Endoscopic reappraisal of the morphology of congenital obstruction of the posterior urethra.

Congenital obstruction of the posterior urethra was first systematically classified by Young in 1919. Since then, no-one has seriously challenged the presence of both Type I and Type III "valves", although the presence of Type II lesions has often been disputed. A review of Young's papers and more recent anatomical studies, together with endoscopic findings in our own patients, indicates that most congenital posterior urethral obstructions are anatomically similar. Consequently, Young's classification now seems redundant.     

Sevoflurane and anesthesia for neurosurgery: a review

This review assesses the extent to which sevoflurane fulfills the requirements of the ideal inhalational agent for use in neuroanesthetic practice. Sevoflurane's pharmacokinetic profile is outlined. Data from animal and human studies are used to discuss its effects on cerebral hemodynamics, central nervous system monitoring, and cardiovascular parameters. Where possible, sevoflurane is compared with isoflurane, currently considered the inhalational agent of choice in neuroanesthesia. Sevoflurane's potential for toxicity is reviewed.     

Evidence for cytotoxic T lymphocyte response against human lung cancer: reconstitution of antigenic epitope with peptide eluted from lung adenocarcinoma MHC class I

BACKGROUND: Cancer-associated, major histocompatibility complex (MHC)-restricted peptide antigens have been elucidated in human melanomas and ovarian, breast, and renal carcinomas; but relatively little is known about lung cancer antigens. METHODS: To work toward delineation of lung cancer-associated antigens, we developed tumor infiltrating lymphocytes (TILs), peripheral blood mononuclear cell-derived cytolytic T cell lines (CTL), autologous lung cancer cell lines, and normal lung cell lines from 17 patients undergoing lung cancer resections. The TILs and CTL lines were subsequently evaluated for markers of activation and specific lysis of autologous or allogeneic lung cancer cell lines or both. RESULTS: Freshly isolated TILs contained a more activated T cell population compared with the patients' peripheral blood T cells as evidenced by an increased expression of HLA-DR, CD25, and CD45RO. TILs isolated from 15 patients lysed allogeneic lung cancer lines. TILs lysed autologous lung cancer but not autologous normal lung or Epstein-Barr virus transformed B cell lines (B-LCL) in 4 of 8 cases tested, suggesting tumor specificity. A CTL line (RHPBL57.1) was generated from peripheral blood mononuclear cells of an HLA-A24(+) patient by stimulation against an established HLA-A24(+) allogeneic lung cancer cell line. RHPBL57.1 lysed the lung cancer cell line in an HLA-A24-restricted manner. Moreover, RHPBL57.1 specifically lysed autologous B-LCL pulsed with peptides, eluted from MHC class I and isolated from the HLA-A24(+) lung cancer cell line. CONCLUSIONS: TILs isolated from patients with lung cancer are predominantly an activated population of T cells with evidence of tumor and MHC class I-restricted lysis. Furthermore, we provide evidence for a lung cancer-associated, MHC class I-bound peptide antigen(s) that reconstitutes the epitope recognized by a lung cancer specific CD8(+) T cell line derived from a patient with lung cancer.     

The relationship between dietary fat intake and risk of colorectal cancer: evidence from the combined analysis of 13 case-control studies

The objective of this study was to examine the effects of the intakeof dietary fat upon colorectal cancer risk in a combined analysis of datafrom 13 case-control studies previously conducted in populations withdiffering colorectal cancer rates and dietary practices. Original datarecords for 5,287 cases of colorectal cancer and 10,470 controls werecombined. Logistic regression analysis was used to estimate odds ratios (OR)for intakes of total energy, total fat and its components, and cholesterol.Positive associations with energy intake were observed for 11 of the 13studies. However, there was little, if any, evidence of anyenergy-independent effect of either total fat with ORs of 1.00, 0.95, 1.01,1.02, and 0.92 for quintiles of residuals of total fat intake (P trend =0.67) or for saturated fat with ORs of 1.00, 1.08, 1.06, 1.21, and 1.06 (Ptrend = 0.39). The analysis suggests that, among these case-control studies,there is no energy-independent association between dietary fat intake andrisk of colorectal cancer. It also suggests that simple substitution of fatby other sources of calories is unlikely to reduce meaningfully the risk ofcolorectal cancer.     

Semi-quantitation of urokinase plasminogen activator and its receptor in breast carcinomas by immunocytochemistry.

Urokinase plasminogen activator (uPA) is a serine protease involved in cancer invasion and metastasis. uPA acts in vivo by binding to a membrane receptor known as uPAR. In this study, uPA and uPAR levels were semiquantitated by immunocytochemistry in 36 primary breast carcinomas. Using monoclonal antibody HD-UK 1, uPA was detected both in stromal and in malignant cells. However, the predominant location was in the stromal cells. Using double-staining, cells containing uPA were also found to coexpress either cytokeratin (an epithelial cell marker) or more frequently KP1 (a macrophage/monocyte cell marker). With monoclonal antibody HD-uPAR 13.1, uPAR was localized principally to spindle- or macrophage-like stromal cells, especially when these cells surrounded invasive breast cancer. In contrast, uPAR was only rarely detected in cancer cells and was not detected in normal epithelia surrounding tumour or in areas of adenosis. uPA levels in both stromal and epithelial cells were significantly correlated with those for uPAR. We conclude that both uPA and its receptor are mostly present in stromal cells in invasive breast carcinomas. These results suggest that stromal cells collaborate with malignant cells to mediate metastasis.     

Inhibition of alveolar neutrophil immigration in endotoxemia is macrophage inflammatory protein 2 independent

BACKGROUND: Altered transendothelial migration and delayed apoptosis of neutrophils (PMN) have been implicated as contributing to infection in patients with gram-negative sepsis. Macrophage inflammatory protein 2 (MIP-2) signals PMN immigration and may alter other PMN functions. We tested the hypothesis that sequential endotoxin challenge in vivo alters PMN apoptosis and chemotactic responses. MATERIALS AND METHODS: Endotoxemia was induced in male Wistar rats (250 g) via intraperitoneal (IP) administration of LPS (4 mg/kg). After 18 h, intratracheal (IT) injection of LPS (400 microg/kg) was performed. Control animals received saline injections. Four hours after IT-LPS, circulating and bronchoalveolar lavage (BAL) PMN were isolated. PMN yields were calculated, and apoptosis was quantified after 18 h in culture by annexin V-fluorescein isothiocyanate FACS analysis. BAL MIP-2 concentrations were determined by ELISA. PMN chemotaxis to MIP-2 and IL-8 was determined using a fluorescent in vitro migration assay. RESULTS: Endotoxemia (IP-LPS) significantly decreases BAL PMN yield in response to an in vivo IT-LPS challenge. IT-LPS inhibits BAL PMN apoptosis to the same extent as sequential IP/IT-LPS. Alveolar MIP-2 concentrations are similar in the two groups. In vitro migration to IL-8 and MIP-2 was inhibited in PMN from endotoxemic versus control animals. CONCLUSIONS: These data demonstrate that endotoxemia inhibits PMN migration despite similar MIP-2 concentrations in the alveolus. Sequential insults do not affect the inhibition of apoptosis. In vitro, PMN from endotoxemic animals display impaired chemotaxis to MIP-2 and interleukin-8. This may result in an inadequate host defense that contributes to increased ICU-acquired pneumonia in septic patients.