Early activation of mucosal dendritic cells and macrophages in acute Campylobacter colitis and cholera: An in vivo study

Background and Aim: Macrophages and dendritic cells are closely related mononuclear phagocytic cells. Little is known about their in vivo role in acute intestinal bacterial infections in humans. We undertook to evaluate these cells in rectal mucosal biopsies of patients with acute colitis. Methods: All mucosal mononuclear phagocytic cells in rectal biopsies of patients with acute Campylobacter colitis (n = 5), shigellosis (n = 5), and cholera (n = 10) were evaluated ultrastructurally and compared with those in controls (n = 5). Results: Mononuclear phagocytic cells in the superficial rectal mucosa showed a higher prevalence of ultrastructural features of activation in Campylobacter colitis and cholera than in controls. A lower prevalence of features of activation with increased monocytes was seen in shigellosis. Cells with the ultrastructural morphology of activated dendritic cells constituted 41% and 45% of all mononuclear phagocytic cells in two of five patients with Campylobacter colitis and 4–22% of cells in four of 10 patients with cholera. Their presence in patients with Campylobacter colitis was associated with significant surface epithelial damage and prominent acute inflammatory changes in the mucosa. Conclusions: This is the first ultrastructural study to show activated macrophages and dendritic cells in vivo in acute Campylobacter colitis and cholera. Dendritic cell activation occurred early in the clinical course of these infections. Surface epithelial damage may play a role in the activation of dendritic cells.     

Safety and Efficacy of Oral Transmucosal Fentanyl Citrate Compared to Morphine Sulphate Immediate Release Tablet in Management of Breakthrough Cancer Pain

Aim:

To compare the efficacy and safety of oral transmucosal fentanyl citrate (OTFC) and oral morphine in Indian patients with breakthrough episodes of cancer pain.

Materials and Methods:

In this randomized, open label, active controlled, clinical study, total 186 patients who regularly experienced 1-4 episodes of breakthrough cancer pain (BTCP) daily, over the persistent pain controlled by taking oral morphine 60 mg/day or its equivalent were randomized to receive either OTFC 200 mcg or oral morphine 10 mg for the treatment of BTCP for 3 days. Improvement in pain as determined by numerical rating scale (NRS) at 5, 15, 30, and 60 minutes of drug administration and percentage of BTCP episodes showing reduction in pain intensity by >33% at 15 minutes were primary efficacy endpoints. Secondary efficacy endpoints were requirement for rescue analgesia and global assessment by physician and patient. Data of both treatment groups were analysed by appropriate statistical test using software, STATISTICA, version 11.

Results:

Patients treated with OTFC experienced significantly greater improvement in pain intensity of breakthrough episodes compared to those treated with oral morphine at all assessment time points (P < 0.0001). 56% of breakthrough pain episodes treated with OTFC showed a greater than 33% reduction in pain intensity from baseline at 15 minutes compared to 39% episodes treated with oral morphine (P < 0.0001). Patient''s and physician''s global assessment favoured OTFC than oral morphine (P < 0.0001). Requirement of rescue analgesia in both the study groups was similar (P > 0.05). Both study drugs were well tolerated.

Conclusions:

OTFC was found to provide faster onset of analgesic effect than immediate release oral morphine in management of breakthrough cancer pain.     

2D, 3D-QSAR and docking studies of 1,2,3-thiadiazole thioacetanilides analogues as potent HIV-1 non-nucleoside reverse transcriptase inhibitors

ABSTRACT: BACKGROUND: The discovery of clinically relevant inhibitors of HIV-RT for antiviral therapy has proven to be a challenging task. To identify novel and potent HIV-RT inhibitors the quantitative structure-activity relationship (QSAR) approach became very useful and largely widespread technique for ligand based drug design. METHODS: We perform the two- and three-dimensional (2D and 3D) QSAR studies of a series of 1,2,3-Thiadiazole thioacetanilides Analogues to elucidate the structural properties required for HIV-RT inhibitory activity. RESULTS: The 2D-QSAR studies were performed using multiple linear regression method (MLR), giving r2 = 0.97 and q2 = 0.94. The 3D-QSAR studies were performed using the stepwise variable selection k-nearest neighbor molecular field analysis approach; a leave-one-out cross-validated correlation coefficient q2=0.89 and a non-cross-validated correlation coefficient r2=0.97 were obtained. Docking analysis suggests the new series have comparable binding affinity with the standard compounds. CONCLUSIONS: This approach showed that hydrophobic & electrostatic effects dominantly determine binding affinities which will further useful for development of new NNRTIs.     

Simultaneous papillary muscle avulsion and free wall rupture during acute myocardial infarction. Intra-aortic balloon pump: a bridge to survival

Mechanical complications of acute myocardial infarction (AMI) are rare, but often fatal. Medical therapy does not provide adequate risk reduction, and surgical correction is recommended when feasible. Supplemental hemodynamic support utilizing intra-aortic counterpulsation with a balloon pump provides an improvement in morbidity and mortality when combined with a corrective surgical approach. We report a case of an elderly male with a progressive 2-week history of ischemic symptoms presenting with acute pulmonary edema, hypotension and an inferior wall ST-elevation MI. His hospital course was complicated by ischemic mitral regurgitation (MR) and cardiogenic shock, which resulted in a papillary muscle rupture/avulsion from the inferolateral myocardial wall, and a communication for blood from ventricle to pericardial space. Initial management included mechanical ventilation, pharmacologic inotropic support, percutaneous revascularization of the culprit lesion and intra-aortic balloon counterpulsation. The patient underwent further successful cardiovascular surgical correction of his incompetent mitral valve, free wall rupture and other obstructive coronary arteries, leading to discharge and survival. Mechanical complications from AMI and the role of intra-aortic balloon support are discussed.     

Chandipura virus: a major cause of acute encephalitis in children in North Telangana, Andhra Pradesh, India

A hospital-based surveillance was undertaken between May 2005 and April 2006 to elucidate the contribution of Chandipura virus (CHPV) to acute viral encephalitis cases in children, seroconversion in recovered cases and to compare the seroprevalences of anti-CHPV IgM and N antibodies in areas reporting cases with those without any case of acute viral encephalitis. During this period, 90 cases of acute encephalitis were hospitalized in the pediatric wards of Mahatma Gandhi Memorial (MGM) Hospital, Warangal. There were 49 deaths (Case Fatality Rate, i.e., CFR of 54.4%). Clinical samples and records were obtained from 52 suspected cases. The cases were below 15 years, majority in 0-4 years (35/52, 67.3%). Computerized tomography (CT) scans and cerebro-spinal fluid (CSF) picture favored viral etiology. No neurological sequelae were observed. CHPV etiology was detected in 25 cases (48.1%, n = 52; RNA in 20, IgM in 3 and N antibody seroconversion in 2). JEV etiology was detected in 5 cases (IgM in 4 cases and seroconversion in 1 case). Anti-CHPV IgM seroprevalence in contacts (26/167, 15.6%) was significantly higher (P < 0.05) than in non-contacts (11/430, 2.6%); which was also observed in children <15 years (19/90, 21.1% vs. 3/109, 2.7%). Anti-CHPV N antibody seroprevalence in <15 years contacts (66/90, 73.3%) and non-contacts (77/109, 70.6%) was significantly lower (P < 0.05) than in contacts (75/77, 97.4%) and non-contacts (302/321, 94.1%) more than 15 years respectively. CHPV appears to be the major cause of acute viral encephalitis in children in endemic areas during early monsoon months.