Opioid binding in DYT1 primary torsion dystonia: an 11C-diprenorphine PET study.

The opioid transmitters enkephalin and dynorphin are known to regulate pallidal output and consequently cortical excitability. Indeed, abnormal basal ganglia opioid transmission has been reported in several involuntary movement disorders, including levodopa-induced dyskinesias in Parkinson's disease (PD), tardive dyskinesias/dystonia, Huntington's disease, and Tourette's syndrome. Moreover, a previous 11C-diprenorphine PET study investigating levodopa-induced dyskinesias found reduced opioid receptor availability in PD with but not without dyskinesias. We wished to investigate if a similar alteration in basal ganglia opioid binding was present in DYT1 primary torsion dystonia (PTD). Regional cerebral 11C-diprenorphine binding was investigated in 7 manifesting carriers of the DYT1 gene and 15 age-matched normal controls using a region-of-interest (ROI) approach and statistical parametric mapping (SPM). No difference in regional mean 11C-diprenorphine binding was found between DYT1-PTD and controls, and no correlation between the severity of dystonia and opioid binding was seen. We conclude that aberrant opioid transmission is unlikely to be present in DYT1-PTD and altered opioid transmission is not a common mechanism underlying all disorders of involuntary movement.     

Selachyl alcohol as an oral antihypertensive agent: a preliminary note

Selachyl alcohol (SA) is a mono-oleyl glyceryl ether. It has certain biologic activities similar to those of the antihypertensive neutral renomedullary lipid (ANRL) derived from the renal papilla and its renomedullary interstitial cells (RIC). These include a vaso-depressor effect following bolus injection and a requirement for hepatic activation for the development of biological activity. In view of this similarity to ANRL, it appeared worthwhile to test the antihypertensive action of SA when given via the GI tract. Accordingly, pure SA was given either by gavage or by tube into the stomach or duodenum of one-kidney, one-clip hypertensive rats (5-10 mg per dose). The role of hepatic activation was demonstrated by comparing the BP response to bolus injection of SA and ANRL with and without the presence of an intact circulation to the liver. Administration of SA via the GI tract resulted in a significant decline in BP without tachycardia or weight loss. In the absence of a circulation to the liver, neither SA nor ANRL was active. SA appears to be an effective antihypertensive agent when given via the GI tract.     

Survival of corneal endothelium in McCarey-Kaufman (M-K) medium subjected to agitation

Studies were made comparing the corneal endothelium of bisected human corneas; one half of each was mechanically agitated in McCarey-Kaufman (M-K) medium, while the other half remained static in M-K medium for an equal period of time. Scanning electron microscopic (SEM) analysis of the corneal endothelium suggested that the endothelium of the corneas undergoing agitation does not show deterioration in morphology when compared with the non-agitated group. This finding is significant as donor corneas are now being transported in greater numbers.     

Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients

High serum fluoride (F-) in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD) is associated with risk of renal osteodystrophy and other bone changes. This study was done to determine F- in normal healthy controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l. Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such correlation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal osteodystrophy.      

Focal testicular infarction from laparoscopic inguinal hernia repair.

A 53-year-old Caucasian male underwent laparoscopic total extraperitoneal repair of a right indirect inguinal hernia. Postoperatively, the patient developed right testicular swelling and pain that increased over the course of a week. On examination, the patient was found to have a tender, swollen, high-riding testicle, and testicular torsion was of main concern. Doppler sonography and testicular scan suggested an infarction only to the upper pole of the right testicle. Subsequent exploration of the right testicle revealed a hydrocele and focal ischemia to the upper pole of the right testicle. Intraoperative Doppler study and a urology consultation were obtained with an initial impression of possible intermittent torsion. This report describes a rare complication seen in laparoscopic inguinal hernia repairs.     

Placental p,p''-dichlorodiphenyldichloroethylene and cord blood immune markers

Placental p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) concentration and cord blood atopic markers were determined in 19 neonates. Increased placental p,p'-DDE was associated with a statistically significant increase in cord plasma interleukin (IL)-13. Furthermore, both cord plasma IL-4/interferon (IFN)-gamma and IL-13/IFN-gamma ratios were significantly positively associated with placental p,p'-DDE concentration.     

Cricoid split for subglottic stenosis in infancy

Historically, tracheostomy has been used for infants with airway obstruction caused by congenital or acquired subglottic stenosis. Postoperative morbidity and mortality with this provisional operation led Cotton, in 1980, to substitute anterior cricoid split as the primary definitive procedure. Within the past three years, anterior cricoid split has been performed in 4 infants, aged 3 to 9 months, with acquired (3 patients) or congenital (1 patient) subglottic stenosis requiring ventilation through an endotracheal tube. Following cricoid split, the trachea is stented for 12 to 14 days by a nasotracheal tube, with extubation and rigid bronchoscopy in the operating room with the patient under anesthesia to confirm healing and patency. During an 18- to 24-month follow-up in these 4 patients, morbidity has been minimal, patency has persisted, and stridor has not recurred. Accordingly, a conclusive operation, cricoid split, rather than a temporizing tracheostomy may be employed for certain obstructive tracheal lesions early in life.     

Neurometabolism of active neuropsychiatric lupus determined with proton MR spectroscopy.

PURPOSETo determine the neurometabolism of patients with active neuropsychiatric systemic lupus erythematosus (NPSLE) by using proton MR spectroscopy.METHODSThirty-six patients with SLE and eight control subjects were studied with proton MR spectroscopy to measure brain metabolites. Peaks from N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and at 1.3 parts per million (ppm) lipid, macromolecules, and lactate were measured. Patients were classified as having major NPSLE (seizures, psychosis, major cognitive dysfunction, delirium, stroke, or coma) (n = 15) or minor NPSLE (headache, minor affective disorder, or minor cognitive disorder) (n = 21). Patients with major NPSLE were severely ill and hospitalized.RESULTSSLE patients had lower NAA and increased metabolites at 1.3 ppm than did control subjects (NAA/Cr(SLE) = 1.90 +/- 0.35, NAA/Cr(Control) = 2.16 +/- 0.26; 1.3 ppm/Cr(SLE) = 0.49 +/- 0.41, 1.3 ppm/Cr(Control) = 0.27 +/- 0.05). NAA/Cr in patients with current or prior major NPSLE was lower than in patients without major NPSLE. Increased peaks at 1.3 ppm were present in all SLE subgroups, but particularly in patients with major NPSLE. These resonances were not evident at an echo time of 136, indicating that these signals were not lactate.CONCLUSIONMajor NPSLE, past or present, is associated with decreased levels of NAA. Elevated peaks around 1.3 ppm do not represent lactate even in severely ill patients, indicating that global ischemia is not characteristic of NPSLE. Neurochemical markers determined by MR spectroscopy may be useful for determining activity and degree of brain injury in NPSLE.     

Strangulation of the Colon Complicating Acute Pancreatitis

We report a patient with alcohol-induced necrotizing pancreatitis who developed a severe ileus followed by incarceration of a portion of the transverse colon within a ventral hernia. Laparotomy 9 days after the onset of symptoms revealed infarction of the transverse colon and infection of the pancreas. This is the first report of a case of acute pancreatitis that led to a strangulated ventral hernia of the colon. We believe that the enteric organisms that infected the pancreas originated in the incarcerated transverse colon.     

Efficacy and safety of xaliproden in amyotrophic lateral sclerosis: results of two phase III trials.

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and fatal motor neuron disease. We carried out two randomized, double-blind, placebo-controlled, multi-centre, multi-national studies with xaliproden (a drug with neurotrophic effect) to assess drug efficacy and safety at two doses. Patients with clinically probable or definite ALS of more than 6 months and less than 5 years duration were randomly assigned to placebo, 1 mg or 2 mg xaliproden orally once daily as monotherapy in Study 1 (n=867); or to the same regimen with addition of riluzole 50 mg bid background therapy in Study 2 (n=1210 patients). The two primary endpoints were defined as: 1. Time to death, tracheostomy, or permanent assisted ventilation (DTP), and 2. Time to vital capacity (VC)<50% or DTP before (log-rank test) and after adjustment using a Cox proportional hazard model for prespecified prognostic factors. Secondary endpoints were rates of change of various functional measures. In Study 1, primary outcome measures did not reach statistical significance. For the 2 mg group, for time to VC<50% analysis (without DTP) a significant 30% RRR was obtained (95% confidence interval [CI]: 8.46, P=0.009). In Study 2, no significant results were obtained. However, there was a trend in favour of add-on 1 mg dose xaliproden vs. placebo (RRR 15% [-6.31, ns] for time to VC<50%; RRR 12% [CI: -6.27, ns] for time to VC<50% or DTP). Adjusted RR ratios were consistently more favourable for the xaliproden groups. Tolerability was good, and dose-dependent side effects were largely associated with the serotonergic properties of xaliproden. An effect of xaliproden on functional parameters, especially VC, was noted. Although this effect did not reach statistical significance, xaliproden had a small effect on clinically noteworthy aspects of disease progression in ALS.