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Biomedical subjects

A F Macklon

Publications and source records attributed to A F Macklon.

7 recordsLinked to original sources

Primary biliary cirrhosis: geographical clustering and symptomatic onset seasonality.

Patients with primary biliary cirrhosis (primary non-suppurative destructive cholangitis) in the north east region of England were studied over a five year period and, to evaluate epidemicity, compared with two contemporaneous disease series of known occurrence. These were: terminal renal failure, all causes (low or absent epidemicity n = 106) and an outbreak of echovirus 19 disease (high epidemicity n = 201). Eight primary biliary cirrhosis-affected men and 109 women from an estimated catchment population of 2.08 million were identified. The current diagnosis rate was 1.0/100 000 (1.8/100 000 for women of 15 or more). There were 18 deaths, mean survival from diagnosis 4.0 years. Within the region prevalence varied from 3.7/100 000 in rural areas to 14.4/100 000 in industrial urban areas. In the conurbation, prevalence rates varied insignificantly. Here, most cases were concentrated in central districts, where the proportion of asymptomatic presentations was 50%. Outside the conurbation the asymptomatic proportion fell to 21%, suggesting low incidental diagnosis rates. When compared with echovirus 19, primary biliary cirrhosis was of low or absent epidemicity, and similar to renal failure in its uniform geographical distribution and lack of clustering. Forty three patients (37% of the total), however, had significantly seasonal symptomatic presentations (p less than 0.01), although scan statistic testing failed to show clustering of onset in time. Apparently provocative factors associated with primary biliary cirrhosis symptomatic onset were identified in only 11 (9.4%) of patients. Age-specific onset rates rose linearly between ages 35 and 65, and nearly one third of patients presented after 65 years, two thirds of deaths occurring in this age group. There is thus no evidence in north east England of geographical anomalies in the distribution of primary biliary cirrhosis. International differences may be partly explained by environmental factors influencing seasonal presentation, such as sunlight. Diagnosis rates are profoundly influenced by increased medical awareness, especially in the elderly, of this now relatively common disease and increased use of the mitochondrial (AMA) antibody test.

Adolescent↗

Primary biliary cirrhosis--a revised clinical spectrum.

The presentation or method of detection of 93 patients with primary biliary cirrhosis (PBC) from Northern England is reported. Almost half (45/93) the patients had no symptoms of liver disease when PBC was diagnosed; in many of them serum antimitochondrial activity (AMA) was detected during immunological screening for other diseases. 13 patients with normal liver function tests had symptomless PBC. Liver histology in 6 of these was diagnostic for PBC, and 7 had histology suggestive of PBC; all had a positive AMA titre greater than or equal to 1/40. The mortality of the symptom-free AMA-positive patients over a mean follow-up of 4-5 years did not differ from that of the general population. Only 1 out of 45 initially symptom-free patients died in the follow-up period (8 months-12 years). 37 patients had disorders which may be associated with PBC--including 16 with thyroid disease, 9 with rheumatoid arthritis, and 5 with mixed connective tissue disease. It is suggest that, as with autoimmune thyroid disease, overt organ damage never develops in many patients with symptomless PBC.

Adult↗

The effect of age on the pharmacokinetics of diazepam.

1. After intravenous administration to 19 subjects, aged 18-95 years, plasma diazepam concentrations were measured over 160 h. Plasma protein binding of diazepam was also measured in each subject. 2. The terminal plasma half-life of diazepam ranged from 15.0 to 125 h and was positively correlated with age (r = 0.797). Total plasma diazepam clearance was not correlated with age (r = -0.017). 3. The free fraction of diazepam ranged from 0.0137 to 0.0386 and was significantly correlated with age (r = +0.863). Free diazepam clearance, which ranged from 432 to 1870 ml/min, was also correlated with age (r = -0.717). 4. It is concluded that the increased sensitivity of the elderly to diazepam is, at least in part, due to pharmacokinetic factors.

Adolescent↗

Aspirin and analgesic nephropathy.

Renal function was studied in 17 patients with rheumatoid arthritis who had each consumed between 5 and 20 kg of aspirin. After an interval of two years 14 of these patients-seven of whom had consumed a further mean of 2 kg of aspirin-had their renal function retested. No relation was found between total dose, rate, or duration of ingestion and any aspect of renal function that was studied. All patients had plasma creatinine levels within the normal range, though slight depression in creatinine clearance was not uncommon.From this study and other published data we conclude that aspirin rarely if ever causes analgesic nephropathy when prescribed alone in doses appropriate to the treatment of rheumatoid arthritis.

Adult↗

Gilbert's syndrome and drug metabolism.

Gilbert's syndrome is an inherited disorder which is characterised by unconjugated hyperbilirubinaemia. In patients with Gilbert's syndrome, both bilirubin clearance and in vitro hepatic microsomal uridine diphosphoglucuronyl transferase (UDPGT) activity are reduced. In addition, there is evidence suggesting impaired hepatic uptake of bilirubin in Gilbert's syndrome. Glucuronidation of a number of substrates appears to be impaired in Gilbert's syndrome, but the significance of the reported changes in oxidation and acetylation are less clear.

Acetaminophen↗