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Biomedical subjects

D Simon

Publications and source records attributed to D Simon.

At least 127 records · Page 7Linked to original sources

T cells and T cell-derived cytokines as pathogenic factors in the nonallergic form of atopic dermatitis.

A subgroup of patients with atopic dermatitis are known to have normal serum total immunoglobulin E levels, undetectable specific immunoglobulin E, and negative skin prick tests towards allergens. This form of the disease has been termed nonallergic atopic dermatitis. In this study, we found that, among 1151 chronic atopic dermatitis patients, about 10% had normal serum immunoglobulin E levels with no evidence for immunoglobulin E sensitization. We investigated immunologic mechanisms of patients with "allergic" and "nonallergic" atopic dermatitis using peripheral blood and skin biopsy samples. Our data suggest that T cells are likely involved in the pathogenesis of both forms of atopic dermatitis. Skin T cells equally responded to superantigen, staphylococcal enterotoxin B, and produced interleukin-2, interleukin-5, interleukin-13, and interferon-gamma in both forms of the disease. Interleukin-4, however, was not detectable in the skin biopsies of both atopic dermatitis types and was secreted in very low amounts by T cells cultured from the skin biopsies. Moreover, skin T cells from nonallergic atopic dermatitis patients expressed lower interleukin-5 and interleukin-13 levels compared with allergic atopic dermatitis patients. Accordingly, T cells isolated from skin biopsies of atopic dermatitis, but not from the nonallergic atopic dermatitis, induced high immunoglobulin E production in cocultures with normal B cells that was mediated by interleukin-13. In addition, B cell activation with high CD23 expression was observed in the peripheral blood of atopic dermatitis, but not nonallergic atopic dermatitis patients. These data suggest, although high numbers of T cells are present in lesional skin of both types, a lack of interleukin-13-induced B cell activation and consequent immunoglobulin E production in nonallergic atopic dermatitis.

Adult↗

Influence of diabetes on revascularisation procedures of the aorta and lower limb arteries: early results.

OBJECT: to evaluate the influence of diabetes mellitus on the therapeutic indications and the one-month results in patients with occlusive disease of the aorta and/or lower limbs arteries. MATERIAL: a retrospective study of fully computerised data of 1003 patients (753 men, 250 women) admitted consecutively to our vascular surgery unit over a 5-year period (1992-1996). Of the total, 169 were diabetics (group I) and 834 were non-diabetics (group II). Sixty-two per cent of patients in group I vs. 40% in group II presented with critical ischaemia or trophic changes (p<0.001). RESULTS: 15.4% of patients in group I vs. 4.1% in group II had primary amputation because of irreversible ischaemia or because arterial reconstruction was impossible. Of those who underwent revascularisation, 80% were infrainguinal in group I vs. 50% in group II. Forty-five per cent of patients in group I and 37% in group II had a percutaneous transluminal angioplasty (PTA) and approximately 3% in both groups had a combination of the two techniques. At one month, patients alive without major amputation numbered 64.4% in group I vs. 93.6% in group II, patients alive with major amputation numbered 26.6% in group I vs. 5.5% in group II, and mortality rates were 8.9% in group I vs. 0.8% in group II (P<0.001). CONCLUSIONS: the 5-times higher amputation and 10-times higher mortality rates for diabetics compared to non-diabetics call for better collaborative management of diabetics between general practitioners, vascular surgeons, diabetologists and cardiologists. PTA with a 90% initial success rate is indicated for short lesions even in the presence of limited gangrene.

Aged↗

Increased I-131 uptake in local recurrence and distant metastases after second treatment with retinoic acid.

We present a case of increased I-131 uptake in a patient with papillary thyroid carcinoma with local recurrence and distant metastases after a second treatment with retinoic acid as a sign of redifferentiation of the tumor cells. When fine-needle aspiration cytology before and after a second course of retinoic acid treatment were compared, signs of tumor cell redifferentiation were found. This was accompanied by biochemical reexpression of thyroid marker proteins.

Carcinoma, Papillary↗

Growth hormone treatment of short stature and metabolic dysfunction in juvenile chronic arthritis.

Severe growth retardation and profoundly altered body composition are observed in children treated with glucocorticoids for systemic forms of juvenile chronic arthritis. The aim of this study was to assess the effects of 1 year of treatment with growth hormone (GH) on height velocity and body composition, and the potential effects of such treatment on glucose tolerance. Fourteen children receiving steroid therapy for juvenile chronic arthritis were treated with GH, 1.4 IU/kg/week (0.47 mg/kg/week), for 1 year and were then followed up for 1 year after cessation of treatment. Baseline GH secretion and plasma levels of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) were at the lower limit of normal, but increased with GH treatment. During the year of GH treatment, mean height velocity increased from 1.9 to 5.4 cm/year (p < 0.001), mean lean body mass increased by 12% (p < 0.01) and mean fat mass fell by 20% (p < 0.01) compared with baseline. Decreased glucose tolerance and increased glycosylated haemoglobin levels were also observed. This may have been a result of insulin resistance, as indicated by induced hyperinsulinaemia. Following the 1-year GH treatment period, height velocity fell to pretreatment values, and the height SDS at the end of the second year was lower (p < 0.01) than before treatment. Weight and fat mass increased markedly after cessation of GH treatment. These results suggest that GH may partially counteract the adverse effects of glucocorticoids on growth and metabolism in patients with chronic inflammatory disease. Long-term controlled studies are needed to determine the risks and benefits of GH therapy in such patients.

Adolescent↗

Expansion of cortical interstitium is limited by converting enzyme inhibition in type 2 diabetic patients with glomerulosclerosis. The Diabiopsies Group.

Renal interstitial expansion is now considered a useful marker of progression of several nephropathies. This study describes a multicenter, prospective, double-blind, placebo-controlled, randomized trial of the effects of Perindopril (4 mg/d) on kidney structure and function over 2 yr in 26 type 2 diabetic patients with proteinuria ranging from 70 to 4210 mg/d and relatively preserved GFR (creatinine clearance >60 ml/min). All patients underwent baseline renal biopsy, but four (15%) were not randomized because of the presence of nondiabetic nephropathy. The remaining 22 were randomized ( 11 to Perindopril [PE], 11 to placebo [PO]), and 19 (9 PE, 10 PO) underwent follow-up biopsy at 2 yr. BP was controlled equally in both groups throughout. Proteinuria increased in PO patients (+1562 mg/d) but declined in PE patients (-156 mg/d) (P < 0.05). Morphometric analysis was performed by light microscopy using a Biocom computer. Over the 2 yr, mean cortical interstitial fractional volume identical at baseline increased significantly in PO patients (31.7 +/- 5.3 versus 40.2 +/- 11.1%; P = 0.001) but was unchanged in PE patients (33.8 +/- 4.9 versus 34.7 +/- 6.6%; P = 0.50). It is concluded that: (1) nondiabetic nephropathy is present in approximately 15% of albuminuric type 2 diabetic patients; and (2) Perindopril prevents interstitial expansion in hypertensive patients with biopsy-proven diabetic glomerulopathy. These results support a role of angiotensin II in the progression of interstitial changes in type 2 diabetic patients with nephropathy.

Adult↗

Criterion-related validity of a clinical measurement to determine the medial/lateral component of patellar orientation.

STUDY DESIGN: Repeated measures design using a sample of convenience. OBJECTIVE: To assess the criterion-related validity and intrarater reliability of a clinical measurement used for determining the medial/lateral position of the patella. BACKGROUND: Patellar taping is a common treatment for patellofemoral pain. Application of this intervention requires accurate assessment of patellar orientation; however, the validity of this clinical procedure has not been documented. METHODS AND MEASURES: Fourteen subjects (10 women, 4 men; average age, 41 +/- 16 years) were evaluated. Clinical assessment of medial/lateral patellar orientation using the technique described by McConnell was compared with the actual position of the patella as determined through magnetic resonance imaging (MRI). Imaging was done on 7 knees of 4 subjects who were asymptomatic and 11 knees of 10 subjects who were symptomatic. Both clinical and MRI assessments were made with the subjects supine, the knee extended, and the quadriceps relaxed. Agreement between the 2 techniques and the intrarater reliability of each measurement were quantified by means of the intraclass correlation coefficient (ICC). RESULTS: Both the clinical and MRI measures of medial/lateral patellar displacement were found to demonstrate good intrarater reliability (ICC = 0.91 and 0.85, respectively). The agreement between the clinical and MRI determinations of medial/lateral patellar position was poor (ICC = 0.44). The average amount of lateral patellar displacement as determined by the clinical method was more than twice that established through MRI. CONCLUSIONS: The clinical assessment of the medial/lateral position of the patella overestimates the true amount of lateral patellar displacement. A more valid clinical method of assessing the medial/lateral component of patellar orientation is necessary.

Adult↗

[Laparoscopy in abdominal trauma].

Laparoscopy is very useful in penetrating abdominal trauma, in particular to exclude intraabdominal lesions in stab wounds. In blunt abdominal trauma laparoscopy is not the first choice of diagnostic means though it warrants comparable good results to CTscan and ultrasound. Invasiveness, high costs, and time consuming procedure require a critical and specific application making it suitable especially in unclear clinical situations and equivocal diagnostic findings. Without doubt laparoscopy is only useful in hemodynamically stable patients and is of secondary value in polytraumatized patients. In the future it has to be thought about laparoscopy in local anesthesia and in bedside procedure e.g. on the intensive care unit. Laparoscopy should be regarded as an integral part of diagnostic spectrum in blunt abdominal trauma.

Abdominal Injuries↗

DNA aneuploidy as a specific marker of neoplastic cells in FNAB of the thyroid.

OBJECTIVE: To investigate whether DNA image cytometry (ICM) could be of value in the specific identification of neoplastic cells in cytologic specimens of the thyroid. STUDY DESIGN: FNABs of thyroid from 162 patients with different benign and neoplastic diseases were investigated. Nuclear DNA content in thyroid cells was measured after Feulgen staining using a TV image analysis system. Data were correlated with clinical and histologic patient follow-up. The occurrence of abnormal DNA stemlines was used as a marker for aneuploidy and thus for neoplasia. RESULTS: None of the 89 cases without tumor cells revealed DNA aneuploidy. An abnormal DNA stemline was found in 55% of histologically proven benign thyroid tumors (follicular or oncocytic adenomas) and in 59.5% of malignant tumors. The positive predictive value of DNA aneuploidy in FNABs of the thyroid for neoplasms was 100%. The negative predictive value of DNA nonaneuploidy for the prediction of tumor-free histologic or clinical follow-up was 79.4%. CONCLUSION: DNA image cytometry may be helpful in the specific identification of neoplastic follicular cells. DNA ICM on FNABs of the thyroid is an additional tool to achieve early identification of patients with nodular lesions of the thyroid that have to be operated on. DNA euploidy excludes the presence of neither malignancy nor neoplasia.

Adolescent↗

A physical map of 30,000 human genes.

A map of 30,181 human gene-based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known function, and is twofold to threefold more accurate than the previous version. A redesigned, more informative and functional World Wide Web site (www.ncbi.nlm.nih.gov/genemap) provides the mapping information and associated data and annotations. This resource constitutes an important infrastructure and tool for the study of complex genetic traits, the positional cloning of disease genes, the cross-referencing of mammalian genomes, and validated human transcribed sequences for large-scale studies of gene expression.

Animals↗

Functional retinoid and thyroid hormone receptors in human thyroid-carcinoma cell lines and tissues.

Thyroid carcinomas no longer accessible to radio-iodide or TSH-suppressive T4 therapy, due to loss of thyroid-specific functions, might be sufficiently re-differentiated by retinoic acid (RA) to be treated by conventional methods again. To help evaluate the feasibility of RA re-differentiation therapy in thyroid carcinomas, we examined the functionality of RA receptors (RARs/RXRs), central RA signal mediators, in human thyroid-carcinoma cell lines as model systems. [3H]-RA binding assays with nuclear extracts from follicular thyroid-carcinoma cell lines FTC-133 and -238 revealed high-affinity binding sites for RA. Electrophoretic mobility shift and super-shift assays using a DR2 ("direct repeat" 2) RA response element demonstrated DNA-binding of RARalpha, RARgamma, RXRalpha and RXRbeta in nuclear extracts of FTC-133 and anaplastic HTh74 cells. Use of a DR5 RA response element revealed no difference in DNA binding. In supershift assays with a DR4 T3 response element, we found DNA-binding by TRalpha1, TRalpha2, and TRbeta. Northern-blot analysis showed low expression of RXRbeta mRNA in FTC-133 and of TRalpha1 mRNA in FTC-133 and FTC-238 cells. Using RT-PCR, we detected mRNA for RARalpha, RARbeta, RARgamma, RXRalpha, and RXRbeta in the 4 cell lines and in human thyroid-carcinoma samples. RARbeta mRNA was reduced in FTC-238 cells and RXRbeta mRNA was decreased in anaplastic C643 cells and 9 of 12 tumor samples. Differential RA regulation of RA-receptor-mRNA expression was observed in the various cell lines. Thus, RA and T3 nuclear receptors are present in thyroid-carcinoma cell lines or tissues, albeit with cell-line and tumor-dependent variations; in the cell lines, they were shown to be functional with respect to DNA and/or ligand binding.

Carcinoma↗

[Evaluation of 452 patients with erectile dysfunction treated by combinations of vasoactive agents by penile injection].

In the past 15 years there has been continuous increase in the use of injections into the corpora cavernosa of different vasoactive drugs for treatment of erectile dysfunction (ED). However, some of these drugs are very expensive, are not available everywhere, and have side effects. We therefore compared the success rate of the most widely used compounds, papaverine and regitine, in 452 patients (age range 26-85) with different types of ED. Each patient received in the clinic injections of papaverine, 6-25 mg, and regitine, 0.05-1.5 mg. When maximal rigidity of the penis (MRP) was > 80%, we instructed the patient to self-inject the drug at home, 5-30 minutes before coitus. If after 3 injections MRP was not > 80%, prostaglandin E1 (PGE1) in an average dose of 10-25 mcg was added. If there was no response, papaverin + regitine + PGE1 were given in higher dosage, and atropine sulfate, 0.02 + 0.06 mg, was added if necessary. Of 452 patients, 305 (67.4%) had MRP > 80% after 3 injections of papaverine plus regitine. The other patients received PGE1 in addition. This was helpful in 61 patients (41.5%), while 55 (63.9%) required papaverine + regitine + prostin in higher doses. Of these, only 31 received papaverine + regitine + PGE1 + atropine sulfate. Of these, 20 (64.5%) reached MRP > 80%, and 11 (2.4%) MRP < 60. For these 11 patients, we recommended a penile prosthesis. Thus in 67.4% of the 452 patients, papaverine + regitine injections were effective; in 41.5%, PGE1; in 63.9%, papaverine + regitine + prostin + atropine sulfate. Only 11 (2.4%) did not react to intracorporeal injection. This progressive method of treatment enabled us to select the optimal dosage and combinations of compounds in 441/452 patients (97.5%) according to the severity of their dysfunction. During follow-up of 6 months, spontaneous erections without injection were achieved in 115 (26.0%).

Adult↗

Interleukin-1 receptor deficiency in the hippocampal formation of (NZB x NZW)F2 mice: genetic and molecular studies relating to autoimmunity.

Interleukin-1 receptor (IL-1R) deficiency has been previously described in the dentate gyrus of autoimmune NZB and (NZB x NZW) F1 (or BWF1) mice. In this study, the genetic and molecular characterization of this defect were investigated in BWF2 mice in relation to anti-DNA antibody production and microsatellite D1Nds4 (near the IL1r1 gene) polymorphism. IL-1R density was quantified in the brain, spleen and pancreas, using in vitro quantitative autoradiography with recombinant human [125I]-IL-1alpha as the ligand. This study of the dentate gyrus of F2 mice revealed three phenotypes: NZW-like, NZB-like and F1-like, which occurred in a ratio of 1:1:2, with IL-1R densities of 100%, 17% and 59%, respectively as compared to control NZW mice (100%). In contrast, IL-1R densities observed in the choroid plexus and peripheral organs were similar. Moreover a high production of IgG2a anti-DNA antibodies was observed in F2 mice, as in their parents, particularly those with the NZB-like phenotype. Microsatellite mapping of D1Nds4 revealed polymorphism in both parents and BWF2 mice in relation to the level of IL-1R density in the dentate gyrus. In spite of the acute defect in IL-1 binding in the dentate gyrus of NZB mice, molecular analysis of IL-1R mRNA (type I, II and accessory protein) showed similar amounts of mRNA, measured following RT-PCR amplification, in the hippocampal formation of both NZB and control C3H/He mice. In conclusion, the transmission of the IL-1R defect in the dentate gyrus of NZB mice is monofactorial and the defect appears to be at the post-transcriptional level of IL-1R synthesis. The lack of IL-1R in the dentate gyrus seems to correlate with some autoimmune characteristics. Correlation of D1Nds4 polymorphism with the level of IL-1R density suggests that it could be a predisposing gene to disease or a marker for other closely linked predisposing genes.

Animals↗

[From limited to extensive radical operation in thyroid carcinoma].

The incidence of malignant thyroid tumors in Germany is about 1-2 cases per 100,000 inhabitants and year with a preponderance of female to male 3:1. Thus malignant thyroid tumors are rare and account for about 0.5% to 1% of all malignancies. Special consideration, however, has to be paid to the fact, that thyroid lesions associated with the risk of malignancy are much more frequent. Therefore identification of patients with particular risk for thyroid malignancy out of the 15% to 20% of the German population with thyroid lesions has to be the main scope. Prognosis of differentiated thyroid carcinomas is excellent and requires operative procedures adapted to histological tumor type and tumor stage. Hemithyroidectomy for small papillary tumors can be as adequate as total thyroidectomy including bilateral neck dissection plus mediastinal lymph node dissection in medullary thyroid carcinoma. Generally radical resection of tumor is the aim. Palliative modalities in distant metastatic disease or undifferentiated tumors are indicated to optimize additive or adjuvant therapy resp. to improve prognosis.

Female↗

Epidemiology of tension-type headache.

CONTEXT: Tension-type headache is a highly prevalent condition. Because few population-based studies have been performed, little is known about its epidemiology. OBJECTIVES: To estimate the 1-year period prevalence of episodic tension-type headache (ETTH) and chronic tension-type headache (CTTH) in a population-based study; to describe differences in 1-year period prevalence by sex, age, education, and race; and to describe attack frequency and headache pain intensity. DESIGN: Telephone survey conducted 1993 to 1994. SETTING: Baltimore County, Maryland. PARTICIPANTS: A total of 13 345 subjects from the community. MAIN OUTCOME MEASURES: Percentage of respondentswith diagnoses of headache using International Headache Society criteria. Workdays lost and reduced effectiveness at work, home, and school because of headache, based on self-report. RESULTS: The overall prevalence of ETTH in the past year was 38.3%. Women had a higher 1-year ETTH prevalence than men in all age, race, and education groups, with an overall prevalence ratio of 1.16. Prevalence peaked in the 30- to 39-year-old age group in both men (42.3%) and women (46.9%). Whites had a higher 1-year prevalence than African Americans in men (40.1% vs. 22.8%) and women (46.8% vs 30.9%). Prevalence increased with increasing educational levels in both sexes, reaching a peak in subjects with graduate school educations of 48.5% for men and 48.9% for women. The 1-year period prevalence of CTTH was 2.2%; prevalence was higher in women and declined with increasing education. Of subjects with ETTH, 8.3% reported lost workdays because of their headaches, while 43.6% reported decreased effectiveness at work, home, or school. Subjects with CTTH reported more lost workdays (mean of 27.4 days vs 8.9 days for those reporting lost workdays) and reduced-effectiveness days (mean of 20.4 vs 5.0 days for those reporting reduced effectiveness) compared with subjects with ETTH. CONCLUSIONS: Episodic tension-type headache is a highly prevalent condition with a significant functional impact at work, home, and school. Chronic tension-type headache is much less prevalent than ETTH; despite its greater individual impact, CTTH has a smaller societal impact than ETTH.

Absenteeism↗

Marrow stromal cells as a source of progenitor cells for nonhematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta.

Marrow stromal cells from wild-type mice were infused into transgenic mice that had a phenotype of fragile bones resembling osteogenesis imperfecta because they expressed a human minigene for type I collagen. In mice that were irradiated with potentially lethal levels (700 cGy) or sublethal levels (350 cGy), DNA from the donor marrow stromal cells was detected consistently in marrow, bone, cartilage, and lung either 1 or 2.5 mo after the infusions. The DNA also was detected but less frequently in the spleen, brain, and skin. There was a small but statistically significant increase in both collagen content and mineral content of bone 1 mo after the infusion. Similar results were obtained with infusion of relatively large amounts of wild-type whole marrow cells into the transgenic mice. In experiments in which male marrow stromal cells were infused into a female osteogenesis imperfecta-transgenic mouse, fluorescense in situ hybridization assays for the Y chromosome indicated that, after 2.5 mo, donor male cells accounted for 4-19% of the fibroblasts or fibroblast-like cells obtained in primary cultures of the lung, calvaria, cartilage, long bone, tail, and skin. In a parallel experiment in which whole marrow cells from a male mouse were infused into a female immunodeficient rag-2 mouse, donor male cells accounted for 4-6% of the fibroblasts or fibroblast-like cells in primary cultures. The results support previous suggestions that marrow stromal cells or related cells in marrow serve as a source for continual renewal of cells in a number of nonhematopoietic tissues.

Animals↗