Noncarious cervical lesions restored with three different tooth-colored materials: two-year results.

INTRODUCTION: The aim of this two-year prospective clinical study was to evaluate and compare the clinical performance of three different adhesive esthetic materials in noncarious cervical lesions. MATERIAL AND METHODS: A total of 90 restorations (30 per material) were placed in 30 patients who ranged in age between 18 and 50 years and of both genders, by a single operator with no previous preparation. The restoration of noncarious cervical lesions was done with either a microfilled composite (Esthet.X/Dentsply/De Trey, Konstanz, Germany, and Prime&Bond NT/Dentsply/De Trey), a nanohybrid composite (TetricEvoCeram/Vivadent, Schaan, Liechtenstein, and AdheSE/Vivadent), or a compomer (Dyract eXtra/Dentsply/De Trey and Xeno III Dentsply/De Trey). All restorations were evaluated by independent examiners using a modified US Public Health Service criteria at baseline and after 12 and 24 months for six clinical categories. Data were analyzed statistically by Pearson's chi-square or the Fisher's exact test at 5% significance level (p<0.05). RESULTS: Results showed that most of the restorations were clinically satisfactory after 12 and 24 months, with no statistically significant differences among the three groups for all evaluated criteria. CONCLUSION: Treatment of noncarious cervical lesions using composite and compomer materials, combined with the appropriate adhesive systems and properly implemented restorative procedures, gives satisfactory results after a two-year evaluation period.

Donor-derived Coccidioides immitis fungemia in solid organ transplant recipients.

We report disseminated coccidioidomycosis in 3 transplant recipients from a donor in an endemic area found to have unrecognized meningeal coccidioidomycosis. All 3 transplant recipients presented within 3 weeks of receipt of their organ. Only 1 organ recipient survived the acute presentation of coccidioidomycosis. Serologic testing for Coccidioides immitis infection should be considered for organ donors residing in endemic areas.

Novel human malignancy-associated gene (MAG) expressed in various tumors and in some tumor preexisting conditions.

We have identified a novel human malignancy-associated gene (MAG) expressed in various malignant tumors including glioblastomas and hepatocellular carcinomas (HCCs) and in tumor preexisting conditions such as hepatitis C virus- and hepatitis B virus-induced liver cirrhosis. The expression of MAG was characterized using reverse transcription-PCR (RT-PCR), rapid amplification of cDNA ends PCR, RNA dot blotting, RNase protection assay, and Northern blot analysis. Rapid amplification of cDNA ends PCR yielded a 536-bp MAG fragment in HCC, macroregenerative liver nodules with dysplasia, and liver cirrhosis but not in normal liver or placenta. By RT-PCR, MAG expression was not found in 12 different normal tissues but found in 46 of 51 (90%) premalignant and malignant tissues of various sites. Embryonic liver and brain were positive for MAG expression together with tumors from the same organs, but the corresponding normal adult tissues were negative. By RNase protection assay, MAG mRNA was expressed in the HepG2 liver tumor cell line and in an ovarian carcinoma but not in normal liver. The estimated transcript size from Northern blot analysis was 8.8 kb. This novel gene may play a role in the progression of premalignant conditions and in the development of HCC and other cancers.

Multidisciplinary Treatment of Complicated Crown-Root Fractures: A Case Study.

Traumatic dental injuries usually occur among children and adolescents, with maxillary central incisors as the most often affected teeth. Complicated crown-root fractures are particularly challenging for esthetic and functional rehabilitation and often require a multidisciplinary approach. A 21-year-old male patient came to the Dental Clinic due to fractured maxillary incisors caused by trauma during a sporting activity. Clinical examination revealed horizontal fractures of teeth 7, 8, and 9, initiating in the labial cervical third and extending subgingivally on the palate, with exposed pulp tissues. On provisional repositioning and splinting the fragments, root canal treatment was performed. Definitive repositioning was accomplished by raising a full-thickness gingival flap, using fiber-reinforced composite posts, by an endodontist and an oral surgeon. Reattachment was accomplished under surgical conditions to ensure precise positioning of fragments by exposing the palatal aspect of the fracture lines and providing a dry operating field. Definitive composite resin veneers were performed after seven days.

Autophagy inhibits oxidative stress and tumor suppressors to exert its dual effect on hepatocarcinogenesis.

The role of autophagy in carcinogenesis is controversial and apparently complex. By using mice with hepatocyte-specific knockout of Atg5, a gene essential for autophagy, we longitudinally studied the role of autophagy in hepatocarcinogenesis. We found that impairing autophagy in hepatocytes would induce oxidative stress and DNA damage, followed by the initiation of hepatocarcinogenesis, which could be suppressed by the antioxidant N-acetylcysteine. Interestingly, these mice developed only benign tumors with no hepatocellular carcinoma (HCC), even after the treatment with diethylnitrosamine, which induced HCC in wild-type mice. The inability of mice to develop HCC when autophagy was impaired was associated with the induction of multiple tumor suppressors including p53. Further analysis indicated that the induction of p53 was associated with the DNA-damage response. Tumorigenesis studies using an established liver tumor cell line confirmed a positive role of autophagy in tumorigenesis and a negative role of p53 in this process when autophagy was impaired. Our studies thus demonstrate that autophagy is required to maintain healthy mitochondria and to reduce oxidative stress and DNA damage to prevent the initiation of hepatocarcinogenesis. However, once hepatocarcinogenesis has been initiated, its presence is also required to suppress the expression of tumor suppressors to promote the development of HCC.

Expression of HGF, its receptor c-met, c-myc, and albumin in cirrhotic and neoplastic human liver tissue.

Hepatocellular carcinoma (HCC) is a common type of cancer, with approximately 260,000 new cases each year, and liver cirrhosis is generally considered a major predisposing factor for HCC. However, specific changes of gene expression in liver cirrhosis and HCC remain obscure. The expression of genes for hepatocyte growth factor (HGF), its receptor c-met proto-oncogene, c-myc proto-oncogene, and albumin was analyzed. Gene expression was studied by PCR in seven normal human livers, nine cases of hepatitis C cirrhosis, 12 cases of alcoholic cirrhosis, two cases of liver adenoma, and 12 cases of HCC. HGF and c-met protein were revealed by immunofluorescent staining. HGF mRNA was not expressed in normal livers but was detected in adenomas, in 80% of HCC, and in some cirrhoses. Paraffin-embedded and fresh-frozen tissue samples yielded similar results. Immunohistochemical data correlated with PCR results regarding the overexpression of the HGF/c-met system in HCC. Albumin gene expression was decreased in HCC vs normal livers, consistent with altered function of tumor hepatocytes. The elevated expression of the HGF/c-met system in HCC may play a role in tumor development and/or progression. Tissue localization studies of HGF and its receptor c-met protein support the existence of both autocrine and paracrine mechanisms of action of HGF in HCC vs only a paracrine mechanism in normal liver.

Successful treatment of Whipple disease diagnosed 36 years after symptom onset.

Whipple disease is a rare infectious disorder with multiorgan manifestations and a widely varied clinical presentation. Involvement of the small intestine with resultant malabsorption is a classic finding, although extraintestinal manifestations such as fever and arthralgias may precede gastrointestinal symptoms by many years. We describe a 63-year-old man in whom Whipple disease was diagnosed 22 years after his initial presentation (36 years after symptom onset) with lymphadenopathy, when a biopsy yielded nonnecrotizing granulomas. His recent symptoms included persistent fatigue, weight loss, fever, and arthralgias. Endoscopic biopsy specimens from the distal duodenum showed features consistent with Whipple disease, and Tropheryma whippelii DNA was detected in both the small bowel biopsy specimen and the blood specimen by polymerase chain reaction and DNA probe hybridization. His symptoms resolved with long-term co-trimoxazole therapy. We discuss the protean manifestations of Whipple disease, the difficulties in clinical diagnosis, and the recent advances in the molecular diagnosis of this disorder.

Activation of hepatic stellate cells in liver tissue of patients with fulminant liver failure after treatment with bioartificial liver.

We studied the explanted livers from 12 patients with fulminant hepatic failure who were treated with a bioartificial liver and subsequently underwent orthotopic liver transplantation and from 18 patients who underwent orthotopic liver transplantation without previous treatment. Ten normal livers were used as controls. In addition to morphologic evaluation, an immunohistochemical analysis was performed with the monoclonal antibodies for alpha-smooth muscle actin and proliferation marker Ki-67. The expression of these markers was graded semiquantitatively from 0 to 3+ in a blinded fashion. The zonal distribution of activated hepatic stellate cells was also evaluated. In all cases, the hepatic stellate cells were activated and expressed alpha-smooth muscle actin. In all patients with submassive or massive liver cell necrosis, the distribution of activated hepatic stellate cells was predominantly in zone 1 of the acinus (periportal area). In contrast, in cases with early nodular regeneration and no significant fibrosis, the activated hepatic stellate cells were distributed throughout the liver parenchyma, involving zones 2 and 3 of the acinus. Expression of the proliferation marker Ki-67 was graded 3+ in all patients treated with the bioartificial liver who had orthotopic liver transplantation and 2+ in patients who underwent orthotopic liver transplantation only.

Hepatitis C virus is not recoverable from liver tissue in cryptogenic cirrhosis: failure to identify hepatitis C virus-RNA using reverse transcription-mediated polymerase chain reaction.

Polymerase chain reaction (PCR) has been used to study liver biopsy tissue in patients with known or suspected hepatitis C virus (HCV). Recent studies of cryptogenic cirrhosis using PCR have been based on study of sera, and HCV has not been shown. The failure to show HCV in patients so studied has left unanswered the question of whether or not patients with cryptogenic cirrhosis could still harbor the virus in the liver. The authors studied liver tissue, obtained at the time of orthopic liver transplantation from 10 patients clinically diagnosed as having end-stage liver disease without demonstrable origin, so-called cryptogenic cirrhosis, using reverse transcription (RT)-PCR to try to recover HCV-RNA. Formalin-fixed, paraffin-embedded tissue was used. For comparison, the authors also studied similarly obtained samples from 10 patients with typical hepatitis C-associated cirrhosis and 10 patients with end-stage liver disease resulting from autoimmune hepatitis. The authors recovered HCV-RNA from 9 of 10 livers from patients with cirrhosis resulting from HCV, and 3 of 10 livers from patients with autoimmune hepatitis. HCV-RNA was not recovered from any of the livers of the 10 patients designated as having cryptogenic cirrhosis.

Metastatic pancreatic adenocarcinoma to the heart diagnosed antemortem.

Pancreatic tumors frequently metastasize widely, though it is rare to diagnose pancreatic cardiac metastases in the antemortem state. We report an unusual case of metastatic pancreatic adenocarcinoma to the right atrium. Transesophageal echocardiography showed that the tumor was attached to the superior aspect of the right atrium, prolapsing through and obstructing the tricuspid valve in diastole and retracting back into the right atrium during systole. The tumor was excised, and histologic examination confirmed the presence of moderately differentiated adenocarcinoma with a papillary architectural pattern and with desmoplastic stroma, features comparable to the original primary pancreatic neoplasm.

Primary liposarcoma of the liver: a case report and review of literature.

Liposarcoma is a rare mesenchymal malignant tumor, which usually originates in the retroperitoneum and the extremities. Seven cases of primary liposarcoma of the liver have been previously reported. We present the eighth case, which occurred in an adult female patient. Primary liposarcoma of the liver, although extremely rare, must be considered in the differential diagnosis of a hepatic mass that develops in a noncirrhotic liver, especially in patients who are potential candidates for orthotopic liver transplantation. Liposarcoma is an absolute contraindication for liver transplantation.

The role of chemokines as inflammatory mediators in chronic hepatitis C virus infection.

Hepatitis C virus (HCV) is a leading cause of chronic liver disease that can progress to cirrhosis and/or hepatocellular carcinoma. Intrahepatic inflammation and liver cell injury are defining features of chronic HCV infection. Chemokines, chemotactic cytokines that attract leucocytes to inflammatory sites, may be important in the development of intrahepatic inflammation. As T-helper (Th)1 inflammatory cells, characterized by interferon (IFN)-gamma and interleukin (IL)-2 secretion, predominate in the liver during chronic HCV infection, chemokines that attract these cells might be particularly important in disease progression. In this review, we focus on the role of Th1 chemokines, which are all members of the CXC or CC subfamilies. Among the CXC chemokines, the non-ELR group comprised of IFN-gamma-inducible protein 10 (IP-10), monokine induced by IFN-gamma (Mig) and IFN-inducible T-cell-alpha chemoattractant (I-TAC), attract Th1 cells through the interaction with their receptor, CXCR3. Among the CC subfamily, Th1-associated chemokines include regulated upon activation, normal T-cell expressed and secreted (RANTES) and macrophage inflammatory proteins (MIP)1alpha and beta. These chemokines attract cells through an interaction with their receptor, CCR5. While peripheral blood and intrahepatic levels of all of these chemokines are elevated in chronic hepatitis C patients, only select chemokines have been found to be correlated with hepatic inflammation. Among the six chemokines, IP-10 has uniquely been shown to have prognostic utility as a marker of treatment outcome. In the future, chemokines might be used to monitor the natural course and progression of HCV-associated liver disease, to identify patients with a high likelihood of achieving a therapeutic response, and they may even have potential as therapeutic targets.

Benign hepatocellular tumors and tumor-like lesions.

Benign tumors of the liver are uncommon, and their diagnosis has never been easy. This chapter highlights the most useful criteria for the diagnosis of benign tumors and tumor-like lesions and emphasizes histologic and immunohistochemical approaches that are helpful in differentiating these conditions.

Anti-HBs- and anti-HBc-containing plasma cells in livers of patients with chronic type B hepatitis.

Plasma cells are commonly found in liver biopsies in acute and chronic type B hepatitis. Their specificities have not hitherto been examined. In this study, anti-HBs and anti-HBc were looked for in paraffin sections of liver biopsies from 16 patients with chronic type B hepatitis, all seropositive for HBeAg. The technique used was a reversed immunoperoxidase procedure in which purified antigens were applied to sections and detected by means of a further layer of the appropriate monoclonal antibody. Small numbers of plasma cells stained for anti-HBs and anti-HBc in 6 and 4 of 16 biopsies, respectively. Some plasma cells appeared to contain neither antibody. The two antibodies were detected together in only one biopsy. In spite of the small numbers of positive cells as revealed by the technique used, antiviral antibodies produced locally by plasma cells may play a part in the pathogenesis of viral hepatitis.

Overview of hepatitis B and transplantation in the hepatitis B patient.

Hepatitis B is a disease that infects 300,000 people in the United States each year, resulting in 15,000-30,000 cases of chronic hepatitis. Outcomes include death; development of chronic carrier state, chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Hepatitis B surface antigen (HBsAg) carriers, especially those with cirrhosis, are at high risk for development of hepatocellular carcinoma. Histologically, chronic carriers of HBsAg may have a range of degree of tissue changes, ranging from normal, to varying degrees of portal or lobular inflammation, to significant cell injury with widespread necrosis, fibrosis and cirrhosis. Current histological grading systems reflect both graded inflammation and stage of fibrosis.

Hepatic sinusoidal endothelium: Ulex lectin binding.

The sinusoidal endothelial cells of human liver can be identified by light and electron microscopy, but there appear to be no specific immunocytochemical markers of these cells. Among specific markers available for vascular endothelial cells in general, Ulex europaeus I lectin (UEA I) is the most sensitive. In the present study, 37 liver biopsies were examined for UEA I binding and for Factor VIII related antigen (F VIII RAg) to determine if sinusoidal endothelial cells were positive. The material included normal liver, biopsies from patients with cirrhosis and biopsies in a variety of other liver diseases. Three embryonal human livers were also included in the immunocytochemical analysis. Eleven oesophageal rings obtained at mechanical transection for variceal bleeding in cirrhotic patients were used as control tissue. Sinusoidal endothelial cells of normal liver did not stain with UEA I, but six of seven with alcoholic cirrhosis and only one of 25 non-cirrhotic liver specimens (a case of acute hepatitis with bridging necrosis) were positive. In two of the six cirrhoses the sinusoidal endothelial cells were stained for F VIII RAg as well. Embryonal sinusoidal endothelial cells were stained with UEA I but were negative for F VIII RAg. The results of the study confirm that sinusoidal endothelial cells of normal adult human liver are phenotypically different from those lining blood vessels in other sites. In cirrhosis, positive staining may be related to the transformation of hepatic sinusoids into true capillaries and thus be a marker of the severity of physiological disturbance in the liver.

Uterine pleomorphic rhabdomyosarcoma in a patient receiving tamoxifen therapy.

INTRODUCTION: Tamoxifen has been used as adjuvant therapy for the treatment of breast cancer. Its use has been associated with the development of proliferative endometrial lesions such as polyps, hyperplasia, and carcinoma. Mesenchymal tumors including malignant mixed mullerian tumors, endometrial stromal sarcomas, adenosarcomas, and leiomyosarcomas have been more recently described with tamoxifen use. CASE REPORT: This report describes the first case of a pure uterine rhabdomyosarcoma in a patient receiving tamoxifen therapy. DISCUSSION: Although uterine rhabdomyosarcomas are rare tumors and may arise de novo, we discuss the possible role of tamoxifen in the development of these mesenchymal tumors.