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Biomedical subjects

O F James

Publications and source records attributed to O F James.

At least 127 records · Page 7Linked to original sources
PubMed1990

Reactivity of primary biliary cirrhosis sera with Escherichia coli dihydrolipoamide acetyltransferase (E2p): characterization of the main immunogenic region.

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in the serum. The major antigens recognized by the antibodies are the E2 components of the 2-oxo acid dehydrogenase complexes, all of which possess covalently attached lipoic acid cofactors. A bacterial etiology has been proposed for the disease, and patients' antibodies are known to recognize the E2 subunits (E2p) of both mammalian and bacterial pyruvate dehydrogenase complexes. Immunoblotting and ELISA inhibition techniques using extracts of Escherichia coli deletion strains, genetically restructured E2 polypeptides, and isolated lipoyl domains demonstrate that (i) the E2o subunit of the E. coli 2-oxoglutarate dehydrogenase complex is recognized by patients' antibodies; (ii) the main immunogenic region of E2p lies within the lipoly domains; (iii) the presence of a lipoly residue within the domain is crucial for effective recognition by the antibodies; and (iv) octanoylated E2p, octanoylated E2o, and octanoylated lipoyl domain, produced by a mutant deficient in lipoate biosynthesis, are recognized by patients' antibodies but not as effectively as their lipoylated counterparts. These findings indicate that antibodies in PBC patients' sera bind to a unique peptide-cofactor conformation within the lipoyl domains of the E2 polypeptides and that this epitope is partially mimicked by substituting the lipoyl cofactor with an octanoyl group.

Acetyltransferases↗
PubMed1990

Motor recovery following acute stroke.

There is little information available from which normal patterns of recovery from acute stroke can be ascertained. Most attention has been directed towards functional recovery in stroke patients but the neurological basis on which this occurs needs to be documented in a large cohort of patients. One hundred and fifty-seven patients admitted to hospital with a clinical diagnosis of acute stroke were examined daily for up to 28 days to determine the patterns of recovery of limb tone, power and reflexes. Changes in these variables during the first 28 days after stroke are described.

Adult↗
PubMed1990

Historical risk factors for stroke: a case control study.

The aim of this study was to determine the risk factors for admission to hospital with stroke by means of a case-control study recruiting age- and sex-matched controls from the local community. Four hundred pairs of patients and controls were recruited. Of historical factors, preceding cerebrovascular disease contributed the greatest odds of stroke (odds ratio 9.8). Taking prescribed medicines (odds ratio 2.6), regular snoring (odds ratio 3.2), smoking (odds ratio 1.7) and some factors in the family history were also significant risk factors.

Adult↗
PubMed1990

A randomized double-blind controlled trial of naftidrofuryl in acute stroke.

There is evidence to support the use of naftidrofuryl in acute stroke with claims of increased recovery, reduced fatality and reduced bed occupancy in patients treated with either oral or intravenous preparations. One hundred patients presenting with acute hemisphere stroke (less than 72 hours) were randomized to receive either a new oral formulation of naftidrofuryl or placebo on a double-blind basis. Treatment was given for a total of 12 weeks and patients followed for 26 weeks with serial neurological and functional assessments by a single observer. Cumulative fatality and hospital-bed occupancy were determined at each assessment interval. No significant difference was demonstrated in cumulative fatality, hospital-bed occupancy or recovery of motor function in patients treated with either naftidrofuryl or placebo. There is no evidence from this study to support the use of oral naftidrofuryl in acute stroke.

Acute Disease↗
PubMed1990

Potassium supplementation in the treatment of idiopathic postural hypotension.

We studied the effects of potassium supplementation (60 mmol/day) and matching placebo on the postural blood-pressure fall in ten elderly patients with symptomatic idiopathic postural hypotension in a double-blind, randomized cross-over trial. There was a significant decrease in the orthostatic fall in systolic blood pressure (SBP 33 +/- 5 mmHg to 16 +/- 9 mmHg, p less than 0.01) and in supine SBP (162 +/- 7 to 150 +/- 7 mmHg, p less than 0.01) between placebo and potassium phases. Supine diastolic and erect blood pressures were unchanged, though pulse rate showed a greater orthostatic increase (7 +/- 3 beats/min to 14 +/- 2 beats/min, p less than 0.05) following potassium therapy. No significant changes were seen in intracellular electrolytes, plasma renin activity, aldosterone levels or body weight. Seven patients reported symptomatic improvement with potassium, but none during the placebo phase. Potassium therapy was well tolerated and may be a successful and safe method of treating idiopathic postural hypotension.

Aged↗
PubMed1990

The association of age and frailty with paracetamol conjugation in man.

The association of age, physical frailty and liver size upon hepatic conjugation reactions was studied using paracetamol as a model drug. Nineteen fit subjects (mean age 26 years), 20 fit subjects (mean age 73 years), and eight frail, hospitalized subjects (mean age 82 years) were recruited. Paracetamol clearance expressed in terms of body weight was significantly lower in the fit elderly than in the fit young subjects, and was lowest in the frail elderly subjects (p less than 0.01). There was no difference in paracetamol clearance expressed per unit volume of liver between the fit young and fit elderly subjects but it was significantly reduced in the frail subjects. Although the partial metabolic clearance to paracetamol sulphate was preserved per unit volume of liver with ageing and frailty, the partial metabolic clearance to paracetamol glucuronide per unit volume of liver was markedly reduced in the frail elderly (p less than 0.01) when compared with the fit subjects. These results show that age-associated changes in paracetamol clearance are attributable to both changes in liver volume and in general health. The findings underline the important influences of the elderly person's physical state upon drug clearance.

Acetaminophen↗
PubMed1990

Hepatic drug metabolism and ageing.

The hepatic clearance of many drugs is reduced in the elderly. Contrary to previously held views we suggest the following: 1. Specific activities of several cytochrome P-450 Phase I enzymes are not reduced with age per se in primate and man, nor is enzyme affinity for substrate changed. 2. An important contribution to the reduced hepatic elimination is made by reduction in liver size and blood flow with advancing age. 3. Major changes in liver drug metabolism may occur in frail old people. Future studies of hepatic drug metabolism and ageing must closely define the subject groups under study.

Aged↗
PubMed1990

Hepatic drug clearance: the effect of age using indocyanine green as a model compound.

The hepatic extraction ratio and clearance of indocyanine green (ICG) were determined and used to derive apparent liver blood flow in nine subjects between the ages of 22 and 83 years. There was no correlation between the hepatic extraction ratio of ICG and age (rs = -0.435, NS). There was a significant negative correlation between both ICG clearance and age (rs = -0.710, P less than 0.05) and apparent liver blood flow and age (rs = -0.750, P less than 0.05). These results validate the comparison of liver blood flow values derived from ICG clearance in humans over a wide age range and confirm that liver blood flow does fall with age.

Adult↗
PubMed1990

Alpha 1-antitrypsin granules in the liver--always important?

We have studied the clinical histories and liver biopsy findings in 1951 consecutive adult patients with suspected chronic liver disease, and in four known PiZ-homozygous alpha 1-antitrypsin-deficient patients with emphysema (candidates for lung transplant) and no known liver disease, in order to assess the importance of periportal alpha 1-antitrypsin granules in the liver and their possible causal role in liver disease, and to assess the value of possible screening tests. Periportal granules were found in 30 (1.5 per cent) of the 1951 liver biopsies and in all four known PiZ-homozygous subjects. They were the sole putative aetiological agent in eight of 85 patients (9.4 per cent) with otherwise cryptogenic cirrhosis and present in 2.5 per cent of patients with cirrhosis of known aetiology (alcohol, autoimmune etc.). All but one were Z phenotype (seven homozygotes, 22 heterozygotes). alpha 1-Antitrypsin granules were seen in 12 patients (including three of four lung transplant candidates) with no histological chronic liver disease. Determination of serum alpha 1-antitrypsin levels was quite unhelpful in identifying these patients. This study does not support the concept that periportal alpha 1-antitrypsin granules are necessarily pathogenic, but in some cases they may be causally related to otherwise cryptogenic liver disease. The presence of granules gave no important diagnostic, therapeutic or prognostic information.

Adult↗
PubMed1990

The epidemiology of primary biliary cirrhosis in north-east England: an increasingly common disease?

The reported incidence and prevalence of primary biliary cirrhosis has risen in the past 10 years in Northern Europe. In order to determine whether this is a genuine increase in the disease or an apparent increase due to increased awareness of physicians and more ready diagnosis, we have carried out a comprehensive epidemiological study of primary biliary cirrhosis. All possible cases from 1965-1987 were examined using the best case finding methods available. In a relatively stable population of about 1.92 million we identified 471 patients with 'possible' primary biliary cirrhosis and 347 with a definite, histologically confirmed, diagnosis. Prevalence rose from 18/1,000,000 in 1976 to 128.5/1,000,000 in 1987 (276/1,000,000 in women greater than 18 years). Increased awareness and availability of interested physicians seemed to be important contributing factors to the rise in prevalence. No important geographical clustering of cases was noted.

Adult↗
PubMed1990

Vasculitis in primary biliary cirrhosis--response to prednisolone.

Immunosuppressive doses of prednisolone were used to treat severe vasculitis in two patients with early primary biliary cirrhosis. Liver-specific blood tests of both patients returned to normal. The response of both the vasculitis and liver disease is discussed and the literature is reviewed.

Aged↗
PubMed1989

Characterisation of the reactivity of autoantibodies in primary biliary cirrhosis.

Autoantibodies in the sera of patients with primary biliary cirrhosis, shown previously to recognise the E2 polypeptide of the mammalian pyruvate dehydrogenase complex (PDC), have been demonstrated to react with the E2 component of PDC from bacteria (E. coli) and yeast (S. cerevisiae). Limited tryptic digestion, which cleaves E2 into well-characterised domains, followed by Western blotting indicates that the main immunodominant region of PDC E2 lies within the lipoic acid-containing domains of the polypeptide.

Acetylation↗
PubMed1989

The effect of age upon liver volume and apparent liver blood flow in healthy man.

The aim of this study was to determine the effect of aging upon liver volume and apparent liver blood flow in healthy man. Sixty-five subjects between 24 and 91 years of age were recruited. Liver volume was quantitated by a gray scale B ultrasound scan method. Apparent liver blood flow was determined from the plasma clearance of indocyanine green, based on an assumption of no change in hepatic extraction of the dye with age. A significant negative correlation was observed between age and both liver volume and apparent liver blood flow (p less than 0.001), whether expressed in absolute terms or per unit body weight. Similarly, a significant negative correlation was observed between apparent liver blood flow per unit volume of liver (liver perfusion) and age (p less than 0.005). The reduction in liver volume, apparent liver blood flow and perfusion may at least partly account for the decline in the clearance of many drugs undergoing liver metabolism which has been noted to occur with aging in man.

Adult↗