Construction and calibration of a low-cost bandage pressure monitor

Pregnant sheep with a microdialysis probe implanted in the fetal cerebral cortex were used to determine if nitrate and nitrite anions (nitrate/nitrite) could be quantitated in the microdialysate as an indirect index of in vivo nitric oxide formation. Pregnant ewes (term, about 147 days) were surgically instrumented at gestational day (GD) 90 (n = 3; preterm) and GD 121 (n = 3; nearterm). Three days later, following an overnight probe equilibration period, five dialysate samples were collected continuously on ice at 1-h intervals (infusion rate of 1 (microl/min). The nitrate/nitrite concentration was determined by reducing a 10-microl aliquot of each dialysate fraction with hot acidic vanadium followed by chemiluminescence quantitation of the nitric oxide product. The lower limit of quantitative sensitivity of the method is 25 picomoles. Nitrate/nitrite concentration was 16.6+/-7.3 microM for the preterm fetus and 19.7+/-1.9 microM for the nearterm fetus. The data demonstrate that nitrate/nitrite, as an index of in vivo nitric oxide formation, can be quantitated in microdialysate samples collected from the intact fetal sheep cerebral cortex.     

The application of the modified method of determination of aldosterone in plasma

Concentrations of triglycerides, free fatty acids (FFA) and glycerol were measured in umbilical venous blood from 99 infants with a birth weight of between 1100-2700 g and a gestational age of 27-41 weeks. Thirty infants were small for gestational age (SGA), 58 were appropriate (AGA) and 11 were of uncertain gestational age. In AGA infants with a gestational age of less than or equal to 35 weeks. FFA values were lower than in those with a gestational age of less than 35 weeks; otherwise concentrations of triglycerides, FFA and glycerol were independent of birth weight and gestational age in AGA infants. In SGA infants, higher FFA values were found compared with both AGA and term infants of normal birth weight. Triglyceride values were higher in SGA than in AGA infants. In SGA infants, a significant positive correlation was found between gestational age and concentrations of both FFA and triglycerides. No differences in FFA, glycerol and triglyceride concentrations were seen between asphyxiated and non-asphyxiated AGA infants.     

Urine but not plasma nitric oxide metabolites are decreased in women with preeclampsia

OBJECTIVE: Nitric oxide is a potent vasorelaxant produced by endothelial cells. We tested the hypothesis that urinary and perhaps plasma nitric oxide metabolites would be reduced in women with preeclampsia. STUDY DESIGN: Plasma and urine from 14 women meeting strict clinical criteria for the diagnosis of preeclampsia and 20 normal nulliparous women were assayed for the stable metabolites of nitric oxide, nitrate and nitrite. RESULT: There was no significant difference of plasma concentrations of nitrate and nitrite between women with preeclampsia and women with normal pregnancies (32.7 +/- 3.1 vs 25.8 +/- 2.4 micromol/L). Plasma creatinine levels were elevated in women with preeclampsia (0.85 +/- 0.09 vs 0.66 +/- 0.02 mg/dl, p<0.01), indicating a reduced glomerular filtration rate. Urine concentrations of nitrate and nitrite normalized by creatinine excretion were significantly lower in women with preeclampsia compared with normal pregnant women (0.37 +/- 0.06 vs 0.69 +/- 0.11 micromol of nitrite per milligram creatinine, p. <0.05). CONCLUSIONS: Our study using concomitant measurement of plasma and urine nitrate and nitrite suggests a reduced production of nitric oxide in women with preeclampsia compared with normal pregnant women.     

Preterm and term births of small for gestational age infants: a population-based study of risk factors among nulliparous women

OBJECTIVE: To study risk factors for small for gestational age (SGA) infants by gestational age among nulliparous women and to estimate mortality rates among SGA and appropriate-for-gestational-age (AGA) infants by gestational age. DESIGN: A population-based study from the Swedish Medical Birth Register. Setting Sweden 1992 1993. POPULATION: Liveborn singleton infants to nulliparous women (n = 96,662). MAIN OUTCOME MEASURES: Crude and adjusted odds ratios of risk factors for SGA by gestational age. Rates of neonatal and postneonatal mortality. RESULTS: Older maternal age (> or = 30 years) was foremost associated with increased risks of very and moderately preterm SGA (> or = 32 weeks and 33-36 weeks, respectively), but also with term SGA (> or = 37 weeks). Risks of SGA increased with decreasing maternal height at all gestational ages. Smoking increased the risks of moderately preterm and term SGA. Short maternal education increased the risk of preterm SGA and low pre-pregnancy body mass index slightly increased the risk of term SGA. Pre-eclampsia and essential hypertension foremost increased the risk of very preterm SGA (OR = 40.5 and 32.4, respectively) and moderately preterm SGA (OR = 17.4 and 10.6, respectively), but also increased the risk of term SGA. Neonatal and postneonatal mortality rates of SGA infants were substantially influenced by gestational age, and mortality rates were consistently higher among preterm SGA infants compared with AGA infants. Conclusions: Risk factors for SGA and mortality rates among SGA infants vary by gestational age. A subdivision of risk factors by gestational age adds knowledge, particularly about risks of preterm SGA, where the highest rates of mortality were observed.     

Acute and chronic fetal hypoxia in monochorionic and dichorionic twins

OBJECTIVE: To assess the risk for acute and chronic fetal hypoxia in twin pregnancies. METHODS: We investigated 50 sets of twins (24-38 weeks' gestation, 660-3200 g birth weight) admitted consecutively to our neonatal intensive care unit. Seventy-six infants were appropriate for gestational age (AGA; tenth to 90th percentile), 20 were small for gestational age (SGA; below the tenth percentile), and four were large for gestational age (above the 90th percentile). Twenty-six singleton AGA term newborns served as controls. Umbilical arterial pH was used as a marker for acute and umbilical venous erythropoietin concentration for chronic fetal hypoxia. The results are given as median followed by quartiles. RESULTS: We identified 40 sets of diamniotic-dichorionic twins and ten sets of diamniotic-monochorionic twins with transplacental vascular shunts. In the second-born twin, umbilical arterial pH was lower (7.29, 7.23-7.33) than in the firstborn (7.31, 7.25-7.34) (P = .03), and the incidence of a low pH (less than 7.20) was higher (19 versus 11%). Two second-born twins and none of the firstborn twins had an umbilical arterial pH less than 7.05. In SGA twins, the erythropoietin concentration was elevated (34.8, 22.8-325 mU/mL) compared with that in AGA twins (16.2, 8.2-26.6 mU/mL) (P < .01). In AGA twins, erythropoietin concentration did not differ from that in AGA singleton newborns (19.6, 14.7-31.6 mU/mL). In 12 of 17 twin sets with weight discordancy greater than 15% and in all five twin sets with weight difference greater than 25%, erythropoietin concentration was higher in the smaller twin. The proportion of infants and of complete sets with elevated erythropoietin levels was higher (P < .01) in monochorionic than in dichorionic pregnancies. CONCLUSION: The second-born twin is at increased risk for acute birth asphyxia. Fetal growth restriction in twin pregnancies is associated with chronic fetal hypoxia. Monochorionic twins are at higher risk for chronic fetal hypoxia than are dichorionic twins.     

Follow-up study on physical and mental development in small-for-gestational age infants

A follow-up study on physical and mental development was carried out in 35 small-for-gestational-age (SGA) and 35 appropriated-for-gestational age (AGA) infants. Excluded for congenital abnormality, intrauterine infection, and neonatal asphyxia SGA and AGA infants were similar in maternal education level, infant sex, illness, and feeding history. The results revealed that the body weight (8.09 +/- 0.73kg), height (69.55 +/- 2.49 cm), head circumference (43.27 +/- 1.67cm), Kaup index (16.17 +/- 1.05), and development quotient (96.37 +/- 5.76, Gesell diagnostic method) level at 40 weeks of age in SGA infants was lower than that in AGA infants (P < 0.001), and the development quotient (DQ) in SGA infants was especially low in language and receptive regions. Cord serum insulin level was significantly correlated with follow-up body weight, height, and DQ level (P < 0.01). This article proposed that infants with intrauterine growth retardation have a physical development delay at 40 weeks of age, and which could be predicted by measuring cord insulin level.     

Relationship between concentration of serum leptin and fetal growth

The serum leptin concentration reflects the amount of adipose tissue in the body. Although fat deposition in the fetus in the third trimester markedly increases, the role of leptin during pregnancy has not been clarified. In the present study, whether or not the serum leptin concentration correlates with growth in utero was investigated, in addition to how leptin levels change in the first few days after birth. One hundred sixteen Japanese infants were divided into term (n = 91) and preterm groups (n = 25). Term infants were divided into 3 subgroups: birth weight appropriate for gestational age (AGA) (n = 44), birth weight large for gestational age (LGA) (n = 28), and birth weight small for gestational age (SGA) (n = 19). Longitudinal changes in the concentration of serum leptin after birth were examined in 48 infants. The serum leptin concentration was determined by RIA. No significant difference in leptin levels between cord sera and infants' sera obtained within the first 6 h of life (n = 28) was observed. Within the first 6 h of life, the concentration of serum leptin in LGA infants (12.8 +/- 10.2 ng/mL) and SGA infants (1.6 +/- 1.1 ng/mL) was significantly higher and lower, respectively, than that in the AGA infants (4.4 +/- 3.0 ng/mL) (P < 0.01). A significant positive correlation was found between the leptin concentration within 6 h of life and birth body weight (r = 0.59, P < 0.01). After birth, the concentration of leptin in LGA and AGA infants significantly decreased to the level in SGA infants within 72 h [corrected] of delivery (P < 0.05). After 72 h [corrected] of life, no significant differences in the concentration of leptin were observed among the three groups, and low levels continued to 7 days of age. These findings indicate that serum level of leptin correlates with fetal body weight gain.     

The nitric oxide system and cortisol-induced hypertension in humans

1. The aim of the present study was to assess the role of the nitric oxide (NO) system in cortisol-induced hypertension in humans. 2. Plasma and urinary nitrate/nitrite concentrations and plasma concentrations of arginine and symmetric (SDMA) and asymmetric (ADMA) dimethyl arginine were measured in six subjects on a restricted nitrate diet who were treated with 80 mg/day cortisol and in subjects on an unrestricted nitrate diet who were treated with cortisol (80 mg/day, n = 6, or 200 mg/day, n = 10) for 5 days. 3. Cortisol significantly increased systolic and mean arterial pressure. Significant reductions in plasma nitrate/nitrite concentrations were observed in subjects on a restricted nitrate diet on days 3, 4 and 5 of cortisol treatment (to 11 +/- 1, 10 +/- 1, 11 +/- 1 pmol/L, respectively) compared with pretreatment (16 +/- 1 pmol/L; P < 0.01). There were no significant changes in plasma arginine, ADMA or SDMA concentrations. 4. Cortisol treatment significantly increased blood pressure and reduced plasma nitrate/nitrite concentrations. Reductions in plasma nitrate concentrations are not explained by changes in substrate availability or in endogenous nitric oxide synthase inhibitors. These data support a role for the NO system in cortisol-induced hypertension in humans.     

Results of selective goiter resection in functional autonomy

BACKGROUND: Active colitis in patients with inflammatory bowel disease is associated with mucosal vasodilation, increased intestinal permeability and abnormal colonic motility. Nitric oxide is a messenger molecule with many functions, including regulation of local blood flow, vasomotor tone, and inflammation. Increased nitric oxide production and inducible nitric oxide synthase activity have been demonstrated in experimental models of colitis. This study was designed to determine the relationship between nitric oxide production and colonic inflammation in children with active colitis and in control subjects and whether expression of inducible nitric oxide synthase protein is demonstrable in the intestinal epithelium of these patients. METHODS: Nitrate + nitrite were measured in urine, stool, and plasma using the Griess assay. Expression of inducible nitric oxide synthase protein in intestinal tissue was determined by immunohistochemical localization. RESULTS: Urinary nitrate + nitrite levels were not significantly different in patients and control subjects. In contrast, stool and plasma nitrate + nitrite concentrations were significantly higher in children with inflammatory bowel disease compared with levels in control children (stool: 162.4 +/- 31.0 mumol/l versus 77.2 +/- 22.1 mumol/l; plasma: 65.2 +/- 9.9 mumol/l versus 38.1 +/- 6.6 mumol/L; p < 0.05). Stool nitrate + nitrite levels significantly correlated with plasma values. Immunohistochemical staining of colonic tissue from children with inflammatory bowel disease demonstrated inducible nitric oxide synthase protein located exclusively in epithelial cells. CONCLUSION: Increased nitric oxide production and enhanced intestinal epithelial cell expression of inducible nitric oxide synthase protein are associated with active colonic inflammation.     

Circulating methemoglobin and nitrite/nitrate concentrations as indicators of nitric oxide overproduction in critically ill children with septic shock

OBJECTIVES: To examine the relationship between circulating methemoglobin and nitrite/nitrate concentrations and to compare these markers of nitric oxide overproduction with clinical variables in children diagnosed with septic shock. DESIGN: Prospective, controlled, clinical study. SETTING: Pediatric intensive care unit and outpatient clinic in a children's hospital. PATIENTS: Twenty-two children diagnosed with septic shock and ten age-matched healthy control patients. INTERVENTIONS: Patients diagnosed with septic shock had blood specimens taken on study entry and every 6 hrs for 72 hrs for methemoglobin and nitrite/nitrate determinations. Single blood specimens were obtained from controls. MEASUREMENTS AND MAIN RESULTS: Circulating methemoglobin and nitrite/nitrate concentrations were significantly higher in children diagnosed with septic shock in comparison with healthy control children (p = .01 and .05, respectively). Peak nitrite/nitrate concentrations correlated with serum creatinine (r2 = .19; p = .04) and were inversely correlated with arterial pH (r2 = .28; p = .01) and urine output (r2 = .21; p = .03) when analyzed by log-linear regression. There were no significant relationships between methemoglobin and nitrite/nitrate or between methemoglobin and any other clinical variable. CONCLUSIONS: Circulating methemoglobin and nitrite/nitrate concentrations are increased in children diagnosed with septic shock. Plasma nitrite/nitrate values correlate with selected clinical variables in these children. Circulating methemoglobin measurements are not superior to plasma nitrite/nitrate concentrations as an indicator of endogenous overproduction of nitric oxide in children diagnosed with septic shock. A need remains to develop markers of endogenous nitric oxide activity that have greater accuracy and reliability.     

Recombinant human O6-alkylguanine-DNA alkyltransferase induces conformational change in bound DNA

We aimed to assess the impact of a preconceptional clinic (PC) on the perinatal outcome (PO) of diabetic pregnancies attended in our centre. We studied 185 pregnancies attended in the 1986-1996 period (152 in women with insulin dependent diabetes mellitus (IDDM) and 33 with non insulin-dependent diabetes mellitus (NIDDM)) and we analysed the perinatal outcome for both mother and fetus. Sixty-six women (36.1%) had enrolled in the PC, 41.4% for IDDM and 9.1% for NIDDM pregnancies, p < 0.01. First pregnancy HbA1c (in SD around the mean) was 3.98 +/- 3.00 in non-attenders (NA) vs 2.57 +/- 2.41 in attenders (A), p < 0.01. The final HbA1c was in the normal range in both groups. D-R class according to White classification was 33.0% for NA vs 54.5% for A, p < 0.01. There were no differences in the rates of abortion and major malformations (8.8% NA vs 3.6% A, ns). Both groups differed in the rate of cesarean sections (54.9% NA vs 71.0% A, p < 0.05) and in the rate of small for gestational age infants (SGA) (8.7% NA vs 1.8% A, p < 0.05). There were no differences between groups in maternal or neonatal outcomes. In this group of diabetic women with a moderate although less than optimal metabolic control at the beginning of pregnancy, the impact of PC on PO is less evident than described.     

Resolution limits for optical transillumination of abnormalities deeply embedded in tissues

For the quantification of nitrite and nitrate, the stable metabolites of L-arginine-derived nitric oxide (NO) in human urine and plasma, we developed a gas chromatographic-mass spectrometric (GC-MS) method in which [15N]nitrite and [15N]nitrate were used as internal standards. Endogenous nitrite and [15N]nitrite added to acetone-treated plasma and urine samples were converted into their pentafluorobenzyl (PFB) derivatives using PFB bromide as the alkylating agent. For the analysis of endogenous nitrate and [15N]nitrate they were reduced to nitrite and [15N]nitrite, respectively, by cadmium in acidified plasma and urine samples prior to PFB alkylation. Reaction products were extracted with toluene and 1-microliter aliquots were analyzed by selected-ion monitoring at m/z 46 for endogenous nitrite (nitrate) and m/z 47 for [15N]nitrite ([15N]nitrate). The intra- and inter-assay relative standard deviations for the determination of nitrite and nitrate in urine and plasma were below 3.8%. The detection limit of the method was 22 fmol of nitrite. Healthy subjects (n = 12) excreted into urine 0.49 +/- 0.25 of nitrite and 109.5 +/- 61.7 of nitrate (mean +/- S.D., mumol/mmol creatinine) with a mean 24-h output of 5.7 mumol for nitrite and 1226 mumol for nitrate. The concentrations of nitrite and nitrate in the plasma of these volunteers were determined to be (mean +/- S.D., mumol/l) 3.6 +/- 0.8 and 68 +/- 17, respectively.     

Monitored outpatient management of mild gestational hypertension remote from term in teenage pregnancies

OBJECTIVE: Our purpose was to compare maternal and perinatal outcomes of teenage and adult pregnancies with mild gestational hypertension remote from term managed with an outpatient program. STUDY DESIGN: A matched cohort design was used. Maternal and perinatal outcomes of 60 teenage pregnancies with mild gestational hypertension remote from term were compared with 120 adult controls 20 to 42 years old. The groups were matched for race, gestational age, and proteinuria status at enrollment. All were monitored on an outpatient basis with four times daily automated blood pressure measurement and daily assessment of weight, proteinuria, and fetal movement. RESULTS: The mean gestational age at enrollment was 33.5 +/- 2.6 weeks for both groups (range 27 to 36 weeks). Only 60% of teenagers had a high school degree or equivalent compared with 76% of adults (p = 0.024). The teenagers were more likely than the adults to be of single marital status (75% vs 13%, p = 0.015). The mean gestational age at delivery (37.0 +/- 2.0 vs 37.0 +/- 2.2 weeks), mean pregnancy prolongation (23.5 +/- 19.0 vs 24.5 +/- 17.4 days), and mean birth weights (2915 +/- 669 vs 2879 +/- 678 gm) were not statistically different between the teenagers and adults (all p > 0.05). There were no stillbirths, neonatal deaths, or cases of eclampsia in either group. CONCLUSIONS: In spite of a study population characterized by limited education, single marital status, and young age at enrollment, monitored outpatient management of mild gestational hypertension remote from term in teenage pregnancies is associated with maternal and perinatal outcomes similar to those observed in adults.     

Effects of various flow types on maternal hemodynamics during fetal bypass: is there nitric oxide release during pulsatile perfusion?

OBJECTIVE: This study investigates the role of various flow conditions on maternal hemodynamics during fetal cardiopulmonary bypass. METHODS: Normothermic fetal bypass was conducted under pulsatile, or steady flow, for a 60-minute period. Fetal lamb preparations were randomly assigned to 1 of the 3 groups: steady flow (n=7), pulsatile flow (n=7), or pulsatile blocked flow bypass (n=7), where fetuses were perfused with Nomega-nitro-L-arginine after the first 30 minutes of pulsatile flow to assess the potential role of endothelial autacoids. RESULTS: Maternal oximetry and pressures remained unchanged throughout the procedure. Under fetal pulsatile flow, maternal cardiac output increased after 20 minutes of bypass and remained significantly higher than under steady flow at minute 30 (8.8+/-0.7 L x min(-1) vs 5.9+/-0.5 L x min(-1), P=.02). Maternal cardiac output in the pulsatile group also remained higher than in both steady and pulsatile blocked flow groups, reaching respectively 8.7+/-0.9 L x min(-1) vs 5.8+/-0.4 L x min(-1) (P=.02) and 5.9+/-0.3 L min(-1) (P=.01) at minute 60. Maternal systemic vascular resistances were significantly lower under pulsatile than under steady flow after 30 minutes and until the end of bypass (respectively, 9.1+/-0.6 IU vs 12.7+/-1.1 IU, P=.02 and 8.9+/-0.5 IU vs 12.9+/-1.2 IU, P=.01). Infusion of Nomega-nitro-L-arginine was followed by an increase in systemic vascular resistances from 9.3+/-0.7 IU, similar to that of the pulsatile group, to 13.5+/-1 IU at 60 minutes, similar to that of the steady flow group. CONCLUSIONS: Maternal hemodynamic changes observed under fetal pulsatile flow are counteracted after infusion of Nomega-nitro-L-arginine, suggesting nitric oxide release from the fetoplacental unit under pulsatile fetal flow conditions.     

Etiology and outcome of acute renal failure in elderly patients

OBJECTIVE: To test the usefulness of the fetal transverse cerebellar diameter/abdominal circumference (TCD/AC) ratio in predicting known small-for-gestational-age (SGA) infants. METHOD: The relationship between fetal TCD and AC throughout the second half of pregnancy was investigated in 635 well-dated, normal pregnancies and examined with regard to gestational age and infant birth weight percentiles. RESULTS: One hundred eighteen (19%) fetuses were excluded due to inadequate visualization of the fetal cerebellum. A strong correlation was noted between gestational age determined by the last menstrual period and both fetal TCD (r2 = 0.91338) and AC (r2 = 0.89361) in fetuses with birth weights between the 10th and 90th percentiles (n = 407; mean 14.4, S.D. 1.2). Although the TCD/AC ratio showed a poor correlation with gestational age (r2 = 0.15788), a slight increase was noted during gestation. A TCD/AC ratio greater than 15.5 was present in 80% of SGA infants when measurements were performed within 1 week of delivery. CONCLUSION: Fetal TCD/AC ratio as a gestational age-independent method could improve diagnostic sensitivity and specificity in the early detection of fetal growth abnormalities.     

Influence of nutritional status on the pharmacokinetics of acetylsalicylic acid and its metabolites in children with autoimmune disease

OBJECTIVE: To determine whether serum measures of nitric oxide production correlate with disease activity in patients with systemic lupus erythematosus (SLE). METHODS: We assayed the levels of serum nitrate/nitrite from 26 patients with SLE followed for 1-3 years and nitrotyrosine levels in sera from 28 additional patients with SLE; sera from 19 controls were tested in both assays. Lupus disease activity was determined via the physician's global assessment, the Lupus Activity Index, and the SLE Disease Activity Index (SLEDAI) at the time of serum collection for the initial set of 26 patients. Statistical correlations were determined using the Wilcoxon rank sum method and one-way ANOVA testing. RESULTS: Serum levels of nitrate/nitrite were significantly higher in 26 patients with SLE compared to 19 controls (SLE, mean 29.5 microM/ml, range 1-438; controls, mean 9.6 microM/ml, range 0-51; p = 0.0004). Overall, there was a significant correlation between serum nitrate/nitrite levels and SLEDAI scores (p = 0.0065). Renal variables within the SLEDAI had the highest correlation with serum nitrate/nitrite (p = 0.0028). Serum nitrotyrosine levels were also significantly higher in patients with SLE versus controls (p = 0.007) and in active SLE versus those with inactive SLE (p = 0.008). CONCLUSION: Serum nitrate/nitrite levels correlated with SLE disease activity, especially nephritis, in the majority of patients studied. Serum nitrotyrosine levels also differentiated controls from patients with lupus and patients with active from those with inactive disease. Due to the ease and low cost of these assays, serum measures of nitric oxide production appear a potentially useful adjunctive laboratory measure of disease activity in SLE and further implicate nitric oxide as an important mediator of disease in SLE.     

Sputum eosinophilia is more closely associated with airway responsiveness to bradykinin than methacholine in asthma

OBJECTIVE: We investigated the change in the plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, in early-, mid-, and late-gestation normotensive pregnancies and in gestational age-matched preeclamptic pregnancies and compared the observed changes with changes in blood pressure. STUDY DESIGN: Blood pressure and peripheral plasma asymmetric dimethylarginine concentrations were measured in 20 nonpregnant and 145 pregnant women (33 first-trimester, 50 second-trimester, and 44 third-trimester normotensive pregnancies and 18 third-trimester pregnancies complicated by preeclampsia). In 23 normotensive pregnancies serial plasma asymmetric dimethylarginine concentrations were measured. Statistical analysis was by analysis of variance and linear regression. RESULTS: The blood pressures recorded throughout normal pregnancy were significantly lower than in nonpregnant subjects (p < 0.0001). The mean systolic, diastolic, and average blood pressures were significantly higher in the second-trimester groups than in the first-trimester groups, whereas in the third trimester average and diastolic blood pressures were significantly higher than in the second trimester. The mean (+/-SD) systolic and diastolic blood pressures in third-trimester preeclamptic patients was 157.7 +/- 11.2 and 110.9 +/- 8.5 mm Hg. The mean plasma asymmetric dimethylarginine concentration in nonpregnant women was 0.82 +/- 0.31 micromol/L (significantly higher than in normotensive pregnancy, p < 0.0001). The plasma asymmetric dimethylarginine concentration was also significantly higher in second-trimester than in first-trimester normotensive groups (respectively, 0.52 +/- 0.20 micromol/L and 0.40 +/- 0.15 micromol/L, p = 0.001) and was higher in third-trimester normotensive pregnancy 0.56 +/- 0.23 micromol/L than it was in the second trimester. The asymmetric dimethylarginine concentration in third-trimester preeclamptic patients was 1.17 +/- 0.42 micromol/L (p < 0.0001 vs normotensive third-trimester subjects). CONCLUSIONS: It is well recognized that blood pressure falls in early normal pregnancy and rises again toward term. These studies show that the early fall in blood pressure is accompanied by a significant fall in the plasma asymmetric dimethylarginine concentration. Later in pregnancy circulating concentrations increase and, when pregnancy is complicated by preeclampsia, concentrations are higher than in the nonpregnant state. Our data support a role for both asymmetric dimethylarginine and nitric oxide in the changes in blood pressure seen in both normal and preeclamptic pregnancy.     

Aspects of fetal physiology from 18 to 37 weeks' gestation as assessed by blood sampling

OBJECTIVE: To construct reference ranges for fetal pH, oxygen pressure (PO2), and hematologic and biochemical blood constituents, which can be used to analyze changes with gestation and differences with maternal values, thus elucidating some aspects of fetal biology and the effects of the maternal and placental environments. METHODS: We assayed venous pH, PO2, hematocrit, glucose, uric acid, urea, creatinine, total protein, total and direct bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, lactic dehydrogenase, amylase, pseudocholinesterase, creatine kinase, triglycerides, and cholesterol concentrations in 157 fetuses and 134 mothers who underwent fetal blood sampling from 18 to 37 weeks' gestation. None of the fetuses was infected or had chromosomal, hematologic, or hormonal abnormalities. RESULTS: All the variables analyzed were similar in fetuses sampled at the placental cord insertion (n = 125) or at the intrahepatic vein (n = 32). Maternal and fetal concentrations of glucose (r = 0.79, P < .001), urea (r = 0.96, P < .001), creatinine (r = 0.83, P < .001), and uric acid (r = 0.94, P < .001) correlated significantly, and their differences exhibited significant changes: the maternal-fetal differences of glucose and urea increased, whereas those of uric acid and creatinine decreased with advancing gestation. Fetal pH and PO2 decreased with gestational age, whereas hematocrit increased, similar to what has been described previously. All of the other variables, with the exception of amylase and cholesterol, changed significantly during the investigated period of pregnancy. Gestational age explained at least 40% of the variance in values of fetal total protein, pseudocholinesterase, alanine aminotransferase, creatine kinase, and triglycerides, but only 3-25% of the variation in the remainder. Most enzymes were higher in the fetus than in the maternal circulation, and all except alkaline phosphatase increased with gestational age. The maternal-fetal glucose difference correlated significantly with hematocrit, pH, and PO2, independent of gestational age and independent of each other. CONCLUSION: With the exception of aspartate aminotransferase, all of the analyzed fetal variables were different from the maternal values, and most changed with gestational age. The mechanisms leading to these fetal specificities remain mostly uncertain, but the provision of reference ranges for several blood constituents may be useful in the differential diagnosis of fetal disease.     

Nitrite and nitrate levels in cerebrospinal fluid of normal subjects

In order to evaluate the involvement of nitric oxide in neurologic disorders it is important to generate controlled values of its metabolites nitrite and nitrate in human cerebrospinal fluid (CSF). Samples of CSF obtained from 14 patients without neurologic diseases were analysed for nitrite and nitrate concentration by reverse phase chromatography with ultraviolet (UV) detection. For comparison, the levels of nitrite in the same samples were also measured by reverse phase chromatography coupled with electrochemical detection and those of nitrate by ion chromatography coupled with UV detection. A good correlation was found for the concentration values of both ions obtained with the two procedures. Then, 10.41 +/- 0.47 ng/ml of nitrite and 2.92 +/- 0.37 ng/ml of nitrate could be regarded as reliable values in control subjects. No correlation between age and levels of nitrite and nitrate was observed.     

Experimentally contaminated reabsorbable meshes: their evolution in abdominal wall defects

The effect of maternal hyperglycemia on fetal regional circulation in appropriate for gestational age and small for gestational age fetuses was evaluated. Color Doppler flow imaging and pulsed Doppler ultrasonographic assessments were made on 15 appropriate for gestational age and 19 small for gestational age fetuses, ranging from 33 to 40 weeks' gestation before, 60 minutes, and 120 minutes after a maternal 75 g glucose load. The pulsatility index (PI) was calculated for middle cerebral artery, descending aorta, splenic artery, renal artery, femoral artery, and umbilical artery. Simultaneously, maternal plasma glucose concentration was measured. Baseline PI value (1.50 +/- 0.31) for middle cerebral artery in small for gestational age fetuses was significantly lower than that (1.89 +/- 0.37) in appropriate for gestational age fetuses (p < 0.05); however, there were no significant differences in baseline PI values for other arteries in both groups. In appropriate for gestational age fetuses, the mean PI decreased from 1.89 +/- 0.37 to 1.47 +/- 0.33 at 60 minutes, and to 1.55 +/- 0.32 at 120 minutes (p < 0.05), but no changes were found in the other arteries. In small for gestational age fetuses, there was no significant change in PI value for each artery before and after maternal glucose load. Maternal hyperglycemia induces a significant decrease in cerebrovascular resistance in appropriate for gestational age fetuses but not in small for gestational age fetuses. These results provide a foundation for evaluating the effect of maternal hyperglycemia on fetal regional circulation.