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1.
Identifying women at risk of venous thrombosis (VT) under combined oral contraceptives (COC) is a major public health issue. The aim of this study was to investigate in COC users the impact on disease of genetic polymorphisms recently identified to associate with VT risk in the general population. Nine polymorphisms located on KNG1, F11, F5, F2, PROCR, FGG, TSPAN and SLC44A2 genes were genotyped in a sample of 766 patients and 464 controls as part of the PILGRIM (PILl Genetic Risk Monitoring) study. Cases were women who experienced an episode of documented VT during COC use, while controls were women with no history of VT using COC at the time of inclusion. Among the studied polymorphisms, only F11 rs2289252 was significantly associated with VT. The F11 rs2289252‐A allele was associated with a 1.6‐fold increased risk of VT (p < 0.0001). Besides, the combination of the rs2289252‐A allele with non‐O blood group, present in 52% of the cohort, was associated with an odds ratio of 4.00 (2.49–6.47; p < 10?4). The consideration of this genetic risk factor could help to better assess the risk of VT in COC users.  相似文献   

2.
The results of three independent studies of venous thromboembolic disease (VTE) and oral contraceptives are reviewed together with two further cohort/case-control studies which we conducted using the MediPlus and General Practice Research Database (GPRD) databases. These latter studies jointly involved 395 cases and uniquely examined the association between VTE and individual combined oral contraceptive (COC) formulations. The two studies yielded very similar results. Crude incidence rates for idiopathic VTE of 4.6 and 3.8 were found per 10,000 exposed woman-years (EWY), in the MediPlus and GPRD studies respectively. Incidence rates increased markedly with age, and in both databases the rates amongst users of levonorgestrel products were lower than those amongst users of desogestrel and gestodene products. A case fatality rate of 3% and a mortality rate of 10 per million EWY were estimated. Odds ratios (OR) were calculated for confounding variables and different COC formulations. Both database studies indicated an excess of current smokers and women with high body mass indices amongst cases. There were significantly more cases with asthma in the GPRD study and cases who had been using their COC for less than a year. No statistically significant differences between COC formulations were found in the analyses where controls were matched to cases by practice and year of birth in both the MediPlus and GPRD studies. In the GPRD study we also ran a study where controls were matched by practice and within 5 year age bands. In this study the OR were consistently higher for the newer or 'third generation' products than when controls were matched by year of birth. However only the acne formulation/OC containing cyproterone acetate and 35 microg ethinyloestradiol yielded a significant OR of 2.3. It may be concluded that improvements in prescribing are paramount as the results strongly indicate that overweight women and those who smoke are at a greater risk of VTE. Further study is required to elucidate the possibility that asthma or its treatment may predispose to VTE, alone or in combination with other risk factors. However, neither the MediPlus nor GPRD studies indicate that any one COC formulation poses a greater risk of VTE than another.  相似文献   

3.
Whether arterial conduits are superior to venous grafts in coronary artery bypassing has been debated. The aim of this study was to investigate clinical outcomes after total arterial revascularization versus conventional coronary bypassing using both arterial and venous conduits in isolated three-vessel coronary disease. Between 2003 and 2005, 503 patients who underwent isolated coronary artery bypass grafting for three-vessel coronary disease were enrolled. A total of 117 patients underwent total arterial revascularization (Artery group) whereas 386 patients were treated with arterial and venous conduits (Vein group). Major adverse outcomes (death, myocardial infarction, stroke and repeat revascularization) were compared. Clinical follow-up was complete in all patients with a mean duration of 6.1 ± 0.9 yr. After adjustment for differences in baseline risk factors, risks of death (hazard ratio [HR] 0.96; 95% confidence interval [CI] 0.51-1.82, P = 0.90), myocardial infarction (HR 0.20, 95% CI 0.02-2.63, P = 0.22), stroke (HR 1.29, 95% CI 0.35-4.72, P = 0.70), repeat revascularization (HR 0.64, 95% CI 0.26-1.55, P = 0.32) and the composite outcomes (HR 0.83, 95% CI 0.50-1.36, P = 0.45) were similar between two groups. Since the use of veins does not increase the risks of adverse outcomes compared with total arterial revascularization, a selection of the conduit should be more liberal.  相似文献   

4.
In this article we present management of water resources in Croatia as a model of integral approach in public health interventions. The links between provision of clean water, sanitation and good health are so strong that today management and water protection are deeply integrated in primary health care. This article is a follow up on topics presented on 2nd Croatian congress on preventive medicine and health promotion which gave us "state of art" in Croatian public health. We strongly believe that every system has its own advantages and downsides, and only by knowing the system well and continuous improvement we can protect ourselves in time of health, social or economic crisis. The model of water protection showed that to prevent and overcome the variety of water-related health risks, implementation of various activities that include general environmental protection, development of water management system, permanent water quality monitoring and control, and improvement of standards and legislative is needed. On the other hand if there is no holistic approach, to the public health problems, all the efforts in just one field will not result in health indicators improvement. Constant monitoring and uniform analysis of data could help to identify possible risks of adverse effects of various environmental factors and possible burden of disease as a consequence. That information could be a point of arguing with local governments and communities for public health interventions. It is important that epidemiological and environmental data do not remain in the domain of academic discussion or statistics, and never reach primary health care which could use them in direct health care providing. Information exchange in real time is important for the real time public health intervention. Primary health care is the front line in communication with patients and diagnostics of disease as well as prevention, and they need to have access to all relevant data.  相似文献   

5.
The term aneurysm is used to indicate a permanent and irreversible localized vascular dilatation that involves all three layers of the blood vessel wall. It may develop in any part of the circulatory system, including veins, and its history, presentation, and management differ depending on the location. A venous aneurysm is defined as a solitary area of fusiform or saccular dilatation occurring in the course of a major vein or connected by a single channel to a major venous structure. The lower extremities are the most frequently affected, with the popliteal vein being the most common site. Although different theories have been advanced, the etiology of the disease remains uncertain. Mechanical stress and/or degenerative changes within the vein wall are believed to represent the most likely causes of venous aneurysm. To date, there are only a few publications dealing with the histological appearance of popliteal vein aneurysm, and no studies that specifically describe its ultrastructural details have been published to our knowledge. In an attempt to fill this gap and to provide better insights into the pathophysiological mechanisms possibly involved in aneurysmal venous disease, we describe the fine structure of popliteal vein wall and valve in health and disease using both scanning and transmission electron microscopy.  相似文献   

6.
The effect of progestin-only therapy on the haemostatic system has mainly been studied in premenopausal women. Although these studies are difficult to compare, most authors agree that there is no consistent pattern of effects on haemostasis. Oestrogen-progestin combinations have been extensively studied in pre- (combined oral contraceptives) and postmenopausal women (sequential and continuous combined hormone replacement therapy), but mostly with emphasis on the effects of oestrogens. Comparative studies into the differential effects of progestins in combined preparations are scarce. Based on these studies, there is evidence for modifying effects of progestins on oestrogen-induced changes, particularly on fibrinogen, factor VII and the fibrinolytic system. The modifying effects appear to vary among certain progestins, the variation being most likely due to differential effects on lipid metabolism. The clinical interpretation of steroid-induced effects on the haemostatic system is difficult. Retrospective analyses linking certain patterns of haemostatic regulation to the risk of venous or arterial vascular diseases are subject to bias, and no interventional studies are yet available. In the absence of such prospective studies and well-designed comparative studies, the available data do not support the notion of a superiority of certain progestins with regard to cardiovascular risks of combined preparations.  相似文献   

7.
BACKGROUND: The effects of contraception on subsequent fecundity are yet to be substantiated. METHODS: A total of 2841 consecutive pregnant women in Hull and Sheffield completed questionnaires inquiring about time to pregnancy (TTP), contraceptive use, pregnancy planning, previous pregnancies, age and lifestyle characteristics of each partner. Outcome measures were mean TTP, conception probability and odds of subfecundity after discontinuing each contraceptive method. RESULTS: TTP following long-term combined oral contraceptive (COC), short-term intrauterine device (IUD) or any duration of injectable use were 2.0-, 1.6-, 3.0-fold longer than TTP after condom use, respectively. Within 6 months of discontinuing COC or injectable use, conception probabilities were 0.86 and 0.34, respectively, whereas those relevant to other methods were not significantly different. All levonorgestrel intrauterine system (IUS) users conceived within 1 month. Relative to condoms, odds of subfecundity after COC, injectable and short-term IUD use were 1.9, 5.5, 2.9, respectively. The effect of COC and injectables was stronger with long-term use, in older, obese or oligomenorrhoeic women. Similar results were obtained after adjustment for potential confounders. CONCLUSIONS: A significant reduction in fecundity occurs after COC, IUD or injectables, which is dependent on the duration of use. The effect of COC and injectables is evident in women with a potentially compromised ovarian function. Use of progesterone-only pills or IUS is not associated with a significant effect.  相似文献   

8.
Health effects of air pollution   总被引:7,自引:0,他引:7  
The general public, especially patients with upper or lower respiratory symptoms, is aware from media reports that adverse respiratory effects can occur from air pollution. It is important for the allergist to have a current knowledge of the potential health effects of air pollution and how they might affect their patients to advise them accordingly. Specifically, the allergist-clinical immunologist should be keenly aware that both gaseous and particulate outdoor pollutants might aggravate or enhance the underlying pathophysiology of both the upper and lower airways. Epidemiologic and laboratory exposure research studies investigating the health effects of outdoor air pollution each have advantages and disadvantages. Epidemiologic studies can show statistical associations between levels of individual or combined air pollutants and outcomes, such as rates of asthma, emergency visits for asthma, or hospital admissions, but cannot prove a causative role. Human exposure studies, animal models, and tissue or cellular studies provide further information on mechanisms of response but also have inherent limitations. The aim of this rostrum is to review the relevant publications that provide the appropriate context for assessing the risks of air pollution relative to other more modifiable environmental factors in patients with allergic airways disease.  相似文献   

9.
BACKGROUND: In vitro maturation (IVM) of mammalian oocytes has potential health benefits for patients undergoing assisted reproduction as an alternative to gonadotrophin treatment. This procedure is also useful for studying the process of oocyte and early embryo development. However, oocytes undergoing IVM have much lower competence than in vivo matured oocytes. Efforts to optimize IVM success have focused on replicating in vivo timing, hormonal milieu and cumulus cell responses associated with maturing oocytes. We have previously identified two extracellular matrix proteins, the protease Adamts1 and hyaluronan-binding proteoglycan Versican, produced by mural granulosa cells that selectively incorporate into the periovulatory cumulus-oocyte complex (COC). METHODS: Murine COC were cultured in the presence of epidermal growth factor and/or FSH. mRNA and protein were measured by real time PCR and Western blot and compared to in vivo derived COC. RESULTS: COCs from mice that underwent IVM for 6 or 20 h in the presence of epidermal growth factor, FSH or in combination had a > 10-fold reduction in mRNA (P < 0.05) for Adamts1 and Vcan when compared with in vivo matured COCs. Hyaluronan synthase 2 expression was up-regulated up to 8-fold (P < 0.05) over the unstimulated control, demonstrating successful induction of cumulus gene expression by the IVM conditions. While in vivo matured COCs showed abundant levels of these proteins, COCs that underwent IVM had neither detectable Adamts1, nor intact or Adamts1-cleaved Vcan. Human cumulus and granulosa cells matured in vivo contained abundant mRNA for Adamts1 and Vcan, demonstrating the potential relevance to human IVM. CONCLUSION: These results indicate that extensively altered COC matrix composition is present during IVM and may contribute to the observed poorer competence of the derived oocytes.  相似文献   

10.
Inspection of the age-incidence curve of ischaemic heart disease in both sexes shows an increase in slope for women around the menopause, approaching that of men at older ages. Although the increase is likely to be related to the menopause, epidemiological evidence is not defined. Likewise, there is some suggestion that reproductive factors may be related to the subsequent risk of cardiovascular diseases, since a few studies found an elevated risk in women with an earlier first birth. In terms of prevention and public health considerations, treatments via exogenous hormones are, however, much more important. A systematic overview of the available epidemiological evidence indicates that oestrogen replacement treatment is protective against ischaemic heart disease. The overall relative risks based on 18 studies and greater than 3300 cases was 0.81, with a narrow 95% confidence interval (0.76-0.85), thus suggesting a protective effect of 15-25%. This protection has a plausible biological interpretation in terms of increased high density lipoprotein (HDL) levels. The serum lipoprotein pattern can be unfavourably influenced by progestin supplementation. With reference to oral contraceptives, the relative risk for cardiovascular mortality was increased about twofold in current users. There appears now to be convincing evidence that the elevated risk is restricted to current users.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

11.
The relatively short history of hormonal contraception has been marked by a series of 'pill scares', all of which--after creating panic among users--were proven to be unfounded in terms of public health impact. The latest pill scare, provoked by regulatory action in the United Kingdom and the Federal Republic of Germany in response to the publication of a series of articles indicating a doubling of risk of deep venous thrombosis in users of oral contraceptives containing third-generation progestins, seems finally settled: both the British and the German Drug Regulatory Authorities have now reverted their verdict. The damage unfortunately stays: hundreds of thousands of women have been compelled to abandon the pill of their choice, often deciding to drop contraception altogether, thereby exposing themselves to unwanted pregnancy and--in a number of cases--to pregnancy termination. This latest episode should be turned into something positive: we need to learn that, in the case of drugs in widespread use, before restrictive action is taken--and except for very rare and specific instances--the scientific community must carry out an exhaustive debate on the reality and importance of the observed effects. Although the public should, in each instance, be properly informed, it is only after this process has been completed that restrictive action should be taken. It is hoped that, after this last episode, all concerned have learned this simple principle and will accept being guided by it from now on.  相似文献   

12.
BACKGROUND: This trial was conducted to compare cycle control with vaginal ring a combined contraceptive vaginal ring, and a combined oral contraceptive (COC) delivering 30 mug ethinylestradiol (EE) and 150 mug levonorgestrel. METHODS: This open-label, randomized, multi-centre, Phase III study involved adult women from 11 countries. Subjects were treated with either vaginal ring or a COC for 13 cycles (12 months). RESULTS: A total of 1030 subjects (vaginal ring, n=512; COC, n=518) comprised the intention-to-treat (ITT) population. The percentage of women in the ITT population who completed the trial was 70.9% for vaginal ring and 71.2% for the COC group. The incidence of breakthrough bleeding and spotting over cycles 2-13, the primary efficacy parameter, was lower with vaginal ring (range 2.0-6.4%) than the COC (range 3.5-12.6%), and for cycles 2 and 9 the lower incidence with vaginal ring was confirmed as statistically significant (P=0.003 and P=0.002 respectively). The incidence of intended bleeding was significantly higher over all cycles with vaginal ring (58.8-72.8%) than with the COC (43.4-57.9%). CONCLUSIONS: Cycle control with vaginal ring was excellent and superior to that of a COC containing 30 mug EE.  相似文献   

13.
Combined oral contraceptives in the treatment of polycystic ovary syndrome   总被引:6,自引:0,他引:6  
Combined oral contraceptives (COC) are the most often used treatment modality for polycystic ovary syndrome (PCOS). Undisputedly, COC suppress androgen production, thus ameliorating skin androgenic symptoms and improving menstrual dysfunction. On the other hand, there are still many unresolved issues concerning their metabolic effects. COC could decrease insulin sensitivity and deteriorate glucose tolerance, although the negative influence on insulin sensitivity is dependent on other factors (especially obesity) and this need not be expressed in non-obese patients. It is probable that the impairment of glucose tolerance is reversible, as the incidence of diabetes is not increased in past COC users. The effects of COC on the lipid spectrum are dependent on the type of gestagen, but lipid levels usually remain within the reference limits. Combination therapy of COC with weight reduction or insulin sensitizers could further suppress androgen levels and improve metabolic parameters. The establishment of COC after laparoscopic ovarian drilling may further decrease androgen levels. The combination of COC and GnRH analogues is not superior to COC therapy alone. Prospective data about the influence of COC on the risk of diabetes mellitus, coronary artery disease and endometrial cancer in PCOS women are lacking.  相似文献   

14.
BACKGROUND: Neither oral contraceptives (COC) nor metformin are an optimal modality for the long-term treatment of polycystic ovary syndrome (PCOS). The aim of this study was to evaluate whether a combination of both is beneficial over COC monotherapy. METHODS: Altogether, 30 women were included in the study and 28 finished the protocol. The patients were randomly assigned to two groups treated with either COC (COC group) or COC and metformin (1500 mg/day) (METOC group) for 6 months. Anthropometric parameters, androgens, lipids, fasting insulin, glucose and sex hormone binding globulin (SHBG) concentrations were measured before and at the end of the sixth cycle of treatment. The insulin sensitivity index was evaluated using the euglycaemic clamp. RESULTS: There were no significant changes in anthropometric parameters, fasting glucose or insulin sensitivity in either group. Total testosterone, free androgen index, androstenedione and dehydroepiandrosterone decreased and SHBG increased significantly in both groups. When comparing the effect of both treatments, only a more pronounced decrease in free androgen index was found in the METOC group. CONCLUSIONS: Adding metformin slightly modified the treatment effect of COC, causing a more significant decrease in the free androgen index but having no additional positive impact on lipids, insulin sensitivity, SHBG or testosterone. The available data do not offer enough evidence to advocate the standard use of combined treatment in PCOS. Whether the combination might be beneficial for specific subgroups of patients is of further interest.  相似文献   

15.
Eighteen patients with severe chronic obstructive lung disease (arterial PCO2 greater than 45 mmHg arterial PCO2 less than 55 mmHg) were studied during a stable period of their disease. Samples of arterial blood and blood from the main pulmonary artery, internal jugular vein, hepatic vein, renal vein and femoral vein were taken by manipulating a Cournand catheter to each of these sites in rapid succession. An estimate of the regional distribution of blood flow was derived from the arterio-venous oxygen content difference of each organ. Expired air was collected into a spirometer. There was a redistribution of blood flow in these patients with chronic lung disease in accord with the observations made by others in the past. Carbon dioxide concentration in the venous blood depends on 1. the blood flow to an organ, and 2. the carbon dioxide production by the organ. The total body CO2 production was within normal limits and there is no reason to suspect any alteration in carbon dioxide production by individual organs in these resting patients. Thus the venous CO2 levels are intimately linked with organ blood flow but even a substantial increase in organ blood flow cannot always compensate for the disorder in the lung. The exact role of CO2 in regulating the peripheral circulation cannot be assessed from this study but they do emphasize the importance of regional blood flow in regulating the concentration of CO2 in the venous blood and presumably in the tissues making up the organ.  相似文献   

16.
In non-mandatory vaccination policies, individual choice can be a major driver of vaccine uptake. Choice thereby influences whether public health targets can be achieved. Individual vaccinating decisions can be influenced by perceptions of vaccine risks or infection risks. There is also the potential for non-vaccinators to strategically 'free-ride' on herd immunity provided by vaccinators. This strategic interaction between individuals generates a social dilemma--a conflict between self-interest and what is best for the group as a whole. Game theory and related mathematical approaches that couple mechanistic models of vaccinating decisions with mechanistic models of disease spread can capture this social dilemma and address relevant questions. The past decade has seen significant growth in the theoretical literature developing and analyzing such models. Here, we argue that using these models to address specific public health challenges will require more work that integrates information from empirical studies into the development and validation of such models, as well as more collaboration between mathematical modelers, psychologists, economists and public health experts.  相似文献   

17.
BACKGROUND: The effects on ovarian function of the combined contraceptive vaginal ring NuvaRing and a combined oral contraceptive (COC) were compared. METHODS: This randomized, open-label study was performed in 40 healthy female volunteers, who were randomized by a computer-generated list after stratification for the ovulation day in a pretreatment cycle. They received two cycles of NuvaRing (21 subjects) or a COC (30 microg ethinylestradiol and 150 microg levonorgestrel, 19 subjects). NuvaRing was started on cycle day 5, COC on cycle day 1. Follicular diameter, endometrial thickness and FSH, LH, 17beta-estradiol (E2) and progesterone concentrations were determined. RESULTS: The median maximum follicular diameter (maxFD) was < or =11 mm during treatment. In the first treatment cycle the maxFD was lower in the COC than in the NuvaRing group, due to the different starting procedures. MaxFD were not different in the second treatment cycle. In both groups, E2 and progesterone levels remained low during treatment. Ovulations did not occur. CONCLUSIONS: In both groups, ovarian activity was adequately suppressed. Due to the different starting procedures, lower ovarian activity was observed in the COC group in the first treatment cycle. In the second cycle, ovarian suppression was comparable with NuvaRing and COC treatment.  相似文献   

18.
目的:建立卵巢癌顺铂耐药细胞株COC1/DDP,探讨马蔺子素对COC1/DDP的逆转作用。方法:采用逐步递增DDP浓度、体外间歇诱导法诱导卵巢癌细胞系COC1,建立卵巢癌顺铂耐药细胞株COC1/DDP;以麟8试剂盒(Cell Counting Kit-8)检测马蔺子素对COC1/DDP细胞增殖的抑制作用;以GSH和GSSG试剂盒检测细胞内GSH的水平;以高效液相色谱测定细胞内顺铂的含量。结果:历时5个月建立COC1/DDP,对顺铂耐药性稳定,耐药指数为9.44,对卡铂、长春新碱和阿霉素均有不同程度的交叉耐药性;马蔺子素对COC1/DDP的顺铂耐药性有逆转作用,逆转倍数达到3.44倍;与COC1比较,COC1/DDP细胞内GSH的水平增高,顺铂含量下降,但经马蔺子素干预后,COC1/DDP胞内的GSH的水平降低,顺铂的含量增加(P〈0.01)。结论:马蔺子素对COC1/DDP有逆转作用,其机制可能与干预COC1/DDP细胞内GSH/GSTπ解毒系统,增加细胞内顺铂的含量有关。  相似文献   

19.
BACKGROUND: Varicocele is a bilateral vascular disease, involving a network of collaterals and small, retroperitoneal bypasses. The right and the left testicular venous drainage systems are complex and not identical to each other. It was considered a predominantly unilateral (left-sided) disease. Its pathophysiology has not been clearly delineated and the treatments offered do not seem to be effective. The medical literature is replete with articles demonstrating inconsistent and even contradictory results which have led clinicians to dissociate varicocele from male infertility. Since male fertility is preserved with only one healthy testis, male infertility perforce represents bilateral testicular dysfunction. This poses an enigma to clinicians: How can left-sided varicocele causes bilateral testicular dysfunction? METHODS: We investigated the internal spermatic veins by venography to understand testicular damage due to varicocele. A total of 740 venographies of the internal spermatic veins (ISVs) were performed, with sclerotherapy of the ISV as treatment for varicocele. Epon-embedded testicular tissue sections were used to identify blood stagnation in the testis. RESULTS: Varicocele is predominantly a bilateral disease in 84% of cases, associated with collaterals and retroperitoneal venous bypasses in 70% in the left side and 75% in the right side. Histopathology demonstrate stagnation in the testicular microcirculation and hypoxic-ischaemic degenerative changes in all cells' types in the sperms' production site. CONCLUSION: Based on our findings (i) varicocele is a bilateral disease; (ii) the disease is expressed earlier in the left side and is more intense because the blood column is longer in the left side than the right; (iii) partial treatment to the left side only and ignoring bypasses is not adequate to correct the problem; (iv) hypoxia leading to ischaemic damage to both testes is the effect of varicocele due to hydrostatic pressures in the impaired venous drainage system, which exceeds the pressures in the testicular arterial microcirculation due to blood columns produced in the disease; (v) hydrostatic pressure does not depend on vein diameter but on blood column height, only; and (vi) thermography alone or combined with ultrasonography with special attention to the bilaterality of the disease are the best non-invasive tools for its detection.  相似文献   

20.
Antiphospholipid syndrome is an autoimmune disease characterized by venous and/or arterial thrombosis and/or recurrent fetal loss and the presence of antiphospholid antibodies. Among the causes of death of antiphospholipid syndrome there are the myocardial infarction and stroke. Comorbidities could worsen the evolution of these patients, and the knowledge about these situations could prevent or minimizethe risks associated with the disease. In this article, we review the literature about cardiovascular comorbidities, such as traditional risk factors for atherosclerosis, metabolic syndrome and vitamin D deficiency, and how these could influence the prognosis of antiphospholipid syndrome patients.  相似文献   

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