Pharmacodynamic and efficacy profile of TGN 255, a novel direct thrombin inhibitor, in canine cardiopulmonary bypass and simulated mitral valve repair

Heparin-induced thrombocytopenia can be a life-threatening sequel to conventional use of unfractionated heparin in cardiopulmonary bypass (CPB). This study evaluated the pharmacokinetic/pharmacodynamic (PK/PD) and efficacy profile of a novel direct thrombin inhibitor, TGN 255, during cardiac surgery in dogs. Point-of-care coagulation monitoring was also compared against the plasma concentrations of TRI 50c, the active metabolite of TGN 255. The study was conducted in three phases using 10 animals: phase 1 was a dose-ranging study in conscious animals (n = 6), phase 2 was a similar but terminal dose-ranging study in dogs undergoing CPB (n = 6), and phase 3 was with animals undergoing simulated mitral valve repair (terminal) using optimal TGN 255 dose regimens derived from phases I and II (n = 4). During the study, PD markers and drug plasma levels were determined. In addition, determinations of hematologic markers and blood loss were undertaken. Phase 1 studies showed that a high-dose regimen of a 5-mg/kg bolus and infusion of 20 mg/kg/h elevated PD markers in conscious animals, at which time there were no measured effects on platelet or red blood cell counts, and the mean plasma concentration of TRI 50C was 20.6 microg/mL. In the phase 2 CPB dose-ranging study, this dosing regimen significantly elevated all the PD markers and produced hemorrhagic and paradoxical thrombogenic effects. In the phase 3 surgical study, a lower TGN 255 dose regimen of a 2.5-mg/kg bolus plus 10 mg/kg/h produced anticoagulation, elevated PD markers, and produced minimal post-operative blood loss in the animals. Plasma levels of TRI 50C trended well with the conventional point-of-care coagulation monitoring. TGN 255 provided effective anticoagulation in a canine CPB procedure, enabling successful completion with minimal blood loss. These findings support further evaluation of TGN 255 as an anticoagulant for CPB.     

Scoring satisfaction among patients,attending ART Centre of a medical college in north-west India

Patient satisfaction is a measurable concept comprising multidimensional elements such as access to care, quality of the provider patient interpersonal relationship and affordability of care. This further influences the decisions to seek care and outcomes of diseases. Although stigma and discrimination are potential barriers to effective implementation of the antiretroviral therapy (ART) programme, higher satisfaction levels of patients are also crucial for treatment adherence. A hospital-based cross-sectional study was conducted at the ART centre of IG Medical College, Shimla from November 2008 through May 2009. Three hundred and eighty four consecutive adult (≥18 years) patients attending the ART centre and on ART who consented to participate in the study were enrolled. Of the 384 patients, 209 (54.4%) were males. Majority were in the age bracket of 25–44 years. About 61.6% of the patients were satisfied to the services being provided. Mean Patient Satisfaction Questionnaire (PSQ) scores were the highest for technical quality of care and lowest for financial aspects. About 69.4% of the patients were satisfied towards their care provider. Although a majority of the patients were satisfied, several areas of patient care need improvement.     

Negative chronotropic effect of proton pump inhibitors on frog-heart preparation

Proton pump inhibitors (PPIs) have been known to cause bradycardia. We evaluated the effect of three PPIs, i.e. omeprazole, rabeprazole and pantoprazole on the heart rate of frog. The in situ frog heart preparation was set up. Heart rate and amplitude of contraction were studied following administration of different doses of the three PPIs. Statistical analysis was done by using Graphpad statistical software system. After 1 mg of omeprazole and rabeprazole, and 2 mg pantoprazole, the heart rate was similar as compared to baseline (p >0.05). After 2 mg of omeprazole and rabeprazole, and 4 mg pantoprazole, the reduction in heart rate was significant (p <0.05). In addition, pantoprazole caused negative ionotropic effect. The three PPIs showed a dose-dependent negative chronotropic effect in the frog heart prepration.     

Arterial complications of thoracic outlet syndrome

Objective: Arterial vascular complications resulting from thoracic outlet compression, although rare, can be substantial and potentially limb threatening. These complications are due to compressions at the thoracic outlet, the treatment of which continues to be a dilemma. The objective of the present study was to review our experience with this problem with particular reference to its management. Methods: We performed a retrospective study of 12 years and retrieved data from the medical records department of Nizam’s Institute of Medical Sciences, Hyderabad, India. A retrospective review identified 35 patients (age range 15–50 years). In 31 patients, the vasculopathy was caused by a cervical rib, soft tissue anomalies (n = 31), and an elongated transverse process (n = 4). Evaluation included assessment with colour duplex and arteriography with positional maneuvers. Thirty‐two patients presented with a fixed pulse deficit, 22 patients had palpable mass and 15 patients had distal embolization. Results: In 31 patients with cervical rib, the rib was excised via a supraclavicular approach, Scalenectomy was performed and the arterial pathology was repaired on its merit, usually by a vein graft replacement or bypass. The elongated process was excised in the other four patients. Twelve patients required thrombectomy of the distal arteries and a bypass procedure (with a vein/prosthetic graft) was performed in 14 patients. Dorsal sympathectomy, as an adjunct, was carried out in 10 patients. In view of their advanced distal disease, four patients were given prostaglandin therapy. Short‐term follow up of 2 years showed good results. Conclusion: Our results show that simple excision of the cervical rib with scalenectomy via supraclavicular approach, together with arterial reconstruction (if required) is adequate for arterial vascular complications resulting from thoracic outlet compression. Patients with severe distal disease may require other adjunct procedures like dorsal sympathectomy or prostaglandin infusions along with proximal reconstruction.     

Inborn errors of amino acid metabolism in North India

Summary We screened 2560 referred cases for inborn errors of amino acid metabolism by chemical tests and thin-layer chromatography of urine/plasma. In 62(2.4%) cases, eleven inherited Mendelian disorders of amino acids were identified. The four commonest disorders were homocystinuria, alcaptonuria, maple syrup urine disease and nonketotic hyperglycinaemia. Ornithinaemia was detected in two cases (0.08%), and phenylketonuria and cystinuria in two cases each (0.08%). Generalized hyperaminoacidurias were found in 90 (3.52%) subjects. The frequency pattern of the various amino acid disorders in North India was found to be remarkably different from that observed in the West.     

Trends in Early Mortality From Multiple Myeloma: A Population-Based Analysis

IntroductionDespite significant improvements in multiple myeloma (MM) treatment modalities, patient mortality early in the course of disease has been identified as a persistent phenomenon with variable reported rates and causes. Trends in early mortality over time have not been clearly defined.Patients and MethodsThe Surveillance Epidemiology and End Results (SEER) database was used to identify adult patients with MM between 1975 and 2015. Association of available sociodemographic factors with all-cause and MM-specific early mortality (death within 6 months after the diagnosis of MM) was conducted by multivariate analysis. Trends in early mortality were studied by joinpoint regression analysis.ResultsOf the 90,975 MM cases included in this analysis, early mortality was noted in 21%. Median age was 68 years overall, and 75 years for the early mortality cohort (P < .01). The most common causes of death for early mortality were MM itself, followed by cardiovascular, infections, and renal failure. Male gender, “other” race/ethnicity group, advancing age, and West, Midwest or South regions (reference Northeast) were associated with increased risk of both all-cause and MM-specific early mortality. Joinpoint regression analysis of trends data resulted in 1 joinpoint for all-cause 6-month mortality (2006-2015), while 2 joinpoints were noticed for myeloma-specific 6-month mortality (1975-1987 and 2003-2015).ConclusionEarly mortality remains a significant unmet need for MM patient care, despite improving trends in recent years. Understanding the factors associated with early mortality can help develop individualized plans of patient care and mitigate circumstances that may contribute to early mortality among MM patients.