Neutral oligosaccharide content of preterm human milk

Human milk oligosaccharides are known to play a role in protection against certain infectious diseases. Previous reports indicate that the content of human milk oligosaccharides varies widely among individuals at term but such information on preterm milk is lacking. After removal of the fat, protein and most of the lactose from non-pooled human milk samples, a total neutral oligosaccharide fraction was isolated by ion-exchange chromatography followed by gel filtration. A Dionex high-performance anion-exchange chromatography system equipped with a pulsed electrometric detector was then employed to measure the levels of ten neutral oligosaccharides in the individual milk samples. Twenty-three milk samples from thirteen mothers who delivered at a mean gestational age of 29.5 (SD 3.1) weeks were collected between days 0 and 33 of lactation, and compared with three samples of term milk from two mothers. The ranges of the total and individual levels of the ten neutral oligosaccharides in preterm milk were similar to those in term milk. Further, as previously described in term milk, preterm milk exhibited a quantitative individual variation. This variation was independent of the gestational age, day of lactation, and postconceptional age. In conclusion, levels of ten neutral oligosaccharides did not differ between preterm and term human milk.     

Optic nerve hypoplasia with posterior pituitary ectopia: male predominance and nonassociation with breech delivery

PURPOSE: To determine whether posterior pituitary ectopia in children with optic nerve hypoplasia has a male predominance or an increased incidence of breech delivery. METHOD: Retrospective analysis of 12 children with optic nerve hypoplasia and posterior pituitary ectopia. RESULTS: Eleven of 12 patients with posterior pituitary ectopia were boys. No child had a history of breech delivery. Two children had a history of breech positioning but were delivered by cesarean section. CONCLUSION: Posterior pituitary ectopia with optic nerve hypoplasia shows a strong male predominance but no association with breech delivery.     

Riddle: what do aplastic anemia, acute promyelocytic leukemia, and chronic myeloid leukemia have in common?

Secondary myelodysplastic syndrome (MDS)/acute leukemia frequently evolves from severe aplastic anemia (SAA) following immunosuppressive therapy. Secondary clonal cytogenetic abnormalities have now been reported after noncytotoxic therapy in two additional settings: all trans retinoic acid (ATRA) treatment of acute promyelocytic leukemia (APL) and imatinib for chronic myeloid leukemia (CML). We propose that SAA, APL, CML, and MDS represent different manifestations of generalized insults to the bone marrow. In SAA, the insult to hematopoietic progenitors leads to an immune attack, while in APL, CML, and MDS, it gives rise to the malignant clones. A primary insult to bone marrow could simultaneously lead to several abnormal hematopoietic cell clones, with one dominating and the others present but below the level of detection. Such a 'field leukemogenic effect' would be analogous to the 'field cancerization effect' described in solid tumors. Nonspecific cytotoxic therapies, including antileukemic chemotherapy and allogeneic transplantation, have broad activity that could inhibit both the overt disease and other undetectable coexistent abnormal clones. In contrast, disease-specific targeted therapy such as immunosuppressive therapy in aplastic anemia, ATRA in APL, or imatinib in CML would have no activity against other abnormal clones, allowing them to expand and become detectable as the dominant clone declines.     

Clinical Classification as a Guide to Treatment of Sinusitis in Children

Evaluation of all 153 children undergoing CT scan of the paranasal sinuses for recalcitrant sinusitis symptoms between January 1988 and July 1992 was performed. Clinical categorization into groups of patients presenting with chronic sinusitis (CS) and recurrent acute sinusitis (RAS) was based upon pattern of disease and presentation. Clinical symptoms and signs, radiological examination, treatment, and outcome were compared between these distinct clinical groups. Eighty-two (55%) children were categorized as RAS and 68 (45%) as CS. Children with CS presented more frequently with a persistent cough, purulent nasal discharge, immune deficiency, and more severe mucosal disease on CT than children with RAS. Medical therapy successfully controlled the symptoms of sinusitis in 79 (96%) with RAS versus 27 (40%) with CS. Surgery was performed in 44 children: 3 (3.6%) with RAS versus 41 (60%) with CS, p<0.01. At a mean follow-up of 2.0 years, >80% of all the children were either asymptomatic or improved regardless of treatment modality. These data support the use of clinical classification as a guide to medical versus surgical therapy in children with sinusitis.     

Beta2 integrin/ICAM-1 adhesion molecule interactions in cutaneous inflammation and tumor promotion

The beta2 integrin (CD 18/CD 11 a, b, c) family of proteins mediate adherence of leukocytes to vascular endothelium and the associated ligand, intercellular adhesion molecule-1 (ICAM-1; CD 54), interacts with beta2 integrin proteins to allow transendothelial migration of leukocytes into sites of inflammation. The present study examines the function of these proteins in a murine model of acute cutaneous inflammation induced following topical application of 12-O- tetradecanoylphorbol-13-acetate (TPA) to the dorsal epidermis of SENCAR mice and in a model of skin multistage carcinogenesis. At 24 h following topical application of TPA to the dorsal epidermis of mice, dermal leukocytes expressed higher levels of beta2 integrin protein compared with the lower levels of beta2 integrin protein expression by peripheral blood leukocytes. ICAM-1 protein was localized to epidermal keratinocytes and vascular endothelium in TPA-treated skin and to proliferating papilloma cells. Intravenous (i.v.) injection of either 50 microg anti-beta2 integrin antibody alone or in combination with anti-ICAM-1 antibody significantly inhibited both TPA-stimulated neutrophil infiltration into the dermis (P < 0.001) and myeloperoxidase (MPO) activity (P < 0.03 anti-beta2 integrin antibody; P < 0.01 anti- beta2 integrin + ICAM-1 adhesion molecule antibodies), but had no effect on TPA-induced epidermal hyperplasia. In addition, injection of either anti-ICAM-1 adhesion molecule antibody alone (P < 0.004) or in combination with anti-beta2 integrin antibody (P < 0.001) significantly inhibited TPA-induced production of 7,8-dihydroxy-2'-deoxyguanosine (8- OHdG) immunoreactive proteins by epidermal keratinocytes. Beta2 integrin/ICAM-1 adhesion molecules work in concert to regulate migration, retention and functional activation of leukocytes within the dermis during TPA-induced skin inflammation and within stromal tissue of papillomas that form during multi-stage carcinogenesis. Agents that inhibit these receptor/ligand interactions may be useful in defining the roles of specific cell populations in cutaneous inflammation and multistage carcinogenesis and may also have potential as anti-promoting and anti-progression agents.      

Chordoma: Radiological–pathological correlation

This review correlates the imaging findings and histological appearances seen in chordomas in a series of patients presenting at our institution, together with a published literature review. A parallel presentation of photographs of imaging findings and microscopic histological findings is made, with the aim being to enhance recognition of this uncommon but clinically significant entity.