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Biomedical subjects

A Sciarra

Publications and source records attributed to A Sciarra.

At least 19 recordsLinked to original sources

Importance and evaluation of comorbidity in rehabilitation.

PURPOSE: The aim of this study is to evaluate the relationship between comorbidity and the disability in patients referred to a rehabilitation centre. Patients often suffer from associated diseases which may negatively influence the outcome. METHOD: After evaluation of several scales, the Cumulative Illness Rating Scale (CIRS) was selected. For the study 413 consecutive patients were enrolled. RESULTS: In this series, neurological patients presented with higher severity and higher comorbidity than orthopaedic patients. Orthopaedic cases were older but neurological cases had higher severity and higher comorbidity. Indeed, a significant negative correlation between severity and dependence scores was found. Comorbidity, also, showed a significant negative correlation with FIM both in the orthopaedic and in the neurological patients. These data show that severe comorbid conditions influence functional autonomy. Severity and Comorbidity were correlated both in orthopaedic cases and in neurological cases as well. CONCLUSIONS: A review of geriatric literature demonstrates lower values in the patients in rehabilitation. The difference is due to our accurate selection of patients at admission, where general health conditions are considered. In conclusion the CIRS scale should be used as a method for selecting patients at admission or as a prognostic index for improvement at discharge. CIRS, however, has some inconveniences and amelioration is necessary, such as the inclusion of a double testing (admission-discharge), psychiatric disturbances and a new item for skin alone. CIRS should not be applied if a patient referred for rehabilitation has the worst score in even a single item.

Aged↗

[Heredity and urologic tumors].

Most human malignant tumours derive from a series of several mutations in cell growth regulatory genes. Neoplastic transformation is a multistep, or at times multigenic event where several mutations must intervene. Hereditary forms have been identified for a number of human neoplasias. In hereditary forms, the individual already inherits one or more of these mutations and assumes an increased risk of developing a specific carcinoma and at an earlier age. On the other hand, in sporadic forms, the risk is lower because the environmental factors must provoke in sequence all the mutations necessary for neoplastic transformation. These genic mutations are often associated with the deletion of oncosuppressor genes which negatively regulate cell proliferation and/or with the hyper-expression and activation of protoncogenes which favour cell proliferation. The products of these genes are often growth factors or receptors of growth factors. The present review analyses the definition and more or less proven identification of familial and hereditary forms in neoplasias of urological interest.

Humans↗

Very old people can have favorable outcome after hip fracture: 58 patients referred to rehabilitation.

We examined both impairment and disability of 58 patients who were referred to our rehabilitation center after surgery of hip fracture. The mean age was 86.7 years. The impairment was measured by the Motricity Index (MI) scale and disability by means of the Functional Independence Measure (FIM) scale. At admission, the MI median value was 64 and at discharge the value was 84 (range of scale, 0-100). The FIM median value was 57.5 at admission and 82 at discharge (range of scale, 18-126). Our data indicate that, on average, patients recover, even at very advanced age, but still require supervision at discharge. Twelve patients died after complications of previous risk factors. When general conditions were satisfactory, no complications arose.

Journal Article↗

Independent value of tumor size and DNA ploidy for the prediction of disease progression in patients with organ-confined renal cell carcinoma.

BACKGROUND: Greater than 20% of patients with apparently localized renal cell carcinoma (RCC) present with disease progression after surgery. The objective of the current study was to improve the ability of clinicians to predict prognosis in patients with localized RCC. METHODS: The authors studied 154 patients with organ-confined RCC classified as pT1 to pT2-pN0-M0 who underwent radical nephrectomy. Follow-up ranged from 24-128 months (median, 72 months). Several morphologic parameters of the tumor were considered. DNA content was analyzed by flow cytometry and tumor size was determined from the surgical specimen. A Cox proportional hazards regression model was used to identify significant independent prognostic factors for disease progression. RESULTS: At 5 and 10 years of follow-up, disease free survival was found to be 87% and 86%, respectively. Univariate analysis revealed that DNA content, Furhman grade, and tumor size had a statistically significant predictive value for disease progression, whereas, with regard to grade, the difference was significant only between patients with Grade 3 tumors and all other patients with Grade 1-2 tumors (P < 0. 0001). Although DNA content was found to correlate with tumor size (P < 0.0001), multivariate analysis showed that these were the only significant independent predictors of disease progression. The sum of DNA content and tumor size therefore was considered to distinguish separate risk groups. For a patient with diploid RCC, the risk of progression increased from 4% if the tumor size was 3 cm to 43% if the tumor size was 10 cm. For a patient with nondiploid RCC, this risk was 32% if the tumor size was 3 cm, increasing to 99% for tumors measuring 10 cm. CONCLUSIONS: Stratification of organ-confined RCC according to tumor size and DNA content could possibly provide more information that could be useful in the selection of individuals with significantly different risks of disease progression.

Adult↗

Intermittent androgen deprivation (IAD) in patients with biochemical failure after radical retropubic prostatectomy (RRP) for clinically localized prostate cancer.

We report a study in which our objective was to analyze the clinical response during IAD in patients with biochemical failure after RRP for clinically localized prostate cancer. Between February 1994 and May 1996, 34 patients who exhibited a primary postoperative decrease in PSA to below the detection limit after RRP and then showed PSA progression during follow-up were included as group 1 and 17 patients in whom PSA did not decrease after RRP were included as group 2. Patients were offered IAD when PSA progressed over 0.4 ng/ml in group 1 and over 4.0 ng/ml in group 2. Median follow-up is 184 weeks in group 1 and 206 weeks in group 2. The median time "off" therapy increased from 25% (1st cycle) to 68.7% (5th cycle) of the entire cycle in group 1 and from 33.3% to 58.3% in group 2. Nine out of 12 cases with Gleason score > or =8 failed to respond to IAD and all developed metastatic and/or local failure. No case with Gleason score <7 failed to respond to IAD. Our conclusions suggest that IAD may be effective in patients with biochemical progression after RRP. In our experience, Gleason score seems to be an important variable.

Adenocarcinoma↗

[Role of nitric oxide in the urogenital system: physiology and pathology].

A review has been made on the role of nitric oxide in the physiology and pathophysiology of penis, bladder, prostate and the nervous structures involved in the urinary control. NO is an essential mediator in penile erection and his action can be modulated by sildenafil. Nitric oxide could be involved in bladder detrusor relaxation and in the development of interstitial cystitis. Little is known about the role of nitric oxide in the physiology and pathophysiology of the prostate: this molecule is released by the epithelial and stromal cells of the prostate, and by the prostatic nerves. Actually some studies hypothesize a role played by nitric oxide in benign prostatic hyperplasia development.

Humans↗

Intermittent androgen deprivation (IAD) in patients with localized prostate cancer and a biochemical progression after radical prostatectomy.

BACKGROUND: To analyze the modifications in serum PSA levels during IAD in patients with an initial PSA progression after radical retropubic prostatectomy (RRP). METHODS: Between February 1994 and May 1996, 34 consecutive patients with an initial PSA progression (> 0.4 ng/ml) after RRP were selected. All men had localized adenocarcinoma of the prostate, stage pT2 pN0 M0. Patients were offered IAD when PSA progressed over 0.4 ng/ml. The initial treatment period with complete androgen deprivation (CAD) lasted 24 weeks in all cases. After, an acceptable nadir PSA level was considered to be a value < or = 0.4 ng/ml. CAD was then with held until serum PSA increased to a value over 0.4 ng/ml. RESULTS: Follow-up ranges from 144 to 228 weeks. The median time for the first 5 treatment cycles was 32, 24, 28, 32 and 32 weeks respectively, with a median time "off" therapy that increased from 8 weeks (first cycle) to 22 weeks (fifth cycle). The median nadir PSA value during "on" treatment period was 0.20 ng/ml in all 5 cycles. So far, in none of the patients did a serum PSA fail to decrease during "on" treatment period. CONCLUSIONS: We suggest that IAD may be an effective therapy in patients with an initial PSA progression after RRP. However, large prospective studies are needed to confirm these results and to better understand the meaning of PSA variations.

Adenocarcinoma↗

Hormone-refractory prostate cancer? Anti-androgen withdrawal and intermittent hormone therapy.

OBJECTIVE: To separate hormone-dependent from hormonally relapsed prostate cancers, a D3 category has been proposed. The term has become synonymous with a hormone-refractory state with the implication that any further hormonal treatment would not be beneficial. In this review we examine some data on androgen receptor expression, anti-androgen withdrawal syndrome and intermittent androgen deprivation (IAD) in patients with advanced prostate cancer. MATERIALS: The literature on the mechanism of the withdrawal phenomenon in patients with prostate cancer submitted to hormone therapy was reviewed. Experimental and clinical data are reported. RESULTS: The progression of prostate cancer in patients treated with combined androgen blockade (CAB) is associated with the activation of previously androgen-repressed genes, some of which may code for autocrine and paracrine growth factors that substitute for androgens in maintaining the viability of the tumorigenic stem cells. If androgens are replaced before progression begins, the surviving stem cells should give rise to an androgen-dependent tumor, which would be amenable to retreatment by CAB. This theory provides the rationale for intermittent androgen deprivation. We suggest that IAD could be more effective in patients with initial prostate-specific antigen (PSA) progression after radical prostatectomy. CONCLUSIONS: Response to withdrawal therapies or second-line treatments is an example of a "hormonal" therapy that may benefit a proportion of patients with hormone-refractory disease, suggesting that the tumor is still androgen-dependent. Whether IAD enhances progression-free survival or overall survival must be verified in randomized clinical trials. Until further studies have been completed, the therapeutic concept of IAD should be treated as experimental.

Androgen Antagonists↗

Can the intraprostatic concentration of epidermal growth factor influence the variance of serum prostate specific antigen levels in patients with benign prostatic hyperplasia?

PURPOSE: Except for prostate volume, little is known about the factors influencing serum prostate specific antigen (PSA) levels. Considering that dihydrotestosterone and epidermal growth factor are regulators of the proliferation and differentiation in the epithelial component of human prostate tissue and that PSA is produced only by the epithelial cells of the gland, studies were performed on patients with a histological diagnosis of benign prostatic hyperplasia (BPH) to establish whether a significant association exists between the intraprostatic concentration of dihydrotestosterone or epidermal growth factor and serum PSA levels. MATERIALS AND METHODS: A total of 20 patients with BPH who had not been previously treated were part of a larger study on the correlation among PSA, prostate volume and age, and were evaluated according to the algorithm in the guidelines of the international consultation on BPH. All men underwent open suprapubic prostatectomy to enucleate the entire adenoma and in each case sections were made in the periurethral, subcapsular and intermediate zones of the BPH tissue. Dihydrotestosterone and epidermal growth factor concentrations were evaluated by radioimmunoassay in the periurethral zone and in total BPH tissue. RESULTS: In these 20 patients with BPH serum PSA levels were significantly associated with epidermal growth factor but not with dihydrotestosterone concentrations in total BPH tissue (r = 0.7762, p = 0.00002836 and r = 0.3923, p = 0.0956307, respectively). A stronger association was found between PSA levels and the periurethral concentration of epidermal growth factor and dihydrotestosterone (r = 0.8117, p = 0.000005 and r = 0.5656, p = 0.0098326, respectively). On the contrary, epidermal growth factor and dihydrotestosterone were not significantly associated with prostate volume (p = 0.957415 and p = 0.531439, respectively). CONCLUSIONS: To our knowledge this study is the first report in the literature to demonstrate an association between serum PSA, and dihydrotestosterone and epidermal growth factor levels, particularly in the periurethral zone of human BPH tissue. These data suggest the importance of epidermal growth factor and dihydrotestosterone in influencing serum PSA levels.

Aged↗

[Limitations on the interpretation of prostate-specific antigen serum levels].

Recent data suggest that PSA expression can be directly influenced by some factors, independently from the variation in prostate cell growth. Some growth factors such as fibroblast growth factor, transforming growth factor beta and epidermal growth factor, seem to be directly involved in the regulation of mRNA-PSA expression, whereas androgens could have an indirect activity. On the basis of these experimental data, this review tries to analyze some limits of PSA and some recent data on the role of PSA-isoforms, in particular in the follow-up of prostate cancer patients submitted to radical prostatectomy or hormone-therapy. Moreover, relevant informations can be obtained analyzing the variance of PSA in patients submitted to intermittent androgen deprivation.

Androgens↗

Effects of long-term treatment with Serenoa repens (Permixon) on the concentrations and regional distribution of androgens and epidermal growth factor in benign prostatic hyperplasia.

BACKGROUND: The n-hexane lipido-sterol extract of Serenoa repens (LSESr, Permixon, Pierre Fabre Medicament, Castres, France), a phytotherapeutic agent used in the treatment of benign prostatic hyperplasia (BPH), has a multisite mechanism of action including inhibition of types 1 and 2 5alpha-reductase and competitive binding to androgen receptors in prostatic cells. Here, the response of testosterone (T), dihydrotestosterone (DHT), and epidermal growth factor (EGF) in BPH tissue of patients treated with LSESr (320 mg/day for 3 months) is analyzed. METHODS: BPH samples were sectioned in periurethral, subcapsular, and intermediate regions: in each region T, DHT, and EGF were determined by radioimmunoassay after purification on celite columns or Sep-pak C18 cartridges. RESULTS: In the untreated group, T, DHT, and EGF presented the highest concentrations in the periurethral region (615 +/- 62 (SE) pg/g tissue, 7,317 +/- 551 pg/g tissue, and 20.9 +/- 3.3 ng/g tissue, respectively) with respect to the peripheral subcapsular region (425 +/- 45 pg/g tissue, 4,215 +/- 561 pg/g tissue, and 10.8 +/- 1.4 ng/g tissue, respectively). In the LSESr-treated group, a statistically significant reduction was observed, mainly in the periurethral region of DHT (2,363 +/- 553 pg/g tissue, P < 0.001) and EGF (6.98 +/- 2.48 ng/g tissue, P < 0.01), with increased T values (1,023 +/- 101 pg/g tissue, P < 0.001). CONCLUSIONS: The decrease of DHT and the rise of T in BPH tissue of patients treated with Permixon confirms the capacity of this drug to inhibit in vivo 5alpha-reductase in human pathological prostate. A marked decrease of EGF, associated with DHT reduction, was also observed. These biochemical effects, similar to those obtained with finasteride, are particularly evident in the periurethral region, whose enlargement is responsible for urinary obstruction, with respect to the subcapsular region. A possible speculation is that the preferential reduction of DHT and EGF content in the periurethral region is involved in the clinical improvement of the obstructive symptoms in BPH during LSESr therapy.

Aged↗

Relationship among age, prostate-specific antigen, and prostate volume in men with lower urinary tract symptoms (LUTS) and in different groups of men with and without benign and malignant prostate diseases.

BACKGROUND: In order to enhance prostate-specific antigen (PSA) as a predictor of prostate cancer, it is necessary to understand the characteristics of this tumor marker in a population of men without evidence of prostate cancer but who are at risk for developing the condition. METHODS: In an age-stratified population of 328 men with lower urinary tract symptoms (LUTS), we analyzed the distribution of PSA levels as a function of age and prostate volume, and we analyzed the percentage of age-related variance in PSA that can be explained by the age-related variance in prostate volume. RESULTS: Classifying the 328 cases with LUTS according to four age groups, a correlation was found between PSA and prostate volume, becoming stronger from the younger (correlation coefficient, -0.1265) to the older group (correlation coefficient, 0.6044). Serum PSA variance per milliliter of prostate volume also increased from the younger (not significant, P > 0.1) to the older age decades (7.3% in men age 70 years or over). Moreover, the results of the regression analysis suggest that 10% of the variance in PSA with age can be accounted for by prostate volume in men under age 50 years, reaching 37% in men age 70 years or more. CONCLUSIONS: These data confirm that the serum PSA concentration increases with advancing age in the absence of clinically evident prostatic malignancy. In younger patients with LUTS, serum PSA variance with age seems to be less dependent upon the age-related variance in prostate volume.

Adult↗

Relationship among symptom score, prostate volume, and urinary flow rates in 543 patients with and without benign prostatic hyperplasia.

BACKGROUND: Studies on the relationship among symptom score, urinary flow rate, and prostate volume in men with lower urinary tract symptoms (LUTS) continue to be of great interest. METHODS: A total of 2,418 men, aged 30-86 years, agreed to participate in an interview and to complete a questionnaire regarding voiding patterns. All subjects answering positively to one or more of the questions were submitted to a diagnostic assessment, based on the algorithm outlined by the guidelines of the International Consultation on Benign Prostatic Hyperplasia (BPH). Five hundred forty-three out of the 2,418 participants (22.45%) were evaluated. At the end of the diagnostic evaluation, 400 men with LUTS but without concomitant conditions (except BPH) known to interfere with normal voiding were selected. Descriptive statistics were used to characterize age, symptom score (International Prostate Symptom Score), prostate volume, and urinary flow rate distribution in these patients. Correlations among the aforementioned parameters were evaluated by means of a multivariate, multiple linear regression and logistic regression model. RESULTS: As reported in other studies, only weak or modest correlations were found. Moreover, the 400 cases were classified according to four age decades. The decrease in peak and mean flow rate per decade of age was similar (0.5 and 0.4 ml/sec); the increase in prostate volume and in total symptom score per decade was 3.3 cc and 0.6, respectively. In patients less than 50 years old, most of the correlations were stronger than those observed in the entire population of 400 men (age and prostate volume, c.c. 0.2864; age and peak flow rate, c.c. -0.2689; age and mean flow rate, c.c. -0.3034). However, symptom score continued to be weakly correlated with age and prostate volume (c.c. 0.0498 and 0.1966, respectively). In the last part of the study, men were assigned to different treatment strategies. Patients who were assigned to surgical treatment had higher prostate volume and IPSS and lower urinary flow rate than those assigned to nonsurgical treatment. CONCLUSIONS: We believe that the reason for the weak statistical association frequently reported in the literature is mainly the urology clinic-based population from which the patient samples were drawn. Data emerging from this analysis support the hypothesis that age is one of the principal factors influencing the relationship among symptom score, urinary flow rate, and prostate volume.

Adult↗

[Nonobstructive cor triatriatum].

Our experience refers to a 50-years-old man with isolated nonobstructive cor triatriatum sinistrum. He was evaluated casually for essential hypertension.

Cor Triatriatum↗

[The role of prostate specific antigen and its derivatives (age-specific PSA, PSA density, velocity, free/total PSA) in the diagnosis of prostate cancer].

PSA is the most useful tumor marker for the diagnosis and treatment of prostate cancer. Its clinical use, however, still lacks the necessary sensitivity and specificity to be considered as ideal. In fact PSA is not specific for adenocarcinoma of the prostate: an elevated serum level of the marker does not necessarily mean malignant growth and normal levels too often hide an occult and potentially lethal cancer. With the discovery of different molecular PSA forms in the serum, an improved discrimination between benign prostate hyperplasia (BPH) and prostate cancer appears possible. This may be particularly useful in cases with equivocal PSA values and unpalpable prostate neoplasm to reduce the number of unnecessary prostate biopsies and increase the number of biopsies in cases without palpable or ultrasonic visible anomalies. The clinical use of PSA age-referenced levels is discussed. Their use is invaluable in screening programs where the routine adoption of age-specific values can help to pick-up younger patients with potentially curable prostate cancer and older patients with BPH where additional tests would be unnecessary. The role of PSA velocity (PASAV) s also discussed. An elevation rate of PSA of 0.75 ng/ml over 18 months on 3 serial samples appears to be the best cut-off to distinguish BPH from prostate cancer. However, the use of PSAV seems to be less useful in patients with elevated PSA levels and negative biopsy results. Free to total PSA ratio is probably the best parameter to reduce the number of unnecessary biopsies in men with a serum total PSA of 4 to 10 ng/ml. The advantages and limitations for different levels of cut-off are shown. A flow chart illustrating the role of various PSA "derivatives" in screening and subsequent evaluation of men over 50 years of age is also presented.

Age Factors↗

New aspects on prostate cancer: hereditary form, developmental estrogenization and differentiation therapy.

Three new different aspects of prostate cancer have been considered in this review: the existence of an hereditary form, the role of estrogens as predisposing factors and the efficacy of differentiation therapies. Prostate cancer shows a stronger familial aggregation than colon and breast carcinoma. Hereditary prostate cancer is distinguished by early age at onset and autosomal dominant inheritance within families. However, only 2% of all prostate cancer in United States white men occur in those 55 years old or younger. Thus, the impact of hereditary prostate cancer in the population is the greatest at younger ages but this accounts for only a small proportion of the total disease burden. Using the developmentally estrogenized mouse model, an alternative role for estrogens as a predisposing factor for prostate diseases was proposed: estrogen exposure during development may initiate cellular changes in the prostate which would require estrogens and/or androgens later in life for promotion to neoplasia. A combination therapy employing both differentiation therapy and hormone therapy may be effective in the treatment of advanced prostate cancers. Recent advances in the field of differentiation therapy have resulted in the development of novel retinoic acid metabolism blocking agents. Unlike previous differentiating agents such as the retinoids, these agents increase the endogenous levels of retinoic acid by inhibiting its breakdown in cancer cells.

Animals↗