Valvular heart disease in Antiphospholipid antibody syndrome: Isolated Tricuspid stenosis

Antiphospholipid antibody syndrome (APLS) is a rare disorder characterized by a hypercoagulable state. Manifestations include arterial or venous thrombosis, recurrent fetal wastage, coronary artery disease, valvular heart disease, dilated cardiomyopathy, pulmonary artery hypertension, and intracardiac thrombus. Most commonly mitral valve is affected followed by aortic and then tricuspid valve. In this report, a rare case of spontaneous aortic thrombosis with tricuspid stenosis uncomplicated by other valve lesions is presented with clinical and echocardiographic studies and computed tomographic images.     

Binding mode of conformations and structure-based pharmacophore development for farnesyltransferase inhibitors

Farnesyltransferase (FTase) is one of the prenyltransferase family enzymes that catalyse the transfer of 15-membered isoprenoid (farnesyl) moiety to the cysteine of CAAX motif-containing proteins including Rho and Ras family of G proteins. Inhibitors of FTase act as drugs for cancer, malaria, progeria and other diseases. In the present investigation, we have developed two structure-based pharmacophore models from protein–ligand complex (3E33 and 3E37) obtained from the protein data bank. Molecular dynamics (MD) simulations were performed on the complexes, and different conformers of the same complex were generated. These conformers were undergone protein–ligand interaction fingerprint (PLIF) analysis, and the fingerprint bits have been used for structure-based pharmacophore model development. The PLIF results showed that Lys164, Tyr166, TrpB106 and TyrB361 are the major interacting residues in both the complexes. The RMSD and RMSF analyses on the MD-simulated systems showed that the absence of FPP in the complex 3E37 has significant effect in the conformational changes of the ligands. During this conformational change, some interactions between the protein and the ligands are lost, but regained after some simulations (after 2 ns). The structure-based pharmacophore models showed that the hydrophobic and acceptor contours are predominantly present in the models. The pharmacophore models were validated using reference compounds, which significantly identified as HITs with smaller RMSD values. The developed structure-based pharmacophore models are significant, and the methodology used in this study is novel from the existing methods (the original X-ray crystallographic coordination of the ligands is used for the model building). In our study, along with the original coordination of the ligand, different conformers of the same complex (protein–ligand) are used. It concluded that the developed methodology is significant for the virtual screening of novel molecules on different targets.     

Clinical and histopathological findings of ''psoriatic neurodermatitis'' and of typical lichen simplex chronicus

BACKGROUND: We have seen several patients with itchy lichenified plaques located bilaterally on the elbows and/or knees and have named this condition 'psoriatic neurodermatitis' (PN). OBJECTIVE: The purpose of this study was to compare clinical and histopathological characteristics of these patients to those of patients with typical lichen simplex chronicus (LSC). METHODS: Nineteen patients with PN and 34 patients with typical LSC were included. Besides clinical dermatological evaluation, the prick test was carried out on 49 patients; the Phadiatop test on 40 patients; the patch test with European standard series on 47 patients; histopathological evaluation on 39 patients; and clinical psychiatric examination on 38 patients. RESULTS: Almost exclusively, PN was seen in females and was located on the extremities. It caused more plaques than typical LSC did. In PN, the plaques were smaller, sharper, more keratotic and less excoriated, and had fewer lichenoid papules around them. Itching was usually more severe in the evening, while resting and in a hot environment in typical LSC, but not in PN. In plaques of PN, microabscesses in the horny layer, hypogranulosis, regular acanthosis and thinning of the suprapapillary plates were more frequent, and hyperpigmentation in the basal layer was less. In patients with PN, depressive disorder was found more frequently; and generalized anxiety disorder or psychosomatic characteristics, less. There were no significant differences in the results of prick, Phadiatop and patch tests between patients with PN and those with typical LSC. CONCLUSION: In our opinion, it is most likely that the so-called PN is itchy psoriasis superimposed by LSC.     

Treatment of refractoriness to platelet transfusion by protein A column therapy

Ten thrombocytopenic patients (platelets < 10–24 × 10(9)/L) who were refractory to platelet transfusion were investigated for their responsiveness to staphylococcal protein A column therapy. Nine patients had previously been treated with steroids, intravenous immune globulin, and/or other forms of immunosuppressive therapy without improvement in their transfusion response. All patients were receiving multiple platelet transfusions without achieving 1-hour corrected count increments (CCIs) > or = 7500. Eight patients had antibodies that reacted with platelets and were directed against HLA class I antigens, ABO antigens, and/or platelet-specific alloantigens. Plasma (500-2000 mL) from each patient was passed over a protein A silica gel column and then returned to the patient. Patients received from 1 to 14 treatments. A positive response to protein A therapy was defined as at least a doubling of the pretreatment platelet count and/or two successive 10- to 120-minute posttransfusion CCIs > or = 7500. Following plasma treatments, 6 of 10 patients responded with daily platelet counts that averaged 48 +/− 11 × 10(9) per L as compared with counts of 16 +/− 7 × 10(9) per L (p < 0.0005) before treatment. Posttransfusion CCI values determined in four of these patients averaged 2480 +/− 810 and 10,010 +/− 3540 (p < 0.005) before and after treatment, respectively. In contrast, among the four unresponsive patients, platelet counts averaged 10 +/− 9 and 13 +/− 10 × 10(9) per L (p = NS), respectively, while posttransfusion CCIs were 700 +/− 1410 and 1520 +/− 2460 (p = NS), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Quadrivalvular rheumatic heart disease

Three cases of chronic rheumatic heart disease with involvement of all four valves are presented. The involvement of tricuspid and pulmonary valves was suspected clinically and was confirmed by two-dimensional echo, Doppler, hemodynamic and angiographic findings. These findings were also verified surgically and histopathologically in 2 cases. One of the cases died after cardiac catheterization; the other 2 cases were treated surgically with success.     

Solitary bronchioloalveolar carcinoma: CT criteria

The computed tomographic (CT) scans of 30 patients with solitary bronchioloalveolar carcinoma were reviewed. Common features at CT included the peripheral or subpleural location of a pulmonary mass (25 cases), pseudocavitation (18 cases), heterogeneous attenuation (17 cases), irregular margins forming a star pattern (22 cases), and pleural tags (21 cases). Using these CT criteria, four independent observers attempted to identify cases of bronchioloalveolar carcinoma from a larger sample of lung cancers and benign lesions by categorizing a series of test cases into four probability categories. Although the bronchioloalveolar carcinomas were correctly ranked in the two highest probability categories 75% of the time (in 45 of 60 cases), there was considerable overlap with other lung lesions, particularly with adenocarcinoma and large cell undifferentiated carcinoma. However, even though the typical features of bronchioloalveolar carcinoma are not invariable or highly specific, they are characteristic enough to suggest the diagnosis.     

Laparoscopic transhiatal surgery of the esophagus.

OBJECTIVE: Esophagectomy is an operation with high morbidity and mortality. Its adoption as a minimally invasive operation worldwide has been slow, but the potential benefits of reducing the trauma of surgery need to be considered. Our 30-month experience with transhiatal esophagectomy in a district general hospital is presented herein. METHODS: Patients were considered for surgery after radiological staging had excluded inoperable disease. Laparoscopic staging was initially performed. Patients with tumors of the esophagus and high-grade dysplasia in a Barrett's esophagus were included. RESULTS: Twenty-nine patients were referred for consideration for resectional surgery. Nine underwent outpatient laparoscopy only. Twenty patients (age range, 34 to 78, 15 males:5 females) underwent resectional surgery. Seventeen transhiatal resections were completed, 2 were converted to open procedures, and 1 transhiatal resection of a benign tumor was performed. Median time of surgery was 415 minutes (range, 320 to 480) and blood loss was 300 mL (range, 200 to 350). The median length of post-operative ventilation and critical care stay were 1 (range, 1 to 4) and 4 (range, 2 to 8) days. Median duration of hospitalization was 17 days (range, 10 to 28). Thirty-day mortality was 0; 1 patient who was converted to an open procedure died after a cerebrovascular event on day 34. CONCLUSION: A zero mortality rate for laparoscopic resection and a low-morbidity rate compare well with morbidity and mortality in reported series using this method and open surgery. Laparoscopic transhiatal esophagectomy is an advanced, complex procedure that can be performed safely in a district general hospital setting.