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Biomedical subjects

W Havers

Publications and source records attributed to W Havers.

At least 37 records · Page 2Linked to original sources
PubMed1999

Intrapulmonary protein leakage in immunocompromised children and adults with pneumonia.

BACKGROUND: Pulmonary infections are associated with an increase in capillary permeability but information regarding age related differences in the local inflammatory response is lacking. To quantify the degree of capillary leakage during inflammation, the concentrations of the plasma proteins albumin, alpha1-antitrypsin, alpha2-macroglobulin and the locally produced proteins elastase, myeloperoxidase, lactoferrin and fibronectin were studied in the bronchoalveolar lavage (BAL) fluid of immunosuppressed children and adults with pneumonia. METHODS: Sixteen children aged 2-16 years and 15 adults who developed pneumonia while receiving immunosuppressive therapy for haematological malignancies were included in the study. Bronchoalveolar lavage was performed via a flexible bronchoscope with three aliquots of 1 ml/kg body weight in children and 200 ml in adults. Protein concentrations in BAL fluid were determined using highly sensitive immunoluminometric assays. RESULTS: Despite considerable variability, the median concentrations of all proteins in BAL fluid were significantly higher in both patient populations than in previously collected age adjusted reference values. The concentrations of serum derived proteins were significantly higher in children with pneumonia than in adult patients. In contrast, no differences were observed between the two groups for locally produced proteins. CONCLUSIONS: These data suggest that the degree of protein exudation is more pronounced in immunosuppressed children with pneumonia than in adults in a similar clinical situation. This is in agreement with our studies in healthy individuals and may reflect a greater permeability of the alveolar-capillary membrane in children, regardless of disease status.

Adolescent↗
PubMed1997

Transplantation of filgrastim-mobilized peripheral blood stem cells from HLA-identical sibling or alternative family donors in patients with hematologic malignancies: a prospective comparison on clinical outcome, immune reconstitution, and hematopoietic chimerism.

The clinical results, cellular immune reconstitution, and hematopoietic chimerism obtained after transplantation of recombinant human granulocyte colony-stimulating factor mobilized allogeneic peripheral blood stem cells (PBSCs) from genotypically human leukocyte antigen (HLA)-identical sibling (n = 36) or alternative family donors (n = 24) were prospectively compared in patients with hematologic malignancies. Thirty-two of 34 evaluable patients with HLA-identical sibling donors and all patients with alternative family donors achieved trilineage engraftment. The median time intervals to reach peripheral neutrophil counts <500/microL (13 v 17 days) or <1,000/microL (16 v 19 days) and unsupported platelet counts <20,000/microL (11 v 15 days) or <50, 000/microL (19 v 24 days) as well as red blood cell and platelet transfusion requirements were not significantly different between both patient subsets. The cumulative probability of grades II through IV acute graft-versus-host disease (GVHD) for the 60 study patients was 48% +/- 10% but ranged between 86% +/- 12% in patients whose donors had at least one HLA-A,B,DR,DQ,DP antigen disparity in direction to acute GVHD, and 25% +/- 9% in recipients of GVHD-matched transplants (P < .003). The 2-year survival estimates were 54% +/- 10% for patients with alternative family donors and 65% +/- 9% for patients with HLA-identical sibling donors. Multivariate analysis identified the pretransplantation disease stage, patient age, and acute GVHD as independent predictors of overall and disease-free survival, whereas alternative family donors alone had no adverse effect on these clinical endpoints. Monthly monitoring of peripheral blood T-helper cell subsets, B cells, and monocytes during the first year posttransplantation showed a nearly identical course of immune cell reconstitution in both patient subsets. In addition, no differences in the proportions of complete chimeric patients were detectable between the two patient subsets by sex chromosome and variable number of tandem repeats analysis up to 12 months posttransplantation. In conclusion, PBSCs from alternative family donors represent an attractive source for allogeneic transplantation in patients lacking HLA-identical sibling donors and should be further evaluated in comparison with marrow transplants from alternative family donors.

Adolescent↗
PubMed1997

Postoperative radiotherapy of spinal and intracranial ependymomas: analysis of prognostic factors.

PURPOSE: Postoperative radiation therapy adds significantly to disease control and survival of patients with ependymoma. However, much controversy exists about the radiation treatment policy. We report the long-term results of a cohort of 56 patients with primary intracranial and spinal ependymomas. Special effort has been taken to define prognostic indicators as a basis for future treatment strategies. PATIENTS AND METHODS: Between November 1963 and May 1995, 56 patients with histological proven ependymoma were referred to our clinic for further treatment following surgery. Thirty patients had a high grading tumor and 26 had low grade tumors. Seventeen patients had supratentorial tumors and 24 had infratentorial tumors. Fifteen patients suffered from localized spinal tumors. RESULTS: The mean survival time for all patients was 77 months. Five- and 10-year survival probabilities were 60 and 51%, respectively. The mean progression free survival (PFS) probability for all patients was 67 months with corresponding 5- and 10-year PFS probabilities of 53 and 39%, respectively. On univariate analysis initial performance status, age and tumor grade were significant for survival probability. Concerning PFS radiation dose was significant with improved survival with doses > 45 Gy. On multivariate analysis, tumor grade and initial performance status proved to be the only independent prognostic factors. CONCLUSIONS: Tumor grade, age, initial performance status and radiation dose are significant factors for the clinical course of patients and have to be taken into account for the urgently needed prospective trials.

Adolescent↗
PubMed1996

Differential cytology of bronchoalveolar lavage fluid in immunosuppressed children with pulmonary infiltrates.

OBJECTIVE: Bronchoalveolar lavage (BAL) is a well established technique for the detection of pathogens in immunosuppressed children, but its diagnostic yield is variable. The aim of this study was to investigate whether BAL differential cell counts are helpful in the evaluation of pulmonary infiltrates in immunocompromised children. STUDY DESIGN: BAL was performed 28 times in 27 febrile immunocompromised children with pulmonary infiltrates. All patients were pretreated with broad spectrum antibiotics; 11 children also received amphotericin B. BAL was conducted with a flexible bronchoscope wedged in the area of maximal pathology as suggested by the chest radiograph or in the middle lobe in patients with diffuse interstitial radiographic changes. Differential cell counts were performed from cell smears obtained after centrifugation of BAL fluid. RESULTS: Bacterial or fungal organisms were detected in BAL fluid of 12 patients. Patients with bacterial or fungal infections (group 1) had a significantly higher percentage of granulocytes in BAL fluid both compared with patients with sterile BAL cultures (group 2) and with a control group of children without pulmonary disease (p < 0.001, Wilcoxon test). The proportion of lymphocytes was not different from the control group in group 1 but significantly increased in group 2 (p < 0.001, Wilcoxon test). Blood differential cell counts were not different in the two patient groups. Lymphocyte subsets of BAL fluid obtained in a subgroup of patients were not significantly different from controls. CONCLUSION: These data suggest that BAL differential cell counts may be a useful adjunct in the differential diagnosis of pulmonary infection in immunocompromised children.

Adolescent↗
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↗
PubMed1993

Temporal and regional trends of cancer mortality in West Germany.

Age-specific and cumulative mortality rates are presented for different cancer sites from 1970 until 1988 for the 11 individual federal states of West Germany (FRG). Sex- and age-specific evaluations are performed and temporal and regional trends in mortality from different cancer sites are revealed. In the FRG there is no comprehensive cancer registry with national coverage for recording cancer patients of all ages (nationwide incidence rates are available only for childhood cancers). Therefore, in view of the lack of a nationwide cancer registry the importance of long-term cancer mortality studies for health policy is emphasized. Methodological aspects of certification regulations and classification of cancer sites are discussed.

Age Factors↗
PubMed1993

[Information system on cancer mortality and district characteristics of the Rhineland TUV].

On account of the lack of a comprehensive cancer registry with national coverage for the Federal Republic of Germany, the long-term and interregional evaluation of cancer mortality data is of particular relevance. Therefore, the TUV Rheinland instructed by the Federal Ministry for the Environment, Nature Protection, and Reactor Safety maintains an "Information System on Cancer Mortality and District Characteristics (IKK)" using official cause of death and resident population statistics. Mortality data for a variety of different cancer sites are documented with local and temporal separation for the area of the Federal Republic of Germany (before the German unification) and for a period of 20 years. The IKK data can be employed as a meaningful tool for epidemiological investigations relating to the correlation of cancer mortality and environmental agents. In the present paper the principles of the IKK are described and some examples of results are presented.

Adolescent↗
PubMed1991

Long-term treatment effects in patients with bilateral retinoblastoma: ocular and mid-facial findings.

A total of 99 patients with bilateral retinoblastoma who had been treated between 1965 and 1982 were reexamined in April 1988 to study the late effects of treatment. Their median age at the follow-up visit in 1988 was 16 years (range, 6-27 years), and the median follow-up was 15 years (range, 6-26 years). All patients underwent a full eye examination, morphometric measurements of the mid-face and genetic counselling. Each eye or orbit and the corresponding side of the patient's mid-face were evaluated separately, resulting in 198 data sets from 99 individuals. Subjects were divided into four treatment groups according to whether photo- and cryo-coagulation, enucleation, radiation therapy or various combinations thereof were used. In all, 81 eyes had a visual acuity of greater than 0.4 (in 23 of these, however, only with low-vision aids). Within a dose range of 36-51 Gy, the location of the tumor (36%) or cataract (15%) were the main factors responsible for poor visual acuity, whereas radiation retinopathy and/or optic neuropathy occurred in only three cases. Cataracts were more frequently observed following orthovoltage as compared with megavoltage therapy (P = 0.012). A total of 72 eyes had been enucleated and had not received radiation therapy at any time. Cosmetic results (as measured by several parameters) in these cases were significantly better then those in 28 subjects who underwent combined radiation therapy and enucleation. As defined by various subjective as well as objective findings, mid-facial hypoplasia occurred significantly more often following orthovoltage as compared with megavoltage therapy.

Adolescent↗
PubMed1991

Risk factors for metastases in patients with retinoblastoma.

The study is based upon a review of data from 583 consecutive patients with retinoblastoma over the years 1956 to 1986. Mean follow-up was 8 years, and median was 5.5 years. In 41 patients, metastases developed within 5 years. The influence of clinical and histopathologic risk factors on the occurrence of metastases was first analyzed by univariate tests. Significant variables were then reevaluated using the Cox proportional hazards method. Four factors were found to be independently associated with the development of metastases: optic nerve invasion with and without involvement of the resection line, choroidal invasion and enucleation of an affected eye more than 120 days after initial diagnosis. The 5-year metastatic risks associated with these factors were 67%, 13%, 8%, and 4%, respectively. The relative risk estimate, calculated from the Cox model, was used for a score classification with groups of low, medium, and high metastatic risk. The 5-year incidence of metastases was 4%, 43%, and 68%, respectively.

Adolescent↗
PubMed1991

[Risk of metastasis in retinoblastoma].

580 patients with retinoblastoma were analysed retrospectively. Median follow up was 5.5 years. 41 patients developed metastases within 5 years. Clinical and histopathological risk factors were analysed by univariate tests with regard to the occurrence of metastases. Significant variables were then reevaluated using Cox proportional hazards method. Four factors correlated independently with the development of metastases: optic nerve invasion with involvement of the resection line, optic nerve invasion without involvement of the resection line, choroidal invasion and enucleation of an affected eye more than 120 days after initial diagnosis. The regression coefficient beta of the Cox-model was used for a score classification with groups of high, medium and low metastatic risk. The 5-year incidence of metastases was 68%, 43% and 4% respectively.

Adolescent↗
PubMed1990

New and recurrent tumor foci following local treatment as well as external beam radiation in eyes of patients with hereditary retinoblastoma.

The study is based on a retrospective analysis of data from 200 patients with hereditary retinoblastoma. Apart from four unilateral cases with a positive family history all patients had bilateral disease; 229 appeared suitable for conservative treatment while 167 eyes had to be enucleated. Primary local treatment was performed in 102 eyes, while 127 eyes received primary external beam radiation using a linear accelerator. Follow-up was adjusted by life tables, with 75% of the patients being observed longer than 2 years. Using life-table statistics new and recurrent tumors were found in 41% of all patients and in 95% of these cases they were noted within 26 months after initiation of therapy. Among eyes treated with primary external beam radiation new and recurrent tumors were observed significantly less frequently when 50 Gy (22% compared with 49% after 40 Gy) and a highly accurate beam alignment technique (22% compared with 48% after alignment to the outer bony canthus) were applied. The incidence of recurrent tumors following primary local treatment did not differ significantly with regard to the application of either photo- or cryocoagulation (28% vs 33%), while no recurrence was observed among tumors that were suitable for primary treatment using ruthenium or cobalt plaques.

Brachytherapy↗
PubMed1990

[Cross-sectional study of elementary school children for assessing suspected effects of regional hemato-toxic environmental pollutants].

To investigate the suspicion of an increased incidence of leukopenia in school children living in the more industrialised northern region of the city of Essen, blood counts of these children were compared to those of pupils from the southern region in a two-phased study. In 469 1st and 2nd grade children, neither the mean leukocyte count nor the number of individual abnormal results differ between the two regional groups. A difference in the mean hemoglobin value found in the first series of investigations could not be reproduced in a control study of 255 children, the analysis of the data pointing to a methodological reason for the difference. Feasibility, planning and interpretation of results of such a cross-sectional study are discussed.

Air Pollutants↗
PubMed1989

[Spontaneous remission in disseminated histiocytosis X].

An 8 months old girl presented with biopsy-proven, disseminated histiocytosis X affecting at least two organ systems. Within one year there was spontaneous regression of the disease lasting for 10 years until today. Considering this case and others from literature the necessity of aggressive chemotherapy in selected cases is discussed.

Biopsy↗
PubMed1987

[Non-ocular, malignant secondary tumor following spontaneous healing of a retinoblastoma ("retinoma", "retinocytoma")].

In a 47-year-old patient, the father of a child with bilateral retinoblastoma, three retinomas or retinocytomas were observed in the right eye, which had never been treated, in the course of a routine checkup. The left eye had been enucleated at age three-and-a-half because of a tumor of unknown etiology. At age 55 the patient died of lung cancer. The autopsy revealed a metastasized small-cell bronchial carcinoma. Histopathological examination of the right eye showed, in the region where the tumors had been observed clinically, merely disorganized retinal tissue with proliferations of pigment epithelium in some areas, and well-differentiated retinoblastomas in others. Tumor regression and differentiation appear to be the mechanisms responsible for spontaneous healing of the retinoblastoma. This case also emphasizes the threat posed by non-ocular secondary tumors to carriers of retinoblastoma genes.

Calcinosis↗
PubMed1987

The prognosis of retinoblastoma in terms of globe saving treatment. A computer assisted study. Part I.

At present there is no satisfactory classification or staging system. In order to compare the Reese classification (Reese & Ellsworth, 1963), the Essen classification (Höpping, 1983) and a new classification, a method of evaluating different parameters was created to get an optimal classification of globe saving treatment. A computer score table for the Essen eye clinic was established and this table could be valuable for all clinics using modern methods of treatment.

Decision Making, Computer-Assisted↗
PubMed1987

Short-term effects of testolactone compared to other treatment modalities on longitudinal growth and ovarian activity in a girl with McCune-Albright syndrome.

In a 6 1/2-month-old girl with McCune-Albright syndrome, gonadotropin-independent isosexual precocity and recurrent ovarian cysts, the short-term effects of surgical therapy, cyproterone acetate (120 mg/m2/d), combined medroxyprogesterone acetate (10 mg/d), and spironolactone (50-75 mg/d) treatment, and testolactone (40 mg/kg/d) were evaluated sequentially. No significant reduction of cyst frequency was achieved with any of the medical treatments. The rate of bone maturation (delta BA/delta CA) was increased and the height standard deviation score (SDS) for bone age as a potential indicator of final height was decreased with surgical treatment alone and combined medroxyprogesterone acetate and spironolactone. Both parameters normalized with cyproterone acetate and testolactone. Height velocity SDS, however, was higher with testolactone (0.97 vs. 0.45).

Androgen Antagonists↗