Putative roles of hepatitis B x antigen in the pathogenesis of chronic liver disease

Under most circumstances, hepatitis B virus (HBV) is noncytopathic. However, hepatocellular regeneration that accompanies each bout of hepatitis appears to be associated with increased integration of HBV DNA fragments expressing the virus encoded hepatitis B x antigen (HBxAg). Intrahepatic HBxAg staining correlates with the intensity and progression of chronic liver disease (CLD), and additional work has shown that HBxAg blocks immune mediated killing by Fas and by tumor necrosis factor alpha (TNFα). This is not only associated with the blockage of caspase activities by HBxAg, but also by the constitutive stimulation of hepatoprotective pathways, such as nuclear factor kappa B (NF-κB), phosphoinositol 3-kinase (PI3K), and beta-catenin (β-catenin). HBxAg also appears to promote fibrogenesis, by stimulating the production of fibronectin. HBxAg also stimulates the production and activity of transforming growth factor beta1 (TGFβ1) by several mechanisms, thereby promoting the profibrogenic and tumorigenic properties of this important cytokine. In addition, HBxAg appears to remodel the extracellular matrix (ECM) by altering the expression of several matrix metalloproteinases (MMPs), which may promote tumor metastasis. Hence, HBxAg appears to promote chronic infection by preventing immune mediated apoptosis of infected hepatocytes, by promoting the establishment and persistence of fibrosis and cirrhosis preceding the development of HCC, and by promoting the remodeling of EMC during tumor progression.     

No Strong Association Between HER-2/neu Protein Overexpression and Gene Amplification in High-grade Invasive Urothelial Carcinomas

The generation of urothelial carcinoma is caused by the accumulation of various molecular changes, as in most malignancies. There are conflicting data about the status of HER-2/neu oncogene in urothelial carcinomas. The aim of this study was to determine the status of HER-2/neu oncogene in high-grade invasive urothelial carcinoma of urinary bladder both in protein and DNA level. We evaluated HER-2/neu protein overexpression by immunohistochemistry (IHC) and gene amplification by fluorescent in situ hybridization (FISH) and real-time quantitative PCR in paraffin-embedded samples of high-grade invasive urothelial carcinoma obtained from 36 patients. Polysomy 17 was also assessed by FISH. Immunohistochemically, HER-2/neu protein overexpression was observed in 22 (61.1%) tumors (ten tumors with score 3+ and 12 with score 2+). Fourteen of 36 tumors (38.9%) were evaluated as negative (score 0 or 1+). Complete concordance between FISH and the PCR was seen in all of the samples scored as 0 and 1+ by IHC. HER-2/neu gene amplification was observed in three of 27 (11.1%) tumors by FISH (nine samples were non-informative) and in eight of 36 (22.2%) tumors by the PCR. The complete concordance between HER2-2/neu protein overexpression and gene amplification was seen only in three of 27 tumors. Polysomy 17 was seen in nine tumors (33.3%). The results indicated that, in contrast to breast cancer, there was no strong association between HER-2/neu overexpression and gene amplification in invasive urothelial carcinomas, and polysomy 17 was higher in tumors showing HER-2/neu overexpression.     

Kidney loss due to periureteral fibrosis and ureteral obstruction secondary to migration of subureterically injected calcium hydroxylapatite

Vesicoureteral reflux (VUR) is one of the significant urologic diseases of childhood and its endoscopic treatment is a viable option in terms of both simplicity and reduced morbidity. However, despite intensive research, no ideal injection material that yields the best long-term results with the least side effects has been introduced as yet. Synthetic calcium hydroxylapatite is one of the materials that has recently been under trial. Although favorable short-term success rates have been reported with the subureteric injection of calcium hydroxylapatite without any side effects, this case report shows its potential to migrate. To our knowledge, we present the first case where the migration of subureterically injected calcium hydroxylapatite resulted in periureteral fibrosis, ureteric obstruction and subsequent renal loss.     

Caustic gastroesophageal lesions in childhood: an analysis of 473 cases

Ingested corrosive agents produce oropharyngeal and gastroesophageal injuries ranging from minor burns to severe necrosis, depending on the agent amount, concentration, and duration of exposure. The aim of this study was to present our patients with corrosive ingestion retrospectively. Four hundred seventy-three children younger than 16 years of age (mean age, 3.7+/-0.1 years) who were admitted to our hospital for suspected corrosive ingestion between the years 1995 and 2003 were studied. Two hundred eighty-six (60.5%) of 473 patients were males. Household bleaches (36.6%) and oven cleaners (23%) were the most frequently encountered corrosive agents. During endoscopy, lesions in the esophagus were recorded in 379 children. Eighty-one of the cases had gastric lesions. During the follow-up, esophageal stricture, esophageal perforation, and gastric outlet obstruction (GOO) developed in 11 cases, 1 case, and 2 cases, respectively. Caustic ingestion of alkali substances such as oven cleaner seem to cause more severe injuries. Early admission to the hospital with clinical and endoscopic evaluation and early surgery when required may reduce morbidity and mortality.     

Atypical traumatic craniocervical junction focal spinal subdural hematoma

Spinal subdural hematoma (SSDH) is a rare entity and post-traumatic cervical SSDH is very rare. Review of the literature revealed 8 reported cases of traumatic SSDH and only 2 were cervical. The exact mechanism and pathogenesis of SSDHs are unclear. There are still controversies about the source of bleeding and mechanisms of formation of a hematoma. Here we report a case of a unique traumatic craniocervical junction focal subdural hematoma in an 8-year-old boy and discuss the possible mechanisms of SSDHs in trauma cases.     

The comparison of the responsiveness of human isolated internal mammary and gastroepiploic arteries to levcromakalim: an alternative approachto the management of graft spasm

Aims We studied the effectiveness of levcromakalim, a potassium channel opener (KCO), in the prevention and reversal of spasm in arterial grafts used in coronary artery bypass operations, namely, internal mammary artery (IMA) and gastroepiploic artery (GEA).
Methods Spasm was mimicked in vitro in arterial rings from 109 patients by increasing the vascular tension with noradrenaline, the thromboxane analogue U46619, endothelin-1 and K⁺ .
Results GEA displayed considerably higher contractile force to these agents than IMA. Pretreatment with levcromakalim depressed significantly the maximal contractile responses (either absolute or relative) to noradrenaline and U46619 but did not affect those of endothelin-1 and K⁺ in both of the arteries. Sensitivities (to all agents, except to endothelin-1) decreased significantly after levcromakalim. In experiments evaluating the antispasmodic activity of levcromakalim, a higher relaxant capacity was observed in GEA than IMA (for K⁺ contraction; IMA: 31.32±3.83%, n =13 vs GEA: 98.01±0.71%, n =7, P <0.05). This different activity of levcromakalim between two arterial grafts was apparent even when GEA rings were contracted to higher force (g) than that of IMA (for K⁺ contraction; GEA: 72.56±4.96%, n =7). Responses to levcromakalim were similar in IMA and GEA when endothelin-1 was used as the spasmogenic agent (IMA: 80.98±4.85%, n =10 vs GEA: 91.93±3.17%, n =7, P >0.05).
Conclusions Our results provide evidence that levcromakalim may have a therapeutic value in the treatment of spasm of coronary artery bypass grafts, especially GEA.     

Clinical improvement of a patient with severe Wilson's disease after a single session of therapeutic plasma exchange

Here, we report a case of a 17‐year old female with Wilson's disease presenting with progressive Coombs' negative hemolytic anemia and hepatic cirrhosis who was treated with one session of therapeutic plasma exchange (TPE) and clinically improved. In clinical situations where multiple sessions of TPE may not be possible, the use of a single session of TPE in conjunction with conventional therapy may be of benefit in preventing further clinical deterioration. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.     

99Tcm-MIBI scintimammography in the evaluation of breast lesions and axillary involvement: a comparison with mammography and histopathological diagnosis.

The aim of this prospective study was to determine the diagnostic value of prone lateral 99Tcm-MIBI scintimammography in the detection of primary breast cancer and axillary lymph node involvement in patients with breast lesions. We evaluated 83 palpable and 22 non-palpable lesions in 77 consecutive patients with a clinically palpable mass and/or suspicious mammographic finding. Early and late scintimammograms were performed after the intravenous injection of 740 MBq 99Tcm-MIBI. The overall sensitivity of both scintimammography and mammography in the detection of primary breast cancer was 94%. The overall specificity was 84% and 56% for scintimammography and mammography respectively. In the patients with palpable masses, the sensitivity of scintimammography was 97% and the specificity was 84%; in those with non-palpable masses, the sensitivity was 35% and the specificity 100%. For the detection of axillary lymph node involvement, the sensitivity and specificity of scintimammography were 68% and 93% respectively. However, conventional mammography showed 37% sensitivity and 86% specificity. In conclusion, scintimammography is an accurate and clinically valuable tool for evaluating palpable and non-palpable breast abnormalities. In addition to its high sensitivity, it improves the specificity of mammography both in the evaluation of breast masses and in the detection of axillary involvement.     

Seawater and Shellfish (Geukensia demissa) Quality Along the Western Coast of Assateague Island National Seashore, Maryland: An Area Impacted by Feral Horses and Agricultural Runoff

We evaluated the quality of seawater and ribbed mussels (Gukensia demissa) at six sites along the West Coast of Assateague Island National Seashore (ASIS), a barrier island popular with tourists and fishermen. Parameters evaluated were summertime temperature, pH, salinity, dissolved oxygen, total phosphorus, total ammonia nitrogen, and nitrite levels for seawater and total heterotrophic plate counts and total Vibrionaceae levels for the ribbed mussels. Approximately 150 feral horses (Equus caballus) are located on ASIS and, combined with agricultural runoff from animals and croplands, local wildlife, and anthropogenic inputs, contribute to nutrient loads affecting water and shellfish quality. The average monthly dissolved oxygen for June was 2.65 mg L⁻¹, below the minimum acceptable threshold of 3.0 mg L⁻¹. Along Chincoteague Bay, total phosphorus generally exceeded the maximum level of 0.037 mg L⁻¹, as set by the Maryland Coastal Bays Program management objective for seagrasses, with a high of 1.92 mg L⁻¹ in June, some 50-fold higher than the recommended threshold. Total ammonia nitrogen approached levels harmful to fish, with a maximum recorded value of 0.093 mg L⁻¹. Levels of total heterotrophic bacteria spiked to 9.5 × 10⁶ cells g⁻¹ of mussel tissue in August in Sinepuxent Bay, leading to mussels which exceeded acceptable standards for edible bivalves by 19-fold. An average of 76% of the bacterial isolates were in the Vibrionaceae family. Together, these data suggest poor stewardship of our coastal environment and the need for new intervention strategies to reduce chemical and biological contamination of our marine resources. This study was performed in partial fulfillment of the requirements for a Master’s Degree in Natural Resources in the Agriculture and Natural Resources Graduate Program at Delaware State University. The mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture.