Phospho-akt expression is associated with a favorable outcome in non-small cell lung cancer.

Akt, a Serine/Threonine protein kinase, mediates growth factor-associated cell survival. Constitutive activation of Akt (phosphorylated Akt, P-Akt) has been observed in several human cancers, including lung cancer and may be associated with poor prognosis and chemotherapy and radiotherapy resistance. The clinical relevance of P-Akt in non-small cell lung cancer (NSCLC) is not well described. In the present study, we examined 82 surgically resected snap-frozen and paraffin-embedded stage I to IIIA NSCLC samples for P-Akt and Akt by Western blotting and for P-Akt by immunohistochemistry. P-Akt protein levels above the median, measured using reproducible semiquantitative band densitometry, correlated with a favorable outcome (P = 0.007). Multivariate analysis identified P-Akt as a significant independent favorable prognostic factor (P = 0.004). Although associated with a favorable prognosis, high P-Akt levels correlated with high tumor grade (P = 0.02). Adenocarcinomas were associated with low P-Akt levels (P = 0.039). Akt was not associated with either outcome or clinicopathologic variables.Cytoplasmic (CP-Akt) and nuclear (NP-Akt) P-Akt tumor cell staining was detected in 96% and 42% of cases, respectively. Both CP-Akt and NP-Akt correlated with well-differentiated tumors (P = 0.008 and 0.017, respectively). NP-Akt also correlated with nodal metastases (P = 0.022) and squamous histology (P = 0.037).These results suggest P-Akt expression is a favorable prognostic factor in NSCLC. Immunolocalization of P-Akt, however, may be relevant as NP-Akt was associated with nodal metastases, a known poor prognostic feature in this disease. P-Akt may be a potential novel therapeutic target for the management of NSCLC.     

Effects of tumor necrosis factor alpha on parathyroid hormone-induced increases in osteoblastic cell cyclic AMP

Summary Tumor necrosis factor α (10⁻¹⁰–10⁻⁸M) had no effects on cyclic AMP production by the osteoblastic osteosarcomal cells, Saos-2 and G292, or normal rat calvarial cells. The cytokine did, however, inhibit the parathyroid hormone (PTH)-induced effect on cyclic AMP in the Saos-2 and normal rat osteoblastic cells. This inhibitory effect did not occur on prostaglandin E₂-induced cyclic AMP increases in the osteoblastic cells. Interleukin-1 (10 U/ml −100 U/ml) did not produce any effect on basal levels or PTH-induced cyclic AMP increases in these cells.     

Effect of the calcium entry blocker verapamil on renal ischemia

The ability of the calcium entry blocker verapamil to ameliorate the effects of renal ischemia was studied in ten sheep. Postanesthesia, bilateral cutaneous ureterostomies were placed in each sheep to facilitate urine collection and analysis. Both kidneys were made ischemic for one hour by occluding each renal artery. However, immediately before occlusion of the right renal artery, 0.05 mg/kg of verapamil was injected into the artery. Comparison of urinary creatinine excretion and urine volume for 72 h after reversal of ischemia demonstrated that those kidneys pretreated with verapamil had greater functional preservation (p less than .05). In this study, verapamil appeared to provide protection against renal damage after an ischemic insult.     

Familial risk of cancer among randomly selected cancer probands

Several investigators have reported that relatives of lung cancer probands have a greater-than-normal likelihood for developing some form of cancer. To evaluate whether this familial risk is general for probands with cancer at any site or limited to lung cancer probands, we did a case-control study in which probands having cancer affecting any body site were identified and their pedigree data were tabulated. Telephone interviews and a mailed questionnaire were used to obtain cancer histories and environmental exposures on the families of 41 lung cancer probands, 105 probands with cancer other than lung, and 127 spouse families. Cumulative tobacco exposure (P less than .05), occupational hazards (P less than .005), and age of the family relatives (P less than .0001) were found to be statistically significant predictors of cancer risk. With consideration given for these variables, we determined that siblings of lung cancer probands were at slightly greater risk of cancer of any kind (odds ratio [OR] = 1.43, P = .06) than siblings in the control group. Much of the elevated risk was attributable to an excess of lung cancer (OR = 2.49, P = .06). Siblings of non-lung/non-breast cancer probands were also determined to be at increased risk of lung cancer as well (OR = 1.61, P = .06). For parents, the risk was lower, although parental information may have been underreported.     

Creating empowering meaning: an interactive process of promoting health with chronically ill older Canadians

Many health promotion approaches afford education about disease prevention and enhancement of one's health status. But strategies for enabling older people with chronic illness to better mobilize their resources for everyday living still require development. This practical action research study explored the experiences of 13 purposefully selected older persons who participated in a health promotion intervention premised on the adult education theory of perspective transformation. Findings illuminate health promotion through a holistic interactive process in which professional and chronically ill older person together evolved a caring relationship and enhanced conscious awareness of life and health experiences. Five health-promoting strategies were identified: building trust and meaning; connecting; caring; mutual knowing; and mutual creating. Researchers suggest several important directions to refine professional practice approaches and health care delivery systems in order to promote the health of older persons with chronic conditions.     

Mediation of bradykinin-induced contraction in canine veins via thromboxane/prostaglandin endoperoxide receptor activation

1. Canine jugular and femoral veins were studied to determine the possible importance of thromboxane (TXA2) and prostaglandin endoperoxides (prostaglandin H2, PGH2) in mediating bradykinin(BK)-induced contraction. 2. Isolated vein rings incubated in modified Krebs solution contracted to TXA2/PGH2 analogs SQ26655 and U44069 with potency of contraction exceeding that for BK. The potency ranking for both veins was SQ26655 greater than U44069 greater than BK greater than PGF2 alpha greater than TXB2 much greater than PGD2. 3. The cyclo-oxygenase inhibitors indomethacin (3 x 10(-7) M) and flufenamic acid (10(-5) M) reduced BK contractions without affecting those induced by noradrenaline (NA). 4. TXA2/PGH2 receptor antagonists SQ29548 (10(-8) M) and BM13177 (10(-6) M) strongly inhibited BK-induced tension. The action of antagonists was reversible with negligible influence on NA-elicited contraction. Selective removal of endothelium had no effect on BK-induced contraction or the action of the antagonists. 5. The thromboxane synthase inhibitors dazoxiben (10(-4) M) and CGS 12970 (10(-5) M) had no significant inhibitory effect on BK-induced tension. 6. These results suggest that in canine jugular and femoral vein, the action of BK is largely dependent upon stimulation of the cyclo-oxygenase pathway to produce PGH2 and possibly TXA2, which can activate a smooth muscle TXA2/PGH2 receptor to elicit vasoconstriction.     

Parish nursing: renewing a long tradition of caring.

Parish nurses are experienced registered nurses committed to helping people meet the health needs of their body, mind, and spirit. To fulfill this goal, parish nurses must be health educators and counselors, referral sources, facilitators, patient advocates, healthcare plan interpreters, and multitalented coordinators. The parish nurse uses the skill of nursing assessment of individual and congregational needs and matches the assessment findings to available resources. The parish nurse also advocates increased awareness of health-related issues that lead to earlier and more effective treatment and care. All ages benefit within a context of personal caring and attention offered by a parish nursing model that is often lacking from healthcare delivery systems. Congregations of all sizes, both urban and rural, have successfully started parish nurse programs. Parish nursing programs are a religious response to help bring wholeness and healing to the faith community. The purpose of this article is to explore parish nursing as it has evolved into a model of health care delivery contributing to the empowerment and health of both the individual and the community.     

Canine pancreas and kidney transplantation following total-lymphoid irradiation

The effect of total-lymphoid irradiation on survival of canine pancreas and kidney allografts was studied. TLI had a marked immunosuppressive effect as measured by in vitro immune responses and reduced circulating leukocytes. Despite the changes, median graft survival times for animals treated with 800 cGy (9 days) or 1800 cGy (9.5 days) were not significantly different from untreated control animals (7 days). The addition of low-dose antithymocyte globulin (10 mg/kg/day) on post-transplant days 0, 2, 4, 6, 8, and 10 had no measurable synergistic effect. Similarly, median segmental pancreas allograft survival times after 1700-2200 cGy of TLI treatment (16.5 days) were only marginally longer than those of untreated controls (9 days). The only animal to maintain a graft for greater than 200 days was matched to the donor in mixed lymphocyte culture (MLC). This animal was able to reject a third-party skin graft after 8 days while a graft from the original donor was still surviving after 21 days when the pancreas graft failed from a chronic-type rejection. These results indicate that TLI alone or in combination with ATG will not be predictably effective as a method of prolonging allograft survival. The role of matching major histocompatibility complex antigens in TLI treatment requires clarification.     

Compatibility of cisplatin and fluorouracil in 0.9% sodium chloride injection

The effect of drug concentration and light on the compatibility and stability of cisplatin and fluorouracil in i.v. admixtures was studied. Two sets of admixtures were prepared in 0.9% sodium chloride injection in polyvinyl chloride bags--(1) cisplatin 200 micrograms/mL and fluorouracil 1,000 micrograms/mL and (2) cisplatin 500 micrograms/mL and fluorouracil 10,000 micrograms/mL. Half of the admixtures were protected from light. All admixtures were stored at room temperature (24-26 degrees C), and those admixtures not protected from light were stored under room fluorescent light. After visual inspection, the pH of each admixture was determined, and an aliquot was assayed for drug concentration using a stability-indicating high-performance liquid chromatographic assay. Over a four-hour period, no visual changes were observed and the pH changes observed were negligible. In admixtures containing the lower concentrations of cisplatin and fluorouracil, it took approximately 1.5 hours for the concentration of cisplatin to reach 90% of the initial concentration. By four hours (lower concentration range) and three hours (higher concentration range) after the admixtures were prepared, less than 75% of the initial cisplatin concentration remained. There was less than a 5% decrease measured in the fluorouracil concentrations over the observation time. Admixtures of cisplatin and fluorouracil in 0.9% sodium chloride injection at the concentrations evaluated in this study must be used within one hour of preparation, whether or not they are protected from light. Intravenous administration of fluorouracil and cisplatin by continuous infusion will require alternative approaches to mixing the two drugs in the same container.