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Biomedical subjects

D E Carlson

Publications and source records attributed to D E Carlson.

At least 37 records · Page 2Linked to original sources

Consensus radiation protection practices for academic research institutions.

Under the auspices of the Howard Hughes Medical Institute, a set of consensus guidelines for Radiation Protection Practices has been developed for biomedical research using radioactive materials. The purposes of the guidelines are (1) to promote good radiation protection practices consistent with the needs of biomedical research, the ALARA principle, and regulatory requirements; (2) to establish common goals and consistent practices within radiation safety programs; and (3) to build a meaningful partnership between radiation safety professionals and the biomedical research community. These practices are intended to enhance radiation protection and the efficiency of the research staff. The consensus guidelines will lessen the variability in radiation safety practices that is evident among many academic research institutions and will encourage better acceptance and regulatory compliance by users of radioactive materials in biomedical research.

Academies and Institutes↗

Impairment of blood volume restitution after large hemorrhage: a mathematical model.

A mathematical model tests possible mechanisms for the progressive failure of blood volume restitution seen after larger hemorrhages ( > 26%) with increasing changes in plasma osmolality. After 10% hemorrhage, the model requires a decrease in net hydrostatic capillary pressure, the release of solute into the extracellular space, and the release of Na+ and K+ from a bound pool in equilibrium with the interstitium to match the experimental data. The solute and released cations expand the interstitium to drive the restitution of volume and protein from 3 to 24 h. After 30% hemorrhage, the best prediction of the average experimental responses occurs when the Na(+)-K(+)-adenosinetriphosphatase (ATPase) in the cell membrane is inhibited by 38.7% from 0.8 to 3 h, and the proportionality between capillary pressure and blood volume is reduced by 68% from its value for 10% hemorrhage. When the change in plasma osmolality is doubled after 30% hemorrhage, an increase in the inhibition of the ATPase to 85% and extension of its duration to 24 h are necessary to match experimental findings. The associated defect in sodium transport may occur after large hemorrhage so that sodium and water move into cells. This response may oppose osmotically driven expansion of the interstitium and thus account for the failure of restitution.

Animals↗

Conjugated hyperbilirubinemia in a newborn infant after maternal (transplacental) treatment with flecainide acetate for fetal tachycardia and fetal hydrops.

An infant with intrauterine supraventricular tachycardia and fetal hydrops, successfully treated with administration of flecainide acetate to the mother had conjugated hyperbilirubinemia shortly after birth. An extensive evaluation failed to disclose a known cause. We believe that in utero exposure to flecainide acetate resulted in conjugated hyperbilirubinemia in this infant.

Female↗

A circulating shock protein that depolarizes cells in vitro depresses myocardial contractility and rate in isolated rat hearts.

Previously, we identified the presence of a circulating shock protein (CSP) in the plasma of hemorrhaged rats that depolarizes a variety of cells in vitro. In isolated perfused rat hearts, partially purified CSP produced dose-dependent decreases in contractility and heart rate associated with an increase in coronary perfusion pressure (CPP). Electrical pacing failed to prevent the negative inotropic effects. Preventing the coronary vasoconstriction with nitroglycerin or attenuating it with a cyclooxygenase inhibitor also failed to prevent the inotropic or chronotropic effects of CSP. Carbocyclic thromboxane A2 (50ng/min) caused a similar increase in CPP to CSP but had no effect on contractility or rate during the first minute of infusion. These data indicate that the protein that appears in rat plasma after hemorrhage produces negative inotropic and chronotropic effects on the isolated heart that are independent of changes in CPP. Vasoactive arachidonic acid metabolites elicited by CSP are partially responsible for the increase in coronary vascular resistance.

Animals↗

Corticotropin-releasing hormone but not glutamate elicits hormonal responses from the parabrachial region in cats.

Corticotropin-releasing hormone (CRH)-containing processes were found by immunohistochemistry in the dorsal and lateral parabrachial nucleus extending medially over the dorsal aspect of the brachium and then along the lateral and medial aspects of the mesencephalic trigeminal tract. Reactivity of lesser density extended ventrally from the medial parabrachial nucleus into the locus ceruleus and subceruleus. To determine if CRH acts in these areas to modulate plasma adrenocorticotropic hormone (ACTH) and arginine vasopressin (AVP), acutely prepared, chloralose-anesthetized cats were tested with microinjections (100 nl/min, 2 min). Plasma ACTH increased significantly after injections of CRH (2 pmol) along the dorsal aspect of the brachium and in the locus subceruleus (P < 0.05 and P < 0.01, respectively). Plasma AVP increased significantly after injections of CRH into the medial parabrachial nucleus (P < 0.01). These responses of ACTH and AVP differed significantly from those to injections of either vehicle or glutamate at identical sites and from those to CRH injected in other areas. None of these latter responses was significant. CRH was without effect on arterial pressure even though glutamate (30 nmol) injected into the area ventral and medial to the brachium elicited a significant pressor response. We suggest that excitatory amino acids such as glutamate act in this area to activate neurons with descending projections that influence autonomic function. In contrast, CRH appears to activate other neurons with ascending projections that drive neuroendocrine release.

Adrenocorticotropic Hormone↗

Prospective multicenter study of second-trimester nuchal skinfold thickness in unaffected and Down syndrome pregnancies.

OBJECTIVE: To determine the distribution of nuchal skinfold thickness in normal and Down syndrome pregnancies and to evaluate the use of this sonographic measurement as a screening test for fetal Down syndrome. METHODS: A prospective, multicenter, population-based study was performed by experienced obstetric sonographers on 1382 women with sonographically normal fetuses undergoing second-trimester amniocentesis for the indication of advanced maternal age. A standard, well-defined sonographic image was obtained at all collaborating centers. The distributions of nuchal skinfold thickness were compared between euploid and Down syndrome fetuses. RESULTS: There were 1346 chromosomally normal pregnancies, 13 fetuses with Down syndrome (1:106), and 23 other chromosome abnormalities. Seventeen fetuses had measurements of 6 mm or greater, and one of these had Down syndrome. The median nuchal skinfold thickness in Down syndrome was 3.2 mm and in euploid fetuses was 3.1 mm. By the Mann-Whitney rank-sum test, there was no statistically significant difference in nuchal skinfold between the euploid and Down syndrome fetuses (P = .5). Overall, using a nuchal skinfold thickness of 6 mm or greater as a screening test, the detection rate for Down syndrome was one of 13 (8%), the false-positive rate was 16 of 1382 (1.2%), the positive predictive value was one of 17 (6%), and the probability of detecting Down syndrome was 6.5%. CONCLUSION: In this investigation, excess nuchal skinfold thickness was a poor and unreliable screening test for Down syndrome.

Adult↗

Determinants of utilization of Tay-Sachs screening.

OBJECTIVE: To identify the characteristics of patients associated with optimal utilization of Tay-Sachs screening. METHODS: Medical records of patients undergoing amniocentesis for genetic diagnosis were reviewed. Three hundred twenty-nine of 537 charts evaluated were from individuals at risk for Tay-Sachs heterozygosity. Among these, 213 couples had previously been screened for Tay-Sachs. In 116 couples, neither member of the couple had been screened before amniocentesis. A concurrent reference group consisted of 208 couples without an indication for Tay-Sachs screening. Patient characteristics, including ethnicity, genetic screening history, parental ages, and pregnancy history, were reviewed for each group. Analysis of variance and likelihood chi 2 test were used for statistical analysis. RESULTS: There were no significant differences in maternal age or reproductive history among the groups. The most common indication for amniocentesis was advanced maternal age for all three groups. However, the previously screened group was more than twice as likely to self-refer because of a positive family history or patient anxiety than was the unscreened group (P = .006). Conversely, the unscreened group was more than twice as likely as screened couples to be referred because of a positive high or positive low maternal serum alpha-fetoprotein level (P = .002). CONCLUSION: Despite 2 decades of professional and lay education, many couples are unaware of their individual risk for Tay-Sachs heterozygosity. Additional education, most likely at the professional level, is needed to maximize informed participation.

Fathers↗

Transvaginal ultrasound: does it help in the diagnosis of placenta previa?

The purpose of this study is to evaluate the use of transvaginal ultrasound in the diagnosis of placenta previa and to assess the risk of bleeding secondary to the placement of the vaginal transducer. Thirty-eight patients with an estimated gestational age equal to or greater than 26 weeks and the diagnosis of suspected placenta previa gave their consent and were randomized to two groups. Randomization was stratified by patient weight and anterior or posterior placental location. Group 1 (n = 20) had complete obstetric ultrasounds using linear and sector transducers. Group 2 (n = 18) had similar examinations followed by transvaginal ultrasound scans. Patients were rescanned to follow placental location and fetal growth parameters. On abdominal ultrasound, the posterior placenta (n = 17) was often shadowed by fetal parts. The ease of placental visualization was rated on a four-point scale with 1 being the clearest. The mean clarity score for posterior placentas on abdominal ultrasound in Group 2 was 1.6 and on transvaginal ultrasound was 1.0, p < 0.04. The use of transvaginal ultrasound consistently revealed greater clarity of diagnosis in these patients. No patient in either group experienced increased vaginal bleeding following the scanning sessions. Transvaginal ultrasound was most beneficial for those patients with posterior placenta previas because of increased clarity of diagnosis, decreased time of scanning, and no increased incidence of hemorrhage.

Clinical Trial↗

Prenatal diagnosis of human parvovirus B19 in nonimmune hydrops fetalis by polymerase chain reaction.

OBJECTIVE: Nonimmune hydrops fetalis is a potentially lethal condition reflecting the clinical manifestation of several pathologic processes. Recently maternal infection by human parvovirus B19 has been reported to result in nonimmune fetal hydrops. We sought to develop a rapid and sensitive test to detect the presence of this agent in utero. STUDY DESIGN: Using a cloned isolate of the virus, we developed an assay based on enzymatic amplification of a segment of the human parvovirus B19 genome that allows direct detection of this agent in samples of fetal blood and amniotic fluid. RESULTS: The method detected as few as 100,000 genome equivalences and was specific for the viral genome alone. We used this assay to evaluate nine fetuses initially seen with nonimmune hydrops. Three cases were found to be positive for the human parvovirus B19 genome. CONCLUSION: The method is powerful in that it is rapid, sensitive, and simple. This assay may have general applicability in evaluation of nonimmune hydrops and in documentation of the natural history of fetal human parvovirus infections.

Erythema Infectiosum↗

Screening for Down syndrome with the femur length/biparietal diameter ratio: a new twist of the data.

OBJECTIVE: The purpose of this study was to determine the value of discordant morphometric measurements as identifiers of Down syndrome by evaluating the relationship of biparietal diameter, femur length, biparietal diameter/femur length ratio, and cephalic index between a group of fetuses with trisomy 21 and a control population. STUDY DESIGN: Biometric measurements from 48 fetuses with trisomy were reviewed and compared with 107 normal fetuses of similar gestational age. Data were analyzed in 2-week gestational age intervals to determine the effect of gestational age on ultrasonographic detection of Down syndrome. Outcome measures were subject to least-squares linear regression and the t test for analysis. RESULTS: A positive relationship between abnormal morphometric measurements and fetuses with Down syndrome was detected but only during specific weeks of pregnancy. CONCLUSION: Although it appears that biometric measurements may be useful for Down syndrome, further study is needed before its widespread introduction into clinical practice.

Down Syndrome↗

Saline resuscitation after fixed-volume hemorrhage. Role of resuscitation volume and rate of infusion.

The authors have reported previously that small-volume resuscitation (1.8 x bled volume) with 0.9% NaCl restores blood volume and attenuates hormonal responses after large hemorrhage without correction of arterial hypotension. The authors studied the role of rate of infusion in this observation in chronically prepared dogs (aortic flow probe, right atrial pressure and volume, and arterial catheters) after 30% hemorrhage (24.1 +/- 0.4 mL/kg). After 30 minutes, subjects were observed either without treatment (no resuscitation) or with infusion of 43 mL/kg 0.9% NaCl over 3 hours by one of three protocols: (1) impulse infusion over 10 minutes, (2) variable rate infusion, bolus with tapering infusion, or (3) constant rate infusion. Significant improvement in cardiac output and in blood volume and significant decreases of vasopressin and arterial catecholamines were observed in all fluid-treated groups. This benefit was relatively independent of rate of infusion, although impulse infusion produced greater early improvement, which dissipated with time, and constant rate infusion produced better late results. In none of the fluid-treated groups were these improvements reflected in improved mean arterial pressure compared with the no resuscitation group. The authors conclude that small-volume, slow-rate saline infusion produces physiologic benefits that cannot be assessed by easily measured clinical parameters. Thus, early resuscitation after trauma could aid patients even if arterial pressure is unchanged. This benefit might be even greater in patients with uncontrolled bleeding because arterial pressure, and hence bleeding, may not be increased by resuscitation of this type. A reassessment of the value of prehospital fluid resuscitation in the injured patient is warranted.

Animals↗

Alpha-adrenergic input in the locus coeruleus modulates plasma adrenocorticotropin in cats.

Previous evidence suggested that noradrenergic activity in the vicinity of the ventrorostral locus coeruleus (LC) increased in response to hemorrhage. To investigate the possible role of this response in the control of ACTH release, microinjections (100 nl/min for 2 min) of several agents were made at 59 sites in 35 cats anesthetized with chloralose. Injections were as follows: vehicle (all sites); 150 mM L-glutamate (GLU; 51 sites); an alpha 2-agonist, 1 mM clonidine (19 sites); an alpha 2-antagonist, 1 mM yohimbine (32 sites); an alpha 1-agonist, 1 mM phenylephrine (PE; 42 sites); and an alpha 1-antagonist, 0.05 mM prazosin (20 sites). Plasma ACTH was measured by RIA. Responses were tested statistically by repeated measures analysis of variance. GLU at 12 sites in the region of the ventrorostral LC facilitated plasma ACTH (P less than 0.01), whereas GLU at 6 sites in the caudal LC inhibited ACTH (P less than 0.05). Clonidine at 9 sites in an area that included the ventrorostral LC inhibited ACTH (P less than 0.05), and yohimbine at 7 sites within this latter area facilitated ACTH (P less than 0.01). PE within the ventrorostral LC had no effect on ACTH. However, PE at 10 sites within the caudal LC and along the ventromedial border of the ventrorostral LC facilitated ACTH. The responses for all of these areas to the respective agents differed from those to vehicle, whereas responses from other areas to the former agents or from all areas to prazosin did not. An increase in noradrenergic turnover in the LC may provide inhibitory alpha 2 modulation to the neurons in the LC that are activated by hemorrhage. This modulation and possible alpha 1 input in areas adjacent to the ventrorostral LC may influence the hemodynamic control of ACTH release.

Adrenocorticotropic Hormone↗

Ultrasound detection of genetic anomalies.

The prenatal detection of genetic diseases has improved remarkably. This review highlights several diagnoses that are possible to identify by ultrasound examination of the fetus, including cystic fibrosis, skeletal dysplasias, kidney diseases, cardiac disease and central nervous system disorders. Ultrasound clues to the possible existence of several syndromes and aneuploidy are also outlined.

Chromosome Aberrations↗

The ultrasound triad of fetal hydramnios, abnormal hand posturing, and any other anomaly predicts autosomal trisomy.

Our definition of hydramnios is an amniotic fluid index of 24 cm or greater. We evaluated by ultrasound examination 49 consecutive patients who met this definition of hydramnios. Of these, 22 (44.9%) had anomalies visible by ultrasound. The combination of hydramnios, abnormal hand posturing, and any other anomaly created a constellation of sonographic findings enabling us to predict six specific autosomal trisomies (27.27%): three trisomy 18, two trisomy 21, and one trisomy 13. The 27 fetuses with "idiopathic hydramnios" (no identifiable anomaly or abnormal hand posturing) had normal karyotypes. We recommend that any patient with confirmed hydramnios have a detailed ultrasound examination by an experienced sonographer, with special attention paid to the heart, face, and hands. If no abnormality is seen and the hands are normally postured, expectant management may be appropriate. If the late second- or third-trimester fetus displays abnormal hand posturing with any other abnormality, rapid karyotyping by funipuncture or placental biopsy should be recommended to facilitate appropriate management.

Chromosomes, Human, Pair 13↗