Morphometric study of human hepatic cell modifications induced by fenofibrate

We have studied liver biopsies obtained in 12 hyperlipoproteinemic (HLP) patients (type II, 6; type IV, 6) treated with diet and fenofibrate, and in 15 patients (type II, 11; type IV, 4) receiving diet only. Electron microscopy of liver biopsies and the morphometric analysis according to the method of Weibel and Rohr showed mitrochondrial changes in patients treated with fenofibrate, these changes depending on the type of hyperlipoproteinemia. In type II HLP, we found a decreased volume of normal mitochondria (fenofibrate, 125.72 +/- 17.04 X 10(-3) cm3/cm3; diet only, 185.84 +/- 8.96 10(-3), P less than .05). In type IV HLP we found a decreased number of giant mitochondria (fenofibrate, 0.08 +/- 0.03 X 10(10) cm-3; diet only, 0.32 +/- 0.08 X 10(10) cm-3, P less than .05) and a decreased volume of altered mitochondria (fenofibrate, 6.00 +/- 1.44 X 10(-3) cm3/cm3; diet only, 13.61 +/- 1.17 X 10(-3), P less than .05). In contrast with the rodent studies, the present study shows no change in the number of volume of peroxisomes.     

Inhibition of growth hormone and thyrotropin release by growth hormone-release inhibiting hormone

Addition of increasing doses of synthetic growth hormone-release inhibiting hormone (GH-RIH) leads to a progressive decrease of the basal and N⁶monobutyryl cyclic AMP-,theophylline- and prostaglandin E₂-induced release of immunoreactive growth hormone (GH) and thyrotropin (TSH) release from rat anterior pituitary cells in monolayer culture. A halfmaximal effect is measured at 3 × 10^?9 M GH-RIH while a maximal inhibition to 10–20% of the control level is found at 1 × 10^?7 M. Using rat hemipituitaries and measurement of GH release by both polyacrylamide gel electrophoresis and radioimmunoassay, a maximal effect of GH-RIH was found in the first 5 min of incubation. The inhibitory effect of GH-RIH on GH release remained constant for at least 3 h. GH-RIH does not affect the basal or induced release of prolactin and luteinizing hormone nor the high K ⁺-induced release of GH and TSH.     

Cutaneously applied 4-hydroxytamoxifen is not carcinogenic in female rats.

Tamoxifen is widely used to treat oestrogen-dependent carcinoma of the breast. Previous long-term studies have shown that oral administration of tamoxifen induces hepatoproliferative lesions and hepatocellular tumours in rats. 4-hydroxytamoxifen is an active metabolite of tamoxifen undergoing clinical evaluation for the treatment of various non-malignant breast diseases by topical application. In the present study, 4-hydroxytamoxifen was administered daily by cutaneous application for 101 weeks to groups of 50 female Sprague-Dawley rats at 20, 140 or 1000 microg/kg/day. The product was applied with no occlusive bandage and oral ingestion was avoided by application of an Elizabethan collar for 6 h after administration. Treatment with 4-hydroxytamoxifen was clinically well tolerated and induced changes such as decreased food consumption and body weight gain, uterine and ovarian atrophy, mucification of vaginal epithelium and reduced mammary development, all of which were attributed to its pharmacological action. Mortality was significantly lower in the treated animals. The number of animals with palpable masses was similarly reduced. The incidence of mammary tumours and hypophyseal tumours was markedly lower in 4-hydroxytamoxifen-treated animals. The incidence of chronic tubulo-interstitial nephropathies, a common cause of mortality, was also lowered. There was no evidence of a carcinogenic action of 4-hydroxytamoxifen on the liver, genital organs or skin. Plasma levels of 4-hydroxytamoxifen were stable over the duration of the study and were proportional to the administered dose, exceeding clinical plasma levels by 60-fold at the high dose-level. In conclusion, 4-hydroxytamoxifen is not carcinogenic in the rat and reduces the incidence of spontaneous mammary and hypophyseal tumours.     

Rearrangement of BCR genes in malignant lymphoma.

The Philadelphia chromosome, originally thought to be associated solely with chronic myelogenous leukemia (CML), has since been identified in acute leukemias and in some cases of lymphoma. The Philadelphia chromosome results from reciprocal translocation of genetic material between chromosome 9 and 22 involving the c-abl and BCR genes respectively. Southern blot analysis of the BCR genes was carried out on biopsy specimens from 49 patients presenting with malignant lymphoma without a previously documented CML phase. In two patients, BCR gene rearrangements were detected in the malignant lymph nodes but not in the bone marrow samples. A third patient showed BCR gene rearrangements in the bone marrow but not in the lymph node. From this limited study, it seems that the overall incidence of BCR gene rearrangement in malignant lymphoma is similar to that observed in adult AML.     

Feasibility of using finger arterial pressure in neonates

The feasibility of using a Finapres device to reproduce the beat to beat signal of arterial blood pressure in eight neonates was assessed and compared with intra-arterial measurement of arterial blood pressure in the umbilical artery, using a catheter. The two methods gave similar results. Continuous recording of arterial blood pressure in neonates using Finapres is feasible and reliable.