Interrelationship between TP53 gene deletion, protein expression and chromosome 17 aneusomy in gastric adenocarcinoma

Background  

This study evaluates the existence of numerical alterations of chromosome 17 and TP53 gene deletion in gastric adenocarcinoma. The p53 protein expression was also evaluated, as well as, possible associations with clinicopathological characteristics.     

Preparing caregivers for the death of a loved one: a theoretical framework and suggestions for future research

Caring for a terminally ill loved one and the death of that person are two of the most stressful human experiences. Recent research suggests that a substantial number of caregivers are unprepared for the death and that these caregivers may be at greater risk of psychological distress. The literature on preparedness and mental health, however, is in its infancy. The purpose of this paper, therefore, is to summarize the literature in order to stimulate discussion and research on preparedness. It is our view that preparedness for the death of a loved one is an important contributor to caregiver well-being and bereavement outcomes and that more work in this area is needed in order to improve the care provided to caregivers of seriously or terminally ill patients. We briefly review the literature on preparedness, present a theoretical model delineating the relationships between preparedness, caregiver-health care provider communication, and caregiver well-being, and provide suggestions for future research.     

Systematic mechanism-orientated approach to chronic pancreatitis pain

Pain in chronic pancreatitis(CP) shows similarities with other visceral pain syndromes(i.e.,inflammatory bowel disease and esophagitis),which should thus be managed in a similar fashion.Typical causes of CP pain include increased intrapancreatic pressure,pancreatic inflammation and pancreatic/extrapancreatic complications.Unfortunately,CP pain continues to be a major clinical challenge.It is recognized that ongoing pain may induce altered central pain processing,e.g.,central sensitization or pro-nociceptive pain modulation.When this is present conventional pain treatment targeting the nociceptive focus,e.g.,opioid analgesia or surgical/endoscopic intervention,often fails even if technically successful.If central nervous system pain processing is altered,specific treatment targeting these changes should be instituted(e.g.,gabapentinoids,ketamine or tricyclic antidepressants).Suitable tools are now available to make altered central processing visible,including quantitative sensory testing,electroencephalograpy and(functional) magnetic resonance imaging.These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes.The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved.Future research should address the circumstances under which central nervous system pain processing changes in CP,and how this is influenced by ongoing nociceptive input and therapies.Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy,leading to improved treatment of chronic pain in CP and other visceral pain disorders.     

The effect of donor red cell sedimentation rate on efficiency of granulocyte collection by centrifugal leukapheresis

BACKGROUND: Granulocyte collection relies on the use of a red cell- sedimenting agent and is influenced by poorly defined intrinsic donor characteristics. The donor's baseline red cell (erythrocyte) sedimentation rate (ESR), a readily measurable intrinsic donor variable, may influence the effectiveness of red cell-sedimenting agents and affect the granulocyte yield. STUDY DESIGN AND METHODS: The in vitro and in vivo effects of 6-percent hydroxyethyl starch on the donor ESR were prospectively studied in 67 granulocytapheresis procedures with a blood cell separator, and the findings were correlated with granulocyte collection efficiency (GCE). A relationship that predicts the GCE on the basis of the donor ESR was then derived and tested. RESULTS: The 3.7-fold mean increase in the donor ESR measured after in vitro addition of hydroxyethyl starch approximated the 3.3-fold increase measured when it was administered to the donors. Higher baseline ESR correlated with larger in vitro and in vivo hydroxyethyl starch-induced increases in ESR and predicted more efficient cell collections and greater cell yields. Furthermore, both ESR and GCE, which varied significantly among donors, remained constant for a given donor undergoing repeat procedures. The results could be summarized by a simple predictive formula that relates the GCE (%) to the ESR (mm/hour): GCE = 1.3ESR + 45. The GCE and yield as predicted by the formula were accurate within 10 percent of the observed values in six subsequent procedures. CONCLUSION: In granulocyte harvests using a blood cell separator with hydroxyethyl starch as the sedimenting agent, 1) both ESR and GCE vary widely among donors yet may remain relatively constant for a given donor; 2) the baseline ESR correlates with hydroxyethyl starch-modified ESR and with GCE; and 3) it may be possible to predict GCE and yield from the donor's baseline ESR.     

Inhibition of prostaglandin E2 restores defective lymphocyte proliferation and cell-mediated lympholysis in recipients after allogeneic marrow grafting

Prostaglandins are said to influence T and B cell function by inhibiting the generation of interleukin 2 (IL 2) and the formation of suppressor lymphocytes. After bone marrow transplantation, patients usually have a profound immunodeficiency that persists in recipients with chronic graft-v-host disease (GVHD) and generally resolves in long- term survivors without GVHD. In vitro tests of lymphocyte function such as allogeneic mixed lymphocyte culture (MLC) and cell-mediated lympholysis (CML) have been shown to be impaired in many patients. We postulated that prostaglandin E2 (PGE2) plays a role in the impaired in vitro tests. To test this hypothesis, we studied in vitro tests in the presence of PGE2 antagonists, indomethacin, and anti-PGE2 antiserum with cells from 22 short-term patients (less than 100 days postgrafting) and 32 long-term survivors with or without GVHD. Results show that blockade of PGE2 release by indomethacin and anti-PGE2 significantly (P less than .01) enhanced the MLC (+67%) and the CML responses (+10.5%) of cells from long-term survivors with chronic GVHD but not from those of long-term, stable recipients. No enhancement of MLC and CML activity was observed with cells from donors of long-term recipients. In patients shortly after marrow grafting, enhancement in the MLC was not significant. However, CML activity in this patient group was significantly increased (+12.5% in recipients with no GVHD, 8.5% in those with acute GVHD, P less than .01). Indomethacin also suppressed the activity of nonspecific suppressor cells in patients with chronic GVHD. When cells from patients with chronic GVHD were treated with recombinant IL 2 and IL 2 combined with indomethacin, it was possible to get an additional augmentation of lymphocyte proliferation after the addition of indomethacin to IL 2-treated cultures. Thus it is very likely that PGE2 inhibits T lymphocyte proliferation, not exclusively by inhibition of IL2 production or activity. We conclude that PGE2, among other factors, may play a role in the pathogenesis of the immunodeficiency after transplantation. PGE2 does not act primarily by interfering with IL2 but presumably by inducing a suppressorlike activity.