Development and results of the Spanish registry of patients with alpha-1-antitrypsin deficiency

The Spanish registry of alpha-1 antitrypsin deficiency was founded in 1993 and became a member of the International Registry (AIR) in 1999. We describe the updating process following its incorporation into AIR and compare the data collected in the first period (1993–1999) and the second period (1999–2005), during which time patients were included exclusively by internet.The registry included 301 patients during period 1, 69% males and 46% had a history of smoking. Their mean age was 46 years (SD = 13) and 284 (94%) had the ZZ phenotype, 49% received augmentation therapy. During period 2, 161 new cases were included, 63% of whom were males with a mean age of 44 years (SD = 16). A total of 126 (78%) had the ZZ phenotype. Only 12% received augmentation therapy. A total of 462 different patients were included in both periods. Significant differences were observed in the number of cases with the SZ phenotype and the severity of FEV₁ impairment between the two periods.Implementation of an internet-based collection of data did not result in a lower rate of reporting to the registry. However, data from a significant number of patient included in period 1 could not be actualized in the new data base.     

The tuberous breast revisited.

BACKGROUND: The tuberous breast presents a problem for which many surgical solutions have been described. Current teaching describes how the tuberous breast deformity is the result of skin shortage as well as herniation of breast tissue through the nipple-areola complex. However, through careful clinical observation we now believe that the only abnormality present is herniation of breast tissue through the nipple-areola complex. METHODS: Using this principle, we have refined a one-stage surgical procedure that can be used to correct any type of tuberous breast deformity. Since 2001 we have performed our technique on a series of 13 tuberous breasts of widely varying appearances in eight patients (age 17-24 years) with a follow up varying between 3 and 56 months. Our new understanding of the tuberous breast deformity has also made it possible to develop an objective, reproducible method for defining the tuberous breast based on the degree of areola herniation. RESULTS: All patients reported high levels of satisfaction with the procedure. Assessment of the results by an independent panel of attending surgeons showed all results to be good/excellent. Moreover, the results have improved with time and no revisions have been needed. Our method of defining the tuberous breast (based on the ratio of areola herniation:areola diameter) enabled us to identify a cut-off to decide (objectively) when a breast was tuberous. This allowed us to anticipate when an areola reduction/tightening procedure would be necessary to avoid a 'double-bubble' deformity. CONCLUSION: We propose a one-stage surgical procedure which is applicable to all degrees of tuberous breast deformity. The results appear to confirm our theory that the only abnormality present in the tuberous breast is herniation of breast tissue through the nipple-areola complex. In patients with small breasts and a tuberous deformity, correction of the herniation changes the tuberous breast into a simple hypoplastic breast. The volume deficit can then be corrected by augmentation (if desired by the patient). In patients with sufficient breast volume, correction of the herniation alone will correct the deformity.     

Two great cardiac veins: demonstration by computed tomography, conventional coronary angiography, and during surgery

A 62-year-old man with typical angina pectoris was referredfor imaging of the coronary arteries to detect stenoses. Multislicecomputed tomography (CT) demonstrated significant     

A large mediastinal tumour?

A 72-year-old man with increasing shortness of breath and atypicalangina pectoris received a chest radiograph     

Synthesis and antimalarial activity of new atovaquone derivatives

In this paper we describe the design and synthesis of 18 derivatives of the antimicrobial atovaquone which were substituted at the 3-hydroxy group by ester and ether functions. The compounds were evaluated in vitro for their activity against the growth of Plasmodium falciparum, the malaria causing parasite. All the compounds showed potent activity, with IC₅₀ values in the range of 1.25–50 nM, comparable to those of atovaquone and much higher than chloroquine or quinine.     

Performance in population models for count data,part II: A new SAEM algorithm

Analysis of count data from clinical trials using mixed effect analysis has recently become widely used. However, algorithms available for the parameter estimation, including LAPLACE and Gaussian quadrature (GQ), are associated with certain limitations, including bias in parameter estimates and the long analysis runtime. The stochastic approximation expectation maximization (SAEM) algorithm has proven to be a very efficient and powerful tool in the analysis of continuous data. The aim of this study was to implement and investigate the performance of a new SAEM algorithm for application to count data. A new SAEM algorithm was implemented in MATLAB for estimation of both, parameters and the Fisher information matrix. Stochastic Monte Carlo simulations followed by re-estimation were performed according to scenarios used in previous studies (part I) to investigate properties of alternative algorithms (Plan et al., 2008, Abstr 1372 []). A single scenario was used to explore six probability distribution models. For parameter estimation, the relative bias was less than 0.92% and 4.13% for fixed and random effects, for all models studied including ones accounting for over- or under-dispersion. Empirical and estimated relative standard errors were similar, with distance between them being <1.7% for all explored scenarios. The longest CPU time was 95 s for parameter estimation and 56 s for SE estimation. The SAEM algorithm was extended for analysis of count data. It provides accurate estimates of both, parameters and standard errors. The estimation is significantly faster compared to LAPLACE and GQ. The algorithm is implemented in Monolix 3.1, (beta-version available in July 2009).     

Benefits of arthroscopic tuberculoplasty in posterior ankle impingement syndrome

The purpose of this work was to describe the posterior ankle impingement syndrome related to the posterolateral tubercle of the talus bone and to present a retrospective analysis of our results after arthroscopic plasty of the tubercle in 15 ankles with a mean 3-year follow-up. Fifteen cases of posterior ankle impingement (PAI) underwent arthroscopic excision of an impinging bone spur. All the patients (13) were retrospectively evaluated at an average of 36 months after index surgery. There were seven women (bilateral in two of them) and six men. Ten were involved in different kinds of sport and three were professional ballet dancers. Preoperative symptoms included pain localized in the posterior ankle, limitation of motion, weakness and swelling. All patients had failed a course of conservative therapies. Surgery was performed through posterolateral and posteromedial portals as described by van Dijk. After soft tissue debridement, partial resection of the posterolateral process was performed until there was complete plantar flexion without bone impingement. Postoperatively, all patients followed the same rehabilitation protocol. Improvement in their impingement symptoms was recorded in all of them according to AOFAS score. One of them (7%) still had occasional discomfort. The results suggest that arthroscopic bone decompression of the posterolateral tubercle in cases of PAI resistant to non-surgical therapies is an effective treatment.     

Distribution of α-integrin subunits in fetal polycystic kidney diseases

An alteration in cell/matrix interactions is one of the suggested mechanisms leading to cyst formation in polycystic kidney diseases. Most of these interactions are mediated by β1-integrins, a subfamily of integrin receptors, formed by the association of the β1-chain with different α-subunits. To date, no study on α-integrin subunit distribution during the early stages of cyst development has been reported. Using immunofluorescence, we analyzed the distribution of α-integrin subunits (α1, α2, α3, α5, and α6) and basement membrane proteins in kidneys of fetuses with autosomal dominant (ADPKD) or autosomal recessive polycystic kidney disease (ARPKD). The distribution was compared with that observed in normal fetal and post-natal kidneys, and in fetal cystic dysplasia and Meckel syndrome. Marked increase in α1-integrin staining was observed in normal and cystic collecting duct cells of both polycystic diseases (PKD), compared with normal and cystic controls. The distribution of integrin subunits α2, α3, and α6 was irregular in cyst epithelial cells of PKD and cystic controls. The increased expression of the α1-subunit specifically observed in PKD collecting duct cells may be an early consequence of the genetic defect in ARPKD. In ADPKD it parallels the reported expression of polycystin, the protein product of PKD1. The irregular expression of α2, α3, and α6 integrin subunits observed in all types of cysts suggests that cell/matrix interactions are altered early and may participate in the development of cysts, perhaps by contributing to the deregulation of cell survival in cystic diseases. Received May 28, 1996; received in revised form October 2, 1996; accepted October 25, 1996     

Microscopic haematuria as a relative contraindication for tranexamic acid

Tranexamic acid has been advocated for patients with severe bleeding tendency due to thrombocytopenia not responding to platelet transfusions. Macroscopic haematuria is a well-known contraindication for its use in such patients. We present three clinical cases with microscopic haematuria, in whom tranexamic acid caused problems of clot formation in the urinary tract, indicating that microscopic haematuria should also be considered as a contraindication for tranexamic acid.