HIV vaccination and blood transfusion.
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Biomedical subjects
Publications and source records attributed to D Fuchs.
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BACKGROUND: PCT has recently drawn attention as a quite specific marker for bacterial, fungal, and parasitic origin of severe sepsis-syndrome. These specific properties could make PCT to an important tool for sepsis monitoring in severely immunocompromised children. The clinical value of PCT in comparison to CrP was investigated in children after bone marrow transplantation (BMT). METHODS: PCT was measured in the serum of 48 children (median age 12.4 years) after BMT in a prospective study. Results were correlated with the clinical findings and compared to the C-reactive protein (CrP). RESULTS: PCT showed a sensitivity for diagnosing a sepsis-syndrome of 56%, a specificity of 87%, a positive predictive value of 69%, and a negative predictive value of 80%. Regarding CrP they were 100%, 41%, 46% and 100% respectively. The relative risk to die due to sepsis-syndrome was 26.4 for PCT levels over 10 ng/ml and 4.0 for CrP levels over 200 mg/l. It could be shown furthermore that there can be a significant liberation of PCT even during hematological aplasia. CONCLUSION: (1) Measuring PCT levels in the sera of children undergoing BMT improves the possibility of diagnosing severe infection and gives an important prognostic tool. (2) Measuring PCT can be recommended if severe sepsis-syndrome is suspected and there is an additional need for differential diagnosis and prognostic evaluation.
We report on a 17-year-old young man with rhabdomyosarcoma in the right parotid area. Relapse therapy was performed with high dose chemotherapy and consecutive autologous stem cell rescue. During this therapy heparin-induced thrombocytopenia was diagnosed. Because of its proven antithrombotic activity Danaparoid-Sodium, a natural low molecular glycosaminoglycan preparation, was used for further antithrombotic prophylaxis. We discharged our patient from the laminar air flow unit six months ago. The alternative antithrombotic therapy was tolerated without any problems. No bleeding events occurred, thrombotic complications and veno-occlusive disease of the liver were avoided.
We report on a 16-year old boy with non-Hodgkin's lymphoma who acquired a therapy-induced ascites and pleural effusion during initial chemotherapy. This life-threatening condition could be controlled by intensive care measures including pleural tap and drainage. Chemotherapy could then be continued. The patient has been in continuous complete remission for 18 months.
OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by flare-ups, the causes of which are not known. In accordance with new concepts in stress research, this study investigated whether daily psychosocial stressors interfere with immunological processes in SLE. Because such processes are unique to each individual, single-case design using time-series analysis (Box and Jenkins) was applied. METHODS: A 40-year-old woman with SLE (last flare-up September 1995) was interviewed initially to determine major life events and difficulties (using the Life Events and Difficulties Schedule) in the previous 2 years. She was then observed for 63 days. Urine neopterin, an immunological parameter demonstrated to parallel disease activity in SLE patients, was measured in daily overnight urine. Daily incidents were identified weekly by the Incidents and Hassles Inventory and independently rated. Intervening factors, including infections, medication, and lifestyle, were controlled. RESULTS: Retrospectively, data obtained from the Life Events and Difficulties Schedule indicated that major life events and difficulties had preceded the patient's last flare-up in 1995. Although there were no clinical signs of SLE during this prospective study of 63 days, cross-correlational analyses revealed that "moderately" stressful incidents associated with higher levels of emotional irritation (lag 0: +0.271, p < .05) predicted an increase in urine neopterin the following day (lag 1: +0.441, p < .05). Moreover, a 7-day cyclicity in neopterin levels that corresponded to the weekly examinations and interviews was found. CONCLUSIONS: This study showed a causal relationship between psychosocial stressors and urine neopterin concentrations that may be related to SLE disease activity. Furthermore, the workability of an integrative approach using single-case design and time-series analysis in psychoneuroimmunology was demonstrated for the first time.
Tennessee data were analyzed longitudinally from 1979-80 to 1987-88 in terms of numbers of children placed in a variety of service options. In 1983-84, the Tennessee funding formula was changed from a "flat" rate to a "weighted" formula. The weighted formula was associated with a statistically significant decrease in less restrictive placements and a reliable increase in more restrictive placements. A statewide survey of district special education directors suggested that service needs may have been more likely than monetary incentives to explain the observed changes.
Deficits in phonological processing are theorized to be responsible for at least some reading disabilities. A considerable amount of research demonstrates that many students can be taught one of these phonological processes-phonemic awareness. However, not all students have responded favorably to this instruction. Research has suggested that these nonresponders may be unable to retrieve phonological codes quickly from long-term memory. The purpose of this study was to examine whether such a deficiency, which we refer to as lexical retrieval weakness, blunts the effectiveness of combined phonemic awareness and decoding training. To this end, we compared the effectiveness of phonemic awareness and decoding training for students with and without severe lexical retrieval weaknesses. All students in both groups demonstrated poor phonemic awareness. The results suggested that students with relatively strong lexical retrieval skill responded more favorably to beginning reading instruction than did students with weak lexical retrieval skill. In other words, lexical retrieval weakness may influence reading development independently of the effects of phonemic awareness. Implications for instruction are discussed.
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The successful integration of students with learning disabilities into mainstream reading classes may require teachers to adapt instruction and curricula in major ways. In this article, we discuss the relation between the instruction prescribed by standardized commercial curricula and the reading achievement of mainstreamed students with learning disabilities and other low-performing nonhandicapped students. An instructional template designed to complement commercially published reading lessons is described and its effects on the reading achievement of mainstreamed students with learning disabilities examined. Next, the limitations of generic instructional procedures to rectify the deficiencies of mainstream curricular programs for students with greater-than-average instructional needs are reviewed. We conclude with a discussion of the complexity of educating instructively needy learners in mainstream settings and the significance of well-designed instruction.
Recent research and development has integrated computer-managed classwide curriculum-based measurement (CBM) and peer tutoring (PT) to help general educators adapt instruction to address the diverse needs of their students. The purpose of this study was to gain insight into the teachers' perspective on the advantages and disadvantages of these methods. Twenty general education teachers participating in a project that combined CBM and PT were interviewed regarding (a) ways in which the project had affected their students and their instruction, (b) their level of satisfaction with the project, and (c) shortcomings of the project. An unusual feature of this study was that in attempting to take advantage of the insider information possessed by the educators, we involved the teachers in developing the actual interview questions. Teachers specified a large number of academic, social, and instructional benefits of the methods, and they identified several weaknesses that should be addressed. Implications are discussed in terms of the development of other educational innovations and the use of CBM and PT in general education classrooms that include students with learning disabilities.
The original intent of special education pull-out services was to remove students from general education temporarily for intensive, individualized instruction in deficit areas. In many school districts, however, it seems that once students participate in pull-out services, there is little effort to return them to general education. One explanation for this is that not much is known about how best to prepare students for movement up the cascade of services, including reintegration into the mainstream. A promising reintegration approach is transenvironmental programming (TP). Research suggests that supplementing TP with continuous progress monitoring, specifically via curriculum-based measurement (CBM), better prepares students for reintegration than either TP or CBM alone. Findings from the present study provide a possible explanation: Results suggest that special educators using TP who receive CBM information about their students' academic progress are more likely to plan and implement academic interventions in preparation for students' transition than are those special educators who do not receive this information. This supports the hypothesis that the relatively greater success of TP + CBM is due to increased attention to academic preparation. Implications for practice and future research are discussed.
Antibodies against human immunodeficiency virus, other infectious agents and neopterin levels were determined in 253 patients in a rural area of North-West Tanzania. Seroprevalence for HIV was 3.2%. In one case serology was positive for HIV-1 and HIV-2 antibodies and questions whether there was a real double infection or a cross reaction not only concerning core region proteins but also transmembrane protein. The specificity in the diagnosis of HIV-infection is markedly increased with newer serological methods using recombinant peptides but did not improve sensitivity on African sera. Neopterin was determined as a sensitive indirect marker for the activation of T-cells and is therefore correlated with the susceptibility of HIV infection and with progression of disease. High seroprevalence rates for various infectious agents were determined and may explain the high rate of elevated neopterin levels in 80% of the Africans. Neopterin levels were even higher in HIV patients. Viral p24 antigen was found only in two persons, one of whom had no antibodies detectable.
An autologous bone marrow transplantation (ABMT) was carried out on a 4-year-old boy following the second pulmonary relapse of a nephroblastoma. Glomerular and tubular function of the remaining kidney before ABMT was normal. Etoposide, carboplatin, and melphalan were used in the conditioning regimen. The patient developed acute renal failure (ARF), and hemodialysis was required for 3 weeks. The situation was further complicated by his requiring mechanical ventilation for 12 days. Today, the patient is in good general health and in stable remission 32 months after bone marrow transplantation. This report shows that even serious tubular and glomerular dysfunction may be completely reversible in children. The background for high-dose chemotherapy with ABMT or stem cell rescue is discussed.
In vitro, large amounts of neopterin are produced by human monocytes/macrophages upon stimulation with interferon-gamma. In vivo increased neopterin concentrations in human serum and urine indicate activation of cell-mediated (Th1-type) immune response, e.g., during virus infections, autoimmune diseases, allograft rejection and in certain types of malignancy. In various groups of patients with malignant diseases neopterin concentrations correlate to the stage of disease, and higher neopterin concentrations in serum, urine or ascitic fluid were shown to significantly predict worse prognosis regarding relapse and survival. The amounts of neopterin produced by activated monocytes/macrophages correlate with their capacity to release reactive oxygen species (ROS). With this background, neopterin concentrations in body fluids can be regarded as an indirect estimate of the degree of oxidative stress emerging during cell-mediated immune response. Moreover, recently neopterin was found itself to be capable of enhancing toxic effects induced by ROS. In vitro, neopterin derivatives were able to interfere with intracellular signal transduction pathways involved in, e.g., programmed cell death and the induction of proto-oncogene c-fos or nuclear factor-chi B. The data support the view that increased production of ROS--indicated by increased neopterin concentrations--could modulate the development, the proliferation and the survival of malignant cells.
OBJECTIVES: Treatment with interferon (IFN) reduces viral replication and normalizes aminotransferase levels in a significant percentage of patients with non-A, non-B hepatitis or hepatitis C. Soluble immune activation markers were evaluated in patients with hepatitis. PATIENTS AND METHODS: Serum concentrations of soluble immune activation markers neopterin and beta 2-microglobulin (B2M) were compared to endogenous IFN-gamma levels in 17 patients with chronic hepatitis C before, during and after 9-months of treatment with IFN-alpha 2b. RESULTS: Before therapy some patients had increased concentrations of the studied variables. During therapy neopterin and B2M concentrations further increased whereas IFN-gamma decreased. IFN-gamma and neopterin levels were correlated before but not during therapy. The correlations between neopterin and B2M were significant throughout the study. CONCLUSION: The data indicate that IFN-gamma decreases during treatment and IFN-alpha 2b appears to enhance formation of neopterin and B2M.
High neopterin excretion is closely associated with activation of cell-mediated immunity. We studied urine and serum neopterin concentrations and serum interferon-gamma concentrations in normal pregnant women. In our study population, neopterin concentrations exceeded the normal range in 663 of 840 samples (79%). Neopterin levels increased with the time of pregnancy. Serum samples drawn from women in the third trimester of pregnancy also showed high neopterin concentrations in almost all cases; however, no circulating interferon-gamma was detected. Whereas neopterin is able to penetrate into the blood stream because of its small size (M = 253 D), diffusion of interferon-gamma is limited. Raised neopterin levels provide evidence for activated cell-mediated immunity during pregnancy.
Genetic diseases can be treated by transplantation of normal allogeneic bone marrow. Four patients with congenital disorders of their hematopoietic and/or lymphoid stem cells have been transplanted. One patient had a congenital aplastic anemia (Blackfan-Diamond), one had Gaucher's disease, one had congenital agranulocytosis Kostmann and one had chronic granulomatous disease. All patients received busulfan, cyclophosphamide and total nodal irradiation as preparatory regimen. Total nodal irradiation and cyclophosphamide were used as immunosuppressive agents. In all cases hematopoietic ablation and donor lymphoid and hematopoietic engraftment were achieved. The basic disorders of all transplanted children could be corrected completely. All children are alive and well.
Bone marrow transplantation (BMT) was mainly used for the treatment of immunological, hematological and oncological diseases. Genetic diseases can also be treated by transplantation of normal histocompatible allogeneic bone marrow. This type of marrow transplantation is used for the treatment of inborn errors whose clinical expression is restricted to lymphoid or hematopoietic cells. The therapeutic role of bone marrow transplantation in the treatment of generalized genetic diseases is under investigation. Genetic disorders that can be cured include congenital immune deficiencies, infantile malignant osteopetrosis, thalassemia, infantile agranulocytosis, chronic granulomatous disease, lysosomal storage diseases and others. The use of autologous bone marrow after the insertion of a normal gene (gene therapy) in vitro circumvents the need for a histocompatible donor.