Cytokine-activated natural killer cells exert direct killing of hepatoma cells harboring hepatitis C virus replicons.

Hepatitis C virus (HCV)-specific impairments in host immunity have been described at multiple levels of the innate and adaptive response, which may lead to viral persistence in the majority of infections. Understanding of HCV-associated immune defects could lead to novel therapeutic advances. Natural killer (NK) cells, the major effector cells of the innate immune system, are functionally impaired in chronic HCV infection. It has been suggested that this phenotype is a result of virus-specific defects in antigen-presenting cells (APCs) that regulate NK cell activity, as normal NK function is restored when they are stimulated ex vivo. In this study, we used human NK cell cytotoxicity assays to evaluate the activation-induced effects of NK cells on the HCV replicon-containing hepatic cells. We found that cytokine-activated NK cells were capable of inducing an HCV-associated, perforin/granzyme-dependent lysis of human hepatoma cells and that this required direct cellular contact and was independent of MHC class I expression levels. In contrast, on removal of cytokine stimulation, NK cells failed to exert any direct cytolytic effect on replicon targets. These findings suggest an important underlying mechanism by which NK cells control HCV infection and, with appropriate understanding of HCV-associated immune defects, could lead to novel therapeutic advances.     

Left pulmonary artery evaluation through transesophageal echocardiography.

INTRODUCTION: Transesophageal echocardiography (TEE) has become increasingly useful in the study of patients with suspected pulmonary thromboembolism. OBJECTIVE: The aim of this study was to prospectively evaluate the usefulness of TEE in the study of the distal part of the left pulmonary artery (LPA) as well as the influence of this procedure on total echocardiographic exam duration. METHODOLOGY: A prospective study in two groups of consecutive patients referred for TEE with a one- year interval between evaluation of Group A: 33 patients, 17 male, mean age 54 +/- 24 years, and Group B: 42 patients, 20 male, mean age 48 +/- 27 years (p = NS). The procedure was considered long when it took more than 3 min to evaluate the distal part of the LPA. RESULTS: In group A we were able to visualize the distal part of the LPA in 24 patients (73%) without significant prolongation of total exam duration in 16 patients (48% of group A). In one of the patients with suspected pulmonary thromboembolism thrombi were only observed in the distal part of the LPA. In group B we were able to visualize the distal part of the LPA in 36 patients (86%) without significant prolongation of total exam duration in 26 patients (61% of group B). CONCLUSIONS: 1. Visualization of the distal part of the LPA was possible in more patients, and with TEE time prolongation in less patients, in group B. These differences can be accounted for by the training of the operator in this technique. 2. The importance of visualization of this part of the LPA in guiding treatment in the subset of patients with pulmonary thromboembolism confirms the usefulness of this specific procedure.     

15 Years in surgical management of pulmonary hydatidosis.

OBJECTIVES: Echinococcosis remains an endemic surgical problem in countries where sheep and cattle raising is carried out, particularly in many Mediterranean countries. This study aims to evaluate the management of different presentations of pulmonary hydatidosis and their outcome over 15 years. DESIGN: Retrospective study.Setting: Thoracic surgical department, Chest Diseases Hospital, Kuwait. PATIENTS: Sixty patients operated upon for hydatid disease were evaluated pre- and post- operatively; 35 males, 25 females with a mean age of 28.4 years. Most patients were investigated by laboratory, serological and radiological studies. Different surgical techniques were used to remove the hydatid cyst from the lung. RESULTS: The most common presenting symptoms were cough (41 patients), and 12 patients were asymptomatic. Chest X-ray showed a rounded shadow in 42 patients; 19 cases were of vigorous size >10 cm. Thoracotomy was done in 57 patients; two chest wall cases were managed by minimal skin incision and enucleation, one hydatid cyst of the heart was approached through a median sternotomy. The mean hospital stay was 9 days. Postoperative complications occurred in 9 patients; prolonged air leak in 4 patients, pleural effusion in 3, pneumothorax, and wound infection in one patient each. One patient (65 years old) died on the 6th post-operative day most probably from pulmonary embolism. In a follow-up period of 2-15 years, 4 recurrences have been noted. CONCLUSION: Surgical excision of pulmonary hydatidosis with maximum preservation of the lung parenchyma is the main stay of treatment.     

Human apolipoprotein B. Evidence for its immunochemical heterogeneity using monoclonal antibodies and an immunoenzymometric assay

Predefined monoclonal antibodies (Mabs) were used in an immunoenzymometric assay to study the immunochemical heterogeneity of lipoproteins and to search for potential epitopes with pathological importance. By measuring apolipoprotein B (apo B) epitopes in patients with and without angiographically documented coronary artery disease and in patients with type IIa hyperlipoproteinemia, we have found that both types of patients have a significant increase in Apo B-containing particles specifically recognized by one Mab (BL3). We have also observed that the effects of fenofibrate on type IIa patients vary greatly depending on the plasma concentrations of various Apo B-containing lipoproteins. The greatest effects occurred in patients with epitopes recognized by BL3. Lastly, by sequential precipitation of specific epitopes by BL3, we have obtained evidence that the residual epitope(s) may be related to one or more lipoprotein particles.     

Freezing of gait in postmortem-confirmed atypical parkinsonism.

The frequency and pathophysiology of freezing of gait (FoG) in atypical parkinsonism is unknown. We analysed the frequency of FoG in postmortem-confirmed atypical parkinsonian disorders (APD) comprising corticobasal degeneration (CBD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Sixty-six patients with pathologically confirmed APD (CBD, n = 13; DLB, n = 14; MSA, n = 15; PSP, n = 24) formed the basis for a multicenter clinicopathological study. Clinical features at first and last clinical visit were abstracted from patient records on standardized forms following strict instructions. At the first visit (median 36 months after symptom onset), 24% of APD had FoG (CBD, 8%; DLB, 21%; PSP, 25%; MSA, 40%). Logistic regression analysis showed a significant association of FoG and urinary incontinence (P = 0.04) at first visit. At last visit, 47% of APD had FoG (CBD, 25%; PSP, 53%; DLB, 54%; MSA, 54%). Clinicopathological correlation based on routine postmortem examination failed to identify a consistent neuropathological substrate of FoG. This study demonstrates that (1) FoG is common in APD, and (2) urinary incontinence is significantly associated with FoG in these disorders. Whether FoG and urinary incontinence share similar neuropathological substrates remains to be determined by future studies.     

Adult coeliac disease within a defined geographic area in Sweden. A study of prevalence and associated diseases

An epidemiologic study of coeliac disease in a geographically defined area of Sweden showed that the prevalence was 95.5/10(5) inhabitants aged 15 years or more. The highest prevalence, 178/10(5) inhabitants, was found in the age group 65-74 years. The lowest prevalence, 39/10(5) inhabitants, was found in patients aged 15-24 years. Among the associated diseases an especially high incidence of associated thyroid disease was observed: thyrotoxicosis occurred in 5.0% and hypothyroidism in 5.8% of the patients.