Showing papers by "St Thomas' Hospital published in 1973"

A comparative study on the metabolism of human insulin and porcine proinsulin in man.

Abstract: SUMMARY 1. The metabolism of unlabelled monocomponent human insulin and porcine proinsulin was studied in ten normal subjects (five males and five females) by using a priming dose-constant-infusion technique. In each subject, the metabolic clearance rate (MCR) was measured at four separate steady-state hormone concentrations averaging 16-21 6 punitslml (insulin) and 4-2-42.8 ng/ml (proinsulin). 2. For insulin the MCR fell progressively from 34 ml kg-' min-' at a mean fasting insulin concentration of 3.8 punitslml to 11.4 ml kg-' min-' at the highest concentration achieved (280 punits/ml); for proinsulin MCR averaged 3.7 ml kg - ' min-' at a mean plasma concentration of 4.2 ng/ml and fell to 2.71 ml kg-' min-' at 10.7 ng/ml, remaining constant thereafter at concentrations up to 71 ng/ml. 3. The half-disappearance time (T+) from the plasma, after the end of the infusion, averaged 4.3 min for insulin and 25.6 min for proinsulin. 4. The apparent distribution space (DS) was similar for both hormones (83 ml/kg of insulin and 98.9 ml/kg of proinsulin). 5. There was a direct correlation between T+ and DS for both hormones. 6. Although the higher MCR of insulin was reflected in its shorter T+, there was, for each hormone, no relationship between MCR and T+. 7. The biological potency of porcine proinsulin, as judged by its effect on plasma glucose, was approximately 5% of that of insulin. 8. The responses of serum growth hormone and cortisol were shown to be directly related to the degree of hypoglycaemia induced.

Studies on the metabolic clearance rate, apparent distribution space and plasma half-disappearance time of unlabelled human growth hormone in normal subjects and in patients with liver disease, renal disease, thyroid disease and diabetes mellitus.

Abstract: . The metabolic clearance rate (MCR), half-disappearance time (T½ and apparent distribution space (DS) of unlabelled human growth hormone (HGH) have been studied using the priming dose – constant infusion technique. In 11 normal subjects MCR averaged 2.99 ml/kg/min., T½ 19.0 min. and DS 79.3 ml/kg. There were no differences between males and females and MCR was constant at HGH levels ranging from 5 to 50 ng/ml. In 10 out of 17 patients with chronic liver disease of varying severity MCR/kg was reduced below the lower limit of normal. TV2 was prolonged in 15 of these patients. There was a very close correlation between MCR/kg and DS/kg in liver disease (r = 0.8219). Increased DS/kg accounted for the normal MCR/kg seen in some patients with severe hepatocellular failure. MCR/kg was markedly reduced in three patients'with chronic renal failure. T72 and DS/kg were both significantly increased in this group (48.0 min. and 117.0 ml/kg, respectively). MCR/kg and T72 were normal in one patient with the nephrotic syndrome but normal glomerular filtration rate. MCR/kg was not significantly different from normal in patients with thyrotoxicosis, myxoedema and uncontrolled diabetes mellitus, despite the fact that T½ shorter than normal in thyrotoxicosis and longer than normal in myxoedema. It is suggested that HGH does not normally diffuse freely from the vascular to extravascular extracellular fluid, and that normally a substantial concentration gradient exists between the vascular and extravascular compartments; under these circumstances, the liver and kidneys are the major sites of HGH metabolism. In hepatic and renal failure, this gradient is reduced and extravascular degradation sites may assume more importance in the metabolism of growth hormone. Acute fluctuations in the peripheral blood concentrations of growth hormone indicate alterations in secretion rate and not alterations in metabolism.

Sodium and potassium flux rates in normal human leucocytes in an artificial extracellular fluid.

Abstract: 1. Sodium and potassium efflux and influx rates were studied in normal human leucocytes in an artificial extracellular fluid using radioactive isotopes. 2. The rate constant for sodium efflux was 4.2 h −1 corresponding to a sodium efflux rate of 487 mmol kg cell dry weight −1 h −1 . Approximately three-quarters of this flux was ouabain sensitive. 3. Potassium influx was 346 mmol kg cell dry weight −1 h −1 . Approximately two-thirds of the potassium influx was ouabain insensitive.

Sensori-neural hearing loss in Jamaicans with SS disease.

Abstract: The pure-tone hearing levels in 83 Jamaican patients aged from 10-39 with homozygous sickle cell disease were compared with appropriate controls. A sensori-neural hearing loss, defined as a deficit of at least 25 dB in one or more frequencies, was found in 18/83 (22%) patients and in 3/83 (4%) controls. Both sexes and ears were equally affected, but the extremes of the tested range, especially the high tones, were involved most frequently. The hearing loss was of slow onset. The relative contributions of thrombosis, anaemia, atherosclerosis and Jamaican neuropathy are discussed. It is felt that the most likely aetiology is a thrombotic process.

Eczéma craquelé as the presenting feature of myxoedema.

Abstract: SUMMARY Three cases of advanced myxoedema are reported who presented with Eczema craquele.

Various Regimens of Trimethoprim-Sulfamethoxazole Used in the Treatment of Gonorrhea

Abstract: The combination of trimethoprim (TMP) and sulfamethoxazole (SMZ) was used in a variety of regimens to treat 2,687 male and female patients with gonorrhea. Large doses given over short periods gave good results, the best two regimens being four tablets twice daily for two days (98% cure) and five tablets twice on the first day and once on the second day (96.7% cure). The poorest results (82.5% cure) came from a regimen of one tablet four times daily for five days. Most of the patients who failed to respond were infected with strains that had

The in Vitro Action of Dapsone and its Derivatives on Normal and G6PD‐deficient Red Cells

Abstract: Summary. In an attempt to define the mechanism of dapsone-induced haemolysis the in vitro action of dapsone (4,4′, diaminodiphenylsulphone) and some of its derivatives on normal and G6PD-deficient red cells has been investigated. Dapsone, its N′ acetyl- and hydroxy-derivatives have no measurable effect on metabolism, haemoglobin or the membrane in either normal or G6PD-deficient red cells. 4, hydroxylamino-4′ aminodiphenylsulphone (HADS) and 4, hydroxylamino-4′ acetaminodiphenylsulphone (HMDS) have oxidant effects on red cells. Both of these compounds readily form methaemoglobin but in normal red cells higher levels of methaemoglobin are achieved with HMDS than with HADS. With both compounds less methaemoglobin is formed in glucose-deprived or in G6PD-deficient red cells. In normal red cells hexose monophosphate pathway (HMP) activity is increased, HADS being a more potent stimulus than HMDS. It is suggested that methaemoglobin formation is dependent upon the recycling of these compounds via the HMP. Normal red cells incubated with the two hydroxylamine compounds did not show any change in reduced glutathione (GSH), globin or the membrane, apart from increased sensitivity to peroxide lysis. G6PD-deficient red cells, on the other hand, did lose GSH rapidly and underwent increased autohaemolysis. The mechanism of these effects is discussed. Some, but not all, of the in vivo effects of dapsone can be reproduced by the hydroxylamine derivatives in vitro. It is concluded that either some other derivatives are involved or that the effect of long exposure to these oxidant compounds in vivo is different.

Low factor-VIII-like antigen in acquired Von Willebrand's syndrome and response to treatment.

Abstract: Summary Measurements of factor-VIII-like antigen have been made in three previously reported cases of acquired von Willebrand's syndrome Antigen levels correlated well with biological activity of factor VIII over a wide range, providing a further similarity between the acquired and classical forms of the disorder

The haemolytic action of dapsone: changes in the red-cell membrane.

Abstract: Summary. Some aspects of red-cell membrane structure and function have been investigated in patients with haemolysis due to dapsone (4,4′ diaminodiphenylsulphone). Osmotic fragility and potassium flux were not increased but red-cell membrane changes occurred which suggested instability. These included loss of phospholipid, decrease in acetylcholinesterase activity and increased autohaemolysis. In addition, there was evidence for lipid peroxidation, which might have been the primary lesion. Red-cell membrane sulphydryl group activity was either reduced or altered because these cells were abnormally sensitive to the action of the sulphydryl group inhibitor p-chloromercuribenzoate, as measured by increased potassium leakage aiid haemolysis. Dapsone also caused abnormal peroxide lysis in the presence of normal hydrogen peroxide detoxification mechanisms and in the absence of vitamin E deficiency. This was prevented by excess vitamin E but not by the sulphydryl compounds, reduced glutathione or cysteine, and it was increased by previous treatment with p-chloromercuribenzoate. It is suggested that reduced membrane sulphydryl group activity, probably due to the formation of mixed disulphides with precipitated haemoglobin, and lipid peroxidation may be responsible for in vitro and, possibly, in vivo dapsone-induced haemolysis.

The Haemolytic Action of Dapsone: The Effect on Red-Cell Glycolysis

Abstract: Summary. Some aspects of red-cell metabolism were studied in blood samples taken from patients on long-term dapsone therapy. Glucose consumption by the Enibden-Meyerhof pathway (EMP) was not abnormal and adenosine-triphosphate (ATP) levels lay within the normal range and were well maintained during incubation. Hexose monophosphate pathway (HMP) activity was increased above that which would be expected from the age of the red-cell population. Red-cell reduced glutathione (GSH) levels tended to be lower than normal, proportional to the dose of dapsone and GSH levels were unstable on incubation. Red-cell fractionation studies showed that the older cell fraction had lower GSH levels and more Heinz bodies but proportionally greater HMP activity than the younger cell fraction. It is suggested that the low GSH levels are probably due to the binding of GSH to sulphydryl groups in haemoglobin and possibly the red-cell membrane. The increased HMP activity in the older cells may, in part, be a compensatory mechanism.

Antifibrinolytic Treatment in Haemophilia: A Controlled Trial of Prophylaxis with Tranexamic Acid

Abstract: Summary. A randomized controlled trial of the antifibrinolytic agent amino-methylcyclohexane carboxylic acid (AMCA, Tranexamic acid) in the prophylactic treatment of haemophilia is reported. The active treatment (2 g daily) or indistinguishable inert tablets were given for 12 consecutive periods of 28 days. The effect of the active treatment was minimal and incapacity from the disease and the need for the administration of factor VIII were not reduced. It is considered that sound evidence does not exist for recommending the prophylactic use of antifibrinolytic drugs in haemophilia.

Quinsy tonsillectomy: a safe procedure

Abstract: The generally accepted management of peritonsillar abscess (quinsy) is to give antibiotics until they resolve or to drain the abscess with a stab incision under local analgesia, but immediate quinsy tonsillectomy under general anaesthesia at St Thomas‘ Hospital has proved to be a safe, reliable and economical method of treatment.’ 3 This procedure gives complete relief of severe symptoms with the certainty of drainage of the peritonsillar abscess, avoids a second operation and is technically simple to perform, whereas the so called ‘simple’ incision is a painful and awkward procedure for patient and surgeon alike and the symptoms subside very slowly; the subsequent interval tonsillectomy is also often technically difficult. Primary quinsy tonsillectomy has been condemned because of the dangers of respiratory obstruction, of soiling the trachea by pus, haemorrhage and septicaemia4 but these risks are more supposed than real where the staff and facilities for safe general anesthesia exist.

Studies on the pathogenesis of fever in renal carcinoma.

Abstract: 1. Endogenous pyrogen (EP) was detected in tumour extracts from four patients with renal carcinoma and fever. No EP was detected in extracts of tumours from six afebrile patients or in extracts of normal kidney. 2. Tumour slices from one febrile patient released EP into a nutrient incubation medium; this process was suppressed by the presence of cycloheximide. Tumour slices from an afebrile patient did not release EP on incubation. 3. Leucocytes from the peripheral blood of two febrile patients with renal carcinoma did not yield EP on incubation in saline. 4. The production of EP by leucocytes ‘activated’ by 2 h incubation with a Proteus endotoxin was not inhibited by cycloheximide. 5. It is suggested that fever associated with renal carcinoma is caused by the release of EP within the tumour.

Monitoring successive batches of British Comparative Thromboplastin.

Abstract: Summary. Procedures used in the independent monitoring of British Comparative Thromboplastin are described. Recent results from batches of similar thromboplastin have been analysed for differences in their sensitivity to the anticoagulant defect. On the basis of observed variability, the minimum number of tests required to achieve a given level of discrimination between standardized and modified thromboplastins has been calculated to determine the number of readings which should be obtained to give a reasonable certainty of detecting unsatisfactory batches.

The bioassay of human endogenous pyrogen.

Abstract: 1. A method is described for the quantitative assay of human endogenous pyrogen in saline and plasma which is valid in the presence of exogenous pyrogens. 2. The value of the assay is demonstrated by a study of the relation between endotoxin concentration and endogenous pyrogen production by human leucocytes in vitro.

The Response of the Human Leucocyte to Alterations in Extracellular Osmolality

Abstract: 1. The effect of variations in extracellular osmolality from 249 to 345 mosmol/kg upon the sodium, potassium and water content of human leucocytes has been studied. 2. Similar studies were performed using human erythrocytes. 3. Changes in the leucocyte water content were not explicable in terms of passive movement of water across an ‘ideal’ semi-permeable membrane. 4. Hypo-osmolal swelling was associated with a rise in intracellular sodium content and hyperosmolal shrinkage was associated with a fall in intracellular sodium content. 5. There were no significant changes in sodium and potassium content of the erythrocyte with altered external osmolality.

Maternal and umbilical cord plasma-cortisol-concentrations related to different types of deliveries.

Abstract: Maternal and cord plasma cortisol concentrations have been measured after vaginal deliveries (spontaneous and forceps) or Caesarean sections. The plasma samples were analyzed by a competitive protein binding assay before and after fractionation using Sephadex LH-20 columnchromatography. The method is described in detail. With the application of chromatography the results for the cortisol concentrations were in the maternal plasma approx. 30% and in the cord plasma approx. 70% lower than those obtained without previous plasma purification. Chromatography is thought to eliminate certain compounds from maternal and cord plasma which compete with cortisol for the binding sites on the cortisol binding globulin. Its application seems an essential methodological step in cortisol measurements. The maternal cortisol concentration is after a vaginal delivery twice as high as the prelabour values, whereas a Caesarean section is accompanied only by a moderate rise in the plasma cortisol. The cortisol level in the newborn delivered vaginally is twice to threetimes as high as that after a Caesarean section. The highest values are found in the forceps group. There is no direct correlation between the maternal and cord plasma cortisol concentrations. On the contrary it seems that the newborn is able to increase its own plasma cortisol concentration independently, e.g. in response to the stress caused by the delivery. The absence of such a stress, as in the case of a Caesarean section, results in low cord plasma cortisol levels, a fact that could be hazardous for the newborn.

Carcinoma of Meckel's diverticulum.

Abstract: Meckel's diverticulum is a developmental abnormality of the alimentary tract occurring in up to 3% of the population, and carcinoma of the diverticulum is a rarity. A further case occurring in a 43-year-old Caucasian man is reported with clinical details and pathologic findings. The literature of the condition is reviewed. The case described brings the total number recorded to 18.

Cytochemical Analysis of Left Ventricular Biopsies in Open-Heart Surgery: A Pilot Study

Abstract: Summary 1. In previous studies three histochemical tests have been useful in detecting myocardial dysfunction. 2. These have been applied to left ventricular biopsies from 37 patients who underwent prolonged open-heart surgery. The immediate objective was to investigate whether these tests could be used as a guide to prognosis. 3. There was good correlation between the graded response to the histochemical tests and the clinical assessment of the myocardium. The tests over-warned in 3 cases out of 15, and did not warn of myocardial dysfunction in 2 cases out of 22 which showed clinical dysfunction. 4. One of the most difficult aspects of the pre-operative assessment of left heart lesions is the evaluation of the state of the myocardium. The development of cardiac biopsy methods that can be performed at the time of catheterisation would allow such histochemical analyses of myocardial function to be more widely used.

Acute scleroderma (morphoea) with myositis.

Abstract: I J, male, aged 18. Schoolboy History: In August 1971 he developed patchy erythematous plaques on the left side of the neck. These remained stationary for 2-3 months, and then spread rapidly to give extensive areas of cedematous, erythematous and tender skin on the left side of the body. By May 1972 he had gross deformity of the left hand and forearm with muscle wasting. The disease was still predominantly left-sided, with the occasional patch on the right arm and side of the face and neck. He suffered from gross fatigue. There was no Raynaud's phenomenon and no dysphagia.