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M Mohr

Publications and source records attributed to M Mohr.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Attempted CPR in nursing homes - life-saving at the end of life?].

AIM: We studied the course and success rate of cardiopulmonary resuscitation (CPR) attempted on nursing home residents by a physician-staffed pre-hospital advanced cardiac life support (ACLS) team. METHODS: Ambulance records of nursing home residents from Goettingen/Germany who had a cardiac arrest were examined retrospectively. RESULTS: During a seven-year period (1992 - 1998) the ACLS team was called to 71 residents (mean age 81.8 years) who sustained cardiac arrest. In 25 patients no CPR was attempted: 20 were pronounced dead by the arriving emergency physician, though only in 7 patients obvious clinical signs of death were present. Five patients suffered from a continuous deterioration of their health status and the ACLS team arrived after the process of dying had already started. No CPR attempt was initiated. The ACLS team performed CPR on 46 nursing home residents. In 33 patients (72 % of CPR attempts) no return of spontaneous circulation (ROSC) was achieved. In three patients (6%) palpable pulse returned only transiently. Ten patients (22 %) who showed ROSC were transported to the hospital. Six patients died within 24 hours after having been admitted to the hospital, two patients within the next 8 days. Two patients survived to hospital discharge. The first was a 79-year old woman who returned to the nursing home after three weeks and survived severely mentally disabled another five days. The second was an 83-year-old man who was hospitalised for 20 days, returned in a persistent vegetative state to the nursing home and died 10 months later. A comparison of the arrest characteristics demonstrated that in patients with successful CPR there was a higher incidence of a witnessed collapse, bystander CPR, ventricular fibrillation and cardiac aetiology of arrest. CONCLUSION: In a high rate (35 %) the ACLS team with the emergency physician at the scene withheld CPR efforts in nursing home residents. Even if CPR was initiated, the benefits were very limited with only two patients (4,3 %) surviving severely disabled to hospital discharge.

Aged↗
PubMed2001

Medical and socioenvironmental predictors of hospital readmission in patients with congestive heart failure.

BACKGROUND: Patients with chronic congestive heart failure (CHF) require frequent rehospitalization because of the exacerbation of CHF. It is of clinical importance to determine predicting factors for readmission to reduce this likelihood. Previous studies have focused primarily on the demographic and medical characteristics in selected subsets of patients. Therefore, within a broad cohort of consecutively hospitalized patients, we sought to identify not only demographic and medical predictors but also socioenvironmental factors associated with readmission. METHODS: We assessed demographic (age, sex), medical (etiology of CHF, New York Heart Association functional class, left ventricular ejection fraction, previous admission for CHF, length of hospital stay, comorbidity, and medications), and socioenvironmental variables (occupation, financial resources, living alone, and follow-up visits) in 230 patients discharged with a diagnosis of CHF and recorded hospital readmission. RESULTS: Within 1 year after discharge, 81 patients (35%) were readmitted. Five variables, including poor follow-up visits (odds ratio [OR] 4.9, 95% CI 2.0-11.8), previous admission for CHF (OR 3.3, 95% CI 1.8-6.1), no occupation (OR 2.6, 95% CI 1.2-5.5), longer hospital stay (OR 3.2, 95% CI 1.2-8.5), and hypertension (OR 2.0, 95% CI 1.1-3.7), were identified as significant independent predictors for readmission by multivariate logistic regression analysis. CONCLUSIONS: Our independent predictors of readmission support the importance of medical and socioenvironmental factors in the deterioration of CHF. Therefore interventions to decrease readmission should also target social management in all hospitalized patients.

Acute Disease↗
PubMed2001

Simultaneous immunomagnetic CD34+ cell selection and B-cell depletion in peripheral blood progenitor cell samples of patients suffering from B-cell non-Hodgkin's lymphoma.

The reduction of residual tumor cells is one of the main targets of leukapheresis product (LP) processing. Immunomagnetic enrichment/selection of CD34+ progenitor cells (Baxter Isolex 300i) can achieve a reduction of contaminating B-cells of approximately 2-3 logs in B-cell non-Hodgkin's lymphoma patients. Specific release of the enriched CD34+ cells (stem cell releasing agent PR34+; Baxter) and the use of antibody-coated immunobeads targeted against B-cell markers (CD10, CD19, CD20, CD22, CD23, and CD37) during this procedure allows the GMP-like simultaneous capture of residual B cells within a closed system. This combination of two purging techniques enhances the B-cell depletion capacity up to 4.5 logs. By performing 10 clinical-scale purging procedures, we could show that the simultaneous immunomagnetic purging method is easy to perform and highly efficient. We evaluated B-cell log depletion by flow cytometry for cases with marker-positive cells detectable before and after the purging procedure. The mean reduction of B-cells in these cases was 3.5 logs; the mean CD34+ cell yield and purity were 47 and 92%. Using three LPs, we tested the procedure on a modified Baxter Isolex 300i device with software adaptations for this procedure (software version 2.0) in direct comparison with CD34+ cell selection only, using the former version (version 1.12). The CD34+ cell yield was 49% (40-54%) for the CD34+ cell selection and 51% (19-72%) for simultaneous double selection. The mean purity was 96% for CD34+ cell selection and 98% for simultaneous double selection. B-cell depletion was 1.9 logs for CD34+ cell selection, and after simultaneous double selection, the B-cell content was decreased by 3.7 log steps (P = 0.0495). Clinical application of double-purged cells has not prolonged the hematopoietic recovery times after high-dose therapy as compared with nonpurged peripheral blood progenitor cell autotransplants. In conclusion, we could show that the simultaneous double selection protocol developed leads to a highly increased B-cell purging efficacy when compared with CD34+ cell selection without any negative effects regarding CD34+ cell yield and engraftment times after high-dose therapy.

Antigens, CD34↗
PubMed2000

A 7-kDa prion protein (PrP) fragment, an integral component of the PrP region required for infectivity, is the major amyloid protein in Gerstmann-Sträussler-Scheinker disease A117V.

Gerstmann-Sträussler-Scheinker disease (GSS) is a cerebral amyloidosis associated with mutations in the prion protein (PrP) gene (PRNP). The aim of this study was to characterize amyloid peptides purified from brain tissue of a patient with the A117V mutation who was Met/Val heterozygous at codon 129, Val(129) being in coupling phase with mutant Val117. The major peptide extracted from amyloid fibrils was a approximately 7-kDa PrP fragment. Sequence analysis and mass spectrometry showed that this fragment had ragged N and C termini, starting mainly at Gly88 and Gly90 and ending with Arg148, Glu152, or Asn153. Only Val was present at positions 117 and 129, indicating that the amyloid protein originated from mutant PrP molecules. In addition to the approximately 7-kDa peptides, the amyloid fraction contained N- and C-terminal PrP fragments corresponding to residues 23-41, 191-205, and 217-228. Fibrillogenesis in vitro with synthetic peptides corresponding to PrP fragments extracted from brain tissue showed that peptide PrP-(85-148) readily assembled into amyloid fibrils. Peptide PrP-(191-205) also formed fibrillary structures although with different morphology, whereas peptides PrP-(23-41) and PrP-(217-228) did not. These findings suggest that the processing of mutant PrP isoforms associated with Gerstmann-Sträussler-Scheinker disease may occur extracellularly. It is conceivable that full-length PrP and/or large PrP peptides are deposited in the extracellular compartment, partially degraded by proteases and further digested by tissue endopeptidases, originating a approximately 7-kDa protease-resistant core that is similar in patients with different mutations. Furthermore, the present data suggest that C-terminal fragments of PrP may participate in amyloid formation.

Adult↗
PubMed2000

Dementia with Lewy bodies in a neuropathologic series of suspected Creutzfeldt-Jakob disease.

Discriminating Creutzfeldt-Jakob disease (CJD) from dementia with Lewy bodies (DLB) may be clinically difficult to achieve. The authors describe 10 patients with DLB initially referred to the French Network of Human Spongiform Encephalopathies as having suspected CJD. In a series of 465 autopsied cases, DLB ranked second among degenerative alternative diagnoses to CJD. The authors analyzed the factors that contributed to misleading the diagnosis, and suggest that the detection of 14-3-3 protein in CSF may be useful to distinguish CJD from DLB.

Aged↗
PubMed2000

Solvation of radical cations in water--reactive or unreactive solvation?

The solvation and reaction of ethylene radical cation in aqueous solution has been studied with Car-Parrinello molecular dynamics simulations. All ab initio simulations were performed using a system of 56 water and one ethylene molecule. Using a favorable symmetrically solvated radical cation as the starting point of the simulation a fast addition of water (within 90 fs) to the radical cation is observed. The primary addition product is rapidly deprotonated (within 100 fs) to yield the ethanol-2-yl radical. A second simulation was initiated through vertical ionization of neutral hydrated ethylene, representing a significantly less favorable situation for the addition process. No addition of water can be observed in this second simulation over a time span of 1.7 ps. Taken together the two simulations are indicative of a rearrangement of the solvent shell which represents the major part of the overall reaction barrier. Under these circumstances, the reaction rate of an otherwise spontaneous reaction is limited by the intrinsic solvent relaxation time. This interpretation of the reactivity of hydrated radical cations reconciles previously conflicting experimental condensed phase and theoretical gas phase studies.

Journal Article↗
PubMed2000

Pallido-Luysio-Nigral atrophy revealed by rapidly progressive hemidystonia: a clinical, radiologic, functional, and neuropathologic study.

Pallido-luysio-nigral atrophy (PLNA) is a rare neurodegenerative disease in which the clinical and radiologic correlates have not yet been clearly established. A 62-year-old man insidiously developed dystonic postures, choreoathetoid movements, slowness, and stiffness, which initially affected the right hand and foot and progressively spread to the entire right side. T2-weighted magnetic resonance imaging showed increased signal intensity in both left and right medial pallida and in the left substantia nigra. Tests using HMPAO-SPECT and FDG-PET demonstrated left cortical hyperperfusion and hypermetabolism, whereas the left lenticular nucleus was slightly hypometabolic. At age 65, abnormal movements and postures involved all four limbs and the axis causing major gait disturbances, and facial and bulbar muscles atrophied resulting in dysarthria, dysphagia, and impaired breathing. Diffuse amyotrophy and fasciculations also appeared. Death occurred at age 66, 4 years after onset. At autopsy, severe bilateral neuronal loss and gliosis restricted to the pallidum, the subthalamic nucleus, the substantia nigra, and the hypoglossal nucleus were noted, accounting for the diagnosis of PLNA with lower motor neuron involvement. Progressive hemidystonia with adult onset represents an unusual clinical presentation for this disorder. Moreover, this observation indicates that a diagnosis of PLNA should be considered for specific magnetic resonance imaging, SPECT, and/or PET data, and suggests that in PLNA, pallidal dysfunction might play a key role in the dystonic presentation.

Age of Onset↗
PubMed2000

[Euthanasia in Europe--ten countries with special consideration of the Netherlands and Germany].

This article presents an overview of the current situation of euthanasia in Europe. Emphasis is given to the positions discussed in the Netherlands and in Germany. The current situation, the development of the legal positions, and the resulting debate are established by analysing English and German anesthesiological and medical-ethical journals. It has to be noted that many physicians are not satisfied with the terminology of euthanasia. The traditional concepts of euthanasia do not cover the aspect of accompanying terminally ill persons until they have died. The differentiation of active, passive, and indirect euthanasia does not correspond to the practical handling of the problem. Many physicians are in need of an open discussion of euthanasia-related issues. The way euthanasia is practiced in the Netherlands has strongly influenced the further development of the debate in Europe. Even though the Dutch model is rejected by the jurisdications of virtually all other countries, and official statements of medical corporations stick to the disapproval of active euthanasia, studies examining the attitudes towards euthanasia and the treatment of it in daily routine show that active interventions to shorten life are performed to different degrees outside of the Netherlands as well.

Europe↗
PubMed1999

Fused bicyclic Gly-Asp beta-turn mimics with specific affinity for GPIIb-IIIa.

Disubstituted isoquinolones 2 and 3 have affinity for GPIIb-IIIa and represent leads for further structural evaluation. Structure-activity studies centered on the bicyclic beta-turn mimic contained in these molecules indicated that this moiety could accommodate a variety of modifications. Specifically, monocyclic, 6, 5-bicyclic, and 6,7-bicyclic structures provide compounds with affinity for GPIIb-IIIa. Within the 6,6-series, isoquinoline, tetralin, tetralone, and benzopyran nuclei yield potent antagonists that are specific for GPIIb-IIIa. Attachment of the arginine isostere (benzamidine) to the supporting nucleus can be accomplished with an ether or amide linkage, although the latter enhances activity. Several compounds in this series provided measurable blood levels after oral dosing. Conversion of the acid moiety in these molecules to an ester generally provided compounds which gave greater systemic exposure after oral administration. Absolute bioavailabilities in the rat for the ethyl ester prodrug derivatives of the tetralin, tetralone, and benzopyran analogues of 3 were 28%, 23%, and 24%, respectively.

Administration, Oral↗
PubMed1999

Basis of phenotypic variability in sporadic Creutzfeldt-Jakob disease.

OBJECTIVE: To determine the correlation of clinical and pathologic features with prion protein (PrP) gene polymorphism at codon 129 and with biochemical characteristics of the protease-resistant PrP (PrPres) in sporadic Creutzfeldt-Jakob disease (CJD). METHODS: Clinical data acquisition, determination of the codon 129 genotype of the PrP gene, brain pathologic study, and immunoblot analysis of crude brain extracts were carried out in 14 patients. RESULTS: The first group of 10 subjects showed the classic clinical triad, with dementia, myoclonus, and periodic sharp waves on EEG. None of the subjects had amyloid plaques, but PrP immunoreactivity was of diffuse synaptic type in the cerebellar cortex. All subjects were methionine-methionine at codon 129 and the PrPres had a biochemical profile of type 1 (unglycosylated band of 21.5 kD). A second group of three patients showed cerebellar ataxia and later dementia. Periodic sharp waves on EEG were absent. PrP amyloid plaques predominated in the cerebellar cortex, along with diffuse PrP immunoreactivity. These subjects were valine-valine at codon 129 and had a type 2 PrPres (unglycosylated band of 19.4 kD). In the last patient cerebellar ataxia and dementia appeared simultaneously. Many Kuru-type plaques were present in the cerebellar cortex; many PrP amyloid plaques were present in the basal ganglia. This patient was methionine-valine at codon 129 and the PrPres was of type 1. CONCLUSIONS: The codon 129 genotype is only one of the factors determining CJD phenotype, and the biochemical pattern of PrP has no direct correlation with this phenotype.

Aged↗
PubMed1999

A mutation at codon 279 (N279K) in exon 10 of the Tau gene causes a tauopathy with dementia and supranuclear palsy.

Recently intronic and exonic mutations in the Tau gene have been found to be associated with familial neurodegenerative syndromes characterized not only by a predominantly frontotemporal dementia but also by the presence of neurological signs consistent with the dysfunction of multiple subcortical neuronal circuitries. Among families, the symptomatology appears to vary in quality and severity in relation to the specific Tau gene mutation and often may include parkinsonism, supranuclear palsies, and/or myoclonus, in addition to dementia. We carried out molecular genetic and neuropathological studies on two patients from a French family presenting, early in their fifth decade, a cognitive impairment and supranuclear palsy followed by an akinetic rigid syndrome and dementia. The proband died severely demented 7 years after the onset of the symptoms; currently, his brother is still alive although his disease is progressing. In both patients, we found a Tau gene mutation in exon 10 at codon 279, resulting in an asparagine to lysine substitution (N279K). Neuropathologically, widespread neuronal and glial tau accumulation in the cortex, basal ganglia, brain stem nuclei as well as in the white matter were the hallmark of the disease. These deposits were shown by immunohistochemistry and immunoelectron microscopy, using a battery of antibodies to phosphorylation-dependent and phosphorylation-independent epitopes present in multiple tau regions. In the neocortex, tau-immunopositive glial cells were more numerous than immunopositive neurons; the deeper cortical layers as well as the white matter adjacent to the cortex contained the largest amount of immunolabeled glial cells. In contrast, some brain stem nuclei contained more neurons with tau deposits than immunolabeled glial cells. The correlation of clinical, neuropathological and molecular genetic findings emphasize the phenotypic heterogeneity of diseases caused by Tau gene mutations. Furthermore, to test the effect of the N279K mutation and compare it with the effect of the P301L exon 10 mutation on alternative splicing of Tau exon 10, we used an exon amplification assay. Our results suggest that the N279K mutation affects splicing similar to the intronic mutations, allowing exon 10 to be incorporated more frequently in the Tau transcript.

Adult↗
PubMed1999

Improvement of tumor cell depletion by combining immunomagnetic positive selection of CD34-positive hematopoietic stem cells and negative selection (purging) of tumor cells.

One possible reason for relapse after high-dose chemotherapy is retransplantation of tumor cells contaminating autologous hematopoietic stem cell transplants. Residual tumor cells can be diminished by various purging methods. We studied tumor cell depletion by sequentially combining immunomagnetic positive selection of CD34+ hematopoietic stem cells using Isolex50 or Isolex300SA and negative tumor cell depletion using MACS, MaxSep or Isolex50 systems. Using these separation systems in different selection sequences, i.e. positive followed by negative selection (+/- selection) or vice versa, four groups of double selections (Isolex50/MACS, Isolex50/MaxSep, MaxSep/Isolex50, Isolex300SA/Isolex50) were studied. Testing these double-purging procedures mean additional tumor cell depletion (deltaTCD) achieved by the second selection step ranged from 1.1+/-0.58 log (n = 5, +/- Isolex50/MACS) to 2.0+/-1.1 log (n = 7, -/+ MaxSep/Isolex50). Loss of CD34+ cells during double selection sometimes was extensive and mean yield of CD34+ cells ranged from 12.8+/-11.5% (n = 6, +/- Isolex50/MaxSep) to 43.2% (n = 2, +/- Isolex300SA/Isolex50). Calculated values for mean yield-corrected deltaTCD ranged from 0.64+/-0.3 log (n = 5, +/- Isolex50/MACS) to 1.4+/-1.3 log (n = 7, -/+ MaxSep/Isolex50). During positive selection of -/+ selection (MaxSep/Isolex50) relative tumor cell enrichment was detectable leading to an increment of mean tumor cell contamination rate. Best results for total TCD were achieved by the combination of Isolex50/MaxSep (n = 6; TCD: 4.2 log; yield CD34+: 12.8%) and Isolex300/Isolex50 (n = 2; TCD: 3.8 log; yield CD34+: 43.2%). Furthermore, we have established and tested a new simultaneous +/- selection method by using CD34-specific releasing agent PR34+ in the Isolex300i. With this method we have obtained a mean total yield-corrected TCD of 4.7 log (n = 4; range: 4.1-6.0 log) with high CD34+ cell yield (mean: 69.8%) and CD34+ cell purity (mean: 92.8%). Since this new simultaneous +/- purging procedure is safe, applicable within a closed system (GMP-like) and most effective, we recommend it for further testing in a clinical setting.

Antigens, CD34↗
PubMed1999

Efficacy and safety of simultaneous immunomagnetic CD34+ cell selection and breast cancer cell purging in peripheral blood progenitor cell samples used for hematopoietic rescue after high-dose therapy.

We have established a new simultaneous positive/negative selection procedure using the Baxter Isolex 300i system. We tested its tumor cell (TC) purging efficacy by tumor contamination tests ex vivo and its safety in a group of 17 breast cancer (BC) patients by measuring hematopoietic recovery after high-dose (HD) therapy and autologous stem cell rescue with the selected cells. Tumor contamination tests resulted in a TC depletion of 4.1-6.0 log steps. The CD34+ cell yield in this experimental setting was 38.9-91.5%, and the CD34+ cell purity was 86.0-96.0%. In a group of 17 BC patients (5 high-risk adjuvant, > or = 10 lymph nodes positive, and 12 metastatic), we processed leukapheresis products (LPs) by simultaneous positive/negative selection. In these clinical samples, the mean CD34+ cell yield was 56.2% (range, 14.0-80.1%), and the CD34+ cell purity was 94.5% (range, 69.0-99.8%). Additionally, we screened samples of the patients' LPs before and after the purging procedure for contaminating TC by immunocytochemistry. In 15 of 17 tested cases, TCs were detectable prior to the purging procedure. After the procedure, we could not detect residual TCs in 16 of 17 cases. In one case, we found a highly reduced number of TCs. Furthermore, we evaluated the times for hematopoietic reconstitution in a group of five BC patients in the high-risk adjuvant situation who underwent HD chemotherapy and hematopoietic rescue with positive/negative selected stem cells and compared it with our own data from 10 BC patients who, after identical HD therapy, received only positively selected CD34+ cells and 14 patients who, after identical HD therapy, received autografts purged by incubation with toxic ether lipids (ET-18-OCH3). In all groups, a leukocyte count of >2000 cells/microl was reached at day +10. A platelet count of > 50,000 cells/microl was reached at day +12 in the ET-18-OCH3 group and at day +14 in the other two groups. Furthermore, 12 patients with metastatic disease rescued with positive/negative selected stem cells after HD therapy also showed fast and comparable hematopoietic recovery. The new simultaneous immunomagnetic positive/negative selection using a closed system is effective and safe. Processing LPs leads to a similar CD34+ cell yield, a higher TC depletion compared to standard CD34+ cell selection, and no delay in hematopoietic recovery.

Antigens, CD34↗
PubMed1999

Gerstmann-Sträussler-Scheinker disease and the French-Alsatian A117V variant.

Gerstmann-Sträussler-Scheinker disease is a rare familial form of prion disease. This autosomal dominant disorder is constantly associated with a point mutation on the PrP gene. Eight mutations affecting respectively codons 102, 105, 117, 145, 202, 212 and 218, have been so far described. Symptoms are variable and include ataxia and dementia. They generally appear between the fourth and sixth decade. Mean duration of the disease (5 years) is on the whole longer than that of other familial forms of prion diseases. Gerstmann-Sträussler-Scheinker disease is neuropathologically characterized by the presence of numerous multicentric or unicentric PrP amyloid deposits widespread throughout the encephalon. Spongiform change is inconstant. Neurofibrillary tangles have been described in some families. Clinicopathological features show considerable variability. Pathogenesis of amyloidosis and associated lesions as well as factors underlying the phenotypic polymorphism of the disease remain only partially known.

Adult↗
PubMed1998

Magnetic resonance imaging of PLP-induced experimental allergic encephalomyelitis in Lewis rats.

An in vivo magnetic resonance (MR) imaging study was performed on experimental allergic encephalomyelitis (EAE) induced in Lewis rats through proteolipid protein (PLP). PLP was solubilized in water or in an aqueous solution of 1% 10-tridecyl ether (TDE), a non-ionic detergent used in membrane protein research. All 16 rats immunized with 500 microg of TDE-solubilized PLP developed clinical signs and MR abnormalities fully comparable to those observed in MBP-induced EAE. Total paraplegia was observed in 12.5% of rats, mild or moderate paraparesis in 68.8% of rats and tail paralysis in the remaining 18.7% of rats. Whereas only 37.5% of the eight rats immunized with 500 microg of water-solubilized PLP developed minor clinical signs (tail weakness or paralysis). Our observations confirm that the difficulties encountered when trying to induce EAE by means of PLP arise from the highly hydrophobic nature of this protein. Accordingly, if a reproducible model is to be developed, it seems more judicious to use non-ionic detergents in both the extraction and solubilization phases of PLP preparation, this would allow maximal solubilization of the protein while avoiding aggregates, which may otherwise form during either of the PLP preparation.

Animals↗