Relationships between severe neonatal thrombocytopenia and maternal characteristics in pregnancies associated with autoimmune thrombocytopenia

In pregnant women with antecedents of autoimmune thrombocytopenia (AITP), no predictive factor for severe fetal thrombocytopenia has been identified. We evaluated the relationships between the course of the maternal disease before and during pregnancy and the risk of severe fetal thrombocytopenia, in 64 pregnant women with known chronic AITP antecedents, over a 12-year period. 28 pregnant women had undergone splenectomy before pregnancy and 17 experienced severe thrombocytopenia (< 50 × 10⁹/l) during pregnancy (monthly determination). Eight infants presented with severe thrombocytopenia at birth (12.5%), and four in the following days (6.25%). No severe haemorrhage was observed. Severe thrombocytopenia at birth was present in 57% (CI 95% 18–90%) of the infants born to mothers with severe pregnancy-associated thrombocytopenia and splenectomy antecedents, and in 0% (CI 95% 0–15%) of the infants born to mothers who presented none of these antecedents ( P  = 0.001). In thrombocytopenic mothers the infant platelet counts at birth were positively correlated to the nadir maternal platelet count during the index pregnancy ( r  = 0.42, P  = 0.0075).
These results suggest that severe autoimmune disease is a risk factor for severe fetal thrombocytopenia, and that pregnant women with no antecedent of splenectomy nor severe thrombocytopenia during pregnancy have a very low risk of severe fetal thrombocytopenia.     

Pulsed high-dose dexamethasone in chronic autoimmune haemolytic anaemia of warm type

The management of patients with autoimmune haemolytic anaemia of warm type (AIHA) is often problematic. Recently, pulsed high-dose dexamethasone (HDD) has been shown to be effective in the treatment of autoimmune thrombocytopenic purpura (AITP).
In this study we treated seven patients with AIHA with HDD. The regimen recommended for treatment of refractory AITP (40 mg dexamethasone for 4 d at the beginning of each 28 d cycle) was employed in almost all cases. Prior to dexamethasone administration, haemolysis was decompensated in all seven patients. HDD was well tolerated and led to an improvement of haemolysis in all cases.     

Sustained decrease of peripheral lymphocytes after allogeneic blood stem cell aphereses

48 healthy donors underwent peripheral blood stem cell (PBSC) apheresis for allogeneic transplantation beginning on day 4 of G-CSF (2 × 5 μg/kg) mobilization. In one to four (median two) large-volume mononuclear cell aphereses, a median of 55.9 × 10⁹ of lymphocytes (range 21.0–109.2 × 10⁹) were collected, an amount comparable to lymphocyte numbers removed by therapeutic lymphaphereses in autoimmune diseases. Mean peripheral lymphocyte counts decreased from premobilization values of 2.31 × 10⁹/l to 1.31 × 10⁹/l at a median of 34 d (1 month) and 1.53 × 10⁹/l at a median of 327 d (11 months). The decrease in peripheral lymphocyte counts was significantly correlated with the number of lymphocytes removed and the number of aphereses. Neutrophil and platelet counts returned to normal values after 1 month whereas monocyte counts and haemoglobin concentrations were significantly decreased at 1 month but not at 11 months.     

Parenteral iron increases serum erythropoietin concentration during the 'early anaemia' of 10–20-day-old mice

Parenteral iron abolishes the 'early anaemia' in all mammals tested and increases packed cell volume (PCV) and haemoglobin concentration (Hb) significantly above adult levels. In the present study we examined the effect of parenteral iron upon serum immunoreactive erythropoietin (siEpo) concentration in young mice (age 6–24 d) and in adult iron-deficient mice.
Young BALB/CJ mice, from 5 to 23 d of age, and adult (60–100 d old) mice, some of which were iron deficient due to a low iron diet from the time of weaning, were given iron subcutaneously (iron sorbitol, Fe⁺⁺⁺, 1.2 mg iron/100 g body weight/injection). Iron was given as one single dose and the animals killed 20–24 h later. Control mice were similarly treated with saline.   In young mice, from the age 10 d to weaning at 20 d, the siEpo level, measured 20–24 h after a single subcutaneous dose of iron, was 5 times greater than that in control mice ( P  < 0.0001). In contrast, there was no change in siEpo 20–24 h after a single subcutaneous dose of iron in adult mice, whether iron-deficient anaemic or normal.
Thus, during the 'early anaemia' in young mice over 10 d old, iron increased siEpo levels, whereas it had no such effect in iron-deficient and normal adult mice, This suggests that between ages 10 and 20 d, iron has additional effects in the regulation of erythropoiesis, which may not occur in adult or in 6-d-old mice.     

The effect of treatment with Campath-1H in patients with autoimmune cytopenias

We describe 21 patients with severe and life-threatening autoimmune cytopenias resistant to standard immunosuppression who were treated with the monoclonal antibody Campath-1H. Four patients had autoimmune neutropenia, four had autoimmune haemolytic anaemia, four had pure red cell aplasia, one had immune thrombocytopenia purpura (ITP), three had autoimmune haemolytic anaemia and ITP (Evan's syndrome), three had autoimmune pancytopenia (ITP, autoimmune neutropenia and autoimmune haemolytic anaemia), one had ITP (associated with acquired Glanzmann's disease) and autoimmune neutropenia, and one had ITP and red cell aplasia. Campath-1H was administered at a dose of 10 mg/d as an intravenous infusion for 10 d. Responses were seen in 15 patients, which were sustained in six. Relapse occurred in eight patients after Campath-1H treatment. Patients entering the study later, received cyclosporine after Campath-1H in an attempt to reduce the incidence of relapse. Three patients received a second course of Campath-1H; all responded but later relapsed. Fourteen patients are alive at a median of 12 months (range 4-61) after Campath-1H. Campath-1H represents an alternative therapeutic option for severe, refractory autoimmune cytopenias.     

Allogeneic bone marrow transplantation for agnogenic myeloid metaplasia

Agnogenic myeloid metaplasia is a rare indication for allogeneic bone marrow transplantation (BMT). We have retrospectively studied 12 patients allografted for this disease within the French BMT group. Prior to BMT, the mean age was 40 years (range 14–49). Diagnosis was based on the Polycythaemia Vera Study Group criteria. Before BMT, 10 patients had been splenectomized, eight required transfusions, and four had received at least two lines of chemotherapy. Cyclophosphamide and total body irradiation was the main conditioning regimen used ( n= 8). The donor was an HLA-identical sibling except in one case where there was one HLA-DR mismatch. Acute graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate and cyclosporine A. 11 patients engrafted with median times to achieve absolute neutrophil count > 0.5 × 10⁹/l and platelet count > 50 × 10⁹/l of 17 (range 12–44) and 29 (range 12–196) days respectively. One primary graft failure occurred. 10 patients developed grade II–IV acute GVHD, four developed extensive chronic GVHD. One patient relapsed 16 months post-BMT and was untreated and well 14 months later. Three patients died from the BMT procedure. In May 1996 the median follow-up was 25 months and the 4-year overall and event-free survivals were 71% and 59%, respectively. Thus, we conclude that extensive myelofibrosis is not associated with delayed engraftment, and that HLA-identical sibling allogeneic BMT can be considered in a small proportion of patients with agnogenic myeloid metaplasia.     

Cyclosporine therapy in patients with steroid resistant autoimmune hepatitis

Autoimmune hepatitis is a form of chronic liver disease characterized by progressive hepatocellular inflammation, which usually responds to treatment with corticosteroids. However, 10% of patients with autoimmune hepatitis are refractory to corticosteroids and develop progressive liver disease and cirrhosis. We describe five patients with autoimmune hepatitis who did not respond to conventional corticosteroids and azathioprine therapy who were then treated with cyclosporine A. Cyclosporine A was started at 2–3 mg/kg/day and induced biochemical remission in four of five patients within 3 months. One of the four responders relapsed within 1 month of discontinuing cyclosporine on two occasions. Each time, liver tests promptly normalized after reinitiation of cyclosporine. Two responders were managed with cyclosporine alone. The single patient who did not respond to cyclosporine developed progressive liver failure, underwent orthotopic liver transplantation, and subsequently died of disseminated cytomegalovirus infection. Cyclosporine was generally well tolerated and none of the patients developed renal insufficiency. These data and review of 11 cases in the literature show that cyclosporine can induce remission of liver disease in patients with autoimmune hepatitis who are refractory to corticosteroids.     

Tucaresol increases oxygen affinity and reduces haemolysis in subjects with sickle cell anaemia

The primary pathophysiological event in sickling is the intracellular polymerization of deoxygenated haemoglobin S. Tucaresol (589C80;4[2-formyl-3-hydroxy-phenoxymethyl] benzoic acid), a substituted benzaldehyde, was designed to interact with haemoglobin to increase oxygen affinity and has been shown to inhibit sickling in vitro . We administered tucaresol to sickle cell patients in the steady state to examine the anti-sickling effect in vivo. Oral doses of tucaresol or placebo were given to nine stable sickle cell patients (aged 17–39 years; tucaresol, six; placebo, three) for 10 d. The first two patients on tucaresol were scheduled to receive a loading dose of 800 mg or 1200 mg (depending on bodyweight) for the first 4 d, followed by maintenance doses of 200 or 300 mg for the next 6 d. Due to concerns over the sharp rise in haematocrit in one patient, subsequent cohorts received 300 mg tucaresol daily throughout the dosing period. The oxygen affinity of haemoglobin S was increased in all patients receiving tucaresol, with between 10% and 24% of the haemoglobin modified, dependent on dose. In all patients on tucaresol, haemolysis was reduced with rises in haemoglobin of 0.9–3.7 g/dl (mean 2.2 g/dl), falls in lactate dehydrogenase of 16–52%, and a halving of the irreversibly sickled cell counts. These effects were apparent within a few days and persisted for 1–2 weeks following discontinuation of the drug. Three of the six patients on tucaresol developed fever and cervical lymphadenopathy, with onset between days 7 and 11 from start of drug. Further evaluation of the tolerability and efficacy of tucaresol in sickle cell patients is necessary.     

Granulocyte colony-stimulating factor given in addition to interferon-α to mobilize peripheral blood stem cells for autologous transplantation in chronic myeloid leukaemia

In order to potentially mobilize and harvest the Ph⁻ cells observed in most patients with chronic myeloid leukaemia (CML) during interferon-α (IF-α) therapy, G-CSF (filgrastim), 5 μg/kg/d, was administered subcutaneously together with IF-α to 30 CML patients in haematological remission but with various degrees of cytogenetic remission, after IF-α therapy. Peripheral blood stem cells (PBSC ) were harvested using standard aphereses from day 5 of G-CSF. Patients underwent one to four (median three) aphereses. Median total yields/kg were 7.6 (range 3.8–25) × 10⁸ MNC, 3.4 (0–140) × 10⁶ CD34⁺ cells, and 17 (1.1–107) × 10⁴ CFU-GM. No patient had a significant increase in the percentage of Ph⁺ cells in the bone marrow under G-CSF therapy. The percentage of Ph⁺ cells in apheresis products tended to decrease between the first and the last apheresis ( P  = 0.05). 14 patients who were not responsive to IF-α were transplanted after conditioning with busulphan 16 mg/kg and melphalan 140 mg/m². Median time to neutrophils > 0.5 × 10⁹/l was 20 d (16–114 d) and to platelets > 50 × 10⁹/l 18 d (12–149 d). Nine patients had a major cytogenetic response post graft, which correlated with the amount of Ph⁺ cells reinfused with the graft ( P  = 0.02). We conclude that this procedure is feasible, allowing the harvest of enough PBSC, some of them Ph⁻ in patients who responded to IF-α, to allow autologous transplantation.     

Marrow transplantation for Fanconi anaemia: conditioning with reduced doses of cyclophosphamide without radiation

Nine patients with Fanconi anaemia (FA) were conditioned for HLA-identical sibling bone marrow transplant (BMT) with reduced dose of cyclophosphamide (Cy) without radiation or antithymocyte globulin (ATG). The total dose of Cy was 140 mg/kg ( n =2) or 120 mg/kg ( n =7). The median patient age was 8 years (range 4–19). Graft-versus-host disease (GVHD) prophylaxis was with methotrexate and cyclosporine ( n =8) or cyclosporine alone ( n =1). All patients had sustained engraftment and two developed grade ≥II acute GVHD. Cy toxicity included grade ≥2 mucositis seen in all evaluable patients and haemorrhagic cystitis in two patients. The Kaplan-Meier survival estimate is 89% with a median follow-up of 285 d (range 56–528).
For the purpose of comparison, this report also reviews and updates long-term follow-up data on 32 previously reported FA patients conditioned with 140–200 mg Cy/kg without radiation.
The lowest dose of Cy (without radiation or ATG) after which HLA-identical sibling marrow transplant can be successfully performed in FA patients has yet to be determined, but it appears that uniform and sustained engraftment can be achieved with a Cy dose of as low as 120 mg/kg.     

Long-term follow-up of patients with hyperprolactinaemia

AIM  To determine the frequency with which hyperprolactinaemic illnes tends to resolve with time.
STUDY DESIGN  A retrospective case-notes review from a specialist endocrine unit in a provincial teaching hospital and tertiary referral centre.
PATIENTS  Seventy women with hyperprolactinaemia referred to the unit in the 15 year period between May 1979 and May 1994. All those with a non-pituitary cause or with macroadenoma had been excluded, as were those who did not have high-resolution imaging, or who were on treatment at the time of referral.
INTERVENTION  Intermittent course of treatment with dopamine receptor agonists according to individual need.
ENDPOINTS  Latest serum PRL concentration in those who had discontinued treatment, and whether serum PRL tended to be lower in any particular group
RESULTS  There was a significant fall in median PRL concentration from 2000 (714–8000) to 1000 mU/l (220–5600) in the 31 women who had discontinued therapy ( P <0.0005), and serum PRL was normal (<700 mU/l) in 11 of them. Serum PRL also fell to normal in three of ten women who had no treatment at all. Final PRL concentration was normal in 35% of women who had had at least one pregnancy during the period of follow-up compared to 14% who had not ( P <0.05).
CONCLUSIONS  These data confirm the findings of others that hyperprolactinaemia will prove self-limiting in up to one-third of women, and that pregnancy may be one factor which triggers a return to normal function     

Increased liver stiffness measurement by transient elastography in severe acute exacerbation of chronic hepatitis B

Background and Aims:  The proposed cut-off values for the degree of fibrosis as assessed by liver stiffness measurement (LSM) might not be applicable in severe acute exacerbation of chronic hepatitis B (CHB). We aimed to assess the effect of necroinflammatory activity on LSM in this condition.
Methods:  We prospectively recruited consecutive patients with severe acute exacerbation of CHB (alanine aminotransferase or ALT > 10× upper limit of normal). The relationship of ALT levels and LSM were serially assessed and liver biopsy was carried out after ALT normalization.
Results:  Eleven patients (10 male, median age 43 years) were followed up for 25 weeks; nine patients received antiviral therapy. Overall, LSM was positively correlated with ALT levels ( r  = 0.67, P  < 0.001). At initial presentation, the median serum ALT and LSM was 1136 (581–2210) IU/L and 26.3 (11.1–33.3) kPa. A progressive reduction in LSM was observed during subsequent visits in parallel with the reduction of ALT levels. At the last visit, the median ALT was 27 (11–52) IU/L and LSM was 7.7 (4.7–10.8) kPa. Among the five patients who had liver biopsy carried out at week 25, four patients had F2 fibrosis (LSM 5.7–8.1 kPa) and one patient had F3 fibrosis (LSM 8.6 kPa).
Conclusions:  LSM using transient elastography with the current proposed cut-off values might misdiagnose liver cirrhosis in patients suffering from severe acute exacerbation of CHB. LSM should be assessed after normalization of ALT levels in order to accurately assess the degree of fibrosis.     

Clinical characteristics predict response to antithymocyte globulin in paroxysmal nocturnal haemoglobinuria

Seven patients with paroxysmal nocturnal haemoglobinuria (PNH) were treated with antithymocyte globulin (ATG). Each patient received ATG (20 mg/kg/d) for 8 d and prednisone to prevent or control serum sickness. Three patients experienced a sustained improvement in at least one peripheral blood cytopenia, including one patient who had a complete trilineage response. Several pre-treatment clinical features appeared to be associated with response to ATG. All responding patients had hypoproliferative features including depressed platelet counts (<30×10⁹/l), and a minor degree of chronic haemolysis as indicated by relatively low reticulocyte counts (<100×10⁹/l), lactate dehydrogenase (<1000 U/l) and total bilirubin (<17μmol/l) levels. Responding patients continued to have chronic low-grade haemolysis after their response to immunosuppression that was similar to that observed prior to treatment. The non-responding patients had a classic haemolytic form of PNH characterized by elevated reticulocyte counts (>100×10⁹/l), lactate dehydrogenase (>2000 U/l) and total bilirubin (>17μmol/l) levels.
The impaired haemopoiesis that occurs in hypoproliferative PNH may respond to ATG treatment, but the haemolytic component of the disease, and hence the PNH clone, is not altered by immunosuppressive therapy.     

Evaluation of a new, integral, whole blood filter (RS2000) system for prestorage leucodepletion of SAG-M red cells

Residual donor leucocytes are responsible for many adverse transfusion reactions. Prestorage leucodepletion may ameliorate these effects and enhance product quality. We studied a bottom and top (BAT) system incorporating an integral filter for whole blood leucodepletion. Our evaluation assessed leucodepletion efficiency as well as in vitro SAG-M red cell quality and storage characteristics.   Sixty-six units of blood were collected; test units into the Optipac^®- p L u S system and controls into the standard triple pack configuration. Test units were held for 4–6 h at room temperature (rt) or 12–18 h at 4°C. The mean leucocyte counts for the SAG-M red cells in the quality and storage trial were 0.6×10⁶ (rt hold), 0.05×10⁶ (4°C hold) and 2500×10⁶ (controls). We observed no significant differences between the groups for Na⁺, ATP, 2,3-DPG, glucose, lactate and pH during the 49 d storage. The control group, however, showed a greater increase in haemolysis and K⁺ with time. Autologous in vivo 24 h red cell recovery, after 42 d storage, was >75%. Adjustment of processing parameters in subsequent studies gave leucodepleted SAG-M red cells with minimal cell loss (9–19%) plus acceptable haemoglobin content (46–76 g/U) and haematocrit (54–62%). This system achieved >3.5 log leucodepletion with all but one unit containing <1×10⁶ leucocytes. The product quality is good and the system suitable for routine use in blood centres.     

Longitudinal study on activated factors XII and VII levels during normal pregnancy

Levels of activated factor XII (FXIIa) and VII (FVIIa) were determined in 100 women with uneventful pregnancies. Samples were divided into five study intervals: three during pregnancy, one at delivery and one 3 d postpartum.
The median (range) for FXIIa levels were 3.4 ng/ml (1.2–9.1) from 11 to 20 weeks, 4.6 ng/ml (1.4–15.2) from 21 to 30 weeks, 5.4 ng/ml (1.9–14.3) from 31st week to delivery, 5.2 (1.3–11.4) at delivery and 4.3 (1.8–8.5) ng/ml in the postpartum sample. For FVIIa the median and range levels for the five periods were 4.9 (1.7–77.3), 7.2 (2.5–80.4), 11.1 (2.9–90.6), 12.0 (3.1–64.1) and 8.2 (4.0–23.5) ng/ml. Although the increase of FVIIa was higher than that of FXIIa during pregnancy, the overall changes of FXIIa and FVIIa were highly correlated ( P  < 0.0001). At each time period the changes of FVIIa correlated with FVII:C which was not the case with FVII:Ag. These data indicate that during pregnancy both the contact phase and extrinsic pathway are activated.     

Immune response to measles vaccine in 6 month old infants in Papua New Guinea

Objective  To assess the efficacy of the current measles immunization schedule in Papua New Guinea, which is to give the first dose at 6 months of age and the second at 9 months.
Methods  Humoral immune response study of 140 Papua New Guinean infants at 6 months of age, measuring measles IgG antibodies by enzyme immunoassay before and 85 days after the 6-month dose of measles vaccine.
Results  After vaccination at 6 months, 35.7% of infants developed a level of measles antibodies consistent with protection (IgG >330 IU/ml); 17.7% had an antibody response (150–330 IU/ml) that is likely to afford some protection; 46.8% had no detectable antibody response (IgG <150 IU/ml). Among 53 infants with no antibody response, 37 (69.5%) developed an antibody response, while 42.4% (37/87) of those with maternal antibodies sero-converted ( P  = 0.002).
Conclusions  Antibody response to measles vaccine was lower than expected at 6 months. While the presence of maternally derived antibodies accounted for some of the limited seroconversion in young infants, other factors are involved. Issues to be considered in determining the value of the first dose of measles vaccination in mid infancy in poor countries are complex and antibody responses are only one factor. Others, such as cell mediated immune responses, the non-specific protective effect of measles vaccine in preventing illness and death and the practicalities of uptake of vaccines at different ages, are also important.     

Prevalence of undiagnosed celiac disease in the parents of preterm and/or small for gestational age infants

OBJECTIVES:  The aim of this study was to estimate the prevalence of undiagnosed celiac disease (CD) in the parents of preterm and/or small for gestational age (SGA) infants.
METHODS:  A sample of 1,714 parents (868 women, 846 men) of 905 preterm (<37 wk of gestational age) and/or SGA (<10th percentile of birthweight) infants consecutively born in Lombardy, Northern Italy, and not diagnosed with CD prior to pregnancy, were tested for CD. Diagnosis was based on antitissue transglutaminase and anti-endomysial antibodies and confirmed by duodenal biopsy.
RESULTS:  The overall prevalence of undiagnosed CD was 0.64% (95% confidence interval [CI] 0.32–1.15%), 0.92% (0.40–1.81%) in women and 0.35% (0.07–1.03%) in men. In the mothers of preterm infants prevalence of CD was 0.39% (0.05–1.39%). In the mothers of SGA infants prevalence of CD was 1.60% (0.64–3.27%), and the observed number of mothers with CD was 2.25 times higher than the expected one in the Italian female population ( P = 0.039). Undiagnosed CD in mothers was associated with an increased risk of SGA birth (odds ratio 6.97, 95% CI 1.11–43.55%).
CONCLUSIONS:  While additional powered studies are needed, the present results suggest that the prevalence of undiagnosed CD in the mothers of SGA infants is higher than in the general female population.     

Prospective evaluation of haemoglobin oxygen saturation at rest and after exercise in paediatric sickle cell disease patients

Low steady state haemoglobin oxygen saturation in patients with sickle cell anaemia has been associated with the degree of anaemia and haemolysis. How much pulmonary dysfunction contributes to low saturation is not clear. In a prospective study of children and adolescents with sickle cell disease aged 3–20 years at steady state and matched controls, 52% of 391 patients versus 24% of 63 controls had steady state oxygen saturation <99% ( P  < 0·0001), 9% of patients versus no controls had saturation <95% ( P  = 0·008) and 8% of patients versus no controls had exercise-induced reduction in saturation ≥3%. Decreasing haemoglobin concentration ( P  ≤ 0·001) and increasing haemolysis ( P  ≤ 0·003) but not pulmonary function tests were independent predictors of both lower steady-state saturation and exercise-induced reduction in saturation. Neither history of stroke nor history of acute chest syndrome was significantly associated with lower steady-state oxygen saturation or exercise-induced reduction in saturation. Tricuspid regurgitation velocity was higher in patients with lower steady state haemoglobin oxygen saturation ( P  = 0·003) and with greater decline in oxygen saturation during the six-minute walk ( P  = 0·022). In conclusion, lower haemoglobin oxygen saturation is independently associated with increasing degrees of anaemia and haemolysis but not pulmonary function abnormalities among children and adolescents with sickle cell disease.     

An original method to study autoantibody specificity in haemoglobin stained eluates by the column agglutination techniques

Summary When studying autoantibody specificity by the indirect antiglobulin test with column agglutination techniques ether and xylene elution techniques result in haemoglobin stained eluates which give a red colouration to the gel or glass beads and do not allow the identification of positive reactions. Xylene eluates were incubated with commercially available group 0-test red cell panels at 37°C for 45 min in the wells of a microtitre plate in a 3:1 eluate:red cell ratio. After washing with normal saline, sensitized red cells, resuspended in low ionic strength solution (LISS), were applied onto the microtubes containing the antiglobulin serum and positive reactions were recorded after centrifugation. We studied the specificity of 35 autoantibody containing eluates from 12 patients with lymphoproliferative disorders (six having autoimmune haemolysis) and 23 HIV patients without autoimmune haemolysis. All patients had a gel or column positive (IgG) direct antiglobulin test while the tube direct antiglobulin test failed to show red cell bound IgG. We found a reactive indirect antiglobulin test in 20/23 eluates from HIV infected patients (with a panreactive specificity), in all patients with autoimmune haemolysis (one with anti-C, two with anti-E, one with anti-K and two with a panreactive specificity) and in all patients with positive direct antiglobulin test but without immune mediate haemolysis (in all cases with panreactive specificity). The method proposed is a promising tool for the study of the specificity of antibody containing haemoglobin stained eluates; in this study it allowed us to confirm that some HIV patients have specific binding of IgG on their RBC and to identify the specificity of tube test non-reactive eluates.     

Mental and motor development before and during growth hormone treatment in infants and toddlers with Prader-Willi syndrome

Background  Prader–Willi syndrome (PWS) is a neurogenetic disorder characterized by muscular hypotonia, psychomotor delay, feeding difficulties and failure to thrive in infancy. GH treatment improves growth velocity and body composition. Research on the effects of GH on psychomotor development in infants with PWS is limited.
Objective  To evaluate psychomotor development in PWS infants and toddlers during GH treatment compared to randomized controls.
Design/patients  Forty-three PWS infants were evaluated at baseline. Twenty-nine of them were randomized into a GH group ( n  = 15) receiving 1 mg/m²/day GH or a non-GH-treated control group ( n  = 14). At baseline and after 12 months of follow-up, analysis with Bayley Scales of Infant Development II (BSID-II) was performed. Data were converted to percentage of expected development for age (%ed), and changes during follow-up were calculated.
Results  Infants in the GH group had a median age of 2·3 years [interquartile range (IQR) 1·7–3·0] and in the control group of 1·5 years (IQR 1·2–2·7) ( P =  0·17). Both mental and motor development improved significantly during the first year of study in the GH group vs. the control group: median (IQR) change was +9·3% (–5·3 to 13·3) vs. –2·9% (–8·1 to 4·9) ( P  < 0·05) in mental development and +11·2% (–4·9 to 22·5) vs. –18·5% (–27·9 to 1·8) ( P  < 0·05) in motor development, respectively.
Conclusion  One year of GH treatment significantly improved mental and motor development in PWS infants compared to randomized controls.