Significant and persistent improvement of thrombocytopenia after splenectomy in an adult with the Wiskott-Aldrich Syndrome and intra-cerebral bleeding.

The Wiskott-Aldrich syndrome is an X-linked inherited immunodeficiency disorder characterized by thrombocytopenia, recurrent infections and eczema. Its best management option is HLA-identical bone marrow transplantation; when this is not feasible, splenectomy, followed by continuous prophylactic antibiotics, represents the alternative of choice. The present case report relates the excellent outcome of an adult with the Wiskott-Aldrich syndrome who suffered his first major complication of the disease at age 33 years, an intracerebral hemorrhage. Since an uneventfull splenectomy, thrombocytopenia has significantly improved, and he has remained free of infections for a follow-up period of 3 years while being treated with prophylactic antibiotics.

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.

[Acute dehydration in children]. / Die akute Dehydratation bei Kindern.

The acute loss of fluids and electrolytes in children can result in critical situations of emergency. Infants and young children are at particular risk for these events. The main cause of dehydration in this age group is acute diarrheal disease. A careful history and the clinical signs allow an approximative estimation of the severity of the fluid loss. The type of dehydration is determined by the measurement of the sodium concentration in blood. The isonatremia type is the most common one and is present in 70% of all children with dehydration. The fluid therapy consists in restoring the deficits of water and electrolytes, in covering the basic needs and in replacing the continuing losses. The oral rehydration with appropriate glucose-electrolytes solutions, which are commercially available, is very effective in mild and moderate dehydration. This method allows a rapid rehydration and will markedly reduce the number of hospitalizations; furthermore, a prompt refeeding (realimentation) within 24 hours is possible. The parenteral rehydration for certain moderate and for severe forms is reserved to treatment in a hospital or an emergency department. The practical proceeding of both types of rehydration is described.

Megakaryocyte growth in vitro predicts outcome in idiopathic thrombocytopenic purpura.

PURPOSE: The impact of megakaryocyte growth in vitro on clinical data, especially outcome, was studied in 25 consecutive children with idiopathic thrombocytopenic purpura (ITP). PATIENTS AND METHODS: Twenty children with untreated de novo ITP and five children with pretreated ITP were evaluated. The number of megakaryocyte colonies (cloning efficiency), the mean cell number per colony (mitotic amplification) and the percentages of polyploid megakaryocytes after 7 and 12 days in culture (relative size of the endomitotic compartment) were determined in two separate clonal assays. The culture data were related to clinical findings and outcome of the thrombocytopenia. RESULTS: The mean cell number per megakaryocyte colony was significantly correlated with the observed increase in the platelet count 5 days after starting therapy (n = 23; r = 0.642), and a significant negative correlation was found between the relative size of the endomitotic compartment and the duration of thrombocytopenia after bone marrow culture analysis (n = 25; r = -0.503). If all 25 children with ITP (untreated de novo and pretreated ITP) were considered, a normal frequency of polyploid megakaryocytes was associated with a duration of ITP for < 6 months in 14 of 16 cases, whereas an impaired polyploidization predicted a persistence of ITP for > 6 months in 9 of 9 cases (p < 0.0005); if only children with untreated de novo ITP (n = 20) were considered, 13 of 15 children with a normal polyploidization had an acute course of their ITP and 5 of 5 children with an impaired polyploidization developed chronic ITP (p < 0.003). CONCLUSIONS: The results in this small group of patients suggest that the assessment of the relative size of the endomitotic compartment after 7 and 12 days in plasma clot culture actually appears to be the best method for predicting a chronic course in children with ITP.

[Hemolytic-uremic syndrome in children: a 19-year retrospective study]. / Hämolytisch-urämisches Syndrom bei Kindern: Retrospektive über 19 Jahre.

Forty-two children (22 girls and 20 boys, ranging in age between 2 months and 13 years, median age 17 months) were admitted with acute hemolytic-uremic syndrome to the University Children's Hospital, Berne from 1973 to 1991. Seventeen patients developed hypertension and 30 renal failure. Three out of the 19 cases necessitating acute dialysis progressed to end stage renal failure. Four out of the 7 patients with signs of severe central nervous system involvement died. The initial clinical course was consistently more favourable in 35 patients with diarrheal prodrome. Increased protein excretion in association with high blood pressure was observed in 4 patients with initial favourable course who were examined one year after disease onset. This study indicates the generally favourable immediate prognosis of childhood hemolytic uremic syndrome and the possible persistence of high blood pressure and pathological proteinuria on follow-up.

[Eye complications in chronic juvenile arthritis]. / Augenkomplikationen bei juveniler chronischer Arthritis.

BACKGROUND: The relationship between uveitis anterior in childhood and juvenile chronic arthritis (JCA, respectively JRA) has been known since 1950. In a review, the clinical picture of uveitis anterior, its prevalence, pathogenesis, prognosis and current therapy of ocular complications are presented. In addition, we will report our results of a clinical study. PATIENTS AND METHODS: In a cross-sectional study, 64 patients with juvenile chronic arthritis (JCA) had an ophthalmological screening for eye complications either from the disease itself or from the treatment. RESULTS: In 16% of the patients, an iridocyclitis was found, in one case acute, in 9 cases chronic. The cases of chronic uveitis anterior showed in 43% a combination with the classic risk factors (ANA-positive, oligoarticular, female). At the beginning of uveitis, the patients had a mean age of 81 months, at the beginning of JCA disease a mean age of 37 months. Four of 10 patients (= 40%) had eye complications from uveitis (cataract, posterior synechiae, glaucoma). Complications from therapy were found in 27%, mostly cataract as a complication of systemic and topical steroid treatment. Eighteen % had a visual acuity of 0.4 or less. CONCLUSIONS: Because of the often asymptomatic progression of chronic uveitis anterior, the risk of severe undetected eye complications is high. Therefore, an intensive interdisciplinary cooperation between rheumatologists, pediatrics and ophthalmologists is required.

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.

Recovery of megakaryocytopoiesis in vitro in children with acute lymphoblastic leukemia during induction of remission.

In children with acute lymphoblastic leukemia (ALL), megakaryocytopoiesis was investigated in vitro by the semisolid agar culture technique. In untreated ALL the median number of committed megakaryocyte progenitor cells (CFU-Mk) in the bone marrow was 2 (range less than 0.1-8) per 10(5) bone marrow cells instead of 30 (range 14-93) in controls, the impairment being dependent on the degree of leukemic bone marrow infiltration. However, if the number of CFU-Mk was related to residual nonleukemic bone marrow cells only, two-thirds of the children investigated had a frequency of CFU-Mk within the normal range. After 2 weeks of induction therapy the majority of the children had a low number of CFU-Mk in the bone marrow (median 6, range 0.5-40), a fact that could no longer be explained by a dilution of CFU-Mk by leukemic cells. After 4 weeks of chemotherapy (day 29) the frequency of CFU-Mk had risen to 18 (range 3-67) per 10(5) bone marrow cells, a value still significantly (p less than 0.01) below the normal range. In contrast to the changes in the number of CFU-Mk the median cell number per megakaryocyte colony remained constant during induction of remission. After cessation of long-term chemotherapy all children investigated had a normal number of CFU-Mk, suggesting that no permanent chemotherapy-related damage to committed megakaryocyte progenitor cells was induced.

Acute megakaryoblastic leukemia in children identified by immunological marker studies.

Acute megakaryoblastic leukemia (AMkL), defined by the presence of the platelet-associated glycoprotein IIb/IIIa complex on malignant cells, was diagnosed in 4 (4%) of 103 consecutive children with untreated acute leukemia or 4 (21%) of 19 children with acute nonlymphoblastic leukemia (ANLL). Particular features in the four children with AMkL were an age below 12 months at diagnosis (two patients), the absence of a significant hepatosplenomegaly (three patients), a leukocyte count below 20 x 10(9)/L with only a few blast cells in the peripheral blood (four patients), a technically difficult bone marrow aspiration (three patients), the presence of many megakaryocytes in marrow particles (two patients), and an inconclusive cytochemistry (four patients). The four children with AMkL were treated according to protocols for ANLL and a complete remission was obtained in all patients. One patient died from relapse after 3 months, one patient is a long-term survivor (38+ months), and two patients still on chemotherapy are disease-free for 11+ and 13+ months.

[Transient erythroblastopenia in childhood]. / Die transitorische Erythroblastopenie des Kindesalters.

Clinical and laboratory findings in 9 patients with transient erythroblastopenia of childhood (TEC) are presented and compared with the literature. TEC mainly affects infants presenting with normochromic, normocytic anemia and reticulocytopenia. Liver, spleen and lymph nodes are not enlarged. As a rule the white blood cell count is normal and the platelet count elevated. Bone marrow examination reveals absence of erythropoiesis. TEC is a self-limiting disorder which needs no therapeutic measures other than transfusion where necessary.

Ehlers-Danlos syndrome type IV: a multi-exon deletion in one of the two COL3A1 alleles affecting structure, stability, and processing of type III procollagen.

We have studied a patient with severe, dominantly inherited Ehlers-Danlos syndrome type IV. The results indicate that this patient carries a deletion of 3.3 kilo-base pairs in the triple helical coding domain of one of the two alleles for the pro-alpha-chains of type III collagen (COL3A1). His cultured skin fibroblasts contain equal amounts of normal length mRNA and of mRNA shortened by approximately 600 bases, and synthesize both normal and shortened pro-alpha 1(III)-chains. In procollagen molecules containing one or more shortened chains, a triple helix is formed with a length of only about 780 amino acids. The mutant procollagen molecules have decreased thermal stability, are less efficiently secreted, and are not processed as their normal counterpart. The deletion in this family is the first mutation to be described in COL3A1.

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.

Biotin and Rett syndrome.

A protein load with an ensuing 20 hr fast was performed to assess the function of biotin dependent carboxylases in 3 girls with Rett syndrome. In plasma a moderate increase of ammonia and propionate was found. The fact that these discrete biochemical alterations were found in all of the patients supports earlier conclusions that further studies on biotin metabolism and carboxylase function should be performed, perhaps preferably in cerebrospinal fluid.

[Pregnancy in a representative Swiss population (study of pregnancy and newborn infants in Aarau). 3. Diseases and drugs in pregnancy]. / Schwangerschaftsverlauf in einem repräsentativen Schweizer Kollektiv (Aarauer Schwangerschafts- und Neugeborenenstudie). III. Krankheiten und Medikamente in der Schwangerschaft.

As part of an overall study, a cohort of 996 Swiss mothers was interviewed upon admission to the labour ward regarding illnesses, disorders and the use of drugs during pregnancy. The data are presented and compared with analogous data on the entire female population of the same age group in Switzerland, and with epidemiologic reviews of pregnancy events from other countries. Somatic illness, particularly the common cold, were reported by 55%, and complaints of a more psychosomatic character by 47%. Illness related to pregnancy was found in more than 40% of the women. Only 16% reported no illnesses or complaints during the course of pregnancy. On the other hand, 33% of the mothers had taken no medication during pregnancy. Compared with studies from other countries the use of medication in this group of women was lower, particularly self-medication for minor complaints. The women reported an average intake of 1.6 drugs. In the offspring of these mothers only a few minor somatic effects were demonstrable. The Brazelton behavioral assessment did, however, reveal some significant correlations.

[Benefits of routine automatic blood picture differentiation]. / Nutzen der routinemässigen automatischen Blutbilddifferenzierung.

The benefits of automated blood smear differential cell counting as a supplementary laboratory examination have been studied. The investigations focussed on patients of whom hematology requisitions were limited to total leukocyte count and hemoglobin determination. The specimens were derived from patients of departments of surgery and obstetrics and gynecology. For specimen collection the vacutainer system was used. The blood smears were prepared in a Coulter Electronics slide spinner, stained with a Hematek II slide stainer and analyzed in the Coulter Electronics Diff 3-50 cell classifier. A total of 1700 blood smears were examined. Following processing of each sample, the classification of each cell was inspected. Corrections were performed, if necessary, and the number of classification changes performed for each smear was registered. Using the in-house normal ranges, 34.5% were pathological smears. Since this group included a large number of borderline cases, new discrimination limits for clinically relevant pathological findings were set empirically. According to these wider ranges, the fraction of pathological slides amounted to 15.2%. Among these, immature granulocytes, eosinophilia and lymphopenia were the most frequent pathological findings. Microscopic control proved in 57.6% of the total number of smears. This complemental procedure was not found to be time-consuming.

[The course of pregnancy in a representative Swiss sample (Aarau Pregnancy and Newborn Infant Study). II. Stimulants in pregnancy]. / Schwangerschaftsverlauf in einem repräsentativen Schweizer Kollektiv (Aarauer Schwangerschafts- und Neugeborenenstudie). II. Genussmittel in der Schwangerschaft.

Within the framework of a study on the course of pregnancy, a cohort of 996 Swiss mothers was interviewed upon admission for delivery at Aarau Maternity Hospital regarding nicotine, alcohol, caffeine and narcotics consumption. The data are presented and compared with analogous data on the entire female population of the same age group in Switzerland and with epidemiologic reviews of pregnancy events from other countries. The relationship between these data and effects on the newborn is also discussed. This group of mothers aged 20-40 years had, even prior to pregnancy, below-average alcohol and nicotine consumption. During pregnancy nicotine use in the last trimester, though reduced, was still admitted by 18% of the gravidae despite the fact that about 3/4 of the mothers were well informed about detrimental effects on the offspring. Nicotine use by the mother had several somatic effects on the newborn, in contrast to consumption of caffeine and small amounts of alcohol. The behavioral assessment was altered by previous use of nicotine and caffeine.

[The course of pregnancy in a representative Swiss population (the Aarau Pregnancy and Newborn Infant Study). I. Social medicine aspects]. / Schwangerschaftsverlauf in einem repräsentativen Schweizer Kollektiv (Aarauer Schwangerschafts- und Neugeborenenstudie). I. Sozialmedizinische Aspekte.

Excluding multiple births, a cohort of 996 Swiss mothers was interviewed upon admission to the labour ward regarding the overall course of pregnancy, illnesses, disorders, use of drugs, and nicotine and alcohol consumption. During the postnatal stay at the hospital additional information on socioeconomic background, mental and physical stress and the pattern of medical care during pregnancy was obtained. The data are presented and compared with analogous data on the entire female population of the same age group in Switzerland and with epidemiologic reviews of pregnancy events from other countries. This group of pregnant women represents a cross-section of the average mixed small town and rural population of German-speaking Switzerland. The socioeconomic conditions for motherhood appear favorable, though the percentage of women from lower socioeconomic classes was lower than in the general population. Employment during pregnancy had no influence on birthweight and neonatal morbidity, in contrast to chronic physical and emotional stress. On average the women had eight medical checkups during pregnancy.

Clinical effect of rectal application of suprofen in children. An open controlled study.

Antipyretic effect, tolerability, and acceptance of alpha-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol) suppositories were tested in an open study including 90 hospitalized children with fever of various etiology. The mean rectal temperature prior to treatment was 39.3 degrees C. The dose regimen was chosen depending upon the body weight: Up to 4 suppositories were administered for maximally 4 days. Body temperature as well as pulse and respiratory rates were recorded prior to insertion of the suppository and 0.5, 1, 1.5, 2, 3, 4, 5 and 6 h following first application of the preparation. Regardless of sex and age the temperature was reduced in 85.5% of the cases; as compared to the initial values this reduction was after first application statistically significant at all rating times. The only adverse reaction - vomiting - was seen in 3 cases.