The impact of body temperature abnormalities on the disease severity and outcome in patients with severe sepsis: an analysis from a multicenter,prospective survey of severe sepsis

Introduction

Abnormal body temperatures (T_b) are frequently seen in patients with severe sepsis. However, the relationship between T_b abnormalities and the severity of disease is not clear. This study investigated the impact of T_b on disease severity and outcomes in patients with severe sepsis.

Methods

We enrolled 624 patients with severe sepsis and grouped them into 6 categories according to their T_b at the time of enrollment. The temperature categories (≤35.5°C, 35.6–36.5°C, 36.6–37.5°C, 37.6–38.5°C, 38.6–39.5°C, ≥39.6°C) were based on the temperature data of the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring. We compared patient characteristics, physiological data, and mortality between groups.

Results

Patients with T_b of ≤36.5°C had significantly worse sequential organ failure assessment (SOFA) scores when compared with patients with T_b >37.5°C on the day of enrollment. Scores for APACHE II were also higher in patients with T_b ≤35.5°C when compared with patients with T_b >36.5°C. The 28-day and hospital mortality was significantly higher in patients with T_b ≤36.5°C. The difference in mortality rate was especially noticeable when patients with T_b ≤35.5°C were compared with patients who had T_b of >36.5°C. Although mortality did not relate to T_b ranges of ≥37.6°C as compared to reference range of 36.6–37.5°C, relative risk for 28-day mortality was significantly greater in patients with 35.6–36.5°C and ≤35.5°C (odds ratio; 2.032, 3.096, respectively). When patients were divided into groups based on the presence (≤36.5°C, n = 160) or absence (>36.5°C, n = 464) of hypothermia, disseminated intravascular coagulation (DIC) as well as SOFA and APACHE II scores were significantly higher in patients with hypothermia. Patients with hypothermia had significantly higher 28-day and hospital mortality rates than those without hypothermia (38.1% vs. 17.9% and 49.4% vs. 22.6%, respectively). The presence of hypothermia was an independent predictor of 28-day mortality, and the differences between patients with and without hypothermia were observed irrespective of the presence of septic shock.

Conclusions

In patients with severe sepsis, hypothermia (T_b ≤36.5°C) was associated with increased mortality and organ failure, irrespective of the presence of septic shock.

Trial registration

UMIN-CTR ID UMIN000008195     

Impact of eating rate on obesity and cardiovascular risk factors according to glucose tolerance status: the Fukuoka Diabetes Registry and the Hisayama Study

Aims/hypothesis

Medical nutrition therapy plays a critical role in the prevention and treatment of type 2 diabetes. However, appropriate measures of eating behaviours, such as eating rate, have not yet been clearly established. The aim of the present study was to examine the associations among eating rate, obesity and cardiovascular risk factors.

Methods

A total of 7,275 Japanese individuals aged ≥40 years who had normal fasting glucose levels, impaired fasting glucose or diabetes were divided into four groups according to self-reported eating rate: slow, medium, relatively fast and very fast. The associations between eating rate and various cardiovascular risk factors were investigated cross-sectionally.

Results

The proportions of participants who were obese or who had elevated waist circumference levels increased progressively with increases in eating rate (p for trend <0.001), regardless of glucose tolerance status. These associations remained significant after adjustment for potential confounders, namely, age, sex, total energy intake, dietary fibre intake, current smoking, current drinking and regular exercise (p for trend <0.001). Blood pressure and lipid levels also tended to increase in association with eating rate. HbA_1c rose significantly as eating rate increased, even after multivariate adjustment, including BMI, in diabetic patients on insulin therapy (p?=?0.02), whereas fasting plasma glucose did not increase significantly.

Conclusions/interpretation

Our findings suggest that eating rate is associated with obesity and other cardiovascular risk factors and therefore may be a modifiable risk factor in the management of cardiovascular risk factors and diabetes.     

Impact of Sleep Duration on Obesity and the Glycemic Level in Patients With Type 2 Diabetes: The Fukuoka Diabetes Registry

OBJECTIVE

Few studies are currently available regarding the influence of sleep duration on glycemic control in diabetic patients. The objective of the current study was to examine the relationship between sleep duration, obesity, and the glycemic level in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS

A total of 4,870 Japanese type 2 diabetic patients aged ≥20 years were divided into six groups according to their self-reported sleep duration: less than 4.5 h, 4.5–5.4 h, 5.5–6.4 h, 6.5–7.4 h, 7.5–8.4 h, and more than 8.5 h. The associations of sleep duration with obesity and the HbA_1c levels were examined in a cross-sectional manner.

RESULTS

The HbA_1c levels showed a quadratic association with sleep duration; namely, a shorter or longer sleep duration was associated with a higher level compared with a sleep duration of 6.5–7.4 h (P for quadratic trend <0.001). This association remained significant after adjusting for potential confounders, including the total energy intake and depressive symptoms. Furthermore, additional adjustments for obesity, which also showed a U-shaped relationship with sleep duration, did not attenuate the U-shaped sleep-HbA_1c association. A significant interaction between sleep duration and age or the use of insulin was observed for the HbA_1c levels.

CONCLUSIONS

Sleep duration was shown to have U-shaped associations with obesity and the HbA_1c levels in type 2 diabetic patients, independent of potential confounders, and therefore may be an important modifiable factor for the clinical management of patients with type 2 diabetes.An increasing prevalence of type 2 diabetes and its complications, including macro- and microvascular diseases, is a growing public health concern in both developing and developed countries (1). This is probably because of population growth, aging, and the increasing prevalence of obesity, which results from environmental factors such as urbanization, physical inactivity, and the increased consumption of food. More recently, it has been reported that the habitual sleep duration has decreased (2) as a result of the modern lifestyle and 24-h society, and epidemiological evidence has suggested that this is associated with adverse consequences such as obesity or weight gain (3,4), hypertension (5), cardiovascular diseases (6,7), and increased mortality (6). The negative impacts of prolonged sleep duration on these outcomes have also been described (3–7), thus suggesting that there is a U-shaped relationship between sleep duration and health disorders. A possible association between an inadequate sleep duration and the development of type 2 diabetes among nondiabetic subjects has been described as well (8–14), but epidemiological evidence concerning the relationship between sleep duration and glycemic control or obesity among diabetic patients is scarce (15–17). Furthermore, to the best of our knowledge, no study has so far examined this relationship among diabetic patients in Asia, despite the fact that racial differences have been suggested in the association between sleep and diabetes (12,18). In this context, the objective of the current study was to investigate the association of sleep duration with the HbA_1c levels, as well as with obesity, which is the major factor related to poor glycemic control, among Japanese type 2 diabetic patients.     

Dynemicins, new antibiotics with the 1,5-diyn-3-ene and anthraquinone subunit. I. Production, isolation and physico-chemical properties.

Dynemicin A, a novel antibiotic containing the bicyclo[7.3.1]-1,5-diyn-3-ene and 1,4,6-trihydroxyanthraquinone functionalities, was isolated from the culture broth of Micromonospora chersina sp. nov. M956-1. The antibiotic exhibited potent in vitro antibacterial and cytotoxic activity, and in in vivo, it cured mice from lethal Staphylococcus aureus infection and prolonged survival time of mice inoculated with murine tumors. Three satellite components, dynemicins L, M and N, were also isolated from the culture broth and chemically characterized.     

MRI demonstration of uncal herniation caused by arachnoid cyst in the Sylvian fissure

Summary We report a case of arachnoid cyst in the Sylvian fissure which progressed to uncal herniation. MRI was shown to be superior in visualizing uncal herniation.     

Expression of mRNA for Gs alpha and Gi2 alpha in primary cultured mouse cerebral cortical neurons.

Developmental changes of mRNAs for alpha-subunits of GTP binding protein (G-protein) such as Gs alpha and Gi2 alpha during neuronal development were examined in both primary cultured cerebral cortical neurons and cerebral cortices obtained from age-matched mice. The expression of mRNAs for both G-protein alpha-subunits in primary cultured neurons showed a development pattern similar to that in the cerebral cortex in vivo. Both mRNAs were expressed at an early stage of neuronal development, and the expression patterns of mRNA for both G-protein alpha-subunits were found to be only slightly changed during development. These results suggest that the G-protein appears at an early stage of neuronal development and may play an important role therein.     

Contribution of Lysosomes to the Subcellular Distribution of Basic Drugs in the Rat Liver

Purpose. We examined the subcellular distribution of the basic drugs, chlorpromazine (CPZ), imipramine (IMP) and biperiden (BP), in rat liver, and evaluated the contribution of lysosome (Lys) to their intracellular distribution in comparison with that of mitochondria (Mit). Methods. In an in vivo distribution, the concentrations of CPZ, IMP and BP in the liver subcellular fractions were determined. In an in vitro study, uptake of [³H]IMP into Lys and Mit fractions was determined in the presence or absence of several agents. Results. The distribution of these drugs 10 min after administration was quite similar. However, the relative specific contents (the drug concentration per protein of each fraction divided by that of the total homogenate) in Lys were 7.3, 9.6 and 4.2, respectively for CPZ, IMP and BP, whereas those in the other organella were only 0.4 ~ 1.7. In an in vitro uptake study, the dose response of IMP uptake into Lys was biphasic, while that into Mit fractions was monophasic. The binding of IMP to the high affinity sites of Lys was pH dependent and disappeared in 50 mM NH₄C1 or 50 µM CPZ, both of which increased the intralysosomal pH. the low affinity sites were not affected by these drugs. Conclusions. The results indicated that Lys has the highest affinity for the basic drugs in the liver and that its contribution to their subcellular distribution depends on the intralysosomal pH, which is also affected by these drugs. The importance of these effects may become significant in combination therapy using various basic drugs.     

Molecular pathomechanism of distal myopathy with rimmed vacuoles]

Distal myopathy with rimmed vacuoles (DMRV) and hereditary inclusion body myopathy (HIBM) are genetically identical autosomal recessive muscle disorders caused by mutations in the GNE gene. This gene encodes a bifunctional protein with UDP-GlcNAc 2-epimerase and ManNAc kinase activities that catalyze the rate limiting step and the succeeding step, respectively, in the sialic acid biosynthetic pathway. V572L mutation is the most prevalent among Japanese DMRV patients and accounts for about 60% of mutant alleles. Clinical spectrum of DMRV/HIBM seems to be wider than previously thought in terms of both the severity of the disease and the range of affected organs. There are rare asymptomatic homozygotes with missense GNE mutations, indicating the presence of mitigating factors. Surprisingly, more than 10% of the patients had a variety of cardiac abnormalities, suggesting that skeletal muscle may not be the only organ involved. Studies on recombinant GNE demonstrate a loss-of-function nature of the missense mutations identified. Patients' cells show decreased sialylation status which can be recovered by adding GNE metabolites, such as ManNAc and NeuAc. This indicates the possibility of developing a therapy for DMRV/HIBM by giving these metabolites to patients although we have to await the model mice that are currently being produced at several laboratories.     

Ontogeny of beta-adrenergic receptor-mediated cyclic AMP generating system in primary cultured neurons.

The developmental changes in the beta-adrenergic receptor/cyclic AMP generating system were examined using mouse cerebral cortical neurons in primary culture. During neuronal growth in vitro, the number of binding sites for [3H]dihydroalprenolol (DHA) showed a tendency to increase (Bmax), while the affinity (Kd) for [3H]DHA did not show any noticeable changes. Basal and isoproterenol-stimulated adenylate cyclase activities as well as the activation of adenylate cyclase by 5'-guanylylimidodiphosphate (GppNHp), NaF and forskolin showed progressive and parallel increases during neuronal growth on a polylysine-coated surface. The treatment of primary cultured neurons with islet-activating protein (IAP), one of the pertussis toxins, attenuated the inhibitory effect of carbachol, a muscarinic agonist, on isoproterenol-induced activation of adenylate cyclase activity. These results indicate that primary cultured neurons possess a cyclic AMP generating system coupled with beta-adrenergic and muscarinic receptors, which is regulated via stimulatory and inhibitory GTP-binding proteins, respectively. The results described above also suggest that the beta-adrenergic receptor, stimulatory and inhibitory types of GTP-binding proteins and adenylate cyclase may develop in a parallel fashion during neuronal growth on a polylysine-coated surface.