Folding of apominimyoglobin.

The acid unfolding pathway of apominimyoglobin (apo-mini-Mb), a 108-aa fragment (aa 32-139) of horse heart apomyoglobin has been studied by means of circular dichroism, in comparison with the native apoprotein. Similar to sperm whale apomyoglobin [Hughson, F. M., Wright, P. E. & Baldwin, R. L. (1990) Science 249, 1544-1548], a partly folded intermediate (alpha-helical content approximately 35%) is populated at pH 4.2 for horse heart apomyoglobin. For this intermediate, Hughson et al. proposed a structural model with a compact subdomain involving tertiary interactions between the folded A, G, and H helices, with the remainder of the protein essentially unfolded. As described in this paper, a folding intermediate with an alpha-helical content of approximately 33% is populated at pH 4.3-5.0 also in apo-mini-Mb. The acid unfolding pathway is similarly affected in both the native and the mini apoprotein by 15% trifluoroethanol, a helix-stabilizing compound. Thus, the folding of the apo-mini-Mb intermediate is similar to that observed for the native apoprotein, in spite of the absence in the miniprotein of the A helix and of a large part of the H helix, which are crucial for the stability of apo-Mb intermediate. Our results suggest that acquisition of a folded state in apo-mini-Mb occurs through an alternative pathway, which may or may not be shared also by apo-Mb.     

Vulvar papillary hidrocystadenoma. Description of a case]

Papillary hidradenoma of the vulva is a benign neoplasm arising from apocrine sweat glands of the skin. The treatment of choice is local excision. The prognosis for the patient is excellent. We present one case observed recently.     

Intrahepatic biliary lithiasis: endoscopic transpapillary treatment

Six cases of intrahepatic biliary lithiasis, condition rarely observed in western countries, are reported. Following a review of the literature and on the basis of personal experience, stress is laid on problems of classification, clinical and instrumental diagnosis and, in particular, the therapeutic approach to intrahepatic biliary lithiasis by the endoscopic transpapillary way.     

Endoscopic sphincterotomy in the treatment of biliary lithiasis. Our experience

Endoscopic Sphincterotomy (E.S.) is a simple and efficacious method for the management of bile duct stones and papillary stenosis. In this series, the E.S. was attempted in 25 patients and performed in 23 (92%). Nine patients had common bile duct stones. Eleven patients (48%) had common bile duct and gallbladder stones. Two patients (8.7%) had intrahepatic lithiasis and one patient (4.3%) had papillary stenosis without gallstones. After E.S. all patients underwent instrument removal of bile duct stones, using "Dormia" basket and "Fogarty" balloon catheter. Transnasal bile duct drainage was performed in 20 patients (86.9%). Early complications were observed in three patients (13%); one sphincterotomy side bleeding and two acute pancreatitis, which were treated successfully conservatively. Mean follow-up was 10.7 months (range 3-27 months). Late complications did not occur for the method and/or for gallbladder stones. Four patients over 80 years of age, died for unrelated causes during follow-up.     

Growth and development in thalassaemia major patients with severe bone lesions due to desferrioxamine

Nine transfusion-dependent -thalassaemia major patients (seven males and two females), aged 4–15 years, with growth retardation and severe rickets-like radiological lesions due to continuous subcutaneous chelation therapy with desferrioxamine (45–75 mg/kg body weight, 6–7 times/week), were seen in our centre during the last 8 years. Serum ferritin levels ranged from 976 to 4115 g/l. There was a progressive decline in growth velocity in these patients 2–3 years before the appearance of rickets-like radiological lesions. All patients underwent surgery to correct genu valgum and/or slipped capital epiphyses. The final height was below the 3rd percentile in six patients (SDS: from –2.9 to –5.2). The short stature was mainly due to a disproportion between upper and lower segments. Six of the patients had an associated sensorineural hearing loss.Conclusion Our data emphasize the importance of an accurate surveillance of the toxic effects of desferrioxamine treatment and warn of the risk of overtreating patients with low iron overload and also suggest a possible individual idiosyncrasy to the adverse effects of chelation therapy.     

Unusual phenotype (Leu 7+, OKT4+, OKM1+) expressed by cells from a patient with an abnormal expansion of granular lymphocytes

We report the case of a 70-year-old female with a lymphocytosis which was casually detected during a routine examination. Immunological studies revealed the expansion of granular lymphocytes (GL) with the following, previously undescribed phenotype: Leu 7+, OKT3+, OKT4+, OKT8-, OKM1+. These cells were tested for their functional activities and found to exert neither helper nor suppressor functions in in vitro tests. Cytotoxic activities demonstrated a strong ADCC and a markedly reduced NK function. 1 year later the clinical course has remained good without any treatment and we suggest that this case should be classified as an abnormal expansion of GL, despite the OKT4 positivity of the cells. Our data point out the importance of a careful immunological study of cells from these rare patients and suggest the existence of a normal GL population expressing the OKT4 phenotype, which is possibly expanded in this patient.     

Rivaroxaban for thromboprophylaxis among patients recently hospitalized for acute infectious diseases: a subgroup analysis of the MAGELLAN study

Essentials

• Net benefit of venous thromboprophylaxis (VTE) in patients hospitalized for infections is unknown.
• MAGELLAN trial subgroup analysis was performed for patients hospitalized for acute infectious diseases.
• At day 35, prolonged rivaroxaban prophylaxis reduced VTE compared to enoxaparin (4.2% vs. 6.6%).
• Rivaroxaban prophylaxis reduced VTE in patients hospitalized for active lung infections.

Summary

Background

Despite the well‐established association between infection and venous thromboembolism (VTE), there are few data specifically assessing the efficacy and safety of the VTE prophylaxis strategies for patients hospitalized for acute infectious diseases.

Objectives

To estimate the incidence of VTE and bleeding outcomes, comparing prolonged prophylaxis with rivaroxaban 10 mg daily for 35 days with enoxaparin 40 mg daily for 10 days.

Patients/Methods

A subgroup analysis of patients hospitalized for acute infectious diseases in the MAGELLAN trial was performed. The primary efficacy outcome was the composite of asymptomatic proximal or symptomatic VTE at days 10 and 35. The principal safety outcome was the composite of major or clinically relevant non‐major bleeding.

Results

Three thousand one hundred and seventy‐three patients with acute infectious diseases leading to hospitalization were randomized to either rivaroxaban (n = 1585) or enoxaparin/placebo (n = 1588), and received at least one dose of study medication. At day 10, primary composite efficacy outcomes did not differ between prophylaxis strategies (rivaroxaban, 2.7%; and enoxaparin, 3.7%). At day 35, there were fewer VTE events with rivaroxaban (4.2%) than with enoxaparin (6.6%) (relative risk [RR] 0.64; 95% confidence interval [CI] 0.45–0.92). Patients with pulmonary infections randomized to rivaroxaban had a lower incidence of VTE both at 10 days (RR 0.50, 95% CI 0.28–0.90) and at 35 days (RR 0.54, 95% CI 0.33–0.87). Primary safety outcome events were increased with rivaroxaban (RR 2.42, 95% CI 1.60–3.66).

Conclusions

Prolonged rivaroxaban prophylaxis reduced the incidence of VTE in patients hospitalized for acute infectious diseases, particularly those involving the lungs. Efficacy benefits were, in part, offset by bleeding outcomes. ClinicalTrials.gov Number: NCT 00571649.