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Biomedical subjects

J Thompson

Publications and source records attributed to J Thompson.

At least 379 records · Page 21Linked to original sources

In vitro development and stability of tolerance to cloxacillin and vancomycin in Staphylococcus aureus.

The stability of tolerance of Staphylococcus aureus during subculturing at 37 degrees C and development of this property after repeated exposure to cloxacillin or vancomycin were investigated in vitro. Four of five tolerant strains lost this property during repeated subculturing at 37 degrees C for 50 days. Conversely, tolerance emerged in two of four nontolerant strains after repeated cycles of exposure to 25 micrograms of cloxacillin/ml or 10 micrograms of vancomycin/ml alternating with growth in antibiotic-free medium. Previous in vivo exposure to cloxacillin did not enhance the development of tolerance in vitro. MICs of both cloxacillin and vancomycin did not change significantly during this procedure. Whether the conversion of nontolerant strains to the tolerant state can also occur during antibiotic exposure in treatment of patients remains to be determined.

Cloxacillin↗

Mapping the genetic locus implicated in cytoadherence of Plasmodium falciparum to melanoma cells.

Many lines of Plasmodium falciparum undergo a deletion of the right end of chromosome 9 during in vitro cultivation accompanied by loss of cytoadherence to melanoma cells. The deletion also results in loss of expression of PfEMP1, the putative cytoadherence ligand, suggesting that PfEMP1 or a regulatory gene controlling PfEMP1 expression is encoded in this region. Initially a library of short fragments highly enriched for the right arm of chromosome 9 was constructed in bacteriophage lambda. Clones from this library were obtained randomly by the polymerase chain reaction (PCR) technique, sequenced and used to screen a yeast artificial chromosome (YAC)-P. falciparum library by PCR so that the region could be cloned and physically mapped in detail. We have used probes from this region to demonstrate that clones derived from ITG2 have undergone a deletion of intermediate length on chromosome 9. This could explain the unusual stability of cytoadherence in these clones.

Animals↗

In situ detection of Pbs21 mRNA during sexual development of Plasmodium berghei.

The patterns of expression of ribosomal RNA and mRNA encoding the parasite surface antigen Pbs21 have been investigated during the sexual stages of development of the malaria parasite, Plasmodium berghei, using the technique of non-radioactive in situ RNA hybridisation. An RNA probe complementary to a region of the small subunit of P. berghei ribosomal RNA hybridised to parasites at all stages of development in a smear of blood taken from mice infected with P. berghei. Messenger RNA encoding Pbs21, in contrast, was detected only within parasites committed to sexual development within the vertebrate host and, furthermore, was shown to be expressed in a sex-specific manner, exclusively within female gametocytes. At later stages of sexual development, Pbs21 mRNA was detected at high levels in female gametes and ookinetes. We have previously shown that Pbs21 protein is first detectable only after the initiation of gametogenesis which occurs following transmission to the insect vector. These results suggest, therefore, that post-transcriptional mechanisms operate to regulate the translation of Pbs21 mRNA as it accumulates during female gametocytogenesis.

Animals↗

Prosthetic valve endocarditis: analysis of risk factors for mortality.

Between 1975 and 1990, 70 episodes of prosthetic valve endocarditis (PVE) were diagnosed in 65 patients at Leiden University Hospital. The overall mortality rate was 27%. Antecedent endocarditis attributable to the same micro-organism (mortality 63%, P = 0.02) and Staphylococcus aureus as the causative micro-organism (mortality 100%, P = 0.001) were significant predictors for mortality. Sex, type and position of the valve and therapy had no significant influence on the mortality. All patients infected with S. aureus died, irrespective of whether they received medical treatment alone or in combination with surgery. None of the patients with streption, endocarditis had abscesses at reoperation; the mortality rate for this group was 14%. Abscess formation, especially in aortic valves, was the most important finding at reoperation and corresponded with a mortality rate of 55%. Ring abscesses occurred equally in patients with mechanical and bioprosthetic valves. Seven of the 15 patients (47%) with significant prosthetic valve dehiscence died. In patients with mitral valve endocarditis, localized dehiscence of the valve was observed. In conclusion a previous endocarditis attributable to the same micro-organism and the causative micro-organism (S. aureus) were important risk factors for mortality due to PVE.

Adolescent↗

Native-valve endocarditis due to CDC coryneform group ANF-3: report of a case and review of corynebacterial endocarditis.

Endocarditis due to a bacterium of CDC coryneform group ANF-3 developed in the native aortic valve of a patient without predisposing factors other than valvular calcification. A review of the literature indicates that corynebacteria are an increasingly important cause of endocarditis. Problems in identification and treatment remain. Techniques for the culture and quick identification of these organisms and effective regimens for treatment of the infections they cause are needed.

Actinomycetales↗

Primary influenza A virus infection induces cross-reactive antibodies that enhance uptake of virus into Fc receptor-bearing cells.

Sera of young children who had had a primary infection with influenza A virus or were immunized with a live attenuated influenza A virus vaccine were examined for antibody responses that neutralized virus or enhanced uptake of virus into Fc receptor-bearing cells, because antibodies that enhance uptake of influenza virus into Fc receptor-bearing cells have been reported using mouse immune serum and monoclonal antibodies. The neutralizing antibody titers to the homologous infecting virus and to another H1N1 virus isolated several years later were higher after natural infection than after infection with the live attenuated virus. Natural infection and the attenuated vaccine induced antibodies that enhanced uptake of homologous virus and H1N1 virus isolated several years later. These results demonstrate that primary influenza A virus infection results in the induction of infection-enhancing antibodies.

Animals↗

Tetravalent rhesus rotavirus vaccine in young infants.

A study of a tetravalent live oral rhesus rotavirus vaccine was conducted in 26 healthy infants 6-22 weeks of age to evaluate safety, viral shedding, and immunogenicity in a double-blind, placebo-controlled fashion. The tetravalent rhesus rotavirus vaccine (RRV-TV) contained equal amounts of RRV (serotype 3) and the VP7 reassortants DxRRV (serotype 1), DS1xRRV (serotype 2), and ST3xRRV (serotype 4). RRV-TV was highly infectious; 16 of 18 recipients shed virus. However, the recovered virus was almost exclusively the parent rhesus strain, RRV. Humoral immune responses were largely limited to the RRV strain. The most consistent response, seen in 14 of 18 vaccines, was an ELISA IgM response to purified RRV. Mucosal antibody responses were not seen. The limited immune response may be a function of age, presence of maternal antibody, timing of the convalescent specimens, or the polyvalent nature of the vaccine.

Administration, Oral↗

Paradoxical dose effect of continuously administered cloxacillin in treatment of tolerant Staphylococcus aureus endocarditis in rats.

The efficacies of different doses of cloxacillin administered by continuous infusion were compared in the treatment of endocarditis in rats caused by a beta-lactam tolerant strain of Staphylococcus aureus and its non-tolerant variant. In-vitro killing of the tolerant strain was maximal at a concentration near the MIC, while at higher concentrations the rate of killing gradually decreased, a paradoxical effect, not found for the non-tolerant strain. During treatment of endocarditis caused by a tolerant strain, the reduction of bacterial numbers in the infected vegetations decreased significantly with increasing doses of cloxacillin. Thus for the tolerant strain a paradoxical dose effect was also apparent in vivo. For the non-tolerant strain this paradoxical effect was not found. Furthermore, continuous administration of cloxacillin was significantly less effective in reducing bacterial numbers in the vegetations for the tolerant strain than for the non-tolerant strain. The results of this study suggest that the phenomenon of tolerance, demonstrated in vitro, may have a significant influence on the outcome of treatment of S. aureus endocarditis with continuously administered cloxacillin, particularly when high doses of antibiotic are used.

Animals↗

Efficacy of ciprofloxacin in treatment and prophylaxis of experimental Staphylococcus aureus endocarditis caused by a cloxacillin-tolerant strain and its non-tolerant variant.

The efficacy of ciprofloxacin in treatment and prophylaxis of Staphylococcus aureus endocarditis in rats infected with a strain tolerant to the standard anti-staphylococcal antibiotics cloxacillin, vancomycin and teicoplanin was compared with its non-tolerant variant. After 5 days of treatment with ciprofloxacin 30 mg/kg subcutaneously every 8 h bacterial densities in vegetations from animals infected with the tolerant and the non-tolerant strain were similar. Resistance to ciprofloxacin did not emerge in either strain of S. aureus during treatment. In prophylaxis experiments a single dose of ciprofloxacin (30 mg/kg) administered 30 min before bacterial challenge afforded almost full protection for both the tolerant and the non-tolerant strain. At a lower dose of 6 mg/kg the protective effect was less compared with the higher dose, but no difference in the proportion of sterile vegetations was found between the two strains. Thus tolerance influenced neither treatment nor prophylaxis with ciprofloxacin. For strains of S. aureus tolerant to the usual anti-staphylococcal antibiotics ciprofloxacin could be a useful alternative for the treatment of infections.

Animals↗

Severity of substance use disorders among psychiatric inpatients.

This study compares the severity of DSM-III-R psychoactive substance use disorders (PSUDs) among dually diagnosed psychiatric inpatients with independent axis I mental disorders (IMDs) with the severity of PSUDs among: a) patients from the same hospitals with PSUD-related organic mental syndromes (PSUD-OMD) and b) patients from a residential drug-treatment program with PSUDs but no axis I mental disorders. The drug-use disorders among the group 1 (IMD+PSUD) patients were less severe on multiple indicators from the Structured Clinical Interview for DSM-III-R (SCID) and the Addiction Severity Index compared with the drug-use disorders among the other two groups. This did not hold for alcohol disorders. These findings carry potential implications for treatment strategies for the mentally ill with drug use.

Adolescent↗

Kinetics of 13CO2 elimination after ingestion of 13C bicarbonate: the effects of exercise and acid base balance.

In order to investigate the effects of muscular work and preceding exercise on the retention of exogenous labelled bicarbonate, we studied the effects of oral administration of [13C]bicarbonate (0.1 mg kg-1) in five subjects at rest before exercise and during and after 1 h of treadmill walking at 73% VO2max on three separate occasions. Elimination of CO2 from labelled bicarbonate was 62.6 +/- 8.1% at rest, 103.6 +/- 11.3% during exercise (P < 0.01) and 43.0 +/- 4.7% during recovery from exercise (P = 0.01). During exercise mean residence time (MRT) was shorter than at rest (35 +/- 7 min vs. 54 +/- 9 min, P < 0.02) and CO2 pool size was larger (998 +/- 160 ml CO2 kg-1, vs. 194 +/- 28 ml CO2 kg-1, P < 0.001). Compared to values obtained at rest, during recovery from exercise, MRT and CO2 pool size were reduced (34 +/- 5 min, P < 0.05; 116 +/- 19 ml CO2 kg-1, P < 0.02, respectively). In an additional five subjects acidosis and alkalosis were induced prior to administration of oral [13C]bicarbonate at rest. Elimination of bicarbonate was lower during acidosis (46.1 +/- 5.6%, P < 0.01) but was unaltered (50.9 +/- 5.6%, NS) during alkalosis, compared to the values obtained at resting pH. During acidosis MRT and CO2 pool size decreased (37 +/- 3 min, P < 0.01 and 123 +/- 10 ml CO2 kg-1, P < 0.01, respectively) whereas in alkalosis MRT was unchanged (65 +/- 8 min NS) but CO2 pool size was increased (230 +/- 23 ml CO2 kg-1, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

The Marchioness disaster: preliminary report on psychological effects.

The psychological after-effects on 27 survivors of the Marchioness riverboat disaster of 20 August 1989 are described. On measures of intrusive memories and psychological difficulties these subjects are significantly higher than population norms, and somewhat higher than psychiatric in-patient populations. Personality measures taken after the disaster show that neuroticism scores are very much higher than population norms, but personality measures were not correlated with distress.

Adult↗

Increased antifungal activity of L-733,560, a water-soluble, semisynthetic pneumocandin, is due to enhanced inhibition of cell wall synthesis.

The pneumocandins are natural lipopeptide products of the echinocandin class which inhibit the synthesis of 1,3-beta-D-glucan in susceptible fungi. The lack of a corresponding pathway in mammalian hosts makes this mode of action an attractive one for treating systemic infections. Substitution by an aminoethyl ether at the hemiaminal and dehydration and reduction of the glutamine of pneumocandin B0 produced a semisynthetic compound (L-733,560) with intrinsic water solubility, significantly increased potency, and a broader antifungal spectrum. To evaluate the mechanism for the improved antifungal efficacy, we determined that L-733,560 was a more potent inhibitor of glucan synthase activity in vitro, did not affect the other membrane-bound enzymes tested, conferred susceptibility to lysis in the absence of osmotic support, and did not disrupt currents in liposomal bilayers or 86Rb+ fluxes from liposomes. In Aspergillus species L-733,560 also produced the same morphological alterations as pneumocandin B0. A stereoisomer of L-733,560 with poor antifungal activity was a weak inhibitor of glucan synthase. All of these results support the notion that the enhanced antifungal activity of L-733,560 is achieved by superior inhibition of glucan synthesis and not by nonspecific membrane effects or a second mode of action.

Animals↗

Role of tolerance in treatment and prophylaxis of experimental Staphylococcus aureus endocarditis with vancomycin, teicoplanin, and daptomycin.

The role of Staphylococcus aureus tolerance in the treatment and prophylaxis of endocarditis in rats was investigated. The efficacies of vancomycin, teicoplanin, and daptomycin, alone and in combination with rifampin, were compared in rats with endocarditis infected with a tolerant strain of S. aureus and in rats with endocarditis infected with its nontolerant variant. In vitro the cloxacillin-tolerant strain was also tolerant to vancomycin and teicoplanin, but not to daptomycin. However, tolerance to these antibiotics did not influence the results of treatment of experimental S. aureus endocarditis. There was no difference in the bacterial densities in the vegetations of rats infected with either the tolerant or the nontolerant strain after 5 days of treatment with any of the antibiotic regimens. Of all antibiotics, daptomycin was the most effective in reducing bacterial numbers in vegetations. Combination of rifampin with vancomycin or teicoplanin improved the results of treatment for the tolerant as well as the nontolerant strains. Daptomycin was as effective alone as in combination with rifampin. In contrast, tolerance influenced the prophylactic effects of vancomycin and teicoplanin. The proportion of rats with sterile vegetations after prophylaxis with vancomycin or teicoplanin at a low dose was lower for those infected with the tolerant strain than for those infected with the nontolerant strain. A low dose of daptomycin was equally effective against the tolerant and the nontolerant strains. However, higher doses of all three antibiotics afforded almost full protection against both strains.

Animals↗

Stimulation of monocyte tissue factor expression in an in vitro model of bacterial endocarditis.

The coagulation system plays a major role in the formation of the infected endocardial vegetation in bacterial endocarditis. Since monocytes can express tissue factor (TF) on their surfaces, they are thought to be responsible for the extrinsic activation of the coagulation cascade during this disease. The present study used an in vitro model in which fibrin plates, isolated adherent monocytes, and Streptococcus sanguis were used as an analog for endocardial vegetations. Adherence to fibrin by itself was found to stimulate TF expression on the monocytes, but stimulation by S. sanguis significantly increased TF expression, which was found to be maximal at a bacterium-to-monocyte ratio of 9 or more.

Blood Coagulation↗

Phosphoenolpyruvate-dependent maltose:phosphotransferase activity in Fusobacterium mortiferum ATCC 25557: specificity, inducibility, and product analysis.

Phosphoenolypyruvate-dependent maltose:phosphotransferase activity was induced in cells of Fusobacterium mortiferum ATCC 25557 during growth on maltose. The disaccharide was rapidly metabolized by washed cells maintained under anaerobic conditions, but fermentation ceased immediately upon exposure of the cell suspension to air. Coincidentally, high levels of a phosphorylated derivative accumulated within the cells. Chemical and enzymatic analyses, in conjunction with data from 1H, 13C, and 31P nuclear magnetic resonance spectroscopy, established the structure of the purified compound as 6-O-phosphoryl-alpha-D-glucopyranosyl-(1-4)-D-glucose (maltose 6-phosphate). A method for the preparation of substrate amounts of this commercially unavailable disaccharide phosphate is described. Permeabilized cells of F. mortiferum catalyzed the phosphoenolpyruvate-dependent phosphorylation of maltose under aerobic conditions. However, the hydrolysis of maltose 6-phosphate (to glucose 6-phosphate and glucose) by permeabilized cells or cell-free preparations required either an anaerobic environment or addition of dithiothreitol to aerobic reaction mixtures. The first step in dissimilation of the phosphorylated disaccharide appears to be catalyzed by an oxygen-sensitive maltose 6-phosphate hydrolase. Cells of F. mortiferum, grown previously on maltose, fermented a variety of alpha-linked glucosides, including maltose, turanose, palatinose, maltitol, alpha-methylglucoside, trehalose, and isomaltose. Conversely, cells grown on the separate alpha-glucosides also metabolized maltose. For this anaerobic pathogen, we suggest that the maltose:phosphotransferase and maltose 6-phosphate hydrolase catalyze the phosphorylative translocation and cleavage not only of maltose but also of structurally analogous alpha-linked glucosides.

Aerobiosis↗

Potentiation of Ca(2+)-activated secretory activity by a cAMP-mediated mechanism in avian salt gland cells.

In the avian salt gland carbachol (CCh) evokes oscillations in K+ and Cl- current that are sufficient to fully activate secretory activity. Employing the perforated patch-clamp technique, we demonstrate that beta-adrenergic receptor activation stimulates a sustained adenosine 3',5'-cyclic monophosphate (cAMP)-dependent Cl- current with no increase in K+ current. This evokes only a modest increase in secretory activity. However, application of isoproterenol in the presence of a threshold dose of CCh results in maximal secretory activity. Membrane potential measurements demonstrate that isoproterenol stimulates a sustained membrane depolarization from approximately -45 mV to the Cl- equilibrium potential (ECl), whereas CCh evokes oscillations in membrane potential to levels more negative than ECl, representing a mixture of K+ and Cl- conductances. We conclude that, in agreement with current models of fluid secretion, maximal stimulation can only be achieved with simultaneous activation of both K+ and Cl- currents. Because isoproterenol fails to stimulate a K+ current, Cl- secretion is reduced as the driving force for Cl- secretion is dissipated. However, if a driving force is imposed by increasing K+ channel activity (by coadministering CCh), Cl- efflux is sustained. These results could provide a basis for the marked potentiation of Ca(2+)-mediated secretion by agonists that increase cAMP seen in in vivo studies of salivary glands and other exocrine tissues.

Animals↗

An analysis of infectious failures in acute cholangitis.

To determine the factors responsible for therapeutic failures in acute cholangitis, a series of 127 patients was analyzed. There were 64 females and 63 males whose mean age was 57.2 years. Ninety-four (74.0%) of these patients were clinically cured with initial measures, whereas 33 patients (26%) failed initial therapy for an infectious reason. No differences were observed between the two groups in regard to age and gender. However, more patients in the group that failed had a malignant cause for their bile duct obstruction (72.7% vs. 42.6%, p < 0.01) and had a pretreatment positive blood culture (45.5% vs. 13.8%, p < 0.01). Patients who failed had a higher mean total bilirubin level (9.7 mg/dl vs. 5.5 mg/dl, p < 0.005) and more of them had a level greater than 2.2 mg/dl (97% vs. 69.9%, p < 0.001). Also, more bile cultures were initially positive (93.9% vs. 76.6%, p < 0.05) and more organisms were isolated per culture (3.88 vs. 2.86, p < 0.03) in the patients who failed. In addition, more patients failed who had two or more organisms in the bile (33% vs. 8.3%, p < 0.02). Patients in whom Candida, or any panresistant organism was isolated also tended to fail. Multivariant analysis showed that malignancy, bacteremia, bilirubin > or = 2.2 mg/dl, > or = 2 organisms in the bile and a panresistant organism were the best predictors of treatment failure with a serum bilirubin level > or = 2.2 mg/dl being the variable that increases a patient's log-odds ratio of failure the greatest.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗