PubMed Health⌕ Search

Biomedical subjects

P J Gow

Publications and source records attributed to P J Gow.

At least 19 recordsLinked to original sources
PubMed2000

Conjugation of para-nitrophenol by the isolated perfused neonatal sheep liver.

We examined the metabolism of para-nitrophenol (PNP) in the isolated perfused neonatal sheep liver (n = 8, 0.25-11 days) and compared the findings with our previous data from the perfused near-term fetal sheep liver (Ring, J. A., et al. Drug Metab Dispos 1996, 24, 1378). A three-step dosage regimen was used (72, 144, and 288 micromol of PNP). At the end of each dosage phase, PNP had fallen below detectable levels, and 101 +/- 16% of the dose was accounted for as PNP conjugates. Elimination of PNP from perfusate varied with dose. Elimination was first order with the 72-micromol dose; with the 144-micromol dose, elimination was first order in four livers but Michaelis-Menten kinetics in the remaining four. With all the 288-micromol doses, elimination was Michaelis-Menten and gave the following biochemical parameters: K(m) = 255 +/- 138 microM (fetal = 14.7 microM, P < 0.01), V(max) = 515 +/- 285 nmol/min/g liver (fetal = 34.3 nmol/min/g liver, P < 0.01), and intrinsic hepatic clearance = 2.36 +/- 1.21 mL/min/g liver (fetal = 4.74 mL/min/g liver, P > 0. 05). The mean shunt-corrected hepatic extraction ratio of PNP was 0. 82 (range, 0.40-1.0) and strongly correlated with neonatal age (r = 0.90, P < 0.05). We conclude that PNP is highly extracted by the isolated perfused neonatal sheep liver at much higher efficiency than in the near-term fetal sheep, reflecting a maturation of conjugation that progresses further in the early neonatal period.

Animals↗
PubMed2000

Neonatal hepatic propranolol elimination: studies in the isolated perfused neonatal sheep liver.

Using the isolated perfused neonatal sheep liver model, we examined the disposition of propranolol (n = 8, age 0.25-10 days) and compared our findings with our previous study from the perfused near-term fetal sheep liver (Ring JA, et al. 1995. Drug Metab Dispos 23:190-196). Within 45 min of dosage, perfusate propranolol levels had fallen by three orders of magnitude to be less than the limit of detection. Perfusate disappearance curves were monoexponential in six experiments and biexponential in two experiments. The mean shunt-corrected hepatic extraction ratio was 0.92 +/- 0.09, much greater than that seen in the fetal sheep liver (0.26 +/- 0.13, P < 0.0001) but still less than values in the adult sheep (0.97). At the conclusion of the perfusion, 4-hydroxypropranolol was the major metabolite present and 5-hydroxypropranolol and N-desisopropylpropranolol were minor metabolites. We conclude that the isolated perfused neonatal sheep liver is a useful model with which to study the maturation of neonatal hepatic drug oxidation. Our study shows that propranolol is rapidly eliminated by the neonatal liver to form several metabolites at rates far greater than in the fetal liver, but rates of elimination have not yet reached that reported in the adult sheep liver.

Adrenergic beta-Antagonists↗
PubMed2000

Liver transplantation for primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology that is progressive in most symptomatic patients, advancing toward cirrhosis and liver failure. Liver transplantation is the only therapeutic option for patients with end stage liver disease resulting from this disorder. The results of transplantation for PSC are excellent with one-year survival rates of 90-97% and five-year survival rates of 80-85%, but are closely related to pre-transplant Child-Pugh stage. Recurrence of PSC after liver transplantation is common, occurring in up to 20% of patients, but it appears to have little effect on patient survival, as survival of patients with recurrent PSC is similar to that of those without evidence of recurrence. Cholangiocarcinoma is a catastrophic complication of PSC and as yet no reliable screening method exists. The results of liver transplantation for patients with clinically apparent cholangiocarcinoma are extremely poor, however in patients in whom a microscopic tumour is detected in the explanted liver, survival is similar to those transplanted with PSC without cholangiocarcinoma. Activity of inflammatory bowel disease (IBD) appears to be more severe after transplantation, especially in units where steroid immunosuppression is withdrawn early. Colon cancer appears within the first few years after transplantation in approximately 7% of patients with IBD who are transplanted for PSC. Annual colonoscopy in this population seems prudent.

Bile Duct Neoplasms↗
PubMed2000

Simultaneous occurrence of focal nodular hyperplasia and primary sclerosing cholangitis in a young female.

We report the case of a 22-year-old female with primary sclerosing cholangitis who was found, during hepatic imaging, to have a large liver mass. Imaging techniques and histological examination confirmed the mass to be focal nodular hyperplasia. A review of the literature indicates that the simultaneous occurrence of these two hepatic pathologies is unique. The differential diagnosis of hepatic masses in primary sclerosing cholangitis is discussed. Focal nodular hyperplasia needs to be included in the differential diagnosis of hepatic lesions in primary sclerosing cholangitis.

Adult↗
PubMed2000

Diagnosis of Wilson's disease: an experience over three decades.

BACKGROUND: Wilson's disease is a rare but treatable condition that often presents diagnostic dilemmas. These dilemmas have for the most part not been resolved by the identification and cloning of the Wilson's disease gene. AIMS: To report our experience over three decades with patients with Wilson's disease in order to illustrate the diverse patterns of presentation and thereby broaden the approach to diagnosis. METHODS: Clinical and laboratory findings of 30 patients with Wilson's disease were reviewed. RESULTS: Twenty two patients presented with liver manifestations (eight with fulminant hepatic failure and 14 with chronic liver disease), three with neurological disease, and one with haemolysis; four were asymptomatic siblings of patients with Wilson's disease. Seventy per cent were diagnosed within six months of the onset of symptoms, but diagnosis was delayed for up to nine years. Age range at diagnosis was wide (7-58 years) and five patients were over 40. In patients presenting with non-fulminant disease, 18% had neither Kayser-Fleischer rings nor low caeruloplasmin concentrations. Increased liver copper concentrations were found in all but one patient who had undergone six years of penicillamine treatment. In fulminant hepatic failure (n=8) additional features helpful in the diagnosis included evidence of haemolysis, increased urinary copper (range 844-9375 microg/24 h), and a high non-caeruloplasmin copper (range 325-1743 microg/l). CONCLUSIONS: The diagnosis of Wilson's disease still depends primarily on the evaluation of clinical and laboratory evidence of abnormal copper metabolism. No one feature is reliable, but the diagnosis can usually be made provided that it is suspected. Wilson's disease should be considered in patients of any age with obscure hepatic or neurological abnormalities.

Adolescent↗
PubMed1999

Uptake and excretion of sodium taurocholate by the isolated perfused neonatal sheep liver.

We present a model for perfusion of the isolated perfused neonatal sheep liver which allows examination of drug disposition by the intact organ. We studied the disposition of sodium taurocholate (TC) in seven neonatal lambs (ages 2-11 days) and compared the results with earlier data from the perfused fetal sheep liver (Ring, J. A. et al. Biochem. Pharmacol. 1994, 48, 667-674). Measurements of perfusion pressure, oxygen consumption, lactate:pyruvate ratio, bile flow, and liver histology indicated that the preparation was both viable and stable over a 2 h period. [14C]-labeled TC was added to the reservoir by constant infusion (30 micromol/h) and the ductus venosus shunt quantitated by injection of [153Gd]-labeled microspheres. Shunt-corrected hepatic extraction ratio of TC was 0. 56 +/- 0.14 (fetal 0.23 +/- 0.16, p < 0.005) and clearance of TC was 0.92 +/- 0.35 mL/min/g liver (fetal 0.44 +/- 0.23 mL/min/g, p < 0. 01). We conclude that the isolated perfused neonatal sheep liver is a useful experimental model which will facilitate the study of the developmental physiology and pharmacology of the liver. There is considerable maturation of the biliary excretion of TC between the late fetal and early neonatal periods in the lamb.

Aging↗
PubMed1999

Paracetamol overdose in a liver transplantation centre: an 8-year experience.

BACKGROUND: Paracetamol is a readily available, widely used analgesic that can cause serious hepatic injury when taken in overdose. The aims of this study were to assess the frequency of attendance at the Austin and Repatriation Medical Centre for paracetamol overdose, the frequency of referral to the Victorian liver transplant unit after serious overdoses, the morbidity and mortality rates in all patients treated and the appropriateness of treatment. METHODS: A review of the Austin and Repatriation Medical Centre medical records and of the Victorian liver transplant unit database of all patients attending because of paracetamol overdose from 1988-1995 was undertaken. One hundred and fifty-two patients (103 females, 49 males) files were reviewed. RESULTS: One hundred and thirty-one patients presented directly from the community and 21 were referred specifically for consideration for possible transplantation. The most important predictor of liver injury was time between overdose and arrival at hospital (P< 0.01). Thirteen patients developed fulminant hepatic failure, one of whom received a liver transplant; this patient died post-transplantation and was the only death in the series. CONCLUSIONS: We found that serious liver injury following overdose was uncommon, liver transplantation was rarely needed and death was rare. Although inappropriate delay in instituting N-acetylcysteine treatment after admission to hospital or failure to treat still occurred in a number of cases, delay in presentation to hospital was the main predictor of liver damage.

Acetaminophen↗
PubMed1995

Variation in ANA titres in Auckland.

AIM: To determine the intralaboratory and interlaboratory variation in reported ANA titres in three Auckland laboratories, and to see if this has improved since a similar study was performed in 1981. METHODS: Serum samples on 26 subjects with rheumatological symptoms were sent to the three laboratories on two separate days in 1993, and the presence and titre of ANA determined. RESULTS: The number of titre dilutions by which duplicate samples differed within each laboratory has decreased since the previous study, and variation within each laboratory of greater than two dilutions was not observed. The correlation between the laboratories has improved since the previous study, particularly for Lab A vs. Lab B. CONCLUSION: The ANA test, as expressed in titres, is more reproducible in Auckland laboratories than has been the case in the past.

Antibodies, Antinuclear↗
PubMed1991

A survey of current prescribing practices of antiinflammatory and urate-lowering drugs in gouty arthritis.

OBJECTIVE: to assess the prescribing habits in late 1988 of rheumatologists (NZR) and a random sample of general practitioners (NZGP) managing gout and hyperuricaemia. DESIGN: self administered questionnaires containing two demographic questions and 24 items probing the selection and prescription of antirheumatic drugs in patients with acute gout, chronic tophaceous gout and asymptomatic hyperuricaemia were sent to every rheumatologist and a 10% random sample of general practitioners in active practice. RESULTS: replies were received from 26 of 27 (96%) rheumatologists and 163 of 207 (79%) of general practitioners Rheumatologists were more likely to use indomethacin as the preferred drug for acute gout, and colchicine either alone or as adjunctive therapy for prophylaxis in chronic gout to prevent acute attacks occurring following the introduction of urate lowering agents, although nonsteroidal antiinflammatory drugs (NSAIDs) were more commonly used for this purpose by both groups. Prior to prescribing urate lowering therapy general practitioners were more likely to attempt control of alcohol intake, and rheumatologists more likely to avoid concomitant low dose salicylates. Allopurinol was the preferred hypouricaemic drug, with rheumatologists more likely to prescribe an initial dose of 100 mg daily, and gradually increase the dose according to the serum urate (SeUa). Although a minority of respondents prescribed allopurinol for asymptomatic hyperuricaemia, general practitioners were more likely to do so at a lower level of serum urate. CONCLUSION: there was a high level of adherence to what is considered optimal contemporary practice, with a number of differences in prescribing habits probably reflecting differences in case selection between patients attending rheumatologists and general practitioners. The data indicates a continuing need for education programmes for both specialists and general practitioners.

Acute Disease↗
PubMed1990

Rapidly progressive calcific periarthritis occurring in a patient with lupus nephritis receiving chronic ambulatory peritoneal dialysis.

We present a patient who developed rapidly progressive calcific periarthritis while receiving chronic ambulatory peritoneal dialysis. She developed chronic renal failure on the basis of lupus nephritis. Hydroxyapatite crystals were isolated from periarticular deposits and identified using phase contrast light microscopy and electron microscopy. Conservative management using phosphate binding agents and nonsteroidal antiinflammatory drugs was unsuccessful and lesions were excised surgically.

Adult↗
PubMed1988

Bilateral hypoglossal nerve palsy due to vertical subluxation of the odontoid process in rheumatoid arthritis.

Two patients with rheumatoid arthritis involving the cervical spine developed a rapidly progressive dysarthria due to bilateral hypoglossal nerve palsies, in one patient as an isolated lesion, and in the other in conjunction with dysfunction of the vagus and glossopharyngeal nerves. Both patients showed upward movement of the axis, relative to the foramen magnum, which has been termed 'vertical subluxation of the odontoid' or 'cranial settling'. Mechanical injury to the nerves, secondary to this process, is the most likely mechanism.

Aged↗
PubMed1987

Bicipital swelling in adult-onset Still's disease.

A patient with typical features of adult-onset Still's disease is described in whom bicipital swellings were a feature. Arthrography of shoulders and elbow joints failed to demonstrate communication with the cyst, suggesting the swelling was due to inflammation in a bursa overlying biceps muscle.

Adult↗
PubMed1987

Juvenile rheumatoid arthritis in Auckland: a long term follow-up study with particular reference to uveitis.

Although features of juvenile rheumatoid arthritis (JRA) have been well described in British, American, and to a lesser extent Australian communities we can find no previous study of the clinical characteristics of this disease in a New Zealand population or indeed in any population containing Polynesians. In a follow-up study of 55 Auckland residents with juvenile rheumatoid arthritis, current information was obtained for 78% of the study group with a mean interval from disease onset to follow up of 9.3 years. The outcome for the group as a whole was excellent although patients with a polyarticular course, regardless of onset subtype, had a poorer outcome with respect to both ongoing disease activity and functional disability. Polynesian patients were represented in all onset subtypes in proportion to their frequency in the general community and there was no recognisable influence of race on the course of the disease. Despite careful ophthalmological examination only one case of mild uveitis was detected, a much lower incidence than in British and American reports.

Adolescent↗