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1.  The Lupus Family Registry and Repository 
Rheumatology (Oxford, England)  2010;50(1):47-59.
The Lupus Family Registry and Repository (LFRR) was established with the goal of assembling and distributing materials and data from families with one or more living members diagnosed with SLE, in order to address SLE genetics. In the present article, we describe the problems and solutions of the registry design and biometric data gathering; the protocols implemented to guarantee data quality and protection of participant privacy and consent; and the establishment of a local and international network of collaborators. At the same time, we illustrate how the LFRR has enabled progress in lupus genetics research, answering old scientific questions while laying out new challenges in the elucidation of the biologic mechanisms that underlie disease pathogenesis. Trained staff ascertain SLE cases, unaffected family members and population-based controls, proceeding in compliance with the relevant laws and standards; participant consent and privacy are central to the LFRR’s effort. Data, DNA, serum, plasma, peripheral blood and transformed B-cell lines are collected and stored, and subject to strict quality control and safety measures. Coded data and materials derived from the registry are available for approved scientific users. The LFRR has contributed to the discovery of most of the 37 genetic associations now known to contribute to lupus through 104 publications. The LFRR contains 2618 lupus cases from 1954 pedigrees that are being studied by 76 approved users and their collaborators. The registry includes difficult to obtain populations, such as multiplex pedigrees, minority patients and affected males, and constitutes the largest collection of lupus pedigrees in the world. The LFRR is a useful resource for the discovery and characterization of genetic associations in SLE.
PMCID: PMC3307518  PMID: 20864496
Systemic lupus erythematosus; Registry; Repository; Autoimmune diseases; Genetics; Heritability; Genome-wide association studies; Linkage analysis; Minorities; Women
2.  Male only Systemic Lupus 
The Journal of rheumatology  2010;37(7):1480-1487.
Systemic lupus erythematosus (SLE) is more common among women than men with a ratio of about 10 to 1. We undertook this study to describe familial male SLE within a large cohort of familial SLE. SLE families (two or more patients) were obtained from the Lupus Multiplex Registry and Repository. Genomic DNA and blood samples were obtained using standard methods. Autoantibodies were determined by multiple methods. Medical records were abstracted for SLE clinical data. Fluorescent in situ hybridization (FISH) was performed with X and Y centromere specific probes, and a probe specific for the toll-like receptor 7 gene on the X chromosome. Among 523 SLE families, we found five families in which all the SLE patients were male. FISH found no yaa gene equivalent in these families. SLE-unaffected primary female relatives from the five families with only-male SLE patients had a statistically increased rate of positive ANA compared to SLE-unaffected female relatives in other families. White men with SLE were 5 times more likely to have an offspring with SLE than were White women with SLE but there was no difference in this likelihood among Black men. These data suggest genetic susceptibility factors that act only in men.
PMCID: PMC2978923  PMID: 20472921
Systemic lupus erythematosus; men; autoantibodies; genetics
3.  Socioeconomic indicators and hysterectomy status in the United States, 2004 
Hysterectomy is one of the most common surgical procedures performed in the United States. The purpose of this study is to examine the association between socioeconomic indicators and hysterectomy.
Study Design
We performed a cross-sectional analysis of the 2004 Behavioral Risk Factor Surveillance Survey database. The effect of multiple socioeconomic exposures (education level, annual income, and employment status) on hysterectomy status was evaluated. Logistic regression was used to estimate odds ratios between the multiple exposures and the outcome of hysterectomy status.
Our analytic sample included 180,982 women. Prior hysterectomy was reported by 26.4%. After adjusting for confounders, women who had not graduated from high school had 1.75 times higher odds (95% CI 1.68 to 1.83) of having a hysterectomy compared to women who were college graduates; and women with an annual household income of less than $15,000 had 1.06 times higher odds (95% CI 1.02 to 1.10) of having a hysterectomy compared to women who reported an income of greater than $50,000/year. Women who were unemployed did not have higher odds of having a hysterectomy than women who were employed.
Socioeconomic indicators of education level and income are associated with hysterectomy status, however employment status is not.
PMCID: PMC2883776  PMID: 19947032
Hysterectomy; socioeconomic status; education; income; employment
4.  Complications of hysterectomy in women with von Willebrand disease 
Case reports and small case series suggest that women with von Willebrand disease (VWD) are at a very high risk of bleeding complications with hysterectomy. As the procedure may be beneficial to women who suffer from heavy menstrual bleeding and have completed childbearing, an understanding of the true risks involved is essential for appropriate decision making. To estimate the incidence of bleeding and other complications in women with VWD who undergo hysterectomy. The United States Nationwide Inpatient Sample (NIS) from the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality for the years 1988–2004 was queried for all hysterectomies for non-malignant conditions. Data were analysed based on the NIS sampling design. Bivariate analyses were used to examine the differences between women with and without VWD. Multivariate analysis was used to adjust for potential confounders among women who underwent hysterectomy for heavy menstrual bleeding. 545 of the 1 358 133 hysterectomies were to women with VWD. Women with VWD were significantly more likely to experience intraoperative and postoperative bleeding (2.75% vs. 0.89%, P < 0.001) and require transfusion (7.34% vs. 2.13%, P < 0.001) than women without VWD. One woman with VWD died. While the risk of bleeding complications from hysterectomy in women with VWD is smaller than previously reported, women with VWD did experience significantly more bleeding complications than women without VWD. Nonetheless, for women who have completed child-bearing, the risks of hysterectomy may be acceptable.
PMCID: PMC3740955  PMID: 19473420
hysterectomy; menorrhagia; von Willebrand disease
5.  Risk Factors in Cardiovascular Disease in Systemic Lupus Erythematosus 
Current Cardiology Reviews  2013;9(1):15-19.
Systemic lupus erythematosus (SLE) is a chronic and multisystemic autoimmune disorder which predominantly affecting women. The most common cause of death in SLE patients affected by disease for more than 5 years is cardiovascular disease (CVD). Epidemiological observations suggest that, together with classical conventional risk factors, other mechanisms (non-conventional/disease-specific factors) promote accelerated atherosclerosis in inflammatory diseases like SLE. Traditional CVD risk factors included age, hypertension, diabetes mellitus, dyslipidemia, previous vascular event defined as previous history of cerebrovascular accidents or ischemic heart disease, menopause and smoking. The non-traditional factors presents in SLE are disease-specific like renal disease manifestation as Lupus nephritis (LN), presence of pro-inflammatory cytokines, some of inflammatory mediators, antiphospholipid antibodies, anti-oxLDL antibodies, corticosteroid uses and cumulative dose of glucocorticoids. We will review traditional and non-traditional risk factors associated with CVD in SLE patients.
PMCID: PMC3584302  PMID: 23463953
Nontraditional risk factors; cardiovascular disease; systemic lupus erythematosus.
6.  Patterns and influence of familial autoimmunity in pediatric systemic lupus erythematosus 
A high prevalence of autoimmune disease (AD) has been documented in relatives of adult patients with systemic lupus erythematosus (SLE). However, data on familial inheritance patterns in pediatric SLE patients is scarce.
The charts of 69 patients with pediatric-onset SLE were reviewed retrospectively. The primary aim was to describe the prevalence and types of AD in relatives of children with SLE. The secondary aims were: 1) to compare severity of SLE in children with and without relatives affected by AD, and 2) to evaluate the impact of baseline demographics on severity of SLE in subjects. At diagnosis, 42% of subjects had one or more first, second, or third degree relative(s) with AD; and 32% of subjects had one or more first degree relative(s) with AD. The most common diseases in relatives of children with SLE were SLE (21%) and thyroid disease (15%). Subjects with no family history of AD were more likely to have severe SLE. SLE severity in subjects did not differ by gender. Children presenting with SLE at an earlier age were found to have more severe disease.
This study demonstrated a high prevalence of AD in families of children with SLE, although a family history of AD did not correlate with more severe SLE in subjects. Future larger studies are necessary to elucidate patterns of familial inheritance and baseline patient characteristics that may affect severity of disease in pediatric SLE.
PMCID: PMC3542590  PMID: 22891746
Pediatric systemic lupus erythematosus; Severity; Inheritance patterns
7.  Validation of Self-Reported History of Hysterectomy and Oophorectomy among Women in an Integrated Group Practice Setting 
Menopause (New York, N.Y.)  2009;16(3):576-581.
Classification of menopausal status often relies on self-report and is centrally important to research and clinical practice. This study was designed to assess the validity of self-reported hysterectomy and oophorectomy.
A validation study of self-reported surgical menopause was conducted using survey data and electronic medical records from women enrolled in the Breast Cancer Screening Program within an integrated group practice in Washington State. Sensitivity of self-reported surgical history was estimated from questionnaire data among women with a history of hysterectomy (N = 1,935) and/or oophorectomy (N = 1,010) per medical records. Positive predictive values were quantified by reviewing medical records for a subset of women who self-reported a hysterectomy and/or oophorectomy (N = 122).
Women self-reported hysterectomy history with great accuracy (sensitivity = 91%, positive predictive value = 97%), but were less accurate in reporting oophorectomy history (sensitivity of bilateral oophorectomy = 64%, positive predictive value = 100% and 73% for bilateral and unilateral oophorectomy, respectively). Among women self-reporting a unilateral oophorectomy, 19% had had both ovaries removed.
Self-report is a valid data collection tool for hysterectomy history, but care should be taken in querying for and interpreting self-reported oophorectomy history for determining menopausal status.
PMCID: PMC2695678  PMID: 19169161
hysterectomy; menopause; oophorectomy; sensitivity; validity; positive predictive value
8.  Aspirin for Prevention of Preeclampsia in Lupus Pregnancy 
Autoimmune Diseases  2014;2014:920467.
Preeclampsia, the onset of hypertension and proteinuria during pregnancy, is a common medical disorder with high maternal and fetal mortality and morbidity. The underlying pathology remains poorly understood and includes inflammation, endothelial dysfunction, and an unbalanced thromboxane A2/prostacyclin ratio. For women with systemic lupus erythematosus (SLE), particularly those with preexisting renal disease or with active lupus, the risk of developing preeclampsia is up to 14% higher than it is among healthy individuals. The mechanism is still unknown and the data for preventing preeclampsia in lupus pregnancies are rare. Modulating the impaired thromboxane A2/prostacyclin ratio by administration of low-dose aspirin appears to be the current best option for the prevention of preeclampsia. After providing an overview of the pathogenesis of preeclampsia, preeclampsia in lupus pregnancies, and previous trials for prevention of preeclampsia with aspirin treatment, we recommend low-dose aspirin administration for all lupus patients starting prior to 16 weeks of gestation. Patients with SLE and antiphospholipid syndrome should receive treatment with heparin and low-dose aspirin during pregnancy.
PMCID: PMC3977461  PMID: 24778868
9.  Safe Laparoscopic Removal of a 3200 Gram Fibroid Uterus 
Open laparotomy may be avoided in many cases requiring hysterectomy for benign disease.
Background and Objectives:
Hysterectomy using minimally invasive techniques yields fewer complications, less blood loss, and quicker recovery time compared with traditional abdominal hysterectomy. Despite these advantages, >65% of all hysterectomies in the United States are still performed using traditional laparotomy, and many clinicians still exclude patients with a history of prior abdominal surgery, significant obesity, or a large fibroid uterus from these procedures. Among physicians skilled in minimally invasive surgery, the prior largest uteri removed included a 2421g uterus removed vaginally, and a 2418g uterus removed via hand-assisted laparoscopic hysterectomy.
We performed a laparoscopic-assisted hysterectomy on a significantly obese 50-year-old woman with a 3200g uterus. The patient required a 2-day hospital stay and recovered unremarkably. The patient was able to return to work within one week and quickly returned to activities of daily life.
In the hands of experienced minimally invasive surgeons, laparotomy can be avoided in almost all instances of hysterectomy for benign disease.
PMCID: PMC3083059  PMID: 21605532
Laparoscopic hysterectomy; Fibroid uterus
10.  Genetic basis of systemic lupus erythematosus: a review of the unique genetic contributions in African Americans. 
Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving critical genetic and environmental risk factors. SLE is a relatively common disease among African American women, affecting as many as one in 250. A collection of more than 250 African American and European American pedigrees multiplex for SLE have been collected in Oklahoma over the past decade for the purpose of identifying the genetic risk factors involved in the pathogenesis of SLE. A genome scan has been performed, and interestingly, the linkage results usually dominate in families from one or the other of these ethnicities. For example, the linkage effect at 1q21-22 near FcgammaRIIA is much stronger in the African American pedigrees than in the European American pedigrees. On the other hand, a gene near the top of chromosome4 (at 4p l6-15) contributes to SLE in the European American pedigrees, but not in the African American pedigrees. The racially-specific results lead to the tentative conclusion of genetic differences associated with SLE in African Americans and European Americans. The identification of the genes responsible for the observed linkage effects will provide fundamental knowledge concerning SLE and may even provide new targets for therapy and strategies to defeat this enigmatic and difficult disease.
PMCID: PMC2594259  PMID: 12152922
11.  The United States to Africa lupus prevalence gradient revisited 
Lupus  2011;20(10):1095-1103.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that has a significantly higher prevalence, morbidity and mortality in African Americans compared with Americans of European descent. The pathogenesis of lupus is unclear but appears to be a result of environmental factors interacting with a genetically susceptible host. Despite the high disease load of SLE in African Americans, there is the perception that lupus is relatively rare in Africa. This prevalence gradient suggests that comparative studies of related cohorts from the two continents may provide insight into the genetic/environmental interactions that result in the development of lupus. To define if a lupus gradient exists, we began a study of autoimmunity prevalence utilizing two unique cohorts. The first is the Gullah population of the Sea Islands of South Carolina, who are unique in their low genetic admixture and their known ancestral heritage. The second is the population of young women served by the West Africa Fistula Foundation in Bo, Sierra Leone. Anthropologic studies indicate a direct ancestral link between the Gullah population and Sierra Leoneans. Since it is impossible to perform an epidemiologic study of lupus in Sierra Leone at this time, we assessed the prevalence of lupus serum autoantibodies, serologic evidence of specific infections and levels of serum 25-OH vitamin D in young women in the two cohorts who have no known relatives with lupus. Our results indicate similar prevalence of serum antinuclear antibodies in the two cohorts, though there was a significantly increased prevalence of antiphospholipid and anti-Sm antibodies in the Sierra Leone cohort. Seropositivity to common viral infections was significantly higher in women from Sierra Leone, while serum 25-OH vitamin D levels were markedly lower in the Gullah population. These data suggest that the prevalence of autoimmunity is similar in the two populations, but that there are significant environmental differences that may impact progression to autoimmune disease. Further studies comparing these two cohorts is likely to provide important insight into the impact of environmental factors on development of lupus.
PMCID: PMC3535487  PMID: 21917913
African American; lupus; prevalence gradient; vitamin D
12.  Autoantigen-specific T cell proliferation induced by the ribosomal P2 protein in patients with systemic lupus erythematosus. 
Journal of Clinical Investigation  1994;94(1):345-352.
A role for helper T cells in the induction of pathogenic lupus autoantibodies is increasingly supported by data from studies of murine lupus and patients with systemic lupus erythematosus (SLE). However, the poor in vitro function of SLE T cells has hampered the identification and characterization of autoantigen-specific T cells. We used recombinant fusion proteins to study the T cell proliferative response of 31 lupus patients and 27 healthy subjects to a well-characterized SLE autoantigen, the ribosomal P2 protein. Although PBMC from SLE patients showed marked impairment in the proliferative response to the common recall antigen tetanus toxoid when compared with normal subjects, a significantly greater proportion of SLE patients (32%) than normal individuals (0%) showed a T cell response to a recombinant P2 fusion protein. When the SLE patients were subgrouped according to the presence of serum anti-P autoantibody, 7 of 10 anti-P antibody-positive patients, but 0 of 20 anti-P antibody-negative SLE patients, demonstrated > 2,000 cpm [3H]thymidine incorporation and a P2 stimulation index > 5. The specificity of the T cell proliferative response for the P2 protein was confirmed by studies using a second recombinant human P2 fusion protein and by the specific activation of P2-primed T cells by recombinant P2 in secondary cultures. Moreover, the T cell proliferative response to the P2 autoantigen was mediated by CD4-positive T cells and was inhibited by anti-MHC class II antibodies. These data demonstrate the presence of autoantigen-specific T helper cells in patients with SLE and suggest that these T cells drive the production of autoantibodies by B lymphocytes.
PMCID: PMC296315  PMID: 7913711
13.  Early invasive vulvar squamous cell carcinoma arising in a woman with vulvar pemphigus vulgaris and systemic lupus erythematosus 
BMC Cancer  2010;10:324.
Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucous membranes. Genital involvement occurs when most other common sites are concurrently affected or are in remission. Systemic lupus erythematosus (SLE) is an autoimmune disease that may affect many parts of the body and the skin with occasional bullous lesions. Pemphigus vulgaris and SLE may be associated, albeit rarely. Here, we report the first case of a woman affected with SLE presenting with early invasive squamous cell carcinoma (SCC) arising from Pemphigus Vulgaris of the vulva.
Case presentation
A 27-year-old Caucasian woman was admitted to our Gynaecology Unit for bleeding vegetant lesions of the vulva. Her history was characterized by systemic lupus erythematosus and PV. Biopsy showed concomitant PV and vulvar intraepithelial neoplasia (VIN) grade 3. One month later a new biopsy revealed progression from VIN 3 to early SCC. Despite chemotherapy, no remission of disease was observed. She died six months after diagnosis
Our case underlines PV as another chronic inflammatory disease of the lower genital tract predisposing to VIN-SCC. It suggests the need for careful follow-up of patients with chronic inflammatory disease, especially when concomitant autoimmune disorders are present. Moreover, a biopsy should be always performed if there are PV lesions because of the possibility of neoplastic disease.
PMCID: PMC3087320  PMID: 20573220
14.  Hysterectomy rates and their influence upon mortality from carcinoma of the cervix. 
Cumulative hysterectomy rates for women in England and Wales have been estimated from data in the Hospital In-Patient Enquiry, and the effect of hysterectomy operations on mortality from cancer of the cervix has been calculated. About six to seven per cent of women born at about the turn of the century have had an hysterectomy by the age of 70, and this proportion could rise to about 19% for women born in the 1940s if present operation rates continue. The time trends in mortality from cancer of the cervix between generations of women are not at present distorted by correction for women without a cervix. Operation rates and their effect on cervical cancer mortality rates are much smaller in England and Wales than in the United States of America.
PMCID: PMC1060941  PMID: 711975
15.  State-level Uterine Corpus Cancer Incidence Rates Corrected for Hysterectomy Prevalence, 2004-2008 
The interpretation of uterine cancer rates is hindered by the inclusion of women whose uterus has been surgically removed in the population at risk. Hysterectomy prevalence varies widely by state and race/ethnicity, exacerbating this issue.
We estimated hysterectomy-corrected, age-adjusted uterine corpus cancer incidence rates by race/ethnicity for 49 states and the District of Columbia during 2004-2008 using case counts obtained from population-based cancer registries; population data from the U.S. Census Bureau; and hysterectomy prevalence data from the Behavioral Risk Factor Surveillance System. Corrected and uncorrected incidence rates were compared with regard to geographic and racial/ethnic disparity patterns and the association with obesity.
Among non-Hispanic whites, uterine cancer incidence rates (per 100,000 woman-years) uncorrected for hysterectomy prevalence ranged from 17.1 in Louisiana to 32.1 in New Jersey, mirrored regional hysterectomy patterns, and were not correlated with obesity prevalence (Pearson’s correlation coefficient, r = 0.06, two-sided p = 0.68). In comparison, hysterectomy-corrected rates were higher by 30% (District of Columbia) to more than 100% (Mississippi, Louisiana, Alabama, and Oklahoma), displayed no discernible geographic pattern, and were moderately associated with obesity (r = 0.37, two-sided p = 0.009). For most states, hysterectomy correction diminished or reversed the black/white deficit and accentuated the Hispanic/white deficit.
Failure to adjust uterine cancer incidence rates for hysterectomy prevalence distorts true geographic and racial patterns and substantially underestimates the disease burden, particularly for Southern states.
Correction for hysterectomy is necessary for the accurate evaluation of uterine cancer rates.
PMCID: PMC3538963  PMID: 23125334
endometrium; uterus; hysterectomy; geographic pattern; disparity
16.  Variation in NHS utilisation of vault smear tests in women post-hysterectomy: A study, using routinely collected datasets 
BMC Women's Health  2008;8:6.
20% of women living in the UK have a hysterectomy during their lifetime, levels are higher in the USA, making it one of the most commonly performed major surgical procedures. Understanding of the indications for hysterectomy and of the rationale for follow-up of women post hysterectomy is currently limited. Guidelines concerning follow-up by means of vaginal vault cytology tests exist but these are not based on 'gold standard' evidence. Furthermore, the extent to which current practice reflects these guidelines is unclear. This study aims to determine the factors associated with variability in hysterectomy rates and subsequent follow-up after surgery by use of the vaginal vault smear cytology test.
All women resident in the West Midlands region, of the United Kingdom, who had a hysterectomy operation between 1st April 2002 and 30th March 2003 will be identified from the Hospital Episodes Statistics database which also contains proxy data on deprivation status, derived from postcode and self declared ethnicity. These data will be linked to regional cervical screening records for each woman and histopathology laboratory records from the relevant hospitals. Study objectives are to describe: Indications for the hysterectomy operation, histology at hysterectomy, subsequent follow-up by use or non-use of vaginal vault cytology tests and variation between histological groups. Additionally the data will be categorised according to a woman's cytology screening history prior to surgery (i.e. always normal, borderline, resolved abnormalities, CIN etc) and these different groups compared. Variations in these outcomes according to age, deprivation and ethnic group will also be examined. Analysis will be undertaken using SPSS.
This study will clarify patterns of current practice in one large English region and determine whether this practice reflects existing guidelines. The study will also strengthen the evidence base for future guidelines.
Study registration
National Research Register N0138173331
PMCID: PMC2329610  PMID: 18373859
17.  Pregnancy-associated systemic lupus erythematosus 
Systemic lupus erythematosus (SLE) is an autoimmune disease that classically manifests itself with fever, arthralgia, and rash, predominantly in women of childbearing age. The autoimmunity is against nuclear and cytoplasmic components; therefore, any organ system can be affected, and the clinical presentation spectrum is wide. Although rare, de novo SLE can be diagnosed in pregnancy. Herein, a woman who had SLE diagnosed in early pregnancy is reported. This and a previous report imply that SLE has diverse clinical presentations in pregnancy.
PMCID: PMC4059571  PMID: 24982567
18.  Prevalence of Uterine Leiomyomas in Lymphangioleiomyomatosis 
Fertility and sterility  2011;96(3):711-714.e1.
To determine the frequency of uterine leiomyomas and hysterectomy in patients with lymphangioleiomyomatosis (LAM), a disease characterized by proliferation of abnormal-appearing smooth muscle-like cells.
Retrospective study.
456 patients with sporadic LAM and LAM associated with tuberous sclerosis complex (LAM/TSC).
Natural history study at the National Institutes of Health.
Review of records and pelvic computed axial tomography scans.
Main Outcome Measure(s)
prevalence of uterine leiomyomas and hysterectomy.
A total of 174 women had uterine leiomyomas (38%). One hundred eighteen were diagnosed by CT scan and 56 were diagnosed by hysterectomy. Among 323 patients who did not have hysterectomy, 105 of 270 patients (39%) with sporadic LAM and 13 of 53 (25%) with LAM/TSC had uterine leiomyomas. Hysterectomy was performed in 108 of 378 subjects with sporadic LAM and 25 of 78 with LAM/TSC. Fifty six patients were found to have uterine fibroids at hysterectomy. The most common indications for hysterectomy were uterine leiomyoma, lymphangioleiomyomatosis and endometriosis.
Uterine leiomyomas are not more common in LAM than in the general population. However, in LAM, the frequency of hysterectomy is higher because of it having been recommended for treatment of LAM.
PMCID: PMC3165169  PMID: 21880281
Uterine leiomyomas; hysterectomy; lymphangioleiomyomatosis
19.  Is Previous Tubal Ligation a Risk Factor for Hysterectomy because of Abnormal Uterine Bleeding? 
Oman Medical Journal  2012;27(4):326-328.
Post tubal ligation syndrome (PTLS) is a term used to describe a variety of post tubal ligation side effects or symptoms. These include increased menstrual bleeding and hysterectomy. Whether or not post tubal syndrome is a real entity, it has been a subject of controversy in the medical literature for decades. Numerous studies have reported conflicting conclusions about these symptoms. In this study the incidence of hysterectomy for bleeding disorders among sterilized women was compared with the incidence of hysterectomy for bleeding disorders among non-sterilized female population of the same age.
This study was carried out on 160 women, 38-52 years, who underwent hysterectomy in Amir University Hospital, Semnan, Iran, from September 2008 to September 2011. After gathering of data from medical records, in this study, the incidence of hysterectomy for bleeding disorders among sterilized women was compared with the incidence of hysterectomy for bleeding disorders among nonsterilized female population for the same age.
The mean age of the study group was 44/4±5/7 and the mean age of the control group was 45/2±5/3, (p=0.424).The mean parity of the study group was 3/8±1/8 and the mean parity of the control group was 3/5±1/4, (p=0.220). So, in regard to age and parity, two groups were matched. Hysterectomies were performed for 160 cases and abnormal uterine bleeding was the cause of hysterectomy in 67 cases. Among 67 cases, 19 cases (37.3%) had previous tubal sterilization + hysterectomy (study group) and 48 cases (44%) were not undergoing tubal sterilization but had hysterectomy for abnormal bleeding causes (control group). Statistical analyses showed that there were not significant differences between two groups, (RR=0.85; 95% CI: 0.56-1.28; p=0.418).
The result of this study showed that previous tubal sterilization is not a risk factor for undergoing hysterectomy because of abnormal uterine bleeding.
PMCID: PMC3464743  PMID: 23071889
Tubal ligation; Post tubal ligation syndrome; Hysterectomy
20.  Increased risk of death in pediatric and adult patients with ESRD secondary to lupus 
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that can cause significant kidney disease. Our goal was to assess the relative mortality risk associated with SLE in pediatric and adult populations with end-stage renal disease (ESRD) maintained on hemodialysis (HD). We performed Kaplan–Meier survival analysis from data collected by the United States Renal Data System (USRDS) in strata of pediatric and adult patients. This file includes data on all Medicare-reimbursed renal replacement patients. Cox proportional hazard models were used to assess mortality after adjusting for race and gender. Subjects were censored at transplantation or at end of follow-up. Pediatric patients with ESRD secondary to SLE had a 2-fold increased risk of death compared with other pediatric patients with ESRD (hazard ratio [HR]: 2.4, 95% confidence interval [CI]: 1.5–3.7). Adult patients with ESRD secondary to SLE were also at increased risk of death compared with other adult patients (HR: 1.7, 95% CI: 1.2–2.7). The most common causes of death in both pediatric and adult patients with SLE were cardiovascular disease and cardiac arrest. Our study demonstrates that there is a significant increase in mortality secondary to cardiovascular disease in pediatric and adult patients with ESRD secondary to SLE. Patients with ESRD secondary to SLE may need aggressive monitoring for traditional risk factors for atherosclerosis and the diagnosis of SLE alone may be an independent risk factor for death in patients with ESRD.
PMCID: PMC2992078  PMID: 20890767
Systemic lupus erythematosus; Pediatrics; Dialysis; Mortality
21.  Common Complications of Hysterectomy 
Some of the common complications associated with abdominal and vaginal hysterectomy, performed in a teaching hospital, are reviewed. Case records of 284 abdominal hysterectomies and 101 vaginal hysterectomies are analyzed.
The incidence of blood transfusion and of urinary tract infection was greater following vaginal hysterectomy than abdominal hysterectomy. The morbidity rate of vaginal hysterectomy was two and a half times as great as that of abdominal hysterectomy. Neither the age of the patient nor the factor of previous abdominal or major gynecological surgery influenced the morbidity of vaginal hysterectomy.
It is apparent that the preoperative recognition and treatment of urinary tract infection and anemia should reduce the incidence of postoperative morbidity and the use of postoperative blood transfusion in both abdominal and vaginal hysterectomy.
PMCID: PMC1928058  PMID: 14289138
22.  Laparoscopic subtotal hysterectomy versus laparoscopic total hysterectomy: a decade of experience 
Gynecological Surgery  2009;7(1):9-12.
At present, there are only few data on the surgical outcomes of laparoscopic hysterectomy (LH). Up till now, it has been unclear whether there is a difference in number of complications among the subcategories of laparoscopic total hysterectomy and laparoscopic subtotal hysterectomy (LSH). Therefore, we have performed a retrospective analysis to evaluate the peri- and postoperative outcomes in women undergoing LSH versus LH. This multi-centre retrospective cohort study (Canadian Task Force classification II-2) was conducted in multi-centres (two teaching hospitals and one university medical centre) in the Netherlands, all experienced in minimally invasive gynaecology. In a multi-centre retrospective cohort study we compared the long-term outcomes of laparoscopic subtotal hysterectomy and laparoscopic total hysterectomy (including laparoscopic assisted vaginal hysterectomy, laparoscopic hysterectomy and total laparoscopic hysterectomy). All laparoscopic hysterectomies from the last 10 years (January 1998 till December 2007) were included. Patient characteristics, intra- and postoperative complications, operating time and duration of hospital stay were recorded. The minimum follow-up was 6 months. A total of 390 cases of laparoscopic hysterectomies were included in the analysis: 192 laparoscopic subtotal hysterectomies and 198 laparoscopic total hysterectomies. Patient characteristics such as age and parity were equal in the groups. The overall number of short-term and long-term complications was comparable in both groups: 17% and 15%. Short-term complications (bleeding, fever) were 3% in the LSH group and 12% in the LH group. Long-term complications were (tubal prolapse and cervical stump reoperations) 15% in the LSH group and 3% in the LH group. Laparoscopic subtotal hysterectomy as compared with the different types of laparoscopic total hysterectomy is associated with more long-term postoperative complications, whereas laparoscopic total hysterectomy is associated with more short-term complications.
PMCID: PMC2837242  PMID: 20234836
Laparoscopic hysterectomy; Laparoscopic subtotal hysterectomy; Complications
23.  IRF5 SLE-Risk Haplotype is Associated with Asymptomatic Serologic Autoimmunity and Progression to Clinical Autoimmunity in Neonatal Lupus Mothers 
Arthritis and rheumatism  2012;64(10):3383-3387.
Genetic variation in interferon regulatory factor 5 (IRF5) has been associated with risk of developing systemic lupus erythematosus (SLE), and this association is largely dependent upon anti-Ro autoantibodies. We studied a unique cohort of anti-Ro positive individuals with diverse diagnoses to determine if IRF5 genotype associated with maternal diagnosis or progression of autoimmunity.
We genotyped haplotype-tagging polymorphisms in IRF5 in 93 European ancestry subjects recruited to the Research Registry for Neonatal Lupus who all had high titer anti-Ro autoantibodies and a child with neonatal lupus (NL), and allele frequencies were compared to non-autoimmune controls. The mothers diagnoses included SLE, Sjogren’s syndrome (SS), undifferentiated autoimmune syndrome (UAS), and asymptomatic.
The SLE-risk haplotype of IRF5 was enriched in all anti-Ro positive subjects except those with SS (OR = 2.55, p=8.8×10−4). Even asymptomatic individuals with anti-Ro antibodies were enriched for the SLE-risk haplotype (OR=2.69, p=0.019). The same haplotype was more prevalent in subjects who were initially asymptomatic, but developed symptomatic SLE during follow up (OR=5.83, p=0.0024). Interestingly, SS was associated with two minor IRF5 haplotypes, and these same haplotypes were decreased in frequency in those with SLE and UAS.
The IRF5 SLE-risk haplotype was associated with anti-Ro antibodies in asymptomatic individuals as well as progression to SLE in asymptomatic anti-Ro positive individuals. SS in NL mothers was associated with different IRF5 haplotypes. These data suggest that IRF5 polymorphisms play a role in serologic autoimmunity in humans and may promote the progression to clinical autoimmunity.
PMCID: PMC3449035  PMID: 22674082
systemic lupus erythematosus; interferon; autoantibodies; neonatal lupus; Sjogren’s syndrome
24.  In utero azathioprine exposure and increased utilization of special educational services in children born to mothers with systemic lupus erythematosus 
Arthritis care & research  2013;65(5):759-766.
Azathioprine (AZA) is recognized among immunosuppressive medications as relatively safe during pregnancy for women with systemic lupus erythematosus (SLE) requiring aggressive treatment. This pilot study aimed to determine whether SLE therapy during pregnancy was associated with developmental delays in offspring.
This cohort study included SLE patients with at least one live birth post-diagnosis. Medical histories were obtained via interviews and chart review. Multiple logistic regression was used to examine associations between SLE therapy during pregnancy and maternal report of special educational (SE) requirements (as proxy for developmental delays) among offspring. Propensity scoring (incorporating corticosteroid use, lupus flare, and lupus nephritis) was used to account for disease severity.
Of 60 eligible offspring from 38 mothers, 15 required SE services, the most common indication for which was speech delay. 7 of the 13 (54%) children with in utero AZA exposure utilized SE services versus 8 of 47 (17%) non-exposed (p<0.05). After adjustment for pregnancy duration, small for gestational age, propensity score, maternal education and antiphospholipid antibody syndrome, AZA was significantly associated with SE utilization occurring from age 2 onward (OR 6.6, 95% CI 1.0, 43.3), and bordered significance for utilization at any age or age <2 years.
AZA exposure during SLE pregnancy was independently associated with increased SE utilization in offspring, after controlling for confounders. Further research is indicated to fully characterize developmental outcomes among offspring with in utero AZA exposure. Vigilance and early interventions for suspected developmental delays among exposed offspring may be warranted.
PMCID: PMC3572294  PMID: 23139238
25.  Analysis of autosomal genes reveals gene–sex interactions and higher total genetic risk in men with systemic lupus erythematosus 
Annals of the Rheumatic Diseases  2011;71(5):694-699.
Systemic lupus erythematosus (SLE) is a sexually dimorphic autoimmune disease which is more common in women, but affected men often experience a more severe disease. The genetic basis of sexual dimorphism in SLE is not clearly defined. A study was undertaken to examine sex-specific genetic effects among SLE susceptibility loci.
A total of 18 autosomal genetic susceptibility loci for SLE were genotyped in a large set of patients with SLE and controls of European descent, consisting of 5932 female and 1495 male samples. Sex-specific genetic association analyses were performed. The sex–gene interaction was further validated using parametric and nonparametric methods. Aggregate differences in sex-specific genetic risk were examined by calculating a cumulative genetic risk score for SLE in each individual and comparing the average genetic risk between male and female patients.
A significantly higher cumulative genetic risk for SLE was observed in men than in women. (P = 4.52×10−8) A significant sex–gene interaction was seen primarily in the human leucocyte antigen (HLA) region but also in IRF5, whereby men with SLE possess a significantly higher frequency of risk alleles than women. The genetic effect observed in KIAA1542 is specific to women with SLE and does not seem to have a role in men.
The data indicate that men require a higher cumulative genetic load than women to develop SLE. These observations suggest that sex bias in autoimmunity could be influenced by autosomal genetic susceptibility loci.
PMCID: PMC3324666  PMID: 22110124

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