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Biomedical subjects

P Casale

Publications and source records attributed to P Casale.

At least 19 recordsLinked to original sources
PubMed2003

Importance of premeal injection time in insulin therapy: Humalog Mix25 is convenient for improved post-prandial glycemic control in type 2 diabetic patients with Italian dietary habits.

We investigated the use, in a short period, of Humalog Mix25 (Mix25) in a twice-daily administration regimen compared to a twice-daily injection therapy with Humulin 30/70 (30/70) in diabetic patients with Italian dietary habits. We studied 33 type 2 diabetic patients aged 59.1 +/- 8.1 years, BMI 29.8 +/- 2.7 kg/m2, duration of diabetes and insulin therapy of 14.4 +/- 9.8 and 4.2 +/- 4.6 years, respectively. After a 4-day lead-in period of twice-daily human insulin 30/70 treatment, patients were randomized to one of two treatment sequences: (1) a twice-daily regimen with Mix25 just 5 minutes before the morning and evening meals for 12 days, followed by a twice-daily therapy with human insulin 30/70 given 30 minutes before the morning and evening meals for an additional 12 days; or (2) the alternate sequence. Each patient underwent a mixed meal test: Humulin 30/70 was administered 30 minutes before the meal, while Mix25 was given 5 minutes before. The 2-hour post-prandial glucose concentration after breakfast was significantly lower during treatment with Mix25 than with Humulin 30/70 (157 +/- 43.2 vs. 180 +/- 43.2 mg/dl, p<0.05). The glycemic excursion after dinner on Mix25 treatment was significantly lower than with Humulin 30/70 (12.2 +/- 48.01 vs. 35.5 +/- 36.92 mg/dl, p<0.05). AUCglucose after Mix25 was lower than after Humulin 30/70. Glycemia after test meal was significantly lower with Mix25 than with Humulin 30/70. Insulin and free insulin concentrations after the test meal were significantly higher with Mix25 in comparison to Humulin 30/70. AUC serum insulin and free insulin curves after Mix25 were significantly higher than after Humulin 30/70 (p=0.028 and p=0.005, respectively). Twice-daily injections of Humalog Mix25, compared to human insulin 30/70 in type 2 diabetic patients with Italian dietary habits, provide improved and lasting post-prandial glycemic control, with the great convenience of the injection just before the meal.

Biphasic Insulins↗
PubMed2000

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↗
PubMed2000

Combination enoxaparin and abciximab therapy during percutaneous coronary intervention: "NICE guys finish first".

Data from randomized clinical trials support the administration of both enoxaparin and platelet glycoprotein IIb/IIIa blockade to patients who present with non-ST segment evaluation acute coronary syndromes. Enoxaparin does not activate platelets, has a more predictable dose response that facilitates weight-adjusted dosing and may have enhanced antithrombotic (increased anti-Xa activity) and safety (reduced anti-IIa activity) properties when compared with unfractionated heparin. Abciximab administration during percutaneous coronary intervention reduces the incidence of ischemic adverse outcomes and may improve survival in long-term follow-up. The preliminary experience with combining abciximab and intravenous enoxaparin during percutaneous coronary intervention in the NICE-4 Trial demonstrates a low incidence of minor/major bleeding (TIMI definition) and transfusion and infrequent major cardiac events to 30 days follow-up. Future algorithms to facilitate the transition of patients from the clinical service who have received subcutaneous administration of enoxaparin to the cardiac catheterization laboratory prior to percutaneous coronary intervention are forthcoming and will provide seamless integration of "optimal" adjunctive pharmacology through the course of hospitalization for patients with non-ST elevation acute coronary syndromes.

Abciximab↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

[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↗
PubMed1998

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↗
PubMed1998

Efficacy and safety of a hemostatic puncture closure device with early ambulation after coronary angiography. Angio-Seal Investigators.

A collagen hemostatic puncture closure device has been developed as an alternative to traditional manual pressure techniques for achieving effective femoral arterial hemostasis after coronary angiography. The purpose of the current study was to determine if patients receiving this device can ambulate safely at 1 hour compared with patients receiving traditional manual pressure and bed rest after sheath removal for diagnostic cardiac catheterization. Patients (n = 304) were randomized to either the device group (n = 202) with ambulation at 1 hour after sheath removal or to the manual pressure control group (n = 102) with ambulation at 4 to 6 hours after sheath removal. The device group achieved earlier time to hemostasis (0.9 +/- 3 vs 17.0 +/- 8 minutes, p = 0.0001) and faster time to outpatient discharge (5.0 +/- 4 vs 7.7 +/- 4 hours, p = 0.0001) compared with the control group. There were bleeding or vascular complications in 19 patients (9%) in the device group and in 6 patients (6%) in the manual pressure group (p = 0.397). In patients undergoing diagnostic coronary angiography, this device, compared with traditional techniques for achieving hemostasis after sheath removal, allows for faster time to effective hemostasis with resultant earlier discharge from the hospital.

Aged↗
PubMed1998

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↗
PubMed1998

Molecular resolution of marine turtle stock composition in fishery bycatch: a case study in the Mediterranean.

Based on an extensive sampling regime from both nesting populations and bycatch, frequency analyses of mitochondrial (mt) DNA control region haplotypes in the Mediterranean were used to assess the genetic structure and stock composition of the loggerhead sea turtle, Caretta caretta, in different marine fisheries. The analyses show the following. (i) In drifting longline fisheries working in Mediterranean pelagic habitats 53-55% of turtles caught originated from the Mediterranean stock; (ii) In bottom-trawl fisheries all turtle bycatch is derived from this regional stock; (iii) This regional stock contribution to fishery bycatch suggests that the population size of the Mediterranean loggerhead nesting population is significantly larger than previously thought. This is consistent with a recent holistic estimate based on the discovery of a large rookery in Libya. (iv) Present impact of fishery-related mortality on the Mediterranean nesting population is probably incompatible with its long-term conservation. Sea turtle conservation regulations are urgently needed for the Mediterranean fisheries. (v) The significant divergence of mtDNA haplotype frequencies of the Turkish loggerhead colonies define this nesting population as a particularly important management unit. Large immature and adult stages from this management unit seem to be harvested predominantly by Egyptian fisheries. (vi) Combined with other data, our findings suggest that all the nesting populations in the Mediterranean should be considered as management units sharing immature pelagic habitats throughout the Mediterranean (and possibly the eastern Atlantic), with distinct and more localized benthic feeding habitats in the eastern basin used by large immatures and adults. (vii) Between the strict oceanic pelagic and the benthic stages, immature turtles appear to live through an intermediate neritic stage, in which they switch between pelagic and benthic foods.

Animals↗
PubMed1998

[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↗
PubMed1998

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↗
PubMed1998

Hormonal profile of patients with Leydig cell tumors: a urologic cause of gynecomastia.

It is possible to hypothesize an alternative role for estrogens as a predisposing factor for testicular abnormalities: estrogen exposure during development in perinatal life may initiate cellular changes which would require estrogen and/or androgen later in life for promotion to hyperplasia or neoplasia. We reviewed the literature on Leydig cell tumors and the hormonal modifications they induce. In adult patients with Leydig cell tumors, although the serum estrogen (E2) and testosterone (T) varied, the T/E2 ratio was constantly low, and the chorionic gonadotropin administration produced an higher estrogen response than in normal men. Hormonal follow-up after orchidectomy for Leydig cell tumors has not been frequently described, and both normalization and lack of normalization of T, E2, gonadotropins and hCG have been reported. In the last part of the review we analyzed the principal urologic causes of gynecomastia in men. Testicular failure, either primary or secondary is a frequently found etiology for gynecomastia. Leydig cell tumors may elevate estrogen levels, and approximately 20% of patients with these tumors have gynecomastia.

Adult↗
PubMed1997

1457 years of microsurgical experience.

Microsurgery is a relatively new field of surgery involving various methods and practices that are currently evolving. Our goal was to register the current practices employed by the members of the American Society for Reconstructive Microsurgery. A survey was mailed to the 319 members of the society, resulting in a response rate of 33 percent (106 of 319). The data reflect the combined experience of 10,839 free-tissue transfers and 3487 digital and upper and lower extremity replants over a 4-year period between 1990 and 1994. Practices employed, such as pharmacologic adjuvant therapy, monitoring techniques, flap types, and success rates reported by the members of the American Society for Reconstructive Microsurgery, were analyzed.

Anticoagulants↗
PubMed1996

DNA ploidy, Gleason score, pathological stage and serum PSA levels as predictors of disease-free survival in C-D1 prostatic cancer patients submitted to radical retropubic prostatectomy.

We report our experience with 85 prostatic cancer patients aged 51-79 years, who underwent radical retropubic prostatectomy from 1989 to December 1994 (mean follow-up 35 months). In order to get a more relevant analysis we chose to describe in detail only pathological C-D1 cases and to subdivide the patients, according to the Gleason sum, into G2-G5 and G6-G10 groups. Means of pre- and postsurgery PSA levels were ranked by DNA ploidy and presence or absence of recurrence: aneuploid patients showed lower levels of PSA production that may be due to cell dedifferentiation. However, in patients who developed recurrence, postsurgery PSA levels were higher (p < 0.005). The influence of DNA ploidy on disease-free survival was evaluated: the cumulative survival proportion was better in diploid (0.3581) than in aneuploid patients (0.2996). Using the Cox proportional hazard model with age, Gleason sum, DNA ploidy and presurgery PSA levels as covariates, we demonstrated that, in our series, only the presurgery PSA level was an important and significant predictor of recurrences (p < 0.005). Considering global recurrences with age, Gleason sum and presurgery PSA levels kept fixed, DNA aneuploidy conferred a relative risk 2.3 times higher than diploidy. When, in the same analysis, we introduced postsurgery PSA levels, only DNA ploidy and the latter variable kept statistical significance with a relative risk of 2.5. Considering only local and distant recurrences (with exclusion of those identified by elevated PSA levels) the relative risk was 3.9 and 3.8, respectively. These data support the critical role of nuclear DNA analysis as predictor of outcome after surgery even in this discussed subset of patients (C-D1).

Aged↗
PubMed1996

[Comparative effects of transurethral incision (TUIP) and the combination of TUIP and LHRH agonists in the treatment of benign prostatic hypertrophy].

Between December 1991 and December 1993, 74 BPH patients with an increased operative risk and concomitant diseases such as diabetes mellitus and hypertension were submitted to a transurethral incision of the prostate (TUIP). After TUIP, patients were randomized to two different groups: group 1 was followed without additional treatment and group 2 received an LHRH analogue for the first 6 months of follow-up. With respect to transurethral resection of the prostate (TURP), TUIP has been shown to demonstrate a lower perioperative morbidity. This advantage has lent further support to this technique as a valid alternative for patients in poor general conditions who are at high risk with more invasive procedures. One of the limits of TUIP is the long-term effectiveness. Aim of this study was to ascertain whether in patients with BPH and an increased operative risk who require immediate and definitive treatment but with a low perioperative morbidity, the long-term effectiveness of TUIP can be stabilized by the administration of an LHRH analogue. At present postoperative follow-up ranges from a minimum of 24 months to a maximum 48 months (mean 38.4 months). Perioperative morbidity rate associated with TUIP was 8.1%. In the group randomized to combination therapy (TUIP + LHRH analogue), the clinical condition of the patients was not modified by LHRH analogue treatment and none of the patients withdrew from treatment. Loss of sexual potency occurred in all patients on LHRH analogue, however, none of these patients discontinued treatment for this reason. At the end of the cycle of hormone treatment, sexual potency returned to pretreatment values in 69.5% of patients after a mean of 3.2 months. In this study the objective efficacy of the treatment was evaluated using flow rate measurements, and the subjective assessment of outcomes, using the International Prostate Symptom Score. Statistically significant differences between the two groups (TUIP alone or TUIP + LHRH analogue) (p < 0.01) were reported at 6 months and were still maintained at 24 months of follow up. Results emerging from this investigation confirm that TUIP may be considered extremely safe procedure with low operative risk. In selected BPH patients who are at high risk, with a more invasive procedure and who must be submitted to immediate and definitive treatment, the association of an LHRH analogue seems to increase the long-term effectiveness of TUIP. Five year follow-up studies are still in progress.

Aged↗