Effects of histamine on pulmonary artery system in humans after pretreatment with an H2-receptor-antagonist.
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Biomedical subjects
Publications and source records attributed to T Huber.
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During the past 2 years in Europe and the USA laparoscopic cholecystectomy (LC) has become a widely practiced procedure. Nevertheless, the effects of long-lasting laparoscopic procedures on carbon dioxide elimination have not yet been systematically investigated. METHODS. Approval from the institutional research review board was obtained, as was written informed consent from the patients. Eleven patients undergoing LC were studied. Patient age ranged from 31 to 67 years. All patients received total intravenous anaesthesia (fentanyl, propofol, vecuronium, DHB). Controlled ventilation with a tidal volume of 12-14 ml/kg was administered. Before introduction of anaesthesia a cannula was inserted into the left radial artery. Blood gas analysis was undertaken just before introduction, just before insufflation of carbon dioxide, and thereafter at two intervals, after reaching an intra-abdominal pressure of 12 mm Hg, 15 min apart. Oxygen consumption and carbon dioxide output were measured using a calorimeter (Deltatrac TM, Datex). Intra-abdominal pressure was maintained at 12 mm Hg during the operation. RESULTS. After onset of the pneumoperitoneum inspiratory peak and plateau pressure showed an increase by more than 40%. During the operation respiratory minute volume had to be increased by about 30-40% to maintain normocapnia. Oxygen consumption remained nearly unchanged during the procedure while carbon dioxide output increased up to 38% 60 min after onset of the pneumoperitoneum. D(a-A) CO2 showed no significant change, indicating no increase in dead space. Beginning with the insufflation there was a significant increase in mean arterial pressure that lasted until the end of the procedure. CONCLUSION. The described effects of carbon dioxide insufflation, especially the extent of carbon dioxide resorption, define the need for careful monitoring of respiratory function during LC, especially in patients with preexisting cardiopulmonary disease.
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Modern treatment of symptomatic cholecystolithiasis requires a knowledge of several nonsurgical and surgical treatment options. Extracorporeal shock-wave lithotripsy and oral bile acid therapy offer the possibilities of noninvasive, outpatient treatment in approximately 20% of all symptomatic gallstone patients at a low complication rate. The percutaneous interventional techniques such as contact dissolution by means of ether or mechanical stone removal may in principle be used in a higher percentage of patients but are considerably more invasive. None of the nonsurgical techniques can exclude the relative risk of gallstone recurrence. Laparoscopic cholecystectomy constitutes a major progress in the surgical treatment of gallstone disease, since it is much less invasive than conventional cholecystectomy and requires a much shorter hospital stay and recovery time. The laparoscopic technique is primarily indicated in patients with symptomatic, uncomplicated cholecystolithiasis. Nevertheless, the range of indications is expanding as experience with this technique increases. Under certain circumstances, laparoscopic cholecystectomy is already being combined with endoscopic sphincterotomy in the presence of bile duct calculi. Conventional cholecystectomy remains the treatment of choice for complicated cases.
The pharmaceutical market in the FRG offers about 11,000 different preparations and formulations. A restricted list (pharmacopoeia) containing approximately 1,000 drugs has been proved to cover the routine requirements of a university clinic and most of the additional drugs demanded by the physicians as 'exceptis excipiendis'. Restrictive control of requests for drugs not included in the internal pharmacopoeia by clinical pharmacologists has reduced the absolute number of requests by half, and about 60% of the remaining requests could be replaced by drugs listed in the pharmacopoeia. The majority of the special requests arose from the continuation of drugs presented to out-patients by the resident physicians after admission of the patient to the hospital. The supervision may lead to more critical revision of out-patient medication, but a substantial reduction of drug expenditure was not attained, as the drugs requested amounted only to a minor fraction of the overall drug expenditure by the hospital.
Adverse effects of nonsteroidal antiinflammatory drugs can occur throughout the whole gastrointestinal tract. Recently, several cases of "diaphragmlike" thin ileal strictures have been reported. These strictures seem to result from nonsteroidal antiinflammatory drug-induced inflammatory changes and apparently represent a newly recognized nosological entity. The case of a 61-year-old man who gradually developed similar inflammatory changes in the ascending colon during prolonged intake of a slow-release form of diclofenac is presented, and the literature on nonsteroidal antiinflammatory drug-induced intestinal strictures is briefly reviewed.
The absolute bioavailability F and response (prolongation of the PR interval) of verapamil after single doses of the same oral formulation administered on two different days were investigated in 16 male subjects with an 80 mg fast dissolving and a 240 mg controlled-release preparation and compared with a bolus injection of 5 mg of verapamil. The absolute bioavailability was 23% in both investigations for the 80 mg preparation and 32% in both investigations for the 240 mg dosage form. The individual values obtained for tmax, cmax, F, and AUC0-alpha showed a wide intersubject variability; therefore, no significant differences could be observed between the two trials for each dosage, but significant differences existed between the investigations of the two preparations. After intravenous administration, concentration-effect curves were about twofold left shifted when compared with the 80 mg tablet and about threefold left shifted when compared with the 240 mg tablet. Estimation of the drug input rate showed significantly (p less than 0.05) smaller values when the controlled-release tablet was given (80 mg tablet: 95.1 and 107.7 mg/h; 240 mg tablet; 55.8 and 46.3 mg/h). Thus, the effect and bioavailability of verapamil show sufficient intersubject reproducibility if the same formulation is given. The differences between the responses and the bioavailability after administration of different preparations may be related as well to the drug absorption rate and the stereoselective first pass of verapamil as to saturation of first-pass metabolism.
Bioavailability and Hemodynamic Properties of Sublingually Applied Glyceryl Trinitrate/A new delivery system Bioavailability of glyceryl trinitrate (GTN, CAS 55-63-0) was investigated in 16 healthy subjects after sublingual application of 0.8 mg GTN from either a reference product (B) where GTN release is effected by fluorochlorohydrocarbon (FCH) or a test product (A) (Corangin Nitrospay) where GTN release is effected FCH-independently by a pumping system. Plasma concentrations of GTN and hemodynamic effects (digital plethysmography) were measured until 30 min after application. There was no significant difference (Wilcoxon's matched pairs signed rank test) in AUCo-t (A: 8.9 +/- 7.3 ng x h/ml; B: 8.3 +/- 7.6 ng x h/ml) and Cmax (A: 1.43 +/- 1.26 ng/ml; B: 1.13 +/- 1.06 ng/ml), but tmax was significantly shorter after application of the test product (A: 4.6 +/- 1.0 min; B: 6.7 +/- 2.7 min, p less than 0.01). Nonparametric confidence limits (90%) were 0.80-1.89 for AUCo-t (point estimator of the median 1.14), 0.92-2.78 for Cmax (point estimator 1.06) and 0.61-0.90 for tmax (point estimator 0.75). EC50-values obtained from the individual concentration/effect-curves were linked with the concentration/time-curves to establish the time of reaching EC50 (tEC50). GTN response did not differ for both preparations (EC50A: 0.25 +/- 0.24 ng/ml; EC50 B: 0.34 +/- 0.36 ng/ml), coincident with tmax, tEC50 was significantly shorter after administration of (A) (A: 1.8 +/- 0.3 min, B: 2.7 +/- 1.0 min). With respect to the variability of GTN pharmacokinetics, the test preparation shows superior bioavailability and a faster onset of hemodynamic action.
Transdermal nicotine systems (Nicotinell 30) were applied daily to the skin of healthy nicotine-dependent smokers for 4 days. Blood samples were taken for the measurement of nicotine and cotinine in plasma using capillary gas chromatography with nitrogen detection. The plasma concentration-time profiles of nicotine and cotinine and the pharmacokinetic parameters cmax, tmax, AUC and the elimination half-life were determined under steady-state conditions. Nicotine levels after application of the 30 cm2 patch were in accord with published values for 10, 20 and 2 x 20 cm2 patches. The elimination half-life of nicotine after removal of the patch was longer than reported values obtained after i.v. application.
Bioaequivalence of glycerol trinitrate (GTN, CAS 55630) was investigated in 16 healthy volunteers after sublingual application of 2 x 0.41 mg GTN from two different spray-formulations (A: fluorochlorohydrocarbons (FHC)-dependent formulation; B: FHC-free pumping system). Plasma concentrations of GTN (measured by a gas chromatographic method) and haemodynamic effects (measured by digital plethysmography) were monitored 30 min after application. EC50 of the individual concentration-effect curves were calculated and linked to the individual concentration-time curves to establish the time of reaching EC50 (tEC50). AUC0-infinity, Cmax, tmax and the haemodynamic parameters were compared intraindividually (Wilcoxons matched pairs sign rank test), bioequivalence of B to A was tested on the basis of nonparametric 95%-confidence intervals (Tukey). There was no significant difference in the AUC0-infinity (A: 14.2 ng min/ml, B: 16.3 ng min/ml), but significant differences were obtained in Cmax (A: 1.41 ng/ml, B: 2.77 ng/ml, p less than 0.01) and tmax (A: 6.8 min, B: 3.9 min, p less than 0.01). The confidence intervals of the ratio B/A were 0.81-1.56 for AUC0-infinity, 1.3-3.13 for Cmax and 0.50-0.58 for tmax. The GTN-response did not differ after both formulations (EC50 A: 0.441 ng/ml, EC50 B: 0.421 ng/ml), but significant differences were observed for tEC50 (A: 2.82 min, B: 1.05 min, p less than 0.01). Preparation B exhibits a superior bioavailability and a more rapid onset of haemodynamic efficacy.
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The diagnostic yield of routine esophageal manometrics in evaluating noncardiac chest pain is low. To determine if bethanechol stimulation would increase the diagnostic yield, we examined 87 patients with chest pain but no gastroesophageal reflux, 47 patients with gastroesophageal reflux but no chest pain, and 20 normal subjects. All subjects underwent standard esophageal manometrics before and after two doses of 50 micrograms/kg body wt bethanechol administered subcutaneously 15 min apart. Mean amplitude and duration of contractions and percentage of abnormal contractions were measured in the distal 7 cm of the esophageal body. Pathologic manometric parameters were defined as mean +/- 2 SD of values obtained in normal patients. Patients with chest pain had pathological responses for amplitude of contraction, duration of contraction, and percentage of abnormal contractions of 31%, 14%, and 22%, respectively, in the basal period. This increased to 43%, 66%, and 40%, respectively, after the first dose of bethanechol and to 53%, 85%, and 82% after the second dose of bethanechol. Chest pain was reproduced with new manometric abnormalities in 46% of patients after the first dose of bethanechol and in 77% after the second dose. Our conclusions are that: sequential bethanechol administration significantly increases the diagnostic yield of standard esophageal manometrics in the evaluation of noncardiac chest pain and duration of contraction after pharmacologic provocation with bethanechol is the best parameter to segregate patients with chest pain from normal subjects and gastroesophageal reflux patients.
Emphysematous cholecystitis is a rare form of acute cholecystitis, characterized radiographically by the presence of gas within the gallbladder. We report of a patient, who was admitted to the hospital with the diagnosis of acute abdomen. This patient had an emphysematous cholecystitis caused by Clostridium perfringens. We found the wall of the gallbladder emphysematous and gangrenous, the gallbladder was distended and contained purulent material, but no stones. However, in addition, the films of abdomen showed gas in the ducts. Diagnosis, pathogenesis and the aetiological and therapeutical aspects will be discussed.
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Optokinetic nystagmus (OKN) continues after the cessation of visual stimulation in complete darkness as primary optokinetic after-nystagmus (OKAN I). After variable periods of time, it is followed by secondary OKAN (OKAN II). Short periods of visual fixation during OKAN I in monkey and in man inhibit OKAN I, but enhance OKAN II. The enhanced OKAN II starts earlier, lasts longer, and often reaches higher slow-phase velocities than in control experiments. Therefore, OKAN II depends not on the ocurrence or strength of OKAN I, but mainly on parameters of the preceding optokinetic stimulus. Results suggest that OKAN I duration is partially determined by the development of OKAN II.
The importance of cooperation between physicians and all other services in vocational rehabilitation is shown by demonstration of three follow-up studies. Vocational rehabilitation is understood as a new dimension in the therapy of disabled people.
Plasma renin activity (PRA) was determined in both renal veins of 37 patients with angiographically proven renal artery stenosis. Renal venous PRA was determined in 17 patients without furosemide stimulation and in 20 patients before and 15 and 30 min after intravenous injection of 40 mg furosemide. 21 of 37 patients showed abnormally high peripheral PRA. In the 17 patients in whom renal venous PRA was measured without stimulation, 11 showed a PRA ratio (PRA stenotic side/PRA unaffected side) greater than or equal to 1.5. The 20 patients in whom stimulation with furosemide was performed were divided into 2 groups each containing 10 patients: The first group was characterized by an increase in PRA ratio after furosemide stimulation, while in the second group this PRA ratio decreased. In the first group mean duration of hypertension was 4.5 years compared to 7.5 years in the second group. In 17 of 37 patients renal artery stenosis was corrected by surgery. After operation 12 patients became normotensive and in 2 patients hypertension improved. There was no effect of renovascular surgery on blood pressure in only 3 patients. None of these patients showed an increasing ratio in response to furosemide. Our results suggest that the validity of renal venous PRA measurements is enhanced when the procedure is performed before and after administration of furosemide.
As in other parts of the rehabilitation of disabled, e.g. paraplegics the teamwork of all staff-members together with the integrated patient is indispensable. The occupational therapists combine the experience of a many year's training with their creative phantasy. The amputee learns by the assistance of occupational therapists to become independent. The physician has a coordinative and leading function in the team of nurses, occupational therapists, physiotherapists and the orthopaedical technical workshop.