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Biomedical subjects

N Murray

Publications and source records attributed to N Murray.

At least 19 recordsLinked to original sources
PubMed1992

A retrospective mortality study within operating segments of a petroleum company.

This retrospective mortality study was conducted among 34,597 oil industry workers in diverse operating segments. Employees were traced through Statistics Canada, and overall mortality (SMR = 0.85) was lower than general population rates and similar to other petrochemical cohorts. The most notable finding was a significant excess of malignant melanoma [observed deaths (N) = 16, SMR = 1.87, 95% CI = 1.07, 3.04], which concentrated among upstream workers (N = 6, SMR = 6.00, 95% CI = 2.19, 13.06), and was directly related to employment duration and latency. Specific substances or hydrocarbon (HC) streams could not be implicated, although possible explanations include dermal HC exposure, ultraviolet light exposure, or a synergistic effect between these two factors. Marketing/transportation workers showed a non-significant excess of multiple myeloma (SMR = 1.81), which was also related to employment duration, latency, and commencement of employment before 1950. Lymphatic cancer, skin cancer, and kidney cancer mortality was not elevated in refinery workers, a finding at odds with some previous refinery worker studies. Although the malignant melanoma and possibly the multiple myeloma mortality patterns are consistent with an occupational link, further studies are needed to investigate the relationship of these diseases with particular exposures.

Aortic Aneurysm↗
PubMed1992

Antigen presentation in virus infection.

Important recent advances have been made in our understanding of antigen processing of cytoplasmic antigens and presentation by class I molecules of the MHC. Peptide transporter-like molecules encoded within the MHC have been characterized and have, by transfection, corrected some of the presentation-mutant cell lines. The nature of peptide-MHC class I interactions has been clarified by further resolution of the HLA A2 and B27 crystals and elution of peptides. The differences between antigenicity and immunogenicity for viral antigens have been highlighted by studies in transgenic animals.

Animals↗
PubMed1991

Brief intensive chemotherapy for metastatic non-small-cell lung cancer: a phase II study of the weekly CODE regimen.

Fifty-three patients, 17 with stage IIIB and 36 with stage IV non-small-cell lung cancer, were given CODE (cisplatin, vincristine, doxorubicin, and etoposide) plus antibiotic prophylaxis and an antiemetic regimen in an intensive chemotherapy program emphasizing weekly treatment and a planned brief duration (9-12 weeks); for 45 of these patients, the CODE program also included antifungal prophylaxis and supportive corticosteroids. Of the total study population, 33 patients (62%) responded to treatment, including five (9%) with complete response. The median survival for the entire group was 42 weeks (55 weeks for those with stage IIIB and 39 weeks for those with stage IV). More than 40% were alive at 1 year. Comparison of granulocyte counts of patients receiving prednisone with those of the subgroup to whom no corticosteroids were given showed less granulocytopenia for those receiving prednisone. Use of prednisone thus allowed improved delivery of myelosuppressive drugs. CODE was halted in nine patients because of disease progression. Although more constitutional side effects are associated with weekly chemotherapy than with standard chemotherapy, only 12 of the remaining 44 patients (27%) failed to receive at least 9 weeks of treatment. Serious toxicity was uncommon: There were no treatment-related deaths and only three episodes of neutropenia with fever. CODE is a novel treatment for non-small-cell lung cancer that this pilot study provided entirely in an outpatient setting over a 9-12 week period with an acceptable incidence of toxicity and a promising level of efficacy. Additional testing and comparison with other regimens or supportive care alone are warranted.

Adenocarcinoma↗
PubMed1991

Experience with intestinal lengthening for the short-bowel syndrome.

Patients with the short-bowel syndrome frequently develop dilated intestinal segments that may lead to impaired motility and malabsorption. Although intestinal tapering alone improves motility, the intestine can be lengthened as well. We reviewed our experience with six children undergoing intestinal lengthening to improve intestinal absorption secondary to the short-bowel syndrome. The procedure was performed by dissecting the vessels along the mesenteric border and dividing the intestine longitudinally with a stapler. Five patients were receiving total parenteral nutrition (TPN) and one was becoming malnourished with enteral feedings alone. Bacterial overgrowth was documented in four patients and abnormal liver function in three patients. The intestinal segments were dilated up to 10 cm in diameter and remnant length ranged from 15 to 79 cm. Segments 5 to 25 cm in length were divided, resulting in an average increase in length of 52%. Necrosis of one of the divided limbs necessitated resection in one patient. Follow-up ranged from 2 to 84 months. TPN has been discontinued in four patients and avoided in another. Symptomatic improvement occurred in all patients. We feel the tapering and lengthening procedure should be considered in patients with symptomatic, dilated intestinal segments in whom the need for TPN may potentially be obviated.

Anastomosis, Surgical↗
PubMed1991

Dose-intensity meta-analysis of chemotherapy regimens in small-cell carcinoma of the lung.

To determine if chemotherapy dose intensity (DI) influences treatment outcome, 60 published studies in limited- and extensive-stage small-cell carcinoma of the lung (SCCL) were retrospectively analyzed for relationship between intended DI and response (complete response [CR] or partial response [PR]) or median survival (MS). Agents used in the regimens included cyclophosphamide (C), doxorubicin (A), vincristine (V), etoposide (E), and cisplatin (P). Relative DI (RDI) of each study regimen was calculated against a reference regimen, and weighted regression analysis was used. Additionally, analysis of individual drug RDI within combinations was performed. For CAV, increasing RDI of the regimen showed no correlation with outcome. For the individual drugs, C RDI correlated positively, while A RDI correlated negatively with attainment of CR in limited disease, but both only after unduly influential observations were eliminated. In extensive-stage disease, A RDI correlated positively with CR+, PR but only in randomized trials, and this correlation lost statistical significance after unduly influential observations were eliminated. For CAE and CAVE, the RDI of the regimens correlated positively with MS in extensive-stage disease as did the C RDI. In limited disease, the C RDI correlated negatively with MS. For EP, no significant correlations were seen. We conclude that DI-outcome correlations are not consistent for these chemotherapy regimens in SCCL. Meta-analysis of retrospective data can generate hypotheses for testing in prospective clinical trials, but study sample and method of analysis can appreciably affect conclusions.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Intensive weekly chemotherapy for the treatment of extensive-stage small-cell lung cancer.

The regimen of cisplatin, vincristine, doxorubicin, and etoposide (CODE) was designed to double the dose intensity of these drugs in comparison with a standard regimen (alternating cyclophosphamide, doxorubicin, and vincristine [CAV] and etoposide-cisplatin [EP]) for extensive-stage small-cell lung cancer (SCLC). The dose intensity was increased by more frequent treatments rather than by increasing the dose size. The structure of this outpatient protocol includes weekly administration of chemotherapy, alternation of myelosuppressive and nonmyelosuppressive treatments, supportive corticosteroids, gastroprotective agents, and prophylactic antibiotics. Although the duration of chemotherapy was brief (9 to 12 weeks), the total cumulative doses of drugs delivered were similar to the standard regimen. Patients with no residual disease outside the chest after chemotherapy received thoracic irradiation, and patients with complete responses (CRs) received prophylactic cranial irradiation. Eligible extensive-stage SCLC patients were ambulatory, younger than 66 years of age, and free of brain metastasis. Forty-eight extensive-stage SCLC patients were treated. Forty-five (94%) responded to chemotherapy, with 19 (40%) attaining CR. After consolidative thoracic irradiation, the CR rate was 56%. The median time to progression was 43 weeks, and the median survival was 61 weeks. The 2-year survival rate was 30%. The most common site of first relapse was brain (38%). Although two patients (4%) died of toxicity, overall toxicity was acceptable for an outpatient regimen. We conclude that the CODE regimen reliably produces palliative remissions for selected extensive-stage SCLC patients, and it may be associated with durable remissions for some patients. The results of this pilot study are sufficiently promising to justify a phase III trial of CODE versus standard (alternating CAV and EP) chemotherapy.

Adult↗
PubMed1990

The effect of various hearing protectors on sound localization in the horizontal and vertical planes.

Listeners were tested under free head/torso movement conditions, using a brief pulsed broadband noise signal presented from any 1 of 20 loudspeakers in two intersecting hemicircumferential arrays: one in the horizontal plane, one in the vertical. The listeners' task was to judge the whereabouts of each signal while listening in normal, open-ears conditions or while wearing various types of standard or electronic earmuffs or compressible foam earplugs. Results showed that listeners could accomplish the task successfully in normal (open-ear) conditions. Results using earplugs, nonelectronic earmuffs, and two types of dichotic (dual microphone) electronic earmuffs showed decrements in performance similar to each other. These decrements took the general form of loss of appreciation of the vertical plane and of front-rear differences in the horizontal plane. Lateral discrimination was blurred but otherwise intact. Of two diotic (single microphone) electronic earmuffs, one completely disrupted localization function and the other came close to it.

Auditory Perception↗
PubMed1990

Mitomycin is active against refractory germ-cell tumors. A phase II study.

Mitomycin was used as single-agent therapy in seven male patients with nonseminomatous germ-cell tumors resistant to platinum analogues. The toxicity was high, especially hematological and pulmonary, in this heavily pretreated group. Mitomycin was active in this situation and one complete and one partial response of 18 and 20 weeks' duration, respectively, were seen.

Adult↗
PubMed1990

Counting the costs of chemotherapy in a National Cancer Institute of Canada randomized trial in nonsmall-cell lung cancer.

An economic evaluation was undertaken of a previously reported National Cancer Institute of Canada (NCIC) trial of chemotherapy in advanced nonsmall-cell lung cancer (NSCLC). That trial had demonstrated a survival benefit associated with the use of either vindesine and cisplatin (VP) or cyclosphosphamide, doxorubicin, and cisplatin (CAP) in relation to best supportive care (BSC). The economic technique used in this evaluation was cost-effectiveness analysis (CEA). All costs were determined from the viewpoint of two provincial health care plans. When compared with BSC, the survival benefit of 8 weeks in favor of patients receiving CAP chemotherapy was associated with an economic saving of $949.49 (in 1984 Canadian dollars). This translated into a savings of $6,171.69 per year of life gained. The mean survival benefit of 12.8 weeks that was obtained with VP chemotherapy compared with BSC was associated with an increased cost of $3,637.60 per patient, or $14,777.75 per year of life gained. The economic evaluation demonstrated that the majority of costs on each of the three treatment arms was related to hospitalization and not to the use of chemotherapy agents. These results compare favorably with estimates of cost-effectiveness (CE) of commonly used treatments for other diseases and demonstrate that a policy of supportive care is associated with costs that may exceed those of active treatment. It is concluded that economic factors should not adversely affect decisions regarding the use of chemotherapy in advanced NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Painful crises in sickle cell disease--patients' perspectives.

One hundred and two patients returned structured questionnaires sent to clinics for sickle cell disease in the United Kingdom in order to gain greater insight into the patients' perception of painful crises. Most patients who suffer pain crises experience a prodromal stage that should be investigated further to find out if prophylaxis is possible. Cold, exertion, and tiredness were the most important precipitating factors. Despite the increase in the amount of knowledge about sickle cell disease in recent years, and though 29 out of 88 patients (30-40%) believed that medical services were improving, 33 out of 88 (30-40%) were still experiencing long delays in being treated in hospital. A third of patients do not seem to receive adequate pain relief.

Adolescent↗
PubMed1988

A phase II study of VP-16 and cisplatin in patients with unresectable malignant mesothelioma. An NCI Canada Clinical Trials Group Study.

The National Cancer Institute of Canada (NCIC) Clinical Trials Group has carried out a phase II study of VP-16 100 mg/m2 daily x 3 and cisplatin 25 mg/m2 daily x 3 in untreated patients with malignant mesothelioma. Twenty-seven eligible patients were entered on the trial and the majority had pleural and/or soft tissue disease. Myelosuppression and gastrointestinal symptoms were the most common toxicities, and were usually mild or moderate in severity. Only 3 partial responses were seen in the 26 patients evaluable (12%). We conclude that the combination of VP-16 and cisplatin when used in this fashion has only minimal activity in mesothelioma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

The role of prophylactic brain irradiation in limited stage small cell lung cancer: clinical, neuropsychologic, and CT sequelae.

Ninety-four patients with limited stage small cell lung cancer treated between 1981 and 1985 with a regimen including prophylactic brain irradiation (PBI) after combination chemotherapy were assessed for compliance with PBI, brain relapse, and neurologic morbidity. Seventy-seven percent of patients had PBI and of these, 22% developed brain metastases after a median time of 11 months post treatment. The brain was the apparent unique initial site of relapse in 10% of PBI cases but more commonly brain relapse was preceded or accompanied by failure at other sites, especially the chest. Brain metastases were the greatest cause of morbidity in 50% of PBI failures. Twelve of 14 PBI patients alive 2 years after treatment had oncologic, neurologic, and neuropsychological evaluation, and brain CT. All long-term survivors were capable of self care and none fulfilled diagnostic criteria for dementia, with three borderline cases. One third had pretreatment neurologic dysfunction and two thirds post treatment neurologic symptoms, most commonly recent memory loss. Fifty percent had subtle motor findings. Intellectual functioning was at the 38th percentile with most patients having an unskilled occupational history. Neuropsychologic impairment ratings were borderline in three cases and definitely impaired in seven cases. CT scans showed brain atrophy in all cases with mild progression in those having a pre-treatment baseline. Periventricular and subcortical low density lesions identical to the CT appearance of subcortical arteriosclerotic encephalopathy were seen in 82% of posttreatment CT studies, and lacunar infarcts in 54%. Neuropsychologic impairment scores and the extent of CT periventricular low density lesions were strongly associated (rank correlation 0.7, p less than .05). Overall, PBI after intensive combination chemotherapy did not induce gross dementia or neurologic dysfunction but its risk/benefit ratio is not overwhelmingly favorable, with failure to prevent brain relapse in 1/5 patients and subtle but detectable motor findings and neuropsychologic impairment in the majority.

Atrophy↗
PubMed1988

Sickle cell-hereditary persistence of fetal haemoglobin and its differentiation from other sickle cell syndromes.

Some haematological indices were compared in 13 subjects with sickle cell-hereditary persistence of fetal haemoglobin (S-HPFH) and in 10 patients with homozygous sickle cell (SS) disease and four patients with sickle cell-beta zero thalassaemia, all with fetal haemoglobin (HbF) levels of 20% or above. Sickle cell-beta zero thalassaemia could be differentiated by a high HbA2 level. S-HPFH could be distinguished from SS disease with a high HbF level by red cell count, HbF level, reticulocyte count, total haemoglobin and total bilirubin level in decreasing power of discrimination.

Adolescent↗
PubMed1988

Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial.

The survival benefit of combination chemotherapy to patients with advanced non-small-cell carcinoma of the lung (NSCLC) is controversial. To study this question, the National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a prospective randomized trial comparing best supportive care (BSC) to two chemotherapy regimens, vindesine and cisplatin (VP), and cyclophosphamide, doxorubicin, and cisplatin (CAP). Between February 1983 and January 1986, 23 centers across Canada entered 251 patients on study. Eighteen centers participated in the three-arm schema (150 patients); centers choosing not to participate in a study with a no-chemotherapy arm followed a two-arm schema comparing VP with CAP (101 additional patients). Altogether, 233 patients were eligible. Patients had measurable or evaluable disease, with either distant metastases (82.5%) or bulky limited disease considered inoperable or unsuitable for radical radiotherapy. The treatment groups were comparable in terms of age, sex, performance status, histology, disease extent, and weight loss. The overall response rates (complete response [CR] plus partial response [PR]) on the chemotherapy arms were CAP, 15.3%, and VP, 25.3% (P = .06). Patients on the three-arm portion of the trial had a median survival of 32.6 weeks when treated with VP, 24.7 weeks with CAP, and 17 weeks with BSC. The significance of the differences in survival, adjusted for prognostic factors, is as follows: chemotherapy v BSC, P = .02; VP v BSC, P = .01; and CAP v BSC, P = .05. Toxicity on the chemotherapy arms was significant, with leukopenia of severe or greater degree occurring in 37.8% (CAP) and 40.0% (VP), severe vomiting in 12.2% (CAP) and 23.3% (VP), and severe neurotoxicity in 15.6% (VP).

Antineoplastic Combined Chemotherapy Protocols↗