ETHNIC AND GEOGRAPHIC DIFFERENCES AND SIMILARITIES OE HIV/AIDS-RELATED MUCOCUTANEOUS DISEASES

Background. A study on HIV/AIDS-related mucocutaneous manifestations has been carried out in three different ethnic and geographic areas, namely Brazil, Denmark, and Thailand. Methods. The Brazil cohort comprised 110 patients, the Danish cohort 150, and the Thai cohort 206 patients. The majority of the Brazil and Thai cohort patients belonged to groups III and IV according to the CDC clinical staging system, whereas the patients in Denmark called their doctors earlier and only 8% were classified in groups III and IV. Results. In all three areas the number of mucocutaneous diseases correlated well with the progression of the HIV disease. Ethnic differences were not identified, whereas geographic differences related to skin infections were marked. In the Asian cohort a generalized fungal infection was detected with characteristic mucocutaneous symptoms caused by Penicillium marneffei. Conclusions. Teaching efforts about mucocutaneous signs as markers of HIV infection may be of value, particularly in developing areas, to allow earlier diagnosis. In future guidelines for classification of HIV/AIDS-related mucocutaneous diseases geographic considerations should be included.     

Radioactive synovectomy with Yttrium90 citrate in haemophilic synovitis: Brazilian experience

Summary. Recurrent haemarthroses leading to chronic synovitis and arthropathy remain a major cause of morbidity in patients with haemophilia. Radioactive synovectomy (RS) is considered the first choice of treatment for chronic haemophilic synovitis. The aim of this study was to evaluate the effect of RS with Yttrium⁹⁰ citrate (C‐Y⁹⁰) in the joints of patients with chronic haemophilic synovitis. From 2003 to 2007, 245 joints (118 knees, 76 elbows, 49 ankles and two shoulders) of 190 patients with haemophilia or von Willebrand disease were submitted to RS with C‐Y⁹⁰ at Hemocentro de Mato Grosso, Brazil. Forty joints had radiographic Pettersson scores above 8. There were 36 joints of 22 patients with inhibitors to factor VIII. The procedure was safe with low occurrence of adverse events. The main effect was the overall reduction in joint bleeding frequency, from 19.8 to 2.6 per year post‐RS. Similar results were obtained in cases with high radiographic scores and in inhibitor patients. Pain reduction was observed in most cases. Average range of motion was maintained or increased 1 year post‐RS in most joints. Extension was stable or increased in 88.2% of the knees and 86.5% of the elbows. Ankle plantarflexion was stable or increased in 90.9%, whereas dorsiflexion was maintained or increased in 87.9%. Worsening of the range of motion, when present, ranged from 14 to 17 degrees. We concluded that RS with C‐Y⁹⁰ represents an important resource for the treatment of chronic haemophilic synovitis, markedly reducing joint bleeding frequency and pain, irrespective of the radiographic stage and inhibitor status.     

Apolipoprotein E Mimetics and Cholesterol-Lowering Properties

Apolipoprotein E (apoE) is a ligand for clearance of lipoprotein remnants such as chylomicrons and very low-density lipoproteins. It has anti-atherogenic and anti-inflammatory properties. Therefore, there is extensive ongoing research to create peptides that can mimic properties of apoE. A number of synthetic peptides that encompass different regions of apoE have been studied for inhibiting inflammatory states, including Alzheimer disease. However, peptides that clear atherogenic lipoproteins, analogous to apoE, via enhanced hepatic uptake have not been previously reviewed. Toward this end, we describe the design and studies of a dual-domain apoE mimetic peptide, Ac-hE18A-NH(2). This peptide consists of residues 141-150, the putative receptor-binding region of human apoE, covalently linked to a well characterized class A amphipathic helix, 18A, which has no sequence homology to any other exchangeable apolipoprotein sequences. It demonstrates dramatic effects in reducing plasma cholesterol levels in dyslipidemic mouse and rabbit models. We discuss the scientific rationale and review the literature for the design and efficacy of the peptide. Analogous to apoE, this peptide bypasses the low-density lipoprotein receptor for the hepatic uptake of atherogenic lipoproteins via heparan sulfate proteoglycan (HSPG). ApoE mimetics such as Ac-hE18A-NH(2) may therefore restore or replace ligands in genetically induced hyperlipidemias to enable reduction in atherogenic lipoproteins via HSPG even in the absence of functional low-density lipoprotein receptors. Therefore, this and similar peptides may be useful in the treatment of dyslipidemic disorders such as familial hyperlipidemia and atherosclerosis.     

Dermoscopic Features of Difficult Melanoma

BACKGROUND: The dermoscopic diagnosis of cutaneous melanoma (CM) may be difficult because some CM lack specific dermoscopic features for melanoma diagnosis. OBJECTIVE: To evaluate whether a diagnosis of CM could be achieved using the classic dermoscopic melanoma-specific criteria, we conducted a retrospective multicenter study of 508 CM samples. METHODS: All the dermoscopic images were analyzed to identify the dermoscopic criteria found in dermoscopically difficult melanomas (DDM) and to examine the possible relation of dermoscopic diagnosis with respect to the difficulty of the dermoscopic diagnosis and the melanoma thickness. RESULTS: A significant percentage of melanomas, 89 of 508 (17.5%), were DDM. The criteria leading to a significant increased risk of DDM were presence of streaks [odds ratio (OR), 2.26; 95% confidence interval (CI), 1.15-4.47), absence or presence of regular pigmentation (OR, 3.41; 95% CI, 1.70-6.85), absence of a blue-whitish veil (OR, 4.04; 95% CI, 2.33-6.99), absence of regression structures (OR, 4.31; 95% CI, 2.42-7.66), and the presence of hypopigmentation (OR, 2.61; 95% CI, 1.49-4.58). CONCLUSION: A significant number of melanomas defy even dermoscopic diagnosis. Only a meticulous comparative and interactive process based on an assessment of all the individual's other nevi ("ugly ducking" sign) and a knowledge about recent changes can lead to the recognition of DDM.     

Efficacy and safety of the oral direct factor Xa inhibitor apixaban for symptomatic deep vein thrombosis. The Botticelli DVT dose-ranging study

Summary.  Background:  Apixaban, an oral potent reversible direct inhibitor of activated factor X, has shown promise in the prevention of venous thromboembolism following major orthopedic surgery. We conducted a dose-ranging study in patients with deep vein thrombosis. Methods:  Consecutive patients with symptomatic deep vein thrombosis were included and randomized to receive 84–91 days of apixaban 5 mg twice-daily, 10 mg twice-daily, or 20 mg once-daily, or low molecular weight heparin (LMWH) followed by a vitamin K antagonist (VKA). The primary efficacy outcome was the composite of symptomatic recurrent venous thromboembolism and asymptomatic deterioration of bilateral compression ultrasound or perfusion lung scan. The principal safety outcome was the composite of major and clinically relevant, non-major bleeding. Results:  The mean age of the 520 included patients was 59 years, and 62% were male. The primary outcome occurred in 17 of the 358 apixaban-treated patients [4.7%, 95% confidence interval (CI) 2.8–7.5%] and in five of the 118 LMWH/VKA-treated patients (4.2%, 95% CI  1.4–9.6%) who were evaluable. The incidence in all three apixaban groups was low and comparable without evidence of a dose response. The principal safety outcome occurred in 28 (7.3%) of the 385 apixaban-treated patients and in 10 (7.9%) of the 126 LMWH/VKA-treated patients. No dose response for apixaban was observed. Conclusion:  These observations warrant further evaluation of apixaban in phase III studies. The attractive fixed-dose regimen of this compound may meet the demand to simplify anticoagulant treatment in patients with established venous thromboembolism.     

Lung oxidative stress as related to exercise and altitude. Lipid peroxidation evidence in exhaled breath condensate: a possible predictor of acute mountain sickness

Lung oxidative stress (OS) was explored in resting and in exercising subjects exposed to moderate and high altitude. Exhaled breath condensate (EBC) was collected under field conditions in male high-competition mountain bikers performing a maximal cycloergometric exercise at 670 m and at 2,160 m, as well as, in male soldiers climbing up to 6,125 m in Northern Chile. Malondialdehyde concentration [MDA] was measured by high-performance liquid chromatography in EBC and in serum samples. Hydrogen peroxide concentration [H₂O₂] was analysed in EBC according to the spectrophotometric FOX₂ assay. [MDA] in EBC of bikers did not change while exercising at 670 m, but increased from 30.0±8.0 to 50.0±11.0 nmol l⁻¹ (P<0.05) at 2,160 m. Concomitantly, [MDA] in serum and [H₂O₂] in EBC remained constant. On the other hand, in mountaineering soldiers, [H₂O₂] in EBC under resting conditions increased from 0.30±0.12 μmol l⁻¹ at 670 m to 1.14±0.29 μmol l⁻¹ immediately on return from the mountain. Three days later, [H₂O₂] in EBC (0.93 ±0.23 μmol l⁻¹) continued to be elevated (P<0.05). [MDA] in EBC increased from 71±16 nmol l⁻¹ at 670 m to 128±26 nmol l⁻¹ at 3,000 m (P<0.05). Changes of [H₂O₂] in EBC while ascending from 670 m up to 3,000 m inversely correlated with concomitant variations in HbO2 saturation (r=−0.48, P<0.05). AMS score evaluated at 5,000 m directly correlated with changes of [MDA] in EBC occurring while the subjects moved from 670 to 3,000 m (r=0.51, P<0.05). Lung OS may constitute a pathogenic factor in AMS.