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Biomedical subjects

D Simon

Publications and source records attributed to D Simon.

At least 73 records · Page 4Linked to original sources

[Jejunum diverticulosis--a rare cause of gastrointestinal hemorrhage].

In this case report the diagnostic difficulties of massive intestinal hemorrhage caused by diverticula of the small intestine are demonstrated. After resuscitation of the patient by transfusion of 8 units of packed red cells the segment of the jejunum bearing the diverticula was resected. There was no complication until discharge nor was any recurrent bleeding or functional disorder of the bowel reported during follow-up. The clinical presentation, the different value of diagnostic tools and the therapy are discussed.

Diagnosis, Differential↗

Malignant endocrine tumors in patients with MEN 1 disease.

BACKGROUND: In contrast with multiple endocrine neoplasia type 2, malignancies are of minor importance in multiple endocrine neoplasia type 1 (MEN 1) syndrome. METHODS: The data for 42 patients with MEN 1 syndrome were evaluated. Twelve patients (29%) had 1 or more associated malignancies: malignant gastrinoma (1 patient), neuroendocrine tumors of the thymus (2 patients), neuroendocrine tumors of the lung (3 patients), neuroendocrine tumor of the ileum (1 patient), adrenocortical carcinomas (2 patients), and a combination of neuroendocrine tumors of thymus, lung or pancreas (3 patients). RESULTS: Despite suspected MEN 1 syndrome in 7 patients, malignancies were detected late in 4 patients and could not be resected curatively. The survival rates for 5 years and 10 years after operation of the malignant tumor were 66% +/- 14% (SE) and 33% +/- 15% (SE), respectively. CONCLUSIONS: In patients at risk for the MEN 1 syndrome, genetic screening is indispensable. Gene carriers have to be followed up closely with hormone analysis and routine examination of the thorax, pancreas, and adrenal glands to detect malignancies as early as possible.

Adolescent↗

Long-term biochemical results after operative treatment of primary hyperparathyroidism associated with multiple endocrine neoplasia types I and IIa: is a more or less extended operation essential?

OBJECTIVE: To analyse our long term results in patients operated on for primary hyperparathyroidism associated with multiple endocrine neoplasia types I and IIa. DESIGN: Retrospective (data collection) and prospective (follow-up) analysis. SETTING: University hospital, Germany. SUBJECTS: 39 patients with MEN type I-associated and 7 patients with MEN-type-IIa-associated primary hyperparathyroidism. INTERVENTIONS: Subtotal parathyroidectomy (n = 25 with MEN I and 1 with MEN IIa), total parathyroidectomy and autotransplantation (one in each group) and removal of only enlarged glands (13 with MEN type I and 5 with MEN type IIa). MAIN OUTCOME MEASUREMENTS: Recurrence rate of hyperparathyroidism and permanent hypocalcaemia postoperatively. RESULTS: Subtotal parathyroidectomy in patients with MEN type I gave a significantly lower recurrence rate than removal of only enlarged glands (3/25 compared with 3/13, log rank, p = 0.04). Permanent hypocalcaemia developed in 3/25 compared with 3/13, respectively. 2/5 patients with MEN type IIa developed recurrences after removal of only enlarged glands and the rate was higher than expected. CONCLUSIONS: A more extensive operation is essential for patients with MEN type I; the rate of permanent hypocalcaemia is not increased, but the recurrence rate is reduced. Patients with MEN type IIa should be treated by excision of enlarged glands alone, but this may be extended to subtotal parathyroidectomy in patients with severe symptoms.

Adenoma↗

Characterization of toxicokinetics and toxicodynamics with linear systems theory: application to lead-associated cognitive decline.

We present a theoretical approach to analysis of toxicokinetics and toxicodynamics using linear systems theory. In our approach, we define two impulse response functions that characterize the kinetic behavior of an environmental agent in the body and the dynamic time-course behavior of its effect on the body. This approach provides a formalism for understanding the relation among exposure, dose, and cumulative biologically effective dose and for understanding the implications of an effect time-course on cross-sectional and longitudinal data analyses. We use lead-associated cognitive decline as a specific example where the approach may be applied.

Cognition Disorders↗

Associations of blood pressure and hypertension with lead dose measures and polymorphisms in the vitamin D receptor and delta-aminolevulinic acid dehydratase genes.

Evidence suggests that lead and selected genes known to modify the toxicokinetics of lead--namely, those for the vitamin D receptor (VDR) and delta-aminolevulinic acid dehydratase (ALAD)--may independently influence blood pressure and hypertension risk. We report the relations among ALAD and VDR genotypes, three lead dose measures, and blood pressure and hypertension status in 798 Korean lead workers and 135 controls without occupational exposure to lead. Lead dose was assessed by blood lead, tibia lead measured by X-ray fluorescence, and dimercaptosuccinic acid (DMSA)-chelatable lead. Among lead workers, 9.9% (n = 79) were heterozygous for the ALAD(2) allele, and there were no ALAD(2) homozygotes; 11.2% (n = 89) had at least one copy of the VDR B allele, and 0.5% (n = 4) had the BB genotype. In linear regression models to control for covariates, VDR genotype (BB and Bb vs. bb), blood lead, tibia lead, and DMSA-chelatable lead were all positive predictors of systolic blood pressure. On average, lead workers with the VDR B allele, mainly heterozygotes, had systolic blood pressures that were 2.7-3.7 mm Hg higher than did workers with the bb genotype. VDR genotype was also associated with diastolic blood pressure; on average, lead workers with the VDR B allele had diastolic blood pressures that were 1.9-2.5 mm Hg higher than did lead workers with the VDR bb genotype (p = 0.04). VDR genotype modified the relation of age with systolic blood pressure; compared to lead workers with the VDR bb genotype, workers with the VDR B allele had larger elevations in blood pressure with increasing age. Lead workers with the VDR B allele also had a higher prevalence of hypertension compared to lead workers with the bb genotype [adjusted odds ratio (95% confidence interval) = 2.1 (1.0, 4.4), p = 0.05]. None of the lead biomarkers was associated with diastolic blood pressure, and tibia lead was the only lead dose measure that was a significant predictor of hypertension status. In contrast to VDR, ALAD genotype was not associated with the blood pressure measures and did not modify associations of the lead dose measures with any of the blood pressure measures. To our knowledge, these are the first data to suggest that the common genetic polymorphism in the VDR is associated with blood pressure and hypertension risk. We speculate that the BsmI polymorphism may be in linkage disequilibrium with another functional variant at the VDR locus or with a nearby gene.

Adolescent↗

Endobronchial foreign body extraction: a new interventional approach.

Endobronchial foreign bodies are often difficult to diagnose as the cause of obstructive pneumonias and atelectasis, but once discovered, they can generally be removed, leading to immediate and dramatic resolution of symptoms. The use of flexible fiberoptic and rigid bronchoscopy to extract foreign bodies is well-known. Thoracotomy is generally reserved as a last resort due to the inherent risks of the procedure. We describe a new technique for foreign body removal utilizing steerable hydrophilic guidewires, standard sheaths, and a snare device commonly utilized in intravascular foreign body retrieval.

Aged↗

Reproducibility of the diagnosis of diabetes over a 30-month follow-up: the Paris Prospective Study.

OBJECTIVE: To describe the change in diabetic status over 30 months. RESEARCH DESIGN AND METHODS: Cohort study of 5,400 Caucasian men from the Paris Prospective Study, aged 44-55 years, who were not known as having diabetes at baseline. Oral glucose tolerance tests were performed at baseline and after 30 months. RESULTS: At baseline, diabetes was diagnosed in 2.9% of the men by fasting plasma glucose (FPG) > or =7.0 mmol/l and in 0.9% by isolated postchallenge hyperglycemia (IPH) (FPG <7.0 mmol/l and 2-h plasma glucose concentration > or =11.1 mmol/l), i.e., one in four of all men with newly diagnosed diabetes. Thirty months later, 42% of the men with diabetes diagnosed by FPG reverted to nondiabetic status, compared with 72% of those with diabetes diagnosed by IPH (P < 0.0001). For the men with diabetes diagnosed by FPG at baseline, diabetes had been diagnosed by a physician at 30 months in 11.5%, in contrast to only 3.9% of those with diabetes diagnosed by IPH (P < 0.05). For the 51 men with diabetes diagnosed by IPH at baseline, those who reverted to nondiabetic status had a lower frequency of family history of diabetes (P < 0.1), a higher mean corpuscular volume (P < 0.08), and a significantly higher total cholesterol concentration (P < 0.006) at baseline; in contrast, for the 156 men with diabetes diagnosed by FPG at baseline, the men who reverted to nondiabetic status and those who remained diabetic had similar characteristics. CONCLUSIONS: In this epidemiological study, diabetes diagnosed by one FPG concentration was more stable than diabetes diagnosed by one IPH; in clinical practice, the diagnosis of diabetes requires confirmation of the hyperglycemia.

Adult↗

From policemen to policies: what is the future for 2-h glucose? The Kelly West Lecture, 2000.

OBJECTIVE: To describe the characteristics and vital prognosis of men with diabetes diagnosed by one fasting plasma glucose (FPG) concentration > or =7.0 mmol/l, with diabetes diagnosed by one isolated postchallenge hyperglycemia (IPH) (FPG <7.0 mmol/l and a 2-h plasma glucose concentration > or =11.1 mmol/l), or with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: This study involved a cohort of 6,881 Caucasian nondiabetic men from the Paris Prospective Study, aged 44-55 years, who were followed for cause of death for 20 years. RESULTS: Diabetes was diagnosed in 4.3% of the men (1.0% diabetes diagnosed by IPH), and IGT was diagnosed in 9% of the men. At baseline, the men with diabetes diagnosed by IPH had a lower cardiovascular risk profile than those with diabetes diagnosed by FPG, as did the men with IGT and a normal fasting glucose level (<6.1 mmol/l, IGT and normal fasting glucose), compared with men with impaired fasting glucose (6.1-6.9 mmol/l, IGT and impaired fasting glucose [IFG]). At 20 years of follow-up, all-cause and cancer death rates were higher in men with diabetes diagnosed by IPH than in men with diabetes diagnosed by FPG (55 vs. 44%, P < 0.1 and 31 vs. 17%, P < 0.01, respectively) but were not significantly different for coronary causes (6 vs. 11%). Men with IGT and normal fasting glucose also had significantly higher cancer death rates than men with IGT and IFG. CONCLUSIONS: The most likely explanation for the high cancer and low coronary death rates is that men with diabetes diagnosed by IPH consumed alcohol; the men in this study drank 49 g of pure alcohol on average per day, equivalent to 0.6 l of wine. If these results are confirmed by other prospective studies, screening subjects for isolated postchallenge hyperglycemia may not be worthwhile.

Adult↗

In vitro efficacy of chemotherapeutics as determined by 50% inhibitory concentrations in cell cultures of mammary gland tumors obtained from dogs.

OBJECTIVE: To determine the 50% inhibitory concentration (IC-50) of carboplatin, cisplatin, and doxorubicin in cell cultures of mammary gland tumors obtained from dogs and to assess whether in vitro efficacy was within the range of clinically relevant concentrations, SAMPLE POPULATION: 30 mammary gland tumors excised from dogs. PROCEDURE: Cell cultures were established from the 30 tumors. Cultures then were treated with carboplatin, cisplatin, or doxorubicin. Growth inhibition of cultures was assessed via DNA measurement 24, 48, and 72 hours after treatment. The IC-50 values were calculated by use of linear interpolation. RESULTS: Cultures varied in their pattern of susceptibility. Doxorubicin induced significantly lower IC-50 values than the platinum derivatives. Cisplatin and carboplatin had comparable effects. The IC-50 values for carboplatin and doxorubicin were in the range of clinically relevant concentrations, but only part of the cisplatin cultures had IC-50 values within clinically relevant concentrations. We did not detect differences in the in vitro susceptibility among subtypes of tumors (ie, adenocarcinoma, solid carcinoma, malignant mixed tumor). CONCLUSION AND CLINICAL RELEVANCE: The IC-50 values determined in this study allowed assessment of in vitro drug efficacy of chemotherapeutics in cultures of mammary gland tumors obtained from dogs. Variations in susceptibility were evident and emphasize the importance of assessing susceptibility and resistance patterns for each tumor. Prospective studies to assess direct correlations between in vitro and in vivo efficacy must be performed to determine the clinical predictive value of this in vitro chemosensitivity assay for treatment of dogs with mammary gland tumors.

Adenocarcinoma↗

Associations of lead biomarkers and delta-aminolevulinic acid dehydratase and vitamin D receptor genotypes with hematopoietic outcomes in Korean lead workers.

OBJECTIVES: This study compares and contrasts associations of dimercaptosuccinic acid (DMSA)-chelatable lead, tibia lead, and blood lead with five hematopoietic outcomes and evaluates the effect modification of these relations by polymorphisms in the delta-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genes. METHODS: A cross-sectional study of 798 lead workers and 135 unexposed referents was performed. RESULTS: The DMSA-chelatable lead, tibia lead, and blood lead levels ranged in the lead (Pb) workers from 4.8 to 2103 g, -7 to 338 g Pb/g bone mineral, and 4 to 86 g/dl, respectively. The mean of the hemoglobin, hematocrit, zinc protoporphyrin (ZPP), and urinary (ALAU) and plasma (ALAP) delta-aminolevulinic acid levels of the lead workers were 14.2 (SD 1.4) g/dl, 42.4 (SD 4.4)%, 80.2 (SD 63.5) g/dl, 2.1 (SD 3.7) mg/l, and 17.7 (20.6) g/ml, respectively. After adjustment for the covariates, tibia lead was associated with all five hematopoietic outcomes, while blood lead and DMSA-chelatable lead were associated only with ZPP, ALAP, and ALAU. A comparison of the regression coefficients, total model adjusted R2 values, and delta R2 values revealed that blood lead was the best predictor of ZPP, ALAP, and ALAU. Only tibia lead was significantly associated with hemoglobin and hematocrit levels, but the additional variance explained by tibia lead was (<1%). No clear effect modification of the relations between the lead biomarkers and hematopoietic outcomes studied was caused by ALAD or VDR genotype. CONCLUSIONS: Lead must have a chronic, cumulative effect on hemoglobin and hematocrit levels, and any speculated mechanism cannot merely involve short-term plasma or target organ lead levels.

Adolescent↗

[Insulin sensitivity and ethnic groups].

Epidemiological surveys show a large variation of type 2 diabetes (DT2) prevalence from one country to another, suggesting ethnic discrepancies in insulin sensitivity. Many data seem to confirm this hypothesis. We will show them while concentrating on data provided by surveys performed in French-speaking countries. The mechanisms of the ethnic differences in insulin sensitivity are unclear and further insights are needed. More than genetic factors, environmental factors appear to be involved in the occurence of insulin resistance and DT2. The epidemic nature of obesity and subsequent DT2 in the world urges health authorities in each country to raise campaigns to promote changes in life style and nutritional habits before the announced pandemy of DT2 becomes reality.

Africa↗

Linear growth in children suffering from juvenile idiopathic arthritis requiring steroid therapy: natural history and effects of growth hormone treatment on linear growth.

We assessed linear growth and final height retrospectively in a group of 24 patients suffering from juvenile idiopathic arthritis (JIA) during childhood who had received steroid therapy. In these patients, there was a significant loss of height of more than 2 standard deviations during the first years of the disease, which correlated positively with the duration of prednisone therapy. After remission of the disease and discontinuation of prednisone treatment, 70% of the patients achieved catch-up growth, although 30% showed a persistent loss of height. Their mean final height was strongly correlated with their mean height at the end of steroid therapy and was significantly different between the group of patients with catch-up growth and the group without catch-up growth. This pattern of growth observed in patients with JIA should help us to define strategies of growth hormone (GH) treatment in these patients in order to improve their final height. We have previously reported the beneficial effects on growth and body composition of 1 year of GH treatment in a group of 14 growth-retarded patients suffering from JIA who received glucocorticoid therapy. These patients (n = 13) were treated again with GH at the same dosage (0.46 mg/kg/week [0.07 mg/kg/day]) for another 3-year period. GH treatment markedly increased growth velocity in these patients, but had a minor effect on height SDS, suggesting that these children will remain short when adults. Starting GH therapy in these patients earlier after the onset of the disease may prevent growth deterioration and metabolic complications induced by chronic inflammation and long-term steroid therapy.

Anti-Inflammatory Agents↗

Hepatitis B virus-transfected Hep G2 cells demonstrate genetic alterations and de novo viral integration in cells replicating HBV.

Hepatitis B virus (HBV) is a major etiological factor associated with hepatocarcinogenesis, but its role in the transformation process remains unclear. We previously documented the accumulation of genetic alterations in a HBV-transfected cell line. In the present study, we addressed the effect of HBV and its replication on the genome and phenotype of the host cell. Parental HBV-free Hep G2 cells and two HBV-transfected variant lines Hep G2215 and Hep G2T14. 1, which do and do not replicate HBV, respectively, were used to monitor genetic alterations in conjunction with HBV profile in vitro and in vivo. Comparison of in vitro growth rates showed that Hep G2T14.1 cells grew more rapidly, while Hep G2215 cells, replicating HBV, grew slower than parental Hep G2 cells. Molecular analysis confirmed an HBV integration site (s) in both variants, and reverse trancriptase-polymerase chain reaction (RT-PCR) amplification documented expression of transcript for the HBX protein, which has recently been implicated in the compromised efficiency of cellular DNA repair. Tumorigenisity testing indicate a comparable rate of tumor formation in nude mice of both HBV-transfected variants, giving rise to tumors in 3 weeks; parental Hep G2 cells did not form tumors in nude mice. Tumor tissue from nude mice injected with Hep G2T14.1 cells showed no change in HBV status. However, a new HBV integration site was detected in tumor tissue from Hep G2215-injected mice. Two cell lines derived from the respective tumor tissue grew in vitro at rates compatible to those observe before passage in nude mice. The Hep G2215 tumor-derived line continued to replicate HBV, while HBV status remained unchanged in the Hep G2T14.1 tumor-derived line. Unique genetic alterations were detected in both transfected cell lines, and Hep G2215 cells particularly showed cellular mosaicism and clonal selection when analyzed after the passage in nude mice. Further genetic alterations were detected in tumor-derived cell lines. Interestingly, the de novo genetic alterations in the Hep G2215 cells, which maintain the ability to replicate HBV, included a new HBV integration site, several chromosome rearrangements and loss of heterozygosity (LOH) of one p53 allele. Western analyses of p21/Waf1 protein indicate an upregulation of the protein in cells that replicate HBV. Based on the combined data, we hypothesize that the genetic alterations in the cellular genome could also be generated as a function in the presence of HBV and HBV replication. Possible mechanisms that could be implicated in cumulative mutagenetic events are discussed.

Animals↗

Investigation of the expression of Bin1, a putative suppressor, in human hepatoma cells.

Recent data suggest that Bin1, a novel C-MYC interacting protein, is a suppressor gene whose loss of expression is a frequent aberration associated with several malignancies. The mechanism responsible for loss of BIN1 expression is not understood. The purpose of this study is to investigate DNA profile of the BIN1 gene in human hepatoma Hep G2 cells, previously documented with lack of BIN1 expression. Chromosome and molecular analyses of Hep G2 cells were initiated to exclude the possibility of genetic alterations as a factor affecting BIN1 gene expression in these cells. We used Hep G2 cell line and its hepatitis B virus (HBV) transfected variants--Hep G2T14.1 and Hep G2215 cell lines. The cytogenetic localization of BIN1 was identified in the 2q14 region. Fluorescence in situ hybridization (FISH) with the chromosome 2 whole chromosome painting probe (WCP) demonstrated three or four intact copies of chromosome 2 in all three hepatoma cell lines studied. FISH analyses with the BIN1-specific probe of the Hep G2, Hep G2T14.1, and Hep G2215 metaphase chromosomes document no rearrangement of the BIN1 gene on any of the multiple copies of chromosome 2. FISH with the specific HBV probe did not identify the HBV integration site in Hep G2T14.1 and Hep G2215 cells within the BIN1 locus. Southern blot analyses revealed no genetic rearrangements in the BIN1 gene in any of the cell lines studied. Our RNA analyses (northern blot and RT-PCR) document lack of BIN1 message in Hep G2 cells in contrast to the presence of BIN1 in Hep G2T14.1 and Hep G2215 cells. No difference was identified in other transcripts analyzed, including c-myc. Analyses of BIN1 expression of Hep G2 cells at different passages were initiated and document low levels of BIN1 transcript in Hep G2 cells of passage < 85. Furthermore, BIN1 transcript was identified in additional seven HCC cell lines analyzed. Our data indicate that lack of Bin1 expression in HepG2 cells previously documented is a characteristic of cells of passage > 85 and is not due to genetic loss, or rearrangement within the BIN1 DNA sequence. Loss of the BIN1 transcript is not a characteristic of HCCs analyzed.

Adaptor Proteins, Signal Transducing↗

Restaging with gallium scan identifies chemosensitive patients and predicts survival of poor-prognosis mediastinal Hodgkin's disease patients.

UNLABELLED: Following treatment of mediastinal Hodgkin's disease (HD), residual masses are frequent and gallium scanning has proven to be of value in the evaluation of their specificity (fibrosis or active disease). This study assessed, for relapse and survival, the predictive value of restaging gallium scan of patients with a residual mass on computed tomography scan after induction chemotherapy. Between 1/89 and 12/97, in 53 newly diagnosed HD patients with a residual mediastinal mass, a gallium scan was performed after chemotherapy (3 or 4 courses) and always before consolidative radiotherapy. Characteristics at diagnosis were: nodular sclerosis histology, 89%; bulky mediastinal disease, 79%; B-symptoms, 51%. RESULTS: gallium scan was positive in 16 patients (30%) and negative in 37 (70%). At median follow-up period of 36 months, freedom-from-progression rate was 86% versus 19% (P<0.0001) for patients with negative vs positive gallium scans, respectively. The 5-year overall survival (OS) rate was 68% and differed significantly (P<0.0001) between negative (91%) and positive (25%) gallium scanning groups. The specificity of gallium scanning was 91% and the sensitivity 72% with a positive predictive value of 81% and a negative predictive value of 86%. Evaluation with gallium scan after induction chemotherapy identifies chemosensitive patients among those with poor-prognosis mediastinal HD. Although relapse may occur in patients with negative gallium scan, a postive gallium scan is highly predictive of failure and poor outcome, and treatment should thus be modified.

Adult↗