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Biomedical subjects

N Murray

Publications and source records attributed to N Murray.

At least 37 records · Page 2Linked to original sources
PubMed1999

The origin of chaos in the outer solar system

Classical analytic theories of the solar system indicate that it is stable, but numerical integrations suggest that it is chaotic. This disagreement is resolved by a new analytic theory. The theory shows that the chaos among the jovian planets results from the overlap of the components of a mean motion resonance among Jupiter, Saturn, and Uranus, and provides rough estimates of the Lyapunov time (10(7) years) and the dynamical lifetime of Uranus (10(18) years). The jovian planets must have entered the resonance after all the gas and most of the planetesimals in the protoplanetary disk were removed.

Journal Article↗
PubMed1999

The influence of age on the delivery, tolerance, and efficacy of thoracic irradiation in the combined modality treatment of limited stage small cell lung cancer.

PURPOSE: To assess the impact of age on the delivery, tolerance, and efficacy of thoracic irradiation (TI) for limited small cell lung cancer (L-SCLC). METHODS AND MATERIALS: This is a retrospective review of data from 608 patients 80 years or less with L-SCLC, who participated in two previously reported randomized trials (BR3 and BR.6) of the National Cancer Institute of Canada. All patients received the same chemotherapy, consisting of cyclophosphamide, doxorubicin, vincristine (CAV), and etoposide cisplatin (EP) delivered either in sequential or alternating sequence. In BR.3, TI was given after chemotherapy with randomization to 25 Gy in 10 fractions or 37.5 Gy in 15 fractions. In BR.6, TI (40 Gy in 15 fractions) was given concurrently with EP with randomization to either the early (with cycle 2, week 4) or late (with cycle 6, week 16) arm. RESULTS: A total of 665 patients entered these two trials. Of these, 608 patients were eligible for analysis, 300 in BR.3 and 308 in BR.6. Five hundred and twenty patients were under age 70 and 88 patients were 70 years or older. Baseline characteristics between the two groups were comparable. In BR3, 179 patients (60%) participated in radiotherapy randomization (61% young, 52% elderly), and 176 patients actually received TI. In BR.6, randomization occurred at study entry for all patients, and 282 (91.6%) patients received TI (92% young, 88% elderly). More patients of both age groups randomized to receive late TI did not receive TI (13% and 14%) than those randomized to the early TI arm (3%) of BR.6. We could identify no tendency to reduce field sizes to minimize toxicity in either age group at higher doses of TI. Once TI was started, there was no difference between the two age groups with regards to the proportion of patients who completed TI, although elderly patients were less likely to complete high dose TI. Of those who completed TI, there was no difference in the time to complete TI, mean dose delivered or in the incidence of acute and late TI-related toxicities. No statistical difference in response rate, local relapse rate, or overall survival was seen between young and older age groups. CONCLUSION: In summary, in the dose range examined, age does not appear to impact on the delivery, tolerance or efficacy of TI in the combined modality management of L-SCLC. Potentially curative combined modality treatment should not be withheld on the basis of age.

Age Factors↗
PubMed1999

A longitudinal study of negative affect and self-perceived competence in young adolescents.

In a 4-wave, 2-year longitudinal design, the authors obtained measures of negative affect (NA) and self-perceived competence from 220 boys and 216 girls who were 7th graders at the beginning of this study. NA was operationalized as the common dimension underlying self-reports of depressive symptoms, anxiety symptoms, and negative emotions. Self-perceived competence consisted of 2 higher order constructs: a well-behaved/good-student factor and an attractive/athletic/popular factor. Structural equation modeling revealed very high stability estimates for all constructs. Nevertheless, self-perceived competence in the attractive/athletic/popular domain predicted changes in NA. Conversely, NA predicted changes in self-perceived competence in the well-behaved/good-student domain. The primacy of NA versus self-cognitions depends, in part, on the type of self-cognitions being examined.

Adolescent↗
PubMed1999

Parental influences on students' aggressive behaviors and weapon carrying.

This article describes the association between four family constructs (family structure, relationship with parents, parental monitoring, and perception of parental attitudes toward fighting) and aggressive behaviors and weapon carrying among middle school students. Results are based on a cross-sectional survey of 8,865 6th, 7th, and 8th graders from eight urban schools in Texas (88.5% response rate). The sample was ethnically diverse. An inverse relationship was observed between aggression scores, fighting, injuries due to fighting, and weapon carrying and the family variables: parental monitoring, a positive relationship with parents, and the lack of parental support for fighting. Students who lived with both parents were less likely to report aggression than students in other living arrangements. These four family constructs accounted for almost one-third of the total variance in the aggression score. The perception of parents' attitudes toward fighting was the strongest predictor of aggression. Results provide support for including a strong parental component in the development of violence prevention programs for young people.

Adolescent↗
PubMed1999

Randomized study of CODE versus alternating CAV/EP for extensive-stage small-cell lung cancer: an Intergroup Study of the National Cancer Institute of Canada Clinical Trials Group and the Southwest Oncology Group.

PURPOSE: To determine whether an intensive weekly chemotherapy regimen plus thoracic irradiation is superior to standard chemotherapy in the treatment of extensive-stage small-cell lung cancer (ESCLC). PATIENTS AND METHODS: Patients with ESCLC were considered eligible for the study if they were younger than 68 years, had a performance status of 0 to 2, and were free of brain metastases. Patients were randomized to receive cisplatin, vincristine, doxorubicin, and etoposide (CODE) or alternating cyclophosphamide, doxorubicin, vincristine/etoposide and cisplatin (CAV/EP). Consolidative thoracic irradiation and prophylactic cranial irradiation were given to patients responding to CODE and according to investigator discretion on the CAV/EP arm. RESULTS: The fidelity of drug delivery on both drug regimens was equal, and more than 70% of all patients received the intended protocol chemotherapy. Although rates of neutropenic fever were similar, nine (8.2%) of 110 patients on the CODE arm died during chemotherapy, whereas one (0.9%) of 109 patients died on the CAV/EP arm. Response rates after chemotherapy were higher (P =.006) with CODE (87%) than with CAV/EP (70%). However, progression-free survival (median of 0.66 years on both arms) and overall survival (median, 0.98 years for CODE and 0. 91 years for CAV/EP) were not statistically different. CONCLUSION: The CODE regimen increased two-fold the received dose-intensity of four of the most active drugs in small-cell lung cancer compared with the standard CAV/EP regimen while maintaining an approximately equal total dose. Despite supportive care (but not routine prophylactic use of granulocyte colony-stimulating factor), there was excessive toxic mortality with the CODE regimen. The response rate with CODE was higher than that of CAV/EP, but progression-free and overall survival were not significantly improved. In view of increased toxicity and similar efficacy, the CODE chemotherapy regimen is not recommended for treatment of ESCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Gemcitabine plus cisplatin, an active regimen in advanced urothelial cancer: a phase II trial of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To evaluate the efficacy and toxicity of gemcitabine (2', 2'-difluorodeoxycytidine) plus cisplatin in previously untreated patients with advanced transitional-cell carcinoma. PATIENTS AND METHODS: Thirty-one patients with measurable advanced transitional-cell carcinoma who had received no prior chemotherapy for metastatic disease were scheduled to receive gemcitabine 1,000 mg/m(2) intravenously over 30 minutes on days 1, 8, and 15 and cisplatin 70 mg/m(2) over 1 hour on day 2 of a 28-day cycle. Prior adjuvant or neoadjuvant therapy for locally advanced disease was allowed if this was completed more than 1 year before study entry. RESULTS: There were six complete responses and 10 partial responses in 28 assessable patients, for an overall response rate of 16 of 28 (57%). The response rate on an intent-to-treat basis was 16 of 31 patients (52%). The median survival is 13.2 months, with 18 patients still alive at this time. Toxicity was primarily hematologic, with 12 of 31 patients (39%) having > or = grade 3 granulocytopenia and 17 of 31 (55%) having > or = grade 3 thrombocytopenia. Two patients had febrile neutropenia. All patients required a dose modification of gemcitabine at some point in their therapy; the primary reason was thrombocytopenia and/or neutropenia. CONCLUSION: Gemcitabine plus cisplatin is an active regimen for the treatment of urothelial cancer.

Adult↗
PubMed1998

Migrating planets

A planet orbiting in a disk of planetesimals can experience an instability in which it migrates to smaller orbital radii. Resonant interactions between the planet and planetesimals remove angular momentum from the planetesimals, increasing their eccentricities. Subsequently, the planetesimals either collide with or are ejected by the planet, reducing the semimajor axis of the planet. If the surface density of the planetesimals exceeds a critical value, corresponding to approximately 0.03 solar mass of gas inside the orbit of Jupiter, the planet will migrate inward a large distance. This instability may explain the presence of Jupiter-mass objects in small orbits around nearby stars.

Journal Article↗
PubMed1998

Retroperitoneal lymphadenectomy for post-chemotherapy residual masses: is a modified dissection and resection of residual masses sufficient?

OBJECTIVE: To determine if post-chemotherapy retroperitoneal lymphadenectomy for residual masses can be limited to resection of the residual masses and a modified template dissection, without loss of therapeutic efficacy. PATIENTS AND METHODS: Between 1985 and 1995, 50 patients underwent one of three types of retroperitoneal lymphadenectomy for a residual mass after cisplatin-based chemotherapy for stages II and III testicular non-seminomatous germ cell tumour. The pre-operative imaging, operative record and pathology reports were reviewed to determine the location of the residual masses and whether tumour, defined as teratoma or viable carcinoma, was within the boundaries of the modified template and/or residual masses. The median (range) follow-up was 56 (1-140) months. RESULTS: Of 39 patients undergoing a bilateral dissection, one (2.6%) with a left testicular cancer had teratoma identified outside the boundaries of the modified template and the residual masses. The nine patients who underwent resection of residual masses and a modified-template dissection were relapse-free at a median follow-up of 55 months. One of two patients undergoing resection of residual mass alone had two recurrences arising from incomplete resection. Four of eight patients undergoing a modified dissection retained ejaculation, compared with seven of 25 (28%) undergoing a non-nerve sparing bilateral dissection. CONCLUSION: This retrospective study suggests that in patients whose tumour markers become normal and have a residual mass after chemotherapy, residual masses can be resected with a modified-template dissection with no significant risk of leaving tumour in the retroperitoneum.

Adolescent↗
PubMed1998

Treatment strategies for small bowel bacterial overgrowth in short bowel syndrome.

BACKGROUND: Small bowel bacterial overgrowth is a common complication of short bowel syndrome, and although it is often controlled with antimicrobial therapy, alternative strategies may occasionally be needed. METHODS: Six patients with bacterial overgrowth are described, who did not respond to antimicrobial therapy and required additional medical or surgical measures to control the overgrowth. RESULTS: Recalcitrant bacterial overgrowth was successfully treated with periodic small bowel irrigation with a balanced hypertonic electrolyte solution, colonic flushes, encouraging frequent stooling, intestinal lengthening procedure, or probiotic therapy with Lactobacillus plantarum 299V and Lactobacillus GG. CONCLUSIONS: Small bowel bacterial overgrowth should be aggressively evaluated in patients with short bowel syndrome who are not progressing in a normal manner. Inadequate or incomplete response to antibiotic therapy is common, and several additional treatment possibilities are available.

Anti-Bacterial Agents↗
PubMed1998

Resolution of recurrent hepatitis B in two liver transplant recipients treated with famciclovir.

Recurrent hepatitis B infection after orthotopic liver transplantation remains problematic despite prophylaxis with hepatitis B immune globulin (anti-HBs IgG). Recently, famciclovir (an oral nucleoside analog) has been shown to have potent antiviral activity against hepatitis B in vitro as well as in patients with chronic hepatitis B. We present two patients who developed recurrent hepatitis B after orthotopic liver transplantation and were treated with famciclovir, 500 mg t.i.d. Both patients subsequently responded with marked improvement in biochemical liver tests and histology, with subsequent loss of hepatitis B surface antigen. Famciclovir is a useful agent in the treatment of hepatitis B in the liver transplant recipient.

2-Aminopurine↗
PubMed1998

Development of an intervention map for a parent education intervention to prevent violence among Hispanic middle school students.

This paper describes development of Padres Trabajando por la Paz, a violence prevention intervention for Hispanic parents to increase parental monitoring. The intervention was developed using an innovative new program planning process: intervention mapping. Theory and empirical evidence broadly defined performance objectives and determinants of parental monitoring. These objectives were further refined through group and individual interviews with the target parent group. Learning objectives for the intervention guided the content of the intervention that used modeling as the primary method and role model stories as a strategy delivered through newsletters. Stage-matching members of the target population for their readiness to implement the parental monitoring behaviors further refined the social cognitive message design strategies. Intervention mapping provides an explicit theory- and data-driven guide for intervention development that maximizes intervention impact for a specific target population.

Adolescent↗
PubMed1998

Abbreviated treatment for elderly, infirm, or noncompliant patients with limited-stage small-cell lung cancer.

PURPOSE: To evaluate the efficacy of an abbreviated treatment plan consisting of two cycles of chemotherapy plus thoracic irradiation in a population of limited-stage small-cell lung cancer (LSCLC) patients who were elderly, infirm, or noncompliant with standard-duration therapy. PATIENTS AND METHODS: Fifty-five LSCLC patients (median age, 73) were treated with one cycle of cyclophosphamide, doxorubicin, and vincristine (CAV) followed 3 weeks later by one cycle of etoposide and cisplatin (EP). Both regimens were administered at conventional full dose. Thoracic irradiation (20 to 30 Gy) was delivered concurrently with EP. RESULTS: Complete response occurred in 28 patients (51%) and partial response in 21 (38%). The median survival time was 54 weeks; the 2-year survival rate was 28% and the actual 5-year survival rate was 18%. Three patients died of toxicity. CONCLUSION: Elderly, infirm, or noncompliant LSCLC patients who are unable to receive standard-duration chemotherapy may have useful palliation and potential for long-term survival with abbreviated chemotherapy (two cycles) and thoracic irradiation.

Aged↗
PubMed1998

New combination of the old drugs for elderly patients with small-cell lung cancer: a phase II study of the PAVE regimen.

PURPOSE: A regimen of cisplatin, doxorubicin, vincristine, and etoposide (PAVE) was designed for patients with small-cell lung cancer (SCLC) who were older than 65 years, with the following objectives compared with standard chemotherapy regimens: maintain efficacy, diminish toxicity, enhance compliance, and improve chemotherapy administration convenience at an acceptable cost. PATIENTS AND METHODS: The PAVE regimen consisted of cisplatin 30 mg/m2 intravenously (i.v.) day 1; doxorubicin 40 mg/m2 i.v. day 1; vincristine 1.0 mg/m2 i.v. day 1; and etoposide 100 mg/m2 i.v. day 1 and orally days 3 and 5. Cycles were repeated every 3 weeks for four cycles. Patients with limited-stage disease and selected patients with extensive-stage disease received thoracic irradiation delivered concurrently with etoposide-cisplatin (EP) at the time of the second chemotherapy cycle. RESULTS: Sixty-six eligible patients were treated, which included 25 patients with limited-stage disease and 41 patients with extensive-stage disease. Median survival was 70 weeks and 5-year survival was 25% for limited-stage disease. Median survival was 46 weeks for extensive-stage disease. Only one treatment-related death occurred and severe toxicity was infrequent. The median delivered dose-intensity was according to protocol and the mean delivered total dose was 80% of intended. CONCLUSION: The treatment outcome achieved with PAVE in a phase II study of elderly patients compared favorably with published results of standard regimens in patient populations with better prognostic factors. Because the PAVE regimen can be delivered with good compliance, has acceptable toxicity, and is associated with logistic advantages compared with standard regimens, this protocol is suitable for further investigative trials in elderly patients with SCLC.

Age Factors↗
PubMed1997

Second primary cancers related to smoking and treatment of small-cell lung cancer. Lung Cancer Working Cadre.

BACKGROUND: An increased risk of second primary cancers has been reported in patients who survive small-cell carcinoma of the lung. The treatment's contribution to the development of second cancers is difficult to assess, in part because the number of long-term survivors seen at any one institution is small. We designed a multi-institution study to investigate the risk among survivors of developing second primary cancers other than small-cell lung carcinoma. METHODS: Demographic, smoking, and treatment information were obtained from the medical records of 611 patients who had been cancer free for more than 2 years after therapy for histologically proven small-cell lung cancer, and person-years of follow-up were cumulated. Population-based rates of cancer incidence and mortality were used to estimate the expected number of cancers or deaths. The actuarial risk of second cancers was estimated by the Kaplan-Meier method. RESULTS: Relative to the general population, the risk of all second cancers among these patients (mostly non-small-cell cancers of the lung) was increased 3.5-fold. Second lung cancer risk was increased 13-fold among those who received chest irradiation in comparison to a sevenfold increase among nonirradiated patients. It was higher in those who continued smoking, with evidence of an interaction between chest irradiation and continued smoking (relative risk = 21). Patients treated with various forms of combination chemotherapy had comparable increases in risk (9.4- to 13-fold, overall), except for a 19-fold risk increase among those treated with alkylating agents who continued smoking. IMPLICATIONS: Because of their substantially increased risk, survivors should stop smoking and may consider entering trials of secondary chemoprevention.

Actuarial Analysis↗
PubMed1997

Importance of dose and dose intensity in the treatment of small-cell lung cancer.

This review examines the rationale and outcomes of intensive chemotherapy trials for small-cell lung cancer (SCLC) to determine whether further clinical research in this area is likely to generate improved results. Animal model experiments for intensive chemotherapy were reviewed to determine whether results observed in the laboratory predicted the outcomes seen in clinical trials. In addition, phase III randomized trials that differ only by the quantity of chemotherapy drug delivered were examined, with particular attention being paid to whether the conclusions reached were consistent when limited-stage and extensive-stage SCLC were separately studied. The most clear-cut evidence of benefit in animal model experiments comes from models with curative potential. In clinical trials, when dose and dose intensity are diminished from standard levels the effect is detrimental for both limited- and extensive-stage SCLC. Trials of dose and dose intensity above standard levels have not yet shown advantages for patients with extensive-stage SCLC. However, the only two randomized trials of chemotherapy dose escalation for limited-stage SCLC show statistically significant survival benefits. Therefore, animal model experiments have accurately predicted conclusions reached in SCLC clinical trials. Future studies of intensive chemotherapy for SCLC should focus on the limited-stage group.

Antineoplastic Combined Chemotherapy Protocols↗