Bile duct carcinoma in Egypt: possible etiological factors.

Contrary to an old belief, bile duct carcinoma is not a rare disorder in Egypt. Among 730 patients referred for an ERCP examination, twenty-nine consecutive patients were diagnosed as having bile duct carcinoma. The cause of this type of carcinoma remains unknown. In the present study, only seven of the 29 (24.1%) with bile duct carcinoma patients had associated gallstones. In order to investigate the possible association between typhoid carrier state and bile duct carcinoma, stool cultures were performed for Salmonella typhi and Salmonella paratyphi A and B. Nine out of 23 patients (39.1%) with bile duct carcinoma, 17 out of 50 (34%) with calcular obstructive jaundice, and 1 out of 50 (2%) healthy individuals proved to be salmonella carriers. Statistical analysis of the results confirmed the presence of a significant association between chronic fecal thyphoid carrier state and bile duct carcinoma, while that between calcular obstructive jaundice and bile duct carcinoma was not significant. In conclusion, there might be an association between chronic fecal typhoid carrier state and bile duct carcinoma.     

Detection of Immune Responses in Sentinel Nodes Draining Human Urinary Bladder Cancer

Being the first lymph node to receive drainage from the tumour area, the sentinel node offers a unique possibility to obtain tumour-reactive lymphocytes. We investigated antitumour immune responses in sentinel nodes from patients with bladder cancer, by assaying tumour-specific proliferation and TCR Vβ repertoires. During tumour surgery, sentinel lymph nodes were identified by peri-tumoural injection of blue dye. Fresh specimens of tumour, sentinel and nonsentinel lymph nodes were obtained, and single-cell suspensions were prepared. Cells were assayed for reactivity against autologous tumour extract in [³H]-thymidine incorporation assays and characterized by flow cytometry. Parallel analyses of the expression of Vβ gene families were performed with padlock probes, linear oligonucleotides which upon target recognition can be converted to circular molecules by a ligase. Probes were reacted with cDNA prepared from magnetically separated CD4⁺ cells, and the TCR repertoire was determined by hybridizing the products to oligonucleotide microarrays. Dose-dependent proliferation in response to tumour extract could be detected in sentinel lymph nodes. Common clonal expansions were detected among tumour-infiltrating lymphocytes and in sentinel lymph nodes. Nonsentinel lymph nodes displayed a divergent TCR Vβ repertoire. These results indicate an ongoing immune response against tumour antigens in sentinel nodes, draining urinary bladder cancer. Identification of sentinel lymph nodes makes it possible to obtain tumour-reactive lymphocytes for use in adoptive immunotherapy.     

Role of immunohistochemistry in the diagnosis and progression of follicular epithelium-derived thyroid carcinoma.

Thyroid carcinoma derived from the thyroid hormone-producing follicular epithelium is the most common thyroid malignancy. While the morphologic diagnosis of conventional papillary thyroid carcinoma is simple, thyroid tumors with a follicular pattern are sometimes a diagnostic challenge. It is in the latter group of thyroid neoplasms that ancillary diagnostic tests such as immunohistochemistry may be of great help. Furthermore, while most differentiated thyroid carcinomas have an excellent prognosis, a subset of these tumors may progress to a poorly or undifferentiated phenotype indicating an aggressive biologic behavior that may lead to systemic spread and death. Application of immunohistochemistry to identify a subset of thyroid carcinoma that may progress to a biologically aggressive phenotype may help in the management of patients with thyroid carcinoma. This review discusses the role of immunohistochemistry in the diagnosis and progression of thyroid carcinoma is discussed.     

Induction of mutations by replication of malondialdehyde modified M13 DNA in Escherichia coil: determination of the extent of DNA modification, genetic requirements for mutagenesis, and types of mutations induced

The mutagenicity of the lipid peroxidatlon product, malondialdehyde(MDA), was measured in the lacZ     

Effects of the diuretics mannitol or acetazolamide on nephrotoxicity and physiological disposition of cisplatin in rats

Summary The anticancer drug cisplatin has been known to produce severe renal lesions characterized by high levels of blood urea nitrogen (BUN), toxic nephrosis, and platinum (Pt) retention in the kidney. The effect of IV pretreatment with acetazolamide (ACZ) 30 min before or mannitol (MAN) immediately prior to IP administration of 5 mg/kg cisplatin on Pt excretion, tissue distribution, and nephrotoxicity was investigated in male F344 rats.ACZ pretreatment reduced the cisplatin-induced nephrotoxicity, as indicated by only a slight elevation of BUN, a milder histopathologic lesion, and a more rapid recovery of renal function and structure. Although MAN-pretreated animals exhibited similar changes in BUN to ACZ-pretreated animals, the renal damage was similar to that seen in aninals treated with cisplatin alone. A reduction of kidney Pt content was observed with both diuretics, although there was significantly less retention after ACZ pretreatment.The diuretic ACZ was more effective than MAN in reducing the renal lesions induced by cisplatin and it might be clinically useful in preventing cisplatin nephrotoxicity.     

Leukocytoreduction for acute leukemia.

Both in children and adults, acute leukemia may present with extremely high blast counts; a phenomenon known as hyperleukocytosis. Respiratory failure, intracranial bleeding, and severe metabolic abnormalities frequently occur in acute hyperleukocytic leukemias (AHLs) and are the primary determinants of the high early mortality (20% to 40%) observed. The process leading to these complications has long been known as leukostasis, but the biological mechanisms underlying its development and progression have remained unclear. Traditionally, leukostasis has been attributed to overcrowding of leukemic blasts in the microcirculation, and its treatment has focused on prompt leukocytoreduction. However, it is becoming increasingly evident that leukostasis results from the adhesive interactions between leukemic blasts and the endothelium; a mechanism that none of the current therapies directly addresses. The endothelial damage associated with leukostasis is likely to be mediated by cytokines released in situ and by subsequent migration of leukemic blasts in the perivascular space. The adhesion molecules displayed by the leukemic blasts and their chemotactic response to the cytokines in the vascular microenvironment are probably more important in causing leukostasis than the cell number. This may explain why leukostasis may develop in some patients with AHL and not in others, and why some patients with acute leukemia without hyperleukocytosis (<50,000 blasts/mm(3)) develop leukostasis and respond to leukocytoreduction. Leukapheresis effectively reduces the blast count in many patients with AHL and is routinely used for immediate leukocytoreduction. However, the most appropriate use of leukapheresis in acute leukemia remains unclear, and the procedure may not prevent early death more efficiently than fluid therapy, hydroxyurea, and prompt induction chemotherapy. The use of cranial irradiation remains very controversial and is not generally recommended. The identification of the adhesion molecules, soluble cytokines, and chemotactic ligand-receptor pairs mediating endothelial cell damage in AHL should become a priority if better outcomes are desired.     

Perioperative antinociceptive effects of tramadol. A prospective, randomized, double-blind comparison with morphine

PURPOSE: To compare the efficacy of tramadol and morphine for intra- and postoperative analgesia in patients undergoing laparoscopic cholecystectomy. METHODS: In a prospective, randomized, double-blind study 100 patients were allocated randomly into two groups. Ten minutes before induction of anaesthesia, patients in group 1 received 100 mg tramadol and those in group 2 received 10 mg morphine i.v. Anaesthesia was induced with 5 mg.kg-1 thiopental and was maintained with O2, N2O plus isoflurane with additional doses of tramadol or morphine as decided by the attending anaesthetist. Postoperatively, patients in group 1 and group 2 received tramadol and morphine, respectively, from a patient-controlled analgesia (PCA) device. Pain, analgesic consumption, vital signs and side effects were recorded postoperatively for 24 hr. RESULTS: Intraoperative consumption of tramadol and morphine were 137 +/- 37 and 12.2 +/- 3 mg, respectively. Compared with morphine, patients receiving tramadol had higher blood pressures and required greater mean ETisQ to control haemodynamic variables (P < 0.05). Postoperatively, there were no differences in observer pain score or visual analogue pain score during the first 24 hr between groups except at 30, 45, and 90 min where patients in the tramadol group reported higher pain scores (P < 0.05). The cumulative, 24 hr PCA consumption was 111 +/- 93 and 7.5 +/- 6.6 mg of tramadol and morphine, respectively. CONCLUSIONS: There was no difference between the use of tramadol and morphine to treat pain after laparoscopic cholecystectomy from 90 min after the end of surgery. Morphine was more effective than tramadol as an intraoperative analgesic.     

Enzymes of salvage and de novo pathways of synthesis of pyrimidine nucleotides in human colorectal adenocarcinomas

The activity of uridine-cytidine kinase (Urd-Cyd kinase), a key enzyme in the salvage of pyrimidine nucleosides, averaged 0.86 ± 0.16 (S.E.M.) nmole uridine phosphates · min^?1(mg protein)^?1 in fifty-three specimens of human colorectal adenocarcinomas. The activity of fluorouracil phosphoribosyltransferase (FUPRTase) in thirty-five carcinoma specimens averaged only 0.19 ± 0.07 nmole fluorouridine phosphates · min^?1 · (mg protein)^?1. The activity of the last enzyme in the de novo pathway of biosynthesis of UMP, i.e. orotidine 5'-monophosphate (OMP) decarboxylase, averaged 0.21 ± 0.04 nmole CO₂ · min^?1 · (mg protein)^?1. The activity of Urd-Cyd kinase was increased ~2.3-fold, and that of OMP decarboxylase by about 91%, while that of FUPRTase was increased by only 27%, as compared to that of normal human colonie mucosa. Of the colorectal carcinomas studied, 72% were moderately differentiated, 21% poorly differentiated, and 7% well differentiated. The mean diameter of the fifty-three carcinomas was 5.5 cm, and pathologic staging led to classification of 15% as Dukes' A, 36% as Dukes' B, 47% as Dukes' C, and 2% as carcinoma in situ. No correlations between the level of the enzyme activities studied and any pathologic characteristics of the carcinomas could be discerned.     

Retrospective analysis of sentinel node localization in multifocal, multicentric, palpable, or nonpalpable breast cancer.

Multicentric or multifocal breast cancer is considered as one of the limitations for sentinel lymph node (SLN) localization. We did a retrospective analysis to evaluate the success rate, sensitivity, accuracy, and negative predictive values of SLN localization in multicentric or multifocal breast lesions. METHODS: Fifty-nine patients with multifocal or multicentric breast lesions proven by either fine-needle aspiration (19/59), core biopsy (39/59), or lumpectomy (8/59) underwent SLN localization. Of these patients, 46 had SLN localization by both radiocolloid and blue dye, and 13 had SLN localization by radiocolloid alone. Approximately 10 MBq (99m)Tc-labeled unfiltered sulfur colloid in 0.3-0.4 mL were injected intradermally over the 1 or 2 breast tumor locations 2-4 h before surgery. During surgery, vital blue dye was injected intraparenchymally in 4-6 places around the tumor. All lymph nodes with counts of >10 times that of the background counts, whether or not blue dye positive, and all blue dye-positive lymph nodes, whether or not radiocolloid positive, were excised and labeled accordingly. All lymph nodes underwent frozen sectioning and were examined by hematoxylin and eosin and immunohistologic (cytokeratin) staining. RESULTS: Of the 59 patients, 48 had axillary lymph node dissection irrespective of the results of pathologic examination of the SLN. The success rate, sensitivity, negative predictive value, and accuracy were 93%, 100%, 100%, and 100% using the radiocolloid probe, 87%, 100%, 100%, and 100% using blue dye, and 93.5%, 100%, 100%, and 100% using combined methods, respectively. Concordance between blue dye and radiocolloid was 91% (the incidence of the number of sentinel nodes detected was 37.5%, 30.3%, 10.7%, and 21.4% for 1, 2, 3, and 4 or more lymph nodes, respectively). Metastatic lymph node involvement was found in 39.5% of patients. CONCLUSION: The sentinel node localization approach showed a high negative predictive value in breast cancer patients with multifocal or multicentric lesions, contrary to the common belief of significant false-negative results in these patients.