The 6-min walking distance: long-term follow up in patients with COPD.

The 6-min walking distance (6MWD) test is used in clinical practice and research into patients with chronic obstructive pulmonary disease (COPD). However, little is known about natural long-term change in this parameter. The 6MWD was measured at baseline and then annually for 5 yrs in 294 patients with COPD and its annual rate of decline was determined. Forced expiratory volume in one second (FEV1) was also measured and the relationship between changes in both markers was explored. At baseline, the median 6MWD was 380 m (range 160-600 m). It declined by 19% (16 m.yr(-1)) over the 5 yrs compared with baseline in patients with American Thoracic Society/European Respiratory Society stage III COPD (FEV1 30-50% predicted) and by 26% (15 m.yr(-1)) in patients with stage IV COPD (FEV1 <30% pred). Over the 5-yr follow-up, the proportion of patients with a minimal clinically significant decline of 54 m increased with the severity of the disease. It was 24% in stage II, 45% in stage III, and 63% in stage IV disease. In contrast, the rate of decline of FEV1 was greater in patients with milder airflow obstruction and lesser in patients with lower absolute FEV1 values. In conclusion, the 6-min walking distance test provides increasingly useful information as the severity of chronic obstructive pulmonary disease increases.     

Vascular Centerline Extraction in 3D MR Angiograms for Phase Contrast MRI Blood Flow Measurement

The accuracy of 2D phase contrast (PC) magnetic resonance angiography (MRA) depends on the alignment between the vessels and the imaging plane. PC MRA imaging of blood flow is challenging when the flow in several vessels is to be evaluated with one acquisition. For this purpose, semi-automatic determination of the plane most perpendicular to several vessels is proposed based on centerlines extracted from 3D MRA. Arterial centerlines are extracted from 3D MRA based on iterative estimation-prediction, multi-scale analysis of image moments, and a second-order shape model. The optimal plane is determined by minimizing misalignment between its normal vector and the centerlines’ tangent vectors. The method was evaluated on a phantom and on 35 patients, by seeking the optimal plane for cerebral blood flow quantification simultaneously in internal carotids and vertebral arteries. In the phantom, difference of orientation and of height between known and calculated planes was 1.2° and 2.5 mm, respectively. In the patients, all but one centerline were correctly extracted and the misalignment of the plane was within 12° per artery. Semi-automatic centerline extraction simplifies and automates determination of the plane orthogonal to one vessel, thereby permitting automatic simultaneous minimization of the misalignment with several vessels in PC MRA.     

C2H2-171 : A novel human cDNA representing a developmentally regulated poz domain/zinc finger protein preferentially expressed in brain

We describe a novel human zinc finger cNDA, C2H2-171. This cDNA represents an mRNA which encodes a protein of 484 amino acids and a calculated molecular weight of 54 kD. Four zinc finger-like domains are found in the C-terminal end of the protein. At the N-terminus, C2H2-171 contains a POZ/tramtrack-like domain similar to that found in the tumor associated zinc finger proteins LAZ-3/BCL-6 and PLZ-F, as well as in non-zinc finger proteins. C2H2-171 RNA is preferentially expressed in the brain, and increases during the course of murine development, with maximal expression in the adult. C2H2-171 RNA is differentially expressed in brain regions, with the highest level of expression in the cerebellum. C2H2-171 RNA was expressed at high levels in primary cerebellar granule cell neurons compared to astrocytes. The gene encoding C2H2-171 is highly conserved in vertebrates, and maps to the terminus of human chromosome 1 (1q44-ter). This chromosomal location is associated with a number of cytogenetic aberrations including those involving brain developmental anomalies and tumorigenesis. These data suggest that C2H2-171 may play an important role in vertebrate brain development and function.     

Evidence of melanogenesis in porcine retinal pigment epithelial cells in vitro

Several weeks after porcine retinal pigment epithelial (RPE) cell cultures attain confluence, macroscopically visible brown foci appear. The cuboidal cells that form the foci contain numerous phase dark granules that do not exhibit the autofluorescence characteristic of lipofuscin. The data described here indicate that the granules are melanosomes. Electron microscopy revealed three types of electron-dense granules in these cells: simple spheres 0.3-0.5 microns in diameter, large spheres 1-2 microns in diameter, and lysosomal aggregations of the smaller spheres. The matrix of both spheres is composed of 40-nm microvesicles that were also found free in the cytoplasm and aggregated within vacuolar structures. Reversed-phase high-performance liquid chromatography of RPE cells and their media detected melanogens, i.e. intermediates of melanin biosynthesis, including several indole derivatives. The porcine RPE cultures therefore may be a useful system for studying melanogenic regulation.     

Pharmacokinetics, hepatic biotransformation and biliary and urinary excretion of bromosulfophthalein (BSP) in an experimental liver disease mimicking biliary cirrhosis

We studied the hepatic handling of bromosulfophthalein in healthy rabbits with hepatic coccidiosis 28 days after an experimental infection with sporulated oocysts of Eimeria stiedai, an experimental model of liver disease histopathologically resembling primary biliary cirrhosis in man. A pharmacokinetic study of the results was performed following a multicompartmental model with 7 transfer constants to describe the physiological disposition of the dye. The study showed that the plasma disappearance, distribution volume (Vi), hepatic biotransformation and the biliary and urinary elimination of conjugated (BSPc) and unconjugated (BSPu) bromosulfophthalein were markedly altered. Whereas Vi and urinary excretion of the dye were significantly increased, the hepatic clearance, biotransformation and biliary excretion of BSPc and BSPu were drastically reduced in infected rabbits. Satisfactory agreement was obtained between the experimental and estimated data, particularly those relating to biotransformation clearance and biliary and urinary excretion of the dye. These results demonstrate that severe liver disease in rabbits with histopathological liver alterations resembling several hepatic dysfunctions in man markedly reduce hepatic uptake, metabolism and biliary excretion of a xenobiotic such as BSP.     

Multicentre hospital drug utilization study on the prophylaxis of venous thromboembolism. The Venous Thromboembolism Study Group of the Spanish Society of Clinical Pharmacology.

1. Thromboembolic disease (TED) is an important cause of in-hospital morbidity and mortality. Although different prophylactic approaches have been shown to be effective and cost-effective, surveys have suggested that they are underused. The aim of this study was to estimate the prevalence of use of TED prophylaxis in our hospitals. 2. All patients admitted on a specified day to the Internal Medicine and General Surgery wards of seven Spanish university hospitals were included in the study. They were identified cross-sectionally and followed up until discharge or for 15 days. Information about the following variables was collected: risk factors for venous thromboembolism, prophylactic measures used (if any), contraindications to the use of each specific drug or other prophylactic measure, and dosage schedule of the drug used, if any. 3. Nine hundred and thirty-nine patients (53% men) were studied. The most common risk factors for venous thromboembolism were: age > or = 40 years (802; 85%), major surgery (298; 32%), immobilization > or = 6 days (285; 30%), obesity (241; 26%), and cancer (202; 22%). 4. Prophylactic measures were used in 320 patients (34%). Of these, 297 (93%) received heparin, mainly as low molecular weight heparins (248, 78%); physical measures were rarely used. 5. Five hundred and eighty-three patients (62%) fulfilled criteria for moderate or high risk of venous thromboembolism; only 275 (47%) of them received any form of prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnostic value of telescoping plugged catheters in mechanically ventilated patients with bacterial pneumonia using the Metras catheter

A new guiding technique, Metras catheter (MC), for blindly introducing a telescoping plugged catheter (TPC) was applied to 25 mechanically ventilated patients with suspected bacterial pneumonia (BPN). Results obtained with TPC-MC were compared with those obtained with TPC using a conventional fiberoptic bronchoscope (FB) in random order. The diagnosis of BPN was definitely confirmed in 18 patients. In 7 patients, all TPC samples (MC and FB) were sterile, and a diagnosis other than BPN was proved. In the former group, colony-forming units equal to or greater than 10(3)/ml of one or more microorganisms were obtained in 61% of TPC-MC and in 66% of TPC-FB samples. These percentages increased to 64 and 71%, respectively, when 4 patients with previous antibiotic treatment were excluded from the study group. Agreement was observed between microorganisms cultured from both TPC samples in 11 of 18 patients with proved BPN (61%). Complete disparity was seen only in 2 patients (11%). Two patients developed a self-limiting hemoptysis after the TPC procedure (MC and FB, respectively). We conclude that TPC-MC is both a sensitive and specific technique for the diagnosis of BPN in mechanically ventilated patients. Because the diagnostic value of TPC-MC is similar to that of TPC-FB, we propose that the MC be used in patients receiving mechanical ventilation when the FB is not available. The simplicity and lower cost of this new system are important advantages to be considered over the fiberoptic bronchoscope.