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Biomedical subjects

M C Beduschi

Publications and source records attributed to M C Beduschi.

9 recordsLinked to original sources

Pneumoperitoneum does not potentiate the nephrotoxicity of aminoglycosides in rats.

OBJECTIVES: Pneumoperitoneum is associated with transient renal dysfunction. To our knowledge, the safety of administering nephrotoxins such as aminoglycosides during pneumoperitoneum has not been studied. Our hypothesis was that pneumoperitoneum potentiates the nephrotoxicity of aminoglycosides. METHODS: From 29 rats we obtained preprocedure 24-hour urine collections. In the pneumoperitoneum group (n = 7), carbon dioxide was insufflated intra-abdominally at 15 mm Hg pressure for 2 hours. In the gentamicin group (n = 7), 10 mg/kg gentamicin was administered intravenously. In the combined pneumoperitoneum/gentamicin group (n = 8), the same dose of gentamicin was administered 10 minutes before pneumoperitoneum. Sham rats (n = 7) received anesthesia only. Urine was collected for the 24 hours after the procedure, and 1 week later blood for creatinine determination and final 24-hour urine collections were obtained. All urine samples were assayed for creatinine and N-acetyl-beta-glucosaminidase (NAG). RESULTS: Only the gentamicin and combined pneumoperitoneum/gentamicin groups presented day 1 values for NAG excretion that were significantly greater than same day sham or paired preprocedure values; the rest of the urinary creatinine and NAG day 1 levels and all the day 7 levels were not significantly different from same day sham or paired preprocedure levels. Day 7 serum creatinine and creatinine clearance did not differ significantly among the groups. CONCLUSIONS: We found that intravenous gentamicin transiently increased urinary excretion of NAG in rats, which resolved within 1 week. Pneumoperitoneum for 2 hours at 15 mm Hg did not increase urinary NAG, either alone or in gentamicin-treated rats. Moreover, our data are sufficient to refute with 95% certainty the possibility that gentamicin plus pneumoperitoneum decreases creatinine clearance more than approximately 60%. These results do not support the hypothesis that pneumoperitoneum potentiates the nephrotoxicity of aminoglycosides.

Aminoglycosides

Antifibrinolytic additives to fibrin glue for laparoscopic wound closure in urinary tract.

BACKGROUND AND OBJECTIVES: Fibrinolytic activity of urine may rapidly degrade fibrin glue used in the urinary tract, thereby limiting tissue adhesion. The goals of this study were to verify the ability of antifibrinolytic agents to delay the degradation of fibrin glue in the urinary tract and to assess the results of this delay on subsequent wound healing. MATERIALS AND METHODS: In 25 domestic pigs, a 3.5-cm incision in the urinary bladder was left open (N = 6) or closed laparoscopically with fibrin glue alone (N = 6), fibrin glue containing aprotinin 5000 KIU/mL (N = 6), or fibrin glue containing aprotinin 2500 KIU/mL with (N = 4) or without (N = 3) aminocaproic acid 12.5 mg/mL. At harvest 7 days later, the bladder was tested for leakage. Histologic features were scored by a pathologist blinded to the closure method. RESULTS: There were no significant differences among the groups in the amount of leakage at harvest. Significant fibrin glue material in the wound was noted more often in the pigs treated with fibrin glue plus aprotinin (7 of 13) than in the fibrin glue-only group (0 of 6; P = 0.04). The presence of significant fibrin material in the wound correlated well with absence of granulation tissue (P < 0.001), such that granulation tissue bridging the wound edges was found more often in the fibrin glue-only group (6 of 6) than in the groups treated with fibrin glue plus aprotinin (4 of 13; P = 0.01). CONCLUSIONS: Although aprotinin +/- aminocaproic acid did delay the degradation of fibrin glue used to close a bladder wound, it was associated with inhibition of granulation tissue in the glued wound. These findings suggest that aprotinin alone and aprotinin plus aminocaproic acid are not useful additives to fibrin glue used for wound closure in the urinary tract.

Aminocaproates

Transurethral needle ablation of the prostate: a minimally invasive treatment for symptomatic benign prostatic hyperplasia.

Transurethral needle ablation of the prostate, a relatively new minimally invasive treatment modality for patients with bladder outlet obstruction attributable to an enlarged prostate gland, has undergone extensive evaluation by numerous investigators worldwide. The results to date indicate that needle ablation is safe and effective for relieving symptoms in patients with benign prostatic hyperplasia, and the effect has been demonstrated to be durable for at least 2 years. Nevertheless, additional investigations with longer follow-up data are needed to address the important issues of extended durability (5 to 10 years) and biophysiologic mechanism of action. Comparisons between transurethral needle ablation of the prostate and transurethral resection of the prostate (TURP) have revealed that the subjective and objective measures of response are comparable, although TURP has consistently displayed a slight advantage over needle ablation for most variables analyzed, except quality of life score. The advantages of needle ablation over TURP are (1) performance in the office as an outpatient procedure, (2) no need for general or spinal anesthesia, (3) rapid recovery, (4) minimal side effects, and (5) one-time intervention. The following disadvantages exist with needle ablation: (1) it may not be indicated or effective in patients with large prostate glands (75 g or more); (2) no prostate tissue is available for histologic evaluation; and (3) no long-term efficacy or re-treatment rate data have been published. Overall, the available information indicates that transurethral needle ablation is a viable minimally invasive treatment that may be applicable in men with moderate to severe bladder outlet obstruction as a result of an enlarged prostate gland.

Clinical Trials as Topic

Alpha-blockade therapy for benign prostatic hyperplasia: from a nonselective to a more selective alpha1A-adrenergic antagonist.

Benign prostatic hyperplasia (BPH) is very common in older men, causing symptoms that can markedly impair quality of life. Surgical treatment, typically transurethral resection of the prostate (TURP), is highly effective but can be costly and is associated with the risk for significant morbidity. Medical treatments for BPH are targeted toward reducing bladder outlet obstruction either by androgen blockade to reduce prostatic volume or alpha-adrenergic blockade to relax the smooth muscle tone of the prostate. In recent years, understanding of the sympathetic innervation of the prostate has improved. This has been paralleled by the development of alpha-adrenergic blocking agents, from nonselective alpha-antagonists, to selective alpha1-antagonists, to the more selective alpha1A-antagonists. It is anticipated that more specific agents will optimize the therapeutic effectiveness of alpha-adrenergic blockade in the prostate while reducing the side effects associated with alpha-adrenergic blockade in other areas of the body, such as the vascular system. This article reviews the evolution of alpha-blockade therapy in management of BPH, focusing on tamsulosin, an agent targeted toward the alpha1A-adrenoceptor that predominates in the prostate. Clinical trials in Europe and the United States have provided evidence that tamsulosin is effective at doses of 0.4 and 0.8 mg/day. At both doses, tamsulosin is associated with significant improvements in the American Urological Association symptom score and the mean and peak urinary flow rates as compared with placebo. This once-daily alpha1A-adrenergic antagonist is well-tolerated, with a minimal potential for the side effects associated with alphas-blocker therapy.

Adrenergic alpha-Antagonists

Benign prostatic hyperplasia: use of drug therapy in primary care.

Age and normal male androgenic function are the two most well-established risk factors for benign prostatic hyperplasia. Clinical manifestations of BPH may range from minimally bothersome symptoms to urinary retention and renal failure. Digital rectal examination, serum PSA, urinalysis, serum creatinine, and the AUA symptom score are recommended for the initial evaluation. For mild symptoms, watchful waiting may be all that is needed. For severe symptoms, surgical therapy is the most appropriate option. For men with mild to moderate symptoms, less invasive procedures and several pharmacologic therapies have proved to be effective for treating BPH. The pharmacologic therapies include a 5 alpha-reductase inhibitor (finasteride) and three selective alpha-1 blockers (terazosin, doxasozin, and tamsulosin).

5-alpha Reductase Inhibitors

Stage T1c prostate cancer: defining the appropriate staging evaluation and the role for pelvic lymphadenectomy.

A good staging system should be able to accurately reflect the natural history of a malignant disease, to express the extent of the disease at the time of diagnosis, and stratify patients in prognostically distinctive groups. The staging system for prostate cancer, as it is today, fails to fulfill these requirements. Approximately one third of the patients who undergo surgery for complete excision of prostate cancer in fact do not have a localize disease. The incidence of tumor at the inked margin may reach 30% for T1 stage and up to 60% for clinical T2b prostate cancer according to comparison with pathologic examination of resected specimen. Several concepts have been recently proposed as a means of improving the accuracy of the available staging system. In this paper, we review current aspects of clinical and pathological staging of prostate cancer, and the importance of these new concepts on the early stages of prostate cancer.

Humans

Prostate-specific antigen density.

Nearly 20 years have passed since PSA was definitively identified. Throughout this period, its clinical application as a tumor marker has expanded significantly. Today, besides monitoring prostate cancer therapy, PSA is being used extensively in mass screening programs for early detection of adenocarcinoma of the prostate and has become the most important tumor marker in urologic oncology. Although of unquestionable importance, PSA is not the perfect marker because of its lack of efficacy in discriminating BPH from prostate cancer. In order to enhance its sensibility, specificity, and predictive value, a series of variables influencing PSA levels have been studied and new parameters developed to correct discrepancies or confounding factors. Recognition of the relationship between PSA, prostate volume, and their interference with serum PSA levels made possible the development of the PSAD concept. Its wide application in different sets of patients for diagnostic and staging purposes resulted in enough data to demonstrate its usefulness and cost effectiveness as a second-line screening parameter, helping to distinguish BPH from prostate cancer in patients with PSA levels in the intermediate area, and avoiding some unnecessary biopsies. Even though PSAD does not offer a definitive solution for prostate cancer screening or management, its association with all the other diagnostic methods may offer the best way to assess the population at risk and assure their well-being (Fig. 5).

Humans

An experimental model for the measurement of renal function after temporary ureteral obstruction in the rat.

We present the results obtained with a ureterovesical implant after ipsilateral ureteral obstruction in the rat, suitable for the study of renal function after deobstruction in these animals. Thirty-seven male Wistar rats weighing 260 to 300 g were submitted to distal right ureteral ligation and divided into 3 groups, A (N = 13, 1 week of obstruction), B (N = 14, 2 weeks of obstruction) and C (N = 10, 3 weeks of obstruction). The animals were then submitted to ureterovesical implantation on the right side and nephrectomy on the left side. During the 4-week follow-up period serum levels of urea and creatinine were measured on the 2nd, 7th, 14th, 21st and 28th day and compared with preoperative levels. The ureterovesical implantation included a psoas hitch procedure and the ureter was pulled into the bladder using a transvesical suture. During the first week of the postoperative period 8 animals died, 4/13 in group A (1 week of obstruction) and 4/14 in group B (2 weeks of obstruction). When compared to preoperative serum levels, urea and creatinine showed a significant increase (P < 0.05) on the 2nd postoperative day in groups A and B, with a gradual return to lower levels. However, the values in group B animals were higher than those in group A at the end of the follow-up. In group C, 2/10 animals (after 3 weeks of obstruction) were sacrificed at the time of ureterovesical implantation due to infection of the obstructed kidneys. The remaining animals in this group were operated upon but all of them died during the first week of follow-up due to renal failure. This technique of ureterovesical implantation in the rat provides effective drainage of the upper urinary tract, permitting the development of an experimental model for the study of long-term renal function after a period of ureteral obstruction.

Animals