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A J Watson

Publications and source records attributed to A J Watson.

At least 289 records · Page 16Linked to original sources

Liver damage after paracetamol overdose. Comparison of liver-function tests, fasting serum bile acids, and liver histology.

54 patients have been studied after paracetamol (acetaminophen) overdose. Liver-function tests and fasting serum bile-acids were measured daily; liver biopsy was done in all cases, and slides were examined "blind" to assess liver damage. The plasma-paracetamol was measured on one occasion. A histological abnormality was present in the livers of 53 of the 54 patients, and was minor in 23, moderate in 16, and severe in 14. In 6 patients with moderate and 18 with mild histological abnormality liver-function tests were normal. A serum-aspartate-aminotransferase above 400 units/1 was always associated with severe histological liver damage. Fasting serum bile-acids were raised in 51 of the patients with abnormal liver histology; the serum-bile-acid seemed to be a more sensitive indicator of mild liver-cell damage than was the transaminase level. There was, however, little correlation between increase in bile-acid concentration and the degree of histological abnormality. As a result of these investigations empirically determined levels of plasma-paracetamol have been drawn which give a guide to the likelihood of liver damage after paracetamol overdose.

Acetaminophen↗

Cell population kinetics in the mouse jejunal crypt.

The time parameters of the cell cycle were determined in the jejunal crypts of male Balb/c mice by an FLM experiment. The cell cycle time was 12.42 +/- 0.11 h, and the duration of DNA synthesis was 7.61 +/- 0.99 (mean values +/- S.E.). A stathmokinetic technique using vincristine gave a value of Tc of 11.8 h. The growth fraction (Ip) calculated from cycle parameters and the labelling index was 0.61, while a value of Ip estimated from a labelling index distribution curve was 0.65. For the whole crypt a value of 0.86 h was obtained for the duration of mitosis, longer than that in the rat. The mitotic duration was found to vary with cell position, but values of between 0.8 and 1.2 h prevailed throughout the proliferative compartment; values in the basal cell positions appeared shorter. Apparent cell cycle times were longest in the basal cell positions. A value for crypt migration rate calculated from a cumulative birth rate curve was 1.48 cell positions per h, compared with a value of 1.8 +/- 0.27 cell positions per h as measured from movement of the 50% peak value on the labelling index distribution curve with time after tritiated thymidine. The crypt cell production rate was calculated from microdissected and squashed crypts to be about 14 cells per crypt per h. There was a total crypt population of 282 +/- 65 (S.E.) cells, of which 172 were proliferative.

Animals↗

Cell population kinetics in the rat jejunal crypt.

Cell kinetics in the jejunal crypt of the male Wistar rat were studied using autoradiographic techniques with tritiated thymidine and a stathmokinetic technique with vincristine. The migration rate measured by following the movement of the 50% peak on the labelling index distribution curve with time after injection of tritiated thymidine gave a value of 1-43 +/- 0-14 (SE) cell positions per hour, compared with a value from a cumulative birth rate of 1-78 cell positions per hour. Tht crypt column length was 32-9 +/- 0-2 cells and the column count was 22-3 +/- 0-2. This measurement gave a total crypt population of 734 cells, compared with an estimate of 650 +/- l from direct observation of squashed, microdissected crypts. In each crypt 22-5 +/- 0-5 mitoses were present, and the crypt cell production rate was 32 cells per crypt per hour; this latter value was confirmed using two independent techniques. The crypt growth fraction calculated from the durations of phases of the cell cycle and the labelling index was 0-62. A value of 0-61 was found from the labelling index distribution curve. As assessed from crypt squashes, there were 403 proliferating cells per crypt.

Animals↗

The effect of starvation and refeeding on cell population kinetics in the rat small bowel mucosa.

Male rats were starved for a period of 96 hours. Measurements of crypt cell population showed a small reduction during starvation. The growth fraction remained constant, but the total number of proliferating cells per crypt fell as a consequence of the reduction in crypt population. Both labelling and mitotic indices fell throughout the starvation period. The cell cycle time (Tc), measured by a stathmokinetic technique using vincristine, was increased from 10-4 hours in control rats to 14-7 hours after 96 hours' starvation. Upon refeeding, the proliferative indices were observed to rise. After a small initial fluctuation, the growth fraction remained constant. The crypt population remained substantially unchanged. Sixteen hours after refeeding, the cell cycle time was reduced to 6-5 hours. The hypoproliferative response to starvation is mediated solely by an increase in cell cycle time, and the response to refeeding is interpreted in terms of a reduction in Tc. Changes in the size of the proliferating population are considered not to play an important role in either response, although it is not possible to exclude entirely the presence of resting cells in the proliferative compartment itself.

Animals↗

Incidence of small-intestinal mucosal abnormalities and of clinical coeliac disease in the relatives of children with coeliac disease.

Evidence is presented of a higher than normal incidence both of clinical coeliac disease and of small-intestinal mucosal abnormalities in relatives of children with coeliac disease. In such relatives the incidence of mucosal abnormality may differ from the incidence of clinical coeliac disease. The data show an absence of any simple Mendelian pattern of inheritance: in place of the hypothesis that inheritance is through a dominant gene of reduced penetrance, it is argued that the pathogenesis of coeliac disease is multifactorial, the genetic basis of susceptibility being polygenic and interacting with environmental factors. On this hypothesis the relative contributions of inheritance and environment to liability to the clinical condition are estimated, the genetic component being 45% +/- 9. Environmental factors appear more important in the development of mucosal abnormality.

Adult↗