Penicillin

Presse Med, 1997 Nov 15, 26(35), 1671 - 2
{Pneumopathy caused by minocycline}; Levy A et al.; BACKGROUND: Minocycline has been identified as a pathogenic agent in drug-induced pneumonia . We report a new case . CASE REPORT: A 38-year-old female asthmatic patient was given minocycline (100 mg/j) for facial acne . She was allergic to penicillin . Other treatments were theophylline, salbutamol and inhaled budesonide . Severe bilateral hypoxemia pneumonia developed with high eosinophil blood counts within a few days of treatment onset . The lung disease regressed with minocycline withdrawal . DISCUSSION: This case is exceptional because the minocycline-induced lung disease continued to progress despite high-dose corticosteroids in this asthmatic patient.

Biosens Bioelectron, 1997, 12(9-10), 917 - 23
Application of fuzzy logic in multicomponent analysis by optodes; Wollenweber M et al.; Fuzzy logic can be a useful tool for the determination of substrate concentrations applying optode arrays in combination with flow injection analysis, UV-VIS spectroscopy and kinetics . The transient diffuse reflectance spectra in the visible wavelength region from four optodes were evaluated to carry out the simultaneous determination of artificial mixtures of ampicillin and penicillin . The discrimination of the samples was achieved by changing the composition of the receptor gel and working pH . Different algorithms of pre-processing were applied on the data to reduce the spectral information to a few analytic-specific variables . These variables were used to develop the fuzzy model . After calibration the model was validated by an independent test data set.

Brain Res, 1997 Nov 28, 777(1-2), 86 - 94
The connection between absence-like seizures and hypothermia induced by penicillin: possible implication on other animal models of petit mal epilepsy; Ostojic ZS et al.; In this study we investigated the relationship between penicillin-induced hypothermia and petit mal epilepsy induced by this proconvulsant antibiotic . In order to find a possible dose-dependent relationship, we used two doses: 1500.000 and 1000.000 U/kg b.wt., both known as being sufficient to induce absence-like attacks with subsequent spike and wave discharges (SWD) in electrocorticogram (ECoG) . Because of experimental data suggesting penicillin binding to benzodiazepine receptor recognition site, we also studied penicillin-induced changes in body temperature after diazepam pretreatment . Results of this study clearly show that penicillin in doses known to induce petit mal-like epilepsy concomitantly induces statistically significant dose-dependent decrease in body temperature . Pretreatment with diazepam completely prevents both penicillin-induced hypothermia and SWDs . On the other hand, both the diazepam and mixed diazepam + penicillin treatments did not significantly alter body temperature . These results suggest, however, that at least some of the penicillin effects described could be assigned to its binding to the benzodiazepine receptor recognition site at GABA(A) ionophore . This may have an important clinical implication because the inhibitory action of penicillin at the benzodiazepine receptor recognition site could account for the mechanism of penicillin-induced unspecific encephalopathies in humans . The relationship between petit mal epilepsy and hypothermia sheds new light on the action mechanisms of penicillin-induced absence seizures.

Vojnosanit Pregl, 1997 Jul-Aug, 54(4), 341 - 6
{Clinico-statistical analysis of the approach to retained foreign bodies in the extremities}; Ivanovski A; The investigation in 200 wounded in battles was performed by clinical-statistic analysis . The aim of the study was to analyze the procedure with foreign bodies in the extremities after the primary surgical management of the wound . It was established that primary surgical management of the wound, besides the coexisting difficulties (field work conditions, impaired supply etc.), was correctly performed with the early administration of 2 prophylactic antibiotics (Longaceph, Garamycin, Tolycar and Penicillin) in therapeutical doses during 3 to 10 days after the wounding . The "finishing" which included the repair of incompletely performed primary surgical management of the wound: incomplete nephrectomy, unadequate hemostasis, drainage, incorrect immobilization, etc . was performed in 32% of the wounded . The results imply that the accessible foreign bodies near the wound were removed without the excessive damage to the adjoining soft tissue . After the whole treatment, 3% of war wounds were found to be infected . Two fistulas from foreign bodies and 4 osteites were noticed and they were cured by the surgical treatment and antibiotic therapy.

Epidemiol Infect, 1997 Dec, 119(3), 349 - 56
The relationship between therapeutic injections and high prevalence of hepatitis C infection in Hafizabad, Pakistan; Luby SP et al.; To determine the prevalence and routes of transmission of hepatitis C virus (HCV) infection in Hafizabad, Pakistan, we collected sera in 1993 from a geographically based random sample of residents, and in 1994 identified 15 HCV-infected individuals (cases) and 67 age and sex matched uninfected individuals (controls) . Initially we approached 504 households, and collected serum from a randomly selected household member in 309 (64%) . Twenty persons (6.5%) had anti-HCV antibody; 31% percent had hepatitis B core antibodies, and 4.3% had hepatitis B surface antigen . In the case-control study, persons who received more therapeutic injections (categorized as averaging 1, 2-4, 5-9 or > 10 injections per year in the previous 10 years) were more likely to be infected with HCV (odds ratio 0, 1.5, 2.5 and 6.9 respectively, P = 0.008) compared to persons averaging 0 injections per year . Efforts to limit therapeutic injections to only those that are medically indicated and that use sterile equipment are essential in order to prevent transmission of HCVPIP: To determine the prevalence of hepatitis C virus (HCV) infection in Hafizabad, Pakistan, sera were collected in 1993 from a geographically representative random sample of 309 adults and children . 20 serum samples (6.5%) had anti-HCV antibodies, 89 (31%) had hepatitis B core antibodies, and 12 (4.3%) had hepatitis B surface antigens . The prevalence of HCV increased markedly with age; no cases were detected among children under 10 years old . A follow-up study of 15 of these HCV cases and 67 age- and sex-matched healthy controls was conducted in 1994 . Compared to noninfected controls, HCV cases were significantly more likely to have received 5 or more injections in the previous 10 years (odds ratio, 5.4; 95% confidence interval, 1.2-28.0) . Only 5 HCV cases had received blood transfusions, and none reported intravenous drug use . Inspection of 3 private health clinics in Hafizabad exposed disposable syringes and needles--used primarily for vitamin B complex, chloroquine, and penicillin--soaking in a bowl of tepid water . Extrapolation of this study's findings suggests 800 new cases of HCV and 109 HCV-related deaths in Hafizabad each year . HCV infection could be reduced substantially by efforts to limit injections to those that are medically essential and to ensure the use of sterile equipment .

Adv Biochem Eng Biotechnol, 1998, 59, 1 - 46
Fed-batch bioproduction of spectinomycin; Gomes J et al.; Actinomycetes produce about 67% of the known antibiotics covering a wide range of chemical structures . However, their filamentous growth present several problems during industrial processes . Among these problems oxygen transfer limitation is critical . In this chapter we present the role of oxygen in spectinomycin production by a Streptomyces species . Spectinomycin, a broad spectrum antibiotic effective against penicillin resistant gonorrhea, is an aminoglycoside constituted from two glucose moieties . Its bioproduction is strongly influenced by glucose and oxygen . We have shown that for a fixed dissolved oxygen concentration, there are two specific glucose concentrations which give maximum final titers of spectinomycin . The bi-modal maximum indicates the influence of two intermediate metabolites in spectinomycin biosynthesis . We propose a mechanism for spectinomycin biosynthesis and subsequently develop a model based on this mechanism . The proposed mechanism for spectinomycin biosynthesis is validated by successfully reconstructing the air flow rate profiles . A nonlinear systems theory technique termed External Differential Representation, is implemented to reconstruct the spectinomycin bioconversion process which then predicts the spectinomycin concentration from the air flow rate profile . This signifies that spectinomycin titers in industrial fed-batch processes can be controlled if a priori information about the air flow rate profile yielding maximum spectinomycin is available.

Curr Opin Struct Biol, 1997 Dec, 7(6), 857 - 64
Proteins of the penicillin biosynthesis pathway; Schofield CJ et al.; Two sequential steps are common to the biosynthesis of all penicillin-derived antibiotics: the reaction of three L-amino acids to give L-delta-(alpha-aminoadipoyl)-L-cysteinyl-D-valine, and the oxidation of this tripeptide to give isopenicillin N . Recent studies on the peptide synthetase and oxidase enzymes responsible for these steps have implications for the mechanisms and structures of related enzymes involved in a range of metabolic processes.

Clin Exp Allergy, 1997 Dec, 27(12), 1425 - 31
Allergic reactions to ampicillin . Studies on the specificity and selectivity in subjects with immediate reactions; Romano A et al.; BACKGROUND: Ampicillin (AMP) is a drug that has been prescribed extensively . Reactions that have been reported include exanthema, desquamative contact eczema, urticaria and anaphylaxis . Experimental evidence indicates that the side chain of AMP is a structure that may induce a selective immune response either at the humoral or lymphocyte T-cell level . With regard to IgE reactions, the selectivity and specificity of the response needs to be studied in humans . OBJECTIVES: To study the specificity of the IgE response in a group of subjects who had an immediate allergic reaction after the administration of AMP . METHODS: Subjects developing an immediate response (anaphylaxis or urticaria) after the administration of AMP or an aminopenicillin derivative with the same side chain as AMP were studied . Skin tests were made to determinants generated from benzyl penicillin (BP): benzyl penicilloyl (BPO) and minor determinant mixture (MDM), as well as amoxicillin (AX) and AMP . Specific IgE antibodies were determined to benzyl penicilloyl polylisine (BPO-PLL), amoxicilloyl-polylisine (AX-PLL) and ampicilloyl-polylisine (AMP-PLL) . The specificity of the IgE antibody response was studied by RAST and RAST inhibition . Subjects were classified in three categories: group A: those who were skin test and/or RAST positive to determinants derived from benzylpenicllin, group B: those who were negative to determinants derived from benzylpenicillin but were skin test and/or RAST positive to determinants derived from AX and AMP and group C: those who were exclusively positive to determinants derived from AMP . RESULTS: A total of 48 subjects was included in the study . In group A there were 35 cases, in group B 10 cases, and in group C three cases . RAST inhibition studies showed that in some instances the side chain of AMP could induce specific responses with a variable degree of crossreactivity between BP and AX . CONCLUSIONS: Athough AMP can induce an immediate IgE response in subjects allergic to betalactams and the structure of the side chain may contribute to the specificity of the response, our results indicate that in most instances crossreactivity with the other penicillins exists and that in the groups studied selective reactions to just AMP derived determinants were uncommon.

Prescrire Int, 1998 Feb, 7(33), 16 - 8
Pneumococcal vaccine: a second look . Solution for SC or IM injection: pneumococcal vaccine; Glutamate metabotropic receptors modulate the expression of in vitro epileptiform activity in rat hippocampal slices; Laboratorio di Farmacologia, Istituto Superiore di Sanita, Roma, ItalyThe effects of the mixed class I and II mGLUR agonist (+) 1S,3R-trans-amino-cyclopentane-1,3-dicarboxylic acid (ACPD) and antagonists (+) alpha-methyl-4-carboxyphenylglycine (MCPG) and L-2-amino-3-phosphonopropionic acid (L-AP3) on the basal neuronal excitability and on the expression of in vitro epileptiform activity produced by the convulsant drugs picrotoxin and penicillin were investigated in rat hippocampal slices . The duration of the CA1 epileptiform bursting produced by 0.05 mM picrotoxin or 1 mM penicillin or 0.075 mM ACPD was significantly (p<0.05) and dose-dependently decreased by 0.3-0.5 mM MCPG or L-AP3, but not by 0.05 mM ACPD . The data demonstrate an involvement of class I and II mGLURs in the basal neuronal excitability and in the expression of in vitro epileptiform activity produced by some convulsants.

Bull Soc Pathol Exot, 1997, 90(3), 189 - 91
{Erysipelas of the leg in hospital environment in Lome (Togo)}; Pitche P et al.; A study was conducted during 5 years to determine the epidemiological clinical profile and the evolution of legs erysipelas in patients attending Lome teaching hospital . During this period, 60 subjects (43 females et 17 males) were hospitalized for legs erysipelas . The average age was 40 years old . General facilitating factors were noted in 58% of the patients (n = 35), and local in 50% of cases (n = 30) . The first line treatment was in all patients penicillin G . Satisfactory results were observed in 70% . Local complications were noted in 10% (n = 6), and recurrence in 17% (n = 10) . The erysipela is common in hospital environment . The precocious penicillinotherapy allowed to have satisfactory results.

Can J Neurol Sci, 1997 Nov, 24(4), 343 - 4
Reversal of syphilitic hydrocephalus with intravenous penicillin; Cosottini M et al.; BACKGROUND: CSF shunting procedures are generally considered the fundamental therapy of syphilitic hydrocephalus . METHODS: We followed up with CSF analysis and MR imaging a patient with progressive mental and gait disturbances and tetraventricular hydrocephalus due to tertiary syphilis who was treated for 14 days with high dose intravenous penicillin alone . RESULTS: Clinical and CSF abnormalities resolved within a few months, whereas the hydrocephalus disappeared only 30 months after therapy . CONCLUSIONS: Before consideration of a CSF shunting procedure, a trial of high dose intravenous penicillin is warranted for patients with syphilitic hydrocephalus.

Am J Perinatol, 1997 Oct, 14(9), 553 - 4
Penicillin desensitization in the treatment of syphilis during pregnancy; Chisholm CA et al.; The objective of this study was to compare patients' hospital course, complications, and charges for oral and intravenous (i.v.) desensitization regimens for the treatment of syphilis in the penicillin-allergic gravida . We performed a retrospective search of medical records at two tertiary-level teaching hospitals and reviewed the hospital course of penicillin-allergic gravidas who underwent penicillin desensitization . Between August 1988 and December 1995, 16 procedures for penicillin desensitization were carried out: 11 oral procedures, and 6 i.v . procedures . There were no significant differences between the patients in the oral and i.v . desensitization groups with respect to demographic characteristics, duration of time in a monitored bed, or length of hospital stay . The oral regimen was less expensive than the i.v . regimen ($144.06 vs . $319.48) . In our experience, oral and i.v . regimens provide effective desensitization for the treatment of syphilis in penicillin-allergic gravidas . However, the oral route offers ease of administration and substantial cost savings, making it the preferred method.

J Chromatogr B Biomed Sci Appl, 1997 Oct 10, 699(1-2), 269 - 86
Chromatographic and electrophoretic methods for modified hemoglobins; Frantzen F; The discovery of the clinically important glycohemoglobin adducts and their relation to diabetes mellitus have greatly stimulated the study of other minor post-translational modifications of hemoglobin . Chromatographic and electrophoretic procedures have played an important role in these studies . Today several hemoglobin adducts are known and the formation of adducts with glucose, phosphorylated carbohydrates, urea/cyanate, aspirin, vitamins, acetaldehyde, penicillin and acetyl CoA have been described . Furthermore, new adducts, such as those observed using hemoglobin as a biochemical marker monitoring environmental, occupational and lifestyle exposures to reactive toxic chemicals are constantly being reported . This review deals with chromatographic and electrophoretic separation methods available for the study of non-enzymatic post-translational modifications of hemoglobin . Suitability, perspectives and biomedical applications are discussed.

J Allergy Clin Immunol, 1997 Nov, 100(5), 586 - 91
Skin testing with penicilloate and penilloate prepared by an improved method: amoxicillin oral challenge in patients with negative skin test responses to penicillin reagents; Macy E et al.; BACKGROUND: Penicillin skin testing has been limited by the lack of commercially available penicilloate and penilloate reagents . OBJECTIVE: This project was proposed to produce a stable, well-characterized supply of penicilloate and penilloate for intrastate use by our health maintenance organization and to document clinical safety and efficacy . METHODS: An improved method of extraction for penicilloate and penilloate, which changed the solvents used during recrystallization, was developed . With these newly prepared reagents, penicillin skin testing was performed on 348 subjects . Skin testing was immediately followed by an oral challenge of 250 mg of amoxicillin in 215 of 288 (75%) subjects displaying a negative response to a battery of penicillin skin tests . RESULTS: Nuclear magnetic resonance and mass spectrometry of the newly produced penicilloate and penilloate showed no evidence of organic contamination . Penicillin skin testing resulted in 17.2% (60 of 348) positive test results, with 20% of the subjects with positive results only responding to the newly produced minor determinants . The rate of mild adverse reactions to penicillin skin testing was 1.1% (4 of 348) . The rate of mild acute adverse reactions was 5.1% (11 of 215), and the delayed reaction rate was 0.9% (2 of 215) with the amoxicillin challenge . CONCLUSIONS: This improved penicillin minor determinant extraction method allows for the reproducible production of very pure preparations of penicilloate and penilloate . Large-scale penicillin skin testing, followed by amoxicillin challenge if results are negative is feasible in a large group model health maintenance organization operating within a single state with the use of internally produced penicilloate and penilloate and commercially available penicillin, amoxicillin, and penicilloyl polylysine.

J Tradit Chin Med, 1996 Jun, 16(2), 101 - 4
239 cases of high fever in viral upper respiratory infection (URI) treated with xiang shi qing jie (XSQJ) bag tea; Liu Z et al.; XSQJ bag tea was used to treat 239 cases of high fever caused by viral upper respiratory infection, widely spreading in summer and autumn . For comparison, a control group treated by penicillin combined with Ganmao Qingre Chongji or Banlangen Chongji was set up . The results showed the effect of XSQJ bag tea on the time of abating fever, resolving symptoms and physical signs were significantly better than that of the control group.

Zhen Ci Yan Jiu, 1996, 21(2), 62 - 6
{Effect of electroacupuncture on cholecystokinin gene expression in rat hippocampus during penicillin-induced epileptic seizure}; Yang R et al.; Northern Blot and hybrization in situ techniques were used to investigate the effect of electroacupuncture (EA) on the changes of cholecystokinin (CCK) mRAN levels of the hippocampus in rat penicillin-induced epilepsy model . Epilepsy can significantly increase CCK mRNA levels in dentate gyrus and CA3 areas of hippocampus in diencephalic sections after penicillin-induced seizure, whereas EA not only can attenuate the seizure behaviors and EEG changes, but also can decrease the increase of CCK mRNA contents induced by the seizure . However, in the subiculum, dentate gyrus and CA3 areas of mesencephalic sections of rat hippocampus, EA can further increase the enhancement of CCK mRNA concentration induced by penicillin-induced seizure . The results suggest that EA inhibitory effects on the seizure's behaviors and epileptiform activities may be related to the alteration of CCK gene expression in the different area of hippocampus.

Biochim Biophys Acta, 1997 Oct 23, 1329(2), 278 - 84
Alpha-helical conformation in the C-terminal anchoring domains of E . coli penicillin-binding proteins 4, 5 and 6; Siligardi G et al.; The E . coli low molecular mass penicillin-binding proteins (PBP's) are penicillin sensitive, enzymes involved in the terminal stages of peptidoglycan biosynthesesis . These PBP's are believed to anchor to the periplasmic face of the inner membrane via C-terminal amphiphilic alpha-helices but to date the only support for this hypothesis has been obtained from theoretical analysis . In this paper, the conformational behaviour of synthetic peptides corresponding to these C-terminal anchoring domains was studied as a function of solvent, pH, sodium dodecyl sulphate micelles and phospholipid (DOPC, DOPG) vesicles using circular dichroism (CD) spectroscopy . The CD data showed that in 2,2,2-trifluoroethanol or sodium dodecylsulphate, all three peptides have the capacity to form an alpha-helical conformation but in aqueous solution or in the presence of phospholipid vesicles only those peptides corresponding to the PBP5 and PBP6 C-termini were observed to do so . A pH dependent loss of alpha-helical conformation in the peptide corresponding to the PBP5 C-terminus was found to correlate with the susceptibility of PBP5 to membrane extraction . This correlation would agree with the hypothesis that an alpha-helical conformation is required for membrane interaction of the PBP5 C-terminal region.

Biochem J, 1997 Oct 15, 327 ( Pt 2), 377 - 81
Site-directed mutagenesis of the Actinomadura R39 DD-peptidase; Zhao GH et al.; The role of various residues in the conserved structural elements of the Actinomadura R39 penicillin-sensitive dd-peptidase has been studied by site-directed mutagenesis . Replacement of Ser-298 of the 'SDN loop' by Ala or Gly significantly decreased the kcat/Km value for the peptide substrate, but only by a factor of 15 and had little effect on the other catalytic properties . Mutations of Asn-300 of the same loop and of Lys-410 of the KTG triad yielded very unstable proteins . However, the N300S mutant could be purified as a fusion protein with thioredoxin that exhibited decreased rates of acylation by the peptide substrate and various cephalosporins . Similar fusion proteins obtained with the N300A, K410H and K410N mutants were unstable and their catalytic and penicillin-binding properties were very strongly affected . In transpeptidation reactions, the presence of the acceptor influenced the kcat/Km values, which suggested a catalytic pathway more complex than a simple partition of the acyl-enzyme between hydrolysis and aminolysis . These results are compared with those obtained with two other penicillin-sensitive enzymes, the Streptomyces R61 dd-peptidase and Escherichia coli penicillin-binding protein (PBP) 5.

Nat Biotechnol, 1997 Nov, 15(12), 1276 - 9
Creating a bifunctional protein by insertion of beta-lactamase into the maltodextrin-binding protein; Betton JM et al.; Hybrid proteins were generated by inserting the penicillin-hydrolyzing enzyme, TEM beta-lactamase (Bla), into the maltodextrin-binding protein (MalE) . The inserted Bla was functionally accommodated by MalE when it was placed within permissive sites . The maltose binding and penicillinase activities of purified hybrids were indistinguishable from those of the wild-type MalE and Bla proteins . Moreover, these hybrids displayed an additional unexpected property: maltose stabilized the active site of inserted Bla.

Bioseparation, 1996, 6(6), 343 - 51
An efficient three steps preparative purification of penicillin acylase from Escherichia coli cells; Fargues C et al.; A new and efficient safe system for the purification of the penicillin acylase from Escherichia coli G271 is presented . It was found that after a selective precipitation with ammnonium sulphate, followed by two chromatographic steps (anion exchange followed by adsorption on hydroxyapatite support), the enzyme was enriched 98 times with a 100% activity recovery . An original way has also been used to study the chromatographic separation of the protein mixture in three major categories on DEAE resin, by an analysis of the concentrations of the different species in the breakthrough curve obtained from a complete saturation of the column.

J Appl Microbiol, 1997 Oct, 83(4), 464 - 9
Bacterial influence on the production of paralytic shellfish toxins by dinoflagellated algae; Dantzer WR et al.; This study investigated the role of intracellular and extracellular bacteria in the production of paralytic shellfish toxins by dinoflagellated algal cells . Three strains of the toxic dinoflagellate species, Alexandrium tamarense, were purified by external bacteria using penicillin G (Pen . G) at levels of 500 and 1000 p.p.m . Levels of toxicity of the resulting purified dinoflagellate cultures were similar to those of the original strains contaminated with external bacteria, indicating that the external bacteria had no influence on toxicity . No bacterial colony forming units (cfu) arose from disruption of algal cells derived from penicillin-treated cultures, indicating that intracellular bacteria were not responsible for the toxicity of cultures.

Diagn Microbiol Infect Dis, 1997 Sep, 29(1), 51 - 3
Fusospirochetal superinfection of pre-existing oral lesion in patients with acquired immunodeficiency syndrome; Bottone EJ et al.; Three patients with AIDS presented with nonbleeding, painful, fetid, oral ulcers overlaid with a grayish-black semiadherent membrane at the sites of a pre-existing lesion . These lesions persisted despite treatment directed toward the primary etiology (cytomegalovirus, Kaposi's sarcoma) . Gram- and Giemsa-stained smears of teased membrane fragments revealed an impressive bacterial flora with fusiforms and Borrelia-type spirochetes . Prompt treatment with penicillin brought amelioration of symptoms and sloughing of the overlaying membrane.

Genet Anal, 1997 Jul, 14(2), 51 - 4
Location of regulatory gene in penicillin G acylase operon (pacR) of E . coli D816; Jiang L et al.; Regulatory gene in Penicillin G Acylase operon (pacR) of E . coli D816 was located in a Taq1-Dra1 fragment within the pac structure gene . Two ORFs were found in this fragment and their transcriptional orientations were opposite with pac . ORF2 was determined as pacR by point mutation.

Acta Cardiol, 1997, 52(4), 363 - 8
Tricuspid valve infectious endocarditis associated with dental treatment; Fujito T et al.; A 52-year-old man with neither congenital heart disease nor history of drug abuse had a spiking fever after dental treatment and was diagnosed with pneumonia at a local clinic . He was treated with antibiotics and his fever went down . Ten months later, he had again pyrexia and suffered from congestive heart failure . He admitted to our hospital and tricuspid valve endocarditis was proved by echocardiography . He was treated with penicillin . However, during the treatment, he developed a pulmonary embolism . So he underwent surgical treatment . We should take dental treatment into account one of predisposing causes of tricuspid endocarditis.

Schweiz Arch Tierheilkd, 1997, 139(3), 134 - 43
{Septic arthritis of the hoof joint in the horse--diagnosis, radiologic changes and therapy}; Stanek C; A retrospective study (1984-1994) was made of 10 cases of septic arthritis of the distal interphalangeal joint in horses aged 7 months to 17 years . In 6 cases a hind limb was affected, in 4 cases a front limb . The arthritis was caused either by a puncture wound in the sole area (8 cases), by a perforating wound in the coronary region (1) or iatrogenic (1) . All horses exhibited a severe lameness at the walk . Radiography showed no typical lesions in fresh cases, whilst later an increasing subluxation of the joint was observed followed by periosteal reactions . Therapy included partial resection of the deep flexor tendon and fenestration of the Lig.impar in cases of nail puncture, single or repeated joint lavages carried out either under general anesthesia or on the standing horse, and broad spectrum antibiotic therapy, using mainly penicillin and gentamicin . 5 out of 10 horses were treated successfully.

Eur J Clin Pharmacol, 1997, 52(6), 437 - 40
How Estonian and Finnish primary care doctors rate their need for common drugs; Lember M et al.; OBJECTIVE: To compare ratings of the necessity of drugs in the daily practice of experienced primary care doctors in Estonia and Finland to find out the differences and similarities in the therapeutic traditions of the two different societies . METHODS: A questionnaire was sent to all Estonian district doctors born in the 1940s and to all Finnish specialized general practitioners born in the 1940s, who then evaluated the necessity of the listed drugs on a visual analogue scale . The ratings, from 0 to 100, were entered into a computer, using a graphic tablet and a pressure sensitive pointer . RESULTS: The six most highly-evaluated drugs among the Estonian respondents were digoxin, glyceryl trinitrate, aspirin, calcium-channel blockers, beta-adrenoceptor blockers and frusemide; and among the Finnish general practitioners (GPs) were penicillin, insulin, glyceryl trinitrate, beta-adrenoceptor blockers, frusemide and angiotensin-converting enzyme (ACE) inhibitors . The ratings of 15 out of 33 drugs/drug groups were very similar both in Estonia and Finland . The biggest differences between the opinions of the Estonian and Finnish doctors appeared in the ratings regarding the necessity of antacids, cimetidine, insulin, sulphonylureas, reserpine . ACE inhibitors, oral contraceptives, penicillin, metronidazole, trimethoprim, indomethacin, phenobarbital and theophylline . CONCLUSION: The revealed differences are suggested to be related to the different health care systems (different task profiles of doctors, different pharmaceutical services), different education of doctors, different availability of drugs in the past and different prices, all of which influence therapeutic traditions.

J Bacteriol, 1997 Oct, 179(19), 6005 - 9
The bimodular G57-V577 polypeptide chain of the class B penicillin-binding protein 3 of Escherichia coli catalyzes peptide bond formation from thiolesters and does not catalyze glycan chain polymerization from the lipid II intermediate; Adam M et al.; Because the specificity profile of the membrane anchor-free G57-V577 penicillin-binding protein 3 (PBP3) of Escherichia coli for a large series of beta-lactam antibiotics is similar to that of the full-size membrane-bound PBP, the truncated PBP is expected to adopt the native folded conformation . The truncated PBP3 functions as a thiolesterase . In aqueous media and in the presence of millimolar concentrations of a properly structured amino compound, it catalyzes the aminolysis of the thiolester until completion, suggesting that the penicillin-binding module of PBP3 is designed to catalyze transpeptidation reactions . In contrast, the truncated PBP3 is devoid of glycan polymerization activity on the E . coli lipid II intermediate, suggesting that the non-penicillin-binding module of PBP3 is not a transglycosylase.

Schweiz Rundsch Med Prax, 1997 Jul 16, 86(29-30), 1143 - 6
{Whipple's disease: molecular biology--clinical aspects--therapy}; Blum HE; Whipple's disease is a rare systemic bacterial disease, affecting mostly middle-aged white men . Its clinical presentation is very variable . Arthralgias, fever of unknown origin or central nervous system symptoms may precede the more typical gastrointestinal manifestations with weight loss and chronic diarrhea . The diagnosis is based on the histopathologic demonstration of PAS-positive macrophages in duodenal or jejunal biopsies . In addition, it has become possible to detect the causative actinobacterium Tropheryma whippelii by amplification of a Whipple-specific PCR product . Therapeutic options are a sequential therapy with penicillin-streptomycin, followed by trimethoprim-sulfamethoxazole (TMP-SMX) or a monotherapy with TMP-SMX . These therapeutic modalities usually eradicate the infection and result in a rapid and sustained improvement of the Whipple-specific signs and symptoms . In view of the frequently uncharacteristic initial clinical presentation (arthralgias, fever, CNS symptoms), it is therefore of utmost importance to consider Whipple's disease in the differential diagnosis of the clinical signs and symptoms.

Neuroscience, 1997 Dec, 81(4), 1111 - 22
The role of long-term potentiation in persistent epileptiform burst-induced hyperexcitability following GABAA receptor blockade; Schneiderman JH; Persistent hyperexcitability follows synchronized bursting induced in the CA3 region of hippocampal slices by perfusion with high concentrations (2000 IU/ml) of the GABAA antagonist, penicillin . This hyperexcitable state is characterized by: i) slow recovery from bursting following penicillin washout; ii) persistent "post-burst" field potential oscillations and iii) increased probability of spontaneous bursting with ordinarily sub-convulsant doses of GABAA antagonists . An N-methyl-D-aspartate-independent type of long-term potentiation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate excitatory postsynaptic potentials occurred following bursting . However, similar increases in excitatory postsynaptic potential magnitude also occurred after a subconvulsant dose of penicillin (500 IU/ml) which did not produce the other features of persistent hyperexcitability . Furthermore, long-term potentiation either increased or remained stable after bursting stopped, whereas, post-burst oscillations gradually diminished with time . Low doses of the AMPA/kainate antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, which restored the potentiated excitatory postsynaptic potentials to control levels, reduced but did not eliminate the post-burst oscillation . Tetanus-induced long-term potentiation did not reproduce the hyperexcitable state seen after bursting . These findings indicate that the epileptiform bursting caused by blocking GABAA-mediated inhibition induces long-term potentiation which is partially responsible for persistent burst-induced hyperexcitability but is not sufficient to entirely explain it . The hippocampus which is critical for normal memory is also frequently the generator of intractable epileptic seizures . Seizure-like discharges in the hippocampus induced long-lasting increases in synaptic efficacy similar to those thought to underlie normal memory . This form of long-term potentiation contributed to the network oscillations characteristics of the hyperexcitable state persisting after epileptiform activity but was not sufficient to entirely explain them . Epileptic seizures may engage normal memory mechanisms which increase neuronal excitability and predispose the hippocampal network to further seizures . This may, in part, account for the propensity for hippocampal seizure foci to become intractable.

J Pharm Pharmacol, 1997 Jun, 49(6), 617 - 21
Influence of hydroxypropyl beta-cyclodextrin on the stability of benzylpenicillin in chloroacetate buffer; Ong JK et al.; Hydroxypropyl beta-cyclodextrin (HP beta CyD) has been shown to stabilize a wide variety of chemically distinct pharmaceutical entities through inclusion-complex formation between drug and cyclodextrin . The effect of HP beta CyD on the acid-catalysed hydrolysis of benzylpenicillin (penicillin G) was evaluated in chloroacetate buffer at pH 2.20 . At penicillin G: cyclodextrin molar concentration ratios from 1:1 to 1:10, HP beta CyD effected stabilization of penicillin G by 1.56- to 5.21-fold . At all temperatures, the observed first-order rate constant (kobs) values assumed a non-linear, Michaelis-Menten type decrease as a function of increasing HP beta CyD concentration . Degradation of penicillin G complexed with HP beta CyD (penicillin G-HP beta CyD), was approximately ninefold slower than uncomplexed penicillin G . The proportion of penicillin G degrading in either of these forms was, in turn, determined by the equilibrium constant for the complexation . The apparent thermodynamic and activation parameters for the complexation between penicillin G and HP beta CyD have also been evaluated . The negative standard enthalpy change (delta H degrees) for the complexation implied that the penicillin G-HP beta CyD complex would be predisposed towards enhanced stability, and thus the kobs value for the hydrolysis of penicillin G decreased with reduction of temperature in these systems . The lack of difference between the enthalpies of activation (delta H ++) for the hydrolysis of uncomplexed and complexed penicillin G seemed to be compensated by the significant difference between the entropies of activation (delta S ++) for these hydrolytic reactions . The results indicate that HP beta CyD represents a viable means of stabilization of penicillin G solutions at the pH employed in this study.

Microbiol Immunol, 1997, 41(8), 587 - 93
Cyclophosphamide-induced bacterial translocation in Escherichia coli C25-monoassociated specific pathogen-free mice; Nakayama M et al.; The kinetics of bacterial translocation (BTL) from the intestine to the mesenteric lymph nodes (MLN) and the number of peripheral white blood cells (WBC), macrophages in Peyer's patches (PP) and M-cells on the surface of cecal PP after cyclophosphamide (CY) injection were examined in penicillin-G and streptomycin sulfate decontaminated and Escherichia coli C25-monoassociated specific pathogen-free mice . WBC are counted to confirm the immunological state of the mice . Until 8 days after CY injection, the number of WBC, bacteria in MLN and macrophages in PP decreased, but then significantly increased on day 14 . The levels again decreased to the control levels on day 16 . Although the number of M-cells decreased up to day 8, it did not return to the control level on day 16 . These results indicate that BTL is stimulated in an immunopotentiated state after CY injection, and this phenomenon may be closely related to the number of macrophages in the blood and PP.

Microb Drug Resist, 1997 Fall, 3(3), 243 - 51
Molecular epidemiology of drug-resistant pneumococci: toward an international approach; Hermans PW et al.; An international multicenter study was undertaken to investigate the epidemiological dynamics of penicillin-resistant pneumococci . We compared the molecular epidemiological characteristics of 205 penicillin-resistant isolates originating from The Netherlands, Thailand, United States, Spain, Greece, Poland, Cuba, Germany, Finland, United Kingdom, South Africa, Hungary, Portugal, Croatia, and the Czech Republic . Eighty-four distinct restriction fragment end labeling (RFEL) types were observed . Twenty-eight genetic types were shared by two or more strains . Five genetic clusters consisted of strains originating from different countries, illustrating dissemination of penicillin-resistant pneumococci among countries . The strains displaying the two predominant RFEL types corresponding with the pandemic clones 23F and 9V were found in 10 and 6 different countries, respectively . This clearly demonstrates the pandemic behavior of these two clones . Twelve out of the 28 genetic clusters contained two or more serotypes . This finding indicates frequent horizontal transfer of capsular genes . Within distinct RFEL types, identical penicillin binding protein (PBP) genotypes were often observed, suggesting a high frequency of horizontal transfer of penicillin resistance genes . The most predominant PBP type was found in 15 distinct RFEL types, comprised 44% of the entire collection, and was observed in 11 countries . The vast majority of the strains belonging to the pandemic clones 23F and 9V shared this predominant PBP type . We hypothesize that the clones 23F and 9V are responsible for the worldwide increase of penicillin-resistance, because they serve as a genetic reservoir for susceptible pneumococci to acquire penicillin resistance.

Zhonghua Hu Li Za Zhi, 1997 Mar, 32(3), 128 - 31
{Experimental morphological study of injection nerve injuries in rabbits}; Ding ZH et al.; The sciatic nerve of 16 rabbits were examined with the optical and electron microscope 2, 24, 72 hours and 7 days after injecting penicillin (200,000 U) into nerve or its peripheral in experiment group and control group . The experiment group showed successively nerve fiber tumefaction, myelin sheath lamellar separation and degeneration partly, the construction of axonal change abnormality myelin and axonal obvious degeneration from 2 hours to 7 days . The control group showed perinerve edema, hyperemia, epineurium hyperplasia, the nerve fiber of near epineurium had mild pathologic changes.

Antimicrob Agents Chemother, 1997 Sep, 41(9), 2013 - 5
Penicillin-binding proteins and induction of AmpC beta-lactamase; Sanders CC et al.; In competition assays for radiolabeled penicillin, penicillin-binding proteins (PBPs) 4, 7a, and 7b showed very high affinities for strong inducers of AmpC beta-lactamase . Loss of PBP 4 resulted in diminished inducibility . This suggests that if PBPs are involved in induction of AmpC beta-lactamase, there is probably a redundancy in function among the different PBPs.

Antimicrob Agents Chemother, 1997 Sep, 41(9), 1926 - 32
Rationale behind high-dose amoxicillin therapy for acute otitis media due to penicillin-nonsusceptible pneumococci: support from in vitro pharmacodynamic studies; Lister PD et al.; To evaluate whether increased doses of amoxicillin should be used to treat acute pneumococcal otitis media, an in vitro pharmacokinetic model was used to evaluate the killing of pneumococci by amoxicillin when middle ear pharmacokinetics were simulated . Logarithmic-phase cultures were exposed to peak concentrations of 3, 6, and 9 microg of amoxicillin per ml every 12 h, and an elimination half-life of 1.6 h was simulated . Changes in viable bacterial counts were measured over 36 h . All three doses rapidly decreased the viable bacterial counts of penicillin-susceptible strains below the 10-CFU/ml limit of detection by 6 to 10 h and maintained counts below this limit through 36 h . The 3-microg/ml peak dose was much less effective against two of three strains with intermediate penicillin resistance and all three penicillin-resistant strains, with bacterial counts approaching those in drug-free control cultures by 12 h . The 6-microg/ml peak dose completely eliminated two of three strains with intermediate penicillin resistance and maintained viable counts of the other nonsusceptible strains at 1.5 to 2 logs below the initial inoculum through 36 h . The 9-microg/ml peak dose was most effective, completely eliminating all three strains with intermediate penicillin resistance and maintaining the viable counts of the resistant strains at 3 to 4 logs below the original inoculum . The pharmacodynamics observed in this study suggest that peak concentrations of amoxicillin of 6 to 9 microg/ml may be sufficient for the elimination of penicillin-nonsusceptible pneumococcal strains causing otitis media, especially those with intermediate resistance to amoxicillin . In vivo pharmacokinetic studies are needed to determine if these levels can be achieved in middle ear fluid with amoxicillin at 70 to 90 mg/kg/day divided into two daily doses . If these levels are reliably achieved, then clinical studies are warranted.

Appl Microbiol Biotechnol, 1997 Aug, 48(2), 191 - 7
Stabilization of Escherichia coli penicillin G acylase against thermal inactivation by cross-linking with dextran dialdehyde polymers; Kazan D et al.; The thermostabilization of penicillin G acylase (PGA) obtained from a mutant of Escherichia coli ATCC 11,105 by cross-linking with dextran dialdehyde molecules, at a molecular mass of 11,500, 37,700 and 71,000 Da, was studied . The thermal inactivation mechanisms of the native and modified PGA were both considered to obey first-order inactivation kinetics during prolonged heat treatment, forming fully active but temperature-sensitive transient states . The highest enhancement to the thermostability of PGA was obtained using dextran-71000-dialdehyde modification, as a nearly ninefold increase at temperatures above 50 degrees C . The modification of PGA by dextran-11500-dialdehyde resulted in a considerable reduction of the Vm and Km parameters of the enzyme . However, other dextran dialdehyde derivatives used for modification did not cause a meaningful change in either Vm and Km . Modification by dextran dialdehyde derivatives did not result in significant change to either the optimal temperature or the activation energy of PGA . All modified PGA preparations showed lower inactivation rate constants but higher half-lives for inactivation than those of the native PGA at all temperatures studied . As indicated by the half-life times and Ki values, dextran 71000-dialdehyde was found to be more effective at cross-linking in the thermo-stabilization of PGA than any other agent studied in this work.

J Radiol, 1997 Jul, 78(7), 513 - 6
{Actinomycotic tubo-ovarian abscess . Contribution of pelvic angioscanner}; Bazot M et al.; Pelvic actinomycosis is uncommon and usually responsible for tubo-ovarian abscesses which are similar in aspect with nonactinomycotic abscesses . They are usually a complication of an intra-uterine device (IUD) that can be absent as in this case . The differential diagnosis is ovarian cancer . The role of the dynamic CT scan for differential diagnosis in this case is presented . Preoperative diagnosis in this affection is important because of the excellent response to Penicillin.

J Bacteriol, 1997 Sep, 179(18), 5802 - 11
A promoter for the first nine genes of the Escherichia coli mra cluster of cell division and cell envelope biosynthesis genes, including ftsI and ftsW; Hara H et al.; We constructed a null allele of the ftsI gene encoding penicillin-binding protein 3 of Escherichia coli . It caused blockage of septation and loss of viability when expression of an extrachromosomal copy of ftsI was repressed, providing a final proof that ftsI is an essential cell division gene . In order to complement this null allele, the ftsI gene cloned on a single-copy mini-F plasmid required a region 1.9 kb upstream, which was found to contain a promoter sequence that could direct expression of a promoterless lacZ gene on a mini-F plasmid . This promoter sequence lies at the beginning of the mra cluster in the 2 min region of the E . coli chromosome, a cluster of 16 genes which, except for the first 2, are known to be involved in cell division and cell envelope biosynthesis . Disruption of this promoter, named the mra promoter, on the chromosome by inserting the lac promoter led to cell lysis in the absence of a lac inducer . The defect was complemented by a plasmid carrying a chromosomal fragment ranging from the mra promoter to ftsW, the fifth gene downstream of ftsI, but not by a plasmid lacking ftsW . Although several potential promoter sequences in this region of the mra cluster have been reported, we conclude that the promoter identified in this study is required for the first nine genes of the cluster to be fully expressed.

J Clin Lab Anal, 1997, 11(5), 251 - 7
Determination of IgE antibodies to the benzylpenicilloyl determinant: a comparison of the sensitivity and specificity of three radio allergo sorbent test methods; Garcia JJ et al.; The quantitation of in vitro IgE antibodies to the benzylpenicilloyl determinant (BPO) is a useful tool for evaluating suspected penicillin allergic subjects . Although many different methods have been employed, few studies have compared their diagnostic specificity and sensitivity . In this study, the sensitivity and specificity of three different radio allergo sorbent test (RAST) methods for quantitating specific IgE antibodies to the BPO determinant were compared . Thirty positive control sera (serum samples from penicillin allergic subjects with a positive clinical history and a positive penicillin skin test) and 30 negative control sera (sera from subjects with no history of penicillin allergy and negative skin tests) were tested for BPO-specific IgE antibodies by RAST using three different conjugates coupled to the solid phase: benzylpenicillin conjugated to polylysine (BPO-PLL), benzylpenicillin conjugated to human serum albumin (BPO-HSA), and benzylpenicillin conjugated to an aminospacer (BPO-SP) . Receiver operator control curves (ROC analysis) were carried out by determining different cut-off points between positive and negative values . Contingence tables were constructed and sensitivity, specificity, negative predictive values (PV-), and positive predictive values (PV+) were calculated . Pearson correlation coefficients (r) and intraclass correlation coefficients (ICC) were determined and the differences between methods were compared by chi 2 analysis . Analysis of the areas defined by the ROC curves showed statistical differences among the three methods . When cut-off points for optimal sensitivity and specificity were chosen, the BPO-HSA assay was less sensitive and less specific and had a lower PV- and PV+ than the BPO-PLL and BPO-SP assays . Assessment of r and ICC indicated that the correlation was very high, but the concordance between the PLL and SP methods was higher than between the PLL and HSA or SP and HSA methods . We conclude that for quantitating IgE antibodies by RAST to the BPO determinant, BPO-SP or BPO-PLL conjugates offer advantages in sensitivity and specificity compared with BPO-HSA . These results support and extend previous in vitro studies by our group and highlight the importance of the carrier for RAST assays.

Protein Expr Purif, 1997 Aug, 10(3), 309 - 19
High-level expression of soluble protein in Escherichia coli using a His6-tag and maltose-binding-protein double-affinity fusion system; Pryor KD et al.; Using the maltose-binding protein (MBP) fusion vector pMAL-c1 from C . V . Maina et al . (1988, Gene 74, 365-373), we have constructed expression vectors which contain a sequence encoding six consecutive histidine residues (His6-tag) at the 3' end of the MBP-encoding malE gene which is followed by either a thrombin-binding site (LVPRGS) or a factor Xa-binding site (IEGR) . The benefits of this approach include; (a) high expression levels of soluble MBP fusion proteins (exceeding 2% of the total cellular protein), (b) high-quality purification of proteins under various conditions (high salt, low salt, denaturing, nondenaturing, etc.), and (c) two alternative protease cleavage sites to test for the most efficient cleavage of each fusion protein . We also constructed these MBP-His 6-tag expression vectors with alternative selection markers (Ampr, Kanr) and alternative promoters (tac, T7) . Using these constructs, we expressed and purified several proteins of which we present two, penicillin-binding protein PBP2a and UDP-N-acetylmuramate:L-alanine ligase (MurC), and compare their expression level and purity with other expression systems . We also discuss the use of minimal media with supplements versus rich media and cell growth strategies to optimize the protein yield in general and for isotope labeling.

Antimicrob Agents Chemother, 1997 Aug, 41(8), 1721 - 4
Altered permeability and beta-lactam resistance in a mutant of Mycobacterium smegmatis; Mukhopadhyay S et al.; Beta-lactam resistance in mycobacteria results from an interplay between the following: (i) beta-lactamase production, (ii) affinity of the penicillin-binding proteins (PBPs) for the drugs, and (iii) permeation of the drugs . A laboratory mutant of Mycobacterium smegmatis was studied in order to evaluate the roles of these factors in beta-lactam resistance . Mutant M13 was between 7- and 78-fold more resistant than the wild type to cephaloridine, cefoxitin, cefazolin, cefamandole, and cephalothin . Increased beta-lactamase activity toward these antibiotics was not observed in the mutant . The PBP profiles of the wild type and M13 were comparable . However, the affinities of PBP 1 for the beta-lactams tested were lower for the mutant than for the wild type . The permeation of the drugs measured in intact cells was lower for M13 than for the parent strain . The liposome swelling technique, which could be used for cephaloridine, also supported this view . Reduced permeation was not restricted to the beta-lactams alone . Glycine uptake was also lower in M13 . Taken together, the results suggest that decreased affinities of PBP 1 for beta-lactams, combined with the decreased permeability of the cell wall of the mutant, lead to the development of high-level acquired beta-lactam resistance.

J Bacteriol, 1997 Aug, 179(15), 4761 - 7
Topographical and functional investigation of Escherichia coli penicillin-binding protein 1b by alanine stretch scanning mutagenesis; Lefevre F et al.; Penicillin-binding proteins (PBPs) are the targets of beta-lactam antibiotics . We have used a systematic five-alanine substitution method (called ASS {alanine stretch scanning} mutagenesis) to investigate the functional or structural role of various stretches of amino acids in the PBP1b of Escherichia coli . To probe the specific activity of each variant, the antibiotic discs assay was used with strain QCB1 (delta ponB) in the presence of cefaloridine, which totally inhibits the complementing action of PBP1a . This in vivo test has been combined with a quick and efficient in vitro test of the penicillin-binding activity of each of these variants with fluorescent penicillin . This approach has enabled us to show an unexpected role of the N-terminal and C-terminal tails of PBP1b . Moreover, we have established the correct position in PBP1b of the SMN motif that, with the SXXK and the KTG motifs, constitutes the signature of the penicilloyl serine transferases family . Finally, we have shown that the transglycosylase and the transpeptidase domains are separated by an inert linker region, where substitutions and insertions can be made without hindering the in vivo and in vitro activity of the protein.

N Engl J Med, 1997 Jul 31, 337(5), 307 - 14
A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection . The Syphilis and HIV Study Group; Rolfs RT et al.; BACKGROUND: Reports of neurosyphilis and invasion of cerebrospinal fluid by Treponema pallidum in patients with human immunodeficiency virus (HIV) infection have led to doubts about the adequacy of the recommended penicillin G benzathine therapy for early syphilis . METHODS: In a multicenter, randomized, double-blind trial, we assessed two treatments for early syphilis: 2.4 million units of penicillin G benzathine and that therapy enhanced with a 10-day course of amoxicillin and probenecid . The serologic and clinical responses of patients with and without HIV infection were studied during one year of follow-up . RESULTS: From 1991 through 1994, 541 patients were enrolled, including 101 patients (19 percent) who had HIV infection but differed little from the uninfected patients in their clinical presentations . The rates at which chancres and rashes resolved did not differ significantly according to treatment assignment or HIV status . Serologically defined treatment failures were more common among the HIV-infected patients . The single clinically defined treatment failure was in an HIV-infected patient . Rates of serologically defined treatment failure did not differ according to treatment group (18 percent at six months with usual therapy; 17 percent with enhanced therapy) . T . pallidum was found at enrollment in the cerebrospinal fluid of 32 of 131 patients (24 percent) and after therapy in 7 of 35 patients tested . None had clinically evident neurosyphilis, and the rate of detection of T . pallidum did not differ according to HIV status . CONCLUSIONS: After treatment for primary or secondary syphilis, the HIV-infected patients responded less well serologically than the patients without HIV infection, but clinically defined failure was uncommon in both groups . Enhanced treatment with amoxicillin and probenecid did not improve the outcomes . Although T . pallidum was detected in cerebrospinal fluid before therapy in a quarter of the patients tested, such a finding did not predict treatment failure . The current recommendations for treating early syphilis appear adequate for most patients, whether or not they have HIV infection.

Pharmacoeconomics, 1997 Aug, 12(2 Pt 1), 161 - 74
The cost effectiveness of pneumococcal vaccination strategies; Gable CB et al.; Pneumonia and influenza, combined, are the sixth leading causes of death in the US . The age-adjusted mortality rate for these diseases increased by 20% between 1979 and 1993, perhaps as a result of the emergence of multi-drug-resistant and penicillin-resistant strains of bacteria that cause pneumonia . Of the approximately $US23 billion annual cost of community-acquired pneumonia, pneumococcal pneumonia is currently estimated to account for up to $US18 billion . Considering the clinical and economic consequences of pneumococcal disease, vaccination appears to be a valuable preventive strategy . However, despite Medicare coverage and the recommendations of the Advisory Committee on Immunisation Practices (ACIP), only 28% of elderly and high-risk patients received the pneumococcal vaccine in 1993 . This article reviews the epidemiology and economic factors that determine the cost effectiveness of pneumococcal vaccination strategies . The strategies are taken from a review of 10 published economic analyses of the pneumococcal vaccine . Cost savings and favourable cost-effectiveness ratios are associated with key factors that increase vaccination programme benefits by maximising averted direct medical costs as well as reducing vaccination programme costs, such as through public vaccination campaigns.

J Chromatogr B Biomed Sci Appl, 1997 Jul 4, 694(2), 383 - 91
Simultaneous determination of six penicillins in cows' raw milk by a multiresidue high-performance liquid chromatographic method; Sorensen LK et al.; A high-performance liquid chromatographic method based on C18 solid-phase extraction and ultraviolet detection at 323 nm of analytes derivatized with benzoic anhydride and 1,2,4-triazole mercuric chloride solution was developed for the simultaneous determination of amoxicillin, penicillin G (benzylpenicillin), ampicillin, oxacillin, cloxacillin and dicloxacillin residues in raw milk . The detection limit of the method was 1.3 microg/l for penicillin G; 1.4 microg/l for amoxicillin, oxacillin and cloxacillin, 1.5 microg/l for ampicillin and 2.7 microg/l for dicloxacillin . The mean recovery was 95-102% for amoxicillin, penicillin G and ampicillin, 92-98% for oxacillin and cloxacillin and 87-94% for dicloxacillin, measured by using an internal standard . The relative repeatability standard deviation was 4-9% on level 4-15 micro/l, respectively, 2-7% on level 30-40 microg/l.

J Ind Microbiol Biotechnol, 1997 Jul, 19(1), 18 - 27
Analysis of a commercially improved Penicillium chrysogenum strain series: involvement of recombinogenic regions in amplification and deletion of the penicillin biosynthesis gene cluster; Newbert RW et al.; Several commercially improved strains of Penicillium chrysogenum have been shown to carry amplifications of the entire penicillin biosynthesis gene cluster . Analysis previously carried out using the strain BW 1890 has here been extended to the characterisation of other members of the SmithKline Beecham strain improvement series . We have determined the length of the amplicon to be 57.4 kb and shown a general increase in copy number and penicillin titre through the series . Sequence analyses of the promoter regions of the acvA, ipnA and aat genes in the high titre strain BW 1901, and comparisons with wild-type sequences have not identified any potentially titre-enhancing mutations . In addition, cDNA screening has failed to identify any further transcribed elements within the co-amplified region . The homogeneity of hybridisation patterns and the identification and analysis of a single copy revertant has shown that the amplification is of a direct tandem nature and we propose a model of chromatid misalignment and recombination as its mode of generation . Hybridisation analysis of penicillin non-producing mutants has indicated the loss, in all those investigated, of the entire penicillin biosynthesis gene cluster, similarities between the deletion junctions in these strains and comparison with previously published data indicating the presence of recombinogenic regions flanking the penicillin biosynthesis gene cluster.

Medicine (Baltimore), 1997 Jul, 76(4), 295 - 303
Invasive pneumococcal infections . A comparison between adults and children; Rahav G et al.; A similar number of adults and children had invasive pneumococcal infection . There was male predominance, and different ethnic distribution between children and adults . The majority of adults (78%), had underlying diseases, but this was less frequent in children (24%) . The presenting illness differed between adults and children . Complications of invasive pneumococcal infection occurred more frequently in adults than in children . The mortality rate in adults was 21.5%; in children, only 3.8% . The rate of penicillin-resistant pneumococci at our hospital was 23%, while cefotaxime resistance was 4.2% . Penicillin-resistant pneumococci were not isolated more frequently from children than from adults . Patients with penicillin-resistant pneumococci had longer duration of hospitalization and more nosocomially acquired infections . No difference in the mortality rate was found between patients with resistant or sensitive pneumococci . Ninety-five percent of strains were included in the current vaccine, but less than 2% of patients had been vaccinated . Isolates prevalent in Europe and the United States (19, 5, 1, 14, 6, 18, 12, 4, 9, 23, 7) were also most prevalent in Jerusalem . The distribution of serotypes differed between children and adults, and between patients from whom resistant organisms were isolated as opposed to sensitive organisms.

Clin Exp Rheumatol, 1997 Jul-Aug, 15(4), 445 - 8
Actinomycotic splenic abscesses presenting with arthritis; Quintero-Del-Rio AI et al.; An 18-month-old Caucasian female began with a high fever . She developed swelling in one finger and one toe . Abdominal ultrasound revealed multiple abscesses in her spleen . Multiple blood culture and splenic abscess aspirations grew no pathogens . She had transient response to multiple antibiotics and splenic abscess drainage, but fever returned along with subcutaneous nodules . Culture of splenic tissue from her second splenic drainage eventually grew one organism identified as Actinomyces naeslundii . Therapy with high dose penicillin followed by amoxicillin p.o . and total splenectomy led to complete recovery.

Neth J Med, 1997 Jul, 51(1), 39 - 45
A rare case of disseminated actinomycosis caused by Actinomyces meyeri; van Mook WN et al.; A case of disseminated actinomycosis caused by Actinomyces meyeri in a 43-year-old man is described . The patient presented with signs of pericarditis, weight loss, dry cough, and subsequently an inferior vena cava syndrome . Diagnosis of thoracic as well as abdominal actinomycosis was made 4 months after admission . This article stresses the importance of considering the diagnosis of the disease . Cure was achieved by administering penicillin for several months.

Biosci Biotechnol Biochem, 1997 Jul, 61(7), 1150 - 5
Effects of medium-chain fatty acids and their acylglycerols on the transport of penicillin V across Caco-2 cell monolayers; Shima M et al.; The transport-enhancing effects of medium-chain fatty acids (caproic, caprylic, and capric acids) and their acylglycerols (mono-, di-, and triacylglycerols) were investigated by using Caco-2 cell monolayers as a model of the human intestinal epithelium . Penicillin V was used as a model for a hydrophilic bioactive compound . Among the fatty acids and acylglycerols tested, 1,2-dicaproin, monocaprin, monocaprylin, and capric acid sodium salt effectively enhanced the transport rate, whereas other substances enhanced the rate only slightly or not at all . With each of these four substances, the rate of enhancement was proportional to the concentration at low concentrations, but leveled off at high concentrations . The transport-enhancing effects were well correlated with the reduction in surface tension and with a physico-chemical parameter, denoted by the surface energy-lowering coefficient, characterizing the surface activity of a substance.

Phys Med Biol, 1997 Jul, 42(7), 1415 - 26
An optical phantom with tissue-like properties in the visible for use in PDT and fluorescence spectroscopy; Wagnieres G et al.; The design and characterization of optical phantoms which have the same absorption and scattering characteristics as biological tissues in a broad spectral window (between 400 and 650 nm) are presented . These low-cost phantoms use agarose dissolved in water as the transparent matrix . The latter is loaded with various amounts of silicon dioxide, Intralipid, ink, blood, azide, penicillin, bovine serum, and fluorochromes . The silicon dioxide and Intralipid particles are responsible for the light scattering whereas the ink and blood are the absorbers . The penicillin and the azide are used to ensure the conservation of such phantoms when stored at 4 degrees C . The serum and fluorochromes, such as Coumarin 30, produce an autofluorescence similar to human tissues . Various fluorochromes or photosensitizers can be added to these phantoms to simulate a cancer photodetection procedure . The absorption and fluorescence spectroscopy of the porphyrin-type fluorescent markers used clinically for such photodetection procedures is similar in these phantoms and in live tissues . The mechanical properties of these gelatinous phantoms are also of interest as they can easily be moulded and reshaped with a conventional cutter, so that complex structures and shapes, with different optical properties, can be designed . The optical properties of these phantoms were determined between 400 and 650 nm by measuring their effective attenuation coefficient (mu eff) and total reflectance (Rd) . The microscopic absorption and reduced scattering coefficients (mu a, mu s') were deduced from mu eff and Rd using a Monte Carlo simulation.

Prev Vet Med, 1997 Jul, 31(1-2), 133 - 46
Associations between off-label feed additives and farm size, veterinary consultant use, and animal age; Dewey CE et al.; Data from the United States National Swine Survey collected by the National Animal Health Monitoring System were used to describe the use of feed additives in swine feeds . Data were collected from 710 farms . The concentration of feed additives expressed in grams per ton of complete feed was described by stage of production, and the use of feed additives above the labeled treatment levels (i.e . off-label) was identified . Of the 3328 feeds, about 79% contained feed additives used in the labeled manner . For all classes of pigs, the prevalence of labeled feed additive use was greater than 75% . Penicillin was used according to its label most often, followed by apramycin, bacitracin, tetracyclines, lincomycin, and tylosin . Carbadox had the highest prevalence of off-label use . Of the 699 feeds that included feed additives in an off-label manner, about 57% included additives at greater than the recommended concentrations or were fed to an incorrect class of pig . About 56% of the feeds had off-label combinations of additives . Small farms were more likely to use rations with no feed additives than intermediate or large farms (P < 0.001) . Of those farms using feed additives, the odds of a small farm using all feed additives in the labeled manner was 7.7 times that of an intermediate or large farm (P < 0.0001) . After controlling for herd size, producers who used a veterinary consultant were 2.1 times more likely to use feeds with feed additives (P < 0.0001).

Crit Care Med, 1997 Jul, 25(7), 1187 - 90
Effects of prolonged controlled mechanical ventilation on diaphragmatic function in healthy adult baboons; Anzueto A et al.; OBJECTIVE: To study diaphragmatic strength and endurance after a prolonged period of mechanical ventilation . DESIGN: Prospective animal study . SETTING: Animal research laboratory . SUBJECTS: Seven uninjured adult baboons (Papio cynocephalus) were anesthetized with ketamine, sedated, paralyzed, and mechanically ventilated . Animals were monitored with pulmonary arterial and peripheral arterial catheters . INTERVENTIONS: Mechanical ventilation was provided for 11 days with an FIO2 of 0.21 and tidal volume of 15 mL/kg . Pulmonary function tests, including lung volumes, arterial blood gases, and chest radiographs were also monitored . Nursing care procedures included frequent turning, chest physiotherapy, and endotracheal suction . Antacids and prophylactic antibiotics (intravenous penicillin, topical polymyxin B, and gentamicin sulfate) were administered . In three animals, fishhook electrodes were surgically placed around both phrenic nerves on both day 0 and after 11 days of mechanical ventilation for diaphragmatic stimulation . On day 0, the electrodes were removed after phrenic nerve stimulation studies were performed . After 11 days of mechanical ventilation, animals were electively killed and full autopsy performed . MEASUREMENTS AND MAIN RESULTS: Hemodynamic and pulmonary function parameters were measured at baseline and every day during the 11 days of mechanical ventilation . Diaphragmatic strength and endurance were measured on days 0 and 11 . Diaphragmatic endurance was determined by an inspiratory resistive loading protocol . There were no significant changes in hemodynamics, lung volumes, or gas exchange during the period of mechanical ventilation . On day 7, the chest radiographs showed patchy lobar atelectasis in six animals, which cleared by day 11 in all but two of the animals . Lung pathology showed mild, focal pneumonitis . By day 11, maximum transdiaphragmatic pressure had decreased by 25% from day 0 and diaphragmatic endurance had decreased by 36% . CONCLUSIONS: Eleven days of mechanical ventilation and neuromuscular blockade in healthy baboons resulted in nonsignificant changes in hemodynamics, oxygenation, and/or lung function . However, significant impairment in diaphragmatic endurance and strength were seen . Based on these results, it is likely that prolonged mechanical ventilation by itself impairs diaphragmatic function independent of underlying lung disease.

Arch Pediatr Adolesc Med, 1997 Jul, 151(7), 701 - 4
A randomized controlled trial of penicillin vs clindamycin for the treatment of aspiration pneumonia in children; Jacobson SJ et al.; OBJECTIVE: To compare the effectiveness of intravenous penicillin vs clindamycin for the treatment of aspiration pneumonia . DESIGN: A double-blind, randomized controlled trial . SETTING: A tertiary care pediatric hospital . PATIENTS: We enrolled 42 children, aged 6 months to 18 years, who were admitted to the hospital for the treatment of aspiration pneumonia . All of the children had underlying conditions that predispose to aspiration . INTERVENTION: The patients were randomly assigned to receive intravenous penicillin G sodium, 250,000 U/kg every 24 hours, or intravenous clindamycin phosphate, 30 mg/kg every 24 hours . MAIN OUTCOME MEASURE: The primary outcome measure was "time to ready for discharge" from the hospital . RESULTS: In an effectiveness (intention to treat) analysis, the median time (interquartile range) to ready for discharge from the hospital was 4.9 days (range, 2.8-6.5 days) in the penicillin-treated group and 3.4 days (range, 2.3-6.8 days) in the clindamycin-treated group (P = .66) . Results were not markedly altered when adjusted for the age difference of the groups or in the efficacy analysis (after the exclusion of 9 patients who withdrew from the trial) . Rates for readmission to the hospital were similar in the 2 groups . CONCLUSION: Penicillin and clindamycin seem to be equally effective for the treatment of aspiration pneumonia in children hospitalized for this illness.

Int J Syst Bacteriol, 1997 Jul, 47(3), 763 - 6
Spiroplasma platyhelix sp . nov., a new mollicute with unusual morphology and genome size from the dragonfly Pachydiplax longipennis; Williamson DL et al.; Spiroplasma strain PALS-1T from the gut of the dragonfly Pachydiplax longipennis was shown to be distinct from other species, groups, and subgroups of the genus Spiroplasma as determined by reciprocal serological metabolism inhibition and deformation tests . However, this strain cross-reacted extensively with representatives of other groups when it was used as an antigen . Electron microscopy of cells of strain PALS-1T revealed cells surrounded by a single cytoplasmic membrane . Light microscopy revealed helical cells that exhibited twisting motility rather than rotatory or flexing motility . Variations in the tightness of coiling were transmitted from one end of the helix to the other . The strain was resistant to penicillin, which confirmed that no cell wall was present . The organism grew well in M1D and SP-4 liquid media under either aerobic or anaerobic conditions . Growth also occurred in 1% serum fraction medium and in conventional horse serum medium . The optimum temperature for growth was 30 degrees C, at which the doubling time was 6.4 h . Multiplication occurred at temperatures from 10 to 32 degrees C . Strain PALS-1T catabolized glucose and hydrolyzed arginine but not urea . The guanine-plus-cytosine content of the DNA was 29 +/- 1 mol% . The genome size was 780 kbp, the smallest genome size in the genus Spiroplasma . Strain PALS-1 (= ATCC 51748) is designated the type strain of a new species, Spiroplasma platyhelix.

J Bacteriol, 1997 Jul, 179(14), 4627 - 30
Dual multimodular class A penicillin-binding proteins in Mycobacterium leprae; Lepage S et al.; The ponA gene of cosmid L222 of the Mycobacterium leprae genome library encodes a multimodular class A penicillin-binding protein (PBP), PBP1 . The PBP, labelled with a polyhistidine sequence, has been produced in Escherichia coli, extracted from the membranes with 3-{(3-cholamidopropyl)-dimethylammonio}-1-propane-sulfonate (CHAPS) and purified by Ni2(+)-nitrilotriacetic acid-agarose chromatography . In contrast to the pon1-encoded class A PBP1, PBP1 undergoes denaturation at temperatures higher than 25 degrees C, it catalyzes acyl transfer reactions on properly structured thiolesters, and it binds penicillin with high affinity.

Ann Trop Paediatr, 1997 Jun, 17(2), 175 - 7
Intraosseous infusion in an emergency situation: a case report; Nafiu OO et al.; An 18-month-old boy who had cardiopulmonary arrest secondary to penicillin anaphylaxis was successfully resuscitated by intraosseous administration of emergency resuscitative medications because peripheral vascular access was impossible . He was discharged 2 weeks later in a satisfactory clinical condition.

FEMS Microbiol Lett, 1997 Jun 1, 151(1), 9 - 16
Identification of the pac promoter from Kluyvera citrophila; Roa A et al.; The nucleotide sequence of the 5'-terminal region of the pac gene encoding the penicillin G acylase from Kluyvera citrophila ATCC 21285 has been determined . The transcriptional start site has been identified by primer extension analysis in a different position to that previously found for the homologous pac gene of Escherichia coli W ATCC 11105 . Two nucleotide changes in the -35 box appear to be responsible of the promoter displacement in K . citrophila . A putative upstream promoter element (A+T-rich enhancer sequence) and a binding site for the cAMP receptor protein (CRP) were located upstream of the -35 box . Transcriptional lacZ and cat fusions demonstrated that pac expression was subjected to catabolite repression mediated by cAMP and its receptor protein . Remarkably, phenylacetic acid which is a potent inducer of the penicillin G acylase from E . coli, was only able to cause a significant induction of the pac expression in CRP+ cells cultured in the presence of glucose, suggesting that this effect is CRP-dependent.

Brain Res Mol Brain Res, 1997 Jun, 46(1-2), 177 - 84
Induction of FOS and JUN proteins during focal epilepsy: congruences with and differences to {14C}deoxyglucose metabolism; Gass P et al.; fos and jun belong to multigene families coding for transcription factors . These cellular immediate-early genes (IEGs) are thought to be involved in coupling neuronal excitation to changes of target gene expression . Immunocytochemistry with specific antisera was used to assess regional levels of five IEG-encoded proteins (c-FOS, FOS B, c-JUN, JUN B and JUN D) in a rat model of penicillin-induced focal epilepsy . To assess whether brain regions with post-ictal de novo transcription factor synthesis correspond to those areas with increased glucose metabolism, IEG expression patterns were compared with {14C}deoxyglucose autoradiography performed in a subset of animals . The results demonstrated marked induction of c-FOS, FOS B, c-JUN and JUN B but not JUN D in the cortical epileptic focus . Thereby, individual IEG-encoded proteins exhibited differential temporal and spatial expression patterns . Within the epileptic focus, IEG expression correlated with increased glucose metabolism . In contrast, IEG induction was not observed in brain areas distant from the epileptic focus that also demonstrated increased glucose metabolism, such as homotopic contralateral motor cortex and ipsilateral thalamic nuclei . These findings indicate that in focal epilepsy changes of the genetic programme are restricted to neurons of the epileptic focus . In contrast, the increased {14C}deoxyglucose metabolism in contralateral motor cortex and ipsilateral thalamus seems to indicate functional changes.

J Bacteriol, 1997 Jun, 179(12), 4061 - 5
A putative monofunctional glycosyltransferase is expressed in Ralstonia eutropha; Paik J et al.; A gene, mgt, encoding a protein homologous to the N-terminal module of class A high-molecular-mass penicillin-binding proteins was identified in Ralstonia eutropha . By using specific antibodies, the corresponding Mgt protein was detected in association with the membrane, confirming that the N-terminal hydrophobic segment functioned as a membrane anchor . A derivative in which the hydrophobic sequence was deleted was overexpressed as a maltose-binding fusion protein in Escherichia coli . Cleavage of the product resulted in substantial amounts of soluble Mgt derivative, indicating that folding occurs independently on other proteins or on homologous domains of penicillin-binding proteins.

Infect Immun, 1997 Jun, 65(6), 2206 - 10
Temperature-sensitive mutants of Actinobacillus pleuropneumoniae induce protection in mice; Byrd W et al.; Temperature-sensitive mutants of Actinobacillus pleuropneumoniae 4074, serotype 1, were isolated after treatment with nitrosoguanidine and enrichment with penicillin and D-cycloserine . Of the four temperature-sensitive mutants evaluated in mice, one (A-1) had a tight phenotype (i.e., it ceased replication immediately after transfer to the nonpermissive temperature {37 degrees C}) and three (1-2, 4-1, and 12-1) were coasters that continued replication for up to three generations after transfer to 37 degrees C . The reversion frequencies ranged from 10(-6) to 10(-9), and cutoff temperatures ranged from 33 to 35 degrees C . No major changes were detected in the biochemical profiles; agglutination reactions; electrophoretic profiles of the lipopolysaccharides, outer membrane proteins, and hemolysin proteins; hemolytic titers; or CAMP factor reactions of the mutants and the wild-type bacteria . Groups of 3- to 5-week-old, female ICR mice were immunized intranasally with three doses of 3.5 x 10(6) CFU of the mutants over 3 weeks and subsequently challenged intranasally with 5 50% lethal doses of the parental wild-type . Protection was induced by both the tight and the coaster mutants, with the 4-1 and 12-1 coasters eliciting greater protection (67 and 82%, respectively) than that induced by the A-1 tight mutant (57%) . Intranasal immunization with both phenotypes induced serum antibody responses against the surface antigens and the hemolysin protein.

Schweiz Med Wochenschr, 1997 May 31, 127(22), 940 - 4
{Neurosyphilis 12 years after treatment of primary infection in a meanwhile HIV infected patient}; Eriksson U et al.; A 33-year-old male HIV-positive patient developed pure right motor hemiplegia due to meningovascular neurosyphilis . 12 years ago he was successfully treated for early syphilis with a single dose of 2.4 million units penicillin G benzathine without subsequent evidence of new infection or disease progression . Repeated HIV tests remained negative until 1993 when the HIV infection was diagnosed . It is well known that Treponema pallidum, the etiologic agent of syphilis, may be detected in the cerebrospinal fluid during early infection . Thus the former recommended regimen of single-dose penicillin G benzathine may not reliably eradicate T . pallidum from the CNS . Residual organisms may serve as a reservoir for relapse and dissemination in an immunocompromised host.

Ugeskr Laeger, 1997 May 19, 159(21), 3175 - 7
{Lyme neuro-borreliosis in a 66-year old women . Differential diagnosis of cerebral metastases and cerebral infarction}; Henriksen TB; A 66-year-old woman with medically treated hypertension and a recent operation for breast cancer was admitted because of burning pain localized between her shoulder blades and a paretic, dysaesthetic right arm . CSF examination revealed lymphocytic pleocytosis and specific IgM Borrelia burgdorferi antibodies . CT was normal . The patient was treated intravenously with high doses of penicillin for 14 days, and within one month of admission she had recovered completely neurologically . During the first days of treatment a drop in blood pressure, ECG changes, and further neurological changes were observed, but disappeared spontaneously within three days . The patient did not recall a tick bite, and the case illustrates that neuroborreliosis may be a differential diagnosis to stroke or cerebral neoplasms in elderly patients.

Med J Aust, 1997 May 5, 166(9), 464 - 7
A profile of inpatient STD-related pelvic inflammatory disease in the Top End of the Northern Territory of Australia; Mein J et al.; OBJECTIVE: To obtain a profile of inpatient STD-related pelvic inflammatory disease (PID) in the Top End of the Northern Territory . DESIGN: Review of case records . SETTING: The Royal Darwin Hospital, the tertiary referral centre for the Top End, during the three years from June 1991 to May 1994 . PATIENTS: All admissions with a diagnosis of STD-related PID . MAIN OUTCOME MEASURES: The presentation and incidence of STD-related PID in Aboriginal and non-Aboriginal women . RESULTS: PID was the reason for 14% of admissions of Aboriginal women and 2% of non-Aboriginal women . Of 175 episodes of PID in 169 patients admitted over the three years of the study, 41 (23%) had gonorrhoea, 64 (37%) had chlamydia and 7 (4%) had both organisms isolated on genital swab . Aboriginal women were more than twice as likely to have gonorrhoea (38% versus 18%; risk ratio, 2.12; 95% confidence interval, 1.27-3.53) as non-Aboriginal women . Median time from first symptoms to presentation was six days . All gonococcal isolates were penicillin susceptible . CONCLUSIONS: STD-related pelvic inflammatory disease is an important problem among women in the Top End of the Northern Territory . As PID is a preventable illness, further measures aimed at prevention and earlier, more effective treatment of STDs that cause PID are urgently required.

J Emerg Med, 1997 May-Jun, 15(3), 303 - 7
Unusual presentation of cervicothoracic actinomycosis complicated by pericardial effusion: a case report; Beier KH et al.; Actinomycosis is a chronic-suppurative disease characterized by abscesses and draining sinus tracts, with fibrosis and granulation involving the face and neck and thoracic or pelvic-abdominal regions . Dermatological findings in patients at high risk are the key to the correct diagnosis . Actinomycosis is frequently undiagnosed or misdiagnosed until the correct diagnosis is made after surgical resection . Alcoholic, homeless, and disadvantaged individuals and patients with other factors predisposing to infection including poor dentition, alcoholism, seizures, and trauma are common in the emergency department; thus, emergency physicians should be aware of the different presentations and complications of this disease . The treatment of choice is a high dose of penicillin in conjunction with surgical debridement . The prognosis is excellent with correct diagnosis and therapy.

Analyst, 1997 May, 122(5), 447 - 53
Modified fluorimetric assay for estimating ampicilloate concentrations and its use for detecting beta-lactamase and penicillin acylase activity in bacteria; Baker WL; Sodium ampicilloate concentrations were estimated fluorimetrically by heating solutions with ascorbic acid, EDTA and a modified Lowry A reagent which was prepared by including copper sulfate and potassium sodium tartrate in 0.5 mol dm-3 acetate buffer at pH 4 . A concentration range of 0.5-50 mumol dm-3 was used for the estimations . The reaction was used to estimate beta-lactamase activity on ampicillin but the substrate also showed some fluorescence and a calculation was required to determine the amount of ampicilloate formed when both substances were present in the one reaction mixture . The beta-lactamase was inhibited by treatment with trichloroacetic acid so the procedure could be used to assay the enzyme activity after a fixed time . 6-Aminopenicillanic acid did not fluoresce on treatment with the modified reagent and organisms which contained penicillin acylase lowered the amount of ampicillin which could be converted to ampicilloate . When penicillin acylase and beta-lactamase co-existed in the one organism, the respective activities were determined by use of the copper-ascorbate-EDTA fluorescence assay for ampicilloate coupled with a fluorescamine assay for 6-aminopenicillanic acid determinations . On prolonged incubation, some organisms containing penicillin acylases lowered the amount of ampicilloate which formed a fluorescent product . This effect was attributed to deacylation of ampicilloate by the penicillin acylases.

J Infect, 1997 May, 34(3), 265 - 7
The combined value of chemoprophylaxis and pneumococcal vaccine in the prevention of recurrent pneumococcal meningitis; Hristea A et al.; We report the case of an immunocompetent patient who has been the subject of 39 episodes of recurrent pneumococcal meningitis over a 20 year period . The recurrences of bacterial meningitis due to cerebrospinal fluid leakage and the presence of chronic sinusitis were not influenced by the surgical repair of a fistula and the repeated surgical draining interventions on suppurating chronic sinusital foci . Phenoxymethylpenicillin treatment reduced the number of recurrences and the combination of pneumococcal vaccine and penicillin prophylaxis allowed a 5 year period free of any recurrences.

Pediatr Dermatol, 1997 May-Jun, 14(3), 226 - 8
Congenital syphilis associated with hyperlipoproteinemia; Mestrovic J et al.; An infant with congenital syphilis associated with transient disturbances of lipoprotein metabolism is reported . The dominant clinical sign was hepatosplenomegaly . Laboratory investigation upon admission revealed hyperimmunoglobulinemia and hyperchylomicronemia . After the administration of penicillin, the chylomicronemia ceased, but an increase of very low density lipoprotein fraction was observed . As the infant recovered, all the laboratory findings returned to normal . Hyperchylomicronemia was attributed to hyperimmunoglobulinemia . Absorption of immunoglobulins to lipoproteins can inhibit lipoprotein lipase activity . The increase in the very low density lipoprotein fraction was probably caused by the increase in serum lipoprotein production and the decrease in lipoprotein clearance that are frequently seen in patients with infectious diseases.

Epilepsy Res, 1997 May, 27(2), 127 - 37
Coupling of cortical and thalamic metabolism in experimentally induced visual and somatosensory focal epilepsy; Redecker C et al.; Focal epileptic activity induces widespread metabolic disturbances beyond the area of the electroencephalographically detectable focus . In order to find out whether the metabolic coupling between the epileptic focus and other brain regions depends on the localization of the focus, two groups of rats with epileptic foci at different sites were investigated . In the first group acute epileptic activity was induced by application of penicillin to the secondary visual cortex (Oc2), and in the second group to the primary somatosensory cortex (Par1) . Metabolism was analyzed using the {14C}deoxyglucose autoradiographic method . In both groups of animals, hypermetabolism in the area of the focus and in specific functionally coupled thalamic nuclei was observed . Focal epileptic activity in the secondary visual cortex induced significant hypometabolism in remote ipsilateral cortical areas . In rats with epileptic foci in the primary somatosensory cortex hypometabolism in extrafocal ipsilateral cortical areas was less prominent . These findings provide further support for the integral involvement of the thalamus in modulating metabolism in remote cortical brain regions during focal epileptic activity . The extent of metabolic alterations may depend on the site of the epileptic focus and the connectivity of the recruited thalamic nuclei.

Nippon Rinsho, 1997 May, 55(5), 1200 - 5
{Genetics of multiresistant MRSA}; Ito T et al.; Since the introduction of methicillin, methicillin resistant S . aureus (MRSA) was appeared in 1961 in England . MRSA produces specific penicillin-binding protein PBP2' which shows very low affinity to most of beta-lactam antibiotics . The region around mecA is called additional DNA or mec DNA and is thought to be extraspecies origin . From the study of mec DNA, it was revealed that there were three types of mec DNA . In the case of mec DNA of N315, a transposon Tn554 which encoded erythromysin and spectinomycin resistance, and a plasmid pUB110 which encoded resistance to kanamycin, tobramycin, and bleomycin were integrated . MRSA became resistant to many antibiotics during a few years which were effective at the time of introduction, such as, carbapenems, new quinolones, and minocycline . MRSA has changed their properties by obtaining resistance-genes or generating mutations on its chromosomal DNA.

Ann Emerg Med, 1997 May, 29(5), 683 - 6
Descending necrotizing mediastinitis: complication of a simple dental infection; Haraden BM et al.; Descending necrotizing mediastinitis (DNM) is a rare complication of periodontic infection . The delay in diagnosis of DNM is believed to contribute to its high mortality rate . We report the case of a healthy 23-year-old man who was seen in the urgent care center, given the diagnosis of dental infection, prescribed penicillin, and sent home . He returned 48 hours later complaining of myalgias, purulent drainage from around his teeth, chest pain, and dyspnea . DNM was diagnosed, and aggressive treatment comprising thoracotomy, cervical incision and drainage, and antibiotics was begun . The patient responded well to treatment and was discharged from the hospital on postoperative day 20 . Prompt diagnosis and immediate therapy are imperative for this rare condition.

J Bacteriol, 1997 May, 179(9), 2823 - 34
Murein segregation in Escherichia coli; de Pedro MA et al.; Peptidoglycan (murein) segregation has been studied by means of a new labeling method . The method relies on the ability of Escherichia coli cells to incorporate D-Cys into macromolecular murein . The incorporation depends on a periplasmic amino acid exchange reaction . At low concentrations, D-Cys is innocuous to the cell . The distribution of modified murein in purified sacculi can be traced and visualized by immunodetection of the -SH groups by fluorescence and electron microscopy techniques . Analysis of murein segregation in wild-type and cell division mutant strains revealed that murein in polar caps is metabolically inert and is segregated in a conservative fashion . Elongation of the sacculus apparently occurs by diffuse insertion of precursors over the cylindrical part of the cell surface . At the initiation of cell division, there is a FtsZ-dependent localized activation of murein synthesis at the potential division sites . Penicillin-binding protein 3 and the products of the division genes ftsA and ftsQ are dispensable for the activation of division sites . As a consequence, under restrictive conditions ftsA,ftsI,or ftsQ mutants generate filamentous sacculi with rings of all-new murein at the positions where septa would otherwise develop.

Int Arch Allergy Immunol, 1997 May-Jul, 113(1-3), 342 - 4
IgG and IgE antibodies in subjects allergic to penicillins recognize different parts of the penicillin molecule; Torres MJ et al.; BACKGROUND: IgE and IgG antibodies to penicillins can have different specificities . However, this response, including the recognition of the different parts of penicillin, has never been studied in the same subject . OBJECTIVE: Study of the specificity of IgE and IgG antibodies and the relevant parts of the penicillin molecule that contribute to the hapten binding site in sera from human . METHODS: Specific IgE antibodies were determined by RAST and specific IgG antibodies by ELISA . The recognition of the different molecules was studied by inhibition studies . RESULTS: Seven sera with IgG and IgE antibodies to amoxicillin and benzyl penicillin were analyzed . IgE antibodies recognized mainly two different epitopes: in one, the side chain was a relevant part of the epitope, in the other, it was the nuclear portion . IgG antibodies recognized the nuclear portion in all instances . In the same subject, antibodies of different isotype and specificity were found . CONCLUSIONS: Subjects who develop simultaneously IgE and IgG antibodies to penicillins show different specificities . This proves that different populations of antibodies recognize different epitopes.

Int Arch Allergy Immunol, 1997 May-Jul, 113(1-3), 177 - 80
High IL-5 production by human drug-specific T cell clones; Pichler WJ et al.; To analyze whether and how T cells are involved in drug allergies, we analyzed the drug-induced activation of T cell subsets, T cell receptor V-beta usage and cytokine secretion of T cells from the peripheral blood of drug-allergic individuals . The specificity of the T cells was demonstrated by specific restimulation of drug specific clones . We found that drugs which do not need to be metabolized to become immunogenic (haptens like penicillin G) can stimulate CD4+ and CD8+ T cells in vitro . The T cell response to penicillin can be oligoclonal (use of a certain T cell receptor Vbeta only) or polyclonal . Only polyclonal T cell lines were cross-reactive with other beta-lactam antibiotics . Sulfamethoxazole and lidocaine are thought to gain their ability to bind to proteins by intracellular drug metabolism . They were found to stimulate CD4+ and CD8+ T cells in vitro, and some reactive T cell lines were oligoclonal . The majority of lidocaine-specific clones secreted rather high amounts of IL-5 and IL-4 after PMA/ionomycin stimulations (Th2-like), but some CD4+ and all CD8+ clones had a Th1-like phenotype (high INF-gamma and TNF-alpha) . The data clearly demonstrate the existence of drug-specific alphabeta+ T cells in the circulation of drug-allergic individuals and reveal a great heterogeneity of T-cell-mediated responses . Further studies are needed to correlate the type of T cell response to the clinical picture, which can be quite heterogeneous.

J Clin Microbiol, 1997 May, 35(5), 1157 - 60
Molecular study of persistence of Nocardia asteroides and Nocardia otitidiscaviarum strains in patients with long-term nocardiosis; Provost F et al.; Three Nocardia asteroides and five Nocardia otitidiscaviarum isolates recovered from three patients with long-term nocardiosis were compared by random amplification of polymorphic DNA fingerprinting, antibiotic susceptibility testing, and enzymatic characterization . Results obtained with primer DKU49 (P . Palittapongarnpim, S . Chomyc, A . Fanning, and D . Kunimoto, J . Infect . Dis . 167:975-978, 1993) provide evidence that patient A was infected by two N . asteroides strains during a single episode of nocardiosis and that patients B and C remained infected by the same strain, respectively . Resistance to minocycline that was present in the first isolate recovered from patient B reverted to intermediate resistance in the second isolate and reverted to susceptibility in the third isolate . Resistance to penicillin G and beta-lactams was acquired by the second isolate obtained from patient C.

Ugeskr Laeger, 1997 Apr 14, 159(16), 2389 - 91
{Penicillin treatment of non-nosocomial pneumonia in Danish medical departments . A questionnaire}; Gjersoe P et al.; This study describes the most common penicillin-regime for hospitalized patients with community-acquired pneumonia in Denmark . One hundred and seventy-one consultant physicians received an anonymous questionnaire, 85% were returned and 75% were evaluated . The most common regime is a treatment duration of six to ten days with 3-6 million IU of penicillin daily given in three doses . The most common route of administration is intravenously until the patient's body temperature drops . Then the same dose is given orally . Variations in strategy were revealed and call for further investigations to establish and maintain restrictive antibiotic regimes.

Ned Tijdschr Geneeskd, 1997 Apr 12, 141(15), 723 - 6
{Clinical judgment and decision making in clinical practice . A music conductor with epilepsy followed by memory disorders}; Rinkel GJ et al.; A 40-year-old conductor was admitted because of increasing drowsiness and confusion . Two years before admission he had had a first seizure . One year before admission he had a generalized convulsive status epilepticus; the following months he was less able to concentrate . A second status epilepticus was followed by transient weakness of his left arm and a depressed level of consciousness for several weeks . After awakening, he had delusions, and his wife found him demented . In the following months his confusion and drowsiness gradually deteriorated . He had previously had gonorrhoea, an episode of fever and exanthema, and was found to have oligospermia as cause of his infertility . On examination he was disoriented, and he had dysarthria . His left pupil was smaller, but both pupils reacted normally . There was left hemianopia and cerebellar ataxia . CT and MR showed large ventricles and periventricular diffuse lesions in the white matter . CSF examination revealed leucocytosis and increased protein content . Further examination were focussed on serological evidence of syphilis, and finally neurosyphilis was diagnosed . After treatment with penicillin, the patient started to recover.

Brain Res, 1997 Apr 4, 753(1), 86 - 97
Critical volume of rat cortex and extracellular threshold concentration for a pentylenetetrazol-induced epileptic focus; Schwindt W et al.; The initiation of focal interictal epileptiform activity (FIEA) has been shown to depend on the activation of a sufficiently large volume of brain tissue . We estimated the size of this 'critical volume' for the convulsant pentylenetetrazol (PTZ) by analyzing the diffusion following its microinjection into rat motor cortex . PTZ concentration was monitored 100-200 microm away from the injection site with a PTZ-sensitive microelectrode . Diffusion analysis in 0.3% agar yielded the free diffusion coefficient D (8.50 +/- 0.15 X 10(-6) cm2 x s(-1) at 37 degrees C, median +/- S.E.M.) . In brain tissue, diffusion was modified by extracellular volume fraction (alpha), tortuosity (lambda = (D/ADC)1/2; ADC = apparent diffusion coefficient) and non-specific uptake (k') . Using a value of 0.2 for alpha from previous studies, we found values of lambda = 1.61 +/- 0.01, k' = 3.37 +/- 0.15 X 10(-3) s(-1) and an injected volume U of 5.16 +/- 0.45 X 10(-10) l for pulses without FIEA, and lambda = 1.95 +/- 0.06, k' = 6.24 +/- 1.73 X 10(-3) s(-1) and U = 7.40 +/- 0.66 X 10(-10) l for pulses with FIEA . From the calculated concentration distribution of PTZ during FIEA we estimated a threshold concentration of about 1.77 mM PTZ and a volume with a radius of about 219 microm in which this concentration had to be exceeded . Since this critical volume was comparable in size to foci elicited by penicillin or electric stimuli in previous studies, it is concluded that it is determined by intrinsic tissue properties rather than by the convulsive agent being used.

Rinsho Shinkeigaku, 1997 Apr, 37(4), 341 - 3
{A case of tabes dorsalis observed in an HTLV-1 carrier}; Nagata A et al.; We report a case of a 53-year-old female HTLV-1 carrier with tabes dorsalis . In addition to typical symptoms of tabes dorsalis, she presented HTLV-1 associated myelopathy (HAM) like clinical features such as sensory disturbance with thoracic sensory levels and bladder disturbance (pollakiuria) . Although penicillin treatment did not improve in her neurological symptoms, steroid therapy was effective especially in HAM like symptoms . The CSF neopterin level was markedly decreased after steroid therapy, indicating that inflammation in the spinal cord was settled down after treatment . Our case suggests that CNS infection like tabes dorsalis may be modified by HTLV-1 infection and then present some atypical clinical features based upon altered immunological aspects of HTLV-1 carriers.

Biochimie, 1997 Apr, 79(4), 171 - 4
An investigation into the ability of C-terminal homologues of Escherichia coli low molecular mass penicillin-binding proteins 4, 5 and 6 to undergo membrane interaction; Harris F et al.; The Escherichia coli low molecular mass penicillin-binding proteins (PBP4, PBP5 and PBP6) are a group of penicillin-sensitive enzymes involved in the final stages of cell wall assembly . It has been suggested that these proteins may interact with the periplasmic face of the inner membrane via C-terminal amphiphilic alpha-helices . Theoretical analysis has predicted that these C-terminal helical regions may be membrane interactive . We have tested this hypothesis by assaying PBP C-terminal homologues (P4, P5 and P6) for haemolytic activity . Our results show that the PBP5 and PBP6 C-terminal homologues readily lyse sheep erythrocytes in a pH-dependent manner with LD50's of 3.5 x 10(-6) M and 6.8 x 10(-7) M respectively at pH 7 . These results appear to support the present model for the membrane anchoring of PBP5 and PBP6 . The PBP4 C-terminal homologue shows no evidence of haemolytic activity which could imply a different means of membrane association for PBP4.

Appl Microbiol Biotechnol, 1997 Apr, 47(4), 373 - 8
Localization and characterization of inclusion bodies in recombinant Escherichia coli cells overproducing penicillin G acylase; Sriubolmas N et al.; Various concentrations of isopropyl beta-D-thiogalactopyranoside (IPTG) were used to induce production of the enzyme penicillin G acylase by recombinant Escherichia coli harboring plasmid pQEA11 . The plasmid pQEA11 carries a wild-type pga gene, which is under the control of the tac promoter and lacIq . At low IPTG concentrations (0.025-0.1 mM), enzyme activity increased with increasing IPTG concentrations . At higher IPTG concentrations (0.2 and 0.5 mM), enzyme activity declined progressively . Examination of induced recombinant E . coli cells by transmission electron microscopy showed the presence of only periplasmic inclusion bodies at low IPTG concentrations (up to 0.1 mM) and both periplasmic and cytoplasmic inclusion bodies at high IPTG concentrations (0.2 mM and 0.5 mM) . Results from sodium dodecyl sulfate/polyacrylamide gel electrophoresis and immunoblots of whole-cell proteins, membrane proteins and inclusion body proteins in these cells indicated that cytoplasmic inclusion bodies constituted an accumulation of preproenzyme (i.e., precursor polypeptide containing a signal peptide) and that periplasmic inclusion bodies constituted an accumulation of proenzyme (i.e., precursor polypeptide lacking a signal peptide).

Mech Ageing Dev, 1997 Apr, 95(1-2), 101 - 11
Effects of transforming growth factor-beta 1 and interleukin-1 alpha on matrix synthesis in osteoarthritic cartilage of the temporo-mandibular joint in aged mice; Blumenfeld I et al.; Osteoarthritic lesions were observed in the mandibular condyle cartilage of mice aged 7 months and older . These lesions appeared as fibrillations along the articular surface and were accompanied by reduced extracellular matrix synthesis and chondrocyte proliferation . Explants of mandibular condyle cartilage were cultured in serum-free BGJb medium supplemented with ascorbic acid (300 micrograms/ml), penicillin (100 U/ml) and streptomycin (100 micrograms/ml) for up to 72 h . Cultures were further supplemented with either hTGF-beta 1 (0.1-5.0 ng/ml) or human IL-1 alpha (40 U/ml) . {3H}thymidine (2 microCi/ml) and {35S}SO4 (10 microCi/ml) were added to the culture medium for the last 24 h of culture and incorporation into DNA and sulfated proteoglycans, respectively, studied . The results indicated that protein and DNA contents, {3H}thymidine and {35S}SO4 incorporation, as well as the specific activity of alkaline phosphatase, were increased by TGF-beta 1 . Addition of 1.0 or 5.0 ng/ml hTGF-beta 1 to the cultures for 48 h, had the most stimulatory effect on matrix synthesis and cell proliferation, whereas 0.1 ng/ml hTGF-beta 1 appeared to be inhibitory when compared to controls . Increased {35S}SO4 labeling of chondrocyte clusters was observed by autoradiography in tissue sections from cultures treated with TGF-beta 1 (1.0 and 5.0 ng/ml) . In contrast, IL-1 alpha exerted inhibitory effects on cell proliferation and matrix synthesis . However, it induced the activity of acid phosphatase in these cultures . The results of the present study show that IL-1 alpha had catabolic effect on his tissue, while TGF-beta 1 enhanced proliferation and induced synthetic activity of the cartilage cells . Such action by TGF-beta suggests the existance of a possible repair process in osteoarthritic cartilage of the temporo-mandibular joint of aged mice.

Arch Ophthalmol, 1997 Apr, 115(4), 469 - 73
Syphilitic uveitis in human immunodeficiency virus-infected patients; Shalaby IA et al.; OBJECTIVE: To document the incidence and clinical features of syphilitic uveitis in patients coinfected with human immunodeficiency virus (HIV) . DESIGN: Retrospective chart review . SETTINGS: Single tertiary uveitis referral center . PATIENTS: The charts of HIV-infected patients with uveitis and a reactive fluorescent treponemal antibody absorption test seen between November 1983 and June 1995 were reviewed . RESULTS: Syphilis was the most common bacterial cause of uveitis in this group . Thirteen patients (0.6% of the 2085 HIV-positive patients seen in the clinic during the study period) were dually infected . Twelve patients were male . Six patients (46%) had previously been treated for syphilis, 4 with intramuscular penicillin G benzathine only . Four patients (31%) had isolated anterior uveitis, 3 patients (23%) had anterior and intermediate uveitis, and 5 patients (38%) had panuveitis . One patient (8%) presented with optic nerve and retinal atrophy . Eight patients were treated with intravenous penicillin, 3 with intravenous and intramuscular penicillin, and 1 with intravenous ceftriaxone sodium . Of the 12 patients for whom follow-up examinations were available after treatment, ocular inflammation decreased in 11 (92%) and visual acuity improved in 8 (67%) . Rapid plasma reagin titers decreased a median of 64-fold compared with pretreatment levels, and all patients with reactive cerebrospinal fluid who underwent pretreatment and posttreatment lumbar punctures normalized following therapy with intravenous antibiotics . CONCLUSIONS: Syphilis is an uncommon cause of uveitis in HIV-infected patients . Anterior uveitis is the most common ocular manifestation, but panuveitis is more common than isolated anterior uveitis . Intravenous penicillin is effective therapy.

Pediatr Infect Dis J, 1997 Apr, 16(4), 376 - 81
Continuous twice daily or once daily amoxicillin prophylaxis compared with placebo for children with recurrent acute otitis media; Roark R et al.; OBJECTIVE: To determine the effectiveness of amoxicillin administered continuously twice daily vs . once daily vs . placebo to prevent new episodes of acute otitis media (AOM) . DESIGN: Randomized, double blind, placebo-controlled clinical trial at a hospital-based general pediatric clinic and a private pediatric practice, both in Denver, CO . PARTICIPANTS: One hundred ninety-four children (age 3 months through 6 years) were enrolled with 3 documented AOM episodes within the prior 6 months, without ventilating tubes or associated anatomic defects, immunodeficiency disorders or allergy to penicillin . Thirty-six were noncompliant and were excluded from the study, leaving 158 evaluable subjects . INTERVENTIONS: The amoxicillin dosage was 20 mg/kg/day either bid or qd . After randomization to placebo twice daily (bid), amoxicillin once daily (qd)/placebo qd or amoxicillin bid, patients were followed monthly and were also seen for upper respiratory infection symptoms during enrollment in the trial . Development of two new AOM episodes terminated the patients from the study . MEASUREMENTS/MAIN RESULTS: Incidence density (ID) measurements were calculated for all study subjects and were stratified by age and season . Overall study subjects in all 3 arms of the trial had 7243 days at risk during which time they developed 56 new AOM episodes for a annual ID of 2.82 . There were no significant differences in the IDs between amoxicillin qd vs . bid or amoxicillin (bid or qd) vs . placebo . After stratifying by age and season of enrollment, there were no significant differences in ID rates among the 3 groups . The proportion of subjects remaining otitis-free was 63% for the placebo group, 64% for once daily amoxicillin and 61% for twice daily amoxicillin . CONCLUSION: While once-a-day dosing was equivalent to twice-a-day dosing for amoxicillin prophylaxis, there was no benefit of amoxicillin prophylaxis compared with a placebo control in preventing new AOM episodes . Because of the potential of excessive antibiotic use to promote the acquisition of resistant pneumococci and the lack of effectiveness in this trial, routine use of amoxicillin prophylaxis should be discouraged.

Sex Transm Dis, 1997 Apr, 24(4), 229 - 35
Spontaneous clearance of Chlamydia trachomatis infection in untreated patients; Parks KS et al.; BACKGROUND AND OBJECTIVES: To assess the spontaneous clearance of untreated Chlamydia trachomatis infections and factors correlated with the process . STUDY DESIGN: Spontaneous clearance was assessed through review of laboratory database, chart review, and laboratory testing using direct immunofluorescence (DFA) and polymerase chain reaction (PCR) tests on C . trachomatis culture transport media from patients with negative chlamydial cultures . Specimens (C . trachomatis culture transport media) were obtained from patients attending a Birmingham, Alabama sexually transmitted diseases clinic . The study group consisted of patients with positive cultures for C . trachomatis who had repeat specimens obtained for culture within 45 days of initial observation and who had not received recommended therapy for chlamydial infection in the interval between the two tests . RESULTS: Of 74 evaluable patients, 24 (32%) had negative follow-up cultures . Culture transport media for these 24 culture-negative patients were tested with DFA or PCR assays for chlamydial infection, and 3 (13%) were positive . Culture positivity rates declined significantly with increasing age and duration of follow-up . Interval treatment with benzathine penicillin resulted in apparent resolution of infection in 9 of 10 patients . Neither a history of a C . trachomatis-associated syndrome nor treatment with cefixime, metronidazole, or antifungal agents was associated with clearance of infection . CONCLUSIONS: These results are consistent with host response-mediated resolution of infection in a minority of patients and have implications regarding public health efforts to control chlamydial infection.

Aten Primaria, 1997 Mar 31, 19(5), 263 - 6
{Acute respiratory infections (ARI) in the 0-14 years of age group during the winter period}; Blazquez Hernanz MC et al.; OBJECTIVE: Identification of factors associated with suffering Acute Respiratory Infections (ARI) . DESIGN: A descriptive study using a direct survey . SETTING: "El Naranjo" Primary Care team, Area 9 Madrid . PATIENTS: 362 patients between 0 and 14 . MEASUREMENTS AND MAIN RESULTS: 362 interviews were carried out, covering items connected with personal background, living conditions, situation and quality of life and activities, 180 patients attending with clinical symptoms of ARI were interviewed, as well as 182 who attended during the same period for other reasons . The profile of the patients interviewed was mainly: females between 6 and 10, with more history of catarrh than any other pathology, and who had taken aspirin to treat symptoms and mainly Penicillin as an aetiological treatment . They lived in homes measuring 100 square metres, with three bed-rooms which were shared in the main by two people, and had one brother aged between 1 and 9 . CONCLUSION: No protective factors against ARI were found in the group of children studied.

Med Klin (Munich), 1997 Mar 15, 92(3), 162 - 6
{Moraxella catarrhalis: virulence and resistance mechanisms}; Cullmann W; It is more than a century ago that Moraxella catarrhalis was discovered and described in some detail . However, it was not until the last decade that M . catarrhalis was recognized as a facultative pathogen, namely in otitis media (predominantly in children), sinusitis and nosocomial pneumonia in the group of elderly, debilitated patients . Liberation of endotoxin, histamine, and chemotactically active factors can be considered the major pathogenicity factors . The pathogen can protect itself, on the one hand by binding of the Clq subcomponent of the complement system followed by subsequent formation of a functionally inactive complex with Cl, and on the other hand by inactivation of the terminal (lytic) complement complexes by means of a specific protein on the surface of the outer cell wall . Routine diagnostic procedures require, above all, culture of the pathogen: up to now the detection of specific IgA-antibodies has not been routinely available . More than half of the clinical isolates are known to exhibit beta-lactamase production (BRO-enzymes) . This is the reason why combinations of a penicillin compound with a beta-lactamase inhibitor, the group of the newer cephalosporins (including the orally active ones), doxycycline and the macrolides are therapeutically effective.

Bone Marrow Transplant, 1997 Mar, 19(6), 639 - 41
Stomatococcus mucilaginosus meningitis in a patient with multiple myeloma following autologous stem cell transplantation; Abraham J et al.; Bacterial meningitis is an unusual complication of bone marrow transplantation . We report a case of Stomatococcus mucilaginosus meningitis in a patient with multiple myeloma shortly after an autologous peripheral blood stem cell transplant . The infection resolved with a combination of intravenous penicillin G and chloramphenicol, and intrathecal vancomycin.

Ann Trop Paediatr, 1997 Mar, 17(1), 21 - 3
Dexamethasone in laryngeal diphtheritic croup; Havaldar PV; Eighteen children diagnosed as having laryngeal diphtheria with various degrees of respiratory obstruction were treated with intravenous dexamethasone in addition to penicillin and anti-diphtheritic serum . Reduction in the severity of laryngeal obstruction was assessed 12-hourly . Eleven of 12 children with mild-to-moderate obstruction responded within 24 hours . The 12th child died of toxaemia and renal failure following tracheostomy . Four of six with severe obstruction also responded within 24 hours . The remaining two underwent tracheostomy, one of whom died . Dexamethasone appears to have a role to play in obviating tracheostomy in laryngeal diphtheria.

J Helminthol, 1997 Mar, 71(1), 69 - 71
Growth and development of Gnathostoma spinigerum early third-stage larvae in vitro; Maleewong W et al.; Early third-stage larvae of Gnathostoma spinigerum were cultured in RPMI-1640 supplemented with 25mM NaHCO3,100 units/ml penicillin G, 100 microg/ml of streptomycin, 5 microg/ml of amphotericin B and 10% foetal calf serum at 37 degrees C under 5% CO2 in air for 60 days . After 3 days of cultivation, the larvae moulted . Body sizes increased from 0.49 +/- 0.09 x 0.07 +/- 0.01 mm in length and width to 4.08 +/- 0.48 x 0.32 +/- 0.04 mm after 60 days of cultivation . The maximum body length and width of these larvae were 4.94 mm and 0 . 35 mm, respectively . The survival rate (67.5 %) of the worms was observed at the end of cultivation . The addition of foetal calf serum was found to be essential for growth and development.

J Clin Epidemiol, 1997 Mar, 50(3), 329 - 35
Medical drug utilization patterns for febrile patients in rural areas of Mexico; Leyva-F R et al.; The objective of this study was to evaluate the medication pattern of febrile patients and determine what proportion of these drugs were included in the Mexican Essential Drugs List . A cross-sectional study was conducted in 32 rural communities located in malarial endemic areas near the Mexico-Guatemala border . Of 817 febrile patients interviewed, 55% self-medicated, while 16% consulted a physician . The most frequently used drugs were antipyretics (68%), antibiotics (25%), and antimalarial drugs (37%), despite the fact that only 2% of all febrile patients were diagnosed with malaria . Antipyrine, acetylsalicylic acid, and acetaminophen represented 84% of antipyretics, and ampicillin, penicillin, and sulfadiazine-trimethoprim represented 51% of total antibiotics . Public health service and self-medicating patients used essential drugs (antipyretics and antibiotics) significantly more than those consulting private physicians . These findings demonstrate the need to foster access to primary health care (PHC) facilities, rational drug prescription by private physicians, and to review guidelines for prescription of antimalarial drugs for febrile patients.

Clin Perinatol, 1997 Mar, 24(1), 71 - 90
Syphilis in pregnancy; Sanchez PJ et al.; Syphilis in pregnancy remains a problem despite the availability of adequate diagnostic tests and years of penicillin therapy . During pregnancy, syphilis is compounded by its occurrence among populations that under-use the health care system and by its association with cocaine use and infection with HIV . The potentially devastating effect of syphilis on the fetus and attendant adverse outcomes on the pregnancy continue to make syphilis a global problem of major medical and public health consequences.

Infect Dis Clin North Am, 1997 Mar, 11(1), 177 - 201
Preterm labor and preterm premature rupture of the membranes . Diagnosis and management; Mercer BM et al.; Preterm delivery due to preterm labor and pPROM is responsible for most infant morbidity and mortality in the United States . The patient who presents with suspicious symptoms should undergo a thorough evaluation to confirm the diagnosis of either entity and identify a treatable cause . Determination of gestational age, fetal well-being, and the presence of intrauterine infection is a crucial step in subsequent management . Corticosteroid therapy has been demonstrated to be one of the most effective antenatal interventions to reduce infant morbidity and should be administered to patients with preterm labor, if feasible, when fetal pulmonary maturity is absent or undocumented . We recommend a similar protocol regarding gravidas with pPROM remote from term but recognize the need for further study in this area . Acute tocolytic therapy has been demonstrated to offer short-term benefit to enhance corticosteroid effect . However, all of the available tocolytic agents carry significant risks to the mother and fetus . As such, administration of these agents should be given only when the potential benefits outweigh the risks of administration . Evaluation for fetal pulmonary maturity and intrauterine infection, in concert with evaluation of gestational age-dependent risks of prematurity, may be helpful in determining whether tocolysis should be attempted . Adjunctive antibiotic administration has not been shown to reduce maternal or infant morbidity in the face of preterm labor . However, such treatment offers a reduction of chorioamnionitis, prolongation of latency, and a possible reduction of neonatal infectious and gestational age-dependent morbidity in the setting of pPROM remote from term . Finally, current guidelines recommend the administration of intrapartum GBS prophylaxis when preterm birth or prolonged membrane rupture is anticipated if GBS carrier status is unknown or positive . Intrapartum treatment with intravenous penicillin or ampicillin is appropriate.

FEMS Microbiol Lett, 1997 Mar 1, 148(1), 1 - 10
Molecular regulation of penicillin biosynthesis in Aspergillus (Emericella) nidulans; Brakhage AA; The beta-lactam antibiotic penicillin is produced as end product by only some filamentous fungi, most notably by Aspergillus nidulans and Penicillium chrysogenum . The biosynthesis of this secondary metabolite is catalyzed by three enzymes which are encoded by the following three genes: acvA (pcbAB), ipnA (pcbC) and aat (penDE) . The genes are organized into a gene cluster . In A . nidulans, several studies have indicated that the genes are controlled by a complex regulatory network . The wide-domain regulatory protein PACC binds to the intergenic region between acvA and ipnA and, at alkaline pH, increases at least ipnA gene transcription . An additional DNA binding protein (PENR1) was suggested to repress acvA and to activate ipnA and aat expression . Furthermore, three recessive trans-acting mutations have been characterized (prgA1, prgB1, npeE1) which most likely correspond to positively acting regulatory genes of the penicillin biosynthesis genes.

Laryngorhinootologie, 1997 Feb, 76(2), 101 - 5
{Cultivation of human keratinocytes of mucous membranes of the upper aerodigestive tract}; Saffran S et al.; BACKGROUND: Cultivation of benign epithelial cells under standardized conditions is of major interest in many fields of clinical and basic research . A modified fast and simple method for isolation, growth and passage of epidermal cells has been developed with consideration given to the complex environment of the upper aerodigestive tract . METHODS: Normal human mucosa of the upper aerodigestive tract was taken from 15 patients (4-73 years) during diagnostic and therapeutic operations . The epithelium could be separated easily from the mucosa after incubation the biopsies in disease over night . Subsequently, keratinocytes were isolated enzymatically by dissociation of epidermal sheets in trypsin, resulting a suspension of highly proliferating keratinocytes without contaminating fibroblasts (2 x 10(6) keratinocytes/biopsy) . The cells were washed several times in fresh fetal calf serum before they were plated in untreated culture flasks . The keratinocytes were cultivated in serum-free medium supplemented with epidermal growth factor, bovine pituitary extract, amphotericin B, and penicillin/ streptomycin . RESULTS: An average plating efficiency of 60% in primary cultures and 85% in subcultures was obtained . Passaging was possible every 10-13 days when keratinocytes reached sufficient confluency . The cells could be subcultured up to eight times (lifespan of 120 days), and exhibited the typical epithelial morphology during cultivation . CONCLUSION: Because of the modified pretreatment of the keratinocytes before plating, this culturing protocol for keratinocytes derived from the upper aerodigestive tract enables easy and fast cultivation of keratinocytes, further simplifying currently available methods.

Appl Biochem Biotechnol, 1997 Feb-Mar, 62(2-3), 303 - 15
Immobilization of whole-cell penicillin G acylase by entrapping within polymethacrylamide beads; Hsiau LT et al.; Escherichia coli ATCC 11105 containing the periplasmic penicillin G acylase was entrapped within a copolymer of methacrylamide and N,N'-methylenebisacrylamide . A solution of monomer that was made up from methacrylamide and N,N'-methylenebisacrylamide dissolved in buffer was mixed with lyophilized cells and ammonium persulfate . This suspension was then pumped drop by drop into in soybean oil supplemented with 0.06% (v/v) 3-(dimethylamino)-propionitril . During submerging in the oil phase, the droplets were hardened and induced to polymerize within the droplets . Particles with a volume ranging from 0.013-0.017 mL per bead containing a biomass concentration up to 38.0 g/L were prepared . The optimal condition for the deacylation of penicillin G to 6-aminopencillanic acid (6-APA) catalyzed by the immobilized whole-cell penicillin G acylase was found to be 45 degrees C and pH 8.0 . Product inhibition of this enzyme by 6-APA could be eliminated by controlling pH value at 8 during the course of penicillin G hydrolysis using a pH-stat . Conversion determined by the pH-stat method were 0.3% higher than that by p-dimethylaminobenzaldehyde method . Cell concentration in the matrix was found to be an important factor influencing the maximum velocity and the specific activity retained in the matrix . A kinetic model, in which the mass transfer resistances as a result of external film mass transfer and pore diffusion were assumed to be negligible, could properly describe the hydrolysis of penicillin G by the cells entrapped within the polymethacylamide beads.

Sex Transm Dis, 1997 Feb, 24(2), 94 - 101
Apparent failure of one injection of benzathine penicillin G for syphilis during pregnancy in human immunodeficiency virus-seronegative African women; Donders GG et al.; BACKGROUND: Syphilis remains a major cause of premature birth, fetal and perinatal death, and congenital syphilis in South Africa, despite systematic antenatal screening by rapid plasma reagin and treatment with 2.4 million U of benzathine penicillin G . GOAL: To determine whether one injection of 2.4 million of U of benzathine penicillin G, as recommended by the 1993 Centers for Disease Control and Prevention guidelines, is sufficient treatment for early syphilis during pregnancy . STUDY DESIGN: Outcome of pregnancy was prospectively analyzed after zero to three weekly intramuscular injections of benzathine penicillin G in 180 of 212 human immunodeficiency virus-seronegative black urban women with syphilis in Pretoria, South Africa . RESULTS: One hundred eight women receiving two or three weekly intra-gluteal injections of benzathine penicillin G had a favorable pregnancy outcome . However, after only one injection, lower birth weight, increased immaturity, prematurity, and total preterm birth rate resulted . Total pregnancy loss and perinatal mortality were also increased . After exclusion of patients treated with oral penicillin derivatives and adjustment for the estimated duration of treponemicidal levels at 3 weeks after injection, the perinatal outcome was reanalyzed . Treponemicidal coverage of 3 weeks or less resulted in decreased birth weight (2,748 vs . 3,130 g, P = 0.004) compared with treponemicidal coverage lasting longer than 3 weeks . In addition, the relative risks for prematurity (relative risk {RR}, 8.5; 95% confidence interval {CI95}, 2.5-28), perinatal mortality (RR, 20.5; CI95, 2.3-184), and congenital syphilis (RR 2.0; CI95-0.6-6.8) were increased when coverage was less then 3 weeks . These results were comparable to those obtained when no treatment was given . Most of the incompletely treated women delivered at less than 4 weeks after they received their injection . These also had the worst neonatal outcome . Impaired outcome due to short treatment clustered in early attenders of prenatal care (before the 28th week of gestation) and when the initial rapid plasma reagin titer was higher than 16 . Although numbers were small for a firm conclusion, incompletely treated and untreated women who had taken intercurrent oral ampicillin had an improved birth weight, lower prematurity rate, and lower fetal rate . CONCLUSIONS: One intramuscular injection of 2.4 million U benzathine penicillin G or treponemicidal concentrations lasting 3 weeks or less is not sufficient therapy for pregnant women with syphilis . Although fetal outcome is clearly improved at birth with more than one injection, without follow-up of the neonates, complete cure cannot be predicted from these data . To obtain treponemicidal activity for longer than 3 weeks, the authors recommend administration of two injections of 2.4 million U benzathine penicillin at least 1 week apart, if possible at 4 weeks or more before delivery . This therapy is especially important for patients who attend prenatal care before 28 weeks of pregnancy or when the rapid plasma reagin titer is higher than 16PIP: To determine whether the US Centers for Disease Control guideline of 1 injection of 2.4 million U of benzathine penicillin G is sufficient treatment for early syphilis in pregnant women, this regimen was tested in 180 human immunodeficiency virus-negative urban Black women with syphilis presenting to Kalafong Hospital in Pretoria, South Africa, during 1988-90 . A favorable pregnancy outcome was recorded in 108 women who received 2 or 3 weekly intragluteal injections . On the other hand, 1 injection was associated with lower birth weight, increased prematurity and total preterm birth rate, and increased total pregnancy loss and neonatal mortality . These outcomes were reanalyzed after exclusion of women treated with oral penicillin derivatives and adjusted for the estimated duration of treponemicidal levels at 3 weeks post-injection . Birth weight was significantly lower for treponemicidal coverage of 3 weeks or less compared to coverage lasting more than 3 weeks (2748 and 3130 grams, respectively) . Also increased when coverage was less than 3 weeks were the relative risks for prematurity (8.5), perinatal mortality (20.5), and congenital syphilis (2.0) . Impaired outcome associated with short treatment was clustered in women who attended prenatal care before the 28th week of gestation and those whose initial rapid plasma reagin titer exceeded 16 . These findings indicate that the standard protocol is not adequate in areas where syphilis is endemic . Recommended is administration of 2 injections of 2.4 million U benzathine penicillin at least 1 week apart, preferably 4 weeks or more before delivery .

Allergy, 1997 Feb, 52(2), 200 - 4
The presence of latex can induce false-positive skin tests in subjects tested with penicillin determinants; Terrados S et al.; Latex allergens are ubiquitous, and exposure may occur from different sources in the medical environment and in daily life . The observation that subjects with latex allergy were skin test positive to major and minor determinants of penicillins led our group to carry out an investigation to try to explain these findings . A group of 20 subjects with a history of allergy to latex and with positive skin tests for, but good tolerance of, penicillins was studied . The presence of latex contaminants was studied by RAST and RAST inhibition . Sixteen of the subjects were positive to at least one of the penicillin determinants used, and 14 (87%) of these were positive to at least two determinants . Repetition of skin tests using the container without a stopper changed the skin test results to negative in almost all cases, indicating that some trace contaminants had still been present . RAST-inhibition studies showed that in all penicillin determinants there were trace amounts of latex allergens varying between 3 and 0.03 micrograms/ml . These results indicate that skin tests with penicillin in subjects allergic to latex may give false-positive results and lead to such patients being falsely diagnosed as allergic to betalactams when penicillins are stored in containers with rubber stoppers.

Acta Ophthalmol Scand, 1997 Feb, 75(1), 36 - 40
Intravitreal concentrations of some drugs administered with microdialysis; Waga J et al.; Intraocular microdialysis was used to administer the drugs 5-fluorouracil, benzyl penicillin, daunomycin and dexamethasone into the vitreal space of rabbits . The purpose of the study was to investigate if therapeutic concentrations could be obtained with this administration method . After administering the drugs in labelled form, the attained concentrations were assessed by counting the radioactivity in the entire vitreous . For benzyl penicillin, the concentration was 2 microM, for dexamethasone it was 1.2 x 10(-7) M, and for daunomycin it was 1.2 microM, which are considered to be within the therapeutic ranges . For 5-fluorouracil, the corresponding concentration was 5 x 10(-5) M which probably is below the therapeutic level, when comparing with single-dose injections.

Prenat Diagn, 1997 Feb, 17(2), 119 - 23
In utero infection with Treponema pallidum in early pregnancy; Nathan L et al.; Amniocentesis was performed under sonographic guidance in gravidas (< 20 weeks' gestation) with untreated syphilis . Five to ten millilitres of amniotic fluid from each patient was used for rabbit infectivity testing (RIT) and polymerase chain reaction (PCR) to detect amniotic fluid infection with Treponema pallidum . Gravidas were treated with benzathine penicillin G . Newborns were examined for clinical and laboratory signs of congenital syphilis including immunoglobulin M (IgM) antibody to T . pallidum by Western blotting (immunoblotting) . Eleven patients were enrolled at a mean gestational age of 16.8 weeks . T . pallidum was recovered from amniotic fluid by RIT in four cases (36 per cent), and PCR was positive in three of the amniotic fluid specimens (27 per cent) . There were no false-positive PCR results . None of the newborns had clinical evidence of congenital syphilis and their sera lacked IgM reactivity to T . pallidum antigens by immunoblotting . These findings confirm in utero infection with T . pallidum in continuing early pregnancy and indicate that in utero treponemal infection can be eradicated by maternal treatment.

Clin Exp Allergy, 1997 Feb, 27(2), 175 - 81
The lymphocyte transformation test for the diagnosis of drug allergy: sensitivity and specificity; Nyfeler B et al.; BACKGROUND: The diagnosis of a drug allergy is mainly based upon a very detailed history and the clinical findings . In addition, several in vitro or in vivo tests can be performed to demonstrate a sensitization to a certain drug . One of the in vitro tests is the lymphocyte transformation test (LTT), which can reveal a sensitization of T-cells by an enhanced proliferative response of peripheral blood mononuclear cells to a certain drug . OBJECTIVE: To evaluate the sensitivity and specificity of the LTT, 923 case histories of patients with suspected drug allergy in whom a LTT was performed were retrospectively analysed . METHODS: Based on the history and provocation tests, the probability (P) of a drug allergy was estimated to be > 0.9, 0.5-0.9, 0.1-0.5 or < 0.1, and was put in relation to a positive or negative LTT . RESULTS: Seventy-eight of 100 patients with a very likely drug allergy (P > 0.9) had a positive LTT, which indicates a sensitivity of 78% . If allergies to betalactam-antibiotics were analysed separately, the sensitivity was 74.4% . Fifteen of 102 patients where a classical drug allergy could be excluded (P < 0.1), had nevertheless a positive LTT (specificity thus 85%) . The majority of these cases were classified as so-called pseudo-allergic reaction to NSAIDs . Patients with a clear history and clinical findings for a cotrimoxazole-related allergy, all had a positive LTT (6/6), and in patients who reacted to drugs containing proteins, sensitization could be demonstrated as well (i.e . hen's egg lysozyme, 7/7) . In 632 of the 923 cases, skin tests were also performed (scratch and/or epicutaneous), for which we found a lower sensitivity than for the LTT (64%), while the specificity was the same (85%) . CONCLUSION: Although our data are somewhat biased by the high number of penicillin allergies and cannot be generalized to drug allergies caused by other compounds, we conclude that the LTT is a useful diagnostic test in drug allergies, able to support the diagnosis of a drug allergy and to pinpoint the relevant drug.

Aliment Pharmacol Ther, 1997 Feb, 11(1), 95 - 100
Efficacy and tolerability of a one-week triple therapy consisting of pantoprazole, clarithromycin and amoxycillin for cure of Helicobacter pylori infection in patients with duodenal ulcer; Labenz J et al.; BACKGROUND: Previous studies have shown that one-week triple therapy consisting of omeprazole, clarithromycin and amoxycillin may cure Helicobacter pylori infection in the vast majority of patients . The present study was designed to test the hypothesis that a triple therapy with pantoprazole, clarithromycin and amoxycillin cures the infection in > or = 80% of duodenal ulcer patients infected with H . pylori . METHODS: In an open two-centre study, 60 duodenal ulcer patients were treated with pantoprazole 40 mg b.d., clarithromycin 500 mg b.d . and amoxycillin 1 g b.d . for 1 week . During the second week patients received pantoprazole 40 mg once in the morning . We assessed H . pylori infection before treatment and 4 weeks after cessation of the study medication by a rapid urease test, histology after Warthin-Starry stain and a 13C-urea breath test . RESULTS: Sixty patients (42 males, mean age 47.4 years) entered the trial . All patients were infected with H . pylori . One patient was withdrawn from the study because of allergy to penicillin and six patients were protocol violators . H . pylori infection was cured in 47 out of 53 patients who completed the trial according to the protocol (89%; 95% CI: 80-97%) and in 49 of 60 patients included in the trial (82%; 95% CI: 72-92%) . Four weeks after the last administration of study drugs, 55 out of 60 ulcers had healed (92%) . Twenty-nine patients reported 51 adverse events that were mostly mild to moderate . CONCLUSIONS: One-week triple therapy consisting of pantoprazole, clarithromycin and amoxycillin is a simple and effective approach to the cure of H . pylori infection in patients with duodenal ulcer . In those patients who took the drugs as prescribed the H . pylori cure rate was 89%, with the lower 95% confidence limit being 80%.

Ned Tijdschr Geneeskd, 1997 Jan 25, 141(4), 184 - 7
{Neonatal screening for sickle-cell disease}; Wierenga KJ; Through migration and birth sickle cell disease has become an important health problem in the Netherlands: it is estimated that each year between 25 and 40 children are born with a form of sickle cell disease . A programme designed towards parental education, prevention and early intervention for complications of sickle cell disease (notably penicillin prophylaxis to prevent pneumococcal septicaemia and meningitis) may lead to reduction in morbidity . Early diagnosis is indicated since children with sickle cell disease will benefit most from such a programme in the first few years of life.

Schweiz Arch Tierheilkd, 1997, 139(7), 314 - 8
{Retropharyngeal abscess in cattle . A case report}; Stocker S et al.; This case report describes history, clinical, laboratory, radiographic, and endoscopic findings, therapy, and outcome of a 5-year-old cow, suffering from retropharyngeal abscessation . Clinical findings at admission included elevated body temperature, head and neck held in extended position, excessive salivation, swelling of the retropharyngeal area, and slight inspiratory noise . Radiographic and endoscopic examination confirmed the tentative diagnosis of retropharyngeal abscessation . Treatment consisted of parenteral application of procaine-penicillin for 10 days and local application of linseed rubefacients for 2 weeks . At that time, abscessation had developed . The abscess was subsequently surgically, approached by a modified Whitehouse approach . During this procedure, the abscess drained into the oropharynx, allowing interruption of surgery . Five months later, clinical, radiographic, and endoscopic follow-up examination revealed complete healing of the retropharyngeal abscess.

J Basic Microbiol, 1997, 37(3), 181 - 6
Phenoxyacetic acid induces glutathione-dependent detoxification and depletes the glutathione pool in Penicillium chrysogenum; Emri T et al.; Enzymes of the glutathione-dependent detoxification pathway (glutathione S-transferase and gamma-glutamyl-transpeptidase) were induced, and the glutathione pool was completely depleted by phenoxyacetic acid in Penicillium chrysogenum mycelia incubated for 15 h in a culture medium containing lactose as a carbon source and sodium glutamate as a nitrogen source . A significant increase in both the oxidised glutathione concentrations and the glutathione reductase activities were also observed . 1-Chloro-2,4-dinitrobenzene--a potent substrate and inducer of glutathione S-transferase-initiated very similar physiological changes but no beta-lactam production could be detected in this case . When (NH4)2HPO4 was used as a nitrogen source the penicillin biosynthesis was repressed and the induction of gamma-glutamyltranspeptidase by phenoxyacetic acid was hindered considerably.

Appl Biochem Biotechnol, 1997 Jan, 62(1), 1 - 13
Stabilization of Escherichia coli penicillin G acylase by polyethylene glycols against thermal inactivation; Kazan D et al.; The effects of five polyethylene glycol (PEG) compounds of different molecular weight on the thermal stability of penicillin G acylase (PGA) obtained from a mutant of Escherichia coli ATCC 11105 have been investigated . The molecular weights of PEG compounds were 400, 4000, 6000, 10,000, and 15,000 . The thermal inactivation mechanisms of both native and PEG-containing PGA were considered to obey first order inactivation kinetics during prolonged heart treatments . Optimal concentrations of PEGs at molecular weights of 400, 4000, 6000, 10,000, and 15,000 were found to be 250, 150, 150, 100, and 50 mM, respectively . The greatest enhancement of thermostability was observed with PEG 4000 and PEG 6000, as a nearly 20-fold increase above 50 degrees C . PGA showed almost the same temperature activity profile and optimal temperature values both in the presence and absence of PEG . The addition of PEGs did not cause any change in the optimal temperature value of PGA, but the parameters Vm, K(m), the activation energy, and the Kcat values of enzyme were markedly decreased because of the mixed inhibition by PEG compounds . The type of inhibition was found to be hyperbolic uncompetitive.

Int J Parasitol, 1997 Jan, 27(1), 125 - 8
In vitro culture of Oestrus ovis (Linné 1761) first instar larvae: its application to antiparasitic drug screening; Duranton C et al.; A culture medium in which 1st instar larvae of Oestrus ovis can survive for up to 2 months has been developed with Dulbecco's Modified Eagle's Medium (DMEM) pH 7.7, penicillin 100 U/ml, streptomycin 100 micrograms ml-1, gentamicin 10 micrograms ml-1 and foetal calf serum (50%) added . Larvae were incubated in flat plastic tissue culture bottles (3 ml of medium) in a 5% CO2 atmosphere at 37 degrees C in darkness . Subsequently an antiparasitic in vitro screening test was developed with moxidectin and closantel . These drugs were not as effective in vitro as in vivo . This might be due to the fact that they cause damage to parasites and host immune responses, then contribute to their death.

S Afr Med J, 1997 Jan, 87(1), 62 - 5
Single-dose benzathine penicillin in infants at risk of congenital syphilis--results of a randomised study; Radcliffe M et al.; OBJECTIVE: To determine the efficacy of single-dose benzathine penicillin G in infants at high risk of congenital syphilis . DESIGN: Randomised study comparing benzathine penicillin with no therapy . SETTING: Peninsula Maternal and Neonatal Service, Cape Town . SUBJECTS: Asymptomatic infants born to mothers with untreated syphilis whose VDRL titre was 32 or more . OUTCOME MEASURES: The number of cases of congenital syphilis was determined by results of IgM Western blots and follow-up VDRL titres . RESULTS AND CONCLUSIONS: Of 8 patients followed up in the non-treatment group, 4 had congenital syphilis while 0/11 had the disease (P = 0.035) in the group receiving benzathine penicillin . Although the exact failure rate is unknown, benzathine penicillin is effective in preventing symptomatic congenital syphilis when administered to high-risk newborns.

Allergy, 1997 Jan, 52(1), 89 - 93
Immediate hypersensitivity to penicillins . Studies on Italian subjects; Romano A et al.; The IgE response, the involvement of the different penicillins available for therapeutic use, and the specificity of the IgE antibodies found in a group of penicillin-allergic subjects from Italy were studied . Thirty subjects with a history of allergic reactions to penicillins were studied . In vivo and in vitro specific IgE antibodies were determined to different penicillin determinants . Fifteen subjects developed anaphylactic responses and the remainder urticaria and angioedema . The drug most frequently involved in the patients' allergic reactions was ampicillin (AMP) . The benzylpenicilloyl (BPO) skin test was positive in 16 (53.3%) patients, whereas 23 (76.6%) patients were positive to minor determinant mixture (MDM), benzylpenicillin (PG), AMP, or amoxicillin (AX) . When classified according to initial reaction type, most anaphylactic patients (93.3%) were associated with minor determinant reactivity, whereas most urticaria patients (80%) reacted to BPO . RAST results for the anaphylactic and urticaria subgroups were similar . RAST inhibition showed that most sera contained highly cross-reactive IgE antibodies . There was evidence of a specific response to AX and PG (one patient each) . These data show that in a population of penicillin-allergic patients from Italy, AMP was the main drug inducing the allergic reaction . In skin tests and RAST, patients exhibited heterogeneous IgE responses with little indication of specific reactivity to AMP.

J Dermatol, 1997 Jan, 24(1), 50 - 3
Asymptomatic primary Sjögren's syndrome in a patient with penicillin drug eruption; Takahashi H; A 20-year-old woman visited our clinic because of acral numbness and skin eruptions after administration of oral penicillin . Serological tests revealed an increase of immunoglobulins (G & M), positive rheumatoid factor, anti-nuclear factor, anti-SSA and -SSB antibodies . Ophthalmologic and otolaryngological studies were consistent with those of Sjogren's syndrome . However, a skin biopsy specimen failed to show any specific changes for Sjogren's syndrome and the diagnosis of penicillin drug eruption was considered to be more preferable . We briefly discussed the coexistence of a drug allergy and asymptomatic connective tissue disease.

Biochem J, 1997 Jan 1, 321 ( Pt 1), 133 - 8
Metabolic control analysis of biochemical pathways based on a thermokinetic description of reaction rates; Nielsen J; Metabolic control analysis is a powerful technique for the evaluation of flux control within biochemical pathways . Its foundation is the elasticity coefficients and the flux control coefficients (FCCs) . On the basis of a thermokinetic description of reaction rates it is here shown that the elasticity coefficients can be calculated directly from the pool levels of metabolites at steady state . The only requirement is that one thermodynamic parameter be known, namely the reaction affinity at the intercept of the tangent in the inflection point of the curve of reaction rate against reaction affinity . This parameter can often be determined from experiments in vitro . The methodology is applicable only to the analysis of simple two-step pathways, but in many cases larger pathways can be lumped into two overall conversions . In cases where this cannot be done it is necessary to apply an extension of the thermokinetic description of reaction rates to include the influence of effectors . Here the reaction rate is written as a linear function of the logarithm of the metabolite concentrations . With this type of rate function it is shown that the approach of Delgado and Liao {Biochem . J . (1992) 282, 919-927} can be much more widely applied, although it was originally based on linearized kinetics . The methodology of determining elasticity coefficients directly from pool levels is illustrated with an analysis of the first two steps of the biosynthetic pathway of penicillin . The results compare well with previous findings based on a kinetic analysis.

Int J Syst Bacteriol, 1997 Jan, 47(1), 78 - 80
Spiroplasma diabroticae sp . nov., from the southern corn rootworm beetle, Diabrotica undecimpunctata (Coleoptera:Chrysomelidae); Carle P et al.; Spiroplasma strain DU-1T (T = type strain), which was isolated from hemolymph of the corn rootworm Diabrotica undecimpunctata (Coleoptera:Chrysomelidae), was serologically distinct from other spiroplasma species, groups, and subgroups . Cells of strain DU-1T were shown by light microscopy to be helical motile filaments . Electron microscopy revealed cells bounded by a single cytoplasmic membrane, with no evidence of a cell wall . The organism was not sensitive to 500 U of penicillin per ml . Strain DU-1T grew well in SM-1, M1D, and SP-4 liquid media, in broth supplemented with 1% bovine serum fraction or conventional horse serum, and under both aerobic and anaerobic conditions . This organism did not appear to have a sterol requirement for growth, as has been reported for several other Spiroplasma species or strains . Optimal growth occurred at 32 degrees C, with a doubling time of 0.9 h; strain DU-1T multiplied at 10 to 41 degrees C but failed to grow at 5 or 43 degrees C . It produced acid from glucose but hydrolyzed neither arginine nor urea . The results of reciprocal serologic tests in which antigens or antisera to established Spiroplasma species, groups, subgroups, and putative groups were used indicated that strain DU-1T was serologically distinct . This organism has a DNA guanine-plus-cytosine content of 25 +/- 1 mol% and a genome size of 1,350 kbp . Strain DU-1T is a member of a cluster of fast-growing insect-associated spiroplasmas, as determined by sequence analysis of 16S rRNA . On the basis of the results of this study and previously published data, strain DU-1 (= ATCC 43210) is designated the type strain of a new species, Spiroplasma diabroticae.

J Neurol Sci, 1996 Dec, 144(1-2), 214 - 7
Dementia paralytica in a fifteen-year-old boy; Goeman J et al.; A 15-year-old boy, whose history revealed an unremarkable pregnancy, birth and neonatal period and who had shown a normal motor and mental development, presented at the hospital with deterioration of cognitive functions since the age of 7 . He was bedridden with manifest ataxia involving all limbs, anisocoria and a sluggish to absent pupil reaction to light . Syphilis serology was positive with a Venereal Disease Research Laboratory (VDRL) titer of 1:256 and a Treponema pallidum Haemagglutination Assay (TPHA) titer of 1:163840 . Cerebrospinal fluid (CSF) protein concentration was 55 mg/dl and CSF-leucocyte count was 14/mm3 (85% mononuclear cells) . CSF-VDRL-titer was 1:16 . A diagnosis of congenitally acquired dementia paralytica was made, since the boy's parents' clinical exam and serology results were suggestive for latent syphilis . Although cognition was still very much deteriorated five months following penicillin treatment, clinical examination revealed partial recuperation . Screening for syphilis should be part of routine testing in every subject presenting with cognitive deterioration, regardless of age.

J Neuroimmunol, 1996 Dec, 71(1-2), 37 - 43
Neuroimmune control of interleukin-6 secretion in the murine spleen . Differential beta-adrenergic effects of electrically released endogenous norepinephrine under various endotoxin conditions; Straub RH et al.; In a previous study we demonstrated a superfusion technique which allows for investigation of nerve-immune cell interaction in murine spleen . We demonstrated that under septic-like conditions in the presence of bacteria and lipopolysaccharide (LPS), electrically induced inhibition of interleukin 6 (IL-6) secretion was attenuated by the beta-adrenergic antagonist propranolol . This effect was now investigated more closely under various endotoxin conditions in order to dissect effects of bacteria and endotoxin: (A) bacteria-rich conditions (without penicillin/streptomycin {P/S} and without LPS), (B) LPS-enriched conditions (with P/S and with LPS), and (C) bacteria-free conditions (with P/S and without LPS) . Under bacteria-rich conditions, norepinephrine (Emax = 10(-6) M, p = 0.012) and isoproterenol (Emax = 10(-6) M, p = 0.048) concentration-dependently inhibited IL-6 secretion from murine spleen slices in contrast to bacteria-free conditions . In a bacteria-free environment the beta-adrenergic antagonist propranolol did not attenuate the electrically induced inhibition of splenic IL-6 secretion . The insertion of bacterial filters in front of the superfusion chambers to avoid direct contact between bacteria and cells increased the electrically-induced inhibition of IL-6 secretion (p = 0.0036) . Added LPS did not change the electrically-induced release of norepinephrine from presynaptic nerve terminals in murine spleen . The study demonstrates two different beta-adrenergic effects on IL-6 secretion of murine spleen slices under bacteria-rich or bacteria-free conditions.

Eur J Immunol, 1996 Dec, 26(12), 2890 - 4
Interleukin-10 and interleukin-4 have similar effects on hapten-specific primary antibody responses to penicillin in vivo; Kerdine S et al.; Interleukin (IL)-10 was initially recognized on the basis of its capacity to inhibit production of interferon (IFN)-gamma by T helper (Th)1 lymphocytes; we examined whether this cytokine can bias the primary antibody (Ab) response to the hapten penicillin . We previously reported that BALB/c and SJL mice develop different responses to benzylpenicillin coupled to tetanus toxoid (BPO-TT) . The response of SJL mice was characterized as Th2 on the basis of early and high IL-4 mRNA expression and production of BPO-specific Ab of the IgG1 isotype . In contrast, the response of BALB/c mice was characterized as Th1 on the basis of delayed and weaker IL-4 mRNA expression associated with high anti-BPO IgG2a production (Kerdine, S . et al., Mol . Immunol . 1996 . 33: 71) . In this report, we demonstrate that in naive animals, the level of expression of IL-10 mRNA in LN cells was high in SJL and barely detectable in BALB/c . In addition, injection of BPO-TT resulted in rapid and large increase of IL-10 mRNA expression in SJL . Neutralization of IL-10 in vivo promoted the production of BPO-specific IgG2a in SJL, and injection of IL-10-CHO cells inhibited BPO-specific IgG2a production in BALB/c . Neutralization on administration of IL-10 had effects very similar to neutralization or administration of IL-4 . However, co-neutralization of IL-10 and IL-4 in SJL did not evidence additive or synergistic effects of the two cytokines . Administration of IL-10 or IL-4 in BALB/c inhibited BPO-TT-induced expression of IL-12 p40 mRNA without modulating IFN-gamma mRNA . Together, these data demonstrate that endogenous production of IL-10 regulates the production of IgG2a Ab in response to BPO-TT and that IL-10, like IL-4, is critical for controlling primary responses to antibiotics which behave as haptenic compounds.

J Am Acad Child Adolesc Psychiatry, 1996 Dec, 35(12), 1684 - 91
A putative poststreptococcal case of OCD with chronic tic disorder, not otherwise specified; Tucker DM et al.; A 12-year-old girl presented with an atypical, recurrent, increasingly treatment-resistant case of obsessive-compulsive disorder and chronic tic disorder associated with profound separation anxiety, learning difficulty, and intermittent upper respiratory symptoms . In addition to detailed reviews of history and findings from many clinical caretakers from the prior 7 years, current pediatric, psychiatric, neuropsychological, neuroimaging, and clinical laboratory data were also available . Treatment options were considered from multiple perspectives: psychoanalytically oriented psychotherapy, conventional pharmacotherapy, family interventions, cognitive-behavioral therapy, and learning-supportive strategies . Psychological, neuropsychiatric, and neuroimmunological formulations of etiology were considered . Subsequent treatments included supportive psychotherapy, neuroleptic augmentation of selective serotonin reuptake inhibitors, prophylactic penicillin, and a course of six sessions of plasmapheresis over a 2-week period . The case raises questions for ongoing consideration that juxtapose dynamic, neuropsychiatric, and neuroimmunological perspectives.

J Bacteriol, 1996 Dec, 178(23), 6766 - 71
Role of precursor translocation in coordination of murein and phospholipid synthesis in Escherichia coli; Ehlert K et al.; Inhibition of phospholipid synthesis in Escherichia coli by either cerulenin treatment or glycerol starvation of a glycerol-auxotrophic mutant resulted in a concomitant block of murein synthesis . The intracellular pool of cytoplasmic and lipid-linked murein precursors was not affected by an inhibition of phospholipid synthesis, nor was the activity of the penicillin-binding proteins . In addition, a decrease in the activity of the two lipoprotein murein hydrolases, the lytic transglycosylases A and B, could not be demonstrated . The indirect inhibition of murein synthesis by cerulenin resulted in a 68% decrease of trimeric muropeptide structures, proposed to represent the attachment points of newly added murein . Importantly, inhibition of phospholipid synthesis also inhibited O-antigen synthesis with a sensitivity and kinetics similar to those of murein synthesis . It is concluded that the step common for murein and O-antigen synthesis, the translocation of the respective bactoprenolphosphate-linked precursor molecules, is affected by an inhibition of phospholipid synthesis . Consistent with this assumption, it was shown that murein synthesis no longer depends on ongoing phospholipid synthesis in ether-permeabilized cells . We propose that the assembly of a murein-synthesizing machinery, a multienzyme complex consisting of murein hydrolases and synthases, at specific sites of the membrane, where integral membrane proteins such as RodA and FtsW facilitate the translocation of the lipid-linked murein precursors to the periplasm, depends on ongoing phospholipid synthesis . This would explain the well-known phenomenon that both murein synthesis and antibiotic-induced autolysis depend on phospholipid synthesis and thereby indirectly on the stringent control.

Biochem J, 1996 Nov 15, 320 ( Pt 1), 197 - 200
Biochemical characterization of the 49 kDa penicillin-binding protein of Mycobacterium smegmatis; Mukherjee T et al.; The 49 kDa penicillin-binding protein (PBP) of Mycobacterium smegmatis catalyses the hydrolysis of the peptide or S-ester bond of carbonyl donors R1-CONH-CHR2-COX-CHR2-COO- (where X is NH or S) . In the presence of a suitable amino acceptor, the reaction partitions between the transpeptidation and hydrolysis pathways, with the amino acceptor, behaving as a simple alternative nucleophile at the level of the acyl-enzyme . By virtue of its N-terminal sequence similarity, the 49 kDa PBP represents one of the class of monofunctional low-molecular-mass PBPs . An immunologically related protein of M(r) 52,000 is present in M . tuberculosis . The 49 kDa PBP is sensitive towards amoxycillin, imipenem, flomoxef and cefoxitin.

J Biol Chem, 1996 Nov 15, 271(46), 28825 - 30
Three binding sites for the Aspergillus nidulans PacC zinc-finger transcription factor are necessary and sufficient for regulation by ambient pH of the isopenicillin N synthase gene promoter; Espeso EA et al.; The isopenicillin N synthase (ipnA) gene, encoding a key penicillin biosynthetic enzyme in Aspergillus nidulans, represents a prototype of an alkaline-expressed gene . ipnA is under ambient pH regulation, and its promoter (ipnAp) contains binding sites for the zinc-finger transcription factor PacC . We show here that three of these sites, denoted ipnA2, ipnA3, and ipnA4AB, are efficiently recognized by the protein in an isolated sequence context . Single, double, and triple inactivation of these sites in any possible combination reduced promoter activity under alkaline conditions but had no effect under acidic conditions (under which promoter activity was low), as measured by the expression of wild-type and mutant ipnAp::lacZ fusion genes integrated in single copy into a common chromosomal location . This establishes a physiological role for these PacC binding sites and demonstrates a direct role for PacC in ambient pH regulation of ipnA gene expression . In addition, this confirms our previous proposal that PacC is an activator for alkaline-expressed genes . Notably, our experiments show that ipnA2, the highest affinity site for PacC in the ipnAp, contributes relatively modestly to PacC-mediated activation . By contrast, the lower affinity sites ipnA3 and ipnA4AB contribute more substantially to regulation by ambient pH . Inactivation of these three binding sites reduced promoter activity under alkaline conditions to that observed under acidic conditions, showing that these three PacC sites at ipnAp are sufficient to account for its activation by alkaline ambient pH.

Ginekol Pol, 1996 Nov, 67(11), 574 - 6
{Chorea gravidarum--case report}; Rebes Z et al.; A case of a 19 years old pregnant girl with chorea gravidarum is described, the diagnosis assuming rheumatic background to be the direct cause of the disease . Administered were: relanium, penicillin, solu-medrol and encorton with a positive therapeutic outcome.

Eur J Clin Microbiol Infect Dis, 1996 Nov, 15(11), 849 - 53
Efficacy and safety of azithromycin versus phenoxymethylpenicillin in the treatment of acute maxillary sinusitis; Hayle R et al.; In the treatment of acute maxillary sinusitis, azithromycin offers an advantage over phenoxymethylpenicillin in that a complete course of treatment requires drug administration once daily for only three days . In this double-blind, parallel-group, multicenter study, 438 patients with radiographically verified maxillary sinusitis were randomly assigned to receive either 500 mg azithromycin once daily for three days (221 patients) or 1.3 g phenoxymethylpenicillin three times daily for ten days (217 patients) . Nasal secretion, maxillary tenderness and pain, nasal obstruction, general malaise, and hyposmia, were assessed at the start of the study and on days 4, 11, and 25 of treatment . After 11 days 58% of the patients in the azithromycin group were cured versus 51% in the penicillin group; after 25 days the cure rate was 79% versus 76%, respectively . When both cure and improvement were considered, the corresponding figures after 11 days were 97% (azithromycin) and 95% (penicillin); after 25 days they were 92% and 88%, respectively . Adverse events, predominantly gastrointestinal, occurred in 73 (33%) of the azithromycin-treated patients and in 87 (40.1%) of those treated with penicillin . No difference in efficacy was found between the two drugs in the treatment of acute maxillary sinusitis, and the adverse effects were comparable . The short duration of treatment with azithromycin offers a significant advantage over treatment with phenoxymethylpenicillin.

Nihon Kyobu Shikkan Gakkai Zasshi, 1996 Nov, 34(11), 1277 - 82
{Acute bronchiolitis due to Mycoplasma pneumoniae and successfully treated with steroids}; Mashimoto H et al.; A high fever, coughing, stridor, and dyspnea developed in a 52-year-old woman on October 19, 1995 . She went to a local clinic and was treated with oral penicillin and intravenous cefpirome . The symptoms worsened, and she was admitted to our hospital on October 26 . Coarse crackles and wheezing were heard in both lung fields . The white blood cell count was 9000/mm3 and arterial blood gas analysis revealed a PaO2 of 49.8 Torr on room air . A chest roentgenogram obtained on admission showed a few small bibasilar nodular infiltrates, and a chest CT scan showed thickened bronchial walls along with small nodules having a centrilobular distribution . Of the cells in bronchoalveolar lavage fluid, 88% were neutrophils, but tests for bacteria and mycobacteria were negative . The cold-agglutinin titer was 1:512 . The Mycoplasma pneumoniae antibody titer (IIIA) was 1:640 and viral serology tests were negative . Acute bronchiolitis due to M . pneumoniae was diagnosed and treatment with intravenous minocycline was started . The symptoms (coughing, fever, and stridor) resolved and the small nodules on chest CT scan disappeared, but hypoxemia remained . At the same time, an obstructive ventilatory defect (FEV1% 62.8%) and abnormal ventilation/perfusion lung scans were noted . Development into bronchiolitis obliterans was suspected, so administration of methyl prednisolone (1 g/day for 3 days) and prednisolone was started . The response to steroids was good . Pulmonary function improved and the arterial PaO2 at the time of discharge was 86 Torr (room air) . Use of steroid therapy in the early phase of bronchiolitis obliterans seemed to be effective.

Clin Rheumatol, 1996 Nov, 15(6), 563 - 72
Intermittent compressive load stimulates osteogenesis and improves osteocyte viability in bones cultured "in vitro"; Lozupone E et al.; The effect of mechanical stresses on osteogenesis, the viability of osteocytes and their metabolic activity in organ culture of bones intermittently loaded "in vitro" are reported . Metatarsal bones, isolated from 12-day-old rats, were cultured in BGJb medium (with 10% foetal calf serum, 75 micrograms/ml of ascorbic acid, 100 U/ml of penicillin and 100 micrograms/ml of streptomycin), in humidified air enriched by 5% CO2 and 30% O2, and loaded in our original device for 1/2 an hour at 1 Hz . homotypic isolated and unloaded bones, cultured in the same medium, were taken as controls . The ALP (alkaline phophatase activity) increases in the media of loaded bones in comparison with the control bones . The percentage of viable osteocytes is significantly greater in loaded than in control bones . TEM observations demonstrate that in both loaded and control unloaded bones, osteocytes show well developed organelle machinery and several gap junctions with adjacent cellular processes . In the cells of loaded bones, however, a higher number of cytoplasmic organelles and gap junctions were found . In particular, RER increases twice, gap junctions three times . The induced osteogenesis and the TEM observations demonstrate the suitability of this experimental model and support the recent advanced hypothesis according to which the mechanical loading may exert a trophic function on osteocytes, stimulating both the proteic synthesis in the above-mentioned cells and the cell-to-cell communication . Furthermore, the loading is likely to exert a biological stimulus on osteoblasts via signalling molecules produced by osteocytes.

J Ky Med Assoc, 1996 Nov, 94(11), 500 - 2
Pancoast's syndrome secondary to thoracic actinomycosis; Tolentino A et al.; Pancoast's syndrome is almost exclusively caused by a malignant apical lung tumor invading the structures of the thoracic outlet . We report a case of thoracic actinomycosis as a cause of Pancoast's syndrome . A 65 y/o bm presented with a 6 month history of nonproductive cough, weight loss, a left upper lobe infiltrate, and a positive PPD of 20 mm . He failed to improve with triple antituberculous therapy for 3 months with worsening of left upper lobe disease . CT scan of the chest showed a mass lesion of the left upper lobe . Bronchoscopy with BAL and biopsy as well as percutaneous fine needle aspiration failed to reveal a diagnosis . Patient developed Pancoast's syndrome characterized by reflex sympathetic dystrophy with pain, swelling, and numbness of left shoulder, arm, and hand . A thoracoscopic left upper lung biopsy was performed and histologic examination revealed sulfur granules containing filamentous organisms characteristic of Actinomyces species . All sections were negative for malignancy . AFB stain and culture were negative . Patient was clinically cured following a 6-month course of penicillin with resolution of the left upper lobe mass . Although rare, thoracic actinomycosis must be considered in the differential diagnosis of Pancoast's syndrome . This case emphasizes the importance of obtaining a precise etiologic diagnosis before a treatment decision is made.

Epilepsy Res, 1996 Nov, 25(3), 185 - 90
Antiseizure activity of insulin: insulin inhibits pentylenetetrazole, penicillin and kainic acid-induced seizures in rats; Uysal H et al.; The present study was undertaken to evaluate the antiseizure activity spectrum of insulin against various behavioral seizure models in rats . Insulin was injected intraperitoneally (i.p.) at a test dose of 1 U/kg . Dextrose (3 g/kg) was administered simultaneously with insulin to counteract its hypoglycemic effect and induce a normoglycemic state . Insulin was found to significantly decrease the incidence, intensity and mortality rate and prolong the latency of generalized tonic-clonic convulsions induced by pentylenetetrazole (60 mg/kg i.p.) and significantly decrease the intensity and mortality rate and prolong the latency of generalized tonic-clonic convulsions induced by penicillin (2000 U/intracerebrocortical) . Insulin was not only found to prolong the latency of all the seizure components but was found to reduce the incidence of focal myoclonic twitches and generalized tonic-clonic convulsions induced by kainic acid (12 mg/kg i.p.) as well . Insulin was shown to be ineffective to suppress ouabain (5 micrograms/intracerebroventricular) induced seizures . These findings indicate that insulin possesses a broad spectrum of antiseizure activity in rats . Interaction with brain Na(+)-K(+)-ATPase has been discussed as a possible mechanism of action.

Chem Biol, 1996 Nov, 3(11), 937 - 47
Molecular evolution of bacterial beta-lactam resistance; Knox JR et al.; BACKGROUND: Two groups of penicillin-destroying enzymes, the class A and class C beta-lactamases, may have evolved from bacterial transpeptidases that transfer X-D-Ala-D-Ala peptides to the growing peptidoglycan during cell wall synthesis . Both the transpeptidases and the beta-lactamases are acylated by beta-lactam antibiotics such as penicillin, which mimic the peptide, but breakdown and removal of the antibiotic is much faster in the beta-lactamases, which lack the ability to process D-Ala-D-Ala peptides . Stereochemical factors driving this evolution in specificity are examined . RESULTS: We have compared the crystal structures of two classes of beta-lactamases and a beta-lactam-sensitive D-alanyl-D-alanine carboxy-peptidase/transpeptidase (DD-peptidase) . The class C beta-lactamase is more similar to the DD-peptidase than to another beta-lactamase of class A . CONCLUSIONS: The two classes of beta-lactamases appear to have developed from an ancestral protein along separate evolutionary paths . Structural differentiation of the beta-lactamases from the DD-peptidases appears to follow differences in substrate shapes . The structure of the class A beta-lactamase has been further optimized to exclude D-alanyl peptides and process penicillin substrates with near catalytic perfection.

Curr Genet, 1996 Nov, 30(5), 447 - 54
Factors affecting DNA-binding proteins and pcbC transcript levels in Penicillium chrysogenum; Vichitsoonthonkul T et al.; Proteins extracted from Penicillium chrysogenum grown in either complex or defined medium were used in electromobility shift assays . With a probe DNA covering the region -10 to -132 relative to the pcbC translation start codon, four protein/DNA complexes (designated A-D) were reproducibly observed . Two of the four DNA/protein complexes routinely detected in extracts from liquid cultures (A and B) were also detectable with protein extracts from P . chrysogenum spores . Generally, with proteins from liquid cultures, there was a correlation between increased levels of the complexes and increased levels of the pcbC transcript . In addition, the detectable levels of the complexes and the pcbC transcript showed some relationship to the extracellular pH of the medium . In defined medium, with glucose as the carbon source, the pcbC transcript was not detectable in extracts from the wild-type strain at any time, whereas with the high penicillin-producing strain P-2, a pcbC transcript was detected . In complex medium, the pcbC transcript was detectable during the exponential phase of cultures of the wild-type or P-2, even when glucose levels were as high as 2.5% (w/v).

Neuroscience, 1996 Nov, 75(1), 83 - 97
Anatomical properties of fast spiking cells that initiate synchronized population discharges in immature hippocampus; Cesare CM et al.; Minislices of the CA3 hippocampal subfield were prepared from 10- to 15-day-old rats and exposed to penicillin, a GABAA receptor antagonist . Synchronized population discharges occurred spontaneously but could also be entrained by action potentials in single, fast spiking cells . This was unexpected, since fast spiking cells in the hippocampus are normally thought to be inhibitory interneurons . Experiments were thus undertaken to determine the anatomical identity of these cells . Biocytin injections showed that these cells had the anatomical feature of inhibitory interneurons . Two classes of cells were identified: basket cells (including cells with pyramidal or multipolar dendritic arbors) and bistratified cells . Basket cells had characteristic dense axonal arbors in the stratum pyramidale . They also possessed wide ranging axons in strata radiatum and oriens . The axons of bistratified cells avoided the cell body layer and produced a web-like plexus of axons in strata radiatum and oriens . In the majority of minislices, dye coupling was also observed . Interneurons were preferentially dye-coupled to other interneurons . We speculate that, in early life, hippocampal interneurons may have dualistic synaptic properties . Normally, they inhibit nearby pyramidal cells; however, when GABAA receptors are suppressed a secondary excitatory property of these cells is uncovered.

J Am Vet Med Assoc, 1996 Nov 1, 209(9), 1602 - 3
Atypical villonodular synovitis in a horse; Vickers KL et al.; A 4-year-old sexually intact male Standardbred trotter was evaluated for left forelimb lameness . A presumptive diagnosis of severe cartilage damage was made because the horse had a history of infectious arthritis involving the left metacarpophalangeal joint . Arthroscopic evaluation revealed what was presumed to be a large villonodular lesion . The mass was surgically removed, and the horse was treated with procaine penicillin G, trimethoprim-sulfamethoxazole, phenylbutazone, and polysulfated glycosaminoglycans and eventually returned to racing . Histologic examination of the mass revealed a bed of granulation tissue covered with keratinized epithelium . We hypothesize that the lesion developed secondarily to implantation of epithelial cells into a reactive villonodular lesion.

J Bacteriol, 1996 Nov, 178(21), 6266 - 74
Molecular analysis of a beta-lactam resistance gene encoded within the cephamycin gene cluster of Streptomyces clavuligerus; Paradkar AS et al.; A Streptomyces clavuligerus gene (designated pcbR) which is located immediately downstream from the gene encoding isopenicillin N synthase in the cephamycin gene cluster was characterized . Nucleotide sequence analysis and database searching of PcbR identified a significant similarity between PcbR and proteins belonging to the family of high-molecular-weight group B penicillin-binding proteins (PBPs) . Eight of nine boxes (motifs) conserved within this family of proteins are present in the PcbR protein sequence in the same order and with approximately the same spacing between them . When a mutant disrupted in pcbR was constructed by gene replacement, the resulting pcbR mutant exhibited a significant decrease in its resistance to benzylpenicillin and cephalosporins, indicating that pcbR is involved in beta-lactam resistance in this organism . Western blot (immunoblot) analysis of S . clavuligerus cell membranes using PcbR-specific antibodies suggested that PcbR is a membrane protein . PcbR was also present in cell membranes when expressed in Escherichia coli and was able to bind radioactive penicillin in a PBP assay, suggesting that PcbR is a PBP . When genomic DNAs from several actinomycetes were probed with pcbR, hybridization was observed to some but not all beta-lactam-producing actinomycetes.

J Bacteriol, 1996 Nov, 178(21), 6110 - 5
Direct quantitation of the number of individual penicillin-binding proteins per cell in Escherichia coli; Dougherty TJ et al.; The penicillin-binding proteins (PBPs) are a set of enzymes that participate in the terminal stages of bacterial peptidoglycan assembly . As their name implies, these proteins also covalently bind and are inhibited by beta-lactam antibiotics . Although many studies have examined the relative binding affinities of a number of beta-lactam antibiotics, a surprisingly small number of studies have addressed the absolute numbers of each of the PBPs present in the bacterial cell . In the present study, the PBP values initially reported in Escherichia coli almost 20 years ago by B . G . Spratt (Eur . J . Biochem . 72:341-352, 1977) were refined . The individual PBPs from a known number of bacteria radiolabeled with {3H}benzylpenicillin were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis . The radioactive bands were located, excised, and quantitatively extracted from the gel slices . The radioactivity was measured by scintillation counting, and the absolute disintegrations per minute were calculated . From the specific activity of the labeled penicillin, the absolute disintegrations per minute, and the CFU per milliliter, a determination of the number of each of the PBPs per cell was made . The measurements were performed on multiple samples to place statistical limits on the numbers obtained . The values for the individual PBPs found in E . coli deviated in several ways from the previously reported observations . Of particular significance is the higher number of molecules of PBP 2 and 3 observed, since these PBPs are known to participate in cell morphogenesis . The PBP content in both rich Luria broth medium and M9 minimal medium was determined, with the slower-growing cells in minimal medium possessing fewer of the individual PBPs per cell.

J Membr Biol, 1996 Nov, 154(1), 11 - 21
Effects of mutating leucine to threonine in the M2 segment of alpha1 and beta1 subunits of GABAA alpha1beta1 receptors; Tierney ML et al.; The conserved leucine residues at the 9' positions in the M2 segments of alpha1 (L264) and beta1 (L259) subunits of the human GABAA receptor were replaced with threonine . Normal or mutant alpha1 subunits were co-expressed with normal or mutant beta1 subunits in Sf9 cells using the baculovirus/Sf9 expression system . Cells in which one or both subunits were mutated had a higher "resting" chloride conductance than cells expressing wild-type alpha1beta1 receptors . This chloride conductance was blocked by 10 mM penicillin, a recognized blocker of GABAA channels, but not by bicuculline (100 microm) or picrotoxin (100 microm) which normally inhibit the chloride current activated by GABA: nor was it potentiated by pentobarbitone (100 microM) . In cells expressing wild-type beta1 with mutated alpha1 subunits, an additional chloride current could be elicited by GABA but the rise time and decay were slower than for wild-type alpha1beta1 receptors . In cells expressing mutated beta1 subunits with wild-type or mutated alpha1 subunits (alphabeta(L9'T) and alpha(L9'T)beta(L9'T)), no response to GABA could be elicited: this was not due to an absence of GABAA receptors in the plasmalemma because the cells bound {3H}-muscimol . It was concluded that in GABAA channels containing the L9'T mutation in the beta1 subunit, GABA-binding does not cause opening of channels, and that the L9'T mutation in either or both subunits gives an open-channel state of the GABAA receptor in the absence of ligand.

Rev Prat, 1996 Oct 15, 46(16), 1948 - 51
{Early syphilis}; Morel P; Given the transmission of Treponema pallidum during human sexual contact, syphilis now occurs in France only in sexually high-risk, disadvantaged populations . The English-language terminology of "early syphilis" has progressively replaced that of "primary" and "secondary" in French usage . Induration of the chancre and the papular nature of secondary skin rashes remain the best criteria for clinical diagnosis . Serological tests associate test specific for treponematoses (Treponema pallidum haemagglutination assay, TPHA) and a nonspecific screening test (Venereal diseases research laboratory, VDRL) to confirm clinically suspected disease . Routine use of long-acting penicillin (benzathine penicillin) is consistently effective . The continuing risk of active syphilis in a pregnant woman and the possibility of severe syphilis in HIV patients require vigilance.

Med J Aust, 1996 Oct 7, 165(7), 382 - 5
Congenital syphilis: still a reality in 1996; Humphrey MD et al.; Despite the widespread use of penicillin for more than 50 years, syphilis continues to be a problematic health issue in many parts of the world . In Australia, congenital syphilis is again a significant cause of stillbirth, preterm labour and neonatal disease in some areas (including central and northern Australia) . Control mechanisms based on screening, reliable treatment protocols, contact-tracing and adequate follow-up appear to be less effective than they were in the past . It is difficult to discuss such a socially stigmatizing disease when it is clear that some community groups are at high risk, and may be offended by and feel disempowered in the face of well-meaning medical debate . If congenital syphilis is to be eradicated, new approaches are required . These include public-awareness campaigns to stress the need for antenatal care in affected communities; involving the community in efforts to prevent syphilis; providing culturally appropriate services; improving notification and surveillance systems; improving the management of pregnant women who present to maternity units without prior booking; and improving the management of syphilis in pregnancy . There is a need to raise awareness that antenatal care is important not only for the mother's health but also for the wellbeing of the baby.

Ethiop Med J, 1996 Oct, 34(4), 207 - 16
Rheumatic heart disease in Gondar College of Medial Sciences Teaching Hospital: socio-demographic and clinical profile; Melka A; One hundred fourteen patients with rheumatic heart disease were seen between January 1994 and January 1995 at Gondar College of Medical Sciences Teaching Hospital . These patients were prospectively described using a prepared study protocol consisting of socio-demographic variables, clinical findings and laboratory tests . The mean and median age of the patients were 23 +/- 8 years and 22 years, respectively, (range = 5-50 years) . About 66% of the patients were females with female to male ratio of 1.9:1 . Eighty five cases (74.6%) were on follow up with mean and median duration of 4.32 +/- 4.5 years and 3 years, respectively (range = 1-20 years) . The rest (25.4%) of the patients were new . History findings suggestive of rheumatic fever were obtained in 26% of the patients . Six patients (5.3%) had siblings with similar illness . Frequently encountered valve lesions were combined mitral regurgitation and stenosis seen in 29 (25.4%), followed by pure mitral stenosis in 25 (21.9%) and mitral regurgitation in 21 (18.4%) . The commonest arrhythmia was atrial fibrillation, observed in 22.8% of the cases . Recurrence of rheumatic fever occurred in 11 patients (9.6%) over the study period . Of these, five were regularly taking a four weekly Banzanthine penicillin injections . The functional classes of patients according to the New York Heart Association's classification were 17%, 25%, 26% and 32% for classes I, II, III and IV, respectively . There were 85 episodes of decompensations . The commonest precipitating factor was drug discontinuation followed by infection and arrhythmia . Most episodes have multiple causes for deterioration . Critical evaluation and education of patients during follow up is recommended.

Indian Pediatr, 1996 Oct, 33(10), 813 - 6
Effectiveness of ampicillin and combination of penicillin and chloramphenicol in the treatment of pneumonias: randomized controlled trial; Deivanayagam N et al.; OBJECTIVE: To assess the effectiveness of ampicillin and a combination of benzyl penicillin and chloramphenicol in the treatment of pneumonias . DESIGN: Randomized controlled trial . SETTING: Tertiary care hospital . SUBJECTS: Patients 5 months to 4 years old with pneumonias of < 2 weeks duration . Exclusion criteria included acute bronchiolitis, allergy to penicillin, postmeasles pneumonia or prior administration of trial antibiotics in full dose for more than 2 days . INTERVENTION: Patients were randomized to receive either ampicillin (100 mg/kg/day) or combination of benzyl penicillin (100,000 units/kg/day) and chloramphenicol (100 mg/kg/day) . The outcome measure was cure rate . RESULTS: There were 52 and 49 patients in the ampicillin and the combination groups, respectively . There was no significant difference in the baseline characteristics between groups except, nasal flare and cyanosis which were less in benzyl penicillin plus chloramphenicol group . There was also no difference either in the primary outcome, cure rate or secondary outcomes (days for cure, duration of tachypnea, fever and grunt) in the two . CONCLUSION: Considering the potential toxicity of chloramphenicol and the number of injections and doses to be given for the combination, ampicillin as a single drug could be preferred for the treatment of pneumonias, in this part of the country.

Clin Exp Pharmacol Physiol, 1996 Oct-Nov, 23(10-11), 986 - 9
Renal transport of drugs: specificity and molecular mechanisms; Somogyi A; 1 . The kidney is principally an excretory organ for drugs and their metabolites and has developed high capacity transport systems to rapidly eliminate the large quantities of foreign compounds delivered to it . 2 . There are specific and selective transporters for organic cations and organic anions at the contraluminal and luminal membranes of epithelial cells lining the proximal tubule . 3 . For organic anions, the transporter (termed PAH-transporter) is located at the contraluminal cell membrane and uptake is a tertiary active transport process . Important physico-chemical properties for interaction with this transporter are hydrophobicity, ionic charge strength and electron-attracting side groups . 4 . For organic cations, there is evidence for one common transport system at the contraluminal membrane and substrate requirements are the degree of hydrophobicity, ionic charge strength and hydrogen bond formation . At the luminal membrane, an electroneutral H+/organic cation exchanger in which the degree of substrate hydrophobicity is critical for interaction and a choline transport system have been described . 5 . P-Glycoprotein present in renal brush border membranes transports organic cationic drugs but is dissimilar to the luminal electroneutral H+/organic cation exchanger . 6 . Clinically, several drugs have been implicated in causing interactions via these transport systems . For organic anions, probenecid blocks the tubular secretion of other organic anions and this has been used to prolong the duration of action of penicillin-like compounds . For organic cations, cimetidine and trimethoprim are potent inhibitors of the secretion of a number of organic cations, particularly procainamide, which can result in significant clinical toxicity . 7 . An understanding of the mechanisms of renal tubular secretion of drugs and their metabolites will allow for the prediction of drug interactions involving renal excretory mechanisms.

J Periodontol, 1996 Oct, 67(10), 981 - 5
Porous polysulfone coated with platelet-derived growth factor-BB stimulates proliferation of human periodontal ligament fibroblasts; Mailhot JM et al.; The purpose of this study was to investigate if the treatment of porous polysulfone (PPSF) with various concentrations of platelet-derived growth factor-BB (PDGF-BB) would stimulate the proliferation of the adherent human periodontal ligament fibroblasts (HPDLF) in culture . Sterilized PPSF cylinders were immersed in an Eagle's minimum essential medium supplemented with 0.5% fetal bovine serum and 1% penicillin/streptomycin containing either 0, 10, 20, or 50 ng/ml of PDGF-BB for 24 hours . After 24 hours, the PPSF cylinders were removed and allowed to dry then placed in culture plates for each time point . Pooled HPDLF (8 x 10(4)) and 3H-thymidine in medium were pipetted into each well to cover the treated and control PPSF cylinders and plates were then incubated . At 1, 4, and 10 days the PPSF cylinders were removed and macromolecular precipitation was performed . Incorporation of 3H-thymidine was measured and a 2-way ANOVA with repeated measures was performed . In addition, determination of binding and release was performed using I125-PDGF-BB treated PPSF at 0, 2, 12, and 24 hours, and at 4 and 10 days . Results showed that the effects on HPDLF were significant for dose (P = 0.0012; F = 5.74) and time (P = 0.0001; F = 40.83) . At 4 days, the percent increases above the control for the doses 10, 20, and 50 ng/ml were 192%, 310%, and 162% respectively . In conclusion, our findings suggest that treating PPSF with PDGF-BB results in a significant increase in the proliferation of HPDLF cells adherent to PPSF.

J Vet Pharmacol Ther, 1996 Oct, 19(5), 370 - 5
Bioequivalence study in calves of three commercial penicillin/dihydrostreptomycin fixed combination products for intramuscular injection; Groen K et al.; A bioequivalence study with three penicillin/dihydrostreptomycin fixed combination products for intramuscular administration was performed in dairy calves . In addition to plasma concentrations of penicillin and dihydrostreptomycin, creatine phosphokinase concentrations were determined during a period of 72 h after administration of the drug products . Considerable differences were observed in the pharmacokinetics of penicillin from the three products . Although the extent of absorption was similar for all products, one product showed a significantly slower release from the site of injection . Except for the AUC, the 90% confidence intervals for these parameters exceeded the acceptable range of 0.80-1.20 . Therefore, these products are not bioequivalent with respect to the rate of absorption of penicillin . Concerning the pharmacokinetics of dihydrostreptomycin in calves, it could not be concluded that the products were bioequivalent, since the 90% confidence intervals of the ratios for Cmax, tmax and MRT exceeded the range of 0.80-1.20 . From this study in calves, it was also found that the product with the slowest release of penicillin from the injection site caused the most severe tissue damage, based on plasma creatine phosphokinase concentrations . Comparing the results from this study in calves with those from a previous study in rabbits, it can be concluded that the rabbit is a good animal model that could substitute for large animals, at least calves, in bioequivalence studies for penicillin/dihydrostreptomycin fixed combination products.

J Vet Pharmacol Ther, 1996 Oct, 19(5), 364 - 9
Bioavailability in the rabbit of penicillin and dihydrostreptomycin from three commercial penicillin/aminoglycoside fixed combination products for intramuscular injection; Groen K et al.; The bioavailability of penicillin and dihydrostreptomycin from three penicillin/ aminoglycoside fixed combination products for intramuscular injection was investigated in a four-way, randomized, crossover experiment in rabbits . Attention is focused on bioequivalence based on plasma concentration vs . time profiles to study whether the rabbit is a good model to detect differences in in vivo delivery of penicillin and/or dihydrostreptomycin after intramuscular administration of different products . In all products, penicillin was present as a suspension . Although the extent of absorption of penicillin did not differ between the three products, large differences in the rates of absorption were observed . With respect to dihydrostreptomycin, no significant differences were observed between the products . The results from this study demonstrate that the rabbit is a good model to detect differences in bioavailability of suspended penicillin from penicillin /dihydrostreptomycin fixed combination products for intramuscular injection . A study with the same products is presently being carried out in calves to investigate whether bioequivalence studies in rabbits could replace studies in the target animals.

J Parasitol, 1996 Oct, 82(5), 757 - 62
Simplified methods for obtaining purified oocysts from mice and for growing Cryptosporidium parvum in vitro; Meloni BP et al.; Seven- to 8-day-old Arc/Swiss mice were infected with 100,000-120,000 Cryptosporidium parvum oocysts . At 8 days postinfection (PI) the jejunum, ileum, cecum, colon, and rectum were removed . Using a simple extraction procedure and purification by Ficoll gradient centrifugation, we rountinely obtained between 3-6 million and up to 15 million purified oocysts per mouse . For in vitro cultivation, purified oocysts were pretreated in a low pH (2.5-3) 0.5% trypsin solution for 20 min, resuspended in supplemented RPMI-1640 containing glucose 0.1 g (5.55 mM), sodium bicarbonate 0.3 g, bovine bile 0.02 g, folic acid 25 micrograms, 4-aminobenzoic acid 100 micrograms, calcium pantothenate 50 micrograms, ascorbic acid 875 micrograms, penicillin G 10,000 U and streptomycin 0.01 g per 100 ml, and 1% fetal bovine serum (pH 7.4 before filtration), and used to inoculate confluent monolayers of the human adenocarcinoma cell line HCT-8 . Incubation was in a candle jar at 37 C . We tested numerous supplements to RPMI-1640, different pHs, and atmospheric conditions and found the parameters described above produced the greatest parasite numbers in vitro . We obtained significantly superior growth of C . parvum grown in HCT-8 cells using the conditions described above than in culture conditions described previously.

Microbiology, 1996 Oct, 142 ( Pt 10), 2871 - 7
Dependence of peptidoglycan metabolism on phospholipid synthesis during growth of Escherichia coli; Rodionov DG et al.; The role of phospholipid synthesis in peptidoglycan metabolism during growth of Escherichia coli was determined . The inhibition of phospholipid synthesis, achieved by inhibiting fatty acid synthesis with cerulenin or by glycerol deprivation of gpsA mutant strains, resulted in the concomitant inhibition of peptidoglycan synthesis . These effects on peptidoglycan synthesis were relatively specific in that the treatments did not cause a general inhibition of macromolecular synthesis . Furthermore, the inhibition of phospholipid synthesis also resulted in the rapid development of penicillin tolerance . It was unlikely that penicillin tolerance in these cases were simply due to the inhibition of growth caused by cerulenin treatment or glycerol deprivation because treatments with more effective growth inhibitors, e.g . chloramphenicol or norfloxacin, did not confer penicillin tolerance . Penicillin tolerance was shown to be a direct consequence of the inhibition of phospholipid synthesis and not due to the possible accumulation of guanosine-3',5'-bispyrophosphate (ppGpp), the starvation stress signal molecule known to be responsible for the development of penicillin tolerance in amino-acid-deprived bacteria . Therefore, peptidoglycan metabolism is coupled to phospholipid synthesis during growth of E . coli, and this may represent an important means to ensure the coordination of cell envelope synthesis in growing bacteria.

Int J Syst Bacteriol, 1996 Oct, 46(4), 947 - 50
Spiroplasma corruscae sp . nov., from a firefly beetle (Coleoptera: Lampyridae) and tabanid flies (Diptera: Tabanidae); Hackett KJ et al.; Spiroplasma strain EC-1T (T = type strain), which was isolated from the gut of a lampyrid beetle (Ellychnia corrusca) in Maryland, was serologically distinct from other spiroplasma species and groups . Similar strains were obtained from other E . corrusca specimens, and, later, numerous isolates of similar or partially related strains were obtained from several species of tabanid files . Cells of strain EC-1T were helical, motile filaments that were bound by a single cytoplasmic membrane, and there was no evidence of a cell wall . The cells were filterable through 220-nm-pore-size membrane filters but not through 100-nm-pore-size membrane filters . The organism was absolutely resistant to penicillin (1,000 U/ml) and required sterol for growth . Strain EC-1T grew well in M1D and SP-4 liquid media and could be cultivated in the Edward formulation of conventional mycoplasma medium and in 1% serum fraction medium . Optimal growth occurred at 32 degrees C (doubling time, 1.5 h) . Strain EC-1T multiplied at 10 to 41 degrees C, but not at 5 or 43 degrees C . This organism produced acid from glucose, but did not hydrolyze arginine or utilize urea . The guanine-plus-cytosine content of the DNA was determined to be 26.3 mol% by the melting temperature method and 27.0 mol% by the buoyant density method . As a result of our studies, strain EC-1 (= ATCC 43212) is designated the type strain of a new species, Spiroplasma corruscae.

J Pediatr, 1996 Oct, 129(4), 499 - 505
Problems in the current case definitions of congenital syphilis; Risser WL et al.; During the course of a population-based epidemiologic study of congenital syphilis, we found discrepancies and problems of validity in the case definitions of congenital syphilis of the Centers for Disease Control and Prevention and other experts . We analyzed these problems and determined their impact on case classification in our study . The most important problem that we found was the case definitions' lack of a valid scientific basis for the classification of symptom-free infants born to mothers who have been treated for syphilis but have uncertain infection status (286 infants in our study) . The classification of these infants is based on diagnostic tests whose sensitivity and specificity are unknown . In our study, we found that results of some tests were rarely positive and that values for others were similar to those in uninfected infants . We believe that symptom-free infants of treated mothers of uncertain infection status should be classified as cases, pending the development of better diagnostic tests for congenital syphilis . The economic impact of treating these infants can be lessened by obtaining fewer diagnostic tests and by use of one injection of penicillin rather than a 10- to 14-day course, an approach suggested by a literature review . Use of infants' diagnostic tests to classify any other group of symptom-free infants does not seem appropriate, even though this is often recommended.

Am J Med Sci, 1996 Oct, 312(4), 166 - 74
Review: sickle cell disease: present and future treatment; Steinberg MH; Over the past few decades, the life expectancy of patients with sickle cell disease has improved . This has been because of better supportive care and greater awareness of the complications of this disorder . Recent successes of neonatal screening, childhood prophylactic penicillin, and, perhaps, hydroxyurea in adults may further extend the life of sickle cell disease patients . This review will do the following: 1) briefly highlight the major aspects of the conventional treatment of sickle cell disease, 2) address the present use of hydroxyurea in more depth, and 3) succinctly preview what the near-term future of treatment may bring.

J Infect Dis, 1996 Oct, 174(4), 884 - 8
DNA polymorphisms and variant penicillin-binding proteins as evidence that relatively penicillin-resistant pneumococci in western Canada are clonally related; Swiatlo E et al.; Previous studies have suggested that relatively penicillin-resistant (RPR) capsular group 9L strains in western Canada may be clonally related . To test this hypothesis, restriction fragment length polymorphisms (RFLPs) were examined using DNA probes for pspA and a newly recognized pneumococcal genetic element, IS1167 . Penicillin-binding proteins (PBPs) and PBP genes from representative strains were also studied . All RPR type 9L strains demonstrated an identical RFLP when probed with IS1167, and 12 of 14 RPR strains had the same RFLP when examined with pspA . Amplification of pspA by polymerase chain reaction and restriction endonuclease digestion showed that the 9L strains had common DNA fragments not identified in any of the penicillin-susceptible strains . The 9L strains apparently have a low-affinity PBP 2B distinct from those of other capsular types . These data derived from new genetic markers and PBP analysis strongly support a clonal origin of RPR type 9L pneumococci of western Canada.

FEBS Lett, 1996 Sep 23, 394(1), 31 - 3
Phenoxymethylpenicillin amidohydrolases from Penicillium chrysogenum; Whiteman PA et al.; A phenoxymethylpenicillin amidohydrolase which hydrolyses phenoxymethylpenicillin to 6-aminopenicillanic acid (6-APA) has been isolated from two species of Penicillium chrysogenum . The amidohydrolase had a molecular mass of approx . 42 kDa . Its activity with benzylpenicillin as substrate was only 1.5% of that with phenoxymethylpenicillin and it was inhibited by its products . No penicillin formation from 6-APA and phenoxyacetyl or phenylacetyl coenzyme A was observed . The enzyme is thus distinct from the phenylacetyl coenzyme A:6-APA acyltransferase, which also has amidohydrolase activity and is involved in the final stages of the biosynthesis of penicillins.

Orv Hetil, 1996 Sep 15, 137(37), 2041 - 3
{Thoracic actinomycosis}; Besznyak G et al.; The authors describe in their case study the history of a 51 year old man, at whom they verified without thoracotomy thoracal actinomycosis . They achieved recovery giving permanently high doses of Penicillin . In connection with this rare case the authors review pathogenesis, the symptomatology, the diagnosis and the therapy of actinomycosis . The authors have found only one case in the Hungarian literature, which was recognized without thoracotomy and was cured by antibiotic therapy within a short period of time.

J Mol Recognit, 1996 Sep-Dec, 9(5-6), 706 - 14
Effect of immobilization on the penicillin binding and reactivity properties of DD-peptidase from Streptomyces R61; Eng GY et al.; An affinity gel matrix containing an enzyme (DD-peptidase) with specific beta-lactam binding properties was characterized with respect to its binding and reactivity behavior with penicillin . The data show that immobilization of DDP by reaction with the enzymes susceptible amino groups resulted in changes in catalytic activity on a tripeptide substrate, penicillin binding efficiency and pH stability of drug binding . Properties unaffected by immobilization were the drug-enzyme complex stability, binding reaction mechanism, drug selectivity and method of complex desorption . The affinity of DDP for penicillin-G was investigated by surface plasmon resonance . These characteristics were compared with those of the soluble enzyme . Conditions for elution of the bound drug were determined and a method for immobilizing Streptomyces DDP by which its binding site structure is sustained was also evaluated.

Pediatr Med Chir, 1996 Sep-Oct, 18(5), 495 - 9
{Aminoglycosides, risk factors and neonatal kidney}; Khoory BJ et al.; Antibiotics are the leading cause of drug-induced kidney disease, and among them the aminoglycosides (AMG) are the main nephrotoxic agents, bringing about kidney damage via a direct dose-dependent mechanism . The combination of an aminoglycoside and a penicillin derivative is still the most commonly recommended and used first-line treatment modality in the empirical therapy of neonatal sepsis, despite the low therapeutic index of AMG . The immaturity of neonatal kidney function, particularly in preterm neonates, makes newborn infants particularly susceptible to AMG-induced kidney damage . Numerous factors intervene in bringing about AMG-induced kidney damage, such as factors related to the antibiotic itself (intrinsic toxicity, administration route, type of monitoring of blood concentrations), those related to the subject treated (neonatal age, constitutional sensitivity), and others related to associated pathology (neonatal anoxia, renal hypoperfusion, respiratory distress/mechanical ventilation, hyperbilirubinaemia/phototherapy, electrolyte disorders, and even the acute sepsis calling for antibiotic therapy), as well as pharmacological factors (concomitant therapies such as diuretics, indomethacin and other antibiotics, particularly glycopeptides and cephalosporins).

Actas Luso Esp Neurol Psiquiatr Cienc Afines, 1996 Sep-Oct, 24(5), 261 - 7
{Parenchymal neurosyphilis . Insidious onset (dementia) and acute onset (manic type) forms}; Galindo Menendez A; The increased rates in recent years of primary and secondary syphilis, with a renovated interest of central nervous system infection by the treponema pallidum, justify the presentation of two cases of classic General Paresis: Dementia and Mania . Both patients fulfilled sufficient criteria as to elaborate a process of differential diagnostic of physical illness in patients with mental disorders, which include a battery laboratory tests . The positive response to a protocol with penicillin improved both the clinical symptoms and the laboratory tests.

Nihon Kyobu Shikkan Gakkai Zasshi, 1996 Sep, 34(9), 989 - 92
{Endobronchial actinomycosis}; Hashimoto A et al.; A 63-year-old man was admitted to our hospital with obstructive pneumonia . The chest X-ray film and computed tomogram showed an infiltrative shadow in the right lower lung field . Examination with a fiberoptic bronchoscope showed a mass in the right basal bronchus . These findings suggested the diagnosis of lung cancer with obstructive pneumonia . Histopathological examination of a specimen obtained by transbronchial biopsy revealed sulfur granules with infiltration of neutrophils, which led to the diagnosis of endobronchial actinomycosis . After three months of treatment with penicillin, the mass disappeared . Comparison of bronchoscopic findings before and after penicillin treatment clearly showed the efficacy of therapy.

J Emerg Med, 1996 Sep-Oct, 14(5), 547 - 51
Ceftriaxone versus cefazolin with probenecid for severe skin and soft tissue infections; Brown G et al.; To evaluate the hypothesis that a single daily administration of cefazolin and probenecid and a single daily administration of ceftriaxone and probenecid would be equally effective, in combination with oral antibiotics, for the outpatient treatment of skin and soft tissue infections, a randomized, double-blind study was completed . Patients presenting to the Emergency Department with the primary diagnosis of cellulitis or soft tissue infection, excluding patients requiring immediate hospital admission, received either 2 g of ceftriaxone or 2 g of cefazolin, each with 1 g of probenecid, on a daily basis as outpatients from the Emergency Department . The patients were given a prescription for oral penicillin and cloxacillin for independent procurement . Outcome was assessed based on reduction in the size of the infected area, and the need for additional treatment (other antibiotics or hospital admission) . A total of 194 patients were randomized to receive ceftriaxone (96) or cefazolin (98) . There was no statistical difference in cause of infection, site of infection, duration of treatment, noncompliance or need for incision or drainage of the wound . The outcome, as determined by the ratio of the involved infected area on initial and last treatment day, and the frequency of failure were similar . The single daily administration of 2 g of either cefazolin, in combination with probenecid, or ceftriaxone are equivalent in efficacy in the outpatient treatment of skin and soft tissue infections . There is the potential for significant cost savings in utilizing outpatient cefazolin therapy over ceftriaxone for treatment of these infections.

Lymphology, 1996 Sep, 29(3), 126 - 31
Episodic dermatolymphangioadenitis (DLA) in patients with lymphedema of the lower extremities before and after administration of benzathine penicillin: a preliminary study; Olszewski WL; Dermatolymphangioadenitis (DLA) is a common and serious complication of obstructive peripheral lymphedema . The clinical characteristics of acute DLA are local tenderness and erythema of the skin, sometimes red streaks along the distribution of the superficial lymphatics and enlarged inguinal lymph nodes . Systemic symptoms include malaise, fever and chills . In its subacute or latent form, only skin involvement is observed . Each episode of DLA is commonly followed by worsening of leg swelling . Numerous clinical studies suggest that administration of antibiotic drugs interrupt the acute episodes and prevent their recurrence . We investigated the clinical course of lymphedema with respect to the prevalence of DLA in patients receiving injections of long-acting penicillin (benzathine penicillin) . Forty-five randomly selected patients with obstructive lymphedema of the lower limbs were included in an open clinical trial . The inclusion criteria was stage II-IV lymphedema of postsurgical, posttraumatic, and postdermatitis type with at least 3 previous episodes of DLA . Benzathine penicillin (PCN) was given after the last presenting episode of DLA in a dose of 1,200,000 u, intramuscularly at 3-week intervals, for at least one year . Each patient was reevaluated at 3-month intervals . They were instructed in early diagnosis of DLA and reported promptly to the responsible senior surgeon with prodrome symptoms of recurrent DLA . The duration of lymphedema before initiation of therapy was 7 months to 40 years and the frequency of DLA was 1-6 episodes per year . PCN administration lasted for at least one year but was extended in all patients because of the tendency for recurrence of DLA after cessation of PCN injections . In 26 of these patients, PCN administration extended to over 5 years and in 2 over 10 years . Recurrent episodes of DLA occurred in the PCN-treated group during one year follow-up in only 4 of the 45 patients (9%) . The frequency episodes in 3 patients with recurrent DLA was 1-2/year; in one patient, no positive effect of PCN therapy was observed . There were no apparent side effects of long-term PCN therapy . These data, although evaluated without a placebo group, suggest that long-term PCN administration decreases the frequency of DLA attacks and furthermore provide justification for carrying out a double-blind randomly placebo-controlled clinical trial of the efficacy of prophylactic antibiotic drug treatment in forestalling DLA episodes.

Pediatr Dermatol, 1996 Sep-Oct, 13(5), 382 - 5
Primary Anetoderma in children: report of two cases and literature review; Karrer S et al.; Two boys, age 7 and 9 years, with the diagnosis of primary anetoderma are presented . In one patient a growing number of indolent lesions developed for one year on the neck . The other boy complained of single lesions appearing over four months on the arms, feet, and chest wall . Individual lesions measured up to 1 cm in diameter and showed a palpable herniation phenomenon and wrinkled surface . The lesions did not have an inflammatory onset . Histologically, in both patients the diagnosis of anetoderma was verified by loss of elastic fibers and a lympho-histiocytic infiltration in the middermis . Administration of oral penicillin for three weeks did not result in marked improvement, and atrophic macules continued to appear in the younger boy . Although no autoimmunologic abnormalities or other associated diseases have arisen in our patients, long-term follow-up is mandatory to detect autoimmune disorders that are reported to occur in the course of the disease.

Nippon Rinsho, 1996 Sep, 54(9), 2534 - 8
{Drug-induced hemolytic anemia}; Miura A; Acquired drug-related hemolytic anemia is mainly induced by immune mechanism or microvascular lesion . Three mechanisms of drug-related immunologic injury to red blood cells are recognized . They are hapten or drug adsorption mechanism, ternary or drug-antibody-target cell complex mechanism and autoantibody mechanism . Prototype drugs are penicillin, quinidine and alpha-methyldopa, respectively . Symptoms are mild to moderate in cases of hapten and autoantibody mechanisms and ameliorate by withdrawal of the drugs . Hemolytic anemia due to ternary mechanism may have severe even fetal symptoms, including hemoglobinemia and hemoglobinuria . Some antineoplastic agents can cause hemolytic anemia that resembles the hemolytic uremic syndrome . The prototype drug is mitomycin.

Antimicrob Agents Chemother, 1996 Sep, 40(9), 1973 - 6
Antipneumococcal activities of cefpirome and cefotaxime, alone and in combination with vancomycin and teicoplanin, determined by checkerboard and time-kill methods; Bajaksouzian S et al.; The checkerboard titration method was used to test the synergy of cefpirome and cefotaxime with teicoplanin or vancomycin against 35 penicillin-susceptible, 34 penicillin-intermediate, and 31 penicillin-resistant pneumococci . The MICs at which 50 and 90% of isolates are inhibited (MIC50s and MIC90s, respectively) of both cefpirome and cefotaxime were 0.016 and 0.06 microgram/ml, respectively, for penicillin-susceptible strains and 0.125 and 0.5 microgram/ml, respectively, for penicillin-intermediate strains . The MIC50s and MIC90s of cefotaxime for penicillin-resistant strains were 1.0 and 2.0 micrograms/ml, respectively, and those of cefpirome were 0.5 and 1.0 microgram/ml, respectively . All pneumococci were inhibited by cefpirome at MICs of < or = 1.0 microgram/ml . The MIC50s and MIC90s of vancomycin and teicoplanin (0.25 and 0.25 microgram/ml and 0.03 and 0.03 microgram/ml, respectively) did not differ for the three groups . Checkerboard synergy studies showed that cefpirome and vancomycin showed synergy for 31 strains (fractional inhibitory concentration {FIC} indices, < or = 0.5) cefpirome and teicoplanin showed synergy for 18 strains, cefotaxime and vancomycin showed synergy for 51 strains, and cefotaxime and teicoplanin showed synergy for 27 strains . Cefpirome and vancomycin had FIC indices indicating indifference (2.0) for two strains, and cefotaxime and vancomycin had FIC indices indicating indifference for one strain . All other FIC indices indicating indifference or additivity were > 0.5 to 1.0 . No FIC indices indicating antagonism (> 4.0) were found . Synergy between beta-lactams and glycopeptides for three susceptible, three intermediate, and three resistant strains were tested by the time-kill assay, and all combinations were synergistic by this method . Synergy between cephalosporins and glycopeptides can be demonstrated and may be useful for the treatment of pneumococcal infections, especially meningitis.

J Allergy Clin Immunol, 1996 Sep, 98(3), 535 - 44
The prevalence of anti-latex IgE antibodies among registered nurses; Grzybowski M et al.; BACKGROUND: Recent studies have reported that the prevalence of latex allergy among volunteer populations of health care workers ranges from 2% to 25% . To date, no epidemiologic study has investigated the prevalence of latex allergy and its relationship to possible risk factors among nurses . METHODS: Registered nurses (n = 741) in a large metropolitan hospital participated in a latex allergy prevalence study . Latex exposure data were obtained through self-administered questionnaires . Blood samples were classified as positive or negative for anti-latex IgE antibodies . Associations between potential risk factors for latex allergy and anti-latex antibodies were assessed . RESULTS: The participation rate was 90.6% among eligible nurses . Sixty-five samples were positive for a prevalence of 8.9% (95% confidence interval, 6.7 to 10.8) . No differences in latex positivity among five nursing specialties were noted . Logistic regression indicated that after adjusting for age and sex, the following factors were significantly associated with latex seropositivity: nonwhite race (odds ratio {OR} = 4.2), reported histories of penicillin allergy (OR = 2.2), pruritic skin (OR = 2.2), conjunctivitis (OR = 3.0), localized urticaria (OR = 1.8), hay fever (OR = 2.1), avocado allergy (OR = 9.9), and ragweed allergy (OR = 3.4) . CONCLUSIONS: The prevalence of latex sensitization appeared to be substantial (8.9%) among the nurses studied, and the prevalence did not vary by nursing specialty . The factors associated with latex positivity in the logistic regression model correctly classified 81.3% of the nurses with a sensitivity and specificity of 66.7% and 82.7%, respectively.

Am J Gastroenterol, 1996 Sep, 91(9), 1778 - 82
4-day lansoprazole quadruple therapy: a highly effective cure for Helicobacter pylori infection; de Boer WA et al.; OBJECTIVES: We have advocated quadruple therapy as the optimal therapy for cure of Helicobacter pylori infection . In this study, we investigated the efficacy and tolerability of 4-day therapy with lansoprazole, bismuth, tetracycline, and metronidazole . METHODS: In a prospective open study, 51 consecutive patients, most of them with chronic peptic ulcer disease and biopsy proven H . pylori infection, received 4-day lansoprazole quadruple therapy after 3 days of lansoprazole pretreatment . Repeat endoscopy was performed 6 wk later, with antral and corpus biopsies for rapid urease test, histology, and culture . A patient was considered cured if three methodologies had negative results . RESULTS: By intention-to-treat, 48 of 51 patients (94%) (95% CI 84%-99%) were cured; per protocol, 48 of 49 (98%) (95% CI 89%-100%) were cured . In 14 patients, the bacterial isolates were tested for metronidazole susceptibility: 12/12 with a sensitive strain were cured, as were 2/2 with a resistant strain . The regimen was well tolerated . Most side effects were mild, and none caused treatment to be stopped prematurely . CONCLUSIONS: Four-day lansoprazole quadruple therapy achieves a very high cure rate in an unselected population of mainly ulcer patients . Furthermore, the regimen is short, can be used in patients allergic to penicillin, and is well tolerated, with no dropouts due to side effects . Presently, this regimen should be used only in patients with a metronidazole-sensitive pre-treatment bacterial isolate . When empiric treatment is used, 7-day quadruple therapy remains the therapy of choice, because it has well-documented efficacy against metronidazole-resistant strains . Further studies are needed to define the optimal treatment duration for quadruple therapy in patients with metronidazole-resistant strains.

Pharmacoeconomics, 1996 Sep, 10(3), 239 - 50
Cost saving of 5-day therapy with cefpodoxime proxetil versus standard 10-day beta-lactam therapy for recurrent pharyngotonsillitis in adults . A prospective general practice study; Pelc A et al.; A prospective economic evaluation was undertaken as part of a randomised clinical trial conducted in French general practice . Its aim was to compare the costs and therapeutic outcomes of a 5-day course of cefpodoxime proxetil 100 mg twice daily with 10-day courses of phenoxymethylpenicillin (penicillin V) 1 MIU 3 times daily and amoxicillin-clavulanic acid 500/125 mg 3 times daily for the treatment of recurrent pharyngotonsillitis in 575 adults . Over the 6-month study period, the total cost to society per patient treated with cefpodoxime proxetil was 123 French francs (FF; 1993 values) lower than that for patients treated with phenoxymethylpenicillin and FF227 lower than that for patients treated with amoxicillin-clavulanic acid . This cost saving was primarily attributable to a lower initial drug acquisition cost, and a reduction in the cost associated with lost productivity and general practitioner consultations . Furthermore, as a consequence of a lower relapse rate, the cost-saving ratio for cefpodoxime proxetil, expressed as FF per month free of recurrence, was FF50 less than for phenoxymethylpenicillin and FF60 less than for amoxicillin-clavulanic acid . Thus, a 5-day course of cefpodoxime proxetil is likely to be less costly for treatment of pharyngotonsillitis in the general practice setting than standard 10-day courses of phenoxymethylpenicillin and amoxicillin-clavulanic acid.

Br J Ophthalmol, 1996 Aug, 80(8), 740 - 4
Corneal organ culture: effects of serum and a stabilised form of L-glutamine; Ayoubi MG et al.; AIMS: Organ culture medium for corneas contains labile components, such as L-glutamine, whose loss could be a limiting factor to the length of storage . The medium is also supplemented with fetal bovine serum (FBS), which can vary significantly between different batches . The aim of this study was to establish the need for FBS during corneal organ culture, and to determine whether substitution of L-glutamine by the stable dipeptide L-analyl-L-glutamine was beneficial . METHODS: Porcine corneoscleral discs were suspended in 80 ml of organ culture medium (HEPES buffered Eagle's MEM with Earle's salts, 26 mmol/l NaHCO3, penicillin, streptomycin, and amphotericin B) and kept at 34 degrees C . The medium contained either 2 mmol/l L-glutamine or 2 mmol/l L-analyl-L-glutamine, and was either serum free or contained 2% FBS . At weekly intervals, five corneas from each group were stained with trypan blue and alizarin red S, and the surface area and shape of 100 endothelial cells were determined for each cornea . RESULTS: No differences were observed between corneas in organ culture medium with L-glutamine or L-analyl-L-glutamine . In serum free medium, endothelial cell density remained constant for the first week, but then declined rapidly over the next 2 weeks . With 2% FBS, there was no loss of endothelial cells for the first 2 weeks, but cell density had halved by the fourth week of organ culture . CONCLUSION: The presence of 2% FBS extended the period of endothelial stability, but no advantage was gained from the stabilised form of L-glutamine . The overall loss of endothelial cells was much greater than would be expected for human corneas.

Thromb Haemost, 1996 Aug, 76(2), 239 - 44
Probenecid inhibits platelet responses to aggregating agents in vitro and has a synergistic inhibitory effect with penicillin G; Packham MA et al.; Probenecid is an anion channel blocker and uricosuric agent, originally developed to slow the rate of excretion of penicillin . It is now also administered with many other drugs to reduce their required dosages . Recently, probenecid (2.5 mM) has been used to prevent leakage of fura-2 or fluo-3 when these indicators of cytosolic Ca2+ levels have been introduced into cells . However, we found that probenecid markedly inhibited the increases in cytosolic Ca2+ caused by ADP, thrombin, the thrombin receptor-activating peptide (SFLLRN, TRAP), ADP, sodium arachidonate, the thromboxane A2 (TXA2) mimetic U46619, and platelet-activating factor (PAF) . This finding precluded the use of probenecid with platelets in measurements of cytosolic Ca2+ with indicators such as fura-2 . We then investigated the effects of probenecid on aggregation and release of 14C-serotonin from prelabeled platelets . Responses to all the agonists were inhibited by 2.5 mM probenecid, but concentrations as low as 0.25-0.5 mM inhibited responses to agonists that act largely via TXA2 (collagen, sodium arachidonate and U46619) . Collagen-induced TXA2 formation was inhibited in a dose-dependent manner . Responses of aspirin-pretreated platelets to thrombin, SFLLRN, U46619 and PAF were also inhibited by probenecid, indicating that prevention of TXA2 formation does not account for all the inhibitory effects . The combination of probenecid with penicillin G produced additive or synergistic inhibition of platelet responses; responses dependent on TXA2 were synergistically inhibited by concentrations of the drugs that are reached in vivo . The synergistic inhibitory effect of probenecid on platelet functions could further impair hemostasis if it has already been partially compromised by the administration of other drugs.

Ophthalmic Surg Lasers, 1996 Aug, 27(8), 699 - 705
Rhegmatogenous retinal detachments in HIV-positive patients with ocular syphilis; Williams JK et al.; The purpose of this study is to report retinal manifestations of lues in human immunodeficiency virus (HIV)-positive patients and to suggest a method for treatment of rhegmatogenous retinal detachments in these patients . Two HIV-positive patients with bilateral retinitis were examined and treated at the authors' institution for a period of 14 months . Ocular syphilis was diagnosed clinically, confirmed by cerebrospinal fluid serologic testing, and treated with intravenous penicillin . Both patients experienced bilateral rhegmatogenous retinal detachments complicated by proliferative vitreoretinopathy after resolution of the active retinitis . All four eyes underwent surgical repair with trans pars plana vitrectomy, epiretinal membrane delamination, gas-fluid exchange, endolaser, scleral buckle, and silicone oil instillation . The recognition of ocular syphilis as a cause of retinal detachment in HIV-positive patients is important . Prompt intervention with the appropriate medical and surgical treatments may result in the preservation of vision in these patients.

Pharmacol Biochem Behav, 1996 Aug, 54(4), 759 - 70
Expression of epileptiform activity induced by a penicillin focus within the posterior thalamus in the awake rat; Horn E et al.; Investigations were performed to study the epileptiform activity, induced by a local injection of penicillin (PCN) into the posterior thalamus (pTh) of the awake rat, and to compare it with the epilepsy induced in the same animals 2 weeks later by an injection of PCN into the motor cortex (MC) . Using EEG recordings, 1) the distribution of focal cortical activity, and 2) the severity of the epileptiform activity (frequency of focal activity, occurrence and duration of generalized episodes) were analyzed . The focal activity of pTh rats was characterized by two types of potentials: (a) sharp potentials with a spike-like shape that developed during the first hour after PCN injection only in the visual cortex, but in the transition area between the motor and sensory cortex during the last period of epileptiform activity; and (2) large potentials with a wave- or spike-wave-like shape that had their center of focal expression in the transition zone between the motor and sensory cortex . MC rats exhibited only a spike-like potential with or without short-lasting afterdischarges in the homotopic areas of the MC of both hemispheres . During periods with large potentials only, the number of generalized episodes was significantly reduced with respect to those periods with sharp potentials . When the epileptiform activity changed from large to sharp potentials, the interictal frequency increased significantly . It is postulated (a) and a pTh focus activates the lateral and/or the reticular thalamic areas, which, due to their high intrinsic potential for synchronization, cause a self-sustained interictal activity of the large potential type; and (b) that the wave of the large potentials is involved in an anticonvulsive mechanism that reduces the extent of ictal as well as interictal activity.

Neth J Med, 1996 Aug, 49(2), 73 - 6
Colitis and lower abdominal mass by Actinomyces israelii in a patient with an IUD; Nugteren SK et al.; Abdominal actinomycosis is a rare disorder . The diagnosis is frequently missed preoperatively . We describe a patient who had had an intrauterine contraceptive device in situ for 5 years . She presented with a painful pelvicoabdominal mass, located between the uterus and rectum, and a colitis-like disease of the distal colon . Culture of the removed IUD demonstrated Actinomyces . She was intensively treated with intravenously penicillin for six weeks . Following this conservative treatment the abdominal tumor and the colitis-like symptoms totally disappeared . During two years follow-up she is free of symptoms and no signs of recurrence of the disease have been noticed . The case described here strongly underlines that Actinomyces infection should be born in mind in the differential diagnosis of a young female with an IUD, presenting with colitis, fever and an abdominal mass . Prolonged intravenously administered penicillin is warranted before surgery should be considered.

Epidemiol Infect, 1996 Aug, 117(1), 95 - 102
Pneumococcal meningitis in the North East Thames Region UK: epidemiology and molecular analysis of isolates; Urwin G et al.; One hundred and fourteen cases of pneumococcal meningitis were identified by prospective laboratory based surveillance during 1990-3 in the North East Thames Region . Higher rates of disease were seen in Asians (2.1/100000) than Caucasians (0.8/100000) (P = 0.002) . The incidence of meningitis was higher in children than adults, while mortality rates were highest in adults over the age of 60 (48%) . In 72 cases, both blood and CSF were culture positive . Serotyping of 65 isolates collected identified 22 serotypes (and one non-typable) causing disease, the most common being serotype 6 (13 cases) and serotype 14 (11 cases) . Overall, 90% of serotype antigens identified were represented in the 23 valent vaccine . Ribotyping of 62 isolates identified 35 different patterns, of which 26 were single types . Different ribotypes were found among isolates of the same serotypes, with the exception of serotype 14, where 9 of 11 isolates had the same ribotype pattern . Four percent of isolates had reduced susceptibility to penicillin, but no high level penicillin resistance was found.

Microbiology, 1996 Aug, 142 ( Pt 8), 1919 - 26
Modified peptidoglycan chemical composition in shape-altered Escherichia coli; Signoretto C et al.; Peptidoglycan synthesis and its fine chemical composition were studied in dividing cocci of Escherichia coli carrying the lov-1 mutation and in which the coccal shape was obtained either by mecillinam treatment or by transferring a pbpA mutation (penicillin-binding protein 2- phenotype), as compared to normal rods and non-dividing cocci . Synchronously dividing cocci showed peptidoglycan synthesis only in the cell cycle phase corresponding to cell septation . During the phase corresponding to lateral wall elongation, peptidoglycan synthesis was strongly reduced . This type of synthesis suggests that the dividing cocci consisted only of the two poles . Analysis of the muropeptide composition revealed a specific fourfold increase in the tetra-tetra-tetra trimer in dividing cocci as compared to non-dividing cocci or parental rods . We postulate that, in E . coli, the chemical composition of septal peptidoglycan differs from that of lateral wall peptidoglycan.

Nat Struct Biol, 1996 Aug, 3(8), 688 - 95
Structure-based design of a potent transition state analogue for TEM-1 beta-lactamase; Strynadka NC et al.; The structure of the plasmid-mediated beta-lactamase TEM-1 has been solved in complex with a designed boronic acid inhibitor (1R)-1-acetamido-2-(3-carboxyphenyl)ethane boronic acid at 1.7 A resolution . The boronate inhibitor was designed based on the crystallographic coordinates of the acyl-enzyme intermediate of TEM-1 bound to the substrate penicillin G . The boronate-TEM-1 complex is highly ordered and defines a novel transition state analogue of the deacylation step in the beta-lactamase reaction pathway . The design principles of this highly effective inhibitor (Ki = 110 nM) and the resulting structural and mechanistic implications are presented.

J Am Vet Med Assoc, 1996 Aug 1, 209(3), 589 - 93
Patterns of chemical residues detected in US beef carcasses between 1991 and 1993; Gibbons SN et al.; A study of data from 12 states in the Food Safety Inspection Service's Residue Violation Information System was conducted to describe patterns of violative chemical residues in US beef during 1991, 1992, and 1993 . In 1991, 3,249 violative residues were found in 2,734 carcasses in the 12 states included in the study . In 1992, 3,132 violative residues were found in 2,813 carcasses, and in 1993, 2,317 violative residues were found in 2,051 carcasses . During each of the 3 years, the Calf Antibiotic and Sulfonamide Test and Swab Test On Premises projects detected most of the violative residues, and producers/independent growers and dairy farms were recorded as the responsible sources for most of the violations . Also, most of the animals found to have violative residues were bob calves and culled cows . In bob calves, neomycin was the most frequently identified violative chemical, followed by tetracycline, gentamicin, oxytetracycline, and penicillin . In culled cows, penicillin was the most frequently identified violative chemical and was the chemical most frequently found in combination with other chemicals in cows with multiple violative residues . Distribution patterns of violative chemical residues by slaughter class and residue type varied among the 5 Food Safety Inspection Service regions . These specific regional characteristics support the need for customized intervention, education, assessment, and prevention programs.

Nature, 1996 Aug 1, 382(6590), 468 - 71
Autocatalytic processing of the 20S proteasome; Seemuller E et al.; The Ntn (N-terminal nucleophile) hydrolases are enzymes with an unusual four-layer alpha + beta fold . The amino-terminal residue (cysteine, serine or threonine) of the mature protein is the catalytic nucleophile, and its side chain is activated for nucleophilic attack by transfer of its proton to the free N terminus, although other active-site residues may also be involved . The four currently known Ntn hydrolases (glutamine PRPP amidotransferase, penicillin acylase, the 20S proteasome and aspartylglucosaminidase) are encoded as inactive precursors, and are activated by cleavage of the peptide bond preceding the catalytic residue . It has been suggested that autocatalytic processing is a common feature of Ntn hydrolases, and proceeds by an intramolecular mechanism determined by their common fold . Here we show that propeptide processing in the proteasome from Thermoplasma acidophilum is indeed autocatalytic, but is probably intermolecular . Processing is not required for assembly, is largely unaffected by propeptide length and sequence, and occurs before beta-subunit folding is completed . Although serine is an acceptable active-site nucleophile for proteolysis, and cysteine for processing, only threonine is fully functional in both . This explains why threonine is universally conserved in active proteasome subunits.

Microb Drug Resist, 1996 Summer, 2(2), 163 - 75
Penicillin and beyond: evolution, protein fold, multimodular polypeptides, and multiprotein complexes; Ghuysen JM et al.; As the protein sequence and structure databases expand, the relationships between proteins, the notion of protein superfamily, and the driving forces of evolution are better understood . Key steps of the synthesis of the bacterial cell wall peptidoglycan are revisited in light of these advances . The reactions through which the D-alanyl-D-alanine depeptide is formed, utilized, and hydrolyzed and the sites of action of the glycopeptide and beta-lactam antibiotics illustrate the concept according to which new enzyme functions evolve as a result of tinkering of existing proteins . This occurs by the acquisition of local structural changes, the fusion into multimodular polypeptides, and the association into multiprotein complexes.

Hautarzt, 1996 Jul, 47(7), 510 - 4
{Epidemiology and clinical aspects of cold urticaria}; Moller A et al.; To study the frequency and clinical aspects of cold urticaria in Central Europe, patient data from a university dermatology clinic and a private dermatology office between 1984-94 were analysed and the patients re-examined if possible . The incidence of cold urticaria was found to be 0.05% . Of the 56 patients with cold urticaria (31 women, 25 men), 49 had idiopathic cold urticaria . The mean age was 41.0 +/- 15.6 year, the mean duration of disease 7.9 +/- 5.8 years . Atopy was found in 46.5% of patients, and 23.2% of the patients suffered from other types of urticaria (cholinergic, chronic idiopathic, dermographic, aquagenic and heat-induced) . Laboratory examinations were only rarely abnormal . 44 patients were treated with antihistamines, with generally only moderate symptomatic improvement . Treatment with antibiotics (penicillin, 1-2 mil IU/d over 2-4 weeks, n = 18, or tetracyclines, 2 g/d over 2 weeks, n = 10) induced full remission in 13 patients and symptomatic improvement in 8 . During an average of 6.5 year-follow-up, 20 of 43 symptomatic patients went into spontaneous remission . The good therapeutic response to antibiotics in this study underlines the need for a better elucidation of the cause of cold urticaria, in view of possible infectious causes.

Mol Reprod Dev, 1996 Jul, 44(3), 352 - 9
Natural and endotoxin-induced atresia of preantral and early antral follicles is characterized by DNA internucleosomal cleavage; Bosu WT et al.; Preantral follicles (PAF) and early antral follicles (EAF) were isolated from bovine ovaries and classified under a stereomicroscope as atretic or healthy . The atretic follicles were all considered as group I (in vivo atresia), whereas healthy follicles were assigned to five groups (group II, in vivo normal control; group III, in vitro normal control; group IV, in vitro induced atresia; groups V and VI, Lipopolysaccharide (LPS)-induced atresia in vitro) . Group I and II follicles were immediately snap-frozen (-70 degrees C) until DNA extraction, whereas group III-VI follicles were incubated (39 degrees C, 5% CO2, 95% air) for periods up to 72 hr under various conditions . Group III follicles were maintained in complete medium (M199, bovine calf serum, sodium pyruvate, epidermal growth factor, insulin, transferrin, sodium selenite, penicillin, streptomycin, and amphotericin), whereas group IV follicles were incubated in the same medium, but without serum . Group V and VI follicles were maintained in complete medium, but in the presence of LPS (10 or 50 micrograms/ml, respectively) . Results showed that follicles incubated in the absence of serum and those exposed to both doses of LPS became atretic . DNA isolated from all atretic follicles showed fragmentation typical of that described for apoptosis; this was also confirmed by in situ DNA labeling and histology . Atretic follicles did not produce estradiol (P < 0.001), but progesterone values increased with follicle size (P < 0.001) and time of incubation (P < 0.001) . We concluded that in the absence of serum or in the presence of LPS, follicles undergo atresia via apoptosis.

J Investig Allergol Clin Immunol, 1996 Jul-Aug, 6(4), 256 - 60
Phenomenon of specific inhibition of luminol-dependent chemiluminescence of polymorphonuclear leukocytes under the influence of allergen; Pytsky VI et al.; The purpose of our investigation was to establish how the intensity of induced luminol-dependent chemiluminescence of polymorphonuclear leukocytes is affected by the cultivation of allergen with the blood of allergic patients (pollinosis, bronchial asthma and penicillin allergy) and animals with allergic processes (Arthus' phenomenon, guinea pigs sensitized by horse serum) . The results of all assays were uniform . In all cases three phases of changes in induced chemiluminescence were established . In the first phase with the minimum doses of specific and unspecific allergens, either no changes in chemiluminescence were found or chemiluminescence even increased . With higher doses of allergen came the second phase - inhibition of stimulated chemiluminescence when specific allergen had been added and the absence of changes in the tests with unspecific allergen . We defined this phase as the phase of specific chemiluminescence inhibition . With a further increase in the concentration of allergen came the third phase . It expressed itself in the inhibition of stimulated chemiluminescence under the influence of both specific and unspecific allergen . We viewed this phase as a manifestation of the toxic influence of allergen on polymorphonuclear leukocytes . We suggested using the second phase for diagnosing sensitization.

Clin Infect Dis, 1996 Jul, 23(1), 71 - 5
Capnocytophaga canimorsus septicemia in Denmark, 1982-1995: review of 39 cases; Pers C et al.; Thirty-nine Danish cases of Capnocytophaga canimorsus septicemia were reviewed to determine the clinical course of this infection . The cases of septicemia were related to recent dog bites or other close contact with dogs . The period from the bite to the onset of symptoms ranged from 1 to 8 days . The mean age of the patients was 59.1 years (range, 28-83 years) . Underlying conditions included previous splenectomy and alcoholism . Thirteen patients had previously been in good health . Common initial symptoms were fever, malaise, myalgia, vomiting, diarrhea, abdominal pain, dyspnea, confusion, headache and skin manifestations . Disseminated intravascular coagulation developed in 14 patients, meningitis in 5, and endocarditis in 1 . Twelve of the patients died . All patients except two were treated with penicillin or ampicillin . Five patients had received antibiotics prior to admission . Attention should be drawn to C . canimorsus septicemia in cases of febrile illness following dog bites or contact with dogs, as well as those involving previously healthy persons . The incidence of this condition in Denmark is estimated to be 0.5 case per 1 million people per year.

J Pediatr, 1996 Jul, 129(1), 166 - 7
Semicircular lipoatrophy after intragluteal injection of benzathine penicillin; Kayikcioglu A et al.; A 3-year old girl had localized lipoatrophy after an intragluteal injection of benzathine penicillin G . No associated abnormalities were found.

J Bacteriol, 1996 Jul, 178(13), 3908 - 16
Identification of a major cis-acting DNA element controlling the bidirectionally transcribed penicillin biosynthesis genes acvA (pcbAB) and ipnA (pcbC) of Aspergillus nidulans; Bergh KT et al.; The beta-lactam antibiotic penicillin is produced as a secondary metabolite by some filamentous fungi . In this study, the molecular regulation of the Aspergillus (Emericella) nidulans penicillin biosynthesis genes acvA (pcbAB) and ipnA (pcbC) was analyzed . acvA and ipnA are divergently oriented and separated by an intergenic region of 872 bp . Translational fusions of acvA and ipnA with the two Escherichia coli reporter genes lacZ and uidA enabled us to measure the regulation of both genes simultaneously . A moving-window analysis of the 872-bp intergenic region indicated that the divergently oriented promoters are, at least in part, overlapping and share common regulatory elements . Removal of nucleotides -353 to -432 upstream of the acvA gene led to a 10-fold increase of acvA-uidA expression and simultaneously to a reduction of ipnA-lacZ expression to about 30% . Band shift assays and methyl interference analysis using partially purified protein extracts revealed that a CCAAT-containing DNA element within this region was specifically bound by a protein (complex), which we designated PENR1, for penicillin regulator . Deletion of 4 bp within the identified protein binding site caused the same contrary effects on acvA and ipnA expression as observed for all of the deletion clones which lacked nucleotides -353 to -432 . The PENR1 binding site thus represents a major cis-acting DNA element . The intergenic regions of the corresponding genes of the beta-lactam-producing fungi Penicillium chrysogenum and Acremonium chrysogenum also diluted the complex formed between the A . nidulans probe and PENR1 in vitro, suggesting that these beta-lactam biosynthesis genes are regulated by analogous DNA elements and proteins.

J Bacteriol, 1996 Jul, 178(13), 3818 - 28
Mecillinam resistance in Escherichia coli is conferred by loss of a second activity of the AroK protein; Vinella D et al.; Mecillinam, a beta-lactam antibiotic specific to penicillin-binding protein 2 (PBP 2) in Escherichia coli, blocks cell wall elongation and, indirectly, cell division, but its lethality can be overcome by increased levels of ppGpp, the nucleotide effector of the stringent response . We have subjected an E . coli K-12 strain to random insertional mutagenesis with a mini-Tn10 element . One insertion, which was found to confer resistance to mecillinam in relA+ and relA strains, was mapped at 75.5 min on the E . coli map and was located between the promoters and the coding sequence of the aroK gene, which codes for shikimate kinase 1, one of two E . coli shikimate kinases, both of which are involved in aromatic amino acid biosynthesis . The mecillinam resistance conferred by the insertion was abolished in a delta relA delta spoT strain completely lacking ppGpp, and it thus depends on the presence of ppGpp . Furthermore, the insertion increased the ppGpp pool approximately twofold in a relA+ strain . However, this increase was not observed in relA strains, although the insertion still conferred mecillinam resistance in these backgrounds, showing that mecillinam resistance is not due to an increased ppGpp pool . The resistance was also abolished in an ftsZ84(Ts) strain under semipermissive conditions, and the aroK::mini-Tn10 allele partially suppressed ftsZ84(Ts); however, it did not increase the concentration of the FtsZ cell division protein . The insertion greatly decreased or abolished the shikimate kinase activity of AroK in vivo and in vitro . The two shikimate kinases of E . coli are not equivalent; the loss of AroK confers mecillinam resistance, whereas the loss of Arol, does not . Furthermore, the ability of the aroK mutation to confer mecillinam resistance is shown to be independent of polar effects on operon expression and of effects on the availability of aromatic amino acids or shikimic acid . Instead, we conclude that the AroK protein has a second activity, possibly related to cell division regulation, which confers mecillinam sensitivity . We were able to separate the AroK activities mutationally with an aroK mutant allele lacking shikimate kinase activity but still able to confer mecillinam sensitivity.

Eur J Biochem, 1996 Jun 15, 238(3), 675 - 82
The Aspergillus nidulans penicillin-biosynthesis gene aat (penDE) is controlled by a CCAAT-containing DNA element; Litzka O et al.; Analysis of the promoter of the penicillin biosynthesis aat (penDE) gene of Aspergillus nidulans using band-shift assays led to the identification of a CCAAT-containing DNA element which was specifically bound by a protein (complex) . The identified DNA element was localised about 250 bp upstream of the transcriptional-start sites of aat . Substitution of the CCAAT core sequence by GATCC led to a fourfold reduction of expression of an aat-lacZ gene fusion . The identified binding site thus was functional in vivo and positively influenced at expression . Partial purification of the CCAAT binding protein and cross-competition experiments provided evidence that the binding protein is identical to the identified putative penicillin-regulatory protein PENR1, binding to the CCAAT element in the bidirectional intergenic promoter region between acvA (pcbAb) and ipnA (pcbC) . Hence, PENR1 seems to be involved in the regulation of all three penicillin-biosynthesis genes . Cross-competition experiments demonstrated that the promoter region of the corresponding aat (penDE) gene of Penicillium chrysogenum was capable to dilute the shift of the A . nidulans probe with PENR1, suggesting the presence of a similar regulatory mechanism in this fungus . Taken together with previous data, CCAAT-containing DNA elements thus seem to represent major cis-acting sites in the promoters of beta-lactam-biosynthesis genes.

Mol Gen Genet, 1996 Jun 12, 251(3), 388 - 96
Colicin M is inactivated during import by its immunity protein; Gross P et al.; Colicin M (Cma) displays a unique activity that interferes with murein and O-antigen biosynthesis through inhibition of lipid-carrier regeneration . Immunity is conferred by a specific immunity protein (Cmi) that inhibits the action of colicin M in the periplasm . The subcellular location of Cmi was determined by constructing hybrid proteins between Cmi and the TEM-beta-lactamase (BlaM), which confers resistance to ampicillin only when it is translocated across the cytoplasmic membrane with the aid of Cmi . The smallest Cmi'-BlaM hybrid that conferred resistance to 50 micrograms/ml ampicillin contained 19 amino acid residues of Cmi; cells expressing Cmi'-BlaM with only five N-terminal Cmi residues were ampicillin sensitive . These results support a model in which the hydrophobic sequence of Cmi comprising residues 3-23 serves to translocate residues 24-117 of Cmi into the periplasm and anchors Cmi to the cytoplasmic membrane . Residues 8-23 are integrated in the cytoplasmic membrane and are not involved in Cma recognition . This model was further tested by replacing residues 1-23 of Cmi by the hydrophobic amino acid sequence 1-42 of the penicillin binding protein 3 (PBP3) . In vivo, PBP3'-'Cmi was as active as Cmi, demonstrating that translocation and anchoring of Cmi is not sequence-specific . Substitution of the 23 N-terminal residues of Cmi by the cleavable signal peptide of BlaM resulted in an active BlaM'-'Cmi hybrid protein . The immunity conferred by BlaM'-'Cmi was high, but not as high as that associated with Cmi and PBP3'-'Cmi, demonstrating that soluble Cmi lacking its membrane anchor is still active, but immobilization in the cytoplasmic membrane, the target site of Cma, increases its efficiency . Cmi delta 1-23 remained in the cytoplasm and conferred no immunity . We propose that the immunity protein inactivates colicin M in the periplasm before Cma can reach its target in the cytoplasmic membrane.

J Pak Med Assoc, 1996 Jun, 46(6), 126 - 8
Method of obtaining and preparation of fresh human amniotic membrane for clinical use; Ganatra MA et al.; Amniotic membrane was obtained from 36 mothers seronegative for hepatitis B surface antigen and syphilis, undergoing caesarean section . Membrane was separated from placenta and was washed first with saline and then saline solution containing penicillin . The processed membrane was found to be sterile and useable for up to one week . Of 36 placentas obtained, 33 were utilized in 22 patients, with no history of penicillin allergy, as biological dressing in acute burns . Each patient received three applications of membrane one every other day, over a period of six days . This method of obtaining amniotic membrane was simple and more practical for maintaining the biological effectiveness of membrane, as shown by quantitative reduction of bacterial counts in burn wounds.

Naunyn Schmiedebergs Arch Pharmacol, 1996 Jun, 354(1), 80 - 5
Aconitine inhibits epileptiform activity in rat hippocampal slices; Ameri A et al.; The effect of aconitine, an alkaloid neurotoxin known to bind at site 2 of the sodium channel, was investigated on epileptiform activity in hippocampal slices by use of extracellular recordings in CA1 pyramidal cell layer . Epileptiform activity was induced by bicuculline, picrotoxin, penicillin, pentylenetetrazol or by omission of magnesium from the bathing medium, respectively . In every case aconitine (0.1 and 1 microM) blocked the multiple population spikes representing the epileptiform activity . The onset of inhibition was shorter by use of an increased concentration of the epileptogenic drug . Epileptiform activity evoked by pentylenetetrazol and low magnesium was first increased by aconitine followed by a rapid inhibition, while the bicuculline-, picrotoxin-, and penicillin-induced epileptiform discharges were immediately abolished.

J Pharm Biomed Anal, 1996 Jun, 14(8-10), 1055 - 61
The effect of Fe3+ ion on benzylpenicillin in micellar and nonmicellar aqueous solutions; Carp N et al.; The effect of Fe3+ ions on the hydrolysis of benzylpenicillin in aqueous solution below and above the critical micellar concentration (c.m.c . = 0.26 M) has been studied . The catalytic effect of Fe3+ ions on hydrolysis of this drug has been demonstrated; the reaction rate constant, calculated from UV absorption data of non-micellar solutions, decreases with concentration . It is likely that Fe3+ ions form complexes with the products of degradation . The bright brown slightly soluble product formed in micellar solutions was analyzed by UV - Vis reflection, IR and mass spectroscopy and, in agreement with the results of elemental analysis, is postulated to be an octahedral binuclear complex, Fe2BP4(OH)2 . This study has been linked with the clinical observation that prolonged treatment with penicillin leads to anemia.

Ann Med, 1996 Jun, 28(3), 235 - 40
Lyme neuroborreliosis in children; Christen HJ; Children are more likely than adults to be bitten by ticks and thus more likely to be infected by Borrelia burgdorferi . In a serosurvey the infection rate measured by immunoglobulin G (IgG) antibodies was 2.6% . In a prospective hospital-based multicentre study 169 children with Lyme neuroborreliosis were examined; the infection was diagnosed by detection of specific immunoglobulin M (IgM) antibodies in the cerebrospinal fluid (CSF) using an IgM capture ELISA . The yearly incidence of Lyme neuroborreliosis was 5.8 cases per 100,000 children aged 1-13 . Facial palsy and lymphocytic meningitis account for nearly 90% of all cases with neuroborreliosis indicating striking differences in the clinical spectrum between children and adults . Lyme borreliosis proves to be the most frequently verifiable cause of acute peripheral facial palsy in children, causing every second case of this disorder in the summer and autumn . In cases of facial palsy, nearly all patients with a positive history of tick bite or erythema migrans in the head and neck region show ipsilateral subsequent facial nerve palsy, suggesting a direct invasion via the affected nerve by Borrelia burgdorferi . Lyme borreliosis is the third most frequent cause of lymphocytic meningitis in childhood . Inflammatory changes of the cerebrospinal fluid along with the presence of specific antibodies are mandatory for the diagnosis of Lyme neuroborreliosis . High-dose intravenous penicillin G as well as third-generation cephalosporins prove to be effective in paediatric Lyme neuroborreliosis.

Cutis, 1996 Jun, 57(6), 431 - 2
Fixed drug eruption of the scrotum due to hydroxyzine hydrochloride (Atarax); Cohen HA et al.; Fixed drug eruption describes a sharply localized dermatitis that characteristically recurs at the same site each time the offending drug is administered . Several drugs have been reported to cause this eruption, such as phenolphthalein, barbiturates, penicillin, and others . In this report, two children with fixed drug eruption of the scrotum due to hydroxyzine hydrochloride (Atarax) are described . To the best of our knowledge, no such cases have been reported previously in children.

Zhonghua Yi Xue Za Zhi (Taipei), 1996 Jun, 57(6), 438 - 42
Infective endocarditis complicated with rapidly progressive glomerulonephritis: a case report; Gao GW et al.; A 26-year-old man who had suffered from intermittent chills and fever over a two month period was quite clear of heart or kidney involved developed acute deterioration of renal function . A new pansystolic murmur over the apex of the heart was heard on auscultation, and echocardiography clearly showed a vegetation about 0.7-0.9 cm in size on the atrial site of the mitral value . Laboratory investigation displayed normochromic anemia with negative Coombs' test . Immunological studies were positive for rheumatoid factor and circulating immune complex . High serum levels of erythrocyte sedimentation rate and C-reactive protein, nephritic sediment of urinalysis and negative blood cultures for bacteria, tuberculosis or fungus were also noted . Abdominal sonography showed normal kidney size, bilaterally . Renal biopsy revealed typical crescentic glomerulonephritis . After intravenous penicillin therapy for two weeks, the serum creatinine level recovered from 6.7 mg/dl to 2.0 mg/dl and circulating immune complex disappeared . In consideration of cardiac insufficiency and the potential risk for complications of the vegetation, the patient underwent mitral valve replacement . Four weeks after operation, all the abnormal data had resolved completely . These data suggested that infective endocarditis with rapidly progressive glomerulonephritis is curable by antibiotic therapy and surgical intervention.

J Obstet Gynecol Neonatal Nurs, 1996 Jun, 25(5), 383 - 6
The Jarisch-Herxheimer reaction in pregnancy: a nursing perspective; Rodriguez AC et al.; The Jarisch-Herxheimer reaction is a systemic event that can occur after the first dose of penicillin administration during treatment of syphilis . This article presents a case report of the Jarisch-Herxheimer reaction in a woman who was treated for syphilis at 27 weeks gestation . The proposed pathophysiology of the reaction is described, and complications of this reaction during pregnancy are reviewed . Recommendations for the nursing care of women treated for syphilis are provided.

Genitourin Med, 1996 Jun, 72(3), 160 - 71
Sexually transmitted diseases in South Africa; Pham-Kanter GB et al.; AIM: To review the epidemiology of and data collection for sexually transmitted diseases (STDs) in South Africa . METHODS: Literature published since 1980 on STDs in South Africa were complied and evaluated . Historical reports and salient unpublished literature were also used in the literature review . Studies were critically reviewed in the light of sample populations and study methods, and a baseline picture of the patterns of STD burden was developed . RESULTS: The STD burden in apparently asymptomatic study populations is significant . Ulcerative infections, primarily caused by syphilis and chancroid, are present in 5-15% of asymptomatic clinic attenders; prevalence rates of gonorrhoea average 8%, with up to 13% of gonococcal isolates resistant to penicillin antibiotics . In addition, on average, chlamydia and vaginal infections are detected in 16% and 20-49%, respectively, of antenatal and family planning clinic attenders . HIV seroprevalence rates have reached 7.6% in antenatal clinic attenders . Most South African STD data are derived from ad hoc surveys which have traditionally focused only on several major infections and particular urban centres . Almost all STD studies have been facility-based, with many studies based at STD clinics, thus reporting only relative frequencies and not population-based prevalences of STDs . With the possible exception of HIV, systematic surveillance data for STDs are conspicuously lacking . CONCLUSION: The disease burden of classic sexually transmitted infections has historically been heavy, and continues to be a serious public health problem in South Africa . Morbidity from both ulcerative and non-ulcerative infections, particularly in women, is significant . The body of STD data, although mostly sound, remains incomplete, and with the rapid emergence of HIV in South Africa, surveillance of STDs and focused STD policies will be criticalPIP: Important unpublished literature and literature published since 1980 on sexually transmitted diseases (STDs) in South Africa were reviewed to provide a picture of what is known about the epidemiology of STDs in the country . STD infection is a serious public health problem in South Africa, with significant morbidity from both ulcerative and nonulcerative infections, particularly in women . The body of data on STDs was found to be largely sound, but incomplete . Ulcerative infections, caused mainly by syphilis and chancroid, are present in 5-15% of asymptomatic clinic attenders, while prevalence rates of gonorrhea average 8%, with up to 13% of gonococcal isolates resistant to penicillin antibiotics . Chlamydia and vaginal infections are detected in 16% and 20-49%, respectively, of antenatal and family planning clinic attenders . HIV seroprevalence has reached 7.6% among antenatal clinic attenders .

Biochem J, 1996 Jun 1, 316 ( Pt 2), 409 - 12
Rapid burst kinetics in the hydrolysis of 4-nitrophenyl acetate by penicillin G acylase from Kluyvera citrophila . Effects of mutation F360V on rate constants for acylation and de-acylation; Roa A et al.; The kinetics of release of 4-nitrophenol were followed by stopped-flow spectrophotometry with two 4-nitrophenyl ester substrates of penicillin G acylase from Kluyvera citrophila . With the ester of acetic acid, but not of propionic acid, there was a pre-steady-state exponential phase, the kinetics of which were inhibited by phenylacetic acid (a product of hydrolysis of specific substrates) to the extent predicted from Ki values . This was interpreted as deriving from rapid formation (73 mM-1.s-1) and slow hydrolysis (0.76 s-1) of an acetyl derivative of the side chain of the catalytic-centre residue Ser-290 . With the mutant F360V, which differs from the wild-type enzyme in its ability to hydrolyse adipyl-L-leucine and has a kcat for 4-nitrophenyl acetate one-twentieth that of the wild-type enzyme, the corresponding values for the rates of formation and hydrolysis of the acetyl-enzyme were 11.1 mM-1.s-1 and 0.051 s-1 respectively . The ratio of these rate constants was three times that for the wild-type enzyme, suggesting that the mutant is less impaired in the rate of formation of an acetyl-enzyme than in its subsequent hydrolysis.

Infect Immun, 1996 Jun, 64(6), 1944 - 9
Cytotoxic-T-lymphocyte-mediated cytolysis of L cells persistently infected with Chlamydia spp; Rasmussen SJ et al.; Persistent chlamydial infections have been proposed as a means whereby chlamydiae evade immune resolution of infection . Such a mechanism would require evasion not only of the humoral immune responses but also of cell-mediated immune responses . We hypothesized that if such a mechanism is important, persistently infected cells should not be recognized by cytotoxic T cells . Persistent infections were simulated in vitro by treatment of Chlamydia trachomatis- or Chlamydia psittaci-infected cells with gamma interferon (IFN-gamma), penicillin, or tryptophan depletion . Cultures were examined for induction of a chlamydial stress response (measured by transcription of groesl RNA) and for the effects on viability, infectivity, morphology, and immune recognition . Although both IFN-gamma and penicillin induced aberrant chlamydial morphology and growth, we did not find evidence that these treatments elicited a classical stress response . In addition, T-cell-mediated lysis of Chlamydia-infected target cells treated with IFN-gamma or penicillin or grown in tryptophan-deficient media was examined . The immune cell-mediated lysis of these treated infected cells demonstrated that despite the effects of these compounds on chlamydial growth and development, the infected cells continued to be efficiently recognized and killed by cytotoxic T cells . Thus, it seems unlikely that these in vitro models of persistence represent functional mechanisms to evade immune clearance.

Pediatrics, 1996 Jun, 97(6 Pt 2), 989 - 91
Are the currently recommended doses of benzathine penicillin G adequate for secondary prophylaxis of rheumatic fever?
Currie BJ.
OBJECTIVE . To review the literature on dose and regimens of intramuscular benzathine penicillin G (BPG) for secondary prophylaxis of recurrent rheumatic fever . SETTING . For over 40 years BPG has been the gold standard for secondary prophylaxis, usually as a dose of 1,200,000 U (900 mg) . Although studies have suggested that BPG injections every 3 weeks are superior to injections every 4 weeks, implementation of an every 3 weeks regimen can be problematic with regards to both patient compliance (adherence) and an increased burden on health resources . FINDINGS . Some of the earliest studies of BPG suggested that larger doses resulted in prolongation of detectable penicillin levels . A recent study assessing plasma penicillin levels after BPG doses of 1,200,000 U, 1,800,000 U, and 2,400,000 U suggested there may be benefits in a BPG regimen every 4 weeks with doses higher than the standard 1,200,000 U . CONCLUSIONS . Further studies of higher dose BPG regimens seem justified . In addition, further work is needed on quality and storage options for different BPG preparations; location and method of BPG injections; the importance of weight differences between individuals; and ways of improving access to and compliance with BPG regimens.

Proc Natl Acad Sci U S A, 1996 May 28, 93(11), 5347 - 51
Expression of a renal type I sodium/phosphate transporter (NaPi-1) induces a conductance in Xenopus oocytes permeable for organic and inorganic anions; Busch AE et al.; Two distinct molecular types (I and II) of renal proximal tubular brush border Na+/Pi cotransporters have been identified by expression cloning on the basis of their capacity to induce Na+-dependent Pi influx in tracer experiments . Whereas the type II transporters (e.g., NaPi-2 and NaPi-3) resemble well known characteristics of brush border Na+/Pi cotransport, little is known about the properties of the type I transporter (NaPi-1) . In contrast to type II, type I transporters produced electrogenic transport only at high extracellular Pi concentrations (> or =3 mM) . On the other hand, expression of NaPi-1 induced a Cl- conductance in Xenopus laevis oocytes, which was inhibited by Cl- channel blockers {5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) > niflumic acid >> 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid} . Further, the Cl- conductance was inhibited by the organic anions phenol red, benzylpenicillin (penicillin G), and probenecid . These organic anions induced outwardly directed currents in the absence of Cl- . In tracer studies, we observed uptake of benzylpenicillin with a Km of 0.22 mM; benzylpenicillin uptake was inhibited by NPPB and niflumic acid . These findings suggest that the type I Na+/Pi cotransporter functions also as a novel type of anion channel permeable not only for Cl- but also for organic anions . Such an apical anion channel could serve an important role in the transport of Cl- and the excretion of anionic xenobiotics.

J Med Chem, 1996 May 24, 39(11), 2207 - 18
Modeling study on a hydrolytic mechanism of class A beta-lactamases; Ishiguro M et al.; Comparison of the hydrogen-bond networks at the active site in the crystallographic structures reported for class A beta-lactamases revealed an importance of a switch of the hydrogen-bond network for the catalytic process . Taking account of the conformational mobility of the Lys73 residue, we have constructed putative complex models for beta-lactam antibiotics and the enzymes in the multistep hydrolysis which consists of a Michaelis complex, an acyl-enzyme, and a tetrahedral oxyanion for deacylation . In the acylation, the C3 carboxylate of penicillin derivatives would participate in activation of the Ser130 hydroxyl group and then the oxyanion of the Ser130 residue would deprotonate the ammonium group of the Lys73 residue which will act as a general base for activation of the Ser70 residue . In the deacylation, the deacylating water molecule would be accommodated during a conformational change of the acyl moiety without a structural change of the active-site residues and the unprotonated N4 atom of the penicillins would act as a general base to activate the water molecule . This catalytic process provided a new account for the stability of the acyl-enzyme complexes . This substrate-assisted mechanism would also be extended to a hydrolytic mechanism of class C enzymes.

Biochem J, 1996 May 15, 316 ( Pt 1), 149 - 56
Localization of a putative second membrane association site in penicillin-binding protein 1B of Escherichia coli; Wang CC et al.; We have shown previously that the periplasmic domain of penicillin-binding protein 1B (PBP 1Bper; residues 90-844) from Escherichia coli is insoluble in the absence of detergents, and can be reconstituted into liposomes {Nicholas, Lamson and Schultz (1993) J . Biol . Chem . 268, 5632-5641} . These data suggested that native PBP 1B contains a membrane association site in addition to its N-terminal transmembrane anchor . We have studied the membrane topology of PBP 1B in greater detail by assessing detergent binding and solubility in the absence of detergents for PBP 1Bper and a set of proteolytic fragments of PBP 1B . PBP 1Bper was shown by three independent methods to bind to detergent micelles, which strongly suggests that the periplasmic domain interacts with the hydrophobic milieu of membrane bilayers . Digestion with high weight ratios of thrombin of purified PBP 1B containing an engineered thrombin cleavage site on the periplasmic side of the transmembrane anchor generated four fragments in addition to PBP 1Bper that varied in size from 71 to 48 kDa . In contrast to PBP 1Bper, all fragments of 67 kDa and smaller were eluted from a gel-filtration column in the absence of detergents and did not bind to detergent micelles . The N-terminal sequences of the four fragments were determined, allowing the cleavage sites to be located in the primary sequence of PBP 1B . These data localize the membrane association site of PBP 1B to a region comprising the first 163 amino acids of the periplasmic domain, which falls within the putative transglycosylase domain . Lipid modification does not appear to be the mechanism by which PBP 1Bper associates with membranes.

Infection, 1996 May-Jun, 24(3), 218 - 26
Formation and cultivation of Borrelia burgdorferi spheroplast-L-form variants; Mursic VP et al.; As clinical persistence of Borrelia burgdorferi in patients with active Lyme borreliosis occurs despite obviously adequate antibiotic therapy, in vitro investigations of morphological variants and atypical forms of B . burgdorferi were undertaken . In an attempt to learn more about the variation of B . burgdorferi and the role of atypical forms in Lyme borreliosis, borreliae isolated from antibiotically treated and untreated patients with the clinical diagnosis of definite and probable Lyme borreliosis and from patient specimens contaminated with bacteria were investigated . Furthermore, the degeneration of the isolates during exposure to penicillin G in vitro was analysed . Morphological analysis by darkfield microscopy and scanning electron microscopy revealed diverse alterations . Persisters isolated from a great number of patients (60-80%) after treatment with antibiotics had an atypical form . The morphological alterations in culture with penicillin G developed gradually and increased with duration of incubation . Pleomorphism, the presence of elongated forms and spherical structures, the inability of cells to replicate, the long period of adaptation to growth in MKP-medium and the mycoplasma-like colonies after growth in solid medium (PMR agar) suggest that B . burgdorferi produce spheroplast-L-form variants . With regard to the polyphasic course of Lyme borreliosis, these forms without cell walls can be a possible reason why Borrelia survive in the organism for a long time (probably with all beta-lactam antibiotics) {corrected} and the cell-wall-dependent antibody titers disappear and emerge after reversion.

J Investig Allergol Clin Immunol, 1996 May-Jun, 6(3), 162 - 5
Positive allergological tests may turn negative with no further exposure to the specific allergen: a long-term, prospective, follow-up study in patients allergic to penicillin; Patriarca G et al.; Preliminary literature reports suggest the possibility that, in an allergic patient, a previously positive allergological test may turn negative after a long period of time with no further exposure to the specific allergen . The aim of this study was to evaluate the rate by which a previously positive skin test or RAST may turn negative in a group of patients allergic to penicillin if no further exposure to the specific allergen occurs . Sixty-three patients allergic to penicillin (48 with type I allergy and 15 with type IV allergy) were enrolled in a long-term, prospective, follow-up study, undergoing a successive complete allergological testing within 6 years of the first positive examination . During the follow-up period, skin tests progressively became negative in 28 (58.3%) type I allergic patients and in only one (6.7%) subject with type IV allergy . Similarly, the positive RAST turned negative in as many as 13 subjects (43.3% of cases) . The cumulative skin test positivity (type I allergy) was significantly lower than that of patch tests (type IV allergy) (chi 2 = 10.4; d.f . = 1; p < 0.005, Logrank test) . No significant difference in the progressive rate of decrease in skin test and RAST cumulative positivity was observed in the 30 patients showing both RAST and skin test positivity on entering the follow-up study . Our results provide strong evidence that a positive allergological test performed in a drug-allergic patient may become negative with time, in the absence of further exposure to the specific antigen . A negative allergological test cannot, therefore, rule out the immunological basis of a drug sensitivity . This is why we always suggest advising patients with a personal history of drug hypersensitivity against any further administration of the responsible drug, even in the presence of a completely negative allergological examination.

ORL J Otorhinolaryngol Relat Spec, 1996 May-Jun, 58(3), 178 - 81
Lemierre's syndrome: are we underdiagnosing this life-threatening infection?
Harar RP, MacDonald A, Pullen D, Ganesan S, Prior AJ.
Over a period of 12 months 3 patients presented with severe tonsillitis and subsequently grew Fusobacterium necrophorum (literally-spindle-shaped rod which brings death!) from blood cultures . Two patients responded well to antibiotics and were discharged within 4 days of admission . The third case had a longer history of symptoms and following investigations of a minor but unusual neck swelling was found to have thrombosis of the external and internal jugular vein . This is the first stage in the potentially fatal dissemination of this virulent organism which manifests clinically as Lemierre's syndrome . We describe the clinical histories and discuss whether cases are unrecognised because of the prompt clinical response to penicillin and metronidazole . We stress the importance of taking blood cultures and careful examination of the neck in all patients presenting with a severe tonsillitis.

Arch Pediatr, 1996 May, 3(5), 445 - 51
{Sickle cell anemia: study of the pediatric mortality in Ile de France from 1985 to 1992}; Thomas C et al.; BACKGROUND: Sickle cell anemia is now relatively frequent in France . Its clinical course is punctuated by acute episodes that threaten the life, specially during the first year of life . POPULATION AND METHODS: The files of 26 children (14 boys, 12 girls) dead from sickle cell disease between 1985 and 1992 were retrospectively studied . These files concerned patients from the Ile-de-France area . RESULTS: Their mean age at time of diagnosis was 13.7 months (0 to 3 years 4 months); mean age was 5.5 years at time of death . Infection was the cause of death in 15 patients (S pneumoniae in eight patients despite prophylactic penicillin and pneumococcal vaccine in the majority of them) . Splenic sequestration crisis was the cause of death in three patients less than 5 years of age; vasocclusive crisis resulting in cerebral infarction was the cause in three patients aged 7.5 to 13 years . Mortality calculated from those patients followed since 1987 (total: 2,063 years) was 0.29% person/year . CONCLUSION: Comfort of patients and risk of permanent disability become the main factors of choice for new treatments such as chemotherapy or bone marrow transplantation.

Pathol Biol (Paris), 1996 May, 44(5), 423 - 9
{Molecular epidemiology of pneumococci with decreased susceptibility to penicillin isolated in a Parisian pediatric hospital}; Moissenet D et al.; Pneumococci with decreased susceptibility or resistant to penicillin (PRP) have been isolated with an increasing frequency in France . Among PRP, isolates of serotypes 23F and 9V were the most frequently recovered in our children's hospital . Penicillin-resistance is due to the appearance of altered penicillin binding proteins (PBPs) with reduced affinity for beta-lactam antibiotics . 3 PBPs have been well studied, 2b, 2x and 1a, and the sequences of their genes have been determined . Our molecular epidemiological study of 14 PRP 9V and 26 PRP 23F isolated mainly from otitis in 1993-94, consisted of determining chromosomic restriction patterns (Apa I) by pulsed-field gel electrophoresis, and restriction patterns (Hinf I) of PBP genes pbp 2b, pbp 2x and pbp 1a after PCR . All the PRP 9V exhibited the same pulsotype and identical patterns for each of the genes pbp 2b, pbp 2x and pbp 1a, suggesting a clonal origin . The origins of PRP 23F were more heterogenous: 5 clones could be defined, with one predominant clone composed of 20 isolates . Most of the PRP 23F shared identical profiles for the genes pbp 2b, pbp 2x and pbp 1a with the PRP 9V, suggesting a horizontal transfer of DNA . Molecular markers, which provide more informations than serotyping, were useful to clarify the complex epidemiology of PRP.

Mol Microbiol, 1996 May, 20(3), 529 - 40
Characterization of a Penicillium chrysogenum gene encoding a PacC transcription factor and its binding sites in the divergent pcbAB-pcbC promoter of the penicillin biosynthetic cluster; Suarez T et al.; Previous work established that pH regulation of gene expression in Aspergillus nidulans, a major determinant of penicillin biosynthesis, is mediated by the zinc-finger transcription factor PacC, an activator of transcription of the isopenicillin N synthase gene . We characterize here the pacC gene from the efficient penicillin producer Penicillium chrysogenum, which functionally complements an A . nidulans pacC null mutation . It encodes a 641-residue polypeptide showing 64% identify to A . nidulans PacC and containing three putative zinc fingers specifically recognizing a 5'-GCCARG-3' hexanucleotide . Penicillium pacC transcript levels are higher under alkaline than under acidic growth conditions and elevate at late stages of growth . The gene contains three PacC-binding sites in its 5'-upstream region . Transcript levels of pcbC (encoding P . chrysogenum isopenicillin N synthase) are low on a repressing carbon source and elevated on a derepressing carbon source . With either carbon source, alkaline pH elevates pcbC transcript levels, correlating with the presence of seven PacC-binding sites in the 1.1 kb pcbAB-pcbC intergenic region and strongly suggesting that pcbC is under direct pacC control . However, in contrast to the situation in A . nidulans, alkaline pH does not override the negative effects of a repressing carbon source, revealing differences in the regulation of the penicillin pathway between Penicillium and Aspergillus.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 1996 May, 81(5), 590 - 5
Penicillin as a supplement in resolving the localized acute apical abscess; Fouad AF et al.; PROBLEM . Antibiotics are often prescribed indiscriminately to treat endodontic emergencies . OBJECTIVES . This study examined (1) the effect of penicillin supplementation on reduction of symptoms and (2) the course of recovery of localized acute apical abscess after emergency treatment . STUDY DESIGN . Patients with pulp necrosis and periapical pain and/or localized swelling were considered . Those eligible did not have any signs of spreading infections . Patients received appropriate local treatment, and a double-blind protocol was used to randomly assign them to one of three groups: penicillin VK group, placebo group, or neither medication group . All received ibuprofen 600 mg four times daily for 24 hours . Patients entered their pre- and postoperative pain and swelling experience on a visual analog scale for up to 72 hours . RESULTS . Resolution was fairly rapid in most patients . Statistical analysis of the scores of 32 respondents revealed no significant differences (at p < 0.05) between the three groups in course of recovery or symptoms at any time period . CONCLUSIONS . Patients with localized periapical pain or swelling generally recovered quickly with local treatment . The data did not show a demonstrable benefit from penicillin supplementation.

J Chromatogr B Biomed Appl, 1996 Apr 26, 679(1-2), 129 - 35
Determination of penicillin-V in human plasma by high-performance liquid chromatography and solid-phase extraction; Krauwinkel WJ et al.; A high-performance liquid chromatographic method has been developed for the determination of penicillin-V concentrations between 0.1 and 19 micrograms/ml in human plasma . Penicillin-V was isolated from plasma by solid-phase extraction on a C18/OH cartridge . The extracts were injected onto a reversed-phase HPLC system . A 125 x 4 mm C18 column was used to separate penicillin-V from its main metabolites, 5R- and 5S-penicilloic acid and endogenous compounds . The eluent consisted of 66% 0.02 M phosphoric acid buffer, to which tetrabutylammonium dihydrogenphosphate and 34% acetonitrile were added . The column effluent was monitored by ultraviolet spectrophotometry at 269 nm . Using this method, penicillin-V concentrations in plasma could be determined with an accuracy between -5.4 and 5.2% and a precision between 0.8 and 1.6% . The method has proved to be reliable and was used in bioavailability studies for the development of a new oral penicillin-V formulation.

Schweiz Med Wochenschr, 1996 Apr 6, 126(14), 549 - 58
{Skin and hair}; Briner VA; Data deriving from comprehensive hospital monitoring systems suggest that drug-induced skin effects occur in 2-5% of patients receiving any drug medication . Exanthematous (maculopapular) reaction (75%) and urticaria with/without angioedema (30%) are the most frequent of all cutaneous reactions to drugs . The incidence of cutaneous reactions relates to the quantity of the drugs which is prescribed and consumed worldwide . Thus penicillin, sulfonamides and nonsteroidal antiinflammatory drugs show the highest rate of cutaneous side effects . Drug reactions may be classified as either predictable (e.g . chemotherapy-induced alopecia) or unpredictable . Unpredictable side effects of drugs may be the result of allergic (type I to IV) or non-allergic reactions . Hereditary and acquired enzyme deficiency and variations in metabolic pathway may delay drug metabolism and cause nonallergic, toxic side effects . Such a mechanism is known to occur in patients with a low acetylation rate under hydralazine, INH or sulfonamide treatment . Some immunologic although nonallergic factors may facilitate eruptions in patients with infectious mononucleosis under ampicillin medication and in AIDS patients on co-trimoxazole therapy . When a cutaneous drug reaction is diagnosed, withdrawal of the drug is recommended . In instances in which patients display mild drug eruptions and no alternative therapy is available, the drug may be continued . However, it should be kept in mind that mild morbiliform eruption is often the initial presentation of toxic epidermal necrolysis . In AIDS patients sulfonamides most frequently have been implicated as a risk factor for the development of toxic epidermal necrolysis . In other than type 1 hypersensitivity reactions, skin testing and in vitro tests have low sensitivity and specificity.

J Chromatogr A, 1996 Apr 5, 729(1-2), 229 - 35
High-performance liquid chromatographic determination of penicillins by means of automated solid-phase extraction and photochemical degradation with electrochemical detection; Lihl S et al.; An automated precolumn exchange system for on-line solid-phase extraction (OPS-2) coupled to liquid chromatography with photochemical degradation and electrochemical detection was used for the determination of residual amounts of penicillin G, penicillin V, oxacillin, cloxacillin and dicloxacillin . A 5-10-fold increase in sensitivity was obtained when compared with direct UV detection of penicillins at 225 nm . The system is recommended for samples that have received an immunoaffinity clean-up . Analysis of bovine muscle tissue indicated, however, that this procedure could also be suitable for the determination of penicillin G at its maximum residue limit of 50 micrograms/kg even with conventional solvent partitioning for the first clean-up steps.

Zhongguo Zhong Yao Za Zhi, 1996 Apr, 21(4), 238 - 40 inside backcover
{Pharmacological action of siwei shaoyao decoction}; Fang Y et al.; The Siwei Shaoyao Decoction possesses a marked effect on the alleviation of trigeminal neuralgia in rats caused by penicillin G potassium injection . As shown from the hot-plate test, it also has an obvious analgesic effect on mice . To some extent, the decoction has a significant anti-inflammatory effect on the acute edema in hind paws of rats and the effect is believed to be related to the reduction of capillary permeability.

Microb Drug Resist, 1996 Spring, 2(1), 73 - 6
Purification and light-scattering analysis of penicillin-binding protein 4 from Escherichia coli; Fusetti F et al.; Penicillin binding protein 4 (PBP4) from Escherichia coli is a protein involved in the recycling and maturation of the bacterial cell wall and it is inhibited by beta-lactam antibiotics . PBP4 exhibits D-Ala-D-Ala-endopeptidase as well as D-Ala-D-Ala-carboxypeptidase activity . To provide a structural template for the design of new, more specific antibiotics we started X-ray crystallographic studies of penicillin binding protein 4 from Escherichia coli . PBP4 has been overexpressed in Escherichia coli as a His-tagged protein . A large-sclae purification scheme, yielding a very pure material, has been set up and crystallization experiments have been started . Dynamic light scattering experiments suggested that PBP4 exhibits aggregation behavior with a number of different precipitating agents and additives . Only by addition of EDTA, PEG 4000, and ammonium sulfate is the molecular mass about 110 kDa.

Microb Drug Resist, 1996 Spring, 2(1), 63 - 72
Overproduction of penicillin-binding protein 7 suppresses thermosensitive growth defect at low osmolarity due to an spr mutation of Escherichia coli; Hara H et al.; Escherichia coli delta prc mutants lacking periplasmic protease Prc, which was originally found involved in the C-terminal processing of penicillin-binding protein (PBP) 3, show thermosensitive growth at low osmolarity . We isolated thermoresistant revertants containing extragenic suppressor (spr) mutations . In the prc+ background the mutations also caused thermosensitivity at low osmolarity . They were all mapped at about 48 min on the chromosome and most probably allelic to one another . From this chromosomal region we cloned a gene that could correct the thermosensitive defect of an spr mutant, which turned out to be a multicopy suppressor of spr . Analysis of the nucleotide sequence predicted that the gene would code for a low-molecular-weight PBP, and penicillin-binding experiments revealed the product to be PBP 7 . Disruption of the gene on the chromosome caused no apparent growth defect . PBP 7 seemed to be degraded by protease Prc . Overproduction of mutant PBP 7 that had the active site serine residue replaced with alanine did not correct the spr thermosensitivity, suggesting importance of the DD-endopeptidase activity in the multicopy suppression.

Singapore Med J, 1996 Apr, 37(2), 229 - 32
Cervicofacial actinomycosis with paravertebral spread: a case report; Abisheganaden J et al.; We report a case of cervicofacial actinomycosis with paravertebral extension in a 60-year-old man who presented with recurrent neck masses . Diagnosis was confirmed on culture and histology of pus and debris obtained from surgical drainage . He improved only after lengthy in-hospital high dose penicillin therapy . He is currently well and is on maintenance doxycycline therapy for 6 months following the high dose penicillin therapy.

J Pharm Sci, 1996 Apr, 85(4), 423 - 6
Saturable transport of valproic acid in rat choroid plexus in vitro; Naora K et al.; In order to obtain in vitro evidence for a specific transport system of valproic acid (VPA) at the blood-cerebrospinal fluid (CSF) interface, the uptake of VPA by isolated rat choroid plexus was investigated . The uptake clearance of {3H}VPA decreased with the increase of the unlabeled VPA concentration in the incubation medium . Kinetic analysis yielded an apparent Km of 10.0 mM, Vmax of 0.0871 mumol s-1 g-1 and Kns, a permeability coefficient of the nonsaturable component, of 6.85 microL s-1 g-1, indicating that both saturable and nonsaturable systems may contribute to VPA uptake by choroid plexus . Organic anions, penicillin G, p-aminohippurate, salicylate, and probenecid significantly inhibited VPA uptake by choroid plexus . We suggest that VPA translocation through choroidal membrane is partly operated by the organic anion transport system . A significant decrease of VPA uptake induced by 2,4-dinitrophenol, stilbenedisulfonate, and hypothermia (10 degrees C) indicates the involvement of an energy-dependent, carrier-mediated transport system . These results demonstrate that VPA is actively transported through the rat choroidal epithelium via a saturable system probably shared by organic anions.

Actas Urol Esp, 1996 Apr, 20(4), 316 - 22; discussion 323
{Assessment of the effect of a 5-alpha-reductase inhibitor on cultured explants of human prostate}; Lopez Munnoz A et al.; For the present work, cultures of hyperplastic human prostate explants were performed to evaluate the "in vitro" response of a 5-alpha reductase inhibitor-finasteride . Explants were cultured over a nine-week period in RPMI-1640 media supplemented with Penicillin-Streptomycin 4% and Fetal Bovine Serum 10% . Cultures were divided into one control group, one with testosterone added (1.25 x 10(4) micrograms/ml) and one which received testosterone (1.25 x 10(-4) micrograms/ml) plus finasteride (0,0038 mg/ml) . Control explants showed involutive changes throughout the experience, which occurred later in those treated with testosterone and earlier and more marked in the case of finasteride . The testosterone-treated group showed intense positivity for PSA, a marker which reveals specific tissular functions, which remained uniformed in the control group through the entire experiment, and decreased gradually in the finasteride group . In summary, according to our work, culture of organs would be a useful tool for an in vitro evaluation of the hyperplastic human prostate response to the action of the 5-alpha reductase inhibitor, finasteride.

Eur J Gastroenterol Hepatol, 1996 Apr, 8(4), 393 - 8
Inhibitory effect of gastrin peptides on triacylglycerol secretion in Hep G2 cells; Lindholm M et al.; OBJECTIVES: To determine whether human liver cells respond to gastrin peptides by reducing their secretion of triacylglycerols, as recently observed in rat hepatocytes . DESIGN: Cells of the human hepatoblastoma cell line Hep G2 were incubated with pentagastrin and heptadeca gastrin, followed by lipid analysis of media and cells . METHODS: Cultivation of cells; analyses of triacylglycerols, cholesterol and protein; statistical analysis . RESULTS: As the secretion of triacylglycerols in Hep G2 cells incubated with basal medium (Eagle's minimum essential medium with non-essential amino acids, penicillin, streptomycin and glutamine) is only about 20% of the triacylglycerol secretion reported for human liver cells, the possibility of detecting statistically significant effects of gastrin peptides on lipid secretion is reduced compared to the situation in normal hepatocytes . However, by a combined addition of 0.1 mmol/l albumin-bound oleate, 10 mmol/l sodium butyrate and 0.1 mg/ml dextran sulphate to the basal medium, the triacylglycerol secretion in Hep G2 cells was found to be more than twice as high as in cells incubated with basal medium alone . With this supplemented medium a biphasic concentration-dependent statistically significant inhibitory effect of both pentagastrin and heptadeca gastrin on triacylglycerol secretion in Hep G2 cells was demonstrated . CONCLUSION: These results indicate that gastrin peptides may play a role in the regulation of lipoprotein secretion in human liver cells.

Thorax, 1996 Apr, 51(4), 449 - 50
Transphrenic dissemination of actinomycosis; Zeebregts CJ et al.; Thoracic actinomycosis is an uncommon disease and often presents difficulty in diagnosis . Two cases are presented in which thoracic actinomycosis produced fistulae between the thoracic and abdominal cavities . Surgical drainage and high dose penicillin for at least 4-6 months was the treatment of choice.

Thorax, 1996 Apr, 51(4), 385 - 8
Community acquired pneumonia in adults: a study comparing clinical features and outcome in Africa (Republic of Guinea) and Europe (France); Sow O et al.; BACKGROUND: Community acquired pneumonia is the most common cause of death from infectious disease both in western and developing countries . A study was carried out in Conakry, Republic of Guinea and Tours, France in order to compare signs, symptoms, severity of illness, risk factors, and clinical outcome of community acquired pneumonia in adult patients admitted to hospital . METHODS: The study was performed in the cities of Conakry and Tours over the same one year period . Patients with nosocomial pneumonia, tuberculosis, and those who were HIV positive were excluded . Data were recorded on the same forms in both centres . A severity score was calculated according to American Thoracic Society criteria . Follow up was evaluated at days 2, 7 and 15 . RESULTS: A total of 333 patients (218 from Conakry, 115 from Tours) were included in the study with a diagnosis of community acquired pneumonia, with or without lung abscess or pleural effusion . Mean age was higher and pre-existing illness rate, dehydration, agitation, and stupor were more frequent in patients in Tours . Respiration rates of > 30 breaths/min and the incidence of crackles were identical in the two centres . Fever above 39 degrees C, initial shock, chest pain, and herpes were significantly more frequent in Conakry . Initial chest radiographic abnormalities were similar in the two groups, ranging from unilateral pleuropulmonary involvement (89% and 83% in Conakry and Tours, respectively) to diffuse patchy parenchymal disease . Parapneumonic effusion was present in 17% and 16% of the patients of Conakry and Tours, respectively . Pneumonia was considered to be severe in 33% and 42% of the patients, respectively . In Conakry first line antibiotic therapy was penicillin alone (2 million units a day) for 197 patients (90%) and second line antibiotic therapy was prescribed for 25 patients (12%) . In Tours first line therapy consisted of a single antibiotic (amoxicillin, third generation cephalosporins) for 65 patients (57%) and second line antibiotic therapy was prescribed for 55 patients (48%) . The clinical outcome was similar in Conakry and Tours: 88% and 85% of patients, respectively, were afebrile or clinically cured at day 15 . The mortality rate was similar (6% and 8%, respectively) . CONCLUSIONS: The problems encountered in the management of community acquired pneumonia are quite different in western and developing countries . This study shows that low doses of penicillin can cure 90% of African patients with pneumonia as effectively as more aggregative treatments in European patients who are both older and have greater comorbidity . Although pneumococci with reduced penicillin sensitivity occur in western countries, this does not seem to be the case in black Africa . For these reasons, low doses of penicillin or amoxicillin remain good first line treatment.

Vet Hum Toxicol, 1996 Apr, 38(2), 89 - 91
Putative effect of silymarin on sawfly (Arge pullata)-induced hepatotoxicosis in sheep; Thamsborg SM et al.; The prevention of hepatotoxicity from sawfly larvae (Arge pullata) was studied in 8 lambs by using silymarin, a botanical compound isolated from Silybum marianum . Of 2 lambs dosed orally with larvae only, 1 had a marked toxic response whereas the other responded poorly as judged from clinical parameters, blood biochemistry and pathology . Two lambs treated with penicillin, glucose and silymarin 7 and 24 h after larvae dosing were not affected by toxicosis, whereas 2 lambs treated similarly but without silymarin responded intermediate to the other 2 groups . Our study suggests a favorable effect using silymarin in treatment of sawfly larvae-induced ruminant hepatotoxicosis.

J Nucl Med, 1996 Apr, 37(4), 661 - 4
HMPAO as a regional cerebral blood flow tracer at high flow levels; Duncan R et al.; HMPAO is being used extensively to image rCBF during focal seizures in humans . It is, however, theoretically possible that back-diffusion of tracer causes retention to fall as flow rises at high levels . METHODS: We used a double label 99mTc-HMPAO/14C-IAP autoradiographic technique to compare HMPAO retention and regional cerebral blood flow in penicillin induced focal seizures in rats . RESULTS: Using this protocol, flows of up to 717 ml/100 g per min were observed . The same pattern of uptake was seen on IAP and HMPAO autoradiographs, with the exception of relatively high HMPAO uptake in the choroid plexus, in the fissures and, in one animal only, the supramammilary nucleus . Correlation of HMPAO retention and blood flow showed a linear relationship up to 200 ml/100 g per min all animals . HMPAO retention then showed a falloff in its rise with blood flow, but was still increasing, even at the highest flows seen . At 700 ml/100 g/min, HMPAO retention was 20% of that expected from a linear relationship . CONCLUSION: HMPAO is a suitable tracer of rCBF at high flows and is unlikely to produce anomalous images in human focal seizures.

Nord Med, 1996 Apr, 111(4), 103 - 8
{Epidemiology of penicillin-resistant pneumococci}; Kristinsson KC; Penicillin-resistant and multiresistant pneumococci occur throughout the world and at high prevalence in certain areas . Pneumococci resistant of cefotaxime and ceftriaxone have so far become established in Spain, South Africa and the USA, and the occurrence of such strains was recently reported in the UK . In Iceland, the first penicillin-resistant pneumococci were identified in December 1988, and by 1993 the prevalence was 20 percent . The risk factors appear to be the congregation of children at day-care centres, excessive consumption of antibiotics, and the common use of the sulphamethoxazole-trimethoprim combination (co-trimoxazole) . The consumption of antibiotics in Iceland has been reduced, and the incidence of resistant pneumococci is somewhat lower than formerly.

Chest, 1996 Apr, 109(4), 1109 - 11
Actinomyces odontolyticus thoracopulmonary infections . Two cases in lung and heart-lung transplant recipients and a review of the literature; Bassiri AG et al.; We present the first case of mediastinitis and the third case of pneumonia attributed to Actinomyces odontolyticus . The first patient presented 10 months after single-lung transplant with a subacute apical infiltrate in the native lung and responded to therapy with oral penicillin . The second patient developed pyogenic mediastinitis 25 days after a heart-lung transplant and required sternal debridement and intravenous penicillin . We also review the literature on thoracopulmonary infections due to A odontolyticus.

J Infect Dis, 1996 Apr, 173(4), 870 - 6
Invasive pneumococcal infections in human immunodeficiency virus-infected children; Mao C et al.; Invasive pneumococcal infection (IPI) is the most common serious bacterial infection in human immunodeficiency virus (HIV)-infected children . Data from a population-based pediatric HIV surveillance project were used to determine the incidence of IPI in HIV-infected children and to conduct a case-control study assessing potential risk factors for IPI in HIV-infected children . There were 50 episodes of IPI and a cumulative incidence of 6.1 cases/100 patient-years through age 7 years . Children with IPI were more likely to have a prior AIDS diagnosis (odds ratio, 4.2; 95% confidence interval, 1.2-15.1) and higher levels of IgG and IgM (P=.01) than were controls . In a separate case-control study, the manifestations of IPI in HIV-infected children were compared with those in HIV-negative controls . Focal complication rates in the 2 groups did not differ; however, HIV-infected children were less likely than controls to have leukocytosis (P<.001) and more likely to have isolates with penicillin resistance (P=.03).

Am J Med Sci, 1996 Apr, 311(4), 180 - 5
Case report: penicillin-resistant pneumococcal meningitis: navigating a therapeutic minefield; Greene GS et al.; Pneumococcal meningitis is a common infection in adults for which penicillin has long been the drug of choice . Optimal treatment has recently become controversial, however, owing to an alarming increase in the number of penicillin-resistant isolates . The authors report a representative case of meningitis caused by such an organism, and provide a discussion of the history, mechanisms of resistance, laboratory evaluation, and treatment of these infections . Guidelines for prevention are also reviewed, including a renewed call for utilization of the 23-valent pneumococcal vaccine.

Brain Res, 1996 Mar 25, 713(1-2), 253 - 60
Brainstem stimulation during sleep evokes abnormal rhythmic activity in thalamic neurons in feline penicillin epilepsy; Szymusiak R et al.; Some periods in the sleep-waking cycle are more seizure prone than others . In absence epilepsy, transition periods between nonrapid-eye-movement (nonREM) sleep and waking or REM sleep can be more seizure prone that stable states . One feature of transition periods that is hypothesized to promote seizure activity is the presence of coincident activity in ascending brainstem reticular formation (RF) arousal systems with synchronized thalamo-cortical activity . To evaluate this hypothesis we examined the state-dependent effects of low intensity RF stimulation on thalamic single unit activity in control conditions and following systemic penicillin-G administration to adult cats . In control conditions, RF stimulation during waking and REM sleep typically evoked a short-latency action potential in thalamic neurons . The same stimulation during nonREM sleep commonly evoked a high frequency burst of action potentials followed by a period of suppressed discharge . In 16/26 neurons, a second rebound burst of action potentials followed the period of discharge suppression . The average interval between the initial and rebound bursts was 75.1 +/- 6.0 ms, which was similar to the interburst interval recorded in these same cells during spontaneous EEG spindles . Following administration of penicillin-G, RF stimulation during nonREM sleep evoked high frequency burst firing, followed by 1-2 rebound bursts in 21/22 thalamic neurons . The average evoked interburst interval was 152.5 +/- 7.3 ms, a value comparable to the interburst interval displayed by these same cells during spontaneous spike-wave seizure activity (157.8 +/- 8.7 ms) . RF-evoked rhythmic discharges were dependent upon the presence of thalamocortical synchronization, as responses evoked during waking and REM sleep in penicillin treated cats were similar to those observed in control conditions.

Rev Med Chil, 1996 Mar, 124(3), 359 - 62
{Systemic leptospirosis as a cause of multiple organ failure . Report of a case}; Garrido R et al.; Leptospirosis is a world-spread zoonosis that is incidentally acquired by humans . It causes a diphasic febrile illness in which the Weil syndrome is its severest form, with renal, hepatic, clotting and central nervous system involvement . We report a 73 years old male, that was admitted to an intensive care unit with multiple organ failure due to leptospirosis . The clinical picture initially resembled a sepsis due to biliary tract obstruction and was operated, not finding a biliary tract obstruction . Considering the history of a fall to sewed waters, leptospirosis was suspected and treatment with penicillin was started, obtaining a full recovery of the patient.

Clin Oral Implants Res, 1996 Mar, 7(1), 38 - 47
A novel model system for the study of experimental guided bone formation in humans; Hammerle CH et al.; The aim of the present experiment was to test a novel model system, designed to obtain human specimens of regenerated and also newly regenerated jaw bone, for the study of the biological events under a variety of conditions . Following information and disclosure of possible risks associated with a minor oral surgical procedure, 9 systemically healthy subjects (5 men, 4 women, mean age 31.7 years) signed consent forms and volunteered to participate in this study . Hollow test cylinders with an outer diameter of 3.5 mm, an inner diameter of 2.5 mm, and 4 mm in height were used . They were manufactured from commercially pure titanium and exhibited a highly polished inner surface and a titanium plasma sprayed outer rough surface . A mucoperiosteal flap was raised in the retromolar area of the mandible corresponding to standard retrained third molar surgery . Following flap reflection a standardized hole was drilled through the cortical bone into the bone marrow using round burs . The congruent test cylinders were firmly placed into the prepared bony bed yielding primary stability . One-and-a-half to 2 mm of the test device were submerged below the level of the surrounding bone, while the remainder surpassed the level of the bone surface . The bone-facing end of the cylinder was left open, while the coronal soft tissue facing end was closed by an ePTFE-membrane . The flap was sutured to obtain primary wound closure . In order to prevent infection, penicillin was prescribed systemically and oral rinses of chlorhexidine were administered . After 2, 7, and 12 weeks one test device including the regenerated tissue was surgically harvested, while after 16, 24 and 36 weeks respectively, 2 devices were harvested and processed for soft or hard tissue histology or histochemistry . The two surgical procedures and the presence of the test cylinders during the time of healing were well tolerated by the volunteers . In all 9 subjects generated tissue could successfully be harvested . The tissue generated after 2 and 7 weeks presented with a cylindrical shape, whereas the specimens harvested at 12 weeks and thereafter resembled the form of an hourglass . Specimens of 12 weeks and less regeneration time were almost entirely comprised of soft tissue, while specimens with regeneration time of 4 months and more were composed of both soft and increasing amounts of mineralized tissue . It is concluded that the presented model system is suitable to study temporal dynamics and tissue physiology of bone regeneration in humans with minimal risk for complications or adverse effects to the volunteers.

J Appl Physiol, 1996 Mar, 80(3), 924 - 30
Respiratory motor nerve activities during experimental seizures in cats; Terndrup TE et al.; We evaluated respiratory motor nerve activities during experimental seizures induced with subcortical penicillin . The activities of the phrenic (PH), nasolabial (NL), and hypoglossal (HG) nerves and the recurrent laryngeal motor branches to the thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles were analyzed in 13 anesthetized, vagotomized, paralyzed, and ventilated cats . During ictal and interictal phases of seizures, nerve activities became irregular and peak integrated nerve activities increased, particularly in the case of the PH nerve . The ictal phase of seizures was associated with increased tonic activity and decreased phasic respiratory discharges, particularly in the cases of the HG, NL, and PCA nerves . During some prolonged ictal discharges, entrainment of nerve activities by cortical spiking was associated with irregular uncoordinated activation, particularly in the TA nerve . These studies help explain respiratory impairment during seizures by providing evidence of impaired coordination between activation of muscles that regulate upper airway patency and activation of the diaphragm.

Infection, 1996 Mar-Apr, 24(2), 170 - 3
Therapy of Lyme borreliosis in children; Krbkova L et al.; A retrospective open study was conducted to determine the efficacy of penicillin and ceftriaxone in children with skin manifestations of Lyme borreliosis (solitary erythema migrans, multiple erythemata, borrelial lymphocytoma) and neuroborreliosis, respectively . One hundred sixty children were treated with penicillin and 41 with ceftriaxone for an average of 12 days . Serum antibodies to borreliae were determined before therapy and 2-3 and 4-6 weeks thereafter . At admission 44%/26%,8%/42%, and 40%/35% of erythema migrans, borrelial lymphocytoma and neuroborreliosis patients, respectively, were IgM/IgG positive . Four to 6 weeks after treatment the percentage of seropositives was 20%/15%,8%/61%, and 21%/44%, respectively . A 3 months follow-up was completed with 151 children . No child showed clinical evidence of illness, nor were there abnormalities in laboratory parameters.

Curr Opin Cardiol, 1996 Mar, 11(2), 126 - 30
Rheumatic heart disease; Feldman T; Rheumatic heart disease seems in many ways emblematic of an older era in medicine, without any prospects of new development or change in the current era . Many new findings have come to light in the past few years regarding this illness, which has a relatively low prevalence in the United States . Not only have the diagnostic Jones criteria for acute rheumatic fever changed, but substantial advances have been made in the use of penicillin prophylaxis for recurrent rheumatic attacks, the use of mitral valve repair or reconstruction for rheumatic mitral regurgitation, the management of rheumatic, aortic, and mitral valve disease, and the application of balloon commissurotomy for mitral stenosis . This review details some of these advances.

Clin Exp Allergy, 1996 Mar, 26(3), 335 - 40
Anaphylaxis to penicillins after non-therapeutic exposure: an immunological investigation; Blanca M et al.; BACKGROUND: There are instances where individuals may come into contact with penicillins without being aware of it . This non-therapeutic exposure from different sources may cause sensitization and even clinical manifestations in subjects allergic to penicillins . OBJECTIVE: To determine the capacity that inadvertent contact with penicillins may have in inducing resensitization and symptoms in patients diagnosed as allergic to penicillins who were followed over a long period of time after their initial evaluation . METHODS: A follow-up study of penicillin-allergic subjects who agreed to be regularly tested for in vitro and in vivo control of their sensitivity . Skin tests were carried out with major and minor determinants of benzylpenicillin (BPO and MDM), amoxicillin (AX), and ampicillin (AMP), and specific IgE antibodies were determined by radioallergosorbent test (RAST) . A questionnaire was sent to and answered by the subjects in order to see if they experienced symptoms at any time during the follow-up period . In addition, if any unexplained symptoms occurred, a bleeper system was used to contact the allergy centre . RESULTS: Seven subjects experienced anaphylactic reactions with no obvious cause . At the time of their initial allergic reaction, which was caused by exposure to prescribed penicillin, the subjects had one or more positive skin tests and/or RAST results to penicillin related reagents . However, over the following 2-4 years all their tests became negative . After reporting their unexplained reaction all seven had one or more positive skin tests and/or RAST results again and when retested 1 week later RAST measurements showed that levels of penicillin-specific IgE were maintained or increased . None of the subjects had knowingly received penicillin but the questionnaire showed that six had been exposed to it and in the seventh case exposure was likely . In two cases contact was by sexual intercourse with a partner who was receiving penicillin, three subjects had handled penicillin formulations and one had drunk from a glass previously used for giving penicillin . In the seventh case exposure could have occurred whilst in hospital for surgery, although this was not proven . CONCLUSIONS: these results show that non-therapeutic exposure to penicillin can cause severe symptoms and that in vitro and in vivo testing can help in the diagnosis of such cases.

J Investig Allergol Clin Immunol, 1996 Mar-Apr, 6(2), 89 - 93
Specific IgE determination in the diagnosis of beta-lactam allergy; Sanz ML et al.; Allergic reactions to beta-lactams are the most frequent adverse reactions to drugs, but conventional methods of detection of beta-lactam specific IgE detect only a low number of positivities . In this study we evaluated the diagnostic reliability of one of these methods (CAP FEIA, Pharmacia) which has been proven very useful in inhalant and food specific IgE determinations . We studied specific IgE to penicillin G, penicillin V, amoxicillin and ampicillin in 1078 patients who had been diagnosed with an adverse reaction to beta-lactams, and out of this group, in a selected subgroup of 149 patients with a very suggestive clinical history of beta-lactam anaphylactic reaction . Also, positivity of specific IgE was studied in a group of 58 patients with a clinical history of immediate hypersensitivity to beta-lactams and with positive skin tests, and positivity of skin tests was studied in a subgroup of 13 patients with positive specific IgE . To increase the sensitivity of IgE determinations, we concentrated 5-fold the sera from six selected patients . In the first group we found that penicillin G specific IgE was positive in 28% of the cases when considering a cutoff > or = class 1, and 6% when considering a cutoff > or = class 2 . For penicillin V, positivities were 9% (> or = class 1) and 4% (> or = class 2) . In the second group, we found 31.81% sensitivity and 88.57% relative specificity of CAP FEIA with respect to the skin test . In the group of 58 patients with a clinical history of immediate hypersensitivity to beta-lactams, we found a disagreement between skin testing and specific IgE determination in 28.2%, and a positive agreement in 9.4% of the cases . After sera concentration, there was a significant increase (p < 0.001), from 0.58 to 1.61 kU/l, in beta-lactam specific IgE . Our results suggest that skin testing offers greater reliability and sensitivity than beta-lactam specific IgE determination by CAP FEIA.

Leber Magen Darm, 1996 Mar, 26(2), 109 - 12
{Acute abdomen in abdominal actinomycosis}; Muller R et al.; The case of a female patient aged 34 suffering from abdominal actinomycosis is reported . She underwent emergency surgery for an abscess-forming tumour infiltrating the lateral abdominal wall and giving rise to the clinical picture of acute abdomen . The casuistry is complemented by two further case histories of actinomyces infections in patients with fistulas of the anal region and pilonidal sinus respectively . Abdominal actinomycosis presents itself as a rare chronic bacterial inflammation, usually located in the right lower abdomen, with local abscess or fistula formation as well as tumour-like infiltration of the surrounding tissues . Exceptionally, the diagnosis is ascertained prior to surgery . Postoperative antibiotic therapy with penicillin for several months ist essential.

Minerva Med, 1996 Mar, 87(3), 113 - 5
{Progressive paralysis . A case report}; Trotta M et al.; STUDY OBJECTIVE . A fairly uncommon case of neurosyphilis is reported in a not immunocompromised patient . CASE REPORT . A case of general paresis in a 40 year-old male with the recent onset of mania is described . Psychiatric anamnesis was negative . Neurologic examination was negative . Laboratory tests were performed and serologic tests for syphilis were positive . Cerebrospinal fluid (CSF) examination showed 80 leukocytes/mm3, a reactive Venereal Disease Research Laboratory (VDRL) and normal protein concentration . CSF gamma globulin with an oligoclonal pattern and abnormal IgG index were found . A test for antibodies to Human Immunodeficiency Virus (HIV) was negative . The patient underwent a high dose intravenous penicillin G regimen for two weeks . A follow-up six months later showed a normal CSF even though the IgG index was still abnormal and the mental status was unchanged . CONCLUDING REMARKS . The authors suggest that patients with neurologic and/or psychiatric symptoms with a recent onset and a reactive VDRL should undergo a CSF examination to exclude a possible neurosyphilis.

J Accid Emerg Med, 1996 Mar, 13(2), 114 - 5
Patients' knowledge about their drug allergies; Wyatt JP; OBJECTIVE--To investigate the nature and accuracy of information carried by patients about their drug allergies . SUBJECTS: 2500 new adult patients . SETTING--Accident and emergency department of a tertiary referral centre . METHODS: Patients were questioned about drug allergies . Where they claimed allergies, general practitioners were contacted for corroboration . RESULTS--242 patients (9.7%) claimed 276 allergies; 32 different drugs were implicated . Penicillin was implicated most often (151 patients); 38 patients could not remember what they were allergic to; 21 described severe reactions, but four could not remember the drugs involved . Only seven patients carried evidence of their allergies . General practitioners were contacted about 240 of the drug allergies; only 114 were confirmed as described . CONCLUSIONS--Many patients who believe themselves to have drug allergies are poorly informed about them . Emergency prescribing for these patients may risk anaphylaxis . The future acceptance of "Smart cards"would reduce this risk . In the meantime, patients with drug allergies should be strongly encouraged to carry evidence of their allergies.

Mol Pharmacol, 1996 Mar, 49(3), 494 - 504
Homomeric beta 1 gamma-aminobutyric acid A receptor-ion channels: evaluation of pharmacological and physiological properties; Krishek BJ et al.; The ubiquitous distribution of gamma-aminobutyric acid A (GABAA) receptor beta subunits throughout the central nervous system is in accord with a vital role in receptor structure and function . Homomeric beta subunits have been reported to be either GABA-gated or capable of forming anion-selective channels that lacked GABA-gating properties . With electrophysiological recording techniques, we examined the properties of the murine Beta 1 subunit, addressed whether the homomeric receptor is expressed independently from the host cell's genome, and investigated whether these channels can open spontaneously . Murine beta 1 subunits, expressed in Xenopus oocytes or A293 cells, were unaffected by GABA or bicuculline; however, the resting membrane conductances were reduced by picrotoxin, zinc, or penicillin-G . In comparison, the expression of bovine beta1 subunits formed GABA-gated C1- channels . For murine beta 1 subunits, both pentobarbitone and propofol increased the membrane conductance, although the benzodiazepine ligands flurazepam, flumazenil, and methyl-6,7-dimethoxy-4 ethyl-beta-carboline-3-carboxylate were inactive . Oocytes injected with murine beta 1 cRNA in the presence of actinomycin D (to block host cell DNA transcription) expressed beta1 channels that were indistinguishable from those derived from previous cDNA injections in cells capable of normal transcription . Single-channel recording from murin beta 1 cDNA-injected oocytes revealed spontaneously opening channels with a main state conductance of 18 pS . Picrotoxin inhibited the channel openings by reducing the probability of opening . We concluded that murine beta 1 subunits can form functional ion channels that are not gated by GABA but can be closed by some noncompetitive GABA antagonists . Interestingly, previous observations of spontaneously opening ion channels with properties similar to those found for the murine beta 1 receptor suggest that a limited expression of homomeric beta subunit-ion channels may exist in vivo.

Z Naturforsch {C}, 1996 Mar-Apr, 51(3-4), 243 - 8
Interaction of penicillin G with the human erythrocyte membrane and models; Suwalsky M et al.; Penicillin G (PEN) is a widely used antibiotic whose mechanism of action is related to the interference with the synthesis of bacteria cell wall . In order to evaluate its perturbing effect upon human cell membranes PEN was made to interact with human erythrocytes, isolated resealed human erythrocyte membranes and molecular models . The latter were multibilayers of the phospholipids dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) as well as DMPC large unilamellar vesicles . These studies were performed by scanning electron microscopy, fluorescence spectroscopy and X-ray diffraction methods . The observed results coincide in that PEN did not exert any significant effect upon the structures of the red cell membrane neither on its molecular models . This is in agreement with its reported lack of major toxicity and hematological reactions.

J Bacteriol, 1996 Mar, 178(6), 1707 - 11
Identification and overexpression in Escherichia coli of a Mycobacterium leprae gene, pon1, encoding a high-molecular-mass class A penicillin-binding protein, PBP1; Basu J et al.; Cosmid B577, a member of the collection of ordered clones corresponding to the genome of Mycobacterium leprae, contains a gene, provisionally called pon1, that encodes an 821-amino-acid-residue high-molecular-mass class A penicillin-binding protein, provisionally called PBP1 . With similar amino acid sequences and modular designs, M . leprae PBP1 is related to Escherichia coli PBP1a and PBP1b, bienzymatic proteins with transglycosylase and transpeptidase activities . When produced in E . coli, His tag-labelled derivatives of M . leprae PBP1 adopt the correct membrane topology, with the bulk of the polypeptide chain on the surface of the plasma membrane . They defy attempts at solubilization with all the detergents tested except cetyltrimethylammonium bromide . The solubilized PBP1 derivatives can be purified by affinity chromatography on Ni2+-nitrilotriacetic acid agarose . They have low affinities for the usual penicillins and cephalosporins.

Kansenshogaku Zasshi, 1996 Mar, 70(3), 264 - 7
{A case of Lyme borreliosis which was suspected to be caused by Borrelia japonica infection in Shizuoka, Japan}; Masuzawa T et al.; We report a case of Lyme borreliosis (Lyme disease) found in Shizuoka City, Japan which was suspected to be caused by Borrelia japonica infection . A 8-year-old female was bitten on her head by a tick at a camping ground, near Tamagawa, Shizuoka . The tick was removed by the patient and was discarded before species identification . After one week, lymph node swelling with tenderness developed on her left neck . She consulted a local pediatrician and was suspected to have upper respiratory infection . As oral antibiotic, cefaclor was not effective, the patient was referred to us . The patient's serum showed positive reaction with Lyme Borreliosis ELISA kit (Dakopatts, Denmark) using Borrelia burgdorferi flagellum as antigen . The serum also gave positive results with home-made ELISA to B . japonica strain IKA2, which was isolated from I . ovatus, but not with other borrelial strain isolated in the United States, Europe, and from I . persulcatus and wild rodent in Japan . In western blotting, the serum reacted with flagellin and outer surface protein A (OspA) of B . japonica . We diagnosed her as Lyme disease and got a successful result with oral penicillin, sultamicillin . From a result of our field tick survey, we have not collected I . persulcatus around the area where the patient had a tick bite . These findings indicated that Lyme disease was caused by B . japonica infection with I . ovatus bite.

Nat Struct Biol, 1996 Mar, 3(3), 290 - 7
A potent new mode of beta-lactamase inhibition revealed by the 1.7 A X-ray crystallographic structure of the TEM-1-BLIP complex; Strynadka NC et al.; The structure of TEM-1 beta-lactamase complex with the inhibitor BLIP has been determined at 1.7 angstrom resolution . The two tandemly repeated domains of BLIP form a polar, concave surface that docks onto a predominantly polar, convex protrusion on the enzyme . The ability of BLIP to adapt to a variety of class A beta-lactamases is most likely due to an observed flexibility between the two domains of the inhibitor and to an extensive layer of water molecules entrapped between the enzyme and inhibitor . A beta-hairpin loop from domain 1 of BLIP is inserted into the active site of the beta-lactamase . The carboxylate of Asp 49 forms hydrogen bonds to four conserved, catalytic residues in the beta-lactamase, thereby mimicking the position of the penicillin G carboxylate observed in the acyl-enzyme complex of TEM-1 with substrate . This beta-hairpin may serve as a template with which to create a new family of peptide-analogue beta-lactamase inhibitors.

Nat Struct Biol, 1996 Mar, 3(3), 218 - 21
Cure for a crisis?
Thunnissen AM, Dijkstra BW.
The first look at the three-dimensional structure of an essential penicillin binding protein from a human pathogen, and its complex with a beta-lactam antibiotic provides hope for the future design of improved antibiotics.

J Biotechnol, 1996 Feb 28, 45(2), 149 - 64
Growth energetics and metabolic fluxes in continuous cultures of Penicillium chrysogenum; Henriksen CM et al.; Continuous cultures of the penicillin producing fungus Penicillium chrysogenum have been analyzed with respect to the macromolecular composition of the mycelium . All cultivations were carried out using a chemically defined medium with glucose as the growth limiting component . Biomass was harvested at steady state and analyzed for proteins, lipids, RNA, DNA, and carbohydrates . Carbohydrates present in the cell wall, i.e., glucans and chitin, and carbohydrates serving as storage materials, i.e., glycogen, were measured . It was observed that the levels of DNA and lipids are relative constant, whereas the proteins and stable RNA levels increase with the specific growth rate and the total amount of carbohydrates decreases with the specific growth rate . Glycogen is only present in small amounts, decreasing with the specific growth rate . As an average the measured macromolecules account for 77 +/- 2% (w/w) of the biomass . On the basis of estimations of the metabolic costs for biosynthesis and polymerization of the different macromolecules the total ATP and NADPH requirements for cell biosynthesis from glucose and inorganic salts, i.e., YxATP,growth and YxNADPH, have been quantified . The biosynthesis of 1 g biomass was calculated to require 39.9 mmol of ATP and 7.5 mmol of NADPH when cytosolic acetyl-CoA is formed from citrate by citrate lyase and oxaloacetate is recycled back into the TCA cycle . Other pathways of acetyl-CoA biosynthesis have been considered . The calculations show that the different biosynthetic routes for generating cytosolic acetyl-CoA have a significant influence on the theoretical value of ATP and NADPH requirements for cell biosynthesis . Combining a detailed stoichiometric model for growth and product formation of P . chrysogenum with experimental data on the macromolecular composition of P . chrysogenum and precise measurements of substrate uptake and product formation the intracellular flux distribution was calculated for different cultivation conditions.

Dtsch Med Wochenschr, 1996 Feb 23, 121(8), 237 - 40
{Purulent pericardial effusion with tamponade: a rare initial manifestation of o pneumococcal infection}; Moller A et al.; HISTORY AND FINDINGS: A 70-year-old man, admitted for a haemorrhoid operation, suddenly went into circulatory shock (heart rate 150/min, blood pressure 100/70 mm Hg), necessitating transfer to an intensive care unit . His neck veins were prominent and he had a paradoxical pulse . Heart sounds were distant and there was an arrhythmia (atrial fibrillation in the ECG) . No murmurs were heard . Breath sounds were decreased, especially in the lung bases . INVESTIGATIONS: Differential blood count showed 30% stab cells with 12,200 white cells per microliter . Erythrocyte sedimentation rate was 118 mm in the first hour, C-reactive protein was raised to 11.8 mg/dl . There was a partially compensated respiratory acidosis (pH 7.12; pO 93.4 mm Hg; pCO 16.3 mm Hg; base deficit -22.6 mmol/l) . In the chest radiogram the cardiac silhouette was greatly enlarged bilaterally . The echocardiogram demonstrated a large pericardial perfusion with a "swinging heart" . TREATMENT AND COURSE: At pericardial needle puncture 700 ml of amber-coloured fluid, containing pneumococci, were aspirated with immediate circulatory improvement . Penicillin, 10 mill.U twice daily for 13 days, was administered intravenously, followed by amoxycillin, 1 g three times daily by mouth, for a further 15 days . In addition he was given anti-inflammatory treatment with diclofenac and methylprednisolone . Despite this pericardial effusion recurred after 14 days and 600 ml of sterile fluid were removed . Subsequently the inflammatory signs disappeared . Three months later no effusion was present and there were no signs of constrictive pericarditis.

Arch Intern Med, 1996 Feb 12, 156(3), 321 - 5
Serologic response to treatment of syphilis in patients with HIV infection; Yinnon AM et al.; BACKGROUND: Much controversy exists concerning the manifestations, therapy, and response to treatment of syphilis in patients coinfected with the human immunodeficiency virus (HIV) . OBJECTIVE: To assess the effect of HIV infection on the serologic response to treatment of patients with syphilis . METHODS: Sixty-four HIV-seropositive patients with syphilis were matched with 64 patients with syphilis who were HIV negative . Matching criteria included age (+/- 5 years), sex, race, initial rapid plasma reagin (RPR) titer (+/- 1 dilution), and stage of syphilis at entry . There were 26 matched patients with early syphilis, 26 matched patients with late syphilis, and 12 matched patients with biological false-positive RPR . The HIV-positive patients with early syphilis received three doses of penicillin G benzathine . All other patients received treatment as recommended by the Centers for Disease Control and Prevention, Atlanta, Ga . Our study's major end points were clinical and serologic response to treatment . RESULTS: All 16 patients with symptomatic syphilis were cured . No patient developed clinical signs of neurosyphilis during the 12-month follow-up period . Twenty-nine (56%) of 52 HIV-positive patients with early or late syphilis did not have a fourfold decrease in RPR titer 6 months after treatment compared with 20 (38%) of 52 matched controls (P = .06) . No unique characteristics identifying patients who did not respond serologically could be established . The HIV-positive patients with initial RPR less than 1:32 experienced a significantly slower decrease in RPR at 12 months than did the controls (P < .001) . CONCLUSIONS: Patients with syphilis who are HIV positive are less likely to experience serologic improvement after recommended therapy than are patients with syphilis who are HIV negative . Patients with HIV infection who contract syphilis should receive intensive and prolonged follow-up, and consideration should be given to designing alternative regimens.

Med J Aust, 1996 Feb 5, 164(3), 146 - 9
Acute rheumatic fever and rheumatic heart disease in the top end of Australia's Northern Territory; Carapetis JR et al.; OBJECTIVE: To describe the epidemiological and clinical features of acute rheumatic fever and rheumatic heart disease in the Top End of the Northern Territory . METHODS: A retrospective review (in some instances as far back as the 1960s) of all cases of known or suspected acute rheumatic fever or rheumatic heart diseases, with prospective validation of clinical status where necessary . Cases were ascertained from hospital and community medical clinic records and medical staff; and from records and health staff of 10 rural communities . RESULTS: Three hundred and eighty-six revised Jones criteria-confirmed episodes of acute rheumatic fever were documented in 249 individuals (99% Aboriginal) . The annual incidence of confirmed acute rheumatic fever between 1989 and 1993 was 254 per 100,000 Aboriginal people aged 5 to 14 years . A more accurate estimate of 651 per 100,000 came from 10 rural communities with more complete information . As of 1995, there were 286 people living with established rheumatic heart disease (95% Aboriginal) . The point prevalence of rheumatic heart disease among Aboriginal people was 9.6 per 1000, with a rate of 24 per 1000 in one large rural community . Sydenham's chorea was common, and associated with later rheumatic heart disease in 49% of cases . There was a preponderance of females with acute rheumatic fever, rheumatic heart disease and chorea . CONCLUSIONS: In Aboriginal people in rural northern Australia the incidence of acute rheumatic fever is higher than that reported anywhere in the world, and the prevalence of rheumatic heart disease is among the highest in the world . While continuing attention must be paid to alleviating the causes of these diseases of poverty, immediate action is needed to improve diagnosis of acute rheumatic fever, adherence to secondary benzathine penicillin prophylaxis regimens, and follow-up of rheumatic heart disease cases.

J Formos Med Assoc, 1996 Feb, 95(2), 166 - 9
Concomitant human immunodeficiency virus infection and syphilitic meningitis; Hsieh SM et al.; Syphilis has once again become a public health issue with the advent of human immunodeficiency virus (HIV) infection . We report a 28-year-old Chinese man with recently acquired HIV infection together with early neurosyphilis . His presentation of acute mononucleosis-like syndrome, lymphadenopathy, aseptic meningitis, positive central nervous syndrome and reactive Venereal Disease Research Laboratory test in his cerebrospinal fluid helped to reach the diagnosis . Paired serum Western blot tests for HIV infection performed 1 month apart revealed either a new appearance or an increasing intensity of bands for p17, p24, p31, gp41, p52, p55, p68, gp120 and gp160 suggesting recently acquired HIV infection . The lymphadenopathy disappeared spontaneously and the neurosyphilis responded well to 14 days of penicillin G therapy . The Western blot pattern, clinical course, laboratory data, and therapeutic response indicated that the acute retroviral syndrome and early central nervous system involvement caused by Treponema pallidum occurred concomitantly.

No To Shinkei, 1996 Feb, 48(2), 183 - 93
{A 56-year-old man with fever, backache and tetraparesis}; Hattori T et al.; We report a 56-year-old man who developed progressive paraparesis . He was apparently well, except for left Bell's palsy which developed on May 9 of 1994, for which he received stellate ganglion block on the left side more than ten times until July 2nd of 1994, when he noted pain in his left shoulder and in his lumbar region . On July 5th, he noted some difficulty in urination . On July 6th, he noted tingling sensation in his four extremities and difficulty in gait . He was admitted to another hospital where he was treated with intravenous infusion of glycerol . After this treatment, his gait and sensory disturbance showed some improvement, however, on July 7th, his shoulder and lumbar pain worsened, and he became unable to stand . His temperature went up to 39 degrees C on the next day . Lumbar CSF on that day contained 119 cells/microliters, 112 mg/dl of protein, and 53 mg/dl of sugar . He was transferred to our hospital on July 14th . His past medical history revealed that he had suffered from frequent bouts of osteomyelitis since the age of 13 years . He was operated on several times on osteomyelitis . He had been treated on his tooth ache until shortly before the onset of the present illness . He also received steroid hormone for his Bell's palsy . On admission, his consciousness varied from alert to stupor . His BP was 150/100 mmHg, HR 98/min and regular, BT 39.4 degrees C . The bulbar conjunctiva appeared somewhat icteric . Otherwise, general physical examination was unremarkable . On neurologic examination, there was no apparent dementia . Higher cerebral functions appeared intact . The optic discs were flat . Pupils were round and isocoric reacting to light and accommodation promptly . Ocular movements were full without nystagmus . Some exophthalmos was noted bilaterally . The sensation of the face and facial muscles were intact . The remaining cranial nerves also appeared intact . Nuchal rigidity was present . He was unable to stand or walk . Muscle strength was markedly diminished in all four limbs; manual muscle testing revealed 1 to 2/5 weakness in both upper and lower extremities bilaterally . Muscle stretch reflexes were decreased or lost in both upper and lower limbs, but the plantar response was extensor on the right . Sensation appeared to be diminished in legs, but detail was not clear because of disturbance of consciousness . Pertinent laboratory findings were as follows: WBC 12,800/microliter, GPT 58 IU/l, total bilirubin 2.65 mg/dl, and CRP 16.8 mg/dl . Cerebrospinal fluid contained 34 cells/microliter (approximately two thirds were neutrophils), RBC 1,110/microliter, 2,949 mg/dl of protein, and 119 mg/dl of glucose; stapylococcus aureus was cultured from the CSF . Myelogram showed a filling defect in the anterior epidural space between the low thoracic and the upper lumbar region . The patient was treated with cephotaxim, aminobenzyl penicillin, and chloramphenicol . On the second hospital day, his BT was still 39 degrees C and he was agitated His weakness was worse than the previous day . Spinal MRI was attempted; as he was agitated 5 mg of diazepam was given intravenously at 4 PM . His respiration was rapid and somewhat shallow . At 6 PM, gadolinium DTPA was injected intravenously; at that time, he was breathing and pupils were 3 mm on both sides . At 6:35 PM, an examiner noted that he stopped breathing; the left pupil was dilated to 5 mm . Cardiopulmonary resuscitation was initiated immediately, and intubation was performed . He was placed on a respirator . His blood pressure did not reach 100 mmHg; he was in deep coma . Cardiac arrest occurred at 8:53 AM on the next morning . The patient was discussed in a neurological CPC . Most of the participants thought that the patient had either spinal epidural empyema or spinal subdural abscess . The question was what might be the original focus of infection . Three possibilities were considered, i.e., stellate ganglion block, teeth infection, and osteomyelitis...

Biochem Mol Biol Int, 1996 Feb, 38(2), 315 - 24
PCR-cloning of the pac gene from E . coli ATCC11105--observations on the expression of a recombinant periplasmic protein; Gumusel F et al.; The penicillin acylase gene (pac) amplified by polymerase chain reaction (PCR) from Escherichia coli (E.coli) ATCC11105 genomic DNA was cloned into pUC9, pEMBL9+ and pCP40 vectors . A penicillin acylase precursor was overexpressed at 26 degrees C from pac-pEMBL9+ and pac-pCP40 constructs transformed into E.coli strains JM109 and pCI857 containing HB101, respectively . With the thermo-inducible pac-pCP40 construct some level of mature alpha and beta subunits and varying degrees of enzyme activity were also detected.

Br J Ophthalmol, 1996 Feb, 80(2), 182 - 4
Widespread ocular use of topical chloramphenicol: is there justifiable concern regarding idiosyncratic aplastic anaemia?
McGhee CN, Anastas CN.
A theoretical but as yet not conclusively proved risk of chloramphenicol induced idiosyncratic aplastic anaemia exists with topical ophthalmic therapy, with the absolute, but highly improbable, maximum risk of death (equalling that of systemic therapy) being 1 in 50,000 to 90,000 . To put this in realistic perspective, one must note that the comparable risk of fatal anaphylaxis resulting from penicillin therapy, from any route, is similar at 1 in 100,000 . Indeed, it has been noted recently that with more than 200 million ocular chloramphenicol products dispensed in the UK in the past 10 years, only 11 reports (all non-fatal) of suspected topical chloramphenicol induced blood dyscrasia have been reported to the Committee on the Safety of Medicines since 1966 . One also has to consider that inadvertent exposure to minute quantities of chloramphenicol (ng/ml) may occur through consumption of livestock that have been treated with chloramphenicol . Broad statements condemning topical chloramphenicol need to be tempered with its proved safety, tolerance, cost, and efficacy while acknowledging an extremely remote risk of the very serious adverse effect of drug induced aplastic anaemia . Risk-benefit assessment is the duty of all prescribing physicians and a decision to prescribe or not prescribe must be made on the basis of personal judgment and an awareness of the statistics in perspective . The only known factor to be associated with vulnerability in the case of topical chloramphenicol is family history . There is no evidence to date that suggests children are any more susceptible than adults.

Sangre (Barc), 1996 Feb, 41(1), 43 - 6
{Sickle-cell anemia in the 1st 5 years of life}; Svarch E et al.; PURPOSE: A programme for antenatal diagnosis of sickle-cell anaemia (SA) and SC haemoglobinopathy (SC) was started in Cuba in 1983 . The purpose of this paper is to report the clinical and haematological data of a group of children diagnosed before birth or in the first few months of life . PATIENTS AND METHODS: Between June 1986 and December 1992, 78 children under 5 years of age were studied at the Haemoglobinpathies Clinic of the Instituto de Hematologia e Inmunologia in La Habana; of them, 53 had SA and 25 had SC, there were 41 girls and 37 boys . A comprehensive questionnaire was carried out during the first visit to the clinic, about the onset of the clinical manifestations, as well as a careful physical examination plus peripheral blood study and Hb A2 and Hb F assay . Parents were informed, and folate and prophylactic penicillin were given orally to the children . RESULTS: The yearly average admissions to hospital were 1.6 +/- 3.8 for SA and 0.1 +/- 0.6 for SC . The average number of veno-occlusive crises was 0.2 +/- 0.6 in SA and 0.1 +/- 0.6 in SC (p < 0.04); the average hand-foot crises were 0.3 +/- 1.1 . for SA and nil for SC . The average number of infections per year was 0.3 +/- 0.6 in SA and 0.1 +/-0.3 in SC, without any significant difference . Significant differences were found in the haemoglobin rates and reticulocyte counts between both haemoglobinopathies . Hb F rate was 7.80 +/- 4.78% in SA and 2.83 +/- 3.45% in SC . CONCLUSIONS: Admission to hospital, hand-foot crises, infections and splenic sequestration are the commonest clinical events during the first 5 years of life . The number of infections episodes decreases with prophylactic oral penicillin, and overacute pneumococcal infection is suppressed . Parent education allows one to early treat sequestration crises, and partial splenectomy avoids repetition of this complication, while preserving the splenic function.

J Epidemiol Community Health, 1996 Feb, 50(1), 62 - 7
Epidemiological survey of rheumatic heart disease among school children in the Shimla Hills of northern India: prevalence and risk factors; Thakur JS et al.; STUDY OBJECTIVE: To determine the prevalence of rheumatic heart disease (RHD) and study the relationship of this disease to factors such as age, sex, housing, and socioeconomic status in Shimla town and the adjoining rural area . DESIGN: A cross sectional survey, carried out by a specially trained examiner in cardiology . SETTING: The study involved high risk school children (5-16 years of age) from Shimla town and the adjoining rural area of Kasumpti-Suni Block in the period 1992-93 . SUBJECTS: A total of 15,080 children on the school register (8120 boys and 6960 girls) were examined generally and specifically for evidence of RHD . MAIN RESULTS: Of the 15,080 children screened, the prevalence of rheumatic fever (RF)/RHD was 2.98 per thousand with no significant difference between the age groups of 5-10 and 11-16 years or in either sex (p > 0.05) . The prevalence was significantly greater in rural schools (4.8/1000) than in urban schools (1.98/1000) (p < 0.05) . There was overcrowding and poor housing in most cases . There were fewer cases of RHD with severe valvular lesions in the younger age group than in the older children . The mitral valve was the valve most commonly affected by RF/RHD . CONCLUSIONS: RHD continues to be a serious health problem . Regular surveys are needed to identify cases early and to ensure secondary prophylaxis with penicillin is given thereby preventing recurrence of RF and progression of the severity of the valvular lesion . Echocardiography is necessary to identify cases of RF/RHD . Strategies for preventing RHD should involve primary prevention to avert the first attack of carditis and strengthening of secondary prophylaxis through improved education and motivation of patients, parents, and physicians.

Biochim Biophys Acta, 1996 Jan 31, 1278(2), 233 - 40
Characterisation of penicillin-G uptake in rabbit small-intestinal brush-border membrane vesicles; Poschet JF et al.; Uptake of penicillin-G has been studied in rabbit intestinal brush-border membrane vesicles (BBMV) . Penicillin-G was transported into the lumen of BBMV via an H+-dependent, Na+-independent uptake system . This was a saturable carrier-mediated process, which adhered to Michaelis-Menten kinetics, having a pH optimum of 4.5 and resulting in a net-negative charge transfer . Vmax was 59 nmol penicillin-G (mg protein)-1 (30s)-1 and Km 22.7 mM . Ampicillin, penicillin-V, cefadroxil, cephalexin, cephalothin, cephradine, L-carnosine, glycyl-L-alanine, glycyl-L-tyrosine and glycylglycylglycine inhibited the uptake of penicillin-G . However, glycylsarcosine stimulated uptake by 92% . Countertransport experiments suggested that this effect took place at the active site of the transporter . Penicillin-G uptake appeared to be mediated via a common transport system shared by penicillins, cephalosporins and peptides.

Bioseparation, 1996, 6(5), 293 - 302
Evaluation of affinity and pseudo-affinity adsorption processes for penicillin acylase purification; Fonseca LP et al.; Affinity ligand (6-Aminopenicillanic acid, Amoxycillin, Ampicillin, Benzylpenicillin and 4-Phenylbutylanzine) of penicillin acylase (EC 3.5.1.11) were attached to hydrophilic gels like Sepharose 4B-CNBr and Minileak 'medium' . Ampicillin and 4-Phenylbutylamine were the affinity ligands that presented the higher concentrations attached to both gels . Penicillin acylase adsorption on these affinity gels was mainly dependent on the activated group of the gel, the affinity ligand attached and the experimental conditions of enzyme adsorption . Under affinity conditions only the ligands Amoxycillin, Ampicillin and 4-Phenylbutylamine, immobilized on Minileak, adsorbed the enzyme from osmotic shock extracts at different pH values . These affinity ligand systems were characterized by low adsorption capacities of penicillin acylase activity (1.2-2.1 IU mL-1 gel) and specific activity (1.5-2.9 IU mg-1 prot) . Under pseudo-affinity conditions all the ligands attached both activated to gels (Sepharose 4B-CNBr and Minileak) adsorbed the enzyme . The affinity gels were characterized by higher values of adsorption capacity (3.7 and 55.6 IU mL-1 gel) and adsorbed specific activity (2.0 and 6.1 IU mg-1 prot) than those observed under affinity conditions . The space arm of Minileak gel, shown to be fundamental to enzyme adsorption under affinity conditions, preferentially adsorbed proteins in relation to the enzyme under pseudo-affinity conditions . However, this effect was partially minimized when the gel was derivatized by the affinity ligands at concentrations higher than 6 mumol mL-1 gel . Ampicillin was the affinity ligand that presented the best results for specific adsorption of penicillin acylase under affinity and pseudo-affinity adsorption processes . The Sepharose 4B-CNBr derivatized gel also presented a good adsorption capacity of enzyme activity (26.8 IU mL-1 gel) under pseudo-affinity adsorption processes.

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