[Patients and nurses. Trust--the "certain something"].
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
H Affolter
Publications and source records attributed to H Affolter.
Design of the EPC-9, a computer-controlled patch-clamp amplifier. 2. Software.
The EPC-9 computer-controlled amplifier has no front-panel controls; therefore the user interface to the EPC-9 patch-clamp amplifier is defined entirely by software. This paper describes various user interfaces that have been implemented, including a high-level programming interface, a user interface based on the PostScript language, and graphical user interfaces that control the EPC-9 from data-acquisition programs. Also described are the algorithms used for automatic adjustment of the C-Fast and C-Slow transient cancellation circuitry. An overview of the procedures that perform automatic testing and calibration is given.
Animals↗
[Drug-induced (probably allopurinol) agranulocytosis. Case report and discussion].
Agranulocytosis is a rare but sometimes extremely dangerous adverse drug reaction which can be induced by almost any drug. We report the case of a 89-year-old man with a well-documented granulocyte chart, who received allopurinol in addition to preexisting therapy with cardiovascular drugs. Three weeks later agranulocytosis was found which bone-marrow biopsy indicated was drug-induced. After cessation of all drugs, isolation and antibiotic therapy, the leukocyte count returned to normal but the patient died four weeks later from progressive renal failure. A relation between allopurinol therapy and agranulocytosis was presumed. The drugs which might have caused this adverse reaction are discussed. The incidence, signs, symptoms and treatment are summarized and proposals are made concerning the action to be taken in the event of drug-induced agranulocytosis.
Acute Kidney Injury↗
[Acral vasospasm in Crohn's disease].
55 patients with Crohn's disease and 55 sex- and age-matched healthy controls were studied by nailfold capillary microscopy for evidence of microcirculatory abnormalities. Digital capillary blood flow measurements in combination with a local cooling test were assessed by videocapillaroscopy using the flying-sport technique. We found a blood flow stop with cold exposure in 44 of the 55 patients with Crohn's disease (mean duration 39 seconds) but in 5 of the 55 control subjects only (mean duration 19 seconds). There was no significant difference in skin temperature between the two groups. Intravital microscopy of nailfold capillaries revealed a marked reduction in capillary density (p less than 0.001) compared to normal subjects. The association of vasoconstrictive reaction in finger microcirculation of patients with Crohn's disease suggests a vasospastic tendency in this disorder.
Adult↗
[Fecal occult blood--does a hemoglobin-specific tests improve the diagnosis of relevant colonic neoplasms?].
The object of this study was to assess whether an immunological test specific for human hemoglobin improves the detection of bleeding from colorectal tumors as compared to a conventional guaiac test for occult fecal blood. We examined one stool sample from 134 patients prior to a complete colonoscopy by the Colo-Immun-Test (CI) as well as the Colo-Rectal-Test (CR). CI proved to have a higher sensitivity for occult bleeding from all colonic lesions, but this difference was not statistically significant. There was, however, no difference in the sensitivity of the two tests in detecting bleeding from relevant colonic neoplasms. In this study the immunological CI did not improve the detection of occult fecal blood loss due to adenomas and carcinomas of the colon in comparison with CR.
Colorectal Neoplasms↗
The role of nailbed vasospasm in Crohn's disease.
Local cooling of the nailfold capillaries produces a typical blood flow stop reaction in patients with Raynaud's phenomenon. We applied the same test to 35 patients with Crohn's disease and compared the results with the findings in a control group of 35 healthy subjects matched for age and sex by nailfold videomicroscopy. We found a flow stop with cold exposure in 27 of the 35 patients with Crohn's disease (mean duration 38 s) in contrast to 2 of the 35 control subjects only (mean duration 12 s). There was no significant difference in skin temperature between the two groups. Intravital microscopy of nailfold capillaries revealed an evident reduction of the capillary density (p = 0.001) and crest diameter of the capillary loop (p = 0.02) compared to normal subjects. The strong association of a vasoconstrictive reaction in finger microcirculation in patients with Crohn's disease suggests a vasospastic tendency in this disorder that might manifest in the mesenteric capillaries also. This new finding of microcirculatory disturbance may play a role in the pathophysiology of Crohn's disease and be related to a general vasospastic syndrome.
Adolescent↗
Pathogenesis of Crohn's disease.
Explore the source record for details and available documents.
Blood Flow Velocity↗
[Crohn's disease-- 10 years' experience at a city hospital].
Between 1977 and 1986, 92 patients with Crohn's disease (53 females and 39 males, average age 32 years at diagnosis) were admitted for a total of 158 hospital stays at the St. Claraspital, Basel. In 71 cases the diagnosis was based on one or more of radiologic and endoscopic evaluation and/or operative findings. In 4 cases diagnosis was based solely on clinical findings and in the remaining 17 the original diagnostic workup could not be evaluated retrospectively. 65% of cases were histologically proven, while the rest of the patients were either not biopsied or biopsy yielded inconclusive results. Crohn's disease was located simultaneously in the small and large bowels in 41 patients, in the small bowel only in 23 (25%) and in the large bowel only in 20 (22%). The remaining localizations were either proximal GI tract or anal region only. Surgery was performed a total of 65 times in 44 of the 92 patients (48%), the most frequent procedures being ileocecal resection and surgical treatment of perianal fistulas and abscesses. Accordingly, the main indications for surgery were perianal complications (37%) and stenotic bowel lesions (29%). The resection rate was higher in ileal (35%) than in colorectal (25%) involvement. The 3 rectal amputations eventually necessary were all in patients with anorectal involvement.
Adult↗
[Campylobacter pylori, gastritis and ulcer disease. Microbiological, histological and serological studies].
In a prospective study of 70 patients with epigastric pain, gastroduodenoscopy revealed gastric and/or duodenal ulcers in a total of 41 and no ulceration in the remainder. Biopsies were taken to assess the severity of gastritis and the presence of Campylobacter pylori (CP) by histology and culture. Gastritis was found in 54 patients. CP was detected in 78% of the ulcer patients and 52% of the patients without ulcer (p less than 0.05). CP was demonstrated in 83% of the histologically diagnosed cases of gastritis (all grades) but no CP was detectable in patients with normal gastric mucosa. Among the ulcer patients, CP was more frequent in those with no history of medication with nonsteroidal antiinflammatory drugs (p less than 0.01). Sera from CP-positive ulcer and gastritis patients have significantly higher levels of IgG antibodies to CP than sera from those found to be free of ulcer or gastritis. In 200 blood donors an increasing percentage of elevated CP-antibody titres were found with advancing age (50% over 60 years of age). Quantification of circulating CP antibodies, would thus seem a valuable adjunct in the diagnosis of gastritis and probably also of peptic ulcer. The data presented furnish further evidence of the high rate of association of CP and the gastritis-peptic ulcer complex.
Adult↗
[Failure of doxycycline in Campylobacter pylori-positive gastritis].
Explore the source record for details and available documents.
Campylobacter Infections↗
Preparation and utilization of an ion-specific calcium minielectrode.
Explore the source record for details and available documents.
Animals↗
Sidedness of reconstituted calcium channels from muscle transverse tubules as determined by D600 and D890 blockade.
The verapamil-type calcium antagonist, D600, and its charged quaternary derivative, D890, were used to assess the sidedness of blockade in single calcium channels reconstituted from purified transverse tubules of skeletal muscle. Spontaneous single channel openings were induced with the agonist Bay-K8644 and recordings were made in a two-chamber planar bilayer setup so that drugs could be delivered to either side of the channel. Micromolar drug addition resulted in a greater than 10-fold decrease in probability of open channel events (po) without a significant change in single channel currents. Changes in po occurred in parallel with changes in mean open time and both parameters could be titrated with a similar IC50. At pH 7.2, cis or trans D600 blocked with an IC50 of 5 microM but for D890 the IC50 was cis 3 microM and trans greater than 75 microM (cis is the intracellular-equivalent side as defined by the voltage-dependent activation). The asymmetry of D890 blockade indicates that the drug can readily gain access to the blocking site from the aqueous phase adjacent to the inner but not extracellular end of the channel.
Animals↗
Insulation of the conduction pathway of muscle transverse tubule calcium channels from the surface charge of bilayer phospholipid.
Functional calcium channels present in purified skeletal muscle transverse tubules were inserted into planar phospholipid bilayers composed of the neutral lipid phosphatidylethanolamine (PE), the negatively charged lipid phosphatidylserine (PS), and mixtures of both. The lengthening of the mean open time and stabilization of single channel fluctuations under constant holding potentials was accomplished by the use of the agonist Bay K8644. It was found that the barium current carried through the channel saturates as a function of the BaCl2 concentration at a maximum current of 0.6 pA (at a holding potential of 0 mV) and a half-saturation value of 40 mM. Under saturation, the slope conductance of the channel is 20 pS at voltages more negative than -50 mV and 13 pS at a holding potential of 0 mV. At barium concentrations above and below the half-saturation point, the open channel currents were independent of the bilayer mole fraction of PS from XPS = 0 (pure PE) to XPS = 1.0 (pure PS). It is shown that in the absence of barium, the calcium channel transports sodium or potassium ions (P Na/PK = 1.4) at saturating rates higher than those for barium alone. The sodium conductance in pure PE bilayers saturates as a function of NaCl concentration, following a curve that can be described as a rectangular hyperbola with a half-saturation value of 200 mM and a maximum conductance of 68 pS (slope conductance at a holding potential of 0 mV). In pure PS bilayers, the sodium conductance is about twice that measured in PE at concentrations below 100 mM NaCl. The maximum channel conductance at high ionic strength is unaffected by the lipid charge. This effect at low ionic strength was analyzed according to J. Bell and C. Miller (1984. Biophysical Journal. 45:279-287) and interpreted as if the conduction pathway of the calcium channel were separated from the bilayer lipid by approximately 20 A. This distance thereby effectively insulates the ion entry to the channel from the bulk of the bilayer lipid surface charge. Current vs. voltage curves measured in NaCl in pure PE and pure PS show that similarly small surface charge effects are present in both inward and outward currents. This suggests that the same conduction insulation is present at both ends of the calcium channel.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Verapamil, an antagonist at 5-hydroxytryptamine receptors of human blood platelets.
In human blood platelets verapamil and D600 (2-methoxyverapamil) in therapeutic concentrations inhibited the shape change reaction induced by 5-hydroxytryptamine (5HT) but not that induced by ADP. The N-methylated derivatives (D575 and D890) had much less effect. The inhibitory action of verapamil was independent of external Ca2+. Nitrendipine and diltiazem (20 microM) had no effect on the 5HT- and the ADP-induced shape change reactions. Since both these shape change reactions are mediated by a rise in cytoplasmic free Ca2+, it is concluded that the inhibition of the 5HT effect by verapamil and D600 was not due to their interference with calcium channels but rather to an antagonistic action on 5HT2-receptors. This view is supported by the finding that verapamil but not D575 competed with [3H]ketanserin and [3H]spiroperidol for their specific binding sites on membranes of rat cerebral cortex.
Adenosine Diphosphate↗
Agonists Bay-K8644 and CGP-28392 open calcium channels reconstituted from skeletal muscle transverse tubules.
The recently described calcium channel agonists Bay-K8644 and CGP-28392 have been used to induce long-term opening of calcium channels from purified rat muscle transverse tubules (t-tubules) incorporated into planar phospholipid bilayers. Agonist-open channels are selective for divalent cations (except Mg++), display voltage-dependent kinetics, and are blocked by the calcium channel antagonist, nitrendipine. The sensitivity to dihydropyridine agonists and antagonists indicate that a pool of t-tubule calcium channels remain functional after membrane fractionation and purification.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
(-)-S-[3H]CGP-12177 and its use to determine the rate constants of unlabeled beta-adrenergic antagonists.
The enantiomers of the hydrophilic beta-adrenergic blocker CGP-12177 have been synthesized and the S-enantiomer radiolabeled with tritium. The dissociation constant (Kd) of the S-enantiomer for binding to the beta-adrenergic receptor is one-half of that of the racemic mixture and at least 2 orders of magnitude lower than that of the R-enantiomer. The kinetic parameters of the latter were determined by analyzing its effect on the association kinetics of (-)-S-[3H]CGP-12177. A computer program was developed that allows the association and dissociation rate constants of unlabeled ligands to be calculated. This method was validated using Monte Carlo simulations. In addition, the rate constants of unlabeled S-CGP-12177 and S-alprenolol calculated using this method were in good agreement with those of S-[3H]CGP-12177 and S-[3H]dihydroalprenolol, respectively, determined independently. The method was also used to measure the rate constants of the enantiomers of pindolol. These antagonists as well as S- and R-CGP-12177 form their receptor complexes with similar association rate constants. In contrast, the dissociation of the R-enantiomers from receptor-ligand complexes were found to be at least 100 times faster than those of the corresponding S-enantiomers.
Adrenergic beta-Antagonists↗
Desensitized beta-adrenoceptors of C6-glioma cells have distinct binding properties.
When C6-rat glioma cells were incubated for 20 min with beta-adrenoceptor agonists, a part of the beta-adrenoceptors was localized in light density vesicles. These receptors have the same affinity for dihydroalprenolol as plasma membrane receptors but have a lowered affinity for agonists as well as for the hydrophilic beta-adrenoceptor antagonist CGP-12177. The affinity of these vesicular receptors for a variety of hydrophobic beta-blockers as well as for the hydrophilic beta-blocker timolol is compared with that of plasma membrane receptors. None of the ligands investigated showed any difference in affinity but CGP-12177. Both, introducing a lipophilic side chain into CGP-12177 or altering the benzimidazol-2-one ring system of CGP-12177 led to an increase in the affinity of the vesicular receptors. Since in the presence of the pore-forming agent alamethicin the same affinity was determined for vesicular receptors as for those located on the plasma membrane, it is concluded that the apparent low affinity of the vesicular receptors in the absence of alamethicin is caused by a membrane barrier. The lower affinity of the vesicular receptors for agonists was only slightly increased by alamethicin.
Animals↗
Ca2+ as messenger of 5HT2-receptor stimulation in human blood platelets.
In blood platelets of man, both 5-hydroxytryptamine (5HT) and 80 nM of the Ca2+-ionophore A23187 led to rapid shape change reactions which were inhibited by prostaglandin E1 (PGE1), forskolin, 2-methyl-6-methoxy-8-nitroquinoline ( quin2 ) and chlortetracycline. The IC50-values of the inhibitors were similar in the 5HT- and the A23187-experiments. Higher amounts of A23187 abolished the inhibitory actions of PGE1 and forskolin. Furthermore, 5HT and A23187 enhanced adrenaline-induced platelet aggregation their effects showing similar time dependence. Ketanserin, an antagonist of 5HT2 -receptors, and 8-(N,N-diethyl-amino)octyl-3,4,5-trimethoxybenzoate (TMB-8), an intracellular Ca2+-antagonist, counteracted the effects of 5HT much more than those of A23187, whereas acetylsalicylate and indomethacin did not influence the actions of either 5HT or A23187. In addition, 5HT caused a concentration-dependent rise of intracellular free Ca2+ in platelets which was counteracted by ketanserin. PGE1 and forskolin reduced the resting Ca2+-levels. 5HT did not affect either the basal or the PGE1-stimulated activity of adenylate cyclase, whereas the Ca2+-ionophore A23187 slightly raised the basal activity of the enzyme. In conclusion, the functional effects of 5HT2 -receptor stimulation in human blood platelets (shape change reaction and enhancement of adrenaline aggregation) seem to be mediated by a rise of intracellular free Ca2+.
Adenylyl Cyclases↗