Renal biopsy in the management of lupus nephritis during pregnancy.

The differential diagnosis of proteinuria and hematuria in pregnancy is broad and includes active lupus nephritis. Identification of the correct diagnosis often has a profound therapeutic impact on not only the mother but also the fetus. To date, relatively few reports exist on the role of renal biopsy during pregnancy among women with systemic lupus erythematosus (SLE). We present a case series of 11 pregnant women with SLE who underwent a renal biopsy to evaluate a presumptive flare of lupus nephritis. The electronic medical record was retrospectively analyzed for pre-biopsy serum creatinine, proteinuria, hematuria, antinuclear antibodies (ANA), and antibodies to double-stranded DNA (anti-dsDNA); histologic findings on renal biopsy; and the clinical course of each mother and fetus. From 2001 to 2012, 11 pregnant women with SLE flares during pregnancy underwent a renal biopsy at an academic tertiary medical center. At the time of biopsy, median gestational age was 16 weeks (range 9 to 27), median serum creatinine was 0.6 mg/dl (interquartile range 0.5 to 0.9), six (55%) had hematuria, and all had proteinuria >500 mg/24 hours. Proliferative lupus nephritis was found in 10 (91%) of 11 biopsies (five with ISN/RPS Class III; five with ISN/RPS Class IV). All but one individual underwent a change in management guided by information gleaned from renal biopsy. No apparent biopsy-related complications occurred to mother or fetus. Three women elected to terminate their pregnancy; although many factors were involved, the findings on renal biopsy informed the decision-making process. Among the remaining cases, there were three pre-term deliveries, one fetus with complete heart block, one in utero demise, and one maternal death. Renal biopsy is helpful at informing the management of patients with lupus nephritis during pregnancy.

Umbilical cord plasma 25-hydroxyvitamin D concentration and immune function at birth: the Urban Environment and Childhood Asthma study.

BACKGROUND: Recent studies have reported conflicting data on the association between maternal intake of vitamin D during pregnancy and asthma. OBJECTIVE: To assess the influence of prenatal vitamin D status on immune function at birth. METHODS: In an inner-city birth cohort of 568 newborns, 520 of whom had at least one atopic parent, we measured the umbilical cord (UC) plasma concentration of 25-hydroxyvitamin D (25(OH)D) and the cytokine responses of UC blood mononuclear cells (UCMCs) to stimuli including phytohaemagglutinin (PHA), lipopolysaccharide (LPS), and peptidoglycan. In a subset, the UCMC expression of regulatory T cell markers and the suppressive activity of CD4(+) CD25(+) UCMCs were measured. Results The 25th, 50th, and 75th percentiles of UC plasma 25(OH)D level were 15.0, 20.2, and 25.6 ng/mL, respectively. Most cytokine responses of UCMC were not correlated with UC 25(OH)D concentration; however, IFN-γ release after LPS stimulation was weakly positively correlated with UC 25(OH)D concentration (r=0.11, P=0.01). PHA responses were not significantly correlated with 25(OH)D concentration. The UC plasma 25(OH)D concentration was inversely related to the number of CD25(+) (r=-0.20, P=0.06), CD25(Bright) (r=-0.21, P=0.05), and CD25(+) FoxP3 (r=-0.29, P=0.06) cells as a proportion of CD4(+) T cells in UC blood (r=-0.26, P=0.04) but not to the suppressive activity of CD4(+) CD25(+) cells (r=0.17, P=0.22). CONCLUSION AND CLINICAL RELEVANCE: UC 25(OH)D concentration was not correlated with most UCMC cytokine responses to multiple stimuli. There was a suggestion of a weakly positive correlation with IFN-γ release after LPS stimulation. The proportions of CD25(+) , CD25(Bright) , and CD25(+) FoxP3 cells to total CD4(+) T cells were inversely correlated with UC 25(OH)D concentration. Our findings suggest that higher vitamin D levels at birth may be associated with a lower number of T-regulatory cells. Vitamin D status in utero may influence immune regulation in early life.

Multi-joint vs. Single-joint Resistance Exercises Induce a Similar Strength Increase in Trained Men: A Randomized Longitudinal Crossover Study.

The type of exercise is a relevant resistance training-variable that might be manipulated in order to induce significant increases in muscle strength. The aim of this study was to analyze the influence of multi-joint vs single-joint resistance exercises on maximal strength. Sixteen resistance-trained men (age: 23.1 ± 4.4 years; body mass: 86.0 ± 12.8; height: 177.9 ± 6.4 cm; training experience: 4.2 ± 3.4 years) performed one of the following training protocols for six weeks: MULTI, consisting of only multi-joint exercises or SINGLE, consisting of only single-joint exercises. Subjects were then submitted to a three-week washout period, before being submitted to the other protocol for another six weeks. A linear periodization model was adopted in which external load was increased and the repetition range was decreased every two weeks. Maximal dynamic strength of bench press (1RMBENCH) and squat exercises (1RMSQUAT), a percentage variation of total load lifted (ΔTLL) and internal training load (ITL) were measured. Similar increases in 1RMBENCH (MULTI: 10.8%, p < 0.001; SINGLE: 5.5%, p < 0.001) and 1RMSQUAT (MULTI: 19.7%, p < 0.001; SINGLE: 19.0%, p < 0.001) were observed after the MULTI and SINGLE protocols. A decrease in TLL was detected for both exercise protocols; however, the SINGLE protocol induced a greater decrease, compared to the MULTI protocol (-35 ± 11% vs -42 ± 5%, respectively; p = 0.026). A greater ITL for the MULTI was observed when compared to the SINGLE (12.1%; p < 0.001). In conclusion, resistance training protocols with different exercise modalities seem to produce similar strength increases in resistance-trained men.

Measurement of blood loss at childbirth and postpartum.

OBJECTIVE: To accurately measure blood loss during childbirth in a developing country. METHOD: The alkaline hematin technique was used to quantify blood lost during delivery and 24 h postpartum in 158 women in Pemba Island, Zanzibar. RESULT: Women were found to lose less blood during childbirth and 24 h postpartum than previously reported. Compared with laboratory values, nurse-midwives approximated blood loss accurately (mean difference, i.e., mean underestimation by nurse-midwives, 4.90 mL); however, their imprecision was greater for higher laboratory values. CONCLUSION: This study may prompt further investigation, as no comparable data exist for developing countries where maternal mortality is high and severe anemia prevalent.

Modification of chymotrypsin with the specific cyanate reagent N-acetyl-p-cyanato-l-phenylalanine ethyl ester.

The specific cyanate reagentN-acetyl-p-cyanato-L-phenylalanine ethyl ester (compound 1) was synthesized in an attempt to selectively modify the binding pocket of chymotrypsin (EC 3.4.21.1) while leaving the catalytic residues un touched. The reagent reacts with chymotrypsin to yield chiefly an inactive derivative 3a, with the active site Ser-195 carbamylated and the alpha-amino group, with the reagent 1 yields a modified enzyme(compound 4) with an additional carbamyl group on Ser-195.Neither derivative 3a nor 4reacts with diisopropylfluorophosphate under conditions where chymotrypsinogen is modified, indicating that Ser-195 is altered. Both derivatives 3a and 4 are retained on a 4-phenylbutylamine affinity colomn demonstrating that the substrate binding pocket is intact in both derivatives. The results indicate the potential value of aryl cyanates as protein reagents for the selective modification of nucleophilic sites. However, it is apparent that reaction at unreactive residues in the binding pocket of chymotrypsin with cyanates or similar reagents will require blockage of the more nucleophilic catalytic residues.

Biologic response (antiviral) to recombinant human interferon alpha 2a as a function of dose and route of administration in healthy volunteers.

The kinetics of the antiviral effect of intramuscular and intravenous injections of recombinant human interferon alpha 2a were investigated in healthy volunteers. Cohorts of eight to 11 subjects received single intramuscular injections of either 0.3 X 10(6), 3 X 10(6), or 18 X 10(6) U or an intravenous infusion of 18 X 10(6) U over 30 minutes. Serial samples of peripheral blood mononuclear cells were analyzed for antiviral effects including both (2'-5') oligoadenylate synthetase activity and resistance to vesicular stomatitis virus infection in vitro. A dose-response relationship was established between recombinant human interferon alpha 2a dose and both vesicular stomatitis virus resistance and (2'-5') oligoadenylate synthetase activity. At the 0.3 X 10(6) U dose an antiviral effect occurred without clinical side effects. The presence of clinical side effects is not necessary for an antiviral effect.

Effects of prednisone, aspirin, and acetaminophen on an in vivo biologic response to interferon in humans.

In healthy volunteers receiving a single intramuscular dose of 18 X 10(6) U interferon alone or after 24 hours of an 8-day course of prednisone (40 mg/day), aspirin (650 mg every 4 hours), or acetaminophen (650 mg every 4 hours), the magnitude of the biologic response to interferon was quantified by measuring the time course of the induction of 2'-5'-oligoadenylate synthetase and resistance to vesicular stomatitis virus infection in human peripheral blood mononuclear cells. Prednisone decreased the AUC of 2'-5'-oligoadenylate synthetase activity (p less than 0.05), whereas administration of aspirin or acetaminophen did not affect this biologic response. No measurable effect was seen during administration of prednisone, aspirin, or acetaminophen on the duration or intensity of vesicular stomatitis virus yield reduction. The side effects seen with interferon administration at the dose tested were not altered in a clinically meaningful manner by prednisone, aspirin, or acetaminophen.

Clinical pharmacokinetics in the treatment of rheumatoid arthritis in pregnancy.

Rheumatoid arthritis is a relatively common problem in women of reproductive age. Pregnancy may affect all aspects of the pharmacokinetics of the drugs used in its treatment. The effects of pregnancy on the pharmacokinetics of drugs are, for the most part, not clinically significant. The pharmacokinetics of placental transfer and fetal safety have been specified for many drugs. Drugs used in rheumatoid arthritis can be classified into 3 classes: those with the greatest safety for the fetus, those that are unsafe for the fetus, and those for which there are insufficient data to determine the risk to the fetus.

Modulation of alpha-interferon's antiviral and clinical effects by aspirin, acetaminophen, and prednisone in healthy volunteers.

The magnitude and duration of the antiviral and clinical effect of alpha-interferon was measured in healthy volunteers. A single 3 million unit intramuscular dose of interferon was given either alone (controls) or after 72 h of concomitant medications. These medications included either aspirin (650 mg every 4 h), acetaminophen (650 mg every 4 h), or prednisone (40 mg per day). Peripheral blood mononuclear cells were assayed for resistance to vesicular stomatitis virus infection and induction of 2'-5'-oligoadenylate synthetase activity as evidence of interferon's antiviral effect. Co-administration of acetaminophen increased both antiviral parameters by more than 70% (P < 0.05) and reduced symptoms after interferon dosing, compared to controls. Aspirin and prednisone did not demonstrate any significant differences from controls in antiviral effect. As a group, acetaminophen, aspirin, and prednisone reduced the clinical symptoms by 47% compared to controls (P = 0.03) after interferon dosing, although individual drug comparisons failed to reach statistical significance. Independent of treatment group, the changes in antiviral markers after interferon dosing correlated closely with each other (r = 0.72, P < 0.001), but neither correlated with symptoms or fever (r < 0.30, P > 0.05). Acetaminophen enhances the antiviral effects of a single intramuscular dose of alpha-interferon, considering the parameters measured in these healthy volunteers.

The influence of medroxyprogesterone on the duration of breast-feeding in mothers in an urban community.

OBJECTIVE: To assess the effect of medroxyprogesterone acetate on lactation when it is given immediately post partum. DESIGN: Prospective cohort study with follow-up through 16 weeks post partum. SETTING: Urban teaching hospital in Baltimore, Md. PARTICIPANTS: Consecutive sample (N = 95) of mothers who were delivered of healthy, term newborns, had home telephones, received either medroxyprogesterone or nonhormonal contraception at discharge, and were currently breast-feeding their newborns. MAIN OUTCOME MEASURES: Lactation (duration and frequency) and timing of first introduction of formula were measured by weekly telephone interviews. RESULTS: Maternal characteristics included the mean +/- SD maternal age (24 +/- 5 years), race (90% African American), history of pregnancy (63% multiparous), marital status or relationship (50% married or living with partner), and medical assistance (81% of the recipients received aid). Women who were receiving medroxyprogesterone (n = 43) were older (P < .05) and were more likely to be married (P < .05) compared with those who were receiving nonhormonal contraception (n = 52). No other factors that were likely to influence lactation were significantly different. Groups did not differ in the baseline-planned duration of lactation. Follow-up data were obtained on 90 women (96%). The groups were comparable in the duration of lactation (medroxyprogesterone: 98%, 74%, 55%, 47%, and 42% were breast-feeding at least once per day at 1, 4, 8, 12, and 16 weeks, respectively [median, 10.14 weeks], vs nonhormonal contraception: 86%, 70%, 47%, 36%, and 30%, respectively [median, 6.57 weeks] [P = .19]). The percentage of subjects who were exclusively breast-feeding at these times and the timing of formula introduction also did not differ by group. CONCLUSION: Medroxyprogesterone, when given to mothers in an urban community immediately after delivery, has no detrimental effect on the duration of lactation, frequency of lactation, and timing of introduction of formula within the first 16 weeks post partum.

Negative sonographic findings followed by rapid cervical dilatation due to cervical incompetence.

A case of rapid cervical dilatation due to cervical incompetence within 20 minutes of a negative sonogram is presented. Patients with a history of cervical incompetence should not be followed by sonography to determine which ones require therapy.

Effect of steroid hormones on arachidonic acid metabolites of endothelial cells.

The effect of estrogen, progesterone, testosterone, and hydrocortisone on prostacyclin, thromboxane, prostaglandin E, and prostaglandin F from cultured endothelial cells was investigated. No effect was found on prostacyclin, prostaglandin E, and prostaglandin F. Estrogen increased the release of thromboxane. The significance of this finding with regard to venous thrombolic events associated with estrogen use is discussed.

The role of fetal growth restriction and gestational age on length of hospital stay in twin infants.

OBJECTIVE: To evaluate the association between length of gestation and fetal growth restriction (FGR) and the role of FGR in neonatal morbidity as determined by length of hospital stay among newborn twins. METHODS: Using a race-, gender-, and gestational age-specific birth weight and length of hospital stay singleton standard, 490 twin infants were classified as FGR (at or below the tenth percentile) or non-FGR (above the tenth percentile). Length of stay and length-of-stay ratio (twin stay divided by the 50th percentile singleton stay) were calculated for each twin. Analysis included stepwise multiple regression for length of stay and length-of-stay ratio, and analysis of variance with main effects and second-order interactions for the length-of-stay measures using factors significant in the multiple regression models. RESULTS: For length of stay, significant factors in the multiple regression model included respiratory distress syndrome (RDS), gestation category, FGR, sepsis, time of birth (1979-1984 versus 1985-1989), and cesarean delivery. For length-of-stay ratio, significant factors included FGR, gestation category, sepsis, period of birth, cesarean delivery, and hyperbilirubinemia. The analysis of variance showed that RDS had the greatest effect on length of stay, whereas FGR had the greatest effect on length-of-stay ratio. For both dependent variables, the effect of FGR was magnified when compounded by significant neonatal complications (RDS, sepsis, hyperbilirubinemia) or gestation category. CONCLUSIONS: Fetal growth restriction is a major factor in the neonatal morbidity of twins. Early recognition of and interventions for FGR in twin gestations should be a primary goal for reducing both immediate and long-term adverse outcomes.

Adverse effects of cardiovascular drug therapy on the fetus and neonate.

Possible adverse effects of cardiovascular medications on the fetus and the neonate have been reviewed. The major classes discussed were diuretics, antihypertensives, antiarrhythmics, cardiac glycosides, and anticoagulants. The recommendations given must not be considered definitive because they are based on flawed or incomplete information. It is to be hoped that further investigation will improve this situation and will also improve our understanding of the ways in which these drugs act.

The effects of chronic gastrointestinal medication on the fetus and neonate.

The adverse fetal and neonatal effects of chronic gastrointestinal medication have been reviewed. The major classes discussed are antiemetics, laxatives and antidiarrheal agents, antacids and cimetidine, drugs for irritable bowel syndrome, and drugs for inflammatory bowel disease. The evaluation given are tentative due to the lack of information on most of these drugs. It is hoped that research into the use of this diverse group of medications during pregnancy will be stimulated, so that the large gaps in our knowledge about them can be filled.

Determinants of gestational weight gain outside the recommended ranges among black and white women.

OBJECTIVES: To identify factors influencing risk of gaining outside the Institute of Medicine recommendations for pregnancy weight gain, and to determine whether these factors differ by race. METHODS: Multivariate methods were used to identify risk factors for under- and over-gain among 2617 black and 1253 white women delivering at the Johns Hopkins Hospital during 1987-1989. RESULTS: Only 28.2% of black women and 32.5% of white women gained the recommended amounts of weight during pregnancy. Maternal pre-pregnancy body mass index (BMI), height, parity, education, smoking, hypertension, duration of pregnancy, and fetal sex influenced risk for under-gain or over-gain. Black women were 1.51 (95% confidence interval [CI] 1.23-1.85) times more likely to under-gain, but 0.89 (95% CI 0.74-1.08) times less likely to over-gain than white women. No interactions were found between any factor examined and BMI or race. CONCLUSION: Only about one-third of women are gaining the recommended amounts of weight during pregnancy. Black women are at increased risk for gaining less weight than recommended, and selected maternal characteristics associated with race do not explain this difference. Further, risk factors for under-or over-gain do not differ between black and white women.

Evaluation of preterm delivery in a systemic lupus erythematosus pregnancy clinic.

OBJECTIVE: To identify the primary etiology of preterm birth in women with systemic lupus erythematosus, analyzing prospective data collected on 66 pregnancies in 58 women followed-up at a lupus pregnancy center. METHODS: Hospital records were reviewed and subjects were interviewed for pregnancies delivered after 23 completed weeks' gestation in women cared for at the Hopkins Lupus Pregnancy Center. A control group consisted of all women delivered at the same hospital during 2 years of the study period. RESULTS: Preterm premature rupture of membranes (PROM) occurred in 13 of 33 (39%) pregnancies delivered at 24-36 weeks' gestation. In addition, term PROM also occurred with high incidence in ten of 33 (30.3%) pregnancies delivered after 36 weeks' gestation. The rate of PROM in study subjects differed from that in controls at 34-36 weeks' gestation and after 36 weeks. CONCLUSION: Premature rupture of membranes is more common in pregnancies occurring in women with systemic lupus erythematosus than in control pregnancies. Disease activity, prednisone use, and serologic studies are not predictive. Premature rupture of membranes is the major etiology of preterm birth in this cohort.

Influence of maternal anthropometric status and birth weight on the risk of cesarean delivery.

OBJECTIVE: To determine whether greater weight gain during pregnancy is associated with an increased risk of cesarean delivery, and, if so, whether this effect is explained by the positive influence of weight gain on birth weight and if there is a threshold of pregnancy weight gain above which the risk of cesarean delivery is increased differentially. METHODS: We analyzed live births at Johns Hopkins Hospital for the period 1987-1989. A multiple logistic regression model was used to evaluate the risk of cesarean delivery, recorded in the hospital's perinatal data base. RESULTS: The study sample contained 4346 patients, 1086 of whom delivered by cesarean. Associated independently with an increased risk of cesarean delivery were the following: 1) greater weight gain during pregnancy, 2) older maternal age, 3) greater maternal prepregnant body mass index, 4) maternal height of 1.57 m or less, 5) the diagnosis of preeclampsia during current pregnancy, and 6) carrying a fetus weighing more than 3591 g at birth. An additional risk factor for cesarean delivery was a fetus less than 2847 g at birth, with the risk more marked the lower the gestational age. Maternal height of 1.73 m or more and a history of at least one previous viable pregnancy were associated independently with a decreased risk of cesarean delivery. CONCLUSION: The risk of cesarean delivery increases linearly with pregnancy weight gain, independent of birth weight. No specific threshold of weight gain can be determined above which the cesarean risk climbs more rapidly.

Station at onset of active labor in nulliparous patients and risk of cesarean delivery.

OBJECTIVE: To determine whether term nulliparas with an unengaged vertex presentation at onset of active labor have a higher risk for cesarean delivery. METHODS: A retrospective cohort of 1250 randomly chosen nulliparous patients at 37-42 weeks' gestation who delivered between 1988 and 1989 were selected. Four hundred forty-seven patients were excluded because of nonvertex presentation, cesarean delivery before active phase of labor, multiple gestation, delivery at less than 37 weeks' or greater than 42 weeks' gestation, induction of labor, or missing charts. For the purpose of this study, active labor was defined as regular contractions with cervical dilatation of at least 3 cm. The station at onset of active labor was recorded. Engagement was considered to be at station 0 or below. RESULTS: Of the 803 patients in the study group, 567 presented unengaged and 236 patients presented engaged. The cesarean rates differed significantly between the two groups: 14% of those unengaged compared with 5% of those engaged (chi2 = 11.9, P < .001). After adjusting for confounding variables, engagement at the time of onset of active labor was associated with lower risk of cesarean delivery (odds ratio .512, 95% confidence interval .285, .922). CONCLUSION: Eighty-six percent of nulliparas with an unengaged vertex at onset of active labor delivered vaginally. Engaged vertex at the onset of active labor was associated with a lower risk of cesarean delivery.

Premature rupture of the membranes and prolonged latency.

The aim of this retrospective study in 8320 patients with premature rupture of the membranes (PROM) was to determine the consequences of prolongation of the latent period. Among patients with pregnancies of more than 37 weeks' duration, those with PROM and latent periods of more than 1 day demonstrated an increased incidence of intrapartum fever (IPF), whereas those with latent periods of more than 3 days demonstrated a marked increase in fetal (but not neonatal) deaths. Although IPF and perinatal mortality were more common in preterm pregnancies, neither was found to increase or decrease with prolonged latency, provided differences in gestational ages and race were taken into account. In the absence of chorioamnionitis, there appears to be no benefit to delivery before 37 weeks' gestation.