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Biomedical subjects

P Holzer

Publications and source records attributed to P Holzer.

At least 145 records · Page 8Linked to original sources
PubMed1989

Close arterial infusion of calcitonin gene-related peptide into the rat stomach inhibits aspirin- and ethanol-induced hemorrhagic damage.

Afferent neuron-mediated gastric mucosal protection has been suggested to result from the local release of vasodilator peptides such as calcitonin gene-related peptide (CGRP) from afferent nerve endings within the stomach. The present study, therefore, examined whether rat alpha-CGRP, administered via different routes, is able to protect against mucosal injury induced by gastric perfusion with 25% ethanol or acidified aspirin (25 mM, pH 1.5) in urethane-anesthetized rats. Close arterial infusion of CGRP (15 pmol/min) to the stomach, via a catheter placed in the abdominal aorta proximal to the celiac artery, significantly reduced gross mucosal damage caused by ethanol and aspirin whereas mean arterial blood pressure (BP) was not altered. Intravenous infusion of CGRP (50 pmol/min) did not affect aspirin-induced mucosal injury but significantly enhanced ethanol-induced lesion formation. Intravenous CGRP (50 pmol/min) also lowered BP and increased the gastric clearance of [14C]aminopyrine, an indirect measure of gastric mucosal blood flow while basal gastric output of acid and bicarbonate was not altered. Intragastric administration of CGRP (260 nM) significantly inhibited aspirin-induced mucosal damage but did not influence damage in response to ethanol. BP, gastric clearance of [14C]aminopyrine, and gastric output of acid and bicarbonate remained unaltered by intragastric CGRP. These data indicate that only close arterial administration of CGRP to the rat stomach, at doses devoid of a systemic hypotensive effect, is able to protect against both ethanol- and aspirin-induced mucosal damage. As this route of administration closely resembles local release of the peptide in the stomach, CGRP may be considered as a candidate mediator of afferent nerve-induced gastric mucosal protection.

Animals↗
PubMed1989

Evidence for an involvement of substance P, but not cholecystokinin-like peptides, in hexamethonium-resistant intestinal peristalsis.

It has previously been found that, in the presence of naloxone, the ganglionic blocking drug hexamethonium fails to completely block peristaltic motility in the isolated ileum of the guinea-pig. This hexamethonium-resistant peristaltic activity is coordinated by enteric nerves since it is abolished by tetrodotoxin. In the present study the neurotransmitter circuitry of this type of peristalsis was studied by means of specific antagonists. Atropine totally suppressed hexamethonium-resistant peristalsis. This type of peristalsis was also strongly inhibited by the tachykinin antagonist, spantide, if a concentration sufficient to antagonize neuronally located substance P receptors was employed. In contrast, the cholecystokinin antagonist, lorglumide, caused only a slight inhibition of hexamethonium-resistant peristalsis. Both substance P and the cholecystokinin-related peptide, ceruletide, potently stimulated the hexamethonium-resistant type of peristaltic activity. These data indicate that, after blockade of nicotinic acetylcholine receptors, tachykinins mediate neuroneuronal coordination of peristalsis whereas acetylcholine acting via muscarinic receptors may be primarily responsible for neuromuscular transmission. Cholecystokinin-like peptides appear to play a modulator rather than a mediator role in hexamethonium-resistant peristalsis.

Animals↗
PubMed1989

Intragastric capsaicin enhances rat gastric acid elimination and mucosal blood flow by afferent nerve stimulation.

1. This study investigated the effects of intragastric capsaicin on acid output, clearance of aniline, potential difference, and morphology of the mucosa in the rat stomach. The experiments were carried out on rats anaesthetized with urethane in which the stomachs were continuously perfused with saline. 2. When the stomach was perfused with normal saline (pH approximately 6), intragastric capsaicin (32-640 microM) had no effect on the output of titratable acid. In contrast, when acid output was stimulated by pentagastrin or when the stomach was perfused with acid saline (pH 3), capsaicin reduced acid output. Acid loss which occurred during perfusion with saline of pH 2 was not significantly increased by capsaicin. This suggests that capsaicin does not enhance acid back-diffusion but facilitates acid elimination by other means. 3. The gastric clearance of [14C]-aniline, which is an indirect index of gastric mucosal blood flow, was estimated while the stomach was perfused with saline of pH 3. The clearance of aniline rose by 50-60% following intragastric administration of capsaicin (160 microM) whereas the mean arterial blood pressure was increased by about 2.5 mmHg only. Combined pretreatment of the rats with atropine, phentolamine, and propranolol did not alter the effect of capsaicin on the gastric clearance of aniline. 4. The gastric potential difference was not altered by capsaicin (160 microM) administered together with saline of pH 3. This and the finding that there were no signs of mucosal damage by light and scanning electron microscopy indicate that intragastric capsaicin does not irritate the gastric mucosa. 5. The effects of intragastric capsaicin on gastric acid output and aniline clearance and on blood pressure were absent in rats in which capsaicin-sensitive afferent neurones had been ablated by neonatal treatment with a neurotoxic dose of capsaicin, which indicates that they result from stimulation of afferent nerve endings in the stomach. It is concluded that facilitation of acid elimination and mucosal blood flow may contribute to the previously reported protective action of capsaicin on the gastric mucosa.

Aniline Compounds↗
PubMed1989

Ascending enteric reflex: multiple neurotransmitter systems and interactions.

Isolated segments of the guinea pig small intestine were used to examine the transmitter circuitry of the neural pathways subserving the ascending enteric reflex (AER) contraction of the circular muscle. Inflation of an intraluminal balloon provided the distension stimulus for the AER. The ascending contraction was reduced to 5% of its original amplitude by atropine and to 10% by hexamethonium, which indicates that cholinergic interneurons and cholinergic motor neurons constitute the main AER pathway. However, in the continued presence of atropine or hexamethonium for 60 min, the AER recovered to approximately 30% of its original amplitude. The atropine-resistant AER was blocked by hexamethonium and the tachykinin antagonist spantide [( D-Arg1,D-Trp7,9, Leu11]-substance P) suggesting that it involved cholinergic interneurons and tachykinin-utilizing motor neurons. The hexamethonium-resistant AER was abolished by atropine but left unaffected by spantide, suggesting the participation of as yet unidentified interneurons and cholinergic motor neurons. These findings demonstrate that the AER is mediated by multiple neural pathways with different transmitters and that adaptive interactions between these pathways take place after blockade of one of its neurotransmitters systems.

Analgesics↗
PubMed1989

Calcitonin gene-related peptide action on intestinal circular muscle.

Isolated segments of the guinea pig small intestine were used to examine the effect of calcitonin gene-related peptide (CGRP) on the motor activity of the circular muscle. CGRP (0.3-30 nM) initiated phasic contractions of the circular muscle due to stimulation of cholinergic neurons. Peristalsis, however, was inhibited by CGRP. A further analysis of this effect showed that CGRP had no inhibitory influence on the main, cholinergic, pathway of the ascending enteric reflex (AER) contraction, whereas the hexamethonium- and atropine-resistant pathways of the AER were blocked. The inhibition of the atropine-resistant AER resulted from an action of CGRP on nerves and, since it was antagonized by apamin, might be explained by a CGRP-induced activation of enteric inhibitory neurons. The direct relaxant action of CGRP on the longitudinal muscle was not affected by apamin. These findings indicate a heterogeneity and topical selectivity in the motor actions of CGRP on the gut and suggest that this peptide, when released from nerve endings within the intestine, plays a specific role in the regulation of intestinal motility.

Animals↗
PubMed1989

Endoscopic surgery versus medical treatment for spontaneous intracerebral hematoma: a randomized study.

A controlled randomized study of endoscopic evacuation versus medical treatment was performed in 100 patients with spontaneous supratentorial intracerebral (subcortical, putaminal, and thalamic) hematomas. Patients with aneurysms, arteriovenous malformations, brain tumors, or head injuries were excluded. Criteria for inclusion were as follows: patients' age between 30 and 80 years; a hematoma volume of more than 10 cu cm; the presence of neurological or consciousness impairment; the appropriateness of surgery from a medical and anesthesiological point of view; and the initiation of treatment within 48 hours after hemorrhage. The criteria of randomization were the location, size, and side of the hematoma as well as the patient's age, state of consciousness, and history of hypertension. Evaluation of outcome was performed 6 months after hemorrhage. Surgical patients with subcortical hematomas showed a significantly lower mortality rate (30%) than their medically treated counterparts (70%, p less than 0.05). Moreover, 40% of these patients had a good outcome with no or only a minimal deficit versus 25% in the medically treated group; the difference was statistically significant for operated patients with no postoperative deficit (p less than 0.01). Surgical patients with hematomas smaller than 50 cu cm made a significantly better functional recovery than did patients of the medically treated group, but had a comparable mortality rate. By contrast, patients with larger hematomas showed significantly lower mortality rates after operation but had no better functional recovery than the medically treated group. This effect from surgery was limited to patients in a preoperatively alert or somnolent state; stuporous or comatose patients had no better outcome after surgery. The outcome of surgical patients with putaminal or thalamic hemorrhage was no better than for those with medical treatment; however, there was a trend toward better quality of survival and chance of survival in the operated group.

Adult↗
PubMed1989

[The biostatics of the human sacrum: is there a relationship between the sacral inclination and the spatial orientation of the upper articular process of the sacral plate?].

The orientation of the superior articular processes with regard to the upper end-plate of the sacrum does not depend on the inclination of the sacrum. This assertion can be made by interpreting certain angles already described in literature and may be confirmed by a research following strict biomechanic principles: The orientation of the articular processes is put in relation to the direction of the forward shear brought upon by the Vth lumbar vertebra and caused by the inclination of the sacrum. This is achieved by measuring the angle between the articular facet and a plane normal to the mentioned forward shear. The result is that the size of this angle does not at all depend on the degree of the inclination of the sacrum.

Adult↗
PubMed1988

Endoscopic neurosurgery.

This paper describes an ultrasound-guided, laser-assisted, and TV-controlled endoscopic technique which has been used so far in 133 patients for a variety of intracranial lesions. Following CT or MRI image reconstruction, and a decision on the placement of a 1 cm or a 2 cm burrhole, a 1 cm 5.0 mHz or 7.5 mHz intraoperative ultrasound probe is used to direct the endoscope from the burrhole to the target area. A 22.5 cm long rigid endoscope tube with an outer diameter of 6 mm with an inbuilt suction irrigation system, Neodymium Yag laser with 600 micron Quartz glass-fibre and an inlet for various microinstruments is then introduced. The attachment of a TV camera to the ocular lens allows the operator to control further surgical steps in the target area via the TV screen and thus warrants sterility in the operating field. The technique has been used for evacuation of 77 spontaneous intracerebral haematomas (lobar, putaminal, thalamic), 8 traumatic intracerebral haematomas, 13 ventricular haematomas, 8 cerebellar haematomas and 1 brainstem haematoma. Total or subtotal evacuation was achieved in 33% of intracerebral haematomas, removal of more than 50% of the clot in 55%. Twenty-four brain tumours (12 ventricular, 12 cystic cerebral or cerebellar tumours) were operated on for biopsy, evacuation of cyst, resection or removal of the cyst wall and/or laser irradiation of solid tumour or the inner cyst wall of cystic tumours. The complication rate probably related to surgery was 1.6%, morbidity 1.6%, mortality 0%. This high-tec endoscopic technique with its minimal surgical trauma and short operation time can be recommended as a low-risk alternative to conventional neurosurgical techniques.

Adult↗
PubMed1988

Stimulation of afferent nerve endings by intragastric capsaicin protects against ethanol-induced damage of gastric mucosa.

Ablation of capsaicin-sensitive afferent neurons enhances experimentally induced ulceration in the rat gastric mucosa, which suggests that these neurons are involved in gastric mucosal protection. To provide direct evidence for such a function it was investigated whether stimulation of afferent nerve endings by the intragastric administration of capsaicin could counteract the ulcerogenic effect of 25% ethanol. Capsaicin (3.2-640 microM), administered together with ethanol, inhibited the development of haemorrhagic lesions in a concentration-dependent fashion but did not alter the ethanol-induced fall in the gastric potential difference. This suggests that capsaicin does not prevent ethanol from damaging gastric epithelial cells but can counteract the vascular lesions caused by ethanol. The anti-lesion effect of intragastric capsaicin was absent in adult rats which had been treated with a high dose of systemic capsaicin as neonates in order to achieve a permanent degeneration of unmyelinated afferent neurons. It would appear, therefore, that intragastric capsaicin reduces lesion formation by an action on afferent neurons. The protective effect of intragastric capsaicin was not altered following acute subdiaphragmatic vagotomy, acute removal of the coeliac-superior mesenteric ganglion complex, acute bilateral ligation of the adrenal glands, or pretreatment of the rats with atropine or guanethidine. These findings indicate that stimulation of afferent neurons by intragastric capsaicin affords protection of the rat gastric mucosa against ethanol-induced damage. As the autonomic nervous system is not involved gastroprotection appears to represent a local effector function of sensory nerve endings in the stomach.

Animals↗
PubMed1987

Two types of relaxation due to capsaicin in the guinea pig isolated ileum.

The relaxant effect of capsaicin was investigated on isolated segments of guinea pig ileum precontracted by histamine. Two types of relaxation could be distinguished. Low concentrations of capsaicin (0.033-3.3 microM) caused partial relaxation (type I) which was prevented by in vitro desensitization to capsaicin or by extrinsic denervation and reduced by tachyphylaxis to calcitonin gene-related peptide. At higher concentrations (10-100 microM) capsaicin caused relaxation (type II) to the baseline; this effect was insensitive to capsaicin desensitization or extrinsic denervation. Neither type of relaxation was inhibited by tetrodotoxin or by alpha- and beta-adrenoceptor antagonists. We suggest that type I relaxation results from a specific effect of capsaicin on extrinsic sensory neurones of the gut while type II represents a non-specific smooth muscle depressant effect. Intrinsic enteric neurones are not involved in these effects.

Animals↗
PubMed1987

[Local hyperthermia of malignant brain tumors].

In glioblastoma multiforme and high-grade astrocytomas the following procedure has been implemented to try and prevent recurrence: after extirpation of the tumour its bed is lined with metal powder and the patient's head is exposed to a high-frequency magnetic field every 4 weeks. As a result the temperature is raised by induction to +45 degrees C at the boundary between metal and brain tissue. This ought to be sufficient to prevent tumour recurrence. Varied results were achieved using this technique in 103 patients.

Brain Neoplasms↗
PubMed1987

Calcitonin gene-related peptide is a potent relaxant of intestinal muscle.

The motor effects of calcitonin gene-related peptide (CGRP) on the guinea-pig ileum (GPI) longitudinal muscle were investigated. CGRP (0.1-100 nM) concentration dependently relaxed ilea precontracted with histamine and inhibited electrically induced cholinergic contractions. At higher concentrations (3-100 nM) CGRP also caused a slight contraction of non-stimulated ilea. Further pharmacological analysis of the CGRP-induced relaxation which seems to be the primary CGRP effect in the GPI, indicated that the effect was due to a direct action on the longitudinal muscle.

Animals↗
PubMed1987

CO2 laser surgery of intramedullary spinal cord tumors.

Of a total of 580 patients suffering from expanding spinal disease, 15 cases of intramedullary lesions were dealt with by the use of the CO2 laser. Sharp cutting and precisely controlled depth effect are the advantages that make the CO2 laser very useful for surgery within the spinal cord. In tumors of tough consistency the neoplastic tissue is usually sharply demarcated, in which case the CO2 laser is used for dissection along this borderline, at an output energy of 15-20 W, infocus, continuous wave (CW). In tumors of soft consistency, characterized by a more-or-less diffuse zone of invasion--eg, glioblastomas-vaporization [20 W, out-of-focus, CW] and removal by ultrasound-microsuction is recommended. This procedure should advance layer by layer until normal looking tissue is reached. In this way intramedullary tumors may be removed with minimal side effects. The postoperative course involves less pain and less edematous reaction, and the rehabilitation time is shortened compared with conventional surgical treatment. In benign neoplasms long-term results are good; malignant cases require additional x-ray treatment and chemotherapy.

Humans↗
PubMed1987

Effect of the tachykinin antagonist, [D-Pro4, D-Trp7,9,10] substance P-(4-11), on tachykinin- and histamine-induced inositol phosphate generation in intestinal smooth muscle.

The effect of the tachykinin antagonist, [D-Pro4, D-Trp7,9,10] substance P-(4-11), on inositol phosphate accumulation produced by tachykinins and by histamine in strips of longitudinal muscle from the guinea-pig small intestine was investigated in the presence of 12 mM Li+. The two tachykinins substance P (SP) and kassinin (20 nM-20 microM) caused an accumulation of inositol phosphates in a concentration-dependent manner. This was seen with an agonist contact time of only 30 s. SP and kassinin were roughly equipotent in inducing inositol phosphate accumulation, which is consistent with their relative potencies in causing muscle contraction. The tachykinin antagonist (20 microM) produced a shift to the right of the dose-response curves for inositol phosphate accumulation caused by SP and kassinin. However, the effect of kassinin was inhibited much more than that of SP, which is consistent with a similar differential antagonism of the contractions induced by these agonists. The tachykinin antagonist also depressed histamine-induced accumulation of inositol phosphates whereas histamine-induced contractions had previously been found unaffected by the antagonist. These findings show that the tachykinin antagonist is not totally selective with regard to agonist-induced accumulation of inositol phosphates in intestinal smooth muscle. This may suggest that the antagonist not only acts on tachykinin receptors but also has another site of cellular action.

Animals↗
PubMed1987

Barbiturate poisoning and gastrointestinal propulsion.

Anaesthetic doses of pentobarbitone (50 mg/kg) were found to inhibit gastric emptying and gastrointestinal transit in the rat. Gastric emptying was more profoundly suppressed than gastrointestinal transit. Phenobarbitone (150 mg/kg) had a similar effect. Since pentobarbitone and phenobarbitone also blocked the peristaltic reflex in the isolated small intestine of the guinea-pig, it would appear that the inhibitory effect of anaesthetic doses of barbiturates on gastrointestinal motility is mainly due to a direct action on the digestive tract. Together with the observation that considerable amounts of phenobarbitone were found in the stomach of an intoxicated patient 3 days after drug intake, these results might indicate that gastric lavage should also be considered in the treatment of protracted barbiturate poisoning.

Animals↗
PubMed1987

Neuropeptide Y inhibits excitatory enteric neurons supplying the circular muscle of the guinea pig small intestine.

The effect of neuropeptide Y on the motor activity of the circular and longitudinal muscle of the guinea pig small intestine was investigated. Neuropeptide Y (0.3-30 nM) inhibited, in a concentration-dependent manner, the ascending enteric reflex contraction of the circular muscle; both the cholinergic and noncholinergic component of the ascending enteric reflex were suppressed. Neuropeptide Y also blocked nerve-mediated phasic contractions of the circular muscle, induced by dimethylphenylpiperazinium or ceruletide, and abolished the peristaltic movements of the small intestine. Nerve-mediated cholinergic and noncholinergic contractions of the longitudinal muscle, induced by electrical field stimulation, were only slightly depressed by neuropeptide Y. Further analysis showed that neuropeptide Y did not act directly on intestinal muscle but interrupted excitatory pathways of the enteric nervous system. The effect of neuropeptide Y did not involve activation of alpha-adrenoceptors, opioid receptors, or P1 purinoceptors or the release of endogenous factors stimulating these receptors. These findings suggest a possible physiologic role of neuropeptide Y as a nonnoradrenergic inhibitory transmitter involved in the enteric nervous control of intestinal circular muscle activity.

Animals↗
PubMed1987

Is ganglionic transmission through nicotinic receptors essential for the peristaltic reflex in the guinea-pig ileum?

Peristaltic reflex activity in the guinea-pig isolated ileum was elicited by slow intraluminal infusion of Tyrode solution. The reflex was abolished by the ganglionic blocking drug hexamethonium. However, in more than half of the preparations, the peristaltic reflex was restored by the opioid antagonist naloxone. Hexamethonium-resistant peristaltic waves were blocked by tetrodotoxin or atropine. These data suggest that ganglionic transmission through nicotinic acetylcholine receptors may not be essential for the peristaltic reflex provided that the inhibitory action of endogenous opioids has been eliminated.

Animals↗