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Biomedical subjects

D Engelstein

Publications and source records attributed to D Engelstein.

At least 19 recordsLinked to original sources
PubMed2002

Intracavernous injections for erectile dysfunction in patients with cardiovascular diseases and failure or contraindications for sildenafil citrate.

The aim of this study was to evaluate the effectiveness of a progressive program for the treatment of erectile dysfunction in patients with cardiovascular disease in whom sildenafil citrate (Viagra) was not an option. The study population included 106 patients selected from 267 with cardiovascular disease. The intracavernous injection program consisted of three protocols of increasingly complex combinations of vasoactive drugs, papaverine, phentolamine, prostaglandin E1 and atropine sulfate. Patients who failed the first protocol were switched to the second, and those who failed the second were switched to the third. A positive response was defined as an erection sufficient for vaginal penetration. A positive response was achieved on protocol I in 61 of the 106 patients (57.5%); protocol II in 32 of the remaining 45 patients (71.1%); and protocol III in seven of the remaining 13 patients (53.8%); the total success rate was 94.3%. These 100 patients were included in the 1-year follow-up, and 90 reported successful coitus at the end of that period: 79 patients (87.8%) with intracavernous injection and 11 (12.2%) without injection. The remaining 10 patients (10%) dropped out of the program, seven (7.0%) for health or marital reasons and three (3.0%) because of treatment failure. We conclude that a progressive program of intracavernous injections of vasoactive drugs may be a good alternative for the treatment of erectile dysfunction in patients with cardiovascular disease.

Adrenergic alpha-Antagonists↗
PubMed2001

The effect of cholinergic enhancement during filling cystometry: can edrophonium chloride be used as a provocative test for overactive bladder?

PURPOSE: Overactive bladder, a highly prevalent disorder, is suspected of having a low detection rate due to the lack of sensitive diagnostic tools. Recent studies imply the involvement of the cholinergic system in the pathophysiological mechanism underlying overactive bladder. We determined whether in vivo enhancement of cholinergic activity with edrophonium chloride, a potent cholinesterase inhibitor, would serve as a provocative maneuver to increase the sensitivity of filling cystometry. MATERIALS AND METHODS: A total of 27 patients underwent a multichannel video urodynamic evaluation, followed by filling cystometry with the intravenous administration of 10 mg. edrophonium chloride. The response to edrophonium was defined as a significant change in sensation and decreased bladder capacity, the induction or amplification of involuntary detrusor contractions, or significantly decreased detrusor compliance. Findings were compared in responders and nonresponders. RESULTS: We identified 11 responders and 16 nonresponders. A response was noted in 78% of the patients with the symptomatology of overactive bladder but in none with no specific complaints suggesting bladder overactivity. In 7 of the 12 responders (64%) baseline cystometry was interpreted as normal. In 6 of the 11 responders (54%) uninhibited urinary leakage was observed in response to edrophonium. There were no serious adverse reactions to the drug. CONCLUSIONS: This preliminary study implies that edrophonium may serve as a novel, practical and safe drug for provocative cystometry. By significantly increasing cystometry sensitivity the drug would facilitate the identification of the subset of patients with overactive bladder who are currently classified with sensory urgency.

Adult↗
PubMed2000

Three-year outcome of a progressive treatment program for erectile dysfunction with intracavernous injections of vasoactive drugs.

OBJECTIVES: To perform a comparative evaluation and follow-up of patients with erectile dysfunction (ED) who were treated with intracavernous injection of vasoactive drugs, starting with simple drugs and advancing to complex combinations. METHODS: The study included 625 patients, 26 to 85 years old, with ED. Four intracavernous injection protocols were used: protocol 1, papaverine plus phentolamine; protocol 2, prostaglandin E(1); protocol 3, papaverine, phentolamine, and prostaglandin E(1); and protocol 4, atropine sulfate, papaverine, phentolamine, and prostaglandin E(1). A positive response was defined as an erection sufficient for penetration. Patients for whom the basic protocol failed were successively switched to the more advanced protocols until a positive response was achieved. RESULTS: A positive response was achieved by 415 (66.4%) of the 625 patients given protocol 1; 75 (36%) of the remaining 210 patients given protocol 2; 98 (72.6%) of the 135 patients given protocol 3; and 22 (59.5%) of 37 patients given protocol 4. All four protocols failed in only 15 patients (2. 4%). At the 3-year follow-up visit (n = 610), 349 had achieved coitus, 65 (10.6%) without an injection and 202 (33.1%) with an injection. Eighty-two patients sometimes performed coitus without an injection. Sixty-three patients (10.3%) abandoned the program because of marital or health problems; 198 asked to be switched to Viagra during the follow-up period, and 120 returned to the program. CONCLUSIONS: Overall, our progressive treatment yielded a high positive response rate (97.6%), with 57.2% achieving successful coitus on follow-up. The main advantage of the program is that it spares patients who are responsive earlier from using more complex, painful, and costly drugs.

Adult↗
PubMed2000

Bladder neck involvement at radical prostatectomy: positive margins or advanced T4 disease?

OBJECTIVES: To assess the prognosis of patients with bladder neck (BN) involvement in radical prostatectomy specimens and compare it with patients with seminal vesicle invasion (SVI) presumed to have an inferior stage according to the TNM classification. METHODS: Two hundred eighty-six case files of consecutive radical prostatectomies were reviewed. The records of patients with pathologic BN involvement (pT4a) or SVI (pT3c) were thoroughly analyzed and compared. The mean and median follow-up periods were 30.8 and 35.5 months (range 9 to 40), respectively, for the patients with Stage pT4a and 40.8 and 44.1 months (range 8 to 86), respectively, for the patients with Stage pT3c. Particular attention was paid to the preoperative clinical and pathologic evaluation, the pathologic analysis of the prostatectomy specimen, and the postoperative follow-up data. Progression was defined as a prostate-specific antigen level of 0.2 ng/mL and rising. Adjuvant therapy was not initiated unless prostate-specific antigen failure had occurred. RESULTS: BN involvement was identified in 25 patients (8.7%) and SVI was found in 26 patients (9.1%). In 7 patients (2.4%), the BN was the only site of positive margins. Thirty-six percent of patients with BN involvement and 62% of patients with SVI demonstrated biochemical progression. Disease-free survival and metastasis-free survival rates were significantly better for the patients with Stage pT4a than for the patients with Stage pT3c at 24 and 36 months after surgery. Univariate analysis identified the prostate-specific antigen nadir to be the most significant predictor of prognosis. CONCLUSIONS: In this study, BN involvement in the surgical specimen carried a lower risk of progression than SVI. On the basis of our preliminary results and those in other studies, a conceivable downstaging of BN involvement in the TNM staging system should be considered. Possibly, additional modification of the TNM staging system should be contemplated on the basis of the results of pathologic analysis and prognosis. The significance of BN involvement and the role of adjuvant therapy in this group of patients need further evaluation.

Aged↗
PubMed2000

The rate of the founder Jewish mutations in BRCA1 and BRCA2 in prostate cancer patients in Israel.

Inherited predisposition occurs in 5-10% of all prostate cancer (CaP) patients, but the genes involved in conferring genetic susceptibility remain largely unknown. Several lines of evidence indicate that germline mutations in BRCA1 and BRCA2 might be associated with an increased risk for CaP. Three mutations in these two genes (185delAG and 5382InsC (BRCA1) and 6174delT (BRCA2) occur in about 2.5% of the general Ashkenazi population, and the 185delAG BRCA1 mutation, in up to 1% of non-Ashkenazi Jews. In order to assess the contribution of these germline mutations to prostate cancer in Jewish Israeli patients, we tested 174 unselected prostate cancer patients (95 of Ashkenazi origin) for these mutations by PCR amplification and modified restriction enzyme digests. Patient's age range was 45-81 years (median 66), and in 24 (14.4%) the disease was diagnosed prior to 55 years of age. Nineteen (11%) and 12 (6.9%) patients had a first or second degree relative with CaP or breast cancer, respectively. Overall, five mutation carriers were detected: 2/152 (1.3%) 185delAG, 2/104 (2%) 5382InsC, and 1/158 (0.6%) 6174delT. In all carriers, the disease was diagnosed after the age of 55, and only one of them had a family history of breast and CaP. In addition, no allelic losses at the BRCA1 locus were demonstrated in 17 patients with a family history of CaP, using seven microsatellite markers. We conclude that the rate of the predominant Jewish BRCA1 and BRCA2 mutations in CaP patients does not significantly differ from that of the general population, and that mutational inactivation of the BRCA1 is rare in familial CaP. Thus, germline BRCA1 and BRCA2 mutations probably contribute little to CaP occurrence, to inherited predisposition, and to early onset disease in Jewish individuals.

Aged↗
PubMed1998

Intravesical bacillus Calmette-Guérin treatment for Stage T1 grade 3 transitional cell carcinoma of the bladder.

OBJECTIVES: To retrospectively analyze intravesical bacillus Calmette-Guerin (BCG) treatment for Stage T1 grade 3 (T1G3) transitional cell carcinoma (TCC) of the bladder. METHODS: Between 1984 and 1995, 78 patients with Stage T1 grade 3 tumor were treated by transurethral resection of all visible tumors and adjuvant BCG intravesical instillations. Median follow-up was 56 months (range 12 to 141). RESULTS: After an initial induction course, 52 patients (67%) were tumor-free. Twenty-two patients (28%) had recurrent tumor after a median of 7 months (range 5 to 62). Progression occurred in 6 patients (7.7%) after a median of 18 months (range 5 to 56). CONCLUSIONS: Intravesical BCG appears to be an effective treatment for patients with Stage T1 grade 3 TCC. Patients whose tumors recur after an initial induction course may benefit from a second course of BCG. Intravesical BCG treatment may lower the tumor progression rate. Late recurrence, beyond 2 years, warrants long-term follow-up.

Adjuvants, Immunologic↗
PubMed1998

Management of renal angiomyolipoma: analysis of 15 cases.

OBJECTIVE: We present our experience with 15 patients with renal angiomyolipoma warranting intervention. METHODS: The medical records and radiological studies were reviewed for patient age and sex, tumor location and size, association with tuberous sclerosis, and treatment approach. All patients were regularly followed by ultrasound and computed tomography scan. RESULTS: Presenting symptoms were retroperitoneal bleeding in 9 patients and flank pain in 6. Excluding cases of tuberous sclerosis (mean tumor diameter 11 cm), the mean diameter of the two tumors that bled was 5.4 cm, similar to those in the patients presenting with flank pain. Two patients with retroperitoneal bleeding had tumors < 3 cm. Angioinfarction was performed in 7 patients, partial nephrectomy in 3, and total nephrectomy in 4. One patient with tuberous sclerosis, who was observed only, died of bleeding and sepsis. The mean follow-up period of 4.3 years revealed stable creatinine levels and no recurrent hemorrhage. CONCLUSIONS: The management approach of angiomyolipoma should be aimed at parenchymal preservation which can be effectively accomplished by limited surgery or preferably by selective embolization. Preventive embolization may be feasible even for small tumors. However, any doubt about the diagnosis of angiomyolipoma should be clarified by surgery.

Adult↗
PubMed1996

Penile edema and meatal ulceration after intravesical instillation with bacillus Calmette-Guerin.

Bacillus Calmette-Guérin (BCG) bladder instillation is an accepted treatment modality in the management of superficial transitional cell carcinoma but is associated with frequent side effects. A report of intravesical BCG-induced penile edema and meatal ulceration that occurred in 2 patients is presented. During induction therapy, both patients complained of progressive penile edema. In 1 patient the edema appeared after the second instillation and in the other after the fourth instillation. Edema was associated with ensuing meatal ulceration and enlarged inguinal lymph nodes. BCG instillation was aborted, and oral antituberculous treatment was initiated. There was no report of external spillage during the administration of BCG or of genital or urethral trauma during catheterization. Patients were treated at different clinics but with BCG of the same strain and batch. Symptoms continued for 6 weeks until they abated. Both patients were managed with oral antituberculous drugs for a period of 3 months. Adverse effects of BCG intravesical administration affect several organs in the genitourinary system. The penis and urethra may also be involved, presenting as penile edema and meatal ulceration. Physicians who administer BCG must be familiar with the possible complications and their appropriate management.

Adjuvants, Immunologic↗
PubMed1996

Type II ureteral triplication associated with ectopic ureter.

We report a case of type II ureteral triplication associated with ectopic ureter. The ureter, draining the upper renal segment, entered the vagina, and the other two ureters, draining the middle and lower renal segments, had joined and entered the bladder. The anatomic findings are compatible with those predicted by the Weigert-Meyer law. A thorough evaluation of such an anomaly is essential for effective management.

Abnormalities, Multiple↗
PubMed1996

Citral and testosterone interactions in inducing benign and atypical prostatic hyperplasia in rats.

Citral is a monoterpene in wide use as an aromatic supplement in the cosmetics and food industries. Previous studies in our laboratory have shown that cutaneous application of citral on adolescent rats may induce benign prostatic hyperplasia (BPH)-like and even atypical hyperplastic changes in the ventral lobes. In the present study we investigate the possible interactions between citral and serum testosterone levels on the induction of hyperplastic changes in the ventral prostate of adolescent rats. In addition, the study includes a comparative analysis of normal intact rats showing circadian variations of serum testosterone levels and rats in whom this rhythmic pattern was abolished either by excessive supplementation of exogenous androgen or by castration. Our results demonstrate an induction of benign as well as atypical prostatic hyperplasia following citral application. The most severe atypical changes were noted in the citral-treated rats with high serum testosterone levels. Although the mechanism of action of citral is yet unknown, the present results suggest a synergism between citral and testosterone resulting in hyperplastic changes in the rat ventral prostate. In addition, the results reconfirm that serum testosterone levels fluctuate according to a circadian rhythm in intact young and adolescent male rats. The application of citral tends to lower the morning circadian peaks, and the circadian pattern was abolished in orchiectomized rats and in those treated with testosterone implants.

Acyclic Monoterpenes↗
PubMed1996

Expression of retinoic acid receptor beta in human renal cell carcinomas correlates with sensitivity to the antiproliferative effects of 13-cis-retinoic acid.

The differentiation and growth suppressive effects of retinoic acid are mediated through retinoic acid nuclear receptors (RARs and RXRs), which are ligand-activated transcription factors. Recent data suggest that both altered and regulated expression of RARs are linked to retinoic acid response in a cell context-dependent manner. This study examined the antiproliferative effects of 13-cis-retinoic acid (cRA) on 12 renal cancer cell lines and correlated these findings with the basal and induced expression of RAR-alpha, -beta and -gamma. Eleven of 12 renal cancers that were either resistant to or only minimally inhibited by cRA did not basally express RAR-beta as determined by Northern blot analysis. In these cells, cRA treatment did not induce RAR-beta expression. In contrast, 1 of 12 cell lines (SK-RC-06) was >90% inhibited by cRA and basally expressed RARbeta. Furthermore, RAR-beta mRNA in SK-RC-06 cells was up-regulated by cRA treatment. Amplification of cDNA using PCR and RAR-beta isoform-specific primer pairs revealed that only SK-RC-06 cells expressed the RAR-beta1 isoform. Expression of RAR-alpha transcripts was abundant in all 12 cell lines examined, whereas low levels of RAR-gamma transcripts were detectable in 6 of 10 renal cancers. Expression of RAR-alpha and RAR-gamma was not affected by cRA. These data showing that the majority of renal cancer cell lines are resistant to cRA suggest that: (a) resistance to the antiproliferative action of cRA correlates with repressed RAR-beta mRNA expression; and (b) the antiproliferative effects of cRA in renal cancer cells are mediated through RAR-beta1.

Antineoplastic Agents↗
PubMed1994

A comparison between digitally-guided fine needle aspiration and ultrasound-guided transperineal core needle biopsy of the prostate for the detection of prostate cancer.

OBJECTIVE: To prospectively examine the accuracy of fine needle aspiration (FNA) for the detection of prostate cancer. Ultrasound-guided core needle biopsy of the prostate was used as the standard to which the FNA results were compared. PATIENTS AND METHODS: One-hundred patients who had been referred for urological evaluation were suspected of having prostate cancer on the basis of digital rectal examination (DRE) and/or transrectal ultrasound (TRUS). All were further evaluated by digitally guided transrectal FNA and by TRUS-guided transperineal core needle biopsy. RESULTS: Prostate cancer was identified in 54 patients by core needle biopsy and in 45 by FNA. The sensitivity of FNA was 81% and both specificity and positive predictive value were 98%. CONCLUSION: FNA is easily performed, has negligible morbidity and offers prompt results. These data suggest that FNA is a reasonable initial diagnostic procedure for the detection of prostate cancer. Core needle biopsy may be reserved for patients with negative cytology who are clinically suspected of having prostate cancer. In selected patients, FNA may be used as an alternative to core needle biopsy for diagnosis, treatment planning and follow-up.

Aged↗
PubMed1993

Molecular cloning of the human kidney differentiation antigen gp160: human aminopeptidase A.

gp160 is a cell surface differentiation-related glycoprotein of 160 kDa expressed by epithelial cells of the glomerulus and proximal tubule cells of the human nephron but only by a subset of renal cell carcinomas (RCCs). We have reported that gp160 expression correlates with the resistance of cultured RCCs to the antiproliferative effects of alpha interferon, while lack of expression correlates with sensitivity to alpha interferon. In this study, we have purified gp160 protein, obtained partial sequences of random peptides, and isolated a full-length cDNA. The gp160 cDNA possesses 78% homology to the murine BP-1/6C3 antigen, a B-lymphocyte differentiation protein that exhibits aminopeptidase A (APA; EC 3.4.11.7) activity. Enzymatic assays on human RCC cell lines indicated a 100% concordance between APA activity and gp160 expression. APA activity of gp160-expressing RCC cells was increased or decreased by a panel of APA activators or inhibitors, respectively. Furthermore, anti-gp160 monoclonal antibodies immunoprecipitate APA activity from RCC cell lysates and selectively deplete APA activity from RCC cell extracts. These data indicate that the gp160 human kidney/RCC glycoprotein is human APA.

Amino Acid Sequence↗
PubMed1993

A marker for neoplastic progression of human melanocytes is a cell surface ectopeptidase.

Adenosine deaminase binding protein (ADAbp) is a cell surface glycoprotein that is expressed by normal melanocytes but not by melanoma, the malignant counterpart. ADAbp is specifically downregulated during malignant transformation of melanocytes. Recently, we have developed a system that progressively transforms melanocytes in vitro in defined steps. Transduction with v-Ha-ras oncogene followed by long-term culture leads to a cell phenotype and genotype that specifically mimics human melanoma. Loss of ADAbp expression occurred concomitantly with the emergence of growth factor independence and appearance of specific chromosomal abnormalities. The cellular function of ADAbp has not been defined. To characterize ADAbp, the mature 110-kD form was purified from human kidney. Five tryptic peptides from purified human ADAbp revealed 100% homology to a serine protease, human dipeptidyl peptidase IV (DPP IV), also known as CD26. DPP IV activity was detected in lysates from human melanocytes and renal carcinoma cells but not melanoma cells, and DPP IV activity could be specifically isolated from melanocytes by binding to ADA or to S27 monoclonal antibody against ADAbp. These findings show that ADAbp is a cell surface ectopeptidase that is tightly regulated during neoplastic transformation of melanocytes.

Adenosine Deaminase↗
PubMed1992

[Immunotherapy for metastatic renal cell carcinoma: treatment with PLAK cells and low-dose interleukin-2].

During the past 5 years publications from the NIH (Rosenberg et al.) and other centers have reported encouraging results in the treatment of metastatic renal cell carcinoma. Adoptive immunotherapy was applied, using lymphocytes activated by interleukin-2 (LAK cells) plus high doses of interleukin (IL-2) systemically. The mean clinical response rate was 20-35%. Severe lifethreatening adverse reactions to high doses of IL-2 were noted, although they were all of short duration. Laboratory findings of Novogrodsky et al. from Beilinson Medical Center, Israel showed that oxidizing mitogens can induce lymphocyte activation (PLAK cells). Further studies suggested that a combination of such activated cells with low doses of IL-2 could produce effective toxicity to tumor cells without the need for high doses of IL-2 which could be very toxic for the patient. In the past year we treated 7 patients with PLAK cells and IL-2. 4 completed the treatment, of whom 1 responded partially (regression of more than 50% of lung metastases), 1 is stable and in 1 liver metastases regressed but metastases in lumbar vertebrae and in the pelvis progressed. 1 patient died a month after discharge from hospital, probably due to rapid progression of the disease. Our protocol follows that of the Phase II clinical study of 40 patients treated at the Rogosin Institute, New York Hospital--Cornell Medical Center. The mean clinical response rate was 23.6%. Toxicity of IL-2 is dose-dependent. In this protocol, the low doses of IL-2 gave significantly fewer adverse reactions.

Adult↗
PubMed1992

Rowatinex for the treatment of ureterolithiasis.

A prospective, randomized, double-blind study was performed on 87 patients with ureterolithiasis, assessing the effect of the essential oil preparation Rowatinex (Rowa Pharmaceuticals, Ireland) for the treatment of ureterolithiasis. Forty-three patients were treated with Rowatinex and 44 patients with placebo. Despite the larger average diameter of calculi in the group of patients treated with Rowatinex, the overall stone expulsion rate was significantly higher in the Rowatinex group as compared to placebo: 81% and 59%, respectively (0.025 > p > 0.01). This higher rate of stone expulsion is observed in patients with disappearance of pretreatment ureteral dilatation (when patients with expelled stones are excluded) (0.05 > p > 0.001). Seven patients in the Rowatinex group had mild to moderate gastrointestinal disturbances; no other significant side effects were noted during the treatment in either group. We conclude that early treatment with Rowatinex for patients with ureteral stones is indicated before other more aggressive measures are considered.

Adult↗
PubMed1992

Risk factors and their effect on the results of Burch colposuspension for urinary stress incontinence.

Forty patients with urinary stress incontinence were studied and the results of Burch colposuspension evaluated. Combined detrusor instability and stress incontinence were found in 22.5% of the patients. The results of surgery showed that 87.5% of the patients (35/40) were cured of incontinence. None of the contributing risk factors of incontinence had a significant role in the outcome of surgery. In view of this, all patients with surgically amenable urinary incontinence should be considered for surgical resolution of this condition.

Adult↗