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Biomedical subjects

E Neugebauer

Publications and source records attributed to E Neugebauer.

At least 127 records · Page 7Linked to original sources

[Acute pain in surgery: the significance of a neglected problem].

Acute pain represents a significant problem in surgical patients. However, the management of acute pain in Germany is unsatisfactory, mostly because surgeons are not interested in the pain of their patients, and anesthesiologists do not give pain treatment on surgical wards. The aim of this article is therefore to point out the significance of the problem of "acute pain" for surgeons. Basic knowledge of the production, perception and projection of pain as well as the special aspects of acute versus chronic pain is mandatory. Every surgeon should know about the predictors of postoperative pain, including the surgical and anesthesiological factors and patient characteristics. Efficient management of acute pain requires knowledge of the clinical significance of pain and the different methods for assessment. It is not sufficient to know the methods and advantages of appropriate management of acute pain; one must also understand the dangers. Problems caused by the treatment of pain should be recognized from a clinical point of view. Surgeons must take a greater interest in the problem of "pain", which should lead to the establishment of new concepts in the management of acute pain in surgical patients.

Analgesia↗

Laparoscopic cholecystectomy: technical performance, safety and patient's benefit.

Laparoscopic cholecystectomy seems to be the most promising new technique for the treatment of symptomatic gallstone disease. For different reasons, controlled clinical trials comparing comfort and trauma for the patient of conventional versus laparoscopic cholecystectomy are difficult to perform at our institution. We therefore report on the results of our first 400 laparoscopic cholecystectomies using a strict and detailed protocol on technical performance, safety and benefit for the patient. Data was obtained immediately after the operation and after a short-term follow-up. To analyze the technical performance and the safety of the procedure, we developed a new classification system (I-V) of adverse events, including both the patients' and the surgeons' viewpoints. Our results show that in nearly 80% of the cases an optimal result (no adverse events in any respect) was obtained. For different reasons, the surgical procedure had to be changed during the operation in 20 cases (5%). In 3 cases (0.8%), an injury of the common bile duct occurred; 2 patients died (mortality 0.5%). On the first post-operative day, vomiting occurred in only 8% and nausea in 19% of the patients. Pain intensity was always below the level where patients demand analgesic medication and declined near zero the day after the operation. Patients fatigue was measured on a scale from 0-10 and rose from 2.2 preoperatively to 3.3 postoperatively. Only a short hospital stay of 3 days median was required. At short-term follow-up 6 weeks after the operation, pain was only rarely reported, the patients were fit and only 20% avoided some kind of food. We conclude that laparoscopic cholecystectomy is the treatment of choice for this precisely defined patient population with symptomatic gallstone disease.

Cholecystectomy↗

Pharmacotherapy in shock syndromes: the neglected field of pharmacokinetics and pharmacodynamics.

Promising effects of adjuvant drugs in experimental shock models often are not confirmed in subsequent clinical trials, e.g., steroids, fibronectin, naloxone, immunotherapeutics. A key difficulty in establishing a therapeutic benefit in clinical studies, apart from study design shortcomings, is the lack of knowledge and application of principles of clinical pharmacokinetics and -dynamics. In shock states the relationship between an administered fixed dose regimen and the drug effect is strongly influenced by dynamic changes in absorption, distribution, metabolism, and elimination of the drug, all of which vary between individual patients. This article describes several neglected aspects of clinical pharmacology relevant to shock research under clinical conditions and discusses the indications, prerequisites, and limitations of "applied pharmacokinetics." The inclusion of therapeutic drug monitoring in clinical shock studies should be applied more frequently to establish experimental results in the "real world" of ICU settings.

Animals↗

Conventional versus laparoscopic cholecystectomy and the randomized controlled trial. Cholecystectomy Study Group.

We considered using a randomized trial to assess the value of laparoscopic cholecystectomy in the treatment of symptomatic gallstones. The pros and cons for the timing of such a trial were in favour of not beginning the trial until surgeons learned to use the new procedure safely and effectively, and until key endpoints and outcome indices could be identified and assessed using valid measures. Instead an observational study was implemented to monitor the learning curve of surgeons as they mastered the laparoscopic equipment and procedures, and to assess the responses of the patients to the procedure. In the first 100 patients, the procedure proved to be as safe and feasible to use as conventional surgery, and there were strong benefits in terms of quicker recovery of the patients with less pain, discomfort, and a reduced length of hospital stay. The responses of the surgeons and the patients to the new procedure now place ethical constraints on the planning of a randomized controlled trial. Currently, comprehensive surveillance and monitoring of laparoscopic cholecystectomy is the only realistic method with which to assess the impact of this new technology in our clinic.

Adult↗

[Mediators and their antagonists in shock therapy].

The list of shock mediators currently comprises more than 150 candidates. A careful analysis using the criteria of Koch-Dale together with decision trees for exclusion of bias revealed that only histamine, C5a, beta-endorphin, tumor necrosis factor (TNF) thromboxane B2, platelet-activating factor (PAF), and oxygen free radicals are shown to be causally associated with shock symptoms. Although experimental studies with inhibitors of these mediators were convincing, there is still a lack of evidence under clinical conditions (exception histamine: anaphylactic shock). Combinations of antagonists against different causal mediators are the most promising future approaches.

Acute-Phase Proteins↗

Histamine and the stomach: chemical histamine assays.

Histamine assays in gastroduodenal tissues and body fluids are not an absolute objective of scientific interest but are related to the role of histamine in health and disease. Hence, the reliability of histamine assays has to be assessed in relation to this aim. Sensitivity and specificity of the chemical histamine assays are similar in tissues and body fluids. The modern developments in a fluorometric-fluoroenzymatic assay guarantee the highest sensitivity and specificity, especially by tests that monitor specificity in each single run of histamine determinations. Precision and accuracy of histamine measurement were especially investigated for the fluorometric assay. They included tests on the coefficient of variation over the whole concentration range, long-term precision with double-sample standard control charts, comparison of several methods for histamine assay including bioassay, and long-term accuracy with the use of Cusum charts. Finally, appropriate sample preparation, sample-taking, relevant body fluids and tissues, and the right time for sample-taking were evaluated in extended methodologic studies. Histamine assays are not just methods for a normal routine laboratory. Extended knowledge about histamine release and metabolism will be necessary to analyse data in this particular field with reasonable validity.

Animals↗

[Glucocorticoids in multiple trauma and infection--still a topic for discussion?].

The clinical use of glucocorticoids in trauma and sepsis has not yet been approved on the basis of clinical trials. Current knowledge in the area of pathogenesis is reviewed, and against this background the mechanisms of steroid action will be discussed, the current status of clinical testing in both trauma and sepsis will be evaluated, and ways of testing the effectiveness will be proposed. Although most trials up to now have shown a positive overall effect in trauma patients, a further prospective randomized controlled study with a more homogeneous study population and including trauma scores is necessary before trauma can be reliably accepted as a firm indication for glucocorticoid treatment. In the discussion on sepsis syndrome a variety of reasons are suggested for the failure of earlier studies to show beneficial effects. Besides methodological aspects, one of the main reasons is the neglected field of pharmacologic-pharmacokinetic principles. A new study should be performed under therapeutic drug-monitoring (TDM) conditions once more is known about the target concentration range.

Animals↗

Plasma histamine levels in polytraumatized patients.

In a prospective clinical trial, plasma histamine levels were measured in 28 polytrauma patients on day 1, 5 and 14 after trauma. Only those subjects who died were drop-outs. All patients had severe polytrauma with at least 3 body regions involved. The median plasma histamine levels at all three time points were significantly higher than in patients with single trauma of the extremities or before selective orthopaedic surgery but still in the normal range (less than 1 ng/ml). However, all patients with plasma levels above 1 ng/ml on days 1 and 5 died, as did all patients with levels above 0.5 ng/ml on day 1. Thus the elevation of plasma histamine levels, for whatever reason, appears to be a prognostic factor for bad outcome in polytrauma patients.

Adolescent↗

Reliability of current techniques for histamine determination in human plasma: the European external quality control study 1988.

The increasing importance of measuring histamine in many clinical conditions and the variety of currently used techniques enforced us to organize an external quality control study (ring study) on the reliability of histamine measurements in European laboratories. Three plasma quality control samples in duplicate (lyophilized) with different amounts of histamine (0-5 ng/ml), two different aqueous histamine standard samples and one solvent sample were sent to 10 laboratories for analysis of their histamine content. The following methods were used: gas chromatographic-mass-spectrometric technique (n = 2), single isotope assay (n = 1), fluorometric-fluoroenzymatic assay (n = 3), radioimmunoassay (n = 3), HPLC technique (n = 2). The study was performed and evaluated according to the approved recommendation (1983) of the International Federation of Clinical Chemistry (IFCC). This first report of the study is concentrated on the imprecision and inaccuracy of the different principal methods and laboratories by comparing two unrelated plasma histamine samples of different analyte concentrations (target values and SD: 4.39 +/- 0.51 ng/ml and 0.99 +/- 0.17 ng/ml). This study showed a fairly good agreement between most participants. 7/11 results obtained with 4 different methods were accurate and precise in the plasma range of histamine (Youden plot). Results outside the borderlines turned out to be a problem of the analyst rather than the method itself. It is suggested to define reference values for plasma histamine and to establish reference laboratories and methods according to the IFCC-guidelines.

Adult↗

Determination of histamine in human plasma: the European external quality control study 1988.

There is an increasing interest in measuring human plasma histamine levels in various clinical conditions. A variety of 'old' and newly developed techniques are applied to meet this demand. However, the discrepancy between reported reference values for histamine in human plasma measured using this variety of techniques, suggests the existence of a certain degree of inaccuracy and imprecision. We therefore organized an external quality control study on the reliability of current histamine determinations in European laboratories. Three lyophilized plasma quality control samples, in duplicate, covering the normal and pathological range of histamine concentrations (0-45 nmol/l), two different aqueous histamine standard samples and one solvent sample were sent to 10 laboratories for the analysis of their histamine content. The following methods were used: gas chromatography-mass spectrometry (n = 2), enzymatic single isotopic assay (n = 1), fluorometric-fluoroenzymatic assay (n = 3), radioimmunoassay (n = 3) and high performance liquid chromatography (n = 2). The study was performed and evaluated according to the approved recommendations (1983) of the International Federation of Clinical Chemistry (IFCC). The target values +/- s.d. of the three plasma samples were: 39.5 +/- 4.6 nmol/l (CV = 11.6%), 2.3 +/- 2.2 nmol/l (CV = 96%) and 8.9 +/- 1.5 nmol/l (CV = 17%), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Pain in ambulatory surgery. A prospective follow-up study].

Although acute pain is most often the dominant symptom that causes a patient to visit the out-patient clinic there is a lack of data concerning duration, intensity and quality of pain. Therefore, the physician's treatment is most often insufficient and the patient has to fix the dose of drugs himself. To get reliable and objective data a prospective trial on 161 patients in our out-patient clinic was performed using clinical instruments for measurement. 84% of the patients reported significant pain in the out-patient clinic compared to 96% during the prehospital period. Pain intensity is highly depended on the type of injury (bone injuries hurt more than soft tissue injuries). To get more reliable data on the acute pain situation and to improve therapeutic interventions it is suggested to use the methods presented routinely.

Ambulatory Surgical Procedures↗

Changes in histamine synthesis, tissue content and catabolism in human breast cancer.

The present study in 10 breast cancer patients supports the concept that newly synthetized, nascent histamine is involved in tumour growth. Histidine decarboxylase (HDC) activity is increased in mammary tumour tissue compared to healthy mammary gland-, skin- and muscle tissue in all but one patient studied. The newly formed histamine is probably not stored in the tumour tissue. Significantly decreased histamine concentrations were measured in parallel samples in the tumour tissue. Moreover, the preliminary results from urinary analysis of histamine and N tau-methylhistamine in 3 of the 10 patients studied showed a significant decline after tumour extirpation compared to preoperative values.

Adult↗

Increased histidine decarboxylase (HDC) activity in human colorectal cancer: results of a study on ten patients.

Following numerous reports of high histidine decarboxylase (HDC) activity in tumour-bearing animals, the present work was designed to determine the activity of this enzyme in normal and tumour tissues in a series of ten surgical patients with colorectal carcinoma. Significantly increased HDC activity, almost double that of normal tissues, was found in specimens from extirpated human tumours. These results, obtained under reliable sampling and measurement conditions indicated that changes in the enzymic activity of HDC may have a significant role in the development of colorectal tumour cells. Inhibition of the enzyme activity in human cancer subjects may retard or impede tumour growth and perhaps limit the spread of metastases.

Adult↗

Reliability and practicability of the fluorometric-fluoroenzymatic histamine determination in pathogenetic studies on peptic ulcer: detection limits and problems with specificity.

Histamine, among various "biologic-physiologic" abnormalities, is considered as a pathogenetic factor in chronic duodenal ulcer disease. The 10-30 per cent difference between its concentration in gastric and duodenal mucosa of patients compared to healthy controls, however, has to be demonstrated to be specific for the disease. It has to be shown to be neither a methodological artefact nor a common effect, concomitant factor or consequence. This study, after a series of pathogenetic trials examines systematic errors (biases) in the fluorometric-fluoroenzymatic histamine assay under the conditions of field studies including tests on specificity over a time period of 10 years. It concentrates on sensitivity (detection limits) and specificity of a standard technique described herein. A modified Shore procedure for large scale assays in human biopsies was developed including reference luminescence values for all reagents, cleaning material and glassware, reduction of OPD concentration to 0.05%, purification of n-heptan, omission of centrifugation steps in the extraction procedure and use of 2 ml 1 M HClO4 in the homogenization step to prevent losses of histamine due to adherence to the mechanical homogenizer. This assay was sensitive enough to measure histamine without difficulty in any biopsy taken. The detection limit was 3 ng/biopsy, but the smallest quantities of the amine ever obtained were 10.6 and 18.3 ng/biopsy (depending on both histamine content and biopsy weight). A series of problems had to be solved both in achieving and demonstrating specificity. It had to be defined not only for the assay in general, but also for assessing the difference in histamine content between ulcer patients and healthy controls. Exogenous more than endogenous fluorescing material interfering with the determination had to be excluded. A series of pitfalls were detected which had to be overcome in demonstrating the specificity of the assay by physicochemical and enzymatic tests. The specificity of the identification tests was more often impaired than the histamine assay itself. Fluorescing material interfering with the assay occurred in the homogenization, extraction and condensation steps, was found in water, OPD, the organic solvents, the cleaning material and in all kinds of plastic vessels. Plasticizers were shown by physicochemical characteristics including fluorescence spectra to be most likely responsible for this interfering material. Rules were developed to exclude such hazards in specificity in longterm pathobiochemical studies. Enzymatic identification test were applied to exclude endogenous fluorecing substances interfering with the standard technique. Simil

Biopsy↗