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Biomedical subjects

B Simon

Publications and source records attributed to B Simon.

At least 19 recordsLinked to original sources

Cardiac natriuretic peptide hormones during artificial cardiac pacemaker stimulation and left heart catheterization.

Brain natriuretic peptide (BNP) is synthesized and released predominantly in the ventricular myocardium whereas atrial natriuretic peptide (ANP) is produced mainly in the atria. This study evaluated whether artificial pacemaker stimulation or left heart catheterization results in specific changes in BNP and ANP plasma levels. Both BNP and ANP responded sensitively to changes in pacemaker stimulation (single-chamber pacemakers; pacing rates of 72 and 92/min) and during the left heart catheterization procedure. However, whereas higher pacing resulted in a more pronounced increase in plasma BNP levels, a stronger ANP release followed catheterization. This incongruous rise in ANP and BNP plasma concentrations points to at least partly independent mechanisms governing the release of BNP and ANP.

Atrial Natriuretic Factor

Partial purification of 3 alpha- and 3 beta-hydroxysteroid dehydrogenases from human hyperplastic prostate. Comparison between the two enzymes.

3 alpha-Hydroxysteroid dehydrogenase (3 alpha-HSD) activity has been purified to homogeneity, the enzyme is a monomer with a Mw of 32,000 Da. 3 beta-Hydroxysteroid dehydrogenase (3 beta-HSD) activity has been partially purified and has an apparent Mw of 30,000 Da. Both enzymes have the same cofactor requirements, optimal pH. However, 3 beta-HSD appeared to be an integral protein dependent on protein environment for its activity while 3 alpha-HSD activity is a protein more loosely associated to membranes.

3-Hydroxysteroid Dehydrogenases

Pseudo-streaming potentials in Necturus gallbladder epithelium. I. Paracellular origin of the transepithelial voltage changes.

Apparent streaming potentials were elicited across Necturus gallbladder epithelium by addition or removal of sucrose from the apical bathing solution. In NaCl Ringer's solution, the transepithelial voltage (Vms) change (reference, basolateral solution) was positive with sucrose addition and negative with sucrose removal. Bilateral Cl- removal (cyclamate replacement) had no effect on the polarity or magnitude of the Vms change elicited by addition of 100 mM sucrose. In contrast, bilateral Na+ removal (tetramethylammonium [TMA+] replacement) inverted the Vms change (from 2.7 +/- 0.3 to -3.2 +/- 0.2 mV). Replacement of Na+ and Cl- with TMA+ and cyclamate, respectively, abolished the change in Vms. Measurements of cell membrane voltages and relative resistances during osmotic challenges indicate that changes in cell membrane parameters do not explain the transepithelial voltage changes. The initial changes in Vms were slower than expected from concomitant estimates of the time course of sucrose concentration (and hence osmolality) at the membrane surface. Paired recordings of the time courses of paracellular bi-ionic potentials (partial substitution of apical Na+ with tetrabutylammonium [TBA+]) revealed much faster time courses than those produced by sucrose addition, although the diffusion coefficients of sucrose and TBACl are similar. Hyperosmotic and hypoosmotic challenges yielded initial Vms changes at the same rate; thereafter, the voltage increased with hypoosmotic solution and decreased with hyperosmotic solution. These late voltage changes appear to result from changes in width of the lateral intercellular spaces. The early time courses of the Vms changes produced by osmotic challenge are inconsistent with the expectations for water-ion flux coupling in the junctions. We propose that they are pseudo-streaming potentials, i.e., junctional diffusion potentials caused by salt concentration changes in the lateral intercellular spaces secondary to osmotic water flow.

Action Potentials

Pseudo-streaming potentials in Necturus gallbladder epithelium. II. The mechanism is a junctional diffusion potential.

The mechanisms of apparent streaming potentials elicited across Necturus gallbladder epithelium by addition or removal of sucrose from the apical bathing solution were studied by assessing the time courses of: (a) the change in transepithelial voltage (Vms). (b) the change in osmolality at the cell surface (estimated with a tetrabutylammonium [TBA+]-selective microelectrode, using TBA+ as a tracer for sucrose), and (c) the change in cell impermeant solute concentration ([TMA+]i, measured with an intracellular double-barrel TMA(+)-selective microelectrode after loading the cells with TMA+ by transient permeabilization with nystatin). For both sucrose addition and removal, the time courses of Vms were the same as the time courses of the voltage signals produced by [TMA+]i, while the time courses of the voltage signals produced by [TBA+]o were much faster. These results suggest that the apparent streaming potentials are caused by changes of [NaCl] in the lateral intercellular spaces, whose time course reflects the changes in cell water volume (and osmolality) elicited by the alterations in apical solution osmolality. Changes in cell osmolality are slow relative to those of the apical solution osmolality, whereas lateral space osmolality follows cell osmolality rapidly, due to the large surface area of lateral membranes and the small volume of the spaces. Analysis of a simple mathematical model of the epithelium yields an apical membrane Lp in good agreement with previous measurements and suggests that elevations of the apical solution osmolality elicit rapid reductions in junctional ionic selectivity, also in good agreement with experimental determinations. Elevations in apical solution [NaCl] cause biphasic transepithelial voltage changes: a rapid negative Vms change of similar time course to that of a Na+/TBA+ bi-ionic potential and a slow positive Vms change of similar time course to that of the sucrose-induced apparent streaming potential. We conclude that the Vms changes elicited by addition of impermeant solute to the apical bathing solution are pseudo-streaming potentials, i.e., junctional diffusion potentials caused by salt concentration changes in the lateral intercellular spaces secondary to osmotic water flow from the cells to the apical bathing solution and from the lateral intercellular spaces to the cells. Our results do not support the notion of junctional solute-solvent coupling during transepithelial osmotic water flow.

Action Potentials

"Incest--see under Oedipus complex": the history of an error in psychoanalysis.

This paper is intended as a contribution to the understanding of errors in our field. The title refers to the index entries "incest" in several classic psychoanalytic texts. In a way that is analogous to the defenses utilized by survivors of incest, psychoanalysis has both known and not known, avowed and disavowed, the traumatic impact of actual incest. It is argued that psychoanalysis erred in (a) focusing too heavily on the implications of incest for the Oedipus complex instead of its implications for every stage of development, and (b) missing out on the full and detailed description of the clinical pictures of incest victims and of treatment issues, including transference and countertransference. The author presents an overview of the history prompted by Masson's original attack on Freud for abandoning the "seduction hypothesis." Topics covered are: Freud's early papers, the Freud-Ferenczi controversy (1932), and the state of psychoanalytic awareness in the 1960's of the importance of actual incest. Certain features of our field make it all too likely that new errors can be generated that may similarly take decades to recognize and undo. These include the politics of our discipline, and negative attitudes toward systematic gathering and assessment of evidence.

Austria

Adaptation and renewal of the endocrine stomach.

At present at least seven different endocrine cell types have been identified in the stomach. According to their relative frequency and secretion products the antral gastrin producing G cell and somatostatin producing D cell and the fundic histamine producing ECL cell are the best characterized cell types. Total endocrine cell mass is controlled by various factors from inside and outside the stomach. Density of antral G and D cells depends on the presence and absence of food, on the antral pH and on additional humoral and/or neural factors. Gastrin and not gastric pH has been identified as the most important factor regulating the density of fundic ECL cells. Adaptation of gastric endocrine cells to gastric pH and to the presence, abundance or absence of humoral and neural regulators are well known phenomena though only partially understood. Antral G cells increase and antral D cells decrease during long-term achlorhydria which as a consequence leads to hypergastrinaemia. Examples are pernicious anaemia in man and drug-induced acid suppression under experimental conditions. Interestingly, achlorhydria-induced G cell hyperplasia never progresses to gastrinomas. Fundic ECL cell density increases markedly in the presence of long-lasting hypergastrinaemia independently of gastric pH. In contrast to G cells ECL cell hyperplasia may progress to rarely occurring ECLomas. However, this depends on additional conditioning factors as the presence of severe atrophic gastritis as in pernicious anaemia or a specific genetic trait present in patients with gastrinomas associated with the MEN I syndrome.

Adaptation, Physiological

[Protective effect of ranitidine in the stomach and duodenum against piroxicam. An endoscopy controlled double-blind study].

Protective Effects of Ranitidine in Stomach and Duodenum against Piroxicam / An endoscopically controlled double-blind study In a randomized parallel double-blind study the gastroduodenal effects of 20 mg piroxicam (CAS 36322-90-4) daily in the presence and absence of 300 mg ranitidine nocte was evaluated in 28 healthy volunteers undergoing upper gastrointestinal endoscopy. Drugs were taken over a period of 14 days. Endoscopic controls were performed at entry, and repeated after 7 and 14 days of treatment. A damaging score according to Lanza et al. was used. At entry, both groups displayed comparable mucosal damages in the stomach (0.9 +/- 0.1) and in the duodenum (0.4 +/- 0.2). After 14 days the mean lesion score increased in the piroxicam/placebo group to 6.3 +/- 1.6 in the stomach and to 4.0 +/- 1.4 in the duodenum. The corresponding values in the piroxicam/ranitidine group were 3.4 +/- 1.0 (stomach) and 0.4 +/- 0.2 (duodenum). This protection afforded by ranitidine was significant when compared with placebo (p < 0.05). Our data suggest that 300 mg ranitidine at night markedly protect the stomach and the duodenum against piroxicam.

Adult

Dose-range finding study with the proton pump inhibitor pantoprazole in acute duodenal ulcer patients.

Pantoprazole is a newly developed benzimidazole derivative with strong inhibitory actions on gastric acid secretion by blocking H(+)-K(+)-ATPase. This randomized double-blind multicenter trial investigated the efficacy of 20 mg, 40 mg and 80 mg pantoprazole o.m. on ulcer healing and symptomatic relief in 219 out-patients with endoscopically assessed acute duodenal ulcer. After 2 weeks complete ulcer healing was achieved in 58%, 89% and 82% of the patients with 20 mg, 40 mg and 80 mg pantoprazole o.m., respectively. After 4 weeks, corresponding figures were 93%, 99% and 100%; the difference of the healing rates between the 20 mg and 40 mg groups at 2 weeks was statistically significant (p < 0.0001). A rapid pain relief was achieved in all treatment groups: 72% of the 20 mg group, 89% of the 40 mg group, and 84% of the 80 mg group were pain-free after 2 weeks. The difference between 20 mg and 40 mg was statistically significant (p < 0.05). Pantoprazole was well tolerated. Adverse events occurred in 13 patients; headache, skin alterations, and diarrhea were reported most frequently. Severity and frequency of adverse events did not reveal any dose-dependence. In conclusion, pantoprazole provides fast healing of acute duodenal ulcer as well as rapid improvement of ulcer symptoms. For further clinical trials in peptic ulcer disease a daily dose of pantoprazole 40 mg o.m. is recommended.

2-Pyridinylmethylsulfinylbenzimidazoles

[High-dose ranitidine protects stomach and duodenum completely against piroxicam. An endoscopic double-blind pilot study].

In a randomized placebo-controlled parallel and double-blind study the gastroduodenal effects of 20 mg piroxicam daily was evaluated endoscopically in the presence of ranitidine 150 mg bid or 300 mg bid in 31 healthy volunteers. Drugs were taken over a period of 14 days. Endoscopies were performed at entry and repeated after 14 days of treatment. A damage-score according to Lanza was used. At entry, all groups showed comparable mucosal damages in the stomach and in the duodenum. After 14 days the mean lesion score increased in the piroxicam/placebo group (group A) to 4.5 +/- 1.6 (+/- SEM) in the stomach and to 2.7 +/- 0.8 (+/- SEM) in the duodenum. The corresponding values in the piroxicam/ranitidine 150 mg bid group (group B) were 3.3 +/- 1.2 (stomach) (p > 0.05 vs. group A) and 1.4 +/- 0.7 (duodenum) (p < 0.05 vs. group A). The values in the piroxicam/ranitidine 300 mg bid group (group C) averaged 1.0 +/- 0.0 (stomach) and 0.3 +/- 0.1 (duodenum) (for both p < 0.05 vs. group A). Our data suggest that profound acid inhibition--achieved by doubling the usual dose--afforded complete protection of human stomach and duodenum against piroxicam.

Adult

Sodium fluoride-induced gastric mucosal lesions: comparison with sodium monofluorophosphate.

In a randomized double-blind study with two parallel groups of 10 male healthy volunteers each the response of gastric mucosa after a 7 days ingestion of sodium fluoride tablets (NaF) or sodium monofluorophosphate tablets (MFP) was compared. Gastroscopic evaluations were performed before treatment, day 1 and day 7. Simultaneously blood samples were collected for determination of laboratory data and serum fluoride values. In the MFP-group no severe gastric lesions were observed, whereas in the NaF-group in 7 of the 10 subjects significant gastric mucosal lesions including acute hemorrhages and free blood in the gastric lumen were found. The differences of the lesions scores in both groups were statistically significant (p = 0.0015). The serum fluoride content was comparable in both treatment groups. Possible adverse drug reactions were reported in 4 subjects with NaF and in 1 subject with MFP. In summary, under the experimental conditions used MFP is well tolerated by the stomach while NaF produces significant gastric mucosal lesions.

Adult

[Clinical studies on acid inhibition by ranitidine given simultaneously with pentagastrin].

In recent years there have been some reports of tolerance occurring in man with the antisecretory effect of H2 antagonists. We, therefore, studied the effect of 300 mg and 600 mg ranitidine (CAS 66357-35-5) daily and increasing i.v. doses of pentagastrin (0.37 microgram/kg, 0.75 microgram/kg, and 1.5 micrograms/kg body weight) on gastric acid output (mmol HCl/30 min) in 9 healthy volunteers. The study design was double-blind, randomized and cross-over. Pentagastrin stimulation was performed on day 1, day 8, and day 16. Increasing i.v. doses of pentagastrin induced an almost identical enhancement of volume secretion, total acid output as well as titratable acidity on the 3 study days. A 16-days treatment period with 300 mg and 600 mg ranitidine led to 80% and 90% inhibition of pentagastrin stimulated acid output. The degree of inhibition evoked by 300 mg and 600 mg ranitidine against pentagastrin was not statistically different during the 16-days treatment period; i.e. no significant tolerance did occur within 16 days. Our data suggest that, in contrast to intragastric acidity measurements, no significant decline of inhibitory effectiveness of ranitidine against i.v. pentagastrin could be observed in healthy male volunteers.

Adult

Ba2+ release from soda glass modifies single maxi K+ channel activity in patch clamp experiments.

Glasses used to fabricate patch pipettes may release components which affect ion channels (Cota, G., and C.M. Armstrong. 1988. Biophys. J. 53:107-109; Furman, R.E., and J.C. Tanaka. 1988. Biophys. J. 53:287-292; Rojas, L., and C. Zuazaga. 1988. Neurosci. Lett. 88:39-44). The gating properties of maxi K+ channels from Necturus gallbladder epithelium depend on whether borosilicate glass (BG) or blue tip hematocrit glass (SG) is used to construct the patch pipettes. The data are consistent with solubilization from SG of a component which exerts voltage-dependent, cytosolic-side specific block, closely resembling "slow block" by Ba2+ ions. Ringer's solution preincubated with SG, but not with BG, blocked inside-out maxi K+ channels when used as bathing solution. Mass spectrometry revealed that Ba2+ is released by the glass from fast and slow-release compartments (SG contains 3% wt/wt BaO), and is the only ion found in the solution at concentrations consistent with the observed channel block. Additionally, SG released O2-, Na+, Ca2+, and Mg2+, all to micromolar concentrations. These elements do not interfere with maxi K+ channels but they could in principle alter the properties of other ion channels. Thus, screening for channel-modifying substances released by the glass may be necessary for the adequate interpretation of patch-clamp results.

Animals

In vivo demonstration of the Haldane effect during extracorporeal gas exchange.

During the extracorporeal support (LFPPV-ECCO2R) of 11 patients suffering from severe lung failure (ARDS), we consistently noticed a higher arterial than mixed-venous PCO2 in blood samples drawn at the same time. Two explanations are possible: a) the Haldane effect (HE), b) CO2 from lung tissue metabolism. In order to distinguish changes in PCO2 due to the HE from those due to tissue CO2 production, CO2 content (CCO2) was calculated. The results were compared to animal experiments with hyperoxic apnea, after which arterial and mixed-venous samples were drawn simultaneously. All blood gas samples were analyzed for pH, PCO2, PO2, and O2-saturation, from which CCO2 was calculated. In both groups, PaCO2 was 2.15 mmHg (2.7 mmHg respectively) higher at a lower CaCO2 (-2.87 ml/l, -14.9 ml/l). Oxygen saturation increased by 8.1% in the human group and 17.8% in the animal group. A significant relationship was found between changes in PCO2 and changes in O2-saturation. This is a demonstration of the Haldane effect.

Animals

[75 mg roxatidine nocte protects human gastric mucosa against 300 mg acetylsalicylic acid nocte].

In a randomized double-blind parallel study the gastroduodenal tolerability of 300 mg ASS nocte (8 p.m.) has been evaluated in the presence of 75 mg roxatidine nocte (8 p.m.) or placebo in 20 healthy volunteers using upper GI-endoscopy. The treatment periods lasted 14 days. Endoscopic controls were performed at entry, and repeated at day 7 and day 14. At entry the mean endoscopic score averaged 0.9 +/- 0.1 in the ASS/placebo-group and 0.9 +/- 0.1 in the ASS/roxatidine-group. The median values were 1.0 and 1.0. 300 mg ASS nocte induced in the placebo-experiments marked gastroduodenal lesions both at day 7 and day 14 (6.5 +/- 1.2 and 7.9 +/- 0.7, respectively). The median values were 8.0 and 9.0, respectively. Concomitant administration of 75 mg roxatidine nocte afforded significant protection against 300 mg ASS nocte both on day 7 and day 14 (3.3 +/- 1.0 and 3.1 +/- 0.9, respectively) (p less than 0.05). The corresponding median values were 1.0 and 1.0. Our data suggest that coadministration of roxatidine nocte reduces significantly gastroduodenal lesions evoked by acetylsalicylic acid 300 mg nocte.

Adult

Hemodynamic variables and plasma levels of PGI2, TXA2 and IL-6 in a porcine model of recurrent endotoxemia.

The pulmonary and systemic hemodynamic effects of recurrent endotoxemia were studied in pigs over a 48-hr period. Six pigs of the test group were given 0.5 micrograms/kg of an E. coli endotoxin (WO111: B4) over 60 min at the beginning and in the middle (22 hr) of the experiment. Three pigs given the same amount of physiological saline solution served as controls. The hemodynamic response to the first LPS injection was characterized by severe pulmonary hypertension, a significant increase in systemic vascular resistance, and a marked decrease in cardiac output. Circulating TxB2 levels were higher than those of 6-keto-PGF1 alpha levels, so that the first response to LPS is influenced by the vasoconstrictive actions of TxA2. With the second LPS application, the pulmonary response was attenuated, although a significant increase of pulmonary artery pressure and pulmonary vascular resistance occurred. Once again systemic vascular resistance rose and cardiac output decreased, but this time plasma levels of 6-keto-PGF1 alpha were greater than those of TxB2. Toward the end of the experiment, we noted the progressive onset of a hyperdynamic and hypotensive state. Systemic vascular resistant index decreased to 50% of the baseline value. IL-6, a cytokine of systemic importance during the course of septic shock, markedly and significantly peaked after each LPS injection. Circulating plasma levels in response to recurrent endotoxemia are described.

Animals

[The effect of glycine on the gastroduodenal tolerability of acetylsalicylic acid. An endoscopic, controlled double-blind study in healthy subjects].

In a randomized double-blind study the gastroduodenal tolerability of daily 500 mg acetylsalicylic acid (ASA, CAS 50-78-2) in combination with 250 mg glycine (CAS 56-40-6) (Godamed) and 500 mg ASA without addition of glycine were evaluated in 20 healthy volunteers giving upper GI-endoscopy. Both ASA-preparations have been taken over a period of 4 weeks. Endoscopic controls were performed at entry, and repeated after 7, 14 and 28 days of treatment. Both ASA-preparations induced comparable gastroduodenal damages during the whole test period: The lesions score of both groups on day 7, 14 and day 28 was almost identical. In contrast to plain ASA, where 9 of 10 volunteers reported gastrointestinal side effects, all subjects receiving ASA in combination with glycine did not complain from any dyspeptic symptoms, i.e. epigastric pain etc. The reasons for the apparent better tolerability of ASA in combination with glycine are discussed.

Adult

[Effect of postmortem time on survival of corneal endothelium after cryopreservation].

In corneal cryopreservation and other preservation techniques, the donor tissue post-mortem time is believed to affect endothelial cell survival. In this study, porcine eyes were stored in a moist chamber at 4 degrees C for 2, 4, 8, 32, and 72 h. Then the corneas were subjected to cryopreservation. After thawing, a 24-h interval of organ culture was used as a viability test. The cell density of the central cornea and the percentage of Descemet's membrane denuded of endothelium were determined with vital staining and morphometric methods. Corneas stored 2-32 h before cryopreservation showed no difference in necrotic areas or cell density of surviving endothelium. Corneas stored 72 h before cryopreservation revealed no endothelial cell survival. We conclude that a post-mortem time of up to 32 h before corneal cryopreservation has no influence on endothelial cell survival.

Animals