Procedure for the quantitative evaluation of motor disturbances in cerebellar ataxic patients

Cerebellar ataxia is a complex motor disturbance that involves the planning and execution of movements and reduces movement accuracy and co-ordination. The quantification of ataxic signs is commonly realised through visual examination of motor tasks performed by the patient and assignment of scores to specific items composing the international co-operative ataxia rating scale (ICARS). The present work studied an experimental procedure to characterise specific aspects of motor disturbances in ataxia objectively. Four tests belonging to the ICARS were considered: walking, knee-tibia test, finger-to-nose and finger-to-finger test. Through a kinematic analysis performed during the above tests, specific indices were defined to quantify velocity, linearity, asymmetry, tremor, instability and smoothness of movement or posture. The procedure was applied to five patients with cerebellar ataxia and to ten healthy adult subjects. Results demonstrated that the patients moved significantly more slowly than the healthy subjects (0.67 against 0.97 m s⁻¹ and 0.81 against 1.02 m s⁻¹, respectively, for straight walk and finger-to-nose tests) and showed poorer linearity and smoothness behaviour. Velocity, linearity, tremor, smoothness and instability indices showed moderate to good correlation with the corresponding ICARS score. Some of these indices can separately evaluate aspects that are combined in single ICARS subscores. It is concluded that the combination of clinical assessments and instrumental evaluations allows a better insight into ataxic patients' motor disturbances and is a useful tool for the definition and follow-up of rehabilitation programmes.     

Diltiazem impairs maturation and functions of human dendritic cells

The aim of this study was to define the effects of diltiazem, a calcium antagonist drug used in cardiology and in clinical transplantation, on the differentiation and maturation of human dendritic cells (DC). Herein, we demonstrate that diltiazem, in association with granulocyte macrophage-colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), induces monocytes to differentiate into cells with many of the characteristic of DC. However, diltiazem-induced DC express high levels of mannose receptor and Fc gamma RII and, consequently, manifest a higher endocytic activity compared with GM-CSF+IL-4-induced DC. Importantly, diltiazem-induced DCs have an impaired responsiveness to lipopolysaccharide and CD40 ligand because they produce decreased levels of IL-12 and reveal a reduced ability to stimulate alloreactive T-cell responses as well as in inducing interferon-gamma producing Th1 cells. These effects may contribute to a decreased DC-dependent T-cell activation and may help to explain the immunoregulatory function of diltiazem and its effectiveness in preventing transplant rejection.     

Autosomal-dominant dystrophy with humeroperoneal weakness and cardiopathy: a genetic variant of Emery-Dreifuss disease?

Two females mother and daughter, were affected by a neuromuscular disorder, characterized by slow progression, humeroperoneal weakness and wasting, limited neck flexion, elbow and ankle joint contractures, cardiopathy and myopathic pattern on EMG. Muscle histology and histochemistry showed type I fiber atrophy and predominance in both. Cardiac abnormalities, in the first case, were suggestive of a hypertrophic cardiomyopathy while in the second hypotension and chronic bradycardia were present.Neurological signs, EMG and morphology seemed to point to a genetic variant of the form of dystrophy named Emergy-Dreifuss disease.The mode of transmission and cardiac abnormalities, however, raise the problem of variability even in this well-defined, usually X-linked, disorder.

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Sommario Questa è la prima descrizione di madre e figlia affette da una infrequente malattia muscolare, caratterizzata da progressione lenta, ipostenia con atrofia a distribuzione omero-peroneale, presenza di contratture articolari, cardiopatia e pattern miopatico dell'EMG.Istologia e istochimica muscolare hanno mostrato in entrambi i soggetti atrofia e predominanza delle fibre del I tipo. Le anormalità cardiologiche rilevate nel 1° caso, erano a favore di una cardiomiopatia ipertrofica, mentre nel secondo caso erano presenti ipotensione e bradicardia.Segni neurologici, elettromiografici, reperti istologici ed istochimici sembrano configurare nelle nostre pazienti una variante genetica della forma di distrofia muscolare chiamata Emery-Dreifuss disease. Tuttavia, la modalità di trasmissione e il tipo delle anormalità cardiologiche, diverse nelle due pazienti, sollevano il problema di variabilità fenotipiche, anche in entità clinico-genetiche usualmente ben definite quali la malattia di Emery-Dreifuss.

     

Plasma erythropoietin levels in anaemic and non-anaemic patients with chronic liver diseases

AIM: To investigate the serum erythropoietin (Epo) levels in patients with chronic liver diseases and to compare to subjects with iron-deficiency anaemia and healthy controls. METHODS: We examined 31 anaemic (ALC) and 22 non-anaemic (NALC) cirrhotic patients, 21 non- anaemic subjects with chronic active hepatitis (CAH), 24 patients with iron-deficiency anaemia (ID) and 15 healthy controls. Circulating Epo levels (ELISA; R and D Systems, Europe Ltd, Abingdon, UK) and haemoglobin (Hb) concentration were determined in all subjects. RESULTS: Mean+/-SD of Epo values was 26.9+/-10.8 mU/mL in ALC patients, 12.5+/-8.0 mU/mL in NALC subjects, 11.6+/-6.3 mU/mL in CAH patients, 56.4+/-12.7 mU/mL in the cases of ID and 9.3+/-2.6 mU/mL in controls. No significant difference (P>0.05) was found in Epo levels between controls, CAH and NALC patients. ALC individuals had higher Epo levels (P<0.01) than these groups whereas ID subjects had even higher levels (P<0.001) than patients suffering from ALC. CONCLUSION: Increased Epo values in cirrhotics, are only detectable when haemoglobin was lesser than 12 g/dL. Nevertheless, this rise in value is lower than that observed in anaemic patients with iron-deficiency and appears blunted and inadequate in comparison to the degree of anaemia.     

Neuronal nitric oxide synthase and renin stimulation by sodium deprivation are dependent on the renal nerves

OBJECTIVE: The aim of the present study was to evaluate the role of the renal nerves in the regulation of neuronal nitric oxide synthase (nNOS) gene expression in normotensive rats on different sodium balance. METHODS: Thirty-six male Sprague-Dawley rats were divided into six experimental groups combining three diets with different NaCl content (normal, 0.4%; low, 0.04%; or high, 4.0%), and bilateral renal denervation or sham denervation. After 7 days of dietary treatment, all rats were sacrificed and plasma renin activity (PRA) measured. The nNOS and renin messenger RNA (mRNA) levels in the renal cortex were determined by semiquantitative polymerase chain reaction. RESULTS: PRA was higher in animals with low sodium diet compared with those with standard diet, while it was lower in animals with high sodium diet. Renal denervation decreased PRA in normal and low sodium groups, while it did not alter the PRA values in the high sodium group. The nNOS gene expression significantly increased in rats fed with the low sodium diet compared with the standard diet group, and it significantly decreased in rats with the high sodium diet. Renal denervation significantly reduced nNOS mRNA levels in rats receiving the low sodium diet, but did not significantly influence nNOS mRNA in normal and high sodium groups. Renin mRNA was influenced by diets and denervation in a parallel way to nNOS mRNA. CONCLUSION: The renal nerves mediate the increase of renin and nNOS mRNA during sodium restriction, while the suppression of nNOS and renin gene expression during a sodium load is independent of the presence of the renal nerves. The parallel changes in renin and nNOS mRNA during different sodium intakes suggest that nNOS can be part of the complex, and still largely unclarified, macula densa mechanism of renin regulation.