1/23. Identification of mutations in the c-mpl gene in congenital amegakaryocytic thrombocytopenia.Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disorder expressed in infancy and characterized by isolated thrombocytopenia and megakaryocytopenia with no physical anomalies. Our previous hematological analysis indicated similarities between human CAMT and murine c-mpl (thrombopoietin receptor) deficiency. Because the c-mpl gene was considered as one of the candidate genes for this disorder, we analyzed the genomic sequence of the c-mpl gene of a 10-year-old Japanese girl with CAMT. We detected two heterozygous point mutations: a C-to-T transition at the cDNA nucleotide position 556 (Q186X) in exon 4 and a single nucleotide deletion of thymine at position 1,499 (1,499 delT) in exon 10. Both mutations were predicted to result in a prematurely terminated c-Mpl protein, which, if translated, lacks all intracellular domains essential for signal transduction. Each of the mutations was segregated from the patient's parents. Accordingly, the patient was a compound heterozygote for two mutations of the c-mpl gene, each derived from one of the parents. The present study suggests that at least a certain type of CAMT is caused by the c-mpl mutation, which disrupts the function of thrombopoietin receptor.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
2/23. Establishing the etiology of thrombocytopenia.hemostasis is dependent on an adequate number of well-functioning platelets in the circulating blood. As the number of circulating platelets decreases, the chance of bleeding increases. thrombocytopenia, a platelet count of less than 150,000 per microliter, is a laboratory finding and not a diagnosis. Therefore, once thrombocytopenia is identified, a detailed history, physical examination, and further laboratory tests are used to establish an etiology. This article reviews the assessment, diagnosis, and treatment of thrombocytopenia.- - - - - - - - - - ranking = 10.118419779629keywords = physical examination, physical (Clic here for more details about this article) |
3/23. Compound heterozygosity for two different amino-acid substitution mutations in the thrombopoietin receptor (c-mpl gene) in congenital amegakaryocytic thrombocytopenia (CAMT).Congenital amegakaryocytic thrombocytopenia (CAMT) without physical anomalies is a rare disease, presenting isolated thrombocytopenia and megakaryocytopenia in infancy, which can evolve into aplastic anemia and leukemia. Recently, two heterozygous truncating mutations of the thrombopoietin (TPO) receptor MPL, coded by the c-mpl gene, were identified in a 10-year-old Japanese patient with CAMT transmitted in an autosomal recessive manner. Here, we report for the first time two different MPL amino-acid substitutions in a 2-year-old Italian boy with CAMT and compound heterozygosis for two (c-mpl point mutations. C-to-T transitions were detected on exons 5 and 12 at the 769 and 1904 cDNA nucleotide positions, respectively. The mutation in exon 5 substitutes an arginine with a cysteine (R257C) in the extracellular domain, 11 amino acids distant from the WSXWS motif conserved in the cytokine-receptor superfamily. The mutation in exon 12 substitutes a proline with a leucine (P635L) in the last amino acid of the C-terminal intracellular domain, responsible for signal transduction. As in the Japanese family, the mutations were both transmitted from the parents. TPO plasma levels were highly increased in the patient. The patient's 7-year-old brother, who was a candidate donor for allografting, turned out to be an asymptomatic heterozygous carrier of P635L and showed defective megakaryocyte colony formation from bone-marrow progenitor cells. The present study provides important confirmation that CAMT can be associated with (c-mpl) mutations.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
4/23. pituitary apoplexy in a patient with acute myeloid leukemia and thrombocytopenia.We describe a 72-year-old woman with a history of acute myeloid leukemia who developed pituitary apoplexy associated with thrombocytopenia secondary to chemotherapy. She presented with new onset severe headache, nausea, vomiting and blurred vision. Initial physical examination was unremarkable. CT scan of the head was initially negative. Upon admission for further work up, She developed a high-grade fever, hypotension and obtundation. Subsequent physical examination revealed bitemporal visual fields defects and decreased visual acuity. Repeat imaging of head revealed a hemorrhagic pituitary mass compressing the optic chiasm. Laboratory results were compatible with the diagnosis of pan-hypopituitary syndrome. She received high dose steroids and was transferred for transnasal sphenoidotomy decompression surgery. The visual defects improved postoperatively. A literature review of pituitary apoplexy is presented. pituitary apoplexy secondary to thrombocytopenia has never been reported.- - - - - - - - - - ranking = 20.236839559258keywords = physical examination, physical (Clic here for more details about this article) |
5/23. A bleeding disorder caused by a cardiac tumor: case report.A 22-year-old female developed symptomatic thrombocytopenia. On physical examination, apart from ecchymoses, a loud holosystolic murmur was heard. echocardiography revealed a cardiac tumor. The thrombocytopenia did not respond to corticosteroids, but after surgical removal of the intracardiac tumor, a papillary fibroelastoma, the platelet count normalised. There are no similar case reports in the literature. Our case report illustrates that thrombocytopenia may be associated with a cardiac tumor and that complete physical examination is essential in every patient presenting with easy bruising.- - - - - - - - - - ranking = 20.236839559258keywords = physical examination, physical (Clic here for more details about this article) |
6/23. Congenital thrombocytopenia and radio-ulnar synostosis: a new familial syndrome.The association of bone marrow failure and skeletal defects has been frequently noted, however, the genetic basis for most of these syndromes remains unclear. We describe a previously uncharacterized autosomal dominant syndrome of amegakaryocytic thrombocytopenia associated with radial-ulnar synostosis. The clinical features of this syndrome appear to be distinct from other similar conditions, including Fanconi's anaemia and thrombocytopenia-absent radii (TAR). The physical findings at diagnosis and clinical management of each case are detailed, as well as a discussion of this disorder in the context of other syndromes in which marrow failure and skeletal defects are prominent features. We also review recent developments in molecular genetics that may provide important clues to the underlying aetiology of this condition.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
7/23. A case of head and neck kaposiform hemangioendothelioma simulating a malignancy on imaging.Kaposiform hemangioendothelioma (KH) is an endothelial-derived spindle cell neoplasm often associated with kasabach-merritt syndrome. Most cases arise in infancy and childhood and are soft-tissue tumors. The tumor displays an appearance between capillary hemangioma and Kaposi's sarcoma. We report a case of KH in a 1-year-old girl involving a mass that showed abnormal enhancement of soft tissue superficial to the right temporal bone with partial destruction of the temporal bone, the temporomandibular joint, mandibular condyle, and occipital bone. The physical finding of a discolored mass led clinicians to consider a hemangiomatous lesion, whereas the radiological picture suggested a more aggressive diagnosis of rhabdomyosarcoma and aggressive fibromatosis.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
8/23. heparin-induced thrombocytopenia as the cause of gluteus muscle necrosis: a case study describing the benefits of multidisciplinary physical and psychosocial interventions.heparin-induced thrombocytopenia, an increasingly recognized aspect of heparin therapy, occurs in 0.6% to 30% of patients receiving heparin. Approximately 1% of those patients develop the more severe heparin-induced thrombocytopenia II, also called white clot syndrome, in which synchronous venous and arterial thrombi impede blood flow in central vessels. mortality (as high as 25%) and morbidity are related to the site and extent of thrombi formation. Following vascular surgery, one patient manifested an unusual consequence of heparin-induced thrombocytopenia II when thrombotic blockage of the vessels supplying the bilateral gluteus maximus and minimus muscles resulted in tissue ischemia and death. Supporting the patient through numerous complications and managing the extensive wound healing process required multidisciplinary skills and innovative technology, including use of vacuum-assisted closure therapy, platelet-derived growth factors, parenteral and enteral nutritional support, and spirit-restoring favorite foods. This article describes the patient's life-threatening and long-lasting effects from an allergic reaction to heparin therapy. In addition to information about the diagnosis of heparin-induced thrombocytopenia, this article also describes management of the wound and other aspects of care and comforting that occurred over a 9-month hospitalization.- - - - - - - - - - ranking = 4keywords = physical (Clic here for more details about this article) |
9/23. X-linked thrombocytopenia caused by a mutation in the Wiskott-Aldrich syndrome (WAS) gene that disrupts interaction with the WAS protein (WASP)-interacting protein (WIP).OBJECTIVE: We studied two adult brothers with severe congenital thrombocytopenia in order to determine the genetic etiology of their inherited disorder. Despite the absence of eczema or immunodeficiency, a mutation of the Wiskott-Aldrich syndrome (WAS) gene was suspected because of the presence of microthrombocytes. MATERIALS AND methods: Peripheral blood was obtained for characterization of hematopoietic cells and megakaryocyte progenitors. The coding region of the WAS gene was fully sequenced, and expression of the wiskott-aldrich syndrome protein, WASP, was evaluated by immunoblotting. The ability of WASP to physically associate with the WASP-interacting protein, WIP, was tested by yeast and mammalian two-hybrid techniques. RESULTS: In addition to thrombocytopenia, our investigation revealed an increased frequency of peripheral megakaryocyte progenitors (CFU-Mk) and incomplete cytoplasmic maturation by electron microscopy. Sequencing the WAS gene revealed a single base mutation, resulting in substitution of proline for arginine 138 (i.e., Arg138Pro). immunoblotting demonstrated reduced expression of the mutant WAS protein, and we showed that the Arg138Pro mutation significantly, but incompletely, disrupts WASP-WIP interaction. CONCLUSIONS: In this pedigree, X-linked thrombocytopenia is caused by a rare mutation in the fourth exon of the WAS gene. WASP levels are reduced in lymphocyte cell lines derived from the affected individuals. Furthermore, the mutation significantly but incompletely disrupts WASP-WIP interaction, whereas substitution of alanine or glutamic acid residues at the same position does not. This raises the possibility that protein-protein interaction and WASP stability are related properties.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
10/23. calciphylaxis: a case study with differential diagnosis.calciphylaxis is a relatively rare, but horribly disfiguring, skin condition that is most often associated with end-stage renal disease and long-term dialysis. Unfortunately, calciphylaxis-related morbidity and mortality are significant. The case study presented demonstrates many of the findings associated with the typical calciphylaxis patient; end-stage renal disease and an extensive, painful ulcer. The complexity of the patient s history and medical/surgical interventions, especially medication therapy with coumadin and heparin, complicated initial diagnostic processes. Close scrutiny of multiple physical assessment findings, historical factors, and test results was required for correct diagnosis. Crucial components of differential diagnosis of calciphylaxis versus coumadin-induced skin necrosis or heparin-induced thrombocytopenia necrosis include: patient history and characteristics, clinical presentation, and diagnostic test results.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
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