Cyclosporine and the ischemic rat liver.
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Biomedical subjects
Publications and source records attributed to R Rosati.
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Clinical application in surgery of the large bowel of a compression anastomotic device developed by the Authors is described. The device consists of three plastic rings carried by an instrument that assembles the rings while the bowel is being joined. The rings remain by the anastomotic site until complete healing of anastomosis, then fall into the intestinal lumen and are evacuated with the feces. Sixty-nine patients underwent large bowel anastomosis using this device in our department from May 1986 through June 1989. Forty percent of the anastomoses were located at less than 8 cm from the anal verge. Five intraoperative diverting colostomies were performed (7.2%). The rings were evacuated in average 11 days after the operation, with no or very little discomfort. Operative mortality was 1.4% (one patient died of myocardial infarction). Anastomotic complications were: two (2.8%) clinical and two (2.8%) subclinical dehiscences. This initial clinical experience shows that the anastomotic device is reliable.
As the high risk of sepsis after splenectomy is well recognized, reliable conservative surgical techniques in splenic surgery are widely advocated. Among these, segmental splenectomy carries specific and increasing indications. The use of linear staplers makes this operation quicker and safer. On the basis of a personal observation, Authors examine the anatomical features on which this operation is based, the surgical technique and the technical details to be followed using these devices. The advantages offered by staplers in this surgery allow to widen the indications to partial splenectomy, so as to yield a true primary prophylaxis of the post-splenectomy sepsis.
A clinical series of cysts and fistulas of the thyroglossal tract has been examined. Clinical aspects of this pathology and the results obtained with surgical treatment are compared with reported data.
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A decrease of both hypothalamic and cortical CCK occurred in the brain of rats killed 8 hours after hepatic artery ligation following portocaval anastomosis. Brain CCK depletion was not reproduced by exogenously provoked hyperammonemia nor by insulin-induced hypoglycemia, thus suggesting a central mechanism for the derangement of the CCKergic system in the course of acute liver failure.
In order to investigate the intestinal phase of pancreatic polypeptide (PP) release, the hormonal response to food and cerulein was measured in 19 patients with truncal vagotomy and total gastrectomy (10 with simple esophagojejunal anastomosis and 9 with an additional duodenojejunal anastomosis) and in 7 healthy subjects. After gastrectomy, the early peak of the physiologic biphasic PP response to food was lost but the late predominant phase was unchanged so that the overall postprandial release of the hormone was not significantly lowered. Gastrectomized patients with duodenal bypass had postprandial serum levels only slightly lower than those of patients with preserved duodenal transit of food. Serum PP response to cerulein stimulation was significantly lower in vagotomized patients than in healthy subjects. However, in operated patients as well as in controls, cerulein infusion did induce a rapid increase of plasma PP, followed by persistently elevated levels. The PP response to cerulein was abolished by atropine pretreatment. Our findings indicate that the intestinal phase of meal-stimulated PP response is not dependent on the integrity of vagal pancreatic innervation and that the preservation of the duodenal transit of food after total gastrectomy is not crucial for the maintenance of the enteroinsular axis.
H2-receptor antagonists, such as cimetidine (C), ranitidine (R) and famotidine (F) seem to be effective in the prevention and treatment of stress ulcer in transplant recipients receiving cyclosporin A (CyA). The aim of this study was to detect the possible synergistic nephro- and hepato-toxicity of these drugs, assaying the serum creatinine (SC), ALT, AST levels, and the histological features of 45 young male Sprague-Dawley rats, divided into nine groups of five rats each. After 10 days of treatment the results showed: (i) serum CyA levels were increased in the group receiving daily CyA (5 mg/kg) + R(5 mg/kg) (2430 +/- 403 ng/ml; p less than 0.05 vs. controls) and in the group receiving daily CyA (5 mg/kg) +/- C (10 mg/kg) (2440 +/- 265 ng/ml; p less than 0.01 vs. controls); (ii) ALT and AST levels were increased in this latter group (ALT 223 +/- 133 UL, AST 114.67 +/- 39 UL; p less than 0.01 vs. controls); (iii) SC levels were normal; and (iv) steatosis of the liver was observed in these two groups. These findings suggest that C and R, but not F, may inhibit the hepatic cytochromes P-450 which are involved in the oxidative metabolism of the drugs. Furthermore, the high serum CyA levels seem to play a major role in the appearance of biochemical and histological damage to the liver.
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The effects of low dose Ara-C on cellular oncogene expression were measured in HL-60 and U-937 cell lines and in primary cultures from leukaemic patients. Expression of c-myc was completely abolished in U-937 and greatly reduced in HL-60 after a 3 day exposure to the drug, whereas specific c-fos transcripts were increased. In fresh myeloid leukaemia samples, growth and DNA synthesis were reduced as in the two cell lines. Conversely, changes compatible with the induction of differentiation along the myelomonocytic pathway were much less pronounced than in cell lines treated with the same dose of Ara-C. Cells from one patient did not show any appreciable morphological change. The same sample displayed a greatly reduced expression of c-myc accompanied by a concurrent 10-fold increased expression of c-fos. The data suggest that the action of low dose Ara-C on oncogene expression is comparable to that of other differentiation-inducing agents that display both cytostatic and maturation promoting effects. Evaluation of cellular oncogene expression may therefore represent a useful tool for monitoring effects of low dose Ara-C on leukaemia cells.
The authors report the preliminary results obtained in animal and clinical experimentation of a new mechanical device for circular anastomosis which they have developed. It is a gun that places an apparatus consisting of three polypropylene rings that, through the compression among them of the severed edges of the bowel, realize a sutureless anastomosis and are spontaneously evacuated. Fifty-eight colonic anastomoses were performed in dogs with this device; 23 stapled colonic anastomoses were also executed concurrently. Forty-four animals underwent a relaparotomy to remove the colonic specimen containing the anastomoses. Bursting pressure and the histologic features of the anastomoses were evaluated at different time intervals after operation. A good healing of all compression anastomoses was observed, thereby allowing them to initiate the experience in humans. Thirteen anastomoses (6 colorectal extraperitoneal, 1 colorectal intraperitoneal, 5 colocolonic, 1 ileorectal) were performed at the 1st Surgical Department, Milan University. One subclinical leakage (7.7%) spontaneously healed in a few days. No stenoses were observed.
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Fifteen patients who underwent kidney transplant were studied in order to evaluate the effects of CyA on the gastrointestinal hormonal pattern. Eight patients followed traditional therapy while seven were treated with CyA. The basal gastrinemia values were high only in those patients treated with CyA. This might be due to: an increase in hormone secretion and/or release; a decreased hormone elimination probably due to nephro-hepatic toxicity of CyA; an increase in prostaglandins, caused by CyA, which inhibit secretion of gastri acids.
To evaluate relationships between c-fos proto-oncogene expression and specific lineages of hematopoietic differentiation we analyzed the constitutive and TPA-induced expression of the c-fos gene in a wide variety of fresh human leukemic cells. High constitutive c-fos expression was detected in acute leukemias with monocytic phenotype (FAB M4/M5) and in subsets of B lymphoid leukemias, some of which coexpressed B lymphocytic and monocytic markers. Conversely, low basal levels of c-fos transcripts were found in pure acute granulocytic leukemias (FAB M1/M2/M3), in erythroleukemias (FAB M6), in the great majority of B, and in all T lymphoid leukemias. TPA-induced c-fos expression seems to correlate with monocytoid differentiation only when sustained levels of transcripts (ie, detectable for at least 24 hours) were detected. Sustained c-fos expression was in fact observed only in those myeloid or lymphoid cells that acquired a stable monocyte-like phenotype in response to the phorbol ester. These results indicate that high constitutive c-fos expression may identify myelomonocytic-oriented forms of leukemia, specific subsets of B lymphoid malignancies, and at least some cells terminally differentiated in vitro to a monocyte-like phenotype. c-fos oncogene expression can therefore be regarded as an additional marker for the subclassification of human leukemias.
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