Human thrombopoietin levels are high when thrombocytopenia is due to megakaryocyte deficiency and low when due to increased platelet destruction

Thrombopoietin (TPO), the ligand for c-mpl, stimulates proliferation of committed megakaryocytic progenitors and induces maturation of megakaryocytes. To better understand factors regulating TPO levels, we measured blood levels of TPO in patients with impaired platelet production due to aplastic anemia (AA) and with platelet destructive disorders, including idiopathic thrombocytopenic purpura (ITP), posttransfusion purpura (PTP), drug purpura (DP), and X-linked thrombocytopenia (XLTP). The TPO receptor capture enzyme immunoassay (EIA) used had a detection limit of integral of approximately-150 to 200 pg/mL. TPO was undetectable in 88 of 89 normal individuals. Eighteen of 19 patients with AA and a mean platelet count (MPC) of 18,000/microliters (2,000 to 61,000/microliters) had markedly elevated TPO levels (mean, 1,467 pg/mL; range, 597 to 3,834 pg/mL). Eight AA patients who responded to immunosuppressive therapy with their MPC increasing to 140,000/microliters (92,000 to 175,000/microliters) had substantial decreases in TPO (mean, 440 pg/mL; range, 193 to 771 pg/mL). Initial TPO levels did not differ significantly between responders and nonresponders. In contrast, all 21 patients with ITP and an MPC of 16,000/microliters (1,000 to 51,000 /microliters) had undetectable TPO levels, as did 6 patients with acute PTP or DP and 2 patients with XLTP. Megakaryocyte mass, reflected in the rate of platelet production, appears to be the major determinant of TPO levels in thrombocytopenic patients rather than circulating platelet levels per se. Measurement of serum TPO may be useful in differentiating thrombocytopenias due to peripheral destruction from those due to thrombopoietic failure.     

Endovascular management of pseudoaneurysms of the splenic artery: experience with six patients

The purpose of this paper was to describe our experience with the endovascular management of splenic artery pseudoaneurysms (SAPA). Seven patients with documented SAPA on CT and/or angiography were considered for endovascular treatment. The pseudoaneurysms were located in the main splenic artery (n = 4) or its branches (n = 3). In one patient in whom the pseudoaneurysm was located in a hilar branch, selective catheterization of splenic artery failed. Metallic coils (n = 1), gelfoam and hydrogel particles (n = 1), metallic coils and gelfoam (n = 2), metallic coil, gelfoam and acrylic glue (n = 2) were used as embolization material in the remaining six patients. These patients were followed for a mean period of 11.3 months. Transcatheter embolization was successful in five patients with no procedure‐related complications. In one patient, embolization was incomplete and the patient underwent surgery, but died on the 10th postoperative day because of irreversible shock. Another patient, after successful embolization, underwent surgery for management of an associated pseudocyst. Endovascular treatment is a safe and effective method of management of SAPA.     

Primary and adjunctive uses of botulinum toxin type A in the periorbital region

Chemodenervation with botulinum toxin has become an integral part of the facial plastic armamentarium. Although eyebrow and eyelid cosmetic deformities and asymmetries have traditionally been treated by surgical intervention, Botox can now be incorporated effectively into the treatment plan. When the surgeon has a complete understanding of facial anatomy and muscular interactions, Botox can be used as a primary treatment of the periorbital region or as an adjunct to surgical procedures of the periorbital region.     

The Possible Importance of Glutamine Supplementation to Mood and Cognition in Hypoxia from High Altitude

Hypoxia induced by low O₂ pressure is responsible for several physiological and behavioral alterations. Changes in physiological systems are frequent, including inflammation and psychobiological declines such as mood and cognition worsening, resulting in increased reaction time, difficulty solving problems, reduced memory and concentration. The paper discusses the possible relationship between glutamine supplementation and worsening cognition mediated by inflammation induced by high altitude hypoxia. The paper is a narrative literature review conducted to verify the effects of glutamine supplementation on psychobiological aspects. We searched MEDLINE/PubMed and Web of Science databases and gray literature by Google Scholar for English articles. Mechanistic pathways mediated by glutamine suggest potential positive effects of its supplementation on mood and cognition, mainly its potential effect on inflammation. However, clinical studies are scarce, making any conclusions impossible. Although glutamine plays an important role and seems to mitigate inflammation, clinical studies should test this hypothesis, which will contribute to a better mood and cognition state for several people who suffer from problems mediated by hypoxia.     

Rett syndrome from quintuple and triple deletions within the MECP2 deletion hotspot region

Rett syndrome results from mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene, which are nearly always lethal in males and lead to regression and reduced life expectancy in females. Herein we report one propositus with five tandem deletions and a second propositus with three tandem deletions within MECP2 exon 4 that encode truncated protein products resulting in classic Rett syndrome. These deletion breakpoints and single deletions in 3 other patients were all found within a 185-bp region along with 64 of 69 other reported deletion breakpoints in the MECP2 gene. Illegitimate recombination resulting in deletion at a substantial proportion of the shared MECP2 sites is enhanced by repeated guanosine (G) DNA sequences in the antisense direction, consistent with reports at other gene loci that polypurine (multiple guanosine or adenosine (A)) basepairs enhance sequence deletion. Multiple deletions at the same poly G recombination sites confirm the existence of deletion hotspots in this gene region with numerous repeated antisense sites that are enriched 26- to 161-fold. Deletion by illegitimate recombination within a single allele can occur during mitotic or meiotic cell cycles. Although prone to disease-causing deletion, this region is unique in humans and highly conserved among mammals for the last 75 000 000 years to maintain the MECP2 gene's critical function.     

Prevalence and risk indicators of oral mucosal lesions in an urban population from South Brazil

Oral Diseases (2011) 17 , 171–179 Objective: The objective of the study was to assess the prevalence of oral mucosal lesions (OML) and to perform a multivariable risk assessment of demographic, socioeconomic, behavioral, and oral risk indicators for its occurrence in an urban population in South Brazil. Methods: This cross‐sectional study selected 1586 subjects (719M/867F, age: 14–104 years) using a multistage probability sampling strategy (65.1% response rate). Prevalence, odds ratios (OR), and confidence intervals (95% CI) were calculated accounting for the survey design. Results: Leukoplakia and lichen planus were observed in 1.01% and 1.02% of subjects, respectively. In the multivariable analysis, these lesions were significantly associated with moderate/heavy smoking (OR = 9.0, 95% CI = 2.1–39.1) and heavy drinking (OR = 2.0, 95% CI = 1.1–3.7). Candidiasis and proliferative lesions were observed in 14.09% and 3.80% of the subjects, respectively. These lesions were significantly associated with female gender (OR = 2.2, 95% CI = 1.5–3.2 and OR = 1.7, 95% CI = 1.0–2.8), older age (OR = 22, 95% CI = 8.0–60.8 and OR = 8.9, 95% CI = 3.4–23.7), and low socioeconomic status (OR = 1.9, 95% CI = 1.0–3.5 and OR = 3.0, 95% CI = 1.2–7.2). Conclusions: This population is in need of OML prevention and treatment. Future studies should validate the findings that premalignant lesions are causally related to smoking and alcohol consumption, and that other OML are associated with socioeconomic‐demographic disparities in this and similar populations.