Transient hypophosphataemia associated with acute infectious disease in paediatric patients

The aim of this study was to investigate the prevalence of hypophosphataemia in children with acute infection and the relationship between serum phosphate and C-reactive protein (CRP) concentration. Serum phosphate and CRP levels were measured on admission in 238 patients (aged 1 month to 14 y) with: pneumonia (n = 51), upper respiratory tract-related bacterial infection (n = 70), urinary tract infection (n = 50) and viral infection (n = 67). Patients were classified according to CRP value (0-50, 51-100, 101-150, > or = 151 mg/l) and type of infection. The prevalence of hypophosphataemia was calculated for each group. 30 children with hypophosphataemia on admission had serial measurements of serum phosphate and CRP levels. A significant negative correlation between serum phosphate and CRP levels was found (r = -0.41, p < 0.0001). Patients with CRP > or = 151 mg/l on admission had a lower mean serum phosphate value than those with CRP < or = 50 mg/l (1.17 vs 1.50 mmol/l, p < 0.0001). The overall prevalence of hypophosphataemia for patients with pneumonia, upper respiratory tract bacterial infection, urinary tract and viral infections was 45%, 35.7%, 18% and 4.4%, respectively. Hypophosphataemia occurred during the phase of rising of CRP level and resolved soon after CRP reached a plateau. In conclusion, hypophosphataemia is a relatively frequent but transient phenomenon in children with acute infectious disease. It is associated with an increase in CRP concentration and resolves before the normalization of CRP levels.     

Posterior cerebral artery occlusion associated with Mycoplasma pneumoniae infection

Cerebral infarction is a rare complication of Mycoplasma pneumoniae infection. In all cases previously reported in the literature, vascular occlusion occurred in the anterior brain circulation, either the internal carotid or the middle cerebral artery. We report a case of a child with posterior cerebral artery occlusion and resultant hemiparesis associated with M. pneumoniae infection.     

Association of unstable hemoglobin variants and heterozygous beta-thalassemia: example of a new variant Hb Acharnes or [beta53(D4) Ala --> Thr].

We report here the functional and structural characterization of Hb Acharnes [beta53(D4) Ala --> Thr], an unstable and electrophoretically silent variant, that was found associated in trans with a beta(0)-thalassemic mutation (IVSI-1 G --> A), in a patient with thalassemia intermedia syndrome. This case is discussed in comparison with other sporadic cases that we have previously investigated, resulting from the co-inheritance of a beta(0)-thalassemic mutation (CD39 C --> T) with two other types of unstable hemoglobins, Hb K?ln [beta98(FG5) Val --> Met], and Hb Arta [beta45(CD4) Phe --> Cys]. It may be concluded that, in these associated forms, both the degree of instability of the variant and the altered oxygen binding properties (affecting the degree of tissue hypoxia) are major determinants of their clinical expression.     

Preparation and immunological properties of procaine-protein conjugates

Procaine was conjugated to BSA and rat and rabbit Gf using the carbodiimide method and ¹⁴C-procaine as a tracer. The composition of the conjugates could be varied depending on the time of incubation and the concentration of procaine in the reaction mixture. Procaine-BSA conjugates were soluble in water or saline. However, procaine conjugates to rat or rabbit Gf were not readily soluble in saline. These conjugates were good for immunization purposes, but it was cumbersome to work with them when clear solutions were needed, as in the immunochemical procedures used in this study. The immunological properties of the conjugates were studied in rats and rabbits. Rats responded with production of IgGa and precipitating anbibodies to the procaine group, but IgE antibodies to the immunogen could not be detected. Furthermore, precipitating antibodies towards the procaine group were raised in rabbits. When BSA was the protein carrier, antibodies to the carrier molecule were also detected in both rats and rabbits. The conjugates of procaine to rat or rabbit Gf did not elicit antibody response to the carrier molecule when used in the homologous species. Hapten inhibition studies suggested that, in the rabbit, antibodies were also produced with specificity directed towards the molecular configuration of the hapten-carrier bond.     

Reduced intensity conditioning allogeneic stem cell transplantation for Hodgkin’s lymphoma: identification of prognostic factors predicting outcome

Background

The role of reduced intensity conditioning allogeneic stem transplantation (RICalloSCT) in the management of patients with Hodgkin’s lymphoma remains controversial.

Design and Methods

To further define its role we have conducted a retrospective analysis of 285 patients with HL who underwent a RICalloSCT in order to identify prognostic factors that predict outcome. Eighty percent of patients had undergone a prior autologous stem cell transplantation and 25% had refractory disease at transplant.

Results

Non-relapse mortality was associated with chemorefractory disease, poor performance status, age >45 and transplantation before 2002. For patients with no risk factors the 3-year non-relapse mortality rate was 12.5% compared to 46.2% for patients with 2 or more risk factors. The use of an unrelated donor had no adverse effect on the non-relapse mortality. Acute graft versus host disease (aGVHD) grades II–IV developed in 30% and chronic GVHD in 42%. The development of cGVHD was associated with a lower relapse rate. The disease progression rate at one and five years was 41% and 58.7% respectively and was associated with chemorefractory disease and extent of prior therapy. Donor lymphocyte infusions were administered to 64 patients for active disease of whom 32% showed a clinical response. Eight out of 18 patients receiving donor lymphocyte infusions alone had clinical responses. Progression-free and overall survival were both associated with performance status and disease status at transplant. Patients with neither risk factor had a 3-year PFS and overall survival of 42% and 56% respectively compared to 8% and 25% for patients with one or more risk factors. Relapse within six months of a prior autologous transplant was associated with a higher relapse rate and a lower progression-free.

Conclusions

This analysis identifies important clinical parameters that may be useful in predicting the outcome of RICaIICalloSCT in Hodgkin’s lymphoma.     

Favorable outcomes with alemtuzumab-conditioned unrelated donor stem cell transplantation in adults with high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in first complete remission

Background

Approximately 40% of adults with Philadelphia chromosome-negative acute lymphoblastic leukemia achieve long-term survival following unrelated donor hematopoietic stem cell transplantation in first complete remission but severe graft-versus-host disease remains a problem affecting survival. Although T-cell depletion abrogates graft-versus-host disease, the impact on disease-free survival in acute lymphoblastic leukemia is not known.

Design and Methods

We analyzed the outcome of 48 adults (median age 26 years) with high-risk, Philadelphia-chromosome-negative acute lymphoblastic leukemia undergoing T-cell depleted unrelated donor-hematopoietic stem cell transplantation (67% 10 of 10 loci matched) in first complete remission reported to the British Society of Blood and Marrow Transplantation Registry from 1993 to 2005.

Results

T-cell depletion was carried out by in vivo alemtuzumab administration. Additional, ex vivo T-cell depletion was performed in 21% of patients. Overall survival, disease-free survival and non-relapse mortality rates at 5 years were 61% (95% CI 46–75), 59% (95% CI 45–74) and 13% (95% CI 3–25), respectively. The incidences of grades II–IV and III–IV acute graft-versus-host disease were 27% (95% CI 16–44) and 10% (95% CI 4–25), respectively. The actuarial estimate of extensive chronic graft-versus-host disease at 5 years was 22% (95%CI 13–38). High-risk cytogenetics at diagnosis was associated with a lower 5-year overall survival (47% (95% CI 27–71) vs. 68% (95% CI 44–84), p=0.045).

Conclusions

T-cell depleted hematopoietic stem cell transplantation from unrelated donors can result in good overall survival and low non-relapse mortality for adults with high-risk acute lymphoblastic leukemia in first complete remission and merits prospective evaluation.     

Hereditary vitamin D-resistant rickets in Greek children: genotype, phenotype, and long-term response to treatment

We describe four patients (two pairs of children from two unrelated kindreds) from a Greek island, suffering from hereditary vitamin D-resistant rickets (HVDRR) with alopecia. There were two different homozygous mutations in the vitamin D receptor (VDR) gene of the affected members of the two kindreds that resulted in a truncated or missing receptor. The disorder began in early infancy with similar clinical, biochemical and radiological findings in all four patients, namely, alopecia (which provided the initial diagnostic evidence for HVDRR), rachitic deformities, hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and elevated serum levels of 1,25-dihydroxyvitamin D; however, the patients of kindred B had a more severe clinical expression. Treatment options include oral or intravenous calcium and active vitamin D metabolites. The response varies widely in different cases. Our patients were initially treated with high doses of 1alpha(OH)D3 and oral calcium supplementation. Kindred A patients had a satisfactory response to this regimen, while kindred B patients presented clinical and biochemical improvement when 1alpha(OH)D3 was changed to 1,25(OH)2D3. In the older patients of each kindred, treatment requirements gradually decreased during puberty, and therapy was finally discontinued before adulthood.     

Effects of Rifampin Treatment on Contact Sensitivity Reactions to Oxazolone in Balb/C Mice

Treatment of mice with rifampin (Ri, 100-200 mg/kg) affected the course of contact sensitivity (CS) reactions to oxazolone. The effects which were seen as either partial inhibition or enhancement of the response, under one set of conditions, could be abrogated or even reversed if conditions of either induction, elicitation and time of measuring reactions were altered. In addition, amount of Ri used for treatment and time of treatment in relation to the induction of CS reactions also influenced the effects observed.     

Effects of in Utero Exposure to Cyclophosphamide in Mice II. Assessment of Immunocompetence of Offspring from 5 to 10 Weeks of Age

Offspring of mice treated with cyclophosphamide (Cy; 1, 2.5 or 5 mg/kg) during pregnancy (6-18 days of gestation) and tested for immunocompetence from 5 to 10 weeks of age were found to have defective reticuloendothelial clearance. The main effects were: a) increased elimination half time (T 1/2) of ⁵¹Cr-labeled SRBC from circulation, b) decreased liver uptake of ⁵¹Cr and c) impaired ability of the spleen, mostly affecting the female pups, to compensate for decreased liver uptake. The highest dose group suffered the most pronounced effects. This group was also found to have increased IgG immunoglobulin levels at 7 weeks of age. IgG antibody production in response to specific antigenic stimulation and delayed hypersensitivity reactions to oxazolone did not appear to be affected by Cy treatment.