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M Hofstetter

Publications and source records attributed to M Hofstetter.

13 recordsLinked to original sources

Characterization of polymorphisms in the toxin A and B genes of Clostridium difficile.

We have used six independent polymerase chain reactions (A1-A3 and B1-B3) for amplification of the entire sequence of the two toxin genes tcdA and tcdB of several Clostridium difficile strains. With this approach we have detected (1) restriction site polymorphisms which are distributed all over the genes, and (2) deletions that could be found only in tcdA. Characteristic differences between strains were mainly focused to the 5' third of tcdB (B1 fragment) and/or the 3' third of tcdA (A3 fragment). The possible use of our approach for typing of C. difficile toxin genes is discussed.

Bacterial Proteins↗

Brain abscess. A study of 45 consecutive cases.

Clinical features, findings of diagnostic studies, results of therapy, and prognostic factors were analyzed in 45 patients with brain abscesses. The number of patients diagnosed yearly has increased since CT scanning became available, but despite the enhanced sensitivity, the time from either onset of symptoms or hospital admission until initiation of therapy was not decreased and there was no dramatic effect upon morbidity or mortality in this series. Infections of paranasal sinuses, ears, lungs, and odontogenic foci were predisposing factors in approximately 70% of cases. Single abscesses, present in 75% of patients, were distributed equally in both hemispheres, with more than half in the frontal and parietal lobes. Common signs and symptoms included headache, fever, chills, seizures, nausea, vomiting, altered sensorium, nuchal rigidity, and localizing neurologic signs. Blood cultures were positive in 11%. Lumbar puncture rarely provided data from which a diagnosis could be established; CSF cultures were positive in only 7% of patients, and there was a 15% temporally associated incidence of brain herniation and death. Diagnostic information was most readily obtained using imaging techniques such as CT and 99mTc scanning, and arteriography was invasive and of no added value. CT scans are however, often initially negative in patients presenting with clinical signs of meningitis presumably following rupture of an abscess into the subarachnoid space, and the average time for changes to appear on CT scan is 9 days. It is, therefore, recommended that when the clinical assessment suggests the possibility of brain abscess the patient be treated empirically with antibiotics and that lumbar puncture be performed only after thoughtful assessment of the risk-to-benefit ratio for each patient. Causative organisms were isolated from more than 80% of abscesses despite prior antibiotic treatment; more than half grew a single pathogen, most commonly streptococci. Anaerobic and microaerophilic bacteria accounted for 62% of all isolates, and were the only organisms in 33% of patients. Computerized tomographic scans in 30 patients showed "ring-enhancing" lesions, nodular enhancement, or areas of low attenuation. Complete resolution of abscesses on CT scans rarely occurred during hospitalization and took as long as 5 months. Decrease in the size of abscesses on CT scan correlated well with clinical improvement and was seen within a week when abscesses were excised, but was often not obvious for 6 to 8 weeks if antibiotics were used alone.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Specificity of antibody and cellular immune responses in human schistosomiasis.

Thirty patients infected with Schistosoma mekongi, S. mansoni or S. japonicum had cell-mediated immune responses assessed by lymphocyte transformation in vitro (LT), immediate hypersensitivity responses determined by basophil histamine release in vitro (HR) and IgG antibody responses evaluated in an enzyme-linked immunosorbent assay (ELISA). Species specificity was evaluated with antigens obtained from adult worms or eggs of the three schistosome species. Though cross-reactivity was present in all tests, homologous antigens elicited responses significantly greater than those to heterologous antigens in all comparisons of parasite specific IgG and IgE antibody in these groups of patients. A similar generalization could be made for the lymphocyte responses to the same antigen preparations, but statistically significant differences were achieved only in certain comparisons.

Adolescent↗

Modulation of the host response in human schistosomiasis. IV. Parasite antigen induces release of histamine that inhibits lymphocyte responsiveness in vitro.

Several mechanisms underlying the suppression of in vitro lymphocyte transformation responses to parasite antigens in human schistosomiasis have been previously described, but the role that immediate hypersensitivity reactions may have in regulating these lymphocyte transformation responses has been little explored. Using Hypaque-Ficoll-separated peripheral blood mononuclear cells (PBMC) from patients with schistosome infections, we found that histamine release could be demonstrated routinely in lymphocyte cultures challenged with adult worm, egg, or cercarial antigens. Release occurred within 1 hr of stimulation, and histamine persisted in the cultures for 6 days at levels of 10(-6) to 10(-7) M. That such concentrations were capable of suppressing LT responses in vitro was shown by the addition of exogenous histamine to modified PBMC culture systems from 10 normal individuals and eight patients with Schistosoma mansoni or Schistosoma mekongi infections. Responses to phytohemagglutinin, streptokinase-streptodornase, and tetanus were equivalently suppressed in both groups (50.8 +/- 6% in normals and 55.9 +/- 6.2% in patients), and the doses required for maximal suppression were similar. Passage of PBMC from infected patients over nylon wool, in addition to removing adherent suppressor cells, also markedly reduced the number of histamine-containing basophils (74 +/- 4.5% removed). The enhanced responsiveness to parasite antigen by PBMC depleted by nylon wool passage was abrogated by the addition of exogenous histamine to the cultures. These results indicate that in routine PBMC cultures 'nonspecific' lymphocyte suppression by histamine liberated from basophils in an antigen-specific fashion may help to account for the specific suppression of lymphocyte responses to parasite antigens so characteristic of patients with schistosome and other helminth infections.

Antigens↗

IgE responses in human schistosomiasis. I. Quantitation of specific IgE by radioimmunoassay and correlation of results with skin test and basophil histamine release.

We have developed a non-competitive solid-phase radioimmunoassay (SPRIA) to quantitate human IgE antibodies to Schistosoma mansoni antigens that was capable of accurately measuring IgE antibodies in both high and low titer sera. Ninety sera from "early" or "chronic" schistosomiasis patients were studied. Both levels of parasite-specific IgE antibodies and the proportion of the total IgE response that was parasite-specific were significantly lower in "early infection" sera than in sera of patients with chronic infections. The SPRIA to adult worm antigen was compared with basophil histamine release and direct intradermal skin testing also performed with the adult antigen. Both tests showed significant correlations with the SPRIA in detecting specific anti-parasite antibody.

Adolescent↗

Changes in EEG, blood levels, mood scales and performance scores during long term treatment with diazepam, phenobarbital or placebo in patients.

1. The patient population consisting of fifteen patients was divided into three groups, namely: diazepam group, phenobarbital group and placebo group. After three weeks the medicated groups were switched to placebo for a week and the placebo group was given phenobarbital. 2. The parameters to be assessed once a week comprised frequency-analyzed EEG recordings, performance in two attention tests and subjectively estimated mood modalities. 3. The EEG analysis suggested that EEG patterns: a) were drug-dependent, with a differential distribution for each drug of the four frequency bands analyzed; b) showed no change during the three-week treatment period; c) changed on cessation of medication or on switch from placebo to active medication; d) were task-dependent and changed in a systematic way with the level of activation (stress, vigilance or relaxation). 4. The results would allow a better understanding of the clinical course, the choice of therapeutic measures and of the underlying mechanisms of action.

Adult↗

Treatment of Schistosoma mekongi with praziquantel: a double-blind study.

Praziquantel is a newly developed drug effective in the treatment of schistosomiasis. In order to assess the efficacy and toxicity of praziquantel in the treatment of Schistosoma mekongi, 11 infected Laotian refugees, all belonging to a single extended family, were treated in a double-blind crossover trial with praziquantel and placebo. Initially, one group of five received praziquantel 60 mg/kg body weight in three divided doses orally while the remainder received an identically appearing placebo. Patients were evaluated clinically before, during and following therapy for 2 days. After 2.5 months the patients were re-evaluated and subjected to the opposite treatment, and final follow-up took place 5-7 months later. Three other patients were treated using an open protocol. All but one person was cured (91%). This patient failed to show a decrease in egg excretion 2.5 weeks after praziquantel therapy and was lost to follow-up thereafter. Side effects were common and consisted primarily of abdominal pain, malaise, and fever. These were generally mild and transient. No abnormal laboratory findings were associated with praziquantel therapy. At the final evaluation 6/6 patients with initial hepatomegaly showed a decrease in liver size.

Adolescent↗

Schistosoma mekongi infection in man: cellular immune responses and modulating mechanisms.

Cell-mediated immune responses (CMI), as assessed by lymphocyte proliferation in vitro, were evaluated in 11 Laotian patients harbouring asymptomatic chronic infections by Schistosoma mekongi, a schistosome closely related to S. japonicum. When the mononuclear cells of these patients were cultured in autologous plasma, lymphocyte responses to schistosome antigens were essentially nil, not differing from those of unexposed North American controls. Specific lymphocyte proliferation, however, was seen both after the removal of mononuclear cells that were nylon-wool-adherent and after substitution of the autologous serum in the culture with normal AB serum. Our data suggest that the CMI responses of humans with chronic S. mekongi infections are 'modulated' by adherent suppressor cells and serum-suppressive factors, and that modulation of CMI supports the stable host-parasite relationship in a similar fashion to that described for chronic human Schistosoma mansoni infection.

Adolescent↗

Infection with Schistosoma mekongi in Southeast Asian refugees.

Schistosoma mekongi is a newly recognized species of Schistosoma that is closely related to Schistosoma japonicum and is pathogenic to humans. Like the other forms of schistosomiasis in which the parasites reside in the mesenteric vasculature, S. mekongi infection has hepatosplenomegaly and portal venous hypertension as its most common serious sequelae. Schistosomiasis, although endemic in certain areas of Southeast Asia, has not been recognized as a health problem in Asian refugees who are currently entering the United States. In the present study 12 Laotian immigrants with S. mekongi infection were examined. The clinical, laboratory, and parasitologic findings in these patients are discussed. The diagnosis was made by examination of stool specimens in 11 patients and rectal biopsy specimens in one patient. All patients were asymptomatic, although the six youngest children had hepatomegaly. It is suggested that specific serologic tests may be useful in screening Asian refugees for infection with Schistosoma.

Adolescent↗

Alcohol-induced biphasic background and stimulus-elicited EEG changes in relation to blood alcohol levels.

The effects of 0.8 g alcohol kg-1 on CNS processes as reflected in EEG changes were studied in controlled experiments in 14 subjects in relation to BAC levels. A Two Period Change-Over Design with repeated trials over time allowed us to ascertain the time course and to isolate alcohol-induced changes from diurnal variations and effects of sequence and period. Based on spectral analysis of analog EEG recordings, the study has shown differential patterns of bi-phasic or tri-phasic alcohol-induced EEG changes over time in a number of parameters in background and in stimulus-elicited EEG responses varying with the BAC level and the metabolic phase of alcohol biotransformation. An increase in alpha activity during the absorption phase, a shift in the median of the total spectral power to the right (upwards), a decrease in slow activity in the delta and theta bands, and a decrease in variability of the background EEG on one hand and a reduction in stimulus-elicited EEg responses in total spectral alpha, theta and delta bands on the other are all interpreted as a stimulating excitatory effect during the absorption phase, parallel to the increase in BAC. The reverse pattern in the first part of the elimination phase infers a decrease in cerebral activation reflecting the sedative, depressant action of alcohol in this phase. The effects observed in the last trial, to a certain extent interpreted as stimulating, were simultaneous with the beginning of the post-alcohol hangover phase.

Adult↗