Inhibition of hepatic demethylation of aminopyrine by oral contraceptive steroids in humans.

The effect of oral contraceptive steroids (OCS) on the rate of hepatic demethylation of 14C-dimethylaminoantipyrine (DAP) was studied directly in healthy young volunteers using a newly developed noninvasive breath analysis technique. After oral administration of a trace dose of DAP the specific activity of 14CO2 in breath was determined during 6 h and expressed as half life. The half life of eighteen female and twelve male control subjects was 2.4 +/- 1.2 h (2 SD) and 2.2 +/- 0.6 h (2 SD), respectively. In seven women starting OCS a progressive prolongation of DAP half life during a single menstrual period was observed. In seventeen women who had taken OCS in 21 day cycles, for more than 3 months, the half life was significantly (P less than 0.001) prolonged (4.4 +/- 2.1 h) when measured after 21 consecutive days of OCS intake. On average, stopping OCS for 7 days or giving phenobarbital in addition to OCS shortened DAP half life significantly (from 4.4 +/- 2.1 h to 3.2 +/- 1.1 h, n = 17, P less than 0.005; and from 4.6 +/- 2.0 h to 3.2 +/- 1.0 h, n = 12, P less than 0.01, respectively). Eight of twelve women on OCS responded to OCS intake and to OCS cessation and phenobarbital, whereas four women did not respond to any of these measures. These data suggest that inhibition of hepatic demethylation of DAP by OCS is time dependent and reversible. The extent of inhibition appears to be an individual characteristic of a given person.

PIP: The effect of oral contraceptive (OC) steroids on the rate of hepatic demethylation of carbon-14-dimethylaminoantipyrine (DAP) was studied directly in healthy young volunteers using a newly developed noninvasive breath analysis technique. After oral administration of a trace dose of DAP the specific activity of 14 CO2 in breath was determined during 6 hours and expressed as half-life. The half-life of 18 female and 12 male control subjects was 2.4 + or -1.2 hours (2 standard deviation; SD) and 2.2 + or -.6 hours (2 SD), respectively. In 7 women starting combined OCs a progressive prolongation of DAP half-life during a single menstrual period was observed. In 17 women who had taken OCs in 21-day cycles, for more than 3 months, the half-life was significantly (p .001) prolonged (4.4 + or -2.1 hours) when measured after 21 consecutive days of OC intake. On average, stopping OCs for 7 days or giving phenobarbital in addition to OCs shortened DAP half-life significantly (from 4.4 + or -2.1 hours to 3.2 + or -1.1 hours, n = 17, p .005; and from 4.6 + or -2.0 hours to 3.2 + or -1.0 hours, n = 12, p .01, respectively). 8 of 12 women on OCs responded to OC intake and to OC cessation and phenobarbital, whereas 4 women did not respond to any of these measures. These data suggest that inhibition of hepatic demethylation of DAP by OCs is time-dependent and reversible. The extent of inhibition appears to be an individual characteristic of a given person.

[Liver metastases: diagnostic value of blood tests, scintiscanning, and laparoscopy (author's transl)]. / Lebermetastasen: dignostischer Wert von Bluttests, Szintigraphie und Laparoskopie

In 90 patients with known extra-hepatic malignancy the liver was examined for metastases. The diagnostic value of clinical information, blood examinations, 99mTc scintiscan, and laparoscopy for the diagnosis of the liver metastases was evaluated. Clinical data (age, sex, time since onset of symptoms and localisation of primary tumor) are of no diagnostic value. The most reliable blood tests are alkaline phosphatase (AP) and GOT. The probability of liver metastastases rises with increasingly abnormal values of AP and GOT. However, the probability is not much greater in cases with highly abnormal values than in cases with only moderate elevation of AP and GOT. Diagnostic accuracy of AP is optimal by using a cutoff point of 76 U/l (sensitivity 79%, specificity 64%). Bilirubin, prothrombin time, haemoglobin and blood sedimentation rate are of very little value. Combinations of AP with these blood tests does not improve diagnostic accuracy. Therefore, it is not useful to determine more blood tests than AP alone. Informed reading of liver scans has a specificity of 75% and a sensitivity of 91%. Blind reading of scans has a sensitivity of 94% and a specificity of 95%. This diagnostic accuracy cannot be improved by additional blood tests. Laparscopy has a sensitivity of 85% and a specificity of 95%. Scanning and laparoscopy are complementary methods. When optimal diagnostic accuracy is required both methods should be used.

[The diagnosis of liver metastases and primary hepatomas by means of scintigraphy, laparoscopy and laparotomy]. / Diagnose von Lebermetastasen und primärem Hepatom mit Szintigraphie, Laparoskopie und Laparotomie

To evaluate the presence or absence of hepatic metastases or primary hepatoma 106 patients were examined by liver scintigram as well as laparoscopy or laparotomy. A definite diagnosis was established in all patients by histology, autopsy or observation of clinical course for at least one year. Only scintigrams resulted in false positive diagnosis (in 5%). False negative diagnoses were obtained in 29% of laparoscopies and in 36% of scintigrams when evaluated routinely with knowledge of the clinical findings and laboratory examinations. Analysis of the same scintigrams by an experienced examiner without knowledge of the clinical findings lowered the proportion of false negative scintigrams to 12%. In 5 patients with liver metastases or hepatoma coexisting in liver cirrhosis or advanced chronic liver congestion, both methods of examination gave false negative results.

Is phlorizin or its aglycon the inhibitor of intestinal glucose transport? A study in normal and lactase deficient man.

Inhibition of glucose transport by phlorizin was examined in man by perfusion of an isolated small bowel segment. Inhibition was similar in normal and lactase deficient subjects. Since the small bowel of lactase deficient subjects contains only very small amounts of phlorizin hydrolase, phlorizin and not a product of enzymatic cleavage is the inhibitor of the small intestinal glucose carrier.