Moderate alcohol intake and renal function decline in women: a prospective study.

BACKGROUND: The impact of moderate alcohol consumption on renal function has important public health implications given the high prevalence of alcohol use. Experimentally, alcohol may adversely affect renal function, but clinical data are limited and no large, prospective studies have examined this issue. METHODS: In a prospective study of 1658 nurses enrolled in the Nurses' Health Study, we sought to determine if there was an association between moderate alcohol consumption and rate of decline in renal function. Daily alcohol intake was measured in 1990, 1994 and 1998 using a detailed questionnaire. Maximum daily alcohol intake was measured in 1988. Creatinine, measured from blood samples provided in 1989 and 2000, was used to estimate glomerular filtration rate (GFR) and creatinine clearance (CCr). RESULTS: Compared to individuals with no alcohol intake, the odds ratios (ORs) for developing a >or=25% estimated GFR decline were: 0.98 (95% CI: 0.72-1.32) for 0.1-4.9 g/day, 0.83 (95% CI: 0.56-1.21) for 5-14.9 g/day and 0.81 (95% CI: 0.50-1.31) for 15-59.9 g/day. For women with hypertension (n = 726), the ORs for a >or=25% estimated GFR decline were: 0.98 (95% CI: 0.53-1.21) for 0.1-4.9 g/day, 0.62 (95% CI: 0.34-1.12) for 5-14.9 g/day and 0.53 (95% CI: 0.25-1.12) for 15-59.9 g/day. CONCLUSIONS: Moderate alcohol consumption had no substantial adverse effect on renal function in women over an 11 year follow-up period.     

Analysis During Sinus Rhythm of Critical Sites in Reentry Circuits of Postinfarction Ventricular Tachycardia

Background: Critical sites within reentry circuits of postinfarction ventricular tachycardia (VT) were identified during sinus rhythm (SR) and VT to determine whether electrogram characteristics during SR may be helpful in identifying successful ablation sites. Methods: In 33 patients (mean age 67 ± 11 yrs) with prior infarction, mapping and radiofrequency (RF) catheter ablation of 57 hemodynamically-tolerated VT's (cycle length 478 ± 96) were performed. The morphologies of electrograms (EGM) at sites of concealed entrainment (CE) were compared during SR and VT. RF energy was delivered at 94 sites (51 successful and 43 unsuccessful ablation sites). Results: During SR, isolated potentials (IP), but not late potentials (LP) recorded via the mapping catheter, were associated with successful ablation. At 29/39 sites with an IP during sinus rhythm, an isolated diastolic potential (IDP) also was present during VT, whereas at 4 sites IP's were present only during SR (p < 0.001). At 11/29 sites where isolated potentials were present during SR and VT, the morphology of the isolated potential during VT and SR was similar; and all but one of these sites were successful ablation sites (p = 0.01). The EGM amplitude during VT correlated with the amplitude during SR (R = 0.9, p < 0.001). An identical pacemap was present during SR at 33/94 sites; this was not associated with successful ablation. Conclusion: SR mapping may be helpful in identifying critical sites of reentry in postinfarction VT. At sites within the reentry circuit, characteristics of sinus rhythm EGM's that are associated with successful ablation include the presence of IP's, but not the presence of LP's.     

A rapid protocol for the prevention of contrast-induced renal dysfunction: the RAPPID study

OBJECTIVES: This study was designed to test a rapid protocol of intravenous acetylcysteine for prevention of radiocontrast-induced nephropathy (RCIN). BACKGROUND: Oral acetylcysteine (NAC) may provide better prophylaxis against RCIN than intravenous (i.v.) hydration alone. Current protocols preclude prophylaxis of same-day or emergency patients owing to the need for prolonged pretreatment. METHODS: We prospectively randomized 80 patients with stable renal dysfunction undergoing cardiac catheterization/intervention to a rapid protocol of i.v. NAC (150 mg/kg in 500 ml N/saline over 30 min immediately before contrast followed by 50 mg/kg in 500 ml N/saline over 4 h, n = 41, 67 +/- 10 years, 90% men) or i.v. hydration (1 ml/kg/h N/saline for 12 h pre- and post-contrast, n = 39, 71 +/- 8.8 years, 85% men). RESULTS: Radiocontrast-induced nephropathy occurred in 2 of the 41 patients in the NAC group (5%) and in 8 of the 39 patients in the hydration group (21%; p = 0.045; relative risk: 0.28; 95% confidence interval 0.08 to 0.98). In the NAC group, mean serum creatinine fell from 1.85 +/- 0.59 to 1.77 +/- 0.73 and 1.79 +/- 0.73 mg/dl 48 h and four days post-contrast (p = 0.02 and 0.023 vs. baseline, respectively). In the hydration group, serum creatinine increased from 1.75 +/- 0.41 to 1.81 +/- 0.6 48 h and 1.80 +/- 0.50 mg/dl four days post-contrast (p = 0.99 and 0.23, respectively). NAC infusion was ceased after the bolus in three patients (7%) due to flushing, itching, or a transient rash. CONCLUSIONS: Administration of i.v. NAC should be considered in all patients at risk of RCIN before contrast exposure when time constraints preclude adequate oral prophylaxis, provided the patient is able to tolerate this degree of volume loading.     

Identification of the primary collagen-binding surface on human glycoprotein VI by site-directed mutagenesis and by a blocking phage antibody

Glycoprotein (GP) VI is the major receptor responsible for platelet activation by collagen, but the collagen-binding surface of GPVI is unknown. To address this issue we expressed, from insect cells, the immunoglobulin (Ig)-like ectodomains (residues 1-185) of human and murine GPVI, called hD1D2 and mD1D2, respectively. Both proteins bound specifically to collagen-related peptide (CRP), a GPVI-specific ligand, but hD1D2 bound CRP more strongly than did mD1D2. Molecular modeling and sequence comparison identified key differences between hD1D2 and mD1D2. Ten mutant hD1D2s were expressed, of which 4 had human residues replaced by their murine counterpart, and 6 had replacements by alanine. CRP binding studies with these mutants demonstrated that the exchange of lysine at position 59 for the corresponding murine glutamate substantially reduced binding to CRP. The position of lysine59 on the apical surface of GPVI suggests a mode of CRP binding analogous to that used by the related killer cell Ig-like receptors to bind HLA. This surface was confirmed as critical for collagen binding by epitope mapping of an inhibitory phage antibody against GPVI. This anti-GPVI, clone 10B12, gave dose-dependent inhibition of the hD1D2-collagen interaction. Clone 10B12 inhibited activation of platelets by CRP and collagen in aggregometry and thrombus formation by the latter in whole blood perfusion. Antibody 10B12 showed significantly reduced binding to the hD1D2-E59, and, on that basis, the GPVI:10B12 interface was modeled.     

The validity of the whitaker index of schizophrenic thinking

The Whitaker Index of Schizophrenic Thinking was designed to address an important clinical and research problem–the objective assessment of thought disorder. The present study assessed this test's convergent and discriminant validity and its diagnostic discriminating power (N = 56). We found that the WIST has limited clinical utility as a specific measure of disordered thought and as a diagnostic tool, but that it might still have certain important research applications.     

Negative emotions and quality of life six months after cardiac surgery: the dominant role of depression not anxiety symptoms

The specific syndromal aspects of depression and anxiety have not been explored in relation to changes in health related quality of life (HRQOL) after cardiac surgery. The purpose of this study was to examine the impact of general stress, depression and anxiety on HRQOL after coronary artery bypass graft (CABG) surgery. Utilizing a tripartite conceptual model of depression and anxiety, it was hypothesized that general stress symptoms, rather than unique depressive or anxiogenic symptoms, would be associated with lower HRQOL 6 months after CABG surgery. Elective CABG patients (n = 226) completed baseline and postoperative self-report measures of negative emotions and HRQOL, and 193 patients completed these measures at 6-month follow-up. Multiple linear regression analyses and logit link analyses were performed to test the hypothesis. Elevated depression symptoms before and after surgery showed an association with lower and worse HRQOL for vitality and social role functioning and physical and general health. This study adds to previous research by outlining discrete associations between specific HRQOL domains, and is perhaps the first to test a theoretical model of depression and anxiety in relation to cardiac CABG patients’ perceptions of HRQOL. These findings encourage further research on negative emotions and HRQOL in cardiac surgery patients and the practical implications of these findings are discussed.     

Relationships between motor unit size and recruitment threshold in older adults: implications for size principle

As a part of the aging process, motor unit reorganization occurs in which small motoneurons reinnervate predominantly fast-twitch muscle fibers that have lost their innervation. We examined the relationship between motor unit size and the threshold force for recruitment in two muscles to determine whether older individuals might develop an alternative pattern of motor unit activation. Young and older adults performed isometric contractions ranging from 0 to 50% of maximal voluntary contraction in both the first dorsal interosseous (FDI) and tibialis anterior (TA) muscles. Muscle fiber action potentials were recorded with an intramuscular needle electrode and motor unit size was computed using spike-triggered averaging of the global EMG signal (macro EMG), which was also obtained from the intramuscular needle electrode. As expected, older individuals exhibited larger motor units than young subjects in both the FDI and the TA. However, moderately strong correlations were obtained for the macro EMG amplitude versus recruitment threshold relationship in both the young and older adults within both muscles, suggesting that the size principle of motor unit recruitment seems to be preserved in older adults.