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Biomedical subjects

P Perros

Publications and source records attributed to P Perros.

At least 19 recordsLinked to original sources
PubMed2003

Thyroid disease and male reproductive function.

Despite the high prevalence of thyroid diseases in the general population, male reproductive function in patients with thyroid disease has been the subject of only a few studies. Hyperthyroidism appears to cause sperm abnormalities (mainly reduction in motility), which reverse after restoration of euthyroidism. Radioiodine therapy for hyperthyroidism or thyroid cancer may cause transient reductions in sperm count and motility, but there appears to be little risk of permanent effects provided that the cumulative dose is less than 14 MBq. The effects of hypothyroidism on male reproduction appear to be more subtle than those of hyperthyroidism and reversible. Severe, prolonged hypothyroidism in childhood may be associated with permanent abnormalities in gonadal function.

Humans↗
PubMed2003

CTLA4 gene and Graves' disease: association of Graves' disease with the CTLA4 exon 1 and intron 1 polymorphisms, but not with the promoter polymorphism.

OBJECTIVE: Recent studies have shown that Graves' disease (GD) is linked to and associated with alleles of the cytotoxic T lymphocyte antigen-4 (CTLA4) locus. However, the true pathogenic polymorphism(s) at this locus remains uncertain. Moreover, the association studies of the promoter CTLA4(-318)C/T polymorphism in white GD populations have produced conflicting results. Therefore, we have analysed three CTLA4 single nucleotide polymorphisms, including promoter CTLA4(-318)C/T, exon 1 CTLA4(49)A/G and intron 1 CTLA4(1822)C/T in our GD cohort from the UK. PATIENTS AND METHODS: We studied 301 white patients with GD and 349 healthy ethnically matched local controls. Amongst GD probands, 129 had significant thyroid-associated orbitopathy (TAO; NOSPECS class III or worse). The CTLA4(-318)C/T, CTLA4(49)A/G and CTLA4(1822)C/T polymorphisms were genotyped by using the restriction enzymes MseI, Bst71I and HaeIII, respectively. RESULTS: We found no association between GD and alleles of CTLA4(-318)C/T. GD was found to be associated with the G allele of CTLA4(49)A/G[P = 5.9 x 10(-6), odds ratio (OR) 1.65] and the T allele of CTLA4(1822)C/T (P = 7.7 x 10(-6), OR 1.64). The frequencies of these alleles were significantly higher in GD probands with significant TAO than in those without TAO (G allele: P = 0.001, OR 1.68; T allele: P = 0.001, OR 1.70). CONCLUSIONS: The promoter CTLA4(-318)C/T polymorphism is not in linkage disequilibrium with the pathogenic polymorphism(s) at the CTLA4 locus. The alleles of both the exon 1 CTLA4(49)A/G and the intron 1 CTLA4(1822)C/T polymorphisms are associated with GD, which is stronger in patients with TAO.

Abatacept↗
PubMed2001

Management of a pregnant patient with Graves' disease complicated by thionamide-induced neutropenia in the first trimester.

A 31-year-old woman presented with neutropenia due to thionamide drug therapy for Graves' disease. She also reported 8 weeks of amenorrhoea and had a positive pregnancy test. Her drug therapy was discontinued and her neutropenia resolved uneventfully. The hyperthyroidism recurred a week later. After consideration of all treatment options, it was decided to observe until 14 weeks when an elective thyroidectomy was planned. Mother and fetus were monitored closely and both tolerated moderate hyperthyroidism well. At 14 weeks the patient underwent a total thyroidectomy after rendering her euthyroid with a short course of sodium ipodate. Labour was induced at 41 weeks. Delivery was complicated by fetal distress and precipitated a forceps delivery. A 3250 g male infant was born with poor Apgar score and required 2 h of ventilation. At 1 year, the child had reached all developmental milestones at appropriate times. Both mother and fetus may tolerate moderate thyrotoxicosis well in early pregnancy, an alternative that should be considered when thionamide drug therapy is contraindicated.

Adult↗
PubMed2001

Controversies in the clinical evaluation of active thyroid-associated orbitopathy: use of a detailed protocol with comparative photographs for objective assessment.

Despite many learned publications over recent decades, the assessment of active thyroid-associated orbitopathy (TAO) remains difficult and controversial. There are no biochemical, immunological or imaging investigations which can identify active disease reliably, and clinical assessment is still of paramount importance. We therefore review the strengths and weaknesses of all methods of clinical assessment. A new atlas for clinical assessment of soft tissue signs has been developed, and its reproducibility assessed. It details a suggested protocol that could help standardize descriptions of TAO and allow more objective assessment of its activity and severity. This is relevant to general endocrinologists, who have a crucial role in the identification of patients who require ophthalmological assessment. Certain aspects are more relevant to ophthalmologists and endocrinologists who have a special clinical and research interest in TAO. Unless a reproducible system of assessment is devised and widely adopted, it will remain difficult to interpret research meaningfully, particularly if results appear to contradict.

Clinical Protocols↗
PubMed2001

Evidence for a Graves' disease susceptibility locus at chromosome Xp11 in a United Kingdom population.

Graves' disease (GD), which has a strong female preponderance (female/male ratio, >5:1), is inherited as a complex genetic trait. Loci for GD have started to be defined using genome-wide approaches for genetic linkage. To date, 3 loci have been confirmed in at least 2 cohorts of GD patients, the strongest effect being at the cytotoxic T lymphocyte antigen-4 (CTLA-4) locus on chromosome 2q33 in our population. Two other loci for GD have recently been proposed, but not confirmed, on chromosomes Xq21 (GD3) and 14q31 (GD1). We studied a cohort of 75 sibling pairs with GD from the United Kingdom for linkage to 12 markers over a 83-cM region of the X chromosome and for 8 markers over a 36-cM region of 14q31-q33. A peak multipoint nonparametric linkage score of 2.21 (P = 0.014) was found at marker DXS8083 on Xp11, which increased to a nonparametric linkage score of 3.18 (P = 0.001) in data that had been conditioned for allele sharing at the CTLA-4 locus under an epistatic model. There was no evidence to support linkage of GD to Xq21.33-q22 (GD3) or at the 14q31-q33 (GD1) region in our population. A locus with a moderate contribution to GD susceptibility (lambda(s) = 1.4) is likely to exist in the Xp11 region, but we are unable to confirm that the GD1 or the GD3 regions contain major susceptibility loci in our United Kingdom GD population.

Abatacept↗
PubMed2000

Evidence for a new Graves disease susceptibility locus at chromosome 18q21.

Graves disease (GD) is a common autoimmune thyroid disorder that is inherited as a complex multigenic trait. By using a single microsatellite marker at each locus, we screened the type 1 diabetes loci IDDM4, IDDM5, IDDM6, IDDM8, and IDDM10 and the fucosyltransferase-2 locus for linkage in sib pairs with GD. This showed a two-point nonparametric linkage (NPL) score of 1.57 (P=.06) at the IDDM6 marker D18S41, but NPL scores were <1.0 at the other five loci. Thus, the investigation of the IDDM6 locus was extended by genotyping 11 microsatellite markers spanning 48 cM across chromosome 18q12-q22 in 81 sib pairs affected with autoimmune thyroid disease (AITD). Multipoint analysis, designating all AITD sib pairs as affected, showed a peak NPL score of 3.46 (P=.0003), at the marker D18S487. Designation of only GD cases as affected (74 sib pairs) showed a peak NPL score of 3.09 (P=.001). Linkage to this region has been demonstrated in type 1 diabetes (IDDM6), rheumatoid arthritis, and systemic lupus erythematosus, which suggests that this locus may have a role in several forms of autoimmunity.

Alleles↗
PubMed2000

Evaluation of an on-call diabetes service in a large teaching hospital.

AIMS: To assess prospectively the activity and effectiveness of a diabetes specialist on-call service. METHODS: All requests for specialist advice received by the doctor on-call for diabetes in a large teaching hospital were recorded and analysed over a period of 3 weeks. RESULTS: The total number of calls was 135 (mean 45 per week) of which 48.1% were outside normal working hours. Requests for advice from surgical and medical ward staff accounted for 43% of calls, the remainder were from staff in the maternity ward (12.6%), staff in other hospitals in the city (3.7%), general practitioners (13.3%) and patients (27.4%). The time spent by the on-call doctor for diabetes responding to calls was a mean of 8.6 h per week. The number of acute admissions prevented by this service was estimated to be 11 (3.6 per week). CONCLUSIONS: Open access to specialist advice provided by a doctor with expertise in diabetes is an effective adjunct to the delivery of diabetes care in the setting of a large teaching hospital.

Adult↗
PubMed2000

Serum S-100beta protein is a potential biochemical marker for cerebral oedema complicating severe diabetic ketoacidosis.

CASE REPORT: A 39-year-old man with Type 1 diabetes mellitus was hospitalized with severe diabetic ketoacidosis (DKA). Sixteen hours after admission he suddenly deteriorated having a respiratory then cardiac arrest. A brain computed tomography scan performed 2 h after the respiratory arrest showed severe cerebral oedema. Serial serum samples were stored and analysed for S-100beta protein. The S-100beta protein concentration was initially normal (0.12 microg/l) then rose significantly before the onset of the respiratory arrest (8.5 h = 0.61 microg/l, 14.5 h = 0.9 microg/l, 18 h = 1.6 microg/l, 25.5 h = 3.1 microg/l, 34 h = 4.6 microg/l and44 h = 19.5 microg/l). CONCLUSIONS: In this case of DKA, serum S-100beta concentration rose coinciding with the onset of cerebral oedema, before it became clinically evident. Monitoring serum S-100beta may have a useful role in the management of DKA.

Adult↗
PubMed2000

Prevalence of pernicious anaemia in patients with Type 1 diabetes mellitus and autoimmune thyroid disease.

AIMS: To determine the prevalence of pernicious anaemia in patients with Type 1 diabetes mellitus and autoimmune thyroid disease. METHODS: A randomly selected asymptomatic group of 63 patients with Type 1 diabetes who also had autoimmune thyroid disease was studied. Blood samples were taken and assayed for serum B12. Those subjects with serum B12 concentrations below the reference range had a further blood sample taken for determination of intrinsic factor antibody. RESULTS: One patient had been diagnosed previously to have pernicious anaemia. Three patients had low serum B12 concentration and positive intrinsic factor antibody, confirming the diagnosis of pernicious anaemia. The prevalence of pernicious anaemia in this population with Type 1 diabetes and concomitant autoimmune thyroid disease was 6.3%. In female patients the prevalence of pernicious anaemia was 8.5%. CONCLUSIONS: Patients who have both Type 1 diabetes mellitus and autoimmune thyroid disease are at risk of developing pernicious anaemia.

Aged↗
PubMed2000

Association analysis of the cytotoxic T lymphocyte antigen-4 (CTLA-4) and autoimmune regulator-1 (AIRE-1) genes in sporadic autoimmune Addison's disease.

Although autoimmune Addison's disease (AAD) may occur as a component of the monogenic autoimmune polyendocrinopathy type 1 syndrome (APS1), it is most commonly found as an isolated disorder or associated with the autoimmune polyendocrinopathy type 2 syndrome (APS2). It is likely that sporadic (non-APS1) AAD is inherited as a complex trait; however, apart from the major histocompatibility complex, the susceptibility genes remain unknown. We have examined polymorphisms at two non-major histocompatibility complex candidate susceptibility loci in sporadic (non-APS1) AAD: the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene and the autoimmune regulator (AIRE-1) gene. DNA samples from AAD subjects (n = 90) and local controls (n = 144 for CTLA-4; n = 576 for AIRE-1) were analyzed for the CTLA-4A/G polymorphism in exon 1 of the CTLA-4 gene and for the common mutant AIRE-1 allele (964de113) in United Kingdom subjects with APS1, by using the restriction enzymes Bst7II and BsrBI, respectively. There was an association of the G allele at CTLA-4A/G in AAD subjects (P = 0.008 vs. controls), which was stronger in subjects with AAD as a component of APS2 than in subjects with isolated AAD. In contrast, the mutant AIRE-1 964del13 allele was carried in one each of the 576 (0.2%) control subjects and the 90 (1.1%) AAD subjects as a heterozygote (P = 0.254, not significant), suggesting that this common AIRE-1 gene abnormality does not have a major role in sporadic (non-APS1) AAD.

Abatacept↗
PubMed2000

Current awareness

In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 17 sections: 1 Books, Reviews & Symposia; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Prediction; 7 Prevention; 8 Intervention: a&rpar General; b&rpar Pharmacology; 9 Pathology: a&rpar General; b&rpar Cardiovascular; c&rpar Neurological; d&rpar Renal; 10 Endocrinology & Metabolism; 11 Nutrition; 12 Animal Studies; 13 Techniques. Within each section, articles are listed in alphabetical order with respect to author (8 Weeks journals - Search completed at 23rd Feb. 2000)

Journal Article↗