Skin biopsy for assessment of autonomic denervation in Parkinson's disease.

Autonomic dysfunction in Parkinson's disease (PD) is considered a late complication of the disease or an adverse effect of anti-parkinsonian medications. Morphological changes are demonstrated only by postmortem examination. The study objective was to evaluate peripheral autonomic neural involvement in PD using punch skin biopsy. The study sample included 22 patients (mean age 50 +/- 7.7 years, mean disease duration 5.3 +/- 3.8 years) and 19 controls. Four-millimeter skin biopsies were immunohistochemically stained with anti-PGP 9.5 antibody. Autonomic innervation of the blood vessels, sweat glands, and erector pili muscles was assessed and rated from 0 (normal) to 2 (severe). Cutaneous autonomic innervation was decreased in patients compared to controls. Semi quantitative analysis demonstrated reduced autonomic innervation of the blood vessels (1.0 +/- 0.8 vs. 0.42 +/- 0.8 in controls; p < 0.02), of sweat glands (0.95 +/- 0.67 vs. 0.47 +/- 0.61; p < 0.02) and of the erector pili muscles (1.06 +/- 0.55 vs 0.21 +/- 0.42; p < 0.001). This method demonstrates that the peripheral autonomic system is affected in PD at early stage of the disease and that autonomic involvement in PD may be more prevalent than previously thought.

Neonatal liver failure and Leigh syndrome possibly due to CoQ-responsive OXPHOS deficiency.

CoQ transfers electrons from complexes I and II of the mitochondrial respiratory chain to complex III. There are very few reports on human CoQ deficiency. The clinical presentation is usually characterized by: epilepsy, muscle weakness, ataxia, cerebellar atrophy, migraine, myogloblinuria and developmental delay. We describe a patient who presented with neonatal liver and pancreatic insufficiency, tyrosinemia and hyperammonemia and later developed sensorineural hearing loss and Leigh syndrome. Liver biopsy revealed markedly reduced complex I+III and II+III. Addition of CoQ to the liver homogenate restored the activities, suggesting CoQ depletion. Histological staining showed prominent bridging; septal fibrosis and widening of portal spaces with prominent mixed inflammatory infiltrate, associated with interface hepatitis, bile duct proliferation with numerous bile plugs. Electron microscopy revealed a large number of mitochondria, which were altered in shape and size, widened and disordered intercristal spaces. This may be the first case of Leigh syndrome with liver and pancreas insufficiency, possibly caused by CoQ responsive oxphos deficiency.

Renoprotective effect of angiotensin II receptor antagonists in experimental chronic renal failure.

We compared the antihypertensive and renoprotective effects of the angiotensin II receptor antagonist losartan and the calcium channel blocker verapamil in the rat with chronic renal failure. One month after five-sixths nephrectomy, male WKY rats were treated for 2 months with either losartan or verapamil. Both resulted in a similar reduction in blood pressure: from 147.1 to 112 mm Hg in losartan-treated and from 155 to 118 mm Hg (p = NS) in verapamil-treated rats. Losartan improved the creatinine clearance (difference + 17.1% as compared with + 6.6% for verapamil, p = 0.039) and prevented the increase in proteinuria: 12.26 +/- (SE) 2.33 mg/day before and 18.48 +/- 2.19 mg/day (p = NS) after therapy in the losartan-treated and 17.27 +/- 2.73 mg/day before and 32.27 +/- 10.29 mg/day after therapy (p = 0.0484) in the verapamil-treated group. In addition, losartan resulted in minimal mesangial proliferation and significantly less glomerular sclerosis and thickening of the small arterial and arteriolar walls. The changes in interstitial fibrosis and tubular hypertrophy, however, were similar in both the verapamil- and losartan-treated groups. Treatment with losartan 1 month after five-sixths nephrectomy in male WKY rats resulted in reduced blood pressure, similar to that of the verapamil-treated group. However, despite similar antihypertensive properties, losartan improved creatinine clearance and reduced proteinuria. The losartan-treated group also had a marked reduction in mesangial proliferation and less glomerular sclerosis and less reduced vascular wall thickness in renal small arteries and arterioles. However, losartan did not totally eliminate nephrosclerosis. The tubular and interstitial changes were fewer in the losartan-treated group. Thus losartan has an additional, although only partial, renoprotective effect when compared with verapamil.

Evaluation of a novel continuous real time (13)C urea breath analyser for Helicobacter pylori.

AIM: To evaluate the sensitivity and specificity of a new (13)C urea breath test, Oridion BreathID, for the diagnosis of Helicobacter pylori. METHODS: A total of 97 consecutive symptomatic patients referred for upper endoscopy were included in the 'pre-therapy' part of the study. After endoscopy the patients were analysed for H. pylori by Oridion BreathID. BreathID continuously sampled the subject's breath for 20 min, and displayed the results on the BreathID screen in real time. Results of the BreathID were compared with the 'gold standard' (rapid urease test and histology). We also prospectively tested the validity of BreathID in comparison to isotope ratio mass spectrometry, in 40 patients referred to monitor the efficacy of H. pylori eradication treatment. RESULTS: Complete agreement was observed between the 'gold standard' and the Breath ID test in 96.9% (94 out of 97) of the patients. The sensitivity and specificity of BreathID were 97.8% and 96.1%, respectively. The correlation between BreathID and isotope ratio mass spectrometry breath test was 100%. CONCLUSIONS: The Oridion BreathID has comparable sensitivity and specificity to the claims of the currently available urea breath tests. Furthermore, BreathID has the potential advantages of ease of use with minimal medical staff requirement, and real time rapid results (20 min maximum) which may make the BreathID preferable to other urea breath test assays.