Erythrocyte membrane protein destabilization versus clinical outcome in 160 Portuguese Hereditary Spherocytosis patients

Hereditary Spherocytosis (HS) is a haemolytic anaemia caused by erythrocyte protein membrane defects – spectrin, ankyrin, band 3 or protein 4·2 – that lead to membrane destabilization. This study aimed to evaluate the prevalence of protein deficiencies and the role of membrane proteins or membrane‐linked proteins in membrane disturbance and in HS clinical outcome. A total of 215 Portuguese individuals were studied – 203 from 71 families plus 12 individual unrelated subjects; 160 of them were diagnosed with HS. They were classified as presenting mild, moderate or severe forms of HS according to the degree of haemolytic anaemia. Standardized electrophoretic erythrocyte membrane protein analysis was used to identify and quantify protein deficiencies. Band 3 and ankyrin were found to account for the majority of the erythrocyte protein defects underlying HS. Increasing isolated protein deficiency or increasing imbalance between combined protein deficiencies seemed to underlie HS severity, by increasing membrane destabilization. There was an increased membrane linkage of the cytosolic proteins, glyceraldehyde‐3‐phosphate dehydrogenase and peroxiredoxin 2, and of denatured haemoglobin, suggesting that this linkage could interfere with membrane structure. Our data suggest that the quantification and the analysis of RBC membrane proteins may be helpful in predicting the clinical outcome of HS.     

The BEST study--a prospective study to compare business class versus economy class air travel as a cause of thrombosis.

BACKGROUND: As many as 10% of airline passengers travelling without prophylaxis for long distances may develop a venous thrombosis. There is, however, no evidence that economy class travellers are at increased risk of thrombosis. OBJECTIVES: A suitably powered prospective study, based on the incidence of deep-vein thrombosis (DVT) reported in previous studies on long-haul flights, was designed to determine the incidence of positive venous duplex scans and D-dimer elevations in low and intermediate-risk passengers, comparing passengers travelling in business and economy class. PATIENTS/METHODS: Eight hundred and ninety-nine passengers were recruited (180 travelling business class and 719 travelling economy). D-dimers were measured before and after the flight. A value greater than 500 ng/ml was accepted as abnormal. A thrombophilia screen was conducted which included the factor V Leiden mutation, the prothombin 20210A mutation, protein C and S levels, antithrombin levels, and anticardiolipin antibodies immunoglobulin G (IgG) and immunoglobulin M (IgM). On arrival, lower limb compression ultrasonography of the deep veins was performed. Logistical regression analysis was used to determine the risk factors related to abnormally high D-dimer levels. RESULTS: Only 434 subjects had a full venous duplex scan performed. None had ultrasonic evidence of venous thrombosis. Nine passengers tested at departure had elevated D-dimer levels and these volunteers were excluded from further study. Seventy-four of the 899 passengers had raised D-dimers on arrival. Twenty-two of 180 business class passengers (12%) developed elevated D-dimers compared with 52 of 719 economy class passengers (7%). There was no significant association between elevation of D-dimers and the class flown (odds ratio (OR) 0.61, p = 0.109). The factor V Leiden mutation, factor VIII levels and the use of aspirin were, however, associated with raised D-dimers (OR 3.36, p = 0.024; OR 1.01, p = 0.014; and OR 2.04, p = 0.038, respectively). Five hundred and five passengers were contacted within 6 months and none reported any symptoms of a clinical thrombosis or pulmonary embolus. CONCLUSION: The incidence of ultrasonically proven DVT is much lower than previously reported. However, more than 10% of all passengers developed raised D-dimers, which were unrelated to the class flown. A rise in D-dimers is associated with an inherent risk of thrombosis and/or thrombophilia, demonstrates activation of both the coagulation and fibrinolytic systems during long-haul flights, and may indicate the development of small thrombi.     

'Real' epidemiology of varicose veins and chronic venous diseases: the San Valentino Vascular Screening Project

The aim of this study was to evaluate the prevalence and incidence of venous diseases and the role of concomitant/risk factors for varicose veins (VV) or chronic venous insufficiency (CVI). The study was based in San Valentino in Central Italy and was a real whole-population study. The study included 30,000 subjects in eight villages/towns evaluated with clinical assessment and duplex scanning. The global prevalence of VV was 7%; for CVI, the prevalence was 0.86% with 0.48% of ulcers. Incidence (new cases per year) was 0.22% for VV and 0.18% for CVI; 34% of patients with venous disease had never been seen or evaluated. The distribution of VV and CVI in comparison with duplex-detected incompetence (DI) indicates that 12% of subjects had only VV (no DI), 2% had DI but no VV, 7.5% had DI associated with VV, 2% apparent CVI without DI, 3% DI only (without CVI), and 1.6% both CVI and DI. VV associated with DI are rapidly progressive and CVI associated with DI often progresses to ulceration (22% in 6 years). VV without significant DI (3%) and venous dilatation without DI tend to remain at the same stage without progression for a lengthy time. New cases per year appear to have a greater increase in the working population (particularly CVI) possibly as a consequence of trauma during the working period. In older age (>80 years), the incidence of CVI tends to decrease. Ulcers increase in number with age. Only 22% of ulcers can be defined as venous (due to venous hypertension, increased ambulatory venous pressure, shorter refilling time, obstruction and DI). Medical advice for VV or CVI is requested in 164 subjects of 1,000 in the population. In 39 of 1,000, there is a problem but no medical advice is requested and in only 61 of 1,000, the venous problem is real. In VV in 78% of limbs, there is only reflux, in 8% only obstruction, and in 14% both. In CVI, 58% of limbs have reflux, 23% obstruction, and 19% both. In conclusion, VV and CVI are more common with increasing age. The increase with age is linear. There was no important difference between males and females. These results are the basis for future real, whole population studies to evaluate VV and CVI.     

Popliteal artery entrapment syndrome: more common than previously recognized.

PURPOSE: This report summarizes our experience with the popliteal entrapment syndrome in 88 limbs (48 patients) treated during a 10-year period. METHOD: The study cohort consisted of a retrospective analysis of those patients who were seen with symptoms of claudication or severe ischemia by a single surgical group and in whom unequivocal evidence of popliteal entrapment was shown either with angiography or at the time of operation. The cases were collected prospectively in a private vascular surgical practice. RESULTS: Bilateral popliteal entrapment was found in 40 of the 48 patients. The mean age at the time of presentation was 35.0 years (SD, 11.6 years). Claudication was the most frequent presenting symptom (70 of 88 limbs). Types I, II, III, and IV popliteal entrapment were found in 58 limbs (15 arteries occluded), and 30 limbs (three occlusions) were seen with a "functional" popliteal artery entrapment (apparent absence of a developmental anatomic abnormality). Of the 18 limbs with severe ischemia and associated occlusion of the popliteal artery, 15 underwent bypass grafting with reversed saphenous vein grafts, all of which remained patent during the follow-up period (median follow-up, 4.2 years; range, 1 to 10 years). One popliteal artery occlusion that was treated with thrombectomy and vein patching occluded within 6 months and necessitated subsequent vein grafting. Two limbs with inoperable occluded popliteal arteries were not subjected to reconstruction (one necessitated amputation because of advanced ischemia, and the second had extensive thrombosis of the distal run-off). In two patients (four limbs), moderate presenting symptoms abated without surgery after the discontinuation of an extreme exercise program. The remaining limbs underwent surgical decompression (all popliteal arteries remained patent, with a median follow-up of 3.9 years). CONCLUSION: The popliteal entrapment syndrome is more prevalent than has formerly been appreciated. On the basis of observations made in this series and in the surgical literature, we advise surgical correction in all cases of types I, II, III, and IV entrapment at the time of diagnosis to avoid occlusion as a result of continued arterial wall degeneration. In contrast, decompression is only advised in those patients with "functional entrapment" if they have discrete and typical symptoms because up to 50% of the normal population may display transient popliteal artery compression with extremes of plantar flexion or dorsiflexion. On the basis of the severe histologic changes found in those popliteal arteries that had undergone occlusion at the time of presentation, it is advised that the popliteal artery should be completely replaced, ideally with a vein graft, when significant degeneration or occlusion of the popliteal artery is noted at the time of operation.     

Ectomesenchymoma

Summary Two cases of ectomesenchymoma are reported. This tumor type is defined as a form including ectodermal components represented by neuroblasts or ganglion cells and differentiated mesenchymal structures of various types. Some authors classify this tumor with the peripheral nerve neoplasms but we consider it to be a distinct neoplasm. Clinically and pathologically the tumors have no features of peripheral nerve tumors and may occur with nerves or away from them.