Congenital combined vitamin K-dependent clotting factors deficiency (VKCFD) is a very rare autosomal recessive bleeding disorder. Here we report a case of a girl with novel variant in the gamma-glutamyl carboxylase (GGCX) gene leading to VKCFD. A 3-month-old girl presented to our hospital with a history of bleeding from puncture site. Laboratory evaluation showed markedly prolonged partial thromboplastin time and activated partial thromboplastin time. Activities of vitamin K-dependent factors were all low. Genetic analysis revealed a homozygous currently unreported variant in the GGCX gene further supporting a diagnosis of VKCFD type 1. VKCFD due to GGCX mutation has an overall good prognosis
DISCUSSIONAcute lymphoblastic leukemia can present with proptosis, secondary glaucoma, hetrochromia iris, hypopyon, hyphema, retinal detachment, microaneuresyms, isolated retinal hemorrhages, tortuous blood vessels, and swollen optic disc [1-5]. The differential diagnosis of the swollen optic disc includes benign intracranial hypertension (pseudotumor cerebri), papilledema due to mass lesion, malignant hypertension, optic neuropathy due to Graves disease, metastatic orbital lesion, optic neuritis, diabetes, meningioma, optic glioma, and infiltration of nerve heads with leukemia and lymphoma.
Necrosis Associated with Intrathecal Methotrexate and Cranial Irradiation. 2003; 23(3-4): 167-170 With the advent of chemotherapy, mortality rates in children with acute lymphoblastic leukemia (ALL) have decreased. Though prophylactic treatment of the central nervous system (CNS) to prevent leukemic infiltration has dramatically reduced the incidence of CNS relapse and improved the survival in pediatric acute lymphoblastic leukemia, it is associated with serious sequelae. Various reports of neurotoxicity have been described, ranging from decreased intelligence quotient scores, impaired memory and attention span to severe leukoencephalopathy. 1 We describe a unique case of neurotoxicity associated with prophylactic cranial irradiation and intrathecal MTX.
Case reportA four-year old boy was diagnosed as having central nervous system negative acute lymphoblastic leukemia (ALL) in August 1997. He was treated with a high-risk acute lymphoblastic leukemia protocol Children's Cancer Group (CCG-1882), secondary to unfavorable cytogenetics. He achieved complete remission with induction treatment consisting of weekly intravenous vincristine, daunomycin, daily oral prednisone, and nine doses of intramuscular L-asparginase. Consolidation consisted of cranial irradiation, 1800 cGy in 12 fractions of 150 cGy each, four doses of intrathecal MTX, intravenous Cytoxan and cytarabine. Prior to start of maintenance, he received reinduction/ reconsolidation treatment along with two doses of intrathecal methtrexate. Maintenance consisted of monthly pulses of intravenous vincristine, oral prednisone, weekly oral MTX and daily oral 6-merceptopurine, with intrathecal MTX every 3 months.He was admitted as an emergency, 14 days after the last intrathecal MTX in May 1999, with left focal seizures approximately 20 months after diagnosis. He had received atotal dose of 156 mg MTX intrathecally. A computerized tomography (CT) scan of the brain on the 27 th of May revealed bilateral symmetrical periventricular hypodence white matter changes in the frontoparietal region. There were no calcifications orintracranial bleeding (Figure 1). Magnetic resonance imaging (MRI) on the 30 th of May revealed multiple high intensity areas in the subcortical and periventricular white matter on fluid attenuated inversion recovery (FLAIR) imaging representing leukoencephalopathy (Figure 2). Seizures were aborted with lorazepam, and patient was discharged on carbamezapine. Two weeks later, he was readmitted because he had changed from a talkative boy of superior intelligence into a child that only answered questions with strong stimulation. He was also having seizures. A repeat MRI on the 27 th of June, four weeks after the first MRI, revealed stable diffuse white matter changes described previously, but with emergence of bilateral cortical changes in the parietooccipital lobes, with more on the right, probably representing cortical edema ( Figure 3A). These cortical changes were more readily apparent on FLAIR sequence ( Figure 3B). Lumbar puncture ruled out ...
Pulmonary surfactant has a potential role in modulating inflammation in normal and injured lungs. In lung injury, monocytes become activated and participate in lung inflammation. We therefore, investigated the proinflammatory functions of stimulated human blood monocytes after an overnight preincubation period with modified natural porcine surfactant (Curosurf) (500-1000 micrograms/mL). Monocytes were stimulated either with phorbol myristate acetate (PMA), bacterial extract OM-85, lipopolysaccharide (LPS), or Ca2+ ionophore A23187. The present study shows that Curosurf significantly inhibits: 1) the production of superoxide anions stimulated with OM-85 (1 mg/mL, 30 min), but not with PMA (100 ng/mL, 30 min); 2) the release of cyclooxygenase metabolites prostaglandin E2 and thromboxane B2 stimulated with OM-85 (1 mg/mL, overnight); 3) the release of lipoxygenase metabolite leukotriene C4 stimulated with A23187 (10 microM, 10 min); 4) the release of the cytokine TNF-alpha stimulated overnight with either OM-85 (1 mg/mL) or LPS (10 micrograms/mL)) in a dose-dependent fashion. In addition, Curosurf decreases the spontaneous adherence of monocytes to plastic culture wells in a dose-dependent fashion. Experiments performed with staurosporine, an inhibitor of protein kinase C (PKC) indicate that, in contrast with PMA, the production of superoxide anions stimulated by OM-85 is not related to PKC activation. Consequently, we propose that the mechanism involved in the suppressive effects of Curosurf is PKC-independent. In summary, the present study provides experimental evidence that favors the anti-inflammatory role of modified natural porcine surfactant (Curosurf) in human monocytes in vitro.
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