Bariatric surgery improves cardiac function in morbidly obese patients with severe cardiomyopathy.

BACKGROUND: Longstanding morbid obesity can be associated with severe cardiomyopathy. However, the safety and efficacy of bariatric surgery in patients with severe cardiomyopathy has not been studied, and the effect of surgical weight loss on postoperative cardiac function is also unknown. In addition, morbidly obese patients have significantly increased mortality associated with cardiac transplantation, often precluding them from becoming recipients. METHODS: A retrospective study of patients with a left ventricular ejection fraction < or =35% who underwent bariatric surgery (1998-2005) was performed. Short-term morbidity/mortality, length of stay, excess weight loss, pre- and postoperative left ventricular ejection fraction, and New York Heart Association (NYHA) functional class were assessed. RESULTS: A total of 14 patients (10 men and 4 women) with a mean preoperative body mass index of 50.8 +/- 2.04 kg/m(2) underwent bariatric surgery (10 underwent laparoscopic Roux-en-Y gastric bypass, 1 open Roux-en-Y gastric bypass, 2 sleeve gastrectomy, and 1 laparoscopic gastric banding). The complications were pulmonary edema in 1, hypotension in 1, and transient renal insufficiency in 2. The median length of stay was 3.0 days (range 2-9). The mean excess weight loss at 6 months was 50.4%, with a decrease in the mean body mass index from 50.8 +/- 2.04 kg/m(2) to 36.8 +/- 1.72 kg/m(2). The mean left ventricular ejection fraction at 6 months had significantly improved from 23% +/- 2% to 32% +/- 4% (P = .04), correlating with improved functional capacity, as measured by the NYHA classification. Preoperatively, 2 patients (14%) had an NYHA classification of IV, 6 (43%) a classification of III, and 6 (43%) a classification of II. At 6 months postoperatively, no patient had an NYHA classification of IV, 2 (14%) had a classification of III, and 12 (86%) an NYHA classification of II. Two patients had undergone cardiac transplant evaluations preoperatively and underwent successful transplantation after weight loss. CONCLUSION: The results of our study have shown that bariatric surgery for patients with cardiomyopathy is feasible and effective. Surgically induced weight loss results in both subjective and objective improvement in cardiac function. In addition, surgical weight loss can provide a bridge to transplantation in patients who were prohibited secondary to their morbid obesity.     

A retrospective review of basilic and cephalic vein-based fistulas

This study compares outcomes of basilic and cephalic vein fistulas for hemodialysis. A retrospective review of arteriovenous fistulas in a university hospital system was performed using charts and hemodialysis records. Patency and demographic data were assessed with life table analysis. One hundred fifty-six patients (88 males; 68 females) underwent creation of 172 autogenous fistulas (mean age 61 years; mean follow-up 78 weeks). There were 101 basilic vein transpositions and 71 cephalic vein fistulas. Primary patency did not differ significantly, while assisted primary patency was significantly better for basilic vein fistulas at one year (73% versus 53%: P = 0.024). Secondary patency was significantly better for basilic fistulas through three years (58% versus 52%; P = 0.027). Primary failure (thrombosis before access or failed maturation) was significantly higher for cephalic than basilic fistulas (28% versus 13%; P = 0.01). Maturation time, usage time and complications were not significantly significant. Thirty-three (33%) basilic vein-based fistulas and 12 (17%) cephalic vein fistulas required revision during follow-up. Basilic vein-based fistulas perform as well as or better than cephalic vein-based fistulas in terms of patency, maturation time, and usage time and complication rates, though requiring more re-interventions.     

The interaction index, a novel information-theoretic metric for prioritizing interacting genetic variations and environmental factors

We developed an information-theoretic metric called the Interaction Index for prioritizing genetic variations and environmental variables for follow-up in detailed sequencing studies. The Interaction Index was found to be effective for prioritizing the genetic and environmental variables involved in GEI for a diverse range of simulated data sets. The metric was also evaluated for a 103-SNP Crohn''s disease dataset and a simulated data set containing 9187 SNPs and multiple covariates that was modeled on a rheumatoid arthritis data set. Our results demonstrate that the Interaction Index algorithm is effective and efficient for prioritizing interacting variables for a diverse range of epidemiologic data sets containing complex combinations of direct effects, multiple GGI and GEI.     

Primary cardiac lymphoma masquerading as right atrial myxoma causing complete heart block—a case report

Secondary involvement of the heart and pericardium by systemic lymphoma is well documented. Primary Cardiac lymphomas (PCL) are extremely rare. Incidence of PCL is increasing in immunocompromised patients. However PCL in immunocompetent is much rarer. We report such a case of PCL in an immunocompetent elderly female masquerading as right atrial myxoma causing complete heart block which was surgically debulked successfully. Her rhythm resumed to Sinus rhythm following surgical debulking. Immunohistochemistry of the excised tumour revealed Diffuse Large B cell lymphoma. With combination chemotherapy, she is symptom free on six months follow up.     

Evaluation of Hydro-Alcoholic Extract of Eclipta alba for its Multidrug Resistance Reversal Potential: An In Vitro Study

The development of multidrug resistance (MDR) causes problems in the chemotherapy of human cancer. The present study was designed to evaluate and establish the role of Eclipta alba as MDR reversal agent using multidrug resistant hepatocellular carcinoma cell line (DR-HepG2). To develop DR-HepG2, hepatocellular carcinoma cell line (HepG2) was transfected with 2-Acetylaminofluorene (AAF) and Aflatoxin B1 (AFB). Cytotoxic effects of the Eclipta alba hydroalcoholic extract (EAE) and standard anti-ancer drug Doxorubicin (DOX) were determined in DR-HepG2 and the parental cells HepG2 using MTT assay. The expression level of MDR1 gene and P-glycoprotein (P-gp) level was analyzed by RT-PCR and western blotting. From the present investigation, it was found that EAE (10 and 20 μg/ml) could significantly inhibit cell proliferation in DR-HepG2 whereas DOX (0.5 μg/ml) could not because of enhancement effect of MDR1/P-gp. This study demonstrated for the first time the antiproliferative activities of EAE in multidrug resistant DR-HepG2 cells. The findings revealed that Eclipta alba components are effective inhibitors of MDR1/P-gp.     

Disposition of desloratadine in healthy volunteers

The absorption, metabolism and excretion of desloratadine (DL, Clarinex®) were characterized in six healthy male volunteers. Subjects received a single oral 10-mg dose of [¹⁴C]DL (～104?µCi). Blood, urine and feces were collected over 240?h. DL was well absorbed; drug-derived radioactivity was excreted in both urine (41%) and feces (47%). With the exception of a single subject, DL was extensively metabolized; the major biotransformation pathway consisted of hydroxylation at the 3 position of the pyridine ring and subsequent glucuronidation (3-OH-DL-glucuronide or M13). In five of the six subjects, DL was slowly eliminated (mean t_½?=?19.5?h) and persisted in the plasma for 48–120?h post-dose. This is in contrast to a t_½ of ～110?h and quantifiable plasma DL concentrations for the entire 240-h sampling period in one subject, who was identified phenotypically as a poor metabolizer of DL. This subject also exhibited correspondingly lower amounts of M13 in urine and 3-OH-DL (M40) in feces. Disposition of DL in this subject was characterized by slow absorption, slow metabolism and prolonged elimination. Further clinical studies confirmed the lack of safety issues associated with polymorphism of DL metabolism (Prenner et al. 2006, Expert Opinion on Drug Safety, 5: 211–223).     

Oxaliplatin pharmacokinetics and pharmacodynamics in adult cancer patients with impaired renal function.

PURPOSE: To characterize the pharmacokinetics and pharmacodynamics of oxaliplatin in cancer patients with impaired renal function. EXPERIMENTAL DESIGN: Thirty-four patients were stratified by 24-h urinary creatinine clearance (CrCL) into four renal dysfunction groups: group A (control, CrCL, >or=60 mL/min), B (mild, CrCL, 40-59 mL/min), C (moderate, CrCL, 20-39 mL/min), and D (severe, CrCL, <20 mL/min). Patients were treated with 60 to 130 mg/m2 oxaliplatin infused over 2 h every 3 weeks. Pharmacokinetic monitoring of platinum in plasma, plasma ultrafiltrates, and urine was done during cycles 1 and 2. RESULTS: Plasma ultrafiltrate platinum clearance strongly correlated with CrCL (r2 = 0.712). Platinum elimination from plasma was triphasic, and maximal platinum concentrations (Cmax) were consistent across all renal impairment groups. However, only the beta-half-life was significantly prolonged by renal impairment, with values of 14.0 +/- 4.3, 20.3 +/- 17.7, 29.2 +/- 29.6, and 68.1 h in groups A, B, C, and D, respectively (P = 0.002). At a dose level of 130 mg/m2, the area under the concentration time curve increased in with the degree of renal impairment, with values of 16.4 +/- 5.03, 39.7 +/- 11.5, and 44.6 +/- 14.6 mug.h/mL, in groups A, B, and C, respectively. However, there was no increase in pharmacodynamic drug-related toxicities. Estimated CrCL using the Cockcroft-Gault method approximated the measured 24-h urinary CrCL (mean prediction error, -5.0 mL/min). CONCLUSIONS: Oxaliplatin pharmacokinetics are altered in patients with renal impairment, but a corresponding increase in oxaliplatin-related toxicities is not observed.