[Diagnosis and treatment of male infertility].

A male factor plays a role in half of infertility cases. The causes are summarised in this review, and they include hormonal disturbances, genetic alterations, testicular disease, obstruction, and ejaculatory dysfunction. Evaluation may reveal a correctable cause or uncover underlying disease. In a few cases of pretesticular infertility, medical treatment may have effect, and in cases of obstruction or varicoceles, surgical treatment may correct the problem. In cases with ejaculatory dysfunction, assisted ejaculation often produce viable sperm. Sperm for assisted reproduction may also be obtained by aspiration or surgery.

The influence of sacral nerve stimulation on gastrointestinal motor function in patients with fecal incontinence.

BACKGROUND: Sacral nerve stimulation (SNS) is a well-established treatment for fecal incontinence of various etiologies. However, the mechanism of action remains unclear. The aim of the present study was to determine whether SNS affects gastric emptying, small intestinal transit or colonic transit times. METHODS: Seven patients with a permanently implanted sacral nerve stimulator participated in a double-blind randomized cross-over study. The patients were allocated to stimulation ON or OFF for two 7-day periods separated by at least 1week. On days 4-7 of each 7-day period, the patients were examined by gamma camera imaging to measure gastric emptying, small intestinal transit and colonic transit parameters of a radiolabeled, 1600 kJ mixed solid and liquid meal ingested on day 4. KEY RESULTS: Sacral nerve stimulation did not change gastric retention at 15 min, gastric mean emptying time, gastric half emptying time, small intestinal mean transit time or colonic geometric center after 24, 48 and 72 h. CONCLUSIONS & INFERENCES: Sacral nerve stimulation does not induce major changes in the propulsive capacity of the gastrointestinal tract in patients successfully treated for fecal incontinence with permanent sacral nerve stimulator.

A randomized, placebo-controlled, crossover, double-blind trial of the NK1 receptor antagonist aprepitant on gastrointestinal motor function in healthy humans.

BACKGROUND: Little is known about the role of tachykinins on human gastrointestinal motility and no data exist on the possible effect of an NK1 receptor antagonist. AIM: To examine the effect of an antiemetic dose of the selective NK1 receptor antagonist aprepitant on gastrointestinal propulsion in healthy humans. METHODS: Twelve healthy volunteers participated in a crossover, double-blind study. In random order, each volunteer had a 125-mg capsule of aprepitant or placebo on day 1 followed by an 80-mg capsule of aprepitant or placebo on days 2-5. Gamma camera imaging was used to measure gastric emptying, small intestinal transit and colonic transit of a radiolabelled, 1600-kJ mixed liquid and solid meal ingested on day 2. RESULTS: Aprepitant did not change gastric retention at 15 min, gastric half emptying time, gastric mean transit time, time to small intestinal transit of 10%, small intestinal mean transit time or colonic geometric centre after 24, 48 and 72 h. CONCLUSION: A 125-mg capsule of aprepitant followed by an 80-mg capsule of aprepitant each of the next 2-5 days did not induce major changes in the propulsive function of the gastrointestinal tract in the small number of healthy volunteers investigated.

Q-T interval (QT(C)) in patients with cirrhosis: relation to vasoactive peptides and heart rate.

OBJECTIVE: Prolonged Q-T interval (QT) has been reported in patients with cirrhosis who also exhibit profound abnormalities in vasoactive peptides and often present with elevated heart rate (HR). The aim of this study was to relate QT to the circulating level of endothelins (ET-1 and ET-3) and calcitonin gene-related peptide (CGRP) in patients with cirrhosis. In addition, we studied problems with HR correction of QT. MATERIAL AND METHODS: Forty-eight patients with cirrhosis and portal hypertension were studied during a haemodynamic investigation. Circulating levels of ETs and CGRP were determined by radioimmunoassays. Correction of QT for HR above 60 beats per min was performed using the methods described by Bazett (QT(C)) and Fridericia (QT(F)). RESULTS: Prolonged QT(C) (above 440 ms), found in 56% of the patients, was related to the presence of significant portal hypertension and liver dysfunction (p < 0.05 to 0.001), but not to elevated ET-1, ET-3 or CGRP. When corrected according to Bazett, QT(C) showed no significant relation to differences in HR between patients (r = 0.07, ns). QTF showed some undercorrection of HR (r = -0.36; p < 0.02). During HR variation in the individual patient, QT(C) revealed a small but significant overcorrection (2.6 ms per heartbeat per min; p < 0.001). This value was significantly (p < 0.02) smaller with QTF (1.2 ms per heartbeat per min). CONCLUSIONS: The prolonged QT(C) in cirrhosis is related to liver dysfunction and the presence of portal hypertension, but not to the elevated powerful vasoconstrictor (ET-1) or vasodilator (CGRP, ET-3) peptides. The problems with correction of the QT for elevated HR in cirrhosis are complex, and the lowest HR should be applied for determination of the QT.

Effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function in healthy humans.

BACKGROUND: Glyceryl trinitrate is a donor of nitric oxide that relaxes smooth muscle cells of the gastrointestinal tract. Little is known about the effect of glyceryl trinitrate on gastric emptying and no data exist on the possible effect of glyceryl trinitrate on small intestinal transit. AIM: To examine the effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function after a meal in healthy humans. METHODS: Nine healthy volunteers participated in a placebo-controlled, double-blind, crossover study. Each volunteer was examined during intravenous infusion of glyceryl trinitrate 1 microg/kg x min or saline. A gamma camera technique was used to measure gastric emptying and small intestinal transit after a 1600-kJ mixed liquid and solid meal. Furthermore, duodenal motility was assessed by manometry. RESULTS: Glyceryl trinitrate did not change gastric mean emptying time, gastric half emptying time, gastric retention at 15 min or small intestinal mean transit time. Glyceryl trinitrate did not influence the frequency of duodenal contractions, the amplitude of duodenal contractions or the duodenal motility index. CONCLUSIONS: Intravenous infusion of glyceryl trinitrate 1 microg/kg x min does not induce major changes in gastric or small intestinal motor function after a 1600-kJ meal in healthy volunteers.

Arterial hypertension in cirrhosis: arterial compliance, volume distribution, and central haemodynamics.

BACKGROUND AND AIMS: Arterial hypertension is a common disorder. Hyperkinetic circulation and reduced effective volaemia are central elements in the haemodynamic dysfunction in cirrhosis. The aim of the present study was to investigate whether cirrhotic patients with arterial hypertension are normokinetic and normovolaemic or whether they reveal the same circulatory dysfunction as their normotensive counterparts. MATERIAL AND METHODS: Thirty three patients with arterial hypertension were identified among 648 patients with cirrhosis: 14 in Child class A, 12 in class B, and seven in class C. Controls were 130 normotensive cirrhotic patients, 19 controls with normal arterial blood pressure and without liver disease, and 16 patients with essential arterial hypertension. All groups underwent haemodynamic investigation with determination of cardiac output (CO), plasma volume (PV), central blood volume (CBV), hepatic venous pressure gradient (HVPG), hepatic blood flow (HBF), arterial compliance (AC), and systemic vascular resistance (SVR) in the supine position. RESULTS: Liver function, as evaluated by galactose elimination capacity, indocyanine green clearance, HBF, and Child score, was significantly better in hypertensive cirrhotics than in their normotensive counterparts (p<0.05-0.01) but portal pressure was similar (HVPG 13 v 15 mm Hg; NS). AC was significantly lower and normal in the arterial hypertensive cirrhotic group (1.07 v 1.39 mm Hg/ml; p<0.02) and SVR was significantly higher and normal (1475 v 1020 dynxs/cm5; p<0.01). Arterial hypertensive cirrhotic patients were hyperdynamic (CO 6.80 v 7.14 l/min; NS) and central hypovolaemic (CBV 19.8 v 20.6 ml/kg; NS), as were normotensive patients, but differences were found in relation to arterial blood pressure. Whereas arterial pressure was inversely correlated with CO, PV, and Child score in the normotensive group (p< 0.01), the same correlations were either direct or insignificant in arterial hypertensive cirrhotics. CONCLUSION: Arterial hypertensive cirrhotic patients are hyperkinetic and central hypovolaemic, in common with their normotensive counterparts, but vasodilatation is reduced and regulation of arterial blood pressure may be less deranged.

Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans.

BACKGROUND: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide-stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans. METHODS: Ten healthy male volunteers (21-28 years) participated in a placebo-controlled, double-blind, cross-over study. In random order and on two separate days each volunteer ingested either 50 mg sildenafil (Viagra, Pfizer, New York, N.Y., USA) or placebo. A gamma camera technique was used to measure gastric emptying and postprandial frequency of antral contractions. RESULTS: The area under the curve of gastric retention versus time of liquid or solid radiolabelled marker was not changed by sildenafil intake, nor was the postprandial frequency of antral contractions affected by sildenafil. CONCLUSION: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers.

Effect of sustained-release isosorbide dinitrate on post-prandial gastric emptying and gastroduodenal motility in healthy humans.

Nitric oxide (NO) is an inhibitory neurotransmitter released by non-adrenergic and non-cholinergic neurons that innervate the smooth muscles of the gastrointestinal tract. We examined whether NO, derived from a sustained-release preparation of isosorbide dinitrate, influenced gastric emptying and gastroduodenal motility after a meal. Eleven healthy volunteers participated in a double-blind, placebo-controlled, cross-over study. Each subject ingested 40 mg isosorbide dinitrate orally as a sustained-release formulation or oral placebo, in random order. Gastric emptying and gastroduodenal motility were measured using scintigraphic and manometric techniques. Isosorbide dinitrate did not change the area under the curve of gastric retention versus time, and did not influence the frequency of antral contractions as assessed at 15-min intervals or the integrated duodenal motility index, as recorded over consecutive 15-min periods. A 40 mg single dose of sustained-released isosorbide dinitrate does not seem to alter gastric emptying or gastroduodenal motility after a meal.

Increased circulating pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP) in patients with cirrhosis: relation to cardiovascular dysfunction and severity of disease.

BACKGROUND AND AIMS: Cardiac dysfunction may be present in patients with cirrhosis. This study was undertaken to relate plasma concentrations of cardiac peptides reflecting early ventricular dysfunction (pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP)) to markers of severity of liver disease, cardiac dysfunction, and hyperdynamic circulation in patients with cirrhosis. PATIENTS AND METHODS: Circulating levels of proBNP and BNP were determined in 51 cirrhotic patients during a haemodynamic investigation. RESULTS: Plasma proBNP and BNP were significantly increased in cirrhotic patients (19 and 12 pmol/l, respectively) compared with age matched controls (14 and 6 pmol/l; p<0.02) and healthy subjects (<15 and <5.3 pmol/l; p<0.002). Circulating proBNP and BNP were closely correlated (r = 0.89, p<0.001), and the concentration ratio proBNP/BNP was similar to that of control subjects (1.8 v 2.3; NS). Circulating proBNP and BNP were related to severity of liver disease (Child score, serum albumin, coagulation factors 2, 7, and 10, and hepatic venous pressure gradient) and to markers of cardiac dysfunction (QT interval, heart rate, plasma volume) but not to indicators of the hyperdynamic circulation. Moreover, in multiple regression analysis, proBNP and BNP were also related to arterial carbon dioxide and oxygen tensions. The rate of hepatic disposal of proBNP and BNP was not significantly different in cirrhotic patients and controls. CONCLUSION: Elevated circulating levels of proBNP and BNP in patients with cirrhosis most likely reflects increased cardiac ventricular generation of these peptides and thus indicates the presence of cardiac dysfunction, rather than being caused by the hyperdynamic circulatory changes found in these patients.

Arterial compliance in patients with cirrhosis: stroke volume-pulse pressure ratio as simplified index.

Arterial function may be altered in patients with cirrhosis. We determined compliance of the arterial tree (C(1)) in relation to systemic and splanchnic hemodynamic derangement and clinical variables. C(1) and the stroke volume-pulse pressure index (SV/PP) were significantly higher (+62% and +40%, respectively; P < 0.001) in cirrhotic patients (n = 49) than in control subjects (n = 19), and a close correlation between C(1) and SV/PP was found in both cirrhotic patients (r = 0.86, P < 0.001) and control subjects (r = 0.96, P < 0.001). Univariate analysis showed significant relations between C(1) and SV/PP on one side and age, sex, body weight, portal pressure, systemic hemodynamics, biochemical variables, and severity of disease on the other. In the multiple-regression analysis, sex, age, mean arterial blood pressure, systemic vascular resistance, and biochemical variables were significant independent predictors of SV/PP (P < 0.005-0.00001). In conclusion, arterial compliance is elevated in cirrhosis. A simplified SV/PP index seems to reflect abnormalities in the arterial compliance of these patients.

Gastrointestinal motor function in patients with portal hypertension.

BACKGROUND: Existing data on gastric emptying and small-intestinal transit rates in portal-hypertensive patients are scarce and contradictory, and so far, the motor function of the colon has not been assessed in these patients. In this study we evaluated the propulsive effect of all main segments of the gastrointestinal tract in patients with well-characterized portal hypertension. METHODS: Eight patients with a postsinusoidal hepatic pressure gradient of at least 13 mmHg and eight age- and sex-matched healthy controls participated in the study. Gastric emptying, small-intestinal transit, and colonic transit rates were evaluated in all subjects by means of a gamma camera technique. The technique was also used to measure the frequency of antral contractions. RESULTS: No difference was observed in gastric mean emptying time or small-intestinal mean transit time of liquid and solid markers between patients and controls. After 24 h, however, the geometric center of the liquid marker had a more caudal localization in the colon of the patient group than in the controls (P = 0.04); that is, the patients had a faster colonic transit. No difference was found in the frequency of antral contractions 45 min after the test meal between patients and controls. CONCLUSIONS: These data suggest that the colonic transit is often accelerated in patients with portal hypertension, whereas the motor function of the stomach and the small intestine is unaffected.