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Biomedical subjects

R Hall

Publications and source records attributed to R Hall.

At least 343 records · Page 19Linked to original sources

Transduodenal sphincteroplasty: an analysis of 118 consecutive cases.

The results of 118 consecutive common bile duct explorations via transduodenal sphincteroplasty are presented and analysed. The operations were performed for suspected choledocholithiasis by one surgeon over a 10-year period. Choledocholithiasis was proved in 22 per cent of the cholecystectomies carried out during this period and tended to present significantly earlier in females, 14.5 per cent presenting before 35 years of age. One hundred and four survivors were traced and 93.5 per cent had achieved a good result at a mean 5-year follow-up.

Adult↗

Detection of surgical lesions of the small bowel by enteroclysis.

Enteroclysis is an examination in which barium is infused directly into the small intestine, and compression radiographs are taken on each segment. This method eliminates many of the inherent limitations of the conventional small bowel follow-through examination. This report concerns 45 patients with 48 small bowel lesions. They were missed on the conventional examination but detected within 3 months by subsequent enteroclysis and confirmed surgically. There were 15 patients with Meckel's diverticula, 7 with obstructive adhesive bands, 5 with Crohn's disease, 5 with blind pouch syndrome (1 with a leiomyoma inside the blind pouch), 2 with other leiomyomas, 3 with metastatic carcinoma, two with primary carcinoma 3 with radiation stricture, two with sinus tract lesions and fistulas, and 1 with another lesion. Improved intubation techniques and better barium mixtures make enteroclysis possible in most hospitals. As surgeons appreciate the value of enteroclysis, they can request this examination for appropriate patients to sooner find many surgical lesions of the small bowel which frequently go undiagnosed.

Adult↗

Characterisation and translation studies of messenger RNA from the human malaria parasite Plasmodium falciparum and construction of a cDNA library.

RNA was isolated from trophozoites, schizonts and mixed populations of Plasmodium falciparum. 5% of the total was poly(A+) message, of average length 1.2 kb (10-12 kb maximum) and a poly(A) content of 10%. The mRNA fractions could be translated in vitro by reticulocyte lysates supplemented either with exogenous or P. falciparum tRNA. The patterns from two independent isolates, one cloned (T9-94) and one uncloned (K1) were virtually identical. Major translation products from 16-230 kDa have been measured. The most abundant is lactate dehydrogenase (34.8 kDa). Trophozoite mRNA codes principally for proteins of less than or equal to 93 kDa, while schizont mRNA codes for additional proteins of higher molecular mass. There are marked similarities between the in vitro translation products and proteins synthesised in vivo in synchronous cultures. A number of schizont mRNA translation products (principally those of 230, 203, 185, 170, 115, 101 and 71 kDa) are specifically precipitated without post-translational modification by sera from humans exposed to malaria. A cDNA library has been constructed in phage lambda from total poly(A+) RNA and partially characterised. About 10% of the clones derive from abundant mRNA sequences. Putative actin clones have been isolated from this library and the parasite actin mRNA sized at approx. 2.8 kb.

Actins↗

Processing, polymorphism, and biological significance of P190, a major surface antigen of the erythrocytic forms of Plasmodium falciparum.

A detailed analysis of P190, a major surface associated protein of Plasmodium falciparum erythrocytic stages has been undertaken. We have demonstrated that this protein is recognised by two monoclonal antibodies, one of which recognises a constant feature (2.2) and one a variable feature (7.3). Cell free protein synthesis demonstrates that the variable 7.3 epitope is encoded in the structural gene for P190. The 7.3 epitope is only present on late trophozoites and schizonts whilst the 2.2 epitope is present on all erythrocytic stages. Labelling of synchronised cultures demonstrates that P190 is made only from 30 h onwards, (i.e. by trophozoites and schizonts). By pulse chase analysis we show that P190 undergoes processing and is lost at release/re-invasion, correlating with a lack of 7.3 immunofluorescence reactivity on rings. Sera from Nigeria recognise P190 from a Thai isolate of malaria. They also react with purified P190 in a micro-ELISA assay. A model for the role of P190 in re-invasion is presented, and the possible clinical significance of this protein is discussed.

Animals↗

Rat anterior pituitary cells maintained on artificial capillaries: responses of thyrotrophs and lactotrophs to depolarization, TRH and dopamine.

Rat anterior pituitary cells have been maintained over an 18-day period in a perfusion system designed around artificial capillaries. Using novel methodology the cells have been visualized by light microscopy and appear as aggregates, closely attached to and sometimes stretching around the capillaries. Their morphology is consistent with previous histology at the level of light microscopy. The techniques described are compatible with immunohistochemistry and electron microscopy. The functional integrity of thyrotrophs and lactotrophs maintained in the system has been examined by measuring the dynamics of TSH and PRL secretion in response to depolarization, TRH and dopamine (DA). TSH and PRL were significantly and reproducibly released by TRH over a 7-day period. On each day the release was dose-dependent with a threshold of at least 28 pg. Qualitatively the responses were rapid in onset (within minutes) for both hormones. Similar responses were measured in response to high K+ depolarization. Basal secretion of TSH and PRL was rapidly and significantly inhibited by DA in a dose-dependent manner (ED50 20 +/- 25 nM for TSH and 70 +/- 40 nM for PRL). Inhibition was dependent on the continued presence of DA and could be mimicked by bromocriptine and stereospecifically prevented by the active but not the inactive isomer of the DA receptor antagonist butaclamol. Simultaneous administration of 10(-6) M DA with 10(-8) M TRH prevented the release of TSH and PRL. The effect of DA was transient, subsequent TRH responses being qualitatively and quantitatively normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Salivary cortisol levels in true and apparent hypercortisolism.

Total plasma cortisol measurements may be misleading when there are variations in the plasma cortisol-binding protein capacity resulting from drugs, pregnancy or congenital alterations in cortisol-binding globulin (CBG). Salivary cortisol levels, which represent the free component of plasma cortisol, are less affected by alterations in protein binding and have been used in the investigation of hypothalamic-pituitary-adrenal disorders. This study compares these two indices of adrenal function in conditions of true hypercortisolism and spurious hypercortisolism (resulting from oral contraceptive medication or pregnancy). The circadian variation of cortisol in plasma and saliva was studied in six patients with unequivocal hypercortisolism and compared with normal volunteers. In the normal group, plasma and salivary cortisol levels taken at 0900 h were significantly higher than those taken at 2400 h. Patients with Cushing's syndrome failed to show a significant difference between plasma and salivary cortisol levels collected at 0900 and 2400 h. Five patients with pituitary-dependent Cushing's disease, one patient with an adrenal carcinoma causing Cushing's syndrome and seven normal subjects each received a dexamethasone suppression test using a continuous infusion of dexamethasone sodium phosphate at a rate of 1 mg/h. There was no significant difference in the half-life disappearance rate of endogenous cortisol in either plasma or saliva comparing grouped data from patients with pituitary-dependent Cushing's disease with that of normal subjects. Failure of suppression of both plasma and salivary cortisol levels was observed in the one patient with adrenal carcinoma during dexamethasone infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗

Evidence for an effect of antithyroid drugs on the natural history of Graves' disease.

In the United Kingdom, about half the patients with Graves' disease who are given antithyroid drugs are still in remission one year after treatment is stopped. The most widely held view is that such remission rates are due only to the biochemical effects of the drugs, the disease either spontaneously remitting or abating when the immune system is no longer subject to the stimulatory effects of excessive thyroid hormone. We review here the accumulating evidence against both of these alternatives. In contrast, there is now a large body of work which shows that thyrotrophin receptor antibody levels, central to the aetiology of Graves' hyperthyroidism, fall during antithyroid treatment and that remission may be related to this fall in a fashion which is dependent on the dose and duration of treatment. This immunosuppressive effect is supported by experimental data and on the basis of these results we propose that antithyroid drugs may modify the natural history of Graves' disease and contribute to the remission which occurs in a proportion of treated patients.

Antithyroid Agents↗

Endoscopic examination of the gastric remnant 31-39 years after subtotal gastrectomy for peptic ulcer.

In York between 1941 and 1949, 632 patients underwent Polya partial gastrectomy for peptic ulcer. Of 307 patients who were followed up in the York Gastric Clinic from 1971 to 1980, nine died of gastric cancer, three times the expected number. If gastrectomy was performed for gastric ulcer the risk of later development of carcinoma (7%) was significantly greater than that following operation for duodenal ulcer (1.6%) (p less than 0.001). No cancers were diagnosed in the 54 patients endoscoped. Atrophic gastritis was found in 98% of patients and intestinal metaplasia in 44%. Dysplasia was present in 35% but in no case was it severe. Although we have found that there is an increased risk of cancer developing in the gastric remnant we do not consider routine endoscopic follow up of all postgastrectomy patients to be a practical proposition.

Adult↗

Interactions among epinephrine, thyrotropin (TSH)-releasing hormone, dopamine, and somatostatin in the control of TSH secretion in vitro.

Epinephrine and TRH independently release TSH from rat anterior pituitary cells in primary monolayer culture (ED50, 11 and 5 nM, respectively; maximum responses, 80% and 110%, respectively). The effects of these compounds together are additive, even at concentrations at which each is maximally effective alone. Dopamine inhibited basal and epinephrine-stimulated TSH secretion by 25 +/- 5% (+/-SE; ED50, 50 +/- 9 nM in each case). Somatostatin was effective against epinephrine-stimulated, but not basal, TSH secretion (80 +/- 4% inhibition; ED50, 1 +/- 3 nM). The data show that epinephrine is a potential regulator of TSH secretion by its own action and via its interactions with TRH, dopamine, and somatostatin.

Animals↗

Hypothyroid pituitary cells in culture: an analysis of thyrotropin and prolactin responses to dopamine (DA) and DA receptor binding.

Monolayer cultures were prepared from the anterior pituitary (AP) lobes of normal male rats and male rats made hypothyroid by treatment with aminotriazole. After 3 days in culture, the cells from hypothyroid animals showed significantly greater TSH and PRL secretory activity and significantly less GH secretory activity than did parallel euthyroid cultures. The responses of euthyroid and hypothyroid cultures to dopaminergic agonists and antagonists were examined. Bromocriptine, apomorphine, and dopamine (DA) inhibited euthyroid TSH secretion by approximately 30%, whereas each drug inhibited hypothyroid TSH secretion by approximately 60% (P less than 0.01 for each drug). In contrast, the three agonists were less effective in inhibiting PRL secretion from hypothyroid cells (P less than 0.05 for each drug). The rank order of potency [bromocriptine greater than (+)butaclamol greater than apomorphine greater than DA greater than (-)butaclamol] shown against secretion was the same for TSH and PRL in both euthyroid and hypothyroid cell cultures and is typical of a DA receptor-mediated process. The binding of [3H]dihydroergocryptine (DHE) to DA receptors on euthyroid and hypothyroid cells was examined under the same conditions in which the secretory responses were determined. One micromolar concentration of (+)butaclamol was used to define nonspecific binding. Specific binding was saturable and stereospecific in each case. The rank order of potency of dopaminergic agonists and antagonists in competing for [3H] DHE binding was the same as that demonstrated against the secretion of TSH and PRL. Each compound displaced significantly more [3H]DHE from hypothyroid cells than from euthyroid cells (P less than 0.05 for each drug). Construction of adsorption isotherms for [3H]DHE binding to DA receptors on euthyroid and hypothyroid cells and subsequent Scatchard analysis revealed a 3- to 4-fold increase in receptor number without a significant change in affinity. Immunohistochemistry on AP lobes before and after dispersion revealed an increase in thyrotrophs and thyroidectomy cells in hypothyroid rats relative to those in control animals. In euthyroid animals thyrotrophs were 10.1% of the total AP cell population, in hypothyroid animals they plus the thyroidectomy cells were 36.3% of the total AP cells. Therefore, the increased number of DA receptors per lobe could be accounted for by increased numbers of thyrotrophs. The mechanism of the altered sensitivity to DA induced by hypothyroidism in lactotrophs and thyrotrophs remains to be clarified.

Animals↗

The prevalence and progression of autoimmune thyroid disease in the elderly.

Thyroid antibodies were measured by an enzyme-linked assay system (ELISA) on a random sample of 414 asymptomatic elderly people aged 70 years or more in a South Wales town in 1977. The prevalence of elevated titres of microsomal antibodies was 15.4% and of thyroglobulin antibodies 13.3%; 8.5% had an elevation of both antibodies. Five years later thyroid function was evaluated in 51 (66.6%) of those people with raised antibody titres in 1977 and compared with a control group of 46 old people drawn from the original population. Significant fluctuations of microsomal and thyroglobulin antibody titres were observed in two thirds of the antibody positive group. Three people in the control group developed positive thyroid antibodies during this period. Only 1 person in the antibody positive group became hypothyroid. The prognostic significance of raised thyroid antibodies with or without elevated TSH levels is less in the elderly than in middle aged or younger people. The significance of the fluctuating antibody levels as measured by a more sensitive method remains to be determined.

Age Factors↗

The accumulation of [35S]methimazole by monocytes and macrophages.

We have used an automatic cell harvester and micro culture techniques to examine the accumulation of [35S]methimazole by monocytes, macrophages and lymphocytes. Significant temperature-dependent accumulation of the drug was found in resting monocytes and macrophages; this was increased up to 4-fold by phagocytosis. Lymphocytes accumulated little or no drug and myeloma and leukaemic cell lines accumulated none. These results show that two interrelated cells with endogenous peroxidatic activity take up the antithyroid drug methimazole providing further support for the concept that immunosuppression by this drug in Graves' disease is mediated via an action on antigen-presenting cells.

Animals↗

Effect of tri-iodothyronine on normal human lymphocyte function.

The effect of excessive tri-iodothyronine (T3) in vivo was assessed using normal human lymphocytes. Cells from normal subjects were frozen in liquid nitrogen before and after oral administration of T3 for 1 week to permit a direct comparison under identical culture conditions. Within the group of individuals studied, some subjects did show changes in B or T cell function but hypertri-iodothyroninaemia produced no consistent effect for the whole group on circulating T cell subsets or T and B cell activation measured by short-term culture or stimulation of lymphocyte cultures with phytohaemagglutinin or pokeweed mitogen. Tri-iodothyronine supplementation of cultures in vitro did not affect pokeweed mitogen stimulation. These findings suggest that the immunological abnormalities in Graves' disease are not the result of increased circulating thyroid hormone levels and that remission following medical treatment is due to an immuno-suppressive effect of the drug rather than the restoration of euthyroidism.

Adult↗

The role of the spleen in experimental autoimmune thyroiditis.

We have investigated the role of the spleen in the humoral and cellular immune response of rats with experimental autoimmune thyroiditis (EAT) induced by immunization with thyroglobulin and Freund's complete adjuvant. Animals subjected to splenectomy within 4 days of immunization developed lower thyroglobulin antibody levels and less severe thyroiditis compared to sham operated controls. There was no impairment in the ability of the animals to recover spontaneously from the disease after splenectomy. Together with the results obtained using splenocyte infusions, this suggests that suppressor cell production within the spleen plays only a small part in the normal immunological control which is presumably responsible for spontaneous regression of the disease.

Animals↗

Extrathyroidal sites of autoantibody synthesis in Graves' disease.

Several potential sites of thyroid autoantibody production have been investigated using tissue obtained at thyroidectomy for Graves' disease. Spontaneous thyroglobulin and microsomal antibody synthesis was measured using a plaque forming cell assay or a short term culture system coupled to a direct enzyme linked immunoassay (ELISA); these techniques allow the evaluation of lymphocyte populations which have been activated in vivo. Lymphocytes from the cervical lymph nodes, thyroid and bone marrow all contributed to autoantibody production; in contrast no synthesis was demonstrated using cells obtained from the thymus or peripheral blood. Long term culture of the lymphocytes confirmed these findings. The effect of anti-thyroid treatment, with radioiodine, drugs or surgery, on autoantibody production in Graves' disease must be viewed in the light of these results.

Adult↗