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Biomedical subjects

P Imbach

Publications and source records attributed to P Imbach.

At least 37 records · Page 2Linked to original sources
PubMed1995

Childhood NHL in Switzerland: incidence and survival of 120 study and 42 non-study patients.

Based on the Swiss Pediatric Oncology Group (SPOG) cancer registry data during 1981-1991, a high average incidence of 8 new NHL per million children younger than 15 years per year was found. Of 162 children with NHL registered in 1976-1991, 120 were study patients, i.e., officially registered and treated according to SPOG or Pediatric Oncology Group (POG) protocols, while 42 were non-study patients, i.e., patients not officially enrolled on protocols. Overall, 91 of 120 (76%) study patients remained alive. Seventy-nine study patients were treated according to older SPOG protocols, and 53 (67%) of these survived, while 38 of 41 (93%) study patients treated according to newer POG protocols remained alive (P = 0.0068). Only 22 (52%) of the 42 non-study patients survived (P = 0.0001). There was no improvement if the survival of non-study patients before and since 1986 was compared. Population-based treatment results in Switzerland were similar to those in the United Kingdom. They provided an important base for the development of future treatment strategies.

Adolescent↗
PubMed1995

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↗
PubMed1995

Immunthrombocytopenic purpura as a model for pathogenesis and treatment of autoimmunity.

In honour of Professor Rossi's 80th birthday we review the development of our understanding of the immune and auto-immune nature of the pathogenesis of immune thrombocytopenic purpura (ITP). The immune aspects have been documented by postviral alterations of the cellular and humoral immune system, by new methods of specific auto-antibody detection against platelet glycoproteins and by the therapeutic effect of administering immunoglobulin concentrate from healthy blood donors. The various possible mechanisms of action of immunoglobulin treatment have led to use of this treatment as an alternative for other immune-related disorders. The treatment of severe chronic ITP in children, however, remains unsatisfactory. With a new international clinical and laboratory study of children and adolescents with early chronic ITP we are continuing the investigation of the pathogenesis and treatment of ITP.

Antibody Formation↗
PubMed1995

Immune thrombocytopenia in children: the immune character of destructive thrombocytopenia and the treatment of bleeding.

It is now recognized that different forms of destructive thrombocytopenia due to antibody binding to platelets exist, which can be differentiated by sensitive new assays. Thus, the name has been changed from idiopathic to immune thrombocytopenic purpura (ITP). The immune character of ITP has been further supported by the success of treatment with human antibody concentrate-immunoglobulin treatment. During different studies of ITP in children, it has been recognized that only patients with bleeding in addition to a platelet count less than 20 x 10(9)/L need to be treated. The various forms of treatment are reviewed.

Child↗
PubMed1995

Immunoglobulin subclass concentration in preterm infants treated prophylactically with different intravenous immunoglobins.

The most immature infants have critically low concentrations of all immunoglobulin G (IgG) subclasses, associated with a higher risk for pyogenic, respiratory, and meningeal infection. Selective IgG subclass deficiency is an established indication for intravenous immunoglobulin (IVIG) substitution. However, considering that therapeutic efficacy of IVIG is dependent on its pharmacokinetics, we studied peak and trough IgG subclass serum levels during the neonatal period (28 days) in a group of 34 healthy preterm babies (30.2 +/- 2 weeks gestational age (GA) and 1065 +/- 210 g birthweight (BW) treated prophylactically with three daily standard doses of two different IVIG preparations: Sandoglobulin (SG) (0.5 g/kg/day) and Pentaglobin (PG) (5 mL/kg/day). IgG subclass levels were assayed by radioimmundiffusion (RID) before treatment (day 1) and at days 3, 5, 7, 14, and 28 of life. Statistical analysis was performed by paired t test. In the first week of life only (days 3, 5, 7), for both IVIG preparations, subclass levels were higher than pretreatment values: IgG1, 4.6 +/- 1.7 versus 5.6 +/- 1.6 g/L; IgG2, 1.6 +/- 0.8 versus 2.1 +/- 0.6 g/L; IgG3, 0.2 +/- 0.7 versus 0.3 +/- 0.1 g/L; IgG4, 0.3 +/- 0.1 versus 0.9 +/- 0.1 g/L (p < 0.05). During this time (7 days) IgG2 levels were higher in the SG group and IgG4 was higher in the PG group (p < 0.05). This study shows pretreatment IgG subclass levels 14 days after treatment and different patterns, depending on the used preparation. We conclude that prospective clinical trials should include the study of target serum levels and timing of IVIG administration not only for IgG but also for IgG subclasses.

Bacterial Infections↗
PubMed1995

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↗
PubMed1994

Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura.

The most serious complication of childhood acute immune thrombocytopenic purpura (ITP), intracranial haemorrhage, occurs in about 1% of children with platelet counts below 20 x 10(9)/L. We conducted a randomised study to explore three treatment options in this high-risk group. 146 children (> 6 months and < 18 years old) with typical acute ITP and platelet counts of 20 x 10(9)/L or lower were randomised to receive high-dose intravenous immunoglobulin G (IVIgG) 1 g/kg on 2 consecutive days (n = 34), 0.8 g/kg once (n = 35), intravenous anti-D 25 micrograms/kg on 2 consecutive days (n = 38), or oral prednisone 4 mg/kg per day with tapering and discontinuation of prednisone by day 21 (n = 39). The rate of response as reflected by the number of days with platelet counts at 20 x 10(9)/L or lower and the time taken to achieve a platelet count 50 x 10(9)/L or more was significantly faster for both IVIgG groups than for the anti-D group (p < 0.05); the difference between prednisone and IVIgG was significant (p < 0.05) only for the IVIgG 0.8 g/kg group, and responses to the two IgG groups were similar. These differences in response rates were reflected in the percentages of children with platelet counts of 20 x 10(9)/L or lower at 72 hours following the start of treatment: 3% (IVIgG 0.8 g/kg x 1), 6% (IVIgG 1 g/kg x 2), 18% (anti-D), and 21% (oral prednisone 4 mg/kg/day). Treatment-associated toxicities included a fall in haemoglobin with anti-D (to less than 100 g/L in 24% of cases); weight gain with oral prednisone; and fever, nausea, vomiting, and headache with IVIgG. On the basis of these results, intravenous anti-D cannot be recommended as initial therapy for children with acute ITP and platelet counts of 20 x 10(9)/L or lower. A single dose of 0.8 g/kg IVIgG offers the fastest recovery for the least treatment; additional IgG or oral prednisone can be reserved for the one-third of children who continue to have platelet counts of 20 x 10(9)/L or less at 48-72 hours after the start of treatment.

Adolescent↗
PubMed1993

Diffusion of immunoglobulins into rabbit cornea after subconjunctival injection: experimental demonstration and mathematical model.

To determine whether immunoglobulins of the IgG class diffus up to the corneal center after subconjunctival injection, rabbits were injected with fluorescein-isothiocyanate-labeled human IgG. The inoculum diffused from the entire periphery centrepetally towards the corneal center. The progression of the diffusion front slowed down as the distance to the limbus increased. The first increase of fluorescence in the corneal center was observed on day 6. The intensity increased during the following 10 days despite resorption in the corneal periphery due to the flow of IgG from paracentral toward central areas. The diffusion coefficient of 0.003-0.004 cm2/day was calculated by computer simulation using Fickian diffusion equations adapted for corneal geometry. We conclude that after subconjunctival application, IgG diffuses up to the corneal center with a delay of several days and that the penetration speed decreases as the distance to the limbus increases. This kinetics contributes to our understanding of the role of IgG in corneal pathology and may help to design therapeutic schedules for immunotherapy with IgG.

Animals↗
PubMed1993

Childhood leukaemia in Switzerland: comparison of different sources of data.

Since 1976 the Swiss Paediatric Oncology Groups (SPOG) has registered leukaemia cases occurring in Switzerland. The registration was set up for clinical research; however, since 1985 efforts have been made to complete the registers with cases not taking part in a clinical trial. The data of the SPOG register between 1976 and 1989 are compared to data from cancer registers and the mortality statistics of the Federal Office of Statistics. Between 1985 and 1988 the SPOG register included 91% of the cases recorded by the six cantonal registries. Compared to mortality data, registration was 100% in 1989. The SPOG data file can therefore be assumed to be complete enough to be used for epidemiological studies on incidence of leukaemias and on time trends of leukaemias in Switzerland.

Child↗
PubMed1993

Serial IgG and IgM serum levels after infusion of different Ig-preparations (IgG or IgM-enriched) in preterm infants.

Intravenous administration of Immunoglobulin (IVIG) has been used for prevention or treatment of neonatal sepsis. However, therapeutic efficacy of IVIG is dependent on pharmacokinetic factors. There have been no comparative studies in neonates between licensed IgG and IgM enriched preparations. The aim of this study was to investigate serial IgG and IgM serum levels during the neonatal period in two groups of non-septic, preterm infants treated prophylactically with IVIG. Twenty-two very low birth weight (VLBW) patients (1001-1500g) (gestational age 31.8 +/- 2.0 weeks and 1265 +/- 245g birth weight) and 12 extremely low birth weight (ELBW) patients (< 1000g) (gestational age 28.6 +/- 2.5 weeks and 910-85g birth weight) received at random three standard doses of Sandoglobulin (SG) (0.5 g/kg/day) or IgM enriched Pentaglobin (PG) (5 ml/kg/day). IgG and IgM concentrations were assayed by rate nephelometry before treatment and at day 3, 5, 7, 14 and 28 of life. At any time IgG levels were higher in the SG-VLBW group (p < 0.01), no difference being observed in the ELBW group (p > 0.5). IgM levels were higher at day 3 and 5 in the PG-VLBW group and until day 7 in the ELBW group (p < 0.01). This study indicates a wide range of IgG and IgM kinetics in the healthy premature and suggests frequent monitoring of immunoglobulin serum levels during efficacy studies.

Humans↗
PubMed1992

[Livedo racemosa, skin necrosis at the basal toe joint].

An 81 year old male patient treated by sulfonylurea and diet was known to have type II diabetes for three years. Because of pulmonary embolism phenprocoumon had been administered for four months. Painful livedo racemosa developed acutely on both lateral sides of the feet and the left knee. A necrosis of the skin over the base of the left small toe developed within a few days. On the basis of the clinical picture cholesterol-embolism was diagnosed. Since anticoagulation is known to promote cholesterol-embolism it was discontinued. Prostaglandin E1 infusions into both legs were administered. Within 3 months the cutaneous lesions healed completely.

Aged↗
PubMed1991

Immune thrombocytopenic purpura and intravenous immunoglobulin.

The observation, in 1980, of a rapid increase in platelet counts as a result of administration of intravenous immunoglobulin (IVIG) in a patient with immune thrombocytopenic purpura (ITP) was followed by clinical studies confirming the efficacy of this new treatment alternative in ITP. Simultaneously, new sensitive assays using monoclonal antibodies against platelet glycoproteins showed that chronic ITP in adults and children is often an autoimmune disorder. There seem to be both immediate and long-term effects of IVIG in ITP which may be explained by mechanisms of action other than immunoglobulin G substitution. The mode of action of IVIG could correspond to interference with Fc receptors on phagocytes or be a result of antiidiotypic antibodies in IVIG that may induce secondary changes in the complex immunologic network. These immunomodulatory effects were the basis for the use of IVIG in the treatment of patients with other immune-related disorders. New aspects regarding definition and treatment of ITP, the possible mechanisms of action of IVIG, and the implications thereof are discussed and updated.

Adult↗
PubMed1991

High-dose intravenous IgG treatment and renal function.

In an open trial of high dose intravenous IgG (IVIG) treatment in nephrotic patients with glomerulonephritis, the first six patients so far studied showed a transient rise in plasma creatinine. This increase was not associated with any symptoms and the urinary deposit remained unchanged. Two other patients with pre-existing renal impairment but without nephrotic syndrome had a transient and reversible rise in plasma creatinine immediately after IVIG. These observations suggest that high-dose IVIG infusion can produce short-lived disturbances in renal function in patients with kidney diseases.

Adult↗
PubMed1991

Immunoglobulin serum levels in very low birth weight infants treated with different intravenous preparations.

Parenteral human immunoglobulin (IVIG) administration is widely used in low birth weight (LBW) infants for prevention and therapy of neonatal infection. In previous studies, IVIG preparations containing IgG and low IgM concentrations were commonly used. In this study we compare immunoglobulin serum levels in two groups of healthy preterm infants receiving prophylactically standard IVIG (Sandoglobulin, 0.1 mg/kg IgM) or IgM-enriched IVIG (Pentaglobin, 30 mg/kg IgM). Immunoglobulin levels were assayed by rate nephelometry at birth and at 3, 5, 7, and 14 days after birth. The two groups of patients were matched for gestational age (31 +/- 2.3 weeks), birth weight (1320 +/- 340 g), and serum IgG (4.1 +/- 1.9 milligram) and IgM (0.22 +/- 0.18 milligram) levels at birth. Significantly higher IgM levels were observed at 3 and 5 days after IgM-enriched IVIG administration (p less than 0.01). Higher IgG levels were attained and persisted for 2 weeks after standard IVIG administration (p less than 0.01). These data indicate different IgG and IgM target levels in LBW infants treated with different immunoglobulin preparations.

Bacterial Infections↗
PubMed1991

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↗
PubMed1991

Safety of intravenous immunoglobulin preparations: a prospective multicenter study to exclude the risk of non-A, non-B hepatitis.

The risk of non-A, non-B hepatitis transmission by an intravenous immunoglobulin (IVIG) preparation was assessed in a prospective multicenter trial in 68 patients with primary immunodeficiency disorders (40 children or adolescents and 28 adults). During the 4-week prestudy evaluation period the clinical examinations and liver function tests including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, and bilirubin were normal in all patients. The treatment consisted of three infusions of 200 mg IVIG (pH 4; pepsin procedure) per kilogram body weight at 2-week intervals. During the observation period of 24 weeks following the first infusion of the study IVIG, the patients were monitored at regular time intervals. No clinical and laboratory signs of hepatitis or liver dysfunction were noticed. All patients completed the study. In 5 patients, one isolated alanine aminotransferase value and in another patient one gamma-glutamyl transpeptidase value were moderately elevated, but always below 2.5 times the upper limit of the reference range. Similar isolated and transient elevations were observed for aspartate aminotransferase and alkaline phosphatase. It was concluded that the IVIG preparation did not transmit non-A, non-B hepatitis or other viral liver diseases.

Adult↗
PubMed1990

Immunomodulation by intravenous immunoglobulin.

In 1980, it was observed in a child with idiopathic thrombocytopenic purpura (ITP) that intravenous administration of pooled human immunoglobulin-G (IVIG) was followed by a rapid increase of the platelet count. Prompted by this finding, a pilot study and two prospective multicenter studies on children with ITP were organized. Efficacy of this new treatment for ITP was soon confirmed worldwide. In addition to the immediate effect, long-term observations following administration of IVIG suggested the occurrence of modulation of the immune response. Also, concomitant with studies on the mechanism of action of IVIG, the use of IVIG in the treatment of patients with other immune-related disorders was explored.

Adjuvants, Immunologic↗