Relationship between esophageal motility and transit in patients with type I diabetes mellitus

OBJECTIVES: Delayed esophageal transit and abnormal esophageal motility occur frequently in patients with long-standing diabetes mellitus. However, the relationship between transit and motility has not been assessed directly. The aim of this study was to investigate the patterns of esophageal motor function documented previously to have delayed esophageal emptying and esophageal transit in patients with insulin-dependent diabetes mellitus. METHODS: Concurrent esophageal manometry and radionuclide measurement of transit of liquids and solids were performed in 11 patients with insulin-dependent diabetes, 10 age-matched controls, and 11 young normal subjects. RESULTS: Patients with diabetes had a greater frequency of transit hold-up for solids (96%) than did older controls (65%) or young normals (42%) (p < 0.001), whereas the frequency of transit hold-up for liquid boluses was similar among the three groups (diabetics, 36%; older normals, 17%; young normals, 17%). The major mechanism responsible for bolus hold-up in diabetics was peristaltic failure (liquid, 52%; solid, 67%) and the level of hold-up coincided with the level of bolus hold-up for 10/11 liquid and 27/28 solid boluses. CONCLUSIONS: In insulin-dependent diabetes, retarded esophageal transit usually reflects either peristaltic failure or focal low-amplitude pressure waves.     

Race, gender, and health care service utilization and costs among Medicare elderly with psychiatric diagnoses

OBJECTIVE. To investigate race and gender differences in health care service utilization and costs among the Medicare elderly with psychiatric diagnoses. METHODS. The authors employ a 5% sample of Medicare beneficiaries from Tennessee (N = 33,680), and among those with a psychiatric diagnosis (n = 5,339), they examine health care service utilization and costs by race and gender. RESULTS. African Americans had significantly higher rates of diagnosis for dementia, organic psychosis, and schizophrenia, whereas Whites had significantly higher rates for mood and anxiety disorders. White and African American men have higher rates of utilization of emergency and inpatient services and lower rates of outpatient utilization compared to White women and African American women. African American men have significantly higher health care costs. DISCUSSION. The findings suggest that race and gender interact to influence service utilization and preventive care, thereby driving up costs of care, for elderly persons with psychiatric diagnoses.     

Gender differences in modulation of peripheral vascular adrenoceptors

We have previously demonstrated that women have smaller digital vasoconstrictive responses to intra-arterial phenylephrine and clonidine than men. Subsequent research suggested that women have higher levels of peripheral vascular sympathetic tone than men. We therefore sought to determine if reducing sympathetic tone by reflex heating would affect the sex difference in peripheral vascular α-adrenergic responsiveness. Twenty-two normal male and 21 normal female volunteers were studied during either heated or unhealed conditions while phenylephrine HCL and clonidine HCL were infused through a brachial artery catheter. Phenylephrine caused greater vasoconstriction in men than in women which was unaffected by heating. Clonidine also caused significantly greater vasoconstriction in men than in women. However, heating significantly increased clonidine-induced vasoconstriction in women but not in men. These data suggest that reduction of sympathetic tone elevates peripheral vascular α₂-adrenergic sensitivity in women; this effect does not occur in men. This research was supported by grant HL-30604 from NHLBI.     

Nonsustained Ventricular Tachycardia Induced by Valsalva Manoeuvre in a Patient With Nonobstructive Hypertrophic Cardiomyopathy

Cardiac arrhythmias are rarely inducible in patients with hypertrophic cardiomyopathy on provocative manoeuvres to identify latent obstruction. We present a 40-year-old male with history of nonobstructive hypertrophic cardiomyopathy who presented with lightheadedness. Echocardiogram showed severe asymmetric hypertrophy of the left ventricle without left ventricular outflow tract gradient at rest. On Doppler study with Valsalva manoeuvre, he developed symptomatic nonsustained ventricular tachycardia, which was reproduced on repetition. This emphasizes the importance of provocative manoeuvres to unmask potentially significant physiologic manifestations.     

New ablation techniques for atrial fibrillation and the minimally invasive cryo-maze procedure in patients with lone atrial fibrillation

Atrial fibrillation (AF) is associated with significant morbidity and mortality. Medical management is often palliative but new ablation techniques have enabled curative approaches. Catheter-based ablation has limited success, whilst surgical approaches are widely applicable with favourable results. The minimally invasive Cryo-Maze (MICM) replicates the lesions of the Cox-Maze procedure using cryotherapy. We present our retrospective review of all Cryo-Maze procedures performed at East Carolina University, from October 2003 to January 2006, with analysis of all MICM's for lone AF, via a small right inframammary incision. A total of 41 patients (29 male, 12 female, age 61.6+/-9.7 years) with lone AF underwent an MICM as a primary operation. There were no deaths or early or late strokes. At discharge 36 patients (87.8%) were in sinus. At six weeks, this ratio had increased to 90.2% (37/41). The rate of SR continued to improve and for those out three months, the rate increased to 92.7% (38/41). At six months, 87.2% (34/39) were in SR. SR was seen in 20/23 patients with follow-up beyond one year (87.0%). In conclusion, surgical ablation techniques that replicate the Cox-Maze procedure are associated with high rates of sinus rhythm beyond one year, with wide application. AF is a curable condition, using a combination of catheter-based and surgical approaches. Newer surgical ablation devices allow minimally invasive approaches.     

Cold-induced potentiation of α2-adrenergic vasoconstriction in primary raynaud's disease

Objective. To determine the effects of local cooling on α-adrenergic responses in the fingers of patients with idiopathic Raynaud's disease. Methods. Clonidine HCl and phenylephrine HCl were administered through a brachial artery catheter while blood flow was measured by plethysmography in cooled and uncooled fingers. Results. Cooling potentiated α₂-adrenergic vasoconstriction in the patients but depressed this response in the controls. Vasoconstrictive responses to phenylephrine were not significantly affected by cooling but were significantly greater in the patients than in the controls. Conclusion. Cold-induced sensitization of peripheral vascular α₂-adrenoceptors may be involved in the mechanism by which cooling triggers the vasospastic attacks of Raynaud's disease.     

A case of intra-operative ventricular fibrillation: Electro-cauterization,undiagnosed Takotsubo cardiomyopathy or long QT syndrome?

IntroductionCardiac arrest in the perioperative setting is an extremely serious event that is estimated to occur between 4.6 and 19.7 per 10,000 anesthetics.1, 2, 3, 4, 5 While risk factors for cardiac complications can be identified pre- operatively, in many cases workup of risk factors are not indicated by standard pre-operative testing guidelines.Presentation of caseWe present a case of a 47-year-old female undergoing an elective bilateral mastectomy who suddenly converted to ventricular fibrillation. While ventricular fibrillation is not a unique finding, our search for its etiology revealed two previously undiagnosed cardiac conditions, and possible electro- cautery induced ventricular fibrillation.DiscussionIn this case study, we discuss the possible etiology of ventricular fibrillation in our patient and highlight the importance pre-operative patient investigation and history provide.ConclusionSearching for the potential causes that may have contributed to the cardiac arrest is an extremely useful exercise as it allows us to better prepare patients pre-operatively, improve intra-operative care, and prevent future cardiac events.     

The role of Skp2 in hematopoietic stem cell quiescence, pool size, and self-renewal

Although the maintenance of HSC quiescence and self-renewal are critical for controlling stem cell pool and transplantation efficiency, the mechanisms by which they are regulated remain largely unknown. Understanding the factors controlling these processes may have important therapeutic potential for BM failure and cancers. Here, we show that Skp2, a component of the Skp2 SCF complex, is an important regulator for HSC quiescence, frequency, and self-renewal capability. Skp2 deficiency displays a marked enhancement of HSC populations through promoting cell cycle entry independently of its role on apoptosis. Surprisingly, Skp2 deficiency in HSCs reduces quiescence and displays increased HSC cycling and proliferation. Importantly, loss of Skp2 not only increases HSC populations and long-term reconstitution ability but also rescues the defect in long-term reconstitution ability of HSCs on PTEN inactivation. Mechanistically, we show that Skp2 deficiency induces Cyclin D1 gene expression, which contributes to an increase in HSC cycling. Finally, we demonstrate that Skp2 deficiency enhances sensitivity of Lin(-) Sca-1(+) c-kit(+) cells and leukemia cells to chemotherapy agents. Our findings show that Skp2 is a novel regulator for HSC quiescence and self-renewal and that targeting Skp2 may have therapeutic implications for BM transplantation and leukemia stem cell treatment.     

Supplemental Vitamin D and Calcium in the Management of African Americans With Heart Failure Having Hypovitaminosis D

IntroductionA dyshomeostasis of macro- and micronutrients, including vitamin D and oxidative stress, are common pathophysiologic features in patients with congestive heart failure (CHF). In African Americans (AA) with CHF, reductions in plasma 25(OH)D are of moderate-to- marked severity (< 20 ng/mL) and may be accompanied by ionized hypocalcemia with compensatory increases in serum parathyroid hormone (PTH). The management of hypovitaminosis D in AA with CHF has not been established.MethodsHerein, a 14-week regimen: an initial 8 weeks of oral ergocalciferol (50,000 IU once weekly); followed by a 6-week maintenance phase of cholecalciferol (1400 IU daily); and a CaCO₃ (1000 mg daily) supplement given throughout was designed and tested. Fourteen AA patients having a dilated (idiopathic) cardiomyopathy with reduced ejection fraction (EF, < 35%) were enrolled: all completed the initial 8-week course; and 12 complied with the full 14 weeks. At baseline, 8 and/or 14 weeks, serum 25(OH)D and PTH; serum 8-isoprostane, a biomarker of lipid peroxidation, and echocardiographic EF were monitored.ResultsReduced 25(OH)D at entry (14.4 ± 1.3 ng/mL) was improved (P < 0.05) in all patients at 8 weeks (30.7 ± 3.2 ng/mL) and sustained (P < 0.05) at 14 weeks (30.9 ± 2.8 ng/mL). Serum PTH, abnormally increased in 5 patients at baseline (104.8 ± 8.2 pg/mL), was reduced at 8 and 14 weeks (74.4 ± 18.3 and 73.8 ± 13.0 pg/mL, respectively). Plasma 8-isoprostane at entry (136.1 ± 8.8 pg/mL) was reduced at 14 weeks (117.8 ± 7.8 pg/mL; P < 0.05), whereas baseline EF (24.3 ± 1.7%) was improved (31.3 ± 4.3%; P < 0.05).ConclusionsThus, the 14-week course of supplemental vitamin D and CaCO₃ led to healthy 25(OH)D levels in AA with heart failure having vitamin D deficiency of moderate-to-marked severity. Albeit a small patient population, the findings suggest that this regimen may attenuate the accompanying secondary hyperparathyroidism and oxidative stress and improve ventricular function.