Treatment of uterine leiomyomas with luteinizing hormone-releasing hormone antagonist Cetrorelix

The efficacy of the luteinizing hormone-releasing hormone antagonist Cetrorelix (SB-75) in the medical management of uterine leiomyomas (fibromas) was evaluated. Cetrorelix was administered to 18 pre-menopausal women with myomas with a mean age of 33.3 years, who had been candidates for hysterectomy. The initial dose of Cetrorelix was 5 mg twice daily s.c. for the first 2 days and thereafter 0.8 mg was given twice daily s.c. for at least 3 months. The mean duration of the treatment was 4.4 months. Before the therapy with Cetrorelix, the mean uterine volume, measured by ultrasonography, was 395.4 +/- 69.2 ml (range 89-1166). Sixteen patients showed a progressive reduction in uterine volume from 410.4 +/- 77.1 to a mean of 230.8 +/- 52.6 ml at 3 months. All patients became amenorrhoeic and had hot flushes. After treatment with Cetrorelix, a surgical myomectomy was performed in 12 women. One of the patients subjected to myomectomy after therapy with Cetrorelix became pregnant. These patients have been followed for up to 25 months and only in one case has the uterine volume increased after therapy. Three patients had good responses to therapy with Cetrorelix and it was decided to follow them only by observation. One patient became pregnant 2 months later. In the other patient, the uterine volume remained unchanged for the duration of the follow-up of 2 years and the third patient showed an increase after 21 months. In three patients, it was necessary to perform total hysterectomy. In 14 patients, serum concentrations of luteinizing hormone, follicle stimulating hormone and oestradiol decreased after the administration of the first dose of Cetrorelix and continued at subnormal values throughout therapy. In 15 patients who were not subjected to total hysterectomy, menstrual function returned at 1 month after cessation of treatment. Overall results support the use of Cetrorelix for the management of uterine leiomyomas.     

Terazosin in the treatment of hypertension and symptomatic benign prostatic hyperplasia: a primary care trial

In vitro experimental data show that magnesium increases beta-receptor affinity to agonists. We studied the effect of a mild increase in serum magnesium level on the bronchial dose-response curve to salbutamol in six patients with asthma (age 54 +/- 3.6 years, FEV1 49.2 +/- 4.9 per cent of predicted), with a normal serum magnesium level, in a double blind placebo-controlled design. The salbutamol dose-response curve was obtained on two separate days, starting 30 min after an intravenous infusion of saline or MgSO4 (20 mg/kg over 10 min, followed by 10 mg/kg/h). The baseline FEV1 values and the values after 30 min infusion on the two test days were not significantly different. During MgSO4 infusion, the serum magnesium level increased significantly from 0.86 +/- 0.01 to 1.31 +/- 0.19 mmol/litre after 30 min and 1.29 +/- 0.17 mmol/litre at the end of the study. FEV1 values after salbutamol were significantly higher during MgSO4 than during saline infusion at the low doses of salbutamol: 1480 +/- 253 vs. 1368 +/- 212 ml, P < 0.05, after 5 micrograms, and 1596 +/- 585 vs. 1378 +/- 532 ml, P < 0.01, after 10 micrograms of salbutamol. The maximum increase in FEV1 obtained after the maximum dose of salbutamol (400 micrograms) was not significantly different during saline and MgSO4 infusion. In conclusion, a mild sustained increase in serum magnesium level increases the bronchodilating effect of low doses of salbutamol, possibly through an increased beta-receptor affinity. There was no effect on the maximum bronchodilating effect of salbutamol.     

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.     

Prostate tissue composition and response to finasteride in men with symptomatic benign prostatic hyperplasia

PURPOSE: We sought to quantify prostate tissue changes induced by finasteride and to identify a predictor of finasteride response in men with symptomatic benign prostatic hyperplasia (BPH) via a randomized, placebo controlled, double-blind clinical trial. MATERIALS AND METHODS: Men with symptomatic BPH (52 to 78 years old) were randomly assigned to 6 months of treatment with finasteride (26) or placebo (15). Outcome measures were clinical (urinary symptom score and flow rate), chemical (serum prostate specific antigen and dihydrotestosterone levels), volumetric (transrectal ultrasound, and magnetic resonance imaging for whole and zonal prostate volumes) and histological (morphometry of prostate sextant biopsies, separated into inner and outer gland segments, to measure the percent epithelium, stroma and glandular lumen). RESULTS: In the finasteride group we found a suggestion of decreasing symptom scores and increasing flow rates (not significant) with significant decreases (p < 0.01) in prostate specific antigen (48%), dihydrotestosterone (74%) and prostate volume (21%). Finasteride treatment induced a 55% decrease in inner gland epithelium (p < 0.01) with little effect on stroma or lumina. We also found a linear correlation between pretreatment inner gland epithelial content and prostate volume decrease induced by the drug (tau = 0.58, p = 0.01). CONCLUSIONS: Finasteride treatment results in a major suppression of prostate epithelium, which is most pronounced in the inner gland. Moreover, a finasteride induced prostate volume decrease was predictable by quantification of epithelial tissues of the inner gland. These data lend additional support to the emerging concept of transition zone primacy in symptomatic BPH.     

Sexual readaptation after the surgical treatment of benign prostatic hyperplasia

Lesions of the tongue are often encountered in the process of a dental examination. These can include alterations of the tongue surface texture or colour, ulcers or exophytic lesions (lumps). The latter can represent variations of normal, benign or malignant pathological processes. This article will not provide a detailed list of all possible exophytic tongue lesions but will present a few of the more common conditions to be considered when such lesions are encountered.     

The treatment of benign prostatic hyperplasia using the Mumie-Vitas preparation

Overall thirty-eight patients presenting with stage I-II benign prostate hyperplasia received treatment with a new local drug preparation Mumiyo-Vitas, 0.2 g on a once- or twice-daily basis over six months. Effects were studied of the drug on the urologic symptomatology and quality of life of patients presenting with ongoing micturitional disturbances, functional state of detrusor vesicae, prostate volume and urethral resistance. Efficiency of the treatment given was assessed by the International system, uroflowmetry, ultrasonic investigation. Mumiyo-Vitas appeared to be of therapeutic benefit in those patients with subjective and objective symptoms of the urinary bladder obstruction who had innocent prostate hyperplasia.     

Effects of the opioid antagonist naltrexone-estrone azine on the luteinizing hormone-releasing hormone induced release of luteinizing hormone from the pituitary glands of ovariectomized rats

The effects were studied of in vivo administration of the new opioid antagonist-estrogen hybrid, naltrexone-estrone azine (EH-NX), on subsequent luteinizing hormone-releasing hormone (LHRH)-stimulated luteinizing hormone (LH) release by the pituitary gland in vitro. It is well known that administration of estrogen exerts negative and positive effects on the pituitary LH response to LHRH, respectively after short-term and long-term treatment. Rats were injected subcutaneously with either 17 beta-estradiol-3-benzoate (EB), EH-NX or oil on days 18 and 19 (long-term treatment), and on day 21 (short-term treatment) following ovariectomy. Twenty minutes later the animals were killed and the pituitary glands were incubated in the presence of LHRH (1000 ng/ml) for 4 h. Whereas short-term treatment with EB on day 21 did not affect LH release in vitro, EH-NX significantly decreased the pituitary LH response to LHRH in oil pretreated rats. This inhibitory effect was partially blocked by the opioid antagonist naltrexone. After long-term EB or EH-NX, followed by short-term oil treatment, the pituitary LH response to LHRH was increased considerably, compared to the long-term oil controls. These observations demonstrate that the opioid antagonist estrogen hybrid EH-NX has estrogenic activity at the level of the pituitary gland. This hybridized drug is more effective in time than EB and an equimolar amount of EH (estrone hydrazone) to induce the negative estrogenic effect.     

Modern approach to conservative treatment of benign prostatic hyperplasia

It has been estimated that more than 30 million of people suffer from the symptoms in the lower urinary tract caused by benign hyperplasia of the prostate. According to data from literature the term benign hyperplasia of the prostate should be reserved only for histological diagnosis. The paper presents contemporary approaches to diagnostics and non-surgical, i.e. conservative modalities of the therapy. These modalities include: follow up of the patients, medicamentous therapy and non-surgical invasive therapies. Medicamentous therapy implies phytotherapy, inhibitors of 5-Alpha reductase and antagonists of Alpha-adrenergic receptors. Non-surgical invasive therapies include: balloon dilatation, ureteral stents and thermotherapy. The paper indicates the place of certain options related to the conservative treatment of benign hyperplasia of the prostate. A fact that only 10% of these patients are treated surgically means that majority of them need other, i.e. conservative therapy. New achievements in the treatment of benign hyperplasia of the prostate have aroused new hope for men suffering from this disease.     

Transurethral endoscopic electrovaporization in the treatment of patients with benign prostatic hyperplasia

The adenoid tissue is an immunecompetent lymphoid organ, which has the capacity of reacting against numerous antigens. We have studied the influence that the elimination of the said tissue would have on the total IgE serum levels in 33 patients of an average age of 5 and criteria of adenoidectomy and in whom these levels were measured before and after surgery. We have not noticed any statistically significant differences in the IgE values after adenoidectomy with respect to those prior to surgery, which were normal. Adenoidectomy, like other authors have observed after tonsillectomy, does not alter the IgE serum values.     

Errors in the diagnosis of benign prostatic hyperplasia

Monitor blood glucose level before, during and for up to 24 hours after exercise. Ensure refined carbohydrate snack is taken prior to exercise. Reduce insulin dosage if possible. Inject insulin away from any exercising muscle. Remember that glycogen stores are replenished in two phases: immediately after the exercise and two to three hours later. These are the key risk times for hypoglycaemia. If blood glucose control is poor (14 mmol/litre or higher) prior to exercise, the 'stress' effect of the exercise may cause further increases in the blood sugar level unless control is achieved.     

Expanding role of alpha adrenoceptor blockade in the treatment of benign prostatic hyperplasia

PURPOSE: To evaluate the efficacy and safety of timolol hemihydrate once daily versus timolol maleate gel forming solution once daily in patients with primary open-angle glaucoma or ocular hypertension. METHODS: We prospectively randomized patients with primary open-angle glaucoma or ocular hypertension to receive either timolol hemihydrate 0.5% solution or timolol maleate gel forming solution 0.5% every morning. The primary efficacy variable was the 8:00 AM trough intraocular pressure (IOP) 24 hours after administration. RESULTS: Three months after initiation of therapy, baseline IOP had decreased from 23.6 +/- 1.9 mmHg to 18.3 +/- 2.8 mmHg in the group taking timolol hemihydrate (n = 22) and from 23.7 +/- 2.2 mmHg to 18.4 +/- 3.1 mmHg in the group receiving timolol maleate gel (n = 21) at the 24-hour trough level. This was not a significant difference between groups at 3 months. Also, no difference was observed between groups in the 2-hour post instillation IOP. Visual acuity was decreased in the group receiving timolol maleate gel compared with those receiving timolol hemihydrate one minute after instillation of study medicine at month 3. Otherwise, ocular and systemic safety were similar between groups. No differences between groups in cardiac pulse or systolic and diastolic blood pressure were observed. CONCLUSION: Timolol hemihydrate 0.5% solution given once a day appears to be as efficacious and safe in decreasing IOP as timolol maleate gel 0.5% given once a day.     

Thermosensitive stent (Memotherm) for the treatment of benign prostatic hyperplasia

Recently, more and more alternative therapeutic methods have been used for the treatment of benign prostatic hyperplasia (BPH). We will report on therapeutic results with a new thermosensitive stent system (Memotherm). This wire mesh stent has been designed especially for urological purposes. It is made of Nitinol, a thermoreactive material, and gains its maximum expansion force al body temperature. Due to the properties of the material the stent is flexible and can adapt to the anatomical conditions of the prostatic part of the urethra. Because of individual variations in the length of the prostatic part of the urethra, the system is available in lengths from 2 to 8 cm. The knitted structure for the first time allows atraumatic removal. Between April, 1992, and September, 1993, we treated a total of 54 BPH patients with the stent system. Mean patient age was 76.1 +/- 7.6 years (61-98). Mean prostatic volume was 51.9 +/- 25 ml (20-150), and the length of the applicated stents was 32.3 +/- 9.5 mm (20-70). Patient selection for stent treatment was carried out with regard to the preoperative risk status of this patient group. Fourteen (26%) of the patients treated were able to micturate before operation; in 40 (74%) urinary drainage was accomplished by means of an indwelling catheter. Following stent application, 53 out of 54 patients were able to micturate. With the first group (preoperative voiding ability), maximum flow had increased from 4.5 ml/s to a mean of 15.8 ml/s, while residual urine volume had decreased from 194.4 ml to 11.8 ml and the AUA 6 Symptoms Score had improved from 24 points to 3.5 points 6 months after stent application. All differences were statistically significant (P < 0.02). With the second group (no preoperative voiding ability), the AUA 6 Symptoms Score had improved from 25 points to 3.9 points (P < 0.02) 6 months after the operation, at which time the mean maximum flow rate was 14.8 ml/s and residual urine volume 14.8 ml. There was no statistically significant difference between the patients who were able and those who were unable to micturate before operation. One case of epididymitis was the only major complication observed after stent placement. Frequent urgency symptoms (30 out of 54 patients; 55.5%) subsided after a mean period of 1 week. The Memotherm stent offers an interesting therapeutic alternative for BPH risk patients.     

Transurethral thermotherapy in the management of benign prostatic hyperplasia

To elucidate the intradialytic urea concentration gradients, we examined 26 hemodialysis patients wearing a double-lumen central venous catheter during their first or second fistula-punctured dialysis session. In 17 patients (group A), after 60 and 240 minutes of treatment with a mean blood flow of 196.4 +/- 9.9 mL/min, blood urea nitrogen (BUN) was measured in blood samples taken simultaneously from the central venous catheter, a vein in the arm opposite the access site, and the arterial and venous lines of the dialyzer. In 16 patients (group B), after 60 minutes of treatment with a mean blood flow rate of 197.5 +/- 12.3 mL/min, BUN was measured in blood samples taken from the dialyzer arterial line and then, after decreasing the blood flow to 50 to 60 mL/min for 1 minute, in samples taken from a vein in the arm opposite the access site, the central venous catheter, and the dialyzer arterial line. In group A, the mean BUN values in the dialyzer arterial line at 60 and 240 minutes were found to be 3.7% +/- 3.7% and 3.5% +/- 3.4% higher than the corresponding values in the central veins, respectively (P = NS between 60 and 240 minutes). In group B, after 1 minute of low blood flow, this difference was 1.5% +/- 2.4% (P = 0.06 compared with group A). The peripheral veins in group A patients at 60 and 240 minutes had 9.7% +/- 5.2% and 10.9% +/- 5.3% higher BUN values, respectively, compared with the central veins. This difference in group B patients after 1 minute of low blood flow was 6.8% +/- 4.2%. Urea access recirculation rate in group A, calculated by the classical three-samples method, was found to be 7.6% +/- 5.0% at 60 minutes and 9.9% +/- 5.8% at 240 minutes (P = NS). In group B, BUN values in the dialyzer arterial line after 1 minute of low blood flow increased significantly by 3.4% +/- 4.5% (P < 0.01). Our study shows that during conventional hemodialysis with a blood flow rate of 200 mL/min, urea concentration in the central veins is lower than in the dialyzer arterial line. This gradient after 1 minute of low-flow dialysis had a tendency to decrease. At the same time, however, the urea concentration gradient between the peripheral and central veins remained high, indicating that during conventional hemodialysis, intercompartmental disequilibrium plays a significant role in the arteriovenous gradient.     

An open study on the efficacy and safety of transurethral needle ablation of the prostate in treating symptomatic benign prostatic hyperplasia: the University of Florida experience

PURPOSE: We determine the safety and efficacy of transurethral needle ablation of the prostate in patients with moderate to severe symptoms of benign prostatic hyperplasia. MATERIALS AND METHODS: Transurethral needle ablation of the prostate was performed on 45 consecutive patients. For an average prostate of 2.5 to 3 cm. long treatments were performed in 2 separate planes at 4 quadrants (2, 4, 8 and 10 o'clock positions) each. The 2 planes were 1 cm. below the bladder neck and 1 cm. proximal to the verumontanum. For prostatic urethral lengths longer than 3 cm. a treatment plane was added for each additional centimeter of prostatic urethra. The procedure was performed in 26 patients under local anesthesia using 20 cc 2% intraurethral lidocaine gel (11) or supplemented with intravenous 1.25 to 5 mg. midozolam (15). Of these patients 2 had a supplemental perineal block using a mixture of equal amounts of 15 cc 2% lidocaine without epinephrine and 0.25% bripivacaine, 10 underwent the procedure under general anesthesia, 2 had epidural and 4 had spinal anesthesia, and 3 had managed anesthesia care. Mean length of each procedure was 79 minutes (range 50 to 240). All procedures were done on an outpatient basis and patients were released on the same operative day. RESULTS: Mean prostatic volume on transrectal ultrasound was estimated at 48.1 cc (range 20 to 185). Following treatment the International Prostate Symptom Score decreased from a mean of 20.9 at baseline to 15.4 at 1 month, 16.1 at 3 months, 10.7 at 6 months and 9.9 at 1 year. The peak flow rate improved from a baseline mean of 8.3 to 13.4 at 3 months, 13.1 at 6 months and 14.9 at 1 year. The quality of life score improved from a baseline of 4.8 to 3.5, 2.2, 2.5 and 1.03 at 1, 3, 6 and 12 months, respectively. Of the 2 patients in whom the procedure failed; 1 required a bladder neck incision at 3 months and the other transurethral resection of the prostate. Foley catheters were left in place in all patients for an average of 4.85 days. CONCLUSIONS: After a followup of up to 12 months we conclude that transurethral needle ablation of the prostate is an effective treatment for symptomatic benign prostatic hyperplasia. This procedure has minimal morbidity, is less costly than conventional transurethral resection of the prostate and can be performed as an outpatient office procedure under local anesthesia in a significant number of patients.     

Effect of luteinizing hormone-releasing hormone on rat adrenocortical cells

The effects of luteinizing hormone-releasing hormone (LH-RH) on the function of rat adrenal cortex were investigated by using dispersed zona glomerulosa (capsular) and zona fasciculata-reticularis (inner) cells. LH-RH increased basal (but not adrenocorticotropic hormone (ACTH)-stimulated) corticosterone secretion of inner cells, without affecting either aldosterone or corticosterone production by capsular cells. LH-RH markedly raised basal (but not ACTH-enhanced) cyclic-AMP release by inner cells. The corticosterone secretagogue action of LH-RH was abolished by the protein kinase A inhibitor H-89. The conclusion is drawn that LH-RH specifically stimulates adrenal glucocorticoid secretion in rats through the activation of the adenylate cyclase signaling pathway.     

The treatment of patients with benign prostatic hyperplasia using the selective alpha-blocker alfuzosin

40 patients with benign prostatic hyperplasia (BPH) were treated with the alpha-blocker alfuzosin which was administered per os twice a day in a dose 5 mg. The treatment brought about a decrease of the mean symptom score from 19.6 to 12.2, of quality of life from 5.2 to 2.1, of residual urine from 152 to 82 ml. Mean and maximal urinary flow rates rose by 35 and 45%, respectively. The level of prostate-specific antigen over the treatment course did not change. The findings of the trial evidence for high efficacy of alfuzosin in the treatment of urination disorders in BPH patients.     

Transurethral thermotherapy of the prostate--a very promising treatment method for benign prostatic hyperplasia

Transurethral resection of the prostate remains the most common method for the treatment of benign prostatic hyperplasia (BPH). Due to unsatisfactory results in about 18% of the patients new methods to treat BPH have been developed. We evaluated 45 patients 6 and 12 months after transurethral microwave thermotherapy using the Prostatron device with Prostasoft 2.5 software. There was a significant improvement of the urinary symptoms and of the quality of life index from 18 to 9.5 and from 3.2 to 1.6 points, respectively. Urinary flow rate improved from 8.8 to 12.1 ml/sec and residual urine was reduced from 101 to 52 ml. The treatment was well tolerated and side effects were minimal. High-energy transurethral microwave thermotherapy is an effective and safe minimal invasive alternative to treat BPH in selected patients. As no anesthesia is required transurethral microwave thermotherapy can also be offered to high risk and elderly patients.     

Bladder compliance in patients with benign prostatic hyperplasia

Factors influencing bladder compliance were examined in 116 patients with benign prostatic hyperplasia (BPH), by evaluating patients' histories, response of isolated bladder strips to acetylcholine, and the effect of prostatic urethral anesthesia. Patients' age, frequency of micturition, and duration of voiding difficulty were not correlated with bladder compliance. Bladder compliance was significantly low in patients within 30 days after urinary retention, as compared with bladder compliance in patients without an episode of retention. More than 30 days after retention, however, there was a tendency toward increased bladder compliance. Restricted to patients without an episode of retention, bladder compliance in the overactive detrusor group was found to be significantly lower than in the normal group. The responses to acetylcholine of bladder strips were compared between patients with low and normal-compliance bladders. The dose-response curve of patients with low-compliance bladders did not differ from that of those with normal compliance bladders, even when patients with an episode of retention were excluded. After prostatic urethral anesthesia, a significant increase of bladder compliance was observed in patients with an overactive detrusor, while the increase was not significant in patients with a normal detrusor. Our results strongly suggest that easy irritability of the anatomically altered prostatic urethra, as well as bladder over-distension caused by urinary retention, are important factors affecting bladder compliance in BPH patients.