Elevated total peripheral leukocyte count may identify risk for neurological disability in asphyxiated term neonates.

OBJECTIVE: The present study investigated the relationship between neurologic outcome and total circulating white blood cell (WBC) and absolute neutrophil counts (ANCs) in the first week of life in term infants with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: Long-term neurologic outcome at 18 months was measured retrospectively in 30 term neonates with HIE using the Pediatric Cerebral Performance Category Scale (PCPCS) score with outcomes dichotomized as either good or poor. We then compared white blood cell and ANC levels during the first 4 days of life and magnetic resonance imaging (MRI) obtained within the first month life between the two PCPCS groups. MRI was quantified using a validated scoring system. RESULTS: Neonates with good long-term outcomes had significantly lower MRI scores (indicating lesser injury) than neonates with poor outcomes. More importantly, neonates with poor outcomes had significantly higher WBC and ANC levels as early as12 h after birth and up to 96 h after birth compared to those with good outcomes. These data suggest that elevated peripheral neutrophil counts in the first 96 h of life may signal or predict adverse long-term outcome. CONCLUSIONS: Our findings suggest that elevated peripheral neutrophil counts in the first 96 h of life in term infants with HIE may contribute to abnormal neurodevelopmental outcome.     

Low proliferation activity may be associated with chemoresistance in clear cell carcinoma of the ovary

OBJECTIVE: To estimate whether and how the biologic behavior of clear cell carcinoma contributes to the chemoresistance mechanism. METHODS: Forty-one patients with clear cell carcinoma and 90 patients with serous adenocarcinoma, who had measurable disease after initial surgery, were examined. All patients underwent cytoreductive surgery followed by platinum-based chemotherapy. P-glycoprotein, multidrug resistance-associated protein, and Ki-67 expression were determined by immunohistochemical staining. RESULTS: The 5-year survival rate for patients with clear cell carcinoma was significantly poorer, compared with serous adenocarcinoma (20.0% versus 31.9%). Response rate to chemotherapy was 14.6% for clear cell carcinoma and 72.2% for serous adenocarcinoma. The expression of P-glycoprotein and multidrug resistance-associated protein did not differ between responders and nonresponders in both tumor types. The Ki-67 labeling index (LI) in clear cell carcinoma was significantly lower than serous adenocarcinoma (18.4% versus 38.8%). The LI for responders was significantly higher than that for nonresponders in both tumor types. In clear cell carcinoma, the mean value of LI was 15.3% for nonresponders, but that for responders was 30.2%, which was similar to that for serous adenocarcinoma. When the cutoff value of LI was set at 18.4% (mean value), the 5-year survival rate for high LI (over 18.4%) patients was significantly greater than that for low LI patients (46.3% versus 9.2%). Multivariable analysis revealed that LI and residual tumor size were the independent prognostic factors. CONCLUSION: Lower proliferation of tumor may be a behavior of clear cell carcinoma of the ovary that contributes to its resistance to chemotherapy.     

Increased monocyte chemotactic protein-1 level and activity in the peripheral blood of women with endometriosis

OBJECTIVE: Our purpose was to evaluate monocyte chemotactic protein-1 in the peripheral blood of women with and without endometriosis. STUDY DESIGN: Fifty-seven patients with endometriosis at laparoscopy done for infertility and pelvic pain were compared with 44 fertile women with no evidence of endometriosis at tubal ligation by laparoscopy. Monocyte chemotactic protein-1 concentration in the plasma was determined by enzyme-linked immunosorbent assay and its biologic activity was evaluated by measuring monocyte chemotaxis with use of a human histiocytic cell line (U937). RESULTS: Monocyte chemotactic protein-1 concentrations (median and range of values) found in the plasma were higher in patients with endometriosis (163, 0 to 788 pg/ml) than in normal controls (0, 0 to 355 pg/ml). This elevation was significant only in the minimal stage of endometriosis (revised American Fertility Society stage I). However, increased chemotactic activity (mean number of migrating cells/mm² ± SEM) was found in the stages I (1240 ± 141), II (519 ± 30), and III-IV (523 ± 23) of the disease compared with normal controls (205 ± 20). A total of 35% to 44% of this activity was inhibited in the presence of an antibody specific to monocyte chemotactic protein-1. CONCLUSION: Endometriosis is associated with increased level and activity of monocyte chemotactic protein-1 in the peripheral blood. The elevation and activation of this cytokine could play a relevant role in the immunoinflammatory process associated with the disease. (Am J Obstet Gynecol 1996;175:1620-5.)     

Nucleolar dysfunction may be associated with infertility in humans

Nucleoli are prominent structures present in almost all eukaryotic cells. Some recent findings indicate that their dysfunction in oocytes and embryos may be associated with infertility in humans.     

Increased rate of small-for-gestational-age neonates in pre-eclamptic women with preterm deliveries.

We sought to determine whether hypertensive pregnancies can be considered a distinct subgroup of premature births. All women in our centre who had had singleton preterm spontaneous deliveries over an 8-year period were divided into hypertensive and normotensive groups and compared for maternal characteristics and neonatal outcome. Of the 4175 eligible women, 9.8% (n = 410) had pre-eclampsia. These patients had higher rates of small-for-gestational-age neonates (19%, 78/410), abruptio placenta (7.8%, 32/410) and caesarean section rate (52.7%, 216/410) than the normotensive women (4.3%, 158/3765; 4.6%, 172/3765; and 19.6%, 739/3765, P < 0.001, respectively. The rate of preterm premature rupture of membranes was significantly lower in the hypertensive than in the normotensive group (5.9% vs. 17%, respectively; P < 0.001). We concluded that hypertensive women who deliver prematurely belong to a subgroup with particular characteristics. The increased rate of small-for-gestational-age neonates in pre-eclamptic women suggests that reduced uteroplacental perfusion may cause fetal growth impairment before the onset of the hypertensive disorder.     

Increased ADMA levels are associated with poor pulmonary outcome in preterm neonates

Background: Nitric oxide (NO), synthesized from the amino acid L-arginine by the action of NO synthases (NOS), is a pulmonary vasodilator. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NOS. Preterm infants have higher plasma ADMA concentrations than term infants which could cause inhibition of NO synthesis and deterioration in pulmonary functions. We aimed to investigate the relationship between serum ADMA and L-arginine levels of preterm infants and respiratory distress syndrome (RDS), requirement of surfactant treatment, duration of mechanical ventilation, oxygen treatment, and development of bronchopulmonary dysplasia (BPD).

Methods: A prospective cohort study was conducted including 80 preterm infants born with gestational age (GA) ≤?32 weeks and birth weight (BW) ≤?1500?g. Blood samples were obtained from all infants immediately after birth, and at postnatal 28th day of age. The relationship of first-day serum ADMA and L-arginine levels and surfactant requirement, duration of mechanical ventilation, oxygen treatment was investigated. Serum ADMA and L-arginine levels at 1st and 28th days were compared at patients with and without BPD. The role of serum ADMA levels at postnatal 28th day of age to predict the requirement of oxygen at postmenstrual 36 weeks of age was also investigated.

Results: Eighty preterm infants (42 male, 38 female) were enrolled in the study. Mean BW and GA for the total cohort was 1144.81?±?220.44?g and 28.3?±?1.8 weeks, respectively. Sixty-one infants were diagnosed as RDS and 44 infants treated with surfactant. The first-day ADMA levels were significantly higher in infants with surfactant requirement (1.14?±?0.23 versus 0.86?±?0.37, p?p?>?0.05) but not significantly. Serum ADMA and L-arginine concentrations at first day were not different among infants with and without BPD (p?>?0.05). ADMA concentrations at 28th day was significantly higher in infants with BPD (1.00?±?0.25 versus 0.81?±?0.25, p?Conclus?on: Serum ADMA and L-arginine levels are related to pulmonary morbidities in newborn. The results of this study show that increased ADMA levels are associated with poor pulmonary outcomes in preterm infants.     

Insulin growth factors may be implicated in human sperm capacitation

This study was designed to determine whether or not insulin-like growth factor (IGF)-1 and its receptor are present in the human male genital tract. The IGF-1 receptor was found in seminal plasma from fertile and infertile men, but no IGF-1 receptor was observed in sperm from patients with a history of more failed fertilization. The presence of the IGF-1 receptor in the plasma membrane of human sperm is proposed as a future tool for male sterility assessment.     

Oxidative stress may be a piece in the endometriosis puzzle

OBJECTIVE: To assess the total antioxidant potential of women with endometriosis-associated infertility, women with idiopathic infertility, and fertile controls. DESIGN: Retrospective study. SETTING: University medical hospital. PATIENT(S): Sixty-five women admitted for diagnostic laparoscopy. MAIN OUTCOME MEASURES: Peritoneal fluid samples were analyzed for superoxide dismutase activity and total antioxidant status on spectrophotometry, glutathione peroxidase activity on enzyme-linked immunosorbent assay, and lipid peroxides levels on colorimetry. RESULT(S): Mean activity of superoxide dismutase, glutathione peroxidase, and total antioxidant status was lowest and lipid peroxide level was highest among infertile patients with endometriosis. Women with idiopathic infertility, in contrast, had the highest superoxide dismutase, glutathione peroxidase, and total antioxidant status activity and the lowest lipid peroxide level. CONCLUSION(S): High antioxidant potential is not a contributing factor in women with idiopathic infertility. Low total antioxidant status and low activity of antioxidant enzymes in the peritoneal fluid of infertile women with endometriosis probably do not influence fertility in these women, but these factors may play a role in the development of the disease.     

Increased prevalence of abnormal vertebral patterning in fetuses and neonates with trisomy 21

Purpose: To assess the prevalence of an abnormal number of ribs in a cohort of fetuses and neonates with trisomy 21 and compare this with a subgroup of fetuses without anomalies.

Materials and methods: Radiographs of 67 deceased fetuses, neonates, and infants that were diagnosed with trisomy 21 were reviewed. Terminations of pregnancy were included. The control group was composed of 107 deceased fetuses, neonates, and infants without known chromosomal abnormalities, structural malformations, infections or placental pathology. Cases in which the number of thoracic ribs or presence of cervical ribs could not be reliably assessed were excluded. The literature concerning vertebral patterning in trisomy 21 cases and healthy subjects was reviewed.

Results: Absent or rudimentary 12th thoracic ribs were found in 26/54 (48.1%) cases with trisomy 21 and cervical ribs were present in 27/47 (57.4%) cases. This prevalence was significantly higher compared to controls (28/100, 28.0%, Χ²(1)?=?6.252, p?=?.012 and 28/97, 28.9%, Χ²(1)?=?10.955, p?Conclusions: Rudimentary or absent 12th thoracic ribs and cervical ribs are significantly more prevalent in deceased fetuses and infants with trisomy 21.     

Increased androgenic activity in well-differentiated endometrial adenocarcinoma

Well-differentiated adenocarcinoma of the endometrium was diagnosed in 3 patients with polycystic ovary syndrome (PCO) and in 2 long-term users of an oral contraceptive (ethinylestradiol plus dimethisterone), all 5 at premenopausal age (from 28 to 36 years). These patients had high urinary testosterone. None underwent hysterectomy; the 3 with PCO were treated by wedge resection of the ovaries, and the 2 oral contraceptive users by simple curettage and discontinuation of oral contraception. The treatment was able to revert the endometrial pattern to normal as well as decrease the urinary level of testosterone. These patients were followed up for 3 to 10 years since the hormonal study and none has so far had a recurrence. The testosterone excretion level was determined in an additional 26 patients with well-differentiated adenocarcinoma and in 14 with undifferentiated adenocarcinoma of the endometrium. It was found that the testosterone excretion level was significantly increased in patients with well-differentiated adenocarcinoma but not in patients with undifferentiated adenocarcinoma of the endometrium.     

Increased 5 alpha-reductase activity in idiopathic hirsutism

In vitro, genital skin 5 alpha-reductase activity (5 alpha-RA) was measured in ten hirsute women with normal androgen levels (idiopathic hirsutism [IH]) and in ten hirsute women with elevated androgen levels (polycystic ovary syndrome [PCO]) in order to determine the influence of secreted androgens on 5 alpha-RA. In vitro 5 alpha-RA was assessed by incubations of skin with 14C-testosterone (T) for 2 hours, after which steroids were separated and the radioactivity of dihydrotestosterone (DHT) and 5 alpha-androstane 3 alpha-17 beta-estradiol (3 alpha-diol) in specific eluates were determined. All androgens were normal in IH with the exception of higher levels of 3 alpha-diol glucuronide which were similar to the levels of PCO. The conversion ratio (CR) of T to DHT in IH (17.18% +/- 4.6%) and PCO (17.86% +/- 5.2%) were similar, yet significantly greater than the CR of control subjects (4.48% +/- 0.36% P less than 0.01). The CR of T to 3 alpha-diol in IH (8.00% +/- 1.38%) and PCO (10.36% +/- 1.0%) were similar, yet higher than in control subjects (2.96% +/- 0.32%; P less than 0.05). Serum androgens showed no correlation with 5 alpha-RA, while the CR of T to DHT showed a significant positive correlation with the Ferriman and Gallwey score (r = 0.61; P less than 0.01). The increased 5 alpha-RA in IH appears to be independent of serum androgen levels and is, therefore, an inherent abnormality. The term "idiopathic" is a misnomer, because hirsutism in these patients may be explained on the basis of increased skin 5 alpha-RA.     

Cerebral perfusion pressure,and not cerebral blood flow,may be the critical determinant of intracranial injury in preeclampsia: a new hypothesis

OBJECTIVE: The relationship between cerebral perfusion pressure (CPP) and cerebral blood flow is unclear in preeclampsia. Our objective was to clarify this issue by comparing normal pregnant women to those with mild and severe preeclampsia. STUDY DESIGN: Patients with mild (n = 72) and severe (n = 120) preeclampsia underwent transcranial Doppler (TCD) imaging of the maternal middle cerebral artery (MCA). At the same time, blood pressure was taken with a Dinamap monitor (Dinamap; Criticon Inc, Tampa, Fla). CPP, resistance area product (RAP), and the cerebral flow index (CFI) were calculated by standard formulas. Data were plotted on normative curves for pregnancy (5% and 95%) and compared by chi(2) and Mann-Whitney U tests. RESULTS: CFI is usually normal in both severe (75%) and mild (72%) cases. If CFI is abnormal in severe cases, it may be either increased (14%) or decreased (10%), although in mild cases almost all abnormal CFI (25%) is lower than normal. In those cases with low or normal CFI, severe cases are associated with a significantly higher CPP, RAP, and MAP than mild cases (P <.05), although the CFI is not significantly different. A significant proportion of severe cases have high CPP (52%), whereas in mild cases the CPP is almost always normal (87%). Overall, in severe cases the RAP is abnormally high, although it is within the normal range in mild cases. CONCLUSIONS: One of the fundamental differences between mild and severe cases relates to the degree of cerebral perfusion pressure that the MCAs are subjected to. Because most preeclamptic women, regardless of degree of severity, have a normal CFI, it appears that autoregulation is generally intact. Because women with severe cases are more prone to cerebral catastrophe than those with mild preeclampsia, uncontrolled CPP may cause barotrauma and vessel damage, leading to hypertensive encephalopathy and overperfusion injury. Therapeutic strategies that ensure reduction of the CPP with maintenance of the CFI seem most likely to prevent the cerebral injuries (overperfusion or underperfusion) that cause seizures or death in women with preeclampsia.     

Intrauterine infection may be a major cause of stillbirth in Sweden

AIM OF THE STUDY: To investigate intrauterine infection as a cause for unexplained stillbirth. METHODS: Chorioamnionitis was studied in a material of stillbirths (117 subjects from the years 1985-1994) from a region in the south Sweden. Control material (126 alive and healthy newborns and with healthy mothers) was gathered from the same region. RESULTS: Chorioamnionitis was a common diagnosis both with stillbirths and 'healthy' deliveries (82 and 68%, respectively). Extension of the inflammation to decidua basalis was seven times more common among stillbirths than among controls (odds ratio 7.2, confidence interval 2.8-21.9). The most common bacteria found at cultures were Escherichia coli, Coagulase negative staphylococcus, Enterococcus faecalis and group B Streptococcus. The risk for stillbirth was doubled if both inflammation and bacteria were present (odds ratio 2.3, confidence interval 0.92-5.8). Meconium discharge was more common among stillbirths than controls (odds ratio=4.7, confidence interval 1.7-14). There were no differences in any respect regarding macerated and non-macerated stillbirths. Our findings are similar to the results from studies in developing countries except for the higher incidence of stillbirths in such countries. CONCLUSIONS: Thus, a large part of otherwise unexplained stillbirths might be due to ascending infections.