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Biomedical subjects

C Pfeiffer

Publications and source records attributed to C Pfeiffer.

At least 37 records · Page 2Linked to original sources

Chemotherapy for disseminated actinic keratoses with 5-fluorouracil and isotretinoin.

BACKGROUND: Disseminated actinic keratoses are a therapeutic problem. OBJECTIVE: Our purpose was to evaluate the efficacy of a combination of topical 5-fluorouracil twice a day and 20 mg of oral isotretinoin daily for disseminated actinic keratoses. METHODS: Twenty-seven patients who had disseminated actinic keratoses (3 women, 24 men) were treated with 5-fluorouracil (5%) twice a day applied to the photodamaged area bearing actinic keratoses along with oral isotretinoin, 20 mg daily. The median treatment time was 21 days. RESULTS: Actinic keratoses disappeared and signs of photodamaged skin improved in all patients. Side effects were burning and itching as well as painful erosions during the final stage of treatment. CONCLUSION: The combination of topical 5-fluorouracil and isotretinoin is highly effective in the treatment of disseminated actinic keratoses on photodamaged skin.

Administration, Oral↗

[Childhood and violence: perpetrator and victim perspectives from the viewpoint of criminology].

Police crime statistics show a significant increase in the rates of violent crimes committed by children during the last two years. However, since in Germany children under the age of 14 are not accountable for criminal offences, these statistics are highly selective. On the other hand, police crime statistics also show a huge increase of violent crimes committed by juveniles and young adults which cannot be explained by changes of police intervention strategies. It seems reasonable to attribute this mainly to changed living conditions of young people, particularly the increase proportion of children and adolescents living below the thresholds of poverty. To put the issue of violence and children in perspective, the victimization of children should not be overlooked. Criminological as well as psychological research show the devastating consequences of physical and sexual abuse experiences during childhood. Results of a representative german survey concerning the prevalence of violent victimization experiences during childhood are presented. 13.5% of the male and 16.1% of the female respondents had been victims of severe physical or sexual abuse during childhood. If repeatedly witnessing parental violence is additionally taken into consideration, these rates are 18.3% for male and 20.5% for female respondents. A comparison of age groups failed to identify significant differences of victimization rates, except the rates of minor violence committed by parents. Thus it can be assumed tentatively, that the proportion of children subjected to severe violent acts committed by closely related adults as well as the rate of those witnessing parental violence has remained constant over time.

Adolescent↗

Polymorphisms of apolipoproteins A-IV and E in a Turkish population living in Germany.

Human apolipoproteins (apo) E and apo A-IV are polymorphic with significantly different allele frequencies among different ethnic groups. Whereas the variation at the apo E gene locus affects plasma cholesterol levels in all populations studied so far and is associated with longevity in Caucasians, the influence of the common apo A-IV polymorphism on plasma lipoproteins has not been unanimously accepted. We have therefore determined the common apo E and apo A-IV polymorphisms by isoelectric focusing, calculated the respective allele frequencies and studied their effects on plasma lipoproteins in a random sample of 240 nonrelated Turkish subjects (141 males, 99 females) living in Germany and originating from central and eastern Anatolia. When compared with the German population and other Caucasians in Europe a prominence of the apo epsilon 3 allele frequency (0.885) was accompanied by a decrease in the frequencies of both the apo epsilon 2 allele (0.048) and the apo epsilon 4 allele (0.067). Thus, the Turkish population studied here clustered with populations mainly from southern Europe and Japan, which have low epsilon 2 and epsilon 4 allele frequencies. Also, the frequency of the A-IV-1 allele was higher (0.967) and that of the A-IV-2 allele lower (0.033) in the Turkish subjects studied than in other populations. At an average level of total cholesterol of 194.5 +/- 45 mg/dl, no significant influence of the A-IV alleles on plasma lipoproteins was seen. However, apo E and apo B differed significantly between apo E phenotypes, with high levels of apo E and low levels of cholesterol and apo B in carriers of the epsilon 2 allele, and vice versa for the epsilon 4 allele. The average cholesterol excess for the epsilon 2 allele was -7.95 mg/dl, for the epsilon 3 allele, -1.34, and for the epsilon 4 allele, + 14.15 mg/dl. Thus, despite the unusual frequency distribution of the apo E alleles, their effects on plasma lipoproteins are within the range reported for other populations in Europe.

Adolescent↗

The effects of acute exercise on metabolic control in type II diabetic patients treated with glimepiride or glibenclamide.

The effects of exercise on metabolic control in type II diabetic patients given glimepiride or glibenclamide were studied in a multinational phase II clinical trial (14 centers in 4 countries). A total of 167 type II diabetic out-patients (117 men, 50 women) completed the trial as planned. The study was of parallel group, 2 x 2 factorial design: patients were first stabilized in a randomized, double-blind manner on 3 mg of glimepiride or 10 mg of glibenclamide treatment once daily over 14-28 days and were then assigned in randomized open fashion to a group with or without exercise. Exercise consisted of riding a bicycle ergometer for 1 hour at pulse rate 120 beats per minute. Three-hour blood glucose, insulin, and C-peptide profiles were made after the stabilization phase (baseline profiles) and 7 days later with or without exercise (endpoint profiles). Pairwise comparisons of changes in blood glucose AUC/1-3 h revealed a statistically significant decrease in patients who exercised vs those who did not, which was comparable for both sulfonylureas used. There was a statistically significant decrease in C-peptide AUC/1-3 h and insulin AUC/1-3 h in the glimepiride exercise group vs the glimepiride group without exercise. Physical exercise did not lead to statistically significant changes in C-peptide AUC/1-3 h and insulin AUC/1-3 h under glibenclamide treatment. In conclusion, a blood-glucose-lowering response to acute exercise was demonstrated in type II diabetic patients treated with either sulfonylurea, but a significant suppression of endogenous insulin secretion was observed for glimepiride only.

Adult↗

Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+ T cells.

Naive CD4+ T cells can differentiate into cells predominantly involved in humoral immunity, known as T helper type 2 cells (Th2), or cells involved in cell-mediated immunity, known as Th1 cells. In this report, we show that priming of CD4+ T cells bearing a transgene-encoded T cell receptor can lead to differentiation into Th1-like cells producing abundant interferon gamma when the cells are exposed to high antigen doses, while low doses of the same peptide induce cells with the same T cell receptor to differentiate into Th2-like cells producing abundant interleukin 4. Thus antigen dose is one factor that can control the differentiation fate of a naive CD4+ T cell.

Animals↗

Altered peptide ligands can control CD4 T lymphocyte differentiation in vivo.

Antigen priming of naive CD4 T cells can generate effector CD4 T cells that produce interleukin 4 (T helper [Th]2-like) or interferon-gamma (Th1-like). Using a system in which priming leads to responses dominated by one or the other of these cell types, we show that varying either the antigenic peptide or the major histocompatibility complex class II molecule can determine whether Th1-like or Th2-like responses are obtained. Our results show that peptide/major histocompatibility complex class II complexes that interact strongly with the T cell receptor favor generation of Th1-like cells, while those that bind weakly favor priming of Th2-like T cells. Thus, signals from the T cell receptor can influence the differentiation of CD4 T cells into specific types of effector cells.

Animals↗

Parenteral application of a Pseudomonas aeruginosa flagella vaccine elicits specific anti-flagella antibodies in the airways of healthy individuals.

To test the hypothesis that a Pseudomonas aeruginosa flagella (FLA) vaccine, intramuscularly administered, elicits specific antibodies in the respiratory tract, antibody titers against FLA were determined in sera and bronchoalveolar lavage (BAL) fluids of 10 healthy human adults before and after immunization. Immunization produced significantly increased anti-FLA antibody titers in all sera (mean reciprocal titers: IgG: 26,711; IgA: 2,767; IgM: 421) and on respiratory epithelial lining fluids (mean reciprocal titers: IgG: 112; IgA: 76; sIgA: 26). Significant differences in class-specific serum and BAL anti-FLA titers suggested airway antibody production. The study shows that parenteral immunization provides not only high systemic antibody titers but also local antibody production in the human respiratory tract.

Adult↗

Clozapine therapy for Parkinson's disease and other movement disorders.

Recent research on the role of clozapine in the treatment of Parkinson's disease and other movement disorders is discussed. Most clinical trials have shown resolution of or improvement in psychotic symptoms accompanying Parkinson's disease without worsening of parkinsonian symptoms. Adverse effects appear to be mild at dosages of < 100 mg/day; sedation is the most frequent problem. Most of these studies have serious limitations, however; until better studies have been completed, the decision to use clozapine for Parkinson's disease-related psychosis should be made on a case-by-case basis, with thorough evaluation of risks, benefits, and other therapeutic options. Some patients with Parkinson's disease have shown improvement in tremor and other abnormal movements when given clozapine. Clozapine cannot be recommended for treating tardive dyskinesia on the basis of the research done so far; some trials show dramatic resolution of symptoms, others no benefit. Anticholinergics or dopamine-reuptake inhibitors should be considered before clozapine is given to patients with tardive dyskinesia because of clozapine's potential for serious adverse effects. A few patients with Huntington's disease have responded to clozapine, but again no conclusions can be drawn. Clozapine appears to offer no real advantage over haloperidol for treating choreiform movements in Huntington's disease. The frequency of tics in Tourette's syndrome does not seem to be reduced by clozapine. Clozapine has shown some efficacy as a treatment for psychosis and abnormal movements in Parkinson's disease. Results have been less promising for other movement disorders. Further study in larger populations is needed before any definitive conclusions about clozapine's place in movement disorder therapy can be made.

Clinical Trials as Topic↗

[Dietary folates--a timely review. Stability, physiological significance, bioavailability, analytical determination methods, effect of food handling].

Because of the unequal and, in some instances, low stability of different folate vitamers against extreme conditions the analytical determination of folate and the estimation of folate losses in food processing and preparation cause considerable difficulties. HPLC allows determination of the native folate derivative patterns. As the bioavailability of folates is influenced by a variety of factors and different methods were employed for assessing bioavailability there is a considerable inconsistency in the results of these studies. Folates labeled with radioactive or stable isotopes provide new approaches to metabolic and bioavailability studies.

Animals↗

Major histocompatibility complex (MHC) control of CD4 T cell subset activation. II. A single peptide induces either humoral or cell-mediated responses in mice of distinct MHC genotype.

CD4 T cells activated in vivo in response to human collagen type IV (hCol IV) resemble either T helper type 1 (Th1) or Th2 cells depending on the major histocompatibility complex (MHC) class II genotype of the responding mice. H-2s mice were shown to selectively activate Th1-like cells, releasing interleukin (IL 2 and interferon-gamma in response to hCol IV, whereas H-2b.d mice were shown to selectively activate Th2-like cells, releasing IL 4 and IL 5 in response to hCol IV. These results suggested that MHC class II regulated the type of effector function observed during an immune response. It was of interest to determine if the functional difference observed between the CD4 T cells of the two strains was due to the presentation of different peptides of the hCol IV molecule by the two MHC class II molecules. The present results demonstrate that a single peptide of the collagen IV molecule will elicit a Th1-like response in H-2s strains and Th2-like responses in H-2b.d strains, as was observed when using the intact hCol IV molecule. Furthermore, the failure to generate Th1-like responses in H-2b.d could be overcome by increasing the dose of this peptide in vitro. Compared to H-2s, the Th1-like response in H-2b required 100 times the amount of peptide to reelicit an equivalent response. These data suggest that a single peptide of hCol IV can control the type of effector response observed.

Amino Acid Sequence↗

Bilateral olfactory dysfunction in early stage treated and untreated idiopathic Parkinson's disease.

Decreased olfactory function is among the first signs of idiopathic Parkinson's disease (PD). Whether such dysfunction is present to the same degree on both sides of the nose, however, is unknown. Furthermore, whether the deficit results from or is influenced by anti-Parkinsonian medications has not been definitely established. Odour identification ability was evaluated on the left and right sides of the nose in 20 early-stage untreated PD patients, 20 early-stage treated PD patients, and 20 controls. In all cases, the PD related olfactory dysfunction was bilateral and no difference was observed between the test scores of patients taking or not taking drugs for PD. Although asymmetries of unsystematic direction were present in the test scores of some PD patients, similar asymmetries were observed in the controls and the asymmetries were not related to the side of the major motor dysfunction. As in earlier work, no relation was present between the olfactory test scores and the degree of tremor, rigidity, bradykinesia, or gait disturbance at the time of testing. These findings indicate that the olfactory dysfunction of early stage PD is robust, typically of the same general magnitude on both sides of the nose, and uninfluenced by anti-Parkinsonian medications.

Age Factors↗

Characterization of an isoelectric focusing variant of SAA1 (ASP-72) in a family of Turkish origin.

An acidic variant of serum amyloid A (SAA) identified previously by isoelectrofocusing in a family of Turkish origin has been characterized at the genomic level. DNA sequence analysis revealed that individuals expressing the variant pI6.1/pI5.7 isoforms (the mother and three of four children) were heterozygous at the SAA1 gene locus. Their SAA1 gene sequences contained an adenine, as well as the usual guanine, at the position corresponding to the second base of codon 72. The presence of both bases predicts two SAA1 protein sequences, one having aspartic acid and the other glycine at position 72. While the Gly-72 SAA1 (+/- Arg-1) sequence represents the normal pI6.5/pI6.0 isoforms, the Asp-72 SAA1 (+/- Arg-1) sequence corresponds to the variant pI6.1/pI5.7 isoforms.

Adult↗

IL-4 is required for the IgE and IgG1 increase and IgG1 autoantibody formation in mice treated with mercuric chloride.

Previous studies have established that in susceptible mouse strains, such as A.SW (H-2s), repeated injections of subtoxic doses of HgCl2 induce increased serum levels of total IgE and IgG1, high serum titers of antinuclear autoantibodies (ANo1A), and immune-complex glomerulonephritis. Moreover, it has been shown that susceptibility is determined by H-2As and that Th cells are required for the induction of these immunopathologic alterations by HgCl2. In the present study we showed that treatment in vivo with anti-IL-4 mAb completely abrogated the HgCl2-induced increase in total IgE and partially inhibited the increase in IgG1, but failed to suppress the increase in IgG2A. Furthermore, we showed that IL-4 influences the pattern of IgG subclass distribution among ANo1A of HgCl2-treated mice. Whereas treatment with anti-IL-4 mAb significantly reduced the titers of IgG1 ANolA, it increased those of IgG2A, IgG2B, and IgG3 ANolA. Thus, these results show that IL-4 contributes to the optimal formation in vivo of murine IgG1 and that it is involved in the autoantibody formation of a systemic autoimmune disease. The available evidence suggests that HgCl2 induces an increased production of IL-4 by Th2 cells. If this is correct, it implies that MHC class II alleles determine whether the preferential response to HgCl2 is made by Th1 or Th2 cells and, hence, the type of immunopathologic alterations ensuing.

Animals↗

Selective activation of Th1- and Th2-like cells in vivo--response to human collagen IV.

Mice immunized with human collagen IV develop either antibody responses or T-cell proliferative responses as a function of the MHC genotype of the immunized mice. CD4+ T cells, similar to Th1 and Th2 cells, participate in these two types of responses, with CD4+ T-cell proliferative responses associating with IL-2 and IFN gamma release, and antibody production associating with CD4+ T-cell IL-4 and IL-5 release. Thus it would appear that the same antigen can induce responses consistent with either cell-mediated or humoral immunity depending on MHC class II genotype. In attempting to understand how MHC genotype controls the class of immunity observed several models are discussed. It was proposed, based on results obtained upon priming with human collagen IV, that the activation of Th1 and Th2 responses may be regulated at several levels (presentation by different APCs, presentation of different densities of the T-cell receptor ligand and presentation of different T-cell epitopes). With the identification of the peptide recognized by the CD4+ T cells, it was clear that the inability to induce Th1 responses in H-2b and the inability to induce Th2 responses in H-2s could not be accounted for by the failure to generate an immunodominant peptide during processing or the failure of the peptides to bind to the MHC class II molecules. Furthermore, the difference in the type of response generated could not be explained by the use of different peptides of the human collagen IV molecule in the two mouse strains, as a single peptide will induce both types of CD4+ T-cell response. However, it cannot be ruled out that the a2 peptide-class II interaction forms different T-cell ligands in the two strains either because the two class II MHC molecules are different or that the peptide is processed and reveals a different antigenic activity (Fox et al. 1988). Perhaps the most important finding from the peptide studies is that the lack of proliferative response in H-2b mice is not absolute, but can be overcome either by priming with high doses of the a2 peptide or by increasing the amount of peptide needed to elicit a recall response. It seems reasonable to speculate that changes in the dose required for priming Th1 or Th2 responses may reflect differences in the activation requirements of the two types of cells with Th1 cells requiring a high ligand density and Th2 cells a low ligand density.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Assessment of the efficacy, tolerance, and safety of ramipril in diabetic patients with mild-to-moderate hypertension: a retrospective analysis.

Six double-blind studies were designed to assess the efficacy, tolerance, and safety of the angiotensin-converting enzyme inhibitor ramipril in patients with mild-to-moderate essential hypertension. Of 1,189 hypertensive patients in these studies, 105 patients were diabetic. They were randomly assigned either to a ramipril monotherapy group (1.25-10 mg/day) or to one of the following treatment groups: ramipril (5 mg/day) plus piretanide (3 mg/day), captopril (100 mg/day), enalapril (10-20 mg/day), hydrochlorothiazide (50 mg/day), or atenolol (100 mg/day). In all studies, a 4-week single-blind placebo run-in phase was followed by a 6-week double-blind active treatment phase. Significant reductions in blood pressure were achieved with all antihypertensive agents. No statistically significant deleterious effects were observed on concentrations of blood glucose, although diabetics who received hydrochlorothiazide showed slight increases in blood glucose levels. Ramipril was well tolerated by diabetic patients, and no serious adverse events occurred. Adverse events reported were typical of ACE inhibitors.

Adolescent↗

Immunological alterations inducible by mercury compounds. III. H-2A acts as an immune response and H-2E as an immune "suppression" locus for HgCl2-induced antinucleolar autoantibodies.

In responder mouse strains repeated injections of subtoxic doses of HgCl2 induce formation of antinuclear autoantibodies (ANA) and antinucleolar autoantibodies (ANolA). Others have shown that responsiveness to HgCl2-induced formation of ANA and ANolA is linked to H-2. Here, we extend these studies to a variety of mouse strains not tested previously. After confirming that strain B10.S (H-2s) is a high responder we have shown that strains B10.D2 (H-2d) and B10.BR (H-2k) are nonresponders. By comparing a panel of strains carrying appropriate intra-H-2 recombinant haplotypes derived from d, k and s, we were able to map responsiveness to As. Interestingly, among four strains all of which were As, and thus responsive, only the two H-2E- ones, B10.S and B10.RSD2, were high responders whereas the two H-2E+ ones, B10.HTT and B10.S(9R), were significantly less responsive. Thus, the genetics of HgCl2-induced autoantibody formation follow the rules established for immune responses to a variety of different antigens in that expression of H-2E "suppressed" the response.

Animals↗