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Biomedical subjects

M Schrappe

Publications and source records attributed to M Schrappe.

At least 145 records · Page 8Linked to original sources
PubMed1994

Oral supplements in HIV-infected patients with chronic wasting. A prospective trial.

AIM: Supplementation with polymeric formula diet was evaluated as second step of a nutritional intervention program for malnourished, but otherwise clinically stable HIV-infected patients. PATIENTS AND METHODS: 34 patients with weight loss, without opportunistic infections, diarrhea or fever, not responding to nutritional counselling as first intervention, were included. They were given 1000 kcal per day as polymeric formula. If further weight loss occurred, dose was increased to 1500 kcal per day. Nutritional status was determined by body weight and bioelectrical impedance. RESULTS: After four weeks, 7/34 patients already stopped intake. Only 10/34 patients completed three months of treatment. The average intake during three months was 496 +/- 363 kcal/d. Reasons for drop-out were intervening clinical deterioration in eight, early improvement in six, but intolerance or loss to follow-up in ten patients. On average, body weight did not change. Intake of formula diet and weight changes were not correlated. CONCLUSION: Oral supplements are a feasible, cost-effective and safe treatment of malnutrition, but they are accepted only for short time and in limited amount. To estimate efficacy of this treatment, clinical reasons for malnutrition must be considered. More effective nutritional treatments are needed for chronically malnourished HIV infected patients.

Adult↗
PubMed1994

Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86.

In trial ALL-BFM 86, the largest multicenter trial of the Berlin-Frankfurt-Münster (BFM) study group for childhood acute lymphoblastic leukemia (ALL), treatment response was used as an overriding stratification factor for the first time. In the previous trial ALL-BFM 83, the in vivo response to initial prednisone treatment was evaluated prospectively. A blast cell count of > or = 1,000/microL peripheral blood after a 7-day exposure to prednisone and one intrathecal dose of methotrexate (MTX) identified 10% of the patients as having a significantly worse prognosis. In trial ALL-BFM 86 patients with > or = 1,000/microL blood blasts on day 8 were included in an experimental branch EG. Patients with < 1,000/microL blood blasts on day 8 were stratified by their leukemic cell burden into two branches, Standard Risk Group (SRG) and Risk Group (RG). SRG patients received an eight-drug induction followed by consolidation protocol M (6-mercaptopurine, high-dose [HD] MTX 4 x 5 g/m2) and maintenance. RG patients were treated with an additional eight-drug reinduction element. For EG patients protocol M was replaced by protocol E (prednisone, HD-MTX, HD-cytarabine, ifosfamide, mitoxantrone). All patients received intrathecal MTX therapy; only those of branches RG and EG received cranial irradiation. In branch RG, patients were randomized to receive or not to receive late intensification (prednisone, vindesine, teniposide, ifosfamide, HD-cytarabine) in the 13th month. During the trial reinduction therapy was introduced in branch SRG, because in the follow-up of trial ALL-BFM 83 the randomized low-risk patients receiving reinduction did significantly better. Nine hundred ninety-eight evaluable patients were enrolled, 28.6% in SRG, 61.1% in RG, 10.3% in EG. At a median follow-up of 5.0 (range 3.4 to 6.9) years, the estimated 6-year event-free survival was 72% +/- 2% for the study population, 58% +/- 5% in branch SRG for the first 110 patients without reinduction therapy, 87% +/- 3% for the next 175 patients with reinduction therapy, 75% +/- 2% in branch RG, and 48% +/- 5% in branch EG. Late intensification did not significantly affect treatment outcome of RG patients; however, only 23% of the eligible patients were randomized. Prednisone poor response remained a negative prognostic parameter despite intensified therapy. The results confirmed the benefit of intensive reinduction therapy even for low-risk patients. The strategy of induction, consolidation, and intensive reinduction may offer roughly 75% of unselected childhood ALL patients the chance for an event-free survival.

Adolescent↗
PubMed1994

Side effects of AZT prophylaxis after occupational exposure to HIV-infected blood.

UNLABELLED: It was the objective of this study to document and evaluate AZT-induced short-term toxicity in healthy individuals. The study was designed as a longitudinal monocentric side-effect monitoring study with prospective data collection. It was carried out at the Cologne University Hospital. The study population comprised health care workers who were taking AZT prophylaxis after accidental exposure to HIV-infected blood. Fourteen individuals were included into the study; seven of them discontinued treatment prematurely, five due to severe subjective symptoms. In case of one worker AZT had to be stopped due to severe neutropenia (800 cells/microliters) with signs of upper respiratory tract infection. Four of 11 individuals taking AZT for at least 4 weeks developed neutropenia (2 WHO I, 1 WHO II, 1 WHO III). All other laboratory parameters stayed within normal range. In particular, no anemia was observed. IN CONCLUSION: Compared with other studies more neutropenias are observed. Due to side effects 50% of the workers discontinued AZT administration prematurely. The data presented herein show that AZT causes considerable side effects which must be weighed against the potential protective antiviral effect.

Adult↗
PubMed1994

Evaluation of nutritional counselling in HIV-associated malnutrition.

In HIV-infected patients, the outcome of counselling as the first step of a nutritional intervention programme was evaluated, in order to identify clinical and nutritional predictors for its efficacy. 75 HIV-infected patients were investigated, most with advanced disease. Nutritional status was determined by body weight, bioelectrical impedance and 7-day food intake record. Prior mean weight loss was 10% (range = +4% to -31%). Counselling facilitated weight gain in 40 75 patients (1-4 months later, overall mean difference +1.4 +/- 6.2%) and in 14 34 patients (8-11 months later, overall mean difference -1.4 +/- 9.0%). Weight changes correlated with changes in body cell mass (r(2) = .69, p < .001) and in body fat (r(2) = .29, p < 0.05), but not extracellular mass. Underlying conditions such as AIDS definition, fever, and diarrhoea correlated to prior weight loss (p < .001) but not to the outcome of counselling. Low energy intake (before counselling, < 31.5 kcal/kg) did not correlate to prior weight loss but it predicted further weight loss (p < 0.05 towards normal intake). High energy intake (> 38.5 kcal/kg) correlated (p < 0.05) with more prior weight loss but not with further weight changes. Nutritional counselling may be an effective first-line intervention for malnourished HIV infected patients. More than half of patients gain weight without other nutritional treatment. Whereas the severity of malnutrition is influenced by the underlying disease, fever, and diarrhoea, the course of weight change after nutritional intervention is not. Counselling may reduce the nutritional impact of these risk factors. In patients with low spontaneous intake, efficacy of counselling alone is limited, but it may help to identify those who require more invasive nutritional treatment.

Journal Article↗
PubMed1994

Successful treatment strategy for Ki-1 anaplastic large-cell lymphoma of childhood: a prospective analysis of 62 patients enrolled in three consecutive Berlin-Frankfurt-Munster group studies.

PURPOSE: To prove prospectively the efficacy of a short-pulse chemotherapy for treatment of Ki-1 anaplastic large-cell lymphoma (ALCL) of childhood. PATIENTS AND METHODS: From October 1983 to December 1992, 62 patients (median age, 9.7 years) with newly diagnosed Ki-1 ALCL were enrolled onto Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Munster (NHL-BFM) studies 83, 86, and 90. The most frequent immunophenotype was T cell. Ki-1 ALCL differed from other subsets of NHL of childhood by the more frequent involvement of bone, soft tissue, and skin, and by the lack of bone marrow (BM) disease. A 5-day prephase course (prednisone/cyclophosphamide) was followed by two different 5-day courses of chemotherapy: course A consisted of dexamethasone, methotrexate (MTX) 0.5 g/m2 (24-hour infusion), intrathecal chemotherapy, ifosfamide, cytarabine (Ara-C), and etoposide (VP-16); course B consisted of cyclophosphamide and doxorubicin instead of ifosfamide, and Ara-C/VP-16, respectively. Treatment was stratified into three branches. Branch 1 (stage I and stage II resected) received three courses; branch 2 (stage II not resected, stage III), six courses; and branch 3 (stage IV), six intensified courses containing MTX 5 g/m2, and Ara-C 2 g/m2. Local radiotherapy was not performed. RESULTS: Four patients failed to enter remission, and one died of infection. Seven patients relapsed within 9 months after diagnosis; two patients had isolated local relapses, but BM and CNS were never involved. Fifty patients have been in first continuous complete remission (CR) for 0.6 to 9.7 years (median, 2.5), and 56 are alive. The probabilities for survival and event-free survival (EFS) at 9 years are 83% +/- 7% (SE) and 81% +/- 5%. Skin involvement was the only negative prognostic parameter. CONCLUSION: Short-pulse chemotherapy over 2 to 5 months without local therapy modalities is effective in the treatment of Ki-1 ALCL.

Adolescent↗
PubMed1993

Humoral and cellular immunity in HIV positive and HIV negative Helicobacter pylori infected patients.

The prevalence of H. pylori associated gastritis seems to be different in HIV positive and HIV negative patients. Therefore a correlation to immunodeficiency can be postulated. The histology of gastritis, status of H. pylori infection and parameters of humoral and cellular immune response were investigated in 41 HIV positive and 47 HIV negative patients, who were subjected to upper endoscopy for the evaluation of gastrointestinal symptoms. In HIV positive patients 37% had active chronic gastritis against 62% of the HIV negative patients. In 73% of HIV positive cases of active chronic gastritis H. pylori was detected by bacteriological culture and/or Warthin-Starry stain. In HIV negative patients active chronic gastritis was always associated to H. pylori infection. Production of antibodies as measured by two commercially available ELISA tests was significant in HIV positive and HIV negative patients; both tests correlated well with H. pylori detection by culture or direct microscopy. Immunoglobulin class specific immunoblots corresponded to the ELISA results in HIV negative patients but to a lesser extent in the HIV positive group which was assumed to be related to unspecific polyclonal activation in these patients. Systemic cellular immunity was investigated by proliferation assays of peripheral blood mononuclear cells (PBMC). Proliferative response to the unspecific mitogen PHA was reduced in HIV positive patients. A sonicated H. pylori antigen failed to induce lymphocyte proliferation. The antimitogenic effect was also seen in case of coincubation with PHA. This observation was independent of H. pylori and HIV infection status. We conclude that in HIV positive as in HIV negative patients active chronic gastritis is predominantly related to H. pylori infection. The prevalence of H. pylori associated gastritis in HIV positive patients is significantly reduced (p < 0.025) compared to HIV negative controls. Decreased susceptibility to H. pylori infection in HIV positive patients may not be explained by the abnormal reactivity of their humoral or cellular immune response.

Adult↗
PubMed1993

Clinical risk factors for malnutrition in HIV-1-infected patients.

OBJECTIVE: To estimate the influence of fever, diarrhoea, stage of HIV disease, opportunistic infection and anorexia on malnutrition in HIV-infected patients we analysed data of patients undergoing a nutritional counselling programme from November 1989 to April 1992. PATIENTS AND METHODS: Our study group comprised 104 HIV-infected patients (98 homosexual men, 15 asymptomatics, 30 AIDS-related complex patients, 59 AIDS patients). Nutritional status was measured by previous weight loss, bioelectrical impedance analysis and prospective intake protocol. RESULTS: Patients had lost 10 +/- 8.7% of body weight. Compared with controls, body mass index was lower (P < 0.001), and extracellular/body cell mass ratio (ECM/BCM) was higher (P < 0.001). BCM was reduced proportionately to weight loss, percentage of body fat was lower compared with controls (P < 0.001), even in patients with stable weight. Clinical risk factors for malnutrition were identified as fever in 31, diarrhoea in 26, acute infections in 42 and anorexia in 73 out of 104 patients. One single risk factor was predominant in 63 patients: fever in five, diarrhoea in 14, acute infections in 17 and anorexia in 27 patients. Weight loss was not linearly correlated to CD4 count or to time since AIDS diagnosis. Food intake was highly variable (39-165% of calculated needs) without correlation to weight loss. CONCLUSIONS: Loss of body fat was found even in the earlier stages of HIV infection and was more severe than loss of BCM. Important risk factors for malnutrition are anorexia (most frequent), diarrhoea and fever (most severe). Most patients have combined risk factors. Treatment strategies and pathophysiologic studies should consider the heterogeneity of HIV-associated malnutrition.

AIDS-Related Opportunistic Infections↗
PubMed1992

Favorable outcome of B-cell acute lymphoblastic leukemia in childhood: a report of three consecutive studies of the BFM group.

In 1981 the BFM group introduced a new treatment strategy for B-cell acute lymphoblastic leukemia (B-ALL). A cytoreductive prephase (prednisone/cyclophosphamide) was followed by eight 5-day courses of chemotherapy. Fractionated cyclophosphamide, methotrexate (MTX) 0.5 g/m2 (24-hour infusion), and MTX intrathecally were administered at each course and cytosine arabinoside (ARA-C)/teniposide (VM-26) was given alternately with doxorubicin. In study ALL-BFM-83, central nervous system (CNS) chemotherapy was intensified by adding dexamethasone, while MTX/ARA-C was administered intraventricularly. Therapy duration was reduced to six courses. In study ALL-BFM-86, MTX 0.5 g/m2 was replaced by high-dose (HD) MTX, 5 g/m2 (24-hour infusion), and MTX/ARA-C/prednisolone intrathecal therapy was introduced. Doses of ARA-C and VM-26 were increased and fractionated, cyclophosphamide was partially replaced by ifosfamide, and vincristine was added. CNS irradiation was 24 Gy for prevention and 30 Gy for overt disease in studies ALL-BFM-81 and -83, but was omitted in ALL-BFM-86. In all, 87 patients were enrolled, 22 (8 CNS-positive) in study All-BFM-81, 24 (7 CNS-positive) in study ALL-BFM-83, and 41 (0 CNS-positive) in study ALL-BFM-86. The estimated 5-year duration of event-free survival (EFS) was 43% in study ALL-BFM 81, 50% in study ALL-BFM-83, and 78% in study ALL-BFM-86 (minimal follow-up, 25 months). Nineteen of 24 relapses occurred while on therapy or shortly thereafter. In study ALL-BFM 81, the CNS was the most frequent site of failure. In ALL-BFM-83, there were no isolated CNS relapses, but more bone marrow (BM) relapses occurred. In ALL-BFM-86, localized manifestations were the predominant site of failure, no isolated BM relapses occurred, and only one CNS relapse was diagnosed. No single parameter exerted a consistent influence on outcome with one exception. The presence of residual disease after the first two courses was correlated with an increased risk of therapy failure. We conclude that an intensive, short-pulse therapy delivered within a 4-month period is highly effective in the treatment of B-ALL. In addition to fractionated cyclophosphamide/ifosfamide, a 24-hour infusion of HD MTX 5 g/m2 in conjunction with an i.th. therapy is an important component for prevention of both systemic and CNS relapses. CNS irradiation is not needed for CNS-negative patients.

Adolescent↗
PubMed1992

[Mucosa-associated immune system in HIV-1 infection. T-cell subpopulations compared in different segments of the gastrointestinal tract].

T-lymphocyte subsets in duodenal, ileal, coecal, colonal, sigmoidal, and rectal lamina propria were determined in order to compare the distribution of CD2+, CD4+, and CD8+ cell subsets as well as the CD4/CD8 ratio in six different compartments of the gastrointestinal tract. In both HIV1-infected and not HIV1-infected patients, no differences in the distribution of T-lymphocyte subsets could be noted between the compartments examined. The HIV1-infected patients showed a decrease of CD4+ helper cells and CD4/CD8 ratio and an increase of CD8+ suppressor/cytotoxic cells in all examined segments. In terms of lamina propria T-lymphocyte subsets, the intestinal immune system seems to react to HIV1-infection homogenously.

Adult↗
PubMed1992

Long-term growth suppression of human glioma xenografts by chemoimmunoconjugates of 4-desacetylvinblastine-3-carboxyhydrazide and monoclonal antibody 9.2.27.

A conjugate of 4-desacetylvinblastine-3-carboxyhydrazide (DAVLBHY) and the glioma-reactive monoclonal antibody (mAb) 9.2.27 induced long-term suppression of tumor growth in athymic nude mice engrafted with U87MG human glioma cells. In vitro, DAVLBHY had the strongest antiproliferative activity (inhibitory concentration at which incorporation of [3H]thymidine is at 50% of untreated control is 2.0 x 10(-9) M) of seven cytotoxic drugs tested and so was chosen for conjugation to mAb 9.2.27, which reacts specifically with the core protein of chondroitin sulfate proteoglycans found in human glioblastomas. After conjugation of DAVLBHY to the carbohydrate residues of mAb 9.2.27 it retained its full binding capacity. For in vivo studies, DAVLBHY and several conjugate derivatives were evaluated by using two dosages of i.v. injections, each starting 2 days after s.c. tumor inoculation. The control tumors reached a volume of nearly 3000 mm3 within 30 days. Tumor growth was delayed by about 20 days with four i.v. injections of 0.5 mg/kg 9.2.27-DAVLBHY, which was slightly superior to the unconjugated drug. Moreover, 9.2.27-DAVLBHY produced a highly significant suppression of growth so that the average tumor volume was only 3% of that observed in untreated controls after 28 days. Four injections of this conjugate at a larger dose, 2.0 mg/kg, prevented recurrence of the tumors for 130 days in all animals tested, thus demonstrating a significant increase in the therapeutic index, since the unconjugated drug provided limited inhibition of tumor growth for only 40 days. The specificity of the antitumor effect was demonstrated in a comparison with the control conjugate, KS1/4-DAVLBHY, which despite partial tumor suppression had only a transient effect. The specific antitumor effect of 9.2.27-DAVLBHY was unexpected, since the target antigen is expressed at a relatively low density (40,000 sites/cell) on U87MG glioma cells.

Animals↗
PubMed1992

Immunotherapy of human glioma xenografts with unlabeled, 131I-, or 125I-labeled monoclonal antibody 425 to epidermal growth factor receptor.

Monoclonal antibody (mAb) 425 (IgG2a) binds to the external domain of the epidermal growth factor receptor. This determinant is highly expressed by human glioma tissues but rarely by normal brain tissues, and is absent on peripheral blood lymphocytes and bone marrow cells. The mAb exerts variable cytotoxic effects against cultured human glioma cells in conjunction with human and murine effector cells. Inhibition of growth of s.c. glioma xenografts in nude mice by the mAb may be mediated by murine macrophages or may be related to the capacity of the mAb to antagonize growth stimulation of glioma cells by epidermal growth factor. In approaches to radioimmunotherapy of human glioma with mAb 425, the 125I-labeled mAb 425 exhibited more significant antitumor effects than the 131I-labeled mAb both in vitro and in vivo in xenotransplanted nude mice. These differences may be due to enhanced nuclear damage caused by 125I-labeled versus 131I-labeled fragments following their internalization into the glioma cells. Our studies provide the rationale for immunotherapy of glioma patients with either unlabeled or 125I-labeled anti-epidermal growth factor receptor mAb 425.

Animals↗