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Biomedical subjects

M Fischer

Publications and source records attributed to M Fischer.

At least 271 records · Page 15Linked to original sources
PubMed1997

Angiotensin-converting enzyme inhibitors in preventing remodeling and development of heart failure after acute myocardial infarction: results of the German multicenter study of the effects of captopril on cardiopulmonary exercise parameters (ECCE).

Early action of angiotensin-converting enzyme (ACE) inhibitors after myocardial infarction (MI) has been shown in large scale clinical trials to reduce mortality over the first weeks. However, the mechanisms involved are yet unclear and several trials showed a tendency toward a small, albeit unexpected, rise in cardiogenic shock or mortality. Since cardiopulmonary exercise testing (CPX) has become a "gold standard" in assessing the severity of heart failure, we studied--after finishing a pilot trial--the effect of captopril versus placebo in 208 patients who were individually titrated (titrated dose, mean 46/69 mg/day after 7 days/4 weeks, respectively) in order to preserve their blood pressure in the acute phase of myocardial infarction; we followed the development of congestive heart failure (CHF) over 4 weeks by measuring oxygen consumption. After 4 weeks, overall oxygen consumption at the anaerobic threshold (VO2-AT; 13.7 vs 13.1), maximal oxygen consumption (VO2max 19.3 vs 18.9 mL/kg per min) and exercise duration (896 vs 839 sec) showed a nonsignificant difference in favor of the captopril group. The predefined, categorized, combined endpoint of severe heart failure or death (heart failure necessitating ACE inhibition, VO2max < 10 mL/kg per min, or death) was significantly reduced in the captopril group (n = 7/104) versus placebo (n = 18/104; p = 0.03). Differences were mainly caused by fewer CHF events (delta n = 10). We conclude that ACE inhibition with individualized dose titration markedly reduces the 4-week incidence of severe heart failure or death; > 10 patients per 100 treated gained major benefits from this therapy.

Adult↗
PubMed1997

Direct determination of the chemical composition of acetylcholinesterase phosphonylation products utilizing electrospray-ionization mass spectrometry.

While non-reactivability of cholinesterases from their phosphyl conjugates (aging) is attributed to an unimolecular process involving loss of alkyl group from the phosphyl moiety, no conclusive evidence is available that this is the only reaction path and involvement of other post-inhibitory processes cannot be ruled out. To address this issue, molecular masses of the bacterially expressed recombinant human acetylcholinesterase and of its conjugates with a homologous series of alkyl methylphosphonofluoridates, were measured by electrospray-ionization mass spectrometry (ESI-MS). The measured mass of the free enzyme was 64,700 Da (calculated 64,695 Da) and those of the methylphosphono-HuAChE adducts, bearing isopropyl, isobutyl, 1,2-dimethylpropyl and 1,2,2-trimethylpropyl substituents, were 64,820, 64,840, 64,852 and 64,860 Da, respectively. These values reflect both the addition of the phosphonyl moiety and the gradual mass increase due to branching of the alkoxy substituent. The composition of these adducts change with time to yield a common product with molecular mass of 64,780 Da which is consistent with dealkylation of the phosphonyl moieties. Furthermore, in the case of 1,2-dimethylpropyl methylphosphono-HuAChE, the change in the molecular mass and the kinetics of non-reactivability appear to occur in parallel indicating that dealkylation is indeed the predominant molecular transformation leading to 'aging' of phosphonyl-AChE adducts.

Acetylcholinesterase↗
PubMed1997

Sleep and sleep regulation in normal and prion protein-deficient mice.

Mice are the preferred mammalian species for genetic investigations of the role of proteins. The normal function of the prion protein (PrP) is unknown, although it plays a major role in the prion diseases, including fatal familial insomnia. We investigated its role in sleep and sleep regulation by comparing baseline recordings and the effects of sleep deprivation in PrP knockout mice (129/SV) and wild-type controls (129/SV x C57BL/6), which are the mice used for most gene targeting experiments and whose behavior is not well characterized. Although no difference was evident in the amount of vigilance states, the null mice exhibited a larger degree of sleep fragmentation than the wild-type with almost double the amount of short waking episodes. As in other rodents, cortical temperature closely reflected the time course of waking. The increase of slow-wave activity (SWA; mean EEG power density in the 0.25-4.0 Hz range) at waking to nonrapid eye movement (NREM) sleep transitions was faster and reached a lower level in the null mice than in the wild-type. The contribution of the lower frequencies (0.25-5.0 Hz) to the spectrum was smaller than in other rodents in all three vigilance states, and the distinction between NREM sleep and REM sleep was most marked in the theta band. After the sleep deprivation, SWA was increased, but the changes in EEG power density and SWA were more prominent and lasted longer in the PrP-null mice. Our results suggest that PrP plays a role in promoting sleep continuity.

Amyloid↗
PubMed1997

Antioxidant status in patients on chronic hemodialysis therapy: impact of parenteral selenium supplementation.

Reactive oxygen species may be involved in a broad pattern of tissue injury in patients on regular hemodialysis therapy and, in fact, increasing evidence suggests that the antioxidative system is compromized in these patients. One factor contributing to this reduction of antioxidative capacity is selenium deficiency. The present investigation was undertaken to further define the extent and type of impairment of the oxygen radical scavenger system in chronic hemodialysis patients and to evaluate the impact of selenium supplementation. Twelve non-wasted patients (6 male, 6 female, mean age of 58 years) on chronic hemodialysis for a minimum of 5 months (mean 46 months) were supplemented intravenously with 400 mg selenium (as sodium selenite) thrice weekly after each hemodialysis session over 8 weeks. Blood samples were taken before the start, at intervals of 2 weeks during, and 4 weeks after termination of supplementation. Concentrations were evaluated of selenium and alpha-tocopherol in plasma and erythrocytes, of retinol and ascorbic acid in plasma, of glutathione and the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and, catalase (CAT) in erythrocytes. Lipid peroxidation endproducts were measured as malondialdehyde (MDA) in plasma. In patients on hemodialysis multiple alterations of the antioxidative system were present and the concentrations of selenium in plasma, of glutathione and the activity of GSH-Px in erythrocytes were profoundly decreased (p < 0.001). Selenium supplementation improved the selenium status of the patients, as indicated by an increase in selenium concentrations in plasma and erythrocytes and erythrocyte GSH-Px activity. Improvement in antioxidative capacity was further documented by an increase in alpha-tocopherol in erythrocytes. Plasma MDA showed a transient decrease after 6 weeks and increased activities of SOD and CAT were dampened. No effect was seen on plasma concentrations of ascorbic acid, a-tocopherol and retinol. We conclude that patients on chronic hemodialysis therapy manifest a profound depression in antioxidative potential and a selenium deficiency. Selenium supplementation improves the oxygen radical scavenger system and increases selenium concentrations in plasma and erythrocytes and the activity of selenium dependent glutathione peroxidase. Thus, selenium should also be considered for micronutrient supplementation in patients on chronic hemodialysis therapy.

Adult↗
PubMed1997

Results of the Müller acetabular reinforcement ring in revision arthroplasty.

Between April 1984 and December 1987 a Müller acetabular reinforcement ring was employed in 98 revision cases (94 patients). Twenty-two patients died before follow-up evaluation. Forty-seven (66%) of the remaining 72 patients (49 of 75 hips) were examined after a mean of 6.4 years (range 5-9 years). Excluding those who died, the postoperative outcome of 69 patients is known. Migration was measured according to Sutherland by means of a digitising table. Cup position was determined by a new angle (beta) between the sacroiliacal line and a reference line. The reference line connects the centre of the femoral head with the intersection between the sacroiliacal and obturator lines. Aseptic and septic loosening required revision surgery in 2 cases each (4%). The postoperative beta angle showed a high correlation with migration (P = 0.001) as well as with radiolucencies (P = 0.001). In cases which required further revision, beta amounted to 44 deg (craniolateral position), and in stable cases up to 60 deg. A lateral and cranial position of a Müller acetabular reinforcement ring leads to high loosening rates. The beta angle accurately describes cup position, and its postoperative value is highly predictive for loosening.

Acetabulum↗
PubMed1997

Serum fluoride and serum osteocalcin levels in response to a novel sustained-release monofluorophosphate preparation: comparison with plain monofluorophosphate.

In a previous study we found that sustained-release monofluorophosphate (MFP-SR), a novel, sustained-release MFP preparation, acutely maintained the basal therapeutic serum fluoride levels without causing the high serum peak levels associated with plain MFP administration. The objective of the present study was to determine (a) whether chronic MFP-SR administration would provide therapeutic serum fluoride levels, and (b) whether treatment with this new preparation would result in an increase in bone formation similar to that achieved with plain MFP. Bone formation was assessed by serum osteocalcin (OC) determination. We studied 17 postmenopausal women older than 60 years and suffering from primary osteoporosis. All had received a minimum of 6 months of continuous treatment with plain MFP at a dose of 152 mg/day (76 mg b.i.d.). Upon entering the study, the subjects were randomized, in a double-masked protocol, to receive either MFP-SR (76 mg b.i.d.) (n = 9) or placebo (n = 8) for 2 months, after which all subjects returned to the original plain MFP regimen. Serum fluoride and serum OC levels were determined monthly for 3 months. At the beginning of the study serum fluoride levels were in the accepted therapeutic range (5-10 microM) in all patients. Serum fluoride levels were maintained in the patients switched to MFP-SR. In contrast, serum fluoride levels decreased significantly (p < 0.005) in the placebo-treated control subjects and returned to therapeutic levels upon switching back to plain MFP. Similarly, serum OC levels remained elevated in the subjects switched to MFP-SR but dropped significantly (p < 0.001) in the placebo-treated group. Our results demonstrate that chronic MFP-SR administration, at a dose of 152 mg/day, results in maintenance of therapeutic serum fluoride levels and in stimulation of bone formation. Because we have previously reported that high, supratherapeutic post-absorptive serum fluoride levels are avoided by MFP-SR administration, this novel preparation may prevent side effects associated with plain MFP by reducing the amount of fluoride deposited in bone.

Aged↗
PubMed1997

[Single-image roentgen analysis for the measurement of hip endoprosthesis migration].

A method to determine migration of hip endoprostheses is described. Migration is measured by means of standard AP radiographs and therefore can also be evaluated in retrospective studies. Measurement is conducted in X-ray studies displayed on a computer screen. Enhancement of bony structures by application of filters is available. The developed software can be used with common commercially available computers and X-ray scanners, and does not require special hardware. Several methods to determine accuracy are described. The accuracy of the described method is about 1 mm (95% confidence limit), which compares favourably with other methods, but is less accurate than roentgen stereophotogrammetry. For other methods, accuracy was not determined adequately. Two years after implantation, revision within the first 10 years of follow-up can be predicted with a sensitivity and specificity of more than 80%.

Acetabulum↗
PubMed1997

Transient expression of the beta-glucuronidase gene after biolistic transformation of the anaerobic fungus Neocallimastix frontalis.

The rumen anaerobic fungus Neocallimastix frontalis was biolistically transformed using plasmids containing the bacterial beta-glucuronidase gene (GUS) fused to the promoter sequences of the enolase gene from N. frontalis. Multiple copies of the plasmids were precipitated onto tungsten particles and delivered into zoosporangia and a mycelial mat by a helium-driven biolistic device. Transformants were detected by histochemical assay for beta-glucuronidase. It was found that the enolase promoter sequences tested were responsible for the transient expression of the beta-glucuronidase gene. This is the first study presenting results on the transformation of an anaerobic fungus.

Anaerobiosis↗
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↗