Further evidence for a susceptibility locus on chromosome 20q13.11 in families with dominant transmission of Graves disease.
Explore the source record for details and available documents.
Chromosomes, Human, Pair 20↗
Biomedical subjects
W F Kelly
Publications and source records attributed to W F Kelly.
Treatment of immobilisation hypercalcaemia in acute intermittent porphyria: experience from three cases.
Explore the source record for details and available documents.
Acute Disease↗
Metastatic prolactinoma: effect of octreotide, cabergoline, carboplatin and etoposide; immunocytochemical analysis of proto-oncogene expression.
A 49-yr-old woman presented with an extensive prolactinoma (serum PRL > 10,000 mU/L, normal range < 450 mU/L). Over a 5-yr period following transsphenoidal surgery and pituitary irradiation, she became increasingly resistant to high doses of bromocriptine and underwent transfrontal surgery followed by stereotactic radiotherapy. In spite of these treatments, serum prolactin estimations rose progressively to > 100,000 mU/L. Magnetic resonance imaging scanning demonstrated a massive cystic tumor invading the temporal lobes, extending into the cervical and thoracic spine, with metastases to cervical lymph nodes. High-dose cabergoline administration resulted in a 30% decrease in serum PRL. Octreotide was administered as a continuous sc infusion with a profound analgesic effect on facial pain but with no effect on tumor progression. She was treated with a course of chemotherapy consisting of carboplatin and etoposide without any noticeable effect. The patient died 6 months following chemotherapy. Immunocytochemical analysis demonstrated positive nuclear staining for WAF-1, Rb protein, c-myc, and p53 both in the original and metastatic tumors. The metastases but not the primary tumor stained for c-jun. Metastatic prolactinoma remains a therapeutic challenge. It is associated with a variable proto-oncogene expression, which may be coincidental or causal. Cabergoline had no advantage over bromocriptine. Octreotide relieved facial pain but did not alter tumor progression. An effective therapy for metastatic prolactinoma remains to be identified.
Antineoplastic Agents, Hormonal↗
The relationships between cardiovascular risk factors and socio-economic status in people with diabetes.
The hypothesis that the prevalence of cardiovascular risk factors in people with diabetes is inversely related to socio-economic status was tested. Demographic and biochemical data were collected on 1246 patients, aged 20-69 years, attending a hospital diabetes clinic. This is estimated to represent between 71% and 78% of all people of this age with a diagnosis of diabetes in the health authority. In total, 296 people were classified as Type 1 (insulin-dependent) diabetic patients (age of onset < 31, now on insulin). Using data from the 1991 census a deprivation score was ascribed to each individual according to their area (enumeration district) of residence. The total study population was ranked by deprivation score and divided into quintiles. The relationships between means and quintiles of deprivation were assessed by ANOVA for linear trend, and between proportions and quintiles of deprivation by the chi-squared test for trend. In Type 1 diabetes increasing quintiles of deprivation were significantly related to mean serum cholesterol (p < 0.01) and proportion smoking (p < 0.01), and in Type 2 (non-insulin-dependent) diabetes to mean body mass index (p < 0.001), proportion smoking (p < 0.001), and proportion with proteinuria (p < 0.05). The need for health measures to prevent cardiovascular disease in people with diabetes is greatest in deprived areas.
Adult↗
An ovarian lipid cell tumour causing virilization and Cushing's syndrome.
We report a 73-year-old woman with rapidly developing symptoms and signs of Cushing's syndrome and high urinary free cortisol. She was virilized and hirsute with testosterone levels which became exceptionally high. ACTH was suppressed and CT scan of the adrenals and pelvis showed no abnormality. Ultrasound scanning showed enlargement of the left ovary. Venous catheter studies suggested a left ovarian source. A 2-cm diameter lipid cell tumor was removed from the left ovary laparoscopically. Histology was initially benign, and clinical and biochemical cure of Cushing's syndrome was rapid. However, the neoplastic nature of the ovarian tumour was demonstrated 12 months later when peritoneal metastases were detected and there was then clinical and biochemical relapse.
Aged↗
A prospective study of psychiatric and psychological aspects of Cushing's syndrome.
OBJECTIVE: Cushing's syndrome is associated with psychiatric and psychological disturbances. The aim of this study was to ascertain the extent of mental illness in patients before and after treatment for Cushing's syndrome. DESIGN AND PATIENTS: Patients with Cushing's syndrome were identified for a prospective study. Control patients were selected with pituitary adenomas secreting GH or PRL. The aim was to reassess patients after Cushing's syndrome had been treated. MEASUREMENTS: Psychiatric symptoms were measured and classified using the Present State Examination (PSE), and analysed on the Catego Programme. The Hamilton Rating Scale (HRS) was used to measure depression. The Crown-Crisp Experiential Index was used to measure common psychoneurotic symptoms (anxiety, phobia, obsession, somatic, depression and hysteria scales). The Eysenck Personality Inventory was used to assess extroversion and neuroticism. Cortisol, ACTH, and other hormones were measured by conventional methods. Parametric and non-parametric tests were used where appropriate. RESULTS: Catego analysis of psychiatric ratings showed only 8 patients of 43 with active Cushing's syndrome (19%) were normal. Psychiatric diagnoses were obtained as follows: neurotic depression in 20 (46%), possible neurotic depression in 1 (2%), reactive depression in 6 (14%), and non-specific neurotic symptoms in 8 (19%). Additional Catego ratings of suspected other psychoses were made for 3 patients who were also depressed. None of these 43 patients with active Cushing's syndrome had ratings of schizophrenia or mania, obsessional neurosis or pathological anxiety. In the control group 13 (87%) were normal, 1 patient with acromegaly had an anxiety state and one patient with a prolactinoma had neurotic depression. It was possible to reassess the Present State Examination after treatment in 25 patients, when cortisol levels had been substantially reduced (to normal in 88%), the percentage rated as psychiatrically normal increased from 19 to 68 (chi 2 = 11.7, 1 d.f., P < 0.01). Hamilton Rating Scale scores for depression showed significant improvements after treatment for Cushing's syndrome (mean decrease from 9.2 to 2.4, n = 36, P < 0.001). Crown-Crisp experiential index data showed significant improvements in anxiety, somatic symptoms, and depression (n = 25, P < 0.05). Eysenck Personality Inventory assessments showed a significant improvement in neuroticism score (n = 26 P = 0.016), but no significant change in extroversion (P = 0.5) or lie score (P = 0.6). CONCLUSIONS: Most patients with Cushing's syndrome had significant psychiatric pathology, usually depressive illness. As cortisol levels were returned to normal there were significant improvements in scores for depression and anxiety. Management of patients with Cushing's syndrome should include careful assessment of psychological and psychiatric illness.
Anxiety↗
Psychiatric aspects of Cushing's syndrome.
Patients with Cushing's syndrome were studied (n = 209, 78% females). Control patients had pituitary adenomas secreting growth hormone or prolactin. Age at diagnosis of Cushing's syndrome was 8-74 (mean 39) years. Duration of symptoms was 0.2-9 (median 2.0) years. Adverse life events within the 2 years preceding the onset of Cushing's syndrome were not significantly commoner than in controls. Depressive illnesses were associated with the presence of adverse life events (p < 0.001). Depressive illness was more common in females (p < 0.01). There were no significant differences in the severity of depression in the different types of Cushing's syndrome. Pathological anxiety had been diagnosed in 26 patients (12%), mania or hypomania in six patients (3%) and confusion in three patients (1%). Psychotic illness had been diagnosed in 16 patients (8%) and was more common in adrenal carcinomas (p < 0.01). Significant psychiatric illness, usually depressive, preceded the onset of all symptoms and signs of Cushing's syndrome in 25 patients (12%); 23 of these developed pituitary Cushing's disease, and two adrenal adenomas. When Cushing's syndrome was diagnosed, significant psychiatric illness, usually depression, was present or had been a feature of Cushing's syndrome in 120 (57%) patients.
Adenoma↗
Cytologic diagnosis of anal intraepithelial neoplasia using smears and cytyc thin-preps.
To investigate the optimal cytologic method for detecting anal intraepithelial neoplasia, the quality and diagnostic findings in 117 conventionally prepared smears and 191 CYTYC Thin-Preps were compared. Samples were obtained with a dacron swab from subjects participating in a longitudinal study of gay or bisexual men known as the Study to Help the AIDS Research Effort (SHARE). The smear takers were general clinicians who had no experience in obtaining cytologic specimens from the anus. Smears were entirely satisfactory in 48 (41.0%) subjects, limited for interpretation in 41 (35.0%), and unsatisfactory in 28 (23.9%). CYTYC preparations were satisfactory in 158 (82.7%) cases and unsatisfactory in 33 (17.3%). Insufficient cellularity was the most frequent reason for both unsatisfactory smears and CYTYC preparations, but air drying artifact was present in nearly every smear. Squamous intraepithelial lesions (SILs) were detected in four (4.5%) smears compared to 53 (33.6%) CYTYC slides. The detection of SIL correlated with the presence of glandular and metaplastic cells in CYTYC preparations, but this association disappeared if only satisfactory specimens were considered. In conclusion, CYTYC Thin-Preps were satisfactory twice as often as conventional smears (P < 0.005) and detected nearly eight times as many SILs (P < 0.005).
Anus Neoplasms↗
Gs alpha and Gi2 alpha mutations in clinically non-functioning pituitary tumours.
BACKGROUND AND OBJECTIVE: Activating mutations of Gs alpha (gsp) and Gi2 alpha (gip) have been described in various endocrine neoplastic conditions. The objective of this study was to assess the prevalence of gsp and gip mutations in clinically non-functioning pituitary tumours (NFTs) and to compare the clinical phenotypic characteristics of tumours bearing G protein gene mutations with wild-type tumours. DESIGN: Twenty-two NFTs and 20 normal anterior pituitary glands screened for G protein gene mutations. PATIENTS: Twenty-two patients; 14 female (median age 59 years, range 19-76) and 8 males (median age 66.5 years, range 50-77). MEASUREMENTS: Site-directed hybridization or direct sequencing of polymerase chain reaction amplified Gs alpha and Gi2 alpha DNA. RESULTS: G protein gene mutations were identified in 3/22 (13%) of NFTs. Two tumours demonstrated gsp mutations, one at codon 201 arginine to cysteine, and the second at codon 227 glutamine to arginine. Three tumours demonstrated gip mutations at codon 205 glutamine to arginine. Two tumours with gsp mutations also harboured gip mutations. All tumours with G protein gene mutations demonstrated local bone infiltration into the surrounding structures. CONCLUSIONS: G protein gene mutations have been demonstrated in a proportion of non-functioning pituitary tumours. The presence of dual gsp and gip mutations in two tumours suggests the possibility of multiple hits in a stepwise pathogenesis of pituitary neoplasia.
Adenoma↗
Geographical mapping of diabetic patients from the deprived inner city shows less insulin therapy and more hyperglycaemia.
To determine whether or not economic and social deprivation were associated with different diabetic treatment and metabolic control, data of patients from deprived inner city wards and prosperous wards were compared. A database was obtained for 1528 patients attending our hospital Diabetes Care Centre. Demographic data and postcodes were used to construct geographical maps of disease and deprivation. Blood glucose and glycated haemoglobin were measured. Inner city patients were less likely to be taking insulin, but if they were, they were more likely to have higher blood glucose values (p = 0.02) and higher glycated haemoglobin values (p = 0.02), compared to patients from prosperous wards. Insulin-treated patients from socially and economically deprived wards had worse diabetic control than patients from more prosperous wards. The study emphasizes the needs to target deprived patients for education and motivation to understand diabetes, and to optimize metabolic control.
Adult↗
Influence of social deprivation on illness in diabetic patients.
Explore the source record for details and available documents.
Adolescent↗
The role of palatability in the food intake response of rats fed high-protein diets.
Male albino rats, trained to eat over a 3-h period, reduced their food intake from 0.38 +/- 0.04 g of a low-protein diet to 0.14 +/- 0.03 g of a high-protein diet, within 1 min following diet presentation. Since this occurred before the metabolic effects of a high-protein diet should be seen, we suggest that, although neophobia could play a role, poor initial palatability may be a significant factor in this early depression in food intake. To differentiate initial palatability from responses to metabolic feedback, we designed a feeding paradigm using positive or negative taste cues and a 6-h feeding period. Pre-treatment with a 6% casein diet containing 0.15% quinine HCl resulted in near equal consumption of a 75% casein and a 6% casein unadulterated diet during the first 30 min after introduction of the diets. Later, the rate of consumption of the high-protein diet was lower than of the lower-protein diet, likely the result of post-absorptive factors. We suggest that prevention of the early reduction in food intake due to initial palatability may facilitate study of post-absorptive response(s) to high-protein diets.
Animals↗
Necrobiosis lipoidica diabeticorum: association with background retinopathy, smoking, and proteinuria. A case controlled study.
In order to evaluate patients with necrobiosis lipoidica diabeticorum and to compare them with age, sex, and duration of diabetes matched controls, 15 patients with necrobiosis were each matched with 5 control subjects with diabetes mellitus. Complications of diabetes, glycaemic control, and proteinuria were measured. Patients with necrobiosis (mean age 40, range 18-74 years) had a mean duration of diabetes of 14 (range 3-36) years; 8 patients were male, and 7 were female. For necrobiosis versus controls, background retinopathy (67% vs 27%, p = 0.009), proteinuria (53% vs 17%, p = 0.006), and smoking (60% vs 20%, p = 0.003) were all more common with necrobiosis. There were no significant differences between patients with necrobiosis and control patients in the prevalence of vascular disease and neuropathy. Glycosylated haemoglobin concentrations were higher in patients with necrobiosis (p = 0.02). Blood pressure measurements were similar in both groups. We conclude that smoking, proteinuria, and retinopathy were more prevalent in diabetic patients with necrobiosis; the skin lesion may therefore share common aetiological factors which affect the microvascular circulation, leading to damage to basement membranes and vascular endothelial cells.
Adult↗
Evaluation of four commercially available enzyme immunoassays for laboratory diagnosis of Clostridium difficile-associated diseases.
Four commercial enzyme immunoassays (EIAs) for the detection of Clostridium difficile toxin A have recently been developed and marketed (Premier, Meridian Diagnostics, Cincinnati, Ohio; VIDAS, bioMerierux Vitek, Inc., Hazelwood, Mo.; Tox-A-Test, TechLab, Blacksburg, Va.; and Bartels, Baxter Diagnostics, McGaw Park, Ill.). The performances of these EIAs were compared with those of the tissue culture cytotoxicity assay and a definition of C. difficile-associated disease based on both laboratory and clinical criteria for 329 clinical specimens. Two EIAs (Premier and VIDAS) showed good overall agreement (96 and 95%, respectively) with the cytotoxicity assay. However, they were less sensitive (84 and 71%, respectively) than the Bartels (94%) or Tox-A-Test (93%) EIAs. The Bartels and Tox-A-Test assays were much less specific, resulting in poor positive predictive values (56%) of the two assays when compared with that of the cytotoxicity assay. Tox-A-Test had the added drawback of having a significant number of indeterminate results (6.4%). These data indicate that the four EIAs all have specific shortcomings. When using these EIAs, testing strategies that take these shortcomings into consideration should be developed.
Adult↗
The use of a commercially available enzyme immunoassay for the detection of Clostridium difficile toxin A.
A commercially available enzyme immunoassay (EIA) for the detection of Clostridium difficile toxin A (Premier Toxin A EIA, Meridian Diagnostics, Cincinnati, Ohio) was compared with tissue culture cytotoxicity assay, enterotoxigenic culture, and latex agglutination test for the laboratory diagnosis of C difficile-associated disease. When evaluated for detection of C difficile-associated disease using clinical specimens, EIA was the most sensitive (83.1%) and tissue culture cytotoxicity assay was the most specific test with EIA, tissue culture cytotoxicity assay and enterotoxigenic culture having similar correlation values (96.6, 96.1, 94.0%, respectively). The latex agglutination test was not as accurate (89.7% correlation) as the other three tests due mainly to its poor sensitivity (47.9%). The EIA is a rapid, easy-to-use alternative to tissue culture cytotoxicity assay for detection of C difficile-associated disease.
Bacterial Toxins↗
Evaluation of the latex agglutination test for detection of Clostridium difficile.
We compared two Clostridium difficile latex agglutination tests, Meritec from Meridian Diagnostic (Cincinnati, Ohio) and CDT from Becton-Dickinson (Cockeysville, Md), on 289 specimens submitted for tissue culture cytotoxicity using MRC-5 cells. When compared with CDT, the Meritec latex agglutination test had a sensitivity of 90% (26/29), a specificity of 97% (251/260), and a correlation of 96%. Meritec was compared with tissue culture cytotoxicity on 357 specimens. Meritec had a sensitivity of 77% (30/39), a specificity of 93% (298/318), and a correlation of 92%. Clinical review of 10 Meritec +/- tissue culture cytotoxicity minus patients revealed one likely, two probable, and seven doubtful cases of C difficile disease. In contrast, review of 10 Meritec +/- tissue culture cytotoxicity plus patients showed seven likely and three probable cases of C difficile disease. The Meritec is comparable with the CDT latex agglutination test, but is not nearly as sensitive as either tissue culture assay or culture for detection of C difficile disease. A positive latex agglutination test should be confirmed by a tissue culture cytotoxicity assay.
Clostridioides difficile↗
Effect of graded doses of tri-iodothyronine on ventricular myosin ATPase activity and isomyosin profile in young and old rats.
Ventricular myosin ATPase activity, V1 isomyosin content and serum T3 (tri-iodothyronine) values decrease with age in male Fischer 344 rats. To determine if the age decrement in ATPase activity and V1 isomyosin content are caused by decreased T3 levels or an age-related decrease in V1 isomyosin induction by T3, 3-, 12- and 24-month-old male Fischer 344 rats were given constant T3 infusions by osmotic minipump. Rats at all ages were given 0.75, 5 and 15 micrograms(/100 g per 24 h) doses of T3, whereas 12- and 24-month-old rats were given an additional 0.4 microgram dose. In control rats, T3 levels decreased from 97 +/- 2.7 at 3 months to 75 +/- 4.7 ng/100 ml at 24 months. Likewise, Ca2+-activated myosin ATPase activity decreased from 1.04 +/- 0.05 to 0.68 +/- 0.05 mumol of Pi/min per mg of protein, and the relative proportion of V1 of isomyosin decreased from 90 +/- 4.0 to 26 +/- 2.0%. The lowest (0.4 microgram) T3 dose, which was sufficient to restore T3 levels in 24-month-old animals to 3-month control values, abolished the age decrement in myosin ATPase activity and markedly increased the proportion of V1 isomyosin present in the ventricle. These findings indicate that the senescent ventricle responds readily to small doses of T3 and strongly suggest that the age decrement in serum T3 levels is sufficient to contribute to the age-related decrease in myosin ATPase activity and V1 isomyosin content. Since these parameters correlate with ventricular contractility, the age decrement in T3 levels may also contribute to the decreased ventricular contractility and cardiac output observed in senescent rats.
Adenosine Triphosphatases↗
Familial diabetes mellitus with variable B cell reserve; analysis of a pedigree.
Some patients do not fall neatly into the categories of Type 1 (insulin-dependent), Type 2 (non-insulin-dependent) or maturity onset diabetes of young people diabetes. The pedigree and characteristics of the family reported here illustrate this problem. Nine cases of diabetes are known in 4 out of 5 generations, with onset between 17-70 years. Treatment was with insulin in 5 (onset 17-29 years), tablets in 3 (onset 32-70 years), and in one diabetes occurred before the insulin era. Plasma C-peptide was 0.04-0.52 nmol/l (fasting) and 0.35-1.33 nmol/l (peak stimulation with glucagon). HLA typing, available in 7 diabetic patients showed DR2 or DR7 in all, DR4 in 2 and DR3 in none. Pancreatic islet cell antibodies were absent at diagnosis in the most recently diagnosed patient. Diabetic complications remain absent in two insulin-treated patients (duration 28 and 24 years), but have occurred extensively in the remainder. The form of diabetes in this family is therefore characterised by (a) strong family history (possible autosomal dominant with variable penetrance), (b) widely variable age of onset, (c) a variable degree of B cell reserve (d) no association with HLA DR3/4 and the presence of DR2 or DR7 and (e) no protection from complications.
Adult↗