Citations

Animal studies indicate that oversupply of fatty acids derived from the action of cardiac lipoprotein lipase (LPL) on plasma lipoproteins may contribute to myocardial dysfunction. However, the contribution of circulating triglycerides to myocardial fatty acid supply in humans is not known. Six postabsorptive nondiabetic subjects who were scheduled for diagnostic coronary angiography were studied. 14C oleate and a lipid emulsion labeled with 3H triolein were infused to assess myocardial uptake of free fatty acids (FFAs) and triglycerides, as well as myocardial spillover of LPL-generated fatty acids. Six paired blood samples were taken from the femoral artery and the coronary sinus. Coronary sinus concentrations of unlabeled triglycerides were slightly, but not significantly, lower than arterial (P = 0.12), whereas labeled triglyceride concentrations were significantly lower in the coronary sinus than in the artery (P < 0.05; extraction fraction ≅11%). Triglycerides and FFAs accounted for ∼17% and ∼83%, respectively, of myocardial fatty acid uptake. Systemic and myocardial fractional spillover of LPL-generated fatty acids was 49.0 ± 7% and 34.7 ± 13%, respectively. The myocardium was a minor contributor to systemic triglyceride uptake (∼3%) and a trivial contributor to systemic FFA production (∼0.5%). These results indicate that circulating triglycerides may be a significant source of fatty acids for myocardial respiration.

Melanin concentrating hormone (MCH) is a hypothalamic neuropeptide known to play a critical role in energy balance. We have previously reported that overexpression of MCH is associated with mild obesity. In addition, mice have substantial hyperinsulinemia and islet hyperplasia that is out of proportion with their degree of obesity. In this study, we further explored the role of MCH in the endocrine pancreas. Both MCH and MCHR1 are expressed in mouse and human islets and in clonal β-cell lines as assessed using quantitative real-time PCR and immunohistochemistry. Mice lacking MCH (MCH-KO) on either a C57Bl/6 or 129Sv genetic background showed a significant reduction in β-cell mass and complemented our earlier observation of increased β-cell mass in MCH-overexpressing mice. Furthermore, the compensatory islet hyperplasia secondary to a high-fat diet, which was evident in wild-type controls, was attenuated in MCH-KO. Interestingly, MCH enhanced insulin secretion in human and mouse islets and rodent β-cell lines in a dose-dependent manner. Real-time PCR analyses of islet RNA derived from MCH-KO revealed altered expression of islet-enriched genes such as glucagon, forkhead homeobox A2, hepatocyte nuclear factor (HNF)4α, and HNF1α. Together, these data provide novel evidence for an autocrine role for MCH in the regulation of β-cell mass dynamics and in islet secretory function and suggest that MCH is part of a hypothalamic-islet (pancreatic) axis.

Symptomatic arrhythmias are frequently observed in the intensive care unit and often lead to significant hemodynamic compromise because of the presence of multisystem disease. In particular, prompt evaluation of patients with tachycardia is critical because treatment depends on the accurate diagnosis of the arrhythmia mechanism. The electrocardiogram remains the most important diagnostic tool for the evaluation of both wide complex and narrow complex tachycardia. For wide complex tachycardia, evaluation of the atrioventricular relationship and QRS morphology are critical, and for narrow QRS complex tachycardias, evaluation focuses on identification of the location and morphology of P waves. Bradycardia can arise from sinus node dysfunction or atrioventricular conduction block.

The evaluation of chronic wrist pain can be a diagnostic dilemma. Lidocaine injections combined with corticosteroids are often used for both diagnosis and therapy. The purpose of this study was to determine if a midcarpal injection of lidocaine could serve as a diagnostic tool in patients with chronic wrist pain. Specifically, the relationship of pain relief from the injection and improvement of grip strength were compared to the presence of intracarpal pathology as confirmed by wrist arthroscopy. Forty-five patients with chronic wrist pain underwent a midcarpal injection of lidocaine with or without corticosteroids. Forty of the 45 underwent comcomitant steroid injections; a majority of the 40 patients reported relief of pain for two or more weeks. Improvement of pain and improvement of grip strength were determined. Each of these patients subsequently underwent a radiocarpal and midcarpal arthroscopy, and the pathologic findings of arthroscopy were compared to the improvement of pain and grip strength. These data were compared to a cohort of six volunteers without history of wrist pain or trauma that underwent midcarpal injection of lidocaine. Statistical analysis was performed using Reciever-Operator-Characteristic analysis. The average age of patients with chronic pain was 30.3 years, with an average of 9.8 months of wrist pain. The ultimate diagnoses included 35 patients with carpal instability dissociative, two with nondissociative instability, seven with complex instability of the carpus, three with extensor carpi ulnaris tendonitis and one with deQuervain's tenosynovitis. After lidocaine injection, the normal cohort had a mean loss of 2 kg (-5.3%) ( p=0.02) in grip strength, whereas the experimental cohort had a mean improvement in grip strength of 5.73 kg (34.4%). Improvement of pain after injection did not correlate with pathologic arthroscopic findings ( p=0.92). Improvement in grip strength after midcarpal lidocaine injection of 6 kg or 28% had a 73% sensitivity and a 70% specificity ( p=0.02) of having intracarpal pathology at the time of arthroscopy. Of the chronic wrist pain patients, only four had a normal arthroscopy, and the remainder had at least one area of significant pathology attributing to their pain. We conclude that a midcarpal injection of lidocaine can serve as an effective diagnostic tool in the evaluation of the patient with chronic wrist pain. Improvement of grip of 28% with or without relief of pain is highly correlated with intracarpal pathology.

The aim of this study was to examine the safety and efficacy of occipital nerve stimulation for medically intractable headache. Electrical stimulation of large sensory afferents has an antinociceptive effect. Occipital nerve stimulation may be effective for the treatment of medically intractable headache. Retrospective analysis was performed of 15 patients with medically refractory headache who underwent implantation of an occipital nerve stimulator. Pre- and postimplant data regarding headache frequency, severity, disability, depression and post-stimulator complications were collected. Twelve patients were female and three male. Ages ranged from 21 to 52 years (mean 39 years). Eight patients had chronic migraine, three chronic cluster, two hemicrania continua and two had post-traumatic headache. Eight patients underwent bilateral and seven had unilateral lead placement. Patients were measured after 5-42 months (mean 19). All six mean headache measures improved significantly from baseline ( P < 0.03). Headache frequency per 90 days improved by 25 days from a baseline of 89 days; headache severity (0-10) improved 2.4 points from a baseline of 7.1 points; MIDAS disability improved 70 points from a baseline of 179 points; HIT-6 scores improved 11 points from a baseline of 71 points; BDI-II improved eight points from a baseline of 20 points; and the mean subjective percent change in pain was 52%. Most patients (60%) required lead revision within 1 year. One patient required generator revision. Occipital nerve stimulation may be effective in some patients with intractable headache. Surgical revisions may be commonly required. Safety and efficacy results from prospective, randomized, sham-controlled studies in patients with medically refractory headache are needed.

Approximately 57 patients with red ear syndrome have been reported in the literature since it was initially described in 1994. The clinical phenotype therefore continues to be defined and no consistent treatment response has been described. We report three new cases of red ear syndrome and suggest that the disorder may exist as a primary trigeminal or cervical autonomic cephalalgia, coexist with other rare trigeminal autonomic cephalalgias, or may be secondary. The pathogenesis in these different circumstances may be distinct, the triggers specific and, when secondary, the disorder may be more resistant to treatment.

Abstract Rationale Treatment and prognoses of diffuse parenchymal lung diseases (DPLDs) varies by diagnosis. Obtaining a uniform diagnosis among observers is difficult. Objectives Evaluate diagnostic agreement between academic and community-based physicians for patients with DPLDs, and determine if an interactive approach between clinicians, radiologists, and pathologists improved diagnostic agreement in community and academic centers. Methods Retrospective review of 39 patients with DPLD. A total of 19 participants reviewed cases at 2 community locations and 1 academic location. Information from the history, physical examination, pulmonary function testing, high-resolution computed tomography, and surgical lung biopsy was collected. Data were presented in the same sequential fashion to three groups of physicians on separate days. Measurements and Main Results Each observer's diagnosis was coded into one of eight categories. A κ statistic allowing for multiple raters was used to assess agreement in diagnosis. Interactions between clinicians, radiologists, and pathologists improved interobserver agreement at both community and academic sites; however, final agreement was better within academic centers (κ = 0.55–0.71) than within community centers (κ = 0.32–0.44). Clinically significant disagreement was present between academic and community-based physicians (κ = 0.11–0.56). Community physicians were more likely to assign a final diagnosis of idiopathic pulmonary fibrosis compared with academic physicians. Conclusions Significant disagreement exists in the diagnosis of DPLD between physicians based in communities compared with those in academic centers. Wherever possible, patients should be referred to centers with expertise in diffuse parenchymal lung disorders to help clarify the diagnosis and provide suggestions regarding treatment options.

Abstract Innovations and Challenges in Renal Cancer, chaired by Michael B. Atkins, was held April 28 to 29, 2006 in Cambridge, Massachusetts. The conference brought together leading experts in the fields of cancer research, medical oncology, urology, immunology, radiology, and immunotherapy, with the goal of advancing the field of renal cancer treatment by critiquing new data from ongoing clinical trials and stimulating communication among those involved in basic and clinical research. The conference proceedings published in this educational supplement to Clinical Cancer Research are intended to provide timely information and recommendations on important aspects of renal cancer genetics and biology and advances in prognostic classification and treatment.