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.     

Detection of carbamyl phosphate synthetase 1 deficiency using duodenal biopsy samples

The activity of urea cycle enzymes was assayed in duodenal biopsy specimens obtained from a female infant who presented with neonatal hyperammonaemia. All enzyme levels were normal except N-acetyl glutamate-dependent carbamyl phosphate synthetase 1 (CPS1) which was half the mean activity in normal control specimens. A similar deficiency of CPS1 was also shown in duodenal specimens from the patient's mother who became slightly symptomatic after relatively high protein meals and during pregnancy, and had spontaneously modified her diet to one with protein restriction. The patient is growing normally on a dietary regimen similar to that spontaneously adopted by her mother. Urea cycle enzyme activity in the duodenal biopsy material from the controls was similar to that found in the normal human liver and appears to have distinct advantages as a means of assaying for urea cycle defects in patients with hyperammonaemia and their relatives.     

Why is the age-standardized incidence of low-trauma fractures rising in many elderly populations?

Low-trauma fractures of elderly people are a major public health burden worldwide, and as the number and mean age of older adults in the population continue to increase, the number of fractures is also likely to increase. Epidemiologically, however, an additional concern is that, for unknown reasons, the age-standardized incidence (average individual risk) of fracture has also risen in many populations during the recent decades. Possible reasons for this rise include a birth cohort effect, deterioration in the average bone strength by time, and increased average risk of (serious) falls. Literature provides evidence that the rise is not due to a birth cohort effect, whereas no study shows whether bone fragility has increased during this relatively short period of time. This osteoporosis hypothesis could, however, be tested if researchers would now repeat the population measurements of bone mass and density that were made in the late 1980s and the 1990s. If such studies proved that women's and men's age-standardized mean values of bone mass and density have declined over time, the osteoporosis hypothesis would receive scientific support. The third explanation is based on the hypothesis that the number and/or severity of falls has risen in elderly populations during the recent decades. Although no study has directly tested this hypothesis, a great deal of indirect epidemiologic evidence supports this contention. For example, the age-standardized incidence of fall-induced severe head injuries, bruises and contusions, and joint distortions and dislocations has increased among elderly people similarly to the low-trauma fractures. The fall hypothesis could also be tested in the coming years because the 1990s saw many research teams reporting age- and sex-specific incidences of falling for elderly populations, and the same could be done now to provide data comparing the current incidence rates of falls with the earlier ones.     

Antibodies to diphtheria, tetanus and pertussis in infants before and after immunization with DTP (Triple Antigen) vaccine

Objective : To determine antibody levels to the Australian manufactured combined diphtheria, tetanus and pertussis (DTP) vaccine (Triple Antigen, CSL Ltd) in infante before and after their primary immunization course.
Methodology : Serosurvey (antibody prevalence study) in two groups: infants aged 5-9 weeks who had not received any immunizations ( n = 25), and infants aged 7-10 months who had received two ( n = 25) or three immunizations ( n = 57) with DTP, sampled from infants attending the Royal Children's Hospital, Melbourne, either as inpatients or outpatients between February and April 1993. The immunization history for each infant was determined from hospital records, the parent-held child health record, or the local council or family doctor who immunized the infant.
Results : Enzyme immunoassay (EIA) of antibodies to diphtheria and tetanus showed all infants to have adequate protective levels after two or three vaccinations (£0.01 IU/mL). All subjects who had received all three DTP vaccinations had detectable antibody to at least one pertussis antigen. Antibodies to the pertussis antigens filamentous haemagglutinin and pertussigen (pertussis toxin) were comparable to levels determined for whole cell pertussis vaccines used elsewhere in the world. EIA-determined antibodies to pertussis agglutinogen type 2 and agglutinogen type 3 showed substantially higher geometric mean titres when results for pre-immunization and post-immunization subjects were compared.
Conclusions : These data show that the Australian manufactured DTP vaccine has immunogenic properties similar to those of vaccines used elsewhere, and that antibody concentrations following immunization are at levels consistent with efficacy.     

Fetal macrosomia--a continuing obstetric challenge

BACKGROUND: Macrosomic fetuses represent a continuing challenge in obstetrics. OBJECTIVES: We studied maternal risk factors of fetal macrosomia and maternal and infant outcome in such cases. METHODS: A retrospective cohort study was carried out with a total of 26,961 singleton pregnancies between 1989 and 2001. Records of 886 mothers who gave birth to live born infants weighing > or =4,500 g were compared to those of 26,075 mothers with normal weight (<4,500 g) infants. Multiple regression analysis was used to identify independent reproductive risk factors. Perinatal complications were also assessed. RESULTS: The incidence of fetal macrosomia was 3.4%. Diabetes, previous macrosomic birth, postdatism (>42 weeks of gestation), obesity (BMI > 25 before pregnancy), male infant, gestational diabetes mellitus, and non-smoking were independent risk factors of fetal macrosomia, with adjusted risks of 4.6, 3.1, 3.1, 2.0, 1.9, 1.6, 1.4, respectively. In the macrosomic group, birth and maternal traumas occurred significantly more often than in the control group. However, records of subsequent pregnancies (n = 250) after the study period showed that a previous uncomplicated birth appeared to decrease complication risks. CONCLUSIONS: Most cases of fetal macrosomia occur in low-risk pregnancies and evaluation of maternal risks cannot accurately predict which women will eventually give birth to an overweight newborn. After an uncomplicated birth of a macrosomic infant, vaginal delivery may be a safe option for the infant and mother.