An abnormal triglyceride-rich lipoprotein containing excess sialylated apolipoprotein C-III.

An abnormal triglyceride-rich lipoprotein has been isolated from some patients with chronic renal failure or severe hypertriglyceridemia. The abnormal lipoprotein was characterized by an increased content of apolipoprotein (apo) C-III-2 (57.5% of total apo C-III peptides compared with 35.5% for controls, P less than 0.001) as characterized by isoelectric focusing and scanning densitometry. As determined by a substrate competition assay, the abnormal lipoprotein was a less efficient substrate for purified bovine milk lipoprotein lipase than control lipoproteins. Neuraminidase digestion of abnormal or control lipoprotein resulted in a reduction of the apo C-III-2 band with a corresponding increase in the region of apo C-III-0, which suggests that the increased content of apo C-III-2 in the abnormal is due to excessive sialylation of the C-III peptide. Limited incubation of the abnormal lipoproteins with neuraminidase caused a partial loss of sialic acid and resulted in a triglyceride-rich lipoprotein with a normal C-III-2:C-III-1 ratio. This preparation displayed normal substrate interaction with lipoprotein lipase. Three severely hypertriglyceridemic patients with the abnormal lipoprotein showed a marked reduction in serum triglyceride concentration, which is associated with a reversion to a normal C-peptide profile after dietary therapy. The results suggest that the extent of sialylation of the apo C-III peptide carried on triglyceride-rich lipoproteins may be critical for their interaction with lipoprotein lipase.     

Insulin receptors in beta-cells are critical for islet compensatory growth response to insulin resistance

Insulin and insulin-like growth factor 1 (IGF1) are ubiquitous growth factors that regulate proliferation in most mammalian tissues including pancreatic islets. To explore the specificity of insulin receptors in compensatory beta-cell growth, we examined two models of insulin resistance. In the first model, we used liver-specific insulin receptor knockout (LIRKO) mice, which exhibit hyperinsulinemia without developing diabetes due to a compensatory increase in beta-cell mass. LIRKO mice, also lacking functional insulin receptors in beta-cells (beta IRKO/LIRKO), exhibited severe glucose intolerance but failed to develop compensatory islet hyperplasia, together leading to early death. In the second model, we examined the relative significance of insulin versus IGF1 receptors in islet growth by feeding high-fat diets to beta IRKO and beta-cell-specific IGF1 receptor knockout (beta IGFRKO) mice. Although both groups on the high-fat diet developed insulin resistance, beta IRKO, but not beta IGFRKO, mice exhibited poor islet growth consistent with insulin-stimulated phosphorylation, nuclear exclusion of FoxO1, and reduced expression of Pdx-1. Together these data provide direct genetic evidence that insulin/FoxO1/Pdx-1 signaling is one pathway that is crucial for islet compensatory growth response to insulin resistance.     

Are all n-3 polyunsaturated fatty acids created equal?

N-3 Polyunsaturated fatty acids have been shown to have potential beneficial effects for chronic diseases including cancer, insulin resistance and cardiovascular disease. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in particular have been studied extensively, whereas substantive evidence for a biological role for the precursor, alpha-linolenic acid (ALA), is lacking. It is not enough to assume that ALA exerts effects through conversion to EPA and DHA, as the process is highly inefficient in humans. Thus, clarification of ALA's involvement in health and disease is essential, as it is the principle n-3 polyunsaturated fatty acid consumed in the North American diet and intakes of EPA and DHA are typically very low. There is evidence suggesting that ALA, EPA and DHA have specific and potentially independent effects on chronic disease. Therefore, this review will assess our current understanding of the differential effects of ALA, EPA and DHA on cancer, insulin resistance, and cardiovascular disease. Potential mechanisms of action will also be reviewed. Overall, a better understanding of the individual role for ALA, EPA and DHA is needed in order to make appropriate dietary recommendations regarding n-3 polyunsaturated fatty acid consumption.     

The multiple mini‐interview: how long is long enough?

Objectives  The multiple mini-interview (MMI) overcomes the limitations of the traditional panel interview by multiple sampling to provide improved objectivity and reliability. Reliability of the MMI is affected by number of stations; however, there are few data reporting the influence of interview duration on MMI outcome and reliability. We aimed to determine whether MMI stations can be shortened without affecting applicant rankings or compromising test reliability.
Methods  A total of 175 applicants were interviewed and assessed at 10 8-minute stations. Applicants were scored once after 8 minutes at five control stations and twice after 5 minutes and 8 minutes at five experimental stations. Scores at 5 and 8 minutes were compared using t -tests and correlation coefficients. Rankings of applicants based on 5- and 8-minute scores were compared using Spearman's rank order coefficient. The reliability of the MMI was examined for 5- and 8-minute scores using generalisability theory.
Results  Mean scores at 5 minutes were lower than mean scores at 8 minutes. Cumulative scores at 5 minutes were also lower. There were highly significant correlations between 5- and 8-minute scores at all experimental stations (0.82–0.91; P  < 0.01) and between the cumulative scores at 5 and 8 minutes (0.92; P  < 0.01). There was a strong correlation between applicant rankings based on cumulative 5- and 8-minute scores (Spearman's rank order coefficient 0.92). Reliability was not affected.
Conclusions  Reducing the duration of MMI stations from 8 to 5 minutes conserves resources with minimal effect on applicant ranking and test reliability.     

Comparison of conforming and nonconforming retrieved glenoid components

The purpose of this study was to compare differences in wear performance of conforming and nonconforming glenoid designs, using clinical, radiographic, and retrieved polyethylene glenoid component outcome Sixty-three glenoids met the study criteria, and each glenoid was assigned to the conforming group (if the radii of curvature of the humeral and glenoid components were identical) or the nonconforming group (if a mismatch existed between the radii of curvature). The mean length of implantation was 5.6 +/- 5.5 years in the conforming group and 3.1 +/- 3.1 years for the nonconforming group (P < .05). The loosening score was 3.2 +/- 2.0 in the conforming group and 2.4 +/- 1.2 in the nonconforming one (P < .05). The nonconforming group had a significantly greater burnishing score (P < .01), while the conforming group had greater abrasion and delamination scores (P < .05). Articular conformity contributes to differences observed from retrieved polyethylene glenoid components, which are consistent with differences in performance that may influence loosening.     

Elbow arthroscopy

Arthroscopy of the elbow was originally considered to be an unsafe procedure because of the small size of the elbow joint capsule and its proximity to several crucial neurovascular structures. Over the past decade, however, the procedure has become safer and more effective. These improvements can be attributed to a better understanding of elbow anatomy and of the disorders about the elbow as well as to advances in arthroscopic equipment and surgical technique. The most common indications for elbow arthroscopy include removal of loose bodies, synovectomy, débridement and/or excision of osteophytes, capsular release, and the assessment and treatment of osteochondritis dissecans. More recent advances have expanded the indications of elbow arthroscopy to include fracture management (eg, radial head fractures) and the treatment of lateral epicondylitis.     

A single-institution experience with the AneuRx Stent Graft for endovascular repair of abdominal aortic aneurysm

We report our experience of endovascular repair of infrarenal abdominal aortic aneurysms (EVAR) using the modular AneuRx Stent Graft System. We retrospectively reviewed the outcomes of 113 patients who underwent EVAR with the AneuRx system performed at our institution between October 1999 and August 2003. The mean age of this group was 72.5 years, with 71% (n = 80) over the age of 70 years and 95% (n = 107) males. Aneurysm diameter ranged 4.0-9.0 cm, with 33% (n = 37) >6.0 cm. The average duration of late follow-up was 32.6 +/- 24.8 months (median = 37). Successful deployment of the modular AneuRx system was noted in all patients. There were no immediate operative conversions, deaths within 24 hr of operation, or type I or III endoleaks observed at the completion of the procedure. Thirty-day mortality was 3.5% (n = 4). Acute deployment-related complications occurred in 10% (n = 13) of patients and included misdeployment, operative bleeding, arterial perforation/dissection, and access site complications. Acute systemic complications were present in nine patients, predominantly renal and cardiac complications. An endoleak noted at any time occurred in 25% of patients, with 40% of those requiring a secondary intervention. Two patients suffered late aneurysm rupture due to a type I endoleak and graft infection. Kaplan-Meier analysis revealed 5-year freedom from secondary intervention of 72.4%; freedom from aneurysm-related death of 93.9%; and probability of survival based on all-cause mortality of 60.1%. Endovascular treatment with the modular AneuRx Stent Graft System is safe and effective, producing acceptable rates of disease-free survival and mid-term clinical outcome.