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Biomedical subjects

K Dorman

Publications and source records attributed to K Dorman.

18 recordsLinked to original sources

Plasma choline in normal newborns, infants, toddlers, and in very-low-birth-weight neonates requiring total parenteral nutrition.

Choline deficiency is associated with hepatic abnormalities in adult volunteers and patients administered total parenteral nutrition (TPN). Preliminary investigation has suggested that plasma-free choline concentration (PFCh) is greater in neonatal animals, including humans, than in adults. The aims of this study were to determine the normal PFCh and phospholipid-bound choline concentration (PPLBCh) for newborns, infants, and toddlers and to determine the change during TPN. We also sought to determine the degree of fetal choline extraction, the relation between maternal and newborn plasma choline concentrations, and the relation between plasma choline status and normal newborn length, weight, and gestational age. Blood samples were obtained from 104 full-term newborns in two centers (Ben Taub and Maimonides), 25 mothers, 21 normal infants aged 20.3 +/- 11.8 wk, 12 normal infants aged 62.4 +/- 3.9 wk, and 14 preterm infants (gestational age = 28.9 +/- 2.2 wk) who required TPN. The vein PFChs were 28.1 +/- 13.0 nmol/mL (Ben Taub) and 68.1 +/- 16.9 nmol/mL (Maimonides). The artery PFChs were 27.1 +/- 13.0 nmol/mL (Ben Taub) and 57.9 +/- 11.6 nmol/mL (Maimonides). The vein PPLChs were 1004.7 +/- 246.6 nmol/mL (Ben Taub) and 1121.2 +/- 289.6 nmol/mL (Maimonides). The artery PPLChs were 1065.7 +/- 469.3 nmol/mL (Ben Taub) and 1106.9 +/- 285.8 nmol/mL (Maimonides). The vein-minus-artery differences for PFCh were 1.0 +/- 9.7 nmol/mL (Ben Taub) and 10.2 +/- 10.9 nmol/mL (Maimonides). The vein-minus-artery differences for PPLCh were -51.9 +/- 398.2 nmol/mL (Ben Taub General Hospital, Houston, Texas) and 14.4 +/- 254.3 nmol/mL (Maimonides, New York, New York). Maternal venous PFCh was 8.4 +/- 3.1 nmol/mL. Maternal venous PPLCh was 2592.1 +/- 584.0 nmol/mL (range = 1227.8-3729.0). Maternal venous PFCh correlated with newborn arterial PFCh (r = 0.53, P < 0.05) but not with newborn venous PFCh. No correlation was seen between maternal venous and newborn PPLCh. No significant differences were seen in PPLCh or choline extraction in Ben Taub versus Maimonides patients, although PFCh was significantly greater in the newborns from Maimonides (P < 0.05). The mean venous PFCh and PPLCh in the preterm infants before beginning TPN was 21.2 +/- 6.3 and 1366.8 +/- 339.1 nmol/mL, respectively. Just before initiation of tube feeding (4.0 +/- 2.7 d after TPN had been started), mean venous PFCh and PPLCh was 18.4 +/- 5.3 and 2251.8 +/- 686.9 nmol/mL, respectively. When TPN was discontinued and tube feeding increased to goal, after 10.8 +/- 10.4 d, venous PFCh and PPLCh was 22.6 +/- 8.7 and 2072.5 +/- 540.6 nmol/mL, respectively. Venous PFCh and PPLCh was 13.4 +/- 2.5 and 1827.5 +/- 327.0 nmol/mL, respectively in the older infant group. In conclusion, newborn PFCh is significantly greater than PFCh in adults but falls to adult levels within the first year of life. Low maternal PFCh may be associated with low newborn PFCh. Normal newborn plasma choline status has no bearing on intrauterine growth, although the role of maternal choline deficiency in underweight newborns is unknown. Newborn PPLCh is substantially below that of adults, which suggests its use in membrane synthesis during growth.

Adult↗

An endothelial nitric oxide synthase gene polymorphism is associated with preeclampsia.

OBJECTIVE: We sought to test the hypothesis that a polymorphism of the endothelial nitric oxide synthase gene (NOS3) is associated with preeclampsia. METHODS: We collected and performed polymerase chain reaction (PCR) on genomic DNA from pregnant patients with and without preeclampsia. Patient history and clinical course were evaluated. MAIN OUTCOME MEASURE(S): Frequency of the intron 4 polymorphism of NOS3 (designated allele A) among patients with preeclampsia compared with controls. Clinical features of patients with preeclampsia and the A allele compared with those patients with preeclampsia who did not have the A allele. RESULTS: The frequency of the A allele was 0.10 among controls versus 0.39 among patients with preeclampsia (p < 0.01). The odds ratio of developing preeclampsia when at least one A allele was present was 6.5 [95% confidence interval (CI): 2.1-19.7]. After adjusting for ethnic variation, the odds ratio increased to 7.2 (95% CI: 2.0-25.5). Among patients with preeclampsia, systolic blood pressure at the time of admission was higher for patients with at least one A allele compared with patients homozygous for the B allele (168 versus 156 mm Hg; p = 0.03), independent of gestational age (p = 0.01). CONCLUSION: These data provide evidence for an association between NOS3 and preeclampsia. In defined ethnic groups, this NOS3 may offer predictive information regarding the subsequent development of preeclampsia and its clinical course.

Adolescent↗

Use of the World Wide Web in research: randomization in a multicenter clinical trial of treatment for twin-twin transfusion syndrome.

OBJECTIVE: To describe the process involved in using the World Wide Web to coordinate a randomized, multicenter international trial of treatment for twin-twin transfusion syndrome. METHOD: A Web site was designed by members of the research team, a Web consultant, and a senior computer programmer. The original intent was to provide patient randomization only, but the Web site later was designed so that centers could download a data collection form. Data could be entered directly into the Web site and subsequently imported into a database at the coordinating center. EXPERIENCE: The Web site has been active for 3 years, with 13 participating centers and 31 patients enrolled. COMMENT: Use of the World Wide Web to coordinate an international, multicenter trial is an efficient method. Although there are many benefits, the most obvious is the capability to initiate and conduct a large international trial at minimal cost.

Communication↗

A randomized double-blind study comparing the fetal effects of sulindac to terbutaline during the management of preterm labor.

OBJECTIVE: The object of this study was to compare the fetal effects of sulindac and terbutaline used in the management of preterm labor on the ductus arteriosus, middle cerebral artery, renal artery, umbilical artery, fetal urine production, and amniotic fluid index. STUDY DESIGN: In a randomized, double-blind study 20 patients with preterm labor and no evidence of fetal structural anomalies or intra-amniotic infection received either sulindac (200 mg orally every 12 hours for 6 doses) or terbutaline (5 mg orally every 4 hours) for 72 hours of therapy. All medications were administered from identical blister packs. Opaque glucose base tablets were given at 4-hour intervals in the sulindac treatment arm to mimic the dosing interval in the terbutaline arm of the study. The Doppler pulsatility indices for the ductus arteriosus, middle cerebral artery, renal artery and umbilical artery and also the fetal urinary output were obtained at baseline and 5, 12, 24, 48, and 72 hours after the medication was started. Doppler data were analyzed within each group with raw data and between groups with the change in pulsatility indices from baseline. Statistical analysis was performed with the Kolmogorov-Smirnov test for normality, repeated measures analysis of variance, Mann-Whitney rank sum test, and Student t test as appropriate. P <.05 (2-tailed) was used to denote statistical significance. RESULTS: There were 10 patients in each group, with no difference in gestational age between the 2 groups (32.3 vs 31.7 weeks). Sulindac was stopped in 2 patients after severe ductal constriction was noted, in 1 at 12 hours and in the other at 24 hours. One patient at 33 weeks' gestation was delivered because of fetal distress after 46 hours of sulindac therapy. When analyzed across time within groups, the pulsatility index in the ductus arteriosus decreased significantly at 12 and 24 hours in the sulindac group but not the terbutaline group. No significant differences were noted in the middle cerebral artery, umbilical artery, renal artery, or fetal urinary output within either group over time. Significant differences in the change from baseline in pulsatility index of the ductus arteriosus between the sulindac and terbutaline groups were noted at 5, 12, 24, and 48 hours. A similar effect was noted in the change from baseline in pulsatility index of the middle cerebral artery at 48 and 72 hours. There was a significant decrease in the amniotic fluid index in both groups at 24, 48, and 72 hours. The amniotic fluid index in the sulindac group was significantly lower than that in the terbutaline group at 48 and 72 hours of therapy. CONCLUSIONS: Sulindac constricted the fetal ductus arteriosus, with an effect noted within 5 hours of starting therapy. The constriction, which resolved in all cases within 48 hours of discontinuing therapy, had minimal effects on the pulsatility index of the middle cerebral artery, renal artery, and umbilical artery. Sulindac and terbutaline both resulted in a significant reduction in the amniotic fluid index, with sulindac having a greater effect.

Amniotic Fluid↗

An animal model for hemolytic disease of the fetus or newborn in New Zealand white and New Zealand red rabbits: newborn effects.

OBJECTIVE: Our purpose was to study the neonatal effects of red blood cell alloimmunization in a rabbit model. STUDY DESIGN: Eighteen does were alloimmunized to incompatible red blood cells. Does were bred twice, once with a homozygous buck of incompatible blood type and once with a homozygous buck of compatible blood type. Fetal blood sampling was undertaken on day 27 of gestation (term 28 to 31 days). Does were delivered on day 30 and the neonatal pups were anesthetized. Direct cardiac samplings were performed for hemoglobin, reticulocyte count, and direct Coombs' test. Hepatic, splenic, and renal wet weights were measured. RESULTS: Twenty-two pregnancies (12 compatible and 10 incompatible) were studied. Neonatal hemoglobin was higher in the compatible litters (11.1 gm/dL [7.7 to 12.6 gm/dL] vs 4.9 gm/dL [2.1 to 9.1 gm/dL], P <.001), whereas no difference could be detected between the respective reticulocyte counts (34.0/100 red blood cells [27.3 to 36.1/100 red blood cells] vs 32.6/100 red blood cells [26.8 to 43.5/100 red blood cells], P =.55). The direct Coombs' assay was negative in 23 pups from 8 compatible litters and false positive (weakly positive result) in 2 pups of a ninth compatible litter. The Coombs' assay was positive in all 22 incompatible pups tested. Hepatosplenomegaly was noted in affected pups but not in controls. CONCLUSIONS: A disease analogous to human hemolytic disease of the newborn can be induced in the rabbit neonate.

Animals↗

Comparison of intraocular pressure between normotensive and preeclamptic women in the peripartum period.

OBJECTIVE: Our purpose was to determine whether intraocular pressure differs between preeclamptic and normotensive women in the peripartum period. STUDY DESIGN: Eighteen preeclamptic (defined as blood pressure > 140/90 mm Hg and > or = 1+ proteinuria) and 18 normotensive women were studied. Intraocular pressure was determined with a handheld tonometer. Each intraocular pressure determination was obtained by repeatedly touching the cornea until signal averaging produced a single measurement with a variance < 5%. Right and left intraocular pressure, heart rate, and blood pressure were obtained intrapartum and 24 hours post partum with the patient in the seated, supine, and left lateral positions. Data are reported as mean +/- SD or median (range) as appropriate. Significance was set at p < 0.05. RESULTS: No differences existed in race, age, weight, gravidity, parity, cervical dilatation, and heart rate between the preeclamptic and normotensive groups. Gestational age was lower (39 [34 to 42] vs 41 [34 to 42] weeks, p = 0.003), and intrapartum mean arterial pressure (100.2 +/- 9.8 vs 81.0 +/- 8.3 mm Hg, p < 0.001) and degree of proteinuria (3 [1 to 4] vs 0, p < 0.001) were higher in the preeclamptic group. There was no effect of position or delivery on intraocular pressure in either group. Intraocular pressure was higher in the preeclamptic group in the intrapartum (18.8 +/- 3.0 vs 15.3 +/- 2.7 mm Hg, p < 0.001) and postpartum periods (20.2 +/- 4.5 vs 15.7 +/- 3.6 mm Hg, p = 0.002). CONCLUSION: Compared with normotensive women, preeclamptic women have increased intraocular pressure in the peripartum period.

Adult↗

Long polymerase chain reaction amplification of heterogeneous HIV type 1 templates produces recombination at a relatively high frequency.

Studies of HIV molecular evolution and pathogenesis have relied on the polymerase chain reaction (PCR) to provide sequence information from infected tissues. Until recently, studies have been constrained by the limited length of fragments that can be reliably amplified. The addition of a thermostable 3'-exonuclease activity and altered cycling profiles has increased the length of target sequences that can be amplified by more than 10-fold. We have evaluated the fidelity of long PCR (LPCR). We determined that LPCR amplification maintains the distribution of sequences found in a heterogeneous sample and introduces nucleotide misincorporations at a rate comparable to that found with routine PCR. However, a significant proportion of the LPCR-amplified DNA fragments resulted from recombination events. This result suggests that LPCR amplification may have limited utility in the production and analysis of full-length HIV clones.

Base Sequence↗

In vivo sequence diversity of the protease of human immunodeficiency virus type 1: presence of protease inhibitor-resistant variants in untreated subjects.

We have evaluated the sequence diversity of the protease human immunodeficiency virus type 1 in vivo. Our analysis of 246 protease coding domain sequences obtained from 12 subjects indicates that amino acid substitutions predicted to give rise to protease inhibitor resistance may be present in patients who have not received protease inhibitors. In addition, we demonstrated that amino acid residues directly involved in enzyme-substrate interactions may be varied in infected individuals. Several of these substitutions occurred in combination either more or less frequently than would be expected if their appearance was independent, suggesting that one substitution may compensate for the effects of another. Taken together, our analysis indicates that the human immunodeficiency virus type 1 protease has flexibility sufficient to vary critical subsites in vivo, thereby retaining enzyme function and viral pathogenicity.

Amino Acid Sequence↗

Placental transfer of sulindac and its active sulfide metabolite in humans.

OBJECTIVE: Our aim was to investigate whether the human placenta is permeable to sulindac or its active sulfide metabolite. STUDY DESIGN: Nine pregnant patients (median gestational age [range]: 31.8 [24.3 to 36.4] weeks) were given a 200 mg oral dose of sulindac 5.5 (4.4 to 6.7) hours before 18 intravascular transfusions for rhesus or Kell alloimmunization. At each procedure maternal and fetal serum levels of sulindac and the active sulfide metabolite were measured by high-performance liquid chromatography. RESULTS: The maternal sulfide level was significantly higher than the fetal sulfide levels, but no significant difference was noted between maternal and fetal sulindac levels. The sulfide fetal/maternal ratio was significantly lower than the sulindac fetal/maternal ratio. The sulfide/sulindac ratio was significantly higher in maternal serum versus fetal serum. The sulfide/sulindac ratio correlated with time from drug ingestion to sampling on the maternal side only. In patients studied on more than one occasion no consistent relationship between fetal sulindac, fetal sulfide, or fetal sulfide/sulindac ratio, and gestational age could be demonstrated. CONCLUSION: The placenta is permeable to sulindac but less so to its active sulfide metabolite. The reduction of sulindac to its active sulfide metabolite is decreased in the human fetus.

Female↗

An animal model for hemolytic disease of the fetus and newborn. II. Fetal effects in New Zealand rabbits.

OBJECTIVE: The addition of ultrasonography and ultrasonographically directed fetal blood sampling was attempted in an effort to study the fetal effects of red blood cell alloimmunization in a rabbit model. STUDY DESIGN: Nineteen New Zealand does were alloimmunized to incompatible red blood cells. Sensitized does were bred twice, once with a homozygous buck of incompatible blood type and once with a homozygous buck of compatible blood type. Ultrasonographic examinations were performed on days 20 and 27 of gestation (term 28 to 31 days). Fetal blood sampling was undertaken on day 27 of gestation, and hematologic data were compared between compatible and incompatible litters. RESULTS: A total of 41 pregnancies occurred in 19 does. Fetal hemoglobin was higher in the compatible litters (9.7 gm/dl vs 5.8 gm/dl, p < 0.001), whereas no difference could be detected between the respective reticulocyte counts (31.9 vs 36.0/100 red blood cells, p = 0.2). Hydrops fetalis was noted in none of 18 compatible litters versus 12 of 19 incompatible litters (p < 0.01). CONCLUSION: A disease analogous to human hemolytic disease of the newborn can be induced in the rabbit fetus.

Animals↗

Critical care obstetrics: experts' round table discussion.

A panel of leading experts in critical care obstetric (CCOB) nursing met to discuss the specialty and its future, the impact of changes in the health care system, educational opportunities to learn and update CCOB nursing, formation and use of standards for the specialty, patient placement (dedicated obstetric intensive care units [OB ICU], labor and delivery intensive care units [L & D ICU], regular intensive care units [ICU]), patient populations, and interactions and working relationships with the physicians who care for CCOB patients (perinatologists, obstetricians, internists, obstetric medicine specialists, anesthesiologists, other subspecialists). The topics for discussion were chosen by Carol J. Harvey, RNC, MS, who acted as moderator and Mary Ellen Burke, RN, MS, coordinated the publication of the discussion.

Critical Care↗

Mechanical ventilation during pregnancy.

Mechanical ventilatory support is a significant component in the delivery of critical care. With increasing frequency, obstetric critical care nurses face the challenge of caring for women who require mechanical ventilation during pregnancy. It is important that those caring for such patients understand fundamental principles of mechanical ventilation, associated complications, and specific nursing care measures.

Critical Care↗

Pharmacokinetics of the acyclureidopenicillins piperacillin and mezlocillin in the postpartum patient.

The postpartum patient experiences numerous physiologic alterations, which may affect the pharmacokinetics of certain drugs. Six patients received either piperacillin or mezlocillin intravenously immediately after delivery. Serum half-life and clearance were, respectively, 82.4 min and 202 +/- 105 ml/min for mezlocillin and 32.9 min and 456 +/- 88 ml/min for piperacillin. The data revealed that mezlocillin and piperacillin have significantly different pharmacokinetic reactions in the postpartum patient at the doses used.

Chromatography, High Pressure Liquid↗

Cardiovascular alterations in severe pregnancy-induced hypertension: relationship of central venous pressure to pulmonary capillary wedge pressure.

The relationship between central venous pressure and pulmonary capillary wedge pressure was studied in 18 patients with severe pregnancy-induced hypertension. Although statistically a linear relationship for the group as a whole could be identified, analysis on a case-by-case basis revealed different results. In 10 patients, a linear correlation between central venous pressure and pulmonary capillary wedge pressure was observed. However, accurate prediction of pulmonary capillary wedge pressure from central venous pressure was not possible even in this group because of large interindividual variations. In seven patients no correlation between central venous pressure and pulmonary capillary wedge pressure could be identified. In the last patient a curvilinear relationship existed between central venous pressure and pulmonary capillary wedge pressure. Additionally, in five cases of pulmonary edema, a negative gradient of colloid osmotic pressure to pulmonary capillary wedge pressure gradient was observed. Our data suggest that central venous pressure is not a clinically reliable predictor of pulmonary capillary wedge pressure.

Central Venous Pressure↗

Binocular versus monocular acuity in a patient with latent nystagmus.

This is a case of latent nystagmus with a significant improvement in acuity with both eyes open rather than with either eye alone. If this patient's visual acuity was tested only O.D. alone and O.S. alone, the best visual acuity obtainable would have been 20/60. This might have had serious implications for A.F.'s work since a minimum visual acuity of 20/40 is needed to keep a driver's license in New York State. Since binocular acuity was 20/20, I assured him that driving is safe.

Adolescent↗

A simple method to estimate volume for fetal intravascular transfusions.

We derived a constant termed the transfusion coefficient to simplify the estimation of the fetal intravascular transfusion volume. The product of the estimated fetal weight (g) and 0.02 (transfusion coefficient), estimates the transfusion volume (ml) required to increase the fetal hematocrit by approximately 10 percentage points. Our estimation was comparable to Mandelbrot's technique and better than Plecas' method for estimating fetal transfusion volumes. Utilizing the transfusion coefficient to estimate the intravascular transfusion volume for an anemic fetus is simple, rapid and accurate.

Adult↗