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Biomedical subjects

D Payne

Publications and source records attributed to D Payne.

At least 19 recordsLinked to original sources
PubMed1995

Outcome following radiotherapy in verrucous carcinoma of the larynx.

PURPOSE: To evaluate the outcome of patients with verrucous carcinoma of the larynx treated at the Princess Margaret Hospital with respect to control rates with radiotherapy, the salvage of local failure, the risk of regional lymph node metastasis following radiation therapy, and the risk of anaplastic transformation following radiotherapy. METHODS AND MATERIALS: Forty-eight patients underwent primary treatment for verrucous carcinoma of the larynx in the period between January 1961 and December 1990. This represented 1.1% of cases of laryngeal cancer seen in this time period. Forty-three received radiotherapy and 5 had surgery as the primary treatment. Several radiation dose-fractionation schedules were used, the most frequent being 50 Gy in 20 fractions in 4 weeks (31 cases), while eight patients were treated with 55 Gy over 5 weeks. RESULTS: The 5-year rate of local control was 59% for the 43 patients treated with radiotherapy. Surgical salvage was universally successful in all cases where it was attempted. The five cases treated with surgery alone did not experience relapse. Only one patient died of verrucous carcinoma. He had been medically unfit for surgical intervention at the time of initial treatment and at the time of relapse. He underwent a truncated course of radiotherapy (24 Gy in 3 fractions over three weeks in 1975). There was no evidence of increased neck relapse compared to other forms of laryngeal carcinoma following radiation treatment. No evidence to support anaplastic transformation of tumors treated with radiotherapy was evident in this series. CONCLUSIONS: Local control using radiation treatment is less successful than with ordinary invasive and in situ squamous carcinomas of the larynx. Nevertheless, the treatment is effective and provides an appropriate option for laryngeal conservation, especially in advanced lesions where total laryngectomy may be the only treatment alternative. Surgical salvage of radiation failures contributes to very high rates of cure for verrucous carcinoma of the larynx. Anaplastic transformation of cases treated with radiotherapy was not observed in any case in this series.

Adult↗
PubMed1995

Increased buffer pH enhances sensitivity and specificity of human papillomavirus detection using consensus primer based PCR.

Polymerase chain reaction (PCR) buffers were optimized for the specific detection of human papillomavirus (HPV) sequences. The effect of pH, potassium chloride concentration and magnesium chloride concentration of three different consensus primers were examined. Several phylogenetically distinct HPVs (HPV1, HPV2, HPV6, HPV8, HPV16, HPV18, and HPV20) were used to determine the optimal buffer components. Genital types were less sensitive to changes in pH than cutaneous types. Higher buffer pH, with a few exceptions, led to increased sensitivity and specificity of HPV detection.

Base Sequence↗
PubMed1995

Radiation treatment of cervical lymph node metastases from an unknown primary: an analysis of outcome by treatment volume and other prognostic factors.

One hundred and forty-four patients with diagnosis of carcinoma involving cervical lymph nodes from an unknown primary site were seen at the Princess Margaret Hospital, Toronto between 1970 and 1986. This paper addresses the outcome of two treatment approaches using radiation treatment as potentially curative therapy. The treatment approaches compared in a retrospective analysis are radiation to the involved node regions alone (85 cases), and radiation to both the nodes and to potential primary sites in the head and neck (59 cases). The overall 5-year survival rate of the entire group of 144 cases was 41%. There was a trend to increased survival in favour of the group receiving radiation to the nodes and potential primary sites (p = 0.07), however, when differences in extent of nodal involvement were considered and adjusted for using the Cox Proportional Hazard Model, no difference in survival, or cause-specific survival was found between the two treatment groups (p = 0.18 and 0.22, respectively). A total of seven head and neck primary cancers were subsequently discovered, six in the group receiving radiation only to the nodes and one in the group receiving radiation to the nodes and primary sites. The results of this retrospective analysis need to be interpreted with caution but suggest that, for some patients with this diagnosis, radiation to the involved node region alone is adequate. A discussion of the literature is presented with attention to the effect of extent of treatment on outcome.

Carcinoma, Squamous Cell↗
PubMed1995

Assessment of fertilization failure and abnormal fertilization after intracytoplasmic sperm injection (ICSI).

The assessment of fertilization is an important part of intracytoplasmic sperm injection (ICSI) and oocytes are routinely examined about 17 h after injection using Nomarski differential interference contrast optics. However, it is not possible to conclusively determine the aetiology of fertilization anomalies in this manner, so cytological studies were undertaken to determine the causes of failed and abnormal fertilization after ICSI. Oocytes which exhibited no evidence of fertilization, one pronucleus (PN) or 3 PN were fixed in glutaraldehyde, stained with Hoechst 33342 and examined by fluorescence microscopy to identify PN, metaphase chromosomes, sperm heads and polar bodies. A total of 428 unfertilized oocytes were examined from 170 ICSI cycles. Overall, 82% of these unfertilized oocytes were still at metaphase II (non-activated) while the remaining 18% were activated and had 1 PN and two polar bodies. The majority (71%) of the metaphase II oocytes contained a swollen sperm head, which indicates that the spermatozoon was correctly injected but the oocyte did not activate and complete its second meiotic division. The swollen sperm head was located among the metaphase chromosomes in 4.3% of these oocytes, while in some cases (6.6%), the sperm chromosomes had undergone premature chromosome condensation (PCC). Other aetiologies of failed fertilization in these metaphase oocytes were ejection of the spermatozoon from the oocyte (19%) and complete failure of sperm head decondensation (10%). A similar pattern of anomalies was found in 1 PN oocytes, although the ratios were different (swollen sperm head, 51%; ejection of the spermatozoon, 19%; undecondensed sperm head, 30%). Seventy abnormally fertilized oocytes were also examined, of which 63 had 3 PN and a single polar body, indicating that the unextruded second polar body developed into the third PN. In conclusion, the present study demonstrates that the principal cause of fertilization failure after ICSI is failure of oocyte activation and not ejection of the spermatozoon from the oocyte. It is also apparent that further studies are needed to elucidate the mechanisms that control oocyte activation and sperm head decondensation in injected oocytes.

Adult↗
PubMed1995

Intracytoplasmic sperm injection--clinical results from the reproductive medicine unit, Adelaide.

The clinical results of 391 cycles of intracytoplasmic sperm injection (ICSI) performed between June 1993 and July 1994 are presented in this report. A total of 4797 oocytes were collected, of which 3792 were injected. Of these, 2603 (69%) fertilized, with normal and three pronuclear fertilization rates of 65% and 4% respectively. About 6% of the oocytes were destroyed while denuding and during ICSI. There were 373 (95%) embryo transfers from which 119 pregnancies arose, giving pregnancy rates of 32% per transfer and 30% per cycle, and an implantation rate of 15% per embryo. Of the pregnancies, 98 (82%) were ongoing. Supernumerary embryos were frozen in 44% of the cycles and 61 subsequent transfers of 130 frozen-thawed embryos produced 11 pregnancies (18%). Only 47 (12%) patients had less than 50% of their oocytes fertilized (mean 31%) after ICSI, and of these, 8 had no fertilization of 13 eggs. Nevertheless, 37 of these 47 patients had an embryo transfer and 9 achieved a pregnancy with an implantation rate of 14% per embryo. The percent normal sperm morphology weakly correlated with percent fertilization (r2 = 0.027, P < 0.02) but not with the implantation rate (r2 = 0.003, P > 0.05). Fifty-nine patients with only occasional motile sperm in the ejaculate and 23 patients in whom epididymal sperm were aspirated were treated. The fertilization rates (66% and 70% respectively) and pregnancy rates per transfer (32% and 24% respectively) were comparable in these two subgroups. The overall ICSI results were also compared with 515 cycles of routine in vitro fertilization (IVF) which were performed at the same time.(ABSTRACT TRUNCATED AT 250 WORDS)

Australia↗
PubMed1995

Excess nitric oxide does not cause cellular, vascular, or mucosal dysfunction in the cat small intestine.

The overproduction of nitric oxide in the small bowel has been invoked as a cytotoxic event in the vascular, mucosal, and whole organ dysfunction associated with inflammation. We assessed whether exogenous administration of nitric oxide in the form of nitric oxide donors (CAS 754, SIN-1) could cause microvascular and mucosal barrier dysfunction in vivo or epithelial and endothelial cell permeability alterations and cell injury in vitro. Increasing concentrations of CAS 754 or SIN-1 were infused locally into autoperfused segments of cat ileum at 30-min intervals. Baseline epithelial permeability (blood-to-lumen clearance of 51Cr-EDTA) was not affected by CAS 754, whereas vascular protein clearance was reduced. The latter effect could almost entirely be explained by a decrease in intestinal capillary hydrostatic pressure. Therefore, in some experiments venous pressure was elevated and the microvascular reflection coefficient for total proteins was estimated at filtration-independent rates. This direct measurement of microvascular permeability was unaffected by exogenous nitric oxide. CAS 754 did not increase permeability across monolayers of endothelial or epithelial cells and did not cause cell injury. Next, we assessed the possibility that excess nitric oxide may be detrimental, but only in inflamed intestine, by infusing CAS 754 with platelet-activating factor; the latter directly increases microvascular and mucosal permeability. CAS 754 did not exacerbate but rather reduced platelet-activating factor-induced rise in microvascular and mucosal permeability. These results suggest that high concentrations of nitric oxide do not cause breakdown of mucosal or microvascular barrier integrity under normal or inflammatory conditions.

Animals↗
PubMed1995

Therapeutic potential of inhibiting leukocyte rolling in ischemia/reperfusion.

Leukocyte rolling has been postulated to be mandatory for subsequent leukocyte adhesion and tissue injury observed during ischemia/reperfusion. The objective of this study was to systematically assess this hypothesis at the microvascular level by examining the effects of various concentrations of a selectin-binding carbohydrate (fucoidin) on the increased rolling and adhesion of leukocytes in postischemic venules. The contribution of L-selectin and/or P-selectin to leukocyte rolling were also assessed in this model. Using intravital microscopy we observed that 60 min of ischemia followed by reperfusion caused a profound increase in leukocyte rolling and adhesion. A high dose of fucoidin (25 mg/kg) reduced leukocyte rolling by > 90% and significantly reduced leukocyte adhesion, whereas a lower dose of fucoidin still reduced leukocyte rolling by 60% but had no effect on leukocyte adhesion. Moreover, despite the profound reduction in leukocyte rolling with fucoidin, the remaining rolling cells were able to firmly adhere via a CD18-dependent mechanism, particularly in those postcapillary venules with reduced (30-50%) shear rates. The increased rolling was also reduced 60% by either an anti-P-selectin antibody, an anti-L-selectin antibody, or a combination of the two antibodies, but this reduction in rolling cells did not translate into significantly reduced leukocyte adhesion. Our data suggest that L-selectin, P-selectin, and a fucoidin-sensitive pathway contribute to the significant increase in reperfusion-induced leukocyte rolling. However, targeting leukocyte rolling as a form of therapy requires very significant efficacy (> 90%) to achieve reasonable (approximately 50%) attenuation in leukocyte adhesion in postischemic venules.

Animals↗
PubMed1995

Isolation and structure determination of two novel phenazines from a Streptomyces with inhibitory activity against metallo-enzymes, including metallo-beta-lactamase.

Two novel metabolites, SB 212021 and SB 212305, have been isolated from a Streptomyces and shown to have molecular formulae of C15H10N2O5 and C20H17N3O8S, respectively. The structures were deduced by a combination of NMR techniques and mass spectral fragmentation patterns and shown to be novel members of the phenazine group of antibiotics. In the absence of added zinc, both compounds had IC50's of 1-75 microM for the Bacteroides fragilis 262 CfiA and Xanthomonas maltophilia L-1 metallo-beta-lactamases. The compounds also inhibited ACE with IC50's of 55 and 68 microM, respectively. Mode of action studies illustrate that the compounds inhibit some metalloenzymes by chelation of the active site metal ion. They exhibit poor antibacterial activity.

Anti-Bacterial Agents↗
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↗