Biomedical subjects

A Penfornis

Publications and source records attributed to A Penfornis.

At least 19 recordsLinked to original sources

PubMed2006

Immunosuppressive drug-induced diabetes.

Post-transplant diabetes mellitus (PTDM) has emerged as a major adverse effect of immunosuppressive drugs (ISD). As recipients of organ transplants survive longer, the complications of diabetes mellitus have assumed greater importance. The predominant factor for causing PTDM by corticosteroids seems to be the aggravation of insulin resistance, however several studies have displayed deleterious effects on insulin secretion and beta-cells. Calcineurin inhibitors induce PTDM by a number of mechanisms, including decreased insulin secretion and a direct toxic effect on the pancreatic beta-cells. Recent in vitro studies stress on the increased apoptosis of beta-cells when exposed to these drugs. Studies involving other immunosuppressive agents (mycophenolate mofetil [MMF], sirolimus) are scarcer and lead to conflicting results, while daclizumab seems to have a neutral effect. Clinical studies have consistently shown a greater potential of tacrolimus to induce PTDM compared with cyclosporine. Reducing PTDM incidence is a feasible goal while using corticosteroid-sparing regimens and/or lower tacrolimus trough levels. In patients developing PTDM, conversion from tacrolimus to cyclosporine could improve or reverse glucose tolerance abnormalities. In the absence of well-designed studies in this specific indication, treatment of PTDM is based on the same principles as type 2 diabetes mellitus. Thiazolidinediones do not display any pharmacological interaction with calcineurin inhibitors, but their safety and efficacy in PTDM need to be confirmed in large-scale randomized trials. Use of sulfonylureas has to be cautious regarding the suspected interaction of some of them with calcineurin inhibitors. If needed, insulin regimens have to be adapted in patients who display the particular glycaemic profile of corticosteroid-induced diabetes. Incretin-based therapies, due to their specific action on beta-cell apoptosis and proliferation, raise promises that have to be confirmed in clinical studies. Until methods for inducing specific graft tolerance become available, immunosuppressive regimens should be tailored to the individual patient on the basis of predictive criteria for the development of PTDM.

Adrenal Cortex Hormones↗

PubMed2006

Predictive value of admission hyperglycaemia on mortality in patients with acute myocardial infarction.

RATIONALE AND AIM: In patients with an acute myocardial infarction, admission hyperglycaemia (AH) is a major risk factor for mortality. However, the predictive value of AH, when the risk score and use of guidelines-recommended treatments are considered, is poorly documented. METHODS: The first fasting plasma glucose levels after admission, risk level, guidelines-recommended treatment use and 1-year mortality were recorded. Patients with first fasting glucose level after admission > 7.7 mmo/l were considered to have AH. RESULTS: Three hundred and twenty patients with ST segment elevation myocardial infarction (STEMI) and 404 with non-ST segment elevation myocardial infarction (NSTEMI) were included. One hundred and seventy-five (24%) patients had pre-existing diabetes (diabetes group), 154 (21%) had AH (AH+ group) and the remainding 395 (55%) had neither diabetes nor AH (AH- group). The Global Registry of Acute Coronary Events (GRACE) risk score was lower in the AH- group, but the use of guidelines-recommended treatment was comparable in all groups. At 1 year, the mortality rate was higher in the AH+ group compared with the AH- group (18.8 vs. 6.1%, P < 0.01) and similar to that in the diabetes group (18.8 vs. 16.6%, P = NS). The relation between glycaemic status and mortality remained strong [AH+ vs. AH-, OR = 3.0 (1.5, 6.0) and diabetes vs. AH-, OR = 3.6 (1.7, 6.6)] after adjustment for the GRACE risk score [OR = 2.4 (1.8, 3.1) per 10% increase] and for treatment score [OR = 0.7 (0.6, 0.8) per 10% increase]. CONCLUSIONS: In patients without a history of diabetes, the presence of AH indicates an increased risk of 1-year mortality, similar to that of patients with diabetes, even when the risk score and use of guidelines-recommended treatment are controlled for.

Aged↗

PubMed2003

Polymorphisms of the TAP1 and TAP2 genes in human alveolar echinococcosis.

We postulated that TAP genes may influence the susceptibility of some individuals to Echinococcus multilocularis infection. Six coding region variants (codons 333 and 637 in TAP1, and 379, 565, 651 and 665 in TAP2) were typed in 94 patients and 100 controls. Thr/Thr homozygosity at TAP2/665 was more prevalent in patients than in controls [64% vs. 45%, respectively; odds ratio (OR) = 2.1 (95% confidence interval (CI) 1.1; 2.7)] and Thr/Ala heterozygozity was less prevalent (32% vs. 50%, respectively) (P = 0.014). Of the 38 patients with progressive lesions, 76% were Thr/Thr, as compared with 55% of patients without progressive lesions and 45% of controls (P = 0.058 and 0.02, respectively), independent of HLA status. To determine whether this association is functionally relevant, functional analyses and/or confirmation in distinct populations of patients with alveolar echinococcosis would be required.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

[Drug compliance in type 2 diabetes: role of drug treatment regimens and consequences on their benefits].

Compliance is an old issue but crucial in the management of chronic diseases. This is the case in type 2 diabetes mellitus which requires several drugs, either to treat diabetes or to prevent cardiovascular complications. In this review, we discuss the relationships between drug treatment regimens and treatment compliance in type 2 diabetes and other chronic diseases. The greater the number of daily drug intakes, the worst the compliance, even if a single daily intake may cause an increased risk of overdosing. Although the number of tablets or treatments is less frequently linked to compliance level than the number of daily intake, polytherapy is generally associated with a poor compliance. The consequences of a poor compliance on the prognosis or the management of these diseases are analysed based on cardiovascular studies. Even if nearly no studies exist in type 2 diabetes, to improve treatment compliance represents a major challenge in these patients. Such improvement requires to preferentially use once-a-day intake, but this is still difficult with several oral anti-diabetics. Fixed combinations such as the glibenclamide plus metformin combination, cause a decrease in the number of daily tablets and this permit a better compliance. Such approaches, to be fully beneficial, should be part of a global management of these type 2 diabetic patients, taking into account all their difficulties to follow their treatments, and based on a strong physician and patient relationship.

Diabetes Mellitus, Type 2↗

PubMed2003

[Reninoma: a rare but curable cause of high blood pressure, a case report].

We report a case of a renin secreting tumor, which is a very rare cause of secondary high blood pressure. A 22-year-old woman was hospitalised for exploration of high blood pressure (160/110 mmHg) with severe hypokaliemia (2,7 mmol/l) and secondary hyperaldosteronism. Physical examination was normal except the high blood pressure. Bioassays show increased kaliuresis (66 mmol/24h), plasma renin (89 pg/ml in clinostastism--108 pg/ml in orthostatism), pro-renin (1207 pg/ml in clinostastism--1412 pg/ml in orthostatism) and aldosterone (210 pg/ml in clinostastism--566 pg/ml in orthostatism). The rest of the endocrine tests were normal (cortisol and ACTH at 8:00 am, urinary free cortisol, overnight 1 mg dexamethasone suppression test). Doppler ultrasound method, performed by an experienced radiologist, did not show renal artery stenosis. Abdominal computerized tomography showed a nodular formation at the upper pole of the right kidney, isodense to renal medullary. The size tumor was 15 mm. The renal vein sampling shows high values of renin on both sides whereas, for the pro-renin, the values were higher on the tumor side. In spite of treatment with CEI (Converting Enzyme Inhibitors) and calcium antagonists, the blood pressure was not controlled. Hypokaliemia persisted (3 mmol/l) in spite of high daily potassium intake (64 mmol/l of potassium chloride). After tumor resection, reninoma was diagnosed by the pathology examination and blood pressure, plasma rennin, plasma aldosterone level returned to normal.

Adult↗

PubMed2002

TAP1 and TAP2 gene polymorphism in rheumatoid arthritis in a population in eastern France.

The 'transporter associated with antigen processing' (TAP) gene products are involved in the processing of endogenous peptides that bind to class I molecules. Polymorphism within these genes could alter the level of the immune response, a phenomenon relevant to the development of autoimmune diseases. In this study, we examined the polymorphism of TAP1 and TAP2 genes in patients with rheumatoid arthritis (RA). TAP1 and TAP2 typing was performed for 138 Caucasian RA patients and 100 healthy controls, all originating from eastern France. TAP1 polymorphic residues at positions 333 and 637 and amino acid variants 379, 565, 651 and 665 in the TAP2 gene were found using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). This method enabled us to determine four TAP1 alleles (TAP1A to TAP1D) and eight TAP2 alleles (TAP2A to TAP2H). All patients and controls had been HLA-DRB1* genotyped. The polymorphic residues TAP1333 and TAP1637 did not show any difference in their distribution between patients and controls. Similar findings were obtained for TAP2379 and TAP2665. However, we found an increased frequency of Thr homozygosity and heterozygosity at position 565 in the TAP2 gene in RA patients (RA vs. controls: 25.3 vs. 14%; P = 0.032; OR = 2.09; CI = 1.01-4.38). Similarly, the prevalence of subjects who were homozygote and heterozygote for Cys651 was increased in the RA group (RA vs. controls: 36.8 vs. 11%; P = 0.02). The dimorphic site TAP2565 defines TAP2D and TAP2E alleles, while the site at position 651 characterizes TAP2F. Thus, we found that TAP2D and TAP2E alleles were more prevalent in RA, but not significantly so (RA vs. controls: TAP2D: 10 vs. 3.6%; P = 0.24; TAP2E: 3.6 vs. 0%; P = 0.19). Similarly, the frequency of TAP2F was higher in RA patients (24.5%) than in controls (11.3%), but this was not significant after correction (P = 0.029; Pcorr = 0.17). Finally, we found no linkage disequilibrium between DRB1* RA-associated alleles and amino acid substitution Thr565 or TAP2D and TAP2E alleles, whereas Cys651 (and TAP2F) was not independent of DRB1*04, a strongly RA-associated allele. Finally, Thr at position 565 in the TAP2 gene was associated with manifestations of disease severity in only a few patients. Examination of TAP1 and TAP2 gene polymorphisms in RA patients revealed an association between a particular amino acid residue, namely Thr565 in the TAP2 gene, and RA. This association was found to be weak and did not seem to be a predictor for the severity of the disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

Use of a topoisomerase I inhibitor (irinotecan, CPT-11) in metastatic adrenocortical carcinoma.

BACKGROUND: Complete responses are rare after medical treatment of adrenocortical tumors. We performed a single center prospective study of the antitumor effect of irinotecan (CPT-11) in patients with metastatic adrenocortical cancer. PATIENTS AND METHODS: Since 1999, all patients with advanced progressive adrenocortical carcinoma, referred to the Institut Gustave-Roussy, have been enrolled prospectively in this study. CPT-11 (250 mg/m(2)) was administered intravenously on day 1 in a 2-h infusion, every 14 days. World Health Organization (WHO) criteria were used to evaluate tumor response and toxicity. RESULTS: During treatment, no dose or schedule modifications were made. A median of three courses were given (range 1-8), and all but two patients received at least three complete chemotherapy courses. No objective or complete responses were observed. The best response achieved was stabilization in three patients, lasting from 1.5 to 4 months. Significant toxicity occurred in two patients. CONCLUSIONS: Our results do not support a major role of CPT-11 in adrenocortical carcinoma.

Adrenal Cortex Neoplasms↗

PubMed2002

Natural history, prognosis, and management of transplantation-induced diabetes mellitus.

Cardiovascular morbidity and mortality are increased in transplant recipients, and diabetes mellitus is among the main determinants of this increase. This review focuses on the influence of diabetes on survival and functional outcomes in transplant recipients, the prevalences of post-transplantation hyperglycaemia and diabetes, the mechanisms of diabetes in transplant recipients, the respective roles of immunosuppressive drugs, the predictive factors, and the practical implications. Although available studies show that calcineurin inhibitors have diabetogenic effects and that these are more marked with tacrolimus, emphasis should be put on the major diabetogenic role of corticosteroids. This warrants efforts to develop immunosuppressive regimens that eliminate or reduce the need for corticosteroids.

Diabetes Mellitus↗

PubMed2001

Impact of monitoring plasma 1,1-dichlorodiphenildichloroethane (o,p'DDD) levels on the treatment of patients with adrenocortical carcinoma.

BACKGROUND: It has been suggested recently that 1,1-dichlorodiphenildichloroethane (o,p'DDD) elicits a dose effect relation in the treatment of patients with adrenocortical carcinoma (ACC). The authors performed a single-center, prospective study with two major objectives: 1) to confirm the interest of plasma o,p'DDD level measurement as a prognostic factor of response to o,p'DDD therapy; and 2) to look for parameters associated with a therapeutic plasma o,p'DDD level, especially the daily o,p'DDD dose. METHODS: Since 1995, patients with ACC who were referred to the Gustave-Roussy Institute have been enrolled prospectively in the study. Therapy with o,p'DDD was given as first-line therapy in 13 patients with metastatic disease or as adjuvant therapy in 11 patients. Oral o,p'DDD was given in three separate doses up to at least 6-12 g per day together with substitutive adrenal therapy. Plasma o,p'DDD levels were measured using high-performance liquid chromatography every 2 months. The o,p'DDD therapy was monitored to achieve plasma o,p'DDD levels within 14-20 mg/L. World Health Organization criteria were used to evaluate tumor response and toxicity. RESULTS: Twenty-four patients with ACC were studied, and a plasma o,p'DDD level > 14 mg/L was achieved in 14 patients (58%). An objective tumor response was observed in four patients with metastatic lesions (31%): One was response was complete, and three were objective hormonal responses. These tumor responses were observed among the six patients who achieved therapeutic plasma o,p'DDD levels. In contrast, no response was observed among the seven patients with plasma o,p'DDD levels that remained consistently low. Eight of 11 patients who received o,p'DDD as adjuvant therapy had disease recurrence, although the plasma o,p'DDD level was > 14 mg/L in 6 patients. Grade 3 or 4 neurologic toxicity was observed in three patients (12%), all with an o,p'DDD level > 20 mg/L. The daily o,p'DDD dose was the only parameter associated with the highest plasma o,p'DDD trough levels: It explained 35% of the variability in the plasma o,p'DDD level. A median interval of 3.7 months was found necessary to achieve the highest o,p'DDD trough levels. CONCLUSIONS: The results confirm the prognostic impact of the plasma o,p'DDD level in patients with metastatic ACC and its interest in avoiding toxicity.

Adrenal Cortex Neoplasms↗

PubMed2001

Human islet transplantation network for the treatment of Type I diabetes: first data from the Swiss-French GRAGIL consortium (1999-2000). Groupe de Recherche Rhin Rhĵne Alpes Genève pour la transplantation d'Ilots de Langerhans.

AIMS/HYPOTHESIS: Improvements in islet transplantation require clinical series large enough to implement controlled new strategies. The goal of this study was to demonstrate the feasibility of a multicentre network for islet transplantation in Type I (insulin-dependent) diabetic patients. METHODS: The five centres (Besançon, Geneva, Grenoble, Lyon, Strasbourg) of the GRAGIL network allow pancreas procurement, recipient recruitment, transplantation procedure and follow-up. Islet isolation is, however, performed in one single laboratory (Geneva). Pancreata were procured in each of the five centres and transported to Geneva with an ischaemia time of less than 8 hours. Islets were isolated using a standard automated method. If the islet number was too low for a graft (< 6,000 Islet-equivalent/kg), islets were cultured up to 12 days until another isolation was possible. Islets were transplanted by percutaneous transhepatic intraportal injection. Immunosuppression consisted of cyclosporine, mycophenolate mofetil, steroids and an anti-interleukin 2 receptor antibody. RESULTS: From March 1999 to June 2000, 56 pancreata procurements were performed with an average yield of 234500 islet-equivalent, with 32 preparations over 200000 islet-equivalent. Ten C-peptide negative Type I diabetic patients (5 men and 5 women, median age 44 years, median diabetes duration 29 years) with an established kidney graft (> 6 months) received 9,030 +/- 1,090 islet-equivalent/kg with a median purity of 63 %. The number of pancreata required for each graft was 1 (n = 5) or 2 (n = 5). At the completion of a 12 month follow-up, we observed 0% primary nonfunction, 50% graft survival and 20% insulin-independence. CONCLUSIONS/INTERPRETATION: This study demonstrates the interest and the feasibility of a multicentre collaboration in human islet transplantation.

Adult↗

PubMed2001

Use of dobutamine stress echocardiography in detecting silent myocardial ischaemia in asymptomatic diabetic patients: a comparison with thallium scintigraphy and exercise testing.

AIMS: Silent myocardial ischaemia is frequent in diabetic patients. The aim of this study was to compare the efficacy of thallium-201 single-photon emission computed tomography (201Tl SPECT) coupled with exercise stress testing (EST), and dobutamine stress echocardiography (DSE) in the detection of asymptomatic coronary artery disease. METHODS: Fifty-six asymptomatic diabetic patients, with a known duration of diabetes > 15 years for Type 1 and > 5 years for Type 2, having at least three added risk factors, but without rest ECG abnormalities, were enrolled in this prospective study. All of them were submitted to DSE with a maximum infusion rate of 40 microg/kg per min dobutamine +/- i.v. atropine, and to 201Tl SPECT coupled with EST. Coronary angiography was performed if at least one test was abnormal. RESULTS: Diabetic patients were 37 males and 19 females, aged mean (sd) 60 +/- 10 years, 10 Type 1 and 46 Type 2, with a known duration of disease of mean (sd) 17 +/- 9 years. Feasibility of DSE was 91%. No serious complication occurred during the test. Coronary angiography was performed in 26 patients (47%); 17 were abnormal (30% of the whole group): six patients had a one-vessel, six a two-vessel and five a three-vessel disease. Predictive positive value was 69% for DSE, 75% for 201Tl SPECT and 60% for EST. DSE was falsely negative in four cases vs. eight for 201Tl SPECT and nine for EST. CONCLUSIONS: Asymptomatic coronary disease is common in diabetes associated with other risk factors. DSE appears useful in its detection and a good alternative to 201Tl SPECT.

Adult↗

PubMed2001

Bayesian analysis of case control polygenic etiology studies with missing data.

Many genetic studies are based on analysing multiple DNA regions of cases and controls. Usually each is tested separately for association with disease. However, some diseases may require interacting polymorphisms at several regions, and most disease susceptibility is polygenic. In this paper, we develop new methods for determining combinations of polymorphisms that affect the risk of disease. For example, two different genes might produce normal proteins, but these proteins improperly function when they occur together. We consider a Bayesian approach to analyse studies where DNA data from cases and controls have been analysed for polymorphisms at multiple regions and a polygenic etiology is suspected. The method of Gibbs sampling is used to incorporate data from individuals who have not had every region analysed at the DNA sequence or amino acid level. The Gibbs sampling algorithm alternatively generates a sample from the posterior distribution of the sequence of combinations of polymorphisms in cases and controls and then uses this sample to impute the data that are missing. After convergence the algorithm is used to generate a sample from the posterior distribution for the probability of each combination in order to identify groups of polymorphisms that best discriminate cases from controls. We apply the methods to a genetic study of type I diabetes. The protein encoded by the TAP2 gene is important in T cell function, and thus may affect the development of autoimmune diseases such as insulin dependent diabetes mellitus (IDDM). We determine pairs of polymorphisms of genetic fragments in the coding regions of linked HLA genes that may impact the risk of IDDM.

Journal Article↗

PubMed2001

Evaluation of plasma insulin-like growth factor binding protein-2 as a marker for adrenocortical tumors.

OBJECTIVE: Recent studies have pointed to the role of the IGF system in the pathogenesis of adrenocortical tumors, and it was shown recently that malignant adrenocortical tumors exhibit a high insulin-like growth factor binding protein (IGFBP)-2 content. Circulating markers specific for adrenocortical carcinoma are needed and the aim of this study was to evaluate plasma IGFBP-2 as a marker for these malignant tumors. METHODS: Plasma IGFBP-2 was determined in 51 patients referred to our institutions for adrenocortical tumors. Fifteen patients were in complete remission (group 1), eight patients had preoperative localized tumors (group 2) and 28 patients had metastatic tumors (group 3). Thirty-six healthy volunteers constituted a control group. RESULTS: There was no significant difference in plasma IGFBP-2 concentration between healthy controls and patients with complete remission or localized tumors. In contrast, patients with metastatic disease had significantly higher IGFBP-2 plasma levels than the control group (P<0.001). IGFBP-2 levels in patients with metastatic disease were inversely correlated with survival (R2=0.308; P=0.0026). In patients with localized tumors, there was no correlation between plasma IGFBP-2 concentration and tumor size or histological features. Analysis of individual IGFBP-2 concentrations showed that five patients (17.8%) with metastatic tumors had normal IGFBP-2 levels and two patients (13.3%) in complete remission had high plasma IGFBP-2 levels. The influence of nutrition, hormone secretion and treatment on IGFBP-2 levels was examined. Nutritional status was evaluated by determining IGF-I levels and was found to be normal in 16 patients (61.5%) with high IGFBP-2 levels, suggesting that malnutrition was not responsible for the high IGFBP-2 concentrations in these patients. IGFBP-2 levels did not differ significantly according to tumor secretion or mitotane treatment. In a follow-up study, plasma IGFBP-2 concentration remained stable in patients with complete remission or stabilized disease and was a late marker of tumor progression in patients with progressive metastatic disease. CONCLUSIONS: These results indicate that plasma IGFBP-2 is elevated in patients with malignant adrenocortical tumors and that the major factor affecting IGFBP-2 levels in these patients is tumor stage. However, plasma IGFBP-2 was less sensitive than expected for a tumor marker, which may limit its value in the diagnosis and follow-up of adrenocortical carcinoma.

Adolescent↗

PubMed2000

Pancreatic involvement in von Hippel-Lindau disease. The Groupe Francophone d'Etude de la Maladie de von Hippel-Lindau.

BACKGROUND & AIMS: Pancreatic involvement in von Hippel-Lindau (VHL) disease, a genetic disorder with a dominant mode of inheritance affecting various organs, has rarely been studied. We assessed the prevalence, type of lesions, natural history, and impact of pancreatic involvement in patients with VHL. METHODS: A total of 158 consecutive patients from 94 families with VHL disease were studied in a prospective French collaborative study. All patients underwent systematic screening for VHL lesions, including computerized tomography (CT) scanning of the pancreas reviewed by an experienced radiologist. Clinical data, investigations, and treatments performed were also reviewed. RESULTS: Pancreatic involvement was observed in 122 patients (77.2%) and included true cysts (91.1%), serous cystadenomas (12.3%), neuroendocrine tumors (12.3%), or combined lesions (11.5%). The pancreas was the only organ affected in 7.6% of patients. Patients with pancreatic lesions had fewer pheochromocytomas than those without (14/122 vs. 16/36; P<0.0001), and patients with neuroendocrine pancreatic tumors had renal involvement less often than those without (8/99 vs. 6/20; P = 0.013). None of the patients with neuroendocrine tumors had symptoms of hormonal hypersecretion. Pancreatic lesions evolved in half of patients but required specific treatment in only 10 (8.2%) when they were symptomatic or for the resection of large neuroendocrine tumors. CONCLUSIONS: Pancreatic involvement is seen in most patients with VHL disease. Although symptoms are rare, specific treatment of pancreatic lesions is required in selected patients, mainly those with neuroendocrine tumors.

Adult↗

PubMed2000

Sequential occurrence of thyroid autoantibodies and Graves' disease after immune restoration in severely immunocompromised human immunodeficiency virus-1-infected patients.

We analyzed the kinetics of CD4 cells, human immunodeficiency virus (HIV) viral load, and autoantibodies in acquired immune deficiency syndrome patients with Graves' disease (GD) after immune restoration on highly active antiretroviral therapy (HAART; retrospective study). Five patients (median age, 41 yr) were diagnosed with GD after 20 (range, 14-22) months on HAART on the basis of clinical and biological hyperthyroidism, diffuse hyperfixation of thyroid scan, and the presence of anti-TSH receptor (anti-TSHR) antibodies (Ab). GD was diagnosed several months after the plasma HIV ribonucleic acid load became undetectable, when the CD4+ cell count had risen from 14 (range, 0-62) to 340 (range, 163-460) x 10(6) cells/L. Antithyroid peroxidase (anti-TPO) and anti-TSHRAb appeared 14 (range, 9-18) and 14 (range, 11-20) months after starting HAART and 12 (range, 6-15) and 11 (range, 9-17) months after the increase in CD4+ cells. In 3 patients, TPOAb preceded TSHRAb by 3-10 months. No other autoantibodies were detected. Thyroid antibodies were absent in a group of 55 HIV-1-positive patients with comparable response to HAART and no symptoms of hyperthyroidism (cross-sectional study). Thyroid-specific autoimmunity can occur upon immune restoration with HAART. Our observations suggest a relationship between thymus-dependent immune reconstitution after immunosuppression and autoimmunity and may provide insight into the pathophysiology of GD.

Adult↗

PubMed1998

Initiating insulin treatment in insulin-requiring type 2 diabetic patients: comparative efficiency and cost of outpatient and inpatient management. INNOV Study Group.

The main objective of this randomised study was to compare glycaemic control (as determined by HbA1c levels) in two groups of insulin-requiring Type 2 diabetic patients three months after initiation of insulin therapy either on an inpatient (group A, n = 58) or outpatient (group B, n = 56) basis. Evaluation of the safety and cost of both methods was a secondary objective. Although HbA1c level at inclusion was slightly but significantly lower in group A than group B (10.17 +/- 0.19% vs. 10.87 +/- 0.22% respectively, P = 0.019), covariance analysis showed equivalent glycaemic control at 3 months in both groups (adjusted means with respect to inclusion values: 9.00 +/- 1.14% vs. 9.37 +/- 1.14% respectively; equivalence hypothesis: P = 0.01). A low and similar incidence of episodes of hypoglycaemia and hyperglycaemia with ketonuria was observed. Clinical tests, paramedical care and the cost of hospitalisation itself resulted in a direct cost of initiating treatment that was more than four times higher in group A than in group B (mean total cost per patient: FF 15,231 and FF 3,296 respectively). Insulin-requiring Type 2 diabetic patients can be efficiently and safely started on insulin as outpatients, and this approach to initiating insulin therapy is cost-effective.

Adult↗

PubMed1997

Evaluation of TAP1 polymorphisms with insulin dependent diabetes mellitus in Finnish diabetic patients. The Childhood Diabetes in Finland (DiMe) Study Group.

Insulin dependent diabetes mellitus (IDDM) is an autoimmune disease with a strong association between disease and the HLA class II region. Because abnormal antigen processing, in part characterized by altered class I processing, has been identified in patients with IDDM, the TAP (transporter associated with antigen processing) genes located in the HLA class II region make attractive candidate genes for IDDM. Five coding region variants of TAP1 were typed in a cohort of well characterized Finnish patients with diabetes (n = 119) and compared to racially marched control subjects (n = 92). We found that although no single TAP1 polymorphism was associated with IDDM, a genotypic combination of Ile/Val at codon 333 with Asp/Asp at codon 637 was found more frequently in subjects with IDDM (9.4%) compared to controls (1.2%; p = 0.025). This could not be accounted for by an association with any particular haplotype defined by class I or class II serology.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Human TAP1 polymorphisms detected by denaturing gradient gel electrophoresis.

Presentation of endogenous peptides by major histocompatibility complex class I (MHC) molecules is controlled, in part, by the Tap1 and Tap2 genes in the MHC class II region that encode a heterodimeric peptide transporter. Polymorphisms of human Tap1 in normal individuals have now been investigated systematically by denaturing gradient gel electrophoresis (DGGE) analysis of fragments of genomic DNA generated by the polymerase chain reaction. Polymorphisms identified by distinctive DGGE band patterns were confirmed by DNA sequencing. In addition to four previously described polymorphisms in the open reading frame, DGGE detected three new polymorphisms: a G-->T substitution in the promoter region, a 10-bp insert in intron 9, and a G-->T substitution 80-bp downstream of the translation termination codon.

ATP Binding Cassette Transporter, Subfamily B, Mem↗