Assessment of toxicopathological effects in ageing laboratory rodents.
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Biomedical subjects
Publications and source records attributed to R Hess.
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Four patients underwent intraoperative photodynamic therapy after surgery with meso-tetra-(hydroxyphenyl)-chlorin (mTHPC-PDT) for diffuse malignant mesothelioma. Preliminary procedures were performed in two patients in order to establish the efficacy of mTHPC-PDT and to optimise its tumoricidal effect. The tumoricidal effect was related to the mTHPC dose, light dose and the time interval between sensitation and activation. 0.3 mg kg-1 mTHPC activated after 48 h with 10 Joules cm-2 of non-thermal laser light at 650 nm resulted in a 10 mm deep tumour infarction, due to tumour vessel necrosis and thrombosis. The mTHPC tissue concentration was up to 14 times higher in the tumour than in normal tissues. Skin photosensitivity was mild, dose dependent and occurred 3 to 10 days after administration of mTHPC. According to the results obtained, intraoperative mTHPC-PDT was performed following pleuropneumonectomy in two, pleurectomy and lobectomy in one and pleurectomy in one patient. Ten Joules cm-2 were delivered to the diaphragm and the costophrenic sulcus and 5 Joules cm-2 to the remaining thoracic cavity. The postoperative course was marked by loss of appetite, fluid retention, hypoproteinemia and severe chest pain. One patient succumbed from aspiration pneumonia. The remaining patients developed no neural or vascular alterations and no bronchial stump insufficiency during follow-up. mTHPC-PDT following surgical tumour resection deserves further evaluation in good risk patients with diffuse malignant mesothelioma.
A polyclonal antibody detecting S-100 protein (S-100) and a monoclonal antibody demonstrating epithelial cell (Lu-5) were used in addition to routine, hematoxylin-eosin stain to improve the identification of tumors of neural or epithelial origin diagnosed in conventionally treated tissue from rat bioassays. Among 108 lesions tested for S-100, 51 reacted positively; they included benign and malignant schwannoma, endomyocardial disease, some cases of benign and malignant thymoma, and renal tubular adenoma. S-100 protein is considered particularly useful for discriminating of neoplasms of Schwann cell origin from mesenchymal tumors. 31 of 51 lesions tested for Lu-5 reacted positively: they comprised adenoma, carcinoma, benign and malignant thymoma and atriocaval node tumor of the heart. Lu-5 was especially useful to distinguish epithelial from mesenchymal neoplasms and was capable of identifying epithelial elements in lymphocyte-rich thymomas as well as in dedifferentiated or autolytic tumors. The binding of both antibodies in neoplastic tissue was compared with a complete set of anatomically normal rat tissues.
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Since Magnusson and Kligman (1969) first described the maximization test, for assessing skin sensitization potential, the test has been substantially validated and data have been obtained on dose-activity relationships. The original method remains acceptable for qualified risk assessment but several modified protocols have been developed to overcome problems with particular test materials. A modified maximization test is described for compounds that are not soluble in the standard vehicles and, therefore, not injectable, and for formulations, to simulate user exposure conditions. The test compounds 2,4-dinitrochlorobenzene, p-phenylenediamine, 1-(3-chlorophenyl)-3- (4-chlorophenyl)-2-pyrazoline, formaldehyde, benzocain, penicillin G, benzylsalicylate, potassium dichromate and isoeugenol, all gave positive reactions. The incidences of positive reactions varied with the sensitization potentials of the compounds. The results for the first six compounds listed above were compared with those obtained by the standard procedure and were found to be similar. We propose that testing guidelines for skin sensitization should accommodate validated modifications of existing standard procedures.
In the present studies we examined the distribution, release, and biological actions of peptide tyrosine tyrosine (PYY) in the rat. The concentration and distribution of PYY was highest in the ileum and colon as determined by both radioimmunoassay of rat tissue extracts and immunocytochemistry. An ultrastructural comparison of rat and dog colonic PYY cells revealed a bipolar distribution of peptide-containing secretory granules in both species. Serum PYY and pancreatic exocrine secretory responses were monitored after presentation of a meal to meal-trained rats (n = 12). A significant increase in PYY concentrations was not observed until 120 min after meal presentation, a delayed response similar to that previously observed in the dog. PYY responses were also observed in rats after perfusion of the intestine at the level of the duodenum and ileum with an 80 mOsm micellar solution of sodium oleate. Duodenal instillations of the fatty acids resulted in a maximum PYY response after 120 min, whereas rats subject to ileal perfusion of fat exhibited maximum PYY release within the first hour. In other experiments, infusion of exogenous PYY at 100 pmol.kg-1.h-1, which reproduced plasma PYY levels observed after a meal and perfusion of the gut with fat, significantly inhibited CCK-stimulated bile pancreatic volume (P less than 0.02), protein (P less than 0.01), and amylase (P less than 0.01) output. These studies demonstrate a bipolar distribution of PYY-containing secretory granules in cells of the jejunal, ileal, and colonic mucosa, and show that PYY is released in response to a meal in amounts sufficient to inhibit cholecystokinin-stimulated pancreatic secretion. Evidence is presented that PYY may mediate the delayed inhibition of pancreatic secretion that is observed in the rat after ingestion of a meal.
Since Jewelewicz in 1975 first described the luteinization of an unruptured follicle (LUF), clinical evidence for the importance of this syndrome has been given by various groups of investigators. Luteal phase of 14 cycles with ultrasound evidence of unruptured follicles were studied with plasmatic determination of levels of FSH, LH, prolactin, 17 B estradiol and progesterone each one day. Two groups were defined. One, with "ovulatory ranges" of progesterone, probably LUF syndrome and another, with "anovulatory levels", probably follicular cysts.
This article describes a cases of "missing strings" of a Zipper IUD embeded in an intracavitary myoma. Two attempts with classical procedures failed to remove it and the diagnosis was done after a hysteroscopy complicated with uterine perforation. It is very difficult to assure if the myoma grew around the IUD or it was perforated at the time of its insertion. Histological evidences lead to the first option.
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To gain a better understanding of the mechanism of action of intrauterine devices (IUDs), a search was made for ova in the genital tracts of 115 women using no contraception and of 56 women using IUDs, all of whom volunteered for study in conjunction with surgical sterilization. Ova were recovered from tubal flushings between 48 and 120 hours after the midcycle peak of luteinizing hormone in 39% of the IUD users compared with 56% of women in the control group (0.05 less than P less than 0.10). This suggests an action of the IUD before the ovum reaches the uterus. Eggs with a microscopic appearance consistent with fertilization were recovered from the fallopian tubes of half of the women using no contraception who had intercourse within the fertile period of the reproductive cycle and from whom ova were recovered. In contrast (P less than 0.01), no eggs with this appearance were recovered in IUD users who had intercourse within the fertile period. No ova were recovered from the body of the uterus of any of the IUD users. Fertilized ova are less likely to reach the uterine cavity containing an IUD. Thus, the principal mode of IUDs is by a method other than destruction of live embryos.
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