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Biomedical subjects

M Y Morgan

Publications and source records attributed to M Y Morgan.

At least 19 recordsLinked to original sources

Energy expenditure in chronic alcohol abuse.

BACKGROUND: In healthy subjects, alcohol decreases lipid oxidation favouring fat deposition. However, individuals who chronically abuse alcohol are not obese. To investigate this paradox, we measured energy expenditure (EE) and fuel utilization in chronic alcohol abusers in relation to their drinking behaviour. METHODS: Resting and postprandial EE and nonprotein respiratory quotient (NPRQ) were measured using indirect calorimetry, in 36 alcohol abusers [mean (+/- SE) age 42 +/- 2 years; weight 67 +/- 2 kg; 21 with steatosis, eight with hepatitis; seven with cirrhosis] and in 36 gender-, age- and weight-matched healthy controls. Alcoholic patients were re-evaluated either after 14 days (n = 14) or on days 2, 4, 6, 8, 14 and 42 (n = 6) after abstinence. RESULTS: When alcoholics were compared to healthy controls, mean energy intake was greater, 15 +/- 1 MJ day-1 (38 +/- 2% from alcohol) cf. 9 +/- 1 MJ day-1 (P < 0.001), resting EE increased, 82 +/- 2 cf. 65 +/- 2 W (P < 0.001) and NPRQ decreased, 0.75 +/- 0.02 cf. 0.82 +/- 0.01 (P < 0.001). The postprandial increases in EE and NPRQ were of similar magnitude in both groups. Abstinence from alcohol for 14 days was accompanied by reduced energy intake, 16 +/- 1 cf. 11 +/- 1 MJ day-1 (P < 0.005) and decreased resting EE, 84 +/- 5 cf. 73 +/- 4 W (P < 0.05). The decrease in resting EE consistently occurred 4 days after abstinence from alcohol. CONCLUSIONS: Chronic alcohol abuse is associated with energy wasting and inhibition of adipose tissue accumulation. This may explain why alcoholics are not obese despite high total energy intakes.

Adipose Tissue↗

Evaluation of the efficacy and safety of rifaximin in the treatment of hepatic encephalopathy: a double-blind, randomized, dose-finding multi-centre study.

OBJECTIVE: To determine the efficacy, tolerability and safety of oral rifaximin given at three dose levels in patients with cirrhosis and mild to moderate hepatic encephalopathy (HE). DESIGN: Prospective, double-blind, randomized, parallel-group study. SETTING: Multi-centre trial in four university teaching hospitals. PARTICIPANTS: Fifty-four patients with cirrhosis and mild to moderate HE. INTERVENTION: Seven days treatment with rifaximin, 600, 1200 or 2400 mg/day in three divided doses. MAIN OUTCOME MEASURE: Change in the portal-systemic encephalopathy (PSE) index between baseline and day 7, calculated on the basis of mental state, asterixis, number connection test time, EEG mean cycle frequency and blood ammonia concentrations. RESULTS: Treatment with rifaximin was associated with an improvement in the PSE index. There was a trend towards a greater treatment effect of rifaximin with the highest dose of 2400 mg/day. Rifaximin was well tolerated; the few treatment-related adverse events showed no consistent pattern or dose relationship. CONCLUSION: Rifaximin may be useful as alternative or adjuvant therapy for grade I-III hepatic encephalopathy in patients with cirrhosis at a dose of 1200 mg/day.

Administration, Oral↗

Resting energy expenditure should be measured in patients with cirrhosis, not predicted.

Measurements of resting energy expenditure (REE) can be used to determine energy requirements. Prediction formulae can be used to estimate REE but have not been validated in cirrhotic patients. REE was measured, by indirect calorimetry, in 100 cirrhotic patients and 41 comparable healthy volunteers, and the results compared with estimates predicted using the Harris-Benedict, Schofield, Mifflin, Cunningham, and Owen formulae, and the disease-specific Müller formula. The mean (+/- 1 SD) measured REE in the healthy volunteers (1,590 +/- 306 kcal/24 h) was significantly greater than the mean Harris-Benedict, Mifflin, Cunningham, and Owen predictions but comparable with the mean Schofield prediction; individual predicted values varied widely from measured values (95% limits of agreement, -460 to +424 kcal). The mean measured REE in the cirrhotic patients was significantly greater than in the healthy volunteers (23.2 +/- 3. 8 cf 21.9 +/- 2.9 kcal/kg/24 h; P <.05). The mean measured REE in the cirrhotic patients (1,660 +/- 337 kcal/24 h) was significantly different from mean predicted values (Harris-Benedict, 1,532 +/- 252 kcal/24 h, P <.0001; Schofield, 1,575 +/- 254 kcal/24 h, P <.0005; Mifflin, 1,460 +/- 254 kcal/24 h, P <.0001; Cunningham, 1,713 +/- 252 kcal/24 h, P <.05; Owen, 1,521 +/- 281 kcal/24 h, P <.0001; Müller, 1,783 +/- 204 kcal/24 h, P <.0001); individual predicted values varied widely from measured values (95% limits of agreement, -632 to +573 kcal). Simple regression analysis showed that fat-free mass (FFM) was the strongest predictor of measured REE in the cirrhotic patients, accounting for 52% of the variation observed. However, a population-specific prediction equation, derived using stepwise regression analysis, which incorporated FFM, age, and Pugh's score, accounted for only 61% of the observed variation in measured REE. REE should, therefore, be measured in cirrhotic patients, not predicted.

Adult↗

Patterns of energy intake in patients with cirrhosis and healthy volunteers.

Fuel utilization and N economy are optimized in patients with cirrhosis by provision of several small meals throughout the day and a late-night snack of complex carbohydrate. Currently, however, only limited information is available on the patterns of energy intake in patients with chronic liver disease. The aims of the present study were to determine the number of days required to undertake such an investigation and to observe the daily distribution of energy intake in this patient population. Eight patients with cirrhosis and eight matched healthy volunteers kept weighed dietary intake records for fifteen separate days over a 6-month period. The records were analysed for energy intake per hour and the number and size of energy intake episodes per 24 h calculated. Intake was verified against resting energy expenditure. Fourteen separate observational days were required to investigate the pattern of energy intake in the cirrhotic patients while 20 d were required for healthy volunteers. Considerable inter- and intrasubject variations in the number and size of energy intake episodes were observed in both the patients and healthy volunteers. However, no significant differences were observed between the mean total number of daily energy intake episodes (6.3 (SD 1.6) v. 7.0 (SD 1.4)) or in the distribution of daily energy intake between the two groups. Most patients and volunteers tended to eat frequent small meals, often including a late-night snack, rather than two or three large meals daily. It should, therefore, be possible to establish optimum patterns of energy intake in these patients in line with recent guidelines.

Adult↗

Cerebral magnetic resonance imaging in patients with chronic liver disease.

Bilateral, symmetrical hyperintensity of the globus pallidus is observed in T1-weighted cerebral magnetic resonance images in from 52 to 100% of patients with chronic liver disease. No significant relationship exists between the presence of these cerebral changes in image signal intensity and the patients' neuropsychiatric status. However, their presence significantly relates to both the severity of the liver disease and the presence and degree of portal-systemic shunting of blood. This shortening of the T1-relaxation time is associated with pallidal deposition of manganese most likely reflecting the presence of an adaptive process designed to improve the efficacy of ammonia detoxification by astrocytes. Future studies employing magnetic resonance imaging techniques to obtain information on cerebral function or combined with magnetic resonance spectroscopy to obtain localized biochemical information might further our understanding of the pathogenesis of hepatic encephalopathy in cirrhotic patients.

Brain↗

Preservation of macronutrient preferences in cancer anorexia.

Indirect evidence suggests that cancer anorexia is associated with specific aversions to macronutrients. To investigate this, patients with cancer anorexia and hospitalized control subjects devised 3-day menus comprising foods that they wished to eat. These foods were then provided for 3 days and the intakes of each food carefully measured. As expected, patients with cancer anorexia consumed substantially less energy than hospitalized control subjects (6.0 +/- 0.9 MJ vs 9.5 +/- 0.5 MJ, P < 0.001). However, macronutrient composition was consistently maintained in the patients with cancer anorexia. These data argue against cancer anorexia representing a state of macronutrient aversion.

Anorexia↗

Taste perception in cirrhosis: its relationship to circulating micronutrients and food preferences.

Impairment of gustatory acuity may influence nutrient intake and hence nutritional status. The aim of this study was to evaluate gustatory acuity in patients with cirrhosis and its relationship to circulating concentrations of micronutrients, and food preferences. Gustatory evaluation was undertaken, using a rinsing technique, in 75 cirrhotic patients and 75 comparable healthy volunteers. Circulating concentrations of magnesium, zinc, vitamin A, and alpha- and beta-carotene were measured, and food preferences were assessed by questionnaire. The cirrhotic patients showed impaired gustatory function with significantly higher (less sensitive) median thresholds for detection of salt, sweet, and sour and for recognition of bitter, salt, sweet, and sour, together with a higher overall median gustatory score (P < .0001). Mean circulating concentrations of magnesium, zinc, vitamin A, and alpha- and beta-carotene were significantly lower in the patient population. Serum magnesium was significantly negatively associated with detection of salt (P = .02) and gustatory score (P = .02). Patients' subjective assessment of taste acuity did not correspond with objective measurements. Overall, no differences were observed in food preferences between the two groups, nor was any association found between food preferences and gustatory acuity. Patients with cirrhosis have impaired gustatory acuity that is associated with hypomagnesemia but apparently does not affect food selection.

Adult↗

The potential role of dual-energy X-ray absorptiometry in the assessment of body composition in cirrhotic patients.

Very little information is available on body composition in patients with cirrhosis. Difficulties arise in studying these patients because they tend to retain fluid and this results in changes in tissue density and in the hydration fraction of fat-free mass. As the classic body composition techniques rely on the assumption that these variables remain constant, use of these methods will result in either under- or overestimates of body composition variables. Use of multicomponent models, employing two or more measurement techniques, will obviate the need for some of the assumptions inherent in the use of single techniques, thereby increasing the accuracy of the assessments without loss of precision. Dual-energy x-ray absorptiometry can be used to measure total body bone mineral, fat, and fat-free soft tissue mass. In healthy individuals excellent agreement is observed between data obtained using this technique and data obtained from the more established reference methods. However, the degree to which the absorptiometry measurements of soft tissue are sensitive to the hydration is not known. Thus, in order to assess this method of body composition analysis in patients with chronic liver disease, a multicomponent model must be devised which incorporates the absorptiometry technique and allows cross-validation of the individual component measures.

Absorptiometry, Photon↗

The assessment of body composition in patients with cirrhosis.

Very little information is available on body composition in patients with cirrhosis. Difficulties arise in studying these patients because they tend to retain fluid and this results in changes in tissue density and in the hydration fraction of fat-free mass. As the classic body composition techniques rely on the assumption that these variables remain constant, use of these methods will result in either under- or overestimates of body composition variables. Use of multi-component models, employing two or more measurement techniques, will obviate the need for some of the assumptions inherent in the use of single techniques, thereby increasing the accuracy of the assessments, without loss of precision.

Adult↗

Weighed dietary intakes in patients with chronic liver disease.

Poor dietary intake is assumed to be a major causal factor in the malnutrition observed in patients with chronic liver disease. However, the dietary habits of this patient population are poorly documented. The aim of this study was to assess weighed dietary intakes in hospitalized patients with chronic liver disease. Twenty patients with liver disease (10 men, 10 women; mean +/- SD age, 46.2 +/- 10.9 yr, mean weight, 63.3 +/- 8.0 kg, mean body mass index, 22.1 +/- 2.8 kg/m2; 10 alcoholic, 10 nonalcoholic) and 20 general medical patients, matched for age and sex, underwent a 3-d weighed assessment of dietary intake. No significant differences were observed in food intake or dietary composition between the patients with liver disease and the hospital controls. Patients with alcoholic liver disease showed significant differences in dietary energy, protein, and carbohydrate intakes compared with the patients with nonalcoholic liver disease when data were expressed in absolute terms but not when expressed relative to body weight; dietary composition was similar in both groups. Overall, patients with chronic liver disease, especially those with alcohol-related injury, consume a diet comparable with that ingested by other hospital patients both in amount and composition.

Adult↗

Noninvasive neuroinvestigation in liver disease.

The advent of magnetic resonance imaging (MRI) and spectroscopy (MRS) and of single photon and positron emission tomography (SPET:PET) has allowed acquisition of data, not otherwise available, on cerebral metabolic function in patients with hepatic encephalopathy. Hyperintensity of the globus pallidus has been observed in cerebral T1-weighted MR images in patients with sub-clinical or overt hepatic encephalopathy, most likely due to the deposition of manganese; these trace metal deposits reflect either intoxication or the presence of an adaptive process leading to improved efficacy of ammonia detoxification by astrocytes. Cerebral 31P MRS has shown that there is no primary deficit in energy metabolism in patients with hepatic encephalopathy, but rather an impairment of phospholipid membrane metabolism; cerebral 1H MRS shows a characteristic pattern of abnormalities in these patients, namely, a significant increase in glutamine/glutamate and significant reductions in choline-containing compounds associated with phospholipid membrane metabolism and of myo-inositol which functions, in part, as an organic osmolyte. SPET and PET technology have not been adequately exploited in the study of hepatic encephalopathy to date; the few studies available have produced conflicting results, most likely because little or no account was taken of the effects of chronic liver disease, portal-systemic shunting or enhanced blood-brain barrier permeability on tracer-ligand availability. All of these techniques need to be further exploited in well-characterized populations with, wherever possible, standardization of techniques between centers; the factors likely to affect tracer-ligand availability must be adequately controlled to allow correct interpretation of the data obtained.

Animals↗

The treatment of alcoholic hepatitis.

Alcoholic hepatitis is a precirrhotic lesion; it develops in only a minority of chronic alcohol abusers even after decades of abuse. The clinical spectrum of disease varies from asymptomatic hepatomegaly to florid hepatocellular failure with gastrointestinal bleeding and hepatic encephalopathy. Corresponding variation is observed both in morbidity and mortality. The majority of individuals with mild to moderate alcoholic hepatitis improve significantly following abstinence from alcohol and the provision of a diet sufficient to meet their nutritional requirements; their long-term outcome is determined largely by their ability to maintain abstinence from alcohol. Individuals with severe alcoholic hepatitis require intensive nutritional support and vigorous management of the complications of their liver injury; their outcome is generally poor. A small, carefully selected subgroup of these very sick patients may benefit, at least in the short-term, from treatment with corticosteroids; the place of orthotopic hepatic transplantation, in this patient group, is still the subject of debate. No other treatment modalities have been shown to confer benefit consistently. A number of new therapeutic approaches have been proposed and need to be explored.

Adrenal Cortex Hormones↗

The use of serum carbohydrate-deficient transferrin in the assessment of 'high risk offenders' in Great Britain.

The potential role of serum carbohydrate-deficient transferrin (CDT) measurement in the assessment of 'High Risk Offenders (HROs)' applications for licence reinstatement in Great Britain was examined. Serum CDT determination would have provided useful confirmation of licence decisions in 70% of HROs assessed, would have resulted in a change in the licence decision in 8%, and most likely would have confounded the licence decisions made in the remaining 22%. Estimation of serum CDT could provide useful information to assist in decisions regarding licence reinstatement in selected HROs.

Alcoholism↗

In vivo hepatic 31P magnetic resonance spectroscopy in chronic alcohol abusers.

BACKGROUND/AIMS: In vivo hepatic 31P magnetic resonance spectroscopy (MRS) can provide information on hepatic energy metabolism, phospholipid substrates, and hepatocyte lipid bilayers. The aim of this study was to ascertain the effects of alcohol ingestion on hepatic 31P spectral variables. METHODS: Twenty-six chronic alcohol abusers underwent hepatic 31P MRS 6-12 hours after their last alcoholic drink; studies were repeated in 17 individuals following abstinence from alcohol. The reference population comprised 16 healthy volunteers. Ratios of phosphomonoesters (PME), inorganic phosphate, and phosphodiesters (PDE) relative to beta-adenosine triphosphate (ATP) were measured. RESULTS: In patients with minimal liver injury, recent drinking was associated with a significant elevation in the mean PDE/ATP ratio (P < 0.0001) and an increase in mean PME/ATP, which was not significant; abstinence was associated with reductions in both metabolite ratios. In patients with alcoholic cirrhosis, recent drinking was associated with an elevation in mean PME/ATP (P < 0.05) and an increase in mean PDE/ATP, which was not significant; abstinence was associated with no significant change in PME/ATP but with a reduction in PDE/ATP. CONCLUSIONS: In the absence of significant liver injury, chronic alcohol abuse is associated with the elevation of PME/ATP, possibly reflecting changes in hepatic redox potential, and of PDE/ATP, most likely reflecting the induction of hepatocyte endoplasmic reticulum. In the presence of cirrhosis, these changes are attenuated and modified.

Adenosine Triphosphate↗

Effect of functional grade and etiology on in vivo hepatic phosphorus-31 magnetic resonance spectroscopy in cirrhosis: biochemical basis of spectral appearances.

Hepatic phosphorus-31 magnetic resonance spectroscopy (31P MRS) was undertaken in 85 patients with histologically proven cirrhosis of varying etiologies and functional severity. Reference data were acquired from 16 healthy volunteers who had no history or evidence of liver disease or alcohol abuse. In vivo hepatic 31P MR spectra were acquired with pulse angle 45 degrees and repetition times (TR) of 5 and 0.5 seconds. Peak area ratios of phosphomonoesters (PME), inorganic phosphate (Pi), and phosphodiesters (PDE) relative to beta ATP, and of PME relative to PDE were calculated from spectra acquired at TR 5 seconds. Estimates of saturation effects for individual resonances were obtained by dividing the peak height at TR 5 seconds by that at TR 0.5 seconds to yield a T1-related signal height ratio (SHR). When compared with reference values, the patients with liver disease showed a significantly higher PME/ATP (P < .0001), PME/PDE (P < .0001), PME SHR (P < .001), and Pi SHR (P < .02), and a lower PDE/ATP (P < .001) and PDE SHR (P < .001). The magnitude of these changes increased significantly and progressively with increasing functional impairment. In patients with compensated cirrhosis spectral appearances varied with etiology; thus, patients with postviral cirrhosis showed a significantly higher Pi/ATP; those with alcoholic cirrhosis, a significantly lower PDE/ATP; and those with cirrhosis secondary to primary sclerosing cholangitis, a significantly lower Pi/ATP than the healthy volunteers or other etiological groups. However, spectral appearances did not vary with etiology in patients with decompensated disease. In vitro 31P MRS of perchloric extracts of samples of liver tissue obtained from 10 patients with cirrhosis at transplant hepatectomy showed increases in levels of the soluble PME metabolites, phosphorylcholine and phosphorylethanolamine, and reductions in the levels of the soluble PDE metabolites, glycerophosphorylcholine and glycerophosphorylethanolamine. These changes suggest regenerative activity in cirrhotic livers. The increases in soluble phosphomonoesters in the aqueous extracts accounted for the increased PME/ATP ratio seen in the in vivo spectra, and might account for the increase in PME SHR. The reduction in soluble phosphodiesters in the aqueous extracts did not entirely account for the reduction PDE/ATP ratio seen in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

The management of alcohol withdrawal using chlormethiazole.

Chlormethiazole is an extremely useful and flexible drug for use in the management of acute alcohol withdrawal. It is not a treatment for alcohol abuse and should not be used in this patient group, other than in the withdrawal period, and then for less than 10 days. It is extremely safe when used correctly by practitioners familiar with its properties. Problems can arise, however, if used by practitioners unaware of its limitations and the precautions needed for safe prescribing.

Acute Disease↗

Regional variations in cerebral proton spectroscopy in patients with chronic hepatic encephalopathy.

Regional variations in proton magnetic resonance spectroscopy (MRS) were assessed in 26 patients and 14 healthy volunteers using a two dimensional chemical shift imaging technique. Patients were classified as being neuropsychiatrically unimpaired, or as having subclinical or overt chronic hepatic encephalopathy (CHE). Peak area ratios of choline (Cho), glutamine and glutamate (Glx) and N-acetylaspartate (NAA) relative to creatine (Cr) were measured. Significant reductions in mean Cho/Cr and elevations in mean Glx/Cr were observed in the patient population, which correlated with the severity of CHE. There were significant regional variations in these metabolite ratios with the mean Cho/Cr lowest in the occipital cortex and the mean Glx/Cr highest in the basal ganglia. NAA/Cr remained relatively constant in all areas of the brain analysed. The regional variation in the metabolite ratios suggests that spectral information from more than one voxel may be useful in the assessment of patients with CHE.

Adult↗