Inhibition of desmethylimipramine 2-hydroxylation by drugs in human liver microsomes

The 2-hydroxylation of desmethylimipramine (DMI) correlates strongly with the 4-hydroxylation of debrisoquine (D) both in human volunteers and in vitro comparing human liver microsomes from different individuals. D competitively inhibits the 2-hydroxylation of DMI in vitro suggesting that DMI is hydroxylated by the 'debrisoquine hydroxylase' which is under monogenic control in man. We have characterized the effect of drugs on the hydroxylation of DMI in human liver microsomes by measuring the formation of 2-OH-DMI with HPLC using fluorescence detection. Amitriptyline, nortriptyline and metoprolol inhibited the hydroxylation of DMI competitively indicating interaction with the catalytical site for DMI 2-hydroxylation. Antipyrine and amylobarbitone at concentrations similar to their Km-values for metabolism did not inhibit DMI-hydroxylation. Thus, for these compounds there was a good correspondence between the drugs' capacity to inhibit DMI 2-hydroxylation competitively in vitro and their apparent metabolism by the 'debrisoquine hydroxylase' in vivo in man. Thioridazine, chlorpromazine, quinidine and quinine also inhibited DMI-hydroxylation competitively. Thioridazine was an unusually potent inhibitor (apparent inhibition constant Ki = 0.75 microM). Quinidine was also an unusually potent inhibitor (Ki = 0.27 microM) and much more efficient than its isomer quinine (Ki = 12 microM). Theophylline could inhibit DMI hydroxylation but with atypical kinetics. We suggest that this simple DMI in vitro test as well as earlier described inhibition tests with debrisoquine, sparteine and bufuralol can be used to screen if drugs interact with the 'debrisoquine hydroxylase' in human liver.     

Gerota versus Zuckerkandl: the renal fascia revisited

In the medical literature, Gerota fascia is frequently used as a general term to describe both the anterior and posterior pararenal fascia. However, Zuckerkandl's name is also often used to describe either the anterior or posterior fascia. To resolve this confusion, the authors reviewed the original works by Gerota and Zuckerkandl. In 1883, Zuckerkandl described the posterior renal fascia but did not recognize the presence of the anterior renal fascia. In 1895, Gerota documented the presence of the anterior renal fascia and clearly assigned Zuckerkandl's name to the posterior renal fascia. Thus, the terms Zuckerkandl fascia and posterior renal fascia are synonymous, as are Gerota fascia and anterior renal fascia.     

Disengagement and reinforcement in the elderly.

Misinterpretation of disengagement theory as the ideal way of aging has led to a laissez-faire attitude in some settings. The problem is to determine the extent to which disengagement may be related to situational factors, and thus be potentially reversible, rather than the extent to which disengagement may be related to aging per se. In this study, disengagement is conceptualized in behavioral terms as an extinction phenomenon. The relationship between the degree of disengagement exhibited by elderly persons and the self-reported reinforcement occurring in their lives was explored in a survey of two elderly groups. A disengagement index incorporating role-set counts, role participation, role importance, and perceived life space was administered to 50 nursing home residents and 50 community registered voters. A Reinforcement Survey Schedule was used to identify positive reinforcers, level of reinforcement, and anticipated reinforcement. A significant correlation (p < .001) was found between disengagement and reinforcement for both groups: the greater the degree of disengagement, the lower the reported reinforcement. The findings indicate that the application of social learning principles may be useful in retarding disengagement and promoting engagement of the elderly, particularly in nursing homes.     

Screening cord blood for sickle haemoglobinopathies in Brent

Between 1981 and 1983, 3165 consecutive specimens of cord blood were tested at the Central Middlesex Hospital for the presence of an abnormal haemoglobin: the incidence of sickle cell trait was 2.8%, of HbC trait 0.9%, and the overall incidence of an abnormal haemoglobin at birth was 6.9%. Five babies with homozygous sickle cell disease, three with HbSC, and three with either HbCC or HbC beta thalassaemia were detected. Twenty two per cent of the mothers were of Afro-Caribbean origin. The cost of the test was 30p. An H6000 blood count was carried out on 1000 consecutive cord blood samples. The mean red cell volume was 97.95 (SD 3.67) fl. Thirteen cord blood samples had a mean cell volume below 85 fl, and all contained Hb Barts. In addition, six samples with a mean cell volume between 86 and 92 fl also showed Hb Barts on electrophoresis. The overall incidence of Hb Barts was 2.1%. These results indicate that the incidence of HbSS and HbSC on neonatal screening in Brent is similar to that found in the urban areas of North America and that the number may be predicted from the number of births to mothers of Afro-Caribbean origin.