Beneficial effect of combined spironolactone and quinapril treatment on thrombosis and hemostasis in 2K1C hypertensive rats.

A strong correlation between raised aldosterone levels and increased risk of thrombotic disorders has been provided. Clinical studies have demonstrated the benefits of the addition of the aldosterone receptor antagonist to the standard therapy with angiotensin-converting enzyme inhibitor in the reduction of cardiovascular events in patients. We suggest that the benefits of this dual renin-angiotensin-aldosterone system (RAAS) blockade may be related to the drug's effects on the hemostatic and oxidative balance. Thus, we investigated the effect of combined spironolactone (SPIRO) and quinapril (QUIN) administration on thrombosis, hemostasis and oxidative stress in hypertensive rats. A two-kidney, one-clip model of renovascular hypertension in Wistar rats was used. QUIN, SPIRO, or QUIN + SPIRO were administered for 10 days. Venous thrombosis was induced by vena cava ligation. Thrombus weight and incidences of thrombosis were assessed. Bleeding time, platelet adhesion, tissue factor (TF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), thrombin activatable fibrynolysis inhibitor (TAFI), malonyl dialdehyde, and hydrogen peroxide plasma levels were assayed. Aortic expression of NADPH oxidase and superoxidase dismutase were measured. We observed significant RAAS activation associated with hypercoagulability and oxidative stress augmentation in renovascular hypertensive rats. Thrombosis was reduced only in rats treated with QUIN + SPIRO. In all groups, decreases in TF, PAI-1, and TAFI levels were observed, however in the QUIN + SPIRO group those changes were more pronounced. The inhibition of platelet adhesion was also stronger in rats treated with QUIN + SPIRO. The oxidative stress parameters were markedly reduced in rats treated with QUIN or SPIRO, although the most evident changes were observed in the QUIN + SPIRO group. Dual RAAS blockade with aldosterone receptor antagonist and angiotensin-converting enzyme inhibitor provides additional benefits for experimental thrombosis associated with the antiplatelet, anticoagulative, profibrinolytic, and antioxidative effects in renovascular hypertensive rats.

Prevalence of self-reported hysterectomy among Canadian women, 2000/2001-2008.

BACKGROUND: Hysterectomy is one of the most frequently performed surgical procedures among Canadian women. The consequence is a population that no longer requires cervical cancer screening. The objective of our analysis was to provide more accurate estimates of eligible participation in cervical screening by estimating the age-specific prevalence of hysterectomy among Canadian women aged 20 to 69 by province and territory between 2000/2001 and 2008. METHODS: Self-reported hysterectomy prevalence was obtained from the 2000/2001, 2003 and 2008 Canadian Community Health Survey. Age-specific prevalence and 95% confidence intervals (CIs) were estimated for Canada and provinces and territories for the three time periods. RESULTS: Interprovincial variations in hysterectomy prevalence were observed among women in each age group and time period. Among women aged 50 to 59, prevalence was as high as 35.1% (95% CI: 25.8-44.3) (p<.01) in 2008 and appeared to decrease in all provinces from 2000/2001 to 2008. CONCLUSION: Interprovincial and time period variation suggest that using hysterectomy prevalence to adjust the population eligible for cervical cancer screening may be helpful to inform more comparable screening participation rates. In addition, both cervical cancer incidence and mortality rates can be adjusted by hysterectomy to ensure estimates across time and provinces and territories are also comparable.

TITRE: Prévalence de l'hystérectomie autodéclarée chez les Canadiennes, 2000-2001 à 2008. INTRODUCTION: L'hystérectomie est l'une des interventions chirurgicales les plus souvent pratiquées chez les Canadiennes. Le dépistage du cancer du col de l'utérus n'est donc plus nécessaire dans cette population. Notre analyse visait à obtenir des estimations plus exactes de la participation au dépistage du cancer du col utérin dans la population admissible en déterminant la prévalence de l'hystérectomie selon l'âge chez les Canadiennes de 20 à 69 ans, par province ou territoire, entre 2000-2001 et 2008. MÉTHODOLOGIE: Les données relatives à la prévalence de l'hystérectomie autodéclarée ont été tirées de l'Enquête sur la santé dans les collectivités canadiennes de 2000-2001, de 2003 et de 2008. Nous avons estimé la prévalence selon l'âge et les intervalles de confiance (IC) à 95 % pour le Canada et les provinces et territoires pour les trois périodes. RÉSULTATS: Des variations interprovinciales de la prévalence de l'hystérectomie ont été observées chez les femmes dans chaque groupe d'âge et au cours de chaque période. Chez les femmes de 50 à 59 ans, la prévalence a semblé diminuer dans toutes les provinces entre 2000-2001 et 2008, le plus haut taux provincial atteint en 2008 étant 35,1% (IC à 95%: 25,8 à 44,3; p < 0,01). CONCLUSION: Les variations selon les provinces et au cours du temps laissent penser qu'il pourrait être bon d'utiliser la prévalence de l'hystérectomie pour ajuster la population admissible au dépistage du cancer du col de l'utérus, de manière à obtenir des taux plus comparables de participation. Il est en outre possible d'ajuster à la fois les taux d'incidence du cancer du col utérin et de mortalité par cancer du col utérin de façon à ce que les estimations dans le temps et pour l'ensemble des provinces et territoires soient comparables.

Accuracy of assessing Pelvic Organ Prolapse Quantification points using dynamic 2D transperineal ultrasound in women with pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: We determined the relationship between clinical assessment of female pelvic organ prolapse (POP) using the validated Pelvic Organ Prolapse Quantification (POP-Q) and dynamic 2D transperineal ultrasound (TPUS). METHODS: Women attending the urogynecology clinics between July and October 2009 were recruited. Prolapse was assessed using the POP-Q. Points Ba, Bp and C (anterior, posterior and middle compartments, respectively) were measured. TPUS was performed at maximum Valsalva by another clinician. As the TPUS probe compresses the prolapse that extends beyond the hymen, these women were excluded. A reference line was drawn parallel to the inferoposterior margin of the pubic symphysis, perpendicular to which the leading edge of descent was measured. The offset measured from the curved array of the probe to the reference line was added to the prolapse quantification on ultrasound (US) scan to make it objectively comparable with the POP-Q reference of the hymen. Points Ba, Bp and C on POP-Q were then compared with points of maximum descent achieved on TPUS. RESULTS: One hundred and fifty-eight women had a POP-Q and TPUS; 20 scans (12.6 %) were not analysable, and 41 women had prolapse beyond the hymen. Ninety-seven women were thus analysed. The correlation between 2D TPUS (with/without the addition of the offset) and POP-Q was statistically significant (p value <0.0001) for all three compartments. The proportion of correct predictions was 59.6 %, 61.5 % and 32.6 % for bladder, bowel and middle-compartment prolapse, respectively. CONCLUSION: These findings suggest that the accuracy of pelvic floor US staging is limited and that clinical assessment remains the gold standard.

A review of screening mammography participation and utilization in Canada.

INTRODUCTION: Participation rate is an important indicator for a screening program's effectiveness; however, the current approach to measuring participation rate in Canada is not comparable with other countries. The objective of this study is to review the measurement of screening mammography participation in Canada, make international comparisons, and propose alternative methods. METHODS: Canadian breast cancer screening program data for women aged 50 to 69 years screened between 2004 and 2006 were extracted from the Canadian Breast Cancer Screening Database (CBCSD). The fee-for-services (FSS) mammography data (opportunistic screening mammography) were obtained from the provincial ministries of health. Both screening mammography program participation and utilization were examined over 24 and 30 months. RESULTS: Canada's screening participation rate increases from 39.4% for a 24-month cut-off to 43.6% for a 30-month cut-off. The 24-month mammography utilization rate is 63.1% in Canada, and the 30-month utilization rate is 70.4%. CONCLUSION: Due to the differences in health service delivery among Canadian provinces, both programmatic participation and overall utilization of mammography at 24 months and 30 months should be monitored.

Pelvic floor disorders: role of new ultrasonographic techniques.

The paper presents the role of various ultrasound modalities in the diagnostics of female pelvic floor disorders (PFD). It describes the use of two/three/four-dimensional transperineal ultrasound and endocavitary transducers, which, up to now, have been used for proctological examinations and prostate cancer brachytherapy. Ultrasonography is the most widely available imaging modality. As a result of technical progress, novel transducers and more sophisticated software have recently been introduced to the market providing more information about the anatomy of pelvic organs. Some features of these transducers, such as higher frequency and multiplanar imaging, enable better visualisation of pelvic floor organs. In-depth knowledge of the technical and physical properties of modern ultrasonography, as well as its advantages and limitations, could provide an integrated approach to imaging of PFD. Technical modalities, the wide availability of ultrasonographic techniques, and an understanding of the imaging possible with modern ultrasonography could improve our understanding of PFD and allow better assessment in pre- and post-surgical management.

Regulation of heat-induced apoptosis by Mcl-1 degradation and its inhibition by Hsp70.

Cellular stress eliminates irreversibly damaged cells by initiating the intrinsic death pathway. Cell stress is sensed by pro- and antiapoptotic members of the Bcl-2 protein family, which regulate the release of apoptogenic factors, such as cytochrome c, from mitochondria. Exposure of cells to hyperthermia results in the activation of the proapoptotic Bcl-2 family protein Bax, which plays an essential role in cytochrome c release. Heat directly affects Bax activity in vitro; however, antiapoptotic Bcl-2 family proteins, such as Bcl-xL, can suppress this activation, suggesting that a second heat-sensitive step must be breached before apoptosis ensues in cells exposed to hyperthermia. Here we show that heat shock causes the loss of Mcl-1 protein. Depletion of Noxa by short hairpin RNA protected cells from hyperthermia by preventing Mcl-1 degradation. Heat shock caused the dissociation of Noxa from Mcl-1, which allowed binding of the BH3-containing ubiquitin ligase Mule followed by Mcl-1 ubiquitination and degradation. Overexpression of Hsp70, which prevents heat-induced Bax activation, stabilized Mcl-1 protein levels in heat-shocked cells. This resulted from reduced Mule binding and ubiquitination as well as enhanced Mcl-1 expression compared with cells without Hsp70. Our results demonstrate that loss of Mcl-1 is a critical heat-sensitive step leading to Bax activation that is controlled by Hsp70.

Antioxidant status and lipid peroxidation in colorectal cancer.

Colon carcinogenesis is a multistep process where oxygen radicals were found to enhance carcinogenesis at all stages: initiation, promotion, and progression. Since insufficient capacity of protective antioxidant system can result in cancer, the aim of this study was to examine the activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and the levels of reduced glutathione, vitamin C, and vitamin E. The lipid peroxidation products were also determined by measuring malondialdehyde and 4-hydroxynonenal levels in colorectal cancer tissue collected from 55 patients. In these cases the activity of superoxide dismutase, glutathione peroxidase, and glutathione reductase was significantly increased while the activity of catalase was significantly decreased in cancer tissue. However, the level of nonenzymatic antioxidant parameters (glutathione, vitamin C, and vitamin E) was significantly decreased in cancer tissue. Further lipid peroxidation was enhanced during cancer development, manifested by a significant increase in malondialdehyde and 4-hydroxynonenal levels. The obtained results indicate significant changes in antioxidant capacity of colorectal cancer tissues, which lead to enhanced action of oxygen radicals, resulting in lipid peroxidation.

[Thyroid cancer morbidity in the Olsztyn region in 1993-1999]. / Zapadalnosc na raka tarczycy w województwie olsztynskim w latach 1993-1999.

Olsztyn region (in the north of Poland) was classified as an iodine deficiency area with moderate endemic goiter prevalence. Following Chernobyl accident, the population had one of the highest radiation doses affecting thyroid. Aims of the study were to estimate the incidence of thyroid cancer and to determine its histopathological type. The register was carried out in Olsztyn region population including each newly diagnosed case of thyroid cancer in the calendar year. The personal data of patients were collected and processed on in computer. The incidence rate was calculated as the number of newly diagnosed cases in the calendar year per 100,000 inhabitants dependent on sex and age. The results were statistically evaluated. 242 newly diagnosed cases of thyroid cancer were registered including 8 young patients (up to 18 years of age) and 234 adults. The increase in the number of cancer cases was observed year by year. The predominant type of thyroid cancer was papillary carcinoma--66.8%. Follicular carcinoma constituted 17% of cases. A statistically significant increase of incidence rate was observed in women--from 2.8/100,000 to 11.1/100,000.

Antioxidant status and proteolytic-antiproteolytic balance in colorectal cancer.

Free radicals participate in the development of cancer. When the antioxidant defence system is not longer capable to destroy free radicals they may cause lipid and protein oxidation. Lipid peroxidation products also modify proteins. In such a situation the proteolytic-antiproteolytic balance existing in the blood may be changed. Therefore the aim of this study was to examine the correlation between antioxidant status and activity of proteolytic enzymes and their inhibitors in cases of colorectal cancer. This study included 55 patients with colorectal cancer. The blood was taken before surgery and plasma was collected. Total antioxidant status, the levels of lipid peroxidation products (malondialdehyde and 4-hydroxynonenal) and activity of cathepsin G, elastase and their inhibitors (alpha-1-antitrypsin and alpha-2-macroglobulin) were determined in plasma. It was shown that during the development of cancer total antioxidant status was signficantly decreased while lipid peroxidation products were increased. Activity of alpha-2-macroglobulin was decreased and activity of determined enzymes was not significantly changed. The observed changes indicate a shift in proteolytic-antiproteolytic balance which may enhance carcinogenesis.

[Cathepsin A activity in the aqueous humor in patients with cataract, absolute glaucoma and intraocular tumors]. / Aktywnosc katepsyny A w cieczy wodnistej u chorych z zacma, jaskra dokonana i guzami wewnatrzgalkowymi.

PURPOSE: To evaluate cathepsin A activity in the aqueous humor of patients with cataract, absolute glaucoma and intraocular tumors. MATERIAL AND METHODS: The studies were performed on human aqueous humor taken from anterior chamber of eye balls of patients operated because of cataract, absolute glaucoma and intraocular tumors. Cathepsin A activity was determined by the ninhydrin method with synthetic substrate (N-Cbz-Phe-Ala) at its optimum pH 5.0. RESULTS: In the human aqueous humor of the eye with cataract cathepsin A activity was more than three times higher than in the eye with choroid tumors and absolute glaucoma. No differences of enzyme activity in aqueous humor between patients with glaucoma and intraocular tumors were found. CONCLUSION: The increasing proteolytic activity of cathepsin A in aqueous humor of patients with cataract suggests its importance in cataract pathogenesis. This implies that cathepsin A is involved in development of lens opacity and is found in the aqueous humor due to diffusion from cataractous lens in which the proteolytic process prevails.

[Cathepsin A activity in the vitreous body of patients with absolute glaucoma and intraocular tumors]. / Aktywnosc katepsyny A w ciele szklistym u chorych z jaskra dokonana i guzami wewnatrzgalkowymi.

PURPOSE: To evaluate cathepsin A activity in the vitreous body of patients with absolute glaucoma and intraocular tumors. MATERIAL AND METHODS: The studies were performed on human vitreous body taken from eye balls which were enucleated because of absolute glaucoma (18 eyes) and intraocular tumors (14 eyes). Cathepsin A activity was determined by the ninhydrin method with synthetic substrate (N-Cbz-Phe-Ala) at its optimum pH 5.0. RESULTS: Cathepsin A activity in the human vitreous body in absolute glaucoma was twice as high as in intraocular tumors. CONCLUSION: Our results suggest that cathepsin A may participate in the pathogenesis of absolute glaucoma and that proteolysis may play a significant role in local destruction of the retina and the optic nerve.

[The role of apoptosis in physiology and pathology of the retina]. / Znaczenie apoptozy w fizjologii i patologii siatkówki.

Apoptosis is a genetically regulated form of cell death. Specific morphological and biochemical changes characterize apoptosis, including nuclear chromatin condensation, cytoplasmatic condensation, membrane blebbing and, on the molecular level, internucleosomal fragmentation of nuclear DNA. Cell death by apoptosis is essential for normal development and tissue homeostasis, and it is involved also in a variety of pathologic processes. Apoptosis is the final common pathway of photoreceptor cell death in retinal dystrophies and degeneration, retinal detachment, vitreoretinal proliferation, retinoblastoma and retinal injury. The authors present a brief literature review concerning studies on the role of apoptosis in pathogenesis on retinal diseases.

[The results of surgery on squint with pathological muscle attachment]. / Wyniki operacji zeza z patologicznymi przyczepami miesni.

UNLABELLED: The aim of our study was to evaluate the results of the operation on squint with pathological attachment of lateral rectus revealed during surgery. MATERIAL AND METHODS: The study involved 22 children (12 girls and 10 boys) out of 320 children operated on for squint in the years 1993-1996, who had pathological attachment of lateral rectus. Alternating convergent squint was found in 12 children, unilateral in 10. Muscle exposure showed dislocation of lateral rectus attachment--upwards by c. 1.5 mm in 11 children, downwards and obliquely by c. 2 mm in 10 children, in 1 child the upper part of the attachment was shifted forward by 1 mm. During the surgery, in addition to the reduction of squint angle, physiological attachment of the rectus was reconstructed. RESULTS: The operation restored parallel position of the eyes in 22 children, very good vision was obtained in 12 (54%) with alternating convergent squint, significant improvement in 5 (22%) with unilateral convergent squint, and only slight improvement in the remaining 5 (22.7%) with high initial amblyopia and squint angle from +15 degrees to +30 degrees.

[Scanning electron microscopy (SEM) of subretinal fluid in idiopathic retinal detachment]. / Obraz ultrastrukturalny skaningowy (SEM) plynu podsiatkówkowego w samoistnym odwarstwieniu siatkówki.

PURPOSE: To evaluate the cells of subretinal fluid (SRF) by the use of the scanning electron microscope and to determine relationships between morphologic features of SRF and duration of retinal detachment. MATERIALS AND METHODS: Subretinal fluid was taken from 7 patients with retinal detachment. The cytologic preparations were analyzed in electron scanning microscope (IEOL). RESULTS: The highest count of cells (predominantly macrophages and lymphocytes) were seen in SRF obtained in the third week after retinal detachment. Retinal detachment, which lasted more than 3 weeks, caused lower SRF cells count and changes in cells composition. After 6 months normal cells were not present in SRF.

[Orbit pathology and Graves' ophthalmopathy]. / Orbitopatia i oftalmopatia Gravesa.

The contemporary literature has widely described the role of thyroid diseases in incidence and development of Graves' ophthalmopathy. The paper presents the epidemiologic characteristics and clinical course diagnostic criteria and the role of orbital radiotherapy, steroids and immunosuppressive drugs in the treatment of Graves' ophthalmopathy. Indications, methods, results and complications of surgical orbital decompression are widely described.

[Concentration of selected cytokines in subretinal fluid in patients with retinal detachment (IL-8, TNF-alpha, IFN-gamma)]. / Stezenie wybranych cytokin w plynie podsiatkówkowym u chorych z odwarstwieniem siatkówki (IL-8, TNF-alpha, IFN-gamma).

PURPOSE: The aim of this study was to evaluate the presence of IL-8, TNF-alpha, IFN-gamma in subretinal fluid of patients with rhegmatogenous retinal detachment. MATERIAL AND METHODS: We studied 15 patients operated on retinal detachment. The presence of cytokines was evaluated using immunoenzymatic assay. RESULTS: IL-8, TNF-alpha and IFN-gamma were found in all subretinal fluid samples. The concentration of cytokines in patients with retinal detachment lasting to 2 months was higher than in cases of retinal detachment over 2 months.

Cathepsin A activity of normal bovine ocular tissues and pathological human intraocular fluids.

Cathepsin A activity assayed with N-Cbz-Phe-Ala, N-Cbz-Glu-Tyr and N-Cbz-Glu-Phe as substrates, was measured in fresh corneas, lenses, aqueous humor, vitreous humor and choroid plus retinal pigment epithelium taken from normal bovine eye balls and in human intraocular fluids from the eye balls in various ocular diseases (cataract, glaucoma, diabetes, intraocular tumors). Cathepsin A exhibited a pH optimum at 5.0 and showed the highest specificity towards N-Cbz-Phe-Ala as a substrate. In bovine ocular tissues high cathepsin A activity was found in the choroid plus retinal pigment epithelium and in cornea. The lens and the vitreous humor showed low enzyme activity and the aqueous humor none at all. In the human aqueous humor of the eye with cataract cathepsin A activity was more than three times higher then in the eye with choroid tumor. In human vitreous humor in absolute glaucoma the activity was twice as high as in melanoma and almost three times higher than in the case of lung metastatic tumor. Diabetes in glaucoma increased seven fold cathepsin A activity in the vitreous humor.

[Tissue plasminogen activator and plasminogen activator inhibitor in aqueous humor]. / Stezenia tkankowego aktywatora plazminogenu i dzialanie inhibitora tkankowego aktywatora plazminogenu w plynie komorowym galki ocznej.

BACKGROUND: In the anterior segment of the eye, fibrin clots must be rapidly resorbed to prevent fibrosis. Tissue-type plasminogen activator (t-PA), a serine protease that catalyzes the conversion from plasminogen to plasmin, plays an important role in the fibrinolytic system and has therefore in recent years attracted attention in the field of ophthalmology. MATERIAL AND METHODS: The aqueous humor of patients undergoing cataract surgery was analyzed for the presence of components of the fibrinolytic cascade. The quantities of t-PA and plasminogen-activator inhibitor (PAI) were determined using enzyme-linked immunosorbent assays. We determined t-PA and PAI in the aqueous humor of 64 patients between 59 and 82 years of age. RESULTS: The t-PA levels ranged from 0.65 to 1.75 ng/ml and PAI activity from 3.24 to 5.1 AU/ml. Association between t-PA levels and PAI activity and accompanying diseases or metabolic disorders was noted. The highest concentration of t-PA and the lowest activity of PAI has been observed in aqueous humor of patients with senile cataract. The knowledge about the presence of t-PA in aqueous humor is significant for the recognition of pathological events following intraocular fibrin formation and may be an important basis for therapeutic use of t-PA.

[Cataract surgery results with intraocular lens implantation in children and youth in the years 1990-1995 (personal material)]. / Wyniki operacji zacmy z wszczepieniem sztucznej soczewki u dzieci i mlodziezy w latach 1990-1995 (material wlasny).

PURPOSE: Analysis of cataract surgery with intraocular lens implantation in children and youth performed between 1990 and 1995 in Bialystok University Eye Clinic. MATERIALS AND METHODS: Twenty patients between 5 and 19 years of age were operated. The subjects comprised 15 cases of traumatic and 5 of congenital cataract. Intraocular lens implantation was performed as a primary procedure in 18 patients and as a secondary procedure in 2 cases. RESULTS: Visual acuity of 5/50 to 5/12 was achieved in 14 patients and 5/10 to 5/5 in 6 patients. Posterior capsule opacification requiring YAG-laser capsulotomy was found in 12 patients (60%). CONCLUSIONS: Intraocular lens implantation may be a safe and effective technique for optical correction in children with traumatic and congenital cataracts.