Treatment of idiopathic erectile dysfunction in men with the opiate antagonist naltrexone--a double-blind study.

Opiate antagonists can indirectly stimulate the secretion of luteinizing hormone (LH) and testosterone, as well as sexual functions in animals and humans. We therefore treated 20 otherwise healthy men with idiopathic erectile dysfunction aged 46.3 +/- 2.7 years (mean +/- SE, range 23.9-63.3) in a double-blind study with an opiate antagonist, naltrexone, or placebo. The erectile dysfunction of these men had persisted for 3.6 +/- 0.5 years despite libido maintenance; standard procedures had excluded any organic causes. Trial duration was 12 weeks overall. After a 4-week forerun, the patients received at first 25 mg naltrexone/day orally or placebo for 4 weeks followed by 4 weeks of a 50-mg dose of naltrexone/day or placebo. Each day the patients filled out a questionnaire detailing libido, degree of erection, frequency of sexual intercourse, and spontaneous morning erections. Serum concentrations of gonadotropins and testosterone were determined radioimmunologically in the initial stage and at the end of each phase. Both patient collectives had similar initial factors. The group treated with naltrexone showed a significant rise in spontaneous early morning erections during the treatment: from 2.8 +/- 0.3 to 4.2 +/- 0.3 a week (P < 0.001). The placebo group showed no significant change in spontaneous erections (2.4 +/- 0.3 and 2.6 +/- 0.3, respectively). The subjective parameters, however, such as libido, degree of erection, and frequency of sexual intercourse showed no significant difference within each group. There was no difference in LH, follicle-stimulating hormone, or testosterone concentrations in both groups. Thus, treatment with naltrexone significantly raises the rate of spontaneous early morning erections when compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

[Carbon dioxide (CO2) as contrast medium for the new installation and follow-up of a TIPS]. / Kohlendioxid (CO2) als Kontrastmittel zur Neuanlage und Kontrolle von TIPS.

PURPOSE: To determine the efficacy of CO2 as negative contrast medium compared with iodinated contrast medium in creation and control of TIPS. MATERIAL AND METHODS: CO2 was used during TIPS procedures in 33 patients. In 21 patients a wedged hepatic venography was obtained for planning the shunt tract. Additional TIPS-control DSA was performed in 42 cases by direct portal venography to verify the TIPS function and patency. In all cases CO2 gas was used in addition to iodinated contrast medium. RESULTS: CO2 produced excellent wedged hepatic venographies in all patients. Visualisation of the portal veins and collaterals was superior to iodinated contrast medium. The TIPS-control DSA performed with CO2 were comparable to those performed with iodinated contrast medium. Complications were not observed in our study. CONCLUSION: CO2 is an effective contrast medium for TIPS procedures. In particular the visualisation of portal veins performed by CO2-wedged hepatic venography is superior to iodinated contrast medium.

[Percutaneous removal of displaced metal stents in TIPS]. / Perkutane Entfernung von fehlliegenden Metallstents bei TIPS.

PURPOSE: Basing on our experience with three dislocated or displaced stents (one Wallstent, two Plamaz stents) during or after TIPS-procedure, we describe our technique to reposition or remove the stents. METHOD: The stents were moved back into the inferior vena cava by means of a balloon catheter, an alligator forceps, or an Amplatz gooseneck snare. They were secured against further dislocation by a central guidewire. After insertion of a balloon catheter into each dislocated stent, they were coaxially grasped with an Amplatz gooseneck snare. Stent diameter was reduced by forceful closure of the snare, and then the stent was either relocated or removed. CONCLUSION: To prevent further stent migration it is necessary to remove the stent via a guidewire. By using a balloon catheter and a coaxially inserted Amplatz gooseneck snare, reduction of the outer stent diameter is possible even in Plamaz stents, facilitating their relocation or removal.

[Percutaneous drainage of refractory necrotizing tumors: experience in 9 patients]. / Perkutane Drainage von therapierefraktären nekrotisierenden Tumoren: Erfahrungen bei 9 Patienten.

PURPOSE: The ranking of percutaneous drainage treatment in necrolytic advanced tumours was assessed. METHOD: 9 patients with refractory symptomatic necrolytic tumours were treated for alleviation by percutaneous drainage. Additionally, an attempt to sclerose the necrotic cavity was performed in 6 patients (6 x mitoxantrone 30 mg/24 hrs, of which 1 x additionally 98% alcohol). RESULTS: In 5 of the 9 patients symptomatic relief was obtained, but complete sclerosing of the necrotic cavity succeeded in only two patients. In two patients with necrotic tumours of the pelvis there was a bacterial superinfection of the tumour necrosis. CONCLUSION: Percutaneous alleviation is only occasionally successful in patients with necrolytic tumours. Therapy becomes effective probably only in case of successful sclerosing of the tumorous cavity.

[TIPSS: technical and clinical results after 4 years]. / TIPSS: Technische und klinische Ergebnisse nach 4 Jahren.

PURPOSE: Retrospective analysis of the technical and clinical results after transjugular portosystemic stent shunt (TIPSS) procedure. METHOD: Between 1992 and 1996 we tried to establish a TIPSS in 90 patients. The indications were: recurrent variceal haemorrhage (n = 74), refractory ascites (n = 12), hepatorenal syndrome (HRS) (n = 4). Due to advanced liver cirrhosis 16 patients suffered of severe renal dysfunction (HRS). 57 patients had ascites. RESULTS: TIPSS implantation was technically successful in 96.7% (1992-1994: 5.1%, 1995-1996: 100%) of the patients. Complications occurred in 14.9% (1992-1994: 25.6%, 1995-1996: 6.3%). TIPSS-associated mortality was 2.3% (1992-1994: 5.1%, 1995-1996: 0%). 76.1% of the patients required reinterventions. 85.3% of reinterventions were necessary in the first year after TIPSS placement. The survival rate without reintervention was 28%, 21% and 9% for Child A, B, and C patients, respectively. Recurrent variceal haemorrhage occurred in 12.7%. De novo hepatic encephalopathy developed in 13.8%. Ascites improved in 79.2% and renal function in 75% of the patients. CONCLUSION: TIPSS is an effective method to treat recurrent variceal haemorrhage, refractory ascites and HRS. Complication and mortality rate depend on the investigator's experience and on the technique used.

Liver perfusion scintigraphy prior to and after transjugular intrahepatic portosystemic shunts (TIPS) in patients with portal hypertension.

PURPOSE: This investigation was performed to compare the hemodynamic results of the transjugular intrahepatic portosystemic shunt, a new interventional treatment for portal hypertension, with those observed after the established surgical shunt interventions. METHODS: We examined 22 patients with portal hypertension due to liver cirrhosis before and after elective TIPS by liver perfusion scintigraphy. The relative portal perfusion was determined before and after the shunt procedure. Additionally, we measured the portal pressure gradient (PPG: portal-central venous pressure, mmHg). RESULTS: Prior to TIPS, the relative portal perfusion was significantly reduced to 22 +/- 9.1%. After the intervention we calculated values of 23.1 +/- 10.7% in the TIPS-group (p = 0.67; not significant). In spite of unchanged portal perfusion, the portal pressure was significantly (p < 0.001) reduced from 25.6 +/- 5.3 to 14.8 +/- 4 mm Hg. CONCLUSION: These results suggest that the reduction of portal hypertension by TIPS is effective. The portal perfusion is maintained by TIPS suggesting that liver perfusion is preserved to a higher degree.

Pulsatility of serum LH in pathological conditions.

LH pulsatility changes throughout the normal menstrual cycle. The number of LH pulses increases during the first days after menstruation, remains unchanged thereafter until after ovulation and declines progressively during the luteal phase. LH pulse amplitude is highest during midcycle. In hypothalamic amenorrhea, gonadotropin levels are reduced. This appears to be a consequence of a reduction of hypothalamic Gn-RH secretion which is reflected by a diminished frequency and amplitude of LH pulses during the 24-hour span. Administration of an opiate antagonist, naloxone, increases LH pulse frequency in those patients, and in patients with secondary hypothalamic amenorrhea the daily oral administration of naltrexone, another specific opiate antagonist, induces ovulatory cycles. Patients suffering from hyperandrogenemia may present with eumenorrhea, oligomenorrhea or amenorrhea. There is an increase in mean LH levels and of the LH/FSH ratio with increasing severity of the ovarian disturbance. The increase in mean LH levels is a consequence of an increase in LH pulse amplitude while LH pulse frequency is not changed compared to the early follicular phase of the menstrual cycle.

Nitrite and nitrate levels in patients with cirrhosis of the liver: influence of kidney function and fasting state.

BACKGROUND: Increased serum nitrite/nitrate (NOx) levels, the stable metabolites of nitric oxide (NO), have been reported in patients with cirrhosis. NOx levels, however, are influenced not only by endogenous NO synthesis but also by urinary NOx excretion and dietary intake. We attempted to elucidate factors that influence NOx levels independently of endogenous NO production and to determine the conditions under which NOx levels reflect endogenous production in patients with cirrhosis and healthy controls. METHODS: NOx serum concentrations and urinary NOx excretion were determined by means of the Griess reaction in relation to Child-Pugh score, kidney function, fasting state, and after exposure to tap water. RESULTS: Multifactor regression analysis showed inulin clearance (P = 0.0074) and Child-Pugh score (P = 0.0001) to be independent factors predicting NOx levels in patients with cirrhosis. NOx serum levels correlated negatively with the inulin clearance (P < 0.0001), which deteriorated with progressive loss of liver function. NOx levels decreased by about 30% within a 24-h fasting period. After 24 h fasting urinary NOx excretion was not significantly increased in patients with advanced cirrhosis. CONCLUSION: NOx serum levels, taken as a surrogate for endogenous NO formation, have to be viewed with caution in patients with cirrhosis because they often have impaired kidney function. However, in steady-state conditions after an adequate fasting period NOx levels might be good prognostic markers in patients with cirrhosis since they reflect two possible sequelae of liver insufficiency-namely, increased NO formation and impaired kidney function.

Infarction and laceration of liver parenchyma caused by wedged CO(2) venography before tips insertion.

We describe the fatal outcome of an elective TIPS procedure performed in a 43-year-old man with alcoholic cirrhosis. Wedged hepatic venography with CO(2) was the reason for infarction and laceration of liver parenchyma resulting in a subcapsular hematoma and subsequent intra-abdominal bleeding. This is the first report of this complication after the use of CO(2) in a cirrhotic patient.

Acute Budd-Chiari syndrome: treatment with transjugular intrahepatic portosystemic shunt.

The case of a 28-year-old man with acute Budd-Chiari syndrome due to veno-occlusive disease is reported. Transjugular intrahepatic portosystemic shunt (TIPS) was performed after upper gastrointestinal endoscopy, duplex sonographic and abdominal computed tomographic examination, inferior cavogram with hepatic venous catheterization, and transvenous biopsy. A 10-mm parenchymal tract was created. The patient did well after the procedure; ascites resolved and liver function improved markedly. The shunt has remained patent up to now for 6 months.

Comparison of portal vein velocity and the hepatic venous pressure gradient in assessing the acute portal hemodynamic response to propranolol in patients with cirrhosis.

OBJECTIVE: The aim of this prospective study was to compare noninvasive Doppler sonography and invasive measurement of the hepatic venous pressure gradient (HVPG) to determine the acute portal hemodynamic response to propranolol in patients with liver cirrhosis. METHODS: In a blinded study design, portal vein velocity (PVV) and HVPG were simultaneously assessed in 11 cirrhotic patients for 4 h after oral ingestion of 40 mg propranolol. RESULTS: Both HVPG (17.2% +/- 4.3%, p < 0.0001) and PVV (15.6% +/- 2.1%, p < 0.0002) showed a highly significant reduction during the study period versus baseline. Based on HVPG measurements, four patients (36%) were classified as nonresponders. These patients had a significantly lower PVV reduction compared to the responders (responders: 18.8% +/- 2.0% vs nonresponders: 10.0% +/- 2.1%, p < 0.05). Nonresponders were identified by Doppler sonography with a sensitivity of 1.0, specificity of 0.86, and positive predictive value of 0.9 when a threshold of 20% PVV reduction 120 min after drug intake was applied. CONCLUSIONS: Doppler sonography is a useful tool for assessment of the acute portal hemodynamic effect of propranolol. To distinguish portal hemodynamic nonresponders from responders to propranolol, PVV measurements should be carried out 2 h after drug administration, and PVV reduction should be not <20% in propranolol responders.

Attempted protection of spermatogenesis from irradiation in patients with seminoma by D-Tryptophan-6 luteinizing hormone releasing hormone.

Possible protective effects of D-Tryptophan-6 luteinizing hormone releasing hormone (D-Trp-6-LH-RH) against irradiation-induced testicular damage were investigated for the first time in patients with seminoma. After unilateral orchiectomy 12 men were allocated to receive the long-acting gonadotropin releasing hormone (GnRH) agonist D-Trp-6-LH-RH prior to and for the duration of radiotherapy. Eight patients with the same disease served as a control group. In contrast to several trials to protect spermatogenesis from chemotherapy by GnRH agonists, we first suppressed the pituitary-testicular axis before starting the treatment. As a new schedule this adjuvant GnRH agonist treatment was combined with cyproterone acetate for the first 20 days to diminish the amount and the duration of the initial stimulation of gonadotropins and testosterone. Irradiation started after suppression of the pituitary-gonadal axis. In all patients luteinizing hormone and testosterone were completely suppressed throughout the treatment compared to the controls, whereas the initial suppression of follicle-stimulating hormone was not completely maintained until radiotherapy was completed. At the follow-up at 18 months after completion of therapy, all patients reached their initial concentration of gonadotropins, testosterone, and motile spermatozoa independently of D-Trp-6-LH-RH treatment. With the dose and schedule investigated, the GnRH agonist showed no protective effects against testicular damage caused by radiotherapy.

Luteinizing hormone (LH) pulsatility during the oestradiol- and oestradiol/progesterone-induced LH surge in the human female.

Positive feedback reactions were induced in five female volunteers with regular menstrual cycles on the pituitary secretion of luteinizing hormone (LH) during the follicular phase of the cycle by the i.m. administration of oestradiol benzoate ('oestradiol study'), or by oestradiol benzoate followed by progesterone ('oestradiol/progesterone study'). Prior to the administration of the steroids (basal profiles) and during the LH surges following the administration of the steroids (stimulation profiles), blood was drawn at 10-min intervals and the LH pulsatility assessed. The LH pulses occurred at hourly intervals in basal and stimulation profiles, which concurs with data obtained during the normal proliferative phase and the spontaneous mid-cycle surge of the cycle in both the human and the rhesus monkey. Our findings are, however, in sharp contrast with those obtained in the rhesus monkey by the determination of hypothalamic multi-unit activity.

Effects of different octreotide dosages on splanchnic hemodynamics and glucagon in healthy volunteers.

AIMS: This study evaluated the dependence of portal and mesenteric blood flow and plasma glucagon levels on octreotide dosage and its mode of application. METHODS: Two groups of 10 individuals each received octreotide either subcutaneously (placebo, 100 and 200 microgram) or intravenously (100- microgram bolus i.v., 25 and 100 microgram/h) in a double-blind, random order. Using Doppler ultrasound, we examined portal and mesenteric blood flow and measured plasma glucagon levels at regular intervals within a 4-hour period under fasting conditions. RESULTS: Contrary to placebo, octreotide caused a decrease in portal blood flow (PVF) and in superior mesenteric artery blood flow (SMAF) together with an increase in the mesenteric pulsatility index (PI). The same total dose of 100 microgram octreotide caused a similar PVF response, averaged over 4 h, given either subcutaneously (-28.0 +/- 4.8%), intravenously (-29.4 +/- 4.3%) or as a continuous infusion (-29.3 +/- 4.6%). As concerns intravenous infusions, 100 microgram/h was more effective than 25 microgram/h (-37.8 +/- 6.2 vs. -29.3 +/- 4.6%). The PVF reduction remained constant during intravenous infusion, whereas glucagon levels decreased progressively over the entire observation time. CONCLUSIONS: The decrease in PVF is dependent on the octreotide dose. However, this is not constantly paralleled by a decrease in plasma glucagon concentration.