Purpose Our aim was to determine whether cardiovascular (CV) risk in patients with prostate cancer (PCa) differs between those who receive androgen-deprivation therapy by surgical castration and ...those who receive gonadotropin-releasing hormone agonist (GnRHa) therapy. Patients and Methods By using the Taiwan National Health Insurance Research Database, we analyzed data from 14,715 patients with PCa diagnosed from January 1, 1997, through December 31, 2011. The patients were treated with bilateral orchiectomy or GnRHa therapy. We used inverse probability of treatment weighting with propensity scores to adjust for the imbalance in covariate baseline values between these two groups. Cox regression models were used to identify risk factors for myocardial infarction (MI), ischemic stroke (IS), and cardiac-related complications. Results Overall, 3,578 patients with PCa (24.3%) underwent bilateral orchiectomy and 11,137 patients (75.7%) received GnRHa therapy. Both groups had a similar risk of CV ischemic events (ie, MI or IS; hazard ratio, 1.16; 95% CI, 0.97 to 1.38) during a median follow-up time of 3.3 years. However, during the first 1.5 years of follow-up, there were higher CV ischemic events in the orchiectomy group than in the GnRHa group (hazard ratio, 1.40; 95% CI, 1.04 to 1.88), particularly in patients who were ≥ 65 years of age, had hypertension, had a Charlson comorbidity index score ≥ 3, and had a previous history of MI, IS, or coronary heart disease. Conclusion Compared with bilateral orchiectomy, use of GnRHa does not increase the risk of CV ischemic events in patients with PCa. Nonetheless, orchiectomy is associated with higher rates of CV ischemic events in older patients and those with a history of CV comorbidities within 1.5 years of initiating androgen-deprivation therapy. These findings can help clinicians decide on the optimal castration strategy for individual patients.
Malignant gliomas account for more than 60% of all primary brain tumors in adults. Adjuvant chemotherapy in addition to radical
surgery and radiation therapy has provided only a modest increase in ...survival. Retinoic acid has been shown to have growth-inhibitory
activity against glioma cells in culture. This provides the rationale for a Phase II study using 13-cis-retinoic acid (CRA)
in patients with recurrent malignant brain tumors. The objective of this study was to determine the clinical activity of CRA
in patients with a histologically proven diagnosis of malignant brain tumor and documented progressive or recurrent disease
after radiation and chemotherapy. Fifty patients with documented recurrent disease were treated with CRA as a single agent
p.o. at a dose of 60-100 mg/m2 per day. Three weeks of treatment were followed by 1 week of rest. Of the 43 patients who received
more than 4 weeks of therapy, 3 (7%) achieved partial response, 7 (16%) achieved minor response, 13 (30%) remained stable,
and 20 (47%) had disease progression. The median time from onset of treatment to disease progression for the whole group of
43 patients was 16 weeks (19 weeks for glioblastomas and 11 weeks for anaplastic glioma), whereas that for the 23 patients
with partial response and minor response and who remained stable was 66 weeks, and that for the 20 patients with progressive
disease was only 8 weeks. The median survival time for glioblastoma was 58 weeks, and 34 weeks for anaplastic astrocytoma.
Toxicity was mainly dermatological, with dry skin and cheilitis. These preliminary results suggest that 13-cis-retinoic acid
is active against malignant gliomas and is very well tolerated.
Expiration-day effects-An Asian twist Fung, Joseph K. W.; Yung, Haynes H. M.
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Journal Article
ABSTRACT—Mechanosensitive cation channels may be involved in the development of the myogenic tone of arteries. The molecular identity of these channels is not clear, but transient receptor potential ...channels (TRPCs) are good candidates. In the present study, we searched for mechanosensitive channels at the single-channel level in arterial smooth muscle cells using the patch-clamp technique and investigated the channel properties in the light of properties of TRPCs. With 140 mmol/L CsCl in the pipette solution, application of negative pressures to the back of the pipette induced the activation of channels the open probability of which increased with the amount of negative pressure. The current-voltage relationship was linear in symmetrical ionic conditions, and the single-channel conductances for Cs, K, and Na were 30, 36, and 27 pS, respectively. When NMDG was substituted for Cs in the pipette solution, inward currents were abolished, whereas outward currents remained active, indicating that the channels were nonselective to cations. The channel activity was blocked by intracellular Gd and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid and increased by diacylglycerol and by cyclopiazonic acid. Phospholipase C inhibitor (U73122) inhibited not only channel activity but also the development of myogenic tone induced by stretching of the basilar arteries. These results suggest that the ion channel responsible for the development of myogenic tone is the 30-pS mechanosensitive cation channel that exhibits properties similar to those of TRPCs.
How urbanization affects tropical cyclone (TC) rainfall is inferred from station observations over the Great Bay Area (GBA, located on the South China coast) and numerical model experiments. ...Observations from 41 TCs indicate that surface wind is noticeably weaker in urban compared to rural stations during TC passages, while the urban heat island effect is considerably suppressed. Extreme (99th percentile of) hourly rainfall for these TC events during 2008–2017 is more intense over urban compared to rural stations. For eight selected TC cases, dynamical downscaling was carried out using the convection‐resolving Weather Research and Forecasting model, each with three parallel experiments: “Nourban” in which the urban area was replaced by cropland; “AH0” (“AH300”) in which the diurnal maximum anthropogenic heat (AH) was set to 0 (300 W/m2) in city locations. Both AH0 and AH300 show a significant increase in urban hourly rainfall intensity and probability in all ranges (most obvious for heavy rainfall >40 mm/hr), over the GBA mega‐city. Further diagnosis indicates increased moisture flux convergence in urban areas over a 2‐day period during the landfall, contributes to increased rainfall, likely induced by the surface roughness. The influence of AH, however, is found to be insignificant. The increase in accumulated rainfall due to urbanization is proportional to the storm residence time over the city, implying greater rainfall exacerbation for slower or larger TCs. Overall, urbanization intensifies extreme TC rainfall over the coastal GBA mega‐city mainly due to surface frictional convergence, with stronger intensification for storms residing longer over the city.
Plain Language Summary
This study investigates how urbanization can affect tropical cyclone (TC) rainfall over the Greater Bay Area (GBA) based on observations and model. Observations told us that, during TC passage, there would be slower wind speed in urban areas compared to rural. And the temperature difference between urban and rural will become weaker. There is also stronger TC rainfall in the city compared to surrounding rural areas. Moreover, we use model to simulate eight historical TCs with different land use (urban vs. rural) and different value of anthropogenic heat (AH; 0 and 300 W/m2). Model results indicate that, urbanization can strongly enhance TC rainfall intensity and probability, and it is mainly due to higher roughness in the city, the effect of AH is weak. We also found that, such a fractional increase in accumulated rainfall is found to be proportional to the “storm residence time” over the city, which means rainfall enhanced due to urbanization is stronger for slower or larger TCs. Overall, urbanization leads to stronger extreme TC rainfall over the coastal mega‐city mainly due to the surface frictional effect, with stronger intensification for larger storms or those residing longer over the city.
Key Points
Observations and numerical modeling results indicate that urbanization can enhance tropical cyclone rainfall over the Greater Bay Area
Enhanced rainfall is mainly due to the urban roughness effect, while the anthropogenic heat effect is weak
Fractional increase in accumulated rainfall is found to be proportional to the “storm residence time” over the city
1 College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA 2 Bacterial Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Service, US ...Department of Agriculture, Ames, IA 50010, USA 3 Department of Chemistry, University of Oklahoma, Norman, OK, USA
Correspondence Yung-Fu Chang yc42{at}cornell.edu
Received December 15, 2003
Accepted May 20, 2004
The search for novel antigens suitable for improved vaccines and diagnostic reagents against leptospirosis led to the identification of LigA and LigB. LigA and LigB expression were not detectable at the translation level but were detectable at the transcription level in leptospires grown in vitro . Lig genes were present in pathogenic serovars of Leptospira , but not in non-pathogenic Leptospira biflexa . The conserved and variable regions of LigA and LigB (Con, VarA and VarB) were cloned, expressed and purified as GST-fusion proteins. Purified recombinant LigA and LigB were evaluated for their diagnostic potential in a kinetic ELISA (KELA) using sera from vaccinated and microscopic agglutination test (MAT)-positive dogs. Sera from vaccinated dogs showed reactivity to whole-cell antigens of leptospires but did not show reactivity in the KELA assay with recombinant antigens, suggesting a lack of antibodies to Lig proteins in the vaccinated animals. The diagnostic potential of recombinant Lig antigens in the KELA assay was evaluated by using 67 serum samples with MAT 1600, which showed reactivity of 76, 41 and 35 % to rConA, rVarA and rVarB, respectively. These findings suggest that recombinant antigen to the conserved region of LigA and LigB can differentiate between vaccinated and naturally infected animals.
Abbreviations: KELA, kinetic ELISA; MAT, microscopic agglutination test.
The GenBank/EMBL/DDBJ accession numbers for the nucleotide sequences of ligB and C are AF534640 and AY327260 , respectively.
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