PubMed Health⌕ Search

Biomedical subjects

B Schramm

Publications and source records attributed to B Schramm.

At least 19 recordsLinked to original sources
PubMed2006

Improvement in immune parameters and human immunodeficiency virus-1 viral response in individuals treated with 16alpha-bromoepiandrosterone (HE2000).

A randomised, double-blind, placebo-controlled study examined the safety, tolerance, immunological effect and anti-human immunodeficiency virus (HIV) activity of sub-cutaneously administered HE2000 (16alpha-bromoepiandrosterone) as monotherapy in treatment-naïve patients with HIV-1. Twenty-four patients received five sequential daily doses of 50 or 100 mg of HE2000 or placebo every 6 weeks for up to three courses, and were followed thereafter for 3 months. HE2000 was safe, with transient injection site reactions being the main side-effect. Peripheral blood samples, collected serially, were analysed for changes in immune cell phenotypes. Significant increases were observed in the numbers of circulating dendritic cells, early activated (CD69+ CD25-) CD8 T-cells and T-NK cells after administration of 50-mg doses of HE2000 (p < 0.05). Gene expression in peripheral blood mononuclear cells was analysed by real-time RT-PCR. Before treatment, HIV-1-infected patients had significantly elevated transcripts for a number of inflammatory mediators (p < 0.012). After 50 mg or 100 mg HE2000, but not after placebo, there were significant sustained decreases in IL-1beta, TNF-alpha, IL-6 and Cox-2 transcripts (p < 0.05). There were no significant differences in CD4 cell numbers, although patients receiving 50-mg doses demonstrated a significant decrease in viral load (- 0.6 log; p < 0.01). Anti-HIV-1 T-cell responses were analysed serially using GAG-peptides to stimulate cytoplasmic IFN-gamma responses. After three courses, the 50-mg dose group demonstrated a significant increase in CD8 T-cell response against two distinct GAG peptide pools (p < 0.03). These findings suggest that immune-based therapies may be able to impact viral load by decreasing inflammation and/or stimulating CD8 T-cells.

Adult↗
PubMed2006

Changes in clinical research in anaesthesia and intensive care from 1974-2004.

The purpose was to identify how the quality of anaesthesia research has improved from articles published in Anaesthesia and Intensive Care over 25 years. Original papers were included during the periods 1974-1978 and 2000-2004. Each article was classified according to principal research designs and the two five-year periods were compared. All interventional trials were evaluated according to the following a priori criteria: author number; ethics approval; informed consent; competing financial interest; eligibility criteria; sample size calculation; method of randomization; patients accounted for; blind assessment of outcome; adverse outcomes; statistical method stated; type I error; type II error; and anaesthetic department of origin. Comparisons of above criteria were made between the two groups using chi-square test or Fischer's exact test. Two-hundred-and-ninety-two articles were reviewed in 1974-1978 and 529 articles were reviewed in 2000-2004. Animal/laboratory articles decreased from 17.47% to 12.28% (P=0.05). Review articles decreased from 34.35% to 10.4% (P<0.0001). Descriptive trials increased from 28.4% to 52.72% (P<0.0001). Interventional trials increased from 18.84% to 22.31% (P=0.269). Uncontrolled clinical trials decreased from 27.27% to 12.71%, non-randomized controlled trials decreased from 50.91% to 7.63%, and randomized controlled trials increased from 21.82% to 79.66% (P<0.0001). All interventional trials criteria improved and were statistically significant except competing financial interest, method of randomization, patients accounted for; and type II error The quality of anaesthetic research has improved in Anaesthesia and Intensive Care over the past 30 years. However; there is still room for improvement.

Anesthesia↗
PubMed2003

Cost of illness of atopic asthma and seasonal allergic rhinitis in Germany: 1-yr retrospective study.

The purpose of this study was to evaluate the cost of illness of moderate-to-severe atopic asthma and/or seasonal allergic rhinitis (SAR) in Germany from the perspective of third-party payers (TPP) and patients. Five-hundred patients (276 children/adolescents) with moderate-to-severe asthma and/or SAR were included in this cross-sectional study. Information was collected using a specific patient questionnaire and the abstraction of patient records. Overall, annual costs per patient increased with the severity of atopic asthma and if it was associated with SAR. The average annual cost of SAR was Euro1,089 per child/adolescent and Euro1,543 per adult. Annual costs of severe asthma plus SAR increased to Euro7,928 per child/adolescent and to Euro9,287 per adult. For TPPs, the main cost drivers were medication, hospitalisation, and rehabilitation. The most significant costs for patients were household modifications. For children/adolescents, 60-78% of the expenditures were direct costs, while in adults, 58% of expenditures were indirect costs. It was also observed that patients with moderate and severe asthma used inhaled corticosteroids less frequently than recommended by treatment guidelines. In summary, the total cost for patients increases with the severity of atopic asthma and/or seasonal allergic rhinitis and indirect costs represent a large proportion of the total cost.

Adolescent↗
PubMed2001

Cytopathicity of human immunodeficiency virus type 1 primary isolates depends on coreceptor usage and not patient disease status.

It has been hypothesized that human immunodeficiency virus type 1 (HIV-1) evolves toward increased cytopathicity in conjunction with disease progression in infected patients. A viral property known to evolve in some but not all patients is coreceptor utilization, and it has been shown that a switch in coreceptor utilization is sufficient for the development of increased cytopathicity. To test the hypothesis that the evolution of other viral properties also contributes to accelerating cytopathicity in vivo, we used human lymphoid tissue explants to assay the cytopathicity of a panel of primary HIV-1 isolates derived from various stages of disease characterized by the presence or absence of changes in coreceptor preference. We found no evidence of coreceptor-independent increases in cytopathicity in isolates obtained either before coreceptor preference changes or from patients who progressed to AIDS despite an absence of coreceptor evolution. Instead, the cytopathicity of all HIV-1 isolates was determined solely by their coreceptor utilization. These results argue that HIV-1 does not evolve toward increased cytopathicity independently of changes in coreceptor utilization.

CD4-Positive T-Lymphocytes↗
PubMed2001

Coagulation studies in preoperative neurosurgical patients.

Unselected preoperative coagulation testing is known to have low positive yield. However, no study has specifically evaluated neurosurgical patients. A retrospective study of 1211 patients having neurosurgery over a one-year period was therefore conducted. Preoperative test results (activated partial thromboplastin time [aPTT], prothrombin time [PT] and platelet count) and historical factors indicating a potential bleeding tendency were recorded. Abnormality was defined as a test result outside the normal range for our laboratory. Seventeen per cent of all test results were abnormal. However, if abnormality was redefined as a test result indicating potential bleeding tendency (low platelet count, prolonged aPTT and/or PT), only 7.2% of results were abnormal. Many patients had factors on history indicating a potential bleeding tendency, but only a prolonged aPTT, cranial surgery and the use of anti-hypertensive and anaesthetic drugs preoperatively predicted postoperative bleeding. Prolonged aPTT was predictable on history in most patients. We conclude that routine screening of all preoperative neurosurgical patients in our hospital is unnecessary.

Blood Coagulation↗
PubMed2000

Viral entry through CXCR4 is a pathogenic factor and therapeutic target in human immunodeficiency virus type 1 disease.

The chemokine receptors CCR5 and CXCR4 function as the principal coreceptors for human immunodeficiency virus type 1 (HIV-1). Coreceptor function has also been demonstrated for a variety of related receptors in vitro. The relative contributions of CCR5, CXCR4, and other putative coreceptors to HIV-1 disease in vivo have yet to be defined. In this study, we used sequential primary isolates and recombinant strains of HIV-1 to demonstrate that CXCR4-using (X4) viruses emerging in association with disease progression are highly pathogenic in ex vivo lymphoid tissues compared to CXCR4-independent viruses. Furthermore, synthetic receptor antagonists that specifically block CXCR4-mediated entry dramatically suppressed the depletion of CD4(+) T cells by recombinant and clinically derived X4 HIV-1 isolates. Moreover, in vitro specificity for the additional coreceptors CCR3, CCR8, BOB, and Bonzo did not augment cytopathicity or diminish sensitivity toward CXCR4 antagonists in lymphoid tissues. These data provide strong evidence to support the concept that adaptation to CXCR4 specificity in vivo accelerates HIV-1 disease progression. Thus, therapeutic intervention targeting the interaction of HIV-1 gp120 with CXCR4 may be highly valuable for suppressing the pathogenic effects of late-stage viruses.

Animals↗
PubMed2000

Human immunodeficiency virus type 1 coreceptor preferences determine target T-cell depletion and cellular tropism in human lymphoid tissue.

The present study sought to determine how usage of coreceptors by human immunodeficiency virus type 1 dictates cell tropism and depletion of CD4(+) T cells in human lymphoid tissues cultured ex vivo. We found that coreceptor preferences control the marked, preferential depletion of coreceptor-expressing CD4(+) lymphocytes. In addition, there was a strong, but not absolute, preference shown by CXCR4-using strains for lymphocytes and by CCR5-using strains for macrophages.

CD4-Positive T-Lymphocytes↗
PubMed2000

Cytopathicity of human immunodeficiency virus type 2 (HIV-2) in human lymphoid tissue is coreceptor dependent and comparable to that of HIV-1.

Epidemiological studies have shown that human immunodeficiency virus type 2 (HIV-2) is markedly less pathogenic than HIV-1 in vivo. Individuals infected with HIV-2 exhibit a remarkably slow rate of disease development, and these clinical properties have been attributed presumptively to an "attenuated" phenotype of HIV-2 itself. Here, we investigated the impact of coreceptor usage on the cytopathicity of HIV-2 and compared its pathogenic potential with that of HIV-1 in a unique human lymphoid histoculture model. We found that HIV-2 strains, as well as closely related simian immunodeficiency viruses (SIV), displayed mildly or highly aggressive cytopathic phenotypes depending on their abilities to use the coreceptor CCR5 or CXCR4, respectively. A side-by-side comparison of primary X4 HIV-1 and HIV-2 strains revealed similar, high degrees of cytopathicity induced by both HIV types. Furthermore, we found that HIV-2 coreceptor specificity for CCR5 and CXCR4 determined the target cell population for T-cell depletion in lymphoid tissue. Finally, utilization of the alternate coreceptors BOB and Bonzo did not significantly increase the cytopathic properties of HIV-2. These findings demonstrate that coreceptor preference is a key regulator of target cell specificity and the cytopathic potential of HIV-2, with indistinguishable rules compared with HIV-1. Moreover, HIV-2 strains are not characterized by an intrinsically lower cytopathicity than HIV-1 strains. Therefore, direct cytopathic potential per se does not explain the unique behavior of HIV-2 in people, highlighting that other unknown factors need to be elucidated as the basis for their lesser virulence in vivo.

CD4-Positive T-Lymphocytes↗
PubMed1999

CXCR4 utilization is sufficient to trigger CD4+ T cell depletion in HIV-1-infected human lymphoid tissue.

The human chemokine receptors CCR5 and CXCR4 have emerged as the predominant cofactors, along with CD4, for cellular entry of HIV-1 in vivo whereas the contribution of other chemokine receptors to HIV disease has not been yet determined. CCR5-specific (R5) viruses predominate during primary HIV-1 infection whereas viruses with specificity for CXCR4 (R5/X4 or X4 viruses) often emerge in late stages of HIV disease. The evolution of X4 viruses is associated with a rapid decline in CD4+ T cells, although a causative relationship between viral tropism and CD4+ T cell depletion has not yet been proven. To rigorously test this relationship, we assessed CD4+ T cell depletion in suspensions of human peripheral blood mononuclear cells and in explants of human lymphoid tissue on exposure to paired viruses that are genetically identical (isogenic) except for select envelope determinants specifying reciprocal tropism for CXCR4 or CCR5. In both systems, X4 HIV-1 massively depleted CD4+ lymphocytes whereas matched R5 viruses depleted such cells only mildly despite comparable viral replication kinetics. These findings demonstrate that the coreceptor specificities of HIV-1 are a causal factor in CD4+ T cell depletion ex vivo and strongly support the hypothesis that the evolution of viral envelope leading to usage of CXCR4 in vivo accelerates loss of CD4+ T cells, causing immunodeficiency.

Animals↗
PubMed1997

Association of human immunodeficiency virus Nef protein with actin is myristoylation dependent and influences its subcellular localization.

Human immunodeficiency virus (HIV) Nef functions are thought to be mediated via interactions with cellular proteins. Utilizing zone velocity sedimentation in glycerol gradients we found that recombinant HIV-1 Nef non-covalently associates with actin forming a high-molecular-mass complex of 150-300 kDa. This Nef/actin complex was present in human B and T lymphocytes but not in insect cells and was dependent on the N-terminal myristoylation of Nef, whereas the SH3-binding proline motif of Nef was not involved. Despite being myristoylated, HIV-2 Nef did not associate with actin. This might reflect differences in the subcellular localization of Nef since cell-fractionation experiments revealed that HIV-1 Nef was virtually exclusively localized in the cytoskeletal (detergent-insoluble) fraction whereas HIV-2 Nef had significantly reduced affinity for the cytoskeleton. Colocalization experiments in HIV-1-infected CD4+ fibroblasts revealed that Nef/actin complexes may also exist in HIV-infected cells. This novel interaction of HIV-1 Nef with actin provides insight into the association of Nef with cellular structures and reveals general differences in the interactions of the Nef proteins from HIV-1 and HIV-2.

Actins↗
PubMed1996

[Renal problems in elderly patients after interventions on heart, thorax and/or large vessels].

We investigated 2007 patients over a period of 2 years. Of this group we found 25.9% of patients were over 70 years of age. Of the entire pool 97 patients had renal failure, forcing us to perform continuous venovenous hemofiltration (CVVH). Indications for doing CVVH were identical in young and old patients. Of the filtrated patients 29 died. Only 44.8% of the non-survivors belonged to the group of elderly patients. We conclude from our investigation that there is no indication that older patients have worse prognoses than younger patients in the case of renal failure.

Acute Kidney Injury↗
PubMed1995

Refractive indices for volatile anesthetic gases: equipment and method for calibrating vaporizers and monitors.

OBJECTIVE: The objective of our study was to establish the refractive indices and the virial coefficients of the volatile anesthetic vapors. These indices and coefficients will allow refractometry to be used by manufacturers to produce accurate calibration, without requiring expensive high-precision calibration gases. METHODS: We used a precision refractometer to measure the refractive indices for five volatile anesthetic vapors. We prepared our calibration gases by mixing a gravimetrically calibrated amount of liquid agent with a constant gas flow. RESULTS: The refractive indices for the volatile anesthetic vapors are 1,603.2 for halothane, 1,540.4 for enflurane, 1,563.3 for isoflurane, 1,538.3 for sevoflurane, and 1,211.7 for desflurane. The maximum theoretical error in our measurements, due to all sensors and all uncertainty in our measurement of apparatus and physical constants, is +/- 0.56% of the reading (+/- 0.70% for desflurane). CONCLUSIONS: If refractometry replaced calibration gases in cylinders, as a calibration standard, manufacturers might avoid errors that now occur because calibration gases manufactured by numerous companies seem to differ. We propose that our values serve as an interim database.

Anesthesia, Inhalation↗
PubMed1987

Scanning electron microscopy of human prenatal muscle development.

A scanning electron microscopic study of the development of the human quadriceps was performed in 30 fetuses ranging from 6 to 40 weeks gestation. The results clearly illustrate the hyperplastic phase of myogenesis, showing the differentiation, multiplication and fusion of the myoblasts and the subsequent formation of different generations of myotubes. The myoblasts decrease relatively in number within the developing quadriceps until the 19th week of gestation, and remain afterwards as quiescent satellite cells. The maturation of the myotubes to myofibers and the metabolic differentiation of the fibers are not accompanied by significant changes in their external form in terms of scanning electron microscopy. The hypertrophic phase of myogenesis and general fetal growth can be followed with scanning electron microscopy by the increase in size of the fibers or bundles of fibers, as well as by the differentiation of the connective tissue components of the muscle.

Embryonic and Fetal Development↗
PubMed1979

Evaluation of room cleaning procedures in a laboratory animal facility.

Animal room cleaning procedures were developed that could be used routinely and economically in this animal facility. Bacterial samples from the floors of rooms housing rabbits, rats and mice provided a useful way to evaluate the effectiveness of the cleaning procedures, and to determine the in-use effectiveness of disinfectant solutions.

Animals↗