Alzheimer's disease risk genes and the age-at-onset phenotype

Despite the recent identification of several novel risk genes for Alzheimer's disease (AD), little is known about their influence on the age at onset (AAO) of AD. The AAO is a phenotype with a heritable component distinct from disease risk and may be a useful trait to study in the context of developing interventions for delaying the onset of AD. We studied the influence of 10 recently identified AD risk genes and APOE in relation to AAO in a large cohort of AD patients (N = 2569). We find that the novel AD risk gene, PICALM, exerts a small effect on the AAO of AD with earlier disease onset in risk allele carriers. In addition, we confirmed the previously reported association between the APOE ε4 allele and earlier disease onset. None of the other AD risk genes influenced AAO of AD. Our results suggest that besides APOE, other genes associated with AD risk do not exert large effects on the AAO phenotype of AD.     

Quality of life assessment in patients with bipolar disorder treated with olanzapine added to lithium or valproic acid

BACKGROUND: The objective of this study was to determine the clinical and quality of life outcomes associated with adjunctive treatment of olanzapine added to either lithium or valproic acid/divalproex sodium in patients with bipolar disorder. METHODS: Patients with bipolar I disorder, were randomized to receive either olanzapine (5-20 mg) added to mood stabilizer therapy (n=224), or placebo added to mood stabilizer therapy (n=112) for 6 weeks. Changes in clinical outcomes over 6 weeks were measured by the Young Mania Rating Scale (Y-MRS) and the Hamilton Rating Scale for Depression (HAM-D). Quality of life was measured by the Lehman Brief Quality of Life Interview (QLI). RESULTS: Patients treated with olanzapine added to mood stabilizers, experienced significantly greater mean clinical improvements from baseline on both the Y-MRS and the HAM-D compared to those treated with placebo added to mood stabilizers. Over 6 weeks, patients treated with olanzapine added to mood stabilizers had significantly greater mean improvements from baseline on five of the nine subjective scales on the QLI, compared to patients treated with placebo added to mood stabilizers. Changes in scores on the subjective scales of the QLI were more strongly correlated to changes in depressive symptomatology measured by the HAM-D, than to changes in symptoms of mania measured by the Y-MRS. CONCLUSION: The results of this study demonstrate that patients receiving adjunctive treatment have significantly greater improvements in both clinical and quality of life outcomes compared to monotherapy with mood stabilizers.     

Economic and health consequences of selling a kidney in India

Context  Many countries have a shortage of kidneys available for transplantation. Paying people to donate kidneys is often proposed or justified as a way to benefit recipients by increasing the supply of organs and to benefit donors by improving their economic status. However, whether individuals who sell their kidneys actually benefit from the sale is controversial. Objective  To determine the economic and health effects of selling a kidney. Design, Setting, and Participants  Cross-sectional survey conducted in February 2001 among 305 individuals who had sold a kidney in Chennai, India, an average of 6 years before the survey. Main Outcome Measures  Reasons for selling kidney, amount received from sale, how money was spent, change in economic status, change in health status, advice for others contemplating selling a kidney. Results  Ninety-six percent of participants sold their kidneys to pay off debts. The average amount received was $1070. Most of the money received was spent on debts, food, and clothing. Average family income declined by one third after nephrectomy (P<.001), and the number of participants living below the poverty line increased. Three fourths of participants were still in debt at the time of the survey. About 86% of participants reported a deterioration in their health status after nephrectomy. Seventy-nine percent would not recommend that others sell a kidney. Conclusions  Among paid donors in India, selling a kidney does not lead to a long-term economic benefit and may be associated with a decline in health. Physicians and policy makers should reexamine the value of using financial incentives to increase the supply of organs for transplantation.      

The use of ultrasound in evaluating orthopaedic trauma patients

Musculoskeletal ultrasound is a low-cost, noninvasive method of evaluating orthopaedic trauma patients. It is particularly useful for patients with metallic hardware, which may degrade computed tomography or magnetic resonance images. Ultrasound has been used to evaluate fracture union and nonunion, infection, ligamentous injury, nerve compression, and mechanical impingement caused by hardware. Real-time dynamic examination allows identification of pathology and provides direct correlation between symptoms and the observed pathology.     

The impact of intraoperative echocardiography on clinical outcomes following adult cardiac surgery

Over the past 30 years, intraoperative echocardiography has become an invaluable diagnostic tool and monitor of cardiac performance for the management of cardiac surgical patients. The essential information provided by intraoperative echocardiography regarding hemodynamic management, cardiac valve function, congenital heart lesions, and great vessel pathology has contributed to its widespread popularity. Numerous investigations have been conducted in an attempt to specifically demonstrate a beneficial impact of intraoperative echocardiography in cardiac surgery. However, there is a relative paucity of data derived from prospective trials in which the use of intraoperative echocardiography has been randomized among various cardiac surgical patient populations to formally ascertain, rather than simply infer, its putative impact on perioperative decision-making and clinical outcomes. Ironically, the popularity of intraoperative echocardiography has imposed ethical limitations on performing randomized trials in patient populations for whom significant benefit has been previously inferred. Nonetheless, significant evidence has been published to support its almost universal acceptance as an important perioperative diagnostic tool and monitor for cardiac surgical patients. This review focuses on the impact of intraoperative echocardiography on clinical outcomes in the more common adult cardiac surgical scenarios, including coronary artery bypass graft surgery, mitral and aortic valve surgery, and in evaluating the intrathoracic aorta.     

Detecting polio through surveillance for acute flaccid paralysis (AFP)

Accurate surveillance for polio is essential for eradication. Surveillance systems for polio has been developed under the guidance of the global polio eradication initiative. Surveillance of cases of acute flaccid paralysis among children less than 15 years of age is a key component for a well functioning polio surveillance system. The surveillance system works through a network of surveillance medical officers, the responsibility of them lies in assisting the health services departments of all states and maintaining a network of acute flaccid paralysis reporting sites and rapidly investigating the cases. Surveillance activities begin when a child comes in contact with a healthcare provider who in turn informs the officer in charge of acute flaccid paralysis surveillance. The goal of the polio network laboratories is to provide accurate and timely results of wild poliovirus detection in stool samples of cases of acute flaccid paralysis. Strong linkages have been established between the acute flaccid paralysis surveillance system and the laboratory network. Laboratories complete poliovirus isolation and if poliovirus is isolated, these are submitted for intratypic differentiations. Acute flaccid paralysis surveillance in India has demonstrated that the eradication activities implemented in India led to dramatic reduction and restriction in the number of cases and geographic spread of poliovirus transmission.     

Preliminary report on the interaction of apolipoprotein E polymorphism with aortic atherosclerosis and acute nephropathy after CABG

Background

Renal dysfunction is a serious complication of cardiac surgery that is highly associated with short- and long-term adverse outcome. While the apolipoprotein E (APOE) ?4 allele has been linked to the occurrence of both postcardiac surgery acute renal injury (?4 favorable) and ascending aortic arteriosclerosis (?4 unfavorable), the role of ?4 in the relationship between these two conditions is unknown. We hypothesized that patients with and without the ?4 allele (E4/non-E4) would have different associations between atheroma burden and postoperative renal dysfunction.

Methods

Ascending, arch, and descending aorta atheromatous burden and APOE status were evaluated for 130 coronary bypass patients. Multivariable analyses were performed for aortic regions to assess the relationship of atheroma burden and APOE ?4 status with peak in-hospital postoperative serum creatinine. All p < 0.05 were considered significant.

Results

We found an interaction between E4 status (E4/non-E4; 24/106) and atheroma burden, with a much greater predicted peak in-hospital postoperative serum creatinine for increases in ascending aorta atheroma load for non-E4 patients versus E4 patients (beta coefficient −0.13; p = 0.002). We also confirmed the association between ascending aorta atheroma and peak creatinine (beta coefficient 0.11; p = 0.0008), after controlling for E4 status, preoperative creatinine, and the E4-atheroma interaction.

Conclusions

Equivalent ascending aortic atheroma burden is associated with a greater susceptibility to postoperative renal injury among patients undergoing cardiac operation who lack the APOE ?4 allele. Findings may be attributable to APOE-related differences in inflammation, susceptibility to atheroma detachment (eg, during operative aortic manipulation), or renal vulnerability to embolic injury.     

The thermal effects of intramedullary reaming

OBJECTIVE: To study the effect of tourniquet control on intramedullary reaming. DESIGN: An experimental prospective nonsurvival animal study was performed using 5 mongrel dogs. A pneumatic tourniquet was randomized to either the right or left hind limb. Tibial intramedullary reaming was performed with progressively larger reamers. Cortical temperatures were measured using thermocouples inserted into the tibial diaphyseal cortex. Thermocouples were connected to an analog to digital converter that output continuous data that was collected on a computer. Upon completion of the procedure, the animals were killed. RESULTS: The peak and low temperatures for each thermocouple with each reamer passage were recorded. Reamer sizes larger than the internal diameter of the intramedullary canal produced higher peak temperatures. The mean delta t (peak temperature minus low temperature) was calculated for each reamer passage. This measurement represents the overall amount of heat generated during each reamer passage. There were no significant differences between the 2 conditions (P = 0.8, paired t test). Temperatures decreased in between reamer exchange but did not return to baseline levels. CONCLUSIONS: Because similar temperatures were measured both with and without a tourniquet, the risk of thermal necrosis appears to be related more to the process of intramedullary reaming than to the tourniquet. Higher temperatures were measured with reamer sizes larger than the internal diameter of the intramedullary canal. Increasing the time interval between the passage of successive reamers may allow heat to dissipate and decrease the risk of thermal necrosis. The clinical practice of limited reaming ("ream-to-fit") should minimize the occurrence of this complication.     

Predictors of inotrope use during separation from cardiopulmonary bypass

OBJECTIVE: To identify the demographic, clinical, and echocardiographic features that predict the use of inotropic support at separation from cardiopulmonary bypass (CPB). Design: Retrospective study of consecutive patients undergoing coronary artery bypass graft (CABG) surgery. SETTING: Referral center for cardiothoracic surgery at a university hospital. PARTICIPANTS: One thousand nine patients undergoing either CABG or combined CABG and valve surgery with CPB in whom an intraoperative transesophageal echocardiography (TEE) examination was performed. INTERVENTIONS: Inotropic support was defined as the use of dopamine >/=5 microg/kg/min; any dose of epinephrine, norepinephrine, dobutamine, and milrinone; or the insertion of an IABP during separation from CPB. Support was implemented by the anesthesia care team as clinically indicated. Comprehensive TEE examinations were conducted before CPB in all patients according to published guidelines and subsequently reviewed by a single, independent operator. MEASUREMENTS and MAIN RESULTS: Inotropic support was used in a total of 394 patients (39%) at separation from CPB. The study identified 6 significant, independent predictors of inotrope use: (1) Wall Motion Score Index, (2) combined CABG and mitral valve repair or replacement surgery, (3) left ventricular ejection fraction <35%, (4) reoperation, (5) moderate-to-severe mitral regurgitation, and (6) aortic cross-clamp time. CONCLUSIONS: Incorporating data from a comprehensive intraoperative TEE examination, the authors identified 6 reproducible factors that independently predict the use of inotropic support at separation from CPB.