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Biomedical subjects

P H Davies

Publications and source records attributed to P H Davies.

At least 19 recordsLinked to original sources
PubMed2000

A useful form of glue ear.

Children and adults commonly present to the emergency department with a foreign body lodged in the ear. Over the past 15 years techniques for cyanoacrylate ("superglue") assisted foreign body removal have been described, but are not widely employed. Two cases of successful and one of unsuccessful removal using this technique are reported, and some advice is offered to aid others.

Adolescent↗
PubMed1999

Laboratory-based calculation of coronary heart disease risk in a hospital diabetic clinic.

AIMS: To develop an estimation of risk of coronary heart disease (CHD) based on the Framingham equation for use in a diabetes clinic, given concerns about the accuracy of the Sheffield risk tables in this setting. METHODS: A computer program using the Framingham equation based on patients' age, sex, systolic blood pressure, smoking history, presence of diabetes and left ventricular hypertrophy was applied to requests for lipid screening of patients attending the diabetes clinics of Birmingham Heartlands Hospital. The calculated risks for the population were compared with those estimated from the Sheffield tables. RESULTS: Of 1060 patients with diabetes mellitus, 215 (20%) had an annual CHD risk > or =3%, which is considered to be the threshold at which lipid-lowering drugs are cost-effective. Only 24 of these 215 patients (11%) were correctly identified by the Sheffield tables, which we conclude have an unacceptably low sensitivity in diabetes mellitus. CONCLUSIONS: A laboratory-based CHD risk calculation system is a practical alternative to the Sheffield system and may have a greater sensitivity in the diabetic clinic.

Adult↗
PubMed1999

Drug-related erectile dysfunction.

Erectile dysfunction is a highly prevalent medical problem affecting a significant proportion of men. It is important for a number of reasons, causing impairment of quality of life and, if related to drug therapy, leading to non-compliance. Drug therapy accounts for erectile dysfunction in approximately 25% of cases and is mostly readily reversible when the offending agent is stopped, or a suitable alternative is substituted. Many classes of drug may be responsible, interfering with the normal physiological processes leading to penile erection in a dose-related fashion, and in ways which can usually be predicted from their pharmacology. The most commonly implicated classes of drug include antihypertensives such as thiazide diuretics and beta-adrenoceptor antagonists and psychotherapeutic drugs, especially selective serotonin reuptake inhibitor (SSRI) antidepressants. We review the agents which can cause erectile dysfunction, the evidence for this adverse effect and the physiological mechanisms involved. We present an approach to the management of the patient with erectile dysfunction in whom concomitant drug therapy may be responsible. We recommend that drug therapy should always be considered as a possible cause of erectile dysfunction before specific investigation and therapy is considered.

Adrenergic beta-Antagonists↗
PubMed1998

Long-term therapy with long-acting octreotide (Sandostatin-LAR) for the management of acromegaly.

OBJECTIVES: To evaluate the efficacy and safety of a long-acting preparation of the somatostatin analogue octreotide, Sandostatin-LAR (SMS-LAR) for the treatment of acromegaly. DESIGN AND PATIENTS: Thirteen patients with acromegaly received intramuscular injections of SMS-LAR 20-40 mg at 4-6 week intervals for a period of up to 3 years. MEASUREMENTS: Serial measurement of serum GH and IGF concentrations were obtained. Symptoms related to acromegaly were scored by patients at baseline and following each injection. Serial gallbladder ultrasound and pituitary imaging was performed throughout the study. RESULTS: One patient was withdrawn from the study after 6 months because of continued gastrointestinal side effects; 4 patients were treated with monthly injections for 12 months and 8 patients with injections at either 1 month or 6-week intervals for 36 months; hence data is presented for n = 12 for up to 12 months; and thereafter n = 8. SMS-LAR significantly reduced serum GH and IGF-1 values: for the whole group GH concentrations fell from 24.8 +/- 4.2 mU/l (mean +/- SE) at baseline to 5.2 +/- 0.8 mU/l at 12 months (P < 0.01, n = 12). In the 8 patients treated for 3 years GH fell from 27.8 +/- 6.1 mU/l at baseline to 4.2 +/- 0.8 mU/l at the end of 3 years (P < 0.01, n = 8). GH fell to < 10 mU/l in all subjects and was < 5 mU/l in 50% after both 1 and 3 years. IGF-1 concentrations fell from 95 +/- 13 nmol/l at baseline to 63 +/- 13 nmol/l after 1 year (P < 0.01, n = 12; reference range < 65 nmol/l). In the 8 patients treated for 3 years IGF-1 concentrations fell from 119 +/- 14 nmol/l at baseline to 60 +/- 13 nmol/l after 3 years (P < 0.001, n = 8). IGF-1 was < 65 nmol/l in 60% of patients after 1 year and 75% after 3 years. Treatment resulted in trends towards improvement in symptoms of acromegaly and statistically significant improvement in sweating. There was no evidence of tachyphylaxis or evidence to suggest development of glucose intolerance. Only 2 patients (15%) developed gallbladder sludge which was asymptomatic; no patient developed gallstones. CONCLUSIONS: We conclude that SMS-LAR is a safe, effective and well tolerated treatment, making it an important therapeutic option in the management of acromegaly.

Acromegaly↗
PubMed1997

Inflammatory cytokines and type I 5'-deiodinase expression in phi1 rat liver cells.

Administration of tumour necrosis factor-alpha (TNF alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) to animals and humans results in changes in circulating thyroid hormone concentrations similar to those seen in non-thyroidal illness (NTI). Inflammatory cytokines have been postulated as mediators of the euthyroid sick syndrome by inhibiting type 1 5'-deiodinase (5'D-I) enzyme activity. We have investigated direct effects of cytokines upon 5'D-I expression, measuring changes in 5'D-I enzyme activity and mRNA in phi1 rat liver cells. All three cytokines stimulated 5'D-I enzyme activity: TNF alpha 326 +/- 43% (100% in controls, mean + S.E.M., n = 9, P < 0.01 by ANOVA), IL-1beta 297 +/- 8% and IL-6 272 +/- 25%. Co-incubation with cycloheximide abolished stimulation by each cytokine. Kinetic analysis revealed that stimulation of 5'D-I enzyme activity was a result of significantly increased Vmax, (P < 0.01 by ANOVA) with Km relatively unchanged. 5'D-I mRNA abundance was not significantly changed following treatment by any of the three cytokines. These findings do not support the hypothesis that inflammatory cytokines may mediate the euthyroid sick syndrome by causing inhibition of 5'D-I activity.

Animals↗
PubMed1996

Relation between serum interleukin-6 and thyroid hormone concentrations in 270 hospital in-patients with non-thyroidal illness.

OBJECTIVES: Non-thyroidal illness (NTI) is frequently accompanied by alterations in circulating thyroid hormone concentrations, despite patients remaining clinically euthyroid. The mechanisms accounting for these changes in circulating thyroid hormone concentrations remain unknown. Much attention has focussed on the role of inflammatory cytokines which are known to be important mediators of disease. The aim of this study was to investigate the role of the cytokine interleukin-6 (IL-6) in alterations of thyroid hormone metabolism seen in NTI. DESIGN: Longitudinal study of hospital in-patients, correlating serum IL-6 concentrations with circulating thyroid hormone concentrations. PATIENTS: Two hundred and seventy in-patients recruited consecutively, excluding those with known or suspected thyroid disorder. The patients were divided into 5 subgroups reflecting the nature of their NTI and comprised 41 patients with liver disease, 99 with renal disease, 19 intensive care (ITU) patients, 22 with cardiac disease and 89 patients with general medical, or surgical conditions. MEASUREMENTS: Serum IL-6 concentrations were determined using a commercially obtained immunoassay (IL-6 Quantikine assay, R&D Systems, Abingdon, UK). Serum total T4 and total T3 were measured using chemiluminescent immunometric assays (Kodak Clinical Diagnostics Ltd, Amersham, UK) and serum TSH was measured using a third-generation chemiluminescent immunometric assay (Amerlite TSH 30, Kodak Clinical Diagnostics Ltd, Amersham, UK). RESULTS: Ninety-three patients studied (35%) had a serum T3 below the normal range (<1.0 nmol/l), 89 patients (33%) had a serum T4 below the normal range (<65 nmol/l) and in 58 patients (21%) both serum T3 and T4 were below the normal range. There was a significant negative correlation between serum total T3 and IL-6 (r = -0.219; P < 0.001) and total T4 and IL-6 (r = -0.32; P = 0.32), but not between TSH and IL-6 (r = -0.075; P = 0.22). The ITU patient subgroup had the highest IL-6 concentrations (229.3 +/- 48.1 ng/l, mean +/- standard error), whilst also having the lowest T3 (0.93 +/- 0.08 nmol/l), TSH (0.79 +/- 0.25 mU/l) and T4 concentrations (66.6 +/- 7.3 nmol/l). The subgroup of patients under general medical or surgical care had least disturbance of their T3 (low in 19%) and T4 (low in 8%) concentrations, whilst also having the lowest mean IL-6 concentration (39.0 +/- 5.3 ng/l). The renal patient subgroup, whilst including a high proportion of patients with low T3 (39%) and T4 (45%) concentration, demonstrated only modest elevation of IL-6 concentrations (mean 41.4 +/- 8.5 ng/l). CONCLUSIONS: Our data revealed a statistical relation between elevated serum IL-6 concentrations and alterations in circulating thyroid hormone concentrations seen in NTI; however, the findings in patients with renal disease suggest that circulating IL-6 is not the only factor responsible for alteration in thyroid hormone metabolism in NTI.

Euthyroid Sick Syndromes↗
PubMed1996

Regulation of type I 5'-deiodinase by thyroid hormone and dexamethasone in rat liver and kidney cells.

Type I 5'-deiodinase (5'D-I) is crucial for the generation of circulating 3,5,3'-triiodothyronine (T3) and so is a major determinant of thyroid hormone action. Liver and kidney 5'D-I activity is reduced in nonthyroidal illness (NTI), but the exact cause of reduced 5'D-I activity remains unknown. Elevated circulating glucocorticoid hormone concentrations are one factor postulated to play a role. We have studied regulation of 5'D-I expression in cultured rat liver (phi 1) and kidney (NRK-52E) cells in response to treatment with T3 and the glucocorticoid dexamethasone. 5'D-I mRNA was measured by Northern hybridization and 5'D-I activity was measured in a sub-strate conversion assay. Expression of the sodium pump alpha 1-subunit (Na+/K(+)-ATPase alpha 1-subunit) mRNA was measured as an index of T3 and dexamethasone effects. In ø1 liver cells, T3 increased 5'D-I mRNA by 76 +/- 17% and 5'D-I activity by 101 +/- 30% (all results mean +/- SEM; n = 9). Dexamethasone increased 5'D-I mRNA by 55 +/- 16% and 5'D-I activity by 128 +/- 6%. In NRK-52E rat kidney cells, 5'D-I mRNA increased by 87 +/- 15% with T3 treatment and by 76 +/- 14% with dexamethasone. 5'D-I activity in NRK-52E cells was measurable only after stimulation by combined T3 and dexamethasone treatment. Na+/K(+)-ATPase alpha 1-subunit mRNA expression was stimulated following T3 and dexamethasone treatment in both cell lines. These results provide evidence for direct pretranslational regulation of 5'D-I by T3 and dexamethasone in both rat liver and kidney cells. Our findings do not support the hypothesis that glucocorticoids are directly responsible for inhibition of 5'D-I enzyme activity in NTI.

Animals↗
PubMed1992

The significance of TSH values measured in a sensitive assay in the follow-up of hyperthyroid patients treated with radioiodine.

Use of sensitive assays for TSH in the follow-up of patients treated with radioiodine (131I) for thyrotoxicosis has led to questions regarding the significance of abnormal TSH values found in association with normal circulating thyroid hormone levels, especially TSH results below normal. We have investigated the relationship between serum TSH and the likelihood of maintenance of euthyroidism, as well as the relationship between serum TSH and free T4, in 389 subjects treated with 131I 2-35 years previously who had free T4 and free T3 values within the normal range and who were not receiving thyroxine or antithyroid therapy. In those with undetectable TSH (less than 0.05 mU/L), TSH remained undetectable in 54.5% at 1 yr but rose to detectable or normal values in the remainder. In those with low but measurable TSH (0.05-0.5 mU/L), results were similar at 1 yr in 47.5% and returned to normal in 45%. No patient with a TSH value below normal became hypothyroid (defined as a reduction in serum free T4). In those with normal TSH (0.5-5.0 mU/L) at time 0, TSH remained normal in 83%, fell in 4% and became elevated in 13%. The yr 1 incidence of hypothyroidism was 1%; one patient became thyrotoxic. In those with TSH values above normal (5.0-15.0 mU/L), TSH remained elevated in 90.6%; the incidence of hypothyroidism was 14.5% in yr 1. The small risk of development of hypothyroidism in those with subnormal or normal TSH indicates that biochemical testing is not essential for 1-2 yr in such patients; this contrasts with a need for repeat testing within a period not exceeding 1 yr in those with elevated TSH. The relationship between serum-free T4 and TSH suggests that TSH results outside the normal range reflect thyroid hormone excess or deficiency. Persistence of undetectable TSH values during follow-up and the observation of higher free T4 at time 0 in those whose TSH remained undetectable compared with those whose TSH rose suggest that undetectable TSH concentrations are of greater significance than low but detectable values.

Adult↗
PubMed1991

The effects of drugs on tests of thyroid function.

Many drugs affect tests of thyroid function through alterations in the synthesis, transport and metabolism of thyroid hormones, as well as via influences on thyrotrophin (TSH) synthesis and secretion. Despite effects on circulating thyroid hormone and TSH levels, few drugs result in important changes in clinical thyroid state, but difficulty in interpretation of thyroid function tests often results. Commonly prescribed drugs including anti-convulsants, non-steroidal anti-inflammatory drugs, beta-adrenoceptor antagonists, steroid hormones and heparin may result in abnormal thyroid function tests in the absence of clinical features of thyroid dysfunction. In contrast, lithium and iodine containing drugs, including radiographic contrast agents and amiodarone, may result rarely in overt thyroid disease.

Adrenal Cortex Hormones↗
PubMed1984

Intestinal cathepsin B and D activities of suckling rats.

Cathepsin B and D activities were assayed in homogenates of the mucosa of the proximal, middle, and distal sections of the small intestine of suckling rats of various ages and of adult rats. Cathepsin B activity was determined using N-benzoyl-L-phenylalanyl-L-valyl-L-arginine-p-nitroanilide as substrate in the presence of trypsin inhibitor (pH optimum: 5.0-5.5). Cathepsin D activity was determined by measuring the pepstatin A sensitive action on denatured haemoglobin (pH optimum: 3.0-3.5). In the distal intestine, the activities of both cathepsins increased 6- to 10-fold during the first 2 weeks post partum and then sharply declined to the low values seen in adult rats, but in the proximal intestine the activities were low throughout the suckling period. In vitro digestion of casein by ileal mucosa of 8-day-old rats was almost completely inhibited by the combined actions of leupeptin and pepstatin A. The results show that cathepsin B- and D-like proteinases could play an important role in the digestion of milk proteins by suckling rats.

Aging↗