Total insulinlike growth factor 1 and insulinlike growth factor binding protein levels, functional status, and mortality in older adults

OBJECTIVES: To assess the association between total insulinlike growth factor (IGF)‐1, IGF binding protein‐1 (IGFBP‐1), and IGFBP‐3 levels and functioning and mortality in older adults. DESIGN: Cohort study. SETTING/PARTICIPANTS: One thousand one hundred twenty‐two individuals aged 65 and older without prior cardiovascular disease events participating in the Cardiovascular Health Study. MEASUREMENTS: Baseline fasting plasma levels of IGF‐1, IGFBP‐1, and IGFBP‐3 (defined as tertiles, T1‐T3) were examined in relationship to handgrip strength, time to walk 15 feet, development of new difficulties with activities of daily living (ADLs), and mortality. RESULTS: Higher IGFBP‐1 predicted worse handgrip strength (P‐trend_T1‐T3<.01) and slower walking speed (P‐trend_T1‐T3=.03), lower IGF‐1 had a borderline significant association with worse handgrip strength (P‐trend_T1‐T3=.06), and better grip strength was observed in the middle IGFBP‐3 tertile than in the low or high tertiles (P=.03). Adjusted for age, sex, and race, high IGFBP‐1 predicted greater mortality (P‐trend_T1‐T3<.001, hazard ratio (HR)_T3vsT1=1.48, 95% confidence interval (CI)=1.15–1.90); this association was borderline significant after additional confounder adjustment (P‐trend_T1‐T3=.05, HR_T3vsT1=1.35, 95% CI=0.98–1.87). High IGFBP‐1 was associated with greater risk of incident ADL difficulties after adjustment for age, sex, race, and other confounders (P‐trend_T1‐T3=.04, HR_T3vsT1=1.40, CI=1.01–1.94). Neither IGF‐1 nor IGFBP‐3 level predicted mortality or incident ADL difficulties. CONCLUSION: In adults aged 65 and older, high IGFBP‐1 levels were associated with greater risk of mortality and poorer functional ability, whereas IGF‐1 and IGFBP‐3 had little association with these outcomes.     

Leishmania donovani in blood smears of asymptomatic persons

Leishmania amastigotes have been detected in the peripheral blood smears of Indian kala-azar patients mostly during night. It was, therefore, thought worthwhile to find out whether such amastigotes could be shown in healthy subjects who did not have any symptoms by history or signs on clinical examination. Leishmania-stained blood smears of 450 asymptomatic healthy individuals residing in an endemic village in Bihar (India) were examined by oil-immersion microscopy for the detection of amastigote, six people (1.3%) showed the presence of Leishmania amastigotes. Given the low sensitivity of a single smear examination it is likely that a much greater proportion of asymptomatic persons had parasitemia than the observed 1.3%. This finding is important from the point of view of transmission of disease, as also for modifying the current control measures.     

Prevalence and natural history of subclinical hepatic encephalopathy in cirrhosis

BACKGROUND AND AIMS: The natural history of subclinical hepatic encephalopathy (SHE) is unknown. The present study was conducted to study the prevalence and the natural history of SHE in patients with cirrhosis of the liver. METHODS: One hundred and sixty-five patients with cirrhosis of the liver were studied. A total of nine psychometric tests (trail making and Wechsler adult intelligence scale-performance (WAIS-P) tests) were administered. Subclinical hepatic encephalopathy was present if two or more psychometric tests were abnormal. Seventy-two patients (SHE 40, without SHE 32) also underwent serial psychometric testing on follow-up visits at 6-8 week intervals. RESULTS: Subclinical hepatic encephalopathy was present in 103 (62.4%) patients. The number and figure connection, block design and picture completion tests were the most useful in the detection of SHE. Severity of SHE, as assessed by the number of abnormal tests, was greater in patients with more severe liver disease. During follow up, SHE tended to persist or worsen in patients with poorer liver function. Although other clinical complications were similar in different groups, overt hepatic encephalopathy developed more commonly in those patients who had SHE at entry compared to those who did not (22.6 vs 5.6%, P = 0.044). Among the patients with SHE, the development of overt hepatic encephalopathy was more common in patients with Child's score of > 6 than with Child's score of 相似文献   

Polymeric versus elemental diet as primary treatment in active Crohn's disease: a randomized, double-blind trial

OBJECTIVE: Enteral feeding is now an established primary therapy for active Crohn's disease. This first-double blind randomized trial was designed to compare the therapeutic efficacy of a polymeric diet (PD) with an elemental diet (ED). METHODS: Patients with active Crohn's disease (Crohn's disease activity index [CDAI] > 150, increased bowel uptake of Tc-HMPAO-labeled leukocytes, and abnormal C-reactive protein [CRP]), were randomized to receive either an ED or a PD. The two preparations were identical except for the nitrogen source, which was amino acid based in ED and intact protein in PD. Enteral feeding was considered successful if clinical remission was achieved as defined by a final CDAI of < or = 150, a reduction in the CDAI by at least 100 points from baseline level, and a normal CRP. RESULTS: Twenty-one patients were enrolled of whom 11 were randomized to PD and 10 to ED. The two groups were comparable at entry. Clinical remission was obtained in eight (80%) patients receiving ED and six (55%) patients receiving PD, p = 0.1. The treatment failed in three and two patients in the PD and ED groups, respectively. Another two patients were intolerant to the feed (PD). Reduction in the CDAI after treatment with ED (359 +/- 67 to 112 +/- 19) was similar to that seen with PD (303 +/- 27 to 97 +/- 11). Similar changes in the CRP were also observed (16 +/- 5 to 4 +/- 1.6) and (62 +/- 20 to 9 +/- 6), respectively. Overall, enteral feeding was successful in 14 patients (63%). CONCLUSIONS: Enteral nutrition is effective in treatment of active Crohn's disease. Differences in nitrogen sources of enteral feeds are not relevant to their therapeutic efficacy, as polymeric and elemental diets are equally effective.     

Sympathetic (alpha-beta) or calcium channel blockade for hypertensive myocardial infarction? A haemodynamic comparison of labetalol and nifedipine

The haemodynamic impact of alpha- and beta-adrenoceptor blockade (labetalol) was compared with that of slow-calcium channel blockade (nifedipine) in 32 patients with sustained elevation of systemic arterial pressure (systolic blood pressure greater than 160; diastolic blood pressure greater than 95 mmHg) following a recent myocardial infarction (6-22 h). Patients with normal (pulmonary artery occluded pressure; (PAOP less than 18 mmHg; n = 16) or impaired (PAOP greater than 18 mmHg; n = 16) left ventricular function were randomized to labetalol (1 mg/kg i.v. 15 min) or nifedipine (20 mg sublingually) and haemodynamic profile was measured over 2 h. Both drugs equally reduced mean systemic arterial pressure (P less than 0.01 versus pretreatment control), and presumably left ventricular afterload; however, the heart rate (P less than 0.01) and cardiac index (P less than 0.01) increased after nifedipine, contrasting with reductions in both variables following labetalol (P less than 0.01). The elevated left ventricular filling pressure was reduced by both labetalol (P less than 0.05) and nifedipine (P less than 0.01) but the reduction was greater following nifedipine (-2 mmHg versus -5 mmHg, P less than 0.05). Thus both compounds were equally effective hypotensive agents. Labetalol consistently reduced cardiac stroke work and double product, important determinants of myocardial oxygen requirements; however, nifedipine afforded some improvement in cardiac performance in patients with left ventricular dysfunction.     

Serotonin inhibits Na+/H+ exchange activity via 5-HT4 receptors and activation of PKC alpha in human intestinal epithelial cells

BACKGROUND & AIMS: Increased serotonin levels have been implicated in the pathophysiology of diarrhea associated with celiac and inflammatory diseases. However, the effects of serotonin on Na+ /H+ exchange (NHE) activity in the human intestine have not been investigated fully. The present studies examined the acute effects of 5-hydroxytryptamine (5-HT) on NHE activity using Caco-2 cells as an in vitro model. METHODS: Caco-2 cells were treated with 5-HT (.1 micromol/L, 1 h) and NHE activity was measured as ethyl-isopropyl-amiloride (EIPA)-sensitive 22Na uptake. The effect of 5-HT receptor-specific agonists and antagonists was examined. The role of signaling intermediates in 5-HT-mediated effects on NHE activity was elucidated using pharmacologic inhibitors and immunoblotting. RESULTS: NHE activity was inhibited significantly (approximately 50%-75%, P < .05) by .1 micromol/L 5-HT via inhibition of maximal velocity (Vmax) without any changes in apparent affinity (Km) for the substrate Na+ . NHE inhibition involved a decrease of both NHE2 and NHE3 activities. Studies using specific inhibitors and agonists showed that the effects of 5-HT were mediated by 5-HT4 receptors. 5-HT-mediated inhibition of NHE activity was dependent on phosphorylation of phospholipase C gamma 1 (PLC gamma 1) via activation of src-kinases. Signaling pathways downstream of PLC gamma 1 involved increase of intracellular Ca 2+ levels and subsequent activation of protein kinase C alpha (PKC alpha). The effects of 5-HT on NHE activity were not cell-line specific because T84 cells also showed NHE inhibition. CONCLUSIONS: A better understanding of the regulation of Na+ absorption by 5-HT offers the potential for providing insights into molecular and cellular mechanisms involved in various diarrheal and inflammatory disorders.     

Effect of vitamin C on platelet adhesiveness and platelet aggregation in coronary artery disease patients

The effect of oral administration of vitamin C on platelet adhesive index (PAI), platelet aggregate ratio (PAg R) and serum ascorbic acid levels was studied. Feeding 75 g of butter to healthy males (group I, n = 10 cases), enhanced the tendency of platelet adhesiveness (PAd) and platelet aggregation (PAg) to a significant level at the end of 4 h. This was distinctly prevented when 1 g of vitamin C was added to the fatty meal. In coronary artery disease (CAD) patients (group II, n = 20 cases) 10 days of vitamin C administration at 1 g every 8 hours decreased the PAd (p less than 0.001) and PAg (p less than 0.05) significantly. There was also a significant (p less than 0.001) rise in the vitamin C levels. The study brings out a property of vitamin C which may be of considerable importance in prevention of chronic thromboatherosclerotic disease of the arteries.     

Expression and functional activity of receptor-Ck in mononuclear cells of a homozygous hypercholesterolemic family

The study was addressed to explore the expression and functional activity of a novel cholesterol-specific cell surface receptor-Ck in a typical homozygous familial hypercholesterolemic family. Functional activity of receptor-Ck was characterized by its ability to downregulate Bcl-2 gene expression through a 47 kDa factor having an affinity for the sterol-regulatory element in the promoter region of this gene. The result of such a study revealed normal expression and functional activity of receptor-Ck accompanied by a lack of Apolipoprotein B-specific low-density lipoprotein receptor gene expression in the mononuclear cells derived from these patients. On the basis of these results, it is tempting to speculate that receptor-Ck may be involved in the maintenance of cellular cholesterol homeostasis observed in homozygous familial hypercholesterolemic patients.