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Severe Deficiency (severe + deficiency)
Selected AbstractsThrombotic thrombocytopenic purpura: Results of the patients with thrombotic microangiopathies across Japan by ADAMTS13 analysis during 1998,2008ISBT SCIENCE SERIES: THE INTERNATIONAL JOURNAL OF INTRACELLULAR TRANSPORT, Issue n2 2009Y. Fujimura Background, Thrombotic microangiopathies (TMAs) are pathological conditions, characterized by generalized microvascular occlusion by platelet thrombi, thrombocytopenia, and microangiopathic hemolytic anemia. Two typical phenotypes of TMAs are hemolytic-uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Severe deficiency of plasma ADAMTS13 activity (ADAMTS13:AC) is more specific for TTP but not for HUS. Materials & Methods, Since 1998, our laboratory has functioned as a nationwide referral center for TMAs by analyzing ADAMTS13. Of 1564 tested patients from 426 hospitals, 919 were positive for TMAs. Levels of ADAMTS13:AC and the ADAMTS13-neutralizing autoantibodies (ADAMTS13:INH) in these patients were determined by chromogenic act-ELISA and/or by classic von Willebrand factor multimer assay. Results, TMA patients consisted of two groups, those with severe (less than 3% of normal control) and those with non-severe deficiency of ADAMTS13:AC. Additionally, both groups were divided into congenital (n = 65) and acquired (n = 854) TMAs. Of the congenital TMA patients, 41 had ADAMTS13:AC deficiency due to gene mutations, while the remaining 24 had the disease of unknown etiology. The 854 patients with acquired TMAs could be largely grouped into three categories: idiopathic TTP (n = 284), idiopathic HUS (n = 106), and secondary TMAs (n = 464). The secondary TMAs were observed in heterogeneous patient groups and were associated with drugs, connective tissue diseases, malignancies, transplantation, pregnancy, E. coli O157:H7 infection, and other factors. All of the patients with acquired severe ADAMTS13:AC deficiency were positive for ADAMTS13:INH. Conclusion, Although TMAs are highly heterogeneous pathological conditions, one third of TMA patients have severe deficiency of ADAMTS13:AC. Platelet transfusions to such patients are contraindicated. Thus, rapid ADAMTS13:AC assays will be prerequisite in medical facilities where TMA patients are treated. [source] Real-Time quantitative PCR analysis of factor XI mRNA variants in human plateletsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2004A. Podmore Summary., Coagulation factor XI (FXI) plays an essential role in blood coagulation. A deficiency of FXI is an unusual hemorrhagic diathesis in that the bleeding tendency can be highly variable, ranging from severe deficiencies with no symptoms to mild and moderate deficiencies requiring multiple blood transfusions for hemorrhages. This variability in bleeding has been attributed to a number of factors including the presence of a novel form of FXI associated with platelets, which ameliorates the bleeding in some cases of FXI deficiency. However, the nature of this platelet FXI molecule is controversial. Hsu et al. (J Biol Chem 1998; 273: 13787,93) suggest that it is a product of normal FXI , but lacking exon V whilst Martincic et al. (Blood 1999; 94: 3397,404) were unable to detect this alternatively spliced variant using RT-PCR. In order to resolve this controversy, we have employed the highly sensitive technique of real-time quantitative RT-PCR using RNA isolated from FXI-deficient patients. Our results indicate that the platelets of both normal and FXI deficient individuals contain FXI mRNA that is identical to the mRNA found in liver. An exon V deleted splice variant was not detected. Thus the FXI message is not alternatively spliced in platelets and therefore would not be able to produce an unusual FXI protein. [source] Milder clinical presentation of haemophilia A with severe deficiency of factor VIII as measured by one-stage assayHAEMOPHILIA, Issue 1 2001K. Ghosh During the course of investigations we encountered 11 patients with haemophilia A who had severe factor VIII deficiency as measured by one-stage assay but had surprisingly mild clinical presentation. Four of these patients had either a brother, nephew or maternal uncle with severe clinical manifestations. Two patients had low protein S levels, and one was heterozygous for the factor V Leiden mutation. One patient had a combined deficiency of protein C and antithrombin III. Four patients had a two-stage factor VIII assay value that was much higher than the one-stage assay value. Five patients were heterozygous for the MTHFR gene C677T polymorphism, of whom two patients were also deficient for protein S and one had two-stage factor assay values higher than the one-stage assay values. The patient who was both factor VIII deficient and heterozygous for factor V Leiden had mild clinical presentation as compared to his maternal uncle who was only factor-VIII deficient. The maternal cousin of the same patient was heterozygous for factor V Leiden and had suffered two thrombotic episodes. Thus, the present study advocates that the physiological inhibitors of blood coagulation also play an important role in cases of haemophilia A in the final outcome of haemostasis in vivo. [source] Factor XI deficiency and its managementHAEMOPHILIA, Issue 2000Bolton-Maggs Factor XI deficiency has a more variable bleeding tendency than haemophilia A or B. Individuals with severe deficiency have only a mild bleeding tendency, which is typically provoked by surgery, but the risk of bleeding is not restricted to individuals with severe deficiency. The bleeding tendency varies between individuals with similar factor XI levels, and sometimes the bleeding tendency of an individual may vary. The reasons for this are not fully understood, although in cases of severe deficiency there is some correlation between phenotype and genotype. Factor XI is activated by thrombin. The role of factor XI in physiological processes has become clearer since this fact was discovered, and the discovery has contributed to a revised model of blood coagulation. Factor XI deficiency occurs in all racial groups, but is particularly common in Ashkenazi Jews. The factor XI gene is 23 kilobases long. Two mutations are responsible for most factor XI deficiency in the Ashkenazi population, but a number of other mutations have now been reported in other racial groups. Individuals with factor XI deficiency may need specific therapy for surgery, accidents, and dental extractions. Several therapies are available which include fresh frozen plasma, factor XI concentrates, fibrin glue, antifibrinolytic drugs, and desmopressin. Each has advantages and risks to be considered. Factor XI concentrate may be indicated for procedures with a significant risk of bleeding especially in younger patients with severe deficiency, but its use in older patients has been associated with thrombotic phenomena. If fresh frozen plasma is to be used it is preferable to obtain one of the virally inactivated products. Fibrin glue is a useful treatment which deserves further study. [source] Thrombotic thrombocytopenic purpura: Results of the patients with thrombotic microangiopathies across Japan by ADAMTS13 analysis during 1998,2008ISBT SCIENCE SERIES: THE INTERNATIONAL JOURNAL OF INTRACELLULAR TRANSPORT, Issue n2 2009Y. Fujimura Background, Thrombotic microangiopathies (TMAs) are pathological conditions, characterized by generalized microvascular occlusion by platelet thrombi, thrombocytopenia, and microangiopathic hemolytic anemia. Two typical phenotypes of TMAs are hemolytic-uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Severe deficiency of plasma ADAMTS13 activity (ADAMTS13:AC) is more specific for TTP but not for HUS. Materials & Methods, Since 1998, our laboratory has functioned as a nationwide referral center for TMAs by analyzing ADAMTS13. Of 1564 tested patients from 426 hospitals, 919 were positive for TMAs. Levels of ADAMTS13:AC and the ADAMTS13-neutralizing autoantibodies (ADAMTS13:INH) in these patients were determined by chromogenic act-ELISA and/or by classic von Willebrand factor multimer assay. Results, TMA patients consisted of two groups, those with severe (less than 3% of normal control) and those with non-severe deficiency of ADAMTS13:AC. Additionally, both groups were divided into congenital (n = 65) and acquired (n = 854) TMAs. Of the congenital TMA patients, 41 had ADAMTS13:AC deficiency due to gene mutations, while the remaining 24 had the disease of unknown etiology. The 854 patients with acquired TMAs could be largely grouped into three categories: idiopathic TTP (n = 284), idiopathic HUS (n = 106), and secondary TMAs (n = 464). The secondary TMAs were observed in heterogeneous patient groups and were associated with drugs, connective tissue diseases, malignancies, transplantation, pregnancy, E. coli O157:H7 infection, and other factors. All of the patients with acquired severe ADAMTS13:AC deficiency were positive for ADAMTS13:INH. Conclusion, Although TMAs are highly heterogeneous pathological conditions, one third of TMA patients have severe deficiency of ADAMTS13:AC. Platelet transfusions to such patients are contraindicated. Thus, rapid ADAMTS13:AC assays will be prerequisite in medical facilities where TMA patients are treated. [source] Heterogeneity in Serum 25-Hydroxy-Vitamin D Response to Cholecalciferol in Elderly Women with Secondary Hyperparathyroidism and Vitamin D DeficiencyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 8 2010Andrea Giusti MD OBJECTIVES: To compare the effects on parathyroid hormone (PTH) and 25-hydroxy-vitamin D (25(OH)D) of two dosing regimens of cholecalciferol in women with secondary hyperparathyroidism (sHPTH) and hypovitaminosis D and to investigate variables affecting 25(OH)D response to cholecalciferol. DESIGN: Randomized-controlled trial with 6-month follow-up. SETTING: Two osteoporosis centers in northern Italy. PARTICIPANTS: Sixty community-dwelling women aged 65 and older with sHPTH and hypovitaminosis D, creatinine clearance greater than 65 mL/min and without diseases or drugs known to influence bone and vitamin D metabolism. INTERVENTION: Cholecalciferol 300,000 IU every 3 months, once at baseline and once at 3 months (intermittent D3 group) or cholecalciferol 1,000 IU/day (daily D3 group). MEASUREMENTS: Serum PTH, 25(OH)D, calcium, bone-specific alkaline phosphatase, ,-C-terminal telopeptide of type I collagen, phosphate, 24-hour urinary calcium excretion. RESULTS: The two groups had similar baseline characteristics. All participants had vitamin D deficiency [25(OH)D<20 ng/mL)], and 36 subjects (60%) had severe deficiency (<10 ng/mL), with no difference between the groups (severe deficiency: intermittent D3 group, n=18; daily D3 group, n=18). After 3 and 6 months, both groups had a significant increase in 25(OH)D and a reduction in PTH. Mean absolute increase±standard deviation of 25(OH)D at 6 months was higher in the intermittent D3 group (22.7±11.8 ng/mL) than in the daily D3 group (13.7±6.7 ng/mL, P<.001), with a higher proportion of participants in the intermittent D3 group reaching desirable serum concentration of 25(OH)D , 30 ng/mL (55% in the intermittent D3 group vs 20% in the daily D3 group, P<.001). Mean percentage decrease of PTH in the two groups was comparable, and at 6 months, a similar proportion of participants reached normal PTH values. 25(OH)D response to cholecalciferol showed a wide variability. In a logistic regression analysis, body mass index and type of treatment appeared to be significantly associated with normalization of 25(OH)D values. CONCLUSION: Cholecalciferol 300,000 IU every 3 months was more effective than 1,000 IU daily in correcting vitamin D deficiency, although the two groups achieved similar effects on PTH at 6 months. Only 55% of the higher-dose intermittent group reached desirable concentrations of 25(OH)D, suggesting that yet-higher doses will be required for adequate vitamin D repletion. [source] Atypical presentations of thrombotic thrombocytopenic purpura: A review,JOURNAL OF CLINICAL APHERESIS, Issue 1 2009Ravi Sarode Abstract Thrombotic thrombocytopenic purpura (TTP) is diagnosed by the presence of microangiopathic hemolytic anemia and thrombocytopenia in a patient who frequently presents with central nervous system involvement and, to a lesser extent, renal dysfunction. Recent understanding of the pathophysiology of TTP due to severe deficiency of von Willebrand factor cleaving protease, known as ADAMTS13, has improved diagnosis of TTP. Once the diagnosis is suspected, life-saving therapeutic plasma exchange therapy is initiated. Occasionally, an unusual clinical presentation makes TTP diagnosis difficult, thus resulting in a delay in the management of TTP. This review highlights a variety of atypical TTP presentations described in the literature. It is intended to bring unusual scenarios to the clinician's awareness, so that timely treatment can be delivered. J. Clin. Apheresis, 2009. © 2008 Wiley-Liss, Inc. [source] The ubiquitous role of zinc in health and diseaseJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 3 2009DACVIM, Julia E. Cummings DVM Abstract Objective , To review zinc physiology and pathophysiology and the importance of zinc toxicity and deficiency in veterinary patients. Data Sources , A review of human and veterinary medical literature. Human Data Synthesis , There is a significant amount of original research in humans and animals on the role of zinc in multiple organ systems. There is also significant data available on human patients with zinc abnormalities. Veterinary Data Synthesis , Zinc deficiency has been studied in dogs with genetic disease and dietary deficiency leading to dermatological disease and immune deficiency. Zinc toxicity has been described after ingestion of metallic foreign bodies containing zinc. Conclusions , Historically, the role of zinc in health and disease has been studied through patients with toxicity or severe deficiency with obvious clinical signs. As the ubiquitous contribution of zinc to structure and function in biological systems was discovered, clinically significant but subtle deficiency states have been revealed. In human medicine, mild zinc deficiencies are currently thought to cause chronic metabolic derangement leading to or exacerbating immune deficiency, gastrointestinal problems, endocrine disorders, neurologic dysfunction, cancer, accelerated aging, degenerative disease, and more. Determining the causal relationships between mild zinc deficiency and concurrent disease is complicated by the lack of sensitive or specific tests for zinc deficiency. The prevalence of zinc deficiency and its contribution to disease in veterinary patients is not well known. Continued research is warranted to develop more sensitive and specific tests to assess zinc status, to determine which patients are at risk for deficiency, and to optimize supplementation in health and disease. [source] Spontaneous splenic rupture in a patient with factor XIII deficiency and a novel mutationPEDIATRIC BLOOD & CANCER, Issue 1 2008Hassan Khalife MD Abstract We report a novel mutation in factor XIIIA gene that caused severe congenital factor XIII deficiency in a 6 year and 8 month old male. The mutation is a GA deletion in the core domain leading to a premature stop at codon 502. The child had severe deficiency with two episodes of intracerebral hemorrhage. He also developed spontaneous splenic rupture, an unusual complication of this disorder. Pediatr Blood Cancer 2008;50:113,114. © 2006 Wiley-Liss, Inc. [source] Protamine sulphate for treatment of severe post-reperfusion coagulopathy in pediatric liver transplantationPEDIATRIC TRANSPLANTATION, Issue 8 2009Glauber Gouvęa The ROTEM® analysis strongly suggested the presence of either a heparin effect or severe deficiency of coagulation factors. The former diagnosis was supported by a subsequent in-vitro HEPTEM. A small dose of protamine sulphate was then administered, which promptly restored hemostasis. The remainder of the procedure was uneventful. [source] Management of cancer-associated thrombotic microangiopathy: What is the right approach?AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2007Theresa L. Werner Abstract A 49-year-old Caucasian woman presented with features suggestive of thrombotic microangiopathy (TMA). She did not respond to treatment with repeated plasma exchange and corticosteroids. A bone marrow biopsy revealed presence of metastatic carcinoma. A limited autopsy revealed presence of breast cancer with rib metastases. Though severe deficiency of von Willebrand factor-cleaving protease was initially proposed as a key pathogenetic factor for thrombotic thrombocytopenic purpura, subsequent studies involving patients with cancer-associated TMA did not find as severe a deficiency of von Willebrand factor-cleaving protease as is seen in idiopathic cases of thrombotic thrombocytopenic purpura. Here we address one approach of management of these patients with cancer-associated TMA. Am. J. Hematol., 2006. © 2006 Wiley-Liss, Inc. [source] ORIGINAL RESEARCH,BASIC SCIENCE: A Nitric Oxide-Releasing PDE5 Inhibitor Relaxes Human Corpus Cavernosum in the Absence of Endogenous Nitric OxideTHE JOURNAL OF SEXUAL MEDICINE, Issue 1 2005Jasjit S. Kalsi BSc, MRCS ABSTRACT Introduction., In conditions with severe deficiency of endogenous nitric oxide (NO), such as long-term diabetes and cavernosal nerve injury, phosphodiesterase type 5 (PDE5) inhibitors have reduced efficacy in the treatment of erectile dysfunction. NO-releasing PDE5 inhibitors could be an alternative therapeutic approach in such cases. Aim., We therefore aimed to compare sildenafil and NO-releasing sildenafil (NCX-911) in relaxing human corpus cavernosum in the absence or presence of endogenous NO. Methods., The two compounds were compared in reducing the phenylephrine-induced tone of human corpus cavernosum in the presence or absence of an inhibitor of NO synthase (L-NAME; 500 µM) or an inhibitor of soluble guanylate cyclase (ODQ, 10 µM). Results., NCX-911 was as potent as sildenafil in control conditions (EC50 = 733.1 ± 94.4 nM and 800.7 ± 155.8 nM, respectively). The potency of NCX-911 was not altered but that of sildenafil decreased significantly in the presence of L-NAME (EC50 = 980.4 ± 106.7 nM and 2446.7 ± 256.8 nM, respectively; P < 0.001 for sildenafil vs. control). Both compounds below 1 µM failed to induce relaxation in the presence of ODQ (EC50 = 6578 ± 1150 nM and 6488 ± 938 nM for NCX-911 and sildenafil, respectively). Conclusion., These results show that the potency of NCX-911 was maintained unlike sildenafil in the absence of endogenous NO confirming the potential use of NO-releasing PDE5 inhibitors in NO-deficient conditions. [source] Plant virus infection-induced persistent host gene downregulation in systemically infected leavesTHE PLANT JOURNAL, Issue 2 2008Zoltán Havelda Summary Understanding of virus infection-induced alterations in host plant gene expression and metabolism leading to the development of virus disease symptoms is both scientifically and economically important. Here, we show that viruses belonging to various RNA virus families are able to induce efficient host gene mRNA downregulation (shut-off) in systemically infected leaves. We demonstrate that the host gene mRNA shut-off overlaps spatially with virus-occupied sectors, indicating the direct role of virus accumulation in this phenomenon. The establishment of shut-off was not directly connected to active viral replication or the RNA-silencing machinery. Importantly, the induced shut-off phenomenon persisted for several weeks, resulting in severe deficiency of mRNA for important housekeeping genes in the infected plants. Interestingly, we found that some other RNA viruses do not induce or only slightly induce the shut-off phenomenon for the same set of genes, implicating genetic determination in this process. Nuclear run-on experiments suggest that plant viruses, similarly to animal viruses, mediate suppression of host mRNA synthesis in the nucleus. By investigating various host,virus interactions, we revealed a correlation between the intensity of the shut-off phenomenon and the severity of disease symptoms. Our data suggest that efficient and persistent downregulation of host genes may be an important component of symptom development in certain host,virus interactions. [source] Abnormal colour vision is a handicap to playing cricket but not an insurmountable oneCLINICAL AND EXPERIMENTAL OPTOMETRY, Issue 6 2007Ross W Harris BAppSc LOSc FVCO Background:, Two studies have reported that abnormal colour vision is under-represented among cricketers, presumably because cricketers with abnormal colour vision have difficulty seeing the red ball against the green grass of the cricket field and the green foliage around it. We have previously reported on the difficulties of five cricketers with abnormal colour vision but we have also reported that one of Australia's finest cricketers was a protanope. This survey was undertaken to confirm the under-representation of abnormal colour vision among cricketers and to ascertain whether those playing tend to be (1) those with a mild colour vision deficiency, (2) bowlers rather than batsman and (3) prefer to field close to the batsman rather than in the outfield. Methods:, The colour vision of 293 members of seven Melbourne Premier cricket clubs was tested using the Ishihara test. Those who failed were examined further to confirm their abnormal colour vision, to assess its severity with the Farnsworth D15 test and to classify it as either protan or deutan using the Medmont C100 test. A questionnaire about cricketing ability and problems playing cricket was administered. Results:, Twenty-six (8.9 per cent) of the cricketers had abnormal colour vision, of whom six played in the First Grade (6.7 per cent of First Grade players). The proportion of cricketers with a severe deficiency was significantly less than expected for the First Grade players. There were only two protans. Bowlers were not over-represented among the colour vision defective cricketers but those preferring to field close to the batsman were significantly over-represented. Conclusion:, Abnormal colour vision is a modest handicap to playing cricket, especially at the higher levels of the game. It may impede batting and the ability to field in the outfield. [source] | ||||||||||||||||||||||