Brown adipose tissue function is accompanied by cerebral activation in lean but not in obese humans

Brown adipose tissue (BAT) is able to generate heat and dissipate energy in response to cold exposure in mammals. It has recently been acknowledged that adult humans also have functional BAT, whose metabolic activity is reduced in obesity. In healthy humans, the cerebral mechanisms that putatively control BAT function are unclear. By using positron emission tomography (PET), we showed that cold-induced BAT activation is associated with glucose metabolism in the cerebellum, thalamus, and cingulate, temporoparietal, lateral frontal, and occipital cortices in lean participants, whereas no such associations were found under warm control conditions. The cold-induced increase in cerebral glucose metabolism was more robust in lean than obese participants. Cerebral glucose metabolism was not associated with skeletal muscle or white adipose tissue glucose uptake under warm or cold conditions. In conclusion, BAT metabolism was accompanied by the activation of specific cerebral regions, and this shows an uncharacterized role that the brain plays in the regulation of BAT function. In obese participants, the cold-induced response in cerebral activity was attenuated that provides a clue for obesity-induced impairment in BAT metabolism.     

Bone marrow mesenchymal stem cells undergo nemosis and induce keratinocyte wound healing utilizing the HGF/c-Met/PI3K pathway

We previously showed cell–cell contacts of human dermal fibroblasts to induce expression of the hepatocyte growth factor/scatter factor (HGF) in a process designated as nemosis. Now we report on nemosis initiation in bone marrow mesenchymal stem cells (BMSCs). Because BMSCs are being used increasingly in cell transplantation therapy we aimed to demonstrate a functional effect and benefit of BMSC nemosis for wound healing. Nemotic and monolayer cells were used to stimulate HaCaT keratinocyte migration in a scratch-wound healing assay. Both indicators of nemosis, HGF production and cyclooxygenase-2 expression, were induced in BMSC spheroids. When compared with a similar amount of cells as monolayer, nemotic cells induced keratinocyte in vitro scratch-wound healing in a concentration-dependent manner. The HGF receptor, c-Met, was rapidly phosphorylated in the nemosis-stimulated keratinocytes. Nemosis-induced in vitro scratch-wound healing was inhibited by an HGF-neutralizing antibody as well as the small molecule c-Met inhibitor, SU11274. HGF-induced in vitro scratch-wound healing was inhibited by PI3K inhibitors, wortmannin and LY294002, while LY303511, an inactive structural analogue of LY294002, had no effect. Inhibitors of the mitogen-activated protein kinases MEK/ERK1/2 (PD98059 and U0126), and p38 (SB203580) attenuated HGF-induced keratinocyte in vitro scratch-wound healing. We conclude that nemosis of BMSCs can induce keratinocyte in vitro scratch-wound healing, and that in this effect signaling via HGF/c-Met is involved.     

Osteoclasts in neurofibromatosis type 1 display enhanced resorption capacity,aberrant morphology,and resistance to serum deprivation

Neurofibromatosis 1 syndrome (NF1) presents with skeletal involvement suggesting that altered bone dynamics is associated with NF1. Histological analysis of three cases of NF1-related pseudarthrosis revealed numerous osteoclasts in contact with adjacent bone, and within the pseudarthrosis tissue itself. These findings prompted us to evaluate the differentiation and resorption capacity of NF1-osteoclast like cells (OLCs) in vitro. Osteoclast progenitors were isolated from peripheral blood of 17 patients with NF1 and allowed to differentiate into OLCs on bone slices. The following differences were found between NF1 and control samples: samples from NF1 patients resulted in a higher number of resorbing OLCs; NF1 OLCs were larger in size; their nuclei were more numerous; actin rings were more frequent; and the resorption pits in NF1 samples were more numerous and larger. Bone resorption markers revealed that the resorption activity in NF1 OLC cultures was approximately two times higher than in controls. Following deprivation from serum, the number of NF1 OLCs remained essentially the same during 24 h, whereas the number of control OLCs was dramatically reduced during the same time. Three patients had NF1-related lytic bone lesions, and their in vitro results differed from those of other patients. Our results demonstrate that OLCs derived from blood of patients with NF1 display elevated resorption activity under conditions isolated from microenvironment operative in vivo. Thus, increased osteoclast activity may be a phenotypic property of the NF1 syndrome, and at least in part explain selected skeletal findings in NF1, such as osteoporosis/osteopenia.     

Transfer of Lorazepam and its Conjugate Across the Human Placenta

Abstract: The concentrations of lorazepam and its conjugate were determined in maternal venous serum, in umbilical vein and artery serum, and in amniotic fluid after a single 2 mg intramuscular and 2.5 mg oral maternal administration. During normal delivery (2 mg intramuscular injection) and caesarean section (2.5 mg orally) both the unconjugated and conjugated forms of lorazepam were found in the umbilical circulation and amniotic fluid. The serum protein unbound fraction was 14.0±4.8 (S.D.) % in maternal circulation and 20.8 ±3.1% in umbilical circulation. Generally, lorazepam was a useful anxiolytic agent during normal delivery and as a sedative on the night before caesarean section.     

Bilateral hemodynamic responses to auditory stimulation in newborn infants

We studied hemodynamic auditory evoked responses of 20 healthy full-term neonates with near-infrared spectroscopy. The instrument used allows the measurements to be performed simultaneously above both auditory cortices. The stimulation consisted of 5-s trains of sound (700-ms interstimulus interval) with a 25-s silent interval. In response to the stimulation, a significant increase in concentration of oxygenated hemoglobin was detected in 14 out of 21 measurements. The mean latency of the largest response was 9.63+/-2.20 s (mean+/-SD) and the mean amplitude was 1.02+/-0.53 microM. The response amplitude was significantly larger in active (1.28+/-0.59 microM) than in quiet sleep (0.76+/-0.32 microM). The latency of the oxygenated hemoglobin concentration response was significantly shorter (r=-0.70 and p=0.0023) for infants with higher gestational age.     

Associations of functional ability with health-related behavior and body mass index among the elderly

The main purpose of this study was to determine whether functional ability among the elderly associates with body mass index (BMI) and health-related behavior. The secondary aim was to examine whether health behavior and BMI can be seen as mechanisms explaining sociodemographic disparities in functional ability. Cross-sectional biennial surveys from 1985 to 2001 were used to study 11,793 Finnish people aged 65-79 years. Associations of activities of daily living (ADL) with BMI, health behaviors (smoking, alcohol consumption, diet, physical activity), time period, previous occupation, marital status and certain diseases were tested using an ordinal regression model. Current and ex-smoking, heavy and non-alcohol use, unhealthy diet, physical inactivity and obesity were associated with inferior ADL. Alcohol consumption among men showed a U-shaped relation to functional ability. Most of the differences in ADL by occupation and marital status vanished after adjustment of multiple factors. The results showed clear associations of ADL with health-related behaviors and BMI when adjusted for multiple factors. The findings suggesting a U-shaped relation between ADL and alcohol consumption among men and the association between diet and ADL add to our previous knowledge of factors related to functional ability.     

Measurement of the abdominal circumference for the detection of intra-abdominal hemorrhage has no diagnostic value

BACKGROUND: Measuring the circumference of the abdomen is still commonly used when treating a patient with suspicion of intra-abdominal bleeding. In the present study the usefulness of this method for a diagnostic purpose is questioned because of the assumed method-related interindividual variation. METHODS: The study group consisted of 34 end-stage renal failure (ERSF) patients treated with peritoneal dialysis. Each patient was measured by the same nurse at the level of the umbilicus and the level of the iliac crest both before and after an infusion of 2000 ml of peritoneal dialysis fluid into the peritoneal cavity. One healthy female served as a control. Her abdominal circumference was measured at the level of the umbilicus by 10 different emergency medical technicians (EMTs), each of whom performed the measurement three times. The measuring tape was blank and the place of the first measurement was marked as performed in clinical practice. RESULTS: The mean abdominal circumference at the level of the umbilicus before an infusion of peritoneal fluid was 93.2 +/- 9.5 cm (SD), and after filling the peritoneal cavity 96.3 +/- 9.5 cm (difference 3.1 +/- 1.7 cm). These figures at the level of the iliac crest were 96 +/- 8.3 and 97.2 +/- 8.4 cm (difference 1.2 +/- 1.4 cm) (P < 0.0001), respectively. The mean value between the smallest and largest values when measuring the circumference of a healthy control person was 1.85 +/- 1.11 (P < 0.0005). The mean difference in circumference in the peritoneal dialysis patients was smaller than the largest difference among the three measurements taken by the same EMT. CONCLUSION: Measuring the abdominal circumference should not be used as a diagnostic tool when intra-abdominal bleeding is suspected.     

Standard, routine and non-routine processes in health care

Quality management methods have been introduced into health care with variable success. Industrial approaches, such as standardization, are not always applicable professional services, because of fundamental differences in conceptions of aims and the predictability of the results of action. Processes in health care can be classified into standard, routine and non-routine depending on the level of repetition and amount of variation, variety and uncertainty. Quality problems are different in each type: standard processes may produce deviations from targets, routines errors in classification, and non-routines failures in interpretation. Different management approaches for each type are discussed. A metaphor to assist discussion, The Broom, is introduced.