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Biomedical subjects

R R Abraham

Publications and source records attributed to R R Abraham.

32 records · Page 2Linked to original sources

The measurement and characterisation by high pressure liquid chromatography of immunoreactive alpha-melanocyte stimulating hormone in human plasma.

Immunoreactive alpha-MSH was found in human plasma and in normal subjects ranged from less than 10-45 pg/ml. Plasma alpha-MSH concentrations were within the normal range in 13 out of 15 subjects during the last trimester of normal pregnancy and only just outside the normal range in the remaining two. Elevated plasma alpha-MSH concentrations were found in 6 of the 11 patients with Nelson's syndrome and in 10 of the 11 patients with pituitary dependent Cushing's disease. Separation on high pressure liquid chromatography (HPLC) revealed two major peaks of immunoreactivity. These peaks, which were identified as des-acetyl alpha-MSH and alpha-MSH were similar in size in normal subjects and Cushing's disease. In Nelson's syndrome, on the other hand, there was a greater proportion of des-acetyl alpha-MSH and it is possible that this peptide is secreted from tumour cells of anterior lobe origin. Although there was no correlation between the circulating alpha-MSH and the degree of pigmentation the high concentrations of plasma immunoreactive alpha-MSH in Cushing's disease and the HPLC profiles in Nelson's syndrome could provide useful information as to the localization of the defects in these particular disorders.

Adolescent↗

The effects of triiodothyronine on energy expenditure, nitrogen balance and rates of weight and fat loss in obese patients during prolonged caloric restriction.

We studied ten obese patients on prolonged caloric restriction by metabolic balance techniques two weeks before and two weeks after the start of treatment with triiodothyronine (T3) (0.36-1.01 micrograms/kg/d). The rate of weight, nitrogen and fat loss calculated from metabolic balance increased during T3 therapy and these effects were maximal in the second week of treatment. In seven patients studied continuously for four weeks on T3 therapy, the rates of weight and fat loss during the fourth week of treatment were not significantly different from pretreatment values while nitrogen loss was still significantly greater. The increase in nitrogen loss, studied after the period of adaptation to caloric restriction, implies that prolonged treatment with T3 can result in significant losses of lean tissue in addition to that resulting from caloric restriction alone. Mean weight loss increased by 92 g/d during T3 therapy. T3 significantly increased the metabolic rate as measured by two other independent measures: the resting energy expenditure (REE), measured by indirect calorimetry (fourteen patients), and the sleeping heart rate (six patients).

Adolescent↗

A double blind placebo controlled trial of mixed gangliosides in diabetic peripheral and autonomic neuropathy.

Twenty-six patients with signs or symptoms of diabetic neuropathy who also had motor or sensory neurophysiological abnormalities, were intensively studied in the first double-blind, placebo controlled trial of a ganglioside mixture in the U.K. (Cronassial, Fidia Farmaceutici, Abano Terme, Italy; 6 weeks of 20 mg daily intramuscularly). Diabetes control was good in both groups and there was no deterioration in either group during the course of the trial. Of the five neurophysiological parameters measured - the motor nerve compound action potential, motor nerve conduction velocity and minimum f wave latency of the common peroneal nerve and the sensory action potential and conduction velocity of the sural nerve - only the mean motor nerve action potential and conduction velocity increased though the changes were not significant. Four patients showed improvements of greater than 1.0 mV after treatment with Cronassial while none of the placebo group did so (p less than 0.05). Of the four patients who showed dramatic improvements in motor nerve action potentials, three also showed improvements in motor nerve conduction velocity. There were no significant changes in three tests of autonomic function after Cronassial therapy (orthostatic tilt reactions, single deep breath and Valsalva maneuver). Four patients in the Cronassial group (not those showing neurophysiological improvement) but only one in the placebo group reported marked improvements in their symptomatic complaints after treatment. We conclude that Cronassial is a promising new drug for the treatment of diabetic peripheral neuropathy with clear benefits for some patients.

Action Potentials↗

The evaluation of sodium valproate in the treatment of Nelson's syndrome.

It has previously been reported that sodium valproate (Epilim) lowers plasma ACTH levels in Nelson's syndrome. This report describes further experience with its use. Ten patients with Nelson's syndrome were treated with sodium valproate (600-1200 mg/day) for 5-32 weeks. Plasma ACTH was measured by cytochemical methods and RIA. Initial treatment for 5-12 weeks significantly (P less than 0.005) lowered plasma ACTH from a pretreatment mean of 2460 +/- 1870 ng/liter to 480 +/- 330 ng/liter, and the ACTH circadian rhythm was restored in two patients. On discontinuing treatment, plasma ACTH levels remained suppressed for 3 weeks and rose to pretreatment values in 5-12 weeks. Two patients' plasma ACTH levels failed to show a second response to treatment, while a third patient had a favorable second response to treatment over 32 weeks. In six patients, skin pigmentation lightened with treatment, and in one patient, a reduction in size of a pituitary microadenoma, demonstrated radiographically, occurred with treatment. gamma-Aminobutyric acid and sodium valproate were shown to be ineffective in inhibiting ACTH secretion from cultured pituitary tumor cells from a patient with Nelson's syndrome. The results show that sodium valproate is effective in some cases of Nelson's syndrome. We suggest that it reduces the hypersecretion of ACTH by enhancing gamma-aminobutyric acid function in the hypothalamus, thereby inhibiting the release of corticotropin-releasing factor.

Adrenocorticotropic Hormone↗

Effect of treatment with sodium valproate and diazepam on plasma corticotropin in Nelson's syndrome.

Six patients with Nelson's syndrome were given sodium valproate with or without diazepam for 3 or 5 weeks. Initial high plasma adrenocorticotropic hormone (ACTH) concentrations were greatly reduced by treatment and returned to high levels when treatment was stopped. Diazepam did not add significantly to the effects of sodium valproate alone. Three patients reported a decrease in the severity and frequency of headaches while on sodium valproate. In five patients abnormal skin pigmentation was reduced. Sodium valproate is a gamma-aminobutyric acid (GABA) transaminase inhibitor and it is suggested that the drug raises GABA levels in the hypothalamus and that this is responsible for the reduction in ACTH secretion. The data are consistent with the hypothesis that Nelson's syndrome is a neuroendocrine disease caused by a deficiency in the hypothalamic GABA-ergic system.

Adrenocorticotropic Hormone↗

Protein turnover in acute and chronic liver disease.

The method of constant infusion of U14C tyrosine tracer was used to measure whole body protein turnover in 24 patients with liver disease of varying severity. Whilst on a basic diet of glucose alone (5 g/hr), protein turnover and endogenous breakdown was significantly elevated in patients with cirrhosis and fulminant hepatic failure (F.H.F.), breakdown rising to 700 g/d greater than normal in F.H.F. In addition plasma aromatic aminoacids were significantly elevated and positively associated with the increases in endogenous protein breakdown (r = 0.78, p less than 0.05). Fourteen patients had a second infusion after dietary supplementation with either complete aminoacids (3 g/hr, n = 8) or branched chain aminoacids (BCAA, 4 g/hr, n = 6). The complete mixture did not worsen encephalopathy, improved the plasma aminoacid pattern, reduced protein breakdown and resulted in positive aminoacid balance. The BCAA supplements significantly reduced protein oxidation and endogenous breakdown. The results indicate that protein restriction in cirrhosis and fulminant hepatic failure will not significantly affect the load of aminoacids on the liver, nor their accumulation in plasma. Nutritional support of such patients should therefore include 40 - 60 g. protein per day to prevent protein depletion, and hypertonic glucose and insulin to suppress catabolism. BCAA supplementation may play a useful supportive role in increasing the utilisable nitrogen content of the diet and further suppressing catabolism.

Acute Disease↗

Controlled clinical trial of a new non-calorigenic sweetening agent.

In a controlled trial of a double-blind cross-over design, it has been shown that "Marvie', a non-calorigenic sweetener containing 58 per cent maltitol by weight, is an effective sweetener which has no influence on routine haematological and biochemical parameters. The dose that could be tolerated without undesirable symptoms was between 20 and 30 g per day. Above this dose, flatus production with abdominal discomfort could limit tolerance to this sweetening agent.

Adult↗

Absence of the sensory action potential of the medial plantar nerve: a sensitive indicator of diabetic neuropathy.

The sensory action potential of the medial plantar nerve (MPSAP), using needle recording electrodes subcutaneously, was measured in 119 patients with diabetes ((75 insulin-dependent, mean age 43.7 +/- 1.2 SEM years (range 15-73) and in 75 age-matched normal subjects (mean age 44.0 +/- 1.5 years (range 19-75)). The MPSAP was not detectable in 56 out of 119 diabetics; there was only one absent MPSAP response in the normal group, in a patient aged 71 years. Diabetics with absent MPSAP responses were significantly older, heavier and taller and had diabetes of longer duration. The amplitudes and conduction velocities in the sural, common peroneal, and tibial nerves were also significantly smaller. The amplitudes of the MPSAP, when present, correlated with height (r = -0.47(43), p less than 0.001), weight (r = -0.44(43), p less than 0.001), the distal tibial compound motor action potential (r = 0.37(43), p less than 0.01), and the common peroneal nerve conduction velocity (r = 0.32(43), p less than 0.02). The MPSAP was always absent if the sural SAP was less than 5uV but also in 14/59 patients whose sural SAP amplitudes were within 1 sd of the normal mean (greater than 10.7 uV). The MPSAP was absent at a younger age and with diabetes of shorter duration than is seen with unrecordable sural SAPs. It may therefore represent an early manifestation of neuropathy in diabetes.

Action Potentials↗

Small- and large-fiber involvement in early diabetic neuropathy: a study with the medial plantar response and sensory thresholds.

Small- and large-fiber function in diabetic neuropathy was studied in 68 patients (mean age 45.4 +/- 12.9 yr; 27 type I and 41 type II diabetics) with psychophysical tests of vibration and thermal sensation and neurophysiological measurements, including the medial plantar sensory action potential (MPSAP). Thermal sensitivity at the dorsolateral aspect of the foot (Pfizer thermal tester) correlated significantly with vibration thresholds (Somedic vibrameter) at three sites in the foot and two in the hand. Forty patients had normal sensory thresholds, but 18 of these lacked an MPSAP. Smaller groups had a single abnormal sensory threshold: 12 (18%) had an abnormal vibration threshold, and 24 (35%) had abnormal thermal sensitivity; 8 of the former group and 17 of the latter group lacked an MPSAP response. Only 8 (12%) had both abnormal vibration and thermal sensation (6 without an MPSAP). Fifteen of the 17 symptomatic patients had lost the MPSAP, but there was no consistent pattern of sensory loss. In this relatively young group of diabetics, more patients showed absent MPSAP responses than an abnormality in either sensory test on its own. The MPSAP is frequently absent in patients with no abnormalities in psychophysical tests of peripheral large-fiber function (vibration sensation) and small-fiber function (thermal sensitivity).

Action Potentials↗