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Biomedical subjects

D Payne

Publications and source records attributed to D Payne.

At least 19 recordsLinked to original sources
PubMed1992

Second primary malignancies following diagnosis of small-cell lung cancer.

PURPOSE AND METHODS: The records of 800 patients with small-cell carcinoma of the lung (SCLC) treated between 1971 and 1985 at University of Toronto-affiliated hospitals were reviewed for the occurrence and relative risk of second primary malignancies (SPMs). Almost all patients who developed a SPM were treated previously with chemotherapy and radiation therapy. RESULTS: Nineteen metachronous SPMs (MSPMs) and 11 synchronous SPMs (SSPMs) were identified. SSPMs were detected between 1 and 12 months after the diagnosis of SCLC. The MSPMs were identified between 1 and 10 years after the diagnosis of SCLC. MSPMs included non-small-cell lung cancer (NSCLC) (four patients), hematologic malignancies (HM) (three patients), and 12 with other solid tumors (OST). The median survival times after the diagnosis of MSPM was 33 months, 10 months, and 1 month, respectively, for those with NSCLC, OST, and HM. Expected cancer incidence rates were used to compute a relative risk rate for developing a MSPM in a subset of 392 patients on whom accurate follow-up information was available. The calculated relative risk for all tumors was 3.73. The relative risk for the development of secondary NSCLC was 6.83. CONCLUSION: We suggest that increased predisposition to SPM may relate to secondary effects of multimodality treatment and biologic considerations.

Aged↗
PubMed1992

Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? A meta-analysis.

PURPOSE: Our main purpose was to determine whether the addition of thoracic radiation therapy to systemic chemotherapy improves 2-year survival, improves local (intrathoracic) tumor control, and affects treatment-related mortality in patients with limited-stage small-cell carcinoma of the lung. DESIGN: Eleven randomized trials addressing this issue were identified using a computerized literature search (Medline and Cancerline) and by polling senior investigators in the field. A meta-analysis was then performed and the results of the trials were analyzed in two ways, the odds ratio (OR) (Peto) method and the risk difference method (Dersimonian and Laird). RESULTS: The overall OR for benefit of thoracic radiation on 2-year survival (ie, the odds of surviving 2 years among patients allocated to radiation compared with the odds of surviving 2 years among patients allocated to control) is 1.53 (95% confidence interval [CI], 1.30 to 1.76; chi 2 = 12.76; P less than .001). The risk difference method showed that radiation therapy improved 2-year survival by 5.4% (95% CI, 1.1% to 9.7%). Local control results were available for only nine studies, the OR for treatment benefit is 3.02 (95% CI, 2.80 to 3.24; chi 2 = 101.48; P less than .0001), and intrathoracic tumor control was improved by 25.3% (95% CI, 16.5% to 34.1%). The OR for excess treatment-related deaths in the thoracic radiation-treated patients was 2.54 (95% CI, 1.90 to 3.18; chi 2 = 8.24; P less than .01). The risk difference for treatment-related deaths was 1.2% (95% CI, -0.6% to 3.0%). CONCLUSIONS: This meta-analysis shows a small but significant improvement in survival and a major improvement in tumor control in the thorax in patients receiving thoracic radiation therapy. However, this is achieved at the cost of a small increase in treatment-related mortality.

Carcinoma, Small Cell↗
PubMed1991

The dynamics of drug resistance in Plasmodium falciparum.

Drug resistance of Plasmodium falciparum is not a recent phenomenon, but it became a major problem when the parasite became resistant to chloroquine, the cheapest and initially the most effective antimalarial compound that could be used for treatment and suppression. In some areas this problem is compounded by resistance to the first line of alternative drugs, and rapid loss of sensitivity to the next line. The dynamics of drug resistance are regulated mainly by drug related selection pressure and intensity of malaria transmission. Mass drug administration in its various forms, and insufficient treatment are obviously the most important motors of selection.

Animals↗
PubMed1991

A management approach to incompletely excised basal cell carcinomas of skin.

There were 187 incompletely resected basal cell carcinomas (BCC) of skin referred to the Princess Margaret Hospital between 1970 and 1985. Median age at presentation was 62 years. The commonest location of these lesions was in the head and neck region (93%). One hundred twenty lesions were immediately treated: 119 were irradiated and 1 was excised. The remaining 67 lesions were managed expectantly. Follow-up time for the entire population ranged from 1 month to 17 years, with a median time of 2.7 years. The 5-year probability of remaining relapse-free in the group immediately treated was 91% versus 61% if managed expectantly (p = 0.0001). If only lateral margins were positive, the crude probability of local failure was 3/18 (17%), versus 9/27 (33%) if the deep margins were involved (p = 0.2). Once relapse occurred in the group of lesions treated expectantly, 17/20 (85%) of these relapses were salvaged by either radiation or surgery. The 10-year actuarial probability of local control for the lesions immediately treated and observed were similar: 92% and 90%, respectively (p = 0.5). An economic analysis revealed that immediate radiation treatment saved the health system only $223.00 per patient. Since there is no difference in the ultimate local control between these two approaches, and these elderly patients may be spared the morbidity of unnecessary treatments, it is suggested that a policy of observation may be adopted for basal cell carcinomas of skin which have been incompletely excised.

Actuarial Analysis↗
PubMed1991

Experience with zona drilling and zona cutting to improve fertilization rates of human oocytes in vitro.

Zona drilling (ZD) and zona cutting (ZC) were used in an IVF programme to assist fertilization in semen defect patients. Twenty-seven patients consented to ZD where acidified Tyrode's was used to create a hole in the zona pellucida. In 19 patients, ZD increased the fertilization rate to 29% compared with 8% (P less than 0.001) in their routine IVF cycles, and in eight patients precluded from routine IVF, a fertilization rate of 14% was achieved. Twenty-two patients consented to ZC where a slit in the zona is made mechanically. In 12 patients ZC increased the fertilization rate to 31% compared with 14% (P less than 0.01) from previous routine IVF cycles, and in 10 patients precluded from routine IVF, a fertilization rate of 34% was achieved. In 13 cycles, 68 uncut control oocytes were inseminated. In five cycles both control and ZC oocytes were fertilized (n.s.d.). In eight cycles no control oocytes were fertilized compared with 27% of ZC oocytes. The polyspermy rate was 4.6%. Twenty-four per cent of ZD and 12% of ZC (P less than 0.01) oocytes and embryos were degenerate after 42 h. Both ZD and ZC can increase the fertilization rate of sub-optimal semen, however, in our hands neither technique produced a pregnancy.

Cell Survival↗
PubMed1991

The prognostic significance of pretreatment serum lactate dehydrogenase in patients with small-cell lung cancer.

Pretreatment serum lactate dehydrogenase (LDH) levels were assayed in 288 patients presenting with small-cell lung cancer (SCLC) between 1976 and 1985. Patients were routinely staged by physical examination, chest x-ray, bone, brain, and liver scans, and bone marrow evaluation. Clinical response and survival were assessed following treatment with combination chemotherapy as part of four clinical trials. Patients with extensive disease (ED) presented with a higher incidence (108 of 147, 73%) of abnormally elevated LDH (greater than 193 IU/L) than those (65 of 141, 46%) with limited disease (LD) (P = 2 x 10(-6)). Forty percent of patients had an initial normal LDH level and a higher response rate (89 of 108, 82%; complete response [CR], 47%) than those with elevated values of LDH (119 of 156, 76%; CR, 29%). The CR rate varied inversely with the level of LDH in patients with LD (P = .026) but not in those with ED (P = .300). The median survival time and 1-year and 2-year survival rates for patients with elevated LDH were 39 weeks and 33% and 6%, respectively, whereas for those with a normal LDH level these were 53 weeks and 54% and 16%, respectively. Patients with LD and elevated levels of LDH manifested a higher relative death rate (1.63:1) when compared with patients with LD and LDH in the normal range (P = .0083). The survival of patients with ED did not differ between those with normal and elevated levels of LDH (P = .273). A significant survival advantage persisted for patients with LDH in the normal range following adjustments for extent of disease, performance status (PS), and treatment protocol (P = .044, log-rank analysis). In conclusion, serum LDH appears to be a significant independent pretreatment prognostic factor in patients with SCLC that correlates with stage of disease, response to treatment, and survival.

Adult↗
PubMed1991

Small-cell carcinoma of the lung: derivation of a prognostic staging system.

Retrospective data on 22 pretreatment attributes were evaluated in 614 patients with small-cell carcinoma of the lung (SCCL). The series included 284 patients with limited disease (LD) and 328 patients with extensive disease (ED) managed between 1974 and 1986. Prognostic factors were evaluated by univariate analysis and by the Cox multivariate regression model. Recursive partition and amalgamation algorithm (RECPAM), two clustering methods well suited for obtaining strata and adapted for censoring survival data, were developed and used in the formulation of a new prognostic staging system. In univariate analysis, prognosis was significantly influenced by extent of disease (DE), the number of metastatic sites, and the detection of mediastinal spread in LD. Poor performance status (PS), male sex, and advanced age were negatively correlated with survival, as were increased serum levels of alkaline phosphates (AP), lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), total WBC count (WBCC), and low platelet count and low serum sodium. The Cox model identified plasma LDH and mediastinal spread as the only significant factors in LD; the influence of PS, number of metastatic sites, bone metastasis, brain metastasis, and platelet count were identified as significant in ED. The RECPAM model identified four distinct risk groups defined in a classification tree by the following eight attributes: DE, PS, serum AP, serum LDH, mediastinal spread, sex, WBCC, and liver metastasis. The four groups were distinguished by median survival times of 59, 49, 35, and 24 weeks, respectively (P = .0001). Interactions among prognostic factors are emphasized in the RECPAM classification model as evidenced by reassignment of patients across conventional staging barriers into alternate prognostic groups. The advantages of using RECPAM over the more conventional Cox regression techniques for a new staging system are discussed.

Adult↗
PubMed1991

Susceptibility of Plasmodium falciparum to different doses of quinine in vivo and to quinine and quinidine in vitro in relation to chloroquine in Liberia.

Chloroquine-resistant Plasmodium falciparum has been spreading rapidly after its emergence in 1988 in Yekepa. The in vivo and in vitro susceptibilities to quinine and quinidine, compared to chloroquine, were studied by investigating the number of treatment days required for radical cure and estimating the quinine concentrations concomitantly. The minimal inhibitory concentrations (MIC) for schizont maturation in all successful in vitro tests were 5.12 x 10(-6) mol/l for quinine and 1.28 x 10(-6) mol/l for quinidine, indicating that all 50 isolates were sensitive to the two drugs. The IC50 and IC90 values were 0.22 and 0.78 x 10(-6) mol/l for quinine and 0.07 and 0.26 x 10(-6) mol/l for quinidine, respectively. In vitro inhibition of parasites by 1.6 x 10(-6) mol/l of chloroquine was obtained in 31 out of 47 isolates, 16 (34%) being resistant. The IC50, IC90 and geometrical mean MIC for quinine were all about two times higher for the chloroquine-resistant than for the chloroquine-sensitive isolates (P = 0.006). P. falciparum infected children (n = 64) were randomly allocated to four groups and treated with quinine (10 mg/kg body weight twice daily) for 1 day (3 doses), 2, 4 and 7 days, respectively. All cleared their parasitaemias by day 4 but 5 out of 15 of those treated with only three doses showed a recurrence of parasitaemia between days 7 and 14; these were considered to be recrudescences. In the other groups, recurrent parasitaemias only occurred between days 17 and 28 and were considered to be reinfections.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Randomized double-blind study of intravenous tocainide versus lidocaine for suppression of ventricular arrhythmias after cardiac surgery.

To compare the therapeutic efficacy and safety of intravenous tocainide with that of intravenous lidocaine in patients with ventricular arrhythmias after cardiac surgery, 25 patients were randomized to either agent in a double-blind manner. Tocainide was given in 16 patients as a 250 mg bolus followed by a loading infusion of 500 mg over 15 minutes and a maintenance infusion of 33.3 mg/min. Lidocaine was administered in 9 patients as a 100 mg bolus followed by a loading infusion of 60 mg over 15 minutes and a maintenance infusion of 1.4 mg/min. Therapy was continued for 24 hours in initially responding patients. With analysis of 24-h taped electrocardiograms it was found that single premature ventricular complexes (PVCs) were suppressed by tocainide by more than 80% in 94% of patients and by lidocaine in 75% of patients (p = NS). Couplets and ventricular tachycardia events were eliminated in all patients by either drug. Multiform PVCs were abolished in 94% of the patients after tocainide and in 75% after lidocaine (p = NS). Average overall success over the 24 hours with more than 80% suppression of single PVCs and simultaneous elimination of higher forms of arrhythmia was 71% with tocainide and 59% with lidocaine (p = NS). Adverse effects were negligible, with only one patient in the lidocaine group developing diaphoresis without necessitating termination of therapy. Treatment rapidly produced and then maintained blood levels of 4-10 mg/l for tocainide and 1-4 mg/l for lidocaine. We conclude that intravenous tocainide is well tolerated and has comparable efficacy to lidocaine in the acute therapy of postcardiac surgery ventricular arrhythmias.

Adult↗
PubMed1990

Mefloquine therapy for Plasmodium falciparum malaria in children under 5 years of age in Malawi: in vivo/in vitro efficacy and correlation of drug concentration with parasitological outcome.

The in vivo and in vitro response of Plasmodium falciparum to a single oral dose of mefloquine (25 mg/kg body weight (M25) or 15 mg/kg (M15] was studied in children under 5 years of age in Malawi. Of the children who received mefloquine, 35% vomited at least once, and 10% did not tolerate the drug because of vomiting. The therapy failure rates for the M25 group on day 7, 14, and 28 were 15%, 18%, and 42%, respectively, and these did not differ significantly from those for the M15 group (4%, 18%, and 59%). In contrast, 34 in vitro microtests (17 per group) showed schizont inhibition at less than or equal to 32 pmol mefloquine per test well. On day 7, the concentration of mefloquine in samples of blood was significantly lower in both the M25 and M15 groups for children who were parasitaemic on day 7 than in samples from those who were aparasitaemic. A positive blood smear on day 7 was strongly associated with a mefloquine concentration of less than 500 ng/ml blood on day 2 or day 7 (P less than 0.0003). Vomiting was associated with a low mefloquine concentration on day 2 but not day 7. These results suggest that mefloquine is effective against P. falciparum in Malawi but that for young children the therapy appears to be complicated by frequent vomiting.

Animals↗
PubMed1989

Ringing in the new year: the change processes and reported outcomes of resolutions.

This study tracked the coping processes and self-reported outcomes of 213 adults making New Year's resolutions in order to identify prospective variables which predict successful self-change and to examine the relative effectiveness of various coping strategies. Prior to January 1st, participants provided information on their resolutions, demographic characteristics, and five variables previously associated with positive outcome. Subsequent telephone interviews ascertained short-term retrospective accounts of the utilization of 14 coping strategies and self-reported outcomes over six months. Readiness to change and self-efficacy, but not social support or behavioral skills, prospectively predicted successful outcome at both one week and one month. Successful resolvers were also found to report employing significantly more behavioral strategies and less self-blame and wishful thinking than unsuccessful resolvers. These findings are discussed within the context of previous research on self-initiated change, and several implications for clinical practice are offered.

Adaptation, Psychological↗
PubMed1989

Surgical therapy for drug-refractory ventricular tachycardia: results with mapping-guided subendocardial resection.

Surgical therapy with mapping-guided subendocardial resection was used in 30 patients with drug-refractory ventricular tachycardia. Results of preoperative, intraoperative and postoperative electrophysiologic evaluation and long-term clinical follow-up are reported. Left ventricular aneurysm was located in the inferior wall in 8 patients and in the anterior wall in 22. Left ventricular mapping was performed in 15 patients preoperatively and in all 30 patients intraoperatively. Subendocardial resection was supplemented with cryoablation in 26 patients and with laser photocoagulation in 4. Coronary bypass surgery was performed in 27 patients. The surgical mortality rate was 10%; the three deaths were due to cardiogenic shock, pneumonia and sepsis, respectively. At postoperative electrophysiologic study, ventricular tachycardia was inducible in 8 (30%) of 27 patients. Previously ineffective antiarrhythmic drugs were effective in preventing the induction of ventricular tachycardia in four of these eight patients. Two of the remaining four patients received an automatic implantable cardioverterdefibrillator; the other two were treated with amiodarone. At a mean follow-up period of 18 +/- 17 months (range 1 to 52), there has been one sudden death and one nonfatal recurrence of ventricular tachycardia in the 18 patients without inducible arrhythmias postoperatively. Among the eight patients with inducible ventricular tachycardia after subendocardial resection, there has been one nonfatal ventricular tachycardia recurrence. Thus, among the 27 patients surviving surgery, 17 (63%) were cured with surgery alone, and another 7 (26%) had their ventricular tachycardia controlled with drugs (n = 5) or the defibrillator (n = 2). Inability to completely map the tachycardia, a clinical history of cardiac arrest requiring resuscitation and the presence of myocardial infarction within 2 months predicted postoperative arrhythmia inducibility and recurrence.

Adult↗
PubMed1989

Development of a blood culture medium and a standard in vitro microtest for field-testing the response of Plasmodium falciparum to antifolate antimalarials.

The history of the development of the WHO standard in vitro microtest is summarized, and the rationale and methodology that were used to broaden the system for the testing of antifolate drugs such as sulfadoxine and pyrimethamine (in addition to chloroquine, mefloquine, quinine and amodiaquine) are explained. Additional information is given concerning the composition of the basic and replenishment test kits and the means of procuring them.

Animals↗
PubMed1988

Combined modality treatment for resected advanced non-small cell lung cancer: local control and local recurrence.

The purpose of this study was to compare the effect of post-operative thoracic radiation with or without systemic chemotherapy on survival and recurrence patterns in patients subjected to thoracotomy with curative intent, but subsequently found to have residual tumor in the resected margin or metastasis in the highest paratracheal lymph node. All patients were treated with postoperative mediastinal irradiation and randomized to receive or not receive combination chemotherapy (cytoxan, adriamycin, and platinum) for 6 months beginning concurrently with radiation. Of the 172 patients randomized, 164 were eligible for analysis. The mean time since randomization for the eligible patients is 4.2 years. Radiation therapy was administered to all patients by split course regimen [20 Gy in 5 fractions over 5 days]. Two such courses were given with a 3-week interval. The initial recurrence rates for both in-field recurrence and distant relapse were reduced in the combined postoperative radiation therapy and chemotherapy group, although only the latter difference achieved statistical significance (p = 0.01). Also, local recurrence overall (not restricted to initial recurrences) is examined as a function of histology, extent of residual disease after resection, and T and N status. The treatment effect achieves statistical significance only for patients with macroscopic residual (p = .023) or T3 tumor (p = .010). The combined therapy group of patients have a significantly longer recurrence-free survival [p = 0.006 by the two-sided Mantel-Haenszel logrank test] which fails, however, to translate to a significant difference in overall survival (p = 0.146). Median survival of the entire group is 14.5 months with 34% alive 2 years after resection. Most of the initial recurrences (82%) have been systemic, with brain being the most common site. Distant failure, therefore, remains an important problem even in the favorable prognosis subset of patients with advanced NSCLC, but combined modality approaches can produce improved recurrence-free survival.

Adenocarcinoma↗