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Biomedical subjects

M Fischer

Publications and source records attributed to M Fischer.

At least 37 records · Page 2Linked to original sources
PubMed1997

One-year survival after out-of-hospital cardiac arrest in Bonn city: outcome report according to the 'Utstein style'.

Outcome after prehospital cardiac arrest was examined in the EMS system of Bonn, a midsized urban community, and presented according to the Utstein style. The data were collected from January 1st, 1989 to December 31st, 1992 by the Bonn-north ALS unit, which serves 240,000 residents. Fifty-six patients suffered from cardiac arrest of non-cardiac aetiology and were excluded; 464 patients were resuscitated after cardiac arrest of presumed cardiac aetiology (incidence of CPR attempts: 48.33 per year/100,000 population). The collapse was unwitnessed, bystander witnessed or EMS personnel witnessed in 178, 214 or 72 patients, respectively. In these subgroups discharge rates and 1-year survival accounted for 7.3% (4.5%), 22.9% (15.9%) and 16.7% (11.1%), respectively. Thirty-four patients were discharged without neurological deficits (cerebral performance category 1: CPC 1), 22 and nine patients scored CPC 2 or CPC 3, respectively. Nine patients were comatose (CPC 4) when they were discharged and remained in this state until they died. Of the 50 1-year survivors 35 lived without neurological deficit, eight demonstrated mild (CPC 2) and five severe (CPC 3) cerebral disability at 1-year after resuscitation, and, finally, two patients remained comatose for more than 1 year. The Utstein template recommends the selection of patients who were found in VF after bystander witnessed collapse. In our cohort 118 patients met these criteria. Of them 41 (35%) could be discharged from hospital and 28 (24%) lived more than 1 year. The comparison of our data with those from double-response EMS systems of other communities revealed that, in midsized urban and suburban communities the highest discharging rates could be achieved. Our study demonstrated that survival depends crucially on short response intervals and life support which will be performed by well-trained emergency technicians, paramedics and physicians.

Aged↗
PubMed1997

A dose-controlled study of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP) in the treatment of patients with painful bone metastases.

One hundred and fourteen patients with painful bone metastases participated in this randomised, dose-controlled study of the efficacy and safety of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP), a systemically administered radiopharmaceutical. Fifty-five patients received single doses of 0.5 mCi/kg and 59 patients received single doses of 1.0 mCi/kg. Treatment with 153-Sm-EDTMP produced improvement from baseline in all patient-rated efficacy assessments, including degree of pain, level of daytime discomfort, quality of sleep and pain relief. During the first 4 weeks after dose administration, when the patients evaluated efficacy daily, there were statistically significant changes from baseline with the 1.0 mCi/kg dose but not with the 0.5 mCi/kg dose. The difference between doses in visual analogue pain scores was statistically significant at week 4 (P = 0.0476). Among subsets of patients examined, female patients with breast cancer receiving 1.0 mCi/kg had the most noticeable improvement. The physicians judged that approximately half of the patients in each dose group were experiencing some degree of pain relief by week 2. This value increased to 55% for the 0.5 mCi/kg group and 70% for the 1.0 mCi/kg group at week 4. More patients in the higher dose group (54%) than in the lower dose group (44%) completed the 16-week study. A predictable level of dose-related marrow suppression was the only toxicity associated with 153Sm-EDTMP treatment. Values for platelets and WBCs reached nadirs at 3 or 4 weeks with both doses and recovered by 8 weeks. Even at their lowest point, the values were generally higher than those associated with infectious or haemorrhagic complications. Myelotoxicity was no greater in female patients than in male patients. Long-term follow-up revealed longer survival among breast cancer patients who had received the higher dose than among those who had received the lower dose. The results suggest that the 1.0 mCi/kg dose of 153Sm-EDTMP is safe and effective for the treatment of painful bone metastases.

Adult↗
PubMed1997

I. A bioactive designer cytokine for human hematopoietic progenitor cell expansion.

Efficient expansion of hematopoietic progenitor cells requires, at least, the simultaneous stimulation of the receptors c-kit and gp130. While c-kit is activated by SCF; gp130, in cells which do not express sufficient amounts of IL-6R, can be activated by the complex of soluble IL-6R (sIL-6R) and IL-6. The therapeutic use of IL-6/sIL-6R, however, has been hampered by the high concentrations of the sIL-6R protein required. We have designed a fusion protein of sIL-6R and IL-6, linked by a flexible peptide chain, that was expressed to high levels. On gp130 expressing cells the fusion protein turned out to be fully active at 100 to 1,000-fold lower concentration than the combination of unlinked IL-6 and IL-6R. The fusion protein was used to effectively expand human hematopoietic progenitor cells ex vivo in a dose dependent fashion.

Amino Acid Sequence↗
PubMed1997

A hitherto unknown splice site defect in the protein S gene (PROS1): the mutation results in allelic exclusion and causes type I and type III protein S deficiency.

A hitherto unknown splice site mutation, in the splice acceptor of intron B (tctag to tctgg), was identified in a symptomatic patient with type III protein S deficiency. The mutation co-segregated with type I/III protein S deficiency in the patient's family. RNA analysis showed allelic exclusion of the mutant transcript in affected individuals. The apparent type III deficiency in the propositus was not associated with the protein S Heerlen variant.

Humans↗
PubMed1997

[Critical evaluation of vascular embolization in patients with Rendu-Osler disease].

BACKGROUND: As causal therapy of Rendu-Osler-Weber syndrome is not yet possible, there are many different therapeutical approaches. It seemed expedient to investigate the efficacy of super-selective angiography in treating Rendu-Osler-Weber syndrome after this technique proved effective in other therapeutic settings. This method is known to be efficient in controlling tumor bleeding. PATIENTS: Between March 1993 and September 1995, eight patients with an average age of 57 years were treated by super-selective intraarterial embolization. RESULTS: In all cases epistaxis occurred on both sides. Unilateral embolization was performed in ten cases and bilateral embolization in five cases. In two of three patients with nasal packing the embolization permitted removal of the packing. Nevertheless nosebleeds reoccurred on an average of 3.5 days after therapy. Two of eight patients showed long-term improvement after therapy. They suffered fewer nosebleeds than before. Complications included one patient who suffered from partial hemiparesis after embolization, which lasted 1.5 hours and was completely reversible. Another patient died because of pulmonic bleeding caused by manifestation of the disease in this organ. Often patients complained of facial pain or headache which occasionally lasted for a few weeks. CONCLUSIONS: Endovasal embolization obviously is an alternative to artery ligation in emergency cases whereas the long-term success is currently impaired by formation of new anastomoses. Further development of this technique is necessary.

Adult↗
PubMed1997

Interleukin-2 increases transcapillary diffusion of sodium fluorescein in human skin.

Immunotherapy with interleukin-2 (IL-2) has been limited by dose-dependent systemic toxicities secondary effects inducing a "vascular leak" syndrome. The purpose of our study was directly to observe and to quantitate changes in skin capillary permeability in response to microinjection of IL-2 by measuring transcapillary diffusion of sodium fluorescein. Twelve healthy volunteers were studied. IL-2 (2.5 microliters; 45,000 i.u.) was injected into the subepidermal skin layer of the distal tibial plateau by using a new microinjection technique. At the opposite leg, an equivalent amount of the solvent was injected to serve as the intraindividual control site. Three and 24 h after injection, Na-fluorescein was given intravenously, and transcapillary diffusion of the dye was simultaneously recorded with two different video microscopes. Perivascular fluorescent light intensities (FLI) corresponding to transcapillary diffusion of the dye were measured in arbitrary units (AU) by videodensitometry around the sites of microinjection during playback of the videotapes. Mean FLI values representing microvascular permeability 10 s after dye appearance were at 3 h, 1,504 +/- 592 AU for IL-2 and 983 +/- 652 AU for the solvent; and at 24 h, 2,450 +/- 447 AU for IL-2 and 658 +/- 329 AU for the solvent. At 3 and 24 h, the mean values after IL-2 application were significantly enhanced (p < 0.05-0.005) when compared with the mean values after injection of the solvent. The results document that IL-2, as compared with the solvent, significantly increases transcapillary diffusion of Na-fluorescein, reflecting capillary permeability in human skin. The increase in capillary permeability may explain the edema-promoting effect of IL-2 after systemic application.

Administration, Cutaneous↗
PubMed1997

Functional role of beta2-adrenoceptors in the transplanted human heart.

In the transplanted human heart, beta-adrenoceptor subtypes change with time after transplantation: beta1-adrenoceptors tend to decline, whereas beta2-adrenoceptors are upregulated. The aim of this study was to determine whether, in the transplanted human heart, stimulation of beta2-adrenoceptors can induce heart-rate increases. For this purpose, we assessed in eight heart-transplant recipients (mean posttransplant time: 932 days) the effects of infusion of graded doses of isoprenaline (3.5-35 ng/kg/min) 120 min after pretreatment with the beta1-adrenoceptor antagonist bisoprolol (10 mg p.o.; beta1-adrenoceptor occupancy approximately 80%; beta2-adrenoceptor occupancy <5%) on heart rate in the recipient's native (innervated) and transplanted (denervated) sinus nodes. Isoprenaline, acting under these conditions predominantly at beta2-adrenoceptors, increased heart rate both in the recipient's transplanted and native sinus nodes in a dose-dependent manner; at each dose, increases were significantly higher in the transplanted than in the native sinus node. ED20 values (dose to increase heart rate by 20 beats/min) in the transplanted sinus node were 22.2 +/- 1.8 ng/kg/min, and in the native, >35 ng/kg/min (p < 0.01). We conclude that in the transplanted human heart, beta2-adrenoceptor stimulation does evoke increases in heart rate. The enhanced response to isoprenaline in the transplanted sinus node could be caused by the upregulated beta2-adrenoceptors or by the fact that during isoprenaline infusion, vagal activity increases, thus blunting the response in the native (innervated) but not in the transplanted (denervated) sinus node.

Adrenergic beta-Agonists↗
PubMed1997

Tobacco smoke as a risk factor for meningococcal disease.

BACKGROUND: Since 1992 the US Pacific Northwest has experienced a substantial increase in the incidence of serogroup B meningococcal disease. The current meningococcal polysaccharide vaccine is poorly immunogenic in young children and does not protect against N. meningitidis serogroup B. Defining alternative approaches to the prevention and control of meningococcal disease is of considerable public health importance. METHODS: We performed a case-control study comparing 129 patients in Oregon and southwest Washington with 274 age- and area-matched controls. We used conditional logistic regression analysis to determine which exposures remained associated with disease after adjusting for other risk factors and confounders and calculated the proportion of disease attributable to modifiable exposures. RESULTS: After adjustment for all other significant exposures identified, having a mother who smokes was the strongest independent risk factor for invasive meningococcal disease in children < 18 years of age [odds ratio (OR), 3.8; 95% confidence interval (CI) 1.6 to 8.9)], with 37% (CI 15 to 65) of all cases in this age group potentially attributable to maternal smoking. Adult patients were more likely than controls to have a chronic underlying illness (OR 10.8, CI 2.7 to 43.3), passive tobacco smoke exposure (OR 2.5, CI 0.9 to 6.9) and to smoke tobacco (OR 2.4, CI 0.9 to 6.6). Dose-response effects were seen for passive smoke exposure and risk of disease in all age groups. CONCLUSION: Tobacco smoke exposure independently increases the risk of developing meningococcal disease.

Adolescent↗
PubMed1997

Biosynthesis of riboflavin: characterization of the bifunctional deaminase-reductase of Escherichia coli and Bacillus subtilis.

The ribG gene at the 5' end of the riboflavin operon of Bacillus subtilis and a reading frame at 442 kb on the Escherichia coli chromosome (subsequently designated ribD) show similarity with deoxycytidylate deaminase and with the RIB7 gene of Saccharomyces cerevisiae. The ribG gene of B. subtilis and the ribD gene of E. coli were expressed in recombinant E. coli strains and were shown to code for bifunctional proteins catalyzing the second and third steps in the biosynthesis of riboflavin, i.e., the deamination of 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate (deaminase) and the subsequent reduction of the ribosyl side chain (reductase). The recombinant proteins specified by the ribD gene of E. coli and the ribG gene of B. subtilis were purified to homogeneity. NADH as well as NADPH can be used as a cosubstrate for the reductase of both microorganisms under study. Expression of the N-terminal or C-terminal part of the RibG protein yielded proteins with deaminase or reductase activity, respectively; however, the truncated proteins were rather unstable.

Amino Acid Sequence↗
PubMed1997

Accidental intoxication with methylene dianiline p,p'-diaminodiphenylmethane: acute liver damage after presumed ecstasy consumption.

BACKGROUND: MDA is the abbreviation for methylene dianiline (p,p' diaminodiphenylmethane; 4,4'-methylenedianiline; CAS 101-77-9); and for methylendioxyamphetamine (MDMA, N, alpha-dimethyl-1,3-benzodioxole-5-ethanamine; CAS 42542-10-9). While the former is used for the production of polyurethane foams, the latter is a psychometric drug, which is becoming increasingly popular in the techno scene. METHODS: We report six participants of a technoparty (1 female, 5 males, ages 17-25) who were admitted to the hospital with severe colicky abdominal pain and subsequently developed symptoms of hepatotoxicity. They had ingested an alcoholic beverage that had been spiked with a powdery substance they dubbed MDA. RESULTS: All patients showed similar clinical symptoms, with an identical time course. Acute jaundice developed within 2 days after ingestion. Enzymes indicating cholestasis increased steadily over 7 days and reached peak values of 800 U/L (AP) and 380 U/L (GGT), whereas transaminases remained moderately elevated. Between days 5 and 7, all patients became febrile for one day, their body temperatures rising up to 40 degrees C. There was no evidence for hemolysis or an infectious hepatitis. Toxicological analysis revealed the presence of p,p'-diaminodiphenylmethane (4,4'-methylenedianiline) at a concentration of 130 mg/L in one of two urine extracts examined. CONCLUSIONS: The analytical data indicate that the participants of the technoparty assumed the aniline-derivative, the cause of Epping Jaundice, was methylendioxyamphetamine because the same abbreviation, MDA, is used for both compounds. An overview of the acute liver toxicity of aniline derivatives is given and the possibility of amphetamine-induced liver damage is discussed.

3,4-Methylenedioxyamphetamine↗
PubMed1997

[In coronary surgery can both internal mammary arteries be used systematically? Apropos of 560 patients].

The grafts commonly used in coronary bypass surgery are the left internal mammary artery and the saphenous veins of the legs: the use of both internal mammary arteries, with potential long-term benefits, is only justified if the operative risk is not increased. Since 1987, the authors use both internal mammary arteries systematically in patients under 70 years of age and in good general condition. The retrospective analysis of 560 patients having undergone this surgery from 1987 to 1994 was undertaken to determine if this surgical option is justified without increased operative risk. The dissection of the mammary arteries is performed in a special manner by skeletonization technique. The total hospital complication rate was 12% with 9 deaths in the first 30 postoperative days (1.6%). Mediastinitis was observed in 6 patients (1.1%) Early angiographic controls showed a patent mammary graft rate of 98%. The use of both internal mammary arteries does not therefore increase postoperative morbidity or mortality. It may be proposed systematically in patients in good general condition and may provide long-term benefits in graft patency rates.

Adult↗
PubMed1997

[Dangerous thrombocytopenia in thrombolytic therapy of venous thrombosis of the leg].

Two days after 5 days heparin treatment of a superficial thrombophlebitis a 45 year old woman was admitted to hospital with an extended phlebothrombosis of a leg. Before starting thrombolytic treatment a bolus of 5000 U heparin followed by 1000 U/h was administered. During thrombolytic treatment with ultrahigh streptokinase the platelet count dropped from 172,000/microliter to 73,000 and 29,000/microliter. Thrombocytopenia was considered not to be a complication of thrombolytic therapy but by demonstrating heparin induced platelet antibodies to be due to a heparin-associated thrombocytopenia type II (HAT Type II).

Dose-Response Relationship, Drug↗
PubMed1996

Biosynthesis of riboflavin. Lumazine synthase of Escherichia coli.

A gene located at 443 kilobases on the Escherichia coli chromosome (subsequently designated ribE) was expressed in a recombinant E. coli strain and was shown to code for the enzyme 6, 7-dimethyl-8-ribityllumazine synthase. The recombinant enzyme was purified to homogeneity. The protein is an icosahedral capsid of 60 subunits with a mass of about 1 MDa as shown by hydrodynamic studies and by electron microscopy. In contrast to the icosahedral lumazine synthase-riboflavin synthase complex of Bacillus subtilis, the lumazine synthase of E. coli is not physically associated with another enzyme of the riboflavin pathway, and the core of the icosahedral capsid is empty. The RIB4 gene of Saccharomyces cerevisiae was also expressed to a high level (about 40% of cellular protein) in E. coli. The recombinant protein is a pentamer of 90 kDa. An insertion of 4 amino acids into helix alpha4 is likely to hinder the formation of an icosahedral capsid by the yeast protein. The kinetic properties of lumazine synthase of E. coli, B. subtilis, and S. cerevisiae are similar.

Amino Acid Sequence↗
PubMed1996

Normal host prion protein (PrPC) is required for scrapie spread within the central nervous system.

Mice devoid of PrPC (Prnp%) are resistant to scrapie and do not allow propagation of the infectious agent (prion). PrPC-expressing neuroectodermal tissue grafted into Prnp% brains but not the surrounding tissue consistently exhibits scrapie-specific pathology and allows prion replication after inoculation. Scrapie prions administered intraocularly into wild-type mice spread efficiently to the central nervous system within 16 weeks. To determine whether PrPC is required for scrapie spread, we inoculated prions intraocularly into Prnp% mice containing a PrP-overexpressing neurograft. Neither encephalopathy nor protease-resistant PrP (PrPSc) were detected in the grafts for up to 66 weeks. Because grafted PrP-expressing cells elicited an immune response that might have interfered with prion spread, we generated Prnp% mice immunotolerant to PrP and engrafted them with PrP-producing neuroectodermal tissue. Again, intraocular inoculation did not lead to disease in the PrP-producing graft. These results demonstrate that PrP is necessary for prion spread along neural pathways.

Animals↗