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Biomedical subjects

J Orgiazzi

Publications and source records attributed to J Orgiazzi.

At least 19 recordsLinked to original sources

[Screening for bacteriuria in diabetic patients. Is it possible to stop systematic urine cytobacteriological testing?].

OBJECTIVES AND METHOD: The discordance between test by urine dipstick (nitrites and leucocyte-esterase) and analysis in laboratory, with urinary culture on the same sample was studied in diabetic patients, from October 2000 to May 2002, to eventually stop systematic laboratory test. The dipstick result (Clinitek 20 Bayer) was classified as "possibility of bacteriuria" if one of the two tests was positive. Bacteriuria was considered significant if the laboratory test result gave, at least 10(5) bacteria per mL, (one strain), and at least 10(4) leucocytes. The out point was the dipstick negative predictive value (NPV). RESULTS: The study included 683 patients. The dipstick result was "possibility of bacteriuria" in 153 cases (22.4%). Thirty-nine bacteriuria (5.7%) were reported, including 2 dipstick false negatives. The NPV was 99.6% [IC 95% : 99.1-100]. CONCLUSION: The systematic laboratory tests were stopped.

Adolescent↗

[Status of iodine nutrition in France: prevention of iodine deficiency in pregnant and lactating women].

Iodine intake varies with age and physiological status: in pregnant and lactating women, recommended iodine intake ranges from 200 to 250 mg/day. Recent epidemiological studies in France demonstrate the presence of moderate iodine deficiency in the majority of pregnant and lactating women. This iodine deficiency induces maternal thyroid hyperplasia and then development of goiter in women, as well as impaired thyroid parameters. Maternal hypothyroxinemia during the first trimester of pregnancy can be associated with abnormal cognitive development and intellectual outcomes in the newborn and the children. According to the recent World Health Organization recommendations for the prevention and control of iodine deficiency in pregnant and lactating women, systematic iodine supplementation is indicated in France: 100 microg/day for women of reproductive age and 200 microg/day in pregnant and lactating women in order to eradicate iodine deficiency during pregnancy and lactation, and prevent the maternal and fetal consequences.

Female↗

Is there a need to redefine the upper normal limit of TSH?

Mild forms of hypothyroidism--subclinical hypothyroidism--have recently been discussed as being a risk factor for the development of overt thyroid dysfunction and for a number of clinical disorders. The diagnosis critically depends on the definition of the upper normal limit of serum TSH as, by definition, free thyroxine serum concentrations are normal. Cut-off levels of 4-5 mU TSH/l have been conventionally used to diagnose an elevated TSH serum concentration. Recent data from large population studies have suggested a much lower TSH cut-off with an upper limit of 2-2.5 mU/l but application of strict criteria for inclusion of subjects from the general population studies aiming at assessing TSH reference intervals (no personal or family history of thyroid disease, no thyroid antibodies and a normal thyroid on ultrasonography) did not result in an unequivocal upper limit of normal TSH at 2.0-2.5 mU/l. When summarizing the available evidence for lowered upper TSH cut-off values and their potential therapeutic implications there is presently insufficient justification to lower the upper normal limit of TSH and, for practical purposes, it is still recommended to maintain the TSH reference interval of 0.4-4.0 mU/l. Classifying subjects with a TSH value between 2 and 4 mU/l as abnormal, as well as intervening with thyroxine treatment in such subjects, is probably doing more harm than good.

Chemistry, Clinical↗

A questionnaire survey on the management of Graves' orbitopathy in Europe.

OBJECTIVE: To determine management patterns among clinicians who treat patients with Graves' orbitopathy (GO) in Europe. DESIGN AND METHODS: Questionnaire survey including a case scenario of members of professional organisations representing endocrinologists, ophthalmologists and nuclear medicine physicians. RESULTS: A multidisciplinary approach to manage GO was valued by 96.3% of responders, although 31.5% did not participate or refer to a multidisciplinary team and 21.5% of patients with GO treated by responders were not managed in a multidisciplinary setting. Access to surgery for sight-threatening GO was available only within weeks or months according to 59.5% of responders. Reluctance to refer urgently to an ophthalmologist was noted by 32.7% of responders despite the presence of suspected optic neuropathy. The use of steroids was not influenced by the age of the patient, but fewer responders chose to use steroids in a diabetic patient (72.1 vs 90.5%, P<0.001). Development of cushingoid features resulted in a reduction in steroid use (90.5 vs 36.5%, P<0.001) and increase in the use of orbital irradiation (from 23.8% to 40.4%, P<0.05) and surgical decompression (from 20.9 to 52.9%, P<0.001). More ophthalmologists chose surgical decompression for patients with threatened vision due to optic neuropathy, who were intolerant to steroids than other specialists (70.3 vs 41.8%, P<0.01). CONCLUSION: Deficiencies in the management of patients with GO in Europe were identified by this survey. Further training of clinicians, easier access of patients to specialist multidisciplinary centres and the publication of practice guidelines may help improve the management of this condition in Europe.

Decompression, Surgical↗

[Grave's ophthalmopathy: therapeutic strategy. Review of 30 patients].

BACKGROUND: Graves' ophthalmopathy is the primary etiology for exophthalmos in adults. It is a complex orbital disease whose pathophysiology remains controversial. Since its initial description more than 150 years ago, its heterogeneous clinical manifestations and poorly understood links with thyroid pathology remain unresolved issues. Disease activity is the main determinant for the management of Graves' ophthalmopathy, but treatments are often symptomatic, aiming at decreasing orbital inflammation. MATERIAL AND METHODS: We report a retrospective analysis of 30 patients diagnosed with Graves' ophthalmopathy followed in our department between 1991 and 2002. Following a phase of medical management of their disease, all patients underwent surgical orbital decompression. RESULTS: Medical and surgical care provided as well as results are presented with a mean follow-up of 23 months. DISCUSSION: Based on our clinical experience, new concepts in the field of Graves' ophthalmopathy are discussed. Disease activity, evaluated through various means, appears to be the primary guide for therapeutic management. Moreover, the importance of a multidisciplinary approach is highlighted, in order to improve the management of this difficult disorder.

Adult↗

Octreotide (long-acting release formulation) treatment in patients with graves' orbitopathy: clinical results of a four-month, randomized, placebo-controlled, double-blind study.

There are few effective, safe modalities for the management of Graves' ophthalmopathy (GO), a cell-mediated immune comorbidity of thyroid disease. Somatostatin analogs inhibit lymphocyte proliferation and activation, and accumulate in the orbital tissue of patients with GO. A double-blind, placebo-controlled study of a long-acting somatostatin analog [16 wk of long-acting release formulation of octreotide (octreotide-LAR)] was conducted in 51 patients with mild active GO with the aim of preventing deterioration and precluding the need for more aggressive therapeutic modalities, such as glucocorticoids or radiotherapy. No treatment effect was observed for the primary end point (a composite parameter defining the outcome as either success or failure on the basis of changes in class/grade of the severity index and Clinical Activity Scale of GO). The Clinical Activity Scale score was reduced for patients treated with octreotide-LAR, but without any significant difference with respect to patients receiving placebo. However, octreotide-LAR significantly reduced proptosis (as measured by exophthalmometry). This was associated with nonsignificant differences in favor of octreotide-LAR in a series of proptosis-related parameters: class III grade, opening of the upper eyelid, the difference in ocular pressure between primary position and upgaze, and extraocular muscle involvement. By magnetic resonance imaging evaluation the extraocular muscle volumes appeared reduced, but nonsignificantly. No significant correlation between the initial uptake of the somatostatin analog indium-labeled and the response to treatment was observed. One patient in the octreotide-LAR group developed gallstones. In this study, octreotide-LAR did not seem suitable to mitigate activity in mild GO. Surprisingly, it significantly reduced proptosis, one of the most debilitating symptoms of GO. Additional studies are warranted to define the benefit to risk ratio of the somatostatin analogs in this indication.

Delayed-Action Preparations↗

Modulation of antigen presentation by autoreactive B cell clones specific for GAD65 from a type I diabetic patient.

We used a GAD65-specific human B-T cell line cognate system in vitro to investigate the modulation of GAD65 presentation by autoantibody, assessed in a proliferation assay. Generally, if the T cell determinant overlaps or resides within the antibody epitope, effects of presentation are blunted while if they are distant can lead to potent presentation. For three different autoreactive B-T cell line cognate pairs, the modulation of GAD65 presentation followed the mode of overlapping or distant epitopes with resultant potent or undetectable presentation. However, other cognate pairs elicited variability in this pattern of presentation. Notably, one B cell line, DPC, whose antibody epitope did not overlap with the T cell determinants, was consistently poor in presenting GAD65. Using the fluorescent dye Alexa Fluor 647 conjugated to GAD65 to study receptor-mediated antigen endocytosis showed that all the antigen-specific B cell clones were efficient in intracellular accumulation of the antigen. Additionally, multicolour immunofluorescence microscopy showed that the internalized GAD65/surface IgG complexes were rapidly targeted to a perinuclear compartment in all GAD-specific B cell clones. This analysis also demonstrated that HLA-DM expression was reduced strongly in DPC compared to the stimulatory B cell clones. Thus the capability of antigen-specific B cells to capture and present antigen to human T cell lines is dependent on the spatial relationship of B and T cell epitopes as well other factors which contribute to the efficiency of presentation.

Antibodies, Monoclonal↗

Advances in diagnostic practices affect thyroid cancer incidence in France.

OBJECTIVE: To analyse trends in diagnostic practices of thyroid diseases and to relate them to the increase in thyroid cancer incidence in France over time. DESIGN: From 1980 to 2000, a French retrospective multicentric (three endocrinology and three nuclear medicine centres) study of thyroid diseases was conducted on 20 consecutive unselected patients' records, sampled every 5 years in each centre. METHODS: Characteristics of the population and diagnosis procedures (thyroid ultrasonography (US), radionuclide scan, cytology and hormonal measurements) were described over time. Changing trends in operated patients and in cancer prevalence were analysed as well as the impact of practices on cancer incidence. RESULTS: The study included 471 patients (82% female, mean age 46.7, range 9-84 years), referred for nodular thyroid diseases (66.7%) or thyroid dysfunctions (33.3%). A significant increase in US (3 to 84.8%) and cytological practices (4.5 to 23%), and a decrease (89.4 to 49.6%) in radionuclide scan procedures were observed over time. Although the proportion of patients undergoing surgery remained constant (24.8%), the prevalence of cancer increased among operated patients from 12.5 to 37% (P=0.006). In a Cox's proportional hazard model stratified on the clinical characteristics of patients, only the cytological practice, regardless of its results, was significantly associated with the occurrence of cancer: relative risk (RR)=4.4 (95% confidence interval (CI): 1.1-16; P=0.04). CONCLUSIONS: From 1980 to 2000, a major evolution in clinical practices has led to the increase in thyroid cancer reported in France. Such changes in medical, as well as in surgical and pathological, practices must be taken into account in incidence measurement.

Adolescent↗

Kinetics of thyrotropin-stimulating hormone (TSH) and thyroid-stimulating antibody binding and action on the TSH receptor in intact TSH receptor-expressing CHO cells.

The kinetics of TSH binding and the effects of TSH and thyroid-stimulating antibody (TSAb) on cAMP accumulation have been measured in TSH receptor-expressing CHO cells (CHO-TSHR cells). The parallel kinetics of TSH binding to its receptor and of cell cAMP concentration after the addition and withdrawal of TSH show that in the case of this receptor, signal generation and concentration are at all times proportional to occupancy. In physiological ionic medium, TSAb, but not TSH, action is slowed and in some cases almost nonexistent. The kinetics of cAMP disappearance after washout of TSAb is also slower. cAMP accumulation is faster for Fabs than for the TSAb from which they derive. Analysis of the data suggest that 1) serum TSAb are oligoclonal antibodies sets, at low concentrations, with a high affinity for the TSH receptor; 2) ionic interactions are involved in the action of TSAb on the TSH receptor; and 3) TSAb activation of the TSH receptor is at least a two-step process. Among others, a possible explanation is that the full activation of the receptor requires the binding of two or more different antibody molecules on different sites of the same TSH receptor. This analysis provides a benchmark for studies of experimentally induced monoclonal antibodies activating the TSH receptor.

Animals↗

[Antithyroid agents and embryopathies].

First cause of hyperthyroidism among women of childbearing age, Graves' disease raises the risk of maternal and fetal complications, including eclampsia, cardiac failure, abortion, prematurity, fetal death, all of which can be avoided if maternal hyperthyroidism is closely controlled. The risk of transplacental hyperthyroidism has been shown to correlate to the titre of anti-TSH receptor antibodies and has to be evaluated not only in women treated for Graves' disease during pregnancy, but also in women who have previously received radio iodine treatment or undergone surgery for Graves' disease: TSH-receptor antibodies may indeed remain at a high level several years after initial treatment. Both methimazole and propylthiouracil are equally effective to restore maternal euthyroidism. Accumulation of case-reports relating congenital malformations (mostly aplasia cutis, but in some cases, severe malformations) among the offspring of methimazole-treated women suggests the possibility of a teratogenic effect of methimazole. Despite the fact that the link between severe congenital defects and methimazole exposure during pregnancy is not formally established, propylthiouracil should be preferred to methimazole for the treatment of young hyperthyroid women.

Abnormalities, Drug-Induced↗

Primary thyroid lymphoma is a heterogeneous disease.

We retrospectively analyzed 26 patients with thyroid lymphoma (TL). Patients were mostly females, with a median age of 59 yr, presenting a rapidly growing nodular goiter with or without cervical adenopathy, without symptoms related to lymphoma for 81% and hypothyroidism in 61%. A previous history of Hashimoto thyroiditis was observed in 11 patients. Six different subtypes of lymphoma were observed: 13 of 26 (50%) had diffuse large B cell lymphoma, 6 (23%) mucosa- associated lymphoid tissue (MALT) lymphoma, 3 (12%) had follicular lymphoma, 2 (7%) had Hodgkin's disease, 1 (4%) had small lymphocytic lymphoma, and 1 (4%) had Burkitt's lymphoma. Diffuse large B cell lymphoma patients presented a compressive multinodular goiter, cervical adenopathy (66%), disseminated disease (50%), and poor performance status, with a poor prognosis (5-yr survival at 44%) despite a treatment based on a multidrug regimen. MALT lymphoma arose in patients with previous history of Hashimoto disease, was localized in all but 1, and was biologically associated with hypothyroidism and a high level of serum antithyroid antibodies. With total thyroidectomy, prognosis was good (5-yr survival at 100%). We did not find any routine clinical or biological parameters that could predict the evolution from Hashimoto's thyroiditis to MALT lymphoma. In conclusion, we confirmed the histological heterogeneity of TL corresponding to different clinical presentations and different prognoses.

Antineoplastic Combined Chemotherapy Protocols↗

[Patterns physicians use to screen for gestational diabetes: descriptive analysis in a cohort of 701 women].

OBJECTIVE: To study the way physicians screen for gestational diabetes. PATIENTS AND METHODS: Descriptive analysis of the pattern of screening used by physicians for 701 women who gave birth in a public or private maternity in the Rhône district in France. RESULTS: Overall, a screening test was used in 17.7% of the women (95%CI 14.9-20.7). A 50 g glucose tolerance test was performed in 60% of the screening prescriptions and was positive in 37.3%. One-third of the screening tests were achieved after the 28th gestational week. About half of the women were at risk for gestational diabetes. Among them, 24.6% had had a screening test. Factors associated with prescription of a screening test were gestational diabetes or macrosomia in a previous pregnancy, diabetes in relatives, high body mass index, weight gain of more than 15 kg, African origin, and follow-up in a public maternity. The diagnosis of gestational diabetes was made in 9 women. The prevalence of gestational diabetes was 1.28% (95%CI 0.59%-2.42%). CONCLUSION: Guidelines from the national colleges of obstetricians and endocrinologists for systematic screening for gestational diabetes are not properly applied. Questions concerning the implementation, results, and feasibility of these guidelines are raised.

Adult↗

Combination of autoantibody markers and risk for development of type 1 diabetes: results from a large french cohort of family members.

BACKGROUND: The aims of the study were to characterize the relatives at high risk of progression to diabetes and to determine whether rate of progression to diabetes varied according to age, specific combination of antibodies and genetic markers of susceptibility. METHODS: Family members of type 1 diabetic patients were examined through a large medical network for the presence of specific antibodies to beta cell constituents and high risk DQB1 alleles. Antibodies to insulin, GAD and IA-2 as well as ICA were examined in 4,044 family members recruited in a large prospective family study in the Rhone-Alpes region (the GRADI study). Among them, 3,951 non diabetic first degree relatives have been tested on a median of 2.2 occasions and were followed for up to 16 years. RESULTS: Presence of antibodies to GAD (3.6%), IA-2 (4.9%), insulin (2.2%) and ICA at titers equal or above 20JDF units (1.1%) were noticed at the first determination and prevalence increased among ICA positive relatives versus ICA negative relatives. All combinations of markers resulted in specificities above 90%. The positive predictive value of antibodies was dependent on the number of positive antibodies. Combination of antibodies to GAD and IA-2 or GAD and IAA had higher predictive values and sensitivities than ICA titers above 20 JDF units. Additional positivity of IAA increased the predictive value but reduced the sensitivity of the screening procedure. Using a combi GAD/IA-2 assay increased the sensitivity of the screening up to 87.8% but reduced the predictive value to 13.8%. CONCLUSIONS: These data confirm in a large French cohort of first degree relatives of type 1 diabetic patients that combinations of antibodies to beta cell constituents can replace ICA in the first screening procedure. We report that combi GAD/IA-2 assay is well suited for screening purposes. However, time to diabetes in antibody positive relatives appears to be more heterogeneous to what has been described. The importance of genetic markers needs further evaluation.

Autoantibodies↗