Showing papers by "St Bartholomew's Hospital published in 1975"

Possible placental origin of ACTH in normal human pregnancy.

Abstract: IT is well known that the free fraction of plasma cortisol is increased in pregnancy1, but it has not been established whether this is a result of maternal pituitary or placental adrenocorticotrophic hormone (ACTH) secretion. Maternal plasma ACTH levels in human pregnancy have been variously reported as elevated2, or depressed3; but there is no information on the relationship between ACTH levels and the stage of gestation. We now report that maternal ACTH levels increase progressively throughout pregnancy, that urinary free cortisol levels are raised and show resistance to suppression by dexamethasone and we present evidence suggesting that ACTH may be produced by the placenta.

Determination of the Optimum temperature for regional renal hypothermia during temporary renal ischaemia.

Abstract: To determine the optimum temperature at which the in situ kidney should be maintained while it is ischaemic, 47 mongrel dogs were studied. 35 of these underwent 90 minutes of left renal ischaemia with the kidney temperature maintained at 37 degree, 30 degree, 22 degree, 15 degree and 0 degree C respectively. The effect on renal function was determined by measurements of G.F.R. before and at regular 15-minute intervals after the inschaemic period. Computer statistical analysis exposed the optimum temperature to be 15 degree C. Renal artery blood flow, renal histology, 15-Cr labelled platelets and renal arteriography were used to determine the mechanism of ischaemic injury. Quantitation of renal cell injury confirmed that no additional protection to ischaemia could be gained by colling below 15 degree C. 15 degree C is recommended as the optimum temperature for use in clinical renal hypothermia.

Accuracy and limitations of the ultrasonic Doppler blood velocimeter and zero crossing detector.

Abstract: The zero crossing detector processes blood velocity signals from a Doppler ultrasonic velocimeter to give an output that can be recorded on paper. Although this output gives an indication of the instantaneous velocity averaged across the vessel the system does have limitations when used for quantitative work. This paper explains the working of the zero crossing detector and illustrates how errors can arise due to changes in amplitude and frequency content of the signal. Suggestions are made for reducing the errors, and other more accurate methods of analysis are discussed.

Further studies on carrageenan-induced pleurisy in rats.

Abstract: A study has been made of the exudate provoked by intrapleural carrageenan in rats. Various parameters have been measured including volume of exudate, numbers and types of cells. Pharmacological assay has shown the early release of histamine and 5HT into the exudate followed at later times by a release of prostaglandins, and a second release of histamine. The role of complement has been studied. Intrapleural injection of carrageenan after complement depletion produced a reduced migration of polymorphonuclear cells and also a reduction in volume of exudate. Prostaglandins remained unaffected by this treatment.

Conservative renal surgery for adenocarcinoma. The place of bench surgery.

Abstract: Summary A brief review of reported cases of tumours in solitary kidneys and of bilateral simultaneously occurring tumours is reported. 1 case of bilateral simultaneously occurring tumour and 3 cases of tumour occurring in solitary kidneys are reported. The treatment of these cases by simple partial nephrectomy under regional hypothermia is described. The place of ex vivo“Bench Surgery” for this condition is discussed.

A study of desensitization using voltage clamp

Abstract: The onset and offset of desensitization produced by carbachol and hexyl and heptyl TMA at voltage-clamped frog endplates were studied. Desensitization onsets exponentially with a rate constant which is proportional to the agonist concentration. The proportionality constant varies with the agonist used. The plateau current finally attained falls steeply to low values with increasing agonist concentration, and with further increase in concentration varies relatively little. The offset of desensitization is sometimes accompanied by the appearance of a second transient increase in current. It is proposed that desensitization is due to channel blockade by the agonist molecule itself.

Development and validation of a radioimmunoassay for peptides related to beta-melanocyte-stimulating hormone in human plasma: the lipotropins.

Abstract: A radioimmunoassay is described for the measurement of human “β-melanocyte-stimulating hormone” (“βh-MSH”). Two antisera have been used, one of which cross-reacts with synthetic βh-MSH as well as with the two larger pituitary peptides βh- and γh-lipotropin (βh- and γh-LPH) and the other mainly with βh-MSH and γh-LPH. The sensitivity and reliability of the assay have been improved by employing a simple plasma extraction procedure, and the shelf-life of the iodinated βh-MSH tracer has been increased more than five-fold by storage in a concentrated human serum albumin solution. Using a 5 ml plasma sample the detection limit is 6 pg/ml. The mean resting “βh-MSH” level in normal subjects is 21 pg/ml (range 13–38 pg/ml) at 9 am and 12 pg/ml (range 6–20 pg/ml) at 9 pm. Levels are considerably elevated (51–12,000 pg/ml) in patients with Addison's disease, Nelson's syndrome, Cushing's disease and the “ectopic” ACTH syndrome. After administration of insulin or pyrogen, the concentration of plasma “βh-MSH” increases...

Brain concentrations of phenytoin, phenobarbitone and primidone in epileptic patients.

Abstract: Plasma, brain, lumbar CSF, skeletal muscle, skin and bone concentrations of phenytoin, phenobarbitone and primidone have been measured in specimens from patients undergoing temporal lobectomy for chronic epilepsy. A good correlation was found between the plasma and brain concentrations of each drug. Similarly, a good correlation was found between the plasma and CSF concentrations of each drug. Assuming that CSF is an ultrafiltrate of plasma, the percentage of phenytoin, phenobarbitone and primidone which was unbound in plasma was 10–14%, 43% and 81% respectively. Skeletal muscle concentrations of phenytoin and phenobarbitone and the skin concentration of phenytoin, also correlated with the plasma concentrations, but the remaining tissues did not give significant correlations.

Coagulation changes during the steady state in homozygous sickle-cell disease in Jamaica.

Abstract: Coagulation studies were carried out in 117 Jamaicans with homozygous sickle-cell disease in the steady state, and 40 local controls. The patients had significantly higher factor-VIII levels, higher platelet counts, lower factor-V and plasminogen levels, shorter thrombin times and higher serum fibrinogen degradation products (FDP) than the control group. The low factor-V and plasminogen levels, and high FDP levels, might be explained by activation of the coagulation system and continuous clot lysis even in the absence of painful crisis. The high factor-VIII levels and short thrombin times found in these patients could not be explained.

Some aspects of upper respiratory tract reflexes.

Abstract: Respiratory and cardiovascular reflexes have been elicited from receptors in the nose and larynx in the anaesthetized dog Cigarette smoke in the nose causes reflex apnoea, bradycardia and vasoconstriction in the limbs, with late effects consisting of hyperpnoea, tachycardia, hypertension and limb vasoconstriction, probably due to systemic absorption through the nose Stimulation of laryngeal receptors or of the central end of the superior laryngeal nerve also results in reflex apnoea, bradycardia, and limb vasoconstriction When asphyxia supervenes due to apnoea, stimulation of the carotid body chemo-receptors occurs which normally cause, as primary effects, hyperpnoea and bradycardia However, it has been shown that stimulation of the laryngeal receptors inhibits the carotid body respiratory reflex and facilitates the carotid body cardio-inhibitory reflex, the latter leading to temporary cardiac arrest The clinical implications of this finding are discussedZUSAMMENFASSUNGRespiratorische und kardio-vas

The effect of cyproheptadine on hunger, calorie intake and body weight in man.

Abstract: The appetite stimulating action and the weight gaining potential of one month's treatment with the antihistamine and antiserotonergic compound cyproheptadine (Periactin) 4 mg three times daily was compared to placebo in a double-blind crossover trial in sixteen thin but otherwise normal volunteers who wanted to gain weight. Subjects gained significantly more weight on cyproheptadine than on placebo. There was also a corresponding relative increase in subjective hunger ratings and food intake during the period on active drug. Drowsiness was the most frequent side effect observed. These findings are discussed in relation to a possible serotonergic feeding mechanism.

Jejunal absorption of an amino acid mixture simulating casein and an enzymic hydrolysate of casein prepared for oral administration to normal adults.

Abstract: 1. An intestinal perfusion technique was used in six normal human subjects to study absorption of sixteen individual amino acids from an amino acid mixture simulating casein and from an enzymic hydrolysate of casein, prepared for oral administration to these subjects, which consisted of a mixture of oligopeptides and free amino acids. 2. Total absorption of alpha-amino nitrogen was greater from the casein hydrolysate than from the amino acid mixture, and the considerable variation in percentage absorption of individual amino acids from the amino acid mixture was much reduced when the enzymic hydrolysate solution was perfused, as a number of amino acids which were poorly absorbed from the amino acid mixture were absorbed to a greater extent from the casein hydrolysate. 3. These findings indicate that after extensive intestinal resections or in malabsorption there might be significant nutritional advantages in the administration of protein hydrolysates rather than amino acid mixtures.

An analysis of the dose-response curve at voltage-clamped frog-endplates.

Abstract: The agonist concentration—endplate conductance relation was examined for a number of agonists (such as carbachol, alkyl trimethylammonium salts, choline and decamethonium). The endplate current evoked varied asImax [a/(a+K)]2, wherea is the agonist concentration andImax andK are agonist-specific parameters. This finding suggests that the endplate receptor has 2 equivalent subunits which bind agonist approximately non-cooperatively. The liganded subunits then switch to an active conformation with a probability that depends on the nature of the agonist. Both subunits must adopt the active conformation for the channel to open, but the transitions of the subunits could be either independent or concerted.

Airway function in healthy subjects and patients with left heart disease.

Abstract: 1. In forty non-smoking healthy subjects and seventy-two patients with left heart diseases measurements were made of the volume expired in the first second of a forced expiration (FEV1) and the total volume expired in a forced expiration (FVC) before and after inhalation of salbutamol. Before and after salbutamol the healthy subjects and patients also inhaled maximally an inspirate, the first part of which contained 133Xe and, during controlled expiration, the radioactivity of the expirate was measured and plotted against its volume. the resulting curves were divided into phases of different slope by eye, the point at which phase 3 changed to phase 4 being nominated the closing volume. 2. In forty non-smoking healthy subjects inhalation of salbutamol was followed by significant increase in FEV1 but FVC and closing volume did not change. 3. Change in posture from seated erect to supine in thirty of these healthy subjects was accompanied by significant reduction in FEV1 and FVC and as closing volume was not significantly different in the two positions the ratio closing volume/vital capacity was increased with recumbency. 4. In seventy-two patients with left heart diseases without a history of cough or wheeze, FEV1, FVC, closing volume and the ratio closing volume/vital capacity were significantly different from values in the healthy subjects. There was no significant difference between non-smokers and ex-smokers amongst the patients. 5. Significant increase in FEV1, FVC and reduction in closing volume and the ratio closing volume/vital capacity followed inhalation of salbutamol in patients with heart diseases but the values remained significantly different from those recorded in the healthy subjects. 6. In twenty patients with heart diseases, FEV1 and FVC were reduced by change in posture from seated erect to supine but the ratio closing volume/vital capacity and the regression with age of this ratio were not significantly changed by change in position. 7. In patients with heart diseases the ratio closing volume/vital capacity was significantly correlated with severity of breathlessness and length of symptom-history but not with left ventricular end-diastolic or pulmonary vein wedge pressures.

Changes in blood catecholamine levels and blood coagulation and fibrinolytic activity in response to graded exercise in man.

Abstract: Measurements of catecholamines, fibrinogen, factor VIII, thrombelastography, euglobulin lysis time and platelet adhesiveness have been carried out on venous blood obtained from normal males exposed to exercise on a bicycle ergometer at various work loads. Significant increases in adrenaline, factor VIII and fibrinogen were found only after exercise to exhaustion at 1500 kpm min-1 whereas the euglobulin lysis time was inversely proportional to the excercise load. There was no change in platelet adhesiveness. These findings support the results of studies using adrenaline infusions or adrenergic blockade which suggest that stress-induced increases in factor VIII are mediated via adrenergic stimulation but that activation of fibrinolysis is not dependent on adrenaline.

The diagnosis of ‘hysteria’

Abstract: A study of 120 inpatients diagnosed as suffering from hysteria is presented and the validity of the diagnosis questioned. Clinical study showed that 13% showed only hysterical symptoms, 33% showed hysterical symptoms occurring with affective symptoms, 28% showed affective symptomatology only, and the remainder were either of other or uncertain diagnostic grouping. It is concluded that the 13% are suffering from a condition that can only be diagnosed as hysteria.

Changes in Circulating Levels of LH, FSH, LHβ- and α-Subunit After Gonadotropin-Releasing Hormone, and of TSH, LHβ- and α-Subunit After Thyrotropin-Releasing Hormone

Abstract: The effect of the gonadotropin-releasing hormone (LRH) and thyrotropin-releasing hormone (TRH) on the blood levels of LH, FSH and TSH, and LHβ- and α-subunit have been studied in 4 normal subjects during the first 20 min after administration of these releasing hormones. Increases in serum immunoreactive LH, LHβ and α-subunit were seen in all subjects after LRH (100μg iv) but in all subjects the rise in LH was preceded by a rise in α-subunit. All subjects showed an increase in TSH and 3 of the 4 subjects a rise in α-subunit after TRH (200 μg) but the α-subunit responses were smaller and less consistent than after LRH. Levels of LHβ remained unchanged after TRH. The results demonstrate that the immunoreactive α-subunit of the pituitary glycoprotein hormones can be released independently of the intact hormones and that release occurs in response to the same releasing hormones, LRH and TRH, that release the intact hormones.

Growth hormone release inhibiting hormone: actions on thyrotrophin and prolactin secretion after thyrotrophinreleasing hormone.

Abstract: The hypothalamic tetradecapeptide growth hormone release inhibiting hormone (GH-RIH) blocked the thyrotrophin response to thyrotrophin-releasing hormone (TRH) in normal people and in patients with primary hypothyroidism. This inhibition was dose related. The TRH-induced prolactin release was not affected by GH-RIH. This dissociation of the thyrotrophin and prolactin responses to TRH by GH-RIH suggests that there are different mechanisms for release of thyrotrophin and prolactin and that only the former is affected by GH-RIH.