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Few studies have assessed longitudinal changes in circulating cytokine levels during normal pregnancy. We have examined the natural history of maternal plasma cytokines from early- to mid-pregnancy in a large, longitudinal cohort. Multiplex flow cytometry was used to measure interleukin (IL)-2, IL-6, IL-12, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) in early- (median [IQR]: 8.5 weeks [7.1, 10.0]) and mid-pregnancy (25.0 [24.1, 26.1]) from 1274 Danish women delivering singleton term infants. GM-CSF decreased from early- to mid-pregnancy (median percent change [95% CI]: -51.3% [-59.1%, -41.8%]), while increases were observed in IL-6 (24.3% [4.6%, 43.9%]), IL-12 (21.3% [8.9%, 35.7%]) and IFN-gamma (131.7% [100.2%, 171.6%]); IL-2 (-2.8% [-11.5%, 0.0%]) and TNF-alpha (0% [-5.9%, 25.6%]) remained stable. Positive correlations were found between all cytokines, both in early- and mid-pregnancy (all p<0.001). Early- and mid-pregnancy levels were rank-correlated for IL-2, IL-12, TNF-alpha and GM-CSF, but not IL-6 and IFN-gamma; these correlations were generally weaker than correlations between different cytokines at a single time point in pregnancy. Women with a pre-pregnancy BMI <18.5 had reduced levels of IFN-gamma and GM-CSF compared to women in other BMI categories, while women aged >or=35 years had elevated IL-2, IL-6, TNF-alpha and IFN-gamma. Early-pregnancy levels of TNF-alpha were higher in women with a prior preterm delivery. Cytokine levels were not associated with gravidity. In conclusion, cytokines were detected in plasma during early- and mid-pregnancy, with IL-6, IL-12, IFN-gamma and GM-CSF concentrations varying over pregnancy. Concentrations may depend on BMI, maternal age and prior preterm delivery.

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Tests based on three different principles are reported to measure the activity of von Willebrand factor (VWF): ristocetin cofactor (VWF:RCo), collagen binding (VWF:CB), and the so-called "activity ELISA" (VWF:MoAb). We measured these and other diagnostic parameters in a population of 123 randomly selected female study controls, age 18-45 years. Type O subjects had significantly lower levels than non-O subjects in each test. Race differences were seen in all tests except VWF:RCo, with Caucasians having significantly lower levels than African-Americans. ABO differences accounted for 19% of the total variance in VWF:Ag (P < 0.0001) and race for 7% (P < 0.0001), for a total of 26%. Both effects were mediated through VWF:Ag and were independent. VWF:Ag level was the primary determinant of VWF function, accounting for approximately 60% of the variance in VWF:RCo and VWF:CB and 54% of the variance in factor VIII. The ratio VWF:RCo/VWF:Ag differed significantly by race within blood group. The median ratios were 0.97 for type O Caucasians vs. 0.79 for type O African-Americans and 0.94 for non-O Caucasians vs. 0.76 for non-O African-Americans. The ratio VWF:CB/VWF:Ag did not vary. This suggests racial differences in the interaction of VWF with GP1b but not with subendothelium. Alternatively, VWF:RCo may be regulated to maintain a relatively constant plasma level in the presence of excessive VWF:Ag. This heterogeneity within the normal population is partially responsible for the difficulty in defining diagnostic limits for von Willebrand disease.

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In order to describe potential hypofibrinolytic tendencies in young (< 35 years) polycystic ovary syndrome (PCOS) patients, we studied plasminogen activator inhibitor (PAI-1) system components in women without laboratory evidence of hyperinsulinism or hyperandrogenism. The study was a prospective, observational comparison and took place in a major urban infertility referral center. Age, body mass index, ovulatory status, selected androgen levels, fasting insulin and plasma lipids were measured in subjects with PCOS (n = 39) and normal control subjects (n = 20). Women with PCOS had higher mean serum total testosterone and androstenedione levels compared with controls (56.4 versus 40.3 ng/dl, p = 0.03, and 179 versus 133 microg/ml, p = 0.03, respectively). Mean fasting insulin levels were higher among PCOS women (p < 0.01) and were strongly correlated with PAI-1 antigen (Ag) (r = 0.46), PAI-1 activity (r = 0.43), and tissue plasminogen activator (t-PA) (r = 0.5). Correlations were evident in both PCOS and control subjects. Mean PAI-1 Ag, PAI-1 activity, and t-PA levels were significantly elevated (p = 0.003, 0.001, and 0.001, respectively) in PCOS. ANOVA was performed to control for insulin effect; a trend toward elevated PAI-1 in PCOS persisted but was no longer statistically significant (p = 0.24). PAI-1 activity elevation remained in PCOS women with mean fasting insulin levels < 10 mIU/ml (p = 0.02), yet the difference became less significant when insulin was controlled (p = 0.38). Although these data confirm known associations between insulin and PAI-1 derangements, this is the first study to quantify discrete PAI-1 elevations that persist in the setting of PCOS even with normal or low ambient insulin levels. Additional prospective studies are needed to determine whether this altered PAI-1 state is associated with a clinically important hypofibrinolytic condition and subsequent poor reproductive outcome.

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BACKGROUND: Although the prevalence of fetal alcohol syndrome (FAS) varies within the population, few data are available concerning variation in the prevalence of prenatal drinking. METHODS: Postpartum women delivering singleton infants at two Atlanta hospitals in 1993 or 1994 were interviewed. Those delivering infants who were small for gestational age (SGA) (n = 638) were over-sampled relative to those delivering infants with birth weights that were appropriate for gestational age (AGA) (n = 247). The prevalence of prenatal drinking was estimated as a weighted average of reports from mothers of SGA and AGA infants. Estimates of the prevalence of FAS come from the Metropolitan Atlanta Congenital Defects Program (MACDP) of the Centers for Disease Control and Prevention. RESULTS: The prevalence of first-trimester drinking was half that reported for the three previous months (private hospital: 72% vs. 35%; public hospital: 52% vs. 28%). Most women (85%) reported abstaining throughout the second trimester. Fewer than 10% of women delivering at the public hospital (7.5%), but one-quarter of those delivering at the private hospital, reported third-trimester drinking. Binge, moderate and heavy drinking in pregnancy were more common among women delivering at the public hospital. Eight infants born at the public hospital during this period, but none of those born at the private hospital, were identified as possibly having FAS; four of the eight were identified as probably having FAS. CONCLUSIONS: These results have implications for health education programs. For example, obstetricians in private practice may wish to reaffirm their advice to abstain from drinking in the third trimester. They also suggest that prenatal abstinence programs be targeted at populations identified as most likely to engage in risky drinking.

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OBJECTIVE: To assess the medical, gynaecological and reproductive experiences of women with von Willebrand's disease (VWD) and to evaluate the impact of VWD on mental health and life activities. METHODS: A total of 102 women with VWD who were registered in haemophilia treatment Centres (HTCs) in the United States and 88 controls were interviewed regarding medical, gynaecological and reproductive history, life activities and symptoms of depression. Symptoms of depression were measured using the Center for Epidemiological Studies Depression Scale (CES-D). RESULTS: Excessive bleeding symptoms were reported in 74% of VWD cases compared with 6% of controls. Women with VWD had a higher prevalence of menorrhagia, excessive postpartum bleeding, other gynaecological conditions, arthritis and migraine headaches than did controls. More VWD cases than controls reported that menstruation had a negative impact on overall life activities. No difference in the prevalence of depression was found between cases and controls. DISCUSSION: Women with VWD experience menorrhagia and other gynaecological conditions at a higher frequency than women without bleeding disorders. Menstruation in women with VWD has a negative impact on life activities. The prevalence of depression was not elevated in this group of women whose VWD is being managed in an HTC.

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PURPOSE: To determine the diagnostic performance of T(2)-weighted (T2w) and gadolinium-enhanced T(1)-weighted (T1w-Gd-enhanced) MR urographic images for virtual endoscopy of the urinary tract. MATERIALS AND METHODS: 36 patients underwent MR urography at 1.5 T. In each patient a T2w (3D-TSE, respiration-triggered) and a T1w-Gd-enhanced sequence (T1-FFE, breathhold) were acquired. Data reconstruction was performed as maximum intensity projection (MIP) and virtual endoscopy (VE). RESULTS: Combined analysis of MIP and VE delineated 32 of 36 pathologies; 86 % (19/22) of intraluminal pathologies could be depicted by VE and 15 % (3/22) by MIP (p

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OBJECTIVE: To develop a questionnaire to assess the acceptability of amblyopia treatment and its effect on the child and family. METHODS: A 20-item parental survey was developed and pilot tested on 64 subjects, aged 3 to 6 years, participating in the Amblyopia Treatment Study, a randomized trial comparing patching and atropine as treatments for moderate amblyopia. The survey was administered after 4 weeks of treatment. A descriptive item analysis and an internal consistency reliability analysis were performed. RESULTS: Nineteen of the 20 items demonstrated adequate variability as evidenced by the frequency distributions for item responses. Only 4 (<1%) of 1280 possible item responses were missing, one each by 4 different respondents. Factor analysis identified 3 treatment-related factors--"adverse effects," "compliance," and "social stigma"--among 11 of the 20 items. The internal-consistency reliability alpha for the 5-item adverse effects subscale was 0.82, the 4-item compliance subscale alpha was 0.81, and the 2-item social stigma subscale alpha was 0.84. CONCLUSIONS: The Amblyopia Treatment Index appears to be a useful instrument for assessing the impact of amblyopia treatment in 3- to 6-year-old children.

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OBJECTIVE: To describe serum levels of human chorionic gonadotropin (hCG) as a function of hCG injection method (subcutaneous vs. intramuscular) among infertile women undergoing ovulation induction. DESIGN: Prospective, randomized clinical trial. SETTING: Major urban infertility referral center. PATIENT(S): Women presenting for infertility evaluation and ovulation induction. INTERVENTION(S): Controlled ovarian hyperstimulation was followed by 5,000 IU urinary (nonrecombinant) hCG injection, given intramuscularly (i.m.) or subcutaneously (s.c.). MAIN OUTCOME MEASURE(S): Serum hCG levels measured 24 hours after administration of hCG, and patient tolerability of injected hCG. RESULT(S): There were no statistically significant differences in age or body mass index (BMI) among patients receiving hCG s.c. (n = 13) or i.m. (n = 15). Mean [IQR (25; 75)] serum hCG levels in the s.c. and i.m. groups were 171.7 [27.0; 207.0] and 142.2 [102.5; 157.5] mIU/mL, respectively. No adverse events were registered by any patient receiving hCG by either injection method. In this non-IVF population, two pregnancies were established in each subgroup (4 of 28, or approximately 14% pregnancy rate). CONCLUSION(S): The s.c. administration of 5,000 IU hCG (reconstituted in vol. = 0.5 mL) was well tolerated by all women in this study and was associated with postinjection serum hCG levels similar to those observed after administration of an equivalent i.m. hCG dose. This investigation suggests that clinical use of s.c. hCG is suitable for lean women (e.g., BMI <30) undergoing ovulation induction, but additional data are needed to study the appropriateness of s.c. hCG administration in heavier patients.

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Necrotizing fasciitis is a rare soft tissue infection and a life-threatening emergency, often fatal. Its incidence and management are described plentifully in the medical literature regarding the most common anatomical sites involved like the abdomen, lower and upper limbs, and perineum. However, available data and case reports of chest wall necrotizing fasciitis after thoracic procedures are scarce, mainly after major cardiac operations. We report and discuss a case of necrotizing fasciitis of the chest wall occurring in the immediate postoperative period of a cardiac procedure, and include a brief review of the concepts, pathophysiology, and treatment reported in the medical literature. We emphasize the need for early diagnosis and urgent and effective surgical debridement. Of importance is the fact that we have not found any references in the literature to cases similar or equal to the one we describe here, which occurred in the postoperative period of a cardiac procedure.

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OBJECTIVE: To estimate the prevalence of von Willebrand disease and other bleeding disorders in women with and without diagnosed menorrhagia. METHODS: Women with menorrhagia were identified among members of a health maintenance organization in the southeastern United States through a computer search for appropriate International Classification of Diseases, 9th Revision codes. A random sample of members with no such code was selected as controls. The study included 121 women with menorrhagia and 123 controls. Subjects were interviewed in person, and blood was drawn for coagulation testing. Laboratory results for menorrhagia patients were compared with those in controls using race and blood type specific ranges developed from the control group. A test was considered abnormal if it exceeded two standard deviations below the control mean. RESULTS: Bleeding disorders (von Willebrand disease, factor deficiency, or a platelet abnormality) were diagnosed in 10.7% of menorrhagia patients and 3.2% of controls (P =.02). von Willebrand disease was present in eight menorrhagia patients (6.6%) and in one control (0.8%) (P =.02); separate analyses by race revealed a von Willebrand disease prevalence of 15.9% among white and 1.4% among black menorrhagia patients (P =.01). Women with bleeding disorders did not differ significantly from controls in other symptoms of bleeding. CONCLUSION: The prevalence of inherited bleeding disorders among white women with menorrhagia was substantial, consistent with European data published recently. For unknown reasons, the prevalence of von Willebrand disease was lower among black women. These findings indicate the importance of considering inherited bleeding disorders as a cause of menorrhagia.

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White-lipped peccaries are non-seasonal breeders in South America, but little is known about their reproduction in Central America. There are few studies about the sex ratio of this species in the field. We studied the reproduction and sex ratio of white-lipped peccaries during 200 hours of field observation of four radiomarked and two unmarked herds, from July 1996 to April 1997, in Corcovado National Park, Costa Rica. Sex ratio data of three additional, radiomarked herds observed in 1998 were also included. We recorded numbers of mountings, presence of newborns and numbers of nursing interactions. The peccaries showed a distinct reproductive seasonality, with one mating peak in February and another in July. The greatest number of newborns and the peak in nursing activity were observed during July and August, when fruit availability for the peccaries was high. The adult sex ratio was significantly female biased (1.4:1-1.8:1), also in contrast with South American populations.

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PURPOSE: A monkey model was used to evaluate intraocular lenses (IOLs) and extended-wear contact lenses (EWCLs) for the optical treatment of infantile aphakia in humans. Specifically, the relative effectiveness of EWCLs used alone and IOLs used in combination with EWCLs in preventing amblyopia was assessed. METHODS: A total of 33 rhesus monkeys was studied in this project, 24 assigned to experimental treatment groups and 9 to normal controls. Contact lenses made from a diffusing material or dyed opaque were placed on one eye at birth to simulate an infantile cataract. A unilateral lensectomy was then performed on the same eye within 2.5 weeks after birth. In 15 monkeys this was combined with implantation of an IOL. The eyes were left aphakic in the remaining 9 animals. EWCLs were used to adjust the optical correction of both aphakic and pseudophakic eyes to a near point (3-5 D). Opaque lenses were used to maintain daily part-time (approximately 70%) occlusion of the fellow eye. The primary outcome measure was grating acuity assessed with behavioral methods. Some animals were also assessed for acuity with sweep visually evoked potentials (VEPs) and for optotype acuity (Landolt C) with behavioral methods. RESULTS: Two of the animals with IOLs developed complications in the eye that precluded completion of the behavioral assessment protocol. Only behavioral outcomes obtained before or in the absence of surgical complications are presented. There was a developmental delay in the maturation of grating acuity in both eyes of both treatment groups. Normal adult levels of grating acuity were eventually achieved in the group treated with IOLs combined with EWCLs. Grating acuity was significantly poorer than normal in aphakic eyes treated only with EWCLs. Comparison of the two treatment groups revealed that pseudophakic eyes treated with multifocal IOLs had significantly better gating acuity than aphakic eyes. Assessments of optotype acuity and sweep VEP acuity revealed amblyopic deficits in both pseudophakic and aphakic eyes. CONCLUSIONS: Given an absence of serious postoperative complications, neonatal correction of aphakia with IOLs combined with EWCLs can lead to normal grating acuity in a primate model. Correction with EWCLs alone was not sufficient to produce normal grating acuity. Multifocal IOL treatments combined with EWCL provided a significantly better outcome than EWCL methods alone. However, neither IOL nor EWCL methods were able to prevent amblyopia as evaluated using behavioral testing with optotypes or with sweep VEPs.

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The authors evaluated the relation between adequacy of prenatal care and risk of delivery of full term small-for-gestational-age (SGA) infants. Data were derived from maternally linked birth certificates for 6,325 African-American women whose first two pregnancies ended in singleton, full term live births in Georgia from 1989 through 1992. The authors used stratified analysis to assess the effect of prenatal care on the risk of having an SGA baby in the second pregnancy among women with and without an SGA baby in their first pregnancy. The group of women with a history of SGA birth may be more likely to include persons for whom SGA delivery is related to factors, such as genetics, that are not amenable to intervention by prenatal care. Inadequate prenatal care was not associated with the risk of SGA delivery among women who had previously delivered an SGA baby. In unadjusted analyses, inadequate prenatal care was associated with an increased risk of delivering a full term SGA baby in the second pregnancy among women whose first baby was not SGA (risk ratio = 1.28; 95% confidence interval: 1.05, 1.55). The association did not persist when data were adjusted for confounding variables (odds ratio = 1.11; 95% confidence interval: 0.89, 1.38). Regardless of outcome in the first pregnancy, adequate prenatal care did not reduce the risk of full term SGA birth among second pregnancies in this population.

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Misclassification frequently leads to bias in epidemiological studies, and causes concern for perinatal epidemiologists interested in using birth certificates as a data source. We used a maximum likelihood method to estimate the classification probabilities (conditional probabilities that indicate the probability of classification in a particular category, given the person's true category) of two data sources for a three-category outcome of prenatal care. The probability that women receiving adequate or inadequate care were correctly classified was estimated to be greater than 90%. The probability was much lower (< 35%) that women receiving intermediate care were correctly classified. The misclassification women from the intermediate category resulted in poor predictive values (< 70%) of women classified as receiving either adequate or inadequate care. Because of these findings, we combined the adequate and intermediate categories to form a two-category classification system. This revision resulted in higher positive predictive values (> 90%) with only a slightly lower classification probability (> 85%) for the combined category. We conclude that the degree of accuracy for a two-category classification of prenatal care based upon birth certificate information is acceptable, but we question the accuracy of indices of prenatal care with more than two categories.

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A longitudinally linked data set for Georgia was used to identify characteristics, including previous prenatal care use and complications at the first birth, associated with prenatal care use in the second pregnancy among 8,224 African-American women. More than 70% of the women who were < 25 years of age at their first birth (younger women) and almost 40% of women who were > or = 25 years at their first birth received inadequate care with at least one of their first two births. Women who received inadequate care in their first pregnancy were more likely to receive inadequate care in their second pregnancy than women who received adequate care in their first pregnancy. Younger women with a history of a stillbirth, neonatal death, or vacuum extraction were less likely to receive inadequate care in their subsequent pregnancy. Although this study was not able to evaluate the content of prenatal care, it suggested that many African-American women may not receive sufficient care to prevent adverse pregnancy outcomes. Women who receive inadequate care in their first pregnancy must be targeted for interventions that help them overcome economic, situational, or attitudinal barriers to receiving adequate care in their next pregnancy.

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Cholecystokinin (CCK) and related peptides are supposed to be potent analgesic neuropeptides. Studies in rodents suggest a dose-dependent biphasic effect. The present study aimed to examine the pain modulating effect of different doses (0.5 microgram and 5 micrograms) of ceruletide (CRL), infused i.v. for 30 min. Pain thresholds were obtained for ischemic, mechanical, and thermal pain. In addition, pain tolerance was measured for mechanical pain. According to a placebo-controlled double-blind within-subject design 25 healthy men attended three experimental sessions each. Pain perception was measured as a baseline and twice after the infusion. The effect of both doses of CRL to enhance the pain threshold for thermal stimuli is in line with former studies. However, perception of heat stimuli above or below the threshold was not substantially affected by CRL treatment. Algesic properties of CRL are also indicated, because the tolerance for mechanical pain decreased after administration of the high dose of CRL. Perception of ischemic pain was not obviously influenced by any of the treatments. The role of CRL in human pain modulation seems to vary, depending on the type of experimental pain.

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OBJECTIVES: Smoking has been linked to small cognitive, achievement, and behavioral deficits but has not been associated with more severe cognitive impairments. This investigation evaluated the relationship between maternal smoking during pregnancy and idiopathic mental retardation (MR). METHODS: Data on maternal smoking during pregnancy were obtained during face-to-face interviews with the mothers of 221 children with idiopathic MR and the mothers of 400 children attending public school. All children had been born in the five-county metropolitan Atlanta area in 1975 or 1976 and were living in the area when they were 10 years of age. We used exposure odds ratios (ORs) to assess the relationship between maternal smoking and MR, controlling for sex, maternal age at delivery, race, maternal education, economic status, parity, and alcohol use. RESULTS: Maternal smoking during pregnancy was associated with slightly more than a 50% increase in the prevalence of idiopathic MR (adjusted OR, 1.6; 95% confidence interval, 1.0-2.4), and children whose mothers smoked at least one pack a day during pregnancy had more than a 75% increase in the occurrence of idiopathic MR (OR, 1.9; 95% confidence interval, 1.0-3.4). This increase was neither accounted for by other sociodemographic risk factors for MR nor explained by an increase in the prevalence of low birth weight among the children of smokers. CONCLUSIONS: Our data suggest that maternal smoking may be a preventable cause of mental retardation.

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PURPOSE: To compare treatment strategies for Staphylococcus aureus endophthalmitis, we created an animal model in an aphakic rabbit eye and tested six different approaches to treatment. METHODS: Rabbit eyes were rendered aphakic, and three weeks postoperatively, S. aureus organisms were injected into the vitreous cavity. One group was maintained as a control. Twenty-four hours after bacterial injection, six different treatment groups were created for comparison. Clinical inflammation scores, culture results 48 hours after treatment, histopathologic gradings, and development of total corneal opacity three weeks after treatment were assessed. RESULTS: Injection of vancomycin hydrochloride into the vitreous cavity was more effective than injection of cefazolin sodium (P = .01) in reducing the percentage of eyes that had positive culture results and also resulted in lower inflammation scores. Vitrectomy plus injection of either antibiotic was more effective than injection of the same antibiotic alone in reducing culture-positive results and reducing clinical inflammation scores. addition of systemic corticosteroids to intravitreal antibiotic injection did not improve any measure of outcome. Vitrectomy and injection of intravitreal vancomycin was the most effective strategy to sterilize the vitreous cavity, resulting in the lowest inflammation scores and the smallest percentage of eyes with opaque corneas. CONCLUSION: In an animal model of S. aureus endophthalmitis, the combination of vitrectomy and injection of intraocular vancomycin was the most effective strategy for rapidly controlling the infective process and improving the outcomes measured three weeks after treatment.

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BACKGROUND: We created a standardized model of severe Staphylococcus aureus endophthalmitis in the aphakic rabbit eye to test various treatment strategies involving corticosteroid administration in addition to vitrectomy and antibiotic treatment. MATERIALS AND METHODS: In 71 aphakic New Zealand albino rabbit eyes, experimental endophthalmitis was created by injecting 10(5) colony-forming units of Staphylococcal aureus. The animals were divided into 5 groups. One control group was followed up without treatment, while 4 groups were treated with vitrectomy and intraocular cefazolin injection. Two groups were also treated with intramuscular methylprednisolone, 1 group beginning on the day of surgery and 1 group beginning on the following day. In the final group, dexamethasone, 400 micrograms, was injected into the vitreous cavity at the close of surgery. Culture results were compared on the first 2 days after surgery. Inflammatory scores, including development of total corneal opacity, were assessed over a 21-day follow-up period, and histopathologic grading was carried out at the conclusion of the clinical observations. RESULTS: Simultaneous administration of systemic corticosteroids beginning on the day of vitrectomy decreased inflammatory scores 1 week after institution of therapy but did not affect final scores. Delay of initiation of intramuscular corticosteroid until the first postoperative day negated the positive effects. Administration of intraocular corticosteroids was associated with an increase in inflammatory scores throughout the period of observation, an increase in percentage of eyes that developed opaque corneas, an increase in choroidal inflammation graded moderate or severe, and an increase in retinal necrosis compared with vitrectomy and cefazolin injection alone. CONCLUSIONS: This data suggest caution in the use of intraocular corticosteroids in treatment of severe endophthalmitis.

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