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Biomedical subjects

A Zisman

Publications and source records attributed to A Zisman.

At least 37 records · Page 2Linked to original sources

The changing natural history of renal cell carcinoma.

PURPOSE: Our understanding of the natural history of renal cell carcinoma, the role of nephrectomy, the benefits of immunotherapy and the possibilities of new technologies are evolving and being integrated with advances in classification and staging. We reviewed the relevant literature to clarify these pertinent questions and provide a current review of the changes in the epidemiology, treatment and prognosis of patients with renal cell carcinoma. MATERIALS AND METHODS: We comprehensively reviewed the peer reviewed literature on the current management of and results of treatment for renal cell carcinoma. RESULTS: The incidence of and mortality from renal cell carcinoma have continuously increased during the last 50 years. Despite this increase in the number of new patients and consequently the number of deaths yearly the percent of those surviving for 5 years has notably improved. Factors related to improved survival include advances in renal imaging, earlier diagnosis, improved staging, better understanding of prognostic indicators, refinement in surgical technique and the introduction of immunotherapy approaches for advanced disease. CONCLUSIONS: Currently patients with localized and metastatic renal cell carcinoma have had improvements in outlook and the therapeutic options available have expanded.

Carcinoma, Renal Cell↗

The impact of prostate biopsy on patient well-being: a prospective study of voiding impairment.

PURPOSE: We studied the possible association of transrectal ultrasound guided prostate biopsy with voiding impairment. MATERIALS AND METHODS: A total of 211 consecutive patients were prospectively enrolled. International Prostate Symptom Score (I-PSS), subjective voiding complaints and retention were recorded in 3 personal interviews before biopsy, and on postoperative days 7 and 30. RESULTS: Of the 204 patients who voided via the urethra at biopsy 52 (25%) reported subjective voiding impairment on postoperative day 7, including 12% who defined difficult voiding as mild-1 to 2 points on a 0 to 5 scale, 8% as moderate-3/5 and 5% as severe-4 to 5/5. In 5 of the latter cases (2.5%) acute urinary retention necessitated urethral catheter insertion. Transition zone volume, which was 42 ml. or larger in all patients in urinary retention, was the only independent variable associated with patient report of subjective difficult voiding and acute urinary retention during week 1 after biopsy (p = 0.03). Baseline I-PSS greater than 20 points indicated a risk of an acute transient increase in I-PSS on postoperative day 7. CONCLUSIONS: Transient voiding impairment may be precipitated by ultrasound guided prostate biopsy. To decrease this morbidity appropriate evaluation and possible treatment for bladder outlet obstruction are justified in patients with a larger transition zone and in those with preoperative baseline I-PSS greater than 20 points.

Adult↗

Cryosurgical ablation for prostate cancer: preliminary results of a new advanced technique.

BACKGROUND: Cryosurgery is a minimally invasive treatment option for prostate cancer. OBJECTIVES: To report on the first series of cryosurgical ablation for prostate cancer performed in Israel. METHODS: Cryosurgical ablation of the prostate was undertaken in 12 patients aged 53-72 diagnosed with adenocarcinoma of the prostate. The procedures were performed percutaneously and were monitored by real-time trans-rectal ultrasound. The CRYOHIT machine applying Argon gas was used with standard or ultra-thin cryoprobes. The average follow-up was 12.8 months postsurgery (range 1-24 months). RESULTS: No rectal or urethral injuries occurred and all patients were discharged from hospital within 24-48 hours. The duration of suprapubic drainage was 14 days in 10 patients and prolonged in 2. Early complications included penoscrotal edema in four patients, perineal hematoma in three, hemorrhoids in two and epidydimitis in one. Long-term complications included extensive prostatic sloughing in one patient and a perineal fistula in another, both of whom required prolonged suprapubic drainage. Minimal stress incontinence was noted in two patients for the first 8 weeks after surgery. None of the patients has yet regained spontaneous potency. A prostate-specific antigen nadir of less than 0.5 ng/ml was achieved in eight patients and an undetectable PSA level below 0.1 ng/ml in five patients. CONCLUSION: Cryoablation for prostate cancer is safe and feasible, and the preliminary results are encouraging. Further study is needed to elucidate the efficacy of the procedure.

Adenocarcinoma↗

Bladder cancer 2000: molecular markers for the diagnosis of transitional cell carcinoma.

The search continues for better tumor markers to improve the rate of detection of transitional cell carcinoma (TCC) more quickly in larger populations and to predict the possibility of disease recurrence. Among several new tests currently being screened, telomerase and hyaluronic acid/hyaluronidase (HA/HAase) have shown sensitivity and specificity equal to or better than cytology, and other promising tumor markers are being investigated. Although no marker has yet replaced the need to perform cystoscopy and cytology, the new tests can minimize the cost and difficulty of screening and long-term surveillance of patients who have or are at risk for bladder cancer.

Journal Article↗

Gene therapy for prostate cancer at the University of California, Los Angeles: preliminary results and future directions.

The treatment options for patients with advanced prostate cancer are limited. Because of recent advances in the understanding of the molecular biology of prostate cancer, the accessibility of the prostate for injection, and the availability of gene promotors that allow tissue-specific expression of therapeutic gene products, gene therapy for prostate cancer has realized significant achievements in recent years. What once belonged to the realm of basic science is now entering the domain of phase II clinical trials. In this review, current results and future directions in prostate gene therapy at the University of California, Los Angeles, are discussed.

California↗

Diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic syndrome.

Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar nonketotic syndrome (HHNS) are life-threatening acute metabolic complications of diabetes mellitus. Although there are some important differences, the pathophysiology, the presenting clinical challenge, and the treatment of these metabolic derangements are similar. Each of these complications can be seen in type 1 or type 2 diabetes, although DKA is usually seen in patients with type 1 diabetes and HHNS in patients with type 2 disease. The clinical management of these syndromes involves careful evaluation and correction of the metabolic and volume status of the patient, identification and treatment of precipitating and comorbid conditions, a smooth transition to a long-term treatment regimen, and a plan to prevent recurrence.

Diabetes Mellitus, Type 1↗

Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance.

The prevalence of type 2 diabetes mellitus is growing worldwide. By the year 2020, 250 million people will be afflicted. Most forms of type 2 diabetes are polygenic with complex inheritance patterns, and penetrance is strongly influenced by environmental factors. The specific genes involved are not yet known, but impaired glucose uptake in skeletal muscle is an early, genetically determined defect that is present in non-diabetic relatives of diabetic subjects. The rate-limiting step in muscle glucose use is the transmembrane transport of glucose mediated by glucose transporter (GLUT) 4 (ref. 4), which is expressed mainly in skeletal muscle, heart and adipose tissue. GLUT4 mediates glucose transport stimulated by insulin and contraction/exercise. The importance of GLUT4 and glucose uptake in muscle, however, was challenged by two recent observations. Whereas heterozygous GLUT4 knockout mice show moderate glucose intolerance, homozygous whole-body GLUT4 knockout (GLUT4-null) mice have only mild perturbations in glucose homeostasis and have growth retardation, depletion of fat stores, cardiac hypertrophy and failure, and a shortened life span. Moreover, muscle-specific inactivation of the insulin receptor results in minimal, if any, change in glucose tolerance. To determine the importance of glucose uptake into muscle for glucose homeostasis, we disrupted GLUT4 selectively in mouse muscles. A profound reduction in basal glucose transport and near-absence of stimulation by insulin or contraction resulted. These mice showed severe insulin resistance and glucose intolerance from an early age. Thus, GLUT4-mediated glucose transport in muscle is essential to the maintenance of normal glucose homeostasis.

Animals↗

A model to explore the interaction between muscle insulin resistance and beta-cell dysfunction in the development of type 2 diabetes.

Type 2 diabetes is a polygenic disease characterized by defects in both insulin secretion and insulin action. We have previously reported that isolated insulin resistance in muscle by a tissue-specific insulin receptor knockout (MIRKO mouse) is not sufficient to alter glucose homeostasis, whereas beta-cell-specific insulin receptor knockout (betaIRKO) mice manifest severe progressive glucose intolerance due to loss of glucose-stimulated acute-phase insulin release. To explore the interaction between insulin resistance in muscle and altered insulin secretion, we created a double tissue-specific insulin receptor knockout in these tissues. Surprisingly, betaIRKO-MIRKO mice show an improvement rather than a deterioration of glucose tolerance when compared to betaIRKO mice. This is due to improved glucose-stimulated acute insulin release and redistribution of substrates with increased glucose uptake in adipose tissue and liver in vivo, without a significant decrease in muscle glucose uptake. Thus, insulin resistance in muscle leads to improved glucose-stimulated first-phase insulin secretion from beta-cells and shunting of substrates to nonmuscle tissues, collectively leading to improved glucose tolerance. These data suggest that muscle, either via changes in substrate availability or by acting as an endocrine tissue, communicates with and regulates insulin sensitivity in other tissues.

Acute-Phase Reaction↗

Prostate cryoablation without an insertion kit using direct transperineal placement of ultrathin freezing probes.

A modified technique for prostate cryoablation is described. Prostate cryoablation was performed with a gas-based cryomachine using multiple 17-gauge probes. The 17-gauge probes were inserted via a transperineal route directly into the prostate without using an insertion kit. Probe insertion and positioning are simplified, and operative time is reduced. The perineum is less crowded with devices and tubes. Miniaturizing the cryoprobes and their tubing is feasible. The smaller diameter enables direct insertion without an insertion kit. The surgical result does not seem to be inferior to that of conventional ablation, and penetrating trauma to the prostate is minimal. To the best of our knowledge, this is the first report of transperineal prostate cryoablation performed without an insertion kit.

Cryosurgery↗

CL1-GFP: an androgen independent metastatic tumor model for prostate cancer.

PURPOSE: The mechanisms responsible for tumor progression to androgen independence in prostate cancer (CaP) remain unknown. To characterize these changes and provide a basis for rational therapeutic strategies for advanced CaP, an in vivo model from a highly aggressive androgen independent CaP cell line with distinct cellular and molecular properties was developed. MATERIALS AND METHODS: An aggressive androgen-independent cell line designated CL1 was derived from a slow-growing, and androgen-dependent, parental LNCaP cell line through in-vitro androgen-deprivation and selection. CL1 was stably transfected with a green fluorescence protein gene (CL1-GFP) and orthotopically injected into SCID mice. The pathologic behavior, histology, and molecular determinants of CL1 tumor and metastases were determined and characterized by standard light and fluorescent microscopy, and quantitative RT-PCR analysis. RESULTS: CL1 is an anaplastic prostate cancer cell line which demonstrates extensive local invasion and metastases to various organs that can be visualized via GFP expression. When compared with parental LNCaP cells, RT-PCR analysis of the tumor revealed an over-expression of EGFR, b-FGF, VEGF, TGF-beta, IL-8, IL-6, and bcl-2 and a down regulated expression of the p53, E-cadherin and PTEN. In contrast to LNCaP cells, CL1 tumors express lower levels of androgen receptor and barely detectable PSA mRNA. CONCLUSIONS: CL1-GFP represents an aggressive androgen-independent CaP tumor model derived through androgen deprivation whose pathologic development and molecular properties in animals resembles the clinical characteristics of hormone refractory prostate cancer (HRPC). Metastatic sites of CL1-GFP can be visualized with fluorescence microscopy offering a unique therapeutic model for the evaluation of drug sensitivity and other therapeutic modalities.

Androgens↗

Elevated prostate specific antigen serum levels after intravesical instillation of bacillus Calmette-Guerin.

PURPOSE: We determined whether intravesical bacillus Calmette-Guerin (BCG) instillation is associated with elevated prostate specific antigen (PSA). MATERIALS AND METHODS: We treated 36 consecutive patients with bladder cancer with a 6-week course of BCG, followed by cystoscopy at 6 weeks. Blood samples for PSA determination were obtained before each BCG instillation and at cystoscopy with each patient also serving as a control. PSA elevation was defined as 2-fold the baseline level in at least 2 specimens and any PSA level greater than 4 ng./ml. was considered clinically significant. Digital rectal examination was done to identify firm nodules and prostate size. The prostate was examined histologically by transrectal ultrasound guided biopsy or after radical cystectomy. RESULTS: We observed elevated PSA in 27 men (75%) during BCG treatment, of whom 15 (41.6%) had a clinically significant elevation. Overall average PSA increased from 1.3 ng./ml. before BCG instillation to 3.8 during treatment (range 0.1 to 21.5, p <0.0001). In those with a clinically significant elevation average PSA increased from 2.31 ng./ml. at baseline to 6.97 during treatment (p <0.0001) and returned to 3.86 ng./ml. 3 months after treatment. Palpation demonstrated prostatic findings in 10 patients, including firm nodules in 7, while there was significantly elevated PSA in 5 with firm nodules and 2 with diffuse prostatic enlargement. Histological examination of the prostate in 10 patients was diagnostic for granulomatous prostatitis, nonspecific inflammation and benign prostatic hyperplasia in 3, 3 and 4, respectively, of whom none had prostate cancer. CONCLUSIONS: Intravesical BCG therapy is associated with significantly elevated PSA in up to 40% of cases. This effect is self-limited and PSA reverts to normal in 3 months. Therefore, we suggest that prostate biopsy be withheld in such patients and PSA monitored.

Adjuvants, Immunologic↗