Agoraphobics 5 years after imipramine and exposure. Outcome and predictors

Five years after treatment in a controlled trial, in which all had received self-exposure homework, a group of 40 agoraphobic outpatients retained marked improvement in agoraphobia, mood, and free-floating anxiety. Frequency of spontaneous panics decreased as much in those who had placebo and self-exposure as in those who received imipramine and self-exposure. Few patients, however, were completely well at 5 years and over half had received further treatment for agoraphobia during the follow-up. Patients who were still highly phobic at the end of the clinical trial were more often prescribed psychotropic medication during follow-up and remained phobic at 5 years. Phobic improvement had generalized more in those patients with very low than in those with moderate pretreatment Hamilton depression scores. Frequency of initial spontaneous panics did not predict outcome. Improvement in agoraphobia was associated with improved marital adjustment. Those who began with the best marital, work, and social adjustment were more improved in their phobias 5 years later.     

Serum and peritoneal dialysate thyroid hormone levels in patients on continuous ambulatory peritoneal dialysis

Thyroid function tests were performed on 16 clinically euthyroid patients with end-stage renal failure undergoing regular haemodialysis or continuous ambulatory peritoneal dialysis and compared with 8 healthy subjects. The patient groups were carefully matched, especially regarding relative duration of dialysis (mean of 24 months). Total serum thyroxine, total triiodothyronine, free thyroxine, free triiodothyronine and reverse triiodothyronine were significantly lower in both patient groups than control. The thyrothrophin response to the standard thyrotrophin-releasing hormone test was delayed and blunted. Using a novel concentration technique we measured loss of T4 in peritoneal dialysate effluent and found it to be approximately 10% of daily thyroidal T4 release.     

Simple mechanical-chemical systemic pressure-control device

An implantable mechanical-chemical device was constructed to act as a feedback mechanism in controlling the blood pressure. It consisted of a balloon connected to a rubber catheter ending in a slit valve. Flow-pressure curves were derived fromin vitro testings for three valve thresholds (120, 140 and 170 mmHg). Five fast-acting hypotensive drugs subsequently filled the device during 40 noradrenaline infusions in 25 dogs, with the balloon in the abdominal aorta and the catheter in the inferior vena cava. The results were as follows: (i) Following a short initial increase in systolic aortic pressure, significantly lower (p<0·001) than in control experiments, the device prevented any pressure rise above its threshold. (ii) The time needed for pressure lowering at the device's threshold depended on the drug used being 3·34±0·84 (mean ± s.e. in minutes) for sodium nitroprusside, 5·99±0·96 for phentolamin, 11·63±2·97 for hydralazine, 14·54±2·43 for a-methyl-dopa and 23·32±2·07 for diazoxide.     

Morning preprandial plasma ghrelin and catecholamine concentrations in patients with phenylketonuria and normal controls: evidence for catecholamine-mediated ghrelin regulation

Patients with phenylketonuria (PKU) have a diet-controlled deficiency in the conversion of phenylalanine (Phe) to tyrosine (Tyr), leading to decreased production of noradrenaline, adrenaline, and dopamine. Poor diet control results in high plasma Phe and low plasma Tyr and catecholamine concentrations. Ghrelin, a recently described gastrointestinal hormone that is elevated in the fasting state and low in the fed state, is considered a major appetite-stimulating hormone, possibly involved in the generation of obesity and insulin resistance. We evaluated morning preprandial plasma ghrelin levels in 14 diet-controlled and 15 poorly controlled PKU patients and 20 age- and body mass index (BMI)-matched healthy children (controls) and correlated its concentrations with those of Phe and catecholamines as well as with their BMI and 24-h nutrient intake. Plasma ghrelin levels were measured by RIA, plasma catecholamine concentrations were determined by HPLC with electrochemical detection, and Phe and Tyr levels were measured in an amino acid analyzer. The ghrelin concentration (744 +/- 25 ng/liter) in diet-controlled patients did not differ from that in controls (802 +/- 26 ng/liter; P > 0.05). On the contrary, the ghrelin concentration was significantly reduced in poorly controlled patients (353 +/- 23 ng/liter; P < 0.0001). Ghrelin correlated negatively with Phe in all three groups, whereas it correlated positively with catecholamine levels and energy intake and negatively with BMI only in diet-controlled patients and controls. We conclude that ghrelin secretion may receive positive direct or indirect input from catecholamines. The absence of a correlation between ghrelin and catecholamines, energy intake, or BMI in PKU patients on an inadequate diet may be due to dysregulation of their neuroendocrine system and might be affected by high Phe levels in the stomach and/or central nervous system.     

Induction of immune tolerance in patients with hemophilia A and inhibitors treated with porcine VIIIC by home therapy

Home therapy with porcine factor VIIIC was safe and effective when administered to five hemophilic patients over periods of 8 1/2, 6, 4, 3 1/2, and 2 years. No significant transfusion reactions occurred. Before treatment with porcine factor VIIIC, all five had high-level, high- responding anti-human VIIIC inhibitors initially lacking anti-porcine factor VIIIC activity. Although specific anti-porcine VIIIC inhibitors arose in all patients, these were generally transient, and only one patient became refractory to treatment. We believe that porcine factor VIIIC is the treatment of choice in patients whose inhibitors do not cross-react. All five patients lost their original anti-human VIIIC inhibitors after starting treatment with porcine VIIIC, permitting the reintroduction of human VIIIC in three of them. There has been no recurrence of anti-human VIIIC inhibitor activity during 2 to 3 years of regular treatment with human VIIIC in these patients. This suggests that tolerance to human VIIIC has arisen as a result of treatment with porcine VIIIC. Porcine VIIIC may have a role in the desensitization of some factor VIIIC inhibitor patients.