 out of 178 cases only (1.7% of cases, 10.5% of patients) in groups A and B, and in as much as 12.2% of cases (45.5% of subjects) in group C (P < .05) . CONCLUSIONS: Delayed allergy to betalactams (mainly to aminopenicillins) may be exerted by a cell-mediated response . Patch tests and tolerance challenges are extremely useful and safe for diagnosis and further clinical treatment of these patients, helping to identify safe alternative betalactam molecules that could be successfully tolerated by the allergic subjects.

Presse Med, 1999 Sep 4, 28 Suppl 1, 13 - 5
{Pristinamycin in the treatment of acute communicable pneumopathies in adults}; Poirier R; ALTERNATIVE TO BETA-LACTAMS: Due to the rapid and increasing development of resistance in the two main bacteria, S . pneumoniae and H . influenzae, it is important to determine whether pristinamycin, with known efficacy against these germs, could be a useful alternative to beta-lactams for the treatment of adult acute community-acquired pneumonia . PRISTINAMYCIN VS AMOXICILLIN/CLAVULANIC ACID: A double-blind placebo-controlled randomized multicentric study with two treatment arms enrolling hospitalized patients was conducted . Pristinamycin, 1 g b.i.d., demonstrated an efficacy equivalent to that of the amoxicillin/clavulanic acid combination, 500 mg x 4/d . IN CLINICAL PRACTICE: Pristinamycin is effective for the treatment of community-acquired pneumonia . Comparative studies including a large number of penicillin-resistant pneumococci remain to be performed, but the first intention use of pristinamycin is already fully warranted in patients at risk treated in an outpatient setting.

Presse Med, 1999 Sep 4, 28 Suppl 1, 10 - 2
{Pristinamycin in the outpatient treatment of acute sinusitis in adults}; Pessey JJ; TWO MAIN GERMS: The risk of severe complications of acute bacterial sinusitis warrants empirical antibiotic therapy targeted against the two main causal agents: S . pneumoniae and H . influenzae . PRISTINAMYCIN VS CEFUROXIME AXETIL: A double-blind placebo-controlled randomized multicentric study conducted with two treatment arms including 310 patients has demonstrated that pristinamycin, 2 g/d for 8 days, has a clinical efficacy equivalent to cefuroxime axetil, 500 mg/d . IN CLINICAL PRACTICE: Pristinamycin is an interesting alternative to beta-lactams for the first intention treatment of purulent acute sinusitis in adults . Its efficacy against penicillin-resistant pneumococci and H . influenzae is a further reason for its use in case of failure after conventional treatments.

Ann Intern Med, 1999 Sep 21, 131(6), 434 - 7
Azithromycin compared with penicillin G benzathine for treatment of incubating syphilis; Hook EW 3rd et al.; BACKGROUND: Preventive therapy is an important element of syphilis control efforts . No currently recommended, single-dose alternatives to penicillin G benzathine are available for treatment of incubating syphilis . OBJECTIVE: To evaluate the use of a single 1.0-g dose of azithromycin for treatment of persons recently exposed to sexual partners with infectious syphilis . DESIGN: Single-center, open-label, randomized pilot study to compare azithromycin with penicillin G benzathine therapy . Participants were evaluated serologically for 3 months . SETTING: Sexually transmitted disease clinic in Birmingham, Alabama . PARTICIPANTS: 96 participants who in the preceding 30 days had been exposed to partners with infectious syphilis through sexual intercourse . MEASUREMENTS: Syphilis prevention, as indicated by nonreactive serologic tests (rapid plasma reagin and fluorescent treponemal antibody-absorbed), throughout the 3-month follow-up . RESULTS: Among 96 participants enrolled, none of 40 evaluable persons in the azithromycin group and none of 23 evaluable persons in the penicillin group developed evidence of syphilis . Significantly more penicillin-treated participants (21 of 44 {48%}) than azithromycin-treated participants (12 of 52 {23%}) became nonevaluable during follow-up (P = 0.01) . CONCLUSION: A single 1.0-g dose of azithromycin seems to be efficacious for prevention of syphilis in persons exposed to infected sexual partners.

Protein Sci, 1999 Sep, 8(9), 1816 - 24
Functional analyses of AmpC beta-lactamase through differential stability; Beadle BM et al.; Despite decades of intense study, the complementarity of beta-lactams for beta-lactamases and penicillin binding proteins is poorly understood . For most of these enzymes, beta-lactam binding involves rapid formation of a covalent intermediate . This makes measuring the equilibrium between bound and free beta-lactam difficult, effectively precluding measurement of the interaction energy between the ligand and the enzyme . Here, we explore the energetic complementarity of beta-lactams for the beta-lactamase AmpC through reversible denaturation of adducts of the enzyme with beta-lactams . AmpC from Escherichia coli was reversibly denatured by temperature in a two-state manner with a temperature of melting (Tm) of 54.6 degrees C and a van't Hoff enthalpy of unfolding (deltaH(VH)) of 182 kcal/mol . Solvent denaturation gave a Gibbs free energy of unfolding in the absence of denaturant (deltaG(u)H2O) of 14.0 kcal/mol . Ligand binding perturbed the stability of the enzyme . The penicillin cloxacillin stabilized AmpC by 3.2 kcal/mol (deltaTm = +5.8 degrees C); the monobactam aztreonam stabilized the enzyme by 2.7 kcal/mol (deltaTm = +4.9 degrees C) . Both acylating inhibitors complement the active site . Surprisingly, the oxacephem moxalactam and the carbapenem imipenem both destabilized AmpC, by 1.8 kcal/mol (deltaTm = -3.2 degrees C) and 0.7 kcal/mol (deltaTm = -1.2 degrees C), respectively . These beta-lactams, which share nonhydrogen substituents in the 6(7)alpha position of the beta-lactam ring, make unfavorable noncovalent interactions with the enzyme . Complexes of AmpC with transition state analog inhibitors were also reversibly denatured; both benzo(b)thiophene-2-boronic acid (BZBTH2B) and p-nitrophenyl phenylphosphonate (PNPP) stabilized AmpC . Finally, a catalytically inactive mutant of AmpC, Y150F, was reversibly denatured . It was 0.7 kcal/mol (deltaTm = -1.3 degrees C) less stable than wild-type (WT) by thermal denaturation . Both the cloxacillin and the moxalactam adducts with Y150F were significantly destabilized relative to their WT counterparts, suggesting that this residue plays a role in recognizing the acylated intermediate of the beta-lactamase reaction . Reversible denaturation allows for energetic analyses of the complementarity of AmpC for beta-lactams, through ligand binding, and for itself, through residue substitution . Reversible denaturation may be a useful way to study ligand complementarity to other beta-lactam binding proteins as well.

Epilepsia, 1999 Sep, 40(9), 1309 - 11
Intractable epilepsy as the initial manifestation of neurosyphilis; Phan TG et al.; A 29-year-old man experienced intractable partial seizures as the initial manifestation of neurosyphilis . The diagnosis was made after the onset of dementia 9 months later . Both the epilepsy and dementia resolved with penicillin therapy . Syphilis should be considered in patients with adult-onset focal epilepsy, particularly if there is associated dementia . Treatment may be successful even when the diagnosis is delayed.

Zh Vyssh Nerv Deiat Im I P Pavlova, 1999 Mar-Apr, 49(2), 321 - 30
{Changes in the behavior and EEG of rats administered penicillin and a physiological solution into the amygdalar basal nuclei}; Pankova NB et al.; Three weeks after implantation of the electrodes for EEG recording, hyperactivation of the basal nucleus of rat's amygdala was produced by a local injection of penicillin (0.5 mcl, 1% solution) . Saline injection of the same volume served as control . The hyperactivation of the amygdala resulted in a long-lasting (at least for 3 weeks) increase in the locomotor activity against the background and deficit in exploratory behavior and rise of the level of anxiety and fear . The behavioral changes were accompanied by a long-term disruption of the hippocampal theta rhythm, appearance and slowing of the immobility-related high-voltage spindles, and increase in the EEG dominant frequency in the state of emotional tension . Saline injection led to a short-time (up to 1 week) decrease in locomotor and exploratory activity and increase in anxiety . These phenomena were accompanied by a short-time disruption of the theta rhythm and appearance of the 10-13-Hz oscillations characteristic for the state of emotional tension.

Wien Klin Wochenschr, 1999 Aug 20, 111(15), 603 - 7
Pelvic actinomycosis; Gorisek B et al.; Pelvic actinomycosis is a rare chronic infection caused by bacteria of the family Actinomycetaceae . Prolonged use of an intrauterine contraceptive device (IUD) is a well known risk factor . We report six patients with pelvic actinomycosis, all of whom had an IUD inserted for over six years . Diagnostic problems necessitated a laparotomy in all patients . The pathohistological diagnosis was based on the characteristic microscopic image and specific staining . The patients were treated with penicillin and amoxycillin for several months.

Int J Biochem Cell Biol, 1999 Aug, 31(8), 861 - 8
A comprehensive analysis of heat shock protein synthesis in human peripheral lymphocytes: the effect of penicillin/streptomycin; Rao DV et al.; A reliable experimental procedure is described for the simultaneous characterisation of a comprehensive range of heat shock proteins (hsps) in human peripheral lymphocytes . In this system, a mild heat shock from 37 to 42 degrees C for 1 h induced the synthesis of hsps 105, 90, 70, 60, 57, 47, 40, 27 and 16 . Densitometric analyses of 35{S}-methionine labelled protein gels indicated that levels of these hsps peaked at 3 to 4 h, following post-heat shock recovery at 37 degrees C . The presence of penicillin and streptomycin in the cell culture medium, appeared to have little effect on the kinetics of hsp synthesis . The present method can be used for relatively small blood samples and its relative ease of application and reproducibility make it appropriate for screening the expression of hsps in human lymphocytes from a range of individuals.

Ann Allergy Asthma Immunol, 1999 Aug, 83(2), 132 - 6
Systemic reactions to allergy skin tests; Valyasevi MA et al.; BACKGROUND: Skin testing is a common diagnostic tool in allergy . It is considered a safe procedure, although systemic reactions have been reported . OBJECTIVE: To identify the systemic reaction rates of allergy skin tests and to determine the clinical outcome of such reactions . METHOD: This retrospective study used a computerized database at the Mayo Clinic to identify patients who developed systemic reactions to skin tests . Altogether 497,656 skin tests were performed on 18,311 patients from January 1992 to June 1997 . Skin puncture tests were performed on 16,505 patients . Skin puncture and intradermal skin tests were performed on 1,806 patients . Systemic reactions were evaluated and treated by physicians . RESULTS: There were 6 systemic reactions, an overall rate of 33 systemic reactions per 100,000 skin tests . All six patients had asthma . The systemic reaction rates for latex skin testing was 152 or 228 reactions per 100,000 latex skin tests, to penicillin and antibiotics 72 reactions per 100,000 penicillin and antibiotics skin tests, and to aeroallergens 15 or 23 reactions per 100,000 aeroallergen skin tests . The systemic reaction rate for skin puncture test was 30 reactions per 100,000 skin puncture tests, for skin puncture and intradermal skin tests, the rate was 55 reactions per 100,000 skin puncture and intradermal skin tests . All 6 patients were treated and dismissed within 1 hour after treatment . CONCLUSION: The systemic reaction rate to skin tests was very low . Systemic reactions were mild and all patients recovered fully within 1 hour.

Lik Sprava, 1999 Apr-May, (3), 126 - 8
{Serum sickness in diphtheria}; Vozianova ZhI et al.; As many as 2247 patients with different clinical forms of diphtheria were examined . Antidiphtheric serum (ADS) was administered in 1556 children, the dosage being determined by condition of the patient . Serum sickness developed at day 7 to 9 in 24 (1.5%); 10 patients were found to run a mild course, 14--moderately severe . 6 patients had allergic reactions: 3--to antibiotic (penicillin), urticaria type, 1--to pertussoid-tetanic anatoxin, 2 had pollinosis-type reaction . Thus, serum sickness has practical value, which fact requires a detailed allergic history together with skin tests to be performed before the administration of ADS.

Pediatr Dermatol, 1999 Jul-Aug, 16(4), 314 - 6
Effect of penicillin G on corium thickness in linear morphea of childhood: An analysis using ultrasound technique; Mohrenschlager M et al.; Linear morphea is the most common form of localized scleroderma in children . The pathogenesis of this disorder is unknown . We report a child with a 6-year history of linear morphea in whom intravenous administration of 5 MU aqueous penicillin G three times a day for 10 consecutive days caused reduction in the thickness of the corium as demonstrated by ultrasound measurements.

Helicobacter, 1999 Sep, 4(3), 154 - 61
Different penicillin-binding protein profiles in amoxicillin-resistant Helicobacter pylori; Dore MP et al.; BACKGROUND: The beta-lactam group of antibiotics kills bacteria by inhibiting the terminal stages of peptidoglycan metabolism . We have recently identified amoxicillin-resistant Helicobacter pylori, none of which expressed beta-lactamase . Penicillin-binding proteins (PBPs) represent a group of target enzymes for the beta-lactam antibiotic family, and alterations in PBPs have been described in other penicillin-resistant bacteria . The amoxicillin-resistant phenotype characteristically was lost after freezing but could be restored by consecutive transfers into gradient plates . MATERIALS AND METHODS: To determine whether amoxicillin resistance in H . pylori was related to alterations in any of the H . pylori PBPs, five H . pylori strains resistant to amoxicillin and three amoxicillin-sensitive strains were tested . PBPs were extracted from bacteria grown to logarithmic phase, labeled in vivo with 3H-benzylpenicillin, and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fluorography . Four main PBPs were separated from all amoxicillin-sensitive H . pylori strains . RESULTS: Only three of the four main PBPs were found in the amoxicillin-resistant H . pylori strains . The differentially detectable PBP (PBP D) had an apparent molecular weight of 30 to 32 kD . CONCLUSION: These results suggest that PBP D might play a role in the amoxicillin-resistant phenotype of H . pylori strains lacking beta-lactamase activity.

N J Med, 1999 Aug, 96(8), 23 - 5
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