Search PubMed⌕ Search

Biomedical subjects

D Simon

Publications and source records attributed to D Simon.

At least 145 records · Page 8Linked to original sources
PubMed1998

Redifferentiation therapy with retinoids: therapeutic option for advanced follicular and papillary thyroid carcinoma.

During the course of tumor progression the differentiated morphologic and functional characteristics of differentiated thyroid carcinomas (DTC) disappear. This corresponds to more aggressive growth, metastatic spread, and loss of iodine uptake. Experimental data give strong evidence that differentiated functions of iodine metabolism can be reinduced by retinoic acids. Results of a study performed in patients with advanced DTC are presented. Twenty patients with DTC (eight follicular, seven papillary, five oxyphilic) were selected for treatment with retinoic acid 1.5 mg/kg body weight/day over 5 weeks. All patients had advanced tumor stages with prior operative and radioiodine treatment. Extensive tumor invasion, distant metastatic spread, or insufficient or no radioiodine uptake precluded any conventional therapeutic option. The aim was to assess the changes under retinoid treatment. Iodine uptake increased in eight patients (three follicular, three papillary, two oxyphilic). Thyroglobulin (TG) as parameter for tumor mass and differentiation increased in 12 (63%) patients, decreased in 6 (32%), and did not change in 1 (5%). Retinoids do have an effect on differentiation status of DTC, reinducing iodine uptake in 50% of patients. TG levels do not always parallel a response in iodine uptake.

Adenocarcinoma, Follicular↗
PubMed1998

Reoperative surgery for organic hyperinsulinism: indications and operative strategy.

Organic hyperinsulinism has a good chance of cure by operation, although patients with diffuse or multiple disease run a high risk of recurrence or persistence of disease. Surgical management and outcome in these patients are presented and discussed. Between 1986 and April 1997 a total of 62 patients were operated on for organic hyperinsulinism [solitary 48, multiple 3, multiple endocrine neoplasia type I (MEN-I) 2, diffuse 4, malignant 5]. Persistence or recurrence occurred in 10 patients (16%). Among the six that persisted, four were malignant and two benign. All four of those that recurred were benign. Patients with benign disease presented with multiple tumors (n = 3), MEN-I syndrome (n = 1), and diffuse/nodular hyperplasia (n = 2). The duration between diagnosis and reintervention ranged from 1 to 10 years. Preoperative diagnosis was able to localize tumors in three patients (computed tomography 1, angiography 2, calcium stimulation 1). Operative procedures were multiple enucleations in two patients with sporadic disease, subtotal resection plus enucleation in the case of MEN-I syndrome, subtotal resection for diffuse hyperplasia, left resection for adenomatosis, and tumor extirpation after multiple previous operations. Long-term clinical and biochemical cure was achieved in five of six patients (mean follow-up 5 years). Octreotide therapy shows good symptomatic control in the patient with operative failure. Reintervention for organic hyperinsulinism is successful (80% cure) and requires preoperative imaging and individual surgical management.

Adolescent↗
PubMed1998

Prophylactic thyroidectomy in 75 children and adolescents with hereditary medullary thyroid carcinoma: German and Austrian experience.

When mutations of the RETproto-oncogene were found in 1993 to account for hereditary medullary thyroid carcinoma (MTC), surgeons obtained the opportunity to operate on patients prophylactically (i. e., at a clinically asymptomatic stage). Whether this approach is justified, and, if so, when and to which extent surgery should be performed remained to be clarified. A questionnaire was sent to all surgical departments in Germany and Austria. All of the patients who fulfilled the following criteria were enrolled: (1) preoperatively proved RET mutation; (2) age </= 20 years, (3) clinically asymptomatic thyroid C cell disease; and (4) TNM classification pT0-1/pNX/pN0-1/M0. Seventy-five patients were identified, and fifteen mutations were detected in six codons. Two adolescents had unilateral pheochromocytomas as part of the multiple endocrine neoplasia II (MEN-II) syndrome. No hyperparathyroidism was noted. All patients underwent total thyroidectomy, and 57 patients went on to have lymph node dissection. Parathyroid glands were removed in 34 patients and autografted in 11. Histopathology revealed MTC in 46 patients (61%, youngest 4 years); C cell hyperplasia (CCH) only was detected in the other 29 patients. Three patients had lymph node metastases (LNMs) the youngest being age 14 years. Calcitonin levels were not useful for differentiating between CCH and MTC, but in all patients with LNMs at least the stimulated calcitonin levels were assayed. After surgery, five patients (6.7%) sustained permanent hypoparathyroidism, and one patient (1.3%) had a permanent unilateral recurrent nerve palsy. All but three patients (96%) were biochemically cured. In conclusion, prophylactic total thyroidectomy can be performed safely in experienced centers. We recommend prophylactic total thyroidectomy at age 6. Cervicocentral lymph node dissection should be included when calcitonin levels are elevated or if patients are older than 10 years. Bilateral lymph node dissection should be performed if LNMs are suspected or when patients with elevated calcitonin are older than 15 years.

Adolescent↗
PubMed1998

Genetic and biochemical screening for endocrine disease.

The development of biochemical and genetic screening tests for inherited endocrine diseases has dramatically changed our approach to surgical patients with endocrine tumors. Among more than 1800 patients with endocrine tumors and a possible inherited disease operated on between 1986 and 1997, there were 6.1% to 7.3% who were found to have a familial disease associated with familial medullary thyroid cancer, (MTC), multiple endocrine neoplasia type IIa (MEN-IIa), MEN-IIb, or MEN-I. Genetic testing for the RET proto-oncogene is therefore recommended for all patients with MTC, and testing for the MEN-I gene is recommended in patients with suspected MEN-I and in specific clinical subgroups with an increased probability of endocrine tumor heredity. Early treatment based on early diagnosis by genetic testing appears to improve survival and to decrease morbidity in these patients.

Biomarkers↗
PubMed1998

Hormonal status and NIDDM in the European and Melanesian populations of New Caledonia: a case-control study. The CALedonia DIAbetes Mellitus (CALDIA) Study Group.

OBJECTIVE: To assess ethnic differences in androgenic status related to non insulin-dependent diabetes mellitus (NIDDM) in male and female Melanesians and Europeans of New Caledonia. DESIGN: This is a case-control study nested in a prevalence study for diabetes mellitus in the multiracial population of New Caledonia. SUBJECTS: 186 male subjects were included in the survey (77 Melanesians and 16 Europeans in each case and control group). Each case and control group included 104 female Melanesian subjects (69 premenopausal and 35 postmenopausal). METHODS: Diabetic subjects were matched for age, gender, ethnic group and location, with healthy normoglycaemic subjects. Testosterone levels in men and sex hormone-binding globulin (SHBG) levels in women (measured by radioimmunoassay, RIA) were compared between NIDDM and control subjects in relation to obesity, central adiposity and insulin levels. RESULTS: In both ethnic groups, NIDDM was associated with lower testosterone levels but there was a marked difference among Europeans. Testosterone was negatively associated with the body mass index (BMI) (r= -0.35, P <0.01) and fasting insulin (r= -0.37, P <0.001) in control Melanesians only. In Melanesian women, NIDDM was associated with lower SHBG levels in pre- and postmenopausal women (P <0.001). SHBG mean level was not associated with menopausal status. CONCLUSION: Our results confirm in a Pacific population that NIDDM is associated with low levels of testosterone in men and low levels in SHBG in women. In contrast to white populations, Melanesian women have a more androgenic profile, whatever their menopausal status.

Body Constitution↗
PubMed1998

Reliability of an illness severity measure for headache in a population sample of migraine sufferers.

OBJECTIVES: To examine the reliability and related measurement properties of an illness severity measure for headache derived from responses to a 16-item self-administered questionnaire, the Headache Impact Questionnaire (HImQ), and to determine if there is support for combining measures of pain and disability into a single scaled measure of severity. METHODS: A population-based sample of migraine headache sufferers completed the HImQ twice, an average of 38 days apart. The HImQ included questions about number of headaches in the last 3 months, headache duration, last headache, pain intensity (two questions), need for bedrest (two questions), disability in specific domains of activity (seven questions about interference with ability to work, do household chores, and engage in non-work activity), and symptoms (two questions). RESULTS: Test-retest correlations of individual questions ranged from 0.65 to 0.93. In principal components analysis, a single factor with significant loading emerged. One measure of pain intensity (average pain score from 0 to 10) and items related to disability (i.e., missed days due to headache, and reduced effectiveness because of headache) in defined activity domains (work for pay, housework, nonwork activities) had the greatest weights on this single factor, supporting prior work on combining measures of pain and disability into a single scale. The HImQ score was derived as the sum of average pain intensity and total lost time in each of the three domains of activity, expressed as lost days. The latter was derived as the sum of actual missed days in each activity domain and reduced effectiveness day equivalents in each activity with a headache. The test-retest correlation was 0.77 for all eligible subjects and 0.85 when one influential outlier was removed. Cronbach's alpha was 0.83. CONCLUSIONS: The HImQ score, based on eight items, is a highly reliable and internally consistent measure of headache severity.

Activities of Daily Living↗
PubMed1998

Medical consultation for migraine: results from the American Migraine Study.

BACKGROUND: Migraine headaches are often disabling but usually responsive to treatment. Nonetheless, many people with migraine never consult a doctor for headaches. In a sample of the US population, we sought to determine the proportion of active migraineurs who ever consulted a doctor for headache and to identify the headache characteristics and sociodemographic factors associated with consulting. METHOD: A mailed questionnaire survey was sent to 15,000 US households, selected from a panel to be representative of the US population. Of 20,468 eligible respondents ranging in age from 12 to 80 years, 2479 met a case definition for migraine. We mailed a second questionnaire to all migraineurs identified on the first survey and achieved a 69.4% response rate. The second survey assessed headache characteristics, patterns of medical care use, medication use, and method of payment for health care. RESULTS: Sixty-eight percent of female and 57% of male migraineurs reported having ever consulted a doctor for headache. Consultation was more likely with increasing age and in women who ever married. In females, several headache characteristics including pain intensity, number of migraine symptoms, attack duration, and disability were associated with consultation. Of those who never consult, 61% report severe or very severe pain and 67% report severe disability or the need for bed rest with their headaches. CONCLUSION: The results of this survey indicate that a significant proportion of migraine sufferers never consult doctors for their headaches. Given that a large proportion of persons who never consult report high levels of pain and disability, these data suggest that there are opportunities to appropriately increase health care utilization for migraine. Given that 40% of migraineurs who have ever consulted do not report a physician diagnosis of migraine, there is a need to improve headache diagnosis and/or doctor-patient communication about migraine.

Adolescent↗
PubMed1998

Regulation of the HGF-receptor c-met in the thyroid gland.

HGF (hepatocyte growth factor) has been characterised as an important mitogen and motogen in many epithelial cells. The biological and clinical significance of HGF and its receptor c-met in the thyroid is currently under study. Overexpression of c-met is an important feature of papillary thyroid cancer. We developed a quantitative differential RT-PCR method in order to examine HGF-receptor regulation using RNA of about 50 cells per analysis. Experiments were performed in three spontaneously transformed follicular thyroid cancer (FTC) cell lines FTC-133, 236, and 238, 7 primary cultures derived from multinodular goitres, one from Graves disease and 1 from papillary thyroid cancer (PTC). TGF-alpha and to a minor degree HGF were shown to induce a marked up-regulation of the receptor whereas bovine TSH, NaI, dbcAMP or basic FGF had no apparent effect. We conclude that expression of the HGF-receptor is under control of paracrine growth factors activating tyrosine-kinase-dependent pathways. We could demonstrate a minor stimulation of thyroid cell proliferation by HGF in presence but not in absence of 10% fetal calf serum.

Adult↗
PubMed1998

High free fatty acid concentration: an independent risk factor for hypertension in the Paris Prospective Study.

BACKGROUND: An inconsistent relationship has been reported between insulin and hypertension incidence. Free fatty acids are related to insulin-resistance and may have a direct effect on hypertension. We examined the effect of free fatty acids on hypertension incidence, taking into account other abnormalities of the insulin-resistance syndrome. METHODS: In all, 2968 non-hypertensive and non-diabetic Caucasian men were followed for 3 years. Hypertension incidence was defined as systolic blood pressure (SBP) > or =160 mmHg or diastolic blood pressure (DBP) > or =95 mmHg or drug treatment for hypertension. RESULTS: Free fatty acid elevation was a highly significant risk factor for hypertension when controlled for age, family history of hypertension, alcohol consumption, body mass index, iliac circumference and weight change. Further controlling for SBP, heart rate and fasting insulin and glucose did not decrease its predictive power (hazard rate ratio [RR] = 1.58, 95% confidence interval [CI]: 1.30-1.91 comparing the 90th to the 10th percentiles at fasting; RR = 1.54, 95% CI: 1.33-1.79 at 2 h). In a forward stepwise model controlled for age, family history of hypertension, alcohol consumption and SBP, the selected variables explaining the occurrence of hypertension were, in order, weight change, 2-h free fatty acids, iliac circumference and fasting free fatty acids, whereas body mass index, heart rate, insulin, glucose and other lipids did not enter into the model. CONCLUSIONS: Free fatty acids elevation, when controlled for all known risk factors and other abnormalities of the insulin-resistance syndrome, is a risk factor for hypertension. These results highlight the possible benefits of treatment using free fatty acid oxidation inhibitors.

Adult↗
PubMed1998

Timing fracture repair in patients with severe brain injury (Glasgow Coma Scale score <9)

BACKGROUND: Trauma patients with severe brain injury are at risk of secondary brain injury. Femur fractures, if present, should be repaired when potential causes of secondary brain injury have been corrected. METHODS: Sixty-one patients with severe or moderate closed head injury and femur fractures were identified. Patients were divided into groups by time until femur fracture reduction. RESULTS: An inversely proportional trend was demonstrated when comparing time until surgery with the percentage of patients who experienced hypotensive events during surgery. Patients in the 0- to 2-hour group were eight times more likely to become hypotensive during femur repair than patients in the >24-hour group. Seventy-four percent of patients with intracranial pressure monitoring experienced cerebral perfusion pressure <70 mm Hg. CONCLUSIONS: Operation in similar patients should be done when risks are minimized by adequate resuscitation. Secondary brain injury is more common in early femur repair. Operation delay of 24 hours may be necessary to prevent hypoxia, hypotension, and low cerebral perfusion pressure.

Adolescent↗
PubMed1998

A high-resolution microsatellite map of the mouse genome.

The European Collaborative Interspecific Backcross (EUCIB) resource was constructed for the purposes of high-resolution genetic mapping of the mouse genome (). The large Mus spretus/C57BL/6 backcross of 982 progeny has a genetic resolution of 0.3 cM at the 95% confidence level ( approximately 500 kb in the mouse genome). We have used the EUCIB mapping resource to develop a genome-wide high-resolution genetic map incorporating 3368 microsatellites. The microsatellites are distributed among 2302 genetically separated bins with 1.46 markers per bin on average. Average bin separation is 0.61 cM. This high-resolution genetic map will aid the construction of a robust physical map of the mouse genome.

Animals↗
PubMed1998

A double-blind placebo-controlled pilot study of glutamine therapy for abnormal intestinal permeability in patients with AIDS.

OBJECTIVES: Up to 20% of patients with AIDS have abnormal intestinal permeability (IP). Glutamine seems to play an important role in preventing the increase in IP and loss of intestinal mucosal mass associated with total parenteral nutrition, and may be superior to glucose for oral rehydration in the setting of intestinal infection. This study was designed to see if supplemental glutamine could alter the abnormal IP of AIDS. METHODS: Randomly chosen patients with AIDS from the Jacobi Medical Center human immunodeficiency virus (HIV) clinic underwent IP testing using lactulose and mannitol. Those with abnormal IP were enrolled. Duodenal biopsies were performed with a Crosby capsule and the patients were randomized in a double-blind fashion to receive placebo or glutamine (4 g/day or 8 g/day) for 28 days, after which intestinal permeability tests and duodenal biopsies were repeated. Intestinal morphology was graded by ratio of villus height to crypt depth, and by degree of inflammation. RESULTS: All patients complied with the therapy and there were no dropouts or reported side effects. The results showed less worsening of IP with the 4 g/day dose, compared with placebo. At the 8 g/day dose, there was stabilization of IP and improved absorption of mannitol. Intestinal morphology and inflammation did not change in any group. CONCLUSIONS: These results, although not significant, suggest a trend towards improved IP and enhanced intestinal absorption with glutamine. Glutamine doses of at least 20 g/day may be necessary to improve IP. We recommend further studies at higher doses and for longer durations.

Adult↗
PubMed1998

Large-scale identification of virulence genes from Streptococcus pneumoniae.

Streptococcus pneumoniae is the major cause of bacterial pneumonia, and it is also responsible for otitis media and meningitis in children. Apart from the capsule, the virulence factors of this pathogen are not completely understood. Recent technical advances in the field of bacterial pathogenesis (in vivo expression technology and signature-tagged mutagenesis [STM]) have allowed a large-scale identification of virulence genes. We have adapted to S. pneumoniae the STM technique, originally used for the discovery of Salmonella genes involved in pathogenicity. A library of pneumococcal chromosomal fragments (400 to 600 bp) was constructed in a suicide plasmid vector carrying unique DNA sequence tags and a chloramphenicol resistance marker. The recent clinical isolate G54 was transformed with this library. Chloramphenicol-resistant mutants were obtained by homologous recombination, resulting in genes inactivated by insertion of the suicide vector carrying a unique tag. In a mouse pneumonia model, 1.250 candidate clones were screened; 200 of these were not recovered from the lungs were therefore considered virulence-attenuated mutants. The regions flanking the chloramphenicol gene of the attenuated mutants were amplified by inverse PCR and sequenced. The sequence analysis showed that the 200 mutants had insertions in 126 different genes that could be grouped in six classes: (i) known pneumococcal virulence genes; (ii) genes involved in metabolic pathways; (iii) genes encoding proteases; (iv) genes coding for ATP binding cassette transporters; (v) genes encoding proteins involved in DNA recombination/repair; and (vi) DNA sequences that showed similarity to hypothetical genes with unknown function. To evaluate the virulence attenuation for each mutant, all 126 clones were individually analyzed in a mouse septicemia model. Not all mutants selected in the pneumonia model were confirmed in septicemia, thus indicating the existence of virulence factors specific for pneumonia.

Animals↗
PubMed1998

Evaluation of diarrhea in HIV-infected patients.

Diarrhea is a major problem for patients infected with HIV: initial studies indicated that 50% of HIV-seropositive patients developed diarrhea, but this may be an underestimate. Diarrhea has an appreciable adverse affect on the quality of life of these patients; also, they use more health care facilities and health care dollars than HIV-positive patients without diarrhea. Individuals who have homosexuality or bisexuality as their HIV risk factor are more likely to have diarrhea and to have an enteric pathogen identified as the cause of diarrhea than are patients who have heterosexuality or intravenous drug use as their risk factor.

AIDS-Related Opportunistic Infections↗
PubMed1998

[Geographical differences of thyroid carcinoma and basic molecular principles].

Geographical differences have been demonstrated for the cancer incidence and histology of differentiated thyroid cancer. Iodine intake and specific external noxes, such as nitrosamine ingestion or external radiation are important factors. It is still questionable whether histologically identical differentiated thyroid cancers are prognostically different in low and rich iodine areas. Despite increased knowledge of molecular and genetic changes in differentiated cancer, the present therapy is primarily related to patient age, tumor stage and histology.

Cell Transformation, Neoplastic↗