Objectives. The delivery of thermotherapy, cryotherapy, and interstitial radiation with minimal morbidity is dependent on the preservation of the prostatic urethra. Our aim was to determine the ...distribution of the distance between the urethra and the nearest prostate cancer.
Methods. We determined the location of cancer in 350 prostate cancers treated by radical prostatectomy between 1991 and 1993. Each pathologic specimen was totally embedded, serially sectioned, and whole mounted. For each prostate, the radial distance from the urethra to the nearest cancer was determined (urethral-cancer distance). The urethra-cancer distance was correlated with the clinical, pathologic, and laboratory factors. Univariate and multivariate associations with progression-free survival were determined.
Results. The mean follow-up was 6.1 years. Ninety-three patients had biochemical, local, or systemic cancer recurrence. The mean ± SD distance from the urethra to the nearest cancer was 3 ± 3 mm (range 0 to 18). In 58 patients (17%), the cancer touched the urethra. A decreasing urethra-cancer distance was associated with increasing rates of cancer recurrence (
P = 0.009). The urethra-cancer distance correlated with each of the following preoperative factors: preoperative prostate-specific antigen (
r = −0.22,
P <0.001), Gleason score in biopsy specimen (
r = −0.13,
P = 0.02), and percentage of Gleason score 4 or 5 in the biopsy specimen (
r = −0.17,
P = 0.008).
Conclusions. The distance between the urethra and the nearest cancer was associated with prostate cancer outcome. Many patients have cancer close to the urethra. This finding may have implications for nonsurgical ablative therapies for prostate cancer.
Switchgrass (Panicum virgatum L.) is a leading candidate for a dedicated lignocellulosic biofuel feedstock owing to its high biomass production, wide adaptation and low agronomic input requirements. ...Lignin in cell walls of switchgrass, and other lignocellulosic feedstocks, severely limits the accessibility of cell wall carbohydrates to enzymatic breakdown into fermentable sugars and subsequently biofuels. Low‐lignin transgenic switchgrass plants produced by the down‐regulation of caffeic acid O‐methyltransferase (COMT), a lignin biosynthetic enzyme, were analysed in the field for two growing seasons. COMT transcript abundance, lignin content and the syringyl/guaiacyl lignin monomer ratio were consistently lower in the COMT‐down‐regulated plants throughout the duration of the field trial. In general, analyses with fully established plants harvested during the second growing season produced results that were similar to those observed in previous greenhouse studies with these plants. Sugar release was improved by up to 34% and ethanol yield by up to 28% in the transgenic lines relative to controls. Additionally, these results were obtained using senesced plant material harvested at the end of the growing season, compared with the young, green tissue that was used in the greenhouse experiments. Another important finding was that transgenic plants were not more susceptible to rust (Puccinia emaculata). The results of this study suggest that lignin down‐regulation in switchgrass can confer real‐world improvements in biofuel yield without negative consequences to biomass yield or disease susceptibility.
To assess the relationship between clinical course after acute myocardial infarction (AMI) and diabetes treatment.
Retrospective analysis of data from all patients aged 25-64 years admitted to ...hospitals in Perth, Australia, between 1985 and 1993 with AMI diagnosed according to the International Classification of Diseases (9th revision) criteria was conducted. Short- (28-day) and long-term survival and complications in diabetic and nondiabetic patients were compared. For diabetic patients, 28-day survival, dysrhythmias, heart block, and pulmonary edema were treated as outcomes, and factors related to each were assessed using multiple logistic regression. Diabetes treatment was added to the model to assess its significance. Long-term survival was compared by means of a Cox proportional hazards model.
Of 5,715 patients, 745 (12.9%) were diabetic. Mortality at 28 days was 12.0 and 28.1% for nondiabetic and diabetic patients, respectively (P < 0.001); there were no significant drug effects in the diabetic group. Ventricular fibrillation in diabetic patients taking glibenclamide (11.8%) was similar to that of nondiabetic patients (11.0%) but was lower than that for those patients taking either gliclazide (18.0%; 0.1 > P > 0.05) or insulin (22.8%; P < 0.05). There were no other treatment-related differences in acute complications. Long-term survival in diabetic patients was reduced in those taking digitalis and/or diuretics but type of diabetes treatment at discharge had no significant association with outcome.
These results do not suggest that ischemic heart disease should influence the choice of diabetes treatment regimen in general or of sulfonylurea drug in particular.
An alternative non-vascular extracellular material was obtained by decellularisation of porcine urinary bladder and examined for its potential as scaffold for vascular tissue engineering. Analysis ...using Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM) and Laser Scanning Microscopy (LSCM) showed a porous interconnective microarchitecture, an abundance of well preserved fibers on the abluminal side and a micropatterned flat luminal surface. Uniaxial tensile testing revealed a strength of 1.9+/-0.3 MPa for the rehydrated material in a phosphate buffered saline medium for the ECM-UBM sheet and these results comparable to those of native artery of a middle aged human. Multilamination of the UBM increases the tensile properties in general (9+/-0.45 MPa for 2 layer, 30+/-0.6 MPa for 4 layers construct), with no effect on elongation capacities (38-40%) of the material. Contact-angle measurements indicated that the ECM-UBM surface exhibited a hydrophylic characteristic and better wettability than any vascular synthetic materials. Comparison of the initial adhesion in the multiplayer ECM constructs was evaluated and was found not to be altered by the preparation. The HAECs and HSMC shown an excellent adherence, spread and proliferation on the ECM-UBM material with the preservation of the cell phenotype. The level of MMP-1 and MMP-9 produced by endothelial cells was evaluated in this study and provides some data on the remodelling capacity of the scaffold. Vascular cell seeded-UBM constructs may also provide a suitable and affordable in vitro model for cell-physiology and drug development studies, which may elucidate to the mechanisms of vascular disease formation, and its prevention and treatment.
Symptomatic children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for recurrent arrhythmic events. β-Blockers decrease this risk, but studies comparing individual ...β-blockers in sizeable cohorts are lacking. We aimed to assess the association between risk for arrhythmic events and type of β-blocker in a large cohort of symptomatic children with CPVT.
From 2 international registries of patients with CPVT,
variant-carrying symptomatic children (defined as syncope or sudden cardiac arrest before β-blocker initiation and age at start of β-blocker therapy <18 years), treated with a β-blocker were included. Cox regression analyses with time-dependent covariates for β-blockers and potential confounders were used to assess the hazard ratio (HR). The primary outcome was the first occurrence of sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter-defibrillator shock, or syncope. The secondary outcome was the first occurrence of any of the primary outcomes except syncope.
We included 329 patients (median age at diagnosis, 12 interquartile range, 7-15 years, 35% females). Ninety-nine (30.1%) patients experienced the primary outcome and 74 (22.5%) experienced the secondary outcome during a median follow-up of 6.7 (interquartile range, 2.8-12.5) years. Two-hundred sixteen patients (66.0%) used a nonselective β-blocker (predominantly nadolol n=140 or propranolol n=70) and 111 (33.7%) used a β1-selective β-blocker (predominantly atenolol n=51, metoprolol n=33, or bisoprolol n=19) as initial β-blocker. Baseline characteristics did not differ. The HRs for both the primary and secondary outcomes were higher for β1-selective compared with nonselective β-blockers (HR, 2.04 95% CI, 1.31-3.17; and HR, 1.99 95% CI, 1.20-3.30, respectively). When assessed separately, the HR for the primary outcome was higher for atenolol (HR, 2.68 95% CI, 1.44-4.99), bisoprolol (HR, 3.24 95% CI, 1.47-7.18), and metoprolol (HR, 2.18 95% CI, 1.08-4.40) compared with nadolol, but did not differ from propranolol. The HR of the secondary outcome was only higher in atenolol compared with nadolol (HR, 2.68 95% CI, 1.30-5.55).
β1-selective β-blockers were associated with a significantly higher risk for arrhythmic events in symptomatic children with CPVT compared with nonselective β-blockers, specifically nadolol. Nadolol, or propranolol if nadolol is unavailable, should be the preferred β-blocker for treating symptomatic children with CPVT.
Allograft bone was used to reconstruct a defect in the proximal aspect of the tibia or the distal aspect of the femur, or both, in thirty knees of twenty-eight patients who had a revision total knee ...arthroplasty. The average age of the patients at the time of the index procedure was 65.8 years (range, twenty-four to eighty-nine years). At an average of fifty months (range, twenty-four to 132 months; median, thirty-six months) postoperatively, the score for twenty-three knees (twenty-one patients) had increased by at least 20 points, and these knees did not need additional operative treatment. Thus, the rate of success was 77 per cent. The procedure was considered a failure for the remaining seven knees because of infection (three), loosening of the tibial component (two), fracture of the graft (one), and non-union at the allograft-host junction (one). Properly applied allograft can be used to reconstruct massive bone defects, provide stability and support for implants, and restore bone stock in the event that additional operative treatment is necessary.
Use of novel crops for bio-fuel production requires evaluating the potential for sound ecological and economical implementation in a particular region. We examined the pest and generalist beneficial ...insect species associated with various winter cover crops (including narrowleaf lupin, white vetch, Austrian winter pea, crimson clover, faba bean, and rye) as sources of colonists in 2 subsequent summer crops, sorghum and cotton. Sorghum is a potential cellulosic bio-fuel crop and colton is commonly grown in the region and could be a viable low-input rotation for biofuel sorghum. Insects were sampled weekly over 3 ys in winter cover plots beginning in early spring and in the later planted crop plots beginning at the 15 ern height stage of the crops and continuing for 3 - 6 wks. Of the predators, coccinellids (Coleoptera: Coccinellidae) dominated and were consistently abundant in vetch, laba and lupin, as was the pea aphid, Acyrthosiphon pisum Harris (Hemiptera: Aphididae) and the aphid parasitoid, Lysiphlebus testaceipes Cresson (Hymenoptera: Aphiidae). Orius spp. (Hemiptera: Anthocoridae) dominated in lupin. 01 the pest species, thrips spp. (Thysanoptera: Thipidae) were highest in lupin and pea, and stink bugs (Hemiptera: Pentatomidae) were highest in clover. No differences in chinch bugs (Hemiptera: Lygaeidae) were lound among the covers. There was a 'relay' 01 these species into all 01 the summer crop plots from living winter crops. Boll damage from stink bugs was highest in the cotton lollowing lupin, pea and lallow with fertilizer; there was no damage Irom chinch bugs in sorghum. Faba beans had declining stands over the 3 ys, suggesting that this species would not be a reliable winter crop in this system. Vetch and lupin may be the best candidates as banker plants because of their ability to consistently sustain pea aphids and coccinellids, the lormer which is a nonpest of sorghum and cotton.
ABSTRACT
Reverberation mapping measurements have been used to constrain the relationship between the size of the broad-line region and luminosity of active galactic nuclei (AGN). This R–L relation is ...used to estimate single-epoch virial black hole masses, and has been proposed to use to standardize AGN to determine cosmological distances. We present reverberation measurements made with Hβ from the 6-yr Australian Dark Energy Survey (OzDES) Reverberation Mapping Program. We successfully recover reverberation lags for eight AGN at 0.12 < z < 0.71, probing higher redshifts than the bulk of Hβ measurements made to date. Our fit to the R–L relation has a slope of α = 0.41 ± 0.03 and an intrinsic scatter of σ = 0.23 ± 0.02 dex. The results from our multi-object spectroscopic survey are consistent with previous measurements made by dedicated source-by-source campaigns, and with the observed dependence on accretion rate. Future surveys, including LSST, TiDES, and SDSS-V, which will be revisiting some of our observed fields, will be able to build on the results of our first-generation multi-object reverberation mapping survey.
Gemcitabine (2'2'-difluoro-2'-deoxycytidine, dFdCyd) is a potent radiosensitizer of rodent and human tumor cells. Our Phase I clinical trial using once-weekly dFdCyd as a radiosensitizer in the ...treatment of patients with Stage IV squamous cell head and neck cancer has produced a high rate of tumor response and significant normal mucosal toxicity. These findings raised the question of whether we are using dFdCyd in the optimal dose and schedule. In vitro studies suggest that twice-weekly dFdCyd has the potential to be more effective than once-weekly dFdCyd when administered in combination with radiation (RT) given 5 days per week. Therefore, we have used a mouse model to assess whether the therapeutic ratio of combined modality therapy may be improved by using a twice-weekly drug regimen. We asked two questions: 1) Does a once-weekly or twice-weekly dFdCyd regimen cause more normal tissue radiosensitization? 2) Does a once-weekly or twice-weekly dFdCyd + RT regimen produce a better therapeutic index?
To assess normal tissue toxicity, C3H mice underwent mouth (60)Co RT (27.5 Gy in 5 daily fractions) +/- dFdCyd delivered intraperitoneally (IP) either once or twice weekly 6 hours prior to irradiation. Acute lip reactions were quantified according to a standard scoring system, and weight loss was measured. We measured tumor control using squamous cell carcinoma (SCC) VII murine squamous cell flank tumors (50-125 mm(3)) treated with the same regimens used in the mouth irradiation model.
We found that dFdCyd delivered 800 mg/kg once weekly or 150 mg/kg twice weekly caused similar (and maximal tolerable) weight loss; therefore these regimens were chosen to test which schedule produced more acute lip radiosensitization. Twice-weekly dFdCyd + RT was somewhat more toxic by weight loss (800 mg/kg once weekly: 11.9%; 150 mg/kg twice weekly: 17.7%; p = 0.09). To assess therapeutic index, we treated SCC VII flank tumors with RT combined with isotoxic drug/RT regimens (dFdCyd 800 mg/kg once weekly or 100 mg/kg twice weekly). Tumors treated with twice-weekly dFdCyd + RT were significantly smaller than tumors treated with once-weekly drug + RT at 28 days from the start of treatment (p < 0.03).
These findings demonstrate that equitoxic once- versus twice-weekly dFdCyd regimens cause differing levels of oral mucosal radiosensitization. This would suggest that each radiation-dFdCyd schedule will require its own dFdCyd dose escalation trial (which cannot be determined by the maximum tolerated dose (MTD) for dFdCyd alone using that schedule). In addition, our findings suggest that for head and neck cancers twice-weekly dFdCyd may have a higher therapeutic index compared with once-weekly dFdCyd when combined with daily RT.
We have explored the phenotypic and genetic overlap between autophagocytosis and cytoplasm to vacuole targeting in the yeast Saccharomyces cerevisiae. Complementation analysis was performed with ...mutants in each of these groups (aut and cvt, respectively), and three complementation groups were found to overlap. Also, most of the unique aut mutants accumulated precursor aminopeptidase I in the cytoplasm, while maintaining wild type kinetics and maturation of proteins targeted to the vacuole via the secretory pathway. The majority of the non-overlapping cvt mutants were found to be at least partially defective in autophagy. Some mutants in each group, however, appear to be only marginally affected in the other phenotype, implying that these pathways only partially overlap. We propose that import of aminopeptidase I into the vacuole shares a number of components required for bulk autophagocytosis, but is made specific, saturable, and constitutive by the presence of a receptor or other interacting protein(s)
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