Dexamethasone pretreatment attenuates cerebral vasodilative responses to hypercapnia and augments vasoconstrictive responses to hyperventilation in newborn pigs

In the perinatal period, glucocorticoids are frequently administered to enhance pulmonary maturity or prevent chronic lung disease of prematurity. Recently, it has been suggested that the perinatal exposure to glucocorticoids can be associated with unfavorable neurologic development. We studied the hypothesis that 24-h pretreatment with glucocorticoid might modify cerebrovascular responses to high and low partial arterial CO(2) tension in newborn animals in vivo. A closed cranial window was implanted over the left parietal cortex of 20 anesthetized ventilated newborn (<3 d old) pigs. The actual experiments were carried out in 15 pigs: eight pretreated with a total dose of 6 mg/kg of dexamethasone and seven controls. Five pigs were used for preliminary experiments as described in the text. Pial arteriolar diameters were measured during 1) baseline conditions (normocapnia), 2) hypercapnia induced by ventilating the animals with a gas mixture containing 10% CO(2), or 3) hyperventilation with resultant hypocapnia. Under these conditions, the concentrations of 6-keto-PGF(1alpha) in the CSF were measured in five experimental animals and six controls. In summary, the dexamethasone pretreatment 1) attenuated the hypercapnia-induced dilator responses of pial arterioles and prevented the hypercapnia-associated fall in mean arterial blood pressure; 2) caused moderate, although not statistically significant, diminution in 6-keto-PGF(1alpha) levels in the CSF during baseline; 3) blocked hypercapnia-induced elevation of 6-keto-PGF(1alpha); and 4) enhanced vasoconstrictive arteriolar responses to hyperventilation. We speculate that in the clinical setting, the dexamethasone effects may compromise the adjustments of global or regional cerebral blood flow to changing physiologic states in neonates.     

Microsatellite marker association at chromosome region 2p13 in Finnish patients with preeclampsia and obstetric cholestasis suggests a common risk locus

The pathophysiology of preeclampsia is incompletely understood, but the familial nature of the disease has long been recognized. Recent genome-scan studies have indicated linkage at the p23 region of chromosome 2. We have previously reported microsatellite marker association at chromosome region 2p13 in patients with obstetric cholestasis. We conducted population-based association screening with microsatellite markers to find potential preeclampsia-associated loci on chromosome region 2p13-p12 and to test whether preeclampsia and obstetric cholestasis share a single risk locus. The study was carried out among 115 unrelated control women, 133 preeclamptic women and 57 cholestatic women. Screening with microsatellite markers at the 2p13-p12 region revealed that the marker D2S286 was significantly associated with obstetric cholestasis in the overall association analysis (P=0.03), while it revealed only borderline association with preeclampsia (P=0.08). However, single allele association analysis indicated that both preeclampsia and obstetric cholestasis showed a statistically significant association with a common allele (P < 0.05), which was overrepresented in both the obstetric cholestasis (0.42) and preeclamptic (0.37) groups when compared with the control group (0.28). In conclusion, These findings suggest a possible genetic link between chromosome region 2p13-p12, preeclampsia and obstetric cholestasis. More specifically, these data suggest that there may be a common risk locus associated with both obstetric complications located in the vicinity of the 2p13-p12 association region.     

Endothelial nitric oxide synthase polymorphism in preeclampsia

OBJECTIVE: We wished to determine whether genetic variability in the gene encoding endothelial nitric oxide synthase (eNOS) modifies individual susceptibility to the development of preeclampsia. METHODS: The study involved 132 preeclamptic and 113 healthy control pregnant women who were genotyped for the Glu298Asp polymorphism in the eNOS gene. Chi(2) analysis was used to assess genotype and allele frequency differences between preeclamptic women and controls. RESULTS: A statistically similar allelic distribution of eNOS Glu298Asp polymorphism was observed in the two groups, with the frequency of the variant G allele being 74.6% in the preeclampsia group and 67.7% in the control group (P = .091; odds ratio 1.40, 95% confidence interval 0.95, 2.01). Accordingly, the genotype distribution of the NOS polymorphism in the preeclamptic and control groups was found to be similar (P = .233). CONCLUSION: These genotype data in subjects from eastern Finland were not suggestive of an important contribution of the Glu298Asp polymorphism in the NOS gene on preeclampsia across populations. However, the observed association between the G allele and disease risk, of borderline significance, may imply that other polymorphism(s) in the gene may modify disease risk.     

Does hysterectomy with ovarian conservation affect bone metabolism and density?

We evaluated whether hysterectomy with ovarian conservation (HYX) has an effect on bone metabolism and density in 176 healthy Caucasian postmenopausal women aged 48-59 years. Bone properties of the hip, spine, radius, tibia, and calcaneus were measured using different bone assessment modalities. In addition, bone turnover was assessed using serum bone-specific alkaline phosphatase (BAP), osteocalcin (OC), and tartrate-resistant acid phosphatase (TRAP) 5b as biomarkers. Our results showed that women having HYX had a significantly lower level of OC ( P = 0.017) and a marginally lower level of TRAP 5b ( P = 0.051) and higher bone mineral density (BMD) of the femoral neck ( P = 0.037) and lumbar spine ( P= 0.001) than women with no history of HYX. In addition, the cortical BMD and bone strength index (I(polar)) of the tibia also showed higher values at different sections in women having HYX than women with no history of HYX ( P = 0.055 to P< 0.005). These results suggest that the uterus may have a role in regulating bone metabolism that has not been detected previously.     

Weights of placentae from small-for-gestational age infants revisited

The objective of the study was to investigate the association between placental weight and birthweight in appropriate (AGA) and small for gestational age (SGA) infants. Placental weight, birthweight and their ratio in chromosomally normal singleton pregnancies with SGA (n=1569) and AGA (n=15 047) infants were compared, and their determinants were studied by logistic regression. SGA infants had 24 per cent smaller placentae than AGA infants when gestational age was used as a covariate. Placental actual weight was also lower in SGA infants than in AGA infants of the same birthweight (P< 0.001). SGA infants had smaller placentae than the controls, suggesting that fetal growth depends on the actual weight of the placenta. Future studies should evaluate whether growth restriction could be reversed by therapeutic approaches increasing placental weight.     

Thoracic epidural infusions for post thoracotomy pain relief: a clinical study to compare the efficacy of fentanyl — bupivicaine mixtures versus fentanyl alone

Background: Optimum pain relief following thoracotomy is essential for patient comfort and to reduce the incidence of postoperative pulmonary complications. Methods: A randomized clinical trial was conducted on 90 patients scheduled for pulmonary resection. The patients were randomly divided into three groups. Group 1 received 0.125% bupivicaine with fentanyl 10μg.ml⁻¹, Group 2 received 0.25% bupivicaine with fentanyl 10μg.ml⁻¹ and Group 3 received only fentanyl 10μg.ml⁻¹ in a calculated dose as a continuous thoracic epidural infusion. Adequacy of anglesia was assessed at rest and during movement over 24 hours. Analgesic efficacy was assessed using a visual analogue score and an observer verbal ranking scale. Results: Pain scores were significantly higher in Group 3 during the assessment period. (p<0.01) as compared to the other groups. The use of intraoperative vasopressors was significantly higher (p<0.05) in Group 2 as compared to the other groups. No neurological complications were encountered in any of the study groups. Conclusion: We conclude that in the early postoperative period, the use of 0.125% bupivicaine improves fentanyl epidural analgesia in patients undergoing lung resection.     

Administration of nitric oxide into open lung regions: delivery and monitoring

Background. Pulsed administration of nitric oxide has proveneffective in relieving pulmonary hypertension and in improvingoxygenation. With this delivery method the nitric oxide administrationto low ventilated lung regions is avoided with subsequent enhancementin oxygenation. This study presents (i) pulsed administrationtechnique for nitric oxide during artificial ventilation, (ii)evaluation of the delivery in an animal model, and (iii) validationof the delivery device in a laboratory setting. Methods. Nitric oxide was delivered in four different pulsevolumes synchronously with inspiration. The delivery was monitoredwith a fast responding high sensitivity nitric oxide monitorand nitric oxide uptake was calculated. Pulse delivery doserange, accuracy of the delivered dose, and stability of successivedoses were analysed in a laboratory setting. Results. Uptake of the delivered nitric oxide was 87–92%.Measured nitric oxide pulse concentration was 1.6-fold the deliveryconcentration, calculated as the ratio of nitric oxide flowto inspiration flow. Dose accuracy and stability were both 5%or 3 nmol in the validated range of 3–1000 nmol. Conclusion. With pulsed administration nitric oxide therapycan be directed to well-ventilated lung regions. Avoiding administrationto the anatomic dead space eliminates nitric oxide exhalationeffectively, which makes the method optimal for nitric oxidetherapy in a rebreathing circuit. The required dose range frompaediatric to adult is covered by the delivery device with asingle nitric oxide gas supply. Br J Anaesth 2003; 90: 338–42     

Clinical implications of the didelphic uterus: long-term follow-up of 49 cases

OBJECTIVE: The aim of the study was to evaluate reproductive performance of women with didelphic uterus and to consider possible long-term consequences associated with this uterine anomaly. STUDY DESIGN: Forty-nine women were diagnosed as having a didelphic uterus with a longitudinal vaginal septum at Tampere University Hospital, Finland between 1962 and 1998. The presence of other anomalies, gynecologic disorders, fertility and outcome of pregnancies were reviewed. The long-term clinical implications associated with a didelphic uterus were evaluated during the mean (S.D.) follow-up period of 9.1 (6.3) years. RESULTS: An obstructed hemivagina was found in nine (18%) out of forty-nine cases; eight of these had ipsilateral renal agenesis. A longitudinal vaginal septum was excised in twenty-six (53%) cases, but metroplasty in none. Five (13%) patients had primary infertility. Thirty-four (94%) out of thirty-six women who wanted to conceive had at least one pregnancy, and they produced seventy-one pregnancies; 21% miscarried, and ectopic pregnancy occurred in 2%. The fetal survival rate was 75%, prematurity 24%, fetal growth retardation 11%, perinatal mortality 5. 3%, and cesarean section rate 84%. Pregnancy located more commonly (76%) in the right uterus than in the left. During the follow-up period endometriosis was observed in seven (16%) out of forty-five cases. Ovarian neoplasm was found in four (9%) cases, one of them had ovarian cancer. CONCLUSIONS: Fertility in women with didelphic uterus is not notably impaired. The prognosis of pregnancy is comparatively good, while prematurity and fetal growth retardation indicate meticulous prenatal care. Long-term follow-up did not reveal that didelphic uterus is associated with increased frequency of endometriosis or genital neoplasm.     

Assisted reproduction in women with uterine anomalies

A retrospective analysis was performed to evaluate the reproductive performance of 17 women with uterine anomalies who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and embryo transfer (ET). Eight women had a unicornuate uterus, and two a didelphic uterus. Seven women with a subseptate uterus underwent metroplasty before assisted reproduction. Ten (58.8%) out of 17 women achieved 11 (18.0%) pregnancies out of 61 embryo transfers in 55 stimulated cycles. The implantation rate per embryo was 8/83 (9.6%) for women with a unicornuate uterus, one of 17 (5. 9%) for those with didelphic uterus and four of 48 (8.3%) for those with subseptate uterus. Pregnancy rates per embryo transfer were 19. 4, 11.1 and 19.0%, respectively. Three out of 11 pregnancies were ectopic, three were miscarriages and five were full-term deliveries, two sets of twins. Delivery rate per embryo transfer was 5.0% in patients with unicornuate or didephic uterus and 14.3% in women who had a subseptate uterus operated prior to assisted reproduction. Women with uterine anomalies treated by IVF or ICSI had low implantation rates. Pregnancy in a subseptate uterus which has been previously operated had a trend to end more frequently in delivery than that in a unicornuate uterus or in a didelphic uterus.