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Denis Pierard

Publications and source records attributed to Denis Pierard.

5 recordsLinked to original sources

Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes.

BACKGROUND: Type 1 diabetes mellitus is a T-cell-mediated autoimmune disease that leads to a major loss of insulin-secreting beta cells. The further decline of beta-cell function after clinical onset might be prevented by treatment with CD3 monoclonal antibodies, as suggested by the results of a phase 1 study. To provide proof of this therapeutic principle at the metabolic level, we initiated a phase 2 placebo-controlled trial with a humanized antibody, an aglycosylated human IgG1 antibody directed against CD3 (ChAglyCD3). METHODS: In a multicenter study, 80 patients with new-onset type 1 diabetes were randomly assigned to receive placebo or ChAglyCD3 for six consecutive days. Patients were followed for 18 months, during which their daily insulin needs and residual beta-cell function were assessed according to glucose-clamp-induced C-peptide release before and after the administration of glucagon. RESULTS: At 6, 12, and 18 months, residual beta-cell function was better maintained with ChAglyCD3 than with placebo. The insulin dose increased in the placebo group but not in the ChAglyCD3 group. This effect of ChAglyCD3 was most pronounced among patients with initial residual beta-cell function at or above the 50th percentile of the 80 patients. In this subgroup, the mean insulin dose at 18 months was 0.22 IU per kilogram of body weight per day with ChAglyCD3, as compared with 0.61 IU per kilogram with placebo (P<0.001). In this subgroup, 12 of 16 patients who received ChAglyCD3 (75 percent) received minimal doses of insulin (< or =0.25 IU per kilogram per day) as compared with none of the 21 patients who received placebo. Administration of ChAglyCD3 was associated with a moderate "flu-like" syndrome and transient symptoms of Epstein-Barr viral mononucleosis. CONCLUSIONS: Short-term treatment with CD3 antibody preserves residual beta-cell function for at least 18 months in patients with recent-onset type 1 diabetes.

Adolescent↗

Enterobacter hormaechei subsp. oharae subsp. nov., E. hormaechei subsp. hormaechei comb. nov., and E. hormaechei subsp. steigerwaltii subsp. nov., three new subspecies of clinical importance.

Six species and six additional genovars are combined within the so-called Enterobacter cloacae complex, with one of them being the species Enterobacter hormaechei. In a recent population genetic study, two genetic clusters were found in close phylogenetic proximity to the genetic cluster of E. hormaechei. In order to prove the hypothesis that these three genetic clusters belong to the same species, we performed cross-hybridization experiments in microplates with DNAs of representatives of each genetic cluster. The close phylogenetic relationship among the clusters was reflected by their relatively low deltaT(m) values, ranging from 0.3 to 4.8, confirming the hypothesis that the clusters are parts of the same species. These clusters can be distinguished from the other species of the E. cloacae complex, which have deltaT(m) values of 5.6 to 10.3. Forty-eight E. hormaechei strains from the different genetic clusters were phenotypically characterized with 129 biochemical tests. In this way, E. hormaechei could be differentiated from the other species of the E. cloacae complex because it tests negative in the 3-hydroxy-butyrate test. The three genetic clusters of E. hormaechei could also be differentiated from each other by using phenotypic tests. Hence, we propose three new subspecies of E. hormaechei corresponding to genetic clusters VI, VII, and VIII of the E. cloacae complex. E. hormaechei subsp. hormaechei comb. nov. corresponds to the original species description, as it gives negative results for the adonitol, d-arabitol, d-sorbitol, and d-melibiose tests and a positive result for the dulcitol test. E. hormaechei subsp. oharae subsp. nov. gives negative results for the dulcitol, adonitol, and d-arabitol tests and positive results for the d-sorbitol and d-melibiose tests. E. hormaechei subsp. steigerwaltii subsp. nov. gives a negative result for the dulcitol test and positive results for the adonitol, d-arabitol, d-sorbitol, and d-melibiose tests. Among the members of the E. cloacae complex, E. hormaechei seems to be the species most frequently recovered from clinical specimens.

Bacterial Typing Techniques↗

Typhoid fever.

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Acute Kidney Injury↗

Molecular characterization of Escherichia coli O157 contamination routes in a cattle slaughterhouse.

In a cattle slaughterhouse, sampling was performed over a 1-week period to examine the prevalence and possible contamination routes of Escherichia coli O157. Each sampling day, swab samples were collected from the slaughterhouse environment before onset of slaughter, from the slaughterline, and from 20 successively slaughtered animals. Isolation of E. coli O157 consisted of a 6-hour enrichment followed by immunomagnetic separation and selective plating. From the 394 samples taken, 84 (21%) were positive for E. coli O157. Pulsed-field gel electrophoresis (PFGE) of collected isolates produced 26 different profiles, from which 5 PFGE profiles carried two or more Stx genes. The combination of PFGE profiles and Stx types resulted in 32 different E. coli O157 types. E. coli O157 was found in the slaughterhouse environment before the onset of slaughter. The first two sampling days, feces and carcasses were found negative. On the third sampling day, five fecal samples and four carcasses from animals negative in the feces were positive. Hide of the anal region and the shoulder were found positive every sampling day. The shoulder hide was more than twice as contaminated as the anal region hide. Typing of different isolates from a sample showed that frequently different E. coli O157 types were presented. On sampling days 1 and 2, types present in the environment and on the hides of the slaughtered animals differed. On the third sampling day, two dominant types were found in the environment (even before the onset of slaughter), as well as on the hides, feces, and carcasses. Although examined animals originated from different farms, one (two on day 3) dominant E. coli O157 type was present on their hides each sampling day. These data indicated that (i) the progress of contamination can differ from day to day within a slaughterhouse and (ii) contact between animals after the departure from the farm can have a large effect on the spread of E. coli O157 hide contamination.

Abattoirs↗

Acute renal dysfunction in salmonella gastroenteritis.

GOALS: To determine the incidence of renal function deterioration in adult patients with Salmonella infection. BACKGROUND: Renal impairment has been described during severe Salmonella infection and is mainly due to shock, dehydration, or rhabdomyolysis. However, it is unclear whether less severe Salmonella infection also has an impact on kidney function. STUDY: We retrospectively reviewed over a 2-year period the data of all hospitalized adult patients with microbiologically proven gastrointestinal infection. Different biologic parameters were compared between patients infected with Salmonella and patients with other gastrointestinal infections. RESULTS: One hundred and seven patients with positive stool cultures were identified; 44 of them had proven Salmonella infection. Renal dysfunction, defined as an increase in serum creatinine above 1.5 mg/dL in men and above 1.3 mg/dL in women, was observed in 16 (36%) patients infected by Salmonella but only in 3 (5%) comparators (P<0.0001). Hydration status and creatine kinase levels were not different in patients affected by Salmonella as compared with other pathogens. Kidney function recovered in all but 1 patient. CONCLUSIONS: Salmonella gastroenteritis in adults is frequently accompanied by renal dysfunction that is caused by mechanisms other than dehydration or rhabdomyolysis.

Acute Kidney Injury↗