The presenting features of mucopolysaccharidosis type IH (Hurler syndrome)

The presenting features of 39 patients with mucopolysaccharidosis (MPS) type IH are described. The mean age at diagnosis was approximately 9 months and it is difficult to see how this can be reduced without consideration of newborn screening. An earlier age at diagnosis is likely to lead to better results following therapy such as bone marrow transplantation. Clinical features which should arouse suspicion of MPS IH include frequent ENT surgery and recurrent herniae. Clinical vigilance is needed for early diagnosis     

Multilocular cystic nephroma: a radiographic-pathologic correlation of 58 patients

Clinical radiographic, and pathologic findings of multilocular cystic nephroma (MLCN) in 58 patients are presented. The lesion that affects predominantly boys in childhood and women in adulthood is usually solitary but rarely can be multiple, and it commonly occurs as an asymptomatic mass, occasionally with hematuria. Tumors may grow slowly over years or rapidly within months. A mass that is usually identified on plain radiographs occasionally has curvilinear calcification. Excretory urography and retrograde pyelography are helpful when pelvic herniation of the tumor is recognized, or when septae are noted with total body opacification. Angiography showed an avascular mass (six lesions), a hypovascular mass (14 lesions), or a hypervascular mass three lesions). Ultrasonography is helpful when multiple circumscribed sonolucent areas are identified. Similarly, a multilocular mass with septae is usually identified by computed tomography (six of seven cases). Our findings and a review of the literature indicate that this lesion is a neoplasm that can be strongly suspected preoperatively if pelvic herniation or a multilocular pattern is noted on imaging studies.     

Oropharyngeal and esophageal pressures during mono- and binasal CPAP in neonates

Oropharyngeal and esophageal pressures were measured via a tip-transducer during mono- and binasal CPAP in 30 neonates. During nasal CPAP, increasing flows are followed by an increase in oropharyngeal pressure, although thcrc were great variations among the pressures recorded. On the other hand, no increase in the esophageal pressure could be registered during nasal CPAP. It is advisable to use the lowest flow which ameliorates the respiratory status in neonates. To achieve an appropriate pressure in the oropharynx it is advisable to close the mouth during nasal CPAP in the neonate.     

Experimental Pseudomonas pneumonia in leukopenic dogs: comparison of therapy with antibiotics and granulocyte transfusions

Pseudomonas aeruginosa pneumonia was produced in dogs with radiation- induced leukopenia to study the comparative efficacy of several different therapies. In a randomized control trial, five treatment regimens were compared: no antibiotics or granulocytes (controls), gentamicin (5 mg/kg/day), carbenicillin (500 mg/kg/day), gentamicin and carbenicillin (same dosages), and daily granulocyte transfusion (minimum 5 x 10(9) cells/day) plus gentamicin (5 mg/kg/day). The most effective therapy was gentamicin plus granulocyte transfusions. Gentamicin alone was not significantly better than no specific therapy. Carbenicillin with or without gentamicin gave intermediate results. This study further supports the utility of granulocyte replacement therapy of infections in severely granulocytopenic subjects. The results also indicate that the relative value of granulocyte transfusions depends upon the specific antibiotic regimen with which these transfusions are compared.     

Regulation of platelet activation in vitro by the c-Mpl ligand, thrombopoietin

Thrombopoietin (TPO) is a recently identified growth factor that regulates megakaryocytopoiesis. Its receptor, c-Mpl, is expressed in megakaryocyte progenitors, mature megakaryocytes, and human blood platelets. We have observed that TPO treatment of human platelets resulted in tyrosine phosphorylation of several cellular proteins, including the c-Mpl receptor and the 85-kD subunit of phosphatidylinositol 3-kinase (PI3-K). TPO stimulated this tyrosine phosphorylation in a time-dependent manner, reaching a maximum in 5 minutes. The tyrosine phosphorylation of PI 3-K was dependent on the concentration of TPO and reached a maximum at concentrations between 50 and 100 ng/mL. This phosphorylation was independent of extracellular fibrinogen and ligation of the alpha IIb beta 3 integrin. In contrast, TPO, in the presence of exogenous fibrinogen, induced concentration- dependent platelet aggregation, which was blocked by the soluble c-Mpl receptor. Increasing TPO concentrations modulated the degree of the primary wave of aggregation and the lag phase, but not the slope or maximum of the secondary wave of aggregation. This secondary aggregation was controlled by the addition of apyrase, suggesting an adenosine diphosphate (ADP)-dependent mechanism. Treatment of platelets with TPO resulted in augmented binding of 125I-fibrinogen to intact platelets, with a 50% effect (EC50) occurring between 5 and 10 ng/mL. TPO-induced binding of fibrinogen to platelets was comparable in degree with that observed by stimulation with 10 mumol/L ADP. In an immobilized collagen-platelet adhesion assay, a significant increase in the attachment of TPO-stimulated platelets was observed. This effect was dependent on the concentration of TPO. At 50 ng/mL of TPO, platelet attachment to collagen increased threefold compared with the buffer control. Furthermore, the presence of fibrinogen did not significantly alter TPO augmentation of the platelet-collagen interaction. This interaction was mediated by the Arg-Gly-Asp (RGD) adhesion recognition sequence, as it was completely abolished by 100 mumol/L of the RGDS peptide. A fraction of the TPO-dependent platelet attachment to a collagen-coated surface was insensitive to treatment with prostaglandin E1. Furthermore, antibody to alpha IIb integrin partially inhibited platelet attachment to collagen, suggesting that the integrin alpha IIb beta 3 participates in this association. These data indicate that TPO might function not only as a cytokine in megakaryocyte growth and differentiation, but may also participate in direct platelet activation and modulate platelet-extracellular matrix interactions.