Showing papers by "St Bartholomew's Hospital published in 1980"

Met-enkephalin circulates in human plasma

Abstract: The physiological roles of Met-enkephalin and Leu-enkephalin1 are still unknown. They may act as neurotransmitters in the central and peripheral nervous sytems2. Met-enkephalin has been detected in several species in a variety of tissues including brain, spinal cord and gut using bioassays, opiate receptor assays and radioimmunoassays (RIA)3–8. It has also been detected in human gut immunocytochemically and in human brain and cerebrospinal fluid by opiate receptor assay and RIA9–11. However, all reported assays show some degree of cross-reaction with Leu-enkephalin and unequivocal differentiation between the two enkephalins and the larger endorphins has not always been possible. Thus the existence of Met-enkephalin in human tissues and fluids remains in doubt. Using a highly specific RIA, we have now obtained evidence that Met-enkephalin-like material circulates in the plasma of normal subjects and may be secreted by the adrenal gland. Chromatographically the material exists in plasma mainly as the intact pentapeptide and not as the biologically inactive degradation product Gly-Gly-Phe-Met as would be expected from metabolic studies12,13.

The Development of Enzymes of Energy Metabolism in the Brain of a Precocial (Guinea Pig) and Non‐Precocial (Rat) Species

Abstract: Key enzymes of ketone body metabolism (3-hydroxybutyrate dehydrogenase, 3-oxo-acid:CoA transferase, acetoacetyl-CoA thiolase) and glucose metabolism (hexokinase, lactate dehydrogenase, pyruvate dehydrogenase, citrate synthase) have been measured in the brains of foetal, neonatal, and adult guinea pigs and compared to those in the brains of neonatal and adult rats. The activities of the guinea pig brain ketone-body-metabolising enzymes remain relatively low in activity throughout the foetal and neonatal periods, with only slight increases occurring at birth. This contrasts with the rat brain, where three- to fourfold increases in activity occur during the suckling period (0-21 days post partum), followed by a corresponding decrease in the adult. The activities of the hexokinase (mitochondrial and cytosolic), pyruvate dehydrogenase, lactate dehydrogenase, and citrate synthase of guinea pig brain show marked increases in the last 10-15 days before birth, so that at birth the guinea pig possesses activities of these enzymes similar to the adult state. This contrasts with the rat brain where these enzymes develop during the late suckling period (10-15 days after birth). The development of the enzymes of aerobic glycolytic metabolism correlate with the onset of neurological competence in the two species, the guinea pig being a "precocial" species born neurologically competent and the rat being a "non-precocial" species born neurologically immature. The results are discussed with respect to the enzymatic activities required for the energy metabolism of a fully developed, neurologically competent mammalian brain and its relative sensitivity to hypoxia.

Terminal Transferase Enzyme Assay and Immunological Membrane Markers in the Diagnosis of Leukaemia: a Multiparameter Analysis of 300 Cases

Abstract: Summary. Multiparameter analyses have been carried out with recently developed enzyme and membrane markers in 300 patients with various leukaemias including ALL, AML, but excluding Ph1 positive leukaemias. TdT enzyme levels were particularly valuable in the differential diagnosis of adult acute lymphoid and myeloid leukaemias. The levels were raised in 108 (94%) of the 115 patients who were considered to be non-T, non-B ALL on membrane marker and morphological analysis; all seven cases giving negative TdT results in this group were young children. Unexpectedly high levels were seen only in three (4.1%) of 73 cases of acute myeloid leukaemia verified by histochemistry and membrane markers. Anti-ALL serum was a most useful reagent in childhood leukaemias but blasts from 19 patients (10% of childhood ALL cases and 29% of adult ALL cases) failed to react with the serum in spite of TdT positivity. Strongly ALL+ blasts were seen only in non-T, non-B ALL and some undifferentiated leukaemias. Weakly ALL+ blasts were seen in seven of 32 cases of thymic ALL (Thy-ALL) but in other respects these blasts expressed Thy-ALL features, such as strong reactivity with anti-T cell (HuTLA) serum, negativity with anti-Ia-like serum and raised TdT. The combination of tests was particularly useful in 32 cases of undifferentiated leukaemia: in 10 of these cases TdT positivity indicated the probable ‘lymphoblast’, nature of blast cells: the remaining 22 cases remained unclassifiable with the markers used. The analysis revealed other interesting variant forms of leukaemias.

Axonal Transport of Neuropeptides in the Cervical Vagus Nerve of the Rat

Abstract: Accumulations of the neuropeptides substance P (SP), somatostatin (ST), and vasoactive intestinal polypeptide (VIP) proximal to a crush in the cervical vagus nerve of the rat have been measured using sensitive radioimmunoassays. Each of the peptides was rapidly transport towards the peripheral terminals of vagal afferent fibres, with average rates of flow ranging from 0.8 to 2.7 mm h-1. In the rabbit vagus nerve, SP was transported with an average rate of 4 mm h-1, which is more than double the rate for this peptide in the rat. Double crush experiments in rabbit vagus nerves indicated that the rapidly transported proportion of the total content of SP in the nerve free was about 34%. From this, the rate of transport of SP in the rapidly transported pool in the rabbit vagus nerve can be calculated to be 12 mm h-1 (280 mm day-1). Since such double crush experiments were not possible in the rat, it is not clear whether the different average rates of transport of SP in the rat and the rabbit reflect real differences in the rate of rapid transport in the two species. In common with rapid axonal transport of other neurotransmitters, the transport of SP and ST in the rat vagus nerve was blocked by colchicine, a drug that disrupts microtubules.

Circulating somatostatin after food and glucose in man

Abstract: SUMMARY Using a recently validated radioimmunoassay, changes in circulating somatostatin have been measured in normal subjects after food (a standard breakfast), and oral and intravenous glucose. After the standard breakfast, a clear and sustained rise in plasma somatostatin was seen in all subjects from a mean value (± 1 SE) of 28 ± 7 pg/ml to a mean peak value, at 60 min of 57 ± 11 pg/ml. When glucose was taken by mouth a significant but smaller rise was seen, but intravenous glucose caused no significant change in plasma somatostatin. A rise in circulating somatostatin after feeding has not previously been demonstrated in normal man and it is suggested that somatostatin may have an important endocrine role in the gut.

Topical Corticosteroids: Clinical Pharmacology and Therapeutic Use

Abstract: The development of topical corticosteroids has enabled many dermatoses to be more effectively treated than previously, but there is also no doubt that misuse of these preparations can lead to troublesome local effects and potentially serious systemic problems. The most effective assay for comparing different compounds has been their vasoconstrictive activity, and this on the whole correlates well with clinical effect. To be effective, corticosteroid must be absorbed and the importance of concentration, occlusion, the type of vehicle, added penetrants such as urea and the anatomical site, on the amount of absorption and therefore on clinical activity has been demonstrated. Ointments have been shown to be more effective than creams but because of the considerable choice of potencies now available most dermatologists tend to prescribe the different formulations according to the wishes of the patient. For the same reason, dilution of the commercially marketed preparations is now not generally recommended. The main therapeutic activity of topical corticosteroids is their nonspecific anti-inflammatory effect, thought to be primarily a result of their action on the chemical mediators of inflammation. They have also been shown to be antimitotic which may well be relevant not only to the treatment of scaling dermatoses but also to their dermal thinning effect resulting from inhibition of fibroblasts. Combinations of corticosteroids with antibacterial and antifungal agents have been shown to be very effective in flexural eruptions and secondarily infected dermatoses. As a general rule, the use of topical corticosteroids in outpatients, unless badly misused, is not associated with any significant risk of adrenal axis suppression, but care must be exercised as to the amount prescribed, especially if large areas of the body are to be treated with highly potent preparations. Certain groups such as young children and patients with liver failure, and certain anatomical sites such as the flexures and face appear much more prone to side effects, and in these cases mild or moderate compounds should be used in preference to the stronger preparations.

Characterisation of an adrenal zona glomerulosa-stimulating component of posterior pituitary extracts as alpha-MSH.

Abstract: The secretion of aldosterone from the zona glomerulosa of the mammalian adrenal cortex is stimulated by ACTH, potassium, angiotensin II and III, growth hormone, serotonin and E series prostaglandins1–7. Some experimental and clinical studies suggest that additional stimulants of the zona glomerulosa must exist, possibly including pituitary factors other than ACTH6,8–13. The possibility that posterior pituitary extracts may contain a zona glomerulosa stimulant was first suggested 20 years ago14,15, but has since received little attention. We describe here the purification from posterior pituitary extracts of activities that stimulate rat glomerulosa cells and whole tissue in vitro. One of the active compounds has been identified as α-MSH (melano-cyte stimulating hormone).

An assessment of glucose intolerance in acromegaly and its response to medical treatment.

Abstract: The prevalence of abnormal carbohydrate tolerance has been assessed in sixty‐nine acromegalic patients using six different criteria for the definition of diabetes mellitus. Family history, HLA status and the incidence of pancreatic islet cell antibodies have been documented and the effect of 3 months therapy with bromocriptine on oral glucose tolerance has been assessed in sixty‐one patients.

Ethnic minorities and psychiatric services.

Abstract: Black psychiatric out-patients appear to be more likely to receive various physical treatments than do British born patients or white immigrants: major tranquillisers and electroconvulsive therapy. Both black patients and white immigrants are more likely to receive intramuscular medication than the British born and have a pattern of out-patient attendance which involves self-referrals, missed appointments and being seen on booked appointments by the most junior members of the therapeutic team. These findings cannot all be adequately interpreted as the result of demographic differences or differing conceptions of mental illness and readiness to seek treatment. They appear to involve either (a) Differences in psychiatric phenomenology which have not been recognised or (b) Stereotyped attitudes of mental health professionals.

In vitro effects of high molecular weight forms of ACTH on the fetal sheep adrenal

Abstract: The direct involvement of the pituitary–adrenal axis in birth has been well established, at least in sheep, and its removal prolongs pregnancy1,2. As part of the process the fetal sheep adrenal grows rapidly during the 10–15 d prepartum and is associates with a large rise in the plasma corticosteroid concentration3,4. This does not seem to result from an increased ACTH secretion5,6. The fetal adrenal in vivo seems refractory to circulating ACTH and shows poor response to elevation of plasma concentration1,2,7–9. Thus the signal for the adrenal hypertrophy and the initiation of parturition remains unclear. The responsiveness of the fetal adrenal to ACTH has been re-examined using isolated adrenal cells. The study shows that in the fetal sheep these are not inherently unresponsive to ACTH, but that high-molecular-weight forms of ACTH block the action of ACTH1–39. These peptides may be responsible for controlling the activity of the adrenal in situ.

Diphosphonates inhibit bone resorption by macrophages in vitro.

Abstract: The diphosphonates are a group of synthetic compounds which are adsorbed onto hydroxyapatite crystal surfaces and inhibit both the growth and dissolution of these crystals. They also inhibit mineralisation and resorption of bone in vivo. The effects of diphosphonates were tested on the attachment of macrophages to bone and on the dissolution of bone mineral by macrophages. Attachment was unaffected but resorption was inhibited. Diphosphonates were found to be cytotoxic at much lower concentrations when bone mineral was present, and the most likely explanation for the effects of diphosphonate on bone resorption is that the drug is adsorbed onto the mineral surface where it reaches cytotoxic concentrations.

Renal function in lithium and non-lithium treated patients with affective disorders.

Abstract: Renal function was examined in 101 patients maintained on sustained-release lithium carbonate for periods ranging from 1 to 12.5 years. A control group of patients with affective disorders who had never been given lithium was also investigated as well as a control group of normal subjects of comparable age and sex. Creatinine clearance, serum creatinine, maximum urine osmolality after DDAVP administration, urine and plasma β2-micro-globulin and the urinary excretion of N-acetyl-β-glucosaminidase were not significantly different between patients on lithium and depressed patients never on lithium. Side effects that have been related to lithium therapy were not correlated with duration of lithium therapy. It is concluded that there was little evidence of a serious renal functional impairment attributable to lithium therapy.