Quality of Life and Outcomes in African Americans with CKD

Low health-related quality of life (HRQOL) has been associated with increased risk for hospitalization and death in ESRD. However, the relationship of HRQOL with outcomes in predialysis CKD is not well understood. We evaluated the association between HRQOL and renal and cardiovascular (CV) outcomes in 1091 African Americans with hypertensive CKD enrolled in the African American Study of Kidney Disease and Hypertension (AASK) trial and cohort studies. Outcomes included CKD progression (doubling of serum creatinine/ESRD), CV events/CV death, and a composite of CKD progression or death from any cause (CKD progression/death). We assessed HRQOL, including mental health composite (MHC) and physical health composite (PHC), using the Short Form-36 survey. Cox regression analyses were used to assess the relationship between outcomes and five-point decrements in MHC and PHC scores using measurements at baseline, at the most recent annual visit (time-varying), or averaged from baseline to the most recent visit (cumulative). During approximately 10 years of follow-up, lower mean PHC score was associated with increased risk of CV events/CV death and CKD progression/death across all analytic approaches, but only time-varying and cumulative decrements were associated with CKD progression. Similarly, lower mean MHC score was associated with increased risk of CV events/CV death regardless of analytic approach, while only time-varying and cumulative decrements in mean MHC score was associated with CKD progression and CKD progression or death. In conclusion, lower HRQOL is associated with a range of adverse outcomes in African Americans with hypertensive CKD.     

Diagnostic criteria for testing for BRCA1 and BRCA2: the experience of the Department of Defense Familial Breast/Ovarian Cancer Research Project

The Department of Defense Familial Breast/Ovarian Cancer Research Project has offered genetic counseling and testing for BRCA1 and BRCA2 on a research basis to patients meeting specific diagnostic criteria, with risk for BRCA1 and BRCA2 mutations calculated based on the Couch model. In 2.5 years, 250 patients were evaluated and 101 patients met criteria requirements, including 33 who met criteria in more than one category. Ninety patients elected to undergo DNA testing. In this group of 90 patients, 14 mutations (15.5%) and 16 unclassified variants (17.7%) were identified. The most common inclusion criteria were onset of breast/ovarian cancer before age 45 years (n = 32) and onset of breast/ovarian cancer before age 45 years with strong family history (n = 21). However, when number of mutations and unclassified variants found were compared separately across all diagnostic criteria (including those of more than one capacity) using the chi 2 statistic, no significant differences were seen among the categories to suggest that one criterion was more predictive of mutations or variants than another. Couch risk values for patients with mutations showed a mean of 14% and ranged from 3.2 to 43.5% (range for all patients, 1.2-69.7%). These findings emphasize the importance of using multiple diagnostic criteria and suggest that a Couch risk value of > 3% may be useful in selecting patients for testing. The data also underscore the necessity of genetic counseling in the testing process, particularly given the large number of unclassified variants diagnosed and their uncertain status for disease predisposition.     

Local differences in the trabecular bone structure of the proximal femur depicted with high-spatial-resolution MR imaging and multisection CT

RATIONALE AND OBJECTIVES: The authors performed this study to investigate structural variations in the trabecular bone of the proximal femur at high-resolution magnetic resonance (MR) imaging and high-resolution multisection computed tomography (CT). MATERIALS AND METHODS: Bone mineral density (BMD) was measured in 36 proximal human femur specimens by using dual x-ray absorptiometry. High-resolution MR imaging was performed at 1.5 T with an in-plane spatial resolution of 0.195 x 0.195 mm and a section thickness of 0.3 and 0.9 mm. Multisection CT was performed with an ultra-high-resolution protocol; images were obtained with an in-plane spatial resolution of 0.25 mm and a section thickness of 1 mm. In a subset of these specimens, micro CT was performed with an isotropic spatial resolution of 30 microm. Identical regions of interest (ROIs) were used to analyze images obtained with MR imaging, multisection CT, and micro CT. Trabecular bone structural parameters were obtained, and the parameters from the individual imaging modalities and BMD were correlated. RESULTS: Significant differences concerning the trabecular microarchitecture between the individual ROIs were demonstrated with multisection CT and MR imaging. A number of the correlations between structural parameters derived with multisection CT, MR imaging, micro CT, and BMD measurements were significant. For MR imaging, threshold technique and section thickness had an effect on structural parameters. CONCLUSION: Structural parameters obtained in the proximal femur with multisection CT and high-resolution MR imaging show regional differences. These techniques may be useful for depicting the trabecular architecture in the diagnosis of osteoporosis.     

Gastric inhibitory polypeptide and glucagon-like peptide-1 in the pathogenesis of type 2 diabetes

The incretin effect denominates the phenomenon that oral glucose elicits a higher insulin response than does intravenous glucose. The two hormones responsible for the incretin effect, glucose-dependent insulinotropic hormone (GIP) and glucagon-like peptide-1 (GLP-1), are secreted after oral glucose loads and augment insulin secretion in response to hyperglycemia. In patients with type 2 diabetes, the incretin effect is reduced, and there is a moderate degree of GLP-1 hyposecretion. However, the insulinotropic response to GLP-1 is well maintained in type 2 diabetes. GIP is secreted normally or hypersecreted in type 2 diabetes; however, the responsiveness of the endocrine pancreas to GIP is greatly reduced. In approximately 50% of first-degree relatives of patients with type 2 diabetes, similarly reduced insulinotropic responses toward exogenous GIP can be observed, without significantly changed secretion of GIP or GLP-1 after oral glucose. This opens the possibility that a reduced responsiveness to GIP is an early step in the pathogenesis of type 2 diabetes. On the other hand, this provides a basis to use incretin hormones, especially GLP-1 and its derivatives, to replace a deficiency in incretin-mediated insulin secretion in the treatment of type 2 diabetes.     

Is three-dimensional computed tomography reconstruction justified before endovascular aortic aneurysm repair?

OBJECTIVES: The endovascular management of abdominal aortic aneurysm (AAA) relies on accurate preoperative imaging for proper patient selection and operative planning. Three-dimensional (3-D) computed tomography (CT) with reformatted images perpendicular to blood flow has gained popularity as a method of AAA assessment and image-based planning before endovascular aneurysm repair (EVAR). The current study was undertaken to determine the interobserver agreement of AAA measurements obtained with axial CT and reformatted 3-D CT and to compare the consistency of the 2 methods in selecting patients for EVAR. METHODS: Eight observers assessed the axial CT and reformatted 3-D CT scans for 5 patients with AAAs to determine whether the patients were candidates for EVAR. 3-D CT with multiplanar reformatted images was performed by Medical Media Systems (MMS). Each observer measured the length and diameter of the proximal neck, maximal AAA, aortic bifurcation, common iliac diameter, and aortic angulation. The proximal neck and common iliac arteries were also assessed for thrombus, calcification, and tortuosity. Agreement of the measurements on axial CT scans was compared with those on MMS CT scans by calculating the kappa statistic. Complete agreement was defined as kappa = 1.0. The limits of agreement between observers were also calculated. RESULTS: The cumulative interobserver agreement of MMS CT scans (kappa =.81) was greater than for axial CT scans (kappa =.59). The kappa value for each of the diameter measurements was greater with the MMS CT scans. In 79% of cases the observers' measurements were less than 2 mm from the mean with MMS CT, compared with 59% for axial CT. The kappa value for deciding whether a patient was an endograft candidate on the basis of aortic neck was greater with the MMS CT (0.92 vs 0.63). The limits of agreement between observers were also better with the MMS CT. CONCLUSIONS: The interobserver agreement in planning EVAR is significantly better with MMS CT compared with traditional axial CT. The routine use of MMS CT appears justified before EVAR to improve the accuracy and consistency of patient selection.     

Expression of a cDNA encoding a functional 241-kilodalton vesicular stomatitis virus RNA polymerase.

The large gene, L, of vesicular stomatitis virus (VSV), which codes for the multifunctional RNA-dependent RNA polymerase, was assembled from five overlapping cDNA clones. The sequence of the 6.4-kilobase gene of the final construct was identical to the consensus sequence reported earlier. The gene was inserted into the simian virus 40 transient expression vector pJC119. Antibodies directed against synthetic peptides corresponding to the amino and carboxyl termini of the L protein were raised in rabbits. Both antibodies specifically immunostained the cytoplasm of COS cells that had been transfected with the vector DNA. The expressed L protein was immunoprecipitated from cell extracts and it was identical in size to the L protein of the virion (241 kilodaltons). Most importantly, COS cells that expressed the recombinant L protein transcribed, replicated, and consequently complemented and rescued temperature-sensitive RNA polymerase mutants of VSV at the nonpermissive temperature. The kinetics of virus release were similar to those of a wild-type VSV infection. We conclude that the recombinant RNA polymerase protein L is indistinguishable in its size and its functions from the VSV polymerase.     

Percutaneous perfusion of occluded coronary arteries with blood from the femoral artery: a dog study

The idea of perfusing the distal coronary artery with arterial blood during balloon dilatation was implemented in early experimental coronary angioplasty but then abandoned. We pursued this concept in an animal model using a specially designed roller pump. The pump delivers blood from a femoral artery catheter through the central lumen of a balloon catheter occluding a coronary artery. Perfusion of large proximally occluded coronary arteries for at least 60 min was possible in 8 of 11 heparinized dogs. Hemolysis occurring in the pump system due to the small catheter lumen proved a minor problem. For a limited period of time, occluded coronary arteries can be adequately perfused with arterial blood by this percutaneous system that is readily applicable in any catheterization laboratory. Its use is conceivable not only for temporary treatment of acute complications during angioplasty but also for prolonged balloon dilatations of spastic or thrombosed coronary arteries.     

Prolactin permits the expression of a circadian variation in lipogenic responsiveness to insulin in hepatocytes of the golden hamster (Mesocricetus auratus)

Lipogenesis was determined at two times (07.00 and 16.00 h) during a 14-h daily photoperiod (08.00-22.00 h) in freshly prepared hamster hepatocytes with or without addition of insulin. The hamsters were pretreated for 5 days with bromocriptine (to inhibit prolactin secretion), bromocriptine and prolactin replacement, or control saline injections. Lipogenesis was determined by incorporation of [14C]acetate into total cell lipids over a 30-min interval. Lipogenesis was three times greater at 07.00 than at 16.00 h and insulin was effective in stimulating further lipogenesis only at 07.00 h. Bromocriptine pretreatment severely reduced incorporation of radiolabel at 07.00 h to levels comparable with controls at 16.00 h and completely inhibited the stimulatory effect of insulin at 07.00 h. Prolactin replacement in bromocriptine-treated hamsters reversed the inhibitory effect of bromocriptine on hepatocyte lipogenesis and promoted dramatic lipogenic responses to insulin at 07.00 h. These results indicate that insulin stimulates hepatic lipogenesis only during some portion of a day and that prolactin facilitates the lipogenic response.     

Pulsatile Pump Decreases Risk of Delayed Graft Function in Kidneys Donated After Cardiac Death

Organ storage techniques have been under scrutiny to determine the best preservation method, particularly in donation after cardiac death (DCD) kidneys. Conflicting literature on the benefit of pulsatile perfusion (PP) over cold storage (CS) warrants further investigation. We analyzed the risk of developing delayed graft function (DGF) in recipients of DCD and donation after brain death (DBD) kidneys undergoing PP or CS. We stratified on basis of cold ischemic time (CIT) to determine the interaction of preservation techniques, CIT and DCD kidneys on developing DGF. Of 54 136 recipients, 4923 received DCD kidneys of which 3330 (67%) underwent PP. Of 49 213 DBD recipients, 7531 (15%) underwent PP. DCD had a higher risk of DGF versus DBD (adjusted odds ratio, AOR 3.2; 3.0–3.5). PP kidneys had less DGF (AOR 0.59; 0.56–0.63) compared to CS. Interaction models of method by donor type referenced to PP/DBD revealed CS/DBD kidneys had higher DGF (AOR 1.8; 1.7–1.9), whereas CS/DCD kidneys had the highest risk of DGF (AOR 5.01; 4.43–5.67). Even though suggestive for a benefit of PP on DGF, this retrospective analysis cannot address whether this is an intrinsic effect of PP or is associated with the logistics of PP such as discard of DCD kidneys based on pump parameters.     

Robot-Assisted Transaxillary Thyroid Surgery in the United States: Is it Comparable to Open Thyroid Lobectomy?

Background  

The purpose of this study was to compare the outcome of robot-assisted transaxillary thyroid surgery (RATS) to the standard open technique for thyroid lobectomy in the U.S. population.