Colorectal tumor screening in women with a past history of breast, uterine, or ovarian malignancies

Epidemiologic studies have shown that women who have successfully recovered from breast, uterine, or ovarian cancer have about twice the expected risk of developing colorectal cancer. These high-risk women were entered, therefore, into a large bowel screening program based on fecal occult blood detection, flexible sigmoidoscopy, and colonoscopy, when appropriate. The study group consisted of 183 women and the results were compared with 252 comparison subjects of similar age and ethnic origin. Neoplastic lesions, adenomatous polyps, or cancer were 2.5 times more frequent in the study group. However, for the largest group, women with a past history of breast cancer, the relative risk, adjusted for a family history of gastrointestinal cancer, was 3.0 (P = 0.03). This pilot study confirms the value of continuing to screen these patients, especially those with a positive family history of gastrointestinal malignancies. However, for psychological and administrative reasons, it may be better that their colon screening be integrated into a combined colon, breast, and gynecologic tumor follow-up, and not be part of a separate service.     

Cancer risk due to occupational exposure to polycyclic aromatic hydrocarbons

Polycyclic aromatic hydrocarbons (PAHs) demonstrate carcinogenic activity in animal models. Although some epidemiologic studies have implicated PAHs as risk factors for human cancer, the evidence reported to date has not been consistent. The purpose of this report is to describe the associations between occupational exposure to PAHs in the workplace and each of 14 types of cancer. A population-based, case-control study was carried out in Montreal to investigate associations between a large variety of environmental and occupational exposures on the one hand, and several types of cancer on the other. A detailed job history was obtained from each subject along with information on a number of potential confounders. Each job history was reviewed by a team of experts, who used this information to construct a corresponding history of occupational exposures. Among the PAH exposures considered were benzo(a)pyrene (B(a)P) and five categories of PAHs defined on the basis of the source material, namely, wood, petroleum, coal, other sources, and any source. Altogether, 3,730 cancer patients and 533 population controls were interviewed and their job exposure histories coded. For each of 14 types of cancer analyzed, three control groups were available: other cancer patients, population controls, and the pooled set of cancer and population controls. The associations between 14 cancer types and 6 PAH exposures were analyzed using logistic regression methods. For most types of cancer evaluated, there was no evidence of excess risk due to PAHs at the levels encountered in the occupations in which PAH exposure has been prevalent in the Montreal area. For a few cancer sites–the esophagus, the pancreas, and the prostate gland–there were suggestions of excess risk; these observations are noteworthy hypotheses for further investigation. For lung cancer, there appeared to be an increased risk due to PAHs among nonsmokers and light smokers, but not among heavy smokers.     

Evidence of Increased Class I MHC Expression on Human Peripheral Blood Lymphocytes during Acute Ethanol Intoxication

Certain ethanol-related diseases in humans have been linked to disorders of immunity. Although humoral and cellular immunity have been studied, the precise mechanisms whereby ethanol use leads to tissue damage remain unknown. In order to explore the hypothesis that ethanol may lead to alteration in expression of tissue Class I major histocompatibility antigen causing an autoimmune phenomenon, a population of acutely ethanol-intoxicated patients was studied. Measurement of Class I major histocompatibility antigen on peripheral blood lymphocytes in this population showed a highly significant (p less than 0.01) increase over controls. The role that this increased antigenicity may play in the evolution of clinical disease is discussed.     

Best evidence in critical care medicine Selective digestive decontamination decreases mortality and morbidity in the intensive care

SDD reduces ICU and in-hospital mortality, the length-of-stay in the ICU, the frequency of colonization with resistant GNB, and the total costs of antibiotic treatment. This supports the use of SDD in all patients expected to be on mechanical ventilation for at least two days in ICUs that have low prevalence of VRE and MRSA.     

Cyclosporine Interacts with Mycophenolic Acid by Inhibiting the Multidrug Resistance-Associated Protein 2

In mycophenolate mofetil (MMF)-treated organ transplant recipients, lower mycophenolic acid (MPA) plasma concentrations have been found in cyclosporine (CsA) compared with tacrolimus (Tac)-based immunosuppressive regimens. We previously demonstrated that CsA decreases exposure to MPA and increases exposure to its metabolite MPA-glucuronide (MPAG), possibly by interfering with the biliary excretion of MPAG. To elucidate the role of the multidrug resistance-associated protein (Mrp)-2 in the interaction between MMF and CsA, we treated three groups of 10 Mrp2-deficient rats (TR- rat) for 6 days with either vehicle, CsA (8 mg/kg) or Tac (4 mg/kg) by oral gavage. Hereafter, co-administration with MMF (20 mg/kg) was started in all groups and continued through day 14. The 24-h MPA/MPAG area under the concentration-time curve (AUC) was determined after single (day 7) and multiple MMF doses (day 14). On both study days, there were no significant differences in the mean MPA and MPAG AUC between CsA and Tac-treated animals. We conclude that the pharmacokinetics of MMF are comparable in Mrp2-deficient rats receiving either CsA or Tac as co-medication. This finding suggests that CsA-mediated inhibition of the biliary excretion of MPAG by the Mrp2 transporter is the mechanism responsible for the interaction between CsA and MMF.