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Biomedical subjects

R Sayegh

Publications and source records attributed to R Sayegh.

At least 37 records · Page 2Linked to original sources
PubMed1993

Genotypic classification of colorectal adenocarcinoma. Biologic behavior correlates with K-ras-2 mutation type.

BACKGROUND: New measures enabling better prediction of biologic behavior of large bowel cancer are highly desirable. One hundred ninety-four consecutive primary, recurrent, and metastatic colorectal adenocarcinomas, accessioned during 1991 at Rhode Island Hospital, were classified according to the presence and specific type of K-ras-2 point mutation. METHODS: An integrated histopathologic-genetic approach was used to detect mutations starting with minute, topographically selected, tissue samples from formaldehyde-fixed, paraffin-embedded specimens. RESULTS: Each colorectal adenocarcinoma exhibited either no or only one of seven specific types of K-ras-2 mutation. The mutation type of each primary tumor was present consistently in its metastatic deposits. Thirty-five percent of primary colorectal adenocarcinomas were found to be mutated (42 of 119). A significantly higher mutation rate (65%) was seen in lymphogenous-hematogenous metastases as a group (35 of 54; P < 0.005). By contrast, 22% of anastomotic recurrences and transcoelomic metastasis were mutated (4 of 18). Twenty-eight percent of adenocarcinomas with invasion limited to muscularis propria (Tis, T1, T2) were mutated (16 of 57), compared to 41% for more deeply invasive tumors (T3, T4; 26 of 63). When colorectal adenocarcinomas were analyzed by specific K-ras-2 mutation type, it was found that codon 13 mutated tumors did not progress to local or distant metastasis (P < 0.01). Tumors having a codon 12 valine substitution did not metastasize beyond pericolonic-perirectal lymph nodes. In contrast, colorectal cancers with codon 12 aspartic acid substitutions accounted for most of the distant hematogenous deposits (P < 0.01). Tumors with normal K-ras-2 accounted for most intraperitoneal deposits. CONCLUSIONS: Genotyping of colorectal adenocarcinoma by K-ras-2 status can identify subsets of patients likely to pursue indolent and aggressive forms of disease. The integrated histopathologic-genetic approach outlined is feasible for use in diagnostic pathology, providing information that together with clinicopathologic staging may individualize and optimize treatment.

Adenine↗
PubMed1993

Determination of tumor aggressiveness in colorectal cancer by K-ras-2 analysis.

Markers that predict tumor aggressiveness on a case-by-case basis would enable individualization and optimization of oncologic therapy. To achieve this goal, the presence and specific type of K-ras-2 point mutation was determined from formalin-fixed, paraffin-embedded tissue sites in 247 primary and 166 metastatic-recurrent colorectal adenocarcinomas, using a novel approach consisting of topographic tissue selection, DNA amplification, and direct sequencing applicable to large and needle-biopsy-sized specimens. The results provide the basis for a genotypic classification of colorectal cancer capable of predicting individual tumor aggressiveness, including the pattern and extent of metastasis.

Adenocarcinoma↗
PubMed1993

D21S418E identifies a cAMP-regulated gene located on chromosome 21q22.3 that is expressed in placental syncytiotrophoblast and choriocarcinoma cells.

A partial cDNA (D21S418E) whose nucleotide sequence has no significant homologies with known mammalian DNA sequences was isolated from a human placental library. The cDNA hybridized with a 10-kb transcript present in term placenta. Messages of 10 and 7.5 kb were induced in BeWo and JEG-3 choriocarcinoma cells by treatment with 8-Br-cAMP. The mRNA was not detected in human brain, liver, lung, kidney, pancreas, heart, skeletal muscle, or myometrium. The D21S418E locus was assigned to a 3.5-Mb region of chromosome 21q22.3.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1993

[Detection of Helicobacter pylori by the urease test in 244 patients].

The authors report the results of the detection of Helicobacter Pylori (HP) in gastric mucosa by the urease test, in 244 patients between January 1989 and August 1991. The overall prevalence of HP was 38.1%. It was 19.5% in patients with normal upper gastrointestinal endoscopy (UE), 61% in duodenal ulcer (p < 0.001) and 68.7% in congestive antritis (p < 0.001), significantly higher than in controls. There was no significant difference between controls and patients with erosive antritis or healed duodenal ulcers. The prevalence of HP rises with age in all patients and in those with lesions at UE but not in those with normal UE. A rise of this prevalence seems to exist in the months of June and December. The authors conclude by pointing out the rise of the overall prevalence of HP in congestive antritis compared with erosive antritis, the similarity of prevalence in normal subjects and those with healed ulcer and the lack of influence of age on this prevalence in subjects with normal UE. These conclusions are in need of confirmation by further studies on much more longer series.

Adolescent↗
PubMed1993

Late recurrence of ductal carcinoma in situ at the cutaneous end of surgical drainage following total mastectomy.

A 40-year-old woman underwent upper outer quadrantectomy breast biopsy which revealed extensive intraductal carcinoma, predominantly comedocarcinoma type, with high nuclear grade. Involved ducts were transected at the edge of the biopsy. Total mastectomy with low axillary lymph node dissection was performed 2 weeks later, showing residual intraductal carcinoma in the upper inner quadrant and no evidence of metastasis. Eight years later, the patient developed two separate foci of recurrent, invasive ductal carcinoma at the exit sites for mastectomy drainage in the subcutaneous skin of the upper abdomen. The mastectomy scar was clinically free of tumor. The biological basis for this unusual sequela of treated intraductal carcinoma is discussed together with its importance for management of early breast cancer.

Axilla↗
PubMed1992

Regulated expression of the trophoblast alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein. Differentiation and cAMP modulate protein and mRNA levels.

The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2MR/LRP) has several ligands including activated alpha 2-macroglobulin, pregnancy zone protein, and very low density lipoproteins enriched with apolipoprotein E. The diversity of ligands suggests a role for the alpha 2MR/LRP in a variety of processes including tissue remodeling and lipoprotein metabolism. We examined alpha 2MR/LRP in placental trophoblasts, invasive cells that also function in lipid transport and cholesterol metabolism. alpha 2MR/LRP protein was localized by immunohistochemistry in the syncytiotrophoblast of term placenta. Cytotrophoblasts did not stain prominently. alpha 2MR/LRP (protein and message) in primary cultures of human trophoblast cells increased as cytotrophoblasts differentiated into syncytiotrophoblast. 8-Bromo-cAMP prevented this increase and suppressed alpha 2MR/LRP expression. The cyclic nucleotide had similar suppressive effects on alpha 2MR/LRP in BeWo choriocarcinoma cells. In contrast, low density lipoprotein receptor gene expression was increased. We conclude that: 1) there is a differentiation-dependent pattern of alpha 2MR/LRP expression in the human trophoblast; 2) cAMP negatively regulates alpha 2MR/LRP; 3) there is an inverse relationship between alpha 2MR/LRP and low density lipoprotein receptor gene expression in trophoblast cells.

Base Sequence↗
PubMed1992

Ovarian function after conservational ovarian surgery: a long-term follow-up study.

OBJECTIVE: To determine the long-term effects of conservational ovarian surgery on subsequent ovarian function. METHOD: Medical, surgical and menstrual records of 87 reproductive age women who have undergone pelvic surgery for indications including endometriosis, infertility, and pelvic pain between June 1982 and June 1989 were retrospectively reviewed. RESULTS: Sixty-seven patients had ovarian surgery during their procedure; 26 ovarian cystectomies (OC), 19 partial ovarian resections (OR) and 22 ovariolyses (OL). Twenty patients had no ovarian surgery (NOS). The mean follow-up period was comparable in all groups (OL 32 +/- 15 months, OR 34 +/- 26 months, OC 41 +/- 30 months and NOS 37 +/- 21 months). The mean time to onset of the first postoperative menses was not significantly different among the four groups (OL 24 +/- 7 days, OR 24 +/- 13 days, OC 29 +/- 26 days and NOS 22 +/- 6 days). The cumulative conception rates were not significantly different (OL 23%, OR 37%, OC 19% and NOS 25%). Menstrual disturbances, defined as perceived deviations from preoperative patterns, did not appear to be related to the type or extent of ovarian surgery and occurred in comparable frequencies among patients with or without ovarian surgery (OL 23%, OR 37%, OC 23% and NOS 20%). In the majority of cases, menstrual disturbances occurred either in the early postoperative months and were self-limited, or much later in which case they were related to recurrent endometriosis. Premature ovarian failure has so far occurred in one patient suggesting an incidence comparable to that in the general population. CONCLUSIONS: It is concluded that in this group of patients, conservational ovarian surgery had no significant effects on ovulatory and menstrual function over a prolonged follow-up period.

Adolescent↗
PubMed1992

[Famotidine in the treatment of stomach ulcer].

In order to evaluate the efficacity and tolerance of Famotidine in the treatment of gastric ulcer, in Lebanese patients, we conducted a prospective open study in twenty one patients with benign gastric ulcer. A clinical, endoscopic and biological evaluation was done before, at 4 weeks and if necessary at 8 weeks after the start of 40 mg of Famotidine per day. All patients were carefully monitored at regular intervals for adverse drug reactions by clinical and biological examinations. The healing rate at 4 and 8 weeks was 75% and 91% respectively. The treatment was well tolerated and no modifications in laboratory tests were observed. Famotidine therefore proved effective in the treatment of gastric ulcer and was well tolerated on a short term basis.

Adult↗
PubMed1992

Gonadotropin secreting pituitary microadenoma.

FSH and LH secreting pituitary adenomas may not be as rare as has been previously thought. Women in their reproductive years with a normal estrogenic state and hypergonadotropic amenorrhea should be suspected to harbor a pituitary microadenoma secreting gonadotropins. A computerized tomogram of the pituitary confirms the diagnosis. Two such cases who underwent transphenoidal resection of their adenomas are presented. Pituitary dynamic testing is normal in both. Laparoscopic directed ovarian biopsies show primordial follicles in one and a corpus luteum in the other. Transphenoidal resection, with the risk of permanent hypopituitarism, should be weighed against expectant management, with periodic evaluation of pituitary functions, until the natural history of these adenomas is uncovered.

Adenoma↗
PubMed1992

[Therapeutic problem posed by Gardner's syndrome, report of a Lebanese family].

Gardner's syndrome ie an autosomal dominant disease characterized by the association of a polyposis coli with one or more of specific extracolonic manifestations. A lebanese family is reported. Polyposis coli, desmoid tumors, gastroduodenal polyps, procreation counselling etc. are difficult problems to manage in this syndrome.

Adenomatous Polyposis Coli↗
PubMed1989

Hyperkinetic circulatory syndrome in patients with presinusoidal portal hypertension. Effect of propranolol.

This study evaluates systemic and splanchnic haemodynamics and the effect of propranolol in 15 patients with presinusoidal portal hypertension (portal vein obstruction, n = 11; schistosomiasis, n = 4). These patients exhibited a hyperkinetic circulatory syndrome characterized by high cardiac index (4.4 +/- 1.61.min-1.m-2, mean +/- S.D.) and by low systemic vascular resistance despite normal liver function and sinusoidal pressure. Hepatic blood flow was decreased in half of the patients with portal vein obstruction. Azygos blood flow, an estimate of superior portal-systemic collateral circulation, was markedly increased in all patients (0.46 +/- 0.19 l/min, upper limit of normal: 0.19 l/min). Therefore, in these patients with normal hepatic venous pressure gradient, azygos blood flow measurement provides an index of splanchnic haemodynamic changes. Propranolol administration (15 mg, i.v.) reduced the hyperkinetic circulatory syndrome, with a significant decrease in heart rate (-17 +/- 6%), cardiac index (-25 +/- 12%) and azygos blood flow (-40 +/- 26%) and a significant increase in systemic vascular resistance (+40 +/- 40%). These results suggest that the hyperkinetic circulatory syndrome observed in these patients, could be related to an increase in beta-adrenergic activity. The decrease in azygos blood flow, after propranolol administration, was significantly correlated (r = 0.94) with the increase in right atrial pressure. This finding suggests that propranolol may act through an increase in portal-systemic collateral venous tone. These haemodynamic results justify, in patients with presinusoidal portal hypertension, clinical trials investigating the beneficial effect of beta-blockers on gastrointestinal bleeding caused by portal hypertension.

Adult↗
PubMed1985

[Effects of glypressin on the splanchnic and systemic circulation in patients with cirrhosis].

Although not demonstrated in patients with cirrhosis, it is generally claimed that administration of vasopressin in the form of triglycyl-lysine-vasopressin (glypressin) may prevent untoward systemic effects of this former hormone. The aim of this study was to assess the effects of intravenous administration of 2 mg of glypressin on splanchnic and systemic hemodynamics in 9 patients with cirrhosis under stable circulatory conditions. One hour after the injection, the following statistically significant changes were observed as compared to the baseline values (m +/- SEM): wedged hepatic venous pressure, -9 +/- 2 p. 100; hepatic venous pressure gradient, -16 +/- 3 p. 100; azygos blood flow, -24 +/- 6 p. 100; heart rate, -16 +/- 3 p. 100; cardiac index, -23 +/- 2 p. 100; systemic vascular resistances, +47 +/- 11 p. 100; wedged pulmonary arterial pressure, +44 +/- 15 p. 100. In conclusion, in patients with cirrhosis in a stable hemodynamic condition, intravenous administration of glypressin decreased portal venous pressure and blood flow into the superior portal systemic collateral circulation but did not prevent the untoward systemic hemodynamic effects of vasopressin.

Adult↗
PubMedDate not supplied

Propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis: a prospective study of factors associated with rebleeding.

In a previous randomized trial, we demonstrated that propranolol prevented recurrent gastrointestinal bleeding in patients with cirrhosis. We have undertaken the present study in a new group of patients to ascertain the factors associated with rebleeding. Among 232 patients with cirrhosis admitted for gastrointestinal bleeding, 127 were included. They received propranolol orally at a dose reducing the heart rate by 25%. The median follow-up period was 682 days. The following factors were studied: cause of cirrhosis; severity of cirrhosis; hepatocellular carcinoma recognized after inclusion; compliance; persistent decrease in heart rate; dose of propranolol; alcohol abstinence; previous history of hemorrhage; time interval from hemorrhage to onset of propranolol administration, and source of bleeding. The percentage of patients free of rebleeding was 71% at 1 year and 57% at 2 years. Only five factors were significantly and independently associated with rebleeding: occurrence of hepatocellular carcinoma; lack of compliance; lack of persistent decrease in heart rate; lack of abstinence, and previous history of bleeding. In conclusion, this study confirms the results of our previous trial and suggests that certain factors play a role in the mechanism of rebleeding in patients receiving propranolol.

Adult↗
PubMedDate not supplied

Postprandial hemodynamic responses in patients with cirrhosis.

The hemodynamic response to a 800 kcal liquid meal was investigated in 24 patients (study group) with cirrhosis and two control groups. One control group of six cirrhotic patients (volume control) had a calorie-free equivolumic electrolyte solution. The second control group (normal control) of six patients with normal hepatic function had the same test meal. Cardiac index, mean arterial pressure, heart rate, hepatic venous pressures, hepatic blood flow and azygos blood flow (only measured in the study group) were measured before and 30 and 60 min after the meal. Systemic circulatory responses were generally absent. Hepatic blood flow and wedged hepatic venous pressure increased significantly in both cirrhotic patients and normal controls; however, cirrhotic patients tended to have a quicker response (peaks at 30 min) than normals (peaks at 60 min). Azygos blood flow showed large postprandial variability, but overall did not change significantly. These results demonstrate that the splanchnic circulation of the patient with cirrhosis reacts differently from normals to the physiologic stimulus of a meal, and in particular appears to have precocious vasoactive reactivity.

Alcoholism↗