Biomedical subjects
H Müller
Publications and source records attributed to H Müller.
Long term spinal opiate treatment.
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[Efficacy and safety of the benzodiazepine antagonist RO 15-1788].
In a randomized, prospective, double-blind trial we investigated the efficacy and safety of the benzodiazepine antagonist RO 15-1788 in 57 patients undergoing general surgery. Anesthesia was induced and maintained by a combination of Flunitrazepam-Fentanyl-Pancuronium. Inhalation anesthetics were excluded from the study. After reversal of any residual relaxant effect we titrated RO 15-1788 or placebo by repeated i.v. administration of 0.1 mg (= 1.0 ml) up to a maximum dosage of 1.0 mg or to a definite arousal reaction. Before as well as 5, 10, 15, 30, 60, and 120 min after injection of the trial substance we evaluated efficacy (sedation, comprehension and collaboration, orientation in time and space), presence of anterograde amnesia, side-effects, hemodynamics, and subjective patient assessment by a point scale. RO 15-1788 significantly improved the level of consciousness (P less than 0.005) at a dosage of 0.59 +/- 0.29 mg at 5, 15, 30, and 60 min after administration as well as orientation in time and space (P less than 0.005) after 30 min. There was significantly less anterograde amnesia (P less than 0.005) after 15, 30, and 60 min. Symptoms of a benzodiazepine rebound effect after 120 min indicate a short half-life time of RO 15-1788. We did not observe any hemodynamic side effects. Local tolerance was good. Side effects in terms of nausea (1 case), vomiting (4), euphoria or dysphoria (2), benign cardiac arrhythmias (1) or a state of excitation (1) occurred several times after RO 15-1788 as well as after placebo (nausea 2, vomiting 6, muscular tremor 1). Our results indicate the efficacy and safety of RO 15-1788.
[Posthepatic jaundice caused by abnormalities of the pancreaticobile duct system in early childhood].
Anomalies of the pancreatico-biliary tract present the most frequent cause of posthepatic cholestasis in the young child, whereas calculous disease or infections or compression by vascular abnormalities or neoplasms are less frequent. Generally, abdominal pain and jaundice begin acutely and increase following progressive biliary congestion. The preoperative diagnosis by ERCP or PTC or the intraoperative diagnosis of a relevant pancreaticobiliary anomaly stress the necessity of an operative management performing a bypass of the Sphincter Oddi and of the site of the anomaly. Local operative revision alone seems to be associated with a frequent relapse of cholestasis.
[Glass ceramics--a new material for restorative dentistry].
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[Ameloblastoma of the jaw].
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[Postoperative pain therapy by transdermal fentanyl].
INTRODUCTION: Several investigations have shown that constant rate infusions of opioids are highly effective in the provision of postoperative pain relief. However, such treatment require intravenous access, the availability of infusion pumps and adequate monitoring system. We have studied a transdermal fentanyl formulation (F-TTS, developed by ALZA Corporation, Palo Alto, USA) which should avoid these problems. METHODS: The study was performed in orthopaedic patients scheduled for hip arthroplasty. 40 patients were included consecutively in a double-blind parallel comparison of F-TTS (n = 20) and placebo (n = 20) patches. The patches were applied 0.5 hours prior to epidural anaesthesia and changed after 24 hours. F-TTS is designed to deliver fentanyl at the same rate of 75 micrograms/h. For 36 hours blood samples, pain scores, respiratory patterns and vital signs were collected frequently. Patients could have supplemental pethidine on demand (50 mg/2 h) if the pain relief was inadequate. RESULTS: Fentanyl blood concentrations increased (verum) during the 24 hours period (removal) and decreased slightly after that. At the end of the investigation (36 h) fentanyl concentration remained significantly elevated (about 60% of 24-hours value). F-TTS provided good postoperative pain relief although 11 patients (of 20) required supplemental pethidine. Patients with F-TTS, however had very little pethidine compared to patients with placebo. Two patients (one of each group) had to be eliminated from the study due to severe respiratory depression or inadequate pethidine requirement respectively. The incidence of other side effects such as nausea, vomiting and micturition difficulties were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Exogenous matrix precursors promote functional nerve regeneration across a 15-mm gap within a silicone chamber in the rat.
When silicone regeneration chambers are implanted empty, axonal regeneration fails if the interstump gap length is greater than 10 mm. Previous experiments using the 10-mm gap model demonstrated that regeneration success correlated with the dimension and/or consistency of the naturally formed acellular fibrin matrix. Both spatial and temporal parameters of regeneration could be stimulated through modifications of the fibrin matrix by prefilling the chambers at the time of implantation either with phosphate-buffered saline or plasma dialyzed against phosphate-buffered saline. In the present experiments, similar modification of matrix formation was found to promote successful regeneration across 15-mm and 20-mm interstump gap lengths. In addition, prefilling 15-mm-gap chambers with dialyzed plasma resulted in a 3.5-fold increase in the incidence of functional restitution detected at 8 weeks after implantation over the outcome with chambers prefilled with phosphate-buffered saline.
Autopsy findings in AIDS--a histopathological analysis of fifty cases.
Fifty consecutive AIDS autopsy cases were evaluated. All subjects showed one or more opportunistic infections and malignancies included in the AIDS case definition with cytomegalovirus and Kaposi's sarcoma being most prevalent. Mycobacterial and cryptococcal infections occurred only infrequently. Most patients of our series after successful treatment of Pneumocystis carinii pneumonia or cerebral toxoplasmosis later succumbed to less treatable conditions like disseminated cytomegalovirus or fungal infections or malignant lymphoma. In the absence of specific treatment for the HIV infection leading to these lethal complications special emphasis must be put on the prevention of HIV transmission and spread.
Nerve regeneration chamber: evaluation of exogenous agents applied by multiple injections.
In this laboratory, a silicone chamber model for peripheral nerve regeneration in adult rats has been developed and used to define basic principles of the regenerative events, such as the sequential stages being followed during 'spontaneous' regeneration in vivo and the role of neuronotrophic- and neurite-promoting factors as well as extracellular matrix molecules. Each of the defined stages seems amenable to experimental modulation. Previous attempts to enhance regeneration included increasing the volume of the nerve chambers along with the modification of fibrin matrix formation by prefilling with saline (PBS) or matrix precursors. We present here the results of a series of experiments on the effects of exogenous biochemical agents applied by multiple injections into these in vivo chambers. Out of a variety of agents screened, a mixture of laminin (L), testosterone (T), ganglioside GM 1 (G), and catalase (C) was shown to advance substantially the progress of regeneration in 16 day chambers, as compared to PBS-prefilled and PBS-injected controls. LTGC-treatment at day 0, 6, and 10 postimplantation caused an increasingly frequent occurrence of cellular elements in cross-sections obtained from the middle (S5) of the chambers (i.e. 5 mm from the proximal stump), which was 2-fold for vessels, 3-fold for Schwann cells, and 10-fold for axons. When only sections containing axons 3 mm from the proximal stump (S3) were compared in experimental and control groups, computerized area measurements also revealed an average 2-fold difference for the cross-sectional size of the whole regenerate, the endoneurium and the space occupied by blood vessels.
[Estimation of radionuclides on the basis of radioecologic models].
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Human gene therapy: possibilities and limitations.
Gene therapy provides new options for medicine, and implies new responsibilities for making decisions relating to the limitations which reason and morality impose upon manipulation of the human genome for the benefit both of patients and of society. This contribution outlines the possibilities and limits of gene therapy in man from a medico-technical viewpoint.
Maturation of vacuolar (lysosomal) enzymes in yeast: proteinase yscA and proteinase yscB are catalysts of the processing and activation event of carboxypeptidase yscY.
Studies were performed to unravel the activation and maturation mechanism of vacuolar (lysosomal) proteinases in Saccharomyces cerevisiae. In vivo and in vitro studies show that proteinase yscA and proteinase yscB are involved in the activation and processing event of pro-carboxypeptidase yscY. Processing and activation of pro-carboxypeptidase yscY by proteinase yscA depends on an additional factor contained in the vacuolar fraction. Comparable activation can be mimicked by sodium polyphosphate. Optimum pH for processing by this proteinase yscA-triggered event is 5. The proteinase yscA-triggered maturation process of pro-carboxypeptidase yscY leads to an intermediate mol. wt form of the enzyme which is, however, fully active. Proteinase yscB transfers the intermediate mol. wt form of the original precursor to the apparently authentic, mature and active carboxypeptidase yscY. An activation and maturation scheme is devised.
Molecular weight determination of the two segments of double-stranded RNA of infectious bursal disease virus, a member of the birnavirus group.
The molecular weights (mol. wts.) of the two double-stranded (ds) RNA segments of infectious bursal disease virus (IBDV) were determined using previously sequenced reovirus genes M3 and S2 as internal ds RNA reference molecules. Electrophoresis under fully denaturing conditions revealed mol. wts. of 2.26 X 10(6) daltons and 1.98 X 10(6) daltons. By direct length measurements under the electron microscope, using two different spreading conditions, the two segments were calculated to be composed of 3274 +/- 79 base pairs (bp) and 2821 +/- 59 bp or 3299 +/- 68 bp and 2830 +/- 73 bp, resulting in mol. wts. of 2.24-2.26 X 10(6) daltons and 1.93-1.94 X 10(6) daltons, respectively. Base pair distances of 2.67 +/- 0.08 A and 2.71 +/- 0.11 A in ds RNA were close to those of the A-RNA form; in ds DNA included as a control, the rise per base pair was 3.18 A, which is consistent with published results. Mol. wts. obtained for IBDV indicate that the RNAs of the other birnaviruses are also smaller than reported.
The effect of intrathecal baclofen on electrical muscle activity in spasticity.
The efficacy of intrathecally administered baclofen was demonstrated in three patients with different types of muscular hypertonia (supraspinal rigidity, spasms shortly after spinal trauma, spasms for many years induced by multiple sclerosis) using integrated electromyography. Reduction of muscular electrical activity was accompanied by clinical improvement during long-term infusion via an implanted pump. The three patients have been observed for more than 1 year, during which time the antispastic activity of intrathecally infused baclofen has remained stable. Intrathecal application of baclofen may be considered as a possible alternative to surgery.
Splenic haematopoiesis in patients with cirrhosis of the liver.
Hitherto it has generally been assumed that splenic haematopoiesis in adult humans occurs very infrequently and is predominantly associated with haematological disorders. In the present study of patients with cirrhosis of the liver, a marked splenic haematopoiesis was a constant finding. Moreover, low-level splenic erythro- and granulopoiesis was highly prevalent even in haematologically normal controls, while splenic thrombopoiesis was conspicuously absent in both groups. We suggest that splenic haematopoiesis results from entrapment and proliferation of circulating haematopoietic precursor cells in the splenic red pulp. This would account for the presence of splenic haematopoiesis in normal controls as well as in patients with cirrhosis of the liver. In the latter, stimulation of bone marrow haematopoiesis and increased splenic pooling of haematopoietic precursor cells may contribute to the marked increase of splenic haematopoiesis observed.
Hodgkin's disease in the spleen. A morphological study of 140 biopsy cases.
140 spleens involved by untreated Hodgkin's disease were studied utilizing conventional histological methods. Regardless of the subtype of Hodgkin's disease, infiltrates of neoplastic cells were present either in the periarteriolar lymphoid sheath, the marginal zone or in both locations. Initially, infiltrates were confined to the splenic white pulp, later larger nodular foci of Hodgkin's disease developed by coalescence of several infiltrates. Neoplastic cells in Hodgkin's disease may reach the spleen by both retrograde lymphatic spread or the splenic artery; the presence of neoplastic cells in both T- and B-cell areas of the splenic white pulp implies a preference for Hodgkin's disease in the spleen with regard to a suitable microenvironment. This may be provided by certain macrophage subpopulations.