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Biomedical subjects

D L Morris

Publications and source records attributed to D L Morris.

At least 181 records · Page 10Linked to original sources

Serum carotenoids and coronary heart disease. The Lipid Research Clinics Coronary Primary Prevention Trial and Follow-up Study.

OBJECTIVE: To examine the relationship between total serum carotenoid levels and the risk of subsequent coronary heart disease (CHD) events. DESIGN: New analysis of a cohort from the Lipid Research Clinics Coronary Primary Prevention Trial and Follow-up Study (LRC-CPPT). The LRC-CPPT was a multicenter placebo-controlled trial of cholestyramine resin and CHD with a follow-up period of 13 years. Serum carotenoids were measured at baseline. PARTICIPANTS: The placebo group of the LRC-CPPT, which consisted of 1899 men aged 40 to 59 years with type II-a hyperlipidemia and without known preexisting CHD, cancer, or other major illnesses. MAIN OUTCOME MEASURES: Nonfatal myocardial infarctions and deaths attributable to CHD ascertained from hospital records, autopsy reports, and death certificates and reviewed by a panel of cardiologists. RESULTS: After adjustment for known CHD risk factors including smoking, serum carotenoids were inversely related to CHD events. Men in the highest quartile of serum carotenoids had an adjusted relative risk (RR) of 0.64 (95% confidence interval [CI], 0.44 to 0.92) compared with the lowest quartile. For men who never smoked, this RR was 0.28 (95% CI, 0.11 to 0.73). CONCLUSIONS: The LRC-CPPT participants with higher serum carotenoid levels had a decreased risk of incident CHD. This finding was stronger among men who never smoked.

Adult↗

Taurolidine peritoneal lavage as prophylaxis against infection after elective colorectal surgery.

A total of 300 patients undergoing elective colorectal surgery over a 3-year period were randomly assigned to receive intraoperative peritoneal lavage with either taurolidine or saline. Culture swabs were taken from the region of surgery before and after lavage and the development of postoperative infection monitored. Of the positive culture swabs before lavage, a significantly higher proportion were negative after lavage with taurolidine than after that with saline. However, there was no difference in the incidence of postoperative infection between groups, suggesting that taurolidine intraoperative peritoneal lavage confers no clinical benefit over that with saline.

Anti-Infective Agents, Local↗

Cardiac rhythm disturbances due to caval occlusion during hepatic cryosurgery.

Cryoablation is used to treat inoperable hepatic malignancy. We investigated the safety of cryoablation close to the inferior vena cava. Our sheep model showed that it was impossible to create an iceball around the inferior vena cava (IVC) unless this vessel was clamped. When subsequently the IVC was clamped and frozen for 30 min, the anesthetized spontaneously breathing sheep (n = 3) exhibited cardiac arrhythmias typical of hyperkalemia on release of the clamp. The plasma potassium in these sheep rose from a baseline mean (SD) of 5.0 (0.7) mmol/liter to 9.5 (0.9) mmol/liter after release of the clamp at the end of the freeze. These sheep also developed acute hypercapnoea and acidosis. These changes were avoided in subsequent sheep by assisting ventilation mechanically and hyperkalemia and arrhythmias were not seen in this group. Iceball cracking did not occur and the IVC remained intact in all cases. This work suggests that during hepatic cryotherapy of lesions close to the IVC, intraoperative monitoring of potassium is indicated, particularly if caval occlusion is required to achieve adequate iceball thermal distribution.

Acidosis, Respiratory↗

Decreased surface IgM receptor-mediated activation of phospholipase C gamma 2 in B-1 lymphocytes.

Intracellular signaling triggered by the antigen receptor of primary B-1 (CD5+ B) lymphocytes is insufficient to bring about cell cycle progression to S phase; this appears to result from a block in signal propagation prior to the activation of protein kinase C. The present studies were undertaken to evaluate specific elements in the proximal portion of the intracellular signaling cascade to determine the basis for aberrant signal transduction in B-1 cells. There was no evidence for an alteration in src kinase composition or for diminished receptor mediated tyrosine phosphorylation on the part of B-1 cells. Further, phospholipase C gamma 2 was inducibly tyrosine phosphorylated following surface Ig ligation. However, the receptor mediated increase in enzymatic activity of immunoprecipitated phospholipase C gamma 2 was markedly diminished in B-1 as compared with B-2 cells. These results indicate that phospholipase C gamma 2 largely fails to become activated following surface Ig receptor interaction in B-1 cells and suggest that this enzyme may be directly involved in controlling the propagation of progression signals.

Animals↗

The effect of misoprostol on colon cancer.

A synthetic prostaglandin E1 (PGE1) analogue, misoprostol, was investigated for its effects on the growth of colon cancer in two in vivo models. Human colon cancer cell lines C170, LIM2412 and LIM2405 were grown as subcutaneous xenografts on T-lymphocyte deficient ARC(s) nu/nu mice. Tumour volumes were found to be significantly inhibited compared with control in misoprostol-treated animals with two cell lines. C170 was inhibited by 70.5% (P = 0.0001) and LIM2412 by 68.2% (P = 0.01). LIM2405 was inhibited by 33% (P = 0.14) which was not significantly different from the control. In a second experiment, colon cancers were induced in Sprague-Dawley rats using 1,2 dimethyl-hydrazine (DMH). After 10 weeks of treatment, rats were randomized to receive a 5 week course of 20 micrograms/kg per day of oral misoprostol. Misoprostol-treated rats were found to have a similar tumour incidence and staging compared with control animals. Oral administration of misoprostol has an inhibitory effect on early tumour growth of some colonic cancers, but not on established tumours.

Adenocarcinoma↗

CEA reduction after cryotherapy for liver metastases from colon cancer predicts survival.

Serum carcinoembryonic antigen (CEA) levels in 33 Australian patients with hepatic metastases from colorectal cancer were measured before and after treatment with hepatic cryotherapy and intra-arterial chemotherapy. Pre-operative and monthly postoperative CEA measurements were made and the lowest postoperative reading was recorded as a percentage fall from the pre-operative level. There was a highly significant association between the maximum percentage fall in CEA and survival. A 50% increase in the maximum percentage fall in CEA level was associated with one-tenth the risk of death (95% CI RR 0.03 to 0.32, Cox regression). It is estimated that an increase in the maximum percentage fall in CEA of 50% from 25 to 75% was associated with an increase in the median survival from 240 days to over 2 years.

Antineoplastic Agents↗

Cimetidine preserves non-specific immune function after colonic resection for cancer.

Fifty consecutive patients undergoing resection of colorectal cancer were randomized to either receive cimetidine at a dose of 400 mg bd for a minimum of 5 pre-operative days, then intravenously for 2 postoperative days, or to act as controls. Baseline immune function was determined in all patients by in vitro testing of lymphocyte proliferation (LP) in response to mitogen, skin testing for cell mediated immunity (CMI) and measurement of lymphocyte subsets. Immune function was retested in both groups on the second postoperative day. In control patients the mean postoperative LP value was 41% of pre-operative levels (P < 0.0001) and the mean CMI reduced to 29% (P < 0.0001). Patients treated with cimetidine had no significant fall in these parameters. Numbers of T and natural killer (NK) cells fell after surgery in both groups, and B cell numbers were maintained in the cimetidine group. It is concluded that cimetidine reduces the immunosuppression that follows colonic resection.

Aged↗

Influence of socioeconomic status, ethnicity and an educational brochure on compliance with a postal faecal occult blood test.

The study aimed to determine if socioeconomic status and ethnicity affect compliance with postal faecal occult blood test screening, and if compliance can be increased by adding an educational brochure. A pilot intervention study was used in socioeconomically defined postcodes and defined census collection districts of the Southern Sydney Area Health Service. The study population of men and women aged 45 to 75 years was selected from general practice lists in the defined postcodes. Samples were comparable for age, sex, and socioeconomic indices. Compliance, using a general practitioner letter alone, was: for the Australian middle-socioeconomic status sample, 65.8 per cent (95 per cent confidence interval (CI) 59.5 to 72.1), the Australian low-socioeconomic status sample, 63.9 per cent (CI 57.3 to 70.5), the Arabic low-socioeconomic status sample, 33.3 per cent (CI 27.2 to 39.4). With the general practitioner letter plus brochure, compliance was: Australian middle-socioeconomic status sample, 67.0 per cent (CI 60.5 to 73.5), Australian low-socioeconomic status sample, 62.1 per cent (CI 55.3 to 68.9) and Arabic low-socioeconomic status sample, 36.8 per cent (CI 30.6 to 43.0). Compliance was higher in all Australian samples than in Arabic samples. A brochure, designed to increase compliance with testing, had no significant effect in Australian samples. Australian samples of different socioeconomic status complied almost equally. Results suggest that advice from the local doctor is very effective in motivating patients to screen with faecal occult blood testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Cimetidine inhibits in vivo growth of human colon cancer and reverses histamine stimulated in vitro and in vivo growth.

The effect of histamine and cimetidine on the growth of four human colon cancer cell lines was studied. Histamine significantly stimulated the uptake of tritiated thymidine in vitro in a dose dependent manner, to a maximum of 120% and 116% of controls for C170 and LIM2412, respectively. This effect was antagonised by cimetidine, but not diphenhydramine. Histamine also stimulated a dose dependent increase in cyclic adenosine monophosphate accumulation in C170 cells, antagonised by cimetidine. When grown as subcutaneous xenografts in Balb/c nu/nu mice, cimetidine had a significant inhibitory effect on the same two cell lines. The final volume of C170 tumours in animals given cimetidine was 44% of controls. This response was dose dependent, plateauing at a cimetidine dose of 50 mg/kg/day. The final volume of LIM2412 tumours in animals given cimetidine was 60% of controls. Histamine administered locally by a mini-osmotic pump stimulated C170 tumour growth to 164% of controls, was antagonised by cimetidine at a dose of 200 mg/kg/day, but not by lower concentrations. Histamine has a trophic effect on at least two colorectal cancer cell lines in vivo and in vitro. As this effect is antagonised by cimetidine, it may be mediated via tumour histamine type 2 receptors.

Animals↗

Taxotere inhibits in-vitro growth of human colonic cancer cell lines.

Taxotere a semisynthetic analogue of taxol, is prepared from a precursor extracted from needles of the tree, Taxus baccata. It is a mitotic spindle poison more potent than taxol, that increases the rate of microtubule assembly and inhibits depolymerization of microtubules. There has been little research on its effects on colorectal cancer. Five colorectal tumour cell lines were investigated using three modes: flow cytometry (to determine how Taxotere affects the cell cycle), MTT assay, (to examine the cytotoxicity of the drug), and measurement of tritiated thymidine uptake, (to see whether Taxotere affects the rate of DNA synthesis and cell turnover). A time-course experiment, using flow cytometry, showed effects beginning between 0 and 2 hours after exposure. 24-hour assays were conducted for flow cytometry, and showed large changes, arresting most cells in G2/M phases (e.g., cell line LIM 1215 exposed to 1 x 10(-6) M Taxotere showed 72% of cells in G2/M compared to 14.7% in controls). 24 and 48 hour assays were conducted for MTT and measurement of tritiated thymidine uptake. MTT showed significant inhibitory effects, with maximum inhibitions varying between 5 and 70% for different cell lines after 48 hours (P < 0.05), while uptake of tritiated thymidine was not altered. While Taxotere has dose-limited toxicity, our results suggest that many human colonic cancers will be sensitive to Taxotere.

Antineoplastic Agents, Phytogenic↗

Nursing care in Alzheimer's disease.

The care of patients with AD has had an major impact on the practice of nursing. Nurses are concerned with identifying the special care needs of a dementia patient and developing appropriate nursing interventions to maintain the patient's quality of life. AD is a major challenge for clinical nursing and nursing research because of the degenerative nature of the disease and its subsequent functional impairment.

Alzheimer Disease↗