A Kindred with a ß-Globin Base Substitution [ß89(F5)Ser→Arg (AGT>AGG); HBB: c.270T>G] Resulting in Hemoglobin Vanderbilt.

High oxygen affinity hemoglobins (Hbs), characterized by a decreased ability to release oxygen to the tissues and a left-shifted oxygen dissociation curve, are a rare cause of secondary erythrocytosis. Here, we report a base substitution in the ß-globin gene at codon 89 (AGT>AGG) in a kindred with familial erythrocytosis resulting in Hb Vanderbilt, a high oxygen affinity variant.

Update on the management of gastrointestinal varices.

Cirrhosis of liver is a major problem in the western world. Portal hypertension is a complication of cirrhosis and can lead to a myriad of pathology of which include the development of porto-systemic collaterals. Gastrointestinal varices are dilated submucosal veins, which often develop at sites near the formation of gastroesophageal collateral circulation. The incidence of varices is on the rise due to alcohol and obesity. The most significant complication of portal hypertension is life-threatening bleeding from gastrointestinal varices, which is associated with substantial morbidity and mortality. In addition, this can cause a significant burden on the health care facility. Gastrointestinal varices can happen in esophagus, stomach or ectopic varices. There has been considerable progress made in the understanding of the natural history, pathophysiology and etiology of portal hypertension. Despite the development of endoscopic and medical treatments, early mortality due to variceal bleeding remains high due to significant illness of the patient. Recurrent variceal bleed is common and in some cases, there is refractory variceal bleed. This article aims to provide a comprehensive review of the management of gastrointestinal varices with an emphasis on endoscopic interventions, strategies to handle refractory variceal bleed and newer endoscopic treatment modalities. Early treatment and improved endoscopic techniques can help in improving morbidity and mortality.

Goblet cell carcinoid of the appendix - diagnostic challenges and treatment updates: a case report and review of the literature.

BACKGROUND: Goblet cell carcinoid is a rare but distinct entity of appendiceal tumors which is a hybrid or mixed tumor consisting of both epithelial (glandular) and neuroendocrine elements containing goblet cells. This entity is important to recognize and appropriately grade as it tends to be more aggressive than typical carcinoid tumors, often presenting with metastatic disease. As a result, the 5-year overall survival is 14-22% in stage III-IV disease. GCC therefore warrants more aggressive surgical and medical (chemotherapy) interventions than typical carcinoid tumors. Through this case report we give a brief update on GCC pathological features, staging, surgical management, and review the literature as a guide to indications for chemotherapy and choice of agents. CASE PRESENTATION: We present the case of a 77-year-old Caucasian man with a history of stage I adenocarcinoma of transverse colon status post transverse colectomy who was incidentally found on surveillance colonoscopy to have an abnormal appendiceal orifice lesion. A biopsy revealed an appendiceal goblet cell carcinoid and he underwent a right hemicolectomy which revealed a pathologic stage III GCC for which he received eight cycles of adjuvant chemotherapy with capecitabine. CONCLUSIONS: It is essential that patients who have tumors > 2 cm, are pT3 or pT4, have higher grade histology with signet ring (Tang grade B or grade C), locally advanced, or with positive surgical margins on appendectomy undergo a right hemicolectomy. Although there is no category 1 evidence, consensus recommendations are that patients with stage II (particularly Tang B and C) and stage III GCC be offered adjuvant chemotherapy with a regimen based on 5-fluorouracil, as these patients are known to have high rates of relapse.

High-grade undifferentiated small round cell sarcoma with t(4;19)(q35;q13.1) CIC-DUX4 fusion: emerging entities of soft tissue tumors with unique histopathologic features--a case report and literature review.

BACKGROUND: A subset of undifferentiated small round cell sarcomas (USRCSs) is currently being recognized as emerging entities with unique gene fusions: CIC-DUX4 (the area of focus in this article), BCOR-CCNB3, or CIC-FOXO4 gene fusions. CIC-DUX4 and CIC-FOXO4 fusions have been reported in soft tissue tumors, while BCOR-CCNB3 fusion with an X chromosomal inversion was described in both bone and soft tissue tumors. CIC-DUX4 fusion can either harbor t(4;19)(q35;q13.1) or t(10;19)(q26.3;q13), while t(4;19)(q35;q13.1) is reported more commonly. CASE REPORT: The aim of this study is to share a new case report of a 36-year-old woman who had a rapidly growing mass in her right upper thigh, which was found to be an undifferentiated small round cell sarcoma with t(4;19)(q35;q13.1) CIC-DUX4 fusion was confirmed by cytogenetic testing. Combined modality treatment with surgery, radiation, and chemotherapy was used and achieved a good response. A review of the literature of the reported cases with CIC-DUX4 fusions including both t(4;19) and t(10;19) translocations revealed a total of 44 cases reported. Out of these 44 cases, 33 showed t(4;19)(q35;q13.1) translocation compared to 11 cases with t(10;19)(q26.3;q13). CONCLUSIONS: Undifferentiated small round cell sarcomas are aggressive tumors. Their treatment includes surgery, chemotherapy, and radiation. Resistance to chemotherapy is common. Lung and brain are common sites of metastasis, with associated poor prognosis. Generally, median survival is less than 2 years. Newer techniques have been developed recently which helped identify a subset of previously unclassifiable sarcomas, with promising prognostic value.

The miR-124-prolyl hydroxylase P4HA1-MMP1 axis plays a critical role in prostate cancer progression.

Collagen prolyl hydroxylases (C-P4HAs) are a family of enzymes involved in collagen biogenesis. One of the isoforms of P4HA, Prolyl 4-hydroxylase, alpha polypeptide I (P4HA1), catalyzes the formation of 4-hydroxyproline that is essential for the proper three-dimensional folding of newly synthesized procollagen chains. Here, we show the overexpression of P4HA1 in aggressive prostate cancer. Immunohistochemical analysis using tissue microarray demonstrated that P4HA1 expression was correlated with prostate cancer progression. Using in vitro studies, we showed that P4HA1 plays a critical role in prostate cancer cell growth and tumor progression. Expression profiling studies using P4HA1 modulated prostate cells suggested regulation of Matrix metalloproteases 1. The invasive properties of P4HA1 overexpressing cells were reversed by blocking MMP1. Our studies indicate P4HA1 copy number gain in a subset of metastatic prostate tumors and its expression is also regulated by microRNA-124. MiR-124 in turn is negatively regulated by transcriptional repressors EZH2 and CtBP1, both of which are overexpressed in aggressive prostate cancer. Chick chorioallantoic membrane (CAM) assay and mice xenograft investigations show that P4HA1 is required for tumor growth and metastasis in vivo. Our observations suggest that P4HA1 plays a critical role in prostate cancer progression and could serve as a viable therapeutic target.

Case Report: Magnetic resonance imaging in rabies encephalitis.

Rabies encephalitis is an invariably fatal disease characterized by typical clinical symptoms. Although the diagnosis of this condition can be made on the basis of the patient's history and the classical clinical presentation, neuroimaging may still play a role, especially for establishing an early diagnosis in cases with atypical presentations or when the history of animal bite is not forthcoming. We report the MRI findings in a case of furious rabies encephalitis and describe the utility of diffusion imaging in its diagnosis.

Antibacterial properties of an iron-based hemostatic agent in vitro and in a rat wound model.

OBJECTIVES: Topical hemostatic agents are currently employed on the battlefield for control of major hemorrhage and have potential for use in civilian settings. Some of these compounds may also be antibacterial. Given the behavior of these compounds, the purpose of this study was to assess the potential antibacterial properties of an iron oxyacid-based topical hemostatic agent against three problematic species of wound-contaminating microorganisms: Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and methicillin-resistant Staphylococcus epidermidis. METHODS: Bacteria were treated in vitro with the test powder for 30 minutes and then assessed for viability. Long-term (8-hour) inhibition of bacterial growth was also examined. In vivo, a rat full-thickness 1-cm(2) skin wound was studied. Wounds were contaminated, treated, and then quantitatively cultured 24 hours later. RESULTS: The lethal dose for 99% of the organisms (LD(99)) for the compound against each organism ranged from 0.89 (+/-0.28) to 4.77 (+/-0.66) mg/mL (p < 0.05). The compound produced sustained inhibition over 8 hours at both 1 and 5 mg/mL (p < 0.05 for each), for P. aeruginosa, S. epidermidis, and S. aureus. In vivo, activity was noted against only P. aeruginosa, with the largest magnitude reduction being on the order of 3-log colony-forming units (CFU; p < 0.01). CONCLUSIONS: The iron-based agent studied possesses significant in vitro and lesser in vivo antibacterial effects. Further optimization of the delivery, dosing, and evaluation of this agent in a larger animal model with more humanlike skin structures may reveal important wound effects beyond control of bleeding.

MRI interpretation proficiency of musculoskeletal fellows in training.

RATIONALE AND OBJECTIVES: The aim of this study was to evaluate the magnetic resonance imaging (MRI) interpretation proficiency of musculoskeletal fellows in training. MATERIALS AND METHODS: Between July 2003 and June 2007, 14 musculoskeletal fellows were independently tested with 20 MRI studies of the knee and shoulder at four separate time points during their fellowship years. Trends in true-positive and false-positive interpretation results were evaluated. Fellows who completed their residencies at the fellowship institution (internal fellows) were compared with those from other residencies (external fellows). RESULTS: There was a significant improvement in proficiency between the initial and final (9-month) evaluations (P < .0001). At the initial evaluation, there was a mean of 52.8% (41.7 of 79) true-positive results (range, 32-51); at 9 months, there was a mean of 71.0% (56.1 of 79; range, 40-72). The number of false-positive results also declined during this time period from a mean of 8.1 (range, 2-13) at initial evaluation to 4.7 (range, 2-8) at 9 months (P < .001). External fellows had more incorrect diagnoses initially but showed greater improvement than internal fellows at 9 months. CONCLUSION: Fellows continued to improve their MRI interpretation skills throughout the first 9 months of their fellowships. External fellows were slightly less proficient at the start of their fellowships but slightly more proficient at 9 months compared to internal fellows.