J Endod . 2003 Oct;29(10):685. Death from actinomycosis; Ingle JI; Death from actinomycosis, although unusual today, was devastating at one time . Although commonplace today, using antibiotics to save patients from death was unusual when penicillin was first introduced over 50 years ago. Arch Med Res, 2003 Sep-Oct, 34(5), 382 - 7 Rheumatic fever and rheumatic heart disease: clinical profile of 550 cases in India; Ravisha MS et al.; BACKGROUND: The aims and objectives of this paper were to analyze the clinical presentation of children with rheumatic fever (RF) and rheumatic heart disease (RHD), to determine the cardiac sequel of RF and valvular affection due to RF, and to study clinical manifestations in recurrences of RF . METHODS: Our study, a retrospective analysis, was conducted at a tertiary-care teaching hospital with specialty follow-up clinic for patients with RF/RHD . This retrospective study was conducted to include a period of 31 years (from January 1971 through December 2001) . Pre-completed case protocols of patients with RF/RHD were analyzed to record the following information: demographic data; clinical features on admission/presentation; relevant investigations; recurrences; cardiac valvular affection, and outcome . Modified Jones' criteria were used for diagnosis of RF . RESULTS: The study included 550 patients . Mean age of presentation was 9.62 years and sex ratio was 1.15:1 favoring males . A total of 250 patients presented with initial/first attack of RF . Arthritis and carditis were seen in 169 (67.6%) and 105 cases (42%), respectively . Chorea was seen in 47 cases (18.8%) and erythema marginatum, in four . A total of 224 patients presented with recurrence of RF (with pre-existing RHD) . Arthritis and carditis were seen in 109 (48.66%) and 178 cases (79.46%), respectively, in these patients; 76 cases presented with chronic RHD . Mitral regurgitation was the most common cardiac valvular lesion observed (150 cases) followed by a combination of mitral stenosis and mitral regurgitation (98 cases) . Congestive cardiac failure was seen in 201 cases (36.54%) and infective endocarditis in 30 (5.45%) . 2-D echocardiography and/or color Doppler was performed in 201 patients (36.54%) . Average duration of follow-up was 3.19 years; 74.72% of cases were lost to follow-up . Benzathine penicillin prophylaxis was regular in 42.18% cases . Positive family history of RF/RHD was present in 2% of cases . Twenty three patients (4.18%) died . CONCLUSIONS: Arthritis was the most common manifestation in the initial attack of RF, while carditis was the most common manifestation in patients presenting with rheumatic recurrences (with pre-existing RHD) and mitral regurgitation was the most common valvular lesion . Rate of patient dropout from penicillin prophylaxis was high . Clinical manifestations in initial/first attack of RF have not significantly changed in the last 31 years. Anasthesiol Intensivmed Notfallmed Schmerzther, 2003 Nov, 38(11), 716 - 8 {Amanita poisoning during pregnancy}; Schleufe P et al.; A pregnant woman at the 28th gestational week and three other members of the family had mushrooms for dinner . One of these mushrooms was an Amanita mushroom . The morning after, three of them suffered from nausea, vomiting and diarrhoea . The pregnant woman was admitted to hospital, and therapy with Penicillin and Silibinin was started immediately . Hepatic and renal blood parameters were observed repeatedly for early detecting of organ failure . Fetal lung maturation was forced by administration of betamethasone . After five days at the intensive care unit mother and unborn child were dismissed at normal physical condition. Rheumatol Int, 2004 Jul, 24(4), 247 - 9 Epub 2003 Oct 31. Differential diagnosis of optic neuritis in a patient with ankylosing spondylitis; Appenzeller S et al.; The authors report a 38-year-old white man with ankylosing spondylitis (AS) who presented with recurrent ischaemic optic neuritis . The initial diagnosis was of multiple sclerosis, but further investigation showed serology and cerebrospinal fluid culture positive for syphilis . After treatment for tertiary syphilis with penicillin, there was complete remission of the ocular symptoms . This case illustrates the differential diagnosis of optic neuritis in AS and supports the relevance of investigating infectious diseases in the management of ischaemic optic neuritis. Rev Esp Med Nucl, 2003 Nov, 22(6), 424 - 6 {Osteitis in secondary syphilis}; Gomez Martinez MV et al.; BACKGROUND: The aim of this study is to report two patients with osteitis in secondary syphilis . The increase in the number of cases of syphilis, linked to the changes in sexual behavior and to the increase of immigrants from areas of high prevalence of STD, as well as its relationship with HIV infection, makes important to clinicians become aware of unusual presentation of secondary syphilis . PATIENTS: We report two patients diagnosed of secondary syphilis, one of them with HIV infection . Both showed dermatological lesions in palms and soles, malaise and fever . Bone scintigraphy showed significant uptake in parietal and frontal bones in both patients . Clinical response was quickly achieved after penicillin treatment . CONCLUSIONS: In patients with secondary syphilis and osteoarticular symptoms luetic osteitis must be included in differential diagnosis . Bone scintigraphy should be the first diagnostic tool because it possibilities to perform a total body scan which allows localizing asymptomatic lesions . Moreover bone scan shows a high sensitivity. Rapid Commun Mass Spectrom, 2003, 17(21), 2387 - 93 Use of different proteases working in acidic conditions to improve sequence coverage and resolution in hydrogen/deuterium exchange of large proteins; Cravello L et al.; The combination of hydrogen exchange and mass spectrometry has been widely used in structural biology, providing views on protein structure and protein dynamics . One of the constraints is to use proteases working at low pH and low temperature to limit back-exchange during proteolysis . Although pepsin works in these conditions and is currently used in such experiments, sequence coverage is not always complete especially for large proteins, and the spatial resolution of the exchange rate is limited by the size of the resulting peptides . In this study we tried two other proteases, protease type XIII from Aspergillus saitoi and protease type XVIII from Rhizhopus species . The penicillin-binding protein X (PBP-2X*), a 77-kDa protein, was selected as a model . Like pepsin, neither of these proteases is really specific, but we found very good reproducibility in the digestion pattern . Compared with using pepsin alone, combining the results of the three independent proteolyses increased the coverage for the peptide mapping, thus avoiding missing some potentially interesting regions of the protein . Furthermore, we obtained a better spatial resolution for deuterium incorporation data, specifying accurately the deuterated regions . Eur J Cardiothorac Surg, 2003 Nov, 24(5), 694 - 8 The role of surgery in hemoptysis caused by thoracic actinomycosis; a forgotten disease; Lu MS et al.; OBJECTIVE: Thoracic actinomycosis is a relatively uncommon anaerobic infection caused by Actinomyces israelii . Rarely, it may be complicated by an unusual but significant hemoptysis manifestation . We describe our experiences of surgical treatment for hemoptysis in patients with pulmonary actinomycosis . METHODS: From 1984 to 2002, 14 patients with thoracic actinomycosis and hemoptysis were diagnosed after thoracotomy . There were 11 male and three female patients with a mean age of 53.6 years . They all had non-specific symptoms and radiographic findings, and no case was an accurate diagnosis made at the time of hospital admission, including echo-guide aspiration, serial bronchoscopic biopsy and computed tomography biopsy . The indications of surgical intervention in our patients were for treating complications such as hemoptysis, chronic sinus discharge, or empyema, also limited to diagnostic purposes . Preoperative embolization was performed in seven cases; however, none was successful . RESULTS: Among the 14 patients, all the lesions were unilateral . The disease was confined to the lung in all patients; and chest wall involvement in one patient . The surgical procedures included were as follows: pneumonectomy (n=1), bilobectomy (n=1), lobectomy (n=10), wedge resection (n=2), and lung lesion with concomitant chest wall resection and chest wall reconstruction (n=1) . Mean intraoperative and postoperative blood loss within the first 24 h was 192.3 ml, and five patients required blood transfusion . All of the specimens from the lesion site showed histological evidence of Actinomyces infection . All patients regularly took 12 million units per day of intravenous crystalline penicillin G during their hospitalization, and oral procaine penicillin for up to 2 months . During the follow-up, all patients had an uneventful postoperative course . CONCLUSIONS: A high index of suspicion for this disease is advised for the surgeon engaged in the treatment of hemoptysis . Surgical resection of pulmonary actinomycosis is effective in preventing recurrence of hemoptysis . After diagnosis, it is treated using penicillin chemotherapy for at least 2 months. Presse Med, 2003 Oct 11, 32(33), 1557 - 8 {Hypersensitive reaction to abacavir or syphilitic hepatitis?}; Dumouchel-Champagne H et al.; INTRODUCTION: Syphilis remains a current infection in France, with an increase in cases associated with the increase in sexual practices at risk . OBSERVATION: An HIV-seropositive homosexual male presented with a perturbed hepatic profile and roseola-like exanthema 15 days after starting treatment with Trizivir . Because of the combination of hepatitis and cutaneous eruption evoking hypersensitivity to abacavir, treatment was suspended, but no improvement was noted . The diagnosis of syphilitic hepatitis associated with roseola was made following a sero-conversion and improvement was obtained with benzathine-penicillin and the re-introduction of Trizivir without further problem . COMMENTS: This case report underlines the possibility of discovering syphilis when confronted with cholestatic and cytolytic hepatitis that regresses with penicillin and is isolated or associated with evocative cutaneous signs. Sex Transm Infect, 2003 Oct, 79(5), 415 - 6 Treatment of neurosyphilis with ceftriaxone; Shann S et al.; The first choice treatment for late syphilis is penicillin . Other than doxycycline, which penetrates the CNS, there are few alternatives for the treatment of neurosyphilis . We report a case of successful treatment of symptomatic neurosyphilis with parenteral ceftriaxone. Zh Nevrol Psikhiatr Im S S Korsakova, 2003, 103(9), 4 - 8 {Epilepsy and the brain's morphological-functional organization}; Karlov VA; The article summarized the results of long-term studies of the author with using experimental methods--creation of penicillin and aluminium epileptogenic foci, orbito-frontal cortex stimulation and elimination, and clinical investigation of epileptic status, prefrontal epilepsy, absence EEG activity, symptomatic rolandic epilepsy, childhood epilepsy . Based on the results obtained, the author formulates the conceptions on (1) the key role of prefrontal cortex in the antiepileptic defense system and motor activity control, (2) the role of slow activity in antiepileptogenesis, (3) the age-dependent rhythmic possibilities of children's brain, which determined age-dependent epilepsy types, (4) the complexity of between-hemispheric interactions in this disease. Curr Opin Hematol, 2003 Nov, 10(6), 419 - 23 Anaphylactic transfusion reactions; Gilstad CW; PURPOSE OF REVIEW: Although anaphylactic reactions to blood products are rare, the incidence of allergic reactions to blood products is similar to the allergic reaction incidence to penicillin antibiotics, and therefore worthy of proportionate attention.Comprehensive reviews and guidelines of the management of anaphylaxis currently do not include much information on blood products . Current guidelines for the specific management of anaphylactic transfusion reactions are contradictory as to the utility of anti-IgA testing and incomplete by not offering suggestions for the management of non-IgA related reactions . RECENT FINDINGS: Anti-IgA is not responsible for most reactions . Anti-haptoglobin antibodies are responsible for more reactions than anti-IgA in Japan, but the cause of most reactions is still not known . The incidence of reactions to platelets is the highest compared with fresh frozen plasma and red blood cells . Pre-storage white blood cell reduction of platelets does not decrease the incidence of reactions, indicating that white blood cell-derived cytokines are not responsible for most reactions . SUMMARY: The increased incidence of reactions to platelets compared with fresh frozen plasma suggests that a platelet-related factor may be responsible for many of the reactions . The possible role of platelet microparticles or activated platelet membranes, which carry a negative charge similar to ionic radiocontrast media, the major cause of iatrogenic anaphylactic reactions in the hospital, is explored. Joint Bone Spine, 2003 Sep, 70(5), 390 - 2 Nicolau's syndrome after local glucocorticoid injection; Cherasse A et al.; We report three cases of Nicolau's syndrome induced by intraarticular glucocorticoid injections . Nicolau's syndrome is defined as livedo-like dermatitis secondary to acute arterial thrombosis occurring immediately after intravascular injection of an insoluble drug substance . The cases described by Nicolau occurred in association with injections of oily bismuth suspensions . In 1970s and 1980s, cases occurred with delayed-action penicillin suspensions injected intramuscularly . Typically, the injection is followed immediately by excruciating pain in the buttock, sometimes with syncope . Cyanotic patches and a livedoid pattern develop . Rapid resolution of the pain and slower clearing of the skin changes occur in most patients . We report three typical cases with both severe pain and skin changes . In addition, two other patients had incomplete variants without skin abnormalities . Each of these five patients had received an injection in or about a joint of a glucocorticoid in a crystalline suspension . The pathophysiology of this syndrome probably involves acute vascular spasm related to penetration of microcrystals into a blood vessel. J Biol Chem, 2003 Dec 26, 278(52), 52826 - 33 Epub 2003 Oct 10. Crystal structure of wild-type penicillin-binding protein 5 from Escherichia coli: implications for deacylation of the acyl-enzyme complex; Nicholas RA et al.; Penicillin-binding protein 5 (PBP 5) of Escherichia coli functions as a d-alanine carboxypeptidase (CPase), cleaving d-alanine from the C terminus of 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 acylenzyme complex (t(1/2) approximately 10 min) . A Gly105 --> Asp mutation in PBP 5 markedly impairs deacylation with only minor effects on acylation, and abolishes CPase activity . We have determined the three-dimensional structure of a soluble form of wild-type PBP 5 at 1.85-A resolution and have also refined the structure of the G105D mutant form of PBP 5 to 1.9-A resolution . Comparison of the two structures reveals that the major effect of the mutation is to disorder a loop comprising residues 74-90 that sits atop the SXN motif of the active site . Deletion of the 74-90 loop in wild-type PBP 5 markedly diminished the deacylation rate of penicillin G with a minimal impact on acylation, and abolished CPase activity . These effects were very similar to those observed in the G105D mutant, reinforcing the idea that this mutation causes disordering of the 74-90 loop . Mutation of two consecutive serines within this loop, which hydrogen bond to Ser110 and Asn112 in the SXN motif, had marked effects on CPase activity, but not beta-lactam antibiotic binding or hydrolysis . These data suggest a direct role for the SXN motif in deacylation of the acyl-enzyme complex and imply that the functioning of this motif is modulated by the 74-90 loop. Biotechnol Adv, 2000 Jul, 18(4), 289 - 301 Advances in enzymatic transformation of penicillins to 6-aminopenicillanic acid (6-APA); Parmar A et al.; This article elaborates on the important recent developments in the enzymatic transformation of penicillins to 6-aminopenicillanic acid (6-APA), which is the basic raw material for the industrial production of semisynthetic penicillins such as amoxycillin and ampicillin . Particular emphasis is placed on the improvements in purification, stability, and immobilization of the enzymes, (i.e . penicillin acylases) used for these transformations. Braz J Infect Dis, 2003 Aug, 7(4), 273 - 7 Atypical presentation of syphilis in an HTLV-I infected patient; Carnauba D Jr et al.; We report the case of a 44 year-old female, who presented a long-lasting, clinically atypical, secondary syphilis ("malignant syphilis") in the right foot, which started six months before medical evaluation . The patient had a serological diagnosis of HTLV-I infection and syphilis two years before the onset of the skin lesions, following a blood donation . As she believed she was allergic to penicillin, she initially received sulfamethoxazole + trimethoprim, without any improvement of the clinical picture . After failure of this first treatment regimen, she was given penicillin, which promoted complete healing of the lesion . We found evidence that infection by HTLV-I is capable of modifying the clinical course of secondary syphilis. Planta Med, 2003 Aug, 69(8), 692 - 5 Inhibitory effect of jujuboside A on glutamate-mediated excitatory signal pathway in hippocampus; Zhang M et al.; Jujuboside A (JuA) is a main component of jujubogenin extracted from the seed of Ziziphus jujuba Mill var spinosa (Bunge) Hu ex H F Chou (Ziziphus), which is widely used in Chinese traditional medicine for the treatment of insomnia and anxiety . Previously, we reported the inhibitory effects of JuA on hippocampal formation in vivo and in vitro, the present study was carried out to examine the effects of JuA on glutamate (Glu)-mediated excitatory signal pathway in hippocampus . Microdialysis coupled with high-performance liquid chromatography (HPLC) was used to monitor the changes of Glu levels in the hippocampus induced by penicillin sodium, or a mixture of penicillin sodium and JuA . The results showed that penicillin increased the hippocampal Glu concentration (p < 0.01) and a high dose of JuA (0.1 g/L) significantly blocked penicillin-induced Glu release (p < 0.05) . Moreover, the effect of JuA on intracellular Ca2+ changes after the stimulation by Glu was studied in cultured hippocampal neurons with confocal laser scanning microscope (CLSM) . It was found that Glu (0.5 mM) induced an intracellular {Ca2+}i increase (p < 0.01), and JuA significantly inhibited the Glu-induced Ca2+ increase . The calmodulin (CaM) antagonist trifluoperazine (TFP) showed a similar inhibitory effect as JuA . These observations suggested that JuA has inhibitory effects on Glu-mediated excitatory signal pathway in hippocampus and probably acts through its anti-calmodulin action. Biotechnol Prog, 2003 Sep-Oct, 19(5), 1510 - 8 Enzyme distribution derived from macroscopic particle behavior of an industrial immobilized penicillin-G acylase; van Roon JL et al.; The macroscopic kinetic behavior of an industrially employed immobilized penicillin-G acylase, called Assemblase, formed the basis for a discussion on some simple intraparticle biocatalytic model distributions . Assemblase catalyzes the synthesis of the widely used semisynthetic antibiotic cephalexin . Despite the obvious advantages of immobilization, less cephalexin and more of the unwanted byproduct d-(-)-phenylglycine are obtained due to diffusional limitations when the immobilized enzyme is employed . To rationally optimize Assemblase, the parameters particle size, enzyme loading, and enzyme distribution, which severely determine the macroscopic particle performance, were studied on the basis of macroscopic observations . Laser diffraction measurements showed that the particle sizes in Assemblase vary as much as 100-fold . The relative and total enzyme loadings in Assemblase and fractions thereof of different sizes were determined by initial-rate d-(-)-phenylglycine amide hydrolysis, cephalexin synthesis experiments, and active-site titration . These experiments revealed that the loading of penicillin-G acylase in Assemblase was inversely correlated with the particle diameter . Apart from enzyme loadings, estimates on the intraparticle enzyme distribution came from cephalexin synthesis experiments, where mass-transport limitations were present . Although this method cannot provide the level of detail of specific labeling experiments, it is simple, fast, and cheap . Within the set of simple model predictions, a heterogeneous enzyme distribution with most biocatalyst present in the outer region of the particle (within the outer 100 microm) gave the best description of the observed behavior, although no exact correlation was established . Highly detailed determination of intraparticle enzyme distributions must come from immunolabeling. Biotechnol Lett, 2003 Sep, 25(17), 1397 - 402 Galactose induces the expression of penicillin acylase under control of the lac promoter in recombinant Escherichia coli; De Leon A et al.; The expression of penicillin acylase (PA), cloned in the pPA102 plasmid under control of the wild-type lac promoter and using galactose as inducer in Escherichia coli JM101, JM103 and JM105 transformant cells, was analyzed . The E . coli JM101/pPA102 cultures attained the highest specific activity of PA . For large scale PA production based on E . coli JM101/pPA102 a culture media with galactose instead of isopropyl-thio-galactopyranoside as inducer would be as successful and less expensive. J Am Acad Dermatol, 2003 Oct, 49(4), 749 - 51 Secondary syphilis simulating oral hairy leukoplakia; Aquilina C et al.; We describe a case of secondary syphilis of the tongue in which the main clinical presentation of the disease was similar to oral hairy leukoplakia . In a man who was HIV seronegative, the first symptom was a dryness of the throat followed by a feeling of foreign body in the tongue . Lesions were painful without cutaneous manifestations of secondary syphilis . IgM-fluorescent treponemal antibody test and typical serologic parameters promptly led to the diagnosis of secondary syphilis . We initiated an appropriate antibiotic therapy using benzathine penicillin, which induced healing of the tongue lesions . The differential diagnosis of this lesion may include oral squamous carcinoma, leukoplakia, candidosis, lichen planus, and, especially, hairy oral leukoplakia . This case report emphasizes the importance of considering secondary syphilis in the differential diagnosis of hairy oral leukoplakia . Depending on the clinical picture, the possibility of syphilis should not be overlooked in the differential diagnosis of many diseases of the oral mucosa. Int J STD AIDS, 2003 Sep, 14(9), 625 - 9 Gonorrhoea in a south London genitourinary medicine department; Newell A et al.; The management and outcome of all cases of gonorrhoea which presented to a south London genitourinary medicine clinic during 1999 were assessed and compared with published national guidelines . The incidence of penicillin resistance was calculated, as was the rate of co-infection with chlamydia and trichomonas . Information regarding demographic data, microscopy, culture results, test of cure, antibiotic use, sensitivity and health adviser contact was examined . A total of 257 cases of gonorrhoea were diagnosed in 238 patients . Heterosexual men constituted 52.9% of cases, 6.6% were in homosexual men and 40.5% in women . Direct microscopy was positive in 88.8% of men and in 40.5% of women . In women, the rate of gonorrhoea co-infection with chlamydia was 34.7% and with trichomonas was 11.5% . In men the rate of chlamydia co-infection was only 3.3%, however, we do not believe this to be an accurate figure as we are unable to routinely screen all men for chlamydia due to financial restrictions . Amoxicillin with probenecid were the most commonly used antibiotics in line with local guidelines . Penicillin resistance was demonstrated in 4.6% of infected cases . Health advisers saw 73.2% of patients. Med Secoli, 2002, 14(2), 529 - 50 {Images of anti-luetic therapeutic systems and drugs}; Marinozzi S; This article offers a "flash" of images concerning the diffusion and advertising of specific anti-luetic therapeutic systems and drugs, since the beginning of XVI century to the discovery and the therapeutical use of penicillin . Advertisements in medical and scientific magazines and pictures of texts and articles of the Library of the History of Medicine (Universita degli Studi di Roma "La Sapienza") have been used. Curr Genet, 2003 Dec, 44(4), 211 - 5 Epub 2003 Sep 24. 4'-phosphopantetheinyl transferase-encoding npgA is essential for siderophore biosynthesis in Aspergillus nidulans; Oberegger H et al.; Aspergillus nidulans produces two major siderophores: it excretes triacetylfusarinine C to capture iron and contains ferricrocin as an intracellular iron-storage compound . Siderophore biosynthesis involves the enzymatic activity of nonribosomal peptide synthetases (NRPS) . NRPS contain 4'-phosphopantetheine as an essential prosthetic group, which is attached by 4'-phosphopantetheinyl transferases . A . nidulans appears to possess at least one gene, npgA, encoding such an enzyme . Using a strain carrying a temperature-sensitive allele, cfwA2, we showed that NpgA is essential for biosynthesis of both the peptide bond-containing ferricrocin and the ester bond-containing triacetylfusarinene C . The cfwA2 strain was found to be iron-starved at the restrictive temperature during iron-replete conditions, consistent with the siderophore system being the major iron-uptake system-as we recently demonstrated . Northern analysis indicated that, in contrast to other genes which are involved in siderophore biosynthesis and uptake, expression of npgA is not controlled by the GATA-transcription factor SreA . It was shown previously that NpgA is required for biosynthesis of penicillin, pigment, and potentially lysine via the alpha-aminoadipate pathway . Supplementation with lysine plus triacetylfusarinine C restored normal growth of the cfwA2 strain at the restrictive temperature, suggesting that the growth defect of the mutant is mainly due to impaired biosynthesis of siderophores and lysine. Ross Fiziol Zh Im I M Sechenova, 2003 May, 89(5), 505 - 11 {Effect of paleocerebellar cortex electrical stimulation on generalized penicillin-induced seizure activity in rats}; Godlevskii LS et al.; It was shown that low-frequency electrical stimulation (ES) (10-12 Hz, 0.5 ms) of paleocerebellar cortex (nodulus, uvula) is followed by activation of spike discharges which were induced via i.p . administration of sodium benzilpenicillin salt to alert Wistar rats (300,000 IU/kg) . The facilitation of ictal discharges generation was also seen in the course of such an ES . High-frequency (100-300 Hz, 0.25 ms) ES of the same structure was followed by suppression of spike discharges and prevented the ictal discharges precipitation . Antiseizure action was obvious under condition of relatively low level of epileptic activity generation . In the course of such ES the decreasing frequency and amplitude of spike discharges were noted during interstimuli periods . Besides, the life-span of seizure activity was shortened as well . The repeated paleocerebellar ES made after electrocoagulation of irritated tissue did not cause modulations of seizure activity. An Sist Sanit Navar, 2003, 26 Suppl 2, 39 - 47 {Basophil activation test in the diagnosis of allergy to medicines}; Sanz ML et al.; In this paper we study the reliability of the basophil activation test (BAT) in the "in-vitro" diagnosis of allergy to betalactams and to metamizol, and the sensitivity and specificity of the technique are analyzed . To this end, we studied 58 patients allergic to betalactam antibiotics with a positive cutaneous test facing any derivative of penicillin and 30 healthy controls who tolerated betalactams, and 26 patients allergic to metamizol with an immediate reaction and 30 healthy controls who tolerated the medicine . Sensitivity to BAT in allergy to betalactams was 52.8%, and specificity was 92.6% . For metamizol, sensitivity was 42.3% and specificity was 100% . The positive predictive value of BAT in allergy to betalactams was 18.9% and the negative predictive value was 98.4% . For metamizol, the positive predictive value of the technique was 100% and the negative predictive value was 99.4% . The joint use of BAT and CAP (specific IgE) makes it possible to diagnose some 65% of patients allergic to betalactams . The combined use of cutaneous tests and BAT in allergy to metamizol detects 70% of the cases . BAT is a useful, non-invasive technique in the "in-vitro" diagnosis of allergy to betalactams and metamizol. J Comput Aided Mol Des, 2003 Feb-Apr, 17(2-4), 103 - 18 QSAR modeling of beta-lactam binding to human serum proteins; Hall LM et al.; The binding of beta-lactams to human serum proteins was modeled with topological descriptors of molecular structure . Experimental data was the concentration of protein-bound drug expressed as a percent of the total plasma concentration (percent fraction bound, PFB) for 87 penicillins and for 115 beta-lactams . The electrotopological state indices (E-State) and the molecular connectivity chi indices were found to be the basis of two satisfactory models . A data set of 74 penicillins from a drug design series was successfully modeled with statistics: r2 = 0.80, s = 12.1, q2 = 0.76, spress = 13.4 . This model was then used to predict protein binding (PFB) for 13 commercial penicillins, resulting in a very good mean absolute error, MAE = 12.7 and correlation coefficient, q2 = 0.84 . A group of 28 cephalosporins were combined with the penicillin data to create a dataset of 115 beta-lactams that was successfully modeled: r2 = 0.82, s = 12.7, q2 = 0.78, spress = 13.7 . A ten-fold 10% leave-group-out (LGO) cross-validation procedure was implemented, leading to very good statistics: MAE = 10.9, spress = 14.0, q2 (or r2press) = 0.78 . The models indicate a combination of general and specific structure features that are important for estimating protein binding in this class of antibiotics . For the beta-lactams, significant factors that increase binding are presence and electron accessibility of aromatic rings, halogens, methylene groups, and =N- atoms . Significant negative influence on binding comes from amine groups and carbonyl oxygen atoms. Ugeskr Laeger, 2003 Aug 11, 165(33), 3157 - 61 {Investigation of penicillin allergy . Procedures and retrospective statement of results for the period 1997 to 2001}; Borch JE et al.; INTRODUCTION: We describe procedures in and findings of investigation for allergy to penicillin as it was performed at the Dermatological Department and the Allergy Centre of Odense University Hospital in the 5-year period 1997-2001 and compare history with findings on skin tests and systemic challenge . MATERIAL AND METHODS: Retrospective evaluation of findings in the investigation of penicillin allergy . A total of 109 patients with a history of reaction to treatment with penicillins and a negative specific IgE for penicillins G and V were successively skin prick tested, intracutaneously skin tested, challenged orally and by intramuscular injection . Further testing was cancelled when a positive result occurred . RESULTS: Fifteen of 109 (13.7%) had positive reactions on investigation . There was no correlation between the type and severity of cutaneous or systemic reactions to penicillin or presence of other allergies and test positivity or negativity . 20% of the test-positive developed severe systemic reactions (respiratory, cardiovascular) upon systemic challenge . DISCUSSION: 13.7% in a selected patient material with a history of penicillin allergy and negative specific IgE were found to have reaction to penicillin upon investigation . A high percentage of patients (20%) experienced systemic reactions to provocation . This finding has resulted in new procedures for the investigation of allergy to penicillin in our clinic. Hautarzt, 2003 Sep, 54(9), 886 - 93 {The German Society for Control of Sexually Transmitted Diseases (DGBG/GBGK) 1945-1984}; Vogt HJ; The Deutsche Gesellschaft zur Bekampfung der Geschlechtskrankheiten (German Society for Control of Sexually Transmitted Diseases) was founded in 1902 . After World War II, many regional groups existed . The drafting of the Gesetz zur Bekampfung der Geschlechtskrankheiten (Laws regarding Control of Sexually Transmitted Diseases), public education regarding the increasing rates of STDs, continuing medical education especially regarding the use of penicillin in syphilis and gonorrhea, and the major scientific advances in this field stimulated the re-formation of a national organization . Members of the new organization were important in the development of more sophisticated tests for syphilis in the 1960s, for the decrease in incidence of gonorrhea in the 1970s, and for advances in the diagnosis and treatment of mycoplasma, Chlamydia trachomatis, herpes genitalis and human papilloma viruses . This new information was also disseminated via a variety of continuing medical education activities . The hopes of the general public and physicians that such therapeutic advances would make scientific research in the area of STDs unattractive or even unnecessary proved to be overly optimistic . The worldwide epidemic of HIV/AIDS confronted the society with a new major challenge in the early 1980s. An Med Interna, 2003 Jul, 20(7), 373 - 6 {Malignant syphilis in patient with human immunodeficiency virus (HIV): case report and literature review}; Romero-Jimenez MJ et al.; Malignant syphilis is an infrequent manifestation of syphilis in HIV infected patients . Only 21 cases have been published in medical literature . Most frequent in men, 62%, the mean age of presentation is 34 years . The most frequent symptoms are: 100% ulcerative cutaneous lesions, 47% fever and 33% ocular affectation . About 80% of the patients have a CD4 count >200 . Lues serological test was 100% positive and 81% responded to penicillin . We report a 18 year old woman diagnosed of HIV infection, admitted to our service because of fever, painful oral sores, over-elevated eritematous lesions and cratered ulcers all over the body, with the initial suspicion of chickenpox . Lues serology turned out to be positive, as well as the Warthin Starry stain . After penicillin treatment was initiated, skin lesions improved, although residual lesions currently persist . Malignant syphilis should be considered in infected HIV patients with fever and ulcerated skin injuries as a possible diagnosis . Eventhough serological tests allow diagnosis confirmation, Warthin Starry stain can be useful when serology is negative . The first choice of treatment is penicillin and in case of penicillin allergy, a third generation cefalosporine should be used. J Bacteriol, 2003 Sep, 185(18), 5342 - 8 Overproduction of inactive variants of the murein synthase PBP1B causes lysis in Escherichia coli; Meisel U et al.; Penicillin-binding protein 1B (PBP1B) of Escherichia coli is a bifunctional murein synthase containing both a transpeptidase domain and a transglycosylase domain . The protein is present in three forms (alpha, beta, and gamma) which differ in the length of their N-terminal cytoplasmic region . Expression plasmids allowing the production of native PBP1B or of PBP1B variants with an inactive transpeptidase or transglycosylase domain or both were constructed . The inactive domains contained a single amino acid exchange in an essential active-site residue . Overproduction of the inactive PBP1B variants, but not of the active proteins, caused lysis of wild-type cells . The cells became tolerant to lysis by inactive PBP1B at a pH of 5.0, which is similar to the known tolerance for penicillin-induced lysis under acid pH conditions . Lysis was also reduced in mutant strains lacking several murein hydrolases . In particular, a strain devoid of activity of all known lytic transglycosylases was virtually tolerant, indicating that mainly the lytic transglycosylases are responsible for the observed lysis effect . A possible structural interaction between PBP1B and murein hydrolases in vivo by the formation of a multienzyme complex is discussed. Cell Mol Life Sci, 2003 Jul, 60(7), 1460 - 9 BlaB, a protein involved in the regulation of Streptomyces cacaoi beta-lactamases, is a penicillin-binding protein; Raskin C et al.; Streptomyces cacaoi beta-lactamase genes are controlled by two regulators named blaA and blaB . Whereas BlaA has been identified as a LysR-type activator, the function of BlaB is still unknown . Its primary structure is similar to that of the serine penicillin-recognizing enzymes (PREs) . Indeed, the SXXK and KTG motifs are perfectly conserved in BlaB, whereas the common SXN element found in PREs is replaced by a SDG motif . Site-directed mutations were introduced in these motifs and they all disturb beta-lactamase regulation . A water-soluble form of BlaB was also overexpressed in the Streptomyces lividans TK24 cytoplasm and purified . To elucidate the activity of BlaB, several compounds recognized by PREs were tested . BlaB could be acylated by some of them, and it can therefore be considered as a penicillin-binding protein . BlaB is devoid of beta-lactamase, D-aminopeptidase, DD-carboxypeptidase or thiolesterase activity. Guang Pu Xue Yu Guang Pu Fen Xi, 2002 Feb, 22(1), 51 - 3 {Studies of penicillins by micro Raman spectroscopy}; Qian XF et al.; The Raman spectra of three kinds of penicillins were obtained and investigated by micro Raman technique . By comparing these Raman spectra, we find there are many differences among them, and it can be used as an important criterion in distinguishing different kinds of penicillins . In this paper, the characteristic Raman peaks of penicillins have been given . In other hand, we find there is no much difference in the Raman spectra of same kind of penicillin, even though different plants produce them . So, the Raman spectra can't be used to make sure whether certain plant produces one sample. Rev Fac Cien Med Univ Nac Cordoba, 2001, 58(1), 105 - 7 {Arcanobacterium haemolyticum sinusitis}; Notario RD et al.; Arcanobacterium haemolyticum is a bacterial pharyngeal pathogen that predominantly infects adolescents and young adults . It rarely causes severe infection . A case of sinusitis in an 18-year-old female patient with a skin rash is presented . The strain was susceptible to erythromicin, ampicilin, vancomicin, cephalotin, clindamicin, rifampicin and penicillin . Erythromicin has been proposed as first-line therapy. J Dent, 2003 Sep, 31(7), 479 - 85 Formocresol mutagenicity following primary tooth pulp therapy: an in vivo study; Zarzar PA et al.; OBJECTIVES: To investigate whether formocresol, in Buckley's original formulation, is mutagenic in vivo to lymphocyte cultures obtained from the peripheral blood of children aged from 5 to 10 years old . These children were recruited from those attending the dental clinics of Recife City Council and the University of Pernambuco School of Dentistry, Brazil . METHODS: The sample comprised 20 children who had primary teeth with cariously exposed vital pulps . Two venous blood samples were collected (6-8 ml) from each child, the first prior to vital pulpotomy (control group) and the second 24 h after pulpotomy (treated group) . This research is a case-control study . The peripheral lymphocytes were grown in a complete culture medium consisting of 78% RPMI 1640 medium (a), supplemented with streptomycin (0.01 mg/ml), penicillin (0.005 ml(-1)), 20% fetal bovine serum (b) and 2% phytohemagglutinin (c) . The lymphocytes were assessed for chromosomal aberrations via a previously published method which was modified . The cytogenetic analysis was performed in a blind test, where the slides were codified by an annotator and the scorers did not know which group they were analyzing . For each sample, this envolved the analysis of 200 metaphases . The level of significance adopted in the statistical test was 5.0% (p<0.05) . RESULTS: There was no statistically significant difference in clinical doses between the control and treated groups, using Wilcoxon's Signed Ranks test, for the chromosomal aberrations (P=0.251) and for the total chromosomal breaks (P=0.149) . Although there were no statistically significant differences between the control and treated groups, Buckley's formocresol was mutagenic for one patient, raising doubt about the desirability of its use for pulpotomies in children . CONCLUSIONS: The results revealed that, from a statistical standpoint, formocresol is not mutagenic . However, further investigations are required, preferably with a larger sample, in patients needing more than one pulpotomy in order to observe whether an increase in the quantity of the drug would increase the quantity of chromosome aberrations and also to verify individual susceptibility to chromosome alterations with the use of formocresol. Reprod Fertil Dev, 2003 Aug 13, 15(4), 223 - 229 Nuclear morphology, diameter and meiotic competence of buffalo oocytes relative to follicle size; Yousaf MR et al.; The nuclear morphology, diameter and in vitro meiotic competence of buffalo oocytes was compared relative to follicle size . Cumulus-oocyte complexes (COCs) were collected from 1-<2, 2-<3, 3-<4, 4-<6 and 6-<8 mm follicles from abattoir ovaries . Cumulus cells were removed using 3 mg mL(-1) hyaluronidase in saline and repeated pipetting . Denuded oocytes were measured, fixed in 3% glutaraldehyde, stained with 4,6-diamidoino-2-phenylindole and evaluated for nuclear morphology, namely the stage of germinal vesicle (GV) development before in vitro maturation (IVM) . The COCs from >2-mm follicles were matured in vitro in their respective size groups for 24 h in Medium 199 supplemented with 10 mug mL(-1) follicle-stimulating hormone, 10 mug mL(-1) luteinizing hormone, 1.5 mug mL(-1) oestradiol, 75 mug mL(-1) streptomycin, 100 IU mL(-1) penicillin, 10 mM HEPES and 10% fetal bovine serum . Matured oocytes were fixed, stained and evaluated for GV status and meiotic development . The number of oocytes collected from follicles 1-<8 mm in diameter averaged 1.82 per ovary . Oocytes from follicles 1-<2 mm (107.7 +/- 1.6 mum), 2-<3 mm (108 +/- 1.1 mum) and 3-<4 mm (114.6 +/- 1.3 mum) in diameter were smaller in diameter (P < 0.05) than oocytes from follicles 4-<6 mm (124.4 +/- 1.3 mum) and 6-<8 mm (131.9 +/- 1.4 mum) in diameter . A majority of oocytes (P< 0.05) from <4-mm follicles was at the initial stages of GV development (GV-I, II and III), whereas oocytes from 4-<6- and 6-<8-mm follicles were at the final stages of GV-IV (35.0 and 21.6% respectively) and GV-V (49.1 and 67.5% respectively) . Poor IVM rates of 32.0% and 32.7% to metaphase (M)-II were observed for oocytes isolated from 2-<3- and 3-<4-mm follicles, respectively, whereas significantly (P< 0.05) more oocytes from 4-<6- and 6-<8-mm follicles reached M-II (67.1% and 79.1% respectively) . In conclusion, buffalo oocytes displayed a size-dependent ability to undergo meiotic maturation and we suggest that oocytes from >4-mm follicles should be considered in buffalo in vitro fertilization systems for better results. Hist Cienc Saude Manguinhos, 2002, 9 Suppl, 161 - 86 {Physicians, prostitution, and venereal disease in Colombia (1886-1951)}; Obregon D; The article examines the Colombian medical field's fight against so-called venereal diseases between 1886 and 1951, a period when the country was undergoing processes of urbanization, population growth, and the emergence both of industry as well as of a middle class and an urban proletariat . Physicians found a close connection between the spread of syphilis and gonorrhea and the rise of prostitution in cities . At the close of the 19th century, doctors and public health bodies assumed prostitution was inevitable . In 1907 they managed to have it legalized and they opened clinics to dispense mercury therapy and treatment with arsenic compounds . Starting in the 1930s amd 1940s, treatment of venereal diseases was viewed as the State's duty, necessary to protect "la raza" and safeguard progress and civilization . As of 1950, the efficient use of penicillin once again caused the question of prostitution to be posed in more moral and aesthetic terms and brought an end to the regulations groverning its practice, at least in Bogota. Anal Bioanal Chem, 2003 Oct, 377(3), 496 - 506 Epub 2003 Aug 06. Biosensors based on enzyme field-effect transistors for determination of some substrates and inhibitors; Dzyadevych SV et al.; This paper is a review of the authors' publications concerning the development of biosensors based on enzyme field-effect transistors (ENFETs) for direct substrates or inhibitors analysis . Such biosensors were designed by using immobilised enzymes and ion-selective field-effect transistors (ISFETs) . Highly specific, sensitive, simple, fast and cheap determination of different substances renders them as promising tools in medicine, biotechnology, environmental control, agriculture and the food industry.The biosensors based on ENFETs and direct enzyme analysis for determination of concentrations of different substrates (glucose, urea, penicillin, formaldehyde, creatinine, etc.) have been developed and their laboratory prototypes were fabricated . Improvement of the analytical characteristics of such biosensors may be achieved by using a differential mode of measurement, working solutions with different buffer concentrations and specific agents, negatively or positively charged additional membranes, or genetically modified enzymes . These approaches allow one to decrease the effect of the buffer capacity influence on the sensor response in an aim to increase the sensitivity of the biosensors and to extend their dynamic ranges.Biosensors for the determination of concentrations of different toxic substances (organophosphorous pesticides, heavy metal ions, hypochlorite, glycoalkaloids, etc.) were designed on the basis of reversible and/or irreversible enzyme inhibition effect(s) . The conception of an enzymatic multibiosensor for the determination of different toxic substances based on the enzyme inhibition effect is also described.We will discuss the respective advantages and disadvantages of biosensors based on the ENFETs developed and also demonstrate their practical application. Zhongguo Yi Xue Ke Xue Yuan Xue Bao, 2000 Aug, 22(4), 398 - 9 {The diagnosis and treatment of Lyme disease: a report of six cases}; Liu X et al.; We retrospectively analyzed the clinical features, diagnosis, treatment, and prognosis of 6 cases of Lyme disease from November, 1994 to December, 1998 . According to our report, doxycycline, penicillin, and ceftriaxone are effective drugs for Lyme disease . The shorter the disease course is, the better the treatment effect will be . Patients in phase III usually need repeated treatment. Nucleic Acids Symp Ser, 2000, (44), 183 - 4 Trans-kingdom conjugation between bacterial chromosome-less mini-cells and yeasts; Fukumaru K et al.; We introduced a novel convenient method to prepare chromosome-less mini-cells from cell mixture of Escherichia coli P678-54 by using penicillin . The mini-cells prepared by this method could successfully transferred their harboring conjugative plasmids into eukaryotic yeast cells by trans-kingdom conjugation. Chin Med Sci J, 2001 Mar, 16(1), 52 - 5 Spirochetes--the possible etiological factor of the cheilitis granulomatosa; Liu H et al.; OBJECTIVE: To detect spirochetes in sections and to study the therapeutic effect of penicillin in cheilitis granulomatosa (CG) and Melkersson-Rosenthal syndrome (MRS) and the relationship between the spirochetes infection and CG and MRS . METHODS: Routine HE sections and Warthin-Starry special staining were carried out in 20 cases of CG and 6 cases of MRS . Meanwhile there were 9 cases of CG and 2 caes of MRS were treated by penicillin (12 000 000u, i.v., per day) for two courses (14 days) . RESULTS: A kind of spirochete was discovered in the sections of all cases of the CG and MRS . The CG and MRS could be divided into two types histopathologically, that is granuloma type and interstitial inflammatory type (non-granuloma type), those morphological changes tallied with spirochetosis . After treatment by penicillin, the facial and labial swelling of the 11 cases of CG and MRS were abated . CONCLUSION: CG and MRS probably are infectious diseases caused by spirochetes. Biotechnol Prog, 2003 Jul-Aug, 19(4), 1167 - 75 Conjugation of penicillin acylase with the reactive copolymer of N-isopropylacrylamide: a step toward a thermosensitive industrial biocatalyst; Ivanov AE et al.; Conjugation of penicillin acylase (PA) to poly-N-isopropylacrylamide (polyNIPAM) was studied as a way to prepare a thermosensitive biocatalyst for industrial applications to antibiotic synthesis . Condensation of PA with the copolymer of NIPAM containing active ester groups resulted in higher coupling yields of the enzyme (37%) compared to its chemical modification and copolymerization with the monomer (9% coupling yield) at the same NIPAM:enzyme weight ratio of ca . 35 . A 10-fold increase of the enzyme loading on the copolymer resulted in 24% coupling yield and increased by 4-fold the specific PA activity of the conjugate . Two molecular forms of the conjugate were found by gel filtration on Sepharose CL 4B: the lower molecular weight fraction of ca . 10(6) and, presumably, cross-linked protein-polymer aggregates of MW > 10(7) . Michaelis constant for 5-nitro-3-phenylacetamidobenzoic acid hydrolysis by the PA conjugate (20 microM) was found to be slightly higher than that of the free enzyme (12 microM), and evaluation of V(max) testifies to the high catalytic efficiency of the conjugated enzyme . PolyNIPAM-cross-linked PA retained its capacity to synthesize cephalexin from d-phenylglycin amide and 7-aminodeacetoxycephalosporanic acid . The synthesis-hydrolysis ratios of free and polyNIPAM-cross-linked enzyme in cephalexin synthesis were 7.46 and 7.49, respectively . Thus, diffusional limitation, which is a problem in the industrial production of beta-lactam antibiotics, can be successfully eliminated by cross-linking penicillin acylase to a smart polymer (i.e., polyNIPAM). Am Fam Physician, 2003 Jul 15, 68(2), 283 - 90 Diagnosis and management of syphilis; Brown DL et al.; Syphilis is a sexually transmitted disease with varied and often subtle clinical manifestations . Primary syphilis typically presents as a solitary, painless chancre, whereas secondary syphilis can have a wide variety of symptoms, especially fever, lymphadenopathy, rash, and genital or perineal condyloma latum . In latent syphilis, all clinical manifestations subside, and infection is apparent only on serologic testing . Late or tertiary syphilis can manifest years after infection as gummatous disease, cardiovascular disease, or central nervous system involvement . Neurosyphilis can develop in any stage of syphilis . The diagnosis of syphilis may involve dark-field microscopy of skin lesions but most often requires screening with a nontreponemal test and confirmation with a treponemal-specific test . Parenterally administered penicillin G is considered first-line therapy for all stages of syphilis . Alternative regimens for nonpregnant patients with no evidence of central nervous system involvement include doxycycline, tetracycline, ceftriaxone, and azithromycin . In pregnant women and patients with neurosyphilis, penicillin remains the only effective treatment option; if these patients are allergic to penicillin, desensitization is required before treatment is initiated . Once the diagnosis of syphilis is confirmed, quantitative nontreponemal test titers should be obtained . These titers should decline fourfold within six months after treatment of primary or secondary syphilis and within 12 to 24 months after treatment of latent or late syphilis . Serial cerebrospinal fluid examinations are necessary to ensure adequate treatment of neurosyphilis. J Chromatogr B Analyt Technol Biomed Life Sci, 2003 Aug 25, 794(1), 67 - 76 Purification of penicillin G acylase using immobilized metal affinity membranes; Liu YC et al.; The immobilized metal affinity membrane (IMAM) with modified regeneration cellulose was employed for purification of penicillin G acylase (PGA) . For studying PGA adsorption capacity on the IMAM, factors such as chelator surface density, chelating metal, loading temperature, pH, NaCl concentration and elution solutions were investigated . The optimal loading conditions were found at 4 degrees C, 0.5 M NaCl, 32.04 micromol Cu(2+) per disk with 10 mM sodium phosphate buffer, pH 8.5, whereas elution conditions were: 1 M NH(4)Cl with 10 mM sodium phosphate buffer, pH 6.8 . By applying these chromatographic conditions to the flow experiments in a cartridge, a 9.11-fold purification in specific activity with 90.25% recovery for PGA purification was obtained . Meanwhile, more than eight-times reusability of the membrane was achieved with the EDTA regeneration solutions. Gastroenterol Hepatol, 2003 Aug-Sep, 26(7), 417 - 20 {Liver failure due to mushroom poisoning: clinical course and new treatment perspectives}; Catalina MV et al.; Mushroom poisoning, mainly due to the Amanita genus, is an infrequent cause of liver failure in our environment . However, because of its high morbidity and mortality, it constitutes a medical emergency . The characteristic initial symptoms of vomiting, abdominal pain, and diarrhea are nonspecific and may be confused with gastroenteritis . If correct and early treatment is not given, renal and hepatic failure can develop, sometimes requiring liver transplantation . We present three cases of mushroom poisoning, which presented a different clinical course ranging from complete recovery with traditional medical treatment to severe acute liver failure requiring transplantation in one patient and albumin dialysis (molecular absorbent recycling system {MARS}) in another with favorable outcome . Although controlled clinical studies of the treatment of mushroom poisoning are lacking, recommendations based on the experience of various authors have been established . Penicillin G and silymarin seem to be useful . The development of new techniques of extracorporeal detoxification, mainly MARS, may represent an important support system in the treatment of these patients. Pharmacotherapy, 2003 Jul, 23(7), 855 - 60 Assessment of medication errors that involved drug allergies at a university hospital; Jones TA et al.; OBJECTIVES: To determine the reporting accuracy of true patient-related allergies to drugs in a large teaching institution (908 licensed beds), and to identify factors contributing to medication errors that involved drug allergies . Of particular interest was the accuracy of allergy information in the medical record and the occurrence of medication errors that involved penicillin antibiotics . METHODS: From a sample population of 340 patients, 50 adult patients admitted to our university-affiliated hospital who met criteria and had an allergy to selected drugs that was documented in the hospitalwide computer system were randomly selected and interviewed to determine the timing, nature, and extent of the reaction . Furthermore, data were collected from identified Medication Error Reports when an agent was prescribed for a patient with a reported allergy to that agent or class . Prospective data collection was conducted from November 2000-February 2001 . Using the information obtained by the patient interview and chart documentation, we assessed the reported allergy . In addition, contributing factors for medication errors that involved drug allergies were identified . RESULTS: Of the sample population, 133 patients (39%) reported allergies to at least one drug . Allergies to beta-lactams, sulfonamides, and opioid narcotics were reported in 12.6% (43 patients), 9.1% (31), and 14.4% (49) of the sample population, respectively . Most agents involved in medication errors were beta-lactam antibiotics, with an overwhelming number of these errors due to piperacillin-tazobactam (51.4%, 36 errors) . Other drugs involved were ampicillin (10%, 7 errors), other beta-lactams (24.3%, 17 errors), opioid narcotics (10%, 7 errors), and sulfonamides (4.3%, 3 errors) . Most contributing factors were classified as "MD {prescribing physician} not aware of allergy." CONCLUSION: These results suggest a need for ensuring that prescribers review each patient's allergy profile before order entry. Eur Arch Otorhinolaryngol, 2003 Jul, 260(6), 298 - 300 Epub 2003 Jan 10. Tularemia presenting as tonsillopharyngitis and cervical lymphadenitis: a case report and review of the literature; Arikan OK et al.; In this report, we describe a 57-year-old woman with oropharyngeal tularemia who presented with tonsillopharyngitis and cervical lymphadenitis . Clinical and radiological manifestations and histopathological characteristics of this disease are discussed with a review of the world literature . The oropharyngeal form of tularemia should be considered in the differential diagnosis of cases involving tonsillopharyngitis and cervical lymphadenitis, particularly in those not responding to penicillin treatment. Zhonghua Wai Ke Za Zhi, 2003 Apr, 41(4), 253 - 6 {Long-term results of prosthetic mitral valve replacement with home-made tilting disc valve: a report of 125 cases}; Zhang BR et al.; OBJECTIVE: To analyze the early and long-term results after mitral valve replacement for rheumatic valvular disease by using home-made tilting disc valve, and the determinant factors involved and subsequent therapies . METHODS: One hundred and five patients, including 31 patients with rheumatic mitral stenosis, 92 patients with mixed mitral stenosis and regurgitation, and 2 patients with bacterial endocarditis, underwent prosthetic mitral valve replacement with home-made tilting disc valve from September 1978 to June 1982 . Three patients had a history of mitral commissurotomy, and 5 patients had concomitant functional tricuspid regurgitation . All patients were operated on under cardiopulmonary bypass with implantation of 25 - 29 mm size home-made tilting disc valve prosthesis . The associated functional tricuspid lesions were treated at the same time with modified DeVega's valvuloplasty or Kays bicuspidate valvuloplasty . RESULTS: Eleven patients died during the hospital stay with an early operative mortality of 8.8% . The major causes of the early death were low cardiac output syndrome (4 patients), respiratory failure (2), acute renal failure (2), extrinsic prosthesis dysfunction (1), ventricular arrhythmia (1), and left ventricular rupture (1) . Ninety-eight survivors were followed up (total 1,162.2 years) for mean duration of 12.8 years . Eighty-nine patients (78%) survived over 10 years after operation, 58 (51%) over 15 years, and 55 (48%) over 20 years . There were 16 late deaths due to heart failure, anticoagulation related bleeding, thromboembolism and recurrence of rheumatic fever . The survival rates at 10 and 20 years were 82.3% and 51.1% respectively . Among the patients who survived over 20 years, 37 patients had the cardiac functional status returned to Class II, 13 Class III, and Class IV . CONCLUSIONS: Severe post-rheumatic valve deformity may occur in younger patients in China . Long-acting penicillin regimen given for 3 - 5 years for the prevention of rheumatic fever relapse is advocated . A low intensity anticoagulant regimen after mitral valve replacement is advisable in lowing the incidence of anticoagulant related bleeding, while optimizing sufficient protection against thromboembolic complication . Proper operative timing (e.g . when the patient is in sinus rhythm and in NYHA functional class II) is of great importance in achieving satisfied long-term results. Zhonghua Wai Ke Za Zhi, 2003 Apr, 41(4), 243 - 6 {Long-term results of mitral-aortic valve replacement in 1,154 patients with rheumatic valvular disease}; Zhang BR et al.; OBJECTIVE: To analyze the early and long-term results after mitral-aortic valve replacement for rheumatic valvular disease and the determinant factors involved and subsequent therapies . METHODS: 1 154 patients receiving combined mitral-aortic valve replacement for rheumatic valvular disease from May 1981 to May 2001 were reviewed . The mean age of the patients was 41.48 +/- 10.00 years . Concomitant valveplasty was performed for associated tricuspid organic or significant functional lesions . Lateral tilting disc or bileaflet valve prostheses were used for replacement . New York Heart Association functional status showed Class III or IV in 91.77% of the patients . Moderate to severe pulmonary hypertension occurred in 29.38% of the patients . The duration of follow-up varied from 8 months to 20 years . RESULTS: The hospital mortality was decreased from 6.50% to 4.45% . The 5-, 10- and l5-year survival rates were 89.46% +/- 1.35%, 86.50% +/- l.91% and 67.86% +/- 6.16%, respectively . The 5-, 10- and l5-year thromboembolic event free rates were 97.80% +/- 0.74%, 88.3l% +/- 2.20% and 94.08% +/- 2.29%, respectively . the 5-, 10- and l5-year anticoagulant related bleeding free rates were 94.80% +/- 1.09%, 89.32% +/- 2.10% and 83.12% +/- 3.57% respectively . Cardiac functional status returned to Class II in 98% patients and to Class III in 2% during follow-up . CONCLUSIONS: Both left and right ventricular functions may be impaired as a result of rheumatic valvular disease . Tricuspid valve should be explored during surgery and any significant tricuspid annular enlargement and regurgitation showed be corrected in concomitance . Long-acting penicillin regimen is needed for 3 - 5 years for the prevention of rheumatic fever relapse . A low intensity anticoagulant regimen after valve replacement with prothrombin time targeting at 1.5 - 2.0 times is advisable in lessening anticoagulant related bleeding yet optimizing sufficient prevention against thromboembolic complications. Biotechnol Lett, 2003 Mar, 25(6), 485 - 90 Continuous penicillin G hydrolysis in an electro-membrane reactor with immobilized penicillin G acylase; Zadrazil A et al.; Penicillin G (2%, w/v in phosphate buffer, pH 8) was hydrolysed in a flow-through, miniature electro-membrane reactor with the penicillin G acylase immobilized in 5% (w/v) polyacrylamide (diam . 10 mm, thickness 2.6 mm, enzyme activity 24 U ml(-1)) . The conversion of penicillin G increased from 0.15 to almost 0.5 when the electric current applied to the reactor was changed from -600 to +600 A/m2 with a substrate residency of 1 h. Ig Sanita Pubbl, 2002 Jul-Aug, 58(4), 253 - 7 {1946: hygienics and public health}; Bucci R; In Italy, the year 1946 was characterized, on one hand, by the growing concern for the lack of public structures and, on the other, by the hopes placed in the research sector, namely the apparently inexhaustible properties of penicillin and antibiotics . Consistently, Igiene e Sanita Pubblica reflected the general mood of the hygienists, swinging between the strong protests against a far too slow political system incapable of spurring scientific research, and the constant engagement aimed at enhancing the future role of public health . Besides facing many institutional problems, such as claiming an official recognition for their profession, hygienists also managed to make Italians understand the real value of a discipline conceived for the community service. Minerva Stomatol, 2003 Apr, 52(4), 187 - 90 {Mucocutaneous bullous pemphigoid induced by valsartan . A clinical case}; Femiano F; In the presence of immune-mediated vesiculo-bullous diseases, the oral pathologist should focus his attention not only on the diagnosis and treatment of the case, but should particularly investigate the state of genetic predisposition in relation to the HLA haplotype structure and look for the possible trigger factors for the disease . The detection of the trigger may guarantee a faster cure with a minimum therapeutic contribution . In the search for triggering factors, the drugs that are traditionally incriminated such as ACE inhibitors, Fans, antibiotics (penicillin and penicillamine), substances with -SH groups, tranquillisers, are not always involved in inducing vesiculo-bullous diseases . Substances considered innocuous are often to blame . We present a case of mucous-cutaneous bullous pemphigoid induced by an anti-hypertensive of the sartan group, valsartan. World J Biol Psychiatry, 2003 Jul, 4(3), 135 - 8 Dementia paralytica (neurosyphilis): a clinical case study; Ilankovic N et al.; This study reminds clinicians that syphilis presents in many guises . Wars, migration and sexual promiscuity prepare the ground for its return as an important cause of neurological and psychiatric syndromes . Our patient's diagnosis was not suspected at earlier admission . Stage III spirochaetosis was improved by high dose penicillin. Rev Inst Med Trop Sao Paulo, 2003 May-Jun, 45(3), 141 - 5 Epub 2003 Jul 08. Penicillin at the late stage of leptospirosis: a randomized controlled trial; Costa E et al.; There is evidence that an early start of penicillin reduces the case-fatality rate of leptospirosis and that chemoprophylaxis is efficacious in persons exposed to the sources of leptospira . The existent data, however, are inconsistent regarding the benefit of introducing penicillin at a late stage of leptospirosis . The present study was developed to assess whether the introduction of penicillin after more than four days of symptoms reduces the in-hospital case-fatality rate of leptospirosis . A total of 253 patients aged 15 to 76 years with advanced leptospirosis, i.e., more than four days of symptoms, admitted to an infectious disease hospital located in Salvador, Brazil, were selected for the study . The patients were randomized to one of two treatment groups: with intravenous penicillin, 6 million units day (one million unit every four hours) for seven days (n = 125) and without (n = 128) penicillin . The main outcome was death during hospitalization . The case-fatality rate was approximately twice as high in the group treated with penicillin (12%; 15/125) than in the comparison group (6.3%; 8/128) . This difference pointed in the opposite direction of the study hypothesis, but was not statistically significant (p = 0.112) . Length of hospital stay was similar between the treatment groups . According to the results of the present randomized clinical trial initiation of penicillin in patients with severe forms of leptospirosis after at least four days of symptomatic leptospirosis is not beneficial . Therefore, more attention should be directed to prevention and earlier initiation of the treatment of leptospirosis. Allergy Asthma Proc, 2003 May-Jun, 24(3), 199 - 202 The value of routine penicillin allergy skin testing in an outpatient population; Warrington RJ et al.; The aim of this study of patients with a history of allergy to penicillin, conducted in two separate surveys approximately 10 years apart, was to determine if (a) elective penicillin allergy testing was safe in terms of the risk of subsequent reactions on administration of these medications, and (b) if negative penicillin skin testing before the need for antibiotics resulted in the use of penicillin by the patient and referring physician . The first survey took place in 1989 and reviewed patients with negative skin tests to penicillin seen between 1983 and 1986 . This survey was by written questionnaire . The second survey took place in 2001 and reviewed patients between 1993 and 1997 and was conducted by telephone . In the 1983-1986 survey, 41% of the 68 patients reviewed took antibiotics in the subsequent 3-6 years and 50% of these patients took penicillin . Between 1993 and 1997, of the 84 patients contacted, 36 patients (42.8%) had taken antibiotics and 17 of these patients took penicillin . Of the 19 patients who did not take penicillin, 13 patients expressed their reluctance to do so to the family physician, and in 6 cases it was reported by the patient that the physician thought it was safer to use an alternative antibiotic . Overall, only 6% of the total patients in both groups developed an adverse reaction to penicillin, in each case a morbilliform delayed rash occurred . No patient had more than one course of penicillin in the survey period . Elective skin testing for penicillin allergy without immediate challenge after negative tests is safe, associated only with a low incidence (6%) of morbilliform eruptions; however, despite negative skin tests and being informed that they would tolerate penicillin, 52% of patients still prefer to use alternative antibiotics. Health Policy, 2003 Aug, 65(2), 167 - 79 The availability of drugs: what does it mean in Ugandan primary care; Jitta J et al.; Availability of drugs is often considered the most important element in quality of health care in rural African settings . Using material collected through mainly qualitative methods, this article examines drug availability in six primary health care units in southeastern Uganda . Emphasis is on the differing perspectives of three categories of actors: health planners/managers; health workers; and users of health services . The main concern is the availability of chloroquine and penicillin, especially injectable forms, and the needles and syringes for administering them . Health sector reforms have changed the conditions for managing, supplying, and using drugs through decentralization, user fees, and privatization . Patients were dissatisfied when they were not able to obtain all drugs prescribed at the health unit . Government health units both compete with, and use, local commercial sources of drugs . They need to attract patients and, with user fees, they are more able to supplement the drug kit supplies provided through the Ministry of Health . There is a need to revise policy in light of the new situation . Dialogue and realism are needed in order to create policies that respect both good medical treatment standards and the concerns of front line workers and their patients . The exercise of rethinking the meaning of drug availability in primary health care calls for methodologies examining the changing context of health care and the positions of different categories of actors, at national and district setting, to appreciate gaps existing between drug policy and practice. Ann Dermatol Venereol, 2003 May, 130 Spec No 1, 1S35 - 42 {Allergic and pseudo-allergic reactions to foods in chronic urticaria}; Moneret-Vautrin DA; The fact that more than 30 p . 100 of patients with chronic urticaria incriminate foods, and that acute urticaria is a frequent symptom of food allergy, argue in favour of a systematic search for food involvement in chronic urticaria . A global overview of publications through Medline selects 49 out of 189 papers upon strict criteria, devoted to the links between chronic urticaria and foods . Possible links exist between chronic urticaria and intolerance to additives, intolerance or allergy to contaminants, pseudo-allergic reactions to foods and IgE-dependent food allergy . The diagnosis of intolerance to additives relies on double blind placebo-controlled oral challenges, showing positivity in 2 to 3 p . 100 of cases . Flavours are being suspected but have not been validated by such oral challenges . Contaminants are nickel salts, penicillin residues in meats and milk, Anisakis larvae in fish . Intolerance to biogenic amines could be somewhat frequent and is well-documented by experimental studies of the metabolism of histamine and by the results of specific diets with a low content of amines . IgE-dependent food allergy has been evidenced in 1 to 5 p . 100 of cases . The author puts forward a methodology to search for the implication of foods in chronic urticaria, restricting the search to non-inflammatory CU, discarding moreover chronic urticaria due to physical agents, or to contact . Idiopathic chronic urticaria, that might include a subgroup of auto-immune chronic urticaria is under scope . A preliminary study of the regimen during one week needs to be carried out in order to detect an excess of consumption of categories of foods inducing pseudo-allergic reactions, or of additives . An eviction diet for biogenic amines may be proposed first . Its failure may lead to skin prick tests to foods that are daily consumed . Biological tests are not advised . When sensitization is confirmed, a 3 week eviction of the food comes ahead of a double blind placebo-controlled oral challenge . The positivity indicates that this food is likely to be a causal agent and the diagnosis can finally be based on the recovery after the implementation of strict avoidance diets. Biol Pharm Bull, 2003 Jul, 26(7), 1018 - 20 Identification of a penicillin-sensitive carboxypeptidase in the cellular slime mold Dictyostelium discoideum; Yasukawa H et al.; Penicillin binding proteins (PBPs) are penicillin-sensitive DD-peptidases catalyzing the terminal stages of bacterial cell wall assembly . We identified a Dictyostelium discoideum gene that encodes a protein of 522 amino acids showing similarity to Escherichia coli PBP4 . The D . discoideum protein conserves three consensus sequences (SXXK, SXN and KTG) that are responsible for the catalytic activities of PBPs . The gene product prepared in the cell-free translation system showed carboxypeptidase activity but the activity was not detected in the presence of penicillin G . These results demonstrate that the D . discoideum gene encodes a eukaryotic form of penicillin-sensitive carboxypeptidase. Structure (Camb), 2003 Jul, 11(7), 753 - 64 The crystal structure of the first enzyme in the pantothenate biosynthetic pathway, ketopantoate hydroxymethyltransferase, from M tuberculosis; Chaudhuri BN et al.; Ketopantoate hydroxymethyltransferase (KPHMT) catalyzes the first committed step in the biosynthesis of pantothenate, which is a precursor to coenzyme A and is required for penicillin biosynthesis . The crystal structure of KPHMT from Mycobacterium tuberculosis was determined by the single anomalous substitution (SAS) method at 2.8 A resolution . KPHMT adopts a structure that is a variation on the (beta/alpha) barrel fold, with a metal binding site proximal to the presumed catalytic site . The protein forms a decameric complex, with subunits in opposing pentameric rings held together by a swapping of their C-terminal alpha helices . The structure reveals KPHMT's membership in a small, recently discovered group of (beta/alpha) barrel enzymes that employ domain swapping to form a variety of oligomeric assemblies . The apparent conservation of certain detailed structural characteristics suggests that KPHMT is distantly related by divergent evolution to enzymes in unrelated pathways, including isocitrate lyase and phosphoenolpyruvate mutase. J Exp Med, 2003 Jul 7, 198(1), 145 - 51 Epub 2003 Jun 30. Platelet-activating factor-mediated NF-kappaB dependency of a late anaphylactic reaction; Choi IW et al.; Anaphylaxis is a life-threatening systemic allergic reaction with the potential for a recurrent or biphasic pattern . Despite an incidence of biphasic reaction between 5 and 20%, the molecular mechanism for the reaction is unknown . Using a murine model of penicillin V-induced systemic anaphylaxis, we show an autoregulatory cascade of biphasic anaphylactic reactions . Induction of anaphylaxis caused a rapid increase in circulating platelet-activating factor (PAF) levels . In turn, the elevated PAF contributes to the early phase of anaphylaxis as well as the subsequent activation of the nuclear factor (NF)-kappaB, a crucial transcription factor regulating the expression of many proinflammatory cytokines and immunoregulatory molecules . The induction of NF-kappaB activity is accompanied by TNF-alpha production, which, in turn, promotes late phase PAF synthesis . This secondary wave of PAF production leads eventually to the late phase of anaphylactic reactions . Mast cells do not appear to be required for development of the late phase anaphylaxis . Together, this work reveals the first mechanistic basis for biphasic anaphylactic reactions and provides possible therapeutic strategies for human anaphylaxis. J Biochem Biophys Methods, 2003 Jul 31, 57(1), 45 - 55 An evaluation of protein assays for quantitative determination of drugs; Williams KM et al.; We have evaluated the response of six protein assays {the biuret, Lowry, bicinchoninic acid (BCA), Coomassie Brilliant Blue (CBB), Pyrogallol Red-Molybdate (PRM), and benzethonium chloride (BEC)} to 21 pharmaceutical drugs . The drugs evaluated were analgesics (acetaminophen, aspirin, codeine, methadone, morphine and pethidine), antibiotics (amoxicillin, ampicillin, gentamicin, neomycin, penicillin G and vancomycin), antipsychotics (chlorpromazine, fluphenazine, prochlorperazine, promazine and thioridazine) and water-soluble vitamins (ascorbic acid, niacinamide, pantothenic acid and pyridoxine) . The biuret, Lowry and BCA assays responded strongly to most of the drugs tested . The PRM assay gave a sensitive response to the aminoglycoside antibiotics (gentamicin and neomycin) and the antipsychotic drugs . In contrast, the CBB assay showed little response to the aminoglycosides and gave a relatively poor response with the antipsychotics . The BEC assay did not respond significantly to the drugs tested . The response of the protein assays to the drugs was further evaluated by investigating the linearity of the response and the combined response of drug plus protein . The results are discussed with reference to drug interference in protein assays and the development of new methods for the quantification of drugs in protein-free solution. No To Shinkei, 2003 May, 55(5), 439 - 42 {A case report of syphilitic meningitis with right oculomotor nerve palsy}; Kurihara S et al.; A 63-year-old man presented with acute-onset right ptosis and diplopia . The patient reported having engaged in unspecified sexual activities during his third decade and was found to have positive syphilitic serological findings at the age of 56 years . No clinical symptoms were noted at this time . On admission, he showed only right oculomotor nerve palsy . The patient's intelligence, gait and sensory functions were normal . Laboratory analysis revealed positive syphilitic serological findings and examination of the cerebrospinal fluid (CSF) further revealed pleocytosis, a higher IgG index and positive syphilitic reactions . A computed tomographic scan and other imaging studies were diagnostically nonspecific . We made a diagnosis of right oculomotor nerve palsy due to syphilitic meningitis . We treated the syphilitic meningitis with intravenous injections of penicillin G (24 million units per day for 21 days) . Jarisch-Herxheimer reaction and other side effects were not apparent . We first made a thorough examination of the CSF to rule out diagnosis of meningitis, and pursued methylprednisolone pulse therapy (MPP, 1 g/day for 3 days) to treat the oculomotor nerve palsy . The ptosis and diplopia showed signs of improvement following the second MPP therapy session . The present case suggests that neurosyphilis is an important differential diagnosis for presentations of unspecific oculomotor nerve palsy and that MPP therapy may prove an effective treatment for it, even where there has been the long clinical onset. Arch Pediatr, 2003 Mar, 10(3), 227 - 9 {Curable dementia revealing late congenital syphilis}; Ait Sab I et al.; SUMMARY: Late congenital syphilis is a rare disease and its neurological expression is exceptional . We report a case revealed by a curable dementia . CASE REPORT: This 17-year-old patient presented for one year progressive dementia, frontal syndrome and extra pyramidal syndrome . The cerebral CT scan showed a diffuse cortical and subcortical atrophy . Blood and CSF positive antibodies confirmed the diagnosis of late congenital meningoencephalitis due to syphilis . The outcome after 13 months follow-up was favourable with penicillin therapy . COMMENTS: Late congenital syphilis is a rare disease, that may be exceptionally revealed by a curable dementia . Evolution may be favourable with early penicillin therapy. J Neurophysiol, 2004 Jan, 91(1), 63 - 77 Epub 2003 Jun 25. Is spontaneous high-voltage rhythmic spike discharge in Long Evans rats an absence-like seizure activity? Shaw FZ. A distinct high-voltage rhythmic spike (HVRS) discharge characterized by a barrage of negative spikes oscillating at 5-12 Hz was observed in chronically implanted Long Evans rats . Spontaneous HVRS discharges were exhibited in 90% of 40 Long Evans rats and occurred during sudden arrest of ongoing behavior (immobility) with occasional facial/whisker twitching . However, the function of HVRS discharges in Long Evans rats remains inconclusive to date and has been associated with alpha tremor/mu rhythm, attentive mu wave, and absence seizure . To elucidate the function of HVRS discharges in Long Evans rats, several experiments were performed . In a 6-h recording session (12:00-18:00), HVRS activities primarily occurred in several specific vigilance states, being particularly abundant in a short-lasting period before vigilance changes . Several characteristics, such as durations, oscillatory frequencies, and interspike intervals (ISIs) of HVRS discharges, were altered during wake-sleep states . Oscillatory frequencies were negatively correlated with durations of HVRS segments . In addition, ISIs of a HVRS episode exhibited a crescendo-decrescendo pattern . These variable ISIs could explain why a negative correlation was found between oscillatory frequencies and durations of HVRS episodes . Moreover, HVRS discharges were demonstrated to have widespread and near-synchronous distribution to bilateral cortical areas . In addition, innocuous electrical stimuli were unable to stop ongoing HVRS discharges . By contrast, noxious stimuli elicited behavioral arousal and immediately terminated most HVRS discharges . Cortical-evoked potentials in response to mild electrical stimulation under HVRS discharges were different from those under waking state but resemble those under slow-wave sleep with a smaller magnitude . Moreover, the temporal and spectral characteristics of spontaneous HVRS activities were analogous to those of seizure activities induced by penicillin and pentylenetetrazol . The incidence of spontaneous HVRS discharges was significantly decreased by ethosuximide administration . Based on these results, HVRS discharge might not be associated with a voluntary mu-rhythm behavior, instead it behaves as an absence-like seizure activity . These results were also collaborated using other genetic absence-seizure rats, such as WAG/Rij and GAERS rats . Possible mechanisms for the generation and termination of paroxysmal HVRS discharges are also discussed. J Vet Sci, 2003 Apr, 4(1), 67 - 72 Effect of reproductive status on in vitro developmental competence of bovine oocytes; Chohan KR et al.; The objectives of the present study were to compare the in vitro maturation (IVM), fertilization and early embryonic development of bovine oocytes recovered from ovaries during the follicular, metestrus and diestrus stages of the estrous cycle and at anestrus and pregnancy after maturation in a serum free culture medium . Cumulus oocyte complexes (COCs) collected from ovaries at different reproductive statuses were matured in medium 199 supplemented with 10 g/ml FSH, 10 g/ml LH, 1.5 g/m estradiol, 75 g/ml streptomycin, 100 IU/ml penicillin and 10 mM HEPES . COCs were incubated in 200 microl droplets of maturation medium 199 under oil for 24 h at 39 90 degree angle c and 5% CO2 . Matured oocytes were exposed to frozen-thawed TALP swim up, heparin capacitated sperm from two bulls separately in each replicate (20 h, 39C, 5% CO2) . After fertilization, the presumptive zygotes were cultured in medium 199 containing 8 mg/ml BSA-V, 100 IU/ml penicillin-G, 75 g/ml streptomycin and 10 mM HEPES for 144 h at 39C and 5% CO2 without medium freshening or change . Oocytes/embryos were fixed, stained with DAPI and evaluated under fluorescent microscope . The IVM rates were almost similar among oocytes from all reproductive statuses (range: 89.8 to 95.4%) . However, IVM rates for oocytes from the metestrus (90.6%) and pregnant (89.9%) phases were lower than the other groups . The fertilization rates were lower (p<0.05) for oocytes from the diestrus phase (72.4%) than from the other phases (range: 81.1 to 86.6%) . Oocytes, recovered during the metestrus phase of the estrous cycle, resulted in the highest cleavage rate (60.0%), while oocytes from the diestrus phase had the poorest embryonic development (39.8%: p<0.05) . Majority of the embryos from all reproductive phases showed a developmental arrest around 8-cell stage . Although the developmental competence of oocytes from pregnant and anestrus animals was lower than that from the other reproductive stages, they could be potentially used as oocyte donors . Long term, in vitro embryo culture without medium freshening or change was hypothesized to have caused the failure to overcome the 8-cell block to development. Biochim Biophys Acta, 2003 Jun 26, 1649(1), 58 - 67 A novel class of peptide found in scorpion venom with neurodepressant effects in peripheral and central nervous system of the rat; Corona M et al.; A novel toxin, named Cll9, was isolated from the venom of the scorpion Centruroides limpidus limpidus Karsch . It is composed of 63 amino acid residues closely packed by four disulfide bridges . It showed no apparent effect when injected to insects, crustaceans and i.p . to mice . However, when i.c.v . injected in the rat it immediately induced sleep, suggesting that it has a neurodepressant effect . We confirmed this by showing that it has a strong antiepileptic action, as assessed with the penicillin focus model . Its effectiveness in inhibiting Na(+) permeability in (cultured) rat peripheral ganglia further supports its neurodepressant actions . However, this peptide did not affect other Na(+) channels such as those from cerebellum granular cells in culture or the rSkM1 Na(+) channels expressed in HEK293 . The cDNA and genomic regions encoding this peptide were cloned and sequenced . This peptide is synthesized as a precursor of 84 amino acid residues and processed by removing 19 amino acids (signal peptide) from the amino terminal region and a couple of lysine residues from the carboxyl end . The presence of an intron of 777 bases interrupting the region encoding the signal peptide was also revealed . A comparison of its primary sequence, with more than 100 scorpion toxins known, showed that together with toxin CsE9 they constitute a new subfamily of peptides considered to be one of the most divergent groups of scorpion toxin-like peptides discovered. Zhonghua Liu Xing Bing Xue Za Zhi, 2003 Mar, 24(3), 176 - 9 {A cross-sectional survey on injection safety in health facilities in Wulong county, Chongqing city}; Li Q et al.; OBJECTIVE: To provide evidence for intervention measures on safe injection through a survey on the safety of injection in the health facilities in Wulong county, Chongqing city, China . METHODS: An investigation on injection safety was conducted among health care providers with a uniform questionnaire . RESULTS: Glass syringes which were not appropriately sterilized was found in 52.2% (12/23) of the health facilities . Injection practices were not correct in 31.4% (11/35) of the health facilities . Used disposable syringes were discarded directly without any disposal in 63.6% (21/33) of the health facilities . At least one of the unsafe injection practices mentioned above existed in 77.1% (27/35) of the health facilities . CONCLUSIONS: The main unsafe factors in the practice of injection are included: the practice to change needle but not syringe in penicillin allergic test and the injuries caused by used disposable syringes in medical staff . The important measures to improve injection safety were to train the medical staff on the knowledge about safe injection and the risks caused by unsafe injection, and to equip the health facilities with safe tools to destroy the used disposable syringes. J Bacteriol, 2003 Jul, 185(13), 3726 - 34 Probing the catalytic activity of a cell division-specific transpeptidase in vivo with beta-lactams; Eberhardt C et al.; Penicillin-binding protein 3 (PBP3; also called FtsI) is a transpeptidase that catalyzes cross-linking of the peptidoglycan cell wall in the division septum of Escherichia coli . To determine whether the catalytic activity of PBP3 is activated during division, we assayed acylation of PBP3 with three beta-lactams (cephalexin, aztreonam, and piperacillin) in growing cells . Acylation of PBP3 with cephalexin, but not aztreonam or piperacillin, appeared to be stimulated by cell division . Specifically, cephalexin acylated PBP3 about 50% faster in a population of dividing cells than in a population of filamentous cells in which division was inhibited by inactivation or depletion of FtsZ, FtsA, FtsQ, FtsW, or FtsN . However, in a simpler in vitro system using isolated membranes, acylation with cephalexin was not impaired by depletion of FtsW or FtsN . A conflicting previous report that the ftsA3(Ts) allele interferes with acylation of PBP3 was found to be due to the presence of a thermolabile PBP3 in the strain used in that study . The new findings presented here are discussed in light of the hypothesis that the catalytic activity of PBP3 is stimulated by interaction(s) with other division proteins . We suggest that there might be allosteric activation of substrate binding. Chem Commun (Camb), 2003 Jun 7, (11), 1296 - 7 Improved biotransformations on charged PEGA supports; Basso A et al.; PEGA supports functionalised with permanent charges show superior swelling properties in aqueous media when compared to neutral PEGA; a novel positively charged PEGA resin significantly improves penicillin G amidase (PGA) catalysed biotransformation on solid support, by favouring accessibility of the negatively charged enzyme. J Vet Med Sci, 2003 May, 65(5), 637 - 9 Rabbit syphilis diagnosed clinically in household rabbits; Saito K et al.; This paper deals with 16 cases presented from April to December 2001 and diagnosed clinically as rabbit syphilis, because they showed distinct lesions around the nose and/or mouth, responded to chemotherapy, and the "Rapid Plasma Reagin" test was positive . Twelve cases exhibited initial symptoms and four were relapses . Lesions around the genitalia and/or anus as well as the nose and/or mouth were seen in 8 cases, and 6 cases indicated sneezing . Fifteen cases were successfully treated with oral administration of chloramphenicol, and one was treated with long-acting penicillin by intramuscular injection . The mean age of onset was 8.8 months . As none of these cases had any mating history, the disease was likely to be maternally transmitted. J Antimicrob Chemother, 2003 Jul, 52(1), 120 - 2 Epub 2003 Jun 12. Penicillin-binding proteins involved in high-level piperacillin resistance in Veillonella spp; Theron MM et al.; OBJECTIVES: To investigate high-level piperacillin resistance in Veillonella spp . in the absence of beta-lactamase activity . METHODS: Penicillin-binding protein (PBP) competition studies were conducted in Veillonella strains, with piperacillin MICs ranging from 0.5 to >128 mg/L and ampicillin MICs from 0.125 to 4 mg/L . Whole cell lysates were pre-incubated with piperacillin or ampicillin and post-labelled with {3H}benzylpenicillin . RESULTS: PBP competition studies showed that the PBP with greatest affinity for penicillin and ampicillin had a molecular weight of approximately 66 kDa, and exhibited reduced binding of piperacillin in resistant strains . CONCLUSIONS: This unusual focusing of different penicillins on one PBP may be the cause of selective mutants resulting from piperacillin MICs > 128 mg/L . In the absence of beta-lactamases, alterations in penicillin-binding were seen to be major contributors to high-level piperacillin resistance development. Clin Infect Dis, 2003 Jun 15, 36(12), 1507 - 13 Epub 2003 Jun 06. Ceftriaxone compared with sodium penicillin g for treatment of severe leptospirosis; Panaphut T et al.; A prospective, open-label, randomized trial at Khon Kaen Hospital (Thailand) was conducted from July 2000 through December 2001 to compare the clinical efficacies of ceftriaxone and sodium penicillin G for the treatment of severe leptospirosis . A total of 173 patients with severe leptospirosis were randomly assigned to be treated with either intravenous ceftriaxone (1 g daily for 7 days; n=87) or intravenous sodium penicillin G (1.5 million U every 6 h for 7 days; n=86) . The primary outcome was time to fever resolution . Survival analysis demonstrated that the median duration of fever was 3 days for both groups . Ten patients (5 in each group) died of leptospirosis infection . There were no statistically significant differences in the duration of organ dysfunction . Ceftriaxone and sodium penicillin G were equally effective for the treatment of severe leptospirosis . Once-daily administration and the extended spectrum of ceftriaxone against bacteria provide additional benefits over intravenous penicillin. Schmerz, 1999 Feb 18, 13(1), 48 - 50 {Migraine with aura as early symptom of neurosyphilis}; Sartor H et al.; CASE: On the basis of a case report the often difficult classification of migraine with aura and exclusion of symptomatic origin is discussed . In spring 1996 a 34-years old patient started to suffer from attacks of a migraine like headache with focal aura several times a week . While clinical examination was inconspicuous the electroencephalogram showed a general slowing of background activity with intermittent rhythmic delta-activity . NMR was normal . During treatment with flunarizine intensity and frequency of the attacks decreased, but within half a year he developed an increasing psychomotor slowing and cognitive deficit . Now cerebrospinal fluid showed a pleocytosis and highly positive treponema pallidum specific antibody index making the diagnosis of neurosyphilis reliable . Parenteral penicillin caused a delayed normalisation of mental abilities and CSF . DISCUSSION: Headache, especially with the characteristics of migraine, is one of the most frequent symptoms of neurosyphilis and--if untreated--may be followed by transient ischemic attacks or strokes even month later . To detect this kind of symptomatic headache a careful neurological follow-up examination and early CSF-analysis are essentially necessary, because pathological electroencephalograms are not rare in migraine with aura and NMR cannot exclude an inflammatory process. J Zoo Wildl Med, 2001 Mar, 32(1), 74 - 7 Intravenous pharmacokinetics of penicillin G and antipyrine in ostriches (Struthio camelus) and emus (Dromaius novaehollandiae); Clarke CR et al.; Penicillin G and antipyrine, which served as model drugs to assess the relative capacities of renal and hepatic elimination pathways, respectively, were each administered intravenously to six ostriches (Struthio camelus) and to six emus (Dromaius novaehollandiae) . Drug concentrations in blood samples collected over a period of 12 hr after administration were assayed, and elimination half-life, mean residence time, clearance, and steady-state volume of distribution were calculated . Mean values for elimination half-life and mean residence time of penicillin G were significantly higher in emus than in ostriches; no significant differences in antipyrine pharmacokinetics between species were demonstrated. Eur J Emerg Med, 2003 Jun, 10(2), 139 - 42 A case of Lemierre's syndrome; Ma M et al.; Lemierre's syndrome is a rare but potentially life-threatening entity that follows an oropharyngeal infection . The syndrome is characterized by an antecedent acute oropharyngeal infection, with secondary suppurative thrombophlebitis of the internal jugular vein and septic emboli . In the pre-antibiotic era, it had a 90% mortality rate . Now, with the advent of antibiotics, the prognosis is favorable, but delays in diagnosis may result in increased morbidity and mortality . Its incidence appears to be increasing . We present a case of Lemierre's syndrome, most notable for the patient's essentially benign physical examination and lack of clinical improvement with penicillin. Ann N Y Acad Sci, 2003 Mar, 984, 97 - 122 Removal and recovery of metals and other materials by supported liquid membranes with strip dispersion; Ho WS; This paper reviews recent advances in supported liquid membranes (SLMs) with strip dispersion for removal and recovery of metals including chromium, copper, zinc, and strontium; it also discusses potential applications of SLMs for removal and recovery of other materials, including cobalt and penicillin G . The technology for chromium that we developed, not only removes the Cr(VI) from about 100-1,000 ppm to less than 0.05 ppm in the treated effluent allowable for discharge or recycle, but also recovers the chromium product at a high concentration of about 20% Cr(VI) (62.3% Na(2)CrO(4)) suitable for resale or reuse . In other words, we have achieved the goals of zero discharge and no sludge . The stability of the SLM is ensured by a modified SLM with strip dispersion, where the aqueous strip solution is dispersed in the organic membrane solution in a mixer . The strip dispersion formed is circulated from the mixer to the membrane module to provide a constant supply of the organic solution to the membrane pores . The copper SLM system that we have identified, not only removed the copper from 150 ppm in the inlet feed to less than 0.15 ppm in the treated feed, but also recovered the copper at a high concentration of greater than 10,000 ppm in the strip solution . For the zinc SLM system identified, zinc at an inlet feed concentration of 550 ppm was removed to less than 0.3 ppm in the treated feed, whereas a high zinc concentration of more than 17,000 ppm was recovered in the strip solution . For strontium removal, we synthesized a family of new extractants, alkyl phenylphosphonic acids . The SLM removed radioactive (90)Sr to the target of 8 pCi/L or lower from feed solutions of 300-1,000 pCi/L . The SLM removed cobalt from about 525 ppm to 0.7 ppm in the treated feed solution, concentrating it to at least 30,000 ppm in the aqueous strip solution . Concerning penicillin G recovery, the SLM removed penicillin G from a feed of 8,840 ppm and concentrated it to a high concentration of 41,011 ppm in the aqueous strip solution with a high recovery of about 93%. Biotechnol Bioeng, 2003 Aug 5, 83(3), 361 - 8 Continuous cultivations of a Penicillium chrysogenum strain expressing the expandase gene from Streptomyces clavuligerus: Growth yields and morphological characterization; Robin J et al.; The growth stoichiometry of a Penicillium chrysogenum strain expressing the expandase gene from Streptomyces clavuligerus was determined in glucose-limited chemostat cultivations using a chemically defined medium . This strain produces adipoyl-7-aminodeacetoxycephalosporanic acid (ad-7-ADCA) when it is fed with adipic acid . The biomass yield and maintenance coefficients for the strain were similar to those found for penicillin-producing strains of Penicillium chrysogenum . The maximum specific growth rate in the chemostat was found to be 0.11 h(-1) . Metabolic degradation of adipate was found to take place in significant amounts only at dilution rates below 0.03 h(-1) . After three to five residence times, adipate degradation and ad-7-ADCA production disappeared, and this allowed determination of the biomass yield coefficient on adipate . The morphology was measured at different dilution rates and the mean total hyphal length and mean number of tips both increased with an increase in dilution rate from 0.015 to 0.065 h(-1) . Both variables decreased when the dilution rate was increased above 0.065 h(-1) . A correlation between mean total hyphal length and productivity of ad-7-ADCA was found . Biotechnol Bioeng, 2003 Aug 5, 83(3), 353 - 60 Continuous cultivations of a Penicillium chrysogenum strain expressing the expandase gene from Streptomyces clavuligerus: Kinetics of adipoyl-7-aminodeacetoxycephalosporanic acid and byproduct formations; Robin J et al.; The production kinetics of a transformed strain of Penicillium chrysogenum expressing the expandase gene from Streptomyces clavuligerus was investigated in chemostat cultivations . The recombinant strain produces adipoyl-7-aminodeacetoxycephalosporanic acid (ad-7-ADCA) as the major product; however, during the cultivations, the appearance of a major unknown and poorly secreted product was observed . Investigations using high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectroscopy (LC-MS) showed that this byproduct has a six-membered dihydrothiazine ring, which is characteristic for cephalosporins . The byproduct may be formed via isopenicillin N by as-yet unknown mechanisms, but involving expandase . It is likely that the unknown compound (UC) is deacetoxycephalosporin C (DAOC) . Investigation of the instability of the various beta-lactams produced showed higher instability for compounds with a five-membered thiazolidine ring than those with a six-membered dihydrothiazine ring . Furthermore, secretion of products and byproducts was shown to be quite different . The productivity was studied as a function of the dilution rate in the range 0.015 to 0.090 h(-1) . The specific productivity of total beta-lactams was compared with that of the penicillin-G-producing host strain, and it was found to be lower at dilution rates of <0.06 h(-1) . Quantification of the fluxes through the pathway leading to ad-7-ADCA showed a decrease in flux toward ad-7-ADCA, and an increase in flux toward UC as the dilution rate increased . Northern analysis of the biosynthetic genes showed that expression of the enzymes involved in the ad-7-ADCA pathway decreased as the dilution rate increased . Sex Transm Dis, 2003 Jun, 30(6), 502 - 8 The cost-effectiveness of single-dose azithromycin for treatment of incubating syphilis; Blandford JM et al.; BACKGROUND: Treatment of incubating syphilis with intramuscular benzathine penicillin in exposed sex partners is not always practical in the field, and exposed partners may not adhere to referrals for treatment at clinical facilities . The availability of a single-dose oral therapy could increase the number of partners treated and reduce future infections . GOAL: The goal of the study was to evaluate the cost-effectiveness of directly observed oral administration of azithromycin as an alternative to referral for treatment with benzathine penicillin . STUDY DESIGN: Using published probability and cost estimates, we constructed a decision-analysis model to compare the direct costs and effectiveness of field treatment with azithromycin (1-g single dose) versus referral for standard benzathine penicillin therapy . RESULTS: At public-sector pricing ($11.50 U.S . dollars), directly observed field treatment with azithromycin is cost-saving from both the program and healthcare system perspectives at efficacy levels as low as 75% . Azithromycin therapy is cost-saving at the wholesale price of $17.32 U.S . dollars (sachet formulation) when efficacy is at least 90% . The more expensive tablet formulation (average wholesale price of $27.89 U.S . dollars) is not cost-saving from a program perspective, but it remains cost-saving from a healthcare system perspective if efficacy rates are at least 90% . Azithromycin therapy (1-g single dose) will result in fewer cases of early syphilis among exposed partners, provided that the drug's efficacy is at least 87% . CONCLUSIONS: Azithromycin is a cost-effective alternative treatment for incubating syphilis in settings where standard intramuscular therapy is not practical. Zhonghua Er Bi Yan Hou Ke Za Zhi, 2000 Aug, 35(4), 271 - 4 {Otogenic hypertrophic cranial pachymeningitis associated with edema of the temporal lobe and organic mental disorder-case report}; Yi Z et al.; OBJECTIVE: Hypertrophic cranial pachymeningitis(HCP) is a rare disease which might be misdiagnosed . One typical case of otogenic hypertrophic cranial pachymeningitis (HCP) associated with edema of the temporal lobe and organic mental disorder was reported . Literatures associated with HCP were reviewed for reference . METHODS: In July, 1997, a 26-year-old man was admitted for right-sided severe headache, dizziness, nausea, vomiting, facial and abducens nerve palsy . MRI and CT revealed inflammation in the temporal bone and locally thickened dura mater with obvious enhancement as a band in the petrous apex and nearby tentorium cerebellum . The patient then underwent operation including decompression of the facial nerve, labyrinthectomy, and eradication of the inflammatory cells in the mastoid and petrous portion . Postoperatively, the clinical signs disappeared except hearing loss . Seven months later, the patient suffered from mental disorder with interrupted excitement to hit and abuse the family members . He was then treated in a psychosis hospital but no improvement could be seen . On May 13, 1998, MRI and the enhanced MRI demonstrated diffuse thickened tentorium cerebellum and dura mater in the middle cranial fossa . The inferior portion of the temporal lobe was obvious edema . The internal carotid artery was partially occluded due to the thickened wall of cavernous sinus . RESULTS: Hence, the diagnosis of HCP associated with edema of temporal lobe and organic mental disorder was established . The patient was cured by high dosage of penicillin . CONCLUSION: MRI is an essential method for diagnosis of HCP . Antibiotic was an effective treatment. Med Arh, 2002, 56(3 Suppl 1), 54 - 6 {The Stevens-Johnson syndrome--personal experience}; Colic-Hadzic B et al.; Stevens-Johnson syndrome is a disorder of the skin and mucous membranes and a severe bullous forms include systemic toxic effects . In this study, we have analyzed our experiences according to ages, sex, incidence, ethological irritable factors, differential diagnosis, clinical treatment, in children with Stevens-Johnson syndrome at the Pediatric Clinic in Tuzla . In the period January 1997-May 2002, we treated 14 patients with this syndrome . All patients were male, ages from 11 months to 11.6 years (average 4.5 years) . As irritable factors were detected antiepileptics (Phenobarbitol and Tegretol) in 10 children (71.44%), antibiotics (Procain Penicillin and Cephalexin) in 3 children (21.42%), and reason was stayed unknown in 1 child (7.14%) . The problem in differential diagnosis usually was toxic epidermal necrolisis (TEN) and graft versus host disease (GvHD) . All patients demanded treatment in the pediatric intensive care unit supporting with specialists immunologists, ophthalmologists, dermatologists, infectologists . Treatment included, besides vital volume support, systemic administration of corticosteroids, antibiotics and intensive local therapy lesions of skin and mucous membranes, specially eyes in special sterile conditions . Outcome and results of our medical treatment of all patients were good. Allergy, 2003 May, 58(5), 439 - 44 Distinct delayed T-cell response to beta-methasone and penicillin-G in the same patient; Scala E et al.; BACKGROUND: Multiple drug allergy syndrome is a clinical condition characterized by reactions against more than one different class of, both pharmacologically and structurally, unrelated drugs . Scanty data are available to date about a multiple drug delayed hypersensitivity syndrome . Our aim was to report the case of a delayed reaction to both beta-methasone (beta-MT) and penicillin-G (pen-G) occurring in the same patient, and analyse beta-MT- and pen-G-specific T-cell Lines (TCLs) with regard to their specificity, phenotype and cytokine profile . METHODS: We generated two drug-specific TCLs from biopsies at the site of positive intradermal reactions, and analysed their immunophenotype, T-cell receptor Vbeta (TCR-Vbeta) domains expression and cytokine profile . RESULTS: We demonstrated the specificity of the T cells isolated from positive intradermal test reactions to pen-G and beta-MT through the strict dose-dependent proliferation in response to drug-pulsed autologous antigen presenting cells . Fluorescence activated cell sorter (FACS) analysis revealed a predominance of CD4+ cells in the inflammatory cell infiltrate of intradermal test with beta-MT, while a predominance of CD8+ T cells in the site of delayed reaction to pen-G was found . The drug specific CD4+ and CD8+ T cells were heterogeneous, with regard to TCR-Vbeta usage . CD8+ pen-G-TCL displayed a preferential T helper 2 (Th2) profile, while a substantially heterogeneous pattern of cytokine production characterized specific beta-MT TCL . CONCLUSION: The study describes the coexistence in the same patient of a delayed hypersensitivity to both penicillin G and beta-MT, driven, respectively, by pen-G-specificTh2-skewed CD8+ and beta-MT specificTh0 CD4+ T cells . This case further support the existence of a multiple drug allergy syndrome also for delayed hypersensitivity. Am J Trop Med Hyg, 2003 Apr, 68(4 Suppl), 44 - 9 Diagnostic and prescribing practices in peripheral health facilities in rural western Kenya; Phillips-Howard PA et al.; Health facility ledgers of 11 rural health facilities in western Kenya were reviewed to evaluate diagnostic and prescribing practices . Clinics lacked laboratory facilities . Of 14,267 sick child visits (SCVs), 76% were diagnosed with malaria and/or upper respiratory infections . Other diagnoses were recorded in less than 5% of SCVs . Although two-thirds of