Pseudotumor of the mandible as first presentation of hemophilia in a 2-year-old male: a case report and review of jaw pseudotumors of hemophilia.

Pseudotumor of hemophilia (PTH) is a rare complication seen in approximately 1-2% of cases of hemophilia. Although much more common in long bones, the pelvis, and small bones of the hands and feet than in the jaws, occasionally hemorrhage in the jaws occurs with this result. We present a case in a two-year-old male with a one-month swelling of the right mandible without significant medical history or diagnosis of hemophilia who was subsequently diagnosed as having Factor IX deficiency, or hemophilia B. A review of the literature revealed only 15 reported cases of PTH of the jaws and salient features of PTH in the jaws are discussed. The differential diagnosis of masses occurring in the jaws of children is limited and PTH should be considered when a mass presents with rapid growth and the histopathologic features are not diagnostic for a neoplastic process, even in the absence of a prior diagnosis of hemophilia as PTH may be the initial manifestation of this disease.

Orofacial rhabdomyosarcoma in neonates and young children: a review of literature and management of four cases.

Rhabdomyosarcoma (RMS) is an aggressive malignant skeletal muscle neoplasm arising from embryonal mesenchyme. It accounts for over 50% of all pediatric soft tissue sarcomas. The head and neck region is the most common site for this tumor in children. Neonatal presentation of this tumor is rare. We present the management of one neonatal case and three additional cases of orofacial RMS in children under the age of 7 years. All four patients were seen in the department of oral and maxillofacial surgery at Children's Hospital and Regional Medical Center (CHRMC) in Seattle between 1992-2000. Three of the four cases were alveolar RMS and one was botryoid sub-type of embryonal RMS. Three patients were treated with a combination of surgery, chemotherapy and radiation, while the patient with botryoid RMS was treated with surgery and chemotherapy only. The patient with congenital RMS died at 2.5 years of age due to recurrent metastatic disease. The other three patients are alive without evidence of recurrent with a mean follow up was 5.5 years (range 2.5-8.5 years). We discuss the current management, diagnosis, biological behavior, histopathology, prognosis and survival of head and neck RMS in neonates and young children.

Glutathione, cell proliferation, and 1,3-bis-(2-chloroethyl)-1-nitrosourea in K562 leukemia.

We have pursued our findings of glutathione reductase (GSSG-R) deficiency and disturbed glutathione in cancer patients treated with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), by investigating how thiol metabolism, cell proliferation, and the nitrosourea interact in human K562 leukemia. Fasting cells arrested in G greatly increased their reduced glutathione (GSH) in response to growth factors. The rise in thiol began after several hours, peaked before DNA synthesis, and resulted from increased production. BCNU inactivated GSSG-R rapidly, and later retarded, doubled, and greatly prolonged GSH formation before stopping DNA synthesis. Pretreatment unlike post treatment with buthionine-S-R-sulfoximine (BSO) diminished BCNU's ability to block GSSG-R. Enzyme inhibition decreased with falling cellular GSH. In the leukemia system as in vivo, sequential BCNU-induced thiol alterations heralded delayed antiproliferative effects. Drug timing markedly affected both thiol and DNA syntheses. By destroying GSSG-R and delaying the upregulation of thiol synthesis while escalating GSH utilization and requirements, the nitrosourea created a striking and previously unrecognized window of vulnerability for GSH-dependent processes. During this period, altered GSH metabolism could contribute indirectly to BCNU's pleiotropic effects by interfering with DNA alkylation repair, glucose decarboxylation, deoxyribose formation, and possibly by influencing other aspects of proliferation. Acquired GSSG-R deficiency was also an early and sensitive marker for prodrug breakdown and activation.

Mechanism of the effects of glucocorticoids and mineralocorticoids on vascular smooth muscle contractility.

We have previously demonstrated that receptors to both mineralocorticoids (MC) and glucocorticoids (GC) exist in the arterial wall and that treatment with GC markedly increases Na+ and Ca2+ influx in cultured aortic vascular smooth muscle (VSM) cells, whereas treatment with MC increases only Na+ influx. We now report the results of the study aimed at the elucidation of the mechanism(s) of these effects. Unidirectional influx of Na+ and Ca2+ was measured in cultured cells of rabbit aortic media, using 22Na and 45Ca as tracers, in the presence of ouabain. The cells were treated for different periods with dexamethasone (DEX) or aldosterone (ALDO) in physiologic or supraphysiologic concentrations, in the presence or absence of competitive inhibitors of GC-receptor binding, RU 486, or MC-receptor binding, K-prorenoate. DEX in 50 nM concentration increased Na+ influx by 98 +/- 18% and Ca2+ influx by 100 +/- 20%, and the maximum effect was seen after 48 hour cell-treatment. ALDO in 5 nM concentration increased Na+ influx by 90 +/- 12% and had no effect on Ca2+ influx, and the maximum effect was seen after 7-10 days of cell-treatment. The enhancing effect of both DEX and ALDO on the influx rate of Na+ was prevented by actinomycin D and by cycloheximide. RU 486 completely inhibited DEX from exercising its enhancing effect on Na+ influx, but diminished influx rate of Na+ increased by ALDO only by 25%. Prorenoate (PRN) did not have any effect on DEX-increased Na+ influx, but completely inhibited ALDO from exercising its effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Do membrane lipids modify the ouabain-sensitivity of cardiac (Na,K)ATPase?

We investigated whether membrane lipids can alter the affinity of cardiac (Na,K)ATPase (ATP phosphohydrolase, EC 3.6.1.6) for ouabain. We recombined partially (80-95%) delipidated membrane proteins from a digitalis-sensitive species (dog) with membrane lipids from a relatively digitalis-insensitive species (rat) or vice versa, and estimated the affinity of (Na,K)ATPase for ouabain in these hybrid membranes by measuring the half-maximal inhibitory concentration (I50). Delipidation reduced the enzyme activity by 90-95%, but 40-60% of the original activity could be restored with lipids from the same or from the other species and distribution of [14C]phosphatidylcholine showed complete mixing between the native and foreign lipids. In these hybrid cardiac membranes affinity (I50) for ouabain was determined by the origin of the (Na,K)ATPase protein and was not modified by the change in membrane lipids.