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Biomedical subjects

R Bosch

Publications and source records attributed to R Bosch.

At least 55 records · Page 3Linked to original sources

The sympathetic role as an antagonist of erection.

The effects of the lumbar and pelvic sympathetic system on penile erection were studied in a canine model. Erection was induced by cavernous nerve stimulation and detumescence by sympathetic trunk stimulation. Erection induced by cavernous nerve stimulation normally subsides slowly. After discontinuation of electrical stimulation the intracavernous pressure drops within a mean of 291 s to 50% and after a mean of 372 s to 10% of the highest level. However, stimulation of the sympathetic trunk at the level of L4-S1 applied directly after discontinuation of cavernous nerve stimulation accelerated this drop of intracavernous pressure significantly: to 50% after a mean of 19 s and to 10% after a mean of 36 s. If stimulation of the sympathetic trunk was initiated 20 s before cavernous nerve stimulation, the pressure rise was aborted completely. Neurostimulation of the hypogastric nerves alone or in combination with cavernous nerve stimulation did not change the intracavernous pressure. These results were not altered after neurotomy of the pudendal or hypogastric nerves. The main pathway of the fibers from the sympathetic trunk to the penis seems to run via the pelvic plexus. The stimulation voltage and frequency to induce erection or detumescence were equivalent. Our results suggest that an elevated central sympathetic tone may be one of the causes of psychogenic impotence.

Animals↗

Pharmacokinetics, N1-glucuronidation and N4-acetylation of sulfadimethoxine in man.

Sulfadimethoxine is metabolized by O-dealkylation, N4-acetylation and N1-glucuronidation. In man, only N1-glucuronidation and N4-acetylation takes place, leading to the final double conjugate N4-acetylsulfadimethoxine-N1-glucuronide. The N1-glucuronides are directly measured by high pressure liquid chromatography. When N4-acetylsulfadimethoxine is administered as parent drug, 30% of the dose is N1-glucuronidated and excreted. Fast acetylators show a shorter half-life for sulfadimethoxine than slow acetylators (27.8 +/- 4.2 h versus 36.3 +/- 5.4 h; P = 0.013), similarly the half-life of the N4-acetyl conjugate is also shorter in fast acetylators (41.3 +/- 5.2 h versus 53.5 +/- 8.5 h, P = 0.036). No measurable plasma concentrations of the N1-glucuronides from sulfadimethoxine are found in plasma. N1-glucuronidation results in a 75% decrease in protein binding of sulfadimethoxine. N4-acetylsulfadimethoxine and its N1-glucuronide showed the same high protein binding of 99%. Approximately 50-60% of the oral dose of sulfadimethoxine is excreted in the urine, leaving 40-50% for excretion into bile and faeces.

Acetylation↗

High-performance liquid chromatography of sulphadimethoxine and its N1-glucuronide, N4-acetyl and N4-acetyl-N1-glucuronide metabolites in human plasma and urine.

Sulphadimethoxine is metabolized in humans by N1-glucuronidation and by N4-acetylation. Sulphadimethoxine-N1-glucuronide can be measured by the direct high-performance liquid chromatographic analysis and without enzymic deglucuronidation. The N1-glucuronide can be measured by an isocratic as well as by a gradient mobile phase. The group contribution of the N1-glucuronide moiety to the capacity factor is a reduction of 0.24 in the isocratic system and 0.55 in the gradient system. N4-Acetylation increases the capacity factor by a factor 1.4 in the isocratic system and by 1.06 in the gradient system.

Chromatography, High Pressure Liquid↗

The effect of venous incompetence and arterial insufficiency on erectile function: an animal model.

We designed an animal model to elucidate the effect of venous leakage and arterial insufficiency on erectile function. In 10 dogs, electrodes were implanted around the cavernous nerves for electroerection and blood flow in the internal pudendal artery was recorded. Venous leakage was mimicked by inserting needles of varying gauges (30 to 16G) into the corpus cavernosum and the erectile response to neurostimulation was recorded before and after the creation of the leak. The relationship between the size and the amount of the venous leakage, the changes in the intracavernous pressure (peak and drop), and the changes in the peak and maintenance arterial blood flow were documented. Arterial blood flow was then reduced by 25 and 50 per cent by means of a screw clamp on the terminal aorta. The erectile response to neurostimulation was again determined, with the same electrical parameters, first with reduced blood flow alone, then in combination with leakage of varying size. Our results showed that minor cavernous vein leakage in the presence of normal arterial flow and a healthy sinusoidal system had a minimal effect on erectile function owing to a compensatory increase in penile blood flow. However, when reduction of arterial blood flow was superimposed on venous leakage, even of a minor degree, the erectile response to neurostimulation was markedly impaired.

Animals↗

Standardization of electrode positioning and composition of meals for long-term intragastric pH metry in man.

In these prospective studies the influence of two different intragastric positions of electrodes and of four different compositions of standardized meals on 24-hour ambulatory pH recording were compared intraindividually in healthy male subjects. Simultaneous pH monitoring in 12 subjects demonstrated a more pronounced postprandial pH elevation in the fundus body compared to the antral area. The intraindividual comparison of an identical diet given on two different days to 10 subjects revealed nearly identical pH profiles. Variations of carbohydrate, protein and fat content of isocaloric meals given in a randomized order did not significantly alter 24-hour intragastric pH profiles. It is concluded from these data that positioning of the pH electrode in the fundus body area is superior to an antral position. 24-hour ambulatory intragastric pH monitoring in man is well reproducible. A strict standardization of the composition of meals is mandatory only for scientific investigations.

Adult↗

Leydig cell in idiopathic varicocele.

In a group of 31 patients with idiopathic varicocele (IV), testicular biopsy showed a decreased tubular diameter, hyperplasia in the number of Leydig's cells (LC; many with cytoplasmic vacuolization and atrophy) and a decrease in the number of positive LC in testicular tissue sections stained with the testosterone peroxidase-antiperoxidase method. Similar values were seen for the testis with IV and for the contralateral testis. All of this, in addition to the lack of significant differences in the volume of cytoplasmic organelles in the LC, leads us to think that both testes are equally involved. Estradiol levels were significantly increased and testosterone, FSH and LH were normal in peripheral blood (compensated LC dysfunction).

Adolescent↗

Effect of extracellular volume expansion on erythrocyte sodium transport in rats.

The effects of extracellular volume expansion (EVE) on the major sodium transport systems and sodium and potassium contents in rat erythrocytes have been examined in the present study. Study has been performed in anesthetized Wistar rat weighing about 300 g. Acute extracellular volume expansion (EVE) was induced by a constant intravenous saline infusion (3% body wt, 3 hours). Rats anaesthetized and catheterized but not expanded were used as controls. Arterial blood samples from control and expanded rats were obtained at the same time, and assayed immediately. Intracellular sodium and potassium concentration and ouabain sensitive (Na(+)-K(+)-pump) and bumetanide sensitive (Na(+)-K(+)-cotransport system) outward Na+ fluxes in erythrocytes were measured. The effect of plasma on erythrocyte transport was also analyzed by measuring 86Rb uptake. Neither of two plasma cations (Na+ and K+) were modified by the EVE. Also intracellular Na+ and K+ levels remained unvariable. Total Na+ efflux was not modified by EVE, but pump-mediated Na+ efflux was smaller after than before EVE. The ouabain-inhibible Na+ efflux rate constant decreased after EVE (from 687 +/- 81 to 525 +/- 29 h-1 x 10(-3); P less than 0.05). Both Na(+)-K(+)cotransport-mediated Na+ efflux and passive permeability increased significantly after EVE. The incubation with plasma from saline-infused animals induced a significant decrease in Rb uptake rate constant, that was not observed after incubation with plasma from non-expanded rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Evaluation of DDD and VVIR pacemakers with gated radionuclide ventriculography].

Gated radionuclide ventriculography was performed in 53 patients, with 29 DDD and 24 VVIR pacemakers. Ejection fraction and regional contractility was studied in three conditions: a) At rest. b) With tachycardia after exercise. And c) With induced tachycardia at rest. At a rate similar to the one reached with the exercise. Stimulation in different parts of the right ventricule did not show any differences in the ejection fraction. Induced ventricular stimulation in comparison with natural ventricular contractions did not alter or change ejection fraction if the reached rate was the same an not too high in both cases. Induced stimulation at rest with a rate of 110-120/min, decreased the ejection fraction in 10% (p less than 0.001). Induced stimulation by exercise (VVIR. DDD) increased the ejection fraction in 10% (p less than 0.003) and if there were zones of dyskinesia they improved or disappeared. There were no statistical differences between VVIR and DDD pacemakers. It seems that a limited tachycardia is convenient for patients with rate response pacemakers (VVIR).

Evaluation Studies as Topic↗

No short-term effects of 24,25-dihydroxycholecalciferol in healthy subjects.

Seven healthy volunteers were given 25 micrograms of 24,25-DHCC for one week to study the effects on calcium and bone metabolism. Mean plasma 24,25-DHCC concentration increased from 2.2 +/- 1.7 micrograms/l to 10.8 +/- 6.1 micrograms/l (p less than 0.001). No significant change was seen in the fasting plasma concentrations of Ca, Ca++, PTH and alkaline phosphatase activity and in urinary excretion of calcium and hydroxyproline and in tubular reabsorption of phosphate. The area under the curve for plasma ionized calcium concentration and urinary excretion of calcium during a standard calcium infusion of 10 mg/kg of Ca in 2 h did not change by 24,25-DHCC. We conclude that in healthy subjects no effect of 24,25-DHCC on the steady state parameters of calcium and bone metabolism, on renal calcium handling and on the handling of an intravenous calcium challenge by the homeostatic system could be demonstrated.

24,25-Dihydroxyvitamin D 3↗

Acetylcholine as a possible neurotransmitter in penile erection.

We investigated the erectile response to intracavernous injection of increasing doses of acetylcholine (0.5 to 500 micrograms.) in 10 monkeys. To differentiate between nicotinic (ganglionic) and muscarinic (parasympathetic postganglionic) effects, acetylcholine was likewise administered after 1.6 mg. trimethaphan camsylate and 0.1 mg. atropine, alone or sequentially. Erections were induced by cavernous nerve stimulation before and after atropine. Acetylcholine induced a dose-dependent, triphasic erectile response: a first tumescence phase followed by contraction and a subsequent second phase of tumescence. Atropine reduced but did not abolish the erectile response to acetylcholine: attainment of maximal intracavernous pressure after neurostimulation was both delayed and reduced (mean 25 cm. H2O). Only after combined nicotinic and muscarinic blockade was the erectile response to acetylcholine completely abolished. Histologic staining for acetylcholinesterase in five additional monkeys that had not received acetylcholine showed dense staining within the cavernous erectile tissue and around the cavernous arteries. Our data suggest that acetylcholine is a possible neurotransmitter for penile erection in monkeys.

Acetylcholine↗

Possible role for acetylcholine as a neurotransmitter in canine penile erection.

In 15 adult dogs, the possible role of acetylcholine as a parasympathetic neurotransmitter in canine penile erection was investigated. Intracavernous injection of increasing dosages of acetylcholine (0.1-100 micrograms) induced a dose-dependent erectile response with increased arterial flow, cavernous smooth muscle relaxation, and venous occlusion. This erectile response was completely abolished after muscarinic blockade by intracavernous injection of 0.1 mg atropine. After cavernous nerve stimulation, atropine injection significantly reduced the pudendal arterial flow (by 25%) and likewise caused a significant reduction in cavernous outflow restriction. Histologic staining showed acetylcholinesterase-positive fibers around the cavernous arteries and within the cavernous erectile tissue.

Acetylcholine↗

The diagnosis of venogenic impotence: dynamic or pharmacologic cavernosometry?

In an attempt to refine the diagnosis of venogenic impotence, we evaluated different techniques of cavernosometry in 10 dogs. Saline was perfused intracavernously in five dogs to induce erection. Regardless of the amount required for induction, a mean flow rate of 23.4 ml./min. was necessary to maintain an intracavernous pressure level of 110 cm. H2O. In seven dogs, a leak was created by intracavernous insertion of a 19-gauge needle. When erection was induced by either cavernous nerve stimulation or a combination of papaverine injection and saline perfusion, the mean flow through the needle was significantly less than when erection was induced by saline perfusion alone (1.73, 1.78, and 8.77 ml./min., respectively). Sympathetic trunk stimulation at the level of L5 could reduce the intracavernous pressure by 90% in erections induced by neural stimulation or papaverine plus perfusion but had no effect on erection induced by saline perfusion alone. Our findings show that cavernosometry after intracavernous injection of papaverine will provide more valuable information in patients in whom venogenic impotence is suspected.

Animals↗

The rationale for pharmacologic cavernosography.

To refine the diagnostic method for opacification of aberrant venous drainage in venogenic impotence, an experimental study was done in eight monkeys. In all monkeys, cavernosography after induction of erection by saline perfusion showed significant drainage via the cavernous veins. However, when cavernosography was performed after neurostimulation or papaverine injection, no cavernous drainage was visualized, even when the intracavernous pressure had been significantly lowered by creation of an artificial cavernous leak. Because erection can result from saline perfusion only when the volume perfused exceeds the venous outflow capability, cavernosography during saline-induced erection will always demonstrate the entire venous system and, thus, is of no diagnostic value. Pharmacocavernosography imitates the physiologic venous occlusive mechanism and should therefore be used to identify the abnormally draining veins in venogenic erectile dysfunction.

Animals↗

Acute changes in calcium and bone metabolism during methylprednisolone pulse therapy in rheumatoid arthritis.

Corticosteroids (CS) decrease bone formation and enhance bone resorption and this can lead to osteopenia. Bone metabolism was studied during the administration of huge amounts of CS (1000 mg methylprednisolone) over a short period of time in 10 patients with persistently active rheumatoid arthritis. The effects could be divided into those occurring within 24 h: (a) a decrease in bone resorption (urinary excretion of calcium and hydroxyproline) and bone formation (alkaline phosphatase); (b) a decrease in renal excretion of calcium; (c) an increase in concentration of serum 1,25-dihydroxy-cholecalciferol and those secondary effects arising after 24 h; (d) a decrease in serum calcium due to the decrease in intestinal Ca absorption and the decrease in renal tubular reabsorption of Ca; (e) an increase in serum PTH concentrations. In a previous study it was found that these changes normalized within a few days after completion of the CS treatment.

Adult↗

Action and metabolism of dihydrotachysterol2.

Dihydrotachysterol2 (DHT2) is a synthetic analogue of vitamin D2. DHT2 is used extensively in the treatment of renal osteodystrophy and hypoparathyroidism. It is equally efficacious as 1 alpha,25-dihydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3. Moreover, it offers interesting therapeutical advantages and it is surprising that until recently little was known of its metabolism and sites of action. This paper deals with studies on the pharmacology of DHT2 in rats. Following the synthesis of [3H]DHT2 and oral administration, evidence was obtained that DHT2 is metabolized extensively; three of the major metabolites could be identified as 25-hydroxy-DHT2, 1 alpha,25- and 1 beta,25-dihydroxy-DHT2.

Animals↗

Responders and non-responders after fluoride therapy in osteoporosis.

Patients with osteoporosis were treated for two years with sodium fluoride. Fifteen received sodium fluoride in capsules, 56 in enteric coated slow release tablets (Ossin) and 20 in enteric coated tablets (Procal). Seven women treated with Procal were also treated with oestrogens. All patients had a calcium intake between 1000 and 2000 mg/day, used dihydrotachysterol for vitamin suppletion and were advised to exercise. Non-responders were arbitrarily defined as those who had an increase in serum alkaline phosphatase less than 10 U/l, those who had no increase in bone mineral content measured with CT in L4 and those who got a femoral neck fracture during the period of therapy. In the overall group of 91 patients 20% were non-responders based on a serum alkaline phosphatase increase less than 10 U/l. Based on the changes in bone mineral content 40% were non-responders during the first year of treatment, 45% during the second year and 23% over the first plus second year. The impression is that patients with a femoral neck fracture have a higher increase in serum parathyroid hormone concentration than patients without fractures. The urinary excretion of fluoride has a better predictive value than the change in serum alkaline phosphatase concentration for the prediction of an increase in bone mineral content.

Aged↗