Biomedical subjects

D Simon

Publications and source records attributed to D Simon.

At least 91 records · Page 5Linked to original sources

PubMed2000

Growth regulation of thyroid and thyroid tumors in humans.

In a study of growth regulation of the human thyroid gland and thyroid tumors we investigated the impact of iodine and that of the thyroid-specific growth-stimulating hormone TSH. Further studies included locally active growth factors such as the epidermal growth factor, insulin-like growth factor, and tissue transforming growth factors alpha and beta. In addition to studies of growth regulation by the various growth factors in mostly normal thyrocytes, the impact of tumor-specific mutations in oncogenes and tumor-suppressor genes was investigated. The results demonstrated distinct changes in tissue specificity and sensitivity to external stimuli. This rather complex view on thyrocyte growth regulation may be confusing, but it describes the biologic reality more precisely. Increased knowledge of the regulatory processes may lead to the development of new tumor- and patient-specific therapeutic approaches, especially for preventing benign goiter recurrence and for treating follicular and papillary thyroid cancers.

Genes, Tumor Suppressor↗

PubMed2000

Surgery for Graves' disease: total versus subtotal thyroidectomy-results of a prospective randomized trial.

The effect of surgery on Graves' orbitopathy (GO) is still controversial. Retrospective analyses of many authors (including our own group) demonstrated GO improvement after subtotal thyroid resection in up to 70% of operated patients, so the question arose whether total thyroidectomy could add anything to this pronounced positive effect on GO. We therefore performed a prospective randomized trial on 150 patients with Graves' disease (125 women, 25 men; mean thyroid volume 80.5 ml) comparing three surgical procedures (bilateral subtotal thyroid resection-total remnant < 4 ml; unilateral hemithyroidectomy with contralateral subtotal thyroid resection-remnant < 4 ml; total thyroidectomy) and their effect on postoperative GO changes, postoperative thyroid-stimulating hormone receptor (TSH-R) antibody titers, and postoperative complication rates. After a period of at least 6 months (6-36 months) GO had improved in 71% to 74% of all patients regardless of whether total or subtotal thyroidectomy was performed. TSH-R antibody titers showed no differences for the three surgical groups. Postoperative recurrent hyperthyroidism occurred in two patients with subtotal resections, and early postoperative hypoparathyroidism was more frequently detected in patients with total thyroidectomy than in those with subtotal thyroid resection (28% vs. 12%; p < 0.002). In respect to possible postoperative hypoparathyroidism and a lack of difference in postoperative GO changes, we do not advocate total thyroidectomy for patients with Graves' disease and Graves' orbitopathy but prefer radical subtotal thyroid resection with a remnant of less than 4 ml.

Adolescent↗

PubMed2000

Therapeutic experience of 65 cases with organic hyperinsulinism.

INTRODUCTION: The treatment for insulinoma is enucleation or resection, which are associated with various degrees of morbidity, including fistulas, pseudocysts, and necessity for reoperations. PATIENTS: We evaluated the outcome of 65 patients operated on for organic hyperinsulinism at an experienced university hospital (Department of Surgery, Heinrich-Heine University, Düsseldorf, Germany) between 1990 and 1998. Procedures included enucleation (n=37), left-sided resection (n=19), combination of enucleation from the head and left-sided resection (n=4), subtotal left pancreatectomy (n=2), and pancreaticoduodenectomy (n=3). RESULTS: In 47 out of the 65 patients (72%), the expected benign solitary insulinoma was found. Seven patients had malignant tumors and another eight had multiple tumors (including two with multiple endocrine neoplasia type 1 (MEN-1)), and three had nesidioblastosis. In total, 20 patients (31%) developed postoperative drainage of high amylase containing fluid, which in all but three cases resolved with conservative therapy. The three patients who developed fistulas and the three patients who developed pseudocysts underwent reoperative surgery. Seventeen (41%) of the patients who underwent enucleation (10 from the pancreatic head; 50%) and six (25%) of the resected patients demonstrated these complications. Postoperative glucose metabolism was normalized in all patients. CONCLUSION: Resection, especially in the head of the pancreas, demonstrates lower complication rates than enucleation. We propose resection for tumors that are large, malignant, situated close to pancreatic duct, and are multiple, including in MEN-1. For tumors in the head, pancreaticoduodenectomy may be an occasional choice.

Adolescent↗

PubMed2000

Surgical treatment of postoperative, incidentally diagnosed small sporadic C-cell carcinomas of the thyroid.

BACKGROUND AND AIMS: The surgical strategy in small sporadic C-cell carcinomas of the thyroid that are incidentally diagnosed after goiter resection for benign disease is controversial. It remains unclear whether a completion thyroidectomy should be performed in every case. PATIENTS AND METHODS: We present nine patients who were operated on between October 1992 and October 1997 in whom an unexpected, small sporadic C-cell carcinoma (seven with pT1, two with pT2) was found in the postoperative histology. RESULTS: All patients were calcitonin negative and there were no signs of the disease being inherited (no familial history, negative RET proto-oncogene). No patient underwent a completion thyroidectomy. All patients had a follow-up with pentagastrin-stimulated calcitonin and carcinoembryonic antigen (CEA) 3 months, 6 months and annually after the operation. No patient became calcitonin positive or showed any other signs of tumor recurrence after a follow-up period of 2-7 years. CONCLUSION: A completion thyroidectomy is not necessary in small sporadic C-cell carcinoma that is incidentally diagnosed after resection for benign disease if there is no sign of familial cancer and if calcitonin is negative. A close follow-up is necessary.

Adult↗

PubMed2000

Genetic markers of immunoglobulins and diabetes mellitus in the multiracial population of New Caledonia. The CALDIA Study Group.

GM and KM immunoglobulin allotypes, which are the markers, respectively, of the constant parts of the heavy and the light chains of the IgG1, IgG2 and IgG3 subclasses, have been analysed in diabetic mellitus patients and controls living in New Caledonia. We tested 40 Europeans, 256 Melanesians and 44 Polynesians, as well as their 340 matched controls, in order to search for a genetic susceptibility at those polymorphic loci. All the subjects were tested for G1M (1, 2, 3, 17), G2M (23), G3M (5, 6, 10, 11, 13, 14, 15, 16, 21, 24, 28) and KM (1) by the classical hemagglutination method. The frequencies of GM haplotypes and KM alleles have been estimated by a maximum likelihood method. The results are in favour of no influence of the GM and KM loci. The prevalence of diabetes mellitus varies in the populations of New Caledonia: Polynesians are at much higher risk than Melanesians or Europeans. The GM haplotype distribution differs among ethnic groups; so they provide a useful marker to measure genetic admixture. The higher prevalence of diabetes observed among New Caledonians of European origin compared to the prevalence in Europe may be explained by genetic admixture with neighbouring Pacific populations, notably Polynesians (Asian haplotypes are present at a frequency of 9.4%). So, the genetic admixture should be measured in any genetic epidemiological study.

Adult↗

PubMed2000

ACE inhibitors do not induce recombinant human erythropoietin resistance in hemodialysis patients.

Angiotensin-converting enzyme (ACE) inhibitors may exacerbate anemia in patients with chronic renal failure, as well as in dialysis patients. To better answer this question, a prospective, crossover study was conducted to evaluate the effect of ACE inhibitors on recombinant human erythropoietin (rHuEPO) requirements in hemodialysis patients. Patients administered an ACE inhibitor when entering the study remained on this drug for the initial 4 months and were then switched to another antihypertensive agent for 4 more months. Patients not initially administered an ACE inhibitor were switched to lisinopril at 4 months. rHuEPO doses were adjusted using a sliding scale based on weekly laboratory hematocrit values. The inclusion criteria were met by 51 patients undergoing dialysis. Demographics were as follows: 61% were women, 64% were black, 46% had diabetes, average age was 53.2 +/- 13.3 years, and time on hemodialysis was 38.0 +/- 44.5 months. Thirty-three patients completed the study. Hematocrit averaged 32.7% +/- 1.9% while on ACE inhibitor therapy and 33.1% +/- 2.1% off ACE inhibitor therapy (P = 0.217). There was no difference in rHuEPO dose per treatment during each period (3,500 +/- 1,549 U on ACE inhibitor therapy versus 3,312 +/- 1,492 U off ACE inhibitor therapy; P = 0.300). No significant differences were found in degree of blood pressure control or various clinical and laboratory parameters that might be associated with rHuEPO resistance between the two periods. Similarly, no differences were found in hospitalization days, duration of infections, or transfusion requirements. These findings suggest that ACE inhibitors do not contribute to rHuEPO resistance in hemodialysis patients.

Anemia↗

PubMed2000

Antibiotic selection for patients with septic shock.

Early recognition of the sepsis syndrome, prompt administration of broad-spectrum antibiotics, surgical intervention when indicated, and aggressive supportive care in intensive care units remain the therapeutic strategies for patients with sepsis. Antibiotic selection is based on many factors including the most probable source of infection, the most likely pathogens, and knowledge of antibiotic susceptibility patterns for community- and hospital-acquired infections. Unfortunately, with this approach, mortality remains unacceptably high. Adjuvant therapies such as antiendotoxin antibodies, cytokine antagonists, and anti-inflammatory agents aimed at blunting the host immune response to bacterial infection have provided little clinical benefit to date. As our understanding of the pathophysiology of sepsis progresses, perhaps newer modalities will improve clinical outcome. At this time, preventive strategies, including optimal vaccine use, effective infection control practices, judicious use and care of intravascular lines and indwelling urinary catheters, and appropriate use of anti-infective agents to prevent microbial resistance should be used to decrease the incidence of infection and subsequent sepsis.

Anti-Bacterial Agents↗

PubMed2000

Incidence and risk factors of central nervous system relapse in histologically aggressive non-Hodgkin's lymphoma uniformly treated and receiving intrathecal central nervous system prophylaxis: a GELA study on 974 patients. Groupe d'Etudes des Lymphomes de l'Adulte.

BACKGROUND: Incidence of central nervous system (CNS) recurrence in patients with aggressive non-Hodgkin's lymphoma who did not receive meningeal prophylaxis is about 5%. Controversy remains regarding risk factors associated with such an event preventing a rational approach of prophylactic strategies. PATIENTS AND METHODS: We analyzed a cohort of 974 patients with aggressive lymphoma in complete remission (CR). All the patients received a CNS prophylaxis consisting of intrathecal injections and intravenous high-dose methotrexate. The risk repartition on the basis of the international prognostic index (IPI) of these 974 CR-patients was low (L): 41%, low-intermediate (LI): 27%, high-intermediate (HI): 19%, high (H): 13%. RESULTS: The incidence of isolated CNS relapse was 1.6%. In a first multivariate logistic regression analysis an increased LDH (P = 0.05, RR = 5) and the presence of more than one extranodal site (P = 0.05, RR = 3) were identified as independent risk factors for isolated CNS relapse. Another multivariate analysis incorporating IPI as a unique parameter showed that only IPI remained significantly associated with a higher risk of CNS relapse (L-LI: 0.6% vs. HI H: 4.1%, P = 0.002; RR = 7). CONCLUSION: Prophylaxis notably reduces the risk of CNS recurrence in the higher risk patients. By contrast, we propose the deletion of prophylactic intrathecal injections in the lower risk patients.

Antimetabolites, Antineoplastic↗

PubMed2000

High-dose therapy with autologous stem-cell transplantation (ASCT) after first progression prolonged survival of follicular lymphoma patients included in the prospective GELF 86 protocol.

BACKGROUND: Among the 566 patients with follicular lymphomas (FL) included in the GELF 86 prospective trials from October 1986 to September 1995, 372 with progressive/relapsing disease were analyzed retrospectively to identify prognostic factors at first relapse. PATIENTS AND METHODS: For progressive FL, patients received mono- (22%) or polychemotherapy (78%) followed by high-dose therapy (HDT) with ASCT for 83 patients (22%). The median time to progression from initial treatment was 23 months (range 3-102 months) and 24% of documented patients (52 of 217) had histological transformation (HT). Salvage therapy produced an overall response in 64% of patients and the five-year survival from progression was 42%. RESULTS: For patients who underwent HDT with ASCT compared to standard treatment, five-year freedom from second failure was at 42% vs. 16% (P = 0.0001) and five-year survival was 58% vs. 38% (P = 0.0005), respectively. The benefit of HDT and ASCT remained if we consider only patients less than 65 years (five-year survival at 60% vs. 40%; P = 0.001). Multivariate analysis of parameters significant according to univariate analysis found that no ASCT at first progression, age at relapse > 50 years, progression on-therapy were adversely significant on survival. CONCLUSIONS: HDTwith ASCT compared to standard treatment prolonged remission and survival after first progression of FL patients.

Age Factors↗

PubMed2000

Myelodysplasias and leukemias after autologous stem cell transplantation for lymphoid malignancies.

The incidence of secondary myelodysplastic syndromes and acute leukemia (MDS/AL) was reported for 395 patients autografted for Hodgkin's disease (HD) (n = 96) and non-Hodgkin's lymphoma (NHL) (n = 299) between 1987 and 1998. Eleven patients developed secondary MDS/AL (crude rate at 2.8%) including two lymphoblastic AL cases. The mean time of occurrence was at 32 months after autologous stem cell transplantation (ASCT) and 71 months after diagnosis. The estimated actuarial incidence at 10 years was at 6.3% (+/-4%). Karyotyping revealed complex chromosomal aberrations in only one patient, and two translocations [t(8;21) and t(8;16)]. No features of topoisomerase II inhibitor-related leukemia were found. Only one patient had received ASCT in first remission. The remaining 10 patients had received multiple courses of chemotherapy before stem cell collection and four had relapsed after ASCT and before the occurrence of secondary MDS/AL. Five of 11 patients had received localized radiotherapy and five others received TBI in their conditioning regimen. Ten patients died despite chemotherapy and/or supportive care and only one patient is alive and well after genoidentical allogeneic transplantation. We suggest a cumulative leukemogenic role of pre-ASCT radiation and chemotherapy in the occurrence of these secondary MDS/AL more than the high-dose therapy itself.

Acute Disease↗

PubMed2000

Lack of MEN1 gene mutations in 27 sporadic insulinomas.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant familial cancer syndrome characterized by tumours of the parathyroids, anterior pituitary gland and endocrine pancreas. Since the cloning of the MEN1 gene (encoding menin) on chromosome 11q13 by Chandrasekharappa et al. in 1997, it has become possible to identify mutations that are responsible. We examined whether MEN1 gene mutations are present in sporadic insulinomas, a rare sporadic tumour that is seen more frequently in patients with the MEN 1 syndrome. PATIENTS AND METHODS: We sequenced the coding part of the MEN1 gene (exons 2-10) in tumour tissue of 27 patients suffering from an insulinoma (24 benign, three malignant). To validate our methods we also examined tumour tissue from five patients with primary hyperparathyroidism (HPT) at a younger age and/or multiple gland disease, with increased risk of MEN 1. RESULTS: We found no mutations in the nine coding exons of the MEN1 gene in the insulinoma tissues. We could confirm three benign polymorphisms (S145S, R171Q, D418D) reported previously. In the control patients we found two new point mutations (one mis-sense, one non-sense mutation) and one deletion. CONCLUSION: Mutations of the MEN1 gene do not play an important role in the pathogenesis of sporadic insulinomas. Therefore genetic screening is not cost effective in sporadic insulinoma patients without other indicators of MEN 1. Patients with primary HPT at a younger age and/or multiple gland disease should be screened for MEN1 gene mutations.

Adolescent↗

PubMed2000

Sequence analysis of the MEN I gene in two patients with multiple cutaneous lipomas and endocrine tumors.

The discovery of mutations of the menin gene in a few multiple endocrine neoplasma type 1 (MEN I)-associated lipomas and loss of heterozygosity (LOH) on chromosome 11q13 in some sporadic lipomas has stimulated the hypothesis that lipomas may belong to the group of sporadic tumors caused by defects of the gene responsible for MEN I. Since it is unclear if the above hypothesis applies to all patients with lipoma or just to specific subsets, we searched to enlarge the database on this topic. For this purpose, we identified two patients with multiple cutaneous lipomas. One had an additional pituitary adenoma and familial presentation of multiple lipomas, the other had recurrent goiter in the setting of a family history of adenomatous goiter. Deoxyribonucleic acid (DNA) was analyzed by complete direct DNA sequencing of all coding exons and splice junctions of the MEN I gene. No mutation was identified in the coding exons of the menin gene. In contrast to former data on sporadic lipomas, these data are the first to render evidence that mutations of the MEN I gene may not be responsible for the formation of multiple lipomas, even if they appear in the context of other endocrine tumors.

Adenoma↗

PubMed2000

Widespread occurrence of spliceosomal introns in the rDNA genes of ascomycetes.

Spliceosomal (pre-mRNA) introns have previously been found in eukaryotic protein-coding genes, in the small nuclear RNAs of some fungi, and in the small- and large-subunit ribosomal DNA genes of a limited number of ascomycetes. How the majority of these introns originate remains an open question because few proven cases of recent and pervasive intron origin have been documented. We report here the widespread occurrence of spliceosomal introns (69 introns at 27 different sites) in the small- and large-subunit nuclear-encoded rDNA of lichen-forming and free-living members of the Ascomycota. Our analyses suggest that these spliceosomal introns are of relatively recent origin, i.e., within the Euascomycetes, and have arisen through aberrant reverse-splicing (in trans) of free pre-mRNA introns into rRNAs. The spliceosome itself, and not an external agent (e.g., transposable elements, group II introns), may have given rise to these introns. A nonrandom sequence pattern was found at sites flanking the rRNA spliceosomal introns. This pattern (AG-intron-G) closely resembles the proto-splice site (MAG-intron-R) postulated for intron insertions in pre-mRNA genes. The clustered positions of spliceosomal introns on secondary structures suggest that particular rRNA regions are preferred sites for insertion through reverse-splicing.

Ascomycota↗

PubMed2000

Measurement of problem-solving deficits in adults with acquired brain damage.

OBJECTIVE: To compare the relative utility of conventional neuropsychological and social problem-solving approaches to measuring functional problem solving deficits in individuals with acquired brain damage (ABD). DESIGN: In Study I, scores for individuals with ABD were compared to scores for control and normative samples. In Study II, pre- and posttest scores were compared for individuals with ABD who completed a program of outpatient cognitive rehabilitation. PARTICIPANTS: In Study I, individuals with ABD were compared to healthy controls. In Study II, pre- and posttreatment assessments were obtained for 34 individuals with ABD. MAIN OUTCOME MEASURES: Two approaches were used, conventional neuropsychological (WAIS-R/II Comprehension subtest and Wisconsin Card Sorting Test) and social problem solving (Problem Solving Inventory and Rusk Problem Solving Role Play Test). RESULTS: In Study I, the ABD group demonstrated significant deficits on both social problem solving measures; however, neither conventional neuropsychological measure detected significant deficits in the ABD group, relative to control and normative groups. In Study II, significant treatment gains were demonstrated on both social problem-solving measures, however neither conventional neuropsychological measure was sensitive to improvements in functional problem-solving ability. CONCLUSIONS: In higher-level cognitive rehabilitation settings, the evaluation of functional problem-solving deficits in individuals with ABD can be facilitated by augmenting neuropsychological test data with results from social problem-solving measures.

Adult↗

PubMed2000

Pathological femoral fracture due to rhabdomyosarcoma in a cat.

An eight-year-old neutered male domestic shorthaired cat was presented with non-weightbearing lameness of the right hindlimb. On radiography, a pathological, metaphyseal femoral fracture was apparent, with areas of bony lysis directly surrounding the fracture site. The cat underwent amputation of the limb. Histopathological examination revealed the presence of a tumour of mesenchymal cells with cytoplasm-containing vacuoles which stained positive with the periodic acid-schiff reaction, indicative of glycogen granules that may be found in rhabdomyosarcoma cells. In addition, the tumour cells stained positive for vimentin and desmin on immunohistochemical examination, thus confirming the diagnosis of rhabdomyosarcoma. In spite of the radical surgery performed, the cat was euthanased due to a recurrence at the amputation site four and a half months later.

Amputation, Surgical↗

PubMed2000

Identification of upregulated genes in scrapie-infected brain tissue.

The pathogenesis of scrapie, and of neurodegenerative diseases in general, is still insufficiently understood and is therefore being intensely researched. There is abundant evidence that the activation of glial cells precedes neurodegeneration and may thus play an important role in disease development and progression. The identification of genes with altered expression patterns in the diseased brain may provide insight on the molecular level into the process which ultimately leads to neuronal loss. Differentially expressed genes in scrapie-infected brain tissue were enriched by the suppression subtractive hybridization technique, molecularly cloned, and further characterized. Northern blotting and nucleotide sequencing confirmed the identities of 19 upregulated genes, 11 of which were unknown to be affected by scrapie. A considerable number of these 19 genes, namely those encoding interferon-inducible protein 10 (IP-10), 2',5'-oligo(A) synthetase, Mx protein, IIGP protein, major histocompatibility complex classes I and II, complement, and beta(2)-microglobulin, were inducible by interferons (IFNs), suggesting that an IFN response is a possible mechanism of gene activation in scrapie. Among the newly found genes, that coding for 2',5'-oligo(A) synthetase is of special interest because it could contribute to the apoptotic loss of neuronal cells via RNase L activation. In addition, upregulation of the chemokine IP-10 and B-lymphocyte chemoattractant mRNAs was seen at relatively early stages of the disease and was sustained throughout disease development.

Animals↗

PubMed2000

Treatment of juvenile rheumatoid arthritis with growth hormone.

Severe growth retardation and profoundly altered body composition are observed in children with juvenile chronic arthritis receiving glucocorticoids. This study assessed the effects of growth hormone (GH) on height velocity, body composition and bone density. Fourteen patients were treated with GH (1.4 U/kg/week) for 1 year and then studied for a 2nd year off GH. The treatment increased insulin-like growth factor 1 and insulin-like growth factor binding protein 3 plasma levels. All patients showed an increase in height velocity. Lean body mass increased by 12%. After the cessation of GH therapy, height velocity fell to pretreatment values, and weight and fat mass increased markedly. Bone formation and resorption markers significantly increased during treatment and returned to pretreatment values after discontinuation 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.

Age Determination by Skeleton↗

PubMed2000

Complete sequencing and messenger ribonucleic acid expression analysis of the MEN I gene in adrenal cancer.

Adrenal cancer is a rare sporadic disease that has also been observed in the context of multiple endocrine neoplasia type I (MEN I). Adrenal lesions occur in up to 40% of MEN I patients. Loss of heterozygosity of the 11q13 band harboring the menin gene has been reported in more than 50% of patients with adrenal cancer. Despite this high index of suspicion, former screening studies did not reveal mutations of the MEN I gene in 28 patients. We identified loss of heterozygosity of 11q13 microsatellites in five of five patients (100%). In 40%, heterozygosity was retained in codon 418 of the MEN I gene. Complete direct DNA sequencing data of the entire coding region and adjacent splice sites of the MEN I gene were obtained in 14 patients with sporadic adrenal cancer. In only one of them a heterozygous missense mutation, R176Q (exon 3), was identified. Due to the heterozygous pattern and unknown biological effect of this mutation, it is not clear whether there is a causal relationship with adrenal cancer. The total mutation frequency in sporadic adrenal cancer is 1 of 14 (7%). Menin messenger RNA expression was identified in 14 of 14 patients (100%). Transcriptional inactivation of the menin gene is, hence, unlikely to cause loss of its tumor suppressor function in adrenal cancer. Furthermore, we examined three patients who presented adrenal cancer in the context of sporadic multiglandular endocrine tumor disease previously diagnosed on clinical grounds to be MEN I syndrome. An opal stop codon mutation was identified in codon 126 (exon 2) in the adrenal cancer of one of these patients. Formation of the adrenal cancer in this patient may be rather coincidental because the mutation was present in a heterozygous pattern. There was no mutation of the menin gene in the two other patients. This may mean that formation of adrenal cancer in the context of multiglandular endocrine disease denotes an entity different from MEN I in some patients.

Adolescent↗