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Biomedical subjects

K Cole

Publications and source records attributed to K Cole.

34 records · Page 2Linked to original sources

Calcium-mediated signal transduction: biology, biochemistry, and therapy.

The process of proliferation, invasion and metastasis is a complex one which involves both the autonomy of the malignant cells and their interaction with the cellular and extracellular environments. The way in which the tumor cells respond to cellular and extracellular stimuli is regulated through transduction of those signals and translation into cellular activity. Transmembrane signal transduction involves three major categories of events: ion channel activation, transmission through guanine nucleotide binding protein intermediates with production of second messengers, and phosphorylation events. A frequent common denominator of these different pathways is a cellular calcium homeostasis. Calcium may be both a result of and a regulator of many of these signal transduction pathways and has been shown to have a role in the regulation of proliferation, invasion, and metastatic potential. The understanding and application of the basic tenets of these pathways to tumor cell proliferation, invasion, and metastases opens a new target for therapeutic intervention. We have identified a novel agent, CAI, which through inhibition of stimulated calcium influx inhibits proliferation and migration in vitro, and growth and dissemination in human cancer xenografts in vivo. CAI offers a new approach to cancer therapy, signal transduction therapy.

Animals↗

Coronary artery fistulas: a review and case study.

Coronary artery fistula is a congenital abnormality that can present with a variety of cardiovascular complications. This article presents a patient with a coronary artery fistula outlining the pathophysiology and course of hospitalization, with particular emphasis on nursing management of a patient with coronary artery fistula.

Adult↗

Change in metabolic control and functional status after hospitalization. Impact of patient activation intervention in diabetic patients.

OBJECTIVE: To determine whether a short intervention to enhance patient information seeking and decision making during hospitalization results in improved metabolic control and functional status in patients with diabetes mellitus. RESEARCH DESIGN AND METHODS: A randomized clinical trial was conducted in which control patients received a comprehensive 3-day evaluation and educational program, whereas experimental patients received a 45-min patient activation intervention and a 1-h self-administered booster in addition to the program. Metabolic control and functional status were measured at baseline and 4 mo postdischarge. RESULTS: During their discharge discussions, experimental patients asked significantly more questions than control patients (7.4 vs. 3.0, P less than .001) and 4 mo later reported significantly fewer physical limitations in activities of daily living than the control group (P = 0.02). Improvement in metabolic control was statistically significant only for experimental patients (P = 0.02), although their glycosylated hemoglobin levels were not significantly lower than control patients' at follow-up. The intervention did not diminish physician satisfaction with patient interactions, although it may have increased physician frustration with responsibilities that competed with patient care. CONCLUSIONS: These results suggest that the addition of a patient activation intervention to a comprehensive diabetes management program may substantially enhance physical functioning among adults with diabetes mellitus.

Activities of Daily Living↗

Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorder.

In recent years, lower serum levels have been recommended for maintenance therapy with lithium. We studied 94 patients with bipolar disorder in a randomized, double-blind, prospective trial of two different doses of lithium for maintenance therapy: the "standard" dose, adjusted to achieve a serum lithium concentration of 0.8 to 1.0 mmol per liter, and a "low" dose, resulting in a serum concentration of 0.4 to 0.6 mmol per liter. The group medians of the patients' average serum lithium levels were 0.83 mmol per liter for the patients in the standard-range group and 0.54 mmol per liter for those in the low-range group. Six of 47 patients (13 percent) assigned to receive lithium doses that would produce serum levels in the standard range had relapses while on protocol, as compared with 18 of 47 (38 percent) assigned to the low-dose range. The risk of relapse was 2.6 times higher (95 percent confidence interval, 1.3 to 5.2) among patients in the low-range group than among those in the standard-range group. Side effects, including tremor, diarrhea, urinary frequency, weight gain, and a metallic taste in the mouth, were more frequent in the standard-range group. We conclude that doses resulting in serum lithium levels from 0.8 to 1.0 mmol per liter are more effective in treating bipolar disorder than those that result in lower serum lithium concentrations, although the higher doses are associated with a higher incidence of side effects. Recent findings about the limited nephrotoxicity of lithium, along with our observations, suggest that physicians should attempt to maintain serum lithium levels between 0.8 and 1.0 mmol per liter in most patients with bipolar disorder and that they should attempt to enhance patients' understanding of and compliance with this regimen.

Adolescent↗

Dexamethasone suppression tests in patients with obsessive-compulsive disorder.

Obsessive-compulsive disorder and major depressive disorder are associated by several lines of evidence. To explore the possible relationship between the two disorders, the authors administered 1-mg dexamethasone suppression tests to 18 patients with obsessive-compulsive disorder and 51 patients with major depressive disorder. None of the obsessive-compulsive patients were classified as nonsuppressors on the basis of a 4:00 p.m. serum cortisol level, whereas 37% of the depressed patients were nonsuppressors. The mean cortisol levels of the two groups differed significantly. Factors that may influence hypothalamic-pituitary-adrenal function, such as age, depressive symptoms, and severity of illness, are discussed in light of these results.

Adolescent↗

Safety and efficacy of bupropion in elderly patients: preliminary observations.

The efficacy and safety of bupropion, an atypical antidepressant, were assessed in depressed patients aged 55 and above. Data were analyzed for 38 patients who completed 4 weeks of double-blind treatment with bupropion in maximum doses of 150 or 450 mg/day; imipramine, up to 200 mg/day; or placebo. Preliminary results suggest that bupropion does have antidepressant activity and is well tolerated in this population. A particular advantage is suggested in terms of cardiovascular side effects.

Age Factors↗

Reducing cancer risk among Native American adolescents.

BACKGROUND: This article discusses the development, implementation, and preliminary testing of an intervention to reduce cancer risks through tobacco use prevention and dietary modification among Native American youth in the Northeastern United States. METHODS: The intervention outcome study includes a research design and outcome measurement instruments. In collaboration with Native American communities, reservations, and organizations in the Northeastern United States, implementation of the design quantifies the separate and combined effects of a tobacco use prevention and a dietary modification intervention. RESULTS: Native American youths in the tobacco prevention intervention and in the combined tobacco and dietary intervention increased their knowledge of tobacco facts and their awareness of the motives of tobacco advertising, and showed higher ratings for an ability to resist peer pressure and to refuse offers of tobacco use between pretest and posttest. Youths in the combined intervention were significantly less apt to report smoking of any kind. Youths in the tobacco use prevention-only condition reported significantly less smoking than their counterparts in the dietary modification-only condition and control condition on 4 of 8 measurement items. As for dietary variables, pretest to posttest measurement scores showed that, after receiving the curriculum, youths in the dietary modification intervention and in the combined intervention improved their knowledge of the health implications of consuming dietary fat, fiber, fruits, and vegetables. Youths in the dietary modification and combined intervention also improved their scores of knowledge related to cancer risk-reducing nutritional practices, cultural dietary habits, and healthy food choices available for Native American cultures. Youths in the dietary modification-only condition report significantly increasing their consumption of complex carbohydrates and significantly decreasing their fat intake between pretest and posttest occasions. CONCLUSIONS: Data from this longitudinal study suggest the value of the FACETS curriculum for helping Native American youth reduce their risks for cancer associated with tobacco use and dietary preference and consumption patterns. In particular, results indicate the enhanced effects of the combined tobacco use prevention and dietary modification intervention for preventing tobacco use and for improving youths' knowledge and attitudes with regard to tobacco use and diet. Further, the study demonstrates the value of collaborating with Native American organizations to design a cancer risk-reducing curriculum and to implement tests of that curriculum.

Adolescent↗

Analysis of mRNA quality in freshly prepared and archival Papanicolaou samples.

OBJECTIVE: To study the feasibility of utilizing mRNA recovered from cytologic Papanicolaou (Pap) specimens as a resource for gene expression studies of normal and diseased cells. STUDY DESIGN: To assess the effects of fixation on mRNA recovery and analysis, fresh Pap samples were processed by three separate methods: (1) routine cytologic fixation (2) 70% ethanol fixation, and (3) air drying without fixation. One-week-old, 1-month-old, 1-year-old and 10-year-old samples were studied to determine the quality of mRNA in archival samples. mRNA quality was analyzed by RT-PCR for the HPRT gene, and by complete transcript amplification. Both heterogeneous (whole slide scrapes) and microdissected cell populations were studied. RESULTS: Reverse transcriptase-polymerase chain reaction (RT-PCR) for the hypoxanthine guanine phosphoribosil transferase gene was positive in all fresh and archival samples and was not affected by fixative, processing methodology or microdissection. Complete transcript amplification followed by gel electrophoresis showed cDNA smears in all fresh samples with a maximum intensity between 1 and 2 kilobases (kb). Amplification of mRNA was not affected by fixation. Smaller cDNA smears were seen in archival specimens with a maximum intensity between 0.5 and 1.5 kb in both one-week-old and one-month-old samples. Smears of approximately 500 base pairs were observed in the 1-year-old and 10-year-old samples. Successful mRNA amplification was possible from microdissected cell populations. CONCLUSION: Messenger RNA recovery and analysis is possible from archival cytologic specimens, suggesting that they can serve as a useful template for RT-PCR analysis of individual genes as well as newly developing high-throughput gene expression methodologies, such as microarrays. Cytologic samples may be particularly useful for study of archival samples as well as diseases from which tissue samples amenable to mRNA-based studies are not available.

Cervix Uteri↗

Growth suppression of esophageal cancer cells by p16INK4 and p15INK4B in vitro.

PURPOSE: We investigate whether p16INK4 and p15INK4B inhibit cellular proliferation and exert a growth suppressive effect on esophageal cancer cells. MATERIALS AND METHODS: The growth suppressive effects of p16INK4 and p15INK4B were evaluated by transfecting vectors containing the p16INK4 cDNA or the p15INK4B cDNA, or both, constitutively driven by a cytomegalovirus promoter, into two human esophageal cancer cell lines containing or lacking endogenous p16INK4 and/or p15INK4B. RESULTS: These experiments demonstrated that in both cells lines tested, the numbers of cells surviving dramatically decreased in p16INK4-transfected and p15INK4B-transfected cells compared with control vector-transfected cells. There was no significant difference in the degree of growth inhibition between p16INK4-transfected and pI5INK4B-transfected cell lines. CONCLUSIONS: These results suggest that p16INK4 and p15INK4B play important roles in the initiation or promotion of esophageal cancer. The inactivation of p16INK4 and p15INK4B may contribute to uncontrolled growth in human cancer.

Carcinoma, Squamous Cell↗