Measurement of the ratio of branching fractions B(D0--> pi -e+ nu e)/B(D0-->K-e+ nu e).
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to D Payne.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
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.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
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.
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.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
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.
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)
In couples who undergo routine in vitro fertilization (IVF), 17% experience significant problems with fertilization and many others are unable to have routine IVF because the quality of their semen is too poor. Often, the only options previously available to these couples were to use sperm donated by fertile men or to remain childless. Micromanipulative assisted fertilization techniques have improved the treatment of severe male factor infertility significantly and this paper provides a brief overview of the recent methodologies. Initially, techniques such as zona drilling and partial zona dissection, in which a hole or slit is placed in the zona pellucida, demonstrated that fertilization and pregnancies could be achieved with semen of very poor quality, but successes were sporadic. Later, subzonal injection of spermatozoa provided more consistent results with many units reporting pregnancies; however, relatively low rates of fertilization (14-34%) and high rates of polyspermy remained unresolved problems. The latest technique, the injection of a single spermatozoon into the oocyte cytoplasm, although technically difficult in animal models, proved to be highly successful in the human, restoring fertilization rates to those seen in routine IVF (65%) and producing good pregnancy rates from transferred embryos. Intracytoplasmic sperm injection has become the method of choice in the treatment of severe male factor infertility and preliminary data suggest that there is no increase in congenital abnormality among babies born after the transfer of injected oocytes.
The aim of this study was to determine why oocytes remain unfertilized or develop three pronuclei after intracytoplasmic sperm injection (ICSI). Unfertilized and abnormally fertilized oocytes were fixed in glutaraldehyde, stained with Hoechst 33342 and examined by fluorescence microscopy to identify oocyte, sperm and polar body DNA. One-pronuclear oocytes were considered to be unfertilized. A total of 285 unfertilized oocytes were examined (104 ICSI cycles). Overall, 83% of these oocytes were not activated (still at metaphase II) while 17% had activated and formed a single (female) pronucleus. About 66% of the unfertilized, metaphase II oocytes contained a swollen sperm head, indicating that the oocyte was correctly injected but had failed to activate and complete the second meiotic division. Premature chromosome condensation of the sperm DNA was evident in 6% of these metaphase II oocytes (4% of the unfertilized oocytes). The swollen sperm head was located among the oocyte chromosomes in 5% of the metaphase II oocytes. Other causes of failed fertilization in the metaphase II oocytes were the failure of sperm head decondensation (11%) and ejection of the spermatozoon from the oocyte (23%). A similar pattern was observed in one-pronuclear oocytes (52%, swollen sperm head; 28%, intact, undecondensed sperm head; 20%, ejection of the spermatozoon), which indicates that asynchronous pronuclear development does not explain the presence of one-pronuclear oocytes. A total of 41 three-pronuclear oocytes were examined and all had a single polar body, which indicates that the retention of the second polar body leads to the formation of the third pronucleus. In conclusion, this study demonstrates that: (i) the major cause of fertilization failure after ICSI is failure of oocyte activation; (ii) ejection of the spermatozoon into the perivitelline space is not a major cause of fertilization failure; and (iii) sperm head decondensation and oocyte activation after ICSI can occur independently.
Explore the source record for details and available documents.
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.
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.
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.
Explore the source record for details and available documents.