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Fatty liver disease in children.

NAFLD/NASH is now recognised as an increasing clinical problem in children and adolescents. Risk factors include obesity, insulin resistance, and hypertriglyceridaemia. Drug hepatoxicity and genetic or metabolic diseases that can cause hepatic steatosis must be excluded. Affected children are usually asymptomatic although a few may complain of malaise, fatigue, or vague recurrent abdominal pain. Liver biopsy is the gold standard for diagnosis, and is important in determining disease severity and prognosis. The natural history of childhood NASH may be progressive liver disease for a significant minority. Long term follow up studies in this population are still lacking. The mainstay of treatment is weight reduction. The use of pharmacological therapy, though promising, ideally needs further evaluation in well designed randomised controlled studies in children.

Adolescent↗

The percutaneous rotary lithotrite: a new approach to the treatment of symptomatic cholecystolithiasis.

This report evaluates the use of a new device for destruction of gall stones, the Kensey-Nash Lithotrite (Baxter Corporation, California, USA). The principle of the instrument is that of a liquidiser with an impeller that emulsifies stones. Twenty five patients were treated; 13 patients were considered unfit for conventional treatment (complex group) and 12 elected to have the procedure (non-complex group). In the complex group nine patients were treated under local anaesthesia. Only six of the 13 patients had a clear gall bladder at the end of the first procedure, but after further treatments that included cholecystoscopy, endoscopic sphincterotomy, and percutaneous cholecystolithotomy 11 patients had a gall bladder free of stones. The morbidity was high, mainly due to pain and bile leaks, causing prolonged stays in hospital (median 18 days). In the non-complex group six patients had the procedure performed under local anaesthesia. Ten patients had a successful clearance of the gall bladder, and the remaining two patients had the stones removed at cholecystoscopy. Despite good clearance, the morbidity was high, with eight emergency admissions on account of complications and a prolonged duration of stay (median 13 days). In conclusion the technique is effective, but the morbidity is high. Further development is required if this technique is to be included in the alternative treatments for the management of gall stones.

Adult↗

Triazene metabolism. I. The effect of substituents in the aryl group on the kinetics of enzyme-catalysed N-demethylation of 1-aryl-3,3-dimethyltriazenes.

A series of antitumor dimethylaryltriazenes (ArN==N . NMe2) have been studied with respect to enzyme catalysed N-demethylation by liver microsomes and the Km values determined by Lineweaver-Burk treatment. The substituent in the aryl group of the triazene does not significantly effect the magnitude of Km, which is of the same order of magnitude as the Km for aminopyrine. On the other hand, dimethyltriazenes appear to have lower Km values for demethylation than the structurally similar dimethylnitrosamines. Monomethyltriazenes, the proposed active metabolites of the dimethyltriazenes, do not undergo appreciable demethylation in the presence of microsomes and it appears that the dimethyltriazenes only demethylate once during metabolism. Spontaneous formaldehyde release from the hydroxymethyltriazene in the presence of the Nash reagent prevented an analogous study of the metabolism of these compounds.

Animals↗

Identification of a 50-kDa Ca-, cAMP-, and cGMP-dependent epithelial phosphoprotein as a cAMP regulatory protein.

Multiple second messengers, presumably acting via protein phosphorylation mechanisms, regulate flounder intestinal ion transport. We recently reported [C. Toskulkao, N. T. Nash, K. Leach, and M. C. Rao. Am. J. Physiol. 258 (Cell Physiol. 27): C879-C888, 1990] that this tissue possesses adenosine 3',5'-cyclic monophosphate (cAMP)- and guanosine 3',5'-cyclic monophosphate (cGMP)-specific protein kinases, types II and III Ca-calmodulin kinases, and very low levels of protein kinase C. These results correlate with ion transport studies in which cGMP and Ca were shown to inhibit salt absorption, cAMP to increase anion permeability, and phorbol esters to have no effect. In the present study we characterized in detail a 50-kDa protein the phosphorylation of which is regulated by more than one second messenger. The 50-kDa (pI 5.2) phosphoprotein is present in both the cytosol (50 kDa-C) and particulate (50 kDa-P) fractions and appears to be regulated by Ca, cAMP, and cGMP. Although the pI and Mr of the regulated proteins are identical, there are differences in the regulation of 50 kDa-P and 50 kDa-C. The phosphorylation of 50 kDa-P is high in the basal state, and Ca and cGMP enhance this. cAMP has a biphasic effect, increasing it at low and decreasing it at high protein concentrations. The isoquinoline derivatives H-8 [50% effective dose (ED50) approximately 2.3 microM] and H-7 (ED50 approximately 45 microM) inhibit basal 50 kDa-P phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Roles of phosphatidylinositol 3-kinase and osteopontin in steatosis and aminotransferase release by hepatocytes treated with methionine-choline-deficient medium.

Feeding mice a methionine and choline-deficient (MCD) diet serves as an experimental animal model for nonalcoholic steatohepatitis (NASH). In the present study we examined the effect of exposing AML-12 hepatocytes to MCD culture medium in regard to mechanisms of steatosis and alanine amino-transferase (ALT) release. Cells exposed to MCD medium developed significant and progressive steatosis from 6 to 24 h and also had significantly increased loss of ALT into the medium at 18 and 24 hours of incubation. No increased oxidative injury or cell death was observed. Osteopontin (OPN) mRNA in cells and protein expression in medium were significantly increased during 6-24 hours of incubation. MCD medium treatment also resulted in activation of PI3-kinase by 30 minutes and its downstream target p-Akt within 1hour of incubation. Steatosis was associated with increased expression of microsomal triglyceride transfer protein (MTTP) mRNA and increased ALT release with over expression of ALT mRNA, all of which were completely prevented by inhibition of PI3-kinase (LY294002). Blocking OPN signaling by treating with anti-OPN or anti-beta3-integrin antibody prevented the increased ALT release while only partially prevented the increased ALT mRNA expression, but had no effect on either steatosis or MTTP expression. In conclusion, incubation of cultured hepatocytes with MCD medium results in cellular steatosis and OPN dependent ALT release. PI3-kinase plays a central role in signaling the MCD medium-induced steatosis and increased OPN expression, whereas OPN appears to play a role in signaling hepatocyte ALT release but not steatosis.

Animals↗

Clinical characteristics of NonBNonC- HCC: Comparison with HBV and HCV related HCC.

OBJECTIVE: To clarify the frequency and trends of both HBsAg and HCVAb negative hepatocellular carcinoma (NonBNonC-HCC) in all HCC, to clarify the etiology of NonBNonC-HCC, and to elucidate the clinical characteristics of NonBNonC-HCC compared with those of HBsAg-positive HCC (B-HCC) and HCVAb-positive HCC (C-HCC). METHODS: A total of 2,542 patients with HCC examined at three institutions between 1991 and 2004 were categorized based on their serum viral antigen/antibody positivities, and compared between groups for the etiology, annual trend of the incidence, and clinical characteristics. RESULTS: For the etiology, C-HCC was most prevalent, followed by B-HCC, NonBNonC-HCC, and both HBsAg and HCVAb-positive HCC (BC-HCC) in order. For survival, C-HCC had the most favorable prognosis, followed by NonBNonC-HCC, and B-HCC patients had the poorest prognosis in the three groups (C-HCC, B-HCC, and NonBNonC-HCC). In tumor-node metastasis (TNM) stages I+II, however, NonBNonC-HCC patients took the most favorable clinical course. The incidence of NonBNonC-HCC in all HCC was 5-8% from 1991 to 1998, and has increased to 10-12% since 1999. Additionally, the incidence of HBcAb-positive HCC in NonBNonC-HCC declined each year. Among NonBNonC-HCC patients, the morbidity of diabetic complications was significantly higher in HBcAb-negative patients than in HBcAb-positive patients. CONCLUSION: Although the incidence of NonBNonC-HCC among all HCC has an increasing trend recently, the incidence of HBcAb-positive HCC in NonBNonC-HCC has a tendency of decreasing. This fact suggest its etiology might be changing from occult HBV related HCC to unknown etiology such as nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) related HCC. The prognosis of NonBNonC-HCC was fairly good if the HCC was found in its early stage.

Aged↗

Cognitive and affective representations of people and MCMI-II personality psychopathology.

Hibbard, Hilsenroth, Hibbard, and Nash (1995) found that affective, but not cognitive, dimensions of object representations were related to the severity of psychopathology among outpatients. In this study, the Social Cognition and Object Relations Scale (Western, Barends, Leigh, Mendel, & Silbert, 1990) developed for interview data (Relationship Episodes; Luborsky, 1990) was used to assess the object representations of 33 men and 38 women entering psychotherapy. The Millon Clinical Multiaxial Inventory-II was used to assess the personality traits of the 71 participants. The results support earlier findings that only affective dimensions of object representations are related to outpatient personality pathology.

Adult↗

Aggregation of band 3 in hereditary ovalocytic red blood cell membranes. Electron microscopy and protein rotational diffusion studies.

Microaggregation of band 3 proteins in hereditary ovalocytic membranes was investigated by rotational diffusion measurements and by electron microscopy. It was previously shown that band 3 in ovalocytic membranes has decreased rotational mobility compared with band 3 in normal cells (Tilley, L., Nash, G.B., Jones, G.L. and Sawyer, W.L. (1991) J. Membr. Biol. 121, 59-66). This result could arise from either altered interactions with cytoskeletal proteins or from band 3 microaggregation. In the present study it was found that removal of spectrin and actin from the membrane had no effect on the rotational mobility of ovalocytic band 3. Additional removal of ankyrin and band 4.1, as well as cleavage of the cytoplasmic domain of band 3 with trypsin, did enhance band 3 mobility, as is the case in the membranes from normal cells. However, the rotational mobility of ovalocytic band 3 was always considerably less than that of normal band 3 under the same conditions. Scanning electron microscopy and low power electron micrographs of freeze-fracture replicas revealed that the surfaces of ovalocytes were more irregular than those of normal erythrocytes. At higher magnification, numerous linearly arranged intramembranous particles were observed on the P-faces of freeze-fractured ovalocytes but not on normal cells. These clusters consist of straight or slightly curved lines of 10-15 particles in single rows. From these results it is deduced that the reduced rotational mobility of band 3 in ovalocytes is a consequence of the formation of microaggregates, which are very probably induced by the mutation in the membrane-bound domain of ovalocytic band 3.

Adult↗

Synthesis, chemical properties and mutagenicity of 1,6- and 3,6-dinitrobenzo[a]pyrenes.

Nitration of benzo[a]pyrene (BaP) with HNO3 (d = 1.38) produced a mixture of dinitroBaPs (1,6- and 3,6-isomers) and mononitroBaPs (1-, 3- and 6-isomers). Pure 1,6-dinitroBaP and 3,6-dinitroBaP were obtained by the reduction of the dinitroBaPs mixture with NaSH to yield the separable products 1-amino-6-nitroBaP and 3-amino-6-nitroBaP, followed by conversion to dinitroBaPs via the the diazonium salts. The half-wave potentials (E1/2) corresponding to the one-electron reduction of dinitroBaPs were measured and the relationship of these values to the mutagenicity is discussed.

Benzopyrenes↗

Application of game theoretic analysis to a problem in demography.

"Governments in certain countries have tried over the last two decades to draw most industry to the largest cities. The effect has generally been a large increase in both the population and land area of the cities, as the nearby rural areas are taken out of agricultural production and urbanized. Where the land is especially fertile, this can represent a definite loss to the country's agricultural capabilities. By studying the Nash equilibria we show that, given political pressures, there is a very real danger that this process will continue until all, or practically all of the land has been urbanized." The geographical focus is on Colombia.

Agriculture↗

Cerebrospinal fluid rhinorrhea via the fossa of Rosenmuller.

Traumatic cerebrospinal fluid fistulas in children are not rare as described by Harwood-Nash and Caldicott, North, and Simpson. Those involving the sphenoid bone apparently are rare, particularly in early childhood.

Cerebrospinal Fluid Rhinorrhea↗

District nurses' triggers for referral of patients to the Macmillan nurse.

This study aimed to identify the triggers which motivate district nurses to refer patients to the Macmillan nursing service and resulted from observation within the researcher's clinical practice, when it was noted that referral patterns from district nurses to the Macmillan nursing service were very inconsistent. A qualitative exploratory descriptive design was utilised and the analysis of the findings identified three 'key' themes, which motivate district nurses to refer: knowledge and skills, interprofessional issues and perception of Macmillan. Within each theme emerged an amalgam of triggers which were complex in nature, pertaining not only to patient need, but also to the needs of the district nursing service. However, it became apparent during the analysis that there was also a lack of knowledge regarding the role of the Macmillan nurse. This lack of knowledge relating to the Macmillan nurse role had been affirmed previously by several authors (Graves and Nash 1993, Clark et al 2002, Ahmed et al 2004) but the literature also reported that the Macmillan nurse role was open to confusion (Clark et al 2002, Corner 2003). This confusion may potentially affect referrals and prevent patients from receiving the services of the Macmillan nurse. This study has established a need for the development of referral criteria into the Macmillan nursing service and that there is also an identified need for further research, providing scope for the Macmillan nurse and district nurse to work collaboratively to improve palliative services in the community.

Attitude of Health Personnel↗

The rib hump in idiopathic scoliosis. Measurement, analysis and response to treatment.

This paper describes a simple method for the recording of rib deformity in idiopathic scoliosis. The relationships have been recorded between the measured rib hump and rib depression deformities and 1) the rotation of the vertebral bodies (as measured by the method of Nash and Moe on the standing radiograph); 2) the degree of lateral curvature (as measured by the method of Cobb on the standing radiograph); and 3) the rib-vertebra angles and their differences (as described by Mehta). No clear linear relationships were found. Many examples of irregular relationship were recorded, for example, marked spinal rotation with minimal rib hump. The response of the rib deformities to treatment by Milwaukee brace in fifty-two patients is described; the hump is little changed but the depression on the opposite side may be considerably reduced. Harrington instrumentation may have a similar effect.

Adolescent↗

Factors determining conversion from laparoscopic to open Roux-en-Y gastric bypass.

BACKGROUND: Conversion from laparoscopic to open Roux-en-Y gastric bypass (RYGBP) is expensive and time-consuming. METHODS: Data from our first 1,000 laparoscopic RYGBP was entered into a database (Minnesota Database-Bariatric, Exemplo Medical). All patients met NIH criteria for bariatric surgery. RESULTS: 41 (4.1%) of 1,000 consecutive lapRYGBPs were converted to open. Patients requiring conversion to open surgery, analyzed for predictors, revealed: 1) BMI, waist size, and weight all were significantly greater in patients converted to open bypass; 2) Gender: 9 of 109 males (8.3%) and 32 of 891 females (3.6%) were converted (Fischer's exact test, P=0.035); 3) Average age of patients converted was 44.9 compared to 41.3 in the lap group (P=0.02); 4) Conversion was required for 12 large livers (1 palpable preop, 7 had diabetes, 7 had NASH or steatosis); 5) 10 conversions for mechanical/technical reasons - 6 for inability to distend abdominal wall and/or manipulate instruments due to thickness of wall, and 2 due to loss of instruments in abdomen; 6) 9 required conversion for adhesions (2 from previous cholecystectomies with biliary leaks, and 1 from previous transverse colectomy; 7) 4 visceral injuries required conversion (2 stomach, 1 small bowel, 1 esophagus); 8) 3 hemorrhages from spleen with blood loss over 1300 ml required conversion (1 spleen removed, 6 minor not requiring open conversion); 9) 3 conversions were for anomaly/disease (1 malrotation of colon, 1 ovarian teratoma, and 1 intra-thoracic stomach). CONCLUSION: Steatohepatitis, diabetes mellitus, adhesions from various causes, previous bile leaks, large waist size, BMI, and weight are predictors for conversion to open surgery.

Adult↗

Clinical hepatic impairment after the duodenal switch.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is the most common histological finding in morbidly obese patients undergoing liver biopsy. Biliopancreatic diversion has been widely used for the treatment of morbid obesity and hepatic steatosis, and very few cases of liver impairment as a complication of this operation have been reported. METHODS: During the last 9 years, 470 morbidly obese patients were operated by means of a biliopancreatic diversion with duodenal switch ( BPD-DS), and 93 of them were performed laparoscopically. RESULTS: 10 cases of clinical hepatic impairment occurred after the BPD-DS. The clinical course of these patients ranged from transient subclinical alterations of liver function tests to severe cases of jaundice and one death from liver failure. CONCLUSION: Randomized prospective studies with standardization of BPD-DS are needed, to know the real incidence of hepatic impairment and the proper treatment for this condition. Careful follow-up and correction of possible malnutrition should be addressed to avoid hepatic impairment and/or progression of liver disease.

Adult↗

Hepatic outcomes after jejunoileal bypass: is there a publication bias?

BACKGROUND: One of the reasons why jejunoileal bypass (JIB) was abandoned were reports of liver failure. The aim of this study was to describe histological findings in the intraoperative and follow-up liver biopsies of a cohort of super-obese patients who had undergone JIB. METHODS: 50 consecutive patients underwent JIB. Samples of liver biopsies performed intraoperatively (41 patients) and in the follow-up (31 patients) were evaluated. Brunt's scale was used. RESULTS: Mean age at operation was 37.9 +/- 7.6 years, and 15 patients (30.6%) had diabetes type 2, 20 (40.8%) had dyslipidemia, 29 (59.2%) had high blood pressure, and one (0.5%) had hepatitis C. Mean BMI preoperatively was 52.8 +/- 7.5 kg/m(2). Mean follow-up time was 67.0 +/- 42.8 months. At the time of the latest liver biopsy, the mean BMI was 35.7 +/- 7.5 kg/m(2). The % excess weight loss (%EWL) was 62.4 +/- 20.0%. 8 deaths (16%) have occurred, none from liver-related complications. At liver biopsy during the JIB operation, NAFLD was confirmed in 36 patients (86.7%) and NASH in 13 (31.7%). In 25 patients with mean follow-up of 4.8 +/- 4.0 years, there was no statistically significant change in the liver histology regarding the extent of steatosis (P=0.20), steatohepatitis (P=0.74) and fibrosis (P=0.71). CONCLUSIONS: There was a significant metabolic improvement, maintenance of the %EWL, and no worsening of liver histology. There has possibly been a publication bias concerning liver outcomes, where the type of JIB and the concomitance of hepatitis C were not taken into account.

Adult↗

Evaluation of microbial inoculation and vegetation to enhance the dissipation of atrazine and metolachlor in soil.

Four greenhouse studies were conducted to evaluate the effects of native prairie grasses and two pesticide-degrading bacteria to remediate atrazine and metolachlor in soils from agricultural dealerships (Alpha site soil, northwest Iowa, USA; Bravo site soil, central Iowa, USA). The Alpha soil contained a low population of atrazine-degrading microorganisms relative to the Bravo soil. Each soil freshly treated with atrazine or metolachlor was aged for a short or long period of time, respectively. An atrazine-degrading bacterium, Agrobacterium radiobacter strain J14a; a metolachlor-degrading bacterium, Pseudomonas fluorescens strain UA5-40; and a mixture of three native prairie grasses-big bluestem (Andropogon gerardii Vitman), yellow Indian grass (Sorghastrum nutans [L.] Nash), and switchgrass (Panicum virgatum L.)-were added to the soils after the soils were aged for long periods of time. The soils aged for short periods of time were treated with J14a, the prairie grasses, or both after aging. The J14a and the grasses significantly reduced the concentration of atrazine in Alpha soil when the soil was aged for a short period of time. However, these treatments had no statistically significant effect when the soil was aged for a long period of time or on atrazine in Bravo soil. Inoculation with UA5-40 did not enhance metolachlor dissipation in either soil, but vegetation did increase metolachlor dissipation. Our results indicate that the dissipation of atrazine by J14a is affected by the presence of indigenous atrazine-mineralizing microorganisms and probably by the bioavailability of atrazine in the soil.

Acetamides↗

Traditional and emerging forms of dental practice: another view.

Rovin and Nash suggest that alternate dental delivery systems are more competitive and will eventually capture a large share of the dental market presently held by traditional practices. The potential advantages of alternate delivery systems, mainly advertising and capitation payment, have not received careful evaluation. It is therefore premature to conclude that alternate delivery systems are structurally more competitive. (Am J Public Health 1982; 72:662-664.)

Dentistry↗