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Biomedical subjects

D Simon

Publications and source records attributed to D Simon.

At least 181 records · Page 10Linked to original sources
PubMed1997

Hepatitis B vaccination in diabetic patients. Randomized trial comparing recombinant vaccines containing and not containing pre-S2 antigen.

OBJECTIVE: To investigate the immunogenicity of two recombinant hepatitis B vaccines containing S antigen alone (Engerix B) or both S and pre-S2 antigens (GenHevac B) in diabetic patients. RESEARCH DESIGN AND METHODS: Of the adult diabetic patients, 71 (26 IDDM, 45 NIDDM) were randomized to receive Engerix B or GenHevac B at 0, 1, 2, and 12 months in a single-blind clinical trial; if the antibody to hepatitis B surface antigen (anti-HBs) titers were < 10 i.u./l at month 4, a fourth injection of vaccine was given. A positive response was defined by anti-HBs titer > or = 10 IU/l at month 13. RESULTS: The anti-HBs response rate and the titers of anti-HBs did not differ significantly between the two types of vaccine. Overall, > 90% of the patients responded at month 13. In patients vaccinated with GenHevac B, anti-pre-S2 antibodies appeared earlier than anti-HBs. The anti-HBs response tended to decrease with age (P = 0.07) and tended to be higher in IDDM patients than in NIDDM patients (P = 0.06). Metabolic control, as assessed by HbA1c level, did not influence the response rate. The presence of the HLA DQ2 allele was associated with a low response. CONCLUSIONS: A large majority of diabetic patients can be efficiently vaccinated against the hepatitis B virus using a booster dose at month 4. The choice of the vaccine (with or without pre-S2 antigen) appears to have little influence, if any, on the response rate.

Adult↗
PubMed1997

[Significance of lymph node metastases of differentiated thyroid gland carcinomas and C-cell carcinomas for prognosis--a meta-analysis].

Surgical therapy of differentiated thyroid cancer (DTC) includes thyroidectomy plus central lymph node dissection and postoperative radioiodine therapy. In cases of lymph node metastasis, T3/T4 tumors and C-cell-carcinoma (after thyroidectomy) uni- or bilateral modified radical lymph node dissection of the neck (neck dissection) and of the mediastinum is recommended. The importance of lymph node metastasis for prognosis of survival in papillary, follicular and C-cell-carcinoma is discussed controversial, however. Even the kind of surgical radicality is questioned. Thus a metaanalysis of 35 studies in 29 independent publications from a pool of 2186 studies was performed. Univariate analysis demonstrates lymph node metastasis as a negative prognostic factor in papillary carcinoma with a 3.25/2.97, in follicular carcinoma with a 7.62/4.0 and in C-cell-carcinoma with a 3.33/3.37 higher probability of mortality 5 and 10 years after operation. Modification of the present surgical therapy can therefore only be accepted after univariate and multivariate analysis of all prognostic factors (age, sex, cell type, tumor extent, lymph node- and distant metastasis) and after it has proven superiority to the present strategy in prospective randomised trials.

Adenocarcinoma, Follicular↗
PubMed1997

[Primary hyperparathyroidism. Optimization of surgical results with systematic preoperative 99mTc-Sestamibi scintigraphy].

OBJECTIVE: The importance of preoperative 99mTc Sestamibi (MIBI) scintigraphy in case of reoperation for persistent hyperparathyroidism is well recognized, but it use as a systematic exploration technique remains a question of debate. We conducted this study to determine whether preoperative MIBI scans performed in all cases before surgery have any real impact. METHOD: Two successive series of 65 operated patients were included in the study. In the first group, the MIBI scan was not performed prior to surgery while in the second group the MIBI scan was part of the systematic work-up. RESULTS: The sensitivity and positive predictive value of MIBI were 92% and 96% respectively. Sensitivity for unique adenomas was 95% and 80% for multiple forms. In the first group without systematic scans, there were two unproductive procedures. In the second group, all procedures were productive and no reoperations were required. Two mediastinal adenomas were removed at the first cervicotomy in this group. The rate of complications was similar for both groups. Mean operation time was 2 hours in the first group and 1 hour 30 minutes for the second. CONCLUSION: Our series shows that there are three main advantages of using MIBI scintigraphy systematically prior to surgery for hyperparathyroidism: the procedure is easier in patients with cervical adenomas, particularly in case of ectopic localizations; the mean duration of the operation is shortened by 30 minutes; mediastinal ectopic localizations can be removed by sternotomy at the first operation. These advantages appear to be great enough to propose systematic use of MIBI scan prior to surgery. When MIBI scan shows a single gland, the risk of missing a multiple localization is less than 2% in our experience. It appears possible to operate under local anesthesia via a single-sided approach in elderly patients or high-risk patients.

Adenoma↗
PubMed1997

[Surgical concept in sporadic and familial pheochromocytoma].

A retrospective analysis of 61 patients operated upon sporadic and familial pheochromocytomas demonstrates the changes in diagnosis and therapy. Familial pheochromocytomas make up for 28% of all patients and in 13% tumor malignancy was diagnosed. Patients had suffered from endocrine crises in 21% preoperatively but only in 3% intra- and postoperatively. CT was confirmed to visualize more tumors than US or MIBG (> 90%) preoperatively. Operative strategy was based on tumor-size and tumor-localization but increasing importance of endoscopic procedures is conceded. Postoperative complications are rare (infection 8%; Addison's crisis 5%) and life threatening complications (bleeding, post op death) as well as tumor persistence or recurrence almost exclusively occur in patients with malignant disease. Altogether the main changes are the early diagnosis of especially familial disease and the use of endoscopic procedures in the treatment of patients with small benign pheochromocytomas.

Adrenal Gland Neoplasms↗
PubMed1997

[Conventional operation for therapy of incidentaloma].

AIM: The increasing detection rate of incidentalomas imposes not only the question about the necessity of treatment but also with introduction of laparoscopic adrenalectomy the question about operative strategy. Own patients and literature are analysed and discussed. PATIENTS: Between 1985 and 1996 203 patients have been operated on for adrenal disease including 21 patients with incidentaloma. RESULTS: Biochemical analysis revealed latent hormonal activity in 9 patients. All patients were operated conventionally. Pathohistology demonstrated 1 adrenal carcinoma, 9 adrenocortical adenomas, 2 myelolipomas, 2 adrenal cysts, 2 nodular hyperplasias and 5 pheochromocytomas. Postoperative morbidity was 5% and mortality 0%. CONCLUSION: Small and hormonally latent active tumors can be operated laparoscopically or conventionally via dorsal approach. In case of suspected malignancy conventional operation is the more reliable procedure.

Adolescent↗
PubMed1997

[Guidelines in oncologic surgery--malignant thyroid tumors].

Guidelines for a highly effective radical treatment protocol of thyroid cancer are based on its histopathological classification. The bases are total thyroidectomy, including the central lymph node compartment parathyroidal and paratracheal, extended to uni- or bilateral cervical lymph node dissection in case of clinical manifestation or very advanced tumor stage. Postoperative control or treatment by radioiodine is obligatory for all differentiated thyroid carcinoma. Reoperative surgery is useful for locoregional recurrence. Limited unilateral thyroid surgery is only justified in selected cases of primary tumors less than 1 cm diameter in a low-risk patient group.

Combined Modality Therapy↗
PubMed1997

[Instrumental diagnosis for therapeutic decisions--what is possible and desirable, what is essential and what is superfluous--in goiter surgery].

In addition to patient history and clinical examination, the basis of thyroid diagnosis consists of bTSH measurement and ultrasound to provide information on function and morphology. Solitary nodules have to be differentiated into "cold" and "hot" by scintigraphy. For cold nodules, FNA cytology is strongly recommended. Immunogenic hyperthyroidism is proven by positive TRAK measurement. Thyroidal autonomy requires suppressive scintigraphy for morphologic guidance. Special imaging procedures like CT and MRT are reserved for special situations of retrosternal extension.

Diagnosis, Differential↗
PubMed1996

Prevalence of diabetes mellitus in New Caledonia: ethnic and urban-rural differences. CALDIA Study Group. CALedonia DIAbetes Mellitus Study.

The prevalence of diabetes mellitus was assessed in the multiracial population of New Caledonia in the South Pacific with the use of a two-step procedure. The first step included 9,390 subjects aged 30-59 years who were visited at home for screening with glucose strips. All subjects who had a fasting capillary blood glucose value > or = 110 mg/dl were invited to come to the health center for a more detailed examination. In non-fasting subjects, a capillary blood glucose value of 140 mg/dl was chosen as the cut-off point for further examination. A 2-hour glucose tolerance test was performed according to World Health Organization (WHO) recommendations on 424 positive screenees as well as in a sample of 517 negative screenees. In all, 219 previously known diabetic subjects were found; among subjects classified as positive at the first step, 277 were detected as new cases or diabetes. After correction to take into account false negative subjects, the age-adjusted prevalence rate of diabetes was estimated to be 8.9% overall; Polynesians (15.3%) were found to be more at risk than Melanesians or Europeans (8.4% in two other groups). A higher prevalence of diabetes was found in Melanesians who lived in the urban area compared with Melanesians who lived in villages. This finding confirms the deleterious effect of western life in this population subject to rapid modernization.

Adult↗
PubMed1996

The natural mutation Y248C of human angiotensinogen leads to abnormal glycosylation and altered immunological recognition of the protein.

Common molecular variants of the angiotensinogen gene have been associated with human hypertension. The rare Tyr to Cys change at residue 248 of mature angiotensinogen was identified in one pedigree. Heterozygous individuals (Y248C) had a 40% decrease in plasma angiotensinogen concentration and a 35% reduction of the angiotensin I production rate. Recombinant wild-type (Tyr-248) and mutant (Cys-248) proteins were stably expressed in Chinese hamster ovary cells. Angiotensinogen monoclonal antibodies revealed marked differences in the epitope recognition of the mutant protein and allowed the demonstration of its presence in plasma of Y248C individuals. Similar kinetic constants of angiotensin I production with human renin were observed for both proteins. Western blot analysis showed similar heterogeneities; however, a 3-kDa increase in molecular mass for the Cys-248 protein was observed after immunopurification. Metabolic labeling of the intracellular Cys-248 protein showed a 61-kDa band in addition to the 55.5- and 58-kDa bands observed for the Tyr-248 protein, with all bands being sensitive to endoglycosidase H. In addition, pulse-chase studies revealed a slower intracellular processing for the Cys-248 protein. In conclusion, the Cys-248 mutation alters the structure, glycosylation, and secretion of angiotensinogen in Chinese hamster ovary cells and is accompanied by a decrease in plasma angiotensinogen concentration in Y248C individuals.

Amino Acid Sequence↗
PubMed1996

Is there an association between cigarette smoking and gland size in benign prostatic hyperplasia?

Several studies have implied a potential inhibitory effect of smoking on the development of clinical benign prostatic hypertrophy (BPH). None of these studies compared gland size and smoking habits. We prospectively test the hypothesis that the identified "negative risk factor" that cigarette smoke has on the development of clinical BPH is mediated through inhibition of gland growth. One hundred and ninety-five men underwent transrectal ultrasonography with prostate volume calculations. A self-administered questionnaire detailing smoking habits was completed by the subjects. Correlations were looked for between various smoking habit parameters and gland size. Prostate gland size did not differ between current smokers, ex-smokers, and never smokers. Prostate volume did not correlate with smoking years (duration of exposure), nor with intensity of exposure (cigarette packyears). Smoke-mediated changes in enzymatic and endocrine pathways that regulate prostatic growth have been well documented. However, whatever "protective" effects smoke may have on BPH, they are not mediated via direct inhibition on gland growth. Alternatively, cigarette smoke may be involved in changing the dynamic component of BPH. Further testing, with special emphasis on irritative and obstructive symptoms, may help elucidate this possibility.

Adult↗
PubMed1996

Expression and function of the Fas receptor on human blood and tissue eosinophils.

The interaction between activated T cells and eosinophils has been proposed to play an important role in the pathogenesis of allergic diseases. T cell-derived cytokines such as interleukin-5 and granulocyte/macrophage colony-stimulating factor inhibit eosinophil apoptosis and may therefore contribute to the development of tissue and blood eosinophilia in these disorders. Withdrawal of these cytokines leads to eosinophil apoptosis in vitro. In contrast, the mechanisms which actively induce apoptosis in eosinophils are at present not completely understood. In this study, we demonstrate that freshly isolated human eosinophils express mRNA and protein for the Fas receptor. Using anti-Fas monoclonal antibody (mAb), we show that Fas activation accelerates apoptotic eosinophil death in vitro. Moreover, treatment of nasal polyps ex vivo with anti-Fas mAb decreased eosinophilic tissue inflammation. However, we observed that blood as well as tissue eosinophils derived from some eosinophilic donors do not express functional Fas receptors, although Fas protein is normally expressed in these cells. This implies that the susceptibility of the Fas receptor is a matter of regulation in eosinophils as previously observed in other systems. These data suggest that Fas ligand/Fas interactions are involved in the regulation of eosinophil apoptosis and that defects in this system could contribute to the accumulation of these cells in allergic and asthmatic diseases.

Antibodies, Monoclonal↗
PubMed1996

Clinical and molecular heterogeneity of cytochrome c oxidase deficiency in the newborn.

We report 8 cases of severe cytochrome c oxidase deficiency with onset in the neonatal period. Clinical symptoms were heterogeneous: antenatal cerebral malformations, neurological distress with ketoacidosis, severe myopathy, or isolated respiratory control failure. Lactic acid was elevated in blood and/or CSF in 7 cases. Muscle biopsy (7 patients), liver biopsy (4 patients), and cultured skin fibroblasts (7 patients) were used to assess the cytochrome c oxidase deficiency. Among the patients, the enzymatic defect differed in the level of residual activity, expression in different tissues and subunit composition in muscle (as analysed by immunohistochemistry). Southern blot analysis of the mitochondrial DNA was normal in 7 patients. The heterogeneity of cytochrome c oxidase deficiency was therefore demonstrated by these clinical presentations and by the biochemical assessment of the enzyme defect. This reflects, most probably, the diverse nature of the causal mutations.

Cytochrome-c Oxidase Deficiency↗
PubMed1996

Evaluation of clinical and laboratory parameters during 2 years of growth hormone treatment in prepubertal children with chronic renal failure.

UNLABELLED: Twelve prepubertal children with chronic renal failure (CRF) were treated with human growth hormone (GH) (1.2 IU/kg/week) for 2 years. High doses of GH clearly increased growth velocity, from 3.8 +/- 1.3 to 9.6 +/- 1.5 (P = 0.0001) and 6.9 +/0 0.8 cm/year (P = 0.0001) after the 1st and 2nd year of treatment, respectively, leading to a mean height gain of 1.4 SD. During the 1st year of treatment the height increment, expressed in SDS, correlated negatively with chronological age (P = 0.003). Basal insulin-like growth factor 1 (IGF 1) levels were normal or elevated (7/12 patients) and correlated positively with the overnight integrated GH concentration (r = 0.68, P < 0.001). Basal insulin-like growth factor binding protein 3 (IGF-BP3) levels were elevated in 8/12 patients. GH induced a significant increase in IGF 1 and IGF-BP3 levels; IGF 1 peaked after 6 months (when growth velocity was optimal) and IGF-BP3 peaked after 12 months. The mean glomerula filtration rate, measured by inulin clearance and corrected for body surface area, fell after the 1st year of treatment, and significantly so at the end of the 2nd year (P = 0.02). CONCLUSION: Early initiation of GH therapy during CRF may prevent severe growth retardation and allow these children to attain normal height before dialysis and transplantation.

Area Under Curve↗
PubMed1996

Incidence of regional recurrence guiding radicality in differentiated thyroid carcinoma.

Total thyroidectomy has become the routine procedure for treatment of differentiated thyroid carcinoma. However, the necessity of unilateral or bilateral neck dissection is far less standardized. Our usual procedure has been to perform a routine neck dissection in T4 tumors and in all other tumor stages only in the presence of positive diagnostic or intraoperative findings. The results concerning regional tumor recurrence in cervical lymph nodes subsequent to thyroidectomy are studied and discussed. Between April 1986 and December 1992 a group of 252 patients were operated on for differentiated thyroid carcinoma (DTC) (176 papillary, 76 follicular). Postoperative treatment included radioiodine therapy as a rule in all patients more than stage T1, and follow-up encompassed thyroglobulin measurements, cervical ultrasonography, and radioiodine scintigraphy. After a mean follow-up of 6.9 years, 77 (31%) of the patients underwent reoperation because of regional tumor recurrence [46 of 176 (26%) papillary, 31 of 76 (41%) follicular]. In papillary thyroid cancer a significant difference could be demonstrated between patients with thyroidectomy only versus thyroidectomy plus neck dissection in all tumor stages (T2, 13 of 29 (45%) versus 1 of 34 (3%); T3, 10 of 13 (77%) versus 4 of 11 (36%); T4, 6 of 8 (75%) versus 6 of 18 (33%) (p < 0.0001). Similar results could be achieved for follicular thyroid cancer, showing statistical significance with regard to operative procedure (p < 0.009). Our experience demonstrates a positive correlation of regional tumor recurrence with increasing tumor stage for both histologic tumor types. The high rate of regional recurrence justifies a more radical approach, including neck dissection at the initial operation. The impact on survival, however, must be proved by further evaluation.

Adenocarcinoma, Follicular↗
PubMed1996

Postprandial insulin profiles with implantable pump therapy may explain decreased frequency of severe hypoglycemia, compared with intensive subcutaneous regimens, in insulin-dependent diabetes mellitus patients.

PURPOSE: To examine the mechanism of the decreased frequency of severe hypoglycemia with implantable pump therapy compared with subcutaneous intensive therapy. PATIENTS AND METHODS: Eight subjects with insulin-dependent diabetes mellitus (IDDM), enrolled in an implantable insulin pump study, were admitted to the General Clinical Research Center and on 2 separate days were given either a dose of preprandial insulin chosen to maintain normoglycemia for a standard (450 kcal, 50% carbohydrate) breakfast or 1.75 times the dose. The two doses were administered subcutaneously (by syringe or with an external pump) during one inpatient admission and by implantable pump (intraperitoneally, n=6; or intravenously, n=2) during a separate admission. Blood glucose, plasma-free insulin, and neurocognitive function were measured for 4 hours after the meal. RESULTS: Subcutaneous administration resulted in 7 episodes of hypoglycemia (2 with the usual dose and 5 with the 1.75-fold dose), defined as blood glucose less than 50 mg/dL; implantable pump treatment resulted in only 2 episodes, both with the 1.75-fold dose (P <0.05, Fisher's two-tailed test for implantable versus subcutaneous). Compared with subcutaneous delivery, implantable pump therapy provided significantly lower insulin levels during the final 2 hours after administration of the usual dose and the 1.75-fold dose (P <0.005). In addition to the decreased frequency of hypoglycemia, implantable pump therapy resulted in significantly lower area under the glycemia curve during the first 120 minutes with the 1.75-fold dose compared with subcutaneous administration. CONCLUSIONS: The lower frequency of severe hypoglycemia with intensive therapy administered by implantable pump therapy is explained by the more rapid clearance of insulin delivered intraperitoneally or intravenously compared with intensive subcutaneous injection regimens. The lower frequency of severe hypoglycemia with implantable pump therapy compared with subcutaneous therapy demonstrated in clinical trials is confirmed by this study, in which we attempted to induce hypoglycemia.

Adult↗