John Patrick O'Grady

Metabolic cartography: experimental quantification of metabolic fluxes from isotopic labelling studies

For the past decade, flux maps have provided researchers with an in-depth perspective on plant metabolism. As a rapidly developing field, significant headway has been made recently in computation, experimentation, and overall understanding of metabolic flux analysis. These advances are particularly applicable to the study of plant metabolism. New dynamic computational methods such as non-stationary metabolic flux analysis are finding their place in the toolbox of metabolic engineering, allowing more organisms to be studied and decreasing the time necessary for experimentation, thereby opening new avenues by which to explore the vast diversity of plant metabolism. Also, improved methods of metabolite detection and measurement have been developed, enabling increasingly greater resolution of flux measurements and the analysis of a greater number of the multitude of plant metabolic pathways. Methods to deconvolute organelle-specific metabolism are employed with increasing effectiveness, elucidating the compartmental specificity inherent in plant metabolism. Advances in metabolite measurements have also enabled new types of experiments, such as the calculation of metabolic fluxes based on (13)CO(2) dynamic labelling data, and will continue to direct plant metabolic engineering. Newly calculated metabolic flux maps reveal surprising and useful information about plant metabolism, guiding future genetic engineering of crops to higher yields. Due to the significant level of complexity in plants, these methods in combination with other systems biology measurements are necessary to guide plant metabolic engineering in the future.

INFANT SURVIVAL FOLLOWING DELAYED POSTMORTEM CESAREAN DELIVERY

A 19-year-old multipara was delivered of a living infant by postmortem cesarean 22 minutes after documented maternal cardiac arrest and 47 minutes from the fatal injury. Neonatal follow-up at 18 months of age demonstrated no evidence of neurologic damage.

Fetal breathing movements and the response to carbon dioxide in patients on methadone maintenance

Fetal breathing movements were monitored on six methadone maintenance patients and ten healthy control patients, studied while breathing room air and while breathing a prepared gas mixture with 5% carbon dioxide, both before and 2 hours after either the usual daily dose of methadone or a diet drink. There was no difference before and after the diet drink in control patients, who showed a significant increase in the incidence of fetal breathing movements from 37.1% +/- 5.9% (SEM) on room air to 69.4% +/- 2.8% while breathing 5% carbon dioxide (p less than 0.01). In the patients studied on room air before receiving methadone, fetal breathing movements were significantly decreased from those of the control group, 4.7% +/- 1.2% (p less than 0.01), with a further decrease when studied after receiving methadone, 1.3% +/- 0.7%. Fetal breathing movements did increase significantly in response to 5% carbon dioxide both before and after receiving methadone; however, in both instances the incidence was significantly less that that of the control group. The findings of the present study on methadone subjects demonstrate that abnormal function of the respiratory control network is evident in utero, which may be predictive of subsequent neonatal respiratory development.

Vacuum extraction in modern obstetric practice: a review and critique.

The practice of obstetric vacuum extraction is controversial. This article discusses several issues concerning vacuum extraction including maternal and fetal injury risks, failure rates, indications and technique. Recently published articles on these topics are presented and summarized. Throughout this review, vacuum extraction is evaluated against its principal alternatives, forceps and cesarean delivery.

Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatigue syndrome

This investigation tested the hypotheses that women diagnosed with chronic fatigue syndrome (CFS) would exhibit significantly greater systemic indices of exercise-induced leukocyte mobilization and inflammation (neutrophilia, lactoferrin release, complement activation) than controls matched for age, weight, and habitual activity and that responses in the luteal phase of the menstrual cycle would be greater than in the follicular phase. Subjects stepped up and down on a platform adjusted to the height of the patella for 15 min, paced by metronome. Blood samples were collected under basal conditions (the day before exercise) and following exercise for determination of circulating neutrophils and plasma concentrations of lactoferrin, C3a des arg, and creatine kinase. Complete, 24-hr urine collections were made for determination of cortisol excretion. For all subjects, circulating neutrophil counts increased 33% (P < 0.0001) and lactoferrin increased 27% (P = 0.0006) after exercise, whereas plasma C3a des arg and creatine kinase did not increase. No indication of an exaggerated or excessive response was observed in the CFS patients compared to the controls. In healthy women, circulating neutrophil numbers exhibited previously described relationships with physiological variables: basal neutrophil counts correlated with plasma progesterone concentrations (R = 0.726, P = 0.003) and the exercise-induced neutrophilia correlated with both urinary cortisol (R = 0.660, P = 0.007) and plasma creatine kinase (R = 0.523, P = 0.038) concentrations. These relationships were not observed in the CFS patients (R = 0.240, P = 0.370; R = 0.042, P = 0.892; and R = 0.293, P = 0.270; respectively). These results suggest that normal endocrine influences on the circulating neutrophil pool may be disrupted in patients with CFS.

Vascular reactivity to angiotensin II infusion during gestation

We serially tested 26 healthy, young, nulliparous patients, while they were maintained in the left lateral recumbent position, during a four-week interval (29 to 32 weeks), with progressive increments of angiotensin-II (A-II) 2.0 to 15.0 ng. per kilogram per minute). Blood pressure was recorded with an ultrasound device. All patients were followed through delivery. Three patients (12 per cent) developed pregnancy-induced hypertension (PIH); only one of these demonstrated enhanced vasoreactivity prior to PIH. Conversely, 13 patients who did not develop PIH demonstrated enhanced vasoreactivity at least once during the testing interval. Comparison of results obtained from one week to the next was evaluated in 57 test pairs; discordant data, i.e. reaction to less than 8 ng. per kilogram per minute one week and nonreaction the next, was observed in 17 pairs (30 per cent). We conclude that assessment of the risk of PIH, with the use of the diastolic pressor response to infused A-II, is unreliable.

Vernixuria : Another sign of uterine rupture

Uterine rupture complicates approximately 1% of trials of labor after cesarean. Classic signs and symptoms include loss of station, cessation of labor, vaginal bleeding, fetal distress, and abdominal pain. Other signs are also possible. We report a case of uterine rupture at VBAC trial that includes an unusual clinical sign of uterine rupture: vernix caseosa observed in the urine of the parturient. During labor, a bladder catheter was inserted to evaluate oliguria. Vernix caseosa and blood were found in the tubing. Prompt cesarean delivery followed. A tear extending from the original transverse scar into the bladder dome was found. Vernixuria is an additional sign of uterine rupture.

Sampling the fetoplacental circulation: III. Combined laparoscopy-fetoscopy in the pregnant macaque for hemoglobin identification☆

To demonstrate increased technical experience with fetoscopy and fetal blood sampling, two groups of macaques were compared to control animals. Group 2 had a perinatal mortality rate that was not significantly different from that of the control group. A 2.7 mm. Hopkins rod lens endoscope encased in an eccentric cannula, 3.8 mm. outside diameter, was used. When compared to the earlier test group (Group 1), the later test group (Group 2) showed greater adequacy of the fetal blood sample for laboratory analysis (P less than 0.01). Anthropometric and hematologic data collected at term births compared favorably in test and control groups, with the exception of the white blood cell count, which was significantly lower with fetoscopy (P less than 0.01). This is the first report of experimental fetoscopy with the use of a control group to provide precise data to aid in clarification of the ethical issues yet unresolved in this technology.

External cephalic version: a clinical experience

Eighty-five normal women underwent external cephalic version (ECV) for breech presentation in the late 3rd trimester. The protocol included real time ultrasonic scanning and pre- and post-procedure electronic fetal monitoring. Subcutaneous terbutaline sulfate (0.25 mg.) was administered to (43/85 or 50.5%) of ECV candidates and rendered the procedure easier for patient and operator. A single operator, head-over-heels technique assisted by supine Trendelenbergs position was used. Rh negative women were routinely administered 300 mcg of immune globulin. Successful ECV (53/85, 62.5%) was related to maternal parity, but not to gestational age nor eventual delivery weight. In this series only engagement of the breech was reliable in predicting ECV failure. Fifty of 51 (98.1%) successfully verted women delivered a cephalic presentation infant at term. Cesarean section was performed in 5/51 of these patients (9.8%) for routine obstetrical indications. In one case, compound presentation at term resulting in dystocia and eventual cesarean section was believed related to prior successful version. In contrast, 15/30 (50%) of the ECV failure patients went on to operative delivery despite a liberal institutional policy toward term vaginal breech trials. In addition, the only serious fetal complication in this series, meconium aspiration, occurred in a vaginally delivered breech infant. It is unlikely that late 3rd trimester ECV will impact on out overall rate of cesarean delivery. In North America prematurity is the greatest risk factor in malpresentation and our policy increasingly is to permit attempts at term breech vaginal delivery. Nonetheless, ECV deserves serious consideration. When successful, ECV avoids the costs and/or risks of either cesarean section or vaginal trial of breech.(ABSTRACT TRUNCATED AT 250 WORDS)

Sampling the fetoplacental circulation: IV. Preliminary experience in the pregnant baboon (Papio cynocephalus)☆☆☆★

Preliminary experience with fetoscopy and fetoplacental blood sampling in 23 midtrimester pregnant baboons demonstrated the procedure to be successful in 19 cases (83%); seven serious complications (30%) developed, most of which might well have been avoided with operative experience and other complimentary procedures.