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Biomedical subjects

D Dubois

Publications and source records attributed to D Dubois.

At least 37 records · Page 2Linked to original sources

Pancreatic B-cell proliferation in persistent hyperinsulinemic hypoglycemia of infancy: an immunohistochemical study of 18 cases.

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is characterized by severe hypoglycemia related to inappropriate insulin secretion. Morphologically, a tumoral and a nontumoral form are recognized. The tumoral form can be subdivided into adenomatous hyperplasia (in infants) and adenoma (in children). On the other hand, nesidioblastosis, considered until recently as a persistent B-cell replication, has repeatedly been proposed as the condition responsible for the nontumoral form of PHHI. We studied the proliferation rate of B cells in 18 patients affected by PHHI (7 nontumoral and 11 tumoral cases, including 4 adenomas and 7 adenomatous hyperplasias) and in 18 age-matched controls, using a double immunohistochemical technique detecting Ki-67, a nuclear endogenous antigen only present during cell proliferation, and insulin as pancreatic B-cell markers. Our results clearly show that "nesidioblastosis" is not related to an abnormal B-cell proliferation, because the B-cell labeling index (LI), reported as the mean plus or minus the standard error of the mean, is not statistically different between nontumoral PHHI (29.4 +/- 7.4) and age-matched controls (19.6 +/- 5.3). Furthermore, the Ki-67 positivity was not more prominent in small clusters of B cells in nesidioblastosis than in large islets. In tumoral PHHI, the LI was significantly higher in cases of focal adenomatous hyperplasia (77.6 +/- 10.9) than in either age-matched controls (19.9 +/- 6.9; P < .005) or in adenomas (27.9 +/- 13.7; P < .025); the values of this last group did not differ from those of age-matched controls (18.5 +/- 8.5). These data definitely demonstrate that nesidioblastosis does not correspond to an abnormal B-cell proliferation and that the focal forms of PHHI must be subclassified.

Adenoma↗

Immune mechanisms leading to type 1 insulin-dependent diabetes mellitus.

Insulin-dependent diabetes mellitus (IDDM) results from the autoimmune destruction of the endocrine (beta) cells responsible for the secretion of insulin. Experimental and human studies have resulted in unpredicted developments over the past ten years. Against most predictions, a long list of possible autoantigens has been defined, most of which are not beta-cell specific. Seemingly, up to 10 to 20 genetic regions, rather than 2 to 3 as initially predicted, carry markers that associate them with IDDM. Finally, there is accumulating evidence that beta cells are not a passive bystander in the event that leads to the activation of the diabetes autoimmune reaction. Whether the immune system or the islet, or both, are at the initiation of the disease process is a challenge for the near future.

Animals↗

[Arterial hypertension in the elderly. Is there still room for diuretics?].

Hypertension (HTA), whether systolic and diastolic or as isolated systolic hypertension, has been firmly established as a major risk factor of morbidity and cardiovascular mortality in elderly patients. Despite recent controversies that have appeared in the literature on the metabolic disturbances caused by diuretics, especially hypokalemia, and the absence of a significant advantage on coronary mortality, these drugs should nevertheless be considered as extremely important in the treatment of HTA. Prescribed at small doses, their long-term effects are by far the best documented of all antihypertensive drugs. Their mechanisms as well as their main side effects are described below. Finally, the authors give some simple guidelines on their use, more specifically in elderly patients.

Aged↗

Sialosyl-Tn antigen is prevalent and precedes dysplasia in ulcerative colitis: a retrospective case-control study.

BACKGROUND & AIMS: Expression of the carbohydrate-associated sialosyl-Tn (STn) antigen has been correlated with carcinogenesis in sporadic colon cancer. This retrospective study analyzed surveillance colonoscopy biopsy specimens to determine whether STn antigen could serve as a marker for neoplasia risk in patients with long-standing ulcerative colitis. METHODS: Eleven patients who developed dysplasia or cancer and who had undergone at least three surveillance colonoscopies were matched with 11 controls who had not developed neoplasia. Sections from 969 available surveillance biopsy specimens were stained immunohistochemically with monoclonal antibody TKH2 and were interpreted blindly. RESULTS: Compared with controls, patients expressed STn antigen more frequently in their biopsy specimens (44% patient biopsy specimens vs. 11% control biopsy specimens). Patients were also more likely to undergo colonoscopies with two or more colonic segments expressing STn antigen (73% vs. 22%), repeated STn antigen expression in two or more consecutive colonoscopies (91% vs. 27%), and STn antigen expression proximal to the hepatic flexure (64% vs. 0%). STn antigen appearance preceded the detection of neoplasia by 7 or fewer years, and its preferential expression in patients was not confounded by the degree of active inflammation. CONCLUSIONS: Repeated STn antigen expression in nondysplastic colonic mucosa may presage the development of neoplasia in long-standing ulcerative colitis and may be a useful adjunct to dysplasia during colonoscopic surveillance.

Adult↗

Kinetics, safety, and efficacy of ramipril after long-term administration in hemodialyzed patients.

We studied the efficacy and safety of ramipril and the kinetics of its active moiety ramiprilat in 12 hypertensive patients receiving regular hemodialysis, after a single dose and after long-term (28 days) administration. Patients received 2.5 mg ramipril after each hemodialysis. On days 1 and 29, ramipril was administered 4 h before the hemodialysis and serial blood samples were obtained for 9 h for determination of pharmacokinetic parameters. Tolerability was good, and all patients completed the study. There was a high degree of angiotensin-converting enzyme (ACE) inhibition throughout the study. Ramipril had a clear-cut antihypertensive effect. Long-term administration of ramipril did not modify the time to peak ramiprilat concentration, but increased the mean maximal concentration significantly: 20.2 +/- 12.7 vs. 10.4 +/- 7.1 ng center dot ml-1. The mean accumulation ratio was 2.2. Ramiprilat hemodialysis clearance was 31.7 ml/min (range 4.2-64.9 ml/min) on day 1 and 21.0 ml/min (range 7.9-56.5 ml/min) on day 29. Ramipril 2.5 mg, administered after hemodialysis, appears to be safe and effective in hypertensive patients receiving periodic hemodialysis. Despite an increase in ramiprilat concentration from day 1 to day 29, the steady state was reached. We describe the role of nonrenal clearance of ramiprilat.

Adult↗

Moldable tissue equivalent bolus for high-energy photon and electron therapy.

In radiation therapy, there is often a need to treat irregular surfaces with electron and photon beams. These surfaces require smoothing to achieve uniform doses at depth and proper buildup of dose at the surface. The surface smoothing and dose buildup is achieved by applying bolus. To deliver a known dose, produce a known central axis depth dose, and beam flatness for successful treatment, it is necessary that water or tissue equivalent bolus material is used. This material must also be able to fill extremely irregular voids. Several moldable materials, currently or formerly used in dental clinics, were evaluated for adequacy as tissue equivalent bolus. Availability was also considered during evaluation. Polyflex, a hydrocolloid, was found to be near water equivalent for electron and photon beams. It was also inexpensive, readily available, and held up well over time.

Biophysical Phenomena↗

Immunogenic and protective response in mice immunized with a purified, inactivated, Dengue-2 virus vaccine prototype made in fetal rhesus lung cells.

The feasibility of a purified, inactivated vaccine (PIV) against dengue type 2 (DEN-2) virus was explored. Dengue-2 virus strain 16681 was used for producing a monotypic PIV. Virus adapted to fetal rhesus lung (FRhL-2) cells was harvested from roller bottle culture supernatant fluids, concentrated, and purified on sucrose gradients. Analysis of purified virus preparations by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting showed primarily envelope (E) and premembrane (prM) antigens. These preparations had a purity, estimated from silver-stained gels, of approximately 70%, and a yield, based on recovery of virus and viral antigen, of 10-20%. The purified virus was inactivated with 0.05% formalin at 22 degrees C, or alternatively, with 7 mRads from a 60Co source. Vaccinated mice developed high titers of anti-DEN-2 virus neutralizing antibody and were partially protected from virus challenge. These results warrant further testing and development of PIVs for the other DEN virus serotypes.

Animals↗

[Cutaneous localizations of chronic lymphoid leukemia in a zona area].

INTRODUCTION: Leukemia cutis is a rare event in B-cell chronic lymphocytic leukemia. CASE REPORT: A patient with B-cell chronic lymphocytic leukemia developed leukemia cutis at the site of prior cervical (C2-C3) herpes zoster. DISCUSSION: Leukemia cutis on prior site of herpes zoster is exceptional. It should be differentiated from non specific skin reactions secondary to herpes zoster.

Aged↗

Tumor-associated sialylated antigens are constitutively expressed in normal human colonic mucosa.

Immunohistochemical studies have indicated that sialylated carbohydrate antigens such as sialyl-Tn, sialyl-Le(a), and sialyl-Le(x) are expressed in a tumor-associated fashion in human colon. Since sialic acid residues are O-acetylated more extensively in normal colonic epithelium than in colon cancer cells, we examined whether deacetylation of colonic tissues might enable monoclonal antibodies to recognize these tumor-associated sialylated antigens. In normal colon, deacetylation turned most cases (82%) positive with anti-sialyl-Tn mAb TKH2; and in colon cancers, it increased the number of TKH2-positive cells. Sialyl-Le(a) and sialyl-Le(x) detection was also increased after deacetylation of normal and malignant colonic tissues so that the frequency of positive cases in normal tissues was similar to that in the cancers. However, in the stomach and pancreas, the same treatment rarely increased the detection of the sialylated epitopes in normal or cancerous tissues. Thus, the same sialylated epitopes can be expressed in a tumor-associated fashion by different mechanisms in different gastrointestinal organs; in the colon, these antigens are constitutively expressed and O-acetylated, whereas in the upper gastrointestinal tract, they are rarely O-acetylated, suggesting that other mechanisms such as differences in glycosylation account for the cancer-associated expression.

Adenocarcinoma↗

The persistence of insecticidal chemicals in soils treated with granular formulations of disulfoton and their uptake by potato plants.

Potatoes were grown from cut seed in Plainfield sand treated in-furrow with disulfoton (Di-Syston 15G, 3.36 kg AI/ha) in 1983 and from whole seed in similarly treated loam in 1991. Soils were contained in 2 m2 field plots. Soil, seed potato and foliage were analyzed for the insecticide and its sulfoxide and sulfone metabolites during the 8-12 wk following planting. Disulfoton disappeared at different rates from the two soils (ksand = 0.024 day-1, kloam = 0.056 day-1) with partial conversion to the sulfoxide and sulfone in both. Larger quantities of the three insecticidal components were absorbed by the seed potato in the cut-seed/sand combination. The relative amounts of these components in the seed potato also differed between treatments with disulfoton being the largest component of the cut-seed/sand and smallest in the whole-seed/loam. Disulfoton sulfoxide and sulfone were the major insecticidal components of the foliage and concentrations in the initial foliage (each ca. 10 ppm) were similar for both treatments. Sulfoxide concentrations in the foliage decreased more rapidly than the sulfone and the decrease in concentration of each of the components was similar for the two treatments.

Disulfoton↗

Association of eosinophilic fasciitis, multiple morphea and antiphospholipid antibody.

The occurrence of morphea-like changes during the course of eosinophilic fasciitis is considered to be rare. We observed such a case with simultaneous occurrence of both types of lesions. Histologically, fibrosis and inflammatory infiltrate were seen in the entire dermis, the subcutis and the fascia, suggesting that the same process might account for all skin changes. In addition, our patient had an antiphospholipid antibody, neurologic symptoms and livedo-like cutaneous lesions. However, whether the antiphospholipid antibody played a pathogenic role or not remains unclear. Corticosteroid treatment was successful.

Aged↗

Remission of proteinuria following correction of hyperlipidemia in NIDDM patients with nondiabetic glomerulopathy.

OBJECTIVE: Animal studies suggest that hyperlipidemia may play a direct role in glomerular damage. In patients with non-insulin-dependent diabetes mellitus (NIDDM), dyslipidemia occurs early in the course of nephropathy and may be involved in the progression of renal disease. CASES: We report on two young NIDDM patients with marked hyperlipidemia and proteinuria, in whom renal biopsy demonstrated nondiabetic glomerulopathy. In both cases, the decrease in blood lipid levels was associated with a major decrease in proteinuria. Episodes of hyperlipidemia were associated with a resumption of heavy proteinuria in one patient with serum triglyceride levels and proteinuria being closely correlated. CONCLUSIONS: These two cases suggest that hyperlipidemia has an important role in the pathogenesis of glomerular disease.

Adult↗

[Thrombotic microangiopathy disclosing human immunodeficiency virus infection. Histological and ultrastructural study].

Thrombotic microangiopathy has recently been documented in association with human immunodeficiency virus infection. The authors present the clinical laboratory, histologic and electron microscopic kidney study features of one case of thrombotic microangiopathy revealing human immunodeficiency virus infection. They also review 28 previously reported cases of thrombotic microangiopathy associated with human immunodeficiency virus infection and discuss different pathogenic hypothesis which could be involved in genesis of human immunodeficiency virus-associated thrombotic microangiopathy.

Adult↗