Three probiotic strains exert different effects on plasma bile acid profiles in healthy obese adults: randomised, double-blind placebo-controlled crossover study.

Microbial metabolism in the gut may alter human bile acid metabolism in a way that beneficially affects lipid homeostasis and therefore cardiovascular disease risk. Deconjugation of bile acids by microbes is thought to be key to this mechanism but has yet to be characterised in blood and stool while observing lipid markers. The aim of this study was to determine the effect of 3 different probiotic strains on plasma and stool bile acids in the context of lipid and glucose metabolism. In this 18-week, randomised, double-blind crossover study, healthy adults (53±8 years) with a high waist circumference underwent a 1-week pre-baseline period and were then randomised to receive 1 capsule/day of Bacillus subtilis R0179 (2.5×109 cfu/capsule; n=39), Lactobacillus plantarum HA-119 (5×109 cfu/capsule; n=38), Bifidobacterium animalis subsp. lactis B94 (5×109 cfu/capsule; n=37) or placebo for 6 weeks. Following a 3-week washout and second pre-baseline week, participants were crossed to the other intervention for 6 weeks followed by a 1-week post-intervention period. Blood and stool samples were collected at the beginning and end of each intervention to measure bile acids, serum lipid profiles, and glucose and insulin levels. Data from the placebo intervention were combined for all participants for analyses. In obese participants, the difference (final-baseline) in the sum of deconjugated plasma bile acids was greater with consumption of B. subtilis (691±378 nmol/l, P=0.01) and B. lactis (380±165 nmol/l, P=0.04) than with placebo (98±176 nmol/l, n=57). No significant differences were observed for any probiotics for stool bile acids, serum lipids, blood glucose or insulin. These data suggest that B. subtilis and B. lactis had no effect on glucose metabolism or serum cholesterol but increased deconjugated plasma bile acids in obese individuals. Additional studies should be conducted to confirm these findings and explore potential mechanisms. This trial was registered at clinicaltrials.gov as NCT01879098.

Cyclooxygenase-2 inhibitor reduces simvastatin-induced bone morphogenetic protein-2 and bone formation in vivo.

BACKGROUND AND OBJECTIVE: Simvastatin, a cholesterol-lowering drug, also stimulates oral bone growth when applied topically, without systemic side-effects. However, the mechanisms involved in vivo are not known. We hypothesized that bone morphogenetic protein-2, nitric oxide synthase, and cyclooxygenase-2 are involved, based on prior in vitro evidence. MATERIAL AND METHODS: A rat bilateral mandible model, where 0.5 mg of simvastatin in methylcellulose gel was placed on one side and gel alone on the other, was used to quantify nitric oxide, cyclooxygenase-2 and bone morphogenetic protein-2 (via tissue extraction, enzyme activity or immunoassay), and to analyze the bone formation rate (via undecalcified histomorphometry). Cyclooxygenase-2 and nitric oxide synthase inhibitors (NS-398 and L-NAME, respectively) were administered intraperitoneally. RESULTS: Simvastatin was found to stimulate local bone morphogenetic protein-2, nitric oxide and the regional bone formation rate (p < 0.05), whereas NS-398 inhibited bone morphogenetic protein-2 and reduced the bone formation rate (p < 0.05). CONCLUSION: These data suggest an association between simvastatin-induced bone morphogenetic protein-2 and bone formation in the mandibular microenvironment, and the negative effect of cyclooxygenase-2 inhibitors on bone growth.

Profiles of time perspective and personality: developmental considerations.

Time perspective is an important but subtle cognitive construct underlying personality, decision making, and goal setting. This study identified 3 temporal dimensions--temporal extension, temporal attitude, and temporal structure--and reviewed the associations among them. T. J. Cottle's (1969, 1977) work on temporal profiles was briefly reviewed; it suggested that 3 types of temporal profiles can be isolated and that 3 broad personality dimensions--human agency, mood, and temperament--from characteristic associations with each of the temporal profiles. The authors expected the profiles to reflect developmental sensitivities as a person moves from adolescence into early adulthood. Two samples (159 high school students and 236 university students) participated in the study. The results provided some limited support for the actualizer and atomist profiles; somewhat surprisingly, the role of temporal extension appeared to be insignificant. No evidence was found for a developmental transition of time perspective between middle adolescence (15-17 years) and early adulthood (18-25 years).

Time perspective: temporal extension, time estimation, and impulsivity.

It has been proposed that time perspective is an important variable that can, in part, explain the differences between people in terms of the development of self-control. One corollary of this position is that time perspective is somehow related to systematic biases in the way people perceive the passage of time. Such a bias may or may not be augmented by an association between time perspective and impulsivity. Two studies were conducted using measures of temporal extension, time estimation, and impulsivity. In general, no consistent effects were found. Neither time perspective nor impulsivity was related to any characteristic pattern of errors. In the second study, time perspective (mediated by age) was associated with predicting very brief time estimation scores, but not longer time estimation periods. It was concluded that whatever the mechanism might be that underlies the purported effect between time perspective and self-control, it is not related to a differential ability to perceive time moving more or less quickly.

Bifurcations of periodic orbits in axisymmetric scalefree potentials.

We study orbits in potentials with central cusps, emphasizing the spheroidal equidensity (SED) potentials generated by mass distributions with spheroidal equidensity surfaces. The most prominent bifurcations are those related to 1:1 and 4:3 resonances between radial motions and motions perpendicular to the central plane. We find that 1:1 resonances can cause the thin tube orbit, as well as the equatorial plane orbit, to become unstable. We concentrate on period-tripling bifurcations because they appear to be the least understood. We study them via a class of analytic maps. This study suggests that stable period-three orbits generally arise de novo in stable and unstable pairs via a turning-point bifurcation, and not through a bifurcation from the thin tube at a 120 degree rotation angle. The stable period-three orbits typically have only a short span of existence before becoming unstable to a period-doubling instability through a supercritical pitchfork bifurcation.

Effects of inotropes on human leucocyte numbers, neutrophil function and lymphocyte subtypes.

We have investigated the effects of inotropes with different adrenergic receptor specificity on differential white cell count, lymphocyte subtypes and neutrophil function in healthy volunteers. Six healthy, male volunteers were enrolled into this randomized, placebo-controlled pilot study. Each volunteer was studied on four separate occasions during a 2-h infusion of various agents, and for 2 h after stopping the infusion. The agents investigated were adrenaline 0.1 microgram kg-1 min-1, dobutamine 5 micrograms kg-1 min-1, dopexamine 2 micrograms kg-1 min-1 and 5% glucose 0.5 ml kg-1 h-1. Venous blood was sampled at 0, 30, 120 and 240 min. Haemodynamic monitoring was continued throughout the study. Full blood count, white cell differential count and enumeration of lymphocyte subtypes were performed. Neutrophil function tests included chemoluminescence, and assessment of neutrophil chemotaxis, phagocytosis and adhesion. The Wilcoxon signed rank test was used to compare differences between placebo and active drugs at each time compared with baseline. There was a significant increase in white cell count, lymphocyte count and neutrophil count with adrenaline, and a small but significant decrease in these variables with dobutamine and dopexamine. These changes were also apparent for absolute CD3+, CD4+ and CD8+ lymphocyte counts. Neutrophil respiratory burst in response to f-methionyl-leucyl-phenylalanine increased significantly only with adrenaline at 30 min (P = 0.046). There were no other significant changes in tests of neutrophil function. Infusion of inotropes was associated with changes in white cell numbers, lymphocyte subtypes and neutrophil respiratory burst. In healthy volunteers, adrenaline had effects different from those of dobutamine and dopexamine. The clinical relevance of such effects requires further investigation in critically ill patients.

Creatinine and 51Cr-EDTA clearance after liver transplantation.

We have compared glomerular filtration rate measured by creatinine clearance with that measured by 51Cr-EDTA clearance after liver transplantation. Fourteen pairs of values were obtained from seven patients on the first and second days after operation. There were wide discrepancies between the values for glomerular filtration rate measured by the two methods, with a regression co-efficient of 0.43 (p = 0.12). Both methods assume a steady state, with no change of extracellular fluid volume or in the rates of exchange between physiological compartments, that does not apply in the immediate period after operation. The results show the difficulties of using clearance techniques to assess renal function after major surgery. Since drug therapy may be based on these measurements, we suggest that in this group of patients isolated clearance values should not be used.

The use of sedative agents in critically ill patients.

The main aim of sedation in the critically ill patient is to provide relief from anxiety and pain. The current, ideal level of sedation should leave a patient who is lightly asleep but easily roused. No single regimen is suitable for all patients. The level of sedation should be monitored, and the choice of agent, the dose and the route of administration adjusted appropriately. Midazolam is often used to provide sleep and anxiolysis. Alternatives include propofol and isoflurane. Propofol is easily titrated to achieve the desired level of sedation, and its effects rapidly end when the infusion is stopped. Isoflurane also appears promising, but special equipment is needed for its administration. Morphine is the standard analgesic agent. The principal metabolites, morphine-6-glucuronide, is also a potent opioid agonist and may accumulate in renal failure. Of the newer analgesic agents, alfentanil is an ideal agent for infusion, and may be the agent of choice in renal failure. Neuromuscular blocking agents are indicated only in specific circumstances, and used only once it is known patients are asleep and pain free. The actions of these agents are unpredictable in the critically ill patient. Alterations in drug effect and elimination may occur, especially in the patient with hepatic and renal failure. This may also apply to active metabolites of the parent drug. When planning sedation regimens, specific patient needs and staffing levels must be remembered. Attention to the environment is also important. Midazolam and morphine given by intermittent bolus or by infusion are the mainstay of most regimens. Propofol is ideal for short periods of care on the ICU, and during weaning when longer acting agents are being eliminated.

Prolonged action of enoximone in renal failure.

Enoximone was administered on two separate occasions to a 37-year-old woman with renal failure secondary to thrombotic thrombocytopenic purpura. Plasma concentrations of enoximone and its principal metabolite, enoximone sulphoxide, were measured over a 9-day period. As renal function improved the rate of elimination of enoximone sulphoxide increased. The duration of effect of enoximone may be prolonged in patients with renal failure.

Serum acute phase proteins after orthotopic liver transplantation.

Acute phase proteins were measured in six patients before liver transplantation and for 72 h after orthotopic liver transplantation. The ability of the donor liver to mount an acute phase response was demonstrated, although the response was less than that seen in other groups of patients in whom this has been studied. Because of the reduced response to stress, the value of these measurements as indicators of liver function in this group of patients is limited.

Caudal analgesia for pediatric day case surgery: assessment of motor function prior to discharge.

The benefits of caudal analgesia are well recognized in the prevention of postoperative pain following pediatric surgery. The possibility of motor weakness may deter anesthetists from using this technique. This study investigates motor function prior to discharge in boys who, as day case patients, received caudal analgesia for pain relief following circumcision. Motor function was assessed using a simple and clinically relevant scale. Three different dosage regimens of bupivacaine were compared. No important motor weakness was demonstrated, and there was no difference with respect to motor block in the three groups. Caudal analgesia may be recommended as a suitable technique for day case patients.

Anaesthesia for patients with mitochondrial myopathy.

The anaesthetic management for an infant with mitochondrial encephalomyopathy due to fumarase deficiency is described. Mitochondrial myopathies may produce skeletal and cardiac muscle abnormalities, central nervous system effects and metabolic problems. The solutions to the anaesthetic problems posed by these patients are discussed.

Anaesthetic management of caesarean section for a mother with pre-eclampsia, the Klippel-Feil syndrome and congenital hydrocephalus.

A mother with the Klippel-Feil syndrome, congenital hydrocephalus and increased intracranial pressure presented for delivery by Caesarean section at 33 weeks because of pre-eclampsia. Anaesthetic management comprised awake intubation using the fibreoptic bronchoscope, followed by induction and maintenance of general anaesthesia for the delivery of a live male infant. This case report describes the problems arising under these circumstances and the relative merits of different anaesthetic techniques.