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Biomedical subjects

O F James

Publications and source records attributed to O F James.

At least 145 records · Page 8Linked to original sources
PubMed1989

Frequency of IgG and IgM autoantibodies to four specific M2 mitochondrial autoantigens in primary biliary cirrhosis.

We have previously identified four of the M2 antigens in primary biliary cirrhosis as the E2 components (dihydrolipoamide acyltransferases) of pyruvate dehydrogenase complex, branched-chain 2-oxo acid dehydrogenase complex and 2-oxoglutarate dehydrogenase complex and the protein X component of pyruvate dehydrogenase complex (approximate molecular masses: 74, 50, 50 and 52 kD, respectively). In the present study, we have examined by immunoblotting the frequency of IgG and IgM autoantibodies to these four proteins in 129 patients with primary biliary cirrhosis (36 histological Stage I, 42 Stage II/III, 51 Stage IV) and 77 controls (49 non-primary biliary cirrhosis chronic liver disease, 16 primary Sjögren's syndrome, 12 healthy normal women). One hundred twenty-seven of 129 (98%) primary biliary cirrhosis patients had antibodies against at least one of the four M2 polypeptides, compared to 2/77 controls (both had autoimmune chronic active hepatitis and were antimitochondrial antibody positive by indirect immunofluorescence). One hundred twenty-one of 129 (94%) primary biliary cirrhosis sera reacted with the E2 component and protein X of pyruvate dehydrogenase complex, 69/129 (53%) primary biliary cirrhosis sera reacted with E2 of branched-chain 2-oxo acid dehydrogenase complex and 113/129 (88%) reacted with E2 of 2-oxoglutarate dehydrogenase complex. Primary biliary cirrhosis patients with histological Stage I disease had a lower incidence of autoantibodies to each M2 protein, compared to more advanced disease (IgG, p less than 0.05) but only 2/36 Stage I patients had no anti-M2 antibodies. There was no correlation between the presence of IgG or IgM antibodies to the M2 polypeptides and established prognostic markers in primary biliary cirrhosis (serum bilirubin and albumin levels).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1989

A pilot, double-blind, controlled 1-year trial of prednisolone treatment in primary biliary cirrhosis: hepatic improvement but greater bone loss.

A randomized, double-blind, 1-year pilot study of prednisolone treatment for primary biliary cirrhosis was undertaken. Nineteen patients received 30 mg prednisolone per day initially, with a maintenance dose of 10 mg per day. Seventeen patients received placebo. The groups were matched for age, menopausal status, hepatic histological stage and bilirubin. Treatment was well tolerated without dropouts. Two patients receiving prednisolone developed diabetes, one a duodenal ulcer and one depression. One patient receiving placebo died for liver failure after 3 months. Cholestatic symptoms (itch and fatigue) improved on prednisolone. There was significant (prednisolone vs. placebo) improvement in transaminase (p = 0.0214), alkaline phosphatase (p = 0.0032), procollagen III peptide (p = 0.0103), immunoglobulin G (p = 0.0012) and liver histology (p = 0.016); these changes were greatest among noncirrhotic patients. No patient developed skeletal symptoms. Fifty-seven per cent had abnormal triolein breath tests prior to treatment, and 65% had abnormally low calcium absorption tests. Calcium absorption increased significantly in the treated group vs. placebo at 2 weeks (p less than 0.02), but not at 1 year. Femoral photon absorptiometry fell in the prednisolone group after 1 year (-3.5% vs. placebo +0.5%, p less than 0.05), as did trabecular bone volume (-6% vs. -2.8%, p less than 0.005) and resorption surface (-11% vs. +2%, p less than 0.02) on serial bone biopsy. Prednisolone seems to exert a favorable hepatic effect in primary biliary cirrhosis but at the expense of increased bone loss to approximately twice the expected rate. Prednisolone treatment merits further assessment in primary biliary cirrhosis over a longer period, with attention to selection of patients most likely to benefit and continuing observation of bone mass to better establish the "cost/benefit" ratio.

Adult↗
PubMed1989

No specific association between primary biliary cirrhosis and bacteriuria?

160 consecutive patients with primary biliary cirrhosis (PBC) (M:F, 13:147; total samples 286), 140 patients with other chronic liver disease (CLD) (M:F, 75:65; total samples 200), and 28 patients with primary Sjögren's syndrome (all F; total samples 37), were examined for bacteriuria over 6 months by midstream urine (MSU) examination. The overall prevalence of bacteriuria in PBC was 11.2% (7.5% on first MSU), in CLD 12.1% (10.7% on first MSU), 18.4% in the 65 female CLD patients, 10.7% in Sjögren's syndrome patients (3.5% on first MSU). The prevalence of bacteriuria was related to the age of the patient (P less than 0.02) in PBC and to the presence or absence of cirrhosis in both PBC and CLD (P less than 0.02). There was no difference in the prevalence of bacteriuria between PBC and CLD patients taken as a whole or among females alone, cirrhotic or non-cirrhotic groups. In a second prospective study of the cumulative incidence of bacteriuria in PBC versus CLD and Sjögren's no significant differences between groups was observed but among 29 PBC patients the cumulative proportion of positive tests for bacteriuria after 5 months (monthly testing) was 34%. We conclude that there is no specific association between PBC and bacteriuria compared with the prevalence of bacteriuria in other CLD.

Adult↗
PubMed1989

Is measurement of type III procollagen amino propeptide useful in primary biliary cirrhosis?

We have examined the value of serum type III procollagen amino propeptide (PIIINP) measurement both in evaluation of disease activity and in estimation of prognosis in primary biliary cirrhosis (PBC). 55 paired sera from 32 PBC patients not receiving treatment known to affect PIIINP levels not with non-hepatic inflammatory conditions were used to estimate serum PIIINP by radioimmunoassay. Significant correlations were found between serum PIIINP and serum albumin (P less than 0.001), bilirubin (P less than 0.002) and aspartate transaminase (P = 0.01). The mean serum PIIINP level rose with advancing histological stage (P less than 0.001). In 18 patients in whom more than 1 serum was assayed (mean follow-up 42 months) PIIINP often fell, particularly in patients with established cirrhosis and advanced disease. The independent prognostic value of PIIINP was examined using Cox's proportional hazards model with three other prognostic co-variables (bilirubin, albumin, patient age). Stepwise regression analysis selected albumin (P less than 0.001) and bilirubin (P = 0.002) as the most important prognostic factors. PIIINP did not give independent prognostic information. We conclude that PIIINP is another marker of disease activity in PBC which confers no benefit over existing conventional measurements in routine management of this disease.

Adult↗
PubMed1989

Effects of meal composition on the postprandial blood pressure, catecholamine and insulin changes in elderly subjects.

1. The effects of four meals of similar energy, but different nutritional, composition on postprandial blood pressure, heart rate, autonomic function, catecholamines, insulin and packed cell volume levels were studied in seven fit elderly subjects. 2. The high carbohydrate and high protein meals led to a significant overall fall in supine systolic and diastolic blood pressure compared either with no change or a rise after the normal (i.e. mixed) and high fat meals. Similar between-meal differences were seen with erect diastolic but not erect systolic blood pressure. No significant postural blood pressure fall occurred after any of the meals. Supine heart rate was unaffected by meal type or by time, and although erect heart rate showed a small increase during the study there was no between-meal difference. 3. Parasympathetic function was unaffected by meal type. Plasma noradrenaline rose after the high carbohydrate and mixed meals only, remaining elevated for 120 min after meal consumption. This increase was not related to the changes in blood pressure or plasma insulin levels. 4. Plasma insulin and glucose rose after the high carbohydrate and mixed meals, but were unchanged after the high protein and high fat meals. Packed cell volume showed a small decrease towards the end of the study, although there was no between-meal variation. 5. The differences in the cardiovascular changes after the different meals could not be ascribed to alterations in autonomic function, insulin release or fall in plasma volume. We propose that the postprandial changes in blood pressure are due to the nutrient composition of the meal rather than the actual energy load.

Aged↗
PubMed1989

The E1 alpha and beta subunits of the pyruvate dehydrogenase complex are M2'd' and M2'e' autoantigens in primary biliary cirrhosis.

1. Sera from 76 patients with primary biliary cirrhosis (PBC) and 66 control subjects (53 with chronic liver disease and 13 healthy normal women) were immuno-blotted against purified E1 component of bovine pyruvate dehydrogenase complex (PDC) and bacterial PDC. 2. Thirty-one out of seventy-six (41%) sera from PBC patients showed a positive response to bovine E1 alpha, and five of these 31 (7% of total) reacted with bovine E1 beta. None of the control sera reacted with bovine E1 alpha or beta. 3. None of the PBC sera that recognized bovine E1 subunits reacted with bacterial PDC E1. 4. In the PBC patients there was no correlation between presence of antibodies to E1 alpha and beta subunits and histological stage of the disease. 5. Our data demonstrate that the E1 alpha and beta components of mammalian PDC are the M2'd' and 'e' mitochondrial autoantigens, respectively.

Animals↗
PubMed1989

The relation of age to the acute effects of ethanol on acetanilide disposition.

The activity of the major drug-metabolizing enzymes, the mono-oxygenases, can be inhibited by an acute dose of ethanol. We set out to determine whether age has any relation to the degree of inhibition produced by ethanol, using acetanilide as a model substrate. Eight healthy young subjects (mean age 26 years) and eight healthy elderly subjects (mean age 72 years) were studied on two occasions, once receiving acetanilide alone and once acetanilide with 75 ml vodka (30 g ethanol). The clearance of acetanilide was significantly lower (p less than 0.05) in the elderly subjects at 27 +/- 3 l/h compared to 38 +/- 2 l/h in young subjects. No age-related differences in peak blood ethanol concentrations or ethanol elimination rates were noted. After ethanol, acetanilide clearance fell 18% to 31 +/- 3 l/h in young subjects (p = 0.05) and by 15% to 23 +/- 2 l/h in elderly subjects (p = 0.08). This suggests that the elderly do not suffer greater impairment of drug oxidation after acute ethanol ingestion than do the young.

Acetanilides↗
PubMed1989

The effects of old age and immobility on protein turnover in human subjects with some observations on the possible role of hormones.

Protein turnover (PT), synthesis (PS) and breakdown (PB) were studied using L-(1-14C)-leucine and primed continuous infusion of 14C-HCO3 over a 6-h study period in three groups: group 1 (n = 9) fit old; group 2 (n = 6) fit young; and group 3 (n = 13) immobile old. Plasma cortisol, growth hormone (GH) and insulin levels were measured during the studies. There were significant reductions in PT (p less than 0.02), PB (p less than 0.02) and PS (p less than 0.01) in fit old compared to fit young subjects. Comparison between fit old versus immobile old subjects revealed that the immobile group (Group 3) had higher PT (p less than 0.05), PB (p less than 0.05) and PS (p less than 0.01) rates. The rates of protein turnover and components in group 3 were similar to those in group 2. There was greater variance in protein balance in the immobile subjects. Significantly higher plasma cortisols were found in the immobile than in the healthy old subjects. The immobile group had higher GH levels in response to feeding but there was no difference in insulin response to feeding. These higher plasma cortisol and GH levels may be partly responsible for the changes in PT found in immobile elderly patients.

Aged↗
PubMed1989

Protein turnover in malnourished elderly subjects: the effects of refeeding.

A primed constant-rate infusion of L-(l-14C)-leucine was used to assess protein flux, synthesis, and breakdown in a group of malnourished elderly subjects (n = 9) and a group of age-matched healthy elderly control subjects (n = 9). No significant differences between the two groups were observed in measures of protein metabolism. Four out of six malnourished subjects, restudied after a period of dietary replenishment, showed non-significant increases in protein synthesis and breakdown. Plasma insulin concentrations were significantly suppressed (p less than 0.05) and plasma growth hormone and cortisol concentrations significantly elevated (p less than 0.05) in the malnourished subjects before and after refeeding compared with the healthy elderly controls.

Age Factors↗
PubMed1989

The effect of age and frailty upon acetanilide clearance in man.

Six healthy young subjects (aged 23-32 years), six healthy elderly subjects (over 60 years) and six hospitalized long-stay geriatric subjects over 60 years received single oral doses of acetanilide. Acetanilide clearance was similar in the fit and frail elderly subjects at 26.4 +/- 2.5 and 26.3 +/- 3.6 l/h and significantly lower (p less than 0.05) than in the young subjects at 39.0 +/- 1.9 l/h. Liver volumes, measured by ultrasound, were significantly less in the elderly than in the young subjects, whether expressed in absolute terms or per unit body weight (p less than 0.05). When acetanilide clearance was expressed per unit volume of liver, no change occurred with age or frailty. These results suggest that a reduced liver size may be an important contributor to the reduced elimination of capacity limited drugs in elderly man.

Acetanilides↗
PubMed1989

Recovery of visual fields in acute stroke: homonymous hemianopia associated with adverse prognosis.

In a prospective study of 157 patients (median age 73 years) admitted to hospital within 72 hours of acute cerebral hemisphere stroke, there was clinical evidence of homonymous hemianopia (HH) as assessed by confrontation in 99 (63%). Patients were followed with serial neurological examinations for 28 days. Complete recovery of visual fields occurred in 14 (17%) of the 81 patients with a complete HH on admission and in 13 (72%) of the 18 patients with a partial HH on admission. Cumulative fatality at 28 days was greater in patients with a complete HH (49%), compared with patients with a partial HH (11%). These two patterns of recovery and outcome probably reflect the differing extent of cerebral damage in the two groups.

Acute Disease↗
PubMed1989

Increasing age, diabetes mellitus and recovery from stroke.

In a prospective study of 200 patients with acute stroke, blood glucose and glycated haemoglobin (HbA1) were measured within 72 hours of onset. Unrecognized hyperglycaemia as defined by a raised stable HbA1 more than two s.d. above the mean reference value and no previous history of diabetes was present in 27%. No correlation existed between patient age and admission blood glucose or HbA1 levels (r = 0.1). Cumulative mortality and recovery of limb function was assessed in the first 136 patients with carotid distribution events. Admission blood glucose greater than or equal to 8 mmol/l was shown to be associated with a significantly greater mortality at 4 and 12 weeks (P less than 0.05). Multivariate analysis with age, glucose, HbA1 as independent variables demonstrated that age was the only significant predictor for death at 4 weeks (P less than 0.05) but at 12 weeks both age and blood glucose were significant (P less than 0.05). In patients less than 65 years blood glucose was a significant predictor for death (P less than 0.05) but in patients less than or equal to 65 years HbA1 and not glucose was significantly (P less than 0.05). Patients greater than or equal to 65 years with HbA1 greater than or equal to 7.5% were significantly more likely to have a raised admission blood glucose. Hyperglycaemia on admission was not shown to influence recovery of limb function. Increasing age is of greatest importance in predicting mortality although blood glucose is of prognostic value especially in the young stroke patient.

Acute Disease↗
PubMed1989

Progression of autoimmune damage in primary biliary cirrhosis: an immunohistochemical study.

Aberrant MHC Class II antigen expression and the nature of the infiltrating lymphoid cells were studied by immunohistochemical techniques in liver biopsies from 37 patients with Primary biliary cirrhosis (PBC) (11 histological stage I, 13 stage II-III, 13 stage IV) and 15 patients with chronic non autoimmune liver disease. Bile duct epithelial cells expressed HLA-DR, DP and DQ antigens in biopsies from patients with early (Stage I) PBC and less frequently in the late cirrhotic phases of the disease (Stage IV); these observations support the hypothesis that induction of Class II antigens on epithelial cells may be involved in initiating autoimmune responses towards bile duct components. The presence of cytotoxic/suppressor T cells around the bile ducts in Stage I suggests a role for cell mediated destruction of the ducts at this early stage. The nature of the chronic inflammatory cell infiltrate in the portal tracts, periportal areas and lobular parenchyma does not establish the mechanism(s) involved in disease progression. However, the lack of Class II antigen expression on hepatocytes is compatible with the hypothesis that hepatocellular damage is non-specific and may be secondary to the initial bile duct injury.

Adult↗
PubMed1988

The acute and subchronic effects of ketoconazole on hepatic microsomal monooxygenases in the rat.

Female adult Wistar rats were treated with single or repeated doses of ketoconazole ranging from 10 mg/kg to 100 mg/kg. Single dose treatment produced inhibition of hepatic microsomal ethoxyresorufin O-deethylation (EROD) and aldrin epoxidation (AE) 2 hr after oral dosing. Twenty-four hours after a single dose, inhibition was still demonstrable after the low dose of 10 mg/kg, but at higher doses increased microsomal activity was apparent. After 7 days repeated dosing liver weight and microsomal protein content were increased in a dose-dependent fashion. EROD and AE were induced at all doses after repeated treatment when the increase in liver size was considered. These effects were seen at doses within the antimycotic therapeutic range and add support to the suggestion that reported drug interactions with ketoconazole in man are due to the effects of this drug on hepatic microsomal activity.

Animals↗