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Biomedical subjects

M Armitage

Publications and source records attributed to M Armitage.

At least 19 recordsLinked to original sources
PubMed2006

Influences of age, gender, smoking, and family history on autoimmune thyroid disease phenotype.

CONTEXT: Both genetic and environmental factors contribute to susceptibility to Graves' disease (GD) and Hashimoto's thyroiditis (HT), as well as disease manifestations. OBJECTIVE: The objective of the study was to define how endogenous/environmental factors contribute to variation in phenotype. DESIGN/SETTING: This was a multicenter cohort study. PATIENTS/OUTCOME MEASURES: We prospectively collected clinical/biochemical data as part of the protocol for a United Kingdom DNA collection for GD and HT. We investigated, in 2805 Caucasian subjects, whether age at diagnosis, gender, family history (FH), smoking history, and presence of goiter influenced disease manifestations. RESULTS: For 2405 subjects with GD, the presence of goiter was independently associated with disease severity (serum free T4 at diagnosis) (P < 0.001). Free T4 (P < 0.05) and current smoking (P < 0.001) were both independent predictors of the presence of ophthalmopathy. Approximately half of those with GD (47.4% of females, 40.0% of males) and HT (n = 400) (56.4% of females, 51.7% of males) reported a FH of thyroid dysfunction. In GD, a FH of hyperthyroidism in any relative was more frequent than hypothyroidism (30.1 vs. 24.4% in affected females, P < 0.001). In HT, a FH of hypothyroidism was more common than hyperthyroidism (42.1 vs. 22.8% in affected females, P < 0.001). For GD (P < 0.001) and HT (P < 0.05), a FH was more common in maternal than paternal relatives. The reporting of a parent with thyroid dysfunction (hyper or hypo) was associated with lower median age at diagnosis of both GD (mother with hyperthyroidism, P < 0.001) and HT (father with hypothyroidism, P < 0.05). In GD and HT, there was an inverse relationship between the number of relatives with thyroid dysfunction and age at diagnosis (P < 0.01). CONCLUSIONS: Marked associations among age at diagnosis, disease severity, goiter, ophthalmopathy, smoking, and FH provide evidence for interactions between genetic and environmental/endogenous factors; understanding these may allow preventive measures or better tailoring of therapies.

Adolescent↗
PubMed2002

Inflammatory hypophysitis - the spectrum of disease.

BACKGROUND: Inflammatory conditions of the pituitary are rare and consequently there are a number of single case reports of this condition but few reports of series. The condition is often divided into lymphocytic and granulomatous hypophysitis and it has been suggested that these two conditions represent the ends of a spectrum of disease. METHOD: We present our experience with 14 cases of this condition, correlating the presenting symptoms with the neuroradiology, surgical findings and subsequent histology. FINDINGS: The subjects (11 female 3 male) ranged in age from 13 to 64 years. Final histopathological diagnoses included 5 cases of lymphocytic hypophysitis, 4 cases of Rathke's pouch cyst with granulomatous response, 2 cases of granulomatous hypophysitis and 1 case with an inflammatory process that did not fit the current classification. Two subjects did not undergo surgery. Headache was a presenting feature in 11 of 14 cases and fever in 3 of 14 cases. Length of symptoms prior to presentation varied from acute onset to 9 years. One case of lymphocytic hypophysitis was associated with pregnancy. Evidence of hypopituitarism was present in 9 of 10 subjects assessed preoperatively. Preoperative radiology showed three patterns of disease: A cystic appearance was common with low signal content on MRI T1 weighting with an enhancing ring and a thickened enhancing stalk (5 patients). 4 patients showed a solid enhancing mass. A third group (2 patients) showed cysts with high signal content on T1 weighting - both of these were Rathke's cysts on histology. INTERPRETATION: Overall there were no striking features in the clinical presentation to distinguish pituitary inflammation from pituitary adenoma. The prognosis was generally good.

Adenoma↗
PubMed2002

The importance of testing for adrenoleucodystrophy in males with idiopathic Addison's disease.

X linked adrenoleucodystrophy (X-ALD) is considered to be a rare cause of Addison's disease, although several small series suggest a high incidence in young Addisonian males. A survey in the south west of England identified 12 male patients diagnosed with Addison's disease in the period 1987-99. In 10 of these (83%) X-ALD was the underlying cause; the other two were of autoimmune aetiology. Five boys had developed Addison's disease subsequent to the diagnosis of X-ALD. Of the remaining five, in three boys the diagnosis of X-ALD was considerably delayed (by six months to two years from that of Addison's disease) and in two it was only made as a result of this survey. We also identified a patient who presented with Addison's disease at the age of 5 years but was only diagnosed as having X-ALD at the age of 34 years; in the interim his diagnosis of adrenomyeloneuropathy had been missed. Our experience highlights the absolute necessity of measuring very long chain fatty acids in all males with idiopathic Addison's disease.

Addison Disease↗
PubMed2001

An exception to the rule: ectopic ACTH production from functional neuroendocrine tissue in an ovarian dermoid cyst.

Ectopic ACTH production accounts for 15% of Cushing's syndrome presentations and is characterized by the presence of an excess of ACTH precursors. However in the case presented here ectopic ACTH production was from functional pituitary tissue within an ovarian dermoid cyst. Endocrine investigations showed that the problem behaved more like pituitary-dependent Cushing's disease and this is discussed. Furthermore, this case is one of familial dermoid cysts, another unusual phenomenon.

ACTH Syndrome, Ectopic↗
PubMed2001

General medicine in the UK - back stage or centre stage?

Internal medicine, in the UK as well as in the rest of Europe, is in a state of flux. The service has evolved so that the management of acute medical emergencies increasingly dominates the practice of internal medicine, with most outpatient work being dealt with by specialists. As a result, much of the activity of consultant physicians is focused on the delivery of care rather than on the training aspects of internal medicine. Nevertheless, all medical specialists in the UK do pass through a rigorous period of internal medicine during their early training, and there is now increasing emphasis on ensuring that these skills are maintained by practising physicians.

Journal Article↗
PubMed2001

Improving quality measures in the emergency services.

A large and continuing increase in medical emergency admissions has coincided with a reduction in hospital beds, putting the acute medical services under great pressure. Increasing specialization among physicians creates a conflict between the need to cover acute unselected medical emergencies and the pressure to offer specialist care. The shortage of trained nursing staff and changes in the training of junior doctors and the fall in their working hours contribute to the changing role of the consultant physician. The organization of the acute medical service is of paramount importance and requires multi-disciplinary teamwork on an admissions unit with full support services. Excellent bed management is essential. There must be guidelines for all the common medical emergencies and all units must undertake specific audits of the acute medical service. Continuing professional development (CPD) and continuing medical education (CME) should reflect the workload of the physician; that is, it must include time specifically focused on acute medicine and general (internal) medicine, as well as the specialty interest.

Emergency Service, Hospital↗
PubMed2000

What should we do? Papillary thyroid carcinoma in a lymph node but normal thyroid tissue--how should we proceed?

Papillary cell carcinoma of the thyroid is a relatively indolent disease, usually presenting as an asymptomatic mass in the thyroid gland that is either noted by the patient or diagnosed at routine clinical examination. Although the prognosis is generally good there are a number of controversies in the management of this condition. The significance of age at presentation, size of the tumour and the presence of lymph node metastasis are still disputed. We present the unusual case of a woman found to have papillary cell thyroid carcinoma within a lymph node during a cosmetic thyroid lobectomy. The thyroid tissue removed was not found to contain tumour. We describe the evidence behind the decision to proceed to total thyroidectomy and the finding of a tiny focus of papillary cell thyroid carcinoma within the contralateral lobe.

Adult↗
PubMed2000

Computer-assisted venous occlusion plethysmography in the diagnosis of acute deep venous thrombosis.

Suspicion of deep venous thrombosis (DVT) is a common reason for acute medical admission. The clinical diagnosis is difficult, and thus significant numbers are investigated and found to be normal. Provision of 24-h radiology is costly, and there may be a delay in investigation. We assessed computer-assisted venous occlusion plethysmography as a screening test for DVT, compared with standard radiology. The test has the advantage of being performed on the ward and if reliable would significantly reduce the number of radiological investigations required. We enrolled 215 consecutive patients presenting with the possible diagnosis of DVT, of whom 144 had technically adequate plethysmography results. Plethysmography had a sensitivity of 96% (95%CI 88-99%) and a negative predictive value of 97% (95%CI 91-99%). Patients excluded because of technically inadequate results were older (by a mean 7 years, p=0. 003). Computer-assisted venous occlusion plethysmography is a non-invasive method of rapidly screening for DVT which may be safely used as an initial screening test. The test is less useful in older patients, or patients unable to keep still for a period of 2 min.

Acute Disease↗
PubMed1999

Experience with transdermal testosterone replacement therapy for hypogonadal men.

BACKGROUND: None of the existing options for long-term testosterone replacement therapy (TRT) for hypogonadal men are ideal. Depot replacement at frequent intervals and implants are effective but invasive and inconvenient for the patient. Oral therapy results in poor hormone levels. Both are associated with undesirable metabolic changes. A transdermal formulation therefore represents a potential therapeutic advance for testosterone replacement. OBJECTIVE: To carry out a clinical audit of the acceptability and efficacy as a treatment for hypogonadism of the first transdermal testosterone therapy available in the UK (Andropatch, SmithKline Beecham) compared with existing androgen replacement options. PATIENTS AND MEASUREMENTS: Serum testosterone and questionnaire data on treatment efficacy, side-effects, therapy preference, sexual dysfunction and partner's attitudes to therapy were obtained from 50 hypogonadal men prescribed long-term testosterone replacement. RESULTS: Eighty per cent of the men returned analysable questionnaires. Eighty-four per cent experienced adverse effects with transdermal therapy, most commonly dermatological problems; 22% of the sample elected to continue with transdermal therapy, 72% returned to depot and 5% returned to oral therapy. The reservoir patches were judged to be too large, uncomfortable, visually obtrusive and noisy. Testosterone levels were comparable to those obtained with depot replacement with the added advantage of a more physiological pharmacokinetic profile. Men taking oral preparations were consistently under-replaced. CONCLUSIONS: Adverse events were substantially higher than reported from clinical trials but in keeping with the spectrum of yellow card reports received by the Committee on Safety of Medicines. The pharmacokinetic advantages are thus largely outweighed by low patient acceptability. In its present form transdermal therapy remains an expensive option for those who cannot tolerate depot testosterone replacement.

Administration, Cutaneous↗
PubMed1999

Secondary prevention of coronary heart disease in primary care: a healthy heart initiative.

We assessed the effectiveness of secondary prevention of coronary heart disease (CHD) in primary care, in a cross-sectional study of 1015 patients aged < 75 years with documented CHD. Patients records were examined for documentation of CHD risk factors; 722 patients then attended education sessions where blood pressure and cholesterol were measured, a supervised questionnaire detailing modifiable risk factors was completed, and advice on lifestyle modification was given. Management of risk factors was generally poor, and was worse in women. Approximately 20% of subjects remained hypertensive, with half of these receiving anti-hypertensive medication. Examining the primary care records, serum cholesterol was documented in 17.5% of men and 26.5% of women. Of the 722 subjects who had cholesterol measured, 30% of men and 25% of women had cholesterol < 5.2 mmol/l. Mean cholesterol was significantly higher in the women (6.1 mmol/l vs. 5.6 mmol/l, p = 0.001). Lifestyle risk management was also poor, with significant numbers smoking and drinking more than recommended. Women were more overweight than men (mean BMI 27.9 kg/m2 vs. 26.9 kg/m2, p = 0.006). Aspirin was being taken by 56% of patients.

Antihypertensive Agents↗
PubMed1999

The development of Graves' disease and the CTLA-4 gene on chromosome 2q33.

Case-control studies suggest that the CTLA-4 gene may be a susceptibility locus for Graves' disease. The previously reported A/G polymorphism at position 49 in exon 1 of the CTLA-4 gene was, therefore, investigated in a case-control (n = 743) and family-based (n = 179) dataset of white Caucasian subjects with Graves' disease. The relationship between CTLA-4 genotype and severity of thyroid dysfunction at diagnosis was also investigated. An increase in frequency of the G (alanine) allele was seen in Graves' patients compared with control subjects (42% vs. 31.5%, respectively; corrected P<0.0002; odds ratio = 1.58), and a significant difference in the distribution of GG, GA, and AA genotypes was observed between the groups (chi2 = 21.7; corrected P<0.00003). Increased transmission of the G allele was seen from heterozygous parents to affected offspring compared to unaffected offspring (chi2 = 5.7; P = 0.025). Circulating free T4 concentrations at diagnosis were significantly associated with CTLA-4 genotype (F = 3.26; P = 0.04). These results support the hypothesis that CTLA-4 may play a role in regulating self-tolerance by the immune system and in the pathogenesis of autoimmune disorders such as Graves' disease.

Abatacept↗
PubMed1998

Linkage disequilibrium between the human leukocyte antigen class II region of the major histocompatibility complex and Graves' disease: replication using a population case control and family-based study.

Early case control studies found association of the DRB1 allele, DR3, with Graves' disease (GD). Recent reports, claim the DQA1 allele, DQA1*0501, to be the primary susceptibility determinant within the human leukocyte antigen (HLA) class II region. We typed 228 GD patients, 364 controls, and 98 families (parents, GD, and unaffected sibling) at the DRB1, DQB1, and DQA1 loci. The case control study showed an increased frequency in GD, compared to controls, of DRB1*0304 (47% vs. 24%; pc < 1.4 x 10(-5)), DQB1*02 (58% vs. 46%; pc < 0.035), DQB1*0301/4 (42% vs. 28%; pc < 3.5 x 10(-3)) and DQA1*0501 (67%, vs. 39%; pc < 7 x 10(-6)). The DRB1*0304-DQB1*02-DQA1*0501 haplotype was increased in GD (47%) vs. controls (24%; pc < 1.8 x 10(-5); odds ratio = 2.72). No independent association of these alleles was observed. Preferential transmission of DRB1*0304-DQB1*02-DQA1*0501 from parents heterozygous for the haplotype to GD siblings (72%) was seen in the families (chi2 = 11.95; 1 d.f.; P = 0.0005). Lack of preferential transmission to unaffected siblings (53%; chi2 = 0.19; 1 d.f.; P = NS) excluded segregation distortion. These results show that linkage disequilibrium between GD and the HLA class II region is due to the extended haplotype DRB1*0304-DQB1*02-DQA1*0501.

Alleles↗
PubMed1998

Metronidazole sensitivity testing of Helicobacter pylori: the importance of media.

Successful triple-therapy treatment for Helicobacter pylori infection depends upon metronidazole (Mz) susceptibility, and many hospital laboratories routinely screen H. pylori isolates for Mz resistance using disc diffusion methods. We report the importance of culture medium when testing for metronidazole susceptibility. In this laboratory, Mz resistance in strains of H. pylori from patients in our area was found in approximately 80%. In other areas, Mz resistance is found in approximately 30%. This high rate of Mz resistance was not reflected clinically. Added haemin (X factor) and menadione in the culture medium drastically reduced zone size to Mz and also interfered with the minimal inhibitory concentration (MIC) as determined by Etest. When strains of H. pylori were re-tested on media which did not contain X factor or menadione, Mz resistance fell from 80% to 39%, a level similar to that seen in other areas.

Anti-Bacterial Agents↗
PubMed1997

Radiation-induced carcinogenesis: studies using human epithelial cell lines.

It has proved difficult to develop suitable models to study radiation-induced carcinogenesis by using human epithelial cells. However, immortalised human epithelial cell lines have proved useful. Unirradiated cells from the human keratinocyte cell line (HPV-G) and the human embryonic lung cell line (L132) were found to be tumourigenic in T-cell-deficient mice; thus, they are not suitable for transformation studies. Human urothelial cell lines (SV-HUC-1, NT11, BC16) and the human thyroid epithelial cell line (HTori-3) were nontumourigenic. The urothelial cell lines were refractory to radiation-induced carcinogenesis, and only one small tumour was observed in 57 mice that received irradiated cells. Whereas tumours were not produced following irradiation of these urothelial cells, changes in anchorage-independent growth were observed after a single dose of 8 Gy gamma-irradiation but not after 2 or 4 Gy. Irradiation of the human thyroid epithelial cell line (HTori-3) in vitro resulted in tumour formation. Passaging of the cells in vitro before injection did not seem to be critical. Some of the cell lines derived from the primary thyroid tumours exhibited p53 mutations in exons 5, 6, 7, and 8, as detected by single-stranded conformational polymorphism (SSCP) analysis. Thus, the human thyroid epithelial cell line (HTori-3) looks promising as a model for investigating the molecular events in radiation-induced carcinogenesis.

Animals↗
PubMed1996

Prolactinoma presenting in identical twins with multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type one (MEN 1) is characterized by tumours of the parathyroid glands, pancreatic islet cells and the anterior pituitary and follows an autosomal dominant pattern of inheritance. We report identical twins born to a family known to have the MEN 1 syndrome. The twins were identical until puberty. The first twin underwent puberty normally; the second, however, suffered an early pubertal arrest and was subsequently found to have a prolactinoma. Both were also subsequently shown to have primary hyperparathyroidism. Genetic studies have since confirmed the twins identical for the affected haplotype and show that this is inherited from the father who also has MEN 1. The gene for MEN 1 has now been localized to the long arm of chromosome 11. The current hypothesis is that expression of the syndrome involves two separate genetic mutations. The first mutation is inherited and thus present in all cells but the tumour manifests itself in the endocrine tissue only after a second mutation that represents elimination of the normal allele. In the case described the twins are proven genetically identical. The marked phenotypic difference between the two must, by inference, represent a second somatic mutation and is further supportive evidence of the two-mutation model of tumour expression.

Adolescent↗