Treadmill exercise-induced release of endothelin-1 in patients with peripheral arterial occlusive disease at Fontaine stage IIb.

BACKGROUND: Endothelin-1 (ET-1) is an endothelial vasoconstrictor mitogenic peptide which is thought to be a marker of endothelial damage and a potential participant in the pathophysiological processes of the development of atherosclerotic lesions and disease states associated with vasoconstriction and vasospasm. METHODS: To investigate the endothelin-1 release in response to dynamic exercise in patients with peripheral arterial occlusive disease (PAOD), plasma concentrations were determined by radioimmunoassay in 16 patients (14 men, 2 women, mean age 56.2 +/- 8.1 years) with peripheral arterial occlusive disease at Fontaine stage IIb and in 10 control subjects (8 men, 2 women, mean age 58.1 +/- 7.2 years) in normal health during treadmill testing (slope 5%, speed 3 km/hr). Blood samples were collected at rest from an antecubital vein, at the onset of claudication pain, and 10 minutes after exercise. RESULTS: Mean plasma endothelin-concentrations during the stress test increased significantly in the patients with arterial disease, rising from basal values of 4.4 +/- 0.6 pmol/L to values of 8.9 +/- 0.7 pmol/L at the end of the test (p < 0.0001), whereas it did not change significantly in control subjects (rising from 2.6 +/- 0.4 pmol/L to 2.7 +/- 0.5 pmol/L). Further, plasma endothelin- in the patients with arterial disease was at all times higher than in the control subjects (p < 0.0001). CONCLUSIONS: In conclusion, this study shows that in patients with peripheral arterial occlusive disease, plasma endothelin-1 increases after treadmill exercise performed until claudication pain supervenes. Raised endothelin-1 could be a marker of ischaemic acute endothelial damage and/or could contribute to increase the vascular resistance in ischaemic limbs of these patients during dynamic exercise by promoting arterial/arteriolar vasoconstriction or vasospasm.     

Biliary dilatation secondary to lithiasis in a child affected by Langerhans' cell histiocytosis

Langerhans' cell histiocytosis (LCH) is a disease of unknown pathogenesis, caused by clonal proliferation of Langerhans' cells. Liver involvement results in a cholangiopathy, which has the radiologic appearance of sclerosing cholangitis. Only 1 case of obstructive jaundice due to common bile duct stone in a patient with LCH has been described. We present a case of a 31‐month‐old child with LCH and liver involvement on the waiting list for liver transplantation. During the follow‐up, there was a rapid onset of jaundice due to sludge and lithiasis. The patient was treated first with an endoscopic biliary plastic stent and then with percutaneous biliary drainage and bilioenteric anastomosis. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound 2009     

The antiproliferative effects of tyrosine kinase inhibitors tyrphostins on a human squamous cell carcinoma in vitro and in nude mice.

Many human tumors of epithelial origin contain cells overexpressing the epidermal growth factor (EGF) receptor, and there is convincing evidence that cancer cell growth is correlated with the loss of the normal regulation of the EGF receptor signal transduction pathway. Some cancers are clearly dependent on activation of the EGF receptor for their proliferation. Recently, a class of compounds, tyrphostins, which inhibit the protein tyrosine kinase activity of the growth factor receptor, have been described. In this report, we have examined the antiproliferative effects of potent new tyrphostins on a well-characterized human squamous cell carcinoma in vitro and in vivo. We found that two of these compounds (RG-13022 and RG-14620) suppressed not only EGF-stimulated cancer cell proliferation in vitro but also tumor growth in nude mice. RG-13022 also increased the life span of these tumor-bearing nude mice. When administered to tumor-bearing nude mice together with monoclonal antibodies to the EGF receptor at a suboptimal dose which had no effect alone, inhibition of tumor growth was markedly enhanced. These data suggest that tyrphostins have potential as anticancer agents.     

Bronchogenic carcinoma with extramucosal development. Diagnostic problems

Bronchogenic carcinoma is characterized by three different patterns of spread: endobronchial, the commonest, submucosal, and peribronchial. While the diagnostic yield of bronchoscopy is very high for endobronchial masses, both submucosal and peribronchial tumors are more difficult to detect, and standard forceps biopsy can be negative. In such cases transbronchial needle aspiration biopsy allows higher diagnostic accuracy. CT findings of extramucosal neoplastic spread are not specific. Thickening of the bronchial walls is the commonest sign, but CT is inaccurate in predicting whether bronchial thickening will result in endobronchial/extramucosal neoplasm, fibrosis or bronchial wall edema. Despite this inaccuracy, CT is complementary to bronchoscopy since it allows to: 1) detect a pathology in the bronchial walls, which appear thickened; 2) delineate the extent of extraluminal spread; 3) help plan transbronchial needle aspiration biopsy.     

Which type of observation for patients with high-risk mild head injury and negative computed tomography?

OBJECTIVE: Current guidelines suggest hospital admission followed by home monitoring for high-risk patients with mild head injury and negative computed tomography scan. We tested early home monitoring under the care of a competent observer. METHODS: A total of 1480 patients with mild head injury and negative computed tomography scan were prospectively studied. Based on clinical status and available home caretakers, patients were managed by in-hospital observation (n = 646) or early home monitoring (n = 834). Outcome measures were: (1) the detection of previously undiagnosed post-traumatic intracranial injury; (2) neurosurgical intervention; and (3) unfavourable outcome (death, permanent vegetative state or severe disability). RESULTS: In the in-hospital arm, nine cases (1.4%) developed intracranial injuries (in three after discharge). In the early home-monitoring arm, six patients (0.7%) had a previously undiagnosed lesion after re-admission (P = 0.773 versus in-hospital arm). No patients with previously undiagnosed intracranial injuries had a neurosurgical intervention. After 6 months, five patients had died in the home monitoring arm (0.8%) versus eight (1.0%) in the in-hospital arm (P=0.785). No permanent disability or vegetative state was observed. CONCLUSION: Early home monitoring may be safely proposed to selected "high-risk" patients, with an early negative computed tomography scan, normal clinical examination and feasible home monitoring.     

alpha-Tocopherol as an antiretroviral therapy supplement for HIV-1-infected patients for increased lymphocyte viability.

The aim of our study was to evaluate the benefits of supplementation with 800 mg/day of alpha-tocopherol with regard to cellular viability in HIV-1 seropositive patients undergoing anti-retroviral therapy. A total of 29 patients participated in the study, of whom 14 were given the supplement and 15 a placebo. The analyses were carried out before treatment commenced and after 60, 120 and 180 days. The plasma levels of HIV-1 RNA showed a significant decrease as a consequence of treatment time in the groups studied (p = 0.0001), although the difference between the treatments over time was not verified (p = 0.7343). The percentage of viable lymphocytes showed a significant increase as a consequence of treatment time in both groups studied (p = 0.0002) and a significant difference between the treatments over time (p = 0.0472). The percentage of lymphocytes in apoptosis showed a significant reduction over time (p = 0.0003), as well as a significant difference between the treatments over time (p = 0.0321). The significant increase in cellular viability indicates that supplementation with alpha-tocopherol offers an additional positive effect on cellular preservation in HIV-1 individuals undergoing anti-retroviral therapy; however, it represents an additional risk of anti-retroviral therapeutic failure, possibly due to drug-drug interaction involving up-regulation of metabolic clearance.     

Flight muscles in falcons (Falconiformes,Falconinae): A quantitative approach

The family Falconidae has contrasting behaviors on its flight within the subfamilies. Falcons are primarily aerial predators requiring accuracy, high speed, and controlled movements during flight. Caracaras are generalists that seek food while walking and their flight is characterized as slow and erratic. We aimed to explore the muscle mass of the primary wing muscles in several species of Falconinae and to identify possible differences related to the role that these muscles perform during flight. We studied 34 wing muscles in 11 specimens of five species of falcons. The percentage of each muscle with respect to body mass was calculated as well as the total wing muscle mass. The search for differences between muscles of falcons and caracaras was analyzed using Bayesian statistical inference. Published data from Polyborinae were used for comparison. Five muscles were significantly different between both subfamilies mm. latissimus dorsi pars caudalis, biceps brachii, extensor carpi radialis, flexor digitorum superficialis, and extensor digitorum communis. The first two muscles were larger in Polyborinae, which could be useful to achieve more strength and stabilization. In falcons the last three muscles listed were larger, which might be associated with their fast and acrobatic flight. Variations in certain muscles generate, in turn, differences in function, which is reflected in their type of flight and its use. These findings reinforce the modular character of the locomotor system of birds whereby the regions involved in locomotion can have morphological peculiarities according to their lifestyle.