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Biomedical subjects

J Schäffer

Publications and source records attributed to J Schäffer.

At least 19 recordsLinked to original sources
PubMed1992

Dialysis related amyloidosis: a disease of chronic retention and inflammation?

Dialysis related amyloidosis (DRA) has become a major complication of long-term therapy in chronic hemodialysis or peritoneal dialysis patients. DRA is characterized by the presence of beta 2-microglobulin (beta 2m) in the amyloid fibrils. The pathogenesis of DRA is incompletely understood, but most likely is based on the uremic retention of beta 2m. In contrast, current evidence does not favor a significant role of an enhanced beta 2m synthesis rate in uremic patients. Apart from the beta 2m retention, posttranslational modification of the molecule also seems to be an important step in the amyloidogenesis, since, in addition to intact beta 2m, fragmented beta 2m or beta 2, with altered isoelectric properties can be detected in the DRA fibrils. The occurrence of these beta 2m species could be linked to a chronic intermittent stimulation of monokine release or other subclinical inflammatory processes during renal replacement therapy. Thus, it is possible that, as a consequence of repeated cellular activation, protease release and/or intracellular processing of beta 2m occurs. Renal transplantation has been shown to arrest the further progression of DRA. However, since transplantation is not feasible for a significant number of patients, non-transplant strategies to prevent DRA also need to be evaluated. Some, but not all, retrospective studies on DRA associated symptomatology in patients on chronic hemodialysis with high flux membranes have suggested a lesser prevalence in these patients as compared to patients treated with standard cellulosic membranes. To further clarify this issue and to test whether non-transplant therapies indeed may play a role in the prevention of DRA, prospective studies will be needed.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloidosis↗
PubMed1991

[Blood analysis 200 years ago--the theory and practice of hematoscopy in veterinary medicine].

Since antiquity the macroscopic judgement of blood obtained through phlebotomy was an important constituent of the medical diagnostic procedures. In the progress of blood sedimentation, the "eucrasia" or the "dyscrasia" of the humours became visible. This paper summarizes the historical and theoretical basis of the haematoscopy, and offers insight into the haemodiagnostic practices of a veterinarian at the end of the 18th century. The authority is the professor of veterinary art and medical advisor Anton Joseph Will (1752-1821), mental father and founder of the veterinary school in Munich, which opened its doors on the 1st of November 1790. Between 1786 and 1790, A. J. Will developed a research program to control animal diseases in Bavaria and examined several thousands of blood samples from healthy and sick animals. The different components of coagulated blood, infected with anthrax, were given to dogs. In this way, he could demonstrate experimentally the high infectiousness of anthrax.

Animals↗
PubMed1991

The three-dimensional structure of class pi glutathione S-transferase in complex with glutathione sulfonate at 2.3 A resolution.

The three-dimensional structure of class pi glutathione S-transferase from pig lung, a homodimeric enzyme, has been solved by multiple isomorphous replacement at 3 A resolution and preliminarily refined at 2.3 A resolution (R = 0.24). Each subunit (207 residues) is folded into two domains of different structure. Domain I (residues 1-74) consists of a central four-stranded beta-sheet flanked on one side by two alpha-helices and on the other side, facing the solvent, by a bent, irregular helix structure. The topological pattern resembles the bacteriophage T4 thioredoxin fold, in spite of their dissimilar sequences. Domain II (residues 81-207) contains five alpha-helices. The dimeric molecule is globular with dimensions of about 55 A x 52 A x 45 A. Between the subunits and along the local diad, is a large cavity which could possibly be involved in the transport of nonsubstrate ligands. The binding site of the competitive inhibitor, glutathione sulfonate, is located on domain I, and is part of a cleft formed between intrasubunit domains. Glutathione sulfonate is bound in an extended conformation through multiple interactions. Only three contact residues, namely Tyr7, Gln62 and Asp96 are conserved within the family of cytosolic glutathione S-transferases. The exact location of the binding site(s) of the electrophilic substrate is not clear. Catalytic models are discussed on the basis of the molecular structure.

Amino Acid Sequence↗
PubMed1991

[Destructive non-infectious spondylopathy during hemodialysis].

Improvement of long-term treatment with hemodialysis requires an optimized radiological differential diagnosis of bone changes associated with long-term hemodialysis. 85 patients with chronic renal failure on maintenance hemodialysis were examined. In a conventional radiographic skeletal survey of the whole spine, 22 patients (26%) had involved intervertebral discs. The site of predilection was the cervical spine followed by the lumbar spine; oligosegmental involvement was seen in nine patients. Eighteen patients with destructive non-infectious spondyloarthropahy had juxtaarticular cystic bony changes associated with the hip, shoulder and wrist. Bone biopsy in eight patients revealed amyloid as content of these cysts. The interrelation between the duration of preterminal and terminal renal failure on one hand and destructive bone changes in the spine and cysts on the other hand seems to point to destructive spondyloarthropathy as an important complication of renal insufficiency and dialysis.

Adult↗
PubMed1990

Adverse cardiovascular effects of partial correction of renal anemia by recombinant human erythropoietin.

The analysis of the hemodynamic parameters involved in the regulation of blood pressure during correction of anemia shows - although peripheral resistance and cardiac output behave qualitatively as in the nonuremic patient - that the extent of change may be inadequate resulting in an increased blood pressure. The underlying mechanisms are not yet fully understood but to a greater part may be related to preexisting pathology due to a history of long-lasting hypertension. To avoid cardiovascular complications under rhEPO therapy the following should be considered: patients with a history of hypertension, even if they are normotensive in the anemic state, are at a higher risk for developing hypertension under rhEPO. Hypertensive complications may be rare events when anemia is corrected slowly. Further studies will demonstrate whether in addition to the benefit of a very low maintenance dose of rhEPO subcutaneous administration will also contribute to the reduction of the incidence of hypertension.

Anemia↗
PubMed1989

Hemodynamics in hemodialysis patients treated with recombinant human erythropoietin.

The available data from experimental and clinical studies suggest that in the development of hypertension following correction of renal anemia under rhEPO three mechanisms are operative: (1) an increase in whole blood viscosity; (2) possible also a reduction of hypoxic vasodilatation, and (3) at least in some patients an inadequate reduction of cardiac output. To avoid cardiovascular complications under rhEPO therapy, the following should be considered: Patients that were hypertensive before the start of renal replacement therapy, even if they were normotensive in the anemic state - because of morphological alterations of their peripheral vascular bed-may run a higher risk for developing hypertension under rhEPO. As patients with undetected volume contraction may be more endangered by cardiovascular complications, the hematocrit should be monitored before and after dialysis, especially in patients with high weight gain and in children. Patients who are hypertensive under rhEPO therapy should be treated by antihypertensive drugs as appropriate. Drugs of the first choice are beta-blockers and vasodilating agents. Volume removal should not be the sole measure for blood pressure control and should be applied carefully. To avoid hypertensive and rheological complications, the target hematocrit should not exceed 30 vol%.

Anemia↗
PubMed1989

[Local anesthetic level and cardiovascular changes following local anesthesia in cataract operations with 3% mepivacaine].

Are there toxic plasma levels of mepivacaine after local anesthesia for ophthalmic surgery with 3% mepivacaine? What hemodynamic changes occur during injection of the local anesthetics? Fifteen patients undergoing cataract surgery were given 10 ml of mepivacaine (3%) as a local anesthetic regardless of body weight. After inserting an arterial line, blood samples were taken before the beginning of the injection of mepivacaine and after 3, 5, 10, 15, 30, and 60 min. Concentrations of the drug were measured by gas chromatography. During the first 15 min arterial blood pressure and ECG were registered continuously on a multichannel recorder. The maximum mepivacaine plasma levels were estimated after 15 min with a range from 0.28 to 6.95 micrograms/ml (means +/- SD: 4.5 +/- 1.47 micrograms/ml). The blood pressure was elevated over the preoperative value, at the beginning of the evaluation period, but there was no change in the blood-pressure level over the whole period. In 4 patients without known cardiac arrhythmias, ventricular or supraventricular extrasystoles occurred. The mepivacaine plasma levels complied with resorption kinetics, which is an indication that there were few intravascular injections and that the injection technique war correct. On the other hand, in some patients the mepivacaine plasma levels exceeded the toxic level. Even in ophthalmic surgery, local anesthetics should be given in relation to the body weight of the patients. The high blood-pressure levels indicated non-optimal preoperative treatment of the hypertonic patients, which was followed by an intraoperative exacerbation of the blood pressure.

Aged↗
PubMed1988

Glutathione transferase from bovine placenta. Preparation, biochemical characterization, crystallization, and preliminary crystallographic analysis of a neutral class PI enzyme.

A method was developed to purify glutathione transferase from bovine placenta by affinity chromatography and fast protein liquid chromatography. The purified enzyme was homogeneous as judged by sodium dodecyl sulfate gel electrophoresis and isoelectric focusing. The dimeric enzyme is composed of identical subunits with a molecular weight of 23,000; its isoelectric point is 6.9. In contrast to previously described isoenzymes of glutathione transferase, the protein we have purified exists in two forms, an active reduced form and a less active oxidized form. These can be reversibly transformed into each other but behave differently in sedimentation analysis, gel chromatography, and gel electrophoresis. These differences may reflect a change in the molecular shape of glutathione transferase. Chemical modification with iodoacetate, iodoacetamide (presumably of thiol groups), phenylglyoxal, and butadione (presumably of arginyl groups), and their inhibitory effects on the activity were investigated. From substrate specificity studies and N-terminal sequence analysis it is obvious that this glutathione transferase must belong to the isoenzyme class pi. The purified enzyme could be crystallized from 1.4 M ammonium sulfate solution, pH 8.0, in the presence of S-hexyl-glutathione. The crystals are tetragonal, with space group P4(1)2(1)2 or P4(3)2(1)2. The cell constants are a = b = 6.1 nm, c = 23.7 nm, alpha = beta = gamma = 90 degrees. The crystals diffract to 0.26-nm resolution and are suitable for x-ray structure analysis.

Amino Acid Sequence↗
PubMed1988

[Nalbuphine in comparison with piritramid and placebo in postoperative pain therapy following intubation anesthesia with halothane. Side effects and effectiveness].

UNLABELLED: The aim of the study was a comparison of the side-effects and efficacy of nalbuphine, piritramide, and placebo in patients during recovery from halothane anesthesia. METHODS: Neurosurgical (vertebral surgery) and otolaryngological patients (surgery of face and neck) were operated under halothane anesthesia. Postoperatively 20 patients received 20 mg nalbuphine, 21 patients 15 mg piritramide, and 19 patients 0.9% NaCl for pain therapy in a randomized and double-blind manner. Respiratory function was monitored by blood gas analysis, hemodynamic function by noninvasive measurements. The analgetic and sedative effects were estimated by the patients (visual analog scale) and the investigator (4-point scale). If the treatment was ineffective, the study was interrupted and a known analgesic was prescribed. RESULTS: The noninvasively measured hemodynamic parameters were unchanged. On the other hand, in the nalbuphine group mean arterial pCO2 increased significantly (max. 55.4 mmHg after 20 min), over the piritramide group (max. 51.2 mmHg before treatment) and the placebo group (max. 55.1 mmHg before treatment). Drowsiness, in 8 patients in each of the treatment groups and 3 patients in the placebo group, was the most frequent side-effect. After nalbuphine the pain threshold was significantly higher than after treatment with piritramide and placebo. The study was interrupted because of inefficacy in no patients from the nalbuphine group, 2 patients from the piritramide group, and 6 patients from the placebo group. There were no differences in the sedative effects. CONCLUSIONS: Nalbuphine seems to have better analgesic effects then piritramide. Both cause no hemodynamic alterations.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Endotracheal↗
PubMed1988

[Perioperative anxiety and postoperative pain suppression in intraocular operations using general anesthesia and local anesthesia].

UNLABELLED: Intraocular surgery is performed under local or general anesthesia. The indications for these procedures are often dependent on local circumstances. On the one hand, the optimal conditions for operations under general anesthesia, on the other, the negligible stress of local anesthesia, especially for the elderly, are emphasized. To clarify this question, perioperative anxiety behavior and postoperative pain were investigated in geriatric patients undergoing ophthalmic surgery. METHODS: Spielberger's state trait anxiety inventory (STAI) was performed in 31 patients operated on in general (age 71.0 +/- 6.6 SEM) and 31 operated on in local anesthesia (age 71.6 +/- 6.0 SEM) the day before and 4 h after operation. 10 patients in each group were also tested immediately before surgery in the operating room. Postoperative pain was estimated by the patient and postoperative sedation by the investigator using a 4-point scale for each over 8 h. RESULTS: The state (STAI 1) and trait (STAI 2) anxiety scores did not change in these geriatric patients. There were no significant differences between the groups. Postoperative pain was significantly (p less than 0.05) higher after 15 and 60 min after general anesthesia. There was no difference in the frequency of analgetic therapy in both groups, but most opioids were given in the first 90 min after general anesthesia. The patients were more frequently sedated (p less than 0.05) in the first 90 min after general anesthesia then after local anesthesia. DISCUSSION: The scores of state and trait anxiety behavior are comparable to a normal geriatric population, even if normal data cannot always be applied to clinical situations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

[Acute lowering of blood pressure by infusion of hyperosmolal sorbitol solution in brain operations. Dangerous adverse effect or favorable side effect?].

Osmotherapy with sorbitol 40% during intracranial surgery using neurolept analgesia usually produced acute decreases in arterial blood pressure. Haemodynamical measurements during intraoperative infusions of sorbitol in 97 patients showed a rapid decrease of arterial mean pressure from 91 to 72 mm Hg. In 22 of these patients cardiac output measurements were performed. Increases of cardiac index from 2.5 to 4.3 l/min x m2 could be found. The hypotensive side effect can be used for treatment of reactive arterial hypertension in neurosurgical patients during surgery where this therapy is advantageous per se because of its cerebral dehydrating effects. The decrease of blood pressure is obviously caused by peripheral vasodilatation. Cardiac disturbances were not observed. Other side effects, especially the danger of hereditary fructose intolerance are discussed.

Blood Pressure↗
PubMed1987

[Anesthesiological care of female patients with cerebrovascular aneurysms in pregnancy].

This is a report on a patient who suffered subarachnoid haemorrhage from an aneurysm of the a. cerebri media during the 28th week of pregnancy. The aneurysm was clipped under neuroleptanalgesia. Besides monitoring of heart rate, blood pressure and central venous pressure as well as the treatment parameters including end-expiratory CO2, the foetal heart rate was deduced by Doppler sonography. She was hyperventilated intraoperatively with a paCO2 of 3.8-4.1 kPa. During the actual aneurysm surgery, artificial hypotension by 20 mmHg to b.p. values around 100/160 mmHg was initiated by means of nitroglycerin. It is evident from the literature compiled on this occasion that it is mandatory to monitor foetal heart rate during controlled hypotension in pregnancy. Sodium nitroprusside should not be used to initiate artificial hypotension during pregnancy, since it may result in toxic cyanide levels in the foetus. As usual in neurosurgery, hyperventilation can be performed also during pregnancy, since placental blood flow decreases only if the CO2 concentration drops to a very low level.

Adult↗
PubMed1986

[Nalbuphine and tramadol for the control of postoperative pain in children].

The postoperative treatment of pain in children is often inadequate: Periphal acting analgetics are not sufficient, opioids are believed to be dangerous because of their respiratory depression. Nalbuphine and tramadol are two narcotics with only a few side effects. The aim of this trial was to investigate the efficacy and safety of these drugs in postoperative pain therapy in children aged 1-9 years. 30 children in each group received in a double-blind and randomized manner either 0.15-0.2 mg/kg nalbuphine or 0.75-1.0 mg/kg tramadol im. Pain intensity and sleep-awake behaviour were documented by a visual analogue scale for 24 h. After 1 h 70% of the patients in both groups had no pain and were sleeping. There was no change in heart rate and systolic blood pressure. Only the diastolic blood pressure decreased as did the respiratory rate, while the tcpCO2 estimated in some patients remained constant. Narcotic reinjections were necessary three times in the nalbuphine group and four times in the tramadol group. Typical opioid side effects were found to be equal in both groups.

Blood Pressure↗
PubMed1985

[Anesthesiologic aspects of chemonucleolysis in local anesthesia].

After treatment of herniation of a lumbar disc by injection of the enzyme chymopapain, i. e. after chemonucleolysis, anaphylactic reactions can occur in about one per cent of the cases. In order to recognise the pattern of signs associated with such reactions, well in advance, while avoiding the additional risk of general anaesthesia, some authors propagate local anaesthesia. We report on our perioperative procedure in 102 cases of chemonucleolysis under local anaesthesia. Prick's tests were carried out before surgery to exclude sensitization to the substances to be injected. In two cases only due to a positive prick test to chymopapain chemonucleolysis had to be effected with collagenase; as a matter of fact, collagenase is not known to have caused any anaphylactic reactions, but it may be responsible for local side effects, such as destruction of adjacent tissues. The patients were kept under observation by an anaesthetist during and after surgery. No anaphylactic reaction was seen. Chemonucleolysis appears to be a suitable treatment method provided it is carried out under local anaesthesia with the same precautions as applied under regional anaesthesia by the anaesthetist.

Adult↗
PubMed1985

[Veterinary hematoscopy in late antiquity].

The classical humoral theory was no unfounded abstraction. On the contrary, it was based on phenomena which led to the recognition of the nature of the most important of the four humors: the blood of sick people differed from that of healthy persons. Examples from the works of the Greek and Roman veterinarians of the period from the 3rd to the 5th centuries A.D. are given, that hematoscopy was also performed by veterinarians. Bloodletting was not only a routinely applied preventive measure or a panacea, but also a prerequisite for hematoscopy, and thus a part of diagnostic.

Animals↗
PubMed1978

[Increased demethylation of aminopyrine under long-term treatment with anticonvulsive drugs (author's transl)].

Demethylation of aminopyrine was measured in 25 healthy controls and 19 epileptics on long-term treatment with anticonvulsants by the 14C-aminopyrine breath test. Compared to controls epileptics exhibited increased cumulative 14CO2-exhalation rates (88.7% at 30 min, 62.6% at 2 h and 24.8% at 8h) following ingestion of 2 mu Ci 14C-aminopyrine. The results suggest that long-term treatment with antiepileptic drugs results in increased demethylating function of the liver which can be easily detected by a simple breath analysis technique like decreased demethylation in chronic liver disease.

Aminopyrine↗