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Biomedical subjects

D Simon

Publications and source records attributed to D Simon.

At least 91 records · Page 5Linked to original sources
PubMed1999

A solid-phase immobilized epitope immunoassay (SPIE-IA) permitting very sensitive and specific measurement of angiotensin II in plasma.

We have developed a new enzyme immunometric assay for angiotensin II (AII) based on SPIE-IA technology (solid-phase immobilized epitope-immunoassay). A monoclonal antibody with optimal properties (mAb3 131) was selected from a series of 19 anti-AII mAbs. The mAb had to be purified from ascitic fluid in a specific manner in order to remove endogenous AII from the antibody-binding sites. We established a sensitive (minimum detectable concentration 0.5 pg/ml) and precise (CV below 15% in the 2-100 pg/ml range) SPIE-IA. Using different AII-related peptides, we observed that this new assay has a specificity profile that compares favourably with the corresponding competitive immunoassay. We have used the assay to measure AII in 42 plasma samples, and demonstrated a good correlation with values obtained using a commercial radioimmunoassay. Assay specificity was supported by HPLC fractionation experiments, confirming the absence of interference induced by endogenous AII-related products.

Acetylcholinesterase↗
PubMed1999

Neurobehavioral function and tibial and chelatable lead levels in 543 former organolead workers.

OBJECTIVE: To evaluate the associations between tibial lead, dimercaptosuccinic acid (DMSA)-chelatable lead, and neurobehavioral function in former organolead manufacturing workers with past exposure to organic and inorganic lead. METHODS: Data were collected from 543 subjects with a mean age of 58 years and an average of 17.8 years since last lead exposure. Years since last exposure to lead was used to estimate tibial lead levels in the year of last occupational lead exposure, termed "peak tibial lead." Current tibial lead levels, measured by x-ray fluorescence, were extrapolated back using a clearance half-time of lead in tibia of 27 years, assuming first-order clearance from tibia. RESULTS: Peak tibial lead levels ranged from -2.2 to 105.9 microg Pb/g bone mineral, and DMSA-chelatable lead levels were between 1.2 and 136 microg. After adjustment for confounding variables, peak tibial lead was a significant negative predictor of performance on the Wechsler Adult Intelligence Scale-Revised vocabulary subtest (p = 0.02), serial digit learning test (p = 0.04), Rey Auditory-Verbal Learning Test (immediate recall and recognition, p = 0.03 for each), Trail Making Test B (p = 0.03), finger tapping (dominant hand [p = 0.02] and nondominant hand [p < 0.01]), Purdue pegboard (dominant hand, nondominant hand, both hands, and assembly, p < 0.01 for each), and Stroop Test (p < 0.01). Moreover, with one exception, average neurobehavioral test scores were poorer at higher peak tibial lead levels. DMSA-chelatable lead was only significantly associated with choice reaction time (p = 0.01). CONCLUSION: Peak tibial lead was consistently associated with poorer neurobehavioral test scores, particularly in the domains of manual dexterity, executive ability, verbal intelligence, and verbal memory.

Adult↗
PubMed1999

Multiple genetic alterations, 4q28, a new suppressor region, and potential gender differences in human hepatocellular carcinoma.

Primary hepatocellular carcinomas (HCCs) of different etiologies were studied to determine the rate of alteration of several genetic regions previously associated with the HCC phenotype. The focus of our study was to identify the frequency of genetic alterations within individual HCCs and their distribution among male and female cases. Genetic differences were evaluated between DNA isolated from tumor (T) and corresponding non-tumor (N) tissue using short tandem repeat (STR)-microsatellites and restriction fragment length polymorphism (RFLP) analyses. Twenty-eight HCC cases were studied with polymorphic markers from different parts of the genome. Three or more loci were identified with genetic alterations from 28 loci tested in 63% of HCC cases. The highest frequency of alteration occurred in the chromosome regions 1p36, 13q14, 17p13, and the 4q28 region identified in HCCs for the first time. High loss of heterozygosity (LOH) in 1p36, 4q28, 13q14, and 17p13 regions indicates important HCC suppressors within the regions. The study documents no association between cause and specific genetic change or their frequency in HCCs analyzed. The data document a significant gender distortion for genetic alteration in chromosome 13q14 and 17p13 regions and a concordant gender alteration rate in the 1p36 and 4q28 regions. An overall higher frequency of genetic alterations was identified in male cases. Future study with an extended number of HCC cases should substantiate the frequency of alteration between genders and identify tentative suppressors in the 1p36 and 4q28 regions.

Adult↗
PubMed1999

[Cytokine-producing lymphoma T cells in the skin and peripheral blood associated with atopy and hypereosinophilia].

A 47 year old female with a history of hay fever and a family history of atopic eczema developed localized pruritic eczematous lesions over a three year period. The lesions became generalized within just three months. Episodes of recurrent erythroderma followed and became resistant towards any therapy. Many immediate and some delayed hypersensitivity reactions were diagnosed. In the peripheral blood, leukocytosis and hypereosinophilia were observed. In addition, levels of total IgE were highly increased in serum. Immunophenotyping of the peripheral blood T cells revealed evidence for a clonal expansion of highly activated CD4(+) T cells with reduced CD2 and CD5 surface expression. After a three-year course of severe disease, the diagnosis of a pleomorphic T cell lymphoma of the small-cell variant was established by histological examination and a polymerase-chain reaction technique to determine the rearrangements of the gamma chain of the T cell receptor. Moreover, analysis of cytokine gene expression suggested that the high IgE concentrations and eosinophil numbers observed in this patient were likely due to an increased IL-5 and IL-13 production by lymphoma T cells.

CD4-Positive T-Lymphocytes↗
PubMed1999

Studies of oncogenes and tumor-suppressor genes in human thyroid carcinomas, and their clinical implications.

INTRODUCTION AND DISCUSSION: Molecular genetic investigations relating to thyroid cancer have started to gain clinical importance, with discovery of the tumor-specific oncogenes PTC 1-3 in papillary thyroid cancer and the syndrome-specific mutations of the RET protooncogene in MEN-2a, MEN-2b and familial MTC patients. Furthermore, the thyroid-specific sodium-iodine symporter, causing iodine accumulation in thyroid tissue, has been cloned and now offers studies to enhance iodine and radioiodine uptake in thyroid cancer, which could soon prove to be clinically applicable.

Carcinogens↗
PubMed1999

MEN I gene mutations in sporadic adrenal adenomas.

Loss of heterozygosity (LOH) on chromosome 11q13 occurs in about 20% of sporadic adrenal neoplasms. Adrenal lesions, mostly benign, occur in up to 40% of patients from MEN I kindreds. The MEN I gene, positioned on 11q13, has been considered a primary candidate gene in these lesions. We studied a group of 15 patients with sporadic adrenal adenoma, and 1 patient with multinodular hyperplasia. Of the 16 patients, 4 had incidentally discovered masses, 5 had Conn's syndrome, 6 suffered from Cushing's syndrome, and 9 had high sex hormone production. Studies with the markers D11S480, PYGM, D11S449, and D11S987 in 13 patients (12 of whom were from our group of 16) revealed 4 losses of heterozygosity on D11 S480 on 11q13, but the deletion did not affect the MEN I gene in any case. We present complete direct DNA sequencing data of the menin gene in 14 sporadic adrenal adenomas and one with adrenal hyperplasia. We identified one heterozygous missense mutation, T552S, in a hormonally inactive adrenal adenoma. One base exchange was identified close to the intron-exon boundary in intron 9 of a nodular adrenal hyperplasia. mRNA expression studies found that MEN I was transcribed in all 13 samples analyzed. In summary, our study identified the second patient with sporadic benign adrenal tumor presenting a menin gene mutation. Our complete direct sequencing approach adds evidence that menin gene mutations may account only for a minority of benign adrenal tumors if at all. Another tumor-suppressor gene inactivated in sporadic adrenal neoplasms may be located on chromosome 11q13.

Adenoma↗
PubMed1999

Post graft development of short children treated with growth hormone before kidney graft.

Sixteen prepubertal patients with chronic renal failure (CRF) were given daily recombinant human growth hormone (rhGH) treatment (1.2 IU/kg per week) for 2.6+/-1.6 years until kidney transplant. Therapy was then discontinued and the patients followed for a further 3. 5+/-1.4 years. During treatment, mean height increased from -3.0+/-0. 9 standard deviation score (SDS) to -1.9+/-1.4 SDS (P<0.001) at the time of transplantation, corresponding to a mean height gain of +1. 2+/-0.9 SDS. After discontinuation of rhGH therapy, prepubertal children continued a partial catch-up growth with a height gain of +0.5+/-0.8 SDS for the follow-up period. Conversely, negative changes of height were observed in pubertal transplanted children: -0.5+/-0.4 SDS in patients grafted at early stages of puberty (P2-P3) and -0.15+/-0.9 SDS in patients grafted at late stages of puberty (P4-P5). These data confirmed the benefit of rhGH therapy in CRF patients. Nevertheless, only early initiation of rhGH treatment led some of these patients to their target height at transplantation, thus preserving their potential growth. Reinitiation of rhGH therapy after transplantation should be considered in order to complete catch-up growth to target height in prepubertal children.

Age Factors↗
PubMed1999

Involvement of soluble CD95 in Churg-Strauss syndrome.

Deficiency of CD95 (Apo-1/Fas)-mediated apoptosis has recently been found in some autoimmune lymphoproliferative disorders due to inherited mutations of the CD95 gene. In this study, impairment of CD95 ligand-mediated killing of lymphocytes and eosinophils in Churg-Strauss Syndrome (CSS), which was a result of variation of CD95 receptor isoform expression, is demonstrated. Compared to those from healthy individuals, peripheral blood lymphocytes from eight CSS patients exhibit a switch from the membrane-bound CD95 receptor expression to its soluble splice variant, which protects from CD95L-mediated apoptosis. In five out of seven CSS patients recurrent oligoclonal T cell expansions were found, all using a Vbeta-gene from the Vbeta21 family associated with similar CDR3 motifs, indicating the predominance of T cell clones of a similar specificity in the CSS patients. In two of them, the effect of immunosuppressive therapy was studied. In both cases aberrant overexpression of the soluble CD95 receptor isoform and deviations from normal TCR Vbeta-gene usage normalized in parallel with the clinical improvement. Furthermore, soluble CD95 was identified as a survival factor for eosinophils rescuing eosinophils from apoptosis in the absence of growth factors in vitro. Given the role of eosinophils as effector cells in CSS, these findings suggest that soluble CD95 may be mechanistically involved in the disease.

Adult↗
PubMed1999

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

The headache impact questionnaire (HImQ) is used to measure pain and activity limitations from headache over a 3-month recall period. In a prior study, the test-retest reliability of the eight-item HImQ score was found to be relatively high (0.86). In the current study, we examined the validity of the eight-item HImQ by comparing the overall score and individual items to equivalent measures from a 90-day diary. Pain and activity limitations due to headache were assessed in a population-based sample of 132 migraine headache sufferers enrolled in a 90-day daily diary study who completed the HImQ at the end of the study. The HImQ score was derived from four frequency-based questions (i.e. number of headaches, missed days of work, missed days of chores, or missed days of non-work activity) and four summary measures of average experience across headaches (i.e. average pain intensity, and average reduced effectiveness when having a headache at work, during household chores, and in non-work activity). Diary based measures were used as the gold standard in evaluating the HImQ score. Mean and median values of frequency-based HImQ items (e.g. number of headaches) were similar to equivalent diary measures, indicating no systematic bias. In contrast, HImQ measures of average experience across attacks (e.g. average pain intensity) overestimated equivalent diary measures and, in general, better approximated diary measures for migraine headaches, rather than all headaches. The highest correlations between HImQ and diary items were observed for headache frequency and average pain intensity, the two general headache measures, followed by measures of reduced effectiveness. Among frequency-based measures, the strength of the correlation was directly related to the magnitude of the mean. The higher the mean value, the higher the correlation. The correlation between the HImQ score and diary based score was 0.49. The HImQ score is moderately valid. Frequency-based items (e.g. number of missed work days) were found to be unbiased and the highest correlation coefficients were observed for frequency-based items with relatively high mean counts (number of headaches, number of missed non-work days). These findings have implications for measuring severity of chronic episodic conditions like headache, asthma, back pain, arthritis, epilepsy, and panic disorder, which can cause limitations to activities. The validity of illness severity measures may be improved by using frequency-based questions to assess both missed activity days and days with significantly reduced effectiveness or productivity (e.g. by 50% or more). By combining the count for both missed days and days where productivity is substantially reduced, the mean of the frequency-based measure will be increased, a factor which may improve the overall validity of the item. A severity measure can be derived from such items by simple addition and provides a scale with intuitively meaningful units.

Adolescent↗
PubMed1999

Feasibility of tandem autologous stem-cell transplantation (ASCT) in induction failure or very unfavorable (UF) relapse from Hodgkin's disease (HD). SFGM/GELA Study Group.

BACKGROUND: Despite high-dose therapy and ASCT some patients with aggressive HD fail to achieve long-term survival. PATIENTS AND METHODS: Forty-three patients with induction failure (n = 19) or very unfavorable (UF) relapse (n = 24) from HD were included in a multicentric study of tandem ASCT. They planned to receive two course of IVA75 with GCSF and blood stem cell collection. ASCT1 was conditioned with CBV + mitoxantrone (30 mg/m2) and ASCT2 (cytarabine 6 g/m2 melphalan 140 mg/m2 and total body irradiation at 12 Gy or busulfan 16 (n = 4) than 12 mg/kg). After salvage therapy, response > 50% was observed in 63% of the patients (six patients were included for refractory relapse). Four patients had no ASCT for disease progression; seven patients had only ASCT1 (disease progression, n = 3) and thirty-two patients (74%) received the two ASCT. RESULTS: Hematologic recovery was normal after ASCT1 but delayed platelet recovery was observed after ASCT2 with busulfan in the conditioning regimen. Two VOD with one fatal occurred with busulfan at 16 mg/kg and one hemorrhagic cystic, no further grade 4 toxicity was observed with the reduced doses of busulfan (12 mg/kg). After ASCT2, 83% of these UF patients were in remission and 20% relapsed within the first year. On an intent-to-treat analysis, 22 of 43 patients are in continuous CR (including 8 patients with induction failure). For the whole population (n = 43) and for patients receiving the two ASCT (n = 32), the two-year survival from the date of progression were respectively at 65% and at 74%. CONCLUSION: Double ASCT is feasible in very UF relapse from HD and may lead to some prolonged remission.

Adult↗
PubMed1999

Tandem transplant of peripheral blood stem cells for patients with poor-prognosis Hodgkins's disease or non-Hodgkin's lymphoma.

To improve the results of high-dose therapy with autologous stem cell transplantation, new conditioning regimens with acceptable toxicity must be developed. The aim of this study was to evaluate the feasibility and toxicity of two myeloablative regimens performed at a 2-month interval. After salvage chemotherapy and collection of peripheral stem cell progenitors (median CD34+ cells/kg: 11 x 106/kg), (n = 15) patients with aggressive non-Hodgkin's lymphoma with poor prognostic factors or refractory Hodgkin's disease (n= 9) received intensified regimens. The first conditioning regimen, consisting of BCNU-cyclophosphamide-VP16-mitoxantrone was followed by transplantation of a median number of 4 x 10(6) CD34+ cells/kg; then, after a median interval of 56 days, a second preparative regimen, combining busulfan-aracytine-melphalan or TBI + aracytine-melphalan, was followed by transplantation of a median of 4 x 10(6) CD34+ cells/kg. After regimens 1 and 2, respectively: median time to neutrophil recovery >500/microl was 11 days (both times); median time to platelet counts >50,000/microl was 14 and 36 days, but values > 20,000/microl were reached by days 13 and 16 (P = 0.9); mucositis grade III-IV was observed in 11 and 15 cases. The median number of days with fever >38 degrees C was significantly higher (7.8 days) after the second transplant (P <0.05). Three cases of veno-occlusive disease (VOD) were observed after the second transplant. At a median follow-up of 18 months, 14/24 (58%) patients remained in CR, seven patients had died (two of VOD and five after relapse) and two were alive in relapse. These results indicate that tandem transplants performed at a 2-month interval in poor risk lymphoma can be used with acceptable hematotoxicity. VOD remains the major drawback and hepatotoxic drugs, such as busulfan, should be used with caution. Longer term follow-up of a larger cohort of patients is needed to ascertain the overall efficacy.

Adolescent↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗