Long-term mortality and quality of life after prolonged mechanical ventilation

OBJECTIVE: To describe and identify factors associated with mortality rate and quality of life 1 yr after prolonged mechanical ventilation. DESIGN: Prospective, observational cohort study with patient recruitment over 26 months and follow-up for 1 yr. SETTING: Intensive care units at a tertiary care university hospital. PATIENTS: Adult patients receiving prolonged mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured mortality rate and functional status, defined as the inability to perform instrumental activities of daily living (IADLs) 1 yr following prolonged mechanical ventilation. The study enrolled 817 patients. Their median age was 65 yrs, 46% were women, and 44% were alive at 1 yr. Median ages at baseline of 1-yr survivors and nonsurvivors were 53 and 71 yrs, respectively. At the time of admission to the hospital, survivors had fewer comorbidities, lower severity of illness score, and less dependence compared with nonsurvivors. Severity of illness on admission to the intensive care unit and prehospitalization functional status had a significant association with short-term mortality rate, whereas age and comorbidities were related to long-term mortality. Fifty-seven percent of the surviving patients needed caregiver assistance at 1 yr of follow-up. The odds of having IADL dependence at 1-yr among survivors was greater in older patients (odds ratio 1.04 for 1-yr increase in age) and those with IADL dependence before hospitalization (odds ratio 2.27). CONCLUSIONS: Mortality rate after prolonged mechanical ventilation is high. Long-term mortality rate is associated with older age and poor prehospitalization functional status. Many survivors needed assistance after discharge from the hospital, and more than half still required caregiver assistance at 1 yr. Interventions providing support for caregivers and patients may improve the functional status and quality of life of both groups and thus need to be evaluated.     

葛根素和大豆甙元抑制~3H-氟硝西泮和体外大鼠脑膜的结合

目的从中药葛根中提取脑内苯并二氮杂卓(BZ)受体活性化合物。方法用体外的放射配体-受体结合法(RRA)和高压液相法(HPLC)提取、分离、纯化BZ受体活性化合物,用核磁共振和质谱仪确定活性化合物的结构。后用GABA比和Scatchardplot分析确定它们的作用特性。结果从葛根中提取、分离到葛根素和大豆甙元2种活性化合物。它们在体外可抑制3H-氟硝西泮和脑细胞膜的结合,IC50值分别为(18.46±2.34)μmol/L和(15.4±31.89)μmol/L。大豆甙元还可抑制3H-呱唑嗪和α1-肾上腺素受体的结合(IC50值为89μmol/L)。2种化合物的GABA比分别为1.11和1.12,提示2种黄酮化合物是BZ受体的拮抗剂或部分激动剂。Scatchardplot分析显示2种化合物对3H-氟硝西泮和脑膜结合的抑制是通过竞争性与非竞争性混合机制而实现的。结论葛根素和大豆甙元是脑内BZ受体的拮抗剂或部分激动剂。它们的抑制作用是通过竞争性与非竞争性混合机制而实现的。     

从远志中分离鉴定出1种多巴胺受体活性化合物

目的从中药远志中提取脑内多巴胺(DA)受体活性化合物。方法用体外的放射配体-受体结合和高压液相法提取、分离、纯化DA受体活性化合物,用核磁共振和质谱仪确定活性化合物的结构。结果提取、分离到1种四氢非洲防己胺的活性化合物。其在体外可抑制3H-SCH23390(DA1受体亚型)和3H-螺呱隆(DA2受体亚型)与大鼠纹状体细胞膜的结合,其IC50值分别为(0.75±0.08)μmol/L和(0.92±0.10)μmol/L。这种活性化合物还能抑制3H-呱唑嗪和大鼠大脑膜α1-肾上腺素受体的结合(IC50值为46μmol/L),但是不能改变3H-QNB及3H-muscimol对膜的结合。Scatchardplot分析显示此化合物对3H-SCH23390和3H-螺呱隆与纹状体细胞膜的结合的抑制作用是通过竞争性与非竞争性混合机制而实现的。结论远志中提取到的四氢非洲防己胺是脑内多巴胺受体的活性化合物,它的抑制作用是通过竞争性与非竞争性混合机制而实现的。     

毛地黄黄酮和玄参黄酮抑制~3H-地西泮和体外大鼠脑膜的结合

目的从阿拉伯艾蒿中提取脑内苯二氮杂卓(BZ)受体活性化合物。方法用体外的放射配体-受体结合测定(RRA)和高压液相法(HPLC)提取、分离、纯化BZ受体活性化合物,用核磁共振和质谱仪确定活性化合物的结构。后用GABA比和Scatchardplot分析确定它们的作用特性。结果提取、分离到毛地黄黄酮和玄参黄酮2种活性化合物。它们在体外可抑制3H-地西泮和大鼠脑细胞膜的结合,IC50值分别为(1.3±0.1)μmol/L和(22.7±2.5)μmol/L。2种化合物还在体外抑制3H-呱唑嗪和α1-肾上腺素受体的结合,IC50值分别为74μmol/L和700μmol/L。2种化合物的GABA比值分别为1.10和1.20,而且它们均使35S-TBPS与脑膜结合轻度升高,提示2种黄酮化合物是BZ受体的拮抗剂或部分激动剂。Scatchardplot分析显示2种化合物对3H-地西泮和脑细胞膜结合的抑制作用是通过竞争性与非竞争性混合机制而实现的。结论毛地黄黄酮和玄参黄酮是脑内BZ受体的拮抗剂或部分激动剂。它们的抑制作用是通过竞争性与非竞争性混合机制而实现的。     

Comparison of energy-restricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women

OBJECTIVE: To compare the effects of isocaloric, energy-restricted very low-carbohydrate ketogenic (VLCK) and low-fat (LF) diets on weight loss, body composition, trunk fat mass, and resting energy expenditure (REE) in overweight/obese men and women. DESIGN: Randomized, balanced, two diet period clinical intervention study. Subjects were prescribed two energy-restricted (-500 kcal/day) diets: a VLCK diet with a goal to decrease carbohydrate levels below 10% of energy and induce ketosis and a LF diet with a goal similar to national recommendations (%carbohydrate:fat:protein = ~60:25:15%). SUBJECTS: 15 healthy, overweight/obese men (mean +/- s.e.m.: age 33.2 +/- 2.9 y, body mass 109.1 +/- 4.6 kg, body mass index 34.1 +/- 1.1 kg/m2) and 13 premenopausal women (age 34.0 +/- 2.4 y, body mass 76.3 +/- 3.6 kg, body mass index 29.6 +/- 1.1 kg/m2). MEASUREMENTS: Weight loss, body composition, trunk fat (by dual-energy X-ray absorptiometry), and resting energy expenditure (REE) were determined at baseline and after each diet intervention. Data were analyzed for between group differences considering the first diet phase only and within group differences considering the response to both diets within each person. RESULTS: Actual nutrient intakes from food records during the VLCK (%carbohydrate:fat:protein = ~9:63:28%) and the LF (~58:22:20%) were significantly different. Dietary energy was restricted, but was slightly higher during the VLCK (1855 kcal/day) compared to the LF (1562 kcal/day) diet for men. Both between and within group comparisons revealed a distinct advantage of a VLCK over a LF diet for weight loss, total fat loss, and trunk fat loss for men (despite significantly greater energy intake). The majority of women also responded more favorably to the VLCK diet, especially in terms of trunk fat loss. The greater reduction in trunk fat was not merely due to the greater total fat loss, because the ratio of trunk fat/total fat was also significantly reduced during the VLCK diet in men and women. Absolute REE (kcal/day) was decreased with both diets as expected, but REE expressed relative to body mass (kcal/kg), was better maintained on the VLCK diet for men only. Individual responses clearly show the majority of men and women experience greater weight and fat loss on a VLCK than a LF diet. CONCLUSION: This study shows a clear benefit of a VLCK over LF diet for short-term body weight and fat loss, especially in men. A preferential loss of fat in the trunk region with a VLCK diet is novel and potentially clinically significant but requires further validation. These data provide additional support for the concept of metabolic advantage with diets representing extremes in macronutrient distribution.     

A new conceptual framework for ICU performance appraisal and improvement

PURPOSE: This study examined the use of outcomes for the purposes of ICU evaluation and improvement. We reviewed the strengths and weaknesses of an outcomes-centered approach to intensive care unit (ICU) evaluation and present a more comprehensive conceptual framework for ICU evaluation and improvement. MATERIALS AND METHODS: Data was collected from 2 sources: (1) a structured review of the literature, with relevant articles identified using Medline, and (2) 85 semistructured interviews of health care professionals (eg, physicians) and health care administrators (eg, chief executive officer). The interviewees came from 4 institutions: a 900-bed East Coast teaching medical center, a 600-bed East Coast teaching medical center, a 590-bed East Coast teaching medical center, and a 435-bed West Coast private community hospital. A nonrandomized, purposeful sample was used. RESULTS: A conceptual framework for ICU evaluation is presented that identifies and defines 3 different types of variables: performance (eg, appropriateness of care, effectiveness of care), outcome (eg, resource use, mortality), and process (eg, timeliness of treatment, work environment).The framework emphasizes performance variables and the relationships between performance, outcome, and process of care variables, as a logical focus for ICU evaluation and improvement. CONCLUSIONS: Performance variables offer distinct advantages over outcome variables for ICU evaluation. Their use, however, will require additional development of current evaluation tools and methods. They provide the ability to identify the value an ICU adds to patient care in a hospital or to an episode of illness, and to evaluate integrated systems for providing care.     

Recent advances in the clinical application of heart-lung interactions

Clinical applications of heart-lung interactions have centered on the impact of ventilation on regional blood flow and the measures of cardiovascular responsiveness to both positive end-expiratory pressure and fluid resuscitation. These new and exciting applications of established physiology provide new therapeutic options for the caregiver with reduced risk for complications in the patient. This review illustrates several of these studies within the context of known cardiopulmonary physiology.     

Distinct time courses of increase in cytochromes P450 1A2, 2A5 and glutathione S-transferases during the progressive hepatitis associated with Helicobacter hepaticus

Mice naturally infected by Helicobacter hepaticus develop a chronic active hepatitis leading to hepatocellular carcinoma. This mouse model of liver cancer was used to examine the impact of bacterial infection on the hepatic expression and activity of enzymes involved in carcinogen bioactivation (phase I enzymes) and detoxification (phase II enzymes). No major differences in total cytochrome P450 (CYP) content were found between control and infected mice during the course of the study. The most striking modulations of individual isoenzymes were the increases in immunohistochemical staining observed for CYP1A and CYP2A5 in relation to increasing age and liver lesions. The increase in CYP2A5 in mice aged over 12 months was confirmed by the observed increases in coumarin 7-hydroxylation (CYP2A5 substrate) in vitro and CYP2A5 mRNA levels by Northern blot analysis. Immunoblotting confirmed the specific induction of CYP1A2 in infected mice 12 and 18 months of age. Perfusion of liver with nitroblue tetrazolium, an indicator for superoxide formation, demonstrated that in livers of infected mice, hepatocytes often co-expressed CYP2A5 and formazan deposition. Concerning phase II enzymes, an enhancement of glutathione S-transferase (GST) activities, related to the disease process, was observed in infected mice. An age- specific increase of GSTpi and A4.4 (early stage of disease) and GST YaYa (>9 months) expression was also demonstrated by immunohistochemical staining. In contrast, catalase and glutathione- peroxidase activities, as well as reduced glutathione content were decreased in the early stages of disease (3-9 months) in infected mice compared to age-matched control mice. Overall, these results suggest that alterations in CYP and GST expression may contribute to the aetiology of tumour incidence due to H. hepaticus infection via production of reactive oxygen species.      

Relationship between acetylator status, smoking, and diet and colorectal cancer risk in the north-east of England

Some previous studies have suggested that the fast phenotype of the N- acetyltransferase NAT2 may confer susceptibility to colorectal cancer because of greater activation of dietary heterocyclic amines, particularly in individuals who also consume well-done red meat, but other studies have not supported this. We describe a large case-control study examining the interaction between dietary, smoking and drinking habits, and acetylation genotype in relation to susceptibility to colorectal cancer. One-hundred-and-seventy-four incident cases and 174 matched controls were recruited. Genotyping for polymorphisms in NAT2 was performed using a method that detects >95% of slow alleles and data on personal habits were collected using a standardized questionnaire. We found no difference in the frequency of the fast acetylator genotype between cases and controls [odds ratio = 0.95 (95% CI 0.61-1.49)], and analysis by sex, age and site also revealed no difference in acetylator genotype. There was, however, considerable heterogeneity in dietary risk factors between fast and slow acetylators. Analysis by acetylator type shows that recent smoking was more frequent in slow acetylator cases than matched controls [OR = 2.31 (1.16-4.6)] and that heavy alcohol consumption was also more frequent in the slow acetylator cases than controls [OR = 2.5 (1.02-7.29)]. In contrast, frequent fried meat intake was seen more frequently in fast acetylator cases than matched controls [OR = 6.0 (1.34-55)]. The odds ratio for the combination of fast acetylator status and frequent fried meat consumption in cases was 6.04 (1.6-26). Our study suggests that there may be different risk factors for colorectal cancer in slow and fast acetylators, and reveals a new observation that slow acetylators may be at risk of colon cancer from smoking. In our community, the overall effect of acetylator status on colorectal cancer risk is neutral.