Adrenaline attenuates the acute lung injury after intratracheal lipopolysaccharide instillation: an experimental study.

Endotoxin is a major cause of endotoxinemia, sepsis, and pneumonia due to gram-negative bacteria. Experimental endotoxin administration via the tracheal route has been extensively used to study the biological and pathophysiologic pathways of inflammation. In particular, experimental endotoxin instillation in the respiratory tree has allowed an extended research with regard to the local response of the lungs to the pathogenic stimulus. This study aims (a) to define early events in the inflammatory cascade and (b) to evaluate the efficacy of adrenaline to ameliorate the acute pulmonary inflammation in vivo after administration of intratracheal lipopolysaccharide (LPS) in an in vivo animal model. Two groups of animals were used for that purpose, a control group (single LPS administration) and a study group (subcutaneous adrenaline infusion following LPS administration). We found that mononuclear recruitment, along with an increased population of CD4+ T lymphocytes, is an early event during the course of LPS-challenged inflammation. In the study group, we determined that adrenaline mediated the lung inflammation in a statistically significant degree. By the use of immunohistochemistry, we identified (1) an increased population of CD4+ T lymphocytes in the inflammatory infiltrate, further endorsing the hypothesis that T-helper lymphocytes, along with macrophages, secrete cytokines which amplify the inflammatory response, and (2) an upregulation of ICAM-1 expression, suggesting an important role in the early pathogenesis of LPS-induced acute lung injury. Our study establishes that systemic adrenaline administration after LPS instillation may ameliorate the inflammatory lung response in vivo.

Population-based study of human papillomavirus infection and cervical neoplasia in Athens, Greece.

The aim of our study is to describe the prevalence of the different HPV types in women with pre-neoplastic lesions of the cervix in Greece. Cervical scrapes from 841 women were obtained for both cytological evaluation and analysis for the presence of HPV DNA. PCR was performed on specimens from these 841 women. The Pap test results were normal or showed benign cellular changes in 45.8% of the women, atypical squamous cells of undetermined significance (ASCUS) in 23.2%, low-grade squamous intra-epithelial lesion (LSIL) in 27.9% and high-grade squamous intra-epithelial lesion (HSIL) in 3.1%. HPV DNA was demonstrated in 23.6% of cytologically normal women. We detected HPV in 60% of the total samples. Of these, HPV-16 was the most common HPV DNA detected. Interestingly, HPV-58 was inversely correlated with positive cytological findings. A clear pattern of decreasing prevalence of HPV with age was also observed. Our results indicate that HPV infections, especially those with HPV-16, represent a significant public health concern in Greece.

Tissue evaluation of immune markers in endometrial and cervical carcinomas.

Major histocompatibility complex (HLA system) class II molecules including HLA-DR antigens, associate with peptides, which are derived from antigens, for presentation to T4 lymphocytes. Functional and adhesion assays have shown that CD4 molecule interacts with HLA class II molecules, leading to enhanced responses of T4 cells. In the present study, we examined the tissue expression of HLA-DR antigens and the quantitative variance of T4 lymphocytes in a series of 50 "endometrioid" adenocarcinomas of the endometrium and 35 cervical squamous-cell carcinomas. A three-step avidin-biotin immunoperoxidase staining method was applied. As primary antibodies, we used the TAL.1BS monoclonal antihuman HLA-DR alpha (alpha) chain antibody and the OPD4 mouse antihuman antibody; the latter mainly identifies benign T4 lymphocytes. Twenty-four percent (24%) of women with endometrial cancer were high immune responders, while the relative percentage in women with cervical cancer was 40%; the respective tumours were of early clinical and surgical stages. HLA-DR determinants were predominantly expressed in membranes of stromal cells, mainly histiocytes, usually around HLA-DR+ lymphoid cells, as well as on endothelial cells. Greater numbers of OPD4+ aggregated lymphocytes were observed when the tumour stroma was rich in HLA-DR+ cells. Epithelial elements, either cancerous or benign, were seldom HLA-DR+. In those samples, positive immunolabelling was often confined in the intercellular space and did not seem to activate an effective host immune response against neoplastic cells. High expression of HLA-DR molecules in professional antigen presenting stromal cells may be used as a lymphocyte activation marker in endometrial and cervical carcinomas. This activation appears to be an early event in the evolution of invasive endometrial and cervical carcinomas.

Immunohistochemical detection of cell cycle regulators, Fhit protein and apoptotic cells in parathyroid lesions.

OBJECTIVE: The pathological distinction between parathyroid neoplasms and hyperplasias remains difficult. Changes in cell cycle control may lead to clonal proliferation and precede tumorigenesis. The parathyroid adenoma 1 oncogene, subsequently identified as the gene encoding cyclin D1, has been shown to be important to parathyroid tumour development. In addition to cell proliferation, the mechanisms of parathyroid cell turnover include apoptosis. The tumour-suppressor activity of the fragile histidine triad gene (FHIT) is linked to its proapoptotic function and cell cycle control. We attempted to evaluate the cellular proliferative kinetics and apoptotic function of the parathyroid glands in patients with non-familial hyperparathyroidism (HPT). DESIGN: TIssue specimens were taken from 40 patients with primary HPT (17 adenomas, two carcinomas and 21 primary hyperplasias) and from 30 patients with secondary HPT. Normal glands served as controls. METHODS: In a standard immunohistochemical procedure, monoclonal antibodies to Ki-67 antigen and single-stranded DNA were applied to detect cycling and apoptotic cells respectively; polyclonal antibodies to cyclin D1 and Fhit protein were used. Immunostaining was estimated by image analysis and statistical analysis was subsequently performed. RESULTS: Significantly higher proliferative and apoptotic indexes were detected in the diseased glands in comparison with normal controls. In neoplastic and secondarily hyperplastic glands, apoptotic indexes were higher than in primarily hyperplastic glands; the difference between neoplastic and primarily hyperplastic glands was statistically significant (P=0.034). Cyclin D1 was overexpressed in a considerable proportion of tumours (68.4%). A reduction of Fhit protein immunoreactivity was selectively noticed in carcinomas. CONCLUSIONS: In primary hyperplasia, the remarkable proliferation of parathyroid glands may be due to the reduction of the apoptotic process. FHIT gene abnormalities are worthy of investigation in parathyroid carcinogenesis.

Immunohistochemical assessment of basement membrane components in colorectal cancer: prognostic implications.

Loss of basement membrane integrity during neoplastic invasion may have some direct prognostic significance, which is worth investigating. We studied 151 cases of colorectal adenocarcinomas retrospectively. The aim of the study was to investigate the immunohistochemical expression as well as the distribution of laminin and collagen IV within the basement membranes of cancer cell formations. The results were related to histological grade of malignancy (I, II or III) and Dukes' staging of all tumours as well as to 3-year survival status in 52 patients. Using the immunostaining method of strept ABComplex/HRP and appropriate monoclonal or polyclonal antibodies, we assessed the continuity, the discontinuity of the distribution or the total loss of structural basement membrane components alongside the infiltrating borders of each tumour. The results were evaluated statistically. Either a considerable degree of discontinuity or a total loss of basement membrane components was more common in moderately and poorly differentiated adenocarcinomas (p = 0.002 and p = 0.005 for collagen IV and laminin, respectively) and they seemed to be adversely associated with survival status (p = 0.066 and p = 0.014 for collagen IV and laminin, respectively). Interestingly, no association with the stage of disease was noticed. The results of this study reinforce the value of laminin and collagen IV as possible prognostic factors independently to tumour stage. The total loss or considerable discontinuity of the basement membranes of cancerous cells can be considered as indicators of tumour aggressiveness.

Papillary serous carcinoma of peritoneum: case study and review of the literature on the differential diagnosis of malignant peritoneal tumors.

The distinction between malignant mesothelioma and other malignant neoplasms diffusely involving the peritoneum is important for proper patient treatment. The extra-ovarian peritoneal serous papillary carcinoma is a rare, primary, multicentric peritoneal tumor that is morphologically identical to ovarian serous carcinoma of equivalent grade, but can spare or minimally involve the ovaries. We report such a tumor in a 65-year-old female who had abdominal swelling, ascites with positive cytology and a high grade of nuclear atypia in malignant cells as well as elevated serum CA125. Exploratory laparotomy findings of intrabdominal carcinomatosis were not accompanied by any evident primary site; so the diagnosis of a primary papillary serous neoplasia of the peritoneum was strongly considered. Since the amount of residual disease may be an important prognostic determining factor in primary papillary serous carcinoma of the peritoneum, the patient was debulked to no macroscopic disease and was then given platin-based chemotherapy. The tumor's differential diagnosis from malignant mesothelioma was based, apart from morphologic criteria, on the tumor's immunoreactivity to MOC-31, Ber-EP4 and TAG-72, as well as on the lack of immunostaining for keratin 5/6 and calretinin. Differential diagnosis from ovarian cancer was possible only after the pathological examination of the surgically resected ovaries; the tumor showed minimal superficial invasion of the ovarian cortex.

Home blood pressure normalcy: the Didima study.

To evaluate reference values of home blood pressure (HBP) a cross-sectional community study was conducted on 694 adult subjects (aged > or = 18 years) of the village Didima in southern Greece (participation rate 76.4%). Clinic blood pressure (CBP) was measured on two visits (triplicate measurements, mercury sphygmomanometer) and HBP on 3 workdays (duplicate morning and evening measurements, oscillometric devices; Omron HEM 705CP). After exclusion of 132 subjects (103 treated hypertensives and 29 with incomplete data), 562 subjects were analyzed (mean +/- SD aged 51.2 +/- 17.2 years, 42.7% men). Average HBP (120.0 +/- 17.8/72.6 +/- 8.8 mm Hg, systolic/diastolic) was strongly correlated (P < .0001) with CBP (118.7 +/- 17.7/73.8 +/- 10.5 mm Hg). Systolic CBP was 1.3 mm Hg lower than HBP (P < .01, 95% confidence interval 0.4, 2.2), whereas diastolic CBP was 1.2 mm Hg higher than HBP (P < .0001, 95% confidence interval 0.6, 1.7). The threshold of HBP normality determined using three different approaches was 1) 139.7/83.0 mm Hg (systolic/diastolic) using the distribution criterion (95th percentile of the HBP distribution among 476 normotensive subjects); 2) 139.7/85.8 mm Hg using the correspondence criterion (the percentiles of the CBP distribution that correspond to CBP > or = 140/90 mm Hg were estimated, and the levels of BP that correspond to these same percentiles on the HBP distribution were calculated); and 3) 137.4/82.7 mm Hg using the regression criterion (calculation of the levels of HBP that correspond to CBP of 140/90 mm Hg using the regression equation between HBP and CBP). Overall, the findings of the three criteria suggest that average HBP < 137/82 mm Hg might be considered as probably normal, > 140/86 mm Hg as probably abnormal, and within these limits as borderline. Until mortality-based prospective data are available, this approach might be useful in the interpretation of HBP in clinical practice.

Prevalence, awareness, treatment, and control of hypertension in Greece: the Didima study.

To assess the prevalence and the levels of awareness, treatment, and control of hypertension in the rural population of Greece, a cross-sectional survey of the total population age > or =18 years of the village Didima was conducted. The survey included an interview and blood pressure (BP) measurement on two clinic visits. Hypertension was defined as systolic BP > or = 140 mm Hg and or diastolic BP > or = 90 mm Hg or current treatment with antihypertensive drugs. The same BP threshold was used for the assessment of hypertension control. A total of 694 inhabitants participated (response rate 76.4%), and 665 were analyzed. The prevalence of hypertension was 28.4% (men 30.2%, women 27.1%). Of the subjects age > or =65 years, 50% had hypertension. Although 73% of participants were measuring their BP at least once a year, overall, 39.2% of hypertensives were unaware of the diagnosis (men 50%, women 30.5%), 6.3% were aware but not treated (men 4.8%, women 7.6%), 27.5% were treated but not controlled (men 22.6%, women 31.4%), and 27% were treated and controlled (men 22.6%, women 30.5%). These results suggest that, in the rural population of Greece, hypertension is a common risk factor with considerable potential for improvement in levels of control.