A puzzling case of anemia

BACKGROUND: Iron deficiency anemia in adults is most frequently due to chronic blood loss. When the clinical course is complicated by sudden, severe declines in Hb concentration, the cause, nature, and lo- cation of bleeding may require an extensive clinical evaluation. CASE REPORT: A 39-year-old woman was admitted for management of refractory hypoparathyroidism related to total thyroidectomy for Graves' disease. Two weeks before admission, her Hb level was 7.0 g per dL. Despite transfusion with four units of RBCs during this interval, her admission Hb level was 5.7 g per dL. There was no evidence of blood loss or hemolysis. Laboratory values were consistent with an iron-deficient state. The patient's hospital course included repeated instances of sharp Hb drop and appropriate but unsustained response to RBC transfusion. Extensive work-up identified no occult source of bleeding. Clinical suspicion raised the possibility of self-inflicted blood loss. The patient subsequently admitted to repeatedly drawing blood from her indwelling catheter and discarding it in the lavatory. CONCLUSION: Munchausen syndrome should be considered in cases of unexplained anemia, especially in the target demographic group: young, female, healthcare professionals. Early diagnosis may prevent morbidity, multiple hospitalizations, and the risk of invasive diagnostic procedures.     

Expression of vascular endothelial growth factor does not promote transformation but confers a growth advantage in vivo to Chinese hamster ovary cells.

Vascular endothelial growth factor (VEGF) is a mitogen with a specificity for endothelial cells in vitro and an angiogenic inducer in vivo. We tested the hypothesis that VEGF may confer on expressing cells a growth advantage in vivo. Dihydrofolatereductase--Chinese hamster ovary cells were transfected with expression vectors which direct the constitutive synthesis of VEGF. Neither the expression nor the exogenous administration of VEGF stimulated anchorage-dependent or anchorage-independent growth of Chinese hamster ovary cells in vitro. However, VEGF-expressing clones, unlike control cells, demonstrated an ability to proliferate in nude mice. Histologic examination revealed that the proliferative lesions were compact, well vascularized, and nonedematous. Ultrastructural analysis revealed that capillaries within the lesions were of the continuous type. These findings indicate that the expression of VEGF may confer on cells the ability to grow in vivo in the absence of transformation by purely paracrine mechanisms. Since VEGF is a widely distributed protein, this property may have relevance for a variety of physiological and pathological proliferative processes.     

A proposed dosing algorithm for the individualized dosing of human immunoglobulin in chronic inflammatory neuropathies

Dosing guidelines for immunoglobulin (Ig) treatment in neurological disorders do not consider variations in Ig half‐life or between patients. Individualization of therapy could optimize clinical outcomes and help control costs. We developed an algorithm to optimize Ig dose based on patient's response and present this here as an example of how dosing might be individualized in a pharmacokinetically rational way and how this achieves potential dose and cost savings. Patients are “normalized” with no more than two initial doses of 2 g/kg, identifying responders. A third dose is not administered until the patient's condition deteriorates, allowing a “dose interval” to be set. The dose is then reduced until relapse allowing dose optimization. Using this algorithm, we have individualized Ig doses for 71 chronic inflammatory neuropathy patients. The majority of patients had chronic inflammatory demyelinating polyradiculoneuropathy (n = 39) or multifocal motor neuropathy (n = 24). The mean (standard deviation) dose of Ig administered was 1.4 (0.6) g/kg, with a mean dosing interval of 4.3 weeks (median 4 weeks, range 0.5–10). Use of our standardized algorithm has allowed us to quickly optimize Ig dosing.     

Pressure ulcer, fibronectin, and related proteins in spinal cord injured patients.

Pressure ulcer is a common occurrence in spinal cord injured (SCI) patients and can lead to serious complications. With proper management, some patients exhibit satisfactory healing whereas others show slow or nonhealing ulcers. Fibronectin has been shown to accumulate in wound, opsonize macroaggregate debris for phagocytosis, promote revascularization, and facilitate fibroblast migration and proliferation. We explored the relationship of plasma fibronectin with healing potential in 21 SCI men with pressure ulcer. They received standard wound care and were observed for eight weeks. Ten otherwise healthy SCI men without pressure ulcer (SCI-controls) and 32 able-bodied normal individuals (normal controls) were also studied. Plasma fibronectin and related proteins, ie, fibrinogen, plasminogen, alpha 2-antiplasmin and Factor XIII, were measured. Ten of 21 SCI patients with pressure ulcer showed rapid healing within four weeks and had significantly higher fibronectin levels as compared with the 11 patients with poor healing ulcers, SCI controls, and normal controls. Factor XIII and alpha 2-antiplasmin were mildly reduced and fibrinogen values were significantly increased in all SCI groups. Plasminogen concentrations were comparable in all groups studied. It thus appears that plasma fibronectin rises in patients with fast healing ulcers but fails to do so in those with poor healing ulcers and as such may be predictive of the course of pressure ulcers.     

血管闭合器应用的现况与展望

股动脉径路是冠状动脉及外周血管介入诊疗的主要途径。然而,股动脉径路穿刺的围术期血管并发症仍是每个介入医生时常面对的问题。研究显示,与压迫止血比较,血管闭合器可减少围术期血管并发症,缩短患者制动时间,增加患者舒适度。现就相关内容及最新进展进行简要综述。     

New mutations, genotype phenotype studies and manifesting carriers in giant axonal neuropathy

Giant axonal neuropathy (GAN; MIM 256850) is a severe childhood onset autosomal recessive sensorimotor neuropathy affecting both the peripheral nerves and the central nervous system. Bomont and colleagues identified a novel ubiquitously expressed gene they named Gigaxonin on chromosome 16q24 as the cause of GAN in a number of families. We analysed five families with GAN for mutations in the Gigaxonin gene and mutations were found in four families; three families had homozygous mutations, one had two compound heterozygous mutations and one family had no mutation identified. All families had the typical clinical features, kinky hair and nerve biopsy. We report some unusual clinical features associated with GAN and Gigaxonin mutations as well as confirm the heterogeneity in GAN and the identification of two families with manifesting carriers.     

ALS-linked mutant superoxide dismutase 1 (SOD1) alters mitochondrial protein composition and decreases protein import

Mutations in superoxide dismutase 1 (SOD1) cause familial ALS. Mutant SOD1 preferentially associates with the cytoplasmic face of mitochondria from spinal cords of rats and mice expressing SOD1 mutations. Two-dimensional gels and multidimensional liquid chromatography, in combination with tandem mass spectrometry, revealed 33 proteins that were increased and 21 proteins that were decreased in SOD1(G93A) rat spinal cord mitochondria compared with SOD1(WT) spinal cord mitochondria. Analysis of this group of proteins revealed a higher-than-expected proportion involved in complex I and protein import pathways. Direct import assays revealed a 30% decrease in protein import only in spinal cord mitochondria, despite an increase in the mitochondrial import components TOM20, TOM22, and TOM40. Recombinant SOD1(G93A) or SOD1(G85R), but not SOD1(WT) or a Parkinson's disease-causing, misfolded α-synuclein(E46K) mutant, decreased protein import by >50% in nontransgenic mitochondria from spinal cord, but not from liver. Thus, altered mitochondrial protein content accompanied by selective decreases in protein import into spinal cord mitochondria comprises part of the mitochondrial damage arising from mutant SOD1.