Association of vitamin D deficiency and pelvic organ prolapse in postmenopausal women: a cross-sectional study.

BACKGROUND: Vitamin D is vital for skeletal integrity as well as optimal muscle work. High incidence and prevalence of vitamin D deficiency as well as pelvic organ prolapse are found in postmenopausal women, thus raising the question of whether the entities could be related. METHODS: We compared 50 postmenopausal women aged 50 to 75 years with pelvic organ prolapse (POP) with 48 women of same age without POP. The clinical assessment of the disorder was performed using the Pelvic Organ Prolapse Quantification system (POP-Q). An anamnestic questionnaire was filled out by the participants on their anthropometric data, life habits, reproductive history, previous and actual diseases. A blood sample was collected for determination of 25-OH-vitamin D as well as calcium and phosphorus concentrations. RESULTS: The group with POP and the control group were comparable in body mass index, physical activity, life habits and general health, but differed significantly in parity (being higher in POP) and vitamin D blood level concentrations, being lower in POP patients. A significantly higher prevalence of vitamin D deficiency (25-OH-vitamin D < 50 nmol/l) was found in the POP group compared to controls. Taking into account the confounding variables the logistic regression model confirmed the significant role of vitamin D for POP. CONCLUSIONS: Vitamin D deficiency might be an important systemic factor associated to pelvic organ prolapse. The determination of vitamin D levels in postmenopausal women and replenishing its deficiency might also be of importance for the pelvic floor.

Vitamin D and its role in gynecology: emerging importance of checking vitamin D status in certain gynecological entities.

Among non-bone effects of vitamin D, the three main chronological stages in gynecology ‒ menarche, reproductive stage and menopause/postmenopause - are possibly impacted by vitamin D deficiency. A large amount of emerging data show that vitamin D is a confounding factor in these parameters. Gynecology stays at the crossroads with endocrinology and, in the light of the rising knowledge about the involvement of vitamin D in many gynecological disorders, it is worth to investigate the exact role of vitamin D in this area. Especially since vitamin D is easy to substitute in case of deficiency. Authors present some emerging data on the role of vitamin D in gynecology, suggesting when it is necessary to check vitamin D status in order to intervene with vitamin D supplementation and raising gynecologists awareness of the need for further clinical studies.

Newly diagnosed hyperthyroidism in the 25th gestational week of pregnancy presenting with systolic arterial hypertension only.

We present a case of a 30-year-old woman diagnosed with arterial hypertension in the 25th week of pregnancy. Our search for secondary causes of arterial hypertension revealed hyperthyroid Hashimoto's thyroiditis (HT), which was treated with propilthiouracil. Three weeks after delivery, she was normotensive without medication. In the next four months, she developed hypothyroidism and treatment with L-thyroxine was started. In conclusion, in the second half of pregnancy, a hyperthyroid HT can occur - in spite of the well-known amelioration of autoimmune thyroid disorders in that period, and can be the only cause of arterial hypertension.

Glucose transporter-1 (GLUT-1) immunoreactivity in benign, premalignant and malignant lesions of the gallbladder.

GLUT-1 is a transmembrane glucose transport protein that allows the facilitated transport of glucose into cells, normally expressed in tissues which depend mainly on glucose metabolism. Enhanced expression of GLUT-1 can also be found in a large spectrum of carcinomas. This study aimed to investigate GLUT-1 expression in gallbladder tissue: from normal tissue samples, hyperplasias, low-grade and high-grade dysplasias to gallbladder carcinomas. In all, 115 archived samples of gallbladder tissue from 68 patients, presented after cholecystectomy, were immunohistochemically stained for GLUT-1. According to the intensity of GLUT-1 immunoreactivity, samples were divided into negative (stained 0-10% of cells stained), positive with weak to moderate (10-50%) and positive with strong (>50%) GLUT-1 expression. The GLUT-1 immunoreactivity of the samples showed a characteristic increase from premalignant lesions to carcinomas. Normal gallbladder tissue samples did not express GLUT-1 (100%). Weak expression was shown only focally in hyperplasias, but to a greater extent with low-grade dysplasias (20%), high-grade dysplasias (40%) and carcinomas (51.8%). Normal gallbladder tissue is GLUT-1 negative. GLUT-1 expression in carcinoma tissue is significantly higher than in dysplastic lesions. Strong GLUT-1 expression indicates 100% specificity for detecting gallbladder carcinomas. Therefore, GLUT-1 is a candidate as a diagnostic as well as a tissue prognostic marker in gallbladder carcinoma patients.

Cyclooxygenase-2, p53 and glucose transporter-1 as predictors of malignancy in the development of gallbladder carcinomas.

Gallbladder carcinoma is the fifth most common malignancy of the gastrointestinal tract. The absolute characteristics of the disease are the high mortality rate due to the late discovery of a tumor and the low therapeutic possibilities except by surgical intervention. In oncology we can predict the outcome of the disease with a combination of classical standard clinico/pathological parameters (stage of the tumors, differentiation) and the intrinsic genetic and biochemical properties of the tumor. Such intrinzic properties of the tumors that are connected with the outcome of the disease are the denominators (markers). The author searched extensively for the expression and influence of 3 markers included in chronic inflammation and early carcinogenesis, cell cycle regulation and tissue hypoxia: cyclooxygenase-2 (COX-2), p53 gene and glucose transporter-1 protein (GLUT-1). The author discusses their possible role in the development as well as fighting this disease, if specific medications targeting them were available.

Expression of cyclooxygenase-2, glucose transporter-1 and angiogenesis in gallbladder carcinomas and their impact on prognosis.

OBJECTIVE: To investigate the angiogenic and prognostic role of cyclooxygenase-2 (COX-2) in gallbladder carcinomas. We assume COX-2 overexpression, neoangiogenesis and glucose transporter-1 (GLUT-1) to be involved in disease progression. MATERIAL AND METHODS: The carcinoma tissues of 56 patients with gallbladder carcinomas were studied immunohistochemically for the expression of COX-2, GLUT-1 and micro-vessel density. The results were correlated with clinico-pathological features and survival/prognosis. RESULTS: The overexpression of COX-2 in gallbladder carcinomas was significantly associated with increased angiogenesis and GLUT-1 expression. Neither angiogenesis nor the grade of the tumour correlate significantly with poor survival. Age, gender and a strong GLUT-1 expression were significant factors of adverse prognosis. CONCLUSIONS: Next to age and gender of patients, hypoxia of gallbladder tumours is a factor influencing survival. Among hypoxic factors, GLUT-1 expression is an important (significant) denominator of poor prognosis in gallbladder carcinomas, but not COX-2 nor angiogenesis.

Cyclooxygenase-2 expression determines neo-angiogenesis in gallbladder carcinomas.

Neo-angiogenesis may have an important role in the poor prognosis of gallbladder carcinoma. An enhanced expression of COX-2 was found in precancerous lesions and in gallbladder carcinoma, likely to be involved in carcinogenesis as well as in angiogenesis. To study the relationships between the COX-2 expression and degree of vascularization, as well as to evaluate their role in the prognosis of patients with gallbladder carcinoma. 27 cases of gallbladder adenocarcinoma were included, classified grading I-III according the WHO classification. The COX-2 and endothelial antigen CD105 expressions were assessed immunohistochemically. COX-2 expression was evaluated according to the percentage and staining intensity of positive cells into "COX-2 positive" and "COX-2 negative" groups. In order to assess tumor microvessel density (MVD), CD105 positively stained microvessels were counted for each specimen in predominantly vascular areas (hot spots) at 200 x magnification. The MVD ranged from 9 to 46 microvessels/field. 15 tumors belonged to the hypervascular group (MVD > or = 25) and 12 to the hypovascular group. There were 16 (59.2%) COX-2 positive cases. There was difference in the degree of angiogenesis between COX-2 positive vs. COX-2 negative group: 11 (68.8%) out of 16 "COX-2 positive" tumors were hypervascular, in comparison with just 4 (36.4%) of "COX-2 negative" tumors. Our data show that the MVD corresponds to the COX-2 overexpression in gallbladder carcinomas. Augmented tumor neovascularization induced by COX-2 might be responsible for the poor prognosis in gallbladder carcinoma patients.

Expression of cyclooxygenase-2 is associated with p53 accumulation in premalignant and malignant gallbladder lesions.

AIM: To examine the relationship between cyclooxygenase-2 (COX-2) overexpression and p53 accumulation in gallbladder carcinoma and its precursor lesions. METHODS: Sixty-eight gallbladder tissue samples comprising 14 cases of normal gallblader epithelium, 27 cases of dysplasia (11 low-grade dyplasia and 16 high-grade dysplasia) and 27 adenocarcinomas were evaluated by immunohistochemistry for COX-2 expression and p53 accumulation. The relationship among COX-2 expression, p53 accumulation and clinicopathological characteristics was analysed. RESULTS: COX-2 was expressed in 14.3% of normal gallbladder epithelium, 70.3% of dysplastic epite hlium, and 59.2% of adenocarcinomas. When divided into low- and high-grade dysplasia, COX-2 was positive in 5 (45.4%) cases of low-grade and 14 (87.5%) of high-grade dysplasia (P = 0.019). Accumulation of p53 was detected in 5 (31.2%) cases of high-grade dysplasia and in 13 (48.1%) of carcinomas. No p53 accumulation was found in normal epithelium or low-grade dysplasia. COX-2 overexpression was observed in 17 of 18 (94.4%) cases with p53-accumulation in comparison with 20 (40.0%) out of 50 cases without p53 accumulation (P < 0.001). CONCLUSION: The significant differences in COX-2 expression among normal epithelium, low-grade dysplasia and high-grade dysplasia suggest that overexpression of COX-2 enzyme is an early event in gallbladder carcinogenensis. Furthermore, since accumulation of p53 correlates with COX-2 expression, COX-2 overexpression observed in gallbladder high-grade dysplasia and carcinoma might be partly due to the dysfunction of p53.

Histopathologic signs for the inflammatory role of Chlamydia pneumoniae in the high-grade atherosclerotic coronary artery wall.

The aim of the study was to prove the long-lasting and continuously harmful effect of chronic Chlamydia pneumoniae (CPn) infection on vessel walls in patients with diffuse coronary artery disease (CAD). In surgically obtained endarterectomized atherosclerotic plaques grade VI-VIII (Stary classification) from 10 patients with diffuse coronary artery disease and chronic (7) or past (3) CPn infection, signs of inflammatory response of the vessel wall on infectious agents were studied. In all 10 endarterectomized plaque step serial sections, immunologic signs of vessel wall response were present (positive T- and B-lymphocytes, macrophages, and capillarogenesis). In 8 of 10 patients' atherosclerotic plaque, unique features of active vasculitis in the neoarteriolar wall as well as arteriologenesis, were found. Seven of these 8 patients had serologically proven chronic CPn infection, and 1 had past infection. Features of vasculitis as well as arteriologenesis were absent in 2 patients who recovered from CPn infection at the time of surgery. In the endarterectomized segments of 3 randomly chosen patients in this study, the polymerase chain reaction method revealed positive DNA of CPn. Two of these patients had chronic infection, but the third had only a past CPn infection. This study provides evidence that CPn infection has continuous and a long-lasting inflammatory response in the high-grade atherosclerotic coronary artery vessel wall.

Chlamydia pneumoniae infection in Slovenian patients with diffuse coronary artery disease.

Chlamydia pneumoniae (CP) infection might be involved in the pathogenesis of various forms of coronary artery disease (CAD), but there are no data about diffuse CAD with clinical picture of stable angina pectoris. Authors in a prospective study determined serum CP antibody levels (with MIF test) of 71 patients with coronarographically proven diffuse CAD and compared them to the age matched control group of the healthy Slovenian population. After azithromycin treatment in patients with chronic CP infection or reinfection, the CP antibody levels were determined again. A high percentage of chronic infection with CP was demonstrated (83.1%), and almost half (46.5%) of patients with diffuse CAD had reinfection or reactivation of chronic infection. A significantly higher prevalence of chronic CP infection was found in patients with diffuse CAD than in the healthy population (83.1% vs. 15.9%, p< 0.0001). After treatment with azithromycin, IgA seronegativity was achieved in 17.3%, in 23.1% the titer was lowered, however, in 57.7% of patients no change of antibody titers was found. In conclusion, a high prevalence of chronic infection with CP was found in patients with diffuse CAD. With azithromycin therapy, the eradication of chronic infection is difficult to achieve as well as to prove.

Apoptosis and histopathologic changes in diffuse coronary atherosclerosis.

The aims of the study were to investigate the histopathologic characteristics of atherosclerotic lesions and to evaluate the role of apoptosis or programmed cell death in diffuse coronary atherosclerosis. The study included 59 patients who underwent coronary artery bypass grafting coupled with coronary endarterectomy because of diffuse coronary atherosclerosis. Histopathologic analysis of endarterectomy sequesters showed atheroma with confluent extracellular lipid core-type IV lesions in 13 cases (22%); atheroma with lipid core and a cap of fibromuscular layers-type V lesions in 9 cases (15.3%); predominantly calcified fibrous tissue-type VII lesions in 13 cases (22%); and predominantly fibrous tissue-type VIII lesions in 24 cases (40.7%). TUNEL-positive cells were observed in 4 endarterectomy sequesters (6.8%) of subjects with diffuse coronary atherosclerosis. TUNEL-positive cells were demonstrated in the area of mononuclear infiltrates as well as in the vessel wall. The percentage of TUNEL-positive cells in mononuclear infiltrates was 0.5%. Intense mononuclear infiltrates in tunica intima were found in 50% of sequesters, and they consisted of macrophages (40%), T-lymphocytes (17%), and B-lymphocytes (14%). In the area of infiltrates the proportion of MIB-1-positive cells was 2.7%, which was higher than in the intima outside the area of infiltrates (0.5%). In conclusion, apoptosis, which is confined to mononuclear infiltrates, is most likely involved in the development of diffuse coronary atherosclerosis; however, the percentage of apoptotic cells was low (0.5%). A higher proportion of apoptotic cells in the area of infiltrates compared to the rest of the intima was associated with a higher proportion of MIB-1-positive cells. Atherosclerotic lesions in diffuse coronary atherosclerosis were advanced, with a predominance of type VII to VIII lesions.