A circum-corneal conjunctival nevus in a child

An amelanotic, circum-corneal nevus in a 2-year-old child is described. The nevus presented at birth as a red spot in the nasal conjunctiva that subsequently enlarged to completely encircle the cornea. The tumour was partially removed three times, but at the age of 6 years, the nevus still covers the entire limbal region. The case illustrates that circum-corneal redness in a child may be caused by a nevus and that a conjunctival limbal nevus in a child tend to recur after incomplete excision.     

Changes in health complaints after removal of amalgam fillings

The aim of the present study was to investigate whether removal of all amalgam fillings was associated with long-term changes in health complaints in a group of patients who attributed subjective health complaints to amalgam fillings. Patients previously examined at the Norwegian Dental Biomaterials Adverse Reaction Unit were included in the study and assigned to a treatment group (n = 20) and a reference group (n = 20). Participants in the treatment group had all amalgam fillings replaced with other restorative materials. Follow-ups took place 3 months, 1 and 3 years after removal of all amalgam fillings. There was no intervention in the reference group. Subjective health complaints were measured by numeric rating scales in both groups. Analysis of covariance was used to compare changes in health complaints over time in the two groups. In the treatment group, there were significant reductions in intra-oral and general health complaints from inclusion into study to the 3-year follow-up. In the reference group, changes in the same period were not significant. Comparisons between the groups showed that reductions in intra-oral and general health complaints in the treatment group were significantly different from the changes in the reference group. The mechanisms behind this remain to be identified. Reduced exposure to dental amalgam, patient-centred treatment and follow-ups, and elimination of worry are factors that may have influenced the results.     

Protease-induced release of functional peptides from bioplexes.

Linking peptide functions directly to nucleic acids can be used to improve transfection. We have previously demonstrated this by sequence-specific hybridization of a bifunctional peptide nucleic acid (PNA) consisting of a nucleic acid binding moiety conjugated to a peptide. The resulting biological complex of PNA/DNA is called a Bioplex. The bifunctional PNA is continuously synthesized with one or more functional entities. For certain applications, it might be preferable to eliminate a functional entity after it has served its purpose. We have addressed this issue by adding a specific protease cleavage site to the construct. In this first approach, cathepsin L was used to cleave a linker sequence including a cathepsin L site: afrsaaq, thereby releasing the tri-peptide Arg-Gly-Asp (RGD) from the PNA anchor. In vitro and in vivo experiments showed an efficient cleavage of the peptide. Moreover, bifunctional PNA constructs were shown to retain activity of the second entity following removal of the first function. Since cathepsin L is ubiquitously expressed in eukaryotic cells and becomes active as the endosomal pH drops, inclusion of cathepsin sites makes it possible to remove functional entities in late endosomes/early lysosomes.     

Dose study of thymoglobulin during conditioning for unrelated donor allogeneic stem-cell transplantation

BACKGROUND: Thymoglobulin given before allo-hematopoietic stem-cell transplantation (HSCT) from unrelated donors reduces acute graft-versus-host disease (GvHD), but the optimal dose is unknown. METHOD: Four different doses of Thymoglobulin were given to 162 patients with hematologic malignancies undergoing unrelated donor HSCT: 4, 6, 8, and 10 mg/kg. Stem-cell source was bone marrow in 102 cases and peripheral blood stem cells in 60. Conditioning was cyclophosphamide combined with total-body irradiation or busulfan. GvHD prophylaxis was cyclosporine and methotrexate. RESULTS: The lowest dose of Thymoglobulin significantly increased the risk for acute GvHD II or greater (odds ratio [OR] 2.67, P=0.015) and III or greater (OR 4.12, P=0.03). GvHD-associated deaths were more common in the lowest Thymoglobulin dose (6/51) compared with higher doses (2/111), P<0.01. No difference in bacteremia and cytomegalovirus reactivation was found. A trend for more infectious death (11/55 vs. 11/107, P=0.09) was found in the 10 mg/kg group compared with lower doses. Median dose of Thymoglobulin (6-8 mg/kg) was associated with lower transplant-related mortality (TRM) (hazard ratio [HR] 0.35, P=0.03) and better survival (HR 0.45, P=0.027) in multivariate analysis, whereas no effect on relapse and relapse-free survival was found. CONCLUSION: Low-dose (4 mg/kg) of Thymoglobulin increased the risk for severe acute GvHD, whereas 10 mg/kg increased the risk for infectious death. Median doses (6-8 mg/kg) of Thymoglobulin resulted in the lowest TRM and best survival.     

Allogeneic hematopoietic stem cell transplantation for inherited disorders: experience in a single center

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (ASCT) is a possible cure for many inherited disorders. METHODS: We report 20 years of experience in 71 patients. The disorders include 7 immunodeficiencies, 21 hematological disorders, 13 histiocytic disorders, 9 mucopolysaccharoidoses, 7 metachromatic leukodystrophies (MLD), 3 adrenoleukodystrophies (ALD), 2 adrenomyeloneuropathy (AMN), 6 patients with Gaucher's disease, 1 Sandhoff's disease, and 2 patients with aspartylglucosaminuria. Their median age was 4 (0-39) years. The donors were 29 HLA-identical related, 27 matched unrelated (MUD) and 15 HLA mismatches. RESULTS: In recipients of HLA-identical sibling grafts, none developed acute GVHD grades II-IV as against 22% in all others. The overall cumulative incidence of chronic GVHD was 17%. The 5-year survival rates were 93%, 84%, and 46% in recipients of grafts from HLA-identical siblings, MUD and HLA-mismatches, respectively. The overall 10-year survival rate was 69%. All of the surviving patients with immunodeficiencies and hemoglobinopathies are well. Four patients with Hurler's disease are also well, apart from skeletal problems. Five patients with Gaucher's disease are between 14 and 22 years after the transplant. Two infants with MLD deteriorated, a girl with the juvenile form has stable disease and one woman with the adult form has improved. Among four survivors with ALD/AMN, three are well and one has dementia. Two patients with aspartylglucosaminuria have stable disease. CONCLUSION: In patients with inborn errors of metabolism, ASCT gives a high survival rate using HLA-matched donors. Beneficial effects are seen in those who are transplanted early.     

Iron-fortified and unfortified cow's milk: effects on iron intakes and iron status in young children

Iron intakes and iron status were evaluated in 36 young Swedish children given either iron-fortified or unfortified cow's milk. All children had good iron status and had received breast milk or ironfortified formulae during infancy. Twenty 1-y-old children were randomized to a diet with ironfortified milk (7.0 or 14.9 mg Fe l^-1     

Clinical and cytogenetic features of pediatric dic(9;20)(p13.2;q11.2)-positive B-cell precursor acute lymphoblastic leukemias: a Nordic series of 24 cases and review of the literature

Although dic(9;20)(p13.2;q11.2) is a characteristic abnormality in childhood B-cell precursor acute lymphoblastic leukemias (BCP ALL), little is known about its clinical impact or the type and frequency of additional aberrations it may occur together with. We here review the clinical and cytogenetic features of a Nordic pediatric series of 24 patients with dic(9;20)-positive BCP ALL diagnosed 1996-2006, constituting 1.3% of the BCP ALL, as well as 47 childhood cases from the literature. Consistent immunophenotypic features of the Nordic cases included positivity for HLA-DR, CD10, CD19, CD20, and CD22 and negativity for T-cell and myeloid markers; no detailed immunophenotypes were reported for the previously published cases. In the entire cohort of 71 cases, the modal chromosome distribution was 45 (62%), 46 (21%), 47 (7%), 48 (4%), 49 (3%), 44 (1%), and 50 (1%). Additional changes were present in 63%, the most frequent of which were homozygous loss of CDKN2A (33%) and gains of chromosomes 21 (28%) and X (10%). The median patient age was 3 years, the female/male ratio was 2.0, the median white blood cell count was 24 x 10(9)/l, 11% had central nervous system involvement, and 5% had a mediastinal mass at diagnosis. Risk group stratification was nonstandard risk in 79%. The event-free survival and overall survival at 5 years for the 24 Nordic cases was 0.62 and 0.82, respectively. Thus, although relapses are quite common, postrelapse treatment of many patients is successful.