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A Krongrad

Publications and source records attributed to A Krongrad.

At least 37 records · Page 2Linked to original sources
PubMed1997

Competing risks of mortality in prostate cancer.

PURPOSE: We have observed that in prostate cancer older age, black race, high stage and no treatment are independently associated with higher disease specific and overall mortality. Because disease nonspecific mortality was not examined one cannot reasonably infer that higher overall mortality is largely due to higher disease specific mortality. To understand better the interactions of independent prognostic variables with overall mortality we jointly evaluated their effects on type of death and time to death. MATERIALS AND METHODS: Using the prostate cancer patients of the 1973 to 1990 public use tape of the Surveillance, Epidemiology and End Results program, we performed competing risks analysis with multivariate accelerated failure time model to examine if the prognostic factors were associated with type of death and time to death. RESULTS: Older age, black race and no treatment were independently associated with higher relative risk of disease specific and nonspecific mortality. Localized stage was associated with lower and higher disease specific and nonspecific mortality than regional stage, respectively. The relative risks of disease specific and nonspecific mortality were significantly different from each other for all prognostic factors. CONCLUSIONS: To our knowledge, a competing risks analysis in prostate cancer has not been done previously. While all prognostic factors were associated with disease specific and nonspecific mortality, the relative contribution of disease specific and nonspecific mortality to overall mortality varied by prognostic factor, with some prognostic factors associated with relatively high disease specific mortality while others were associated with relatively high disease nonspecific mortality. The similarity of the associations of age, race and treatment with disease specific and nonspecific mortality suggests that they mark an unidentified factor(s) that affects patient health nonspecifically. Such a factor(s) may partly or completely explain the association of treatment with lower disease specific mortality.

Aged↗
PubMed1997

Predictors of general quality of life in patients with benign prostate hyperplasia or prostate cancer.

PURPOSE: Studies in disease specific populations have emphasized disease specific quality of life with little study of general quality of life. Furthermore, studies of general quality of life in disease specific populations have mostly examined the importance of disease specific variables, and have generally yielded poor correlations of such variables and general quality of life. We attempted to model the emotional component of general quality of life in patients with prostate disease. MATERIALS AND METHODS: We integrated prospectively collected disease specific and nonspecific clinical and self-reported patient data. We also applied neural network and more conventional statistical tools to examine the relative use of various available analytical methodologies in modeling general quality of life. RESULTS: Neural networks created reasonably good models of the emotional component of general quality of life. Logistic regression analysis also created reasonably good models and, given current computational schemes, allowed for identification of significant inputs in the models more readily than did the feed-forward, back propagation neural networks. All models of general quality of life relied primarily on disease nonspecific inputs, including social support, activities of daily living and coping. CONCLUSIONS: Our observations suggested that efforts to optimize general quality of life in patients with prostate disease must integrate disease nonspecific variables.

Humans↗
PubMed1997

Reliability of Spanish translations of select urological quality of life instruments.

PURPOSE: Many patients with urological disease do not speak English. In medical studies restricting patients to those who speak only English undermines efforts to understand disease because restrictions decrease efficiency of patient recruitment, and because language and culture are associated with variable outcomes. In Spanish speaking locations, such as South Florida, studies would suffer severe selection bias if patients were required to speak English. To allow grouping in future studies of English and Spanish speaking patients we examined the English-Spanish reliability of select instruments that measure health related quality of life in patients with urological disease. MATERIALS AND METHODS: We assembled available Spanish versions and translated English versions of questions regarding satisfaction, the American Urological Association symptom index, the University of California, Los Angeles Prostate Cancer Index and a pain inventory. We then examined English-Spanish reliability by asking bilingual men 50 years old or older to complete English and Spanish versions at the same sitting. A convenience sample was recruited from outpatients and volunteers at the Miami Veterans Affairs Medical Center and population based subjects living in largely Hispanic Hialeah, Florida. Reliability estimates were calculated with kappa coefficients for categorical data and intraclass correlation coefficients for quantitative data. RESULTS: A total of 100 subjects a median of 59 years old completed the questionnaire, including 55 born in Puerto Rico or Cuba, while the remainder were born at various sites throughout the Americas and Spain. Reliability estimates showed that kappa = > 0.81 for almost all items. For 2 items relating to health and social interactions reliability was poor, and stratification showed that poor reliability was primarily a feature of subjects in good health who are theoretically socially active. CONCLUSIONS: Almost all items tested have excellent English-Spanish reliability in a mixed sample of bilingual men. Nonreliability of 2 items relating to health and social interactions probably originates from the effect of language on perception, and invalidates English and Spanish grouping of these items. Because the sample represents many dialects of Spanish, the translations tested may be transported to other cities. In studies that use these instruments investigators can reasonably group answers from English and Spanish speaking study subjects or study the effects of acculturation on quality of life.

Hispanic or Latino↗
PubMed1997

Variation in prostate cancer survival explained by significant prognostic factors.

PURPOSE: Traditional survival analytical tools do not reveal the ability of significant prognostic factors to predict (that is, explain variation in) survival. We used survival data in patients with prostate cancer to illustrate how the association of factors with survival diverges from their ability to explain variation in survival; bladder cancer was included as a point of general comparison. MATERIALS AND METHODS: We used the 1973 to 1990 records of the Surveillance Epidemiology and End Results program. Multivariate proportional hazards models were used to identify factors that significantly associated with survival. The proportion of variation explained by these factors was estimated with the Schemper method. RESULTS: The dataset included 10,636 patients with prostate cancer and 1,070 with bladder cancer. Median survival was significantly longer in prostate than bladder cancer; other characteristics were similarly distributed. Age, stage and marital status were associated with survival in both cancers (p value range 0.0001 to 0.0009). The total proportion of variation explained was 7.1% and 32.1% for prostate and bladder cancer, respectively. In prostate cancer, age, stage and marital status explained 0.6, 5.5 and 0.4%, of the adjusted proportion of variation explained, respectively, and in bladder cancer, they explained 14.7, 8.9 and 0.6%, respectively. CONCLUSIONS: Proportional hazards models identified but did not reveal the ability of significant prognostic factors to explain variations in survival. The proportion of variation explained analyses illustrate why predicting survival is so difficult, especially in prostate cancer. The prognostic factors used do not possess the ability to explain variation in survival; new prognostic factors must be identified.

Aged↗
PubMed1996

Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group.

OBJECTIVE: To determine whether a nutritional supplement of selenium will decrease the incidence of cancer. DESIGN: A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial. SETTING: Seven dermatology clinics in the eastern United States. PATIENTS: A total of 1312 patients (mean age, 63 years; range, 18-80 years) with a history of basal cell or squamous cell carcinomas of the skin were randomized from 1983 through 1991. Patients were treated for a mean (SD) of 4.5 (2.8) years and had a total follow-up of 6.4 (2.0) years. INTERVENTIONS: Oral administration of 200 microg of selenium per day or placebo. MAIN OUTCOME MEASURES: The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin. The secondary end points, established in 1990, were all-cause mortality and total cancer mortality, total cancer incidence, and the incidences of lung, prostate, and colorectal cancers. RESULTS: After a total follow-up of 8271 person-years, selenium treatment did not significantly affect the incidence of basal cell or squamous cell skin cancer. There were 377 new cases of basal cell skin cancer among patients in the selenium group and 350 cases among the control group (relative risk [RR], 1.10; 95% confidence interval [CI], 0.95-1.28), and 218 new squamous cell skin cancers in the selenium group and 190 cases among the controls (RR, 1.14; 95% CI, 0.93-1.39). Analysis of secondary end points revealed that, compared with controls, patients treated with selenium had a nonsignificant reduction in all-cause mortality (108 deaths in the selenium group and 129 deaths in the control group [RR; 0.83; 95% CI, 0.63-1.08]) and significant reductions in total cancer mortality (29 deaths in the selenium treatment group and 57 deaths in controls [RR, 0.50; 95% CI, 0.31-0.80]), total cancer incidence (77 cancers in the selenium group and 119 in controls [RR, 0.63; 95% CI, 0.47-0.85]), and incidences of lung, colorectal, and prostate cancers. Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group, the blinded phase of the trial was stopped early. No cases of selenium toxicity occurred. CONCLUSIONS: Selenium treatment did not protect against development of basal or squamous cell carcinomas of the skin. However, results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites. These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made

Adult↗
PubMed1996

Mortality in prostate cancer.

PURPOSE: We evaluated in patients with prostate cancer whether treatment is associated with in decreased mortality and whether the association of treatment with mortality varies with calendar time. MATERIALS AND METHODS: Using the 146,979 prostate cancer patients from the 1973 to 1990 public use tape of the Surveillance, Epidemiology and End Results program, we performed survival analysis and multivariate proportional hazards modeling to estimate the relative risk of disease specific and overall mortality. RESULTS: In men with prostate cancer, advanced age, black race, high tumor stage and not having treatment were independently associated with disease specific and overall mortality. The relative risk of mortality in treated patients decreased significantly from 1973 to 1990. CONCLUSIONS: The fact that advanced age and black race are associated with disease specific mortality (even when treatment and stage are controlled) is a new observation, which suggests that tumor biology and/or response to treatment is worse in elderly and black men. Overall, the data are consistent with the hypothesis that treatment of prostate cancer is associated with lower disease specific and overall mortality rates. The decreases in relative mortality in treated patients from 1973 to 1990 indirectly support the theory that changes in patterns of care from 1973 to 1990 had a beneficial effect on mortality. This observation implies that future studies should account for calendar time when interpreting outcomes data.

Aged↗
PubMed1996

Marriage and mortality in prostate cancer.

PURPOSE: We evaluated the association of marital status and survival in patients with prostate cancer. MATERIALS AND METHODS: Using the 146,979 prostate cancer patients of the 1973 to 1990 public use tape of the Surveillance, Epidemiology and End Results program we performed survival analysis and multivariate proportional hazards modeling to estimate the relative risk of mortality. RESULTS: Married patients had significantly longer median survival than those who were divorced, single, separated or widowed. In models that controlled for age, stage, race and treatment, married patients had a significantly lower risk of mortality than those who were divorced, single, separated or widowed. CONCLUSIONS: Several hypothetical models can explain the association of marital status and mortality in men with prostate cancer. The most attractive model relies on the putative salutary effects of being married on social support and/or mood. A social support and depressed mood model of mortality raises the possibility that in prostate cancer quality of life determines quantity of life. Understanding the relationships among marital status, social support, mood and mortality could open the way to rational strategies for postponing death in men with prostate cancer.

Aged↗
PubMed1995

Neuroendocrine peptides in the prostate.

Circulating androgens are required for normal growth and maintenance of function of the prostate. However, the prostate also contains neuroendocrine peptides, found either in nerve terminals or in prostatic neuroendocrine cells, which are likely to regulate prostate growth or function. The neuronal peptides are likely to participate in the regulation of the synthesis and secretion of prostatic secretory products. While the function of the neuroendocrine cells is undefined, there is evidence for growth-regulating effects of several neuroendocrine cell peptides. Since neuroendocrine differentiation has been correlated with tumor grade and poor prognosis in prostate cancer, the peptide products of the neuroendocrine cells may influence cancer cell replication as well. Recent evidence in other tissues suggests that peptide hormone receptor second-messenger systems may interact with steroid receptors to modulate their actions. These findings raise the possibility that prostatic neuroendocrine peptides may modulate the response of prostate to androgens.

Androgens↗
PubMed1995

Involvement of CD44 and its variant isoforms in membrane-cytoskeleton interaction, cell adhesion and tumor metastasis.

CD44s (standard form of CD44) is a transmembrane glycoprotein whose external domain displays extracellular matrix adhesion properties by binding both hyaluronic acid (HA) and collagen. The cytoplasmic domain of CD44s interacts with the cytoskeleton by binding directly to ankyrin. It has been shown that post-translational modifications, such as phosphorylation (by protein kinase C), acylation (by acyl-transferase) and GTP-binding enhanced CD44's interaction with cytoskeletal proteins. Most importantly, the interaction between CD44s and the cytoskeletal protein, ankyrin, is required for the modulation of CD44s cell surface expression and its adhesion function. Recently, a number of tumor cells and tissues have been shown to express CD44 variant (CD44v) isoforms. Using RT-PCR and DNA sequence analyses, we have found that unique CD44 splice variant isoforms are expressed in both prostate and breast cancer cell lines and carcinomas. Most importantly intracellular ankyrin is preferentially accumulated underneath the patched/capped structures of CD44 variant isoform in both breast and prostate cancer cells attached to HA-coated plates. We propose that selective expression of CD44v isoforms unique for certain metastatic carcinomas and their interaction with the cytoskeleton may play a pivotal role in regulating tumor cell behavior during tumor development and metastasis.

Animals↗
PubMed1994

c-fos promoter insensitivity to phorbol ester and possible role of protein kinase C in androgen-independent cancer cells.

In exploring the biological basis of androgen-independent prostate cancer, we observed serum-independent growth of androgen-independent cells. We then discovered that in androgen-independent but not androgen-dependent cells, the serum-responsive gene c-fos is insensitive to phorbol esters, which regulate c-fos through the same mechanisms as serum. Transient expression of protein kinase C, through which phorbol esters activate c-fos, was sufficient to desensitize c-fos in androgen-dependent cells. Incubation in protein kinase C inhibitor chelerythrine killed androgen-independent but not androgen-dependent cells. This finding implicates protein kinase C activity in androgen-independent prostate cancer and suggests novel therapeutic strategies.

Androgens↗
PubMed1992

Temperature mapping in the canine prostate during transurethrally-applied local microwave hyperthermia.

Although the therapeutic effects of heat on tumors have been known for more than a century, only recently has hyperthermia been applied in the treatment of various solid tumors in a scientific fashion. In preliminary clinical trials, heat applied by transurethrally or transrectally placed microwave antennas has been used in the treatment of benign prostatic hyperplasia (BPH) with some success. However, basic information about prostatic temperature distribution and the cellular effects of hyperthermia is lacking. In an attempt to establish the safety of local hyperthermia of the prostate and the precise temperature distribution within the gland, we performed temperature mapping studies in canine prostates. Eight mongrel dogs were anesthetized, and a 16 Fr catheter with three helical coil microwave antennas was placed in the bladder through a perineal urethrostomy. Laparotomy was performed and the bladder opened. The antennas were placed under direct control in the prostatic urethra. Linear array and single point thermometers (Clini-Therm TS1200 thermometry system) were placed (1) within the catheter alongside the antennas, (2) alongside the Foley catheter in the urethra, and (3) longitudinally and radially in the prostate for mapping of tissue temperature. Heating was performed with a 915-MHz ISM frequency Z-80 microprocessor controlled microwave power generator (Prostek 3000, Clini-Therm Corporation, Dallas, TX) using 2-9 watts per channel (6-27 watts total) for 30 min to 1 hr. Baseline body temperatures varied between the individual dogs from 37 degrees to 38 degrees C, but temperature distribution within the prostate was even prior to heating. With relatively low power (6 watts total), temperatures of greater than or equal to 45 degrees C were reached within the catheter. Therapeutic temperatures of approximately 43 degrees C were achieved in the periurethral prostate. Intraurethral temperatures were in general 1-2 degrees C lower than within the catheter. The radial temperature dropoff in the prostate was sharp and about 1 degrees C per 3-mm distance from the catheter. This would limit the area of effectiveness to a periurethral zone of 1 cm in diameter in this model. No unsafe temperature peaks were noted either intraurethrally or between the prostate and the rectum during steady-state conditions. Histologic studies demonstrated an intact rectal wall and varying degrees of prostatic inflammation and/or necrosis despite uniform treatment regimens administered. These studies demonstrate the short-term safety of microwave hyperthermia in the canine prostate. Further studies will be necessary to determine the clinical efficacy and toxicity in men with BPH.

Animals↗
PubMed1991

Androgen increases androgen receptor protein while decreasing receptor mRNA in LNCaP cells.

We have examined the effect of androgen treatment on androgen receptor mRNA and protein expression in the LNCaP human prostate carcinoma cell line. Incubation with androgen caused a decrease in cellular androgen receptor mRNA content that was concentration and time dependent. Maximal suppression to approximately 35% of control level was observed after 49 h of exposure to androgen. By contrast, incubation of LNCaP cells with androgen resulted in a 2-fold increase in the cellular content of androgen receptor protein at 24 h. At 49 h androgen receptor protein increased 30% as assayed by immunoblots and 79% as assayed by ligand binding. These results suggest that ligand-induced changes in androgen receptor stability and/or the translational efficiency of androgen receptor mRNA account for the phenomenon of androgen receptor upregulation observed in cultured LNCaP cells. Furthermore, the suppression of androgen mRNA and protein that is caused by prolonged incubation with androgen is incomplete and is reversible upon removal of ligand.

Androgens↗
PubMed1988

Biliary obstruction complicating extracorporeal shock wave lithotripsy.

An elderly woman with a solitary right kidney and unrecognized cholelithiasis underwent extracorporeal shock wave lithotripsy for renal calculi. Postoperatively, biliary obstruction developed that required emergency surgery. Pathological evaluation of the biliary calculi revealed superficial fragmentation. It is suggested that extracorporeal shock wave lithotripsy was responsible for the gallstone fragmentation and resultant bile duct obstruction.

Aged↗
PubMedDate not supplied

Bladder neck dysynergia in spinal cord injury.

Urodynamic evaluations were performed in 43 male patients with spinal cord injuries, before any therapeutic decisions, and a minimum of 5 mo following the injury. Results were subdivided according to level of injury. Mean detrusor contraction pressures, incidence of detrusor-sphincter dysynergia (DSD), and incidence of detrusor-bladder neck dysynergia (DBND) were calculated. The incidence pattern of DBND was found to follow closely the incidence pattern of DSD, with the highest incidence among the upper thoracic injuries, considerably more than among the cervical injuries. A significantly higher resting detrusor pressure differential was found among the patients with DBND. This was felt to represent sympathetic dysfunction and poor accommodation and is proposed to be secondary to adrenergic detrusor neoinnervation.

Humans↗
PubMedDate not supplied

Cloning and partial sequence of the rabbit androgen receptor: expression in fetal urogenital tissues.

Genetic studies indicate that the actions of testosterone and dihydrotestosterone are mediated by a single androgen receptor (AR). The basis for the differential effects of these hormones during development is not known. To address this problem, we have turned to the rabbit, a species in which the endocrine and metabolic events in male sexual differentiation have been studied in detail. As a first step, we have cloned a partial cDNA encoding the rabbit prostate AR and have analyzed the expression of the cDNA in tissues of rabbit embryos at the time during which male phenotypic differentiation takes place. The coding sequence of the rabbit AR cDNA reveals a high degree of conservation with the sequences of the human, mouse, and rat ARs. By Northern analysis the principal transcript expressed in the mesonephros and the anlage of the external genitalia on gestation day 18 appeared to be identical to the mRNA expressed in adult prostate and epididymis.

Amino Acid Sequence↗