Enhancement of peroxisomal enzymes, cytochrome P-452 and DNA synthesis in putative preneoplastic foci of rat liver treated with the peroxisome proliferator nafenopin

The peroxisome proliferator (PP) nafenopin (NAF) enhanced tumordevelopment in rat liver through promotion of a subtype of putativepreneoplastic cell foci, characterized by weak cytoplasmic basophilia(1,2). In order to elucidate the selective growth advantageof these weakly basophilic foci (WBF) we investigated the effectsof NAF on their metabolic phenotype and DNA synthesis. In WBF,as well as in other foci subpopulations and in hepatocellularcarcinomas the occurrence of five NAF-inducible enzymes, i.e.of peroxisomal ß-oxidation (acyl-CoA oxidase, bifunctionalprotein and thiolase), catalase and cytochrome P-452 was studiedby immunohistochemical methods. In untreated livers almost allfoci were stained with the same intensity as the surroundingtissue. When NAF was applied, most of the liver foci showedconsiderably less staining than the non-focal parenchyma inwhich pronounced enzyme induction had occurred. However, thesubpopulation of WBF showed a more heterogeneous pattern ofenzyme expression varying from less to even more than in theadjacent tissue. A similarly broad range of expression of peroxisomalenzymes was found in hepatocellular carcinomas. On average,however, the tumors exhibited less staining and lower activityof peroxisomal ß-oxidation than the surrounding parenchyma.WBF always showed higher rates of DNA synthesis than other focisubtypes and unaltered liver. In     

SHORT COMMUNICATION: Peroxisomal enzyme induction uncoupled from enhanced DNA synthesis in putative preneoplastic liver foci of rats treated with a single dose of the peroxisome proliferator nafenopin

Putative preneoplastic foci of spontaneous origin could be detectedin the livers of 2 year old, untreated male Wistar rats. Theunaltered and preneoplastic hepatocytes showed an identicalexpression of the peroxisomal marker enzyme acyl-CoA oxidase,as determined by immunohistochemical staining. A single doseof the peroxisome proliferator (PP) nafenopin (NAF) inducedthe enzyme predominantly in hepatocytes around the central venulesand cell replication mainly in the periportal areas. However,upon one NAF application almost all of the preneoplastic focishowed a considerably weaker immunoreaction for peroxisomalacyl-CoA oxidase than the surrounding tissue. ConcomitantlyNAF elevated replicative DNA synthesis index in foci up to     

RENAL TRANSPLANTATION – AN EARLY EXPERIENCE

Renal transplant (RT) is now a therapy of choice for end stage renal disease (ESRD). The Nephrology Unit, Asvini started functioning in Dec 90 and to date 1298 sittings of hemodialysis have been given to 45 patients. Of these, 35 were in ESRD and 11 patients underwent renal transplantation at this hospital during the period Jan 91 – Dec 93. One patient expired after 18 months of transplantation due to infection. Early experience in screening patients for RT, use of immunosuppression, management of rejection episodes and protocol are presented with special emphasis on its relevance to the Armed Forces.KEY WORDS: Transplantation, Renal Failure, Immunosuppression, Rejection     

Health expenditure trends in OECD countries, 1970-1997

This article provides an overview of current trends in health expenditures in 29 OECD countries and recent revisions of OECD health accounts. U.S. health expenditures are compared with those of other OECD countries. The interactions of cost-containment measures with changes in the public-private mix of financing and in the composition of health care spending are discussed.     

Neonatal hearing screening--consequences for public health policy

In Germany 1-2 of every thousand newborns suffer from severe hearing impairment. The fatal consequences of this irreversible condition are avoidable only if therapy is started as early as possible--according to current US-American recommendations before the age of 6 months. In Germany children even with severe hearing loss are identified only when they are 21 months old (average figure). Universal hearing screening before the age of 3 months could be a useful measure to reduce the mean age of children at the time of diagnosis and so to give them a chance of an early and promising therapy. In the USA this has been recommended by the National Institute of Health since 1993.     

Expression of endothelial cell-derived nitric oxide synthase (eNOS) is increased during gastric adaptation to chronic aspirin intake in humans

BACKGROUND: Gastric adaptation to aspirin is well-documented. However, the mechanisms underlying the reduction of aspirin-induced mucosal damage despite continued ingestion of the drug remain poorly understood. METHODS: Eight healthy volunteers who received aspirin 1 g b.d. for 14 days were compared with eight placebo-dosed controls. Gastroscopy with mucosal biopsy was performed, and gastric mucosal blood flow was measured before and following 3, 7 and 14 days of aspirin treatment. At the same time points, tissue concentration and the content of prostaglandin E2 in the gastric juice were determined and expression of endothelial cell-derived nitric oxide synthase (eNOS) in mucosal biopsies was measured using Western blot analysis. RESULTS: Aspirin-induced mucosal damage that reached a maximum on day 3, declining significantly by day 14. Concomitantly, mucosal blood flow significantly increased on day 3 and returned to initial values on day 14. Aspirin intake led to a significant decrease in prostaglandin E2 concentration in the gastric mucosa and in gastric juice during the whole period of aspirin consumption. eNOS expression started to increase on day 7 in oxyntic mucosa and on day 3 in antral mucosa, reaching its highest values at the end of the consumption of aspirin. CONCLUSIONS: The human gastric mucosa adapts to prolonged aspirin intake, and this is accompanied by an increase in mucosal blood flow and reduced prostaglandin synthesis. Increase of mucosal eNOS expression might compensate for reduced prostaglandin synthesis and be responsible for gastric adaptation to chronic aspirin intake in humans.     

Assessment of left ventricular function: comparison between radionuclide angiography and semiquantitative two-dimensional echocardiographic analysis

Measurement of global left ventricular function is important in the follow-up of cardiac patients and is a good prognostic indicator in acute cardiac situations. We compared quantitative measurements of global left ventricular function made with radionuclide angiography (RNA) and contrast cardiac ventriculography (CVG) to visual semiquantitative estimates from two-dimensional echocardiographic images (2D-echo). Three hundred and thirty-nine consecutive patients who underwent RNA were assessed with 2D-echo within 3 months. In addition, 92 of these patients also underwent CVG (correlation of ejection fraction between CVG and RNA:r=0.82;P<0.0001). The RNA mean ejection fractions in the four 2D-echo groups (0=normal, 1=slightly, 2=moderate, or 3=severe reduced left ventricular function) differed markedly (P<0.0001); however, there was overlapping among the groups (2D-echo score/RNA ejection fraction: 0=57.3%±12.8%; 1=46.0%±12.9%; 2=29.6%±12.2%; and 3=24.6%±11.5%) and the difference between 2D-echo scores 2 and 3 was not significant. 2D-echo showed a good concordance in RNA classes (0=505; 1=35%–49%; 2=21%–34%; and 3=520% ejection fraction) 0 (133/166; 80%) and 3 (18/30; 60%) but low concordance in classes 1 (27/82; 33%) and 2 (21/61; 34%). For accurate assessment of global left ventricular ejection fraction, visual semiquantitative judgement of a 2D echocardiographic image is limited in comparison to CVG or RNA, especially in patients with a slight or moderate reduction in left ventricular ejection fraction.     

Radical cystectomy with or without adjuvant polychemotherapy for non-organ-confined transitional cell carcinoma of the urinary bladder: Prognostic impact of lymph node involvement

Objectives

To analyze the effectiveness of adjuvant polychemotherapy after radical cystectomy for nonorgan-confined transitional cell bladder cancer (Stages pT3b, pT4a, and/or pN1 or pN2).

Methods

Of 166 consecutive patients undergoing cystectomy at two institutions from 1987 to 1993, 80 received adjuvant polychemotherapy with methotrexate, vinblastine, and cisplatin plus doxorubicin (MVAC) or epirubicin (MVEC), whereas 86 had cystectomy only. The patients were evaluated for relapse-free survival and length of progression-free interval on the basis of follow-up data obtained in 1995 and 1996.

Results

Kaplan-Meier analysis revealed a significantly higher progression-free rate for patients after adjuvant chemotherapy (P=0.0002, log-rank test). With and without adjuvant chemotherapy, prognosis declined in a stepwise manner, depending on the extent of lymph node involvement. Nevertheless, the superior prognosis of the chemotherapy group could be demonstrated at each lymph node stage. Of the 166 patients, 49 had initially entered a prospective trial comparing adjuvant with no adjuvant treatment. That study was discontinued in December 1990 after an interim analysis revealed a significant prognostic advantage in favor of the 26 patients randomized to receive chemotherapy compared with the 23 control patients. Current follow-up data continue to demonstrate a significant improvement in progression-free survival in favor of patients randomized to receive adjuvant chemotherapy (P=0.0040). The follow-up period of patients living free of disease ranges from 58 to 96 months.

Conclusions

Adjuvant chemotherapy with MVAC/MVEC leads to significant prolongation of relapse-free survival and improvement of the definitive cure rate after radical cystectomy for locally advanced transitional cell carcinoma of the urinary bladder.     

Peri-operative elastase-α-1 proteinase inhibitor in patients with postoperative intervertebral discitis

Summary In a prospective study of 251 patients operated upon for lumbar disc herniation it has been investigated whether the preoperative and early postoperative values of Elastase--1 Proteinase Inhibitor (EPI) — an indicator of inflammatory processes — and C-reactive Protein (CRP) — a well known predictor of some postoperative complications — were correlated to the later development of discitis. Postoperatively discitis developed in 14 patients. A randomly choosen group of 15 complication-free patients out of the total of 251 cases was used as control group.Elevated EPI plasma values, especially in the pre-operative and first postoperative days, turned out to be significantly related to the likelyhood of later discitis development, but no such relation for the CRP plasma values could be established. Thus and early prediction of patients at risk for this complication seems to be possible by pre- and postoperative measurement of EPI. It could be justified —but its usefulness has yet to be proven — to give antibiotics prophylactically and other anti-inflammatory medication in patients with elevated pre- and postoperative EPI values.