[The indications for permanent cardiac pacemaker implantation].
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Biomedical subjects
Publications and source records attributed to N Arber.
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The effect of long-term misoprostol - a synthetic prostaglandin E1 analogue - ingestion on rat gastric morphology and cell turnover was studied. Misoprostol in a daily dose of 90 micrograms/kg or 9,000 micrograms/kg was intragastrically administered to rats. Control rats were treated with the vehicle only. Following 90 days of treatment, 3H thymidine was injected i.v. and rats were sacrificed 1 h later. Tissue sections were prepared from the stomach body and subjected to autoradiography. Misoprostol treatment significantly reduced body weight gain. High dose misoprostol treatment induced significant increases in gastric wall thickness and in gastric gland length. On the other hand, the labelling index was significantly reduced by treatment with high dose misoprostol. These results indicate that chronic administration of misoprostol in high doses increases gastric wall thickness and decreases gastric cell turnover, suggesting that administration of prostanoids causes an increase in cell survival and a decrease in cell shedding.
Thirty male adult rats, were injected with [3H]-thymidine, [3H]TdR. The animals were killed in groups of five, at the following times: 1 h, 14, 30, 60, 90 and 120 days. The livers were fixed in formalin, embedded in paraffin and cut into 5-micron-thick sections, which were then dipped into liquid emulsion and exposed for 3 weeks. The grain content of each sampled cell was counted and its distance from the nearest portal tract rim measured. Since the cells were labelled once and the label was available only for a short period, cell displacement could be followed with time. One hour after labelling, most labelled cells were confined within the 300 micron distance from the portal space rim. From then on, labelled cells advanced at a daily velocity of 2.5 micron toward the terminal hepatic vein. The liver acinus is composed of two compartments: a progenitor compartment extending up to 300 micron from the portal tract and a functional compartment covering the remaining acinus portion. Such an arrangement is known as a two-compartment cell renewal system, and is found in renewing tissues like crypt-villus and epidermis. The hepatocyte moves from the portal space toward the terminal hepatic vein, proceeding along a trajectory, denominated as tissue radius. Since cells move in one direction, the further a cell is from the portal tract, the older it is. One may therefore estimate cell age by measuring its distance from the origin. Since the tissue radius portrays cells of all ages, it describes the entire life history of one cell. The advancing hepatocytes traverse the three acinus zones.(ABSTRACT TRUNCATED AT 250 WORDS)
In previous studies we have shown that hepatocytes stream from the portal tract toward the terminal hepatic vein. The present study provides evidence that littoral cells participate in the same cell stream and that the liver actually streams en masse. Littoral cells stand for sinusoidal endothelia and Kupffer cells. Thirty male adult rats, random bred, were injected with 0.5 microCi [3H]-thymidine, specific activity 5 Ci/mmol/g body weight. The rats were killed in groups of five, at the following times: 1 h, 14, 30, 60, 90 and 120 days. The livers were processed histologically and dipped into liquid emulsion for autoradiography. In each animal 50 labelled hepatocytes and 50 littoral cells were randomly selected and their distance from the nearest terminal portal tract rim was measured. Both cell populations renew their cells continuously. Each consists of two cell types, progenitors, residing around the portal tract up to the distance of 200 microns, and functional cells, which inhabit the rest of the acinus. The two regions where the different cell types reside are known respectively as progenitor (P) and functional (Q) compartments. Both cells are formed in the P-compartment and advance jointly along a trajectory, the tissue radius, toward the terminal hepatic vein where they die. They progress at a daily velocity of 2 micron. Since both advance at the same speed, as long as they exist they remain neighbours. Liver parenchyma and stroma thus stream en masse.(ABSTRACT TRUNCATED AT 250 WORDS)
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The mode of turnover and displacement of cells in the rat parotid gland was studied by means of autoradiography. The parotid parenchyma and stroma act as a two-compartment cell renewal system. Parotid cell progenitors are formed mainly in the intercalated duct from which they progress in opposite directions: to the striated duct on one side, while feeding into the acini on the other. The stroma cells stream along the same tissue radii as the parenchymal cells.
A 76-yr-old woman complained of right lower quadrant abdominal pain, nausea, and fever. There was no history of antibiotic therapy or preceding diarrhea. At laparotomy, a cecal lesion simulating a tumor was found with an otherwise normal colon. Right hemicolectomy was performed. Pathological examination showed pseudomembranous colitis confined to the cecum. It is suggested that pseudomembranous colitis unrelated to prior exposure to antimicrobial agents can occur without diarrhea, and may be a localized process mimicking colonic carcinoma.
Thirty adult male rats were injected with 0.5 microCi [3H]thymidine/g body weight (specific activity 5 Ci/mmol) and killed, in groups of five, 1 h and 14, 30, 60, 90 and 120 days after injection. The displacement of labelled adrenocytes with time was estimated in autoradiograms of adrenal sections. The radial distance of the labelled cell from the capsule was measured with an eyepiece micrometer and expressed in cell location units, i.e. the number of cells separating the labelled cell from the capsule. One hour after labelling, 95% of labelled cells were confined to the outer quarter of the cortex. During the following days, adrenocytes were displaced inwardly, approaching the medulla at a velocity of 0.24 locations/day. They traversed the three cortex zones, reaching the medulla after 104 days. The three adrenal zones represent three differentiation states of the adrenocyte. When young, the adrenocyte secretes aldosterone, after leaving the glomerulosa it produces corticosteroids and on reaching the reticularis it produces sex hormones. The adrenal cortex is a cell renewal system made of two compartments. A progenitor compartment extending between locations 1 and 15, and a functional compartment, covering locations 16-64. The first compartment produces 0.47 cells daily, which enter the second. Half of them die on their way while the rest are eliminated in the reticular zone. The cell stream is nourished by a subcapsular stem cell.
The effects of misoprostol 200 micrograms q.i.d. and cimetidine 300 mg q.i.d. on gastric cell turnover were investigated in duodenal ulcer patients before and after four weeks of therapy. Endoscopic biopsies were incubated with 3H-thymidine. Glandular column length (number of cells per column) and the number of labelled cells per column were determined by autoradiography. There were no significant treatment effects on column length of the gastric pits of either the antrum or fundus. However, misoprostol and cimetidine had opposing effects on cell turnover. Misoprostol significantly decreased the number of labelled cells in antral (P less than 0.01) and fundic (P less than 0.001) gastric pits. However, cimetidine significantly increased (P less than 0.01) the number of labelled cells in antral and fundic columns. The increased gastric cell turnover caused by cimetidine may contribute to its activity in peptic ulcer disease. The decreased cell turnover induced by misoprostol does not appear to be a mechanism responsible for its well-established cytoprotective activity.
The effect of misoprostol and cimetidine on gastric cell turnover was studied. Endoscopic biopsy specimens of fundic and antral mucosa were obtained from duodenal ulcer patients before and after 4 wk of therapy with cimetidine 1.2 g/day or misoprostol 800 micrograms/day. Biopsy specimens were incubated with [3H]thymidine. Glandular column length and number of labeled cells were determined after autoradiography. There was no significant difference in column length of antral or fundic glands before or after therapy with cimetidine and misoprostol. The number of antral and fundic labeled cells was significantly decreased after misoprostol treatment (3.6 +/- 0.3 and 4.6 +/- 0.4, mean +/- SE), as opposed to their respective number before therapy (6.9 +/- 0.5 and 8.3 +/- 0.8) (p less than 0.01). On the other hand, after treatment with cimetidine, the number of antral and fundic labeled cells was significantly higher (11.8 +/- 0.9 and 7.5 +/- 1.0, respectively) as compared with their number before therapy (5.7 +/- 0.5 and 5.6 +/- 0.6, respectively). The decreased gastric cell turnover induced by misoprostol indicates that the trophic effect of prostanoids on gastric mucosa is not due to an increase in cellular kinetics. The increased gastric cell turnover induced by cimetidine may contribute to its therapeutic effect in peptic ulcer disease.
BACKGROUND: Viral infection differs from nonviral infection/inflammation by not producing a significant acute phase response. Since inflammation can cause increased adhesiveness of peripheral white blood cells (WBC), we compared these adhesive properties in individuals with viral infection to those with nonviral infection/inflammation. PATIENTS AND METHODS: The state of leukocyte adhesiveness/aggregation in the peripheral blood of patients with viral versus nonviral infection/inflammation was examined in 101 consecutive patients with acute febrile disease. RESULTS: A significant difference was found between the two groups; 13.6 +/- 7% for viral infection versus 22.8 +/- 8.5% for nonviral infection/inflammation (p < 0.0001). There was also a significant difference in the concentration of fibrinogen (361 +/- 109 mg/dl vs 554 +/- 172 mg/dl, p < 0.0001), and in the CD11b/CD18 cell surface expression (175 +/- 66 vs 210 +/- 100 in peripheral blood polymorphonuclear leukocytes). CONCLUSION: The results of this study could explain, at least in part, the differential adhesive behavior of the WBC in the peripheral blood in the two populations.
Six cases of acute, self-limited colitis that occurred after screening flexible sigmoidoscopy were deduced to be iatrogenic, probably caused by glutaraldehyde residues in the endoscopes after disinfection in an automatic disinfecting machine. The concentration of these residues was indirectly estimated by conductivity measurements of electrolyte concentration in the rinse-water tank of the disinfecting machine during and after five cycles and also in fluid remaining on the surface of the endoscopes and in the endoscope channels. After five cycles, residues in both the rinse water and fluid in the endoscope channels contained the equivalent of 0.2% glutaraldehyde. This was the result of a combination of technical and human errors. It can be prevented by changing the rinse water after each cycle, using forced air to dry the instruments, and washing the endoscopes before use. Users of the automatic disinfecting machine should be aware of the potential accumulation of toxic levels of residues that remain in endoscopes after disinfection.
The question whether there is a transmissible pathogenetic agent as a cause for Crohn's disease, remains unanswered. Measles virus has been the subject of many intensive studies, in the attempt to find a role for it in the pathogenesis of inflammatory bowel disease. Whether an early infection with measles virus may predispose to Crohn's disease in later life is still not clear. We conducted a large scale multicentre study, in order to obtain sufficient data to answer this question. To do so, we compared inflammatory bowel disease patients, with Crohn's disease or ulcerative colitis, with two matched control groups: clinical controls, and community controls. A total of 531 patients, 271 with ulcerative colitis and 260 with Crohn's disease were interviewed, as well as 903 matched controls. Blood from 104 inflammatory bowel disease patients and 50 controls was tested for antibodies to measles virus. We did not find any differences related to measles vaccination, either in Crohn's disease or in ulcerative colitis. Exposure to measles in childhood was more frequent in Crohn's disease patients than in their controls, the difference being statistically significant (p < 0.05) in relation to community controls. The presence of IgG antibodies to measles virus was higher in patients with Crohn's disease than in patients with ulcerative colitis or controls (p = 0.084). Another observation of interest was the finding that Crohn's disease patients who had measles in childhood, more frequently had large bowel disease than those who had not had measles. These data lead us to postulate that there may be a role for measles infection in Crohn's disease, even if, at present, this role remains unclear.
African-American women with breast cancer consistently show a shortened survival when compared with Caucasians with breast cancer, however it is not clear whether this is due to socioeconomic factors or to racial differences in tumor biology. Cyclin D1 overexpression has been demonstrated in 60-80% of female breast cancers, however these studies have not included race or ethnicity data. We examined the level of cyclin D1 protein expression in 139 cases of female breast cancer obtained from different ethnic populations. Using an immunoperoxidase-based technique and a polyclonal anti-cyclin D1 antibody, the rate of overexpression was 68%. Cyclin D1 overexpression tended to be more frequent in cases from non-Caucasian patients when compared with those from Caucasian patients (77% vs. 59%, p=0.051). Our findings suggest that non-Caucasian ethnicity may be important in predicting cyclin D1 overexpression. Cyclin D1 could therefore serve as a possible target in managing breast cancer in the African-American population.
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The purpose of the present study was to document the increased leukocyte adhesiveness/aggregation (LAA) and tissue leukostasis that follow surgical trauma. We found that following major abdominal surgery, the percentage of aggregated leukocytes in the peripheral blood increased from 8.6 +/- 7 to 21.7 +/- 11.5 (p < 0.001), while the respective values for patients undergoing minor surgery were 3.7 +/- 2.4 and 19.7 +/- 7.6% (p < 0.001). The state of LAA was also determined in eight dogs after partial collectomy and four controls. A clear increment in the degree of tissue leukostasis (especially in the spleen, liver and lungs) was noted in the operated as compared to the control animals. In addition, a significant correlation was found between the state of LAA, determined in the venous (p = 0.0004) and arterial (p = 0.002) blood of these animals and the degree of tissue leukostasis. We conclude that a state of increased LAA in the peripheral blood is induced by surgical trauma and that this increased LAA correlates with tissue leukostasis.