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Biomedical subjects

W F Hamilton

Publications and source records attributed to W F Hamilton.

At least 19 recordsLinked to original sources

Low-conductance anion channel activated by cAMP in teleost Cl- -secreting cells.

We studied characteristics and modulation of ion channels in primary cultures of opercular epithelium from the euryhaline marine killifish Fundulus heteroclitus. Primary cultures, 17-28 h old, retain mitochondria-rich Cl- cells identifiable by fluorescence microscopy. Cell-attached patches revealed frequent low-conductance 8.1 +/- 0.35 pS channels that usually became inactive on excision; high-conductance anion channels were not apparent. Ion substitution experiments demonstrated selectivity for Cl- over gluconate of 1:0.07. With addition of 1-isobutyl-3-methylxanthine (0.1 mM) and dibutyryladenosine 3',5'-cyclic monophosphate (1.0 mM) to the bath, incidence of the channel increased from 35.3 to 61.9% of total patches (n = 156 and 21, respectively), and incidence of patches with multiple copies of the channel increased markedly from 2.2 to 38.5%. Epithelial Cl- transport was inhibited by mucosally added diphenylamine-2-carboxylic acid (1.0 mM) but not by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (0.1-1.0 mM). The anion channel was absent from cultured killifish corneal epithelium, a tissue that lacks Cl- cells. We conclude that a low-conductance anion channel of Cl- cells, likely in the apical membrane, may account for adenosine 3',5'-cyclic monophosphate-activated Cl- secretion by marine fish.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid

In situ dissection of cadaver kidneys.

Major anatomic injuries occurred in 18 of 151 (12%) en bloc kidneys. No injuries occurred among the in situ kidneys. The rates of delayed graft function were equal. All the kidneys removed by the in situ method were removed by one surgeon (ALH). The results are good enough to recommend the technique even without a randomized study.

Brain Death

Alfentanil in an anaesthetic technique for penetrating eye injuries.

Alfentanil in three doses (10, 20 and 30 micrograms/kg) was added to an anaesthetic technique suitable for penetrating eye injuries. All three doses proved effective in abolishing the marked present response to tracheal intubation which occurs with this technique, but at least 20 micrograms/kg was needed to obtund the heart rate response significantly and to facilitate early intubation. Transient hypotension and bradycardia occurred in some patients who received the highest dose of alfentanil. The incidence of postoperative sequelae was small in all groups. Thus, the optimal dose of alfentanil in an anaesthetic technique for penetrating eye injuries appears to be 20 micrograms/kg.

Aged

The clinical and metabolic responses to early surgical treatment for hyperthyroid Graves' disease: a comparison of three pre-operative treatment regimens.

We have compared the clinical and metabolic responses of three groups of patients undergoing subtotal thyroidectomy for hyperthyroid Graves' disease. These patients were prepared for surgery with propranolol alone, propranolol plus potassium iodide or the long acting beta-adrenoceptor antagonist nadolol plus potassium iodide. Pre-treatment with potassium iodide reduced serum T4 to normal or subnormal in all patients. Patients in the propranolol group had significantly higher pulse rates and temperatures after operation and one patient developed an exacerbation of the hypermetabolic state. The perioperative rise in serum cortisol and blood glucose was delayed in patients in the propranolol group and this was also noted in one severely hyperthyroid patient on propranolol + potassium iodide. Nadolol was administered once daily as compared to multiple daily doses with propranolol. Despite this, plasma nadolol levels were consistently higher throughout the perioperative period while propranolol levels in patients on both propranolol alone and propranolol + potassium iodide were highly variable and sometimes undetectable. We conclude that, in the rapid preparation of patients with hyperthyroid Graves' disease for surgery, the combination of nadolol + potassium iodide has significant advantages over the other two regimens.

Adult

Beta-adrenoceptor blockade and anaesthesia for thyroidectomy.

The administration of beta-adrenoceptor blocking drugs in the pre-operative preparation and operative management of thyrotoxic patients undergoing subtotal thyroidectomy is reviewed. Particular reference is made to some of the recent advances and it is emphasised that there has been a considerable reduction in the incidence of problems following judicious use of these drugs. The choice of anaesthetic technique employed for thyroidectomy is less important than the degree of control of thyrotoxicosis by the beta-adrenoceptor blocking drug. Propranolol has proved safe and effective for the majority of patients. The longer acting agent nadolol is easier to administer, particularly in the peri-operative period. Patients are rendered less thyrotoxic and safety thereby enhanced by adding potassium iodide for 10 days preoperatively. The combination of nadolol and potassium iodide offers real advantages in the preparation of the thyrotoxic patient for surgery.

Adrenergic beta-Antagonists

Nadolol and potassium iodide in combination in the surgical treatment of thyrotoxicosis.

With the two aims of rapidly reducing circulating thyroid hormone levels and controlling the symptoms of thyrotoxicosis, we have prepared 17 thyrotoxic patients for subtotal thyroidectomy, using a combination of potassium iodide administered for 10 days and the long acting beta-adrenoceptor antagonist nadolol. All 17 patients had normal serum thyroxine levels after 10 days of such treatment although 10 still showed elevation of serum tri-iodothyronine and considerable elevation in the most severely toxic patient. All patients were, however, clinically euthyroid preoperatively. Nadolol was administered once daily, hence avoiding the problems of drug administration in the immediate postoperative period, and plasma nadolol concentrations were high throughout the perioperative period. Serum thyroxine and tri-iodothyronine levels were significantly lower and reverse tri-iodothyronine levels higher 24 h postoperatively than before operation. All patients remained stable throughout the perioperative period. We conclude that this regimen has a number of advantages in the preparation of patients for thyroidectomy, in reducing the degree of thyrotoxicosis, in convenience of drug administration and in ensuring adequate circulating concentrations of beta-adrenoceptor antagonist whilst still retaining a relatively short preoperative phase of drug treatment.

Adrenergic beta-Antagonists

Propranolol in the surgical treatment of hyperthyroidism, including severely thyrotoxic patients.

The perioperative course of 44 hyperthyroid patients prepared for surgery with propranolol alone, including 11 with severe thyrotoxicosis was compared to that of 20 euthyroid patients prepared for surgery with carbimazole. Conventional propranolol at a dosage of 160 mg/day was frequently insufficient to produce a high degree of beta-adrenergic blockade, particularly in severely thyrotoxic patients. A greater than 25 per cent reduction in sitting pulse rate was associated with a high degree of beta-blockade. The clinical course of patients with mild or moderate thyrotoxicosis was similar to that of the patients prepared with carbimazole. In contrast, the course of severely thyrotoxic patients was complicated and, in addition to a higher preoperative propranolol dosage, these patients commonly required supplemental propranolol after operation. Although thyroid crisis did not occur in any patient, we cannot recommend the use of propranolol alone for the severely thyrotoxic patient.

Adult

Altered endocrine response to partial thyroidectomy in propranolol-prepared hyperthyroid patients.

The endocrine response to partial thyroidectomy in a group of twenty hyperthyroid patients prepared with propranolol alone was compared to that of a matched control group of ten euthyroid patients. In propranolol-prepared patients the glucose response to surgery was reduced (P less than 0.05) for up to 4 h post-operatively and biochemical hypoglycaemia was noted in one patient. Both thyroxine and triiodothyronine (T3) fell significantly, associated with a marked rise in reverse T3. Growth hormone levels were higher (P less than 0.05) both pre- and post-operatively in propranolol-prepared patients, whereas prolactin levels, although similar pre-operatively, were lower (P less than 0.05) in these patients post-operatively. Cortisol and ACTH levels were lower (P less than 0.05) both before and following thyroidectomy in propranolol-prepared patients. These results suggest that the endocrine response to surgical stress is markedly altered in propranolol-prepared hyperthyroid patients.

Adrenocorticotropic Hormone

Changes in serum uric acid concentrations after caesarean section using methoxyflurane.

In a study comparing the changes in serum uric acid concentration after methoxyflurane anaesthesia in 10 patients subjected to either Caesarean section or minor general surgical procedures, a significantly greater increase in serum uric acid concentration occurred in those patients undergoing Caesarean section. These results were compared with results from a control group of five patients undergoing Caesarean section, anaesthetized without methoxyflurance and with a second control group of five patients having uncomplicated spontaneous deliveries. Reasons are presented to suggest that although obstetric patients are unlikely to be more vulnerable to methoxyflurane nephrotoxicity, those with pre-eclamptic toxaemia may be more at risk.

Adult

Expectorant action of bromhexine in chronic obstructive bronchitis.

Bromhexine was compared with a placebo in a double-blind clinical trial in bronchitic inpatients with mucoid sputum. Oral bromhexine 16 mg. thrice daily for 11 days compared with placebo resulted in a significant increase in sputum volume and significant decrease in sputum viscosity, and changed markedly the rheological characteristics of the sputum. There was, however, no improvement in ventilatory capacity or in the overall respiratory state as assessed by the patients themselves or their clinician. No patient having the drug had side-effects and there was no change in laboratory findings attributable to it.

Adult