Bilateral agenesis/aplasia of the lungs: report of a second case in the offspring of one woman.

Congenital absence of both lungs is an extremely rare malformation in humans and is thought to occur sporadically. We report the second case of congenital absence of both lungs in the offspring of one woman. In neither case, one female baby (born at term) and one aborted female fetus (21 weeks of gestation), were anomalies or malformations of other organ systems observed. The karyotype of the aborted fetus was 46,XX. To our knowledge, this is the first report describing bilateral pulmonary agenesis in two offspring of one mother. The repetition of virtually the same isolated abnormality with no other malformations supports the hypothesis that it could be caused by a genetic disorder. Other etiologies previously suggested, such as drugs or viruses, cannot be excluded but seem less likely.

Chronic ursodeoxycholic acid- and chenodeoxycholic acid-feeding-induced changes of colon mucosal cell proliferation in rats.

Hyperproliferation has been suggested to play a major role in bile acid-dependent colorectal tumor promotion. Effects of chronic feeding of chenodeoxycholic acid (CDC) and ursodeoxycholic acid (UDC) were tested on cell proliferation in the colon of male noninbred Wistar rats. By use of a dynamic method measuring actual rates of cell production, proliferation was modulated by both bile acids only in the proximal part of the colon. UDC feeding produced mild hyperproliferation of basal crypt cells (cell position 5-8: 7.6 +/- 2.0 vs. 3.5 +/- 1.3 cells/1,000 cells/hr--P less than .05; cell position 9-12: 18.1 +/- 10.7 vs. 10.3 +/- 2.9--P less than .05; cell position 13-16: 18.1 +/- 8.9 vs. 9.1 +/- 2.3--P less than .05). This finding reflected a characteristic compensatory response to superficial cell damage. However, CDC application did not effect cell regeneration in this crypt area but led to a striking drop of cell renewal in higher crypt cell positions (positions greater than or equal to 17), where no proliferation was detectable. These data suggest that CDC exerts its tumor-promoting effect by other means than hyperproliferation.

Isomers of bilirubin glucuronide in serum and bile before and after relief of common duct obstruction.

Isomers of bilirubin glucuronide with the bilirubin acyl group attached to the C1-, C2-, C3- and C4-positions of the glucuronyl residue are present in bile of patients with extrahepatic cholestasis, whereas in normal bile only C1-isomers are found. In the present study, these bilirubin glucuronide isomers, and the fractions of unconjugated bilirubin, and bilirubin mono- and diconjugates were determined in serum and bile of 8 patients before and after relief of common duct obstruction by endoscopic papillotomy. Before papillotomy we found 39.6% C1-isomers (median value), 22.2% C2-isomers, 19.3% C3-isomers and 11.4% C4-isomers in the bile. The values in serum before papillotomy were comparable. Twenty-four hours after papillotomy, the level of C1-isomers in bile increased significantly to 56.3% (P less than 0.05) with a concomitant decrease of the non-C1-isomers. In contrast, in serum the isomers of bilirubin glucuronide did not change significantly at 24 h after papillotomy. Before papillotomy, the fraction of unconjugated bilirubin in bile was 3.6% of the total, with 15.8% bilirubin monoconjugates and 75.5% bilirubin disconjugates. After papillotomy, unconjugated bilirubin decreased to 1.6% (n.s.) and bilirubin monoconjugates to 11.9% (n.s.), while bilirubin diconjugates increased to 86.1% (P less than 0.05). In serum, the elevated fractions of bilirubin diconjugates and monoconjugates decreased from 38.4 to 32.2% (P less than 0.05) and from 29.6 to 23.4% (n.s.), respectively. In parallel, the fraction of unconjugated bilirubin in serum increased from 24.1 to 37.0% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Duodenal gamma-glutamyltransferase activity in human biopsies: effect of chronic ethanol consumption and duodenal morphology.

Gamma-glutamyltransferase activity was determined in duodenal biopsies, and in the sera of forty-six non-alcoholic and eighteen alcoholic patients with a daily alcohol consumption of more than 80 g. Additionally, duodenal morphology was examined in biopsy material obtained at the same time. In both alcoholics (P less than 0.05) and in non-alcoholics (P less than 0.001) the duodenal gamma-glutamyltransferase activity revealed a significant positive correlation with duodenal villus length. In addition, alcoholics exhibited a significant decrease in duodenal villus length (338 +/- 13 vs. 363 +/- 13 microns, P less than 0.01), and a significant increase in duodenal gamma-glutamyltransferase activity (13.0 +/- 1.4 vs. 8.4 +/- 0.6 mU mg-1 protein, P less than 0.01) when compared to controls. No significant correlation was found between duodenal and serum gamma-glutamyltransferase activity in alcoholics and non-alcoholics. During follow up of two patients, duodenal gamma-glutamyltransferase activity decreased and duodenal villus length increased after withdrawing alcohol. These data underline the damaging effect of alcohol on the duodenal mucosa and demonstrate that chronic alcohol intake reversibly effects duodenal gamma-glutamyltransferase. In addition, the small intestine appears of minor importance as an origin for the elevated serum gamma-glutamyltransferase activities seen in the alcoholic.

Determination of HBV DNA by a simplified method of spot hybridization.

Molecular hybridization was employed to detect HBV DNA in sera of patients with acute or chronic hepatitis, by a simplified version of the spot hybridization technique. HBV DNA was found in 21 out of 50 sera obtained in acute hepatitis B. Determination of HBV DNA was negative in sera of patients with hepatitis A, Epstein-Bar virus infections or other HBsAg-negative liver diseases. There was no cross-hybridization between HBV DNA and sera of patients with non-A, non-B hepatitis.

Ethanol and intestinal carcinogenesis in the rat.

The effect of chronic ethanol administration on 1,2-dimethylhydrazine induced rectal carcinogenesis was investigated in 32 paired male Sprague-Dawley rats fed a nutritionally adequate liquid diet containing 36% of total calories either as ethanol or isocaloric carbohydrates. Chronic ethanol ingestion increased the total number of rectal tumors significantly (17 vs. 6, p less than 0.02), whereas no cocarcinogenic effect of ethanol was observed in other parts of the intestine. Alcohol did not influence tumor size or histopathology. A 47% increase in the activity of mucosal alcohol dehydrogenase in the distal colorectum was found between chronically ethanol fed and pair fed controls (0.241 +/- 0.019 vs. 0.164 +/- 0.020 mumol mg protein-1 hr-1, p less than 0.01). This could in part explain the cocarcinogenic effect of alcohol in this tissue. The data give experimental support to the epidemiologic findings of an increased incidence of rectal cancer in the alcoholic.

[Integrated and nonintegrated hepatitis B virus DNA in liver tissue]. / Integrierte und nicht-integrierte Hepatitis B-Virus-DNS im Lebergewebe.

Liver tissue was taken in eight patients with virus hepatitis B and one patient with liver carcinoma by biopsy, as well as in seven other patients at post mortem. HBV-DNA was measured in these tissue specimens by hybridization. In four out of eight patients who had had biopsy, HBV-DNA could be found; in two patients it was present in integrated form. The same was true for the tumor tissue stemming from the patient with liver carcinoma. In five out of eight liver tissue specimens taken at post mortem HBV-DNA could be demonstrated as well; it was integrated into the host genom in two cases. It may be important to find out in patients with chronic hepatitis virus infection, if HBV-DNA is present in free or integrated form before antiviral treatment is considered.

[Frequency of delta infections in Heidelberg]. / Häufigkeit von Delta-Infektionen in Heidelberg.

The frequency of delta infection was studied in sera of 203 patients with acute hepatitis B, further 461 hepatitis B virus surface antigen-(HBsAg)-positive patients and 117 HBsAg-negative controls by determination of anti-delta by a competitive enzyme immunoassay. Sera have been collected since 1974. None of the sera of acute hepatitis B was anti-delta-positive whereas seven of the HBsAg-positive carriers were anti-delta-positive. Two of the anti-delta-positive patients had chronic hepatitis, four had liver cirrhosis. One of the anti-delta-positive patients with liver cirrhosis died of liver failure. Risk factors included Italian origin and parenteral routes of infection. All sera of 19 relatives of three anti-delta-positive index cases remained anti-delta-negative.

Determination of HBV DNA in serum in a case of needlestick hepatitis.

HBV DNA in serum was determined by modified spot hybridization. A nurse of the dialysis staff was inoculated via needlestick with blood of a HBsAg-positive hemodialysis patient, who had 2000 pg HBV DNA per milliliter serum. After insufficient passive immunization the nurse developed transient anicteric hepatitis B. HBV DNA was positive in sera of the recipient before and at the beginning of the elevation of transaminases.

Different effects of dietary chenodeoxycholic acid and ursodeoxycholic acid on colonic adenylate cyclase in the rat.

The oral administration of dietary chenodeoxycholic acid (1%), but not of ursodeoxycholic acid (1%), to male Sprague Dawley rats results in a significant increase in the colonic adenylate cyclase activity without any influence on the colonic cyclic-AMP phosphodiesterase activity. No effect of chronic bile acid feeding on the response of colonic adenylate cyclase to prostaglandin E2 and vasoactive intestinal peptide is observed. These data emphasize a dependence of the cyclic-AMP adenylate cyclase activation on the chemical structure of the bile acid. This may be of pathophysiologic relevance with respect to the frequently observed diarrhea as a side effect of oral chenodeoxycholic, but not ursodeoxycholic acid therapy for cholesterol gallstone dissolution in man.

Stimulation of chemically induced rectal carcinogenesis by chronic ethanol ingestion.

The effect of chronic ethanol administration on 1, 2-dimethylhydrazine-induced rectal carcinogenesis was investigated in 32 paired male Sprague-Dawley rats fed a nutritionally-adequate liquid diet containing 36% of the total calories as either ethanol or isocaloric carbohydrates. Chronic ethanol ingestion increased the total number of rectal tumors significantly (17 vs 6; P less than 0.02), whereas no cocarcinogenic effect of ethanol was observed in other parts of the intestine. Alcohol did not influence tumor size or histopathology. A 47% increase in the activity of mucosal alcohol dehydrogenase in the distal colorectal region was found between chronically-ethanol-fed rats and pair-fed controls (0.241 +/- 0.019 vs 0.164 +/- 0.020 mumol/mg of protein/hr; P less than 0.01). This could in part explain the cocarcinogenic effect of alcohol in this tissue. Faecal bile acids, however, do not play a role as promotors of rectal carcinogenesis under the present experimental conditions. The results give experimental support to the epidemiologic findings of an increased incidence of rectal cancer in the alcoholic.

In vivo interactions between H2-receptor antagonists and ethanol metabolism in man and in rats.

The influence of a 7-day medication of either cimetidine (1,000 mg per day) or ranitidine (300 mg per day) on serum ethanol concentrations after a single oral dose of ethanol (0.8 gm per kg body weight) was investigated in a randomized placebo-controlled study in eight male volunteers. Compared with the placebo, cimetidine but not ranitidine produced a significant increase in both the peak serum ethanol concentration (85.9 +/- 3.5 vs. 73.0 +/- 3.2 mg dl-1, p less than 0.02) and in the area under the serum ethanol concentration time curve (350 +/- 19 vs. 304 +/- 25 mg dl-1 hr-1, p less than 0.05). However, the ethanol elimination rate was not affected by cimetidine. When ethanol (1.0 gm per kg body weight) was administered intravenously, cimetidine failed to induce a change in ethanol metabolism. Furthermore, the effect of H2-receptor antagonists was studied in animal experiments. Female Sprague-Dawley rats received a single dose of ethanol (7 or 3 gm per kg body weight) together with an intraperitoneal injection of either cimetidine (120 mg per kg body weight), ranitidine (120 mg per kg body weight) or isotonic saline. After alcohol absorption, ethanol elimination was significantly inhibited by both cimetidine (3.99 +/- 0.39 vs. 5.68 +/- 0.23 mmoles kg-1 hr-1, p less than 0.02) and ranitidine (4.21 +/- 0.14 vs. 5.68 +/- 0.23 mmoles kg-1 hr-1, p less than 0.02) at high ethanol concentrations (60 to 20 mM) but not at blood ethanol concentrations below 20 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

[Anti-HBc IgM in acute and chronic hepatitis B virus infection]. / Anti-HBc IgM bei akuter und chronischer Hepatitis-B-Virus-Infektion.

Hepatitis B core antigen (HBcAg) synthesized in E. coli was used for determination of immunoglobulin M class-specific antibodies against HBcAg. It was found that 98% of cases with acute hepatitis B surface antigen (HBsAg) positive hepatitis type B were anti-HBc immunoglobulin M (IgM) positive. Atypical hepatitis B was detected in 33% of anti-HBc-positive HBsAg-negative cases with acute hepatitis. Anti-HBc IgM was positive for 6 months in acute resolving hepatitis type B, whereas cases resulting in chronic hepatitis B remained anti-HBc IgM-positive for up to 900 days. Chronic HBsAg carriers with severe liver disease had anti-HBc IgM more often than individuals with minor liver damage; 83% of HBsAg-positive liver cirrhoses, 63% of chronic aggressive hepatitis, 50% of HBsAg-positive liver carcinoma, but only 17% of chronic persistent hepatitis or 7% of healthy blood donors were anti-HBc IgM-positive. Determination of anti-HBc IgM is useful in detecting atypical hepatitis B virus infections without HBsAg in serum and, with some restrictions, in discriminating acute and chronic hepatitis type B.

Detection of hepatitis B viral DNA in sera positive for antibody to delta antigen.

Hepatitis B virus (HBV) DNA was detected in 17 sera positive for antibody to delta antigen (anti-delta). Six sera from two patients were positive for HBV DNA. Analysis by the Southern blot technique showed identity between HBV DNA in anti-delta-positive and anti-delta-negative sera. These results show that anti-delta-positive sera contain HBV DNA, although these sera were also positive for antibodies to hepatitis B e antigen.

Enhancement of 1,2-dimethylhydrazine-induced rectal carcinogenesis following chronic ethanol consumption in the rat.

The incidence, distribution, size, and histopathology of grossly visible intestinal tumors induced by the parenteral administration of 1,2-dimethylhydrazine dihydrochloride were examined in 32 paired rats fed a nutritionally adequate liquid diet containing 36% of total calories either as ethanol or isocaloric carbohydrates. The liquid diets were begun 4 wk before the first of four weekly injections of 1,2-dimethylhydrazine dihydrochloride. At the time of the subcutaneous application of the procarcinogen, liquid diets were omitted for 3 wk, and were replaced by a standard laboratory diet. This feeding schedule was repeated four times, and after 32 wk the animals were killed. Chronic ethanol ingestion increased the total number of rectal tumors significantly (17 vs. 6, p less than 0.02). However, alcohol had no effect on tumor size or histopathology. Chronic ethanol ingestion did not exhibit any cocarcinogenic effect in tissues other than the rectum. A 47% increase in the activity of mucosal alcohol dehydrogenase in the distal colorectum was found between chronically ethanol-fed rats and pair-fed controls (0.241 +/- 0.019 vs. 0.164 +/- 0.020 mumol X mg protein-1 X h-1, p less than 0.01). This could in part explain the cocarcinogenic effect of alcohol in this tissue. Fecal bile acids, however, do not play a role as promoters of rectal cancer under the present experimental conditions. The data give experimental support to the epidemiologic findings of an increased incidence of rectal cancer in the alcoholic.

HBV-DNA in sera of patients with HBsAg-positive primary liver cell carcinoma.

Sera of ten patients with HBsAg-positive primary liver carcinoma were tested for anti-HBc-IgM and HBV-DNA. Five patients were positive for anti-HBc-IgM and six for HBV-DNA. There was no correlation between the presence of anti-HBc-IgM and HBV-DNA. Our study suggests that complete viral replication exists in some HBsAg-positive primary liver carcinomas.

Branched-chain amino acid-enriched elemental diet in patients with cirrhosis of the liver. A double blind crossover trial.

In 14 patients with cirrhosis of the liver and portal-systemic shunts the effect of a branched-chain amino acid-enriched elemental diet on portal systemic encephalopathy, routine laboratory parameters and plasma amino acids was investigated. In addition to the standard therapy including protein restriction (40 g/day) the patients received 44 g of an amino acid-protein mixture containing 30% of branched-chain amino acids and placebo over 3 months in a crossover regimen. Plasma valine and leucine increased significantly, whereas all other amino acids, including the ratio (formula: see text), remained unchanged. The electroencephalogram, number connection test, clinical state and laboratory parameters were not influenced by therapy with branched-chain amino acids. Thus, orally administered branched-chain amino acids probably have no influence on hepatic encephalopathy but are an adequate source of nitrogen in patients with cirrhosis of the liver.

Changes in gastrointestinal DNA synthesis produced by acute and chronic ethanol consumption in the rat: a biochemical study.

The effect of acute and chronic ethanol administration on DNA synthesis in the gastrointestinal tract of the rat was investigated. Acute intragastric ethanol administration (3 g/kg; 50%) decreased significantly in vivo DNA synthesis when measured 1 hour after alcohol application in the stomach and in the upper small intestine, whereas acute intravenous ethanol administration had no significant effect. In contrast, chronic ethanol ingestion resulted in a significant increase of in vivo and in vitro DNA synthesis in the upper gastrointestinal tract. In addition, even a more enhanced stimulation of DNA synthesis after chronic ethanol consumption was found in isolated intestinal cells. These results indicate an inhibition of gastrointestinal cell regeneration directly after the oral application of ethanol. The enhanced cellular regenerativity observed after chronic ethanol consumption may be secondary to the ethanol induced damage of the gastrointestinal tract.