[Show abstract][Hide abstract] ABSTRACT: There has been only one case to date of pregnancy outcome after fundal transverse cesarean section (FTC). We report a pregnancy established after FTC. The FTC was performed at gestational week (GW) 24 in this patient's first pregnancy, but the uterus was preserved. Magnetic resonance imaging studies performed four times in her second pregnancy consistently showed part of the uterine fundus in which the muscle layer was interrupted. Concern regarding spontaneous uterine rupture in the absence of labor pains prompted us to interrupt her pregnancy at GW 31+5, delivering a premature, but otherwise healthy female infant, weighing 1832 g. The infant required transient intratracheal intubation for respiratory distress syndrome (for less than 1 h), but had an otherwise uneventful clinical course. Two cases, including ours, suggest that successful pregnancy outcome is feasible at least in some women with uterine scarring due to FTC.
Journal of Obstetrics and Gynaecology Research 05/2014; 40(5). · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to underscore problems associated with the dipstick test and determination of protein concentration alone in spot-urine (P-test) compared with spot-urine protein-to-creatinine ratio (P/Cr test) and to determine whether urine collection for 24-h test was complete.
Dipstick and P/Cr tests were performed simultaneously in 357 random spot-urine specimens from 145 pregnant women, including 35 with pre-eclampsia. Positive results were defined as ≥1+ on dipstick test, protein concentration ≥30 mg/dL on P-test, and P/Cr ratio ≥ 0.27 (mg/mg) on P/Cr test. Sixty-four 24-h urine tests (quantification of protein in urine collected during 24 h) were performed in 27 of the 145 women. We assumed that P/Cr ratio ≥ 0.27 predicted significant proteinuria (urinary protein ≥ 0.3 g/day). The 24-h urine collection was considered incomplete when urinary creatinine excretion was <11.0 mg/kg/day or >25.0 mg/kg/day.
Forty-four percent (69/156) of specimens with a positive test result on dipstick test contained protein < 30 mg/dL. Dipstick test was positive for 25.7% (69/269) of specimens with protein < 30 mg/dL and for 28.8% (79/274) of specimens with P/Cr ratio < 0.27. P-test results were positive for 7.3% (20/274) and negative for 18.1% (15/83) of specimens with P/Cr ratio < 0.27 and ≥0.27, respectively. Incomplete 24-h urine collection occurred in 15.6% (10/64) of 24-h urine tests. Daily urinary creatinine excretion was 702-1397 mg, while creatinine concentration varied from 16 mg/dL to 475 mg/dL in spot-urine specimens.
Dipstick test and P-test were likely to over- and underestimate risks of significant proteinuria, respectively. The 24-h urine collection was often incomplete.
Journal of Obstetrics and Gynaecology Research 09/2013; · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
To determine how urine dipstick test, edema, and/or excessive weight gain (EWG, defined as ⩾500 g/week) at antenatal visits predict significant proteinuria (defined as a protein-to-creatinine ratio [P/Cr, mg/mg] ⩾0.27) and preeclampsia.Methods
Data from 3279 antenatal visits between 30 and 36 weeks of gestation were studied in 783 women with singleton pregnancies. In 24 preeclamptic pregnancies, data from 89 antenatal visits at and before diagnosis of preeclampsia were used. Spot P/Cr was determined in women with repeated positive dipstick test results in two successive antenatal visits or in those with a positive dipstick test result tested in the presence of hypertension.ResultsProteinuria on dipstick test, edema, and EWG appeared often in both women with and without preeclampsia; 66.7% vs. 27.7%, 83.3% vs. 44.1%, and 91.7% vs. 81.6%, respectively. However, repeated positive dipstick test results in two successive antenatal visits yielded sensitivity of 45.5%, specificity of 95.2%, and positive and negative predictive values of 30.0% and 97.4%, respectively, for detection of significant proteinuria and corresponding figures of 33.3%, 94.1%, 14.0%, and 98.0% for prediction of preeclampsia.Conclusion
Repeated positive dipstick test results in two successive antenatal visits warrant a need for a confirmation test of significant proteinuria.
Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health. 07/2013; 3(3):161–165.
[Show abstract][Hide abstract] ABSTRACT: We performed a retrospective review of medical charts regarding blood d-dimer levels determined cross-sectionally by the latex agglutination assay in 1952 samples from 1185 women to determine changes in d-dimer levels according to the stage of pregnancy. Three of 17 women in whom further investigations were performed were found to have clinical venous thromboembolism (VTE). The median and 95th percentile values of d-dimer (μg/mL) in the 1182 women without clinical VTE, 0.54 and 2.41 at gestational week (GW) 4–13, increased gradually to 1.22 and 5.03 at GW 14–27, 1.81 and 6.18 at GW 28–35, and 2.13 and 5.85 at GW 36–42, respectively. A total of nine women (0.76%), including three women with clinical VTE, exhibited a d-dimer level >14.0 μg/mL, which was well above the 99th percentile for any stage of pregnancy. Thus, 3 (33%) of the nine with a d-dimer level >14 μg/mL developed clinical VTE, while none of the remaining 1176 women with a d-dimer level ⩽14 μg/mL developed clinical VTE. Although further prospective studies are required, our results suggested that there is a certain cut-off d-dimer value that would allow us to differentiate between pregnant women with and without clinical VTE.
Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health. 07/2013; 3(3):172–177.
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: The differences in the d-dimer rise between women with singleton and multifetal pregnancies have not been studied extensively. MATERIALS AND METHODS: d-Dimer levels were determined in 1089 blood specimens from 1089 women in various stages of pregnancy, including 977 and 112 women with singleton and multifetal pregnancies, respectively. None of the 1089 women developed hypertension or clinical venous thromboembolism during pregnancy or in the postpartum period. RESULTS: The d-dimer levels were significantly and positively correlated with gestational week at examination in women with singleton or multifetal pregnancies. The d-dimer levels (μg/ml, mean±SD [number of specimens]) determined at the 1st trimester did not differ significantly (0.81±0.82  for singleton vs. 1.20±0.77  for multifetal), but those at the 2nd (1.61±1.45  vs. 2.62±2.26 ) and 3rd (2.37±2.22  vs. 4.02±2.14 ) trimesters were significantly higher in women with multifetal than singleton pregnancies. The 90th percentile value was 4.31μg/ml for 1089 specimens. A significantly greater number of women exceeded 4.31μg/ml during the 2nd (16.9% vs. 5.6%, P=0.0043) and 3rd (34.8% vs. 10.6%, P<0.0001) trimesters among those with multifetal than with singleton pregnancies. CONCLUSIONS: The degree of d-dimer rise in pregnancy was greater in women with multifetal than with singleton pregnancies.
[Show abstract][Hide abstract] ABSTRACT: Objective
To determine the association of the N-terminal fragment of precursor protein brain-type natriuretic peptide (NT-proBNP) levels with plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in singleton pregnancies.
Serum NT-proBNP levels, PRA and PAC were determined in 215 blood specimens from 139 women with singleton pregnancies, including 34 and 105 women who did and did not develop hypertensive disorders in pregnancy, respectively. Twenty-five blood specimens were obtained from 25 women who later developed hypertension (systolic BP ⩾ 140 mmHg and/or diastolic BP ⩾ 90 mmHg), but were normotensive at the time of blood sampling.
The serum NT-proBNP levels [pg/ml, median (range), 32 (5–142)] did not change in normotensive women, but increased significantly to 97 (23–436) after the development of hypertension (D/H). The PRA [ng/ml/h, median (range), 7.1 (1–20)] did not change in normotensive women, but decreased significantly to 1.9 (1–16) after D/H. PAC (pg/ml) increased significantly from 397 (94–1750) to 667 (123–2010) between the 2nd and 3rd trimesters in normotensive women. However, as PAC of hypertensive women did not change significantly before and after D/H, PAC [293 (116–1720)] after D/H was significantly lower than that [667 (123–2010)] of the 3rd trimester in the normotensive women. The serum levels of NT-proBNP were significantly and negatively correlated with both PRA and PAC.
The renin-angiotensin-aldosterone system is suppressed in pregnant women with cardiac conditions associated with higher NT-proBNP levels.
Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health. 01/2013;
[Show abstract][Hide abstract] ABSTRACT: AimTo examine the incidence of umbilical cord presentation, including cord prolapse (UCP) and cord descent (UCD), after the use of a trans‐cervical balloon catheter (TCBC), such as a Foley catheter and a metreurynter, for the induction of labor (IOL). MethodsA retrospective medical chart review was conducted, focusing on the occurrence of UCP and UCD in 800 women who underwent IOL with a TCBC at five hospitals during the study period (2008–2009 for two hospitals and 2006–2009 for three hospitals). The five hospitals had a total of 8245 deliveries during the study period. UCP and UCD were defined as the descent of the umbilical cord in advance of the presenting fetal part in the presence and absence of rupture of fetal membranes, respectively. ResultsThe frequency of IOL using a TCBC with 70–250 mL of saline varied among the five hospitals from 4.9% to 18.8% (mean ± SD, 10.7 ± 5.0%). UCP and UCD occurred in two and four women, respectively, with the frequency of cord presentation varying among the hospitals from 0.0% to 1.8% (mean ± SD, 0.9 ± 0.9%); the cord presentation was significantly more likely to occur when 180–250 mL of saline was used, compared with when 70–150 mL of saline was used (8.2% [5/61] vs 0.15% [1/662], P Conclusion
The use of a TCBC with 180–250 mL of saline increases the risk of cord presentation.
Journal of Obstetrics and Gynaecology Research 01/2013; 39(3). · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Complete automation of high-performance liquid chromatography (HPLC) for determination of hemoglobin F (%Hb F) and hemoglobin A1c (%Hb A1c) levels has made this procedure available in many clinical laboratories. However, the physiological changes in %Hb F during pregnancy and the effects of physiological and supraphysiological levels of %Hb A1c on measurement of %Hb F have not been studied extensively. METHODS: Simultaneous determination of %Hb F and %Hb A1c was conducted in 490 blood samples obtained before (n=21), during the 1st (n=150), 2nd (n=116), and 3rd (n=192) trimesters of pregnancy, and postpartum (n=11) from 357 women, including 60 women with hyperglycemia but unaffected by clinical fetomaternal hemorrhage, by HPLC. RESULTS: Mean (SD) Hb F levels were 0.71% (0.25%) before pregnancy. The value of 0.82% (0.47%) during the 1st trimester decreased significantly to 0.66% (0.35%) during the 2nd trimester and to 0.58% (0.38%) during the 3rd trimester. The level was 0.62% (0.31%) approximately one year after delivery. Thus, %Hb F was highest during the 1st trimester of pregnancy. The effects of varied %Hb A1c levels on %Hb F measurements were clinically negligible. CONCLUSIONS: The data presented in this work may be used as reference intervals of %Hb F determined with HPLC during pregnancy.
Clinica chimica acta; international journal of clinical chemistry 10/2012; · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Twin pregnancy differs considerably from singleton pregnancy in many aspects and it is unknown how serum NT-proBNP level behaves in women with twin pregnancies. Serum NT-proBNP levels were determined longitudinally at gestational weeks (GW) 24 and 35 in normotensive women with 13 twin and 99 singleton pregnancies. The effects of maternal demographic characteristics on NT-proBNP levels were also analyzed. The serum NT-proBNP levels (pg/ml) in twin pregnancies, which were not different from those in singleton pregnancies at 24 GW (26±15 vs. 40±27, respectively, P=0.0718), increased significantly (P=0.0038) and were significantly higher than those in singleton pregnancies at 35 GW (72±49 vs. 34±24, P<0.0001). In the analysis including women with singleton pregnancies, the serum levels of NT-proBNP at 35 GW were significantly inversely correlated with pre-pregnancy body mass index (BMI, kg/m(2)) and were significantly higher in nulliparous than multiparous women. Thus, women with twin pregnancy were likely to exhibit an increase in serum NT-proBNP levels in the late stage of pregnancy, especially in lean and nulliparous women. The relative greater blood volume expansion occurring in twin than in singleton pregnancies was considered to be responsible for this phenomenon.
Clinica chimica acta; international journal of clinical chemistry 08/2012; 415C:41-44. · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the normal reference values for antithrombin (AT) activity, platelet count (Plt), hemoglobin concentration (Hb), and hematocrit value (Ht) immediately before vaginal delivery among healthy pregnant women with singleton pregnancies and to determine association of these blood parameters with fetal growth.
A complete blood count was performed and the AT activity was examined in 300 consecutive women admitted to hospital at > or = gestational week 36 for labor pains and/or the rupture of fetal membranes. All the women were normotensive and had singleton pregnancies, and none of the women had proteinuria, a weekly weight gain > or = 0.5 kg, or other specific complications upon admission. All the women attempted a vaginal delivery.
The medians (5th-95th percentile) were 90% (71-110%) for AT activity, 234x10(9)/L (150-337x10(9)/L) for Plt, 11.0 g/dL (9.5-12.8 g/dL) for Hb, and 34.0% (30.4-38.6%) for Ht. Women with an Hb value of > or = the median (11.0 g/dL) gave birth to significantly smaller infants than their counterparts.
A considerable number of healthy women exhibit a reduced AT activity and/or platelet count immediately before delivery. Hemoconcentration evidenced by a raised Hb value adversely effects on infant growth. Our data may be helpful when considering the normal ranges of these blood parameters for healthy parturient women.
[Hokkaido igaku zasshi] The Hokkaido journal of medical science 08/2012; 87(4-5):141-6.
[Show abstract][Hide abstract] ABSTRACT: Aim: To assess the usefulness of a new method for cesarean section (CS) that is comprised of a transverse incision into the uterine fundus, developed for women with placentas covering the entire anterior uterine wall, and introduced in September 2006. Material and Methods: Review of medical records of 12 and 29 women who underwent CS by the new and conventional methods, respectively, for placenta previa, placenta accreta (accreta, increta and percreta) or placenta widely covering the entire anterior uterine wall in which placenta accreta cannot be excluded, between June 2003 and March 2011. Results: Placenta accreta (67% [8/12] vs 10% [3/29], P = 0.0006) and cesarean hysterectomy (67% vs 10%) were significantly more frequent in the group with the new compared with the conventional method. There were no significant differences between groups with the new and conventional methods in amount of blood loss (1732 ± 1067 vs 1847 ± 1279 g, respectively), prevalence of blood loss >3000 g (8.3% vs 17%, respectively) or blood transfusion (92% vs 72%, respectively), time required for cesarean hysterectomy (210 ± 58 vs 195 ± 41 min), or neonatal conditions at birth. The amount of blood loss for cesarean hysterectomy was significantly less for the new than conventional method (1959 ± 1025 g vs 4450 ± 1145 g, P = 0.041). Conclusion: The new method was superior to the conventional method with respect to reduction of blood loss during cesarean hysterectomy. However, careful observations are mandatory in women with preserved uterus with respect to a possible increased risk of uterine rupture in future pregnancies.
Journal of Obstetrics and Gynaecology Research 06/2012; · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recurrent spontaneous abortion (RSA) may have immunological etiology. The aim of this study was to assess the efficacy of a high dose intravenous immunoglobulin (HIVIg) therapy, in which 20 g of intact type immunoglobulin was infused daily for 5 days during early gestation, for women who had a history of four or more consecutive spontaneous abortions of unexplained etiology. A total of 60 pregnant RSA women underwent HIVIg therapy, and the pregnancy outcome was assessed. The live birth rate was 73.3% (44/60). Fifteen pregnancies ended in spontaneous abortion, and one ended in intrauterine fetal death. In 11 of the 15 spontaneous abortions, fetuses had abnormal chromosome karyotype. When the 11 pregnancies with abnormal chromosome karyotype were excluded, the live birth rate was as high as 89.8% (44/49). The HIVIg therapy may be effective for severe cases of unexplained RSA.
ISRN obstetrics and gynecology 01/2012; 2012:512732.
[Show abstract][Hide abstract] ABSTRACT: To characterize patterns of insulin secretion in women with overt diabetes and gestational diabetes (GDM) defined by the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. MaTERIAL AND METHODS: A total of 228 Japanese women were examined retrospectively. All 228 women had a positive 50-g glucose challenge test (GCT) result at 25.2±1.2weeks of gestation and underwent a 75-g glucose tolerance test (GTT) at 27.4±1.8weeks of gestation. The immunoreactive insulin levels were determined during the GTT in four groups of pregnant women: five with overt diabetes, 20 with GDM according to both the previous Japan Society of Gynecology and Obstetrics (JSOG) and current IADPSG criteria (traditional GDM group), 43 with GDM according to only the IADPSG criteria (new GDM group), and 160 with non- GDM, but with a positive GCT result.
Attenuated and slow rise in plasma insulin in concert with prolonged hyperglycemia were characteristic in women with overt diabetes, compared with women with GDM in whom excessive insulin secretion in the presence of hyperglycemia was characteristic. The new GDM group did not differ significantly from the traditional GDM group with respect to scores of such indices as the insulinogenic index, the homeostasis model assessment for insulin resistance, and the quantitative insulin sensitivity check index.
Women with overt diabetes have both an impaired capacity for insulin secretion and elevated insulin resistance, while women with GDM exhibit a maintained insulin secretory capacity with an elevated insulin resistance.
Journal of Obstetrics and Gynaecology Research 12/2011; 38(1):220-5. · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Which physical findings and blood parameters predict postpartum hypertension remain to be studied in women with twin pregnancies.
The antenatal systolic and diastolic blood pressures (SBP and DBP, respectively), and 16 laboratory variables were investigated in 150 normotensive women who gave birth to twins.
When the median values of the 18 continuous variables were used as cut-off values, an SBP>120 mm Hg (relative risk [95% confidence interval], 2.81 [1.94-4.08]), a DBP>70 mm Hg (2.42 [1.68-3.49]), an aspartate aminotransferase level>18 U/L (2.22 [1.55-3.19]), and a uric acid level>5.3 mg/dL (1.68 [1.20-2.36]) were independent risk factors for postpartum hypertension.
Antenatal blood pressure measurements and a laboratory work-up may be useful clinically for predicting postpartum hypertension in women with twin pregnancies.
Journal of Perinatal Medicine 10/2011; 40(2):115-20. · 1.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To identify variables which are strongly associated with fetal growth.
The study subjects were 203 Japanese women who had a plasma glucose level ≥140 mg/dL (7.8 mmol/L) on a 50-g glucose challenge test but were normoglycemic when challenged with a 75-g oral glucose tolerance test (GTT) according to the criteria previously used in Japan. All the subjects subsequently gave birth to singleton infants. The correlations between the standard deviation for birthweight (birthweight SD) and 15 other variables, including the maternal body mass index (BMI), plasma levels of glucose and insulin on the GTT, and various indices calculated using data from the GTT, were then examined. Univariate and multivariate regression analyses were performed.
Univariate analyses revealed significant correlations between the birthweight SD and the fasting plasma glucose level (P = 0.0063), the pre-pregnancy BMI (P = 0.0001), and the BMI at delivery (P < 0.0001). Only the BMI at delivery remained as a significant factor that was independently correlated with the birthweight SD after a multivariate regression analysis.
The suppression of maternal weight gain, rather than the suppression of the plasma glucose level, may be effective for avoiding infants with overgrowth among Japanese women with mildly impaired glucose tolerance.
Journal of Obstetrics and Gynaecology Research 07/2011; 37(12):1797-801. · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: we investigated whether ascites samples obtained from pregnant women during cesarean sections contained antithrombin because it is unknown whether antithrombin escapes from the blood and passes into the interstitial space during pregnancy.
the concentration and activity levels of antithrombin were determined in six ascites samples obtained from six consecutive women who exhibited generalized edema, ascites, and a gradual decline in antithrombin activity.
all six ascites samples contained antithrombin (mean ± SD, 4.9 ± 2.2 mg/dL; range, 2.7-8.8 mg/dL) and exhibited an antithrombin activity level of 15.5 ± 6.0% (range, 10-24%).
antithrombin escapes from the blood into the interstitial space in pregnant women. This phenomenon partially explains the gradual decline in antithrombin activity observed in these six pregnant women with generalized edema and large volumes of ascites.
Journal of Perinatal Medicine 11/2010; 38(6):613-5. · 1.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate whether uterotrophic agents increase the risk of fatal hemorrhagic brain stroke.
Between 1991 and 1992, there were 230 maternal deaths among 2,420,000 pregnant women in Japan and the causes of these deaths was investigated in 1994. Using information provided in this report, we identified 35 women who died from or were assumed to die from hemorrhagic brain stroke. We assumed that 93% of women would have tried vaginal delivery. The risk of fatal hemorrhagic brain stroke after uterotrophic agent use was calculated according to the assumption that 5.0-40% of women received uterotrophic agents.
Use of uterotrophic agents for induction/augmentation of labor was confirmed in five (14.3%) of the 35 women who died from hemorrhagic brain stroke. The incidence of fatal brain stroke after the use of uterotrophic agents was only significantly higher than that for spontaneous hemorrhagic brain stroke if these agents were administered in ≤ 6.0% of women.
Because more than 6.0% of women received uterotrophic agents, these agents are unlikely to increase the risk of fatal hemorrhagic brain stroke.
Journal of Perinatal Medicine 10/2010; 39(1):23-6. · 1.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A high dose of intravenous immunoglobulin (HIVIg) therapy is effective in various diseases such as autoimmune diseases, and also is expected to have efficacy in recurrent spontaneous abortion (RSA). The aim of this study was to understand immunological mechanisms of this therapy.
By flowcytometric analyses, we examined phenotypic changes of a variety of immunological cells including natural killer (NK) cells, cytotoxic T cells, regulatory T cells and macrophages in peripheral blood of RSA women with HIVIg therapy (n = 8).
Expression percentages of inhibitory CD94 on NK cells significantly (P = 0.01) increased after the therapy (58.8 +/- 21.4% versus 71.0 +/- 17.6%).
Mechanisms of possible efficacy of HIVIg therapy for RSA may include enhancement of CD94 expression and subsequent suppression of NK cell cytotoxicity.
American Journal Of Reproductive Immunology 11/2009; 62(5):301-7. · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Administration of high-dose intact human immunoglobulin (IH-Ig) has been applied to treat a variety of inflammatory and autoimmune diseases, and is expected to have beneficial effects on human fecundity. In the present study, we investigated whether Ig had anti-resorption effects using polyinosinic-polycytidylic acid sodium salt [poly (I:C)]-induced enhancement of fetal resorption in the mating of CBA/J x DBA/2J resorption-prone mouse model. Furthermore, we investigated the mechanism of the effect by examining the mRNA expression of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, IL-10, IL-4 and TGF-beta(1) in spleens and placentas from the resorption-prone model treated with IH-Ig, by reverse transcription (RT)-polymerase chain reaction (PCR). Administration of high-dose IH-Ig significantly reduced the fetal resorption rate from 55% to 10%. This anti-resorption effect, however, was not detected in mice administered with Fab fragments of human Ig. We then performed adoptive transfer experiments to examine whether cellular components could transfer the effect. A remarkable anti-resorption effect was seen in poly (I:C)-injected pregnant recipients transferred with spleen cells from IH-Ig-treated donor mice. The RT-PCR study showed that IH-Ig reduced the expression of IFN-gamma and TNF-alpha mRNA in placentas of poly (I:C)-injected pregnant mice. The present findings demonstrate that intact Ig, particularly its Fc portion, possesses anti-resorption activity. The effect might be attributed to the suppressed production of pro-inflammatory cytokines at the maternofetal interface.
Molecular Human Reproduction 12/2007; 13(11):807-14. · 4.54 Impact Factor