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D Murray

Publications and source records attributed to D Murray.

At least 145 records · Page 8Linked to original sources
PubMed1995

Evidence for separate mechanisms of cytotoxicity in mammalian cells treated with hydrogen peroxide in the absence or presence of L-histidine.

Treating Chinese hamster ovary cells with 1 mM L-histidine markedly increases their susceptibility to killing by H2O2. The mechanism of this effect has not been firmly established, although previous studies have shown that L-histidine in combination with H2O2, in contrast to H2O2 alone, generates DNA double-strand breaks (DSBs), albeit following supralethal concentrations of the oxidant. Using the highly sensitive pulsed field gel electrophoresis technique, we examined the ability of H2O2-L-histidine combinations to induce DSBs in cells over the same oxidant concentration range that causes cytotoxicity. Thus the correlation between DSB induction and cell killing could be investigated directly without the necessity for extrapolating effects across different concentration ranges. We used a number of treatment protocols that allowed the compartmentation of L-histidine inside or outside the cells, or both. Increased cytotoxicity was invariably associated with the appearance of DSBs, and both parameters were dependent on the intracellular fraction of the amino acid. A linear relationship was found between cytotoxicity and DSB formation when the cells were either treated with H2O2 (at > or = 20 microM) and L-histidine concurrently or were exposed to the oxidant following pre-loading with L-histidine. On the other hand, no DSBs were detected in cells treated with: (a) H2O2 alone; (b) L-histidine plus H2O2 at < or = 20 microM; or (c) H2O2 in association with both L-histidine and excess (20 mM) L-glutamine (which prevents L-histidine uptake). Thus, separate mechanisms appear to underlie the cytotoxic response in cells treated with H2O2 in the absence and presence of L-histidine, with the latter process being associated with the induction of DSBs and having a threshold at approximately 20 microM H2O2. The linear correlation between DSBs and cell killing observed in cells treated with H2O2-L-histidine at H2O2 concentrations > or = 20 microM was similar to (but not superimposable on) the correlation curve established for gamma-irradiated cells; DSBs produced by gamma-rays were associated with more cell killing than those generated by the H2O2-L-histidine combination.

Animals↗
PubMed1995

5-Fluorouracil-radiation interactions in human colon adenocarcinoma cells.

PURPOSE: To determine the effect of cellular proliferation and cell cycle stage on the ability of postirradiation 5-fluorouracil (5-FU) to radiosensitize cultured human colon adenocarcinoma Clone A cells. METHODS AND MATERIALS: Cell survival curves were generated for irradiated: (a) log- and plateau-phase Clone A cells; and (b) Clone A cells separated by centrifugal elutriation into the various phases of the cell cycle; with and without postirradiation treatment with 100 micrograms/ml 5-FU. RESULTS: Postirradiation treatment with 5-FU sensitized proliferating cells to a greater degree than it sensitized cells growing in plateau phase. The beta component of cell kill in log-phase cells was increased by a factor of 1.5 with a sensitizer enhancement ratio of 1.21 at the 0.01 survival level. Plateau-phase cells showed less radiosensitization (sensitizer enhancement ratio of 1.13 at the 0.01 survival level); however, there was a mild increase in both alpha and beta kill in plateau-phase cells. Elutriated G1 cells were the most radiosensitive, independent of treatment with 5-FU. The phase of the cell cycle had little effect on the ability of fluorouracil to radiosensitize Clone A cells. CONCLUSION: Proliferating cells are more susceptible to radiosensitization with 5-FU than plateau-phase cells are, but this effect appears to be independent of the phase of the cell cycle.

Adenocarcinoma↗
PubMed1995

How managed care is roiling internal medicine.

Doctors at the American College of Physicians; annual meeting could talk about little else. We gathered advice there for surviving the marketplace turmoil. We also conducted a poll on job satisfaction (page 31).

Capitation Fee↗
PubMed1995

A phase III randomized, double-blind multiinstitutional trial of vaccinia melanoma oncolysate-active specific immunotherapy for patients with stage II melanoma.

BACKGROUND: In a Phase II trial, surgical adjuvant active specific immunotherapy using a live vaccinia virus-augmented allogeneic polyvalent melanoma cell lysate, vaccinia melanoma oncolysate (VMO), produced a significant disease free interval (DFI) in patients with International Union Against Cancer Stage II melanoma with positive lymph nodes. Therefore, a Phase III randomized prospective, double-blind, multiinstitutional, surgical adjuvant VMO trial was performed to determine the efficacy of VMO to increase the DFI and the overall survival in this group of patients with Stage II disease. METHODS: Two hundred and fifty patients with Stage II melanoma were divided into two postsurgical groups. One group received VMO (total protein equals 2 mg/ml) and the other received the placebo of live vaccinia vaccine virus (V) (10(5.4) TCID50/ml), an adjuvant component of the VMO. Patients initially received these biologics once a week for 13 weeks and then once every 2 weeks for an additional 39 weeks or until recurrence. All surviving patients have been followed for at least 30 months. RESULTS: Statistical analysis of survival data (n = 217) for this first interim analysis shows that there is no statistically significant (P = 0.99) increase in DFI of patients treated with VMO (n = 104) when compared with V (n = 113). The median DFI is 38.0 months for patients treated with VMO and 37.0 months for patients treated with V. At 2- and 4-year intervals, 70 and 38%, respectively, of patients treated with VMO vs. 66 and 36%, respectively, of patients treated with V were free of melanoma. The median overall survival is not available because the patients treated with VMO have not yet reached the 50% mark and the median overall survival is 45.0 months for patients treated with V. At 2- and 4-year intervals, 70 and 38%, respectively, of VMO-treated patients survived when compared with 66 and 36%, respectively, of patients treated with V. Although the overall survival of patients treated with VMO is not statistically significant (P = 0.88) at this point, there is an increasing trend in the overall survival of patients treated with VMO; a 10% increase at the 4-year time point. Moreover, in the subset analysis, VMO-treated male patients (n = 63) showed a 17% improvement in survival at 4-year time point when compared with male patients treated with V (n = 67) (P = 0.19) at the same time point and male patients (n = 20) between the ages of 44 and 57 having 1-5 positive lymph nodes showed a 37% difference in overall survival at the 4-year time point when compared with those patients treated with V (n = 18) (P = 0.13) at the same time point. CONCLUSION: In this first interim analysis, active specific immunotherapy with VMO vs. V showed no difference in the disease free interval or overall survival. Subset analyses likewise showed no significant differences in outcome but the data suggest a potential difference in immunoreactivity between male and female patients with melanoma that awaits further follow up and may merit further investigation.

Adult↗
PubMed1995

Increase of a urokinase receptor-related low-molecular-weight molecule in colorectal adenocarcinomas.

Proteolytic activity is important for tumor growth and metastasis. Plasminogen and urokinase-type plasminogen activator (u-PA) constitute one of the most extensively studied proteolytic systems believed to participate in these processes. u-PA cleaves plasminogen to plasmin, which in turn degrades surrounding extracellular matrix and allows tumor cells to migrate to other areas. The specific receptor for u-PA (u-PAR) has also been implicated as an essential modulator in this pathway. Eleven paired samples of colorectal cancers and normal mucosal tissues from the same patients were removed at surgery. The tissues were homogenized and the supernatants assayed for u-PAR immunoreactivity, u-PAR antigen concentration, u-PAR binding activity and u-PA activity. Immunoblot analysis showed that a major u-PAR species of approximately 55 kDa was present in all tissues. In addition, a protein band of approximately 41 kDa, which crossreacted with anti-u-PAR antibodies, was also found in the tumors. This protein band was either absent, or present in relatively small amounts in the normal colorectal tissues. Cross-linking experiments showed that the approximately 55 kDa band only, and not the approximately 41 kDa band, was able to bind either single chain urokinase-type plasminogen activator (scu-PA) or the amino terminal fragment of urokinase (ATF). The tumor samples also exhibited highly elevated u-PA activity and u-PAR antigen relative to the corresponding normal tissues. Elevated u-PA activity appeared to correlate with elevated u-PAR antigen in colorectal cancers, but not in the normal tissues. These increases were also associated with increase of the u-PAR-related, low-molecular-weight protein in the tumor samples. The measurement of u-PAR and the u-PAR-related protein, in addition to u-PA activity, could have diagnostic or prognostic value in this type of cancer.

Adenocarcinoma↗
PubMed1995

Congestive heart failure in dialysis patients: prevalence, incidence, prognosis and risk factors.

Cardiovascular disease is the most common cause of death in dialysis subjects. Congestive heart failure (CHF) is a common presenting symptom of cardiovascular disease in the dialysis population. Information regarding prevalence, incidence, risk factors and prognosis is crucial for planning rational interventional studies. A prospective multicenter cohort study of 432 dialysis patients followed for a mean of 41 months was carried out. Prospective information on a variety of risk factors was collected. Annual echocardiography and clinical assessment was performed. Major endpoints included death and the development of morbid cardiovascular events. One hundred and thirty-three (31%) subjects had CHF at the time of initiation of dialysis therapy. Multivariate analysis showed that the following risk factors were significantly and independently associated with CHF at baseline: systolic dysfunction, older age, diabetes mellitus and ischemic heart disease. Seventy-six of 299 subjects (25%) who did not have baseline CHF subsequently developed CHF during their course on dialysis. Compared to those subjects who never developed CHF (N = 218) multivariate analysis identified the following risk factors for the development of CHF: older age, anemia during dialysis therapy, hypoalbuminemia, hypertension during dialysis therapy, and systolic dysfunction. Seventy-five of the 133 (56%) subjects with CHF at baseline had recurrent CHF during follow-up. Independent and significant risk factors for CHF recurrence were ischemic heart disease and systolic dysfunction, anemia during dialysis therapy and hypoalbuminemia. The median survival of subjects with CHF at baseline was 36 months compared to 62 months in subjects without CHF. In this study the prevalence of CHF on starting ESRD therapy and the subsequent annual incidence was high.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1995

Complications of nailing in closed tibial fractures.

Reamed intramedullary nailing was used to treat 102 closed tibial shaft fractures. Although a high rate of union was achieved (98%), we noted a higher incidence of complications than previously reported. Thirty-five (37%) patients exhibited one or more components of malunion. In 17 (18%) patients, further operative procedures were required to achieve union or to correct malalignment. New, postoperative peroneal nerve lesions were found in 19 (19%) patients, of which four (4%) failed to resolve. Acute compartment syndrome, requiring fasciotomy, developed in seven (7%) cases after surgery. Two patients developed an atrophic nonunion. In spite of these complications, the overall results were good and we continue to recommend this method of treatment for the displaced, unstable tibial shaft fracture.

Adolescent↗
PubMed1995

SCOTI--a new device for identification of tracheal intubation.

A new lightweight device for the detection of placement of a tracheal tube in the trachea or oesophagus is described. The device utilises a sonic technique detecting resonating frequencies in an open (trachea) or closed (oesophagus) structure. Evaluation of the device in a clinical environment is described and it has been shown to be capable of verifying the correct placement of the tracheal tube in the trachea in 98% of patients studied. Further evaluation of this intubating aid appears justified.

Adolescent↗
PubMed1995

Selection of a hospital based director of pastoral care: process and stakeholders.

Details the steps which were taken in the process of hiring a Director of Pastoral Care for a 274-bed acute care regional referral center in southern Alberta, Canada. Stresses the importance of anchoring the hiring process steps within a relevant context. Offers recommendations for hospitals and clergy faced with a similar project.

Alberta↗