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The effect of month-long naltrexone (NTX) treatment at a daily oral dose of 0.5 mg/kg/day was contrasted with placebo (PLC) in a double-blind study with conjoint clinical and biochemical evaluations of therapeutic effects. Modest clinical benefits were achieved with both PLC and NTX, with marginally better overall results following NTX, and degree of improvement appeared to be related to plasma chemical profiles. Massively elevated levels of beta-endorphin were observed in all children with assays using C-terminal antibody but not with an N-terminal antibody assay. In addition, 70% of the children exhibited abnormally low levels of adrenocorticotropic hormone, and smaller subsets exhibited elevated norepinephrine (60%), arginine-vasopressin (50%), and serotonin (20%). The best clinical responders exhibited the clearest normalization of the elevated plasma chemistries, especially in C-terminal-beta-endorphin and serotonin. There was some evidence of therapeutic carry-over effects in both clinical and biochemical measures in those children who received NTX before PLC. The results suggest that NTX only benefits a subgroup of autistic children, who may be identified by the presence of certain plasma abnormalities. These results suggest a possible linkage between abnormal plasma chemistries, especially those related to the pro-opiomelanocortin system, and autistic symptoms.

Background/aims: In the gastric mucosa of Helicobacter pylori-infected subjects, we previously detected N alpha-methyl histamine (N alpha-MeHA), a minor catabolite of histamine and a potent agonist of histamine H3 receptors. The origin of N alpha-MeHA and its effects on gastric histamine and somatostatin in infected subjects were investigated., Methods: Ten noninfected patients and 13 patients with intense colonization were compared. N alpha-MeHA content and its synthetic enzyme activity, N alpha-histamine methyltransferase, binding of [3H]N alpha-MeHA, histamine and somatostatin contents, and histidine decarboxylase activity were assayed in antral and fundic biopsy specimens and in cultured H. pylori strains., Results: Gastric histamine and somatostatin contents as well as histidine decarboxylase activity were decreased in infected patients and were restored to normal after antimicrobial treatment. Both N alpha-MeHA and N alpha-histamine methyltransferase activity were present in the mucosa of infected patients and in cultured strains and were very low in noninfected patients or after eradication of H. pylori. [3H]N alpha-MeHA bound to gastric mucosa but not to cultured strains. The [3H]N alpha-MeHA specific binding sites were characterized as H3 receptors. The amount of bound [3H]N alpha-MeHA seemed correlated positively with somatostatin content and histidine decarboxylase activity and negatively with N alpha-MeHA content and N alpha-histamine methyltransferase activity., Conclusions: H. pylori is the main source of gastric N alpha-MeHA that may lower histidine decarboxylase activity and somatostatin content through H3 receptors.

Objective: The authors investigated whether there is excessive opioid activity in infantile autism by measuring plasma beta-endorphin in patients with autism compared with patients who had Rett's syndrome and normal comparison subjects., Methods: Radioimmunoassays for beta-endorphin using C-terminally and N-terminally directed antisera were applied to plasma samples from 67 children who met both DSM-III-R and ICD-10 diagnostic criteria for infantile autism, 22 girls with Rett's syndrome, and 67 normal children matched in age and sex with the children with autism., Results: Median N-terminally directed beta-endorphin immunoreactivity appeared to be slightly lower in subjects with autism (7 pg/ml) and clearly higher in the girls with Rett's syndrome (40 pg/ml) than in the comparison subjects (9 pg/ml). Median C-terminally directed beta-endorphin immunoreactivity was higher in the girls with Rett's syndrome (35 pg/ml) and much higher in patients with autism (70 pg/ml) than in comparison subjects (8 pg/ml)., Conclusions: These findings demonstrate the existence of a wide discrepancy between C- and N-terminally directed beta-endorphin immunoreactivity among children with autism. Despite the fact that the nature of the antigen recognized in the plasma of autistic children by the C-terminally directed anti-beta-endorphin serum remains to be characterized, the difference between C- and N-terminally directed beta-endorphin immunoreactivity might suggest an abnormal processing of the pro-opiomelanocortin gene in infantile autism.

The opioid hypothesis suggests that childhood autism may result from excessive brain opioid activity during neonatal period which may constitutionally inhibit social motivation, yielding autistic isolation and aloofness (Panksepp, 1979). This hypothesis has now received strong support and is currently based on three types of arguments: (1) similarity between autistic symptomatology and abnormal behaviors induced in young animals by injections of exogenous opioids, such as increasing social aloofness and decreasing social vocalization; (2) direct biochemical evidence of abnormalities of peripheral endogenous opioids being reported in autism and (3) therapeutic effects of the long lasting opioid receptor blocking agent naltrexone in autism. In this article, we give description of open and double-blind studies of naltrexone in autism. Naltrexone has been tested in several open studies. We performed an open trial with naltrexone in 2 autistic girls, displaying serious self-injurious behavior, reduced crying and a marked preference for salty and spicy foods, symptoms that could be related to a dysfunction of the opioid system. With dosages of 1 mg/kg/day, we observed an immediate reduction of hyperactivity, self-injurious behavior and aggressiveness, while attention improved. In addition, social behaviors, smiling, social seeking behaviors and play interactions increased (Leboyer, Bouvard et Dugas, 1988). Campbell et al. (1988) has also reported a tranquilizing and a stimulating effect in 6 out of 8 children with autism. We did confirm these preliminary results in a double-blind study performed on 4 children with autism. In a cross-over double-blind study, three dosages of naltrexone (0.5, 1 and 2 mg/kg/day) and placebo were compared.(ABSTRACT TRUNCATED AT 250 WORDS)

A new procedure for serum inorganic sulphate determination is described. The method is simple, accurate and highly reproducible. It is based on radioisotopic dilution of 35S-sulphate by protein-free, phosphate-free serum. The decrease in initial 35S-sulphate specific activity (corresponding to added serum sulphate) is determined in the supernatant after partial precipitation of sulphate by barium ion. Serum sulphate is computed thereafter from a standard curve. Recovery of added sulphate from dialysed or undialysed serum was 100%. The intra- and interassay coefficients of variation were 3.5% and 4.1%, respectively. The serum sulphate concentration measured by this method in 93 normal subjects was 400 +/- 90 mumol/l (mean +/- SD), which agreed with the values reported in the literature. Serum sulphate did not correlate with sex (p greater than 0.40, n = 93), but a significant correlation with age was observed (r = 0.25, p less than 0.02, n = 93).

Marked variations in the same individual of serum iron levels may be due to a circadian rhythm. We determined the reference values of serum iron in a population of blood donors who had no blood disease. The very wide reference interval found (0.47 to 1.75 mg/l in man and 0.36 to 1.66 mg/l in women) was due to physiological variations rather than analytical variations. We also demonstrated in individuals with a normal life rhythm, a circadian rhythm for iron with maximal levels in the morning (8 to 12) and minimal levels in the evening (8 p.m. to midnight) the ratio of these levels is usually between 1.5 and 2, but may reach much higher figures. On the other hand, the total fixation capacity varies little over 24 hours. In night workers, one may note a displacement of the cycle with a maximum towards 8 p.m. a minimum at 8 a.m. In diabetics, the circadian rhythm exists but with a lower amplitued than in healthy subjects. In a few cases a hemochromatosis, one may note disappearance of the cycle.

The particularities of percutaneous absorption of a natural androgen, 5 alpha-dihydrotestosterone, were evaluated in substitutive androgen therapy in masculine hypogonadism. Nine men presenting idiopathic haemochromatosis complicated by severe hypogonadism were treated with percutaneous administration of 5 alpha-dihydrotestosterone (125 mg/day) for 5 months. Plasma levels of 5 alpha-dihydrotestosterone and 5 alpha-androstane-3 alpha, 17 beta-diol are greatly increased by treatment (from 0.86 to 18.39 nmol/l and 0.16 to 3.40 nmol/l, respectively). There is no modification of testosterone and oestradiol-17 beta. Double blind study demonstrated the direct stimulating effect of 5 alpha-dihydrotestosterone on sexual behaviour and psychism. Hepatic and metabolic tolerance was excellent in these patients, despite the preceding deleterious effects of the iron excess. The percutaneous route is original, practical and improves the androgen therapy of hypogonadism in men.

We report the effects of sublingual absorption of a single dose (0.5 mg) of oestradiol-17 beta (E2) in 8 post-menopausal women, on plasma E2 and oestrone (E1), urine elimination of total E2 + E1 and on plasma FSH and LH. The results show that sublingual absorption of E2 occurs and that plasma concentrations of E2 obtained (between 133.2 to 320 pmol/l) in this way were higher than those obtained after percutaneous absorption of a single dose (3 mg) of E2. The ratio E1/E2 in plasma is close to that of pre-menopausal women.

The aim of this prospective, randomized, double-blind, placebo controlled study was to investigate the effect of nifedipine on carbohydrate metabolism in diabetic patients after a 3-day and a 3-month course of treatment. Sixteen non obese, well controlled non-insulin dependent diabetics, (HbA1 less than 10%), with moderate untreated hypertension were divided in two groups: nifedipine (group N, 8 patients) and placebo (group P, 8 patients). An oral glucose tolerance test (OGTT, 75 g glucose) and an arginine infusion were performed before, after a 3-day, and a 3-month course, either of nifedipine 30 mg/D or placebo. Blood samples obtained during OGTT were assayed for glucose and insulin, and during arginine infusion for insulin, glucagon and growth hormone. The differences between basal and peak values during tests were compared between both groups before and after treatment using Wilcoxon's rank sum test. Neither acute nor chronic administration of nifedipine or placebo modified the glucose tolerance. However, basal insulin levels were reduced by 3 month-administration of nifedipine (from 19 +/- 2 micromicrons/ml to 10 +/- 1 micromicrons/ml, p = 0,01). Otherwise the basal and peak hormonal values during tests were not significantly affected by nifedipine either at the start of after 3 months of treatment. These results suggest that nifedipine, when given in standard dosage for 3 months, has minor effects on carbohydrate metabolism in non-insulin dependent diabetic patients.

The bulk of experimental evidence indicates that the APUD series of cells is a distinct system based upon common pathophysiological features. The diffuse nature of this system with elements in the central and peripheral nervous system suggests a more complex interaction of the body's homeostasis than has been established. It is probable that as radioimmunological and radioenzymatic assays become more widely available and standardized, other apudomas will be described. Finally, an understanding of the APUD concept, with its peculiar pluripotential for the production of biogenic amines and peptides, the multicentric nature of the disease and the possibility of multiple cell involvement, is of key importance in managing patients. Studies of the apudomas will also advance the understanding of the normal physiologic interrelationships of the APUD cells.

The anti-hypertensive effect of clonidine is closely related to its central alpha-agonist action. In acute administration, the drug provokes a significant increase in the plasma concentrations of growth hormone (GH). In chronic administration, the effects of clonidine on GH secretion are not well documented. Clonidine was administered at a daily dose of 0,15 to 0,30 mg to 10 non-obese diabetic hypertensive male subjects for at least 3 months. Blood glucose and GH plasma concentrations were determined 15 times during the 24-hour cycle. Blood glucose and GH values recorded before the intake and after stopping the drug, in the basal state, after meals, after measured muscular exercise and during the first stage of sleep could be superimposed when on and off clonidine. The effects of prolonged administration of clonidine on GH secretion thus differ markedly from the effects of acute administration as in non diabetic subjects. The long-term use of clonidine does not induce a chronic increase of GH plasma concentrations which might worsen the evolution of the diabetic microangiopathy.