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Biomedical subjects

W Berchtold

Publications and source records attributed to W Berchtold.

At least 19 recordsLinked to original sources

Childhood ITP: 12 months follow-up data from the prospective registry I of the Intercontinental Childhood ITP Study Group (ICIS).

BACKGROUND: Acute and chronic idiopathic thrombocytopenic purpura (ITP) is traditionally based on the duration of thrombocytopenia at the cut-off point of 6 months after diagnosis. Registry I evaluated the diagnosis, definition, management, and follow-up of childhood ITP. This report focuses on children with thrombocytopenia persisting more than 6 months. PROCEDURE: Data were collected by questionnaires to the physicians caring for children with ITP, at diagnosis, 6, and 12 months later. Data were compared regarding initial features and follow-up with emphasis on children with persistent thrombocytopenia, and those with ITP who recovered their platelet counts between 7 and 12 months from diagnosis. RESULTS: At 12 months from diagnosis, 79 of 308 (25.6%) evaluable children recovered from ITP and 229 had ongoing ITP. Children with recovered ITP were younger than children with ongoing ITP (P = 0.043) and exhibited a lower frequency of bleeding symptoms during the first 6 months after diagnosis (P = 0.018). Frequency of hospitalization, bone marrow aspiration, and drug treatment differed regionally. CONCLUSIONS: The high rate of recovery from ITP between 7 to 12 months demonstrates, that the cut-off point of 6 months for the definition of chronic ITP does not adequately differentiate chronic from acute ITP. The majority of children with ITP have variable time to recovery with gradual improvement of platelet counts and disappearance of bleeding signs. ITP is a heterogeneous disorder with a diverse natural history and diverse pattern of treatment response.

Acute Disease↗

Ethnicity and environment may affect the phenotype of immune thrombocytopenic purpura in children.

Little is known about the influence of environmental and ethnic factors on the epidemiology of immune thrombocytopenic purpura (ITP). Therefore we compared the initial presentation and condition after 6 mo in 90 Vietnamese and 89 German and Swiss children with newly diagnosed ITP. Data from the two cohorts were collected within the same time period. No differences in age and sex were observed between the Asian and European cohorts, but significant differences between initial platelet count, the occurrence of dry versus wet bleeding symptoms, and infection preceding the onset of ITP were found. Children who had chronic ITP also differed with respect to platelet count and postinfectious state, but not initial bleeding type. In addition, chronic ITP occurred more often than expected with a male to female ratio of 1.2 in Vietnam and 2 in Germany and Switzerland. The data support the potential influence of environmental or ethnic factors on the different aspects of ITP, and point to the need for further epidemiologic investigations.

Asian People↗

Pediatric medulloblastoma: prognostic value of p53, bcl-2, Mib-1, and microvessel density.

The aim of this study was to retrospectively assess the prognostic value of p53 and bcl-2 protein expression, cell proliferation index (Mib-1 index), and tumor microvessel density (factor VIII-related antigen) in pediatric medulloblastoma patients. Tumor specimens of 55 patients (age 2-18 years) with medulloblastoma treated with a curative intent between 1972 and 1991 were studied. Slides of paraffin embedded tissue were stained with monoclonal antibodies (mAb) and examined under high power light microscopy for the presence of immunoreactivity. Microvessel density was scored both in the area of most intense staining ('Angio-max') and in 3 additional randomly selected areas. The sum of these 4 scores was termed 'Angio-total'. 'Angio-max' and 'Angio-total' were evaluated separately by two independent investigators to assess reproducibility. None of the parameters studied, i.e. p53 or bcl-2 expression, Mib-1 index or microvessel density scores were associated with patient survival. Microvessel scores between observers were significantly but weakly correlated, with correlation coefficients (r) < 0.5 for both 'Angio-max' and 'Angio-total'. Leptomeningeal spread at diagnosis was the only independent factor associated with a poor survival (p = 0.003). There was no association of leptomeningeal metastasis with any of the biological markers tested in this study.

Adolescent↗

Surgical recurrence of perforating and nonperforating Crohn's disease. A study of 101 surgically treated Patients.

PURPOSE: This is a study of the long-term course of surgically treated Crohn's disease designed to identify prognostic factors predictive of the time course and probability of surgical recurrence. PATIENTS AND METHODS: The study is based on the records of 101 patients admitted to our institution for surgical treatment of Crohn's disease from January 1, 1970 to December 31, 1985. Follow-up was complete in 97 (96 percent) and incomplete in 4 patients. Median follow-up from the date of first operation was 13.25 years. The cumulative probability of requiring surgical treatment for recurrent disease was calculated using the life table method and further analyzed with the log-rank test and Cox regression. RESULTS: The time to reoperation in this series was not significantly influenced by sex, age at onset of symptoms, age at diagnosis, age at first operation, anatomic location, and number of sites involved at the time of first operation. The only variable that had a statistically significant effect on the time to reoperation was characterization of disease at the time of operation as being perforating (P) opposed to nonperforating (NP). Median interval between the first and second intestinal operation was 1.7 years for the P group and 13 years for the NP group (P value, 0.005), and the median time between any two operations undergone during the study period was 2 years for the P group and 9.9 years for the NP group (P = 0.0002). The risk of having to undergo reoperation for recurrence was greatest during the first two years after an operation, and this was mainly because of a short time to surgical recurrence in the P group of indications. Therefore, the yearly hazard of requiring further surgery was maintained at approximately 5 percent. CONCLUSION: The cumulative probability of requiring a reoperation for patients undergoing surgery for the P type of Crohn's disease is significantly different from that of patients with NP indications. The risk of having to undergo further surgery is particularly high during the first two years following an operation for perforating disease. The concept of a relatively aggressive perforating type of Crohn's disease and a more indolent nonperforating type is confirmed by the results of this study.

Adult↗

[Sepsis score in surgical intensive care medicine].

In a prospective study (400 patients, intensive care stay > 18 h) the following data were documented daily: Clinical sepsis, a modified sepsis score, Apache II-score, number of organ failure, Elastase-concentrations and injury severity score (ISS > or = 20 = polytrauma). On admission day a prognostic assessment for early diagnosis of septic complications during intensive care could be demonstrated by a combination of the modified sepsis score and the number of organ failures and the presence of polytrauma. All other parameters did not have any predictive value.

APACHE↗

Incidence of deep sepsis in uncemented total hip arthroplasty using clean air facility as a function of antibiotic prophylaxis.

Eight hundred and twenty two uncemented primary total hip arthroplasties (THAs) were performed between September 1980 and December 1992. The population that underwent uncemented THA can be divided into two groups based on the perioperative antibiotic prophylaxis: group 1 contains 439 primary THAs from September 1980 to September 1987 without antibiotic prophylaxis; group 2 contains 383 primary THAs who received short-term cefamandole prophylaxis from October 1987 to December 1992. Laminar air-flow and whole-body exhaust suits were used during the whole period of this study. Both groups consisted of relatively young patients with a mean age of 53.8 years in group 1, and 54.3 years in group 2. Using Kaplan-Meier survivorship analysis, the estimated survival rate of sepsis-free hips in group 1 was 97.9% at one year, 97.6% at two years, and 97.4% at three and up to eleven years. In group 2 with antibiotic prophylaxis no deep infection occurred; the rate of sepsis-free hips at five years is 100%. Under clean air conditions, antibiotic prophylaxis significantly decreased the incidence of deep sepsis (p log-rank 0.004).

Adolescent↗

Incidence of childhood acute lymphoblastic leukemia (ALL) and population-based treatment results in Switzerland: experiences with 507 study and 149 nonstudy patients.

Of 656 patients with ALL (all types) diagnosed in Switzerland during 4 consecutive 4-year periods (1976-1979, 1980-1983, 1984-1987, 1988-1991), 507 were officially registered on protocols ("study" patients) while 149 were not ("nonstudy" patients). The mean incidence of 3.8/100,000 children < 15 years/year is higher than reported for other Western countries. Evidence is presented suggesting that the 656 patients represent only approximately 90% of all children with ALL residing in Switzerland, indicating that the true incidence of ALL might even be higher. The fraction of "nonstudy" patients fell from 40% (1976-1979) to 15% (1984-1987). The rate of survival at 4 years of all patients with ALL ("study" and "nonstudy") increased by 17% during the three consecutive periods 1976-1979, 1980-1983, and 1984-1987. As expected, a higher increase (20%) was observed in "study" patients and a statistically nonsignificant lower one (10%) in "nonstudy" patients.

Adolescent↗

Boys but not girls with T-lineage acute lymphocytic leukemia (ALL) are different from children with B-progenitor ALL. Population-based data results of initial prognostic factors and long-term event-free survival. Swiss Pediatric Oncology Group.

PURPOSE: In a population-based data registry of children with ALL, initial prognostic factors were analyzed with regard to long-term event-free survival. PATIENTS AND METHODS: From 1976-1991 the Swiss Pediatric Oncology Group (SPOG) observed 610 children and adolescents who were diagnosed with ALL before the age of 15 years, and who were prospectively treated according to different study protocols. Immunophenotyping of B-progenitor- or T-lineage ALL was possible in 573 children. Leucocyte count, age, and sex were compared with regard to immunophenotype of lymphoid cells and to event-free survival on Kaplan Meier curves by statistical analyses including multivariate analysis and the Cox regression backward elimination test. RESULTS: Of the 573 patients who were immunophenotyped 86.4% had B-progenitor ALL and 13.6% T-lineage ALL. The differences between B-progenitor ALL and T-lineage ALL with respect to initial white blood cell count, age and gender were significant. A comparison of event-free survival in children with B-progenitor ALL versus T-lineage ALL revealed significant differences in boys (p < 0.001) but not in girls (p = 0.183). Statistical tests showed gender to be an independent risk factor. CONCLUSION: The long-term outcome following identical treatment of both genders was significantly better in girls with T-lineage ALL than in boys. Girls with T-lineage ALL, but not boys with T-lineage ALL, had a prognostic outcome similar to children with B-progenitor ALL.

B-Lymphocytes↗

Preliminary results of a study assessing asthenia and related psychological and biological phenomena in patients with advanced cancer.

Asthenia is a very common symptom of patients with advanced cancer, but its investigation is hindered by a lack of suitable validated measuring instruments. The goal of the present study was to construct and validate a questionnaire for the study of asthenia in cancer patients, as well as to establish correlations with other symptoms and physiological and biochemical parameters. A group of 31 patients with advanced cancer and a control group of 30 healthy volunteers were examined. The proposed questionnaire, based on visual analogue scales, questions with categorical answers and on the hospital anxiety and depression scale was validated by comparing results of the patient and control groups, by the test/retest method and by comparison with the evaluation of an observer. Correlation with various physiological and biochemical parameters was performed. The questionnaire distinguished well among the patients and control groups. VAS of asthenia proved quite stable over a period of 5 days. Correlations of asthenia with lack of appetite, the hospital anxiety and depression scale, weight, heart rate and serum cortisol levels could be established. No significant correlation between asthenia and various serum markers of inflammation and cytokines, including C-reactive protein, tumour necrosis factor, interleukin-1, and interleukin-2 receptors, could be found. The proposed questionnaire for evaluation of asthenia could be validated in a patient sample of limited size and a simplified questionnaire based on visual analogue scales is being developed for further investigations.

Adult↗

Different forms of chronic childhood thrombocytopenic purpura defined by antiplatelet autoantibodies.

To determine whether detection of antiplatelet autoantibodies (AAb) to glycoproteins IIb/IIIa and Ib/IX may be useful in defining different forms of chronic thrombocytopenic purpura (TP) in children, we analyzed for AAb the platelet and plasma samples from 36 children with chronic TP (mean duration 4.4 years), from 31 children with normal platelet counts at the time of blood sampling but with chronic TP in the past (mean duration 2.9 years), and from 23 adults with chronic TP; the results were correlated with the clinical data. Antiplatelet autoantibodies were detected in 26 (72.2%) of 36 children with ongoing TP, 15 (48.4%) of 31 children with TP in the past, and 12 (66.7%) of 18 adults with TP. All children with high AAb ratios (greater than 5 times the control mean + 3 SD) were more than 8 years of age at diagnosis (mean age 12.4 years compared with 7.1 years in children with moderate or negative AAb levels; p = 0.003). The results suggest that the outcome for adolescents with high platelet-associated AAb levels may be similar to that of adults, whereas younger children may have a greater chance of spontaneous remission. The children with chronic TP in the past and elevated platelet-associated AAb levels may have a "compensated" TP and therefore may be at risk for relapses. Future studies aimed at serial AAb determination throughout the patients' courses may further define TP subgroups.

Adolescent↗

Intravenous immunoglobulin (i.v. IgG) for previously treated acute or for chronic idiopathic thrombocytopenic purpura (ITP) in childhood: a prospective multicenter study.

In a prospective multicenter study 42 thrombocytopenic (less than 30 X 10(9) platelets/l) children with chronic idiopathic thrombocytopenic purpura (ITP) or with acute ITP, dependent on or refractory to corticosteroids, were given 0.4 g i.v. IgG/kg body weight/day on 5 consecutive days and thereafter once a week if the platelet count fell to less than 20 X 10(9)/l or if the patient bled. After the initial 5 days of i.v. IgG the platelets rose within a mean of 7-8 days to greater than 30 X 10(9)/l in all and to greater than 150 X 10(9)/l in 33 of 42 patients (79%). After a mean observation time of 26.6 months 26 of 42 patients (62%) showed a satisfactory long-term effect, i.e. no need for treatment for at least 6 months without bleeding and with no platelet counts below 20 X 10(9)/l. No difference in response rate was found between children with chronic and those with previously treated acute ITP. These results indicate that i.v. IgG could be used to control emergency situations, e.g. to stop bleeding or to prepare a patient for surgery. I.v. IgG also represents a good alternative to treatment modalities, such as splenectomy and/or the administration of cytostatic immunosuppressants with potentially serious side effects. In addition to the expected transient rise in serum IgG levels, i.v. IgG induced a more prolonged elevation of serum IgM. Platelet associated IgG, elevated before therapy, was correlated with the clinical long-term outcome.

Acute Disease↗

Radioprotection by pretreatment with deuterated water: cytokinetic changes in the small intestine of the mouse.

All mice partially deuterated by ingestion of 29% heavy water for 12 days survived whole body gamma irradiation (8.5 Gy) from a 60Co source, whereas 42% of nondeuterated control animals died from bone marrow failure. The incorporation of 3HTdR into enterocytic DNA, as measured by autoradiography and liquid scintillation spectrometry, was used to assess the proliferative activity of small intestinal epithelium. The sequence and the magnitude of changes in tritium activity were in good agreement. Deuteration alone resulted in a reduced proliferative activity of small intestinal crypt epithelium, particularly in the basal cell positions and the first positions of the proliferation compartment. The number of positions occupied by the proliferative compartment and the crypt length were, however, barely affected by deuteration. The radiation-induced depression of DNA synthesis in the proliferative compartment was of similar magnitude in both groups. Crypt epithelium in deuterated mice, however, displayed signs of an accelerated and/or enhanced regeneration. The cytokinetic changes in deuterated animals are consistent with a protective effect for clonogenic intestinal epithelium at the time of irradiation.

Animals↗

Isolated central nervous system relapse in acute lymphocytic leukemia (ALL) in children. Experiences of the Swiss Pediatric Oncology Group (SPOG/SAKK) 1976-1986.

The incidence of isolated CNS-relapse in the SPOG ALL studies 1976-1986 was analyzed and the prophylaxis of meningosis leucaemica of the different studies was compared. In the SPOG ALL high-risk study 1979-1983, the incidence of isolated CNS-relapse was significantly higher (17/71, 24%) than in the other studies. In this period, radiotherapy was omitted and the prophylactic treatment consisted only of moderately high doses of intravenous methotrexate and intrathecal methotrexate. In other studies, it was shown that the prophylactic combination of CNS-radiotherapy and intrathecal methotrexate, or the periodic administration of combined intrathecal chemotherapy alone, during the whole therapy of 2 1/2 years, produced comparably good results. The prophylaxis with the combined intrathecal chemotherapy was less neurotoxic and allowed the use of a curative radiotherapy in case of a CNS-relapse.

Adolescent↗

Long-term results of two Swiss AML studies.

The Swiss group for clinical cancer research (SAKK) completed two first line protocols for the treatment of acute myelogenous leukemia (AML). In the first protocol (SAKK AML 74, from August 1974 to April 1977; 107 patients) the effectiveness of immunization with viral oncolysate during maintenance treatment was tested. After successful induction treatment, the patients were randomized in two groups: Group A: monthly maintenance chemotherapy for 2 years and group A+IT, which received the same maintenance chemotherapy regimen plus, on day 15, injection of viral oncolysate. Of the 107 patients, 57 (53%) achieved complete remission, 29 then being randomized to group A, 28 to group A+IT. As of August 1984, there is no statistical difference between the survival times of the two groups (p = 0.288). Ten years after the start of the study there is still no clear plateau of the survival curve. Nine percent of all patients (18% of the remission patients) are alive today. With the treatment of the mid-seventies, therefore, the cure of a patient suffering from AML was a rare event. The second protocol (SAKK AML 77, from April 1977 to April 1982; 162 patients) was designed to evaluate the usefulness of a prolonged maintenance treatment after early consolidation. The 74 patients who were still in remission after early consolidation treatment were assigned to either maintenance chemotherapy or to observation only. At 3.5 years after the last patient's entry there was no difference between the groups in duration of survival (p = 0.332).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Chronic myeloid leukemia: multivariant analysis of initial findings regarding its effect on mean life expectancy].

Clinical signs, complete blood counts and bone marrow differential counts at the time of diagnosis were investigated in 75 consecutive patients with chronic myelogenous leukemia in a study of prognostic parameters. All patients were followed until death (62 patients) or for a mean follow-up time of 69 months (13 patients). Clinical signs and hematological values were analyzed by univariate and multivariate statistical methods. The only parameter relevant to mean survival time in multivariate analysis is the percentage of bone marrow myeloblasts at diagnosis. Patients with less than 5% myeloblasts at diagnosis had a mean survival time of 48 months compared with 16 months for those with greater than or equal to 5% (p less than 0.01).

Analysis of Variance↗

Conformational changes in aspartate aminotransferase. Effect of active site ligands on peptide hydrogen-deuterium exchange.

The conformational responses of aspartate aminotransferase (cytosolic isoenzyme from pig) to the binding of the coenzyme and competitive inhibitors and to the bond rearrangement steps during the transamination reaction were probed by the method of peptide hydrogen deuterium exchange. Binding of the coenzyme to the apoenzyme results in a marked retardation of hydrogen exchange; binding of the competitive inhibitor maleate to the pyridoxal enzyme induces a retardation of exchange somewhat exceeding that observed in the presence of the transaminating substrate pair glutamate and 2-oxoglutarate (Pfister, K., Kägi, J.H.R., and Christen, P. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 145-148). On formation of the complex of apoenzyme with N-(5'-phosphopyridoxyl)-L-glutamate or-L-aspartate, analogs of the covalent coenzyme substrate intermediates, a similar exchange retardation occurs. The extent of the exchange retardation in these different functional states of the enzyme correlates with previous results of differential chemical and proteolytic modifications. Apparently, the diverse methods register shifts in one and the same conformational equilibrium. Moreover, the conditions under which peptide hydrogen exchange indicates a pronounced tightening of the protein matrix correspond with those inducing crystallization of the enzyme in the "closed" form. Thus, the transition between the "open" and "closed" form of the enzyme, i.e. the bulk movement of the small domain, as observed and defined by x-ray crystallography (Kirsch, J. F., Eichele, G., Ford, G. C., Vincent, M. G., Jansonius, J. N., Gehring, H., and Christen, P. (1984) J. Mol. Biol. 174, 497-525) is the major structural correlate of the conformational changes undergone by the enzyme in solution.

Animals↗

Intravenous immunoglobulin versus oral corticosteroids in acute immune thrombocytopenic purpura in childhood.

In a randomised, multicentre study intravenous IgG was compared with oral corticosteroids in 108 children with untreated acute immune thrombocytopenic purpura. IgG was an efficient treatment with no severe untoward reactions. The effects of corticosteroids and IgG were identical for rapid responders, who accounted for 62% of all patients. In contrast, patients requiring more than initial treatment responded better if randomised to IgG. The serum IgG level increased two-fold after IgG. A significant rise in IgM levels was observed after both IgG and corticosteroids. The platelet-associated IgG index was high in 75% of all patients. No significant differences between the two treatment groups were found, but rapid responders had a smaller mean initial platelet-associated IgG index which returned more rapidly and more permanently to normal than that of slow responders.

Acute Disease↗