Association between renal tubular dysfunction and mortality among residents in a cadmium-polluted area, Nagasaki, Japan.

A retrospective cohort study was carried out to clarify the effect of exposure to environmental cadmium (Cd) on mortality. A total of 256 residents aged 50 years or older, living in Sasu, a Cd-polluted area in Tsushima Island in Nagasaki Prefecture, Japan, were followed from July 1979 to February 1989. The expected number of deaths calculated was based on the sex- and age- specific mortality rate in Tsushima Island in 1985. In Sasu residents of both sexes with urinary beta 2-microglobulin (beta 2-m) concentration greater than 1,000 microgram/g creatinine in 1979, observed deaths were greater than expected. However, the p value of the difference was less than 0.05 only in men. The relationships of age, mean blood pressure, urinary beta 2-m and urinary Cd concentration to mortality were examined using Cox's proportional hazards model. Urinary beta 2-m was independently and significantly related to mortality in men but not in women. The results suggest an association between Cd-induced renal tubular dysfunction and mortality.     

Association between renal dysfunction and the mixed plaque of coronary artery on computed tomographic angiography

Coronary artery plaque is related to development of coronary artery disease (CAD), and chronic kidney disease is associated with CAD. However, the association of renal dysfunction (RD) with coronary artery plaque characteristics has not been fully elucidated. We evaluated the association between RD and coronary artery plaque characteristics in patients with suspected CAD, who underwent multislice computed tomographic angiography (CTA). A total of 918 patients were classified into 4 groups: group with no plaque (NP) (48.9%), group with calcified plaque (CP) (16.0%), group with noncalcified plaque (NCP) (22.4%), and group with mixed plaque (MP) (12.7%). NCP is considered as rupture-prone soft plaque, and CP as more stable lesion. The mean of estimated glomerular filtration rate (eGFR) was 82.5 ± 15.4 mL/min/1.73 m(2), and the prevalence of RD (defined as eGFR < 60 mL/min/1.73 m(2)) was 6.3%. The prevalence of RD was 3.3% in the NP group, 10.2% in the CP group, 5.3% in the NCP group, and 14.5% in the MP group (P < 0.001 by ANOVA tests). The adjusted odds ratio for RD was 3.38 (95% confidence interval, 1.27-9.04) for the MP group, compared with the NP group. The presence of RD showed an independent association with the MP counts (r = 0.155, P < 0.001); however, there was no association between RD and other plaque characteristics. In conclusion, RD is associated with MP rather than CP or NCP, compared with NP, which may reflect one of the developmental processes of CAD in patients with RD.     

Autonomic dysfunction in patients with Brugada syndrome: further biochemical evidence of altered signaling pathways

Background: In patients with Brugada syndrome (BrS), life‐threatening ventricular tachyarrhythmias predominantly occur during vagal stimulation at rest or during sleep. Previous imaging studies displayed an impaired autonomic function in BrS patients. However, it remains unclear whether these alterations primarily stem from a reduction of synaptic release of norepinephrine (NE) or an enhanced presynaptic reuptake. Both conditions could lead to reduced NE concentrations in the synaptic cleft. Therefore, we analyzed key components of the sympathoadrenergic signaling pathways in patients with BrS. Methods and Results: Endomyocardial biopsies were obtained from eight BrS patients (seven male; age 49 ± 15 years) and five controls (three male; age 43 ± 13 years; P = ns). The concentrations of NE, epinephrine (Epi), NE transport (NET) carrier protein, cyclic adenosine 5′monophosphate (cyclic adenosine monophosphate [cAMP]), inhibitory G‐proteins (G_i1,2α), troponin‐I (TNI), and phosphorylated TNI were analyzed. Levels of NET, G_i1,2α, TNI, Epi, and phosphorylated TNI were comparable between the groups. Compared to controls, patients with BrS showed reduced cAMP and NE concentrations. Conclusions: The current findings expand the concept of adrenergic dysfunction in BrS: the reduction of NE in BrS could lead to an impaired stimulation of β‐adrenoceptors resulting in a reduction of cAMP and alterations of the subsequent signaling pathway with potential implication for arrhythmogenesis. (PACE 2011; 34:1147–1153)     

Labile testosterone conjugate in human urine: further evidence.

The origin of unconjugated testosterone released in human urine on storage and by dilute sulphuric acid treatment has been studied further. Various extraction procedures of urine have been employed and a new methodology involving anion exchange followed by acid hydrolysis and radioimmunoassay of the released unconjugated testosterone. Results indicate that human urine contains a very labile conjugate of testosterone and 5 alpha-dihydrotestosterone with polar solubility properties and a negative charge.     

Association between hyperkalemia at critical care initiation and mortality

Purpose

To investigate the association between potassium concentration at the initiation of critical care and all-cause mortality.

Methods

We performed a retrospective observational study on 39,705 patients, age?≥18?years, who received critical care between 1997 and 2007 in two tertiary care hospitals in Boston, Massachusetts. The exposure of interest was the highest potassium concentration on the day of critical care initiation and categorized a priori as 4.0–4.5, 4.5–5.0, 5.0–5.5, 5.5–6.0, 6.0–6.5, or?≥6.5?mEq/l. Logistic regression examined death by days 30, 90, and 365 post-critical care initiation, and in-hospital mortality. Adjusted odds ratios were estimated by multivariable logistic regression models.

Results

The potassium concentration was a strong predictor of all-cause mortality 30?days following critical care initiation with a significant risk gradient across potassium groups following multivariable adjustment: K?=?4.5–5.0?mEq/l OR 1.25 (95?% CI, 1.16–1.35; P?<?0.0001); K?=?5.0–5.5?mEq/l OR 1.42 (95?% CI, 1.29–1.56; P?<?0.0001); K?=?5.5–6.0?mEq/l OR 1.67 (95?% CI, 1.47–1.89; P?<?0.0001); K?=?6.0–6.5?mEq/l OR 1.63 (95?% CI, 1.36–1.95; P?<?0.0001); K?>?6.5?mEq/l OR 1.72 (95?% CI, 1.49–1.99; P?<?0.0001); all relative to patients with K?=?4.0–4.5?mEq/l. Similar significant associations post multivariable adjustments are seen with in-hospital mortality and death by days 90 and 365 post-critical care initiation. In patients whose hyperkalemia decreases?≥1?mEq/l in 48?h post-critical care initiation, the association between high potassium levels and mortality is no longer significant.

Conclusions

Our study demonstrates that a patient's potassium level at critical care initiation is robustly associated with the risk of death even at moderate increases above normal.     

轻度肾功能不全与冠状动脉狭窄程度的关系

目的　探讨轻度肾功能不全与冠状动脉狭窄程度的关系。方法　对 6 4例冠状动脉狭窄患者行冠脉造影 ,按入院时血清肌酐是否 >10 6 .0 8μmol/L分为肾功能正常组及肾功能不全组 ,冠状动脉狭窄程度用造影图像处理系统测量 ,并以病变损害的程度评分。分析轻度肾功能不全和冠脉狭窄程度的定性及定量关系。结果　轻度肾功能不全独立于其他冠心病易患因素 ,与冠脉狭窄程度相关。结论　轻度肾功能不全可以作为评估冠心病严重程度的参考指标之一。     

Association between clinically abnormal observations and subsequent in-hospital mortality: a prospective study

BACKGROUND: Patients with unexpected in-hospital cardiac arrest often have an abnormal clinical observation prior to the arrest. Previous studies have suggested that a medical emergency team responding to such patients may decrease in-hospital mortality from cardiac arrest, but the association between any abnormal clinical observation and subsequent increased mortality has not been studied prospectively. The aim of this study was to determine the predictive value of selected abnormal clinical observations in a ward population for subsequent in-hospital mortality. DESIGN AND SETTING: Prospective data collection in five general hospital ward areas at Dandenong Hospital, Victoria, Australia. INTERVENTIONS: None. RESULTS: During the study period, 6303 patients were admitted to the study areas. Of those, 564 (8.9%) experienced 1598 pre-determined clinically abnormal events and 146 of these patients (26%) died. The two commonest abnormal clinical events were arterial oxygen desaturation (51% of all events), and hypotension (17.3% of all events). Using a multiple linear logistic regression model, there were six clinical observations which were significant predictors of mortality. These were: a decrease in Glasgow Coma Score by two points, onset of coma, hypotension (<90 mmHg), respiratory rate <6 min(-1), oxygen saturation <90%, and bradycardia >30 min(-1). The presence of any one of the six events was associated with a 6.8-fold (95% CI: 2.7-17.1) increase in the risk of mortality. CONCLUSIONS: Six abnormal clinical observations are associated with a high risk of mortality for in-hospital patients. These observations should be included as criteria for the early identification of patients at higher risk of unexpected in-hospital cardiac arrest.     

Association between blood alcohol concentration and mortality in critical illness

ObjectiveIn animal models of renal, intestinal, liver, cardiac, and cerebral ischemia, alcohol exposure is shown to reduce ischemia-reperfusion injury. Inpatient mortality of trauma patients is shown to be decreased in a dose-dependent fashion relative to blood alcohol concentration (BAC) at hospital admission. In this study, we examined the association between BAC at hospital admission and risk of 30-day mortality in critically ill patients.DesignWe performed a 2-center observational study of patients treated in medical and surgical intensive care units in Boston, Massachusetts.SettingMedical and surgical intensive care units in 2 teaching hospitals in Boston, Massachusetts.PatientsWe studied 11 850 patients, 18 years or older, who received critical care between 1997 and 2007. The exposure of interest was the BAC determined in the first 24 hours of hospital admission and categorized a priori as BAC less than 10 mg/dL (below level of detection), 10 to 80 mg/dL, 80 to 160 mg/dL, and greater than 160 mg/dL. The primary outcome was all-cause mortality in the 30 days after critical care initiation. Secondary outcomes included 90- and 365-day mortality after critical care initiation. Mortality was determined using the US Social Security Administration Death Master File, and 365-day follow-up was present in all cohort patients. Adjusted odds ratios (ORs) were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both BAC and mortality. Adjustment included age, sex, race (white or nonwhite), type (surgical vs medical), Deyo-Charlson index, sepsis, acute organ failure, trauma, and chronic liver disease.ResultsThirty-day mortality of the cohort was 13.7%. Compared to patients with BAC levels less than 10 mg/dL, patients with levels greater than or equal to 10 mg/dL had lower odds of 30-day mortality; for BAC levels 10 to 79.9 mg/dL, the OR was 0.53 (95% confidence interval [CI], 0.40-0.70); for BAC levels 80 to 159.9 mg/dL, it was 0.36 (95% CI, 0.26-0.49); and for BAC levels greater than or equal to 160 mg/dL, it was 0.35 (95% CI, 0.27-0.44). After multivariable adjustment, the OR of 30-day mortality was 0.97 (0.72-1.31), 0.79 (0.57-1.10), and 0.69 (0.54-0.90), respectively. When the cohort was analyzed with sepsis as the outcome of interest, the multivariable adjusted odds of sepsis in patients with BAC 80 to 160 mg/dL or greater than 160 mg/dL were 0.72 (0.50-1.04) or 0.68 (0.51-0.90), respectively, compared to those with BAC less than 10 mg/dL. In a subset of patients with blood cultures drawn (n = 4065), the multivariable adjusted odds of bloodstream infection in patients with BAC 80 to 160 mg/dL or greater than 160 mg/dL were 0.53 (0.27-1.01) or 0.49 (0.29-0.83), respectively, compared to those with BAC less than 10 mg/dL.ConclusionsAnalysis of 11 850 adult patients showed that having a detectable BAC at hospitalization was associated with significantly decreased odds of 30-day mortality after critical care. Furthermore, BAC greater than 160 mg/dL is associated with significantly decreased odds of developing sepsis and bloodstream infection.     

Association of asymmetric dimethylarginine and endothelial dysfunction.

There is abundant evidence that the endothelium plays a crucial role in the maintenance of vascular tone and structure. One of the major endothelium-derived vasoactive mediators is nitric oxide (NO), which has been characterized as an "endogenous anti-atherosclerotic molecule". Synthesis of NO can be selectively inhibited by guanidino-substituted analogs of L-arginine, which act as competitive inhibitors at the active site of the enzyme. One such analog is asymmetric dimethylarginine (ADMA), a compound that has been found in human plasma and urine and exerts the activity of an endogenous inhibitor of NO synthase. In contrast to ADMA, its regioisomer symmetric dimethylarginine (SDMA) does not inhibit NO synthase. The methyl groups contained within the dimethylarginine molecules are derived from S-adenosylmethionine, an intermediate in the homocysteine/methionine pathway. There is experimental evidence that homocysteine may affect endothelium-dependent vascular function by increasing the formation of ADMA. Both ADMA and SDMA are eliminated from the body by renal excretion. In addition, the metabolism of ADMA, but not SDMA, occurs via hydrolytic degradation to citrulline and dimethylamine by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). Data from experimental studies suggest that ADMA inhibits vascular NO elaboration at concentrations found in pathophysiological conditions (i.e., 3-15 microM). ADMA likely acts as an autocrine regulator of endothelial NO synthase activity. When rabbits are placed on a diet enriched with 1% cholesterol, ADMA levels are increased within 4 weeks of dietary intervention as compared to control animals. Elevated plasma concentrations of ADMA are also present in hypercholesterolemic and hypertensive patients, in patients with chronic heart failure, and in other patient groups at high risk of developing cardiovascular disease. Elevation of ADMA induces dysfunction of the endothelium, which becomes clinically evident by impaired endothelium-dependent vasodilation, hyperaggregability of platelets, and enhanced monocyte adhesion. Recent prospective studies suggest that endothelial dysfunction indicates an increased risk of future cardiovascular events. In line with these observations, we and others found evidence that ADMA is a novel cardiovascular risk factor.     

Association of anticardiolipin antibodies with intraglomerular thrombi and renal dysfunction in lupus nephritis

We studied positivity for anti-cardiolipin antibody, intraglomerular capillary thrombi on renal biopsy, and the progression of renal disease in 51 patients (10 male and 41 female), mean age 37 years (range 17-65 years), with a diagnosis of systemic lupus erythematosis and clinically evident nephritis confirmed by renal biopsy. Serum creatinine, serum indicators of disease activity and biopsies were analysed in subgroups according to thrombi and anticardiolipin status. End-points were death or chronic dialysis requirement and survival. Degree of sclerosis, crescent formation and necrosed glomeruli were all greater in those specimens positive for thrombi and in those specimens of patients who were serum ACA-positive, suggesting a relationship to disease activity/severity at presentation. The increase in serum anti-DNA antibodies and ANA and the reduction in C3 and C4 were significant in ACA-positive patients, with a strong relationship to disease activity when compared with changes in the ACA-negative patients (p < 0.05 in all cases). There was no significant difference when patients were separated according to the presence or absence of thrombi. Renal function at presentation was worse in patients with intracapillary thrombi and ACA positivity (p = 0.085 and p = 0.042, respectively). All patients progressed, but only those with intracapillary thrombi or anti- cardiolipin antibody positivity had a significant deterioration in renal function. Twenty-one thrombotic episodes occurred in 14 patients, of whom 13 were ACA-positive. Anticardiolipin antibody is a strong predictor of the presence of intraglomerular thrombi in SLE patients with renal involvement. The presence of thrombi and/or anticardiolipin antibodies indicate a worse long-term renal outcome. Anti-cardiolipin antibody positivity is a strong predictor of systemic vascular thrombotic complications.      

The relationship between inotrope exposure, six-hour postoperative physiological variables, hospital mortality and renal dysfunction in patients undergoing cardiac surgery

Introduction  

Acute haemodynamic complications are common after cardiac surgery and optimal perioperative use of inotropic agents, typically guided by haemodynamic variables, remains controversial. The aim of this study was to examine the relationship of inotrope use to hospital mortality and renal dysfunction.     

Mitochondrial dysfunction and migraine: evidence and hypotheses

The molecular basis of migraine is still not completely understood. An impairment of mitochondrial oxidative metabolism might play a role in the pathophysiology of this disease, by influencing neuronal information processing. Biochemical assays of platelets and muscle biopsies performed in migraine sufferers have shown a decreased activity of the respiratory chain enzymes. Studies with phosphorus magnetic resonance spectroscopy ((31)P-MRS) have demonstrated an impairment of the brain oxidative energy metabolism both during and between migraine attacks. However, molecular genetic studies have not detected specific mitochondrial DNA (mtDNA) mutations in patients with migraine, although other studies suggest that particular genetic markers (i.e. neutral polymorphisms or secondary mtDNA mutations) might be present in some migraine sufferers. Further studies are still needed to clarify if migraine is associated with unidentified mutations on the mtDNA or on nuclear genes that code mitochondrial proteins. In this paper, we review morphological, biochemical, imaging and genetic studies which bear on the hypothesis that migraine may be related to mitochondrial dysfunction at least in some individuals.     

危重患者急性肾功能不全死亡相关因素分析

目的 :探讨影响急性肾功能不全的危重病患者预后的相关因素。方法 :回顾 1999年 8月— 2 0 0 1年5月北京协和医院加强医疗科 (ICU)收治的危重患者合并急性肾功能不全的资料 ,对住院死亡的高危因素进行分析。结果 :收治的 12 18例危重患者中 ,急性肾功能不全者 14 9例 ,其中病历资料完全者 13 5例 (随访率91% )。住院期间死亡 5 5例 (4 1% )。单因素分析发现 ,全身炎症反应综合征 (SIRS)、全身性感染、严重全身性感染、感染性休克、慢性呼吸功能不全、应用去甲肾上腺素、应用持续静静脉血液滤过 (CVVH)治疗、急性生理和慢性健康状况 (APACHE )评分、全身感染性相关器官功能衰竭 (SOFA)评分是急性肾功能不全患者死亡的危险因素 (P均 <0 .0 5 ) ;而 APACHE 评分、应用去甲肾上腺素和 CVVH是死亡的独立危险因素 (P均 <0 .0 5 )。结论 :急性肾功能不全患者的预后与基础疾病的严重程度相关 ,主要包括少尿、出凝血障碍、中枢神经系统功能不全和全身性感染。虽然应用 CVVH治疗 ,急性肾功能不全本身仍然可使危重患者的病死率升高