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S Schweitzer

Publications and source records attributed to S Schweitzer.

At least 19 recordsLinked to original sources
PubMed2004

[Patients as partners. Tumor patients and their participation in medical decisions].

Between March 2002 and August 2003 as part of the research project "Patients as partners -- tumour patients and their participation in medical decisions" tumour patients undergoing palliative therapy (n=272) were interviewed and asked about their level of information, their desired place to die and whether they had prepared an advance directive. Furthermore, 72 relatives of deceased patients who had been looked after by the project's palliative care team were given a similar questionnaire including questions concerning their knowledge about disease and prognosis, the actual place of death and the relevance of advance directives. According to patients and relatives, information particularly about prognosis is unsatisfactory. Of the inter-viewed patients, 75% said they wanted to die at home and 15% in a hospital. According to their relatives, 36% of the patients looked after by the palliative care team had an advance directive. The survey of the relatives showed a significant relation between the preparation of an advance directive and dying at the desired place. According to the relatives, medical and health reasons, hope for an improvement up to the very end,acute worsening of the condition and deficits in medical care were important reasons for dying in hospital against the patient'swish. In future, advance directives should be used as an aid for communication and the planning of care. Therefore, cooperation between doctors and patients based on a partnership is necessary. The required competence in communication should be improved.

Adolescent↗
PubMed2003

[Ambulant care of patients in the terminal phase of malignant tumor: answers by general practioners in Thuringia to a questionnaire].

BACKGROUND AND OBJECTIVE: Palliative care and care of the dying are not widely taught in medical education. Yet, through the guidelines of the Federal Medical Council (Bundesärztekammer), doctors are obliged professionally to accompany the dying process. Systematic studies concerning doctors' motivation and action in this special situation are rare. This study aims to evaluate the views and attitudes of general practitioners towards the care for cancer patients in the terminal stage of disease. METHODS: In association with the project of the German Ministry of Health "Patienten als Partner-Tumorpatienten und ihr Mitwirken in medizinischen Entscheidungen" ("Patients as partners: patients with malignant tumor and their collaboration in medical decision making"), a questionnaire was designed for general practitioners based on qualitative interviews. The self-guiding questionnaire comprised questions concerning death and dying, patient-doctor relationship and day-to-day medical actions. RESULTS: 505 general practitioners (GPs) received the questionnaires. 170 were filled in and sent back (33%). The GPs felt responsible for the care of the dying patients. Pain control was the main goal (97%). Symptom control was thought to be important/very important in 87%, the application of life-prolonging measures in 12 %. Basic analgesic medication was prescribed by 93% of GPs. 89%/77% of the general practitioners answered that they were satisfied with the technical equipment of the hospital/clinic, whereas there was a dissatisfaction with psychological and spiritual support. CONCLUSION: General practitioners widely accept their responsibility for the care of the dying patients. Pain control is the major goal in this group of patients. Some items (use of co-analgesia, prescription of peak analgesia) seem to be open to improvements. Despite a high motivation, general practitioners show their dissatisfaction with some aspects of the care for dying people. Palliative care teams could be helpful in this situation.

Ambulatory Care↗
PubMed2001

Lipidation of T helper sequences from hepatitis C virus core significantly enhances T-cell activity in vitro.

Successful elimination of the hepatitis C virus (HCV) during acute infection has been linked to strong HCV-specific in vitro T-cell proliferation, whereas T cells from patients with chronic hepatitis C respond only weakly to HCV antigens. Lipid-coupled peptides are immunostimulants, which might provide a basis for novel therapeutic strategies against HCV. Therefore, in 20 patients with chronic hepatitis C, we studied whether tri-palmitoyl-S-cysteine-coupled peptides could modify in vitro T-cell proliferation (by [3H]thymidine uptake) in response to virus core and NS4. The lipopeptides corresponded to five immunodominant T helper epitopes of HCV core. Contrary to unmodified peptides, the lipopeptides specifically enhanced [3H]thymidine uptake in response to HCV antigens but not to a non-HCV related control antigen. They increased the frequency of responders (stimulation index, SI > or = 4) to core (13/20 versus 2/20; p = 0.0008) and NS4 (20/20 versus 7/20; p < 0.0001) among our patients with chronic hepatitis C. This immunostimulatory effect was dose-dependent, and was observed specifically with lipopeptides corresponding to the HCV epitopes. Our data demonstrate that the poor in vitro T-cell proliferation of patients with chronic hepatitis C can be improved when T cells are co-stimulated with HCV core-derived T helper lipopeptides, while the same peptides in unlipidated form had no effects. Thus, lipopeptides corresponding to HCV T-cell epitopes may offer novel immunomodulatory strategies against HCV.

Adult↗
PubMed2000

Flow cytometric analysis of peptide binding to major histocampatibility complex class I for hepatitis C virus core T-cell epitopes.

BACKGROUND/METHODS: To characterize the repertoire of T-cell epitopes on the hepatitis C virus (HCV) core protein, we studied major histocompatibility complex (MHC) class I binding of 75 decapeptides on 20 human B-cell lines and murine spleen cells using a flow cytometric assay. The results were compared with MHC class I stabilization on T2 cells, the SYFPEITHI algorithm, and known T-cell epitopes from the literature. RESULTS: Binding of peptides proved to be specific for MHC class I molecules. We observed peak fluorescence signals at positions amino acids (aa) 35-44, aa 87-96, aa 131-140, and aa 167-176 in virtually all HLA-A2-positive cell lines. These sites corresponded to T-cell epitopes predicted by SYFPEITHI and the positions of known T-cell epitopes, whereas T2 stabilization was at variance for two peptides. The assay was applied to HLA-A2-negative cells and murine spleen cells without further modification, and identified additional peptides, corresponding to known T-cell epitopes. CONCLUSIONS: Peptide binding to different MHC class I alleles can be mapped rapidly by a flow cytometric assay and enables a first orientation on the sites of possible T-cell epitopes. Application of this assay to HCV core suggests a rather limited repertoire of epitopes in the Caucasoid population.

Animals↗
PubMed2000

A hepatitis C virus (HCV) core protein derived peptide inhibits HCV specific lymphocyte proliferation.

T helper lymphocytes are important regulatory cells for the immune response in chronic hepatitis C. They recognize peptides, which are generated from the viral proteins by antigen processing and are bound to MHC (major histocompatibility complex) class II molecules. However, antigen processing might also result in non-immunogenic peptide fragments that can modify T cell activation. - To identify such peptide fragments in hepatitis C, we studied binding of 15 synthetic HCV core derived peptides to MHC class II molecules of 9 human homozygous typing B cell lines (HT-BCLs) as well as T cell proliferation in 41 HLA-typed patients with chronic hepatitis C. - We identified a peptide (HCV core aa 59-83) which bound to 7 HT-BCLs, whereas PBMC of only 2 out of 36 patients with the corresponding HLA-DR alleles proliferated in response to this peptide. Competition experiments indicated that small amounts of peptide aa 59-83 specifically inhibited the proliferative response to the recombinant core protein but not to core derived immunogenic peptides. Our data show that a peptide fragment from the HCV core region aa 59-83 can interfere in vitro with immune recognition of the HCV core protein.

B-Lymphocytes↗
PubMed2000

Effect of sodium benzoate in the treatment of atypical nonketotic hyperglycinaemia.

A 6-month-old girl presented with hypotonia and mild psychomotor retardation. Subsequently, an atypical manifestation of a nonketotic hyperglycinaemia was diagnosed, confirmed by significantly reduced activity of the glycine cleavage system in the liver tissue. After the patient developed hypsarrhythmia and had a single cerebral seizure, treatment with both sodium benzoate and dextromethorphan was started. During the following year, the girl was free of seizures with improvement of the EEG activity and showed retarded but continuously progressing psychomotor development. At the age of 20 months she began to walk freely but had generalized muscular hypotonia and moderate mental retardation. Discontinuation of dextromethorphan medication after one year of treatment did not change the clinical and electroencephalographic status. However, after cessation of sodium benzoate therapy, epileptic activity in the EEG and behavioural changes occurred. These changes disappeared promptly after sodium benzoate therapy was reinstituted. Thus, this case of mild atypical nonketotic hyperglycinaemia with only moderate psychomotor retardation and without epilepsy benefited from treatment with sodium benzoate in terms of electroencephalographic and behavioural changes.

Electroencephalography↗
PubMed1999

Carnitine transporter OCTN2 mutations in systemic primary carnitine deficiency: a novel Arg169Gln mutation and a recurrent Arg282ter mutation associated with an unconventional splicing abnormality.

Systemic primary carnitine deficiency (CDSP, MIM 212140) is a disorder of fatty acid oxidation manifesting in acute metabolic decompensation or in progressive cardiomyopathy and muscle weakness. Mutations in the plasmalemmal organic cation/carnitine transporter OCTN2 were recently identified in CDSP patients of diverse ethnic backgrounds. We have performed OCTN2 mutation analysis in two unrelated German patients with primary carnitine deficiency and identified three molecular abnormalities. On one of the four chromosomes analyzed, we detected an Arg169Gln missense mutation that affects an arginine residue absolutely conserved in the entire transporter superfamily to which OCTN2 belongs. On the three other chromosomes, we found an Arg282ter nonsense mutation in exon 5. This mutation is embedded into different haplotypes of closely spaced intragenic dimorphisms in our two patients and was recently described in a patient of Asiatic Indian background, so it appears to be a recurrent or ancient founder mutation that may account for more CDSP cases. Finally, we found that the Arg282ter nonsense mutation is associated with a splicing abnormality at the intron 6/exon 7 junction. However, no mutations are present in exon 6, intron 6, or exon 7, suggesting that defective splicing of exon 7 on the Arg282ter allele is due to an unconventional, long-distance mechanism.

Adolescent↗
PubMed1999

D-2-hydroxyglutaric aciduria: further clinical delineation.

It has recently been recognized that D-2-hydroxyglutaric aciduria is a distinct neurometabolic disorder with a severe and a mild phenotype. Whereas the clinical and neuroimaging findings of the severe phenotype were homogeneous among the patients, the findings in the mild phenotype were much more variable, leaving the clinical picture poorly defined. We were able to collect the clinical, biochemical and neuroimaging data on an additional 8 patients with D-2-hydroxyglutaric aciduria, 4 with the severe and 4 with the mild phenotype. With the new information, it becomes clear that the mild phenotype shares the essential characteristics of the severe phenotype. The most frequent findings, regardless of the clinical phenotype, are epilepsy, hypotonia and psychomotor retardation. Additional findings, mainly occurring in the severe phenotype, are episodic vomiting, cardiomyopathy, inspiratory stridor and apnoeas. The most consistent MRI finding is enlargement of the lateral ventricles, occipital more than frontal. Regardless of the clinical phenotype, early MRI shows in addition subependymal cysts and signs of delayed cerebral maturation. Later MRI may reveal multifocal cerebral white-matter abnormalities. Two patients had vascular abnormalities, but it is as yet unclear whether these are related to D-2-hydroxyglutaric aciduria or are incidental findings.

Brain↗
PubMed1999

Iron management: innovative solutions to persistent challenges--focus on Ferrlecit.

The use of sodium ferric gluconate in sucrose injection (Ferrlecit) in the treatment of anemia in patients with end stage renal disease (ESRD) was the major topic at the symposium "Iron Management: Innovative Solutions to Persistent Challenges," held April 14, 1999 during the annual ANNA 30th National Symposium in Baltimore, Maryland. Chairperson Susan Vogel, MHA, RN, CNN, addressed the challenges of anemia management and the limitations of oral iron supplements. She described available intravenous (i.v.) iron therapies and reviewed clinical trial data that demonstrated an excellent safety and efficacy profile for the newly approved i.v. iron supplement, sodium ferric gluconate. Suzanne Schweitzer, RPh, MPH, discussed iron metabolism and the U.S. labeling for sodium ferric gluconate, with a focus on dosing and administration. In the final presentation, Suzanne Seiler, RN, described her clinic's experience with sodium ferric gluconate and provided an experimental dosing and monitoring protocol. Together, these presentations suggest that sodium ferric gluconate is an important new tool for meeting the challenges of iron management in ESRD patients.

Anemia, Iron-Deficiency↗
PubMed1998

The combination of interleukin-2 and interferon alpha effectively augments the antibody-dependent cellular cytotoxicity of monoclonal antibodies 17-1A and BR55-2 against the colorectal carcinoma cell line HT29.

Monoclonal antibodies (mAb) are promising substances for the treatment of colorectal carcinoma, but the efficiency of this therapy still needs further improvement. We used a flow-cytometric cytotoxicity test to determine the efficacy of the cytokines interferon alpha (IFNalpha) and gamma (IFNgamma), interleukin-2 (IL-2), macrophage-colony-stimulating factor (M-CSF), granulocyte/macrophage-CSF (GM-CSF) and tumor necrosis factor alpha (TNFalpha) in enhancing the antibody-dependent cellular cytoxicity (ADCC) of the mAb 17-1A and the mAb BR55-2 against the colorectal carcinoma cell line HT29. In experiments performed at an effector to target ratio of 9:1, with peripheral blood mononuclear cells from five healthy volunteers as effector cells, we found that IFNalpha, IFNgamma and IL-2 significantly augmented the ADCC of both mAb at concentrations between 3 ng/ml and 30 ng/ml. The other three cytokines were not effective. In further experiments we examined combinations of the three effective cytokines in different concentrations. The combination of IFNalpha and IL-2 proved to be optimal in enhancing ADCC of both mAb. Thus, the examination of ADCC by flow cytometry may reveal potentially useful combinations of cytokines and mAb for the treatment of colorectal carcinoma.

Antibodies, Monoclonal↗
PubMed1998

A gene on chromosome 11q23 coding for a putative glucose- 6-phosphate translocase is mutated in glycogen-storage disease types Ib and Ic.

Glycogen-storage diseases type I (GSD type I) are due to a deficiency in glucose-6-phosphatase, an enzymatic system present in the endoplasmic reticulum that plays a crucial role in blood glucose homeostasis. Unlike GSD type Ia, types Ib and Ic are not due to mutations in the phosphohydrolase gene and are clinically characterized by the presence of associated neutropenia and neutrophil dysfunction. Biochemical evidence indicates the presence of a defect in glucose-6-phosphate (GSD type Ib) or inorganic phosphate (Pi) (GSD type Ic) transport in the microsomes. We have recently cloned a cDNA encoding a putative glucose-6-phosphate translocase. We have now localized the corresponding gene on chromosome 11q23, the region where GSD types Ib and Ic have been mapped. Using SSCP analysis and sequencing, we have screened this gene, for mutations in genomic DNA, from patients from 22 different families who have GSD types Ib and Ic. Of 20 mutations found, 11 result in truncated proteins that are probably nonfunctional. Most other mutations result in substitutions of conserved or semiconserved residues. The two most common mutations (Gly339Cys and 1211-1212 delCT) together constitute approximately 40% of the disease alleles. The fact that the same mutations are found in GSD types Ib and Ic could indicate either that Pi and glucose-6-phosphate are transported in microsomes by the same transporter or that the biochemical assays used to differentiate Pi and glucose-6-phosphate transport defects are not reliable.

Amino Acid Sequence↗
PubMed1995

Newborn mass screening for galactosemia.

Methods for mass screening of newborns for galactosemia have been available since 1964. Although galactosemia is rare, many countries have included screening for galactosemia in their national screening programs, yet other countries deny the necessity for screening. Despite the early appearance of clinical symptoms, newborns may be reliably diagnosed in time only through mass screening.

Galactosemias↗
PubMed1995

Galactitol in galactosemia.

Urinary galactose and galactitol excretion in controls is age-dependent with the highest concentrations at a younger age. Untreated patients with classical galactosemia excreted highly elevated amounts of galactitol (8000-69,000 mmol/mol creatinine; controls 3-81) which did not correlate with galactose excretion. After treatment, galactose excretion returned to normal in all patients whereas galactitol excretion (45-900 mmol/mol creatinine) remained above the age-matched control range. The excretion of galactitol (96-170 mmol/mol creatinine) in untreated compound heterozygotes was much lower although still above the age-matched control levels, and it returned to normal after treatment. In untreated classical galactosemia patients the galactitol in plasma (120-500 mumol/l) was markedly elevated (controls 0.08-0.86 mumol/l); under treatment, the galactitol concentrations (4.7-20 mumol/l) remained above the control range in all. There was no correlation with age nor with galactose-1-phosphate and UDP-galactose levels. Two untreated compound heterozygotes had elevated plasma galactitol (6.0 and 63 mumol/l) which, when treated, returned to normal.

Age Factors↗
PubMed1995

Biotinidase Km-variants: detection and detailed biochemical investigations.

We describe a simple method for the detection of biotinidase Km-variants and detailed biochemical investigations in 5 such patient. They were detected among 103 patients with plasma biotinidase activity which ranged from undetectable to 30% of the mean normal value. Two different types of biotinidase Km-variants were found. (1) In 3 infants biotinidase had a single 105-430-fold elevated Km for biocytin. Biotinidase showed very low activities (0.2-4% of the mean normal value) in the routine colorimetric assay and was not functional in vivo. Accordingly, these patients presented with classical clinical illness. (2) In two patients biotinidase showed biphasic kinetics indicating the presence of one component with a normal Km and reduced Vmax (1.7% and 12%), and another with 330- and 59-fold elevated Km, respectively. In these two patients, biotinidase proved to be at least partially functional in vivo. However, the first patient developed severe symptoms and biotin deficiency late, at the age of 10-15 years, and the second had marginal biotin deficiency at the age of 2 years but no clinical symptoms. Comparative studies revealed that both patients had more severe biotin deficiency than age-matched patients with similar levels of residual biotinidase activity and a single normal Km. Therefore, all patients with residual biotinidase activity should be evaluated for the presence of a Km-mutation, since such patients should be treated with biotin. These can easily be detected by including a second substrate concentration (1.5 mmol/L) in the routine colorimetric biotinidase assay which is performed with 0.15 mmol/L biotin. Increased activity with the higher substrate concentration indicates the presence of a Km-mutation. Detailed kinetic studies are needed to evaluate the distinct forms of Km-variants.

Amidohydrolases↗
PubMed1993

Long-term outcome in 134 patients with galactosaemia.

In a retrospective study 134 galactosaemic patients, born between 1955 and 1989 in the Federal Republic of Germany were traced and their long-term outcome evaluated. We investigated 83 galactosaemic patients (78 homozygotes, 5 compound heterozygotes) by clinical, psychometric and laboratory testing; 31 patients were evaluated by medical history, the remaining 20 patients had died due to sequelae of the underlying disease. In 48 out of 78 classical galactosaemia patients galactose-free therapy had been started before the 15th day, in 19 between days 15 and 56 and in 11 patients after the 56th day. Physical findings revealed that puberty was delayed in 1 out of 18 males and 6 out of 11 females. Neurological abnormalities included ataxia (n = 6), intention tremor (n = 11) and microcephaly (n = 10). Speech abnormalities were found in 43 out of 66 patients over 3 years of age and disturbance of visual perception and/or arithmetic deficits in 29. Intelligence declined with age, i.e., a DQ or IQ less than 85 was found in 4 out of 34 patients less than 6 years of age (12%), in 10 out of 18 between 7 and 12 years (56%) and in 20 out of 24 older than 12 years (83%). Metabolite patterns (RBC galactose-1-phosphate and UDP-galactose, plasma and urinary galactitol) did not correlate with DQ or IQ. Dietary compliance was good in almost all patients. Compound heterozygotes (n = 5) had normal mental and growth development and all laboratory parameters were in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗