Dystonic attacks related to sleep and exercise.

Two unrelated children displayed attacks of paroxysmal jerky 'puppet-like' movements lasting 2-3 min. The attacks were not kinesigenic and occurred during wakefulness precipitated by physical exercise and during NREM sleep, spontaneous or upon arousal and awakenings. Paroxysmal dystonic choreoathetosis was excluded by the absent family history, and paroxysmal kinesigenic dystonia by the absence of triggering effects by sudden movements and efficacy of anticonvulsants. Pattern and duration of involuntary movements were not those typical of nocturnal paroxysmal dystonia. Our cases emphasize that overlap exists among the different clinical categories of paroxysmal dyskinesia.     

Partially Reversible Chronic Renal Failure Due to Long-term Use of Non-steroidal Anti-inflammatory Drugs

A case of partially reversible chronic renal failure due tolong-term NSAID use is discussed. An analysis of this and similarcases recently reported indicates many similarities betweenchronic NSAID nephropathy and analgesic nephropathy.     

Hormonal and immunological pattern in a patient with acquired immunodeficiency syndrome related complex and Cushing's syndrome.

A case of Cushing's syndrome in a 24-yr-old homosexual with an AIDS-related complex is reported. In this patient certain symptoms common to both diseases, i.e. weakness, myalgia and muscle atrophy were accentuated, whereas other symptoms pathognomic of the human immunodeficiency virus (HIV) infection, i.e. lymphoadenopathies and weight loss, were less pronounced by the high levels of circulating adrenal steroids. Ketoconazole was administered po in order to block adrenal steroidogenesis, the drug caused a remarkable fall of cortisol serum concentrations, but was unable to modify significantly the immunological pattern of the patient. Our data suggest that changes of serum adrenal steroid levels have little effect on the immune network of patients with AIDS.     

Immunohistological study of grumose degeneration of the dentate nucleus in progressive supranuclear palsy

The grumose degeneration observed in the dentate nuclei of 7 cases of progressive supranuclear palsy (PSP) was studied with a panel of antibodies which included 2 neurofilaments, Tau and ubiquitin. Dentate nucleus neurons were negative with all antibodies except ubiquitin which showed a slightly positive homogeneous pattern of staining. The amorphous material surrounding swollen or normal neurons was strongly positive for neurofilament and subunits and numerous torpedoes were observed in the granular layer of the cerebellar cortex. Our results confirm that grumose degeneration consists in degeneration of terminal axons of Purkinje cells in the dentate nucleus. The positivity of dentate nucleus neurons for ubiquitin may support the concept of synaptic dysfunction between Purkinje cells and dentate nucleus neurons.     

High levels of functional endopeptidase 24.11 (CD10) activity on human thymocytes: preferential expression on immature subsets.

Although it is now well established that cells of the immune system express most of the exopeptidases described so far, little information is available concerning the identification and the characterization of the peptidases associated with the surface of human thymocytes. In the present study we have focused on CD10 expression on thymocytes using both FACS and enzymatic analysis. Unfractionated intact human thymocytes were shown to express significant levels of CD10-specific enzymatic activity, as assessed by the hydrolysis of the neutral endopeptidase (NEP) substrate Suc-Ala-Ala-Phe-pNA and of D-Ala2-Leu-enkephalin, a typical NEP substrate. CD10 activity was abolished by specific NEP inhibitors, including thiorphan, retrothiorphan and phosphoramidon. Moreover, high performance liquid chromatography (HPLC) analysis showed that intact thymocytes and purified NEP hydrolysed thymopentin, a thymic factor known to induce the maturation of prothymocytes into thymocytes. Finally, CD 10/NEP was preferentially associated with CD3- CD3low and immature CD4- CD8- thymocytes. The data demonstrate for the first time that human thymocytes express functional NEP and suggest a role for this enzyme in the maturation of human thymocytes.     

Choline acetyltransferase activity in murine thymus.

Murine thymus has been demonstrated to contain both cholinergic receptors and acetylcholinesterase activity. In the present study we have investigated the presence of the enzyme choline acetyltransferase in this organ, which is responsible for the synthesis of acetylcholine. Results reported here demonstrate that (1) an appreciable amount of the enzyme is already present in the thymus on the day of birth; (2) its expression is developmentally regulated; and (3) thymic atrophy, induced in young (2-week-old) and adult (6-week-old) mice by i.p. injection of hydrocortisone for 2 days, is accompanied by significant reduction of choline acetyltransferase activity only in young mice. Altogether these results demonstrate the presence in the murine thymus of functionally relevant markers of the cholinergic system that might interface the interactions between the nervous and immune systems.     

Evidence of tendinitis provoked by fluoroquinolone treatment: a case-control study.

OBJECTIVE: To investigate the association between the use of fluoroquinolone agents and the risk of tendinitis in a large population-based case-control study. METHODS: The study was performed by linking automated health databases from the Region of Lombardia, Italy. Cases were patients aged > or =18 years who had a hospital discharge diagnosis of non-traumatic tendinitis in 2002-3. For each case, up to five controls were randomly selected among those eligible for inclusion in the study. A conditional logistic regression model was used to estimate the odds ratio of tendinitis associated with the current, recent and past use of fluoroquinolones. Odds ratios were adjusted for exposure to other antibacterials and other drugs. RESULTS: 22,194 cases and 104,906 controls met the inclusion criteria. Current use of fluoroquinolones significantly increased the risk of tendon disorders as a whole (odds ratio [OR] = 1.7; 95% CI 1.4, 2.0), tendon rupture (OR = 1.3; 95% CI 1.0, 1.8) and rupture of the Achilles' tendon (OR = 4.1; 95% CI 1.8, 9.6). Concomitant use of corticosteroids and fluoroquinolones increased the risk of both tendon rupture (OR = 3.1; 95% CI 1.5, 6.3) and rupture of the Achilles' tendon (OR = 43.2; 95% CI 5.5, 341.1). DISCUSSION: Evidence that exposure to fluoroquinolones is associated with the sudden occurrence of tendinitis is supported by this large population-based study. We can estimate that a single case of rupture of the Achilles' tendon would occur for every 5958 persons treated with fluoroquinolones (95% CI 2148, 23,085). The corresponding number needed to harm is 979 (95% CI 122, 9172) for patients who concomitantly use corticosteroids and 1638 (95% CI 351, 8843) for those aged >60 years. CONCLUSION: Clinicians should be aware of this adverse effect, and the increased risk for fluoroquinolone-associated tendinitis in elderly patients with corticosteroid use must be considered when these agents are prescribed.     

RESPONSIVENESS AND SENSITIVITY TO CHOLINERGIC AGONISTS AND ANTAGONISTS IN BOVINE ISOLATED BRONCHIAL MUSCLE

1. Airways derived from different levels of the lung exhibit a difference in the reactivity and sensitivity to agonists. We have evaluated the effect of acetylcholine and cholinergic selective (pirenzepine, gallamine and 4-dipherylacetoxymethyl piperidine [4-DAMP]) and non-selective (atropine) antagonists on bovine proximal and distal smooth muscle preparations. 2. The distal preparations are more sensitive to acetylcholine than proximal bronchi. The relaxant effect of three selective antagonists on the distal and proximal tissues was the same when the results for each drug were compared. 3. Atropine and 4-DAMP were more potent than pirenzepine and gallamine in relaxing both proximal and distal bovine smooth muscle preparations. 4. These data suggest that the muscarinic sites on the smooth muscle of bovine airways are of the M3 subtype.     

High serum levels of tumour necrosis factor‐α and interleukin‐8 in severe asthma: markers of systemic inflammation?

BACKGROUND: Severe asthma is characterized by elevated levels of pro-inflammatory cytokines and neutrophilic inflammation in the airways. Blood cytokines, markers of 'systemic' inflammation, may be a feature of amplified inflammation in severe asthma. OBJECTIVE: To detect differences in IL-8, TNF-alpha, IL-16 and IL-13 levels in the serum(s) of stable severe and mild-moderate asthmatics related to blood leucocytes proportion, airway calibre and exhaled nitric oxide (NO) levels. METHODS: We assessed cytokine serum levels by ELISA and blood leucocyte counts by an alkaline peroxidase method in 20 healthy controls, 22 mild-moderate [forced expiratory volume in 1 s (FEV1)(%pred): 89+/-3] and 14 severe asthmatics [FEV1(%pred): 49+/-2]. RESULTS: IL-8 and TNF-alpha levels were higher in severe asthmatics than in mild-moderate asthmatics or in controls (P<0.05). No differences in IL-16 and IL-13 levels were detected. Severe asthmatics showed higher circulating neutrophil and eosinophil number than controls (P<0.05). In severe asthmatics, exhaled NO levels were superior than in controls (P<0.05), but inferior than in mild-moderate asthmatics (P<0.05). We found positive correlation between TNF-alpha levels and exhaled NO (r=0.67; P=0.01) or circulating neutrophil counts (r=0.57; P=0.03) in severe asthmatics. CONCLUSION: sTNF-alpha and sIL-8 are markers of 'systemic' inflammation in severe asthmatics, in conjunction with augmented circulating neutrophils, suggesting the involvement of neutrophil-derived cytokine pattern in severe asthma.