Biomedical subjects

M Y Morgan

Publications and source records attributed to M Y Morgan.

At least 19 recordsLinked to original sources

PubMed1997

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↗

PubMed1997

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↗

PubMed1996

The assessment of body composition in patients with cirrhosis.

Adult↗

PubMed1996

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↗

PubMed1996

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↗

PubMed1996

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↗

PubMed1996

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1994

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↗

PubMed1994

A comparison of skinfold anthropometry and bioelectrical impedance analysis for measuring percentage body fat in patients with cirrhosis.

Percentage body fat was determined by skinfold anthropometry and bioelectrical impedance analysis in 60 patients with cirrhosis, 30 of whom had overt fluid retention, and in 60 age- and sex-matched healthy volunteers. In the control population the mean +/- 1SD percentage body fat assessed using bioelectrical impedance analysis, 22.6 +/- 6.5%, and skinfold anthropometry, 22.5 +/- 6.9%, were comparable. However, there was considerable variation in individual values such that measurements made using bioelectrical impedance analysis could be from 9% less to 8% more than the corresponding anthropometric values. In patients with cirrhosis the mean percentage body fat assessed using bioelectrical impedance analysis, 24.4 +/- 8.9%, was significantly greater than the value obtained using skinfold anthropometry, 20.3 +/- 8.4% (p < 0.01) for the whole group and for the subgroup of patients with fluid retention, 24.5 +/- 8.5% cf. 18.4 +/- 7.1% (p < 0.005); estimates of body fat in the subgroup of patients without overt fluid retention were comparable between methods, 24.4 +/- 9.4% cf. 22.1 +/- 9.2%. In the whole patient group individual measurements made using bioelectrical impedance analysis could be from 10% less to 18% more than the corresponding anthropometric values; similar degrees of variation in individual values were observed in the two patient subgroups. Bioelectrical impedance analysis should not be used interchangeably with skinfold anthropometry for assessment of percentage body fat in patients with cirrhosis, irrespective of their state of hydration.

Adipose Tissue↗

PubMed1994

Cerebral phosphorus-31 magnetic resonance spectroscopy in patients with chronic hepatic encephalopathy.

Cerebral phosphorus-31 magnetic resonance spectroscopy was undertaken in 33 patients with biopsy-proven cirrhosis: 6 had no evidence of neuropsychiatric impairment on standard clinical, psychometric and electrophysiological testing; 8 had evidence of subclinical hepatic encephalopathy; and 19 were classified as having overt hepatic encephalopathy. The reference population comprised 15 healthy volunteers. Unlocalized spectra were acquired from the entire head with a 45-degree pulse angle and repetition times of 1 and 5 sec. Spectra localized to the basal ganglia were acquired with a 45-degree pulse angle and a repetition time of 1 sec. Peak area ratios of phosphomonoesters, inorganic phosphate, phosphodiesters and phosphocreatine relative to beta-ATP were measured in the spectra acquired. We noted no consistent change in the ratios of inorganic phosphate to ATP and phosphocreatine to ATP. Mean values of the ratios of phosphomonoesters to ATP and phosphodiesters to ATP were significantly lower in the total patient population than in the reference population, and they correlated with the patients' neuropsychiatric status. Thus we found no significant reductions in the mean ratios of phosphomonoesters to ATP and phosphodiesters to ATP in patients who were neuropsychiatrically unimpaired, but significant reductions were observed in the mean ratios of phosphomonoesters to ATP and phosphodiesters to ATP in patients with both subclinical and overt hepatic encephalopathy. The most marked reductions in these metabolite ratios were observed in patients with overt encephalopathy.

Adult↗

PubMed1994

The prognosis and outcome of alcoholic liver disease.

Alcoholic liver disease evolves from fatty change through alcoholic hepatitis to alcoholic cirrhosis. Its development is associated with an excess mortality both in relation to the presence of liver disease and to other complications of alcohol abuse. In the majority of patients fatty liver is a benign lesion which will reverse completely following abstinence from alcohol. Continued drinking is associated with the eventual development of cirrhosis in approximately 20% of individuals. Survival rates of 70% are reported both at 2 years and at 10 years. Alcoholic hepatitis is a precirrhotic lesion; progression to cirrhosis is observed more commonly in women, in individuals with severe disease and in those who continue to drink. Thirty-day mortality rates of less than 20% are observed in patients with mild to moderate disease but exceed 40% in individuals with severe liver injury. Corticosteroids may improve short term survival in a small subgroup of patients with severe alcoholic hepatitis. Survival rates of 55 to 60% are reported both at 2 years and at 10 years. Survival is significantly reduced in women and in the elderly and is adversely affected by the presence of severe liver injury, evolution to cirrhosis and continued drinking. Two-thirds of patients with alcoholic cirrhosis present with decompensated disease; 15% will develop hepatocellular carcinoma. Survival rates at 5 years vary from zero to 80%; 60 to 90% of individuals die of their liver disease. Survival is adversely affected by the presence of decompensated disease, superimposed alcoholic hepatitis, continued drinking and the development of hepatocellular carcinoma. The advent of hepatic transplantation, which has a 5-year survival rate in excess of 70%, will influence these survival figures.

Carcinoma, Hepatocellular↗

PubMed1992

The effects of alcohol use on rebleeding and mortality in patients with alcoholic cirrhosis following variceal haemorrhage.

The effect of continued alcohol intake on prognosis in alcoholic cirrhotics who have already bled from varices is controversial. To investigate the effect of alcohol intake on prognosis we studied 189 consecutive alcoholic cirrhotics admitted, for the first time, to the Royal Free Hospital with variceal bleeding. Sixty-six died within 30 days of admission and 23 were excluded from the study for other reasons. Of the 100 remaining 15 remained 'probably abstinent' over long-term follow-up, 29 drank occasionally and 56 continued to misuse/abuse alcohol. The percentage survival probability at 2 years was 66% in the probable abstainers, 68% in the occasional drinkers and 63% in the alcohol abuse/misuse group. There were no significant differences in either mortality or rebleeding rates between the three groups. A rebleeding index (designed to take account of the number of rebleeds per patient and the total length of follow-up) also failed to show any significant difference between the three groups. The Cox proportional hazard model was used to study the effect of the following factors on rebleeding and mortality; age, sex, alcohol use, Pugh's score, acute treatment received for initial variceal bleed and long-term treatment received for prevention of recurrent variceal haemorrhage. Pugh's score was significantly related to risk of death during follow-up (p = 0.0122), but none of the other factors was significantly related to risk of rebleeding or mortality. Using conventional methods to determine alcohol use we were unable to demonstrate significant effects of alcohol intake on rebleeding or mortality in alcoholic cirrhotics who had bled from oesophageal varices.

Alcohol Drinking↗

PubMed1991

The treatment of chronic hepatic encephalopathy.

The neuropsychiatric abnormalities which accompany cirrhosis of the liver vary widely from subclinical impairment of psychometric performance to overt episodic or persistent changes in cerebral function. The pathogenesis of the syndrome is unknown although important rôles are ascribed to circulating gut-derived toxins of nitrogenous origin and to changes in central neurotransmission, particularly of the dopaminergic and GABA-ergic systems. Treatment is, therefore, based on mechanisms to reduce the production and absorption of gut-derived toxins such as decreasing and modifying dietary protein intake, altering the intestinal bacterial flora and bowel cleansing, and on mechanisms designed to modify central neurotransmitter balance either directly by use of dopaminergic agents or benzodiazepine antagonists or indirectly by use of amino-acid mixtures. Some treatment measures, such as use of non-absorbable disaccharides and vegetable protein diets, are known to be efficacious, and are the mainstays of management for all forms of the syndrome. Others are used in more specific circumstances, for example the antibiotic neomycin is effective during acute exacerbations of the syndrome, and the dopamine agonist bromocriptine provides benefit when symptoms are persistent and intractable. Certain treatments such as branched-chain amino acids and the benzodiazepine antagonist, flumazenil, are at present, of unproven value.

Amantadine↗

PubMed1990

Branched chain amino acids in the management of chronic liver disease. Facts and fantasies.

The liver plays a central role in protein and amino acid metabolism. It processes dietary amino acids and reprocesses amino acids released from muscle protein degradation. It utilises amino acids for protein synthesis and gluconeogenesis, regulates the supply of amino acids to peripheral tissues and converts excess amino acids to urea. In patients with liver disease the liver's ability to control both plasma and tissue amino acid fluxes may be seriously disturbed. The resultant changes in amino acid metabolism may be implicated in the genesis of the neuropsychiatric abnormalities and the deterioration in nutritional status commonly observed in patients with hepatic failure. Thus, on theoretical grounds, amelioration of these amino acid abnormalities might benefit patients with liver disease who have hepatic encephalopathy or are malnourished. However, there is, at present, no consensus as to the efficacy, practicality or cost-effectiveness of 'amino acid therapy' in patients with liver disease.

Amino Acids, Branched-Chain↗

PubMed1990

Pharmacokinetics of famotidine in normal subjects and in patients with chronic liver disease.

The pharmacokinetics of famotidine were studied in seven healthy control subjects and in 14 patients with cirrhosis, following single oral and intravenous 20-mg dose administration, and after seven daily doses of 40 mg. Following intravenous (i.v.) administration, the mean (range) total plasma clearance values were not significantly different in the patients with compensated cirrhosis (n = 7), 337 (241-576) ml/min or in the patients with decompensated cirrhosis (n = 7), 270 (120-408) ml/min compared with the control group, 370 (154-612) ml/min. The mean half-life in the compensated cirrhotics, 2.86 (1.87-4.98) h, was similar to that in the control group 2.91 (1.86-6.03) h, but it was insignificantly prolonged in the decompensated cirrhotics 3.35 (2.00-5.77) h. The mean, maximum, plasma famotidine concentrations after single oral doses were comparable between the groups but there was considerable inter-subject variability, with individual values ranging from 17 to 139 ng/ml. Peak plasma concentrations were reached within 2-3 h, although more variability was observed among patients with decompensated cirrhosis. The mean systemic availability of the drug, estimated from urinary recovery, was 0.39 (0.15-0.64) in the healthy controls, 0.35 (0.14-0.51) in the patients with compensated cirrhosis and 0.38 (0.13-0.77) in the patients with decompensated cirrhosis. No significant increases were observed in plasma trough famotidine concentrations following multiple oral dosing in any of the subjects, and the kinetic variables after the seventh dose were not significantly different from those following the single oral dose. No significant changes were observed in psychometric performance in control subjects or in patients between the pre-study day and day seven of the multiple oral dose phase.

Administration, Oral↗