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Biomedical subjects

D Simon

Publications and source records attributed to D Simon.

At least 199 records · Page 11Linked to original sources
PubMed1996

Nasal pyriform aperture stenosis and absence of the anterior pituitary gland: report of two cases.

We describe two female infants with congenital nasal pyriform aperture stenosis and severe pituitary insufficiency. The anterior pituitary gland was undetectable with magnetic resonance imaging. Consanguinity of parents in both cases suggests autosomal recessive inheritance of this disorder. An early fetal developmental defect may explain this syndrome, which affects midline craniofacial structures. In patients with congenital pyriform aperture stenosis, magnetic resonance imaging of the brain and endocrine investigations should be performed for rapid diagnosis and treatment of the latter to avoid major neurologic complications.

Abnormalities, Multiple↗
PubMed1996

Gastrointestinal manifestations.

Gastrointestinal disease is a common problem in the setting of HIV-1 infection. As patients live longer and other opportunistic pathogens are suppressed, these problems are becoming even more important in the quality of life.

AIDS-Related Opportunistic Infections↗
PubMed1996

An improved DNA test for bovine leucocyte adhesion deficiency.

A modified DNA test, based on the polymerase chain reaction, was developed for the monogenic recessive disease bovine leucocyte adhesion deficiency (BLAD). The test was improved by the selection of new primers which facilitated the interpretation of the results. An easily scorable banding pattern makes the test useful in cattle breeding schemes and for clinical diagnosis. A total of 2381 samples was analysed over a period of three years. The carrier rate among young bulls at artificial insemination (AI) stations decreased from 11.6 per cent in 1993 to 9.9 per cent in the first five months of 1995. Continuous screening of young bulls before entering AI is still recommended unless both parents are proven to be genetically free of BLAD. The carrier rate among clinically suspect animals was not increased, and carriers are therefore not expected to be immunodeficient. Despite all efforts to eradicate the disease, calves with BLAD were still observed in 1995.

Animals↗
PubMed1996

131I-6 beta-iodomethylnorcholesterol scintigraphy: an assessment of its role in the investigation of adrenocortical incidentalomas.

OBJECTIVE: Most incidentally discovered adrenal tumours ('incidentaloma') are benign adrenocortical adenomas. It has been suggested that 131I-6 beta-iodomethylnorcholesterol (IMC) scan could specify the degree of functional autonomy of such adenomas depending on whether they prevent contralateral adrenal tracer uptake. Our purpose was to examine this hypothesis in a correlated scintigraphic and endocrine study. DESIGN: Prospective study evaluating the prevalence of unilateral IMC uptake (tumour uptake with no visualization of the contralateral adrenal gland) and bilateral uptake (uptake in both the tumoral and the contralateral adrenal glands) in patients with unilateral incidentaloma. Comparison of adrenocortical function and of IMC scan after dexamethasone (DXM) in the two scintigraphic groups thus defined. PATIENTS: Thirty-five patients with a unilateral mass highly suggestive of benign adrenocortical adenoma on CT scan. MEASUREMENTS: The IMC scan was performed in basal conditions (baseline scan) and after DXM (suppression scan). Adrenocortical function assessment included basal measurements of 11-deoxycortisol, 17 alpha-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulphate (DHEAS), plasma cortisol and ACTH, urinary free cortisol (UFC), overnight and low-dose DXM suppression test, and CRH test. RESULTS: The baseline scan showed 16 patients (46%) with unilateral uptake (group A) and 19 (54%) with bilateral uptake (group B). Patients in group A exhibited lower ACTH values at 0800h (P = 0.05) and higher cortisol values after an overnight DXM suppression test (P = 0.02), than did patients in group B. In addition, 3 patients in group A failed the overnight and the low-dose DXM suppression tests. Adrenal masses were larger in group A than group B (P = 0.04) and an inverse correlation was found in the whole population between tumour size and ACTH value at 0800h (P = 0.05). On the suppression scan performed in 14 patients (7 in each group), patients in group A continued to exhibit unilateral tumour uptake and bilateral uptake was suppressed in 72% of patients in group B. An adrenal mass was removed in 3 patients of group A with confirmed benign adrenocortical adenomas. In the post-surgical period, the contralateral gland was again visualized in a baseline scan and the hormonal evaluation returned to the normal range. CONCLUSION: Unilateral 131I-6 beta-iodomethylnorcholesterol tumour uptake is a frequent feature in benign adrenocortical adenomas. Hormonal data and scintigraphic profiles obtained after dexamethasone, as well as hormonoscintigraphic changes observed after surgery, provide evidence that unilateral uptake is related to functioning adenomas with various degrees of autononomy and suggest that the 131I-6 beta-iodomethylnorcholesterol scan could be a valuable tool for screening 'subclinical' Cushing's adenomas.

Adenoma↗
PubMed1996

Work-related disability: results from the American migraine study.

Migraine headache is a highly prevalent, often severely painful and frequently disabling disorder. The indirect costs related to disability greatly exceed the direct cost of medical care. The objective of this paper is to describe work-related disability associated with migraine headache and predictors of disability. In a two-stage survey of the US population, we estimate missed workdays and impairment at work in a sample of 1663 migraine suffers, age 18 years and older. Lost workday equivalents (LWDE) was derived as the sum of actual missed workdays and the product of percentage effectiveness at work and days at work with the most severe headache. Overall, reported actual lost workdays and reduced effectiveness at work contributed approximately equally to total LWDE. A total of 51.1% of females and 38.1% of male migraineurs experienced six or more LWDE per year. This subgroup of migraine sufferers accounted for about 90% of the total LWDE experienced by all respondents. Among women, headache duration was the strongest predictor of LWDE followed by less significant associations with number of symptoms and pain level. Among men, only pain level was significantly associated with LWDE. Among sociodemographic factors, disability was more likely among older (40+) subjects and less likely among individuals with higher education and higher income (females only), even after adjusting for headache features. Health-care interventions may yield the greatest individual benefit (by reducing pain and disability) and the greatest societal benefit (by reducing indirect costs) if they are directed to those who account for the greatest proportion of disability.

Adolescent↗
PubMed1996

Redifferentiation therapy of differentiated thyroid carcinoma with retinoic acid: basics and first clinical results.

Retinoic acids (RA) regulate growth and differentiation of normal epithelial tissue. They have been employed in anticancer treatment and showed positive effects in hematopoetic and various epithelial tumors. Experimental data with follicular thyroid tumor cells showed strong evidence of induction of differentiated cell function and antiproliferative effects. Based on these data a consecutive series of 10 patients with advanced thyroid carcinoma were treated with 13-cis-retinoic acid (Roaccutan) 1.5 mg/kg body weight for six weeks. Follow-up demonstrated renewed uptake of radioiodine in 4 of 10 patients allowing performance of further radioiodine therapy. Reduction in tumor size due to antiproliferative effects of RA could not yet be verified.

Adenoma↗
PubMed1996

INT-2 gene amplification in differentiated human thyroid cancer.

Oncogene amplification is frequent in many epithelial tumors and often associated with advanced tumor progression. In different epithelial neoplasias it helps to provide prognostic information on individual patients. The present study was performed to evaluate the hitherto unknown prevalence of INT-2 gene amplification and its potential usefulness as prognostic marker in patients with human thyroid cancer. We used differential quantitative polymerase chain reaction and fluorescent DNA technique as a reliable method to detect low copy-number amplification of oncogenes from archival carcinoma specimens. Sequences from the int-2 gene and the single copy gamma-interferon gene were amplified simultaneously by PCR and quantified on a fluorescence activated sequencer. Native tumor tissue from 63 patients with differentiated thyroid cancer (43 papillary, 3 oncocytary, and 17 follicular) and from 12 goiters was analyzed by differential quantitative polymerase chain reaction. The study group contained many far advanced tumors. 40% of tumors were recurrent, 35% were staged T4 tumors and 70% presented with lymph node metastases. The prevalence of INT-2 amplification was 12% for follicular and 7% for papillary carcinomas. In goiter tissue no amplification was found. Amplification was only 2-4fold in positive cases. Low grade amplification is of no apparent importance in differentiated thyroid cancer.

Adenoma↗
PubMed1996

Venous ulcer fibroblasts compared with normal fibroblasts show differences in collagen but not fibronectin production under both normal and hypoxic conditions.

Previous immunocytochemical analysis showed that the base of venous ulcers was deficient in fibronectin compared with surrounding "normal" dermis. Here, we investigate whether impaired synthetic ability of ulcer fibroblasts could underlie this observation. Ulcer fibroblasts, established in culture from biopsies of the edge of chronic venous leg ulcers, were compared with normal fibroblasts grown from biopsies of site-and age-matched normal skin for their ability to synthesize matrix molecules. Collagen and fibronectin synthesis were measured following metabolic labeling, as collagenase susceptible counts and counts with gelatin affinity, respectively. More collagen was produced by normal fibroblasts than ulcer fibroblasts, both when the cells were cultured on plastic and in collagen gels. In fibronectin synthesis, however, there was no major difference between the two cell types on either substratum. The hypoxic environment to which ulcer fibroblasts are exposed may have caused the intrinsic differences in collagen synthesis by the two fibroblast types. When we tested the effect of culturing cells under hypoxic conditions, both cell types produced less collagen, especially normal fibroblasts grown in a collagen gel, but there was no effect of hypoxia on fibronectin synthesis. We conclude that venous ulcer edge-derived fibroblasts have an impaired ability to synthesize collagen in vitro, but synthesize fibronectin normally. Therefore, the low level of fibronectin found in venous ulcers is not likely to be due to the inability of ulcer cells to produce it or to the response to hypoxic conditions but may be due to the degradation of synthesized fibronectin by proteases present in these ulcers.

Cells, Cultured↗
PubMed1996

Competence for genetic transformation in encapsulated strains of Streptococcus pneumoniae: two allelic variants of the peptide pheromone.

The nucleotide sequence of comC, the gene encoding the 17-residue competence-stimulating peptide (CSP) of Streptococcus pneumoniae (L. S. Havarstein, G. Coomaraswamy, and D. A. Morrison, Proc. Natl. Acad. Sci. USA 92:11140-11144, 1995) was determined with 42 encapsulated strains of different serotypes. A new allele, comC2, was found in 13 strains, including the type 3 Avery strain, A66, while all others carried a gene (now termed comC1) identical to that originally described for strain Rx1. The predicted mature product of comC2 is also a heptadecapeptide but differs from that of comC1 at eight residues. Both CSP-1 and CSP-2 synthetic peptides were used to induce competence in the 42 strains; 48% of the strains became competent after the addition of the synthetic peptide, whereas none were transformable without the added peptides.

Alleles↗
PubMed1996

Diagnosis and clinical characteristics of inherited activated protein C resistance.

The diagnostic strategies and clinical characteristics of thrombophilia associated with heterozygous or homozygous factor V Leiden mutation have been determined according to the literature and to a personal study in 51 families. Factor V mutation was present in the 51 propositi and in 84 out of 125 family members (81 heterozygous, 3 homozygous). Venous thrombosis was observed in all the propositi, in 17 of the 84 family members with the mutation and in 6 of the 41 with a normal APC resistance test and no mutation. An associated protein C or protein S deficiency was present in 5 families (10%). The most frequent clinical manifestations were superficial or deep vein thrombosis and/or pulmonary embolism, but also thrombosis at an unusual site (cerebral, mesenteric or central retinal vein). A causal relationship is frequently difficult to demonstrate. A precipitating factor was observed in 84% of cases and a recurrent thrombotic episode occurred in 50% of propositi. The risk of thrombosis associated with pregnancy was high in the post-partum period, especially in homozygous women. In the 28 homozygous subjects, markers of coagulation activation were frequently elevated in untreated patients. Finally, the efficacy of anticoagulant treatment is suggested but the long period often observed between treatment interruption and a recurrence does not militate in favour of long term treatment.

Anticoagulants↗
PubMed1996

Selective recognition of M235T angiotensinogen variants and their determination in human plasma by monoclonal antibody-based immunoanalysis.

The common M235T mutation of human angiotensinogen has been shown to be associated with a 10-20% increase in plasma angiotensinOgen level and increased frequency of essential and pregnancy-induced hypertension. The detection of such a common factor in the plasma of individuals at risk could be a useful tool for modern molecular-based medicine. The recognition of M235T variants was investigated using four monoclonal antibodies (mAbs) directed against human angiotensinogen; two immunometric assays were developed. The first assay (using mAbS 7B2 and 4G3) allowed the direct determination of angiotensinogen concentrations and did not show a significant difference with the enzymatic measurement of angiotensinogen. The second assay (using mAbs 1H8 and 1C11) showed a fine distinction between the T235 mutant and M235 wild-type forms of angiotensinogen, with a greater affinity for the latter, as confirmed by biosensor BIAcore experiments. This assay was extremely sensitive in measuring the proportions of the M235 and T235 forms present in the test samples, the first time such a distinction has been achieved in the serpin family. The simple immunoanalysis of the plasma allowed the direct determination of the M235T genotype of the individual tested. Furthermore, it was shown that the T174M mutation, described as being in complete linkage disequilibrium with the M235T mutation, had no influence on these results. Moreover, this assay suggested the presence of the M235 and T235 angiotensinogens in approximately equal amounts in heterozygous plasmas. In conclusion, the immunometric assay described in this study should provide original tools for investigating the relationship between M235T genotype, plasma angiotensinogen levels, and regulation of blood pressure.

Angiotensinogen↗
PubMed1996

[Endocrine pancreatic tumors].

Endocrine active islet cell tumors of the pancreas are rare and become clinically evident mainly by symptoms of hormone over-production (hypoglycemia, gastric ulcer disease, diarrhea etc.). The tumors may occur sporadically or in connection with the familial MEN-I syndrome. Diagnosis is verified biochemically and does not need further localization studies. Localization studies are important, however, intraoperatively and in detecting persistent or recurrent tumor disease. Principally endocrine pancreatic tumors are excised selectively with exception of MEN-I patients and patients suffering from "Nesidioblastosis", where subtotal resections of the pancreas are indicated. In case of malignant metastatic endocrine pancreatic tumors palliative therapies (surgery, embolization, chemotherapy, therapy of hormone excess etc.) are demanded to improve the quality of life in these patients, since they may survive for years despite their tumor burden.

Adenoma, Islet Cell↗
PubMed1996

Influence of acute or chronic rejection on myocardial collagen density in serial endomyocardial biopsy specimens from cardiac allografts.

BACKGROUND: The knowledge of long-term changes in the transplanted heart is still incomplete. Among these changes that could potentially have an adverse effect on long-term cardiac function, myocardial fibrosis is of great concern. The aim of this study was to investigate the possible influence of acute or chronic rejection on the development of myocardial fibrosis in cardiac allografts. METHODS: We used light microscopic computer-assisted morphometry of collagen density in 200 right ventricular endomyocardial biopsy specimens taken routinely in 21 heart transplant recipients during a mean follow-up period of 36 months (range, 12 to 84). The 21 patients were divided into two groups according to the presence of chronic rejection assessed by coronary angiography. The first group consisted of 11 patients with no chronic rejection; the second group consisted of 10 patients with chronic rejection. Both groups were divided into four subgroups according to the highest grade of acute rejection reached during the follow-up period (subgroup 1, no acute rejection or grade 1A; subgroup 2, grade 1B; subgroup 3, grades 3A or 3B; subgroup 4, grade 4). Patients of both groups were selected on the basis of similarity patterns in clinical characteristics and mean follow-up time. RESULTS: Patients with no chronic rejection had relatively little variation in serial determinations of myocardial collagen density. During the prechronic and chronic phases in patients with chronic rejection, we found no overall increase in myocardial collagen density. In both the chronic rejection and no chronic rejection groups there was no consistent relationship between myocardial collagen density and severity of acute rejection. In both groups there were occasional strikingly elevated myocardial collagen density values that were well above the other serial determinations. These elevated values of collagen density were mainly a result of scars, the sequellae of prior myocyte damage, because neither interstitial nor perivascular fibrosis could be detected. CONCLUSION: During this long-term follow-up study of endomyocardial biopsy samples, we found no significant association between either acute or chronic rejection and the later increase in myocardial collagen density.

Acute Disease↗
PubMed1996

[Is total thyroidectomy and lymph node excision as therapy of differentiated thyroid gland carcinomas in childhood justified?].

The extent of radical resection of differentiated thyroid carcinomas in children (< 18 years) is discussed controversially because of good prognosis, on the one hand, but a high rate of lymph node metastases, greater tumor size, lung metastases and tumor recurrences on the other. Because of our data we advocate thyroidectomy, cervical lymph node dissection and postoperative 131J-therapy as the treatment of choice in patients with manifest disease in order of further detection and/or treatment of lung metastases. Limited radicality (i.e. hemithyroidectomy) should be reserved for children with small and occult tumors.

Adenocarcinoma, Follicular↗
PubMed1995

New monoclonal antibodies directed against the propart segment of human prorenin as a tool for the exploration of prorenin conformation.

Six monoclonal antibodies (MAbs) directed against human prorenin were produced by immunizing BALB/c mice with a peptide corresponding to the sequence (-17 to +9) of prorenin. The new MAbs were screened for their ability to first bind to the immobilized peptide and then to prorenin previously captured by an anti-total renin MAb. The specificity of the MAbs was confirmed by the total lack of binding to active renin. Using BIAcore technology, equilibrium affinity constants of the MAbs were determined and ranged from 3.2 x 10(8) to 5.7 x 10(9) l/mol. Immunoradiometric assays (IRMA) for prorenin were performed using the anti-total renin MAb and the anti-prorenin MAbs. The best results were obtained when an anti-prorenin MAb was immobilized and the anti-total renin MAb was used as tracer in a one-step procedure. Moreover, the signal was significantly increased by the presence of the renin inhibitor SR 43845 suggesting that the inhibitor-induced conformational change of prorenin could be detected by the MAbs.

Amino Acid Sequence↗