Estudio del léxico de las obras de Gutiérrez de Toledo (1498), de Montaña de Monserrate (1551), de Juan Valverde (1556) y de Francisco Díaz (1588), elegidos por ser, unos, los primeros tratados sobre Urología y Anatomía escritos en romance y, otros, los mejores tratados del Renacimiento español.Hemos intentado demostrar cómo una gran cantidad de términos médicos utilizados, usualmente, hasta hoy día aparecen por primera vez en estas obras. En total nuestro léxico contiene 4565 entradas, de las que sólo 500 aparecen en los tres diccionarios consultados -DRAE, DCECH, DETEMA-. Concluimos demostrando que la primera datación de algunas de las voces se halla en estos autores. Su interés estriba en la falta de estudios al respecto y en lo novedoso que resulta en el momento en que los tratados científicos aún se escribían en latín, el hecho de que estos cuatro médicos se decidan a hacerlo en romance. / Research on the vocabulary of the works by Gutierrez de Toledo, by Montaña, by Valverde and by Díaz, chosen as ones are the first treatises on Urology and Anatomy written in Spanish and others because they are the best Spanish Renaissance treatises.We have tried to prove that such a big amount of medical terminology used, usually, even nowadays, appears for the first time in the above mentioned works. In total our lexicon contains up to 4,565 terms, but only 500 appear in the 3 dictionaries checked -DRAE, DCECH, DETEMA-. We conclude proving that the first time these terms appear are in the works of these authors.The interest relies on the lack of research regarding this issue and how innovative is the fact that these four doctors decided to do it in Spanish at a time these type of scientific treatises were still written in Latin.

The natural history of localized prostate cancer is not fully understood. In most patients the tumor will never progress to a lethal disease, while a subset of patients will ultimately die of the disease. Efficient tools to separate indolent from lethal disease is currently lacking which means that many patients will be offered treatment without any benefit, but still be at risk of experiencing treatment related side effects. The aims of these studies were to get more insight into the natural history of untreated localized prostate cancer, to assess the prognostic value of established clinical parameters such as Gleason score, nuclear grade and tumor volume and, moreover, some new prognostic markers Ki-67, AMACR and MUC-1. We also aimed to study time trends in the detection of incidental tumors in Sweden. Patients with localized disease (n=223) and no initial treatment were followed for 21 years. Most patients had a favorable outcome. However, a subset of patients developed lethal disease even beyond 15 years of follow-up and these patients define the group that may benefit most from treatment with curative intent. Patients with poorly differentiated tumors experienced a 9 time higher risk of dying in prostate cancer. The studies on prognostic markers are based on a cohort of patients (n=253) with incidental prostate cancer detected by transurethral resection for presumed benign hyperplasia. All patients were left without initial treatment. Gleason grade, nuclear grade and tumor volume turned all out to be independent prognostic factors. MUC-1, AMACR and Ki-67 also carried prognostic information. However, after adjustment for Gleason grade, nuclear grade and tumor volume only MUC-1 and AMACR remained as statistically significant prognostic factors. When tested for sensitivity and specificity they all failed and, consequently, they seem to be of less value in daily practice for cancelling an individual patient regarding the choice of treatment. Time trends in incidental prostate tumors in Sweden were analyzed in a cohort of patients with prostate tumors detected by transurethral resection (TUR-P). Through linkage of the national registration number (NRN) with several registers, e.g. the Swedish Cancer Registry, the National Inpatient registry and the Cause of Death Registry we identified, during the period 1970 through 2003, in total 23288 patients with incidental prostate cancer, who constituted the study group. As comparison group we choose all patients diagnosed with prostate cancer between 1970-2003 excluding those with incidental cancer, in total 112204 patients. Our result confirms earlier findings that there has been a dramatic change over time in incidence of incidental prostate cancers in Sweden, which parallels the introduction of prostate specific antigen. We also found that the cumulative incidence of prostate cancer death is high in the incidental group, opposing earlier findings that incidental tumours are a non-lethal disease.

Quality-of-life and functional outcomes are important in the choice of treatment for men with localized prostate cancer. These issues were investigated in the present thesis. All living 400 men randomized to radical prostatectomy or watchful waiting from 1989 to 1999 in the Scandinavian Prostate Cancer Group Number 4 (SPCG-4) were included. An additional 281 men compromised an age-matched control group. Physical symptoms, symptom-induced stress, sense of well-being and self-assessed quality of life were evaluated by a study-specific questionnaire. Results showed that prostate cancer men, regardless if they were allocated to radical prostatectomy or watchful waiting were suffering of long term adverse effects, mainly erectile dysfunction, urinary leakage and voiding symptoms. In the prostatectomy group, erectile dysfunction and urinary leakage were often consequences of surgery; in the watchful waiting group the side-effects could be caused by tumor progression. The quality of life deteriorated over time. High self-assessed quality of life was reported by 35 % in the radical, 34 % in watchful-waiting, and 43 % in the control groups after a median follow-up time of 12.2 years. The SPCG-4 men significantly more often reported anxiety than did controls. Erectile dysfunction was associated with the most negative influence on quality of life in both SPCG-4 groups. Men in the prostatectomy group were more distressed by erectile dysfunction than watchful waiting. Androgen deprivation therapy had negative effects on all psychological parameters, including quality of life, for the watchful waiting but not for the prostatectomy group. Information about the prostate-cancer disease was significantly higher in the radical-prostatectomy group than in watchful waiting. Check-ups were associated with worry, especially for those on androgen deprivation therapy. Open radical prostatectomy led to an increased rate of inguinal hernia compared with robot-assisted technique. In conclusion, the data of this thesis emphasize that it takes more than a decade to understand the patterns of adverse effects and time dimension of their occurrence for each treatment. Consideration of quality of life has a high priority to aid the ageing man through the shifting scenarios of localized prostate cancer.

Background: Overtreatment of localized prostate cancer (PCa) is a concern as many men die of other causes prior to experiencing a treatment benefit. This dissertation characterizes the need for assessing other cause mortality (OCM) risk in older men with PCa and informs efforts to identify patients most likely to benefit from definitive PCa treatment. Methods: Using the linked Surveillance Epidemiology and End Results-Medicare Health Outcomes Survey database, 2,931 men (mean age=75) newly diagnosed with clinical stage T1a-T3a PCa from 1998-2009 were identified. Survival analysis methods were used to compare observed 10-year OCM by primary treatment type. Age and health factors predictive of primary treatment type were assessed with multinomial logistic regression. Predicted mortality estimates from Social Security life tables (recommended for life expectancy evaluation) and two OCM risk estimation tools were compared to observed rates. An improved OCM prediction model was developed fitting Fine and Gray competing risks models for 10-year OCM with age, sociodemographic, comorbidity, activities of daily living, and patient-reported health data as predictors. The tools’ ability to discriminate between patients who died and those who did not was evaluated with Harrell’s c-index (range 0.5-1), which also guided new model selection. Results: Fifty-four percent of older men with localized PCa underwent radiotherapy while 13% underwent prostatectomy. Twenty-three percent of those treated with radiotherapy and 12% of those undergoing prostatectomy experienced OCM within 10 years of treatment and thus were considered overtreated. Health factors indicative of a shorter life expectancy (increased comorbidity, worse physical health, smoking) had little to no association with radiotherapy assignment but were significantly related to reductions in the likelihood of undergoing prostatectomy. Social Security life tables overestimated mortality risk and discriminated poorly between men who died and those who did not over 10 years (c-index=0.59). Existing OCM risk estimation tools were less likely to overestimate OCM rates and had limited but improved discrimination (c-index=0.64). A risk model developed with self-reported age, Charlson comorbidity index score, overall health (excellent-good/fair/poor), smoking, and marital status predictors had improved discrimination (c-index=0.70). Conclusions: Overtreatment of older men with PCa is primarily attributable to radiotherapy and may be reduced by pretreatment assessment of mortality-related health factors. This dissertation provides a prognostic model which utilizes a set of five self-reported characteristics that better identify patients likely to die of OCM within 10 years of diagnosis than age and comorbidity-based assessments alone.

Objectif : Estimer la contribution statistique des caractéristiques des hôpitaux et des caractéristiques liés aux patients sur la probabilité de réadmission des patients qui ont subi une PCNL, une procédure endoscopique à haut risque de morbidité, dans les hôpitaux aux États-Unis en 2014 et évaluer les prédicteurs des taux de réadmissions d’une PCNL. Méthode : Nous avons identifié tous les patients qui ont subi une PCNL dans les hôpitaux aux États-Unis en 2014 (janvier-novembre) en utilisant la banque de données nationale de réadmission (NRD). L’issue d’intérêt était une réadmission non planifiée 30 jours après une PCNL. À l’aide d’un modèle multi-niveaux à effets mixtes, nous avons estimé l’association statistique entre les caractéristiques hospitalières ainsi que les caractéristiques individuelles liés aux patients sur la probabilité de réadmission. Un effet aléatoire associée à l'hôpital a été utilisé pour estimer le taux de réadmission au niveau hospitalier. Un pseudo R-carré a été calculé pour évaluer la contribution de chaque catégorie de variables sur les taux de réadmission. Résultats : Notre échantillon pondérée était constitué de 6 974 personnes ayant subi une PCNL dans 485 hôpitaux aux États-Unis en 2014. Le taux de réadmission à 30 jours était de 8,5 % (IC à 95 % 7,4 – 9,7). Après ajustement, les caractéristiques hospitalières n’étaient pas associées à une probabilité accrue de réadmission. Le sexe féminin était associé à une diminution de la probabilité de réadmission (IC à 95% 0.54 – 0.93). Les hôpitaux individuelles n’ont contribué qu’à une infime partie à la probabilité d’être réadmis de leurs patients. Les caractéristiques liés aux patients expliquaient davantage la variabilité dans la probabilité de réadmission que les caractéristiques hospitalières (pseudo-R2 9.50% vs 0.03%). Conclusion : Le risque d’être réadmis après une PCNL varie énormément entre les hôpitaux. Une fraction minime de cette variabilité peut être expliqué par les caractéristiques hospitalières contrairement aux caractéristiques des patients. Ces résultats soulignent les limites potentielles de l’utilisation des réadmissions comme mesure de la qualité des soins. / Objective: Estimate the relative contribution of hospital and patient factors to readmission after a typical high-risk endoscopic procedure, percutaneous nephrolithotomy (PCNL). Methods: We utilized the Nationwide Readmission Database to identify the patients who underwent PCNL in the United States hospitals in 2014 (January-November). The main outcome was unplanned 30-day readmission following a PCNL. Using a multilevel mixed-effects model, we estimated the statistical association between patient and hospital characteristics and readmission. A hospital-level random effects term was added to estimate hospital-level readmission. To assess the relative contribution of each group of variables on readmission rates, a pseudo-R2 was calculated to assess the contribution of hospital effects to the model of readmission. Results: We identified a weighted sample of 6,974 individuals who underwent PCNL at 485 hospitals in the United States in 2014. The 30-day readmission rate was 8.5% (95% CI 7.4 – 9.7). In our adjusted model, hospital characteristics were not associated with increased likelihood of readmission. Female sex was the only characteristic associated with decreased likelihood of readmission (95% CI 0.54 – 0.93). Individual hospitals contributed marginally to their patients probability of readmission. Patient level characteristics explained far more of the variability in readmissions than hospital characteristics (pseudo-R2 9.50% vs 0.03%). Conclusion: The risk of readmission after a PCNL is highly variable in between hospitals. The statistical contribution of individual hospitals and hospital characteristics to the probability of readmission following a PCNL was minimal compare to patient characteristics. These findings underscore the potential limitations of using 30-day post-discharge readmissions as a hospital-level quality metric.

PURPOSE: Our goal was to describe changes in bladder health, defined as "a complete state of physical, mental, and social well-being related to bladder function that permits daily activities, adapts to short-term stressors, and allows optimal well-being," in women over time. MATERIALS AND METHODS: We used data on 15 lower urinary tract symptoms (LUTS) and interference from urinary experiences assessed at the baseline and 5-year followup interviews of the BACH (Boston Area Community Health) Survey to estimate changes in bladder health over time in women. Associations between baseline and followup bladder health (defined as the maximum frequency of LUTS or interference at each time point) were calculated by ordinal logistic regression and generalized linear models. RESULTS: A total of 2,526 women provided complete information on bladder health at baseline and followup. Over the 5-year followup, 6.5% of women maintained optimal bladder health (no LUTS or interference), 33.6% developed worse bladder health (including 10.4% who transitioned from optimal to less than optimal health), 31.4% maintained their less than optimal bladder health status and 28.7% improved. Despite these changes, women with poorer bladder health at baseline were still more likely to have poorer bladder health 5 years later (eg multivariable-adjusted relative risk=3.27, 95% confidence interval: 2.49-4.29 for severe LUTS/interference at followup among those with severe LUTS/interference at baseline). CONCLUSIONS: Findings from our large secondary analysis of BACH Survey data suggest considerable variability in bladder health over time, and underscore the importance of bladder health promotion to prevent the initial onset and progression of poor bladder health in women.

Obesity has been related to a greater incidence of more aggressive, advanced stage prostate cancer. It is expected that serum adipokines related to obesity will promote a more aggressive phenotype in PC cells in vitro. Patient serum (n = 80) was obtained for analysis and divided into four patient groups based on obesity and prostate cancer status. Characteristics of serum-treated PC cells in vitro were measured. In a separate set of analyses, LNCaP and PC3 cells were treated with adiponectin and resistin in vitro, and cell characteristics were analyzed. Serum from obese PC patients induces greater amounts of cell migration and lower amounts of cell proliferation and invasion in vitro. Exogenous treatment of adiponectin on PC cells in vitro does not affect cell migration or invasion. However, adiponectin modulates cytosolic protein levels of soluble β-catenin and GSK-3β, indicating that its mechanism of action may be through the Wnt signalling pathway.

Aims: The overall aim was to determine how lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) affect sleep, health related quality of life and disease specific quality of life, and how the men’s urinary symptoms affect their partners. Subjects and methods: In papers I–II, a descriptive design with a pre-test and post-test was used and in papers III-IV the design was descriptive and comparative. The method was self-administered questionnaires. In papers I- II: The questionnaires were translated in the ethnographic mode. In paper I the reliability of the questionnaire was tested in 122 patients with LUTS/ BPO. The disease specific quality of life was studied before and after intervention in 572 consecutive patients with BPO, aged 45-94 yrs. In paper II, the partner specific quality of life was studied in partners to men with BPO before and after TURP. The reliability and the responsiveness of the questionnaire were tested in two groups with 51 partners each. Papers III-IV: A study of 239 men with LUTS, aged 45-80 yrs, and their partners (n=126) who were compared to randomly selected men from the population (n=213) and their partners (n=131). The men had an extra control group, men with inguinal hernia (n=200). Sleep and health related quality of life was studied in both men and their partners. The partners’ specific quality of life was also studied and the men with LUTS answered questions about urinary symptoms and disease specific quality of life. Results: Papers I-II: All the tested questionnaires showed an acceptable reliability and responsiveness. I: Before and after intervention the prevalence of urinary incontinence was 46 % and 16 % respectively. II: Partners were affected by the patients’ BPO symptoms before and improved after the patients TURPs. III: Most sleep variables were significantly impaired in men with LUTS compared to one or both of the control groups. The men with LUTS had a significantly higher prevalence of insomnia (40 %) than both control groups and significantly lower sleep efficiency (49 %) than men with hernia. The men with LUTS were significantly impaired in most domains of the health related quality of life compared to men in the population. IV: There were no significant differences between the two partner groups regarding the quantity and quality of sleep or the health related quality of life. Conclusions: All tested questionnaires showed an acceptable reliability and responsiveness. The prevalence of urinary incontinence before and after intervention was higher than earlier reported. Men with LUTS had significantly poorer sleep quality, reduced sleep efficiency and a higher prevalence of insomnia than men in the population and men with inguinal hernia. The HRQOL is impaired in men with LUTS compared to men in the population and men with inguinal hernia. Partners are affected by the patients’ symptoms, and it is emotional rather than practical aspects that affect them most. Partners of men with LUTS did not differ significantly from partners in the population with regard to sleep and health related quality of life.

Chronic kidney disease (CKD) progresses faster in males than females; however, the underlying mechanisms remain poorly understood. Sex differences in glomerular capillary morphology has been hypothesized to contribute, in part, to the increased susceptibility to hypertension-induced renal injury and CKD progression in males, but this has not been investigated. The goal of the present study was to assess glomerular capillary morphology in male vs. female rats with intact kidneys and after uninephrectomy (UNX). We hypothesized that glomerular capillary radii (RCAP) and length (LCAP) would be greater in male rats. Male (n=4) and female (n=4) with intact kidneys and UNX (n=4 males, n=4 females) provided a 0.4% NaCl diet and water ad libitum. Kidneys were perfusion-fixed, the left kidney was excised, and a 3 mm transverse section through the midline of the kidney was selected for further processing. Multiple 1 mm3 cubes were randomly excised from the left, middle, and right regions of the outer cortex, embedded in EPONTM, sectioned (1 μm), and stained with toluidine blue. Four glomeruli from each region were randomly selected for stereological analysis. Glomerular tuft volume (VG), RCAP, and LCAP were assessed. In rats with intact kidneys, no significant sex differences were observed in VG, RCAP, or LCAP. VG, RCAP, and LCAP were significant greater in both male and female rats with UNX vs. respective rats with intact kidneys. In rats with UNX, males exhibited a significantly greater VG and LCAP, but not RCAP, as compared to females despite no significant differences in relative kidney weight. These data indicate that males exhibit greater compensatory increases in LCAP following UNX. The greater capillary length may lead to reduced podocyte density, a well-known mechanism that increases the susceptibility to CKD progression.

This thesis addresses the three principal questions concerning the development of CT urography for investigating haematuria and each question is the subject of a separate chapter. The questions are: What is the reasoning behind using CT urography? What is the optimum diagnostic strategy using CT urography? What are the problems with using CT urography and how may solutions be provided? Haematuria can signify serious disease such as urinary tract stones, renal cell cancer, upper tract urothelial cancer (UTUC) and bladder cancer (BCa). CT urography is defined as contrast enhanced CT examination of kidneys, ureters and bladder. The technique used here includes unenhanced, nephrographic and excretory-phases for optimized diagnosis of stones, renal masses and urothelial cancer respectively. The reasoning behind using excretory-phase CT urography for investigating haematuria is based on results showing its high diagnostic accuracy for UTUC and BCa. Patients with haematuria are classified as low risk or high risk for UTUC and BCa, by a risk score, determined by the presence/absence of risk factors: age > 50 years, visible or nonvisible haematuria, history of smoking and occupational exposure. The optimum diagnostic strategy for patients at high risk for urothelial cancer, uses CT urography as a replacement test for ultrasonography and intravenous urography and as a triage test for flexible and rigid cystoscopy, resulting in earlier diagnosis and potentially improving prognosis. For patients at low risk, ultrasonography, unenhanced and nephrographic-phase CT urography are proposed as initial imaging tests. Problems with using CT urography include false positive results for UTUC, which are eliminated by retrograde ureteropyelography-guided biopsy, an innovative technique, for histopathological confirmation of diagnosis. Recommendations for the NHS and possible future developments are discussed. CT urography, including excretory-phase imaging, is recommended as the initial diagnostic imaging test before cystoscopy for patients with haematuria at high risk for urothelial cancer.