Nerve biopsy findings in Niemann-Pick type II (NPC)

The severe infantile form of Niemann-Pick disease type II was diagnosed in a 4-year-old girl and confirmed by demonstrating in cultured skin fibroblasts a deficiency of low-density lipoprotein-stimulated cholesterol ester synthesis of < 5% of normal. Electrodiagnostic studies revealed changes of a predominantly demyelinating motor and sensory polyneuropathy. Light microscope and ultrastructural examination of a peroneal nerve biopsy showed unique changes. Compacted myelin sheaths were disproportionately thin with marked globular irregularities in single teased nerve fibres and evidence of chronic demyelination. The majority of axons were preserved but axonal spheroids and cytoskeletal abnormalities akin to neuroaxonal dystrophy were noted. Membrane-bound multilobulated lysosomal inclusions of floccular and electron-dense material were present in Schwann cells (SC), endoneurial fibroblasts, macrophages, pericytes and endothelial cells. SC of myelinated fibres were stuffed with whorls of concentric osmiophilic membranous profiles and electron-lucent material. The findings are diagnostic and differ from those of classical Niemann-Pick disease.     

Sequential metabolic studies of pancreas allograft function in type 1 diabetic recipients.

We have previously shown that the loss of acute first phase insulin secretion precedes pancreas allograft rejection and development of glucose intolerance in Type 1 diabetic patients. In order to examine whether there is a progressive loss of phases of insulin secretion and beta-cell function in technically successful pancreas transplants during the first year, we measured glucose, insulin, and C-peptide responses to physiological (mixed meal) and pharmacological (IV glucose and IV glucagon) stimulation in 27 glucose-tolerant, insulin-independent allograft recipients at 3, 6, and 12 months. Mean +/- SE fasting serum glucose levels were normalized throughout the study period. Postprandial serum glucose profiles tended to increase by 12 months compared to 3 and 6 months, although peak glucose levels were not statistically different. Following pancreas transplantation, basal serum insulin levels were high at 3 months (163 +/- 17 pM), 6 months (165 +/- 22 pM), and 12 months (248 +/- 54 pM, p = NS) in the Type 1 diabetic pancreas allograft recipients when compared to normal (25 +/- 3 pM). We observed slight elevations in postprandial insulin and C-peptide profiles at 12 months compared to 3 and 6 months. Following IV glucose and glucagon stimulation, serum insulin and C-peptide levels as well as phases of insulin release did not differ over the 12-month study period. Similarly, the glucose decay constant (KG) was nearly identical at 3, 6, and 12 months. In summary, 1 year following successful whole cadaveric, heterotopic pancreas transplantation in Type 1 diabetic recipients, fasting serum glucose remains normalized, while postprandial glucose tends to rise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-lasting effect of ceruletide on dyskinesia and monoaminergic neuronal pathways in rats treated with iminodipropionitrile

In a model of dyskinesia induced by the administration of iminodipropionitrile (IDPN) in the rat, we evaluated the effects of ceruletide, an analogue of cholecystokinin, on behavioral abnormalities and monoaminergic neuronal function. Vertical head twitching in the IDPN-treated animals was inhibited for over 5 h following a single subcutaneous dose of 160 micrograms/kg ceruletide. In animals dosed daily for 2 or 3 days, the number of head twitches at 24 h after the last dose was about one-third of the number before treatment. After repeated daily doses of ceruletide for 6 days, the number of head twitches was reduced to low levels and remained significantly below pretreatment levels until the 4th posttreatment day. These results indicate that the inhibition of dyskinesia by ceruletide was long-lasting. Assays of monoaminergic neurotransmitters and their metabolites in various brain regions indicate that an imbalance between dopaminergic and serotonergic neuronal systems plays a major role in the pathogenesis of the IDPN-induced dyskinesia, i.e. the ratio of (DOPAC+HVA)/5-HIAA was significantly greater in the striatum but significantly smaller in the hippocampus of the IDPN-treated vs normal animals. This initially abnormal ratio of (DOPAC+HVA)/5-HIAA in the striatum and hippocampus of IDPN-treated animals returned to normal following treatment with ceruletide, corresponding with the reduction of the head twitching. The alterations in monoaminergic neuronal function induced by repeated administration of ceruletide persisted for at least 3 days, even though its plasma half-life is several minutes. Ceruletide also exerted a marked effect on monoaminergic neuronal function in the IDPN-treated rats, in contrast to only a slight effect in normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Platelet aggregation,disc haemorrhage and progressive loss of visual fields in glaucoma

Platelet aggregationin vitro, deterioration of visual field defects (VFD) and the prevalence of disc haemorrhages (DH) were assessed in 49 patients with primary open angle glaucoma (POAG) and compared with the findings for 67 individuals with suspected glaucoma (GS) in a seven-year follow-up study (range 5.8 to 8.2 years). The percentage patients with spontaneous platelet aggregation (SPA) was higher for POAG patients with visual field deterioration (60%) than both POAG patients without progressive loss of visual fields (12.5%; P<0.005) and those with suspected glaucoma (22.4%; P<0.005). The occurrence of DH was higher among POAG patients with progressive loss of visual field (28%) compared to the GS group (8.4%; P<0.025) and the group of patients consisting of POAG patients without deterioration of VFD and GS (9.9%; P<0.05). DH also occurred more often in patients with low tension glaucoma (41.6%) than in the remaining POAG patients (13.5%; P<0.05). No relation between the patients with SPA and the patients with DH was observed.Abbreviations NPB normal platelet behavior - SPA spontaneous platelet aggregation - DH disc haemorrhage     

The effects of acute and repeated doses of moclobemide on psychomotor performance and cognitive function in healthy elderly volunteers

The effects of moclobemide, a new selective and reversible MAO-A inhibitor, on cognitive function and psychomotor performance were measured in 12 healthy elderly male volunteers (with a mean age of 72.5 years). Subjects received moclobemide 200 mg, amitriptyline (positive internal control) 25 mg or placebo twice daily and were assessed on a battery of psychometric tests on the mornings following the first (acute) day and seventh (sub-chronic) day. The tests were: Choice Reaction Time; Tracking; Critical Flicker Fusion Threshold; Memory Scanning; Continuous Attention Task; the Leeds Sleep Evaluation Questionnaire and a Visual Line Analogue Rating Scale. The results show that amitriptyline produced impairment of cognitive and psychomotor functions. Moclobemide, however, did not disrupt sleep or cause daytime sedation, and remained neutral in the assessment of behavioural toxicity.     

Long-term outcome and complications of children born with meningomyelocele

The long-term functional outcome of 101 children born with meningomyelocele between 1971 and 1981 was assessed, by a combination of retrospective chart review and follow-up assessments. The children had been managed at birth using a process ofnonstandardized selection. Eighty-three of the 101 patients survived after a minimum follow-up of 8.6 years, for a mortality rate of 18%. Forty-four of 83 children (53%) were community ambulators, and this correlated well with the presence of intact quadriceps function. Forty-eight children (58%) attended normal school and were grade-appropriate. Sixty-two of 83 patients (75%) were socially continent of urine, and 71/83 (86%) were socially continent of stool. Hydrocephalus was present in 93 of the 101 children in the study, and 85 children were shunted. Half of the shunted children required a shunt revision in the first year of life, and thereafter the rate of revision decreased, so that after 2 years the risk of revision was approximately 10% per year.     

Comparison of propofol induction with thiopentone or methohexitone in short outpatient general anaesthesia

The per- and post-operative characteristics of three different i.v. anaesthetic induction agents were studied double-blindly in 75 patients admitted for outpatient gynaecological dilatation and curettage. All the patients were premedicated with midazolam 0.1 mg/kg i.m. Induction started with alfentanil 0.015 mg/kg i.v. 60 s before either: propofol 2.2 mg/kg i.v., or thiopentone 4.0 mg/kg i.v., or methohexitone 2.0 mg/kg i.v. All the patients received 66% nitrous oxide in oxygen. The propofol patients were significantly better relaxed and had a higher incidence of hypotension during the procedure. The methohexitone patients had higher pulse rates and a higher frequency of hiccups during the procedure. Propofol induction resulted in a faster awakening of the patients and a better recovery function compared with methohexitone for the first 15 min and compared with thiopentone for the first 240 min after the procedure. Postoperative side-effects were less frequent in the thiopentone group, and minor abdominal pain was significantly more frequent in the propofol group. There was no significant difference between the groups for any variable after 240 min postoperatively.     

Hypothalamic-pituitary-gonadal function in two infants with Smith-Lemli-Opitz syndrome

We report on the hypothalamic-pituitary-gonadal function in 2 male infants with the Smith-Lemli-Opitz (SLO or RSH) syndrome. Both infants had abnormal external genitalia. Basal and LHRH stimulated plasma gonadotropins were normal for age (1 month). Plasma testosterone, androstenedione, and dehydroepiandrosterone sulfate were normal for age and sex. Some forms of congenital adrenal hyperplasia (17,20-desmolase deficiency, 17α-hydroxylase deficiency, and 3β-hydroxysteroid dehydrogenase deficiency) were ruled out by hormonal studies. The endocrinological findings indicate a normal hypothalamic-pituitary-gonadal function and a normal adrenal steroid biosynthesis in these 2 patients. A partial androgen receptor defect causing the genital malformations seems possible in one patient. Whether 5α-reductase deficiency is the cause of the male pseudohermaphroditism in SLO syndrome remains the subject of future studies. © 1992 Wiley-Liss, Inc.     

Human immunodeficiency virus (HIV)-related chronic relapsing inflammatory demyelinating polyneuropathy with multifocal unusual onion bulbs in sural nerve biopsy

Summary This is obviously the first report on a case with a spontaneous sensu strictu relapsing variant of human immunodeficiency virus (HIV)-related polyneuropathy. Its manifestation preceded LAS. Intrathecal HIV-antibodies developed between the most severe third and fourth episode. Analysis of sural nerve biopsy was consistent with a multifocally accentuated chronic inflammatory demyelination, characterized by unusual onion bulb-like Schwann cell formations with irregular voluminous layers, electron density, aggregation of filaments, multiple indented nuclei, and numerous enclosed collagen pockets. A direct or immune-mediated indirect specific influence on Schwann cell morphology by HIV might be discussed. Virus-like particles and ultrastructural markers of HIV were not detectable.     

Caffeine restores regional brain activation in acute hypoglycaemia in healthy volunteers.

AIMS: Caffeine enhances counterregulatory responses to acute hypoglycaemia. Our aim was to explore its effects on cortical function, which are not known at present. METHODS: Regional brain activation during performance of the four-choice reaction time (4CRT) at different levels of complexity was measured using functional magnetic resonance imaging (fMRI) at euglycaemia (5 mmol/l) and hypoglycaemia (2.6 mmol/l) in the presence and absence of caffeine in six healthy right-handed men. RESULTS: During hypoglycaemia, caffeine enhanced adrenaline responses to hypoglycaemia (2.5 +/- 0.7 nmol/l to 4.0 +/- 1.0 nmol/l, P = 0.01) and restored the brain activation response to the non-cued 4CRT, the linear increases in regional brain activation associated with increased task complexity and the ability to respond to a cue that were lost in hypoglycaemia alone. CONCLUSIONS: Caffeine can sustain regional brain activation patterns lost in acute hypoglycaemia, with some restoration of cortical function and enhanced adrenaline responsiveness. A methodology has been established that may help in the development of therapies to protect against severe hypoglycaemia in insulin therapy for patients with diabetes and problematic hypoglycaemia.