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PubMed1994

Hypnosis and the dream hidden observer: primary process and demand characteristics.

In Study 1, virtuoso (n = 13; passed more than 10 suggestions on the Harvard Group Scale of Hypnotic Susceptibility, Form A [HGSHS:A] and Stanford Hypnotic Susceptibility Scale, Form C), high hypnotizable (n = 14; passed more than 8 suggestions on the HGSHS:A), and medium hypnotizable (n = 17; passed 4-8 suggestions on the HGSHS:A) Ss were administered a hypnotic dream suggestion followed by a "dream hidden observer" suggestion (i.e., access hidden part; have new thoughts and images pertinent to dream). The majority of Ss reported dreams (81.8%) and hidden observers (80%), with hidden reports being characterized by more personal content, less primary processes, and poorer recall than dream reports. Study 2 replicated major findings. Although hypnotized (n = 18) and low hypnotizable simulating Ss (n = 17) responded comparably on most measures, hypnotizable Ss' dreams contained more primary process than did simulating Ss, providing support for M. R. Nash's (1991) psychoanalytic model.

Adult↗

PubMed1987

Goal-directed fantasy, hypnotic susceptibility, and expectancies.

We conducted an initial screening session in which hypnosis was presented as a "test of imagination" and administered with other imagination measures. In a second session, we instructed high- and low-hypnotizable subjects to imagine along with suggestions but to resist responding to motoric suggestions. Subjects received either instructions to use goal-directed fantasies (GDFs) or no facilitative instructions. Sizable individual difference effects were secured. Hypnotizable subjects exhibited more suggestion-related movements and reported greater involuntariness than did low-hypnotizable subjects. With GDF instructions, low- and high-hypnotizable subjects reported equivalent GDF absorption and frequencies. However, hypnotizable subjects exhibited greater responsiveness and reported greater involuntariness than did those low in hypnotizability, even when their GDFs were equivalent. Thus, no support was generated for the hypotheses that sustained, elaborated suggestion-related imagery mediates response to suggestion (Arnold, 1946) or that absorption in suggestions is of particular importance for low-hypnotizable subjects (Zamansky & Clark, 1986). Our finding that measures of response expectancy paralelled responding and reports of nonvolition support the hypothesis that expectancies mediate the relation between imagination, involuntariness, and responding (Kirsch, 1985; Spanos, 1982). Hypnotizable imagining subjects in the study discussed here exhibited greater responsiveness than a comparable sample of subjects did in a previous countersuggestion study (Lynn, Nash, Rhue, Frauman, & Stanley, 1983) in which no attempt was made to foster an association between imagining and involuntary responding in the initial screening session.

Adult↗

PubMed2002

Liver failure complicating non-alcoholic steatohepatitis following allogeneic bone marrow transplantation for Shwachman-Diamond syndrome.

Bone marrow transplantation is potentially curative therapy for the hematologic complications associated with Shwachman-Diamond syndrome (SDS). This syndrome is, however, also associated with significant pancreatic and hepatic dysfunction, which may complicate BMT. We report a case of liver failure due to non-alcoholic steatohepatitis (NASH) following BMT for SDS. This case illustrates the need for assessing liver dysfunction pre-BMT in these patients, in addition to highlighting the potential risk posed by pre-existing steatosis for the development of rapidly progressive hepatic failure following transplantation.

Adult↗

PubMed2005

Effects of oligofructose on glucose and lipid metabolism in patients with nonalcoholic steatohepatitis: results of a pilot study.

OBJECTIVE: In experimental animals, recent results suggest that the addition of inulin-type fructans such as oligofructose (OFS) in the diet decreases triacylglycerol accumulation in the liver tissue. Therefore, we have investigated the effect of daily ingestion of OFS in seven patients with nonalcoholic steatohepatitis (NASH), confirmed by liver biopsies. DESIGN: They received 16 g/day OFS or maltodextrine (placebo) for 8 weeks in a randomized double-blind crossover design. Energy intake, body composition, liver steatosis and blood parameters were analysed after 4 and 8 weeks of dietary supplementation. RESULTS: Compared to placebo, OFS decreased significantly serum aminotransferases, aspartate aminotransferase after 8 weeks, and insulin level after 4 weeks, but this could not be related to significant effect on plasma lipids. CONCLUSION: This pilot study supports the putative interest of OFS in the management of liver diseases associated with abnormal lipid accumulation in humans.

Adult↗

PubMed2002

Cathodically activated nucleophilic aromatic substitution of hydrogen: a novel electrochemical mechanism.

Cathodically activated nucleophilic aromatic substitution of hydrogen (SNArH) is reported for the first time; the 1,3,5-trinitrobenzene radical anion reacts with the nucleophile N-methylformamide leading to high yields of the sigma H-complex radical anion; this intermediate can be easily oxidised electrochemically by means of a three-electron mechanism giving rise to the nucleophilic aromatic substitution product (NASH product) in good yield.

Journal Article↗

PubMed2003

Is oral azithromycin effective for the treatment of cyclosporine-induced gingival hyperplasia in cardiac transplant recipients?

Anecdotal evidence suggests that azithromycin is effective for the treatment of cyclosporine-induced gingival hyperplasia in solid-organ transplant recipients. We present the cases of two heart transplant patients who insidiously developed gingival hyperplasia, likely because of immunosuppression with cyclosporine, which was treated with azithromycin. Evidence supporting the efficacy of azithromycin in the treatment of cyclosporine-induced gingival hyperplasia in solid organ transplant recipients was searched for, identified, and then critically assessed. While no data were found specifically evaluating azithromycin in cardiac transplant patients, there were nine pertinent papers identified that evaluated the clinical question of interest in the renal transplant population [Wahlstrom et al. (1995) The New England Journal of Medicine 332, 753; Boran et al. (1996) Transplantation Proceedings 28, 2316; Gomez et al. (1997) Nephrology Dialysis Transplantation 12, 2694; Ljutic (1997) Dialysis & Transplantation 26, 787; Puig et al. (1997) Transplantation Proceedings 29, 2379; Nash et al. (1998) Transplantation 65, 1611; Nowicki et al. (1998) Annals of Transplantation 3, 25; Wirnsberger et al. (1998) Transplantation Proceedings 30, 2117; Citterio et al. (2001) Transplantation Proceedings 33, 2134]. These studies and case reports are summarized. While more evidence is required to support routine use of azithromycin for the treatment of cyclosporine-induced gingival hyperplasia in cardiac transplant recipients, preliminary published evidence from renal transplant patients is certainly favourable.

Administration, Oral↗

PubMed2002

Kinetic studies of human tyrosyl-DNA phosphodiesterase, an enzyme in the topoisomerase I DNA repair pathway.

Tyrosyl-DNA phosphodiesterase (TDP) cleaves the phosphodiester bond linking the active site tyrosine residue of topoisomerase I with the 3' terminus of DNA in topoisomerase I-DNA complexes which accumulate during treatment of cancer with camptothecin. In yeast, TDP mutation confers a 1000-fold hypersensitivity to camptothecin in the presence of an additional mutation of RAD9 gene [Pouliot, J.J., Yao, K.C., Robertson, C.A. & Nash, H.A. (1999) Science 286, 552-555]. Based on the recently solved crystal structure, human TDP belongs to a distinct class within the phospholipase D superfamily in spite of very low sequence homology [Interthal, H., Pouliot, J.J. & Champoux, J.J. (2001) Proc. Natl Acad. Sci. USA 98, 12009-12014, and Davies, D.R., Interthal, H., Champoux, J.J. & Hol, W.G.J. (2002) Structure 10, 237-248]. To understand the enzymatic mechanism of this novel enzyme, and to facilitate inhibitor screening of human TDP, we have expressed and purified recombinant human TDP variants carrying deletions of 1-39 or 1-174 amino acids. Furthermore, a continuous colorimetric assay in a 96-well format was also developed using p-nitrophenyl-thymidine-3'-phosphate as substrate. This assay system is able to detect enzymatic activity at enzyme concentrations as low as 15 nm. Purified recombinant human TDPNDelta39 cleaved p-nitrophenyl-thymidine-3'-phosphate with Km and kcat values of 211.14 +/- 23.83 micro m and 8.82 +/- 0.57 per min in the presence of Mn2+.

Amino Acid Sequence↗

PubMed2002

Other disease associations with non-alcoholic fatty liver disease (NAFLD).

Non-alcoholic fatty liver disease (NAFLD) is usually seen in middle-aged women with obesity, non-insulin-dependent diabetes mellitus and/or hyperlipidaemia. NAFLD has also been associated with other conditions. Surgical procedures to treat obesity such as jejunoileal bypass and gastroplasty as well as massive small bowel resection have been associated with NAFLD. Mechanisms such as rapid weight loss, certain nutritional deficiencies and bacterial overgrowth have been proposed. Other nutritional conditions such as extreme malnutrition and total parenteral nutrition can also cause NASH. This can be due to abnormal glucose and fat metabolism, deficiencies like carnitine, essential fatty acid and choline or, in the case of parenteral nutrition, excess of calories, glucose or lipids. Several drugs have also been implicated as well as some inborn errors of metabolism and, more rarely, other diseases.

Digestive System Surgical Procedures↗

PubMed2001

Hemochromatosis: diagnosis and management.

HH should be distinguished from the other syndromes of iron overload. Many patients with HH have abnormal serum iron values before the development of any significant symptoms or clinical findings, and liver biopsy is less important in these patients. HFE mutation analysis has strengthened our ability to diagnose HH accurately and is useful in family studies. HFE mutations may play a contributory role in some patients with PCT, NASH, or chronic HCV. Generalized population screening for HH may someday become a reality and lead to the identification and treatment of more patients before they have tissue damage or increased morbidity. With the identification of the HFE gene, we are beginning to unravel many of the mysteries of both normal iron absorption and the disorder of iron metabolism found in patients with HH.

HLA Antigens↗

PubMed2003

CYP2E1 activity before and after weight loss in morbidly obese subjects with nonalcoholic fatty liver disease.

Previous studies suggest that hepatic cytochrome P450 2E1 (CYP2E1) activity is increased in individuals with chronic alcoholism, nonalcoholic steatohepatitis (NASH), and morbid obesity, and may contribute to liver disease. We studied 16 morbidly obese subjects with varying degrees of hepatic steatosis and 16 normal-weight controls. Obese subjects were evaluated at baseline, 6 weeks, and 1 year after gastroplasty, a procedure that leads to weight loss. Hepatic CYP2E1 activity was assessed by determination of the clearance of chlorzoxazone (CLZ), an in vivo CYP2E1-selective probe. Liver biopsy tissue was obtained during surgery for histopathology. Both the total and unbound oral CLZ clearance (Cl(u)/F) was elevated approximately threefold in morbidly obese subjects compared with controls (P <.001). The Cl(u)/F was significantly higher among subjects with steatosis involving >50% of hepatocytes, compared with those with steatosis in < or =50% of hepatocytes (P =.02). At postoperative week 6 and year 1, the median body mass index (BMI) of subjects who underwent gastroplasty decreased by 11% and 33%, total oral CLZ clearance declined by 16% (P <.01) and 46% (P <.05), and Cl(u)/F decreased by 18% (P <.05) and 35% (P =.16), respectively. Moreover, those subjects with a year 1 BMI <30 kg/m(2) exhibited a median Cl(u)/F that was 63% lower (P =.02) than the respective clearance for all other subjects. In conclusion, hepatic CYP2E1 activity is up-regulated in morbidly obese subjects. A positive association between the degree of steatosis and CYP2E1 activity preoperatively and between the extent of obesity and CYP2E1 activity postoperatively, suggests that CYP2E1 induction is related to or caused by hepatic pathology that results from morbid obesity.

Blood Glucose↗

PubMed2000

Human term placental lipoxygenase-mediated N-demethylation of phenothiazines and insecticides in the presence of linoleic acid.

This study investigated the hypothesis that human term placental lipoxygenase (HTPLO) and soybean lipoxygenase (SLO) are capable of mediating N-demethylation of selected phenothiazines and insecticides in the presence of linoleic acid (LA). In addition to being LA dependent, the N-demethylation reaction mediated by HTPLO and SLO was limited by incubation time, pH of the medium, concentration of the enzyme and the substrate. Using Nash reagent to monitor formaldehyde production, the specific activity for LA-dependent N-demethylation of chlorpromazine, a model phenothiazine, was determined to be 1.7+/-0.3 nmoles/min/mg HTPLO. Besides chlorpromazine, N-demethylation of promazine, promethazine and trimeprazine was also observed. The insecticide, aminocarb, displayed a specific activity of 2.2+/-0.3 nmoles/min/mg HTPLO for N-demethylation. Other insecticides, namely chlordimeform, dicrotophos and zectran, were oxidized in a similar manner. As compared with HTPLO, the rates of N-demethylation of phenothiazines and insecticides mediated by SLO were higher. Classical inhibitors of lipoxygenase, as well as antioxidants and free radical scavengers, caused a dose-dependent reduction in the production of formaldehyde from chlorpromazine and aminocarb by HTPLO. These results clearly demonstrate the ability of polyunsaturated free fatty acids to support N-demethylation of xenobiotics via the lipoxygenase pathway.

Carbamates↗

PubMed2004

Hepatotoxicity of drugs used for treatment of obesity and its comorbidities.

Obesity is an increasingly prevalent problem with many associated health risks. Obese patients may present with liver diseases directly attributable to their obesity, such as nonalcoholic steatohepatitis (NASH). However, many such individuals are prescribed various potentially hepatotoxic medications for obesity itself, as well as for the complications of obesity. Clinically, it may be difficult to distinguish the two. Furthermore, many of these medications are in common use, and some are not commonly recognized as potentially injurious to the liver. While some medications have predictable hepatotoxicity, many more have associated idiosyncratic reactions. We review the literature and case-reports of hepatotoxicity associated with four categories of medications: those used primarily in the treatment of obesity, those used in the treatment of diabetes mellitus, those used in the treatment of hyperlipidemia, and those used in the treatment of hypertension. For each class, we present the described epidemiology, clinical presentation, pathology, and prognosis.

Antihypertensive Agents↗

PubMed2004

Hepatitis C and nonalcoholic fatty liver disease.

Hepatitis C virus (HCV) and nonalcoholic fatty liver disease (NAFLD) are the two most common causes of chronic liver disease in North America. NAFLD represents a spectrum of liver lesions that occur in individuals who either do not consume any alcohol or only consume alcohol in quantities generally considered not to be harmful to the liver. This spectrum consists of isolated hepatic macrovesicular steatosis at one end and nonalcoholic steatohepatitis (NASH) at the other. Hepatic steatosis is present in approximately 50% of the subjects with HCV. Genotype 3 is independently associated with hepatic steatosis. In those with genotype 1 infection, steatosis is associated with features of the metabolic syndrome. The presence of hepatic steatosis correlates with the stage of hepatic fibrosis in patients with HCV. This has been related to the presence of insulin resistance. Hepatic steatosis also adversely affects the virologic response rates to anti-HCV therapy. In this article, we will review the epidemiology of HCV and NAFLD, their impact on each other, and the course of the liver disease in individuals afflicted with both conditions.

Adipocytes↗

PubMedDate not supplied

[Primary correction of scoliosis with the Wilmington corset].

QUESTION: As part of our study, the effectiveness and patient's acceptance of the Wilmington-brace is to be evaluated. The effectiveness can be documented with the help of the primary correction achieved, especially in light of the fact, that the primary correction and the long-term results are directly dependant upon one another. MATERIAL AND METHOD: We examined a total of 52 patients with an idiopathic scoliosis treated in a thermoplast brace. The group consisted of 38 female and 14 male patients (average age 11.6 years). The angulation was measured with the help of the Cobb-angle and the rotation with the method described by Nash and Moe. The skeletal age was classified according to Risser's-sign. The angle determinations were carried out at three separate points in time--at first presentation, prior to bracing and four to six weeks following bracing. RESULTS: The patients presented with an average angulation of 31 degrees. The average correction achieved in the Wilmington-brace was 41%. This corresponds to a correction of 13 degrees. The best primary correction (45%) was obtained in the thoracolumbar spine. Those patients with the smallest deformity at the onset of treatment showed the best results. The scoliosis with a large primary deformity and a marked rotation of the vertebral bodies responded poorly to correction. Advanced age or skeletal maturity were also limiting factors. Physical therapy had a positive influence on the amount of primary correction obtained. CLINICAL RELEVANCE: The Wilmington-brace (thermoplast) allows for a good primary correction of idiopathic scoliosis. The simplicity of application and the low production costs are also positive attributes.

Adolescent↗

PubMed2002

Chaos in learning a simple two-person game.

We investigate the problem of learning to play the game of rock-paper-scissors. Each player attempts to improve her/his average score by adjusting the frequency of the three possible responses, using reinforcement learning. For the zero sum game the learning process displays Hamiltonian chaos. Thus, the learning trajectory can be simple or complex, depending on initial conditions. We also investigate the non-zero sum case and show that it can give rise to chaotic transients. This is, to our knowledge, the first demonstration of Hamiltonian chaos in learning a basic two-person game, extending earlier findings of chaotic attractors in dissipative systems. As we argue here, chaos provides an important self-consistency condition for determining when players will learn to behave as though they were fully rational. That chaos can occur in learning a simple game indicates one should use caution in assuming real people will learn to play a game according to a Nash equilibrium strategy.

Game Theory↗

PubMed2004

Self-enforcing climate-change treaties.

In the absence of world government, an effective treaty to control the emissions of greenhouse gases should be self-enforcing. A self-enforcing treaty has the property that, if a country expects other countries to abide by the treaty, it will be in the self-interest of that country to abide by the treaty too. (A difficulty with the Kyoto Protocol is that it does not appear to lay the groundwork for a self-enforcing treaty). A self-enforcing treaty can be modeled as a Nash equilibrium of a suitably defined dynamic game among a large number of sovereign countries of diverse sizes and economic capabilities. We study such a game and characterize its equilibria (typically there are many) and the global-Pareto-optimal solutions. We identify one of the equilibria, which we call "business as usual," with the current situation. The multiplicity of equilibria provides an opportunity to move from the inefficient business-as-usual equilibrium to one or more equilibria that are Pareto-superior. Using a calibrated model with 184 countries, we give numerical illustrations of business-as-usual and global-Pareto-optimal trajectories and estimate the potential welfare gains from a self-enforcing treaty.

Journal Article↗

PubMed2005

Essential equilibria.

The connected uniformly hyperstable sets of a finite game are shown to be precisely the essential components of Nash equilibria.

Journal Article↗

PubMed2005

Punishing and abstaining for public goods.

The evolution of cooperation within sizable groups of nonrelated humans offers many challenges for our understanding. Current research has highlighted two factors boosting cooperation in public goods interactions, namely, costly punishment of defectors and the option to abstain from the joint enterprise. A recent modeling approach has suggested that the autarkic option acts as a catalyzer for the ultimate fixation of altruistic punishment. We present an alternative, more microeconomically based model that yields a bistable outcome instead. Evolutionary dynamics can lead either to a Nash equilibrium of punishing and nonpunishing cooperators or to an oscillating state without punishers.

Altruism↗