THE ABSORPTION AND EXCRETION OF PENTAZOCINE AFTER ADMINISTRATION BY DIFFERENT ROUTES

Some of the factors affecting the absorption and metabolismof drugs are briefly reviewed and the absorption and excretionof pentazocine after administration by different routes to fourhealthy non-smoking male volunteers is described. Significantintersubject variations were found but the intrasubject variationswere small and, regardless of the route of administration, aconsistent pattern of relative rates of metabolism was demonstrated.Data are presented showing blood levels and urinary excretionof pentazocine throughout each study. Pentazocine was well absorbedby all the common routes of administration and the rate of metabolismseemed to be the factor which controlled the blood levels achieved.Faecal excretion was negligible, being less than 2 per centof the administered dose over the first 48 hours. Clinical applicationof this information is possible and it is hoped that studiessuch as this can be useful in providing greater therapeuticefficiency and a reduction in side effects.     

CD44 IS EXPRESSED IN HEPATOCELLULAR CARCINOMAS SHOWING VASCULAR INVASION

CD44 and its variant isoforms are a group of transmembrane glycoproteins which play important roles in immune recognition, in lymphocyte trafficking, and in cell–cell and cell–matrix interactions. Although CD44 is expressed by some normal human epithelial and mesenchymal cells, upregulation of CD44 expression has been related to the metastatic potential of some malignant tumours. In this study of 27 hepatocellular carcinomas (HCCs), an indirect immunohistochemical method was used to investigate the distribution of CD44 in normal liver and to determine whether expression of the standard form of CD44 (CD44s), or two of its variant isoforms (CD44-v3 and CD44-v6), correlated with tumour grade, proliferation indices, or histological evidence of vascular invasion. Fifteen of the tumours were Edmondson grade II, four were grade III, and eight were grade IV. Liver cell dysplasia was present in adjacent liver parenchyma in three cases and vascular invasion was observed in ten HCCs. Vascular invasion was found to be more frequent in high grade HCCs and a significant correlation was observed between tumour proliferation indices and vascular invasion. CD44s was not expressed by epithelial cells of normal liver but was expressed by tumour cells in six HCCs; vascular invasion was present in five of these HCCs. Three CD44s-positive cases also expressed CD44-v3 and two of these also expressed CD44-v6. CD44 was not expressed in areas of hepatocyte dysplasia. There was a significant correlation between CD44 expression and the presence of vascular invasion, but not between CD44 expression and tumour grade or tumour proliferation indices. It is concluded that upregulation of cell surface CD44 expression on malignant hepatocytes is related to their tendency to vascular invasion and may have implications relating to metastasis and prognosis in patients with HCCs.     

CONSISTENCY OF MORNING STIFFNESS: AN ANALYSIS OF DIARY DATA

This study aimed to determine the within-individual daily variationin morning stiffness (MS) of RA patients, and to validate theroutine clinically derived duration of MS against that recordedprospectively by patients Forty-nine RA patients, who duringa detailed clinical interview reported experiencing MS thatweek were studied. They were asked to prospectively record,using a diary, daily information on the duration of their MS.The times both of waking and of getting up were noted, as wellas the times to first improvement, maximum improvement and completedisappearance of MS, providing six possible estimates of MSduration, three of which, using waking as starting points, couldbe compared with the interview. The daily variation of MS wasassessed by the within-patient range. The median duration ofthe diary scores was then compared with the MS estimates recordedat the interview. There was a large intra-individual variationin duration of MS, whichever of the six definitions were used.Half of the patients recorded ranges of MS scores of 3 h ormore within the same week. There was also marked variation betweenthe median diary derived duration and that ascertained by interview.This variation was at its smallest when the duration of MS wascalculated as time until maximum improvement. The routine recordingof the ‘typical’ duration of MS seems to have littleclinical value in the face of the large within-patient variation.Of the possible choices for estimating duration, the time fromwaking to maximum improvement appeared to be the best indicatorof the average duration of MS in RA patients. KEY WORDS: Morning stiffness, Diary, Clinimetrics     

Spectrum of liver pathology in immune mediated liver diseases

Abstract   Immune mechanisms are involved in a wide range of parenchymal liver diseases and are of particular importance in conditions where the pathogenesis appears to be related to loss of tolerance to self antigens. In the liver there are two classical 'autoimmune' conditions: primary biliary cirrhosis and autoimmune hepatitis. It is increasingly apparent however that these may represent ends of a spectrum and overlap syndromes are well recognised. Furthermore there is evidence that primary sclerosing cholangitis may be a further example of autoimmune liver disease and overlpa conditions between this and autoimmune hepatitis are described. Histopathological assessment remains an important diagnostic tool in the investigation of autoimmune liver disease, particularly in the context of outlier and overlap conditions.