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The aim of this study was to evaluate the performance of three antigenic preparations for serological diagnosis of Helicobacter pylori infection: (i) native antigens from Helicobacter pylori strain N6 or its aflagellated isogenic mutant N6flbA –, or an acellular extract (antigen AgFA) from a pool of six clinical strains; (ii) recombinant antigens consisting of CagA fused to MS2 polymerase and HspA or recombinant UreA and UreB fused to the maltose-binding protein, and (iii) the preparations provided with two commercial kits, the Cobas Core (Roche Diagnostic Systems, France) and the Pylori Stat (BioWhittaker, Belgium). All preparations were used in an enzyme immunoassay to test 92 sera from dyspeptic patients for whom the status of Helicobacter infection was established. Sensitivities were higher (90 to 100%) for the native antigens and the commercial kits than for the recombinant antigens. Specificities were higher than 90%, except with UreA + UreB (42%). The most useful antigens were those extracted from strains N6 and N6flbA –.

Resume But de l'etude. – Notre objectif etait d'etudier la prevalence et les caracteristiques des syndromes de Guillain-Barre (SGB) associes a Campylobacter jejuni et au cytomegalovirus (CMV) dans un centre de prise en charge francais. Patients et methodes. – L'etude a porte sur 264 patients atteints de SGB hospitalises a l'hopital Raymond-Poincare (Garches) entre 1996 et 2001. Les donnees cliniques ont ete recueillies prospectivement. Les serums preleves a l'admission ont ete analyses retrospectivement pour la recherche des anticorps anti-C. jejuni, anti-CMV et antigangliosides GM1 et GM2. Resultats. – Les SGB associes a un profil serologique d'infection recente a C. jejuni etaient les plus frequents (58/264, 22 %) ; ils survenaient majoritairement chez des hommes d'âge mur (âge moyen : 51,3 ans ; sex-ratio H/F : 1,76), generalement apres des troubles gastro-intestinaux (52 %) ; ils etaient souvent purement moteurs (57 %), severes (ventilation artificielle : 40 %) et associes a une reponse IgG et/ou IgM anti-GM1 (44 %). Les SGB associes a une primo-infection par le CMV etaient moins frequents (40/264, 15 %), mais de gravite comparable (ventilation artificielle : 37,5 %) ; ils survenaient principalement chez des femmes jeunes (âge moyen : 35,9 ans ; sex-ratio H/F : 0,82), souvent apres une infection du tractus respiratoire (28 %) ou un syndrome pseudogrippal (15 %), et etaient frequemment associes a des troubles sensitifs (73 %) et a une reponse IgM anti-GM2 (47 %). Conclusion. – C. jejuni et le CMV sont deux causes majeures de SGB en France et sont associes a des tableaux distincts mais de severite comparable.

A case of disseminated infection due to Nocardia nova with subcutaneous popliteal and retrosternal abscesses and lung involvement in an immunocompromised patient is reported. The patient did not respond to sulfonamide therapy. Clinical recovery was obtained upon treatment with imipenem then clarithromycin. Western blot studies revealed an antibody response to a known Nocardia-specific 55-kDa antigen in four successive sera samples collected in the period from the time of admission to seven months later. The resolution of the disseminated nocardiosis and efficacy of the clarithromycin treatment were assessed on the basis of disappearance of the antibodies to the 55-kDa antigen, without invasive sampling.

The role of anaerobic bacteria in ventilator-associated pneumonia (VAP) has been little investigated. In this study we analyzed the incidence of anaerobes in patients with a first episode of bacteriologically documented VAP (10(3)CFU/ml), using protected specimen brushes (PSB). We particularly took care to preserve anaerobic conditions during transport and the microbiological procedure. Two groups were considered: group A with anaerobic bacteria recovered from PSB, with or without anaerobes, and group B with aerobic bacteria only. One hundred and thirty patients were included, 30 (23%) in group A, and 100 (77%) in group B. The main anaerobic strains isolated were Prevotella melaninogenica (36%), Fusobacterium nucleatum (17%), and Veillonella parvula (12%). Univariate analysis demonstrated that patients in group A were younger than those in group B (p0.05) and their simplified acute physiologic score was higher (p0.02). The percentage of patients receiving antibiotics before PSB did not differ significantly between group A (57%) and group B (35%). VAP with anaerobes occurred more often in patients orotracheally intubated than nasotracheally intubated (p0.02). Episodes of VAP involving anaerobic bacteria occurred more often in the first five days (early VAP) than after the fifth day (late VAP) (p0.05). The 3-mo mortality rate was similar in the two groups, but death occurred earlier in group B (p0.01). Multivariate analysis demonstrated that presence of altered level of consciousness (p = 0.0002), higher simplified acute physiologic score (p = 0.003), and admission to the medical ICU (p = 0.02) were the factors independently predisposing to the development of VAP with anaerobes.

The recovery of a Salmonella enteritidis strain that acquired resistance to beta-lactams (including cefotaxime), to aminoglycosides and to chloramphenicol subsequent to cefotaxime therapy is reported. This resistance pattern to beta-lactams was due to the presence of an extended-spectrum beta-lactamase. The isoelectric point of this extended-spectrum beta-lactamase was 6.3. The resistance genes were located on a transferable high-molecular-weight plasmid.

Resume Les auteurs rapportent une etude retrospective des resultats des brossages bronchiques proteges distaux, visant a evaluer indirectement la prevalence des germes anaerobies au cours des pneumopathies. Entre janvier 1989 et decembre 1991 (3 ans), 453 brossages distaux proteges ont ete realises chez 388 patients suspects d'avoir une pneumopathie infectieuse (communautaire ou nosocomiale), hospitalises au CHU de Poitiers. Les brosses, transportees dans un bouillon de Schaedler, etaient aussitot ensemencees sur 3 milieux de culture specifiques, incubes en anaerobiose, puis sur les milieux classiques, incubes en aerobiose. Le seuil significatif d'isolement etait de 103 CFU/ml. Dans 176 cas (38,8 %), un germe (aerobie ou anaerobie) etait isole. La culture anaerobie a ete positive 41 fois, ce qui represente 9 % de l'ensemble des brossages distaux realises et 23 % des brossages avec isolement bacteriologique. La prevalence n'etait pas significativement differente d'un service a l'autre. Dans 14 cas, la culture anaerobie etait positive et la culture aerobie negative, et dans 27 cas, il y avait une association aero-anaerobie. Vingt-sept fois (66 %) la culture anaerobie n'a isole qu'un seul germe, 12 fois (29 %) 2 germes, et 2 fois (5 %) 3 germes. Les germes anaerobies les plus souvent isoles etaient Prevotella melaninogenica (28 %), et Veillonella parvula (17,5 %).

We aimed to study prevalence and features of Campylobacter jejuni and cytomegalovirus (CMV)-associated Guillain-Barré syndromes (GBS) in a French care unit.We studied 264 patients with GBS admitted at Raymond Poincaré hospital (Garches) between 1996 and 2001. Clinical data were obtained prospectively. Sera were collected at patients entry and tested retrospectively for anti-C. jejuni, anti-CMV and antigangliosides GM1 et GM2 antibodies.GBS associated with a serological evidence for a recent C. jejuni infection were the more frequent (58/264, 22%); they affected predominantly men of mature years (mean age: 51.3 years; sex-ratio M/F: 1.76), mostly after a gastrointestinal illness (52%); they were often pure motor forms (57%), were severe (mechanical ventilation: 40%) and associated to an anti-GM1 IgG and/or IgM response (44%). GBS cases involving a primary CMV infection were less frequent (40/264, 15%), but were severe too (mechanical ventilation: 37.5%); they occurred preferentially in young women (mean age: 35.9 years; sex-ratio MF: 0.82), often after respiratory tract symptoms (28%) or an influenza-like syndrome (15%) and were frequently associated with sensory loss (73%) and with an anti-GM2 IgM response (47%).C. jejuni and CMV proved to be major triggering agents of GBS in France. They are associated with distinct presentations, which are both severe.

Summary The authors report a case of brucellosis occuring in a technician involved in the isolation of Brucella melitensis from blood cultures of a patient who has contracted brucellosis in Spain.

To compare the efficacy of different regimens in patients in whom previous Helicobacter pylori eradication therapy has failed.In this study named StratHegy patients (n=287) were randomized to receive one of three empirical triple therapy regimens or a strategy based on antibiotic susceptibility. The empirical regimens were omeprazole, 20 mg b.d., plus amoxicillin, 1000 mg b.d., and clarithromycin, 500 mg b.d., for 7 days (OAC7), clarithromycin, 500 mg b.d., for 14 days (OAC14) or metronidazole, 500 mg b.d., for 14 days (OAM14). In the susceptibility-based strategy, patients with clarithromycin-susceptible strains received OAC14, whilst the others received OAM14. The 13C-urea breath test was performed before randomization and 4-5 weeks after eradication therapy.In the intention-to-treat analysis, the eradication rates for empirical therapies were as follows: OAC7, 47.4% (27/57); OAC14, 34.5% (20/58); OAM14, 63.2% (36/57); it was 74.3% (84/113) for the susceptibility-based treatment (P0.01 when compared with OAC7 and OAC14). In patients receiving clarithromycin, the eradication rates were 80% for clarithromycin-susceptible strains and 16% for clarithromycin-resistant strains; in patients receiving OAM14, the eradication rates were 81% for metronidazole-susceptible strains and 59% for metronidazole-resistant strains.Eradication rates of approximately 75% can be achieved with second-line triple therapy based on antibiotic susceptibility testing. If susceptibility testing is not available, OAM14 is an appropriate alternative.

Thrombin activates human platelets via the cleavage of two protease-activated G-protein coupled receptors (PARs), PAR1 and PAR4 that respond to low and high concentrations of thrombin, respectively. The aim of the present study was to examine the relative contributions of GPIbalpha and ADP receptors in response to thrombin-induced PAR1 and PAR4 stimulation. Platelet responses (aggregation, secretion and calcium mobilization) elicited by low thrombin concentrations were impaired when thrombin interaction with GPIbalpha was blocked. In contrast, blockade of thrombin interaction with GPIbalpha had no effect when PAR4-coupled responses were specifically elicited by high thrombin concentrations in the presence of PAR1 antagonists or after PAR1 desensitization. These results confirmed that unlike PAR1, PAR4 does not require GPIbalpha as a cofactor for thrombin-mediated activation. Both apyrase and selective antagonists of P2Y1 and P2Y12 inhibited PAR1-coupled responses but did not modify PAR4-coupled responses, indicating that in contrast to PAR1, PAR4 signals are not reinforced by ADP secretion and binding to the platelets. These results provide the direct evidence that, in human platelets, GPIbalpha and ADP act in synergy to amplify PAR1 coupled responses while PAR4 is activated independently of GPIbalpha and ADP.

A Campylobacter fetus strain was isolated from an abdominal aortic aneurysm in a 56-year-old man who had no significant chronic illness except arteriosclerosis. The strain was identified on the basis of the usual taxonomic markers and fatty acid profiles. The patient's immunological status regarding Campylobacter fetus was studied by Western blot. The strong immune response observed against the 99 kDa protein of the strain confirms that the S-layer protein is the immunodominant antigen of Campylobacter fetus.

Prevalence of methicillin-resistant Staphylococcus aureus is high in the Poitiers teaching hospital, particularly in the intermediate care facilities. We performed a survey of methicillin-resistant Staphylococcus aureus colonization in the intermediate care facilities and 265 patients were included.Nasal, cutaneous and wound swab cultures were done at the time of admission and at the time of the patients' departure. A decolonization procedure of methicillin-resistant Staphylococcus aureus carriers was performed using nasal application of fusidic acid and different soaps for the skin. At entry, 17.7% of patients were methicillin-resistant Staphylococcus aureus carriers (of at least one location). At departure, 30.4% were methicillin-resistant Staphylococcus aureus carriers. Among methicillin-resistant Staphylococcus aureus non-carriers at entry, 24.3% became methicillin-resistant Staphylococcus aureus carriers.The principal risk factor of carriage was the initial presence of a wound (RR = 3.6). The incidence rate of methicillin-resistant Staphylococcus aureus infection among the 265 patients included was 3%.The systematic screening of patients at the time of admission is expensive and isolation technically hard to manage in the intermediate care facilities. The risk factor we found in this study allow us to propose a 'light' screening limited to patients with wounds.

Several series of low-molecular-mass ligands of the neuropeptide receptor subtype Y5 were prepared using a mixed strategy of synthesis on solid phase and in solution. Collections of single compounds were obtained by an automated parallel procedure which allowed quick variation and investigation of the central spacer moiety, as well as of the aromatic substituents on each side. The strategy of parallel synthesis and screening of partially purified analogs helped to select rapidly potent and selective leads which displayed comparable antagonistic potency against neuropeptide Y activity on the Y5 receptor and better receptor selectivity than the original reference compounds.

Neuropeptide Y (NPY), one of the most abundant peptides in rat and human brains, appears to act in the hypothalamus to stimulate feeding. It was first suggested that the NPY Y1 receptor (Y1R) was involved in feeding stimulated by NPY. More recently a novel NPY receptor subtype (Y5R) was identified in rat and human as the NPY feeding receptor subtype. There is, however, no absolute consensus since selective Y1R antagonists also antagonize NPY-induced hyperphagia. Nevertheless, new anti-obesity drugs may emerge from further pharmacological characterization of the NPY receptors and their antagonists. A large panel of Y1R and Y5R antagonists (such as CGP71683A, BIBO3304, BIBP3226, 1229U91, and SYNAPTIC and BANYU derivatives but also patentable in-house-synthesized compounds) have been evaluated through in vitro and in vivo tests in an attempt to establish a predictive relationship between the binding selectivity for human receptors, the potency in isolated organs assays, and the inhibitory effect on food intake in both normal and obese hyperphagic rodents. Although these results do not allow one to conclude on the implication of a single receptor subtype at the molecular level, this approach is crucial for the design of novel NPY receptor antagonists with potential use as anti-obesity drugs and for evaluation of their possible adverse peripheral side effects, such as hypotension.

A cross sectional study was designed to elucidate the factors influencing the argyrophil cell population in patients with gastroesophageal reflux disease treated with omeprazole (N = 201) or H2-receptor antagonists (N = 118) and in control patients (N = 215). Fasting gastrinemia and Helicobacter pylori serology were determined. Gastritis, Helicobacter pylori infection, and argyrophil cell density and hyperplasia were evaluated in gastric biopsies. The argyrophil cell density was higher in both treatment groups than in controls (P = 0.002 and P = 0.051), whereas argyrophil cell hyperplasia was similar in the three groups. According to multivariate analysis, positive Helicobacter pylori serology was an independent parameter that decreased both density and grade of hyperplasia of argyrophil cells. Female gender and hypergastrinemia were independent factors increasing argyrophil cell density and hyperplasia, whereas antisecretory therapy, age and active gastritis were not. In addition, atrophic gastritis independently increased argyrophil cell hyperplasia. The prevalence of atrophic gastritis was significantly higher in Helicobacter pylori-positive than in negative patients and lower in the patients treated long-term with omeprazole than in the other groups.

The method of combinatorial synthesis of peptide and nonpeptide libraries on solid phase is analyzed and the automation of the mix and divide key step described. A set of amino acids leading to a high molecular diversity is proposed as well as a number of scaffolds for the preparation of variable polyamide libraries. Adequacy of the resin bead quantities to library size and to the ratio of the synthesized peptide types is discussed. Examples of the use of capillary electrophoresis and of spectroscopic methods (MS, MS/MS, and NMR) for the analysis of the library content are given. The iterative deconvolution SURF (synthetic unrandomization of randomized fragments) is compared with positional scanning and the success of coupling of mixtures evaluated. It is concluded that extension of the original mix and divide method and the SURF deconvolution (as proposed by Houghten et al. Nature (London), 354: 84-86 1991) to nonpeptide libraries affords new leads that can be optimized towards useful therapeutics.

An enterotoxigenic strain of Bacteroides fragilis was the sole organism isolated from the cerebrospinal fluid of a two-and-a-half-month neonate who had a medullary-colonic fistula as part of a complex congenital malformation, but no brain abscess. A rapid latex particle agglutination test for detection of bacterial antigen was positive for Haemophilus influenzae type b, suggesting that Bacteroides fragilis and Haemophilus influenzae type b might share some capsular antigens. In order to determine the role of the enterotoxin with respect to virulence of the strain, antibodies to a 20 kDa protein were sought in the patient's serum, but Western blot of the culture supernatant revealed only antibodies to a 45 kDa bacterial protein. The patient was successfully treated with metronidazole and imipenem.

The anabolic effect of parathyroid hormone (PTH) on bone is partly due to a stimulation of osteoblast proliferation. The PTH signal is transduced by the pathways of adenylyl cyclase (AC)/protein kinase (PK) A and phospholipase C/PKC/Ca++. There is still uncertainty about the relative contribution of the two pathways to the proliferative effects of the hormone. In our study, PTH(1–34), AC/PKA agonists, and phorbol 12-myristate-13-acetate (PMA, a PKC activator) stimulated cell proliferation in cultured mouse calvariae. In isolated osteoblasts, only PMA stimulated proliferation, whereas AC/PKA agonists and PTH(1–34) inhibited it. As already known, PTH in the presence of supramaximal concentrations of transforming growth factor-β (TGF-β) stimulated osteoblast growth; under these same conditions, AC/PKA agonists reproduced the stimulatory effect of PTH(1–34), whereas PMA became inhibitory. PTH(1–31), which stimulates AC without affecting PKC, acted similarly to the fully active PTH(1–34) in both calvaria and isolated osteoblasts. On the contrary, midregion fragments that activate only PKC stimulated calvaria cell proliferation faintly in comparison with PTH(1–34); no effect was seen in osteoblasts, either with or without TGF-β. Our study shows that the effects of PTH on proliferation can be mimicked by agonists of the AC/cAMP pathway. Although PMA is indeed able to stimulate cell growth in tissue explants, its effects on isolated osteoblasts markedly diverge from those of PTH. We conclude that activation of the AC/PKA pathway is the main component of the proliferative effects of PTH.

The in vitro and in vivo effects of S 16118 [p-guanidobenzoyl-[Hyp3, Thi5,D-Tic7,Oic8]bradykinin (BK)], a new BK receptor antagonist, were studied. S 16118 inhibited the contraction produced by BK in the rabbit jugular vein, but was ineffective in the rabbit aorta, indicating the BK B2 receptor specificity of the compound. In isolated organs from various species including humans, S 16118 was a potent antagonist (Ki, pA2 or pKB value from 9.58-7.37). The effect of S 16118 was specific as it did not show any affinity for a number of other receptors or channels and did not possess residual agonistic properties in most of the tissues studied. Furthermore, S 16118 is a poor secretagogue agent either in the rat or human mast cells and is resistant to degradation with an in vitro half-life in blood from different species, including humans, of more than 24 hr. In vivo, in the rabbit, i.v. injection of S 16118 inhibited the hypotension induced by BK up to 4 hr after administration. In the guinea pig, it was also effective in inhibiting the bronchoconstriction induced by BK, although when administered i.v. it had a shorter duration than in the rabbit. However, in the same species, when aerosolized, S 16118 was effective and long-acting against BK-induced bronchoconstriction. Changes in permeability induced by BK injection in the guinea pig trachea and bronchus, and by BK superfusion in the hamster cheek pouch, were abolished by i.v. pretreatment with S 16118.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of pneumonia caused by Streptococcus pneumoniae occurring in a patient receiving pristinamycin is reported. Despite empirical treatment with pristinamycin, 2 g/day for five days, the patient's condition worsened. Protected brush specimen and blood cultures permitted isolation of Streptococcus pneumoniae. MIC testing indicated that the strain was susceptible to pristinamycin and resistant to erythromycin and penicillin. Streptococcus pneumoniae was eradicated by cefotaxime, and pneumonia resolved. This case underlines the fact that pristinamycin may not be suitable for the treatment of multiresistant pneumococcal infections.

Since the early 1960s when chemists demonstrated their ability to reproduce by chemical synthesis peptides of up to 40 amino acids, a great deal of experience has accumulated in terms of modification and optimization of natural peptides. The purpose of optimization has been both to design selective pharmacological tools as receptor probes and to obtain useful therapeutic agents. Impressive increases in potency, selectivity, and stability of peptide leads have been achieved, including the design of peptide-derived nonpeptide mimetics. In the past few years, new sources of peptide leads have appeared and the technologies of peptide drug design have gained considerably in efficacy. The following short overview is an attempt to analyze the success and potential of these methods and to critically evaluate the specific contribution of molecular modeling and computational methods to the overall optimization process.

Botulism, a food-borne toxin-mediated disease caused by Clostridium botulinum is still a common disease, which is most frequent in the rural environment; 108 cases, 66 males and 42 females, average age 32 years, were recorded from 1965 to 1990 in the infectious disease department of the University Hospital of Poitiers (France). In 83% of patients, the food responsible was home-cured ham. Mean incubation time was 3.4 days; digestive symptoms were observed in 93% of cases, ocular symptoms in 92% and urinary tract dysfunction in 22%. A scale of severity was used to classify the patients into those suffering from severe (6), intermediate (50) and mild (52) forms of the disease. Botulinum toxin type B was found in 36 (52%) of 69 blood samples and in 41 (51%) of 81 samples of the suspected food. From 1965 to 1976, 44 patients were treated with both toxoid and heterologous equine serotherapy. Since 1976, 29 patients have been treated with guanidine hydrochloride (35 mg/kg daily) and 35 patients with guanidine hydrochloride plus heterologous serotherapy. All 108 patients recovered without any sequelae.

The presence of Helicobacter pylori in the human stomach has been highly associated with gastritis and peptic ulcer disease [1–4]. Adherence of H. pylori to gastric cells of infected patients has been directly observed and may be important in the maintenance of infection [5–8]. The attachment of H. pylori to gastric cells may involve bacterial components able to bind to specific cellular receptors. The cellular receptors may be restricted to the gastric cells explaining the exclusive association of H. pylori with those cells, but the specificity of H. pylori for the gastric mucosa may also result from the particular micro-environment of the stomach; in that case, the cellular receptors binding H. pylori could be present on other human cells. It is thus reasonable to study the colonization factors of H. pylori using epithelial cell lines as has been previously described [8–10]. Using microtiter assays, we previously reported [11] a bacterial material easily extracted from the surface of H. pylori which included components that specifically adhered to HeLa cell membranes. This superficial adhering material (SAM) binds to a cellular receptor unrelated to N-acety1-neuraminic acid and is thus different from the N-acetyl-neuraminyl-lactose-binding hemagglutinin previously described [12]. By gel exclusion chromatography, the adhering components of SAM copurify with urease activity in fractions which included antigens of 60, 52, 30, and 15 kDa. In this work, we further identified the adhering components of SAM and we examined the fate of viable epithelial cells coated with these adhering bacterial components.

Immunocrossreactivity between the major outer membrane protein (MOMP) of Campylobacter jejuni 85H and the OmpC porin of Escherichia coli K-12 was observed. These results indicate that a common antigenic domain is conserved in both MOMP and OmpC. This antigenic region is detected only after a 96 degrees C treatment suggesting that it is buried in the native conformation of the respective porins. In addition, differences were observed between the major outer membrane proteins from various C. jejuni strains. About 60% of the C. jejuni pathogenic strains tested contained a protein exhibiting a similar electrophoretic profile to the 85H porin.

The presence of Helicobacter pylori in the human stomach has been highly associated with gastritis and peptic ulcer disease (1–4). Colonization of the mucus layer overlaying gastric tissue is a feature of H. pylori infection and is facilitated by the spiral shape and high motility of H. pylori (5). Adherence of H. pylori to gastric cells of infected patients has been directly observed, and may be important in the maintenance of infection (5–7). The attachment of H. pylori to gastric cells may involve bacterial components able to bind to cellular receptors. The cellular receptors may be restricted to the gastric cells which would explain the exclusive association of H. pylori with those cells, however the specificity of H. pylori for the gastric mucosa may also result from the particular microenvironment of the stomach. In the latter case, the cellular receptors binding H. pylori could be present on other human cells (8). It is thus of interest to study the colonization factors of H. pylori. Using the microscopic reference method (9,10) or microtiter adherence assays (11), all H. pylori strains studied have been found adherent to Hep2, INT407, Y1 or HeLa cells (8, 10). These observations support the hypothesis that the cellular receptor binding H. pylori is not restricted to gastric cells and can be studied using epithelial cell lines. Using methods that were developed for the study of colonization factors of Escherichia coli, Huang demonstrated hemagglutinating properties in H. pylori (12) and Evans described a fibrillar hemagglutinin binding on N-acetyl-neuraminyl-lactose, a receptor not restricted to the gastric cells (13).

Adult spontaneously hypertensive rats (SHR) were daily treated for 2 weeks with perindopril [an angiotensin-converting enzyme (ACE) inhibitor] and nitrendipine (a calcium antagonist) alone or in combination. Blood pressure (BP), heart rate (HR), and diuresis were assessed weekly in conscious rats, and systemic and regional hemodynamics were investigated by the microsphere technique at the end of the treatment in anesthetized rats. Both perindopril (2 mg.kg-1.d-1) and nitrendipine (10 mg.kg-1.d-1) decreased BP to the same extent, but perindopril exerted a longer action. The hemodynamic profile of each drug was respectively consistent with the classic ones of ACE inhibitors and calcium antagonists already described in the literature. With combination of the two treatments, effects were at least additive, except that the nitrendipine-induced tachycardia was partially reduced by perindopril. BP reduction was additive, and significant potentiation was shown at the systemic [cardiac index (CI) increase, total peripheral resistance (TPR) decrease] and some regional (hepatic, muscular, and cutaneous vasodilations) levels. These results, which are in agreement with the different mechanisms of action of the two drugs, emphasize the advantage of combining perindopril with nitrendipine for treatment of hypertension.

The presence of Helicobacter pylori on gastric mucosa has been associated with type B gastritis and peptic ulcer disease. Despite its uncertain role in pathogenesis, gastric mucosa colonization by H. pylori is at least a good indicator for gastroduodenal inflammatory diseases [1,14,19].

Summary A case of Listeria monocytogenes ocurring in an ICU patient is reported. L. monocytogenes was isolated in blood cultures after 23 days of hospitalization in a 61-year-old patient, initially admitted for decompensed chronic insufficiency due to corticodependent asthma. She had fever and chills but no neurologic or digestive disorder. The nosocomial origin was strongly suspected but could not proved because bacteriologic food control was negative.

Summary The authors report the case of a community respiratory tract infection by penicillin resistant pneumococcus in patient with AIDS. This infection was controled by antibiotic therapy with amoxicillin.

Adult spontaneously hypertensive rats (SHR) were daily treated for 2 weeks with perindopril [an angiotensin-converting enzyme (ACE) inhibitor] and nitrendipine (a calcium antagonist) alone or in combination. Blood pressure (BP), heart rate (HR), and diuresis were assessed weekly in conscious rats, and systemic and regional hemodynamics were investigated by the microsphere technique at the end of the treatment in anesthetized rats. Both perindopril (2 mg.kg-1.d-1) and nitrendipine (10 mg.kg-1.d-1) decreased BP to the same extent, but perindopril exerted a longer action. The hemodynamic profile of each drug was respectively consistent with the classic ones of ACE inhibitors and calcium antagonists already described in the literature. With combination of the two treatments, effects were at least additive, except that the nitrendipine-induced tachycardia was partially reduced by perindopril. BP reduction was additive, and significant potentiation was shown at the systemic [cardiac index (CI) increase, total peripheral resistance (TPR) decrease] and some regional (hepatic, muscular, and cutaneous vasodilations) levels. These results, which are in agreement with the different mechanisms of action of the two drugs, emphasize the advantage of combining perindopril with nitrendipine for treatment of hypertension.

Comparative studies on the mechanism of action of ACTH1-39 and ACTH5-24 [corticotropin-(1-39)- and corticotropin-(5-24)-peptides] on isolated rat adrenal cells were performed. The relationship between stimulated steroidogenesis and cyclic AMP was very different, suggesting that cyclic AMP does not play the same role in mediating the action of the two agonists. Data from three separate experiments showed that the competitive antagonist ACTH6-24 [corticotropin-(6-24)-peptide] had mean inhibitor constants of 13.4 +/- 3.1 nM against ACTH1-39 and 3.4 +/- 1.0 nM against ACTH5-24, indicating that the steroidogenic actions of these two agonists are mediated by two different receptor types. We conclude that there are two possible mechanisms for corticotropin action, only one of which involves the necessary production of cyclic AMP.

The proximity effects observed in calculating octanol/ water partition coefficients of bisubstituted aliphatic chains are interpreted as a measure of the hydrophobicity potential of the substituents. These effects and the derived potentials decay exponentially from the center of the molecular fragment (substituent). A hydrophobicity potential is defined that is proportional to the hydrophobic fragmental constant and has its maximal value in the center of the fragment. Summing up the fragmental hydrophobic contributions enables us to assign a potential to any point in space around the molecule. Selected colored representations of the potential, such as those shown here for enalapril, add to the available pictures of bioactive molecules and should be useful for design purposes in molecular pharmacology.

Experiments have been established in order to study the antagonistic effect of cyclophosphamid treatment on the antibiotic activity of gentamicin in vivo. An immunodepressive state in mice (50 % reduction of neutrophil polymorphonuclear) was obtained with a 5 day treatment of cyclophosphamid, at the dose of 15 mg/kg. The mice were inoculated intraperitoneally with 10 LD50 of Klebsiella pneumoniae. Antibiotherapy was applied in 2 ways differing with the dose of gentamicin given twice a day by subcutaneous route (either 2.5 or 25 mg/kg) and with the time at which treatment was started (either at 1 or at 2 h after bacterial challenge). The gentamicin activity decreases in immunosuppressed mice when antibiotic is applied with a low dose (2.5 mg/kg), 1 h after infection challenge. This effect disappears when gentamicin is given with high doses (20 mg/kg) or when antibiotherapy is delayed (2 h after infection challenge). In this case, mortality is important and close to non immunodepressed mice.

Susceptibility to bacterial infections after chronic exposure to cadmium was studied in mice. Cadmium chloride was injected intraperitoneally three times a week for 4 weeks. After this treatment, mice displayed splenomegalia, hyperplasia of the B-dependent areas of spleen. Virulence of bacteria considered as usually having extracellular sites of multiplication (Klebsiella pneumoniae, Pseudomonas aeruginosa), or intracellular (Listeria monocytogenes), was determined. Only L. monocytogenes showed an increased virulence in cadmium-treated mice.

A performance analysis was established between three methods for testing of bacterial susceptibility to sixteen antibiotics: agar dilution or minimal inhibitory concentration (MIC) method, agar diffusion or DISK method, and semi-automatic dilution in liquid medium or ABACR method. Precision of the three methods was determined using three reference strains in repetition experiments (9 repetitions for MIC, 60 repetitions for both DISK and ABAC). The results show that MIC method was the most precise, and that the precision of DISK and ABAC methods was not sifnificantly different. Fidelity of both DISK and ABAC methods was compared in taking as reference the MIC of 200 wild strains of Gram-negative bacteria. Omitting the data concerning trimethoprim-sulfamethozoaxol, the results were found concordant between DISK and MIC methods in 68.6 percent of the cases, between ABAC and MIC methods in 73.6 percent, and between ABAC and DISK methods in 68.9 percent. With regard to MIC, ABAC method gave results slightly better than those of DISK method, especially for five antibiotics: gentamicin, minocyclin, doxycylin, chloramphenicol and polymyxin B. So, the ABAC method looks very interesting for a semi-automatic routine method in testing bacterial susceptibility to antibiotics.

Two toxigenic strains of Escherichia coli possessing a colonization factor antigen (CFA) respectively CFA/I and CFA/II, were studied for adherence to mononuclear cells from human blood of 12 subjects. Significant differences were observed between these two strains in their ability to adhere, using as control strains their laboratory-passed derivatives which no longer possess CFA. Differences were observed in bacterial adhesion ability of mononuclear cells from different subjects but, in the whole, CFA+ bacteria were able to adhere to few cells from each subject only. These results are in opposition to the hypothesis that it is conceivable that histocompatibility antigens expressed on cells play a role in the attachment of bacteria as the first step in an infection.

The incidence of iron deficiency and its relationship with the concentration or iron in sputum and the number of Pseudomonas aeruginosa (PA) colonies was studied in an unselected group of 53 cystic fibrosis (CF) patients with an age range of 3 months to 21 years. Parameters used to assess the iron status included serum iron, the % saturation of transferrin (n = 53). The number of subjects with depletion of iron stores was estimated by levels of ferritin (n = 50). The concentration of iron and of PA was measured in a subgroup (n = 24) and compared to a control group (n = 8) with pulmonary infections of varying etiology. A close correlation was found between serum iron and the % saturation of transferrin (r = 0.952; p less than 0.001). Between 22.6 to 28.3% of patients were found to be iron deficient. An abnormally low ferritin (less than 12 ng/ml) was noted in 28% of cases but no correlation could be established between changes of serum iron and ferritin levels as a function of the degree of infection and/or of inflammation. In 62% of cases (n = 15) the concentration of iron in sputum was found to be within the range of control values (12-27 mumols/l). In 38% of cases (n = 9), ferritin values were above 27 mumols/l. No correlation was found between the concentration of iron and the number of PA colonies in sputum. We can therefore conclude the following: 1) iron deficiency is more common in CF than previously reported; 2) ferritin levels constitute a poor index of iron deficiency; 3) colonisation with PA is not associated with iron content of bronchial secretions.

We have compared the performance of two types of manufactured media, by making 1580 blood cultures from 250 hospitalized people with bacteremia. The results showed that, within the limits of this present study, the Bacto Tryptic Soy Broth w/SPS and Bacto Thiol Broth w/SPS (DIFCO) are better than the brain heart broth and Schaedler broth (Hemoline, BioMérieux). There was no difference in the microbial growth rate and the type of isolated bacteria with the two brands of media. The superior results obtained with the used media from Difco, as compared to the ones from BioMérieux, could be due to a difference of sensitivity of these broths.

Lipophilic, steric, electronic, and enzyme resistance characteristics of carboranylalanine, adamantylalanine, neopentylglycine and tert-butylglycine are described. The first 2 amino-acids display lipophilicities 2 orders of magnitude higher than tryptophan.

Ticarcillin (TCL) activity was studied in vivo in mice immunodepressed by either cyclophosphamide (CY) or methylprednisolone (Mpd). Each type of immunodepression was evaluated by polymorphonuclear enumeration and carbon black blood clearance. Mice were infected intraperitoneally with 3 LD50 of Pseudomonas aeruginosa and then 1,000 or 1,600 mg/kg of TCL was given by subcutaneous route. Mice were treated after 15 min and 3, 18, 24 and 36 h following infection. With 1,000 mg/kg of TCL, non-immunodepressed mice were cured. Mpd-treated mice were cured by 1,600 mg/kg of TCL, while CY-treated mice were not cured by the same dose of TCL.

The potencies of a series of enkephalin derivatives with general structure H . Tyr-D-Ala-Gly-X-Y . NH2 (X and Y are variable amino acid residues), to depress the contractions of electrically stimulated guinea pig ileum and mouse vas deferens preparations, were analyzed. The doses for half-maximal inhibition could be expressed as linear functions of three structural parameters--electronic, hydrophobic, and steric--which characterized the side chains of X and Y. A general methodology was devised for the quantitative estimation of these substituent parameters for amino acid side chains. The excellent statistics obtained for the equation of regression is an indication that no other parameters need to be considered to account for the opiate activity in this series. The relative importance of these factors and their intercorrelation were established, and the predictive value of the model was tested.