Neutropenia induced by platelet-activating factor (PAF-acether) released from neutrophils: The inhibitory effect of prostacyclin (PGI2)

Soluble and phagocytic stimuli released PAF-acether from PMN leucocytes, as determined by chromatography and bioassay by platelet aggregation. The same material caused aggregation of human and rabbit PMN leucocytesin vitro which was inhibited by ETYA and PGI₂. PGI₂ also inhibited PAF-acether release by PMN leucocytes and,in vivo, PGI₂ abolished not only PAF-acether-induced, but also immune complex or C5a-induced thrombocytopenia and neutropenia in rabbits. These data suggest that PAF-acether may be involved in activation of both platelets and PMN leucocytesin vivo.     

Lack of association of the common TaqIB polymorphism in the cholesteryl ester transfer protein gene with angiographically assessed coronary atherosclerosis

The anti-atherogenic effect of cholesteryl ester transfer protein (CETP) genetic variants associated with lowered enzyme activity is controversial. Moreover, in a few studies, this effect has been evaluated in the presence of a certain risk factor constellation. We addressed this issue in a case-control study, where 415 subjects with angiographically documented coronary artery disease (CAD +), 397 subjects without CAD (in 215, CAD was excluded by coronarography (CAD-)), and 188 healthy population controls, were screened for the CETP TaqIB polymorphism. The prevalence of the low-activity TaqIB2 allele was 0.396 in CAD+, and 0.428 and 0.416 in CAD- and population controls, respectively (p = 0.40). Its presence was significantly associated with increased high-density lipoprotein cholesterol (HDL-C) in population controls (1.40 +/- 0.40 mmol/l in B1B1, 1.52 +/- 0.39 mmol/l in B1B2 and 1.58 + 0.46 mmol/l in B2B2; p < 0.03 for trend), but not in the other groups. The CETP TaqIB polymorphism accounted for < 1% of the HDL-C variance in the whole cohort (p = 0.048). After adjustment for other risk factors, the CETP TaqIB2 allele was found not to be associated with significant changes in CAD risk independently of an assumed either dominant (odds ratio (OR) 0.97; 95% confidence interval (CI) 0.66-1.44; p = 0.89) or recessive effect (OR 0.68; 95% CI 0.42-1.12; p = 0.13). The CETP TaqIB polymorphism did not show a significant interaction with other risk factors in influencing CAD risk. Our findings do not support the hypothesis that a genetic variant resulting in lowered CETP activity is associated with reduced risk of coronary atherosclerosis.     

Cesarean Delivery and Risk of Excess Weight Among Brazilian Preschool Children

Maternal and Child Health Journal - To study the relationship between cesarean Delivery (CD) and overweight in preschool children, considering the presence of birth aspects and demographic...     

Aggressive Intraosseous Myofibroma of the Maxilla: Report of a Rare Case and Literature Review

Myofibroma (MF) is a benign mesenchymal myofibroblast-derived tumor, which occurs most frequently in children, and rarely affects the maxilla. We reported a case of an aggressive intraosseous lesion found in the maxilla of a 9-year-old female child. Intraorally, the swelling extended from tooth 12 to 16, causing displacement of teeth 13, 14, and 15. Computed tomography revealed a large osteolytic lesion causing thinning and cortical erosion. Microscopically, the lesion showed a proliferation of spindle-shaped cells, with elongated nuclei and eosinophilic cytoplasm, arranged in interlaced fascicles. The immunohistochemical analysis revealed cytoplasmic positivity for α-SMA and HHF-35, and negativity for desmin, laminin, S-100, β-catenin, and CD34. Ki-67 was positive in 8% of tumor cells. The diagnosis was MF. Herein, we describe an additional case of central MF arising in the maxilla, including clinical, imaging, microscopical, and immunohistochemical features, as well as a review of the literature.     

Prognostic value of CD40 in adult soft tissue sarcomas.

PURPOSE: The purpose is to evaluate the expression of CD40, a membrane protein predominantly expressed on B cells, dendritic cells, and macrophages, in a series of adult soft tissue sarcomas and to test its possible prognostic value. EXPERIMENTAL DESIGN: CD40 expression was studied by immunohistochemistry. Correlations with other baseline characteristics of patients and tumors were analyzed with chi(2) test. The prognostic value was studied with univariable and multivariable analysis adjusted by age, sex, tumor size, grade, location, and distant metastases. RESULTS: Eighty-two patients, between January 1994 and May 2001, were analyzed. Membrane or cytoplasmic staining for CD40 protein was absent in 30% of the tumors but present in <10% of cells in 22 (27%), in 10% to 50% in 23 (28%), and in >50% of cells in 12 (15%) tumors. There was no correlation between CD40 expression and age, sex, size, grade, and location of the primary tumor and distant metastases. With 61 patients (74.4%) progressed and 31 (37.8%) dead, CD40 expression was a significant prognostic factor for disease-free and overall survival at univariable and multivariable analysis. Patients with tumors expressing CD40 in >50% of cells had a dramatically unfavorable prognosis with median disease-free and overall survival of 7 and 17 months, respectively, and hazard ratios of relapse and death as compared with patients with CD40-negative tumors of 2.89 (95% confidence interval: 1.26-6.60) and 6.92 (95% confidence interval: 2.18-22.0), respectively. CONCLUSIONS: These data suggest that expression of CD40 protein in >50% of cells might indicate an unfavorable prognosis in adult soft tissue sarcomas.     

DNA methylation in anal intraepithelial lesions and anal squamous cell carcinoma.

PURPOSE: Anal intraepithelial neoplasia is associated with human papillomavirus infection and may progress to invasive squamous cell carcinoma (SCC), which is increasing in immunocompromised patients. We hypothesize that anal intraepithelial neoplasia is associated with abnormal DNA methylation and that detection of these events may be used to improve screening programs. EXPERIMENTAL DESIGN: Seventy-six patients were identified who underwent anal cytology screening and subsequent biopsy at our institution between 1999 and 2004. The specimens from these patients included 184 anal biopsies [normal, n = 57; low-grade squamous intraepithelial lesion (LSIL), n = 74; high-grade squamous intraepithelial lesion (HSIL), n = 41; and invasive SCC, n = 12] and 37 residual liquid-based anal cytology specimens (normal, n = 11; LSIL, n = 12; HSIL, n = 14). The methylation status of the following genes was determined for each biopsy and cytology sample using real-time methylation-specific PCR: HIC1, RASSF1, RARB, CDKN2A, p14, TP73, APC, MLH1, MGMT, DAPK1, and IGSF4. RESULTS: Methylation-specific PCR analysis of biopsy samples revealed that DNA methylation was more common in SCC and HSIL than LSIL and normal mucosa. Specifically, methylation of IGSF4 and DAPK1 was prevalent in SCC (75% and 75% of cases, respectively) and HSIL (59% and 71%, respectively) but was absent in LSIL and normal biopsy samples. Methylation profiles of cytologic samples were similar to those found in the biopsy samples. CONCLUSIONS: Aberrant DNA methylation is a frequent event in anal HSIL and SCC. Methylation of IGSF4 and DAPK1 is specific for HSIL and SCC, and may serve as a useful molecular biomarker.     

BOOST: a phase 3 trial of sorafenib vs. best supportive care in first line treatment of hepatocellular carcinoma in patients with deteriorated liver function

Aim: Only patients with good liver function {[Child-Pugh (CP)] A class} were eligible for trials testing sorafenib as first-line treatment of hepatocellular car...     

Primary cardiac T-cell lymphoma

Primary cardiac lymphoma (PCL), defined as a lymphoma clinically mimicking cardiac disease, with the bulk of the tumor located intrapericardially, is extremely rare in immunocompetent patients. Clinical manifestations vary depending on sites of involvement in the heart and include chest pain, arrhythmias, pericardial effusion, and heart failure. Diagnosis is often difficult and may require invasive procedures; in some cases, diagnosis is not made until autopsy. Histologically, nearly all cases of PCL reported thus far have been of B-cell origin. In this report, we describe a case of PCL of T-cell origin in an adult immunocompetent patient, the second reported in the literature to the best of our knowledge, and provide a brief overview of the features of previously published PCL cases.     

Prognostic Value of p27, p53, and Vascular Endothelial Growth Factor in Dukes A and B Colon Cancer Patients Undergoing Potentially Curative Surgery

PURPOSE Early-stage colon cancer patients (Dukes A or B; pT1–T3 pNO pMO) are excluded from adjuvant chemotherapy following potentially curative surgery because they are expected to have good long-term survival. However, 20 percent to 30 percent of these patients ultimately succumb from recurrent disease. This indicates that the conventional staging procedures may be unable to precisely predict cancer prognosis.METHODS In 65 early-stage colon cancers, we investigated by immunohistochemistry the role of molecular markers such as p27, p53, and vascular endothelial growth factor in identifying high-risk patients who may benefit from adjuvant treatments.RESULTS No clinicopathologic factor, namely Dukes stage, t parameter, number of resected nodes, and vascular or lymphatic invasion, was found be an independent significant predictor of disease-specific and disease-free survival. In contrast, each molecular marker predicted survival and recurrence rates much better than the conventional Dukes staging system. The best combination of variables for prediction of long-term outcome and recurrence rate included p27, p53, and vascular endothelial growth factor. Interestingly, the greater the number of molecular alterations, the lower the five-year estimated survival function. Nearly all cancer-related deaths were observed among patients whose colon cancers expressed all three molecular alterations. Regardless of Dukes stage, the recurrence rate was found to increase with the increase in the number of molecular alterations. Early-stage colon cancers expressing p27 down-regulation and high p53 and vascular endothelial growth factor immunoreactivity showed a 100 percent actuarial four-year recurrence rate.CONCLUSIONS Assessment of molecular alterations may be useful to identify a higher-risk group of early-stage colon cancer patients who may benefit from adjuvant chemotherapy.