Showing papers in "Obstetrical & Gynecological Survey in 2002"

Use of proteomic patterns in serum to identify ovarian Cancer

Abstract: In this study, a new high-order bioinformatics tool used to identify differences in proteomic patterns in serum was evaluated for its ability to detect the presence of cancer in the ovary. The proteomic pattern is generated using matrix-assisted laser desorption and ionization time-of-flight and surface-enhanced laser desorption and ionization time-of-flight mass spectroscopy from thousands of low-molecular-weight serum proteins. Proteomic spectra patterns were generated from 50 women with and 50 women without ovarian cancer and analyzed on the Protein Biology System 2 SELDI-TOF mass spectrometer (Ciphergen Biosystems, Freemont, CA) to find a pattern unique to ovarian cancer. In the graph of the analysis, each proteomic spectrum is comprised of 15,200 mass/charge (m/z) values located along the x axis with corresponding amplitude values along the y axis. By comparing the proteomic spectra derived from the serum of patients with known ovarian cancer to that of disease-free patients, a profile of ovarian cancer was identified in the peak amplitude values along the horizontal axis. The comparison was conducted using repetitive analysis of ever smaller subsets until discriminatory values from five protein peaks were isolated. The validity of this pattern was tested using an additional 116 masked serum samples from 50 women known to have ovarian cancer and 66 nonaffected women. All of the subjects with cancer and most of the women with no cancer were from the National Ovarian Cancer Early Detection Program at Northwestern University. The nonaffected women had been diagnosed with a variety of benign gynecologic conditions after evaluation for possible ovarian cancer and were considered to be a high-risk population. Serum samples were collected before examination, diagnosis, or treatment and frozen in liquid nitrogen. The samples were thawed and added to a C16 hydrophobic interaction protein chip for analysis. In the validation set, 63 of the 66 women with benign ovarian conditions were correctly identified in the spectra analysis. All 50 patients with a diagnosis of ovarian cancer were correctly identified in the analysis, including 18 women with stage I disease. Thus, the ability of proteomic patterns to detect the presence of ovarian cancer had a sensitively of 100%, a specificity of 95%, and a positive predictive value of 94%. In comparison, the positive predictive value for serum cancer antigen 125 in the set of patients was 35%. Additionally, no matching patterns were seen in serum samples from 266 men with benign and malignant prostate disease.

The 2001 Bethesda system: Terminology for reporting results of cervical cytology

Abstract: The Bethesda System for reporting the results of cervical cytology was introduced in 1988 and revised in 1991 using the actual laboratory and clinical experience with the system. After 10 years of widespread use and advances in biologic understanding of cervical neoplasia, it was felt important to reexamine this terminology. After extensive internet web-based discussion groups on various aspects of the System, a workshop was held at the National Cancer Institute in Bethesda, Maryland, with participation from a broad range of constituents including cytologists, pathologist, clinicians, epidemiologists, patient advocates, and attorneys. This consensus statement is the report of this workshop. The following table (Table 1) is an abstract of the consensus statement.

Prospective multicenter study of pregnancy outcomes in women with Heart disease

Abstract: Either the mother or fetus may decompensate as a result of maternal heart disease, but available risk figures are based chiefly on retrospective studies or have focused on a particular cardiac disorder. This study prospectively enrolled 562 pregnant women with heart disease at 13 Canadian cardiac and obstetrical teaching hospitals. Pregnancies totaled 617. Women with congenital or acquired cardiac lesions or cardiac arrhythmia were eligible for the study. Follow-up assessments were made in the second and third trimesters of pregnancy, the peripartum period, and after 6 weeks and 6 months. Primary cardiac events included pulmonary edema, sustained symptomatic tachyarrhythmia or bradyarrhythmia requiring treatment, stroke, cardiac arrest, and cardiac death. Baseline features did not in any way distinguish the 18 pregnancies ending in miscarriage. Among 546 women having 599 completed pregnancies (more than 20 weeks' gestation), the major cardiac lesion was congenital in 74%, acquired in 22%, and arrhythmic in 4%. Surgery had been performed in 46% of study pregnancies before conception. Cardiac medication, aspirin, or anticoagulants were being taken at baseline in 100 pregnancies (17%) and were initiated in the prepartum period in another 87. The rate of primary cardiac events in completed pregnancies was 13%; more than half took place in the prepartum period. Most of these events were pulmonary edema and/or cardiac arrhythmia. There were four embolic strokes. Predictors of these events included a past cardiac event or arrhythmia; New York Heart Association (NYHA) class III or higher dysfunction or cyanosis; left heart obstruction; and an ejection fraction less than 40%. Secondary cardiac events (NYHA functional deterioration of two or more stages compared with baseline or an urgent need for invasive cardiac procedures) occurred in 6% of study pregnancies. Neonatal events, most commonly premature birth, occurred in 20% of pregnancies. Predictors included NYHA class more than II or cyanosis at baseline, maternal left heart obstruction, smoking during pregnancy, multiple gestations, and anticoagulant therapy throughout pregnancy. Cardiac intervention should be considered in advance of conception when a woman is at high risk for cardiac events but the risk-benefit ratio is favorable. Women at substantial risk might well do best receiving ongoing care at a regional center. Women at low cardiac risk who lack lesion-specific risk factors can safely deliver at a community hospital.

Ectopic pregnancy within a cesarean scar: a review.

Abstract: Implantation of a pregnancy within the scar of a previous cesarean delivery is the rarest of ectopic pregnancy locations. Only 19 cases have been reported in the English medical literature since 1966. If diagnosed early, treatment options are capable of preserving the uterus and subsequent fertility. However, a delay in either diagnosis or treatment can lead to uterine rupture, hysterectomy, and significant maternal morbidity. Although expectant and medical managements have been reported, termination of a cesarean scar pregnancy by laparotomy and hysterotomy, with repair of the accompanying uterine scar dehiscence, may be the best treatment option.

Patient complaints and malpractice risk

Abstract: Although the risk of malpractice suits differs by specialty, some physicians are sued more often than others even within a particular discipline If the risk is in fact related to a substantial degree to patients being dissatisfied with physician behaviors, care, and treatment, it might be possible to create a monitoring system that could alert physicians to their risk of being sued The authors hypothesized that unsolicited patient complaints can distinguish physicians at high and at low risk of malpractice even after adjusting for such factors as specialty area, gender, and years in practice A retrospective cohort study enlisted 645 general and specialist physicians who were members of a large US medical group Longitudinal follow-up from early from 1992 to early 1998 totaled 2546 physician-years of care One third of the physicians were surgeons and the others were in general medicine, pediatrics, or neurology Computerized records of unsolicited complaints were recorded and compared with each physician's risk management records during this period More than one third of the physicians (37%) received no complaints during the study period More than half of all complaints were generated by 9% of the physicians, and 5% accounted for nearly one third of complaints The mean number of complaints for all group members was approximately 8 (53 for nonsurgeons and 130 for surgeons) Complaints correlated positively with the volume of clinical activity, as did risk management data On logistic regression analysis, factors related to total patient complaints after adjusting for clinical activity included opening of a risk management file (RMF), file openings with expenditures, and lawsuits Surgeons named in a single lawsuit generated significantly more complaints that surgeons who were never named Female physicians were relatively less likely to be involved with RMFs or lawsuits For both surgeons and nonsurgical practitioners, frequent complaints and high clinical activity correlated significantly with having an RMF Surgeons received complaints related to care and treatment, billing, communication, access/availability, and "humaneness" more often than did nonsurgeons In this retrospective longitudinal study, unsolicited patient complaints correlated positively with physicians' experience of risk management This association would seem to offer an excellent opportunity to address causes of patient dissatisfaction that might lead to malpractice lawsuits

Congenital Cytomegalovirus Infection: Review of the Epidemiology and Outcome

Abstract: Cytomegalovirus (CMV) is one of the most common viral causes of congenital infection. A future decision to lower its incidence by vaccination will depend on epidemiological conditions within a country and on the safety of the vaccine to be used, because a life vaccine may cause latency and subsequent reactivation that still may harm the fetus. The aim was to review the epidemiological studies published so far, with respect to factors that affect the incidence of congenital CMV infection, and factors that may influence its outcome, such as preexisting maternal immunity. The study included the data of 19 studies that were retrieved from a MEDLINE search during the period 1977 to 1997. The incidence of congenital CMV infection varied between 0.15% and 2.0% and seemed to correlate with the level of preexisting immunity in the population. Although preexisting maternal immunity was reported to strongly reduce transmission, the severity of congenital CMV infection (symptoms at birth and or sequelae later in life) was not significantly greater after virus transmission due to a primary infection of the mother as compared with recurrence or reinfection. The data indicate that preexisting immunity of the mother does not significantly mitigate the outcome of congenital infection. Moreover, life vaccines may bear a serious risk when transmittable to the fetus.

Oral contraceptives and the risk of myocardial infarction

Abstract: Some but not all studies claim an association between oral contraceptive (OC) use and the risk of myocardial infarction (MI). The present study sought to determine whether low-dose combined OC preparations influence the risk of MI. Variables considered were the type of progestogen in third-generation OCs (desogestrel or gestodene) and second-generation OCs (levonorgestrel), the estrogen dose, and the presence or absence of prothrombotic mutations (factor V Leiden and the G20210A mutation in the prothrombin gene). The study group included 248 women 18 to 49 years of age who were hospitalized with a first MI during the years 1990-1995 and 925 control women who lacked a history of coronary, cerebral, or peripheral arterial disease. Patients and control women had mean ages of 43 and 38 years, respectively. The patients more frequently had major risk actors for cardiovascular disease. Women using any type of OC were at twice the risk of MI as were control women after adjusting for age, calendar year, and area of residence. Odds ratios increased in most age categories after further adjustment for possible confounding factors. Nonsmoking OC users without hypertension, high cholesterol, or diabetes had a relative risk of MI of 3.1. Both patients and control subjects had used OCs for a median of 10 years. The odds ratio for MI was 2.8 in women using first-generation OCs (compared with nonusers), 2.4 for those using second-generation OCs, and 1.3 for users of third-generation preparations. Similar results were obtained analyzing only users of second- and third-generation OCs containing 30 pg of ethinyl estradiol. Similar odds ratios were found for third-generation OCs containing desogestrel or gestodene. An impressive odds ratio of 13.6 was found for women who smoked and had used OCs. The odds ratio for MI in women having a prothrombotic mutation was 1.1. This case-control study shows that using current combined OCs increases the overall risk of a first MI. The risk is not great in absolute terms, but it should have a substantial effect on women's health because 35% to 45% of reproductive-aged women use OCs. Screening for conventional cardiovascular risk factors is appropriate before prescribing an oral contraceptive.

Noncardiovascular Disease Outcomes During 6.8 Years of Hormone Therapy: Heart and Estrogen/Progestin Replacement Study Follow-Up (HERS II)

Abstract: The authors have reviewed data from the Heart and Estrogen/Progestin Replacement Study (HERS), a randomized trial of hormone replacement therapy (HRT) in postmenopausal women with coronary disease. The HERS trial, with an initial follow-up duration of 4.1 years and subsequent follow-up extending this to 6.8 years, is the first randomized study large enough to provide useful information on adverse events related to HRT, including (in addition to cardiovascular events) bone fracture, thromboembolism, biliary tract surgery, cancer, and overall mortality. Participants numbered 2763 women with an average age of 67 when enrolling in the HERS. HRT consisted of 0.625 mg of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate daily during the trial proper and open-label hormones prescribed by personal physicians during the extended follow-up period. The rate of adherence to at least 80% of prescribed hormone treatment was 81% in the first year of the trial and 45% in year 6. Both deep venous thrombosis (DVT) and pulmonary embolism increased 2- to 3-fold in women taking HRT during the trial proper, but the increase in DVT was not significant over the total follow-up period. In contrast, the risk of pulmonary embolism persisted during HERS II. The relative hazard for any venous thromboembolic event over 6.8 years was 2.08, 5.9 per 1000 person-years in hormone users and 2.8 in placebo recipients. Three deaths were ascribed to pulmonary embolism. There is some indication that aspirin attenuated the risk of thromboembolism in the hormone group. The overall relative hazard for biliary tract surgery in the HRT group was 1.48, or 1.44 after adjusting for statin therapy. Six women died within 30 days of biliary tract surgery, and one death was viewed as a result of the surgery. No significant group differences in cancer incidence were documented. The overall relative hazard for incident breast cancers, comparing the hormone and placebo groups, was 1.27; for lung cancers, 1.39; and for colon cancers, 0.81. Women assigned to HRT had more hip fractures than the placebo group, with an overall relative hazard during 6.8 years of observation of 1.61. The relative hazard for total mortality in HRT recipients was 1.06 during HERS, 1.14 during HERS II, and 1.10 overall. HRT increases the risk of venous thromboembolism and is associated with more frequent biliary tract surgery in older postmenopausal women having coronary artery disease. At the same time, it has not diminished overall rates of cardiovascular disease, bone fracture, or death from all causes. HRT therefore should be used only for symptomatic relief in the early postmenopausal years or any other indication supported by evidence from randomized trials, providing that the potential benefit outweighs any harmful effects.

Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation

Abstract: In the 6 years from mid-1995 to mid-2001, 177 women from the Genetics Service at Memorial Sloan-Kettering who were found to carry the BRCA1 or BRCA2 mutation were enrolled in a prospective study designed to evaluate the role of salpingo-oophorectomy in reducing the risk of breast or BRCA-related gynecologic cancer. Seven women, four who were lost to follow-up and three who were diagnosed with ovarian (N = 2) or fallopian tube malignancies (N = 1) at the time of salpingo-oophorectomy, were excluded from the analysis. Ninety-eight women elected to undergo salpingo-oophorectomy, and 72 decided to confine their participation to the surveillance program for ovarian cancer, which consisted of twice-yearly examinations including gynecological evaluation, transvaginal ultrasonographic examination, and serum cancer antigen 125 (CA-125) measurement. The two groups were similar in clinical and demographic characteristics. Thirty percent of the women in the surveillance group and 14% of those in the surgery group had undergone bilateral mastectomy before the start of follow-up (P = .02). After 24 months of follow-up, an additional 9% and 8%, respectively, had undergone bilateral mastectomy. During the 24-month follow-up period, four women in the surveillance group were diagnosed with ovarian cancer and one developed peritoneal cancer. The diagnoses were made after suspicious transvaginal ultrasound or serum CA-125 results. Seven women with similar suspicious findings within 2 months of the start of surveillance underwent surgical exploration. Benign conditions were diagnosed in all seven. After 15 months of follow-up, no new ovarian or breast cancers have been diagnosed in these patients. Among the 98 women who underwent salpingo-oophorectomy, there was one patient who developed peritoneal cancer at 16 months after surgery. In the surveillance group, there were 62 women who still had breast tissue. Within 13 months of identification of BRCA mutation, eight of these women (13%) were diagnosed with breast cancer. Of the 69 women in the salpingo-oophorectomy group, three (4%) were diagnosed with breast cancer within 10 months of surgery. Statistical analysis of the differences in rates of development of breast cancer and other gynecologic cancers related to the BRCA mutation found a significantly higher proportion of women in the surgery group free from cancer at 5 years (P = .006). In addition, the time to diagnosis of breast or other gynecologic cancers associated with the BRCA mutation was longer in the salpingo-oophorectomy group than in the surveillance group, yielding a hazard ratio for development of BRCA related cancers of 0.25. No difference between the BRCA1 and BRCA2 mutations in the development of breast or gynecologic cancer was seen. There were four surgical complications reported. They included one wound infection, one bladder perforation during placement of the trocar, one small bowel obstruction caused by adhesions between the distal ileum and staples on the right ovarian vessels, and one perforation of the uterus by a uterine manipulator. There was complete resolution of all complications after appropriate treatment.

New approach to polycystic ovary syndrome and other forms of anovulatory infertility

Abstract: Anovulation can be classified in the clinic on the basis of serum hormone assays. Low gonadotropins along with low estrogen concentrations are suggestive of a central origin of the disease, whereas low estrogen levels along with elevated gonadotropins indicate a primary defect at the ovarian level.

A clinical trial of estrogen-replacement therapy after ischemic stroke

Abstract: Based on observational studies indicating a lower risk of stroke and death in women given estrogen replacement therapy (ERT), the Women's Estrogen for Stroke Trial was designed in 1993 as a randomized, double-blind, placebo-controlled investigation. Treatment with 1 mg of estradiol-17β daily was evaluated in 664 postmenopausal women whose mean age was 71, who within the past 90 days had suffered a transient ischemic attack or ischemic stroke. The study population, representing 26% of all those eligible for the study, was drawn from 21 U.S. hospitals and was followed up for 2.8 years on average. Control women received a matching placebo. Phone contacts were made every 3 months to screen for outcomes using a standardized questionnaire. There were 89 deaths and 103 nonfatal strokes during the trial; neither outcome differed significantly in the estradiol-treated and control women. Death due to stroke, however, was more common in the estradiol group (relative risk, 2.9); the difference was mainly in the incidence of ischemic stroke. Nonfatal ischemic stroke was comparably frequent in the two groups. Similar results were obtained after adjusting for baseline risk factors, including older age, past heart disease, hypertension, diabetes, and current smoking. There were no significant group differences in transient ischemic attacks or nonfatal myocardial infarction. Estrogen-treated women were not at higher risk of venous thromboembolism, breast cancer, or hospital admission with fracture. They were, however, likelier to have vaginal bleeding and endometrial hyperplasia and to require hysterectomy Two women given estradiol developed endometrial adenocarcinoma. This trial, which continues, should clarify the role of estrogen in the primary prevention of cardiovascular disease, including stroke. The findings to date suggest that ERT not be started to secondarily prevent cerebrovascular disease They y also agree with the accumulating evidence that estrogen is not helpful to women with established vascular disease for prevention of cardiovascular disease.

Diet, lifestyle, and the risk of type 2 diabetes mellitus in women

Abstract: Although diet and lifestyle are, by consensus view, important risk factors for type 2 diabetes, previous studies have for the most part examined these factors individually despite the fact that behavioral parameters typically correlate with one another. This study simultaneously evaluated a set of dietary and lifestyle factors simultaneously in relation to the type diabetic risk using data from the Nurses' Health Study. The study population included 84,941 female nurses who at the outset were free of known cardiovascular disease, diabetes, and cancer. Follow-up extended from 1980 to 1996. Behavioral factors were reassessed every 2 years, and diet was assessed using a semiquantitative 61-item food-frequency questionnaire. A low-risk group was distinguished by a body mass index (BMI) below 25, a diet high in cereal fiber and polyunsaturated fat and low in trans fat and glycemic load, daily moderate to vigorous physical activity, no current smoking, and at least half an alcoholic drink each day (on average). BMI proved to be the most important risk factor for type 2 diabetes. The relative risk for those whose BMI was 35 or higher was approximately 39, and that for women with a BMI of 30 to 35 was 20 (compared with women whose BMI was below 23). Even a BMI at the high end of the normal range (23-25) increased the relative risk to 2.7. In all, 61% of cases of type 2 diabetes could be ascribed to being overweight. Other significant risk factors, which remained significant after adjusting for BMI, were lack of exercise, poor diet, current smoking, and abstinence from alcohol. The correlation with physical activity, however, was much stronger without adjusting for BMI. Women who were at low risk for three of the five risk factors had a relative risk of diabetes of 0.12 compared with the rest of the study group. Had all women been in the low-risk cohort, 87% of new cases of type 2 diabetes might have been prevented. Taking surveillance bias into account did not appreciably alter the results. Low-risk status was independent of a family history of diabetes. Using a BMI of 23 rather than 25 as a cutoff point, the population attributable risk increased from 87 to 96%. These findings implicate excessive body fat as the risk factor most predictive of type 2 diabetes. A majority of cases might be prevented by losing weight, exercising regularly, eating a proper diet, abstaining from smoking, and taking limited amounts of alcohol. Of these measures, weight control seems to offer the most benefit.

Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners

Abstract: Virtually all cases of cervical cancer-the second commonest women's cancer worldwide-are a result of infection by oncogenic human papillomavirus (HPV). The authors collated data on 1913 couples enrolled in seven case-control studies of cervical cancer (including carcinoma in situ) to discern the effect, if any, of male circumcision on the risk of both genital HPV infection and cervical cancer. The studies took place in Colombia, Brazil, Thailand, Spain, and the Philippines. Participants were the husbands or stable partners of women with or without cervical cancer. HPV DNA was identified using a polymerase chain reaction assay, which yielded valid results in 1139 men, approximately 75% of those tested. The prevalence of self-reported circumcision was 19.3%, ranging from 1.5% in Colombia to 91% in the Philippines. HPV was detected in 16% of penile specimens overall, in 19.6% of uncircumcised men, and in 5.5% of circumcised men. The odds ratio for infection in circumcised men was 0.37. All studies found an inverse association between circumcision and the risk of HPV infection in men, regardless of whether or not the female partner had cervical HPV infection or had been diagnosed as having cervical cancer. The only other risk factor for penile HPV infection was the number of sexual partners; the odds ratio for men with six or more partners was 2.0. Male circumcision correlated with a moderate, statistically nonsignificant decrease in the risk of cervical cancer in their female partners. The odds ratio for self-reported circumcision was 0.72, and for clinician-confirmed circumcision, 0.69. This relationship was significant for women whose partners engaged in sexual practices known to increase the risk of exposure to HPV. Such practices include intercourse before age 17, six or more sex partners, and contact with prostitutes. This study provides epidemiological evidence that male circumcision lowers the personal risk of genital HPV infection and seems to lower the chance of cervical cancer developing in women who have high-risk sex partners.

The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization

Abstract: Although most studies have failed to demonstrate an elevated risk of major birth defects in children conceived by intracytoplasmic sperm injection (ICSI) or standard in vitro fertilization (IVF), most past work is methodologically problematic and definitions of major defects may differ from those applied to naturally conceived infants. This study examined the prevalence of major birth defects diagnosed within 12 months after birth in infants conceived either naturally or using ICSI or IVF. All births took place in Western Australia in the years 1993 to 1997. Data from a reproductive technology registry identified all pregnancies of at least 20 weeks' gestation. The study population included 301 infants conceived by ICSI; 837 conceived by standard IVF; and 4000 conceived naturally. Infants conceived with assisted methods were likelier than those conceived naturally to be delivered by cesarean section, to be born before term, and to have low birth weight. Major birth defects were identified by age 1 year in 8.6% of infants conceived with ICSI, 9.0% of the IVF group, and 4.2% of naturally conceived infants. In all, infants conceived using assisted reproductive technology were more than twice as likely as those conceived naturally to have a major defect. The difference remained significant when only singleton infants, or only singletons born at term, were analyzed, and after adjusting for maternal age and parity and infant gender. Approximately two thirds of major defects were diagnosed in the first week of life, and more than 90% by age 6 months. Excluding defects that may have been diagnosed early because of close surveillance, the odds ratio for a major defect was 1.8 in the ICSI group and 2.2 in the IVF group. Major defects remained about twice as frequent in these groups as with natural conception after excluding infants known to have inherited conditions and those with metabolic disorders. Musculoskeletal and chromosomal defects were significantly more prevalent with assisted reproductive technology. The IVF group (but not ICSI infants) had significantly more cardiovascular, urogenital, and other defects. Multiple major defects were significantly more frequent in the IVF and ICSI groups. Minor birth defects were diagnosed by age 12 months in less than 1% of all groups. These findings support the possibility of an excessive risk of major birth defects in infants born with the benefit of assisted reproductive technology. Nevertheless caution is in order when establishing associations with particular birth defects.

Primary hyperparathyroidism in pregnancy: evidence-based management.

Abstract: Primary hyperparathyroidism during pregnancy poses significant risks to the mother and the fetus. Fortunately, prompt diagnosis and effective management can improve outcomes for both. There is controversy regarding appropriate management of these patients, especially late in gestation. The objective

A nationwide analysis of complications associated with the tension-free vaginal tape (TVT) procedure

Abstract: This study presents a series of all patients in Finland who underwent the tension-free vaginal tape (TVT) procedure for urinary stress incontinence before the end of 1999. Data regarding numbers of operations and complication rates were collected via questionnaires sent to the 38 hospitals whose staff were trained to perform TVT. The process for teaching this operation was carefully planned. First, urogynecologists from four of the five university hospitals in Finland underwent an extensive training program held at the fifth hospital, where this procedure was developed. Each doctor was approved to perform the procedure only after the main instructor visited his or her facility and observed the local team at work through several TVT operations. The university hospital-based urogynecologist was authorized to train local gynecologists after successfully performing 20 TVT operations with no major problems in 6 months of follow-up. Eventually, a TVT-certified urogynecologist was on the staff at all central and local hospitals in Finland. In all, there were 1455 TVT operations performed in Finland by the end of 1999. The overall rate of complications was 255 per 1000 procedures, including 206 per 1000 in university hospitals, 253 per 1000 in central hospitals, and 283 per 1000 in local hospitals. In the 1455 cases, there were five major complications that required laparotomy (case of arterial bleeding, two undetected bladder perforations, one vesicovaginal fistula, and one case of severe urinary retention) and 362 minor complications that necessitated some form of intervention. Intraoperative blood loss greater than 200 ml was noted in 27 patients (incidence 19/1000). Five cases resolved with minimal vaginal packing. Manual compression, intravenous tranexamic acid, and/or blood transfusion were required in three women. One woman underwent laparotomy for arterial bleeding behind the symphysis with removal of the TVT tape. Bladder perforation occurred in 56 women (38/1000). In 39 cases, the injury was recognized by cystotomy. The TVT needle was removed and reinserted in 36 of these; in 2 others interruption of the operation was required. One perforation was so near the urethral orifice that the TVT tape had to be removed. Nine perforations were noted after the TVT needle had been pulled through the bladder, requiring removal of the tape in two cases and partial removal (behind a midline cut) with reattachment of new tape in seven cases. In six women, the injury to the bladder was not recognized at the time of surgery. The TVT tape had to be partially or wholly removed in all of these patients. Injury of the epigastric vessel injury, which was treated with simple ligation, occurred in one patient. One woman sustained an injury of the obturator nerve that caused her to limp and led to adhesion formation at the Achilles tendon. Surgical evacuation was required for treatment of vagina hematoma in one patient, and the TVT procedure was interrupted in another patient because of a urethral lesion. Postoperatively, 34 women experienced complete urinary retention, with only 1 persisting beyond 3 months (incidence 23/1000). Minor voiding difficulties were reported by 111 patients (incidence 76/1000), 108 of whom resolved spontaneously or with conservative treatment. Two patients were treated by cutting the TVT tape at the midline, and one resolved after 4 months of repeated catheterization.

Incidence and predictors of severe obstetric morbidity: Case-control study

Abstract: Records at 25 maternity units in London covering a 1-year period during 1997-1998 were reviewed to determine the frequency of severe obstetrical morbidity and to identify predictors. The study population of 48,865 women delivering infants during this period included 588 who met criteria for severe obstetrical morbidity. Four conditions were considered: severe bleeding; severe preeclampsia, including hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome and eclampsia; severe sepsis: and uterine rupture. Four control subjects were chosen for each case subject to better detect differences in predictive factors. The incidence of severe obstetrical morbidity in this review was 12 per 1000 deliveries (95% confidence interval, 11.2-13.2). Five maternal deaths were ascribed directly to the study conditions: three to sepsis and one each to bleeding and HELLP syndrome. The ratio of severe morbidity to mortality was 118:1. Disease-specific morbidity rates per 1000 deliveries were 6.7 for severe hemorrhage, 3.9 for severe preeclampsia, ().2 for eclampsia, 0.5 for HELLP syndrome. 0.4 for severe sepsis, and 0.2 for uterine rupture. After adjustment for confounding factors, characteristics independently associated with severe obstetrical morbidity as a whole included age greater than 34 years, nonwhite ethnicity, past or current hypertension, previous postpartum bleeding, emergency cesarean delivery, antenatal hospital admission, multiple pregnancy, and taking iron or an antidepressant before delivery. Few risk factors were independently and significantly associated with the occurrence of severe sepsis or uterine rupture. These findings suggest that severe obstetrical morbidity may be a more sensitive measure of pregnancy outcomes than mortality by itself. Most of these events are related to obstetrical bleeding and severe preeclampsia, and lowering the risk will require attention to the best ways of managing these complications.

Periodontal infection and preterm birth: Results of a prospective study

Abstract: Evidence from past studies suggests that chronic periodontal infection (chronic periodontitis) may be associated with preterm birth. Odds ratios as high as 7.9 are reported for mothers of preterm, low-birth-weight infants. The present prospective study correlated the presence of periodontitis at 21 to 24 weeks' gestation with subsequent preterm birth in 1313 women. Women requiring antibiotic prophylaxis for any reason were excluded. A team of specially trained dental hygienists obtained duplicate estimates of probe depth and attachment level in eight moderately affected nonpregnant patients and were accepted as study participants if their error did not exceed 0.5 mm. Significantly more periodontal disease was found in African American women than in white women. Unadjusted odds ratios for generalized periodontal disease increased with increasing prematurity, but this relationship did not take into account other known risk factors. Odds ratios adjusted for smoking, parity, race, and age disclosed that the risk of preterm birth associated with generalized periodontitis was approximately 4 to 7 times higher than in patients with good periodontal health. Women with severe or generalized periodontitis had an adjusted odds ratio of 4.45 for delivery before 37 weeks' gestational age, 5.3 for delivery before 35 weeks', and 7.1 for delivery before 32 weeks'. These findings support an association between preexisting maternal periodontal disease and preterm birth. A controlled interventional study will be needed to firmly establish a causal link.

Neurological sequelae in children born after in-vitro fertilisation: A population-based study

Abstract: It is recognized that the risk of multiple births, preterm birth, and low birth weight is magnified after in vitro fertilization (IVF), but little is known of the long-term outcome for children born after IVF. This retrospective study, using a population-based cohort of 5680 children born after IVF, sought to clarify the risk of severe neurological disorder, mental retardation, and visual defects. The study children, aged 18 months or older at follow-up, were matched for gender, year of birth, and hospital of birth with 11,360 control children. A second set of control subjects, 4120 twins, was chosen for 2060 of the 5680 study children who were twins born after IVF. Children born after IVF were more likely to require rehabilitation for neurological problems than were control subjects; the odds ratio was 1.7. The risk was 1.4 for singleton infants, whereas for post-IVF twins the risk was not greater than in the control twins. The commonest diagnoses were cerebral palsy (most often spastic diplegia or spastic hemiplegia), suspected developmental delay, congenital malformation, mental retardation, chromosomal aberration, and behavioral disorder. The risk of cerebral palsy was increased nearly 4-fold in post-IVF children. The risk remained after adjusting for gestational age and birth weight. Suspected delayed development also was increased 4-fold in the IVF group; singleton infants had about double the risk of control children. Maternal age did not influence the overall risk of neurological sequelae. The eight post-IVF children with severe visual disorders had an approximately 2-fold increase in risk. Although most children born after IVF are perfectly healthy, they nevertheless are at increased risk for neurological disability or handicap, particularly cerebral palsy. A high rate of twin births is part of the explanation, as are low birth weight and low gestational age. It is estimated that having a single embryo would lower the prematurity rate by approximately 60%. The authors believe that, as a practical clinical matter, only one IVF embryo should be transferred in most cases.

Vaginal evisceration after hysterectomy: A literature review

Abstract: The purpose of this review is to highlight the risk factors, clinical presentation, and different surgical management options for vaginal evisceration after vaginal, abdominal, or laparoscopic hysterectomy. We identified all reports of vaginal evisceration after these procedures using sources in the

Preeclampsia. Part 1: clinical and pathophysiologic considerations.

Abstract: Preeclampsia-eclampsia is still one of the leading causes of maternal and fetal morbidity and mortality. Despite active research for many years, the etiology of this disorder exclusive to human pregnancy is an enigma. Recent evidence suggests there may be several underlying causes or predispositions leading to the signs of hypertension, proteinuria, and edema, findings that allow us to make the diagnosis of the "syndrome" of preeclampsia. Despite improved prenatal care, severe preeclampsia and eclampsia still occur. Although understanding of the pathophysiology of these disorders has improved, treatment has not changed significantly in over 50 years. Although postponement of delivery in selected women with severe preeclampsia improves fetal outcome to a degree, this is not done without risk to the mother. In the United States, magnesium sulfate and hydralazine are the most commonly used medications for seizure prophylaxis and hypertension in the intrapartum period. The search for the underlying cause of this disorder and for a clinical marker to predict those women who will develop preeclampsia-eclampsia is ongoing, with its prevention the ultimate goal. This review begins with the clinical and pathophysiologic aspects of preeclampsia-eclampsia (Part 1). In Part 2, the experimental observations, the search for predictive factors, and the genetics of this disorder will be reviewed.

Cardiovascular outcomes during 6.8 years of hormone therapy: Heart and Estrogen/Progestin Replacement Study follow-up (HERS II)

Abstract: In the Heart and Estrogen/Progestin Replacement Study (HERS), no significant differences in coronary heart disease (CHD) events were noted during 4.1 years of follow-up depending on whether women had or had not been assigned to hormone replacement therapy (0.625 mg of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate daily). There may, however, have been a higher risk of coronary events (nonfatal myocardial infarction, coronary death) in the hormone group in the first 12 months and a decreased risk in years 3 to 5. The present analysis was an attempt to determine whether this later risk reduction persisted during an additional 2.7 years of follow-up, totaling 6.8 years. The 2321 postmenopausal women who continued follow-up in HERS II represented 93% of those who survived. Open-label hormones were prescribed by personal physicians in the second trial phase. Many women randomly assigned to HRT continued on open-label treatment, whereas most of those assigned to placebo chose not to start hormone treatment. In the last 2.7 years of follow-up in HERS II, there was no significant decline in rates of coronary events or secondary cardiovascular events in women assigned to hormones. There was no overall trend toward lower relative hazard figures with a longer duration of hormone treatment. Approximately two thirds of women in the hormone and placebo groups reported having used statins by the end of follow-up. Adjusting for statin use did not substantially alter the results. The relative hazard for CHD events over 6.8 years of follow-up, comparing hormone-treated with placebo women not using statins, was 1.12. For women using aspirin, the figure was 1.01 compared with nonusers. Similar results were obtained when analysis was limited to women who adhered to their assigned treatment. The lower rates of coronary events noted in hormone-treated women in the final years of HERS did not persist during subsequent follow-up. The findings suggest that hormone therapy not be used to lower the risk of cardiovascular events in postmenopausal women with coronary disease.

Noncontraceptive health benefits of intrauterine devices: a systematic review.

Abstract: Most women and their clinicians are unaware that IUDs confer important noncontraceptive health benefits. This review summarizes the evidence from published articles on this topic. We conducted a series of systematic literature searches to identify articles on the noncontraceptive health benefits of IUD use. We reviewed the potentially pertinent ones for content, grouped them according to type of IUD, and evaluated them using the U.S. Preventive Services Task Force rating system. Over 500 titles were identified and several hundred abstracts were reviewed. Use of nonhormonal IUDs (plastic and copper) was associated with a decrease in endometrial cancer. The levonorgestrel intrauterine system can treat a variety of gynecological disorders, including menorrhagia and anemia. The levonorgestrel system has also been used successfully as part of hormone replacement therapy, as adjuvant therapy with tamoxifen, and as an alternative to hysterectomy for women with bleeding problems. Like oral contraceptives, intrauterine contraceptives confer important noncontraceptive health benefits.

Menopausal hormone replacement therapy and risk of ovarian Cancer

Abstract: Most retrospective studies have failed to find an association between hormone replacement therapy (HRT) at menopause and the development of ovarian cancer. In addition, most studies have not distinguished between estrogen-only HRT (ERT) and combined estrogen-progestin therapy (EPRT). The investigators have now analyzed data from the Breast Cancer Detection Demonstration Project (BCDDP) follow-up study, a prospective cohort of 44,241 postmenopausal women seen at 29 US clinical centers. Their mean age at the outset was 56.6 years. Follow-up averaged 13.4 years, totaling close to 590,000 person-years. During this time a total of 329 women developed ovarian cancer. Ovarian cancer correlated inversely with parity, oral contraceptive use, and hysterectomy. No relationship with age at menopause or body mass index was apparent. In the 70% of subjects asked, one fourth of those with ovarian cancer had a first-degree relative with either ovarian or breast cancer. After adjusting for age, type of menopause, and oral contraceptive use, the relative risk (RR) of ovarian cancer in women using ERT only was 1.6. The risk increased with the duration of ERT-only use, reaching 3.2 at 20 or more years of use. Most of these long-term ERT users had undergone hysterectomy. The risk was not limited to particular histological types of ovarian cancer. Compared with women never using ERT, the RR for those using ERT only within the past 2 years was 2.0. Women using EPRT had a RR of only 1.1 compared with those not reporting any form of ERT. When EPRT use followed ERT, the RR was 1.5. The risk of ovarian cancer was not associated with the duration of EPRT. This large-scale prospective study shows that women using ERT, especially for a decade or longer, were at significantly increased risk of developing ovarian cancer. Both long-term ERT users who have had a hysterectomy and others who changed to EPRT were at elevated risk. Short-term EPRT (with no prior ERT) did not seem to increase the cancer risk, but this requires further study.

Intrahepatic cholestasis of pregnancy: review of the literature.

Abstract: Intrahepatic cholestasis of pregnancy (ICP) is a rare disorder of unknown etiology with a symptomatically distressing maternal course with pruritus as the chief complaint. ICP poses little medical risk to the mother, but poses significant risk to the fetus of perinatal mortality, preterm delivery, fetal distress, and meconium staining. ICP has a geographically variable prevalence and appears to have a heritable component. Current evidence suggests a susceptibility to derangements in the sulfation of steroid compounds, affecting the metabolism of progesterone and bile acids in the fetal/placental compartment. This impairs transport of bile acids across the placenta from the fetal to the maternal circulation. Exactly how this leads to fetal compromise is unknown. The most efficacious current medical management that improves both maternal symptoms and laboratory abnormalities is ursodeoxycholic acid (UDCA), a hydrophilic bile acid that alters the composition of the bile acid pool in maternal blood. When ICP is diagnosed, UDCA coupled with close maternal-fetal surveillance is indicated. Delivery should be effected near term, with confirmation of fetal lung maturity or earlier if fetal compromise is identified.

The association of Apgar score with subsequent death and cerebral palsy: A population-based study in term infants

Abstract: Today, fewer newborn children in Norway have low Apgar scores than was formerly the case, but it is not clear whether improved obstetrical practices will affect the score's predictive value. This population-based cohort study estimated the risk of adverse outcomes associated with a low Apgar score in approximately 235,000 children born in Norway in the years 1983-1987. All had a birth weight of 2500 g or greater, and none had birth defects (other than congenital hip dislocation) when followed to age 8 to 12 years. A 5-minute Apgar score of 3 or lower was recorded in 0.1% of infants, whereas 0.6% had scores of 4 to 6. The former group had neonatal and infant mortality rates of 16.4 and 19.2%, respectively. Mortality was 3% between ages 1 and 8 years for children with scores of 0 to 3. Of those who lived beyond age 12 months despite a score of 0 to 3, 6.8% were receiving benefits because of cerebral palsy (CP) by age 8 to 12 years. Compared with infants whose 5-minute Apgar scores were 7 to 10, those with scores of 0 to 3 were 386 times likelier to die neonatally, 76 times likelier to die within the first year of life, and 81 times more likely to develop CP. These effects were even more marked when 1- and 5-minute Apgar scores were combined. Neonatal deaths were increased 642-fold when both scores were 3 or lower. Parent reports of CP coincided completely with a discharge diagnosis of CP. Both low Apgar scores and later CP correlated with seizures, feeding problems, and respiratory difficulty in the first week of life. Low Apgar scores were strongly associated with both infant death and CP in this population, in which low scores are relatively infrequent. These findings suggests that the Apgar score still is important for the early detection of infants at increased risk for serious or fatal conditions.

Development and validation of a multifactorial risk index for predicting postoperative pneumonia after major noncardiac surgery

Abstract: Pneumonia is the third most common postoperative infection and is a frequent component in postoperative fatalities related to pulmonary complications. This article presents a multifactorial risk index for predicting postoperative pneumonia that was developed for the National Surgical Quality Improvement Program (NSQIP). The model was created from the records of patients enrolled in NSQIP who were undergoing major noncardiac surgery in 100 Veterans Affairs medical centers. Included in the analysis were patients who met the Centers for Disease Control and Prevention definition of nosocomial pneumonia after surgery and those with postoperative respiratory failure or unplanned intubation before a diagnosis of post-operative pneumonia. A logistic regression analysis was performed using potential risk factors as the independent variables and postoperative pneumonia as the dependent variable. Factors that did not reach significance were deleted from the logistic regression model. As the model developed, potential variables were reintroduced and retained only if they reached statistical significance. A total of 206,434 patients were enrolled in the study in the 24 months from September 1997 to August 1999. Twenty-two percent of the enrollees had either confounding pulmonary conditions or insufficient recorded data and were excluded from analysis, leaving 160,805 patients available for development of the model. The model was validated using a second cohort of 155,266 patients (20% of 195,046 total enrollees) who were enrolled between August 1995 and September 1997. In the model development group, there were 2466 patients (1.5%) who developed postoperative pneumonia. There was a statistically significant difference in the mean ages of the patients with (68.9 years) and without (61.2 years) postoperative pneumonia (P <.001). Twenty-one percent of the patients who developed pneumonia died within 30 days of surgery, compared with 2% of the patients without postoperative pneumonia (P <.001). Factors that did not have a significant influence on the development of postoperative pneumonia were preoperative serum creatinine concentration, history of diabetes mellitus, congestive heart failure, ascites, dialysis dependence, recent chemotherapy, preoperative renal failure, and dyspnea. Variables that did reach significance were those related to the type of surgery, type of anesthesia, general health and immune status, resporatory status, neurologic status, and fluid status. With this information, a logistic regression model of preoperative predictors of postoperative pneumonia was developed. The types surgery with the lowest risk of postoperative pneumonia included peripheral vascular, dermatological, lower abdominal, urogenital, extremity, spine and back operations,and ear, eye, nose and throat procedures. Abdominal aortic aneurysm repair or thoracic surgery carried the highest risk for postoperative pneumonia. Emergency surgery and use of general anesthesia were each associated with an increased likelihood of developing postoperative pneumonia.

The relation of reproductive factors to mortality from breast cancer

Abstract: Two recent studies report that in women who are less than 45 years old when diagnosed with breast cancer, those ever giving birth to a live infant or giving birth in the past 2 years are likelier to die than are nulliparous patients. The present population-based cohort study examined breast cancer mortality from 1983 through 1992 in 1174 women aged 45 and younger at the time invasive ductal breast cancer was found. Tumor characteristics were compared in nulliparous women and those giving birth 5 years or longer before breast cancer was diagnosed. The mean follow-up was nearly 9 years. A complete histopathological review was carried out, and in 70% of cases enough tumor tissue was available for immunoperoxidase assays of estrogen and progesterone receptors, p53 tumor suppression gene protein, Ki-67 proliferation-related antigen, and c-erbB-2 oncogene protein. Women who ever gave birth had a 40% risk of death from breast cancer within 5 years after diagnosis. The hazard ratio, compared with nulliparous women, was 1.4, and this figure was unchanged at the end of follow-up. Mortality risk in the first 5 years after diagnosis was increased in women whose first or last birth was at age 30 or later. The risk was highest for those whose last birth occurred within 2 years after diagnosis; the hazard ratio was 2.3. At the end of follow-up, 48% of women with a recent birth, 23% of nulliparous women, and 24% of those whose last birth was at least 5 years previously had died. A history of spontaneous or induced abortion did not increase the mortality risk. Women who had ever given birth were likelier to be p53-positive and have an elevated Ki-67 ratio, and they also were more likely to have positive lymph nodes at the time of diagnosis. The chance of having a p53-positive tumor was increased in women whose first or last birth occurred at age 20 or later, compared with nulliparous women. Women giving birth within 2 years of diagnosis were more likely to have high-grade tumors, a high level of mitoses, a high S-phase fraction, and positive lymph nodes. In addition, their tumors were likelier to be progesterone receptor-negative and p53-positive than were tumors from nulliparous women. Women giving birth within 5 years after diagnosis were likelier than others to have large tumors. These findings support an influence of reproductive factors on the behavior of breast cancers in women less than 45 years of age. It is important to recall that women who have delivered a child within the past 5 years have poorer survival than nulliparous women and those whose most recent birth took place some years ago.

Identification of an angiogenic mitogen selective for endocrine gland endothelium

Abstract: The microvascular endothelium in endocrine glands is very permeable to circulating substances and secretory products, reflecting the need for rapid hormone release in response to homeostatic stimuli. Fenestrae, specialized discontinuities of the endothelial plasma membrane, presumably permit high permeability, but their presence does not strictly correlate with the expression of vascular endothelial growth factor (VEGF). The authors have identified a distinct angiogenic mitogen selective for endocrine-gland endothelium. It is very similar biologically to VEGF and is able to induce fenestration in target cells, but it does not exhibit structural homology with the family of VEGF proteins. Expression of this factor, termed endocrine gland-derived VEGF (EG-VEGF), is largely restricted to steroidogenic glands. When a library of purified human secreted proteins was screened for their ability to promote the proliferation of bovine adrenal cortex-derived endothelial (ACE) cells (which respond to VEGF), EG-VEGF was identified as the only one that could induce a reproducibly strong mitogenic response. The increase in ACE cells exposed to EG-VEGF was very similar to that induced by VEGF, and both of these substances induced fenestration of endothelial cells. The expression of EG-VEGF was induced by hypoxia, which strongly promotes angiogenesis under both physiological and pathological conditions. On testing a wide range of human tissues and cell lines, EG-VEGF was found only in ovary, testis, adrenal, placenta, and (to a lesser degree) prostate. Using adenovirus to deliver EG-VEGF locally in a sustained manner, frank angiogenesis was observed with mitotic endothelial cells, edema, and granulation tissue. EG-VEGF protein was produced at a high level in skeletal muscle. Intraovarian delivery of either EG-VEGF or VEGF adenovirus led to marked enlargement of the ovaries, grossly visible blood vessels, and areas of hemorrhage. Microscopy revealed intense angiogenesis at the periphery of ovarian cysts. Steroidogenic glands may have developed highly specific local mechanisms that serve to "fine tune" the action of the VEGF receptors. EG-VEGF is one of a class of highly specific mitogens that help regulate the proliferation and differentiation of vascular endothelium in a tissue-specific manner. Mitogens specific for cardiac or skeletal muscle endothelium might hold great therapeutic potential.

Early Maternal and Neonatal Morbidity Associated With Operative Delivery in Second Stage of Labour: A Cohort Study

Abstract: Obstetricians frequently must decide the best way of minimizing morbidity when labor arrests at full cervical dilation. This prospective cohort study contrasted maternal and neonatal morbidity when selecting either instrumental vaginal delivery or cesarean delivery. The study group, 393 women, all had a singleton pregnancy at term with cephalic presentation, and all delivered a liveborn infant. Cesarean delivery was performed in 209 instances, and instrumental vaginal delivery succeeded in 184 cases. Roughly one fourth of women had immediate section with no attempt at vaginal delivery. Cesarean delivery was likelier after attempted ventouse delivery than after an attempt at forceps delivery. There were 58 deliveries using forceps alone, 67 ventouse deliveries, and 59 utilizing both methods. Risk factors favoring cesarean delivery included a maternal body mass index greater than 30, a birth weight above 4 kg, an occipitoposterior presentation, and station at the ischial spines. Suspected fetal distress was similarly frequent in the two groups. No women died, and none had thromboembolism. Major bleeding was more frequent with cesarean delivery but less likely if done by a senior rather than a middle-grade trainee. Discharge within 48 hours was likelier after vaginal delivery. Serious maternal injuries included extension of the uterine incision and third-degree vaginal tears. There were no perinatal deaths, but two infants had symptoms of hypoxic-ischemic encephalopathy. Trauma such as facial and scalp bruising was significantly less common after cesarean delivery. Six vaginally delivered infants had brachial plexus injuries. Two infants had intracerebral bleeding when cesarean delivery was performed after failed instrumental delivery. Neonatal trauma was significantly likelier after failed vaginal instrumental delivery than after immediate cesarean delivery but less common than with successful instrumental delivery. This study supports the use of safe instrumental vaginal delivery when labor arrests, given appropriate circumstances such as availability of an operating theater and a skilled obstetrician. This approach is favored over cesarean delivery unless cephalopelvic disproportion is clearly present.