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71.
There is a pressing need for new agents for the treatment of hormone-resistant prostate cancer (HRPC). Pyrazoloacridine (PZA) has antitumor activity in several in vitro and in vivo tumor systems, and was selected for testing in clinical trials by the National Cancer Institute (NCI). We conducted a phase II trial of PZA for the treatment of HRPC. Seventeen male patients with HRPC were treated with PZA at 750 mg/m2 i.v. given over a period of 3 hr every 3 weeks. Response to therapy was assessed with serial measurements of serum prostate-specific antigen (PSA) and sequential imaging studies. The 17 patients were treated and fully evaluable. One patient experienced a significant decrease in PSA, from over 10,000 ng/ml to 423 ng/ml, along with an improvement in bone scan findings. However, no other patient obtained an objective or PSA response (overall PSA response rate = 5.9%). Median survival duration was 15.3 months. Toxicity was moderate. If PSA is used as a marker of response, single-agent PZA appears to lack efficacy in the treatment of HRPC. However, the one unambiguous response, and the favorable toxicity profile observed, may warrant further evaluation of this agent. 相似文献
72.
Characterization of the insulin-like growth factor axis in a human hepatoma cell line (PLC) 总被引:4,自引:0,他引:4
Scharf JG; Schmidt-Sandte W; Pahernik SA; Ramadori G; Braulke T; Hartmann H 《Carcinogenesis》1998,19(12):2121-2128
73.
74.
Jean B Kassem Steven E Katz Ashraf M Mahmoud Robert H Small Subha V Raman Cynthia J Roberts 《Indian journal of ophthalmology》2015,63(1):59-61
Ocular pulse amplitude (OPA) is defined as the difference between maximum and minimum intraocular pressure (IOP) during a cardiac cycle. Average values of OPA range from 1 to 4 mmHg. The purpose of this investigation is to determine the source of an irregular IOP waveform with elevated OPA in a 48-year-old male. Ocular pressure waveforms had an unusual shape consistent with early ventricular contraction. With a normal IOP, OPA was 9 mmHg, which is extraordinarily high. The subject was examined by a cardiologist and was determined to be in ventricular bigeminy. In addition, he had bounding carotid pulses and echocardiogram confirmed aortic insufficiency. After replacement of the aortic valve, the bigeminy resolved and the ocular pulse waveform became regular in appearance with an OPA of 1.6–2.0 mmHg. The ocular pressure waveform is a direct reflection of hemodynamics. Evaluating this waveform may provide an additional opportunity for screening subjects for cardiovascular anomalies and arrhythmias. 相似文献
75.
ABSTRACTAcute and complete ischemia of the hippocampi represents a rare cause of amnesia. This paper describes the features of four such cases presenting to a single tertiary care center over a 3-year period. Interestingly, in three instances, toxicology screening was positive for opioids at the time of presentation, while in the fourth, there was a known, reportedly remote, history of heroin use. Taken together with the known literature on the topic, complete hippocampal ischemia appears at least highly suggestive of a toxic exposure. Further case finding is necessary to better understand the etiology, nature, and prevalence of this unusual clinico-radiologic entity. 相似文献
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77.
Aasha I. Hoogland Hailey W. Bulls Brian D. Gonzalez Brent J. Small Lianqi Liu Joseph Pidala Heather S.L. Jim Asmita Mishra 《Journal of pain and symptom management》2019,57(5):952-960.e1
Context
Quality of life (QoL) is increasingly recognized as an important outcome of cancer treatment. Previous studies have examined clinical predictors of QoL, but with the increasing prevalence of wearable sensors that monitor sleep and activity patterns, further investigation into whether these behaviors are predictive of post-treatment QoL is now feasible. Among patients receiving aggressive cancer treatment such as hematopoietic cell transplantation (HCT), analysis of circadian rhythms (24-hour patterns of sleep and activity) via wearable sensors is limited.Objective
To evaluate the relationship between overall QoL and circadian rhythms in patients receiving allogeneic HCT.Methods
Patients wore an ActiGraph GT3X (Pensacola, FL) activity monitor for at least 72 hours before the initiation of conditioning chemotherapy and transplantation and completed a QoL (Functional Assessment of Cancer Therapy-General [FACT-G]) assessment. QoL assessments were also completed 1, 3, and 6 months after HCT.Results
Patients (n = 45, M age = 55) were mostly male (66%) with a total FACT-G score of 80.96 (SD = 16.05) before HCT. Mixed models revealed robust cross-sectional associations between overall QoL and multiple circadian rhythmicity parameters, including durations of high physical activity, overall circadian rhythmicity, and earlier starts of daily activity (P's < .01). Recovery of QoL after transplant was predicted by longer pre-transplant durations of high physical activity (P = .04) and earlier evening retirement (P = .04).Conclusion
Our findings suggest that wearable sensor information is a promising method of predicting recovery of QoL after HCT. Additional studies are needed to confirm these findings in a larger sample. 相似文献78.
Donna M. Small Roberta E. Burden Christopher J. Scott 《Clinical reviews in bone and mineral metabolism》2011,9(2):122-132
Cathepsin S is a lysosomal cysteine protease that has been shown to play a key role in MHC class II antigen presentation.
Consequently, it has been extensively evaluated as a therapeutic target in autoimmune diseases, such as rheumatoid arthritis
and psoriasis. Additionally, clinical and mechanistic evidence is emerging, revealing its inappropriate expression and secretion
in a wide range of disease states including atherosclerosis and tumourigenesis. This review covers the known role and consequences
of cathepsin S activity in these pathological disorders, highlighting various studies that have demonstrated its utility as
a therapeutic target. This review also examines challenges that exist towards the development of agents that specifically
target this protease and discusses the studies to date that have applied cathepsin S inhibitors in disease models. 相似文献
79.
R. Margalit S. Watanabe-Galloway F. Kennedy N. Lacy K. Red Shirt L. Vinson J. Kills Small 《Journal of community health》2013,38(3):538-545
This qualitative study is intended to elucidate Lakota elders’ views on traditional tobacco and commercial/addictive tobacco use, capturing the oral history that depict the cultural protocol regarding traditional tobacco, called Cansasa. Commercial tobacco use has significantly impacted the Northern Plains Indians. National surveillance systems report that tobacco use is more prevalent among American Indian/Alaska Natives than any other population, and is notably higher than the national average. Lung cancer among Native Americans is highest in the Northern Plains and Alaska, where smoking prevalence is also the highest, and smoking is responsible for nearly 90 % of all lung cancer cases. Yet, the use of traditional tobacco is largely ignored by surveillance and seems to have a distinct, positive role. Using a community-based participatory research approach, semi-structured interviews, and qualitative analysis tools, the research team, including 2 Lakota tribe elders, Lakota speaking tribal college students, and university faculty, sought to discern tribal elders’ distinctions between traditional and the addictive commercial tobacco. The team interviewed thirty Lakota elders, transcribed the interviews and field notes, and analyzed them using immersion/crystallization organizing framework. The research design engaged the Lakota tribal community in all stages, from planning to publication. Analysis revealed a clear distinction between traditional and commercial tobacco: tribal elders conveyed strong positive messages connected to traditional tobacco use (i.e., spirituality, respect, health and wellness, humility, and thoughtfulness) versus strong negative messages linked to addictive tobacco (i.e., crime, loss of control and self-esteem, lack of respect to self and others, sickness and death). These messages, along with stories in the Lakota language that were told and recorded during the interviews, can guide new ways to address addictive tobacco prevention in this community, to enhance cultural pride, and to serve as a cross-generation bridge regarding tobacco use. 相似文献
80.
J L Sanchez B M Diniega J W Small R N Miller J M Andujar P J Weina P G Lawyer W R Ballou J K Lovelace 《The American journal of tropical medicine and hygiene》1992,47(1):47-54
An outbreak of cutaneous leishmaniasis occurred in a unit of 608 Puerto Rican national guardsmen conducting jungle warfare training in the Panama Canal Area in July 1984. An epidemiologic investigation of reported nonhealing, ulcerating skin lesions was conducted among 540 (89%) unit members in November and December 1984. Fifteen (88%) of 17 individuals with chronic, ulcerating skin lesions were confirmed as cases of cutaneous leishmaniasis by culture or histopathology. Twelve cases yielded positive Leishmania cultures, identified as L. braziliensis panamensis by cellulose acetate electrophoresis. Evaluation of different diagnostic techniques revealed that direct examination of tissues by Giemsa-stained histological examination was the most sensitive test (87% sensitivity), with an indirect immunofluorescent antibody test being rather insensitive (67%). All but one of the confirmed cases operated in small units that trained and slept overnight at a mortar firing site for a period of three days, yielding a site-specific attack rate of 22% (14 of 64). This contrasted with a much lower attack rate of 0.2% (1 of 476), experienced by unit members who trained at other locations during the same time frame (P less than 0.001). The median incubation period calculated from day of arrival at the mortar firing site was 17 days (range 2-78) for the 15 confirmed cases. Available personal protection methods, such as the use of insect repellents, were not appropriately implemented by unit personnel and thus, were not found to effectively protect against Leishmania infection. This is the largest reported outbreak of cutaneous leishmaniasis in military personnel associated with a single geographic focus of infection and contrasts with the usual sporadic disease experience in Panama. 相似文献