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Biomedical subjects

S Dorudi

Publications and source records attributed to S Dorudi.

29 records · Page 2Linked to original sources

E-cadherin expression in colorectal cancer. An immunocytochemical and in situ hybridization study.

Expression of the epithelial-specific adhesion molecule E-cadherin has been assessed in paraffin-embedded tissue from a series of 72 colorectal carcinomas. Using immunocytochemistry and in situ hybridization it was found that E-cadherin expression was related inversely to tumor differentiation. Out of 44 well- and moderately differentiated tumors, 36 expressed good positivity, whereas 24 of 28 poorly differentiated tumors were E-cadherin-negative. Classification by Dukes stage revealed a highly significant difference (P << 0.001) between A and B (32 positive, four negative) and C1 and C2 (seven positive, 29 negative) stages in terms of immunoreactivity. Of the 32 lymph node metastases studied, 20 were negative for E-cadherin expression, as were seven of eight liver metastases. These results indicate that the down-regulation of E-cadherin levels in vivo is associated with the dedifferentiation, progression, and metastasis of colorectal cancer.

Adenocarcinoma↗

Acute colonic pseudo-obstruction.

The syndrome of acute colonic pseudo-obstruction is well delineated but its aetiology remains poorly understood and patients are still treated inappropriately. This article reviews the pathogenesis and surgical management of this condition. Early diagnosis is stressed as a pivotal factor in reducing morbidity and mortality.

Acute Disease↗

Intestinal ischaemia in the unconscious intensive care unit patient.

This paper highlights the difficulties of diagnosing intestinal ischaemia in unconscious patients on an intensive care unit. We have analysed the clinical details and investigations of eight such patients in whom a preoperative diagnosis of intestinal ischaemia was made on clinical grounds. Intestinal ischaemia was confirmed at laparotomy in only four cases (50%). These patients showed no significant differences in any of the commonly accepted parameters of intestinal ischaemia from the four patients who had a negative laparotomy. In particular, all patients exhibited a metabolic acidosis with fever and a leucocytosis. There was a mean delay of 13.6 h between surgical opinion and laparotomy in the four patients with ischaemia, only one of whom was salvaged. There was no morbidity associated with the laparotomy in this small series. It is suggested that, in the intensive care setting, early laparotomy should be performed immediately the clinical suspicion of intestinal ischaemia arises.

Acute Disease↗

Carcinoma of the gallbladder in ulcerative colitis and primary sclerosing cholangitis. Report of two cases.

The authors present the cases of two patients with carcinoma of the gallbladder complicating chronic ulcerative colitis. Both patients had concomitant primary sclerosing cholangitis. Twelve such cases of gallbladder carcinoma have been reported in the literature. The presence of primary sclerosing cholangitis in patients with ulcerative colitis is associated with malignancy of the extrahepatic biliary tree. It is suggested that, if colectomy is necessary, the liver should be biopsied and a cholecystectomy performed if the gallbladder is deemed abnormal.

Aged↗

Primary restorative colectomy in malignant left-sided large bowel obstruction.

A series of 18 consecutive patients who underwent primary resection and immediate anastomosis as the treatment for malignant left-sided large bowel obstruction are presented. Intraoperative mechanical preparation of the colon was omitted. There was no clinical evidence of anastomotic dehiscence or wound infection. The mean duration of hospital stay was 11 days. It is suggested that colonic continuity can be restored immediately and safely without mechanical bowel preparation, providing attention is directed to constructing an anastomosis that has a good blood supply and is free from tension.

Aged↗

Effects of vasoactive intestinal polypeptide infusions on renal function in patients with liver disease.

1. The effect of intravenous vasoactive intestinal peptide (VIP, 6 pmol/kg per min) on renal function in six patients with cirrhosis of the liver was examined. 2. VIP caused generalized vasodilation and increased plasma renin activity, but diminished the glomerular filtration rate by about one third. 3. The excretion of water, sodium, potassium and calcium also fell significantly. 4. These results differ from our findings in normal man in whom VIP diminished water and electrolyte secretion largely by increasing tubular reabsorption. 5. It is concluded that the elevated VIP levels present in patients with severe liver disease may affect renal function, but that the presence of liver disease may affect renal responses to VIP.

Blood Cell Count↗

Desensitization by noradrenaline of responses to stimulation of pre- and postsynaptic adrenoceptors.

1 The effect of exposing isolated preparations of rat aortic strip, rat atria and mouse vas deferens to perfusions of Krebs solution containing various concentrations of noradrenaline on their sensitivity to the drug has been determined.2 The responses evoked by stimulation of postsynaptic adrenoceptors in all the tissues and presynaptic alpha-adrenoceptors in the mouse vas deferens were diminished by the perfusion of noradrenaline through the organ bath for 30 min.3 The concentration of noradrenaline required to produce desensitization was higher in the mouse vas deferens than in the other tissues and more was required to desensitize the chronotropic responses than the inotropic responses in rat isolated atria.4 The inclusion of cocaine (10(-5) M) in the bathing solution to block uptake(1) increased the sensitivity of most tissues to noradrenaline. With the possible exception of the response to stimulation of presynaptic receptors in the mouse vas deferens, desensitization was somewhat increased in its presence.5 When uptake(2) was blocked by oestradiol (10(-5) M), it was not possible to desensitize the contractor responses of the aortic strip and vas deferens to exogenous noradrenaline, nor the inotropic response of the atria to the drug. However, oestradiol failed to block the desensitization of chronotropic responses and responses to stimulation of presynaptic receptors in the vas deferens.6 Blockade of monoamine oxidase (MAO) with iproniazid (7.2 x 10(-4) M) or with pargyline (5 x 10(-4) M) did not affect the desensitization process in the aortic strip.7 Blockade of catechol-O-methyltransferase (COMT) with U-0521 (5.3 x 10(-5) M) greatly increased desensitization in the aortic strip and desensitization of inotropic responses in the atria. It had no effect on desensitization of chronotropic responses. Its effect on responses in the mouse vas deferens was not determined.8 The perfusion of methoxamine at concentrations about 1000 times higher than those of noradrenaline also produced desensitization in the aortic strip.9 The desensitization of presynaptic receptors in the mouse vas deferens was shown to be specific and that of the responses to postsynaptic receptor stimulation to be non-specific.10 It is concluded that responses to adrenoceptor stimulation may be desensitized by accumulation of noradrenaline inside the cells bearing the receptors and that the desensitization is caused by noradrenaline itself not by a metabolite. Desensitization may also be caused without accumulation of noradrenaline in uptake(2) and for some receptors these may not be alternative mechanisms.

Animals↗

Renal function during vasoactive intestinal peptide (VIP) infusions in normal man and patients with liver disease.

VIP containing nerves are present in the kidney and plasma VIP levels are elevated in cardiac failure and severe liver disease. We studied the effects of intravenous VIP; 6 pmol kg-1 min-1 on 6 normal subjects and 3 patients with liver disease. In normal subjects VIP produced flushing and significant rises in heart rate and pulse pressure but the clearance rates of paraaminohippurate and creatinine did not change significantly. Urine flow fell to about 1/3 and the rate of excretion of electrolytes (except phosphate) fell to about a half of control values. Plasma renin activity rose about 3-fold and there were significant rises in haematocrit and the plasma concentrations of solids, calcium and phosphate. The patients with liver disease responded similarly. Elevated plasma VIP could contribute to salt and water retention in disease states.

Adult↗

Expression of HLA class II in colorectal cancer: evidence for enhanced immunogenicity of microsatellite-instability-positive tumours.

Microsatellite-instability-positive (MSI+) colorectal cancers are characterised by an accumulation of deletion and insertion mutations at simple repeated sequences caused by inactivation of mismatch repair proteins. They share several clinicopathological features, including a better prognosis and a pronounced stromal inflammatory reaction. We have used suppression subtraction hybridisation between normal colonic epithelium and paired carcinomas to generate differential gene expression profiles in MSI+ and MSI- tumours. Following reverse northern blotting analysis, 11 genes were found to be up-regulated in the MSI+ tumour, and one of these specified the HLA-DM gene. This was in contrast to the MSI(-) tumour screen, where none of the clones analysed expressed this class of gene. Our results confirm that MSI(+) tumours may have a greater potential for the efficient presentation of antigens to the helper arm of the immune system and lend further support to the theory that the better prognosis of patients with MSI+ tumours may be linked to an enhanced immunogenicity of these tumours.

Base Sequence↗