Effect of blood transfusion on survival after esophagogastrectomy for carcinoma

BACKGROUND: There is growing evidence that blood transfusion is associated with clinical factors that can lead to transfusion-induced immunosuppression. This effect can be beneficial or deleterious. METHODS: The effect of perioperative allogeneic blood transfusion on survival was studied retrospectively in 524 patients who were discharged from the hospital after esophagogastrectomy for carcinoma performed in a single unit over a 10-year period. RESULTS: The median operative blood loss for the series was 500 mL (range, 50 to 3,750 mL). Three hundred thirty-five patients (64%) received a perioperative allogeneic blood transfusion related to esophagogastrectomy, and 189 (36%) did not. The median perioperative blood transfusion administered was 900 mL (range, 300 to 12,950 mL). Perioperative allogeneic blood transfusion was associated with reduced survival for patients in stage III (p < 0.05) at 1 year, but no significant difference was found in this stage at 3 or 5 years after resection. Stage III disease accounted for 250 (48%) of the 524 patients discharged. CONCLUSIONS: Although perioperative allogeneic blood transfusion does not affect long-term survival after esophagogastrectomy for carcinoma, it does have a significant association with short-term survival in a group whose overall survival is often limited after resection. Attention should be directed toward minimizing operative blood loss and transfusing only for factors known to be clinically important, such as oxygen delivery and hemodynamics, not arbitrary hemoglobin levels.     

A spectrophotometric method for the determination of hydroperoxides in liposomes

A modification of the Asakawa-Matsushita iodometric assay method for the determination of the content of lipid hydroperoxides was developed which permits the simultaneous processing of many samples of high lipid content. The method has the advantages of simplicity as well as good reproducibility, so it is not necessary to process standards with each determination. Our technique exceeds the sensitivity attained with other spectrophotometric determinations reported in the literature. The method requires the total elimination of water from the samples, and this was accomplished using an azeotropic mixture of ethanol:water of 96:4. The results obtained with liposomes indicate that the method is applicable to biological material limited to small volume samples, ranging 5-50 microliters. We want to emphasize that this method permits the study of the peroxidation process as function of time.     

The role of cholecystokinin and the cholinergic system in intravenous amino acid-induced gallbladder emptying

BACKGROUND: Recent studies have demonstrated that separate intravenous infusion of amino acids (IVAA) at high doses induces gallbladder emptying. However, little is known about the mechanisms mediating IVAA-induced gallbladder contraction. OBJECTIVE AND METHODS: To investigate whether the effect of IVAA on gallbladder motility is mediated by the cholinergic system and/or cholecystokinin (CCK), the major hormonal stimulus for gallbladder contraction. Six healthy male volunteers were studied in random order on five occasions using: (a) IVAA, (b) loxiglumide (CR 1505, a selective CCK-A receptor antagonist), (c) IVAA plus loxiglumide, (d) atropine and (e) IVAA plus atropine. Gallbladder volumes (ultrasonography) and plasma CCK levels (radioimmunoassay) were determined every 15 min for 60 min before and for 120 min during intravenous infusion of amino acids (Vamin 18EF; 250 mg protein/kg/h) and/or loxiglumide (10 mg/kg/h) and/or atropine (0.005 mg/kg/h). RESULTS: IVAA significantly (P < 0.05) reduced gallbladder volume from 32 +/- 5 ml to 17 +/- 2 ml but induced only a small and transient increase in plasma CCK levels. Loxiglumide given alone significantly (P < 0.05) increased fasting gallbladder volume to 190% of the basal value. IVAA-induced gallbladder emptying was completely abolished by loxiglumide. Maximal gallbladder relaxation during IVAA plus loxiglumide was not significantly different compared to loxiglumide given alone. Concomitant administration of atropine also significantly (P < 0.05) inhibited IVAA-induced gallbladder emptying. CONCLUSION: In healthy volunteers intravenous infusion of high doses of amino acids results in a significant gallbladder contraction, which is inhibited by CCK-A receptor blockade and by atropine.     

The relationship between genetic polymorphisms and disease, illustrated by the renin-angiotensin-aldosterone system and cardiovascular disease

The role of molecular genetics in the pathophysiology of various diseases is becoming clearer and clearer. In the field of cardiovascular diseases, molecular genetic aspects have been shown to play a definite role in the aetiology of these diseases. Several molecular-genetic variations called polymorphisms, occur in the population. The genes encoding the different components of the reninangiotensin-aldosterone system (RAAS), an important system in the regulation of the function and structure of the heart and vascular wall, also display polymorphisms. For some of these polymorphisms associations with various cardiovascular and renal diseases have been described. At present, this is particularly clear for the relation between angiotensin-converting-enzyme (ACE) polymorphism and the incidence of atherosclerotic complications and diabetic nephropathy, and for the relation between so-called M235 T-variant of the angiotensinogen gene and hypertension. Future research will have to show where it is worthwhile to use these and other polymorphisms as a marker for genetic risk. In what way the different RAAS-polymorphisms relate to functional abnormalities is as yet unclear, as are the potential therapeutic implications.     

Expression and purification of recombinant tick anticoagulant peptide (Y1W/D10R) double mutant secreted by Saccharomyces cerevisiae

In determining levels of expression of HIV-1 Nef protein within the central nervous system (CNS) we assessed antibody responses to the protein both peripherally and in CNS. Antibodies to Nef were not detected within the CNS despite detection of antibodies to both gp41 and Nef in peripheral blood and representative virus isolates derived from CNS and peripheral blood (PB) samples containing full length nef sequence and virus-infected cells expressing Nef protein. We conclude from this that expression of Nef within the CNS is such that little or no antibody production occurs and that these differences indicate that Nef protein may not be directly contributing to the AIDS dementia complex. Expression of Nef protein in PHA-activated peripheral blood mononuclear cells from CNS derived isolates was different to that of coincidental PB derived isolates in that partial surface expression was observed for the latter. The results suggest that antigenic presentation of Nef within the CNS is anomalous and that Nef protein expression, at least for the limited number of in vitro derived isolates tested, has a different localization pattern.     

Integrin alpha1beta1 mediates a unique collagen-dependent proliferation pathway in vivo

Activation of integrins upon binding to extracellular matrix proteins is believed to be a crucial step for the regulation of cell survival and proliferation. We have used integrin alpha1-null mice to investigate the role of this collagen receptor in the regulation of cell growth and survival in vivo. alpha1-deficient animals, which are viable and fertile, have a hypocellular dermis and a deficiency in dermal fibroblast proliferation as embryos. In vitro analysis of alpha1-null embryonic fibroblasts has revealed that their proliferation rate is markedly reduced when plated on collagenous substrata, despite normal attachment and spreading. Moreover, on the same collagenous matrices, alpha1-null fibroblasts fail to recruit and activate the adaptor protein Shc. The failure to activate Shc is accompanied by a downstream deficiency in recruitment of Grb2 and subsequent mitogen-activated protein kinase activation. Taken together with the growth deficiency observed on collagens, this finding indicates that the alpha1beta1 is the sole collagen receptor which can activate the Shc mediated growth pathway. Thus, integrin alpha1 has a unique role among the collagen receptors in regulating both in vivo and in vitro cell proliferation in collagenous matrices.     

Estimating country-specific cost-effectiveness from multinational clinical trials

Awareness of the insufficient degree to which mainstream research has created useful knowledge about women's health has drawn many researchers to feminist methodologies. Such approaches tend to privilege qualitative designs, emancipatory objectives, and cooperative strategies. They challenge the notions of expert power, the appropriation of voice, and ownership of the research products. By uncovering the extent to which power inequities are embedded in our research traditions, including such issues as who conducts research, which questions are studied, and how they are studied, feminist critique can be a powerful tool toward stronger research with more socially relevant findings. However, taken to extremes, feminist methodological requirements can immobilize and discourage active inquiry. In this paper, we articulate major directives of a feminist stance, explain the extremes at which they become problematic, and propose responsive options for women's health researchers. We intend such analysis to overcome divisiveness and promote inclusiveness without sacrificing excellence in research and action.     

Repeated exposure of adult rats to Aroclor 1254 causes brain region-specific changes in intracellular Ca2+ buffering and protein kinase C activity in the absence of changes in tyrosine hydroxylase

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants, some of which may be neurotoxic. In vitro studies from this laboratory indicated that noncoplanar PCBs perturbed intracellular signal transduction mechanisms including Ca2+ homeostasis, receptor-mediated inositol phosphate production, and translocation of protein kinase C (PKC). In the present study, we examined the effects of PCBs in vivo by dosing adult male Long-Evans rats orally with Aroclor 1254 (0, 10, or 30 mg/kg/day; 5 days/week for 4 weeks) in corn oil. At 24 h after the last dose, rats were tested for motor activity in a photocell device for 30 min. Immediately, the rats were euthanized, blood was collected for thyroid hormone analysis, and brains were removed, dissected into regions (cerebellum, frontal cortex, and striatum), and subcellular fractions were obtained for neurochemical analysis. Following Aroclor 1254 treatment, body weight gain in the high-dose group was significantly lower than the control and low-dose groups. Horizontal motor activity was significantly lower in rats dosed with 30 mg/kg Aroclor 1254. Ca2+ buffering by microsomes was significantly lower in all three brain regions from the 30 mg/kg group. In the same dose group, mitochondrial Ca2+ buffering was affected in cerebellum but not in cortex or striatum. Similarly, total cerebellar PKC activity was decreased significantly while membrane-bound PKC activity was significantly elevated at 10 and 30 mg/kg. PKC activity was not altered either in cortex or the striatum. Neurotransmitter levels in striatum or cortex were slightly altered in PCB-exposed rats compared to controls. Furthermore, repeated oral administration of Aroclor 1254 to rats did not significantly alter forebrain tyrosine hydroxylase immunoreactivity or enzymatic activity. Circulating T4 (total and free) concentrations were severely depressed at both doses in Aroclor 1254-exposed rats compared to control rats, suggesting a severe hypothyroid state. These results indicate that (1) in vivo exposure to a PCB mixture can produce changes in second messenger systems that are similar to those observed after in vitro exposure of neuronal cell cultures; (2) second messenger systems seem to be more sensitive than alterations in neurotransmitter levels or tyrosine hydroxylase involved in dopamine synthesis during repeated exposure to PCBs; and (3) the observed motor activity changes were independent of changes in striatal dopamine levels.