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Biomedical subjects

D A Calhoun

Publications and source records attributed to D A Calhoun.

At least 55 records · Page 3Linked to original sources
PubMed1996

Transplacental passage of recombinant human granulocyte colony-stimulating factor in women with an imminent preterm delivery.

OBJECTIVE: We attempted to determine, in a pilot study, whether recombinant human granulocyte colony-stimulating factor, administered to women with an imminent delivery at < or = 30 weeks' estimated gestational age, crosses to the fetal circulation and stimulates fetal neutrophil production. STUDY DESIGN: We measured granulocyte colony-stimulating factor and neutrophil concentrations in the blood of the mothers and in the umbilical venous cord blood after a single intravenous dose (25 micrograms/kg) of recombinant granulocyte colony-stimulating factor given to 11 women in whom preterm delivery was imminent and compared these with values from 34 control women and 35 cord sera. RESULTS: Ten infants were delivered within 30 hours (10.8 +/- 8.9, mean +/- SD) of the granulocyte colony-stimulating factor administration ("early delivery"), and two were delivered after 54 and 108 hours, respectively. In the early delivery group maternal granulocyte colony-stimulating factor concentrations and blood neutrophil levels were higher than in controls. However, no difference was seen in the cord blood neutrophil concentrations. In the late delivery group, although maternal serum and cord blood granulocyte colony-stimulating factor concentrations did not differ from controls, cord blood neutrophil levels were higher (25,900 and 17,700 cells/microliters) than controls (3500 +/- 2000 cells/microliters, p < 0.05) and remained elevated for 1 week. Specifically, the blood neutrophil levels on days 5 and 8 were 12,000 and 17,000, respectively, for these patients, whereas the reference range upper limit for controls was 6000 cells/microliters. CONCLUSION: Administration of recombinant granulocyte colony-stimulating factor to pregnant women with an imminent preterm delivery may result in the transplacental passage of a measurable quantity of granulocyte colony-stimulating factor, an amount that can have a biologic effect on the fetus. These events were most noticeable in those patients who received granulocyte colony-stimulating factor at least 30 hours before being delivered of their infants.

Bacterial Infections↗
PubMed1996

Incidence, significance, and kinetic mechanism responsible for leukemoid reactions in patients in the neonatal intensive care unit: a prospective evaluation.

OBJECTIVE: To prospectively investigate the incidence, significance, and kinetic mechanism responsible for leukemoid reactions in patients in the neonatal intensive care unit (NICU). DESIGN: We prospectively studied all infants admitted to the NICU at the University of Florida who, during a period of 12 consecutive months, had a leukemoid reaction. All those identified had a standardized evaluation consisting of (1) karyotype analysis, (2) bacterial cultures, (3) evaluations for toxoplasmosis, other (congenital syphilis and viruses), rubella, cytomegalovirus, and herpes simplex virus) (TORCH), (4) determination of blood viscosity, (5) use of marrow aspirates for morphology, clonogenic progenitor cell assays, and cell-cycle analysis of progenitors, (6) determination of serum concentrations of granulocyte and granulocyte-macrophage colony-stimulating factors, and (7) serial complete blood cell counts until the leukemoid reaction remitted. RESULTS: During 12 months, 707 patients were admitted to the NICU and 4262 complete blood cell counts were performed on samples from these patients. A leukemoid reaction was identified in nine patients, all of whom were preterm (born at 24 to 38 weeks' gestation). Peak blood leukocyte concentrations were 51.7 +/- 15.6 x 10(3)/microl (mean +/- SD). The leukemoid reactions were detected during the first 4 days of life in seven patients, on day 9 in one, and on day 25 in one. An abnormal karyotype (47, XY, +21) was present in one infant. Mothers of four infants had received betamethasone antenatally. None had elevated whole blood viscosity or positive findings on bacterial or TORCH evaluations. None of the bone marrow findings were consistent with steroid-induced leukocytosis; all studies indicated accelerated neutrophil production. Serum concentrations of granulocyte-macrophage colony-stimulating factor were either negligible or nondetectable. Serum granulocyte colony-stimulating factor was elevated in three patients, low in two, and nondetectable in four. The leukemoid reactions persisted for 5 to 32 days, the longest being in the patient with trisomy 21. CONCLUSIONS: Leukemoid reactions were not particularly rare in our NICU (1.3% of patients). The reactions were not associated with hyperviscosity and, except in one patient with a karyotype abnormality, were transient. The responsible kinetic mechanism was increased neutrophil production, not steroid-induced leukocytosis.

Blood Viscosity↗
PubMed1996

Production of granulocyte colony-stimulating factor by the human placenta at various stages of development.

The human placenta is capable of producing a variety of haematopoietic growth factors in vitro. It is not clear, however, whether the placenta produces such factors in vivo and if so, whether placental production of haematopoietic growth factors has a physiological role in fetal haematopoietic development. As a step toward making this determination, we assessed whether the onset of placental production of granulocyte colony-stimulating factor (G-CSF), in vivo, coincides with the onset of granulocytopoiesis in the developing fetus. To make this assessment, we obtained human placentae between 10 weeks of gestation and term and studied production of G-CSF in several ways. First, we sought to determine whether the onset of production of G-CSF mRNA in the placenta immediately precedes the appearance of neutrophil development in the fetus. Second, we assessed the effect of gestational age on the capacity of the placenta to generate G-CSF in vitro, by incubating cubes of placenta, with or without including interleukin-1 alpha (IL-1 alpha) in the culture media, and quantifying G-CSF in the cell culture supernatants 24 h later. Third, we assessed the rate of G-CSF production by the placenta, by perfusing two normal, term placentae using a membrane-oxygenator system, and quantifying G-CSF, at intervals, in the perfusates. We found: (1) no evidence that placental production of G-CSF is involved in regulating granulocytopoiesis in the fetus, (2) that the healthy placenta contains little or no G-CSF mRNA in vivo, (3) the placenta at term has a far greater capacity to produce G-CSF, when stimulated, than does the placenta before term, and (4) that although the placenta does not normally produce G-CSF in vivo, it has the capacity of generating very large quantities of G-CSF continuously over at least several days.

Blotting, Northern↗
PubMed1996

Atrial natriuretic peptide blunts arterial baroreflex in spontaneously hypertensive rats.

We and other laboratories have reported that arterial baroreflex-mediated control of heart rate is blunted in spontaneously hypertensive rats (SHR) compared with normotensive controls. Recently, we reported that atrial natriuretic peptide (ANP) microinjected into the caudal nucleus tractus solitarii of SHR further blunts this defect. The present study tested the hypothesis that ANP modulates arterial baroreflex-mediated control of sympathetic nervous system activity. Nine-week-old, male SHR (n = 29) and normotensive Wistar-Kyoto control rats (n = 24) were instrumented for microinjection into the caudal nucleus tractus solitarii and for direct measurement of arterial blood pressure, heart rate, and lumbar sympathetic nervous system activity. After urethane- and alpha-chloralose-induced induced anesthesia, arterial baroreflex-mediated control of heart rate and lumbar sympathetic nerve activity was assessed during phenylephrine- (5 to 40 micrograms.kg-1.min-1) induced increases and sodium nitroprusside- (15 to 300 micrograms.kg-1.min-1) induced decreases in mean blood pressure before and after microinjection of ANP (50 ng) or monoclonal antibody to ANP (0.55 micrograms) into the caudal nucleus tractus solitarii. ANP reduced and the antibody enhanced the sensitivity of baroreflex-mediated control of both heart rate and lumbar sympathetic nerve activity in SHR but not in Wistar-Kyoto controls (P < .05). Arterial baroreflex sensitivity was unchanged with control microinjections of vehicle or mouse IgG in SHR. These data suggest that endogenous ANP in the caudal nucleus tractus solitarii may contribute to the development and/or maintenance of hypertension in SHR by blunting baroreflex-mediated control of sympathetic nervous system activity.

Animals↗
PubMed1996

Erythropoietin receptors are expressed in the central nervous system of mid-trimester human fetuses.

Recombinant erythropoietin (rEpo) is an effective treatment for infants with the anemia of prematurity. rEpo was previously thought to act only on erythroid progenitor cells, but evidence now indicates that certain nonerythroid cells also express functional erythropoietin receptors (Epo-R). Such receptors have been observed on cells in the developing murine brain and spinal cord. The objective of this study was to determine whether Epo-R are expressed in the CNS of mid-trimester human fetuses. For this study, spinal cords were collected from five mid-trimester abortuses. RNA was extracted from the washed specimens, and the presence of Epo-R mRNA was sought by reverse transcription followed by polymerase chain reaction. Immunohistochemistry was then used to determine the anatomic location of the cells expressing Epo-R within the fetal spinal cord. The results showed that all fetal spinal cords tested contained Epo-R mRNA. The cells expressing Epo-R were radiating from the ependymal canal toward the anterior and posterior median sulci. We conclude that Epo-R are expressed on cells in the developing human CNS. Further studies are needed to determine whether they are clinically relevant in the premature infant.

Embryonic and Fetal Development↗
PubMed1996

Effect of recombinant granulocyte colony-stimulating factor on erythropoiesis in the human fetus and neonate.

Administration of large doses of recombinant granulocyte colony-stimulating factor (rG-CSF) to mice results in diminished erythropoiesis. Hyporegenerative anemia does not occur in adult humans as a consequence of treatment with rG-CSF, but it is not clear whether this will be a problem in neonates. Because rG-CSF is currently being tested as a treatment for neutropenia in neonates, we assessed the possibility that such treatment will diminish their erythropoiesis. To do this, we added rG-CSF, in vitro, to clonogenic cultures of hematopoietic progenitors obtained from the bone marrow and liver of seven human fetuses and from the umbilical cord blood of five term and five preterm infants. The range of rG-CSF concentrations tested (0.1-10.0 ng/mL) included the peak concentrations measured in the blood of neonates receiving rG-CSF treatment on experimental protocols. Inclusion of rG-CSF in the cultures did not diminish clonal maturation of fetal erythroid (erythroid colony-forming and burst-forming unit) progenitors, nor did it reduce the number of normoblasts generated per erythroid progenitor cell colony. On the basis of these studies we predict that administration of rG-CSF to neonates will not result in down-modulation of erythropoiesis.

Animals↗
PubMed1995

Racial differences in the pathogenesis of hypertension.

Hypertension occurs at an earlier age, is more prevalent, and is more often complicated by target organ damage in African-Americans than whites. Reasons for this increased severity of hypertension in African-Americans remain obscure. Based on studies recently completed in their laboratory, the authors propose that greater sympathetic reactivity to stress and a greater prevalence of NaCl sensitivity contribute to the earlier development of hypertension in African-Americans. Using microneurography to record muscle sympathetic nervous system activity, it was found that normotensive blacks manifest greater increases in sympathetic activity to cold stress than normotensive whites. If true of other types of stressors, greater sympathetic reactivity would predispose blacks to the development of hypertension. Using a telemetry-based monitoring system, the authors recently reported that both spontaneously hypertensive rats and normotensive Wistar-Kyoto rats manifest acute sensitivity to high dietary NaCl ingestion, but that the Wistar-Kyoto rats are able to compensate, thereby avoiding sustained increases in blood pressure. Based on these animal studies, it is proposed that elevated nocturnal pressures observed in blacks by other investigators may reflect the greater prevalence of NaCl sensitivity in the black population. As in animal models of NaCl-sensitive hypertension, blacks may retain ingested NaCl, resulting in sustained increases in blood pressure.

Animals↗
PubMed1995

Gender and dietary NaCl in spontaneously hypertensive and Wistar-Kyoto rats.

We recently reported that high dietary NaCl exposure significantly increases both daytime and nighttime mean arterial pressure in male spontaneously hypertensive rats (SHR) but only nighttime values in male normotensive Wistar-Kyoto rats (WKY). In the present study we used a telemetry monitoring system to evaluate the effects of high dietary NaCl exposure on diurnal variation of mean arterial pressure and heart rate in male and female SHR and WKY. After implantation of a radio-frequency transducer, rats were fed either high (8%) or basal (1%) NaCl diets for 2 weeks. High dietary NaCl ingestion significantly increased both daytime and nighttime mean arterial pressure in male SHR compared with males receiving a basal NaCl diet, resulting in greater 24-hour values (163 +/- versus 154 +/- 1 mm Hg, high versus basal NaCl diet; P < .05). High dietary NaCl ingestion significantly increased only nighttime blood pressure in male WKY, with no significant effect on 24-hour mean arterial pressure (102 +/- 2 versus 101 +/- 3 mm Hg, high versus basal). High dietary NaCl exposure did not affect daytime or nighttime mean arterial pressure in female SHR (24-hour mean arterial pressure, 144 +/- 2 versus 141 +/- 2 mm Hg, high versus basal NaCl diet). Twenty-four-hour mean arterial pressure tended to be lower in female WKY receiving a high NaCl diet than females ingesting a basal diet (101 +/- 3 versus 106 +/- 1 mm Hg), but the difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Mechanisms responsible for sympathetic activation by cigarette smoking in humans.

BACKGROUND: The pressor and tachycardic effects of cigarette smoking are associated with an increase in plasma catecholamines, suggesting the dependence of these effects on adrenergic stimulation. Whether the stimulation occurs at a central or a peripheral level and whether reflex mechanisms are involved is unknown. METHODS AND RESULTS: In nine normotensive healthy subjects (age, 33.0 +/- 3.5 years, mean +/- SEM), we measured blood pressure (Finapres device), heart rate (ECG), calf blood flow and vascular resistance (venous occlusion plethysmography), plasma norepinephrine and epinephrine (high-performance liquid chromatography assay), and postganglionic muscle sympathetic nerve activity (microneurography from the peroneal nerve) while subjects were smoking a filter cigarette (nicotine content, 1.1 mg) or were in control condition. Cigarette smoking (which raised plasma nicotine measured by high-performance liquid chromatography from 1.0 +/- 0.9 to 44.2 +/- 7.1 ng/mL) markedly and significantly increased mean arterial pressure (+13.2 +/- 2.3%), heart rate (+30.3 +/- 4.7%), calf vascular resistance (+12.1 +/- 4.9%), plasma norepinephrine (+34.8 +/- 7.0%), and plasma epinephrine (+90.5 +/- 39.0%). In contrast, muscle sympathetic nerve activity showed a marked reduction (integrated activity -31.8 +/- 5.1%, P < .01). The reduction was inversely related to the increase in mean arterial pressure (r = -.67, P < .05), but the slope of the relation was markedly less (-54.1 +/- 7.5%, P < .05) than that obtained by intravenous infusion of phenylephrine in absence of smoking. The hemodynamic and neurohumoral changes were still visible 30 minutes after smoking and occurred again on smoking a second cigarette. Sham smoking was devoid of any hemodynamic and neurohumoral effect. CONCLUSIONS: These data support the hypothesis that in humans the sympathetic activation induced by smoking depends on an increased release and/or a reduced clearance of catecholamines at the neuroeffector junctions. Central sympathetic activity is inhibited by smoking, presumably via a baroreceptor stimulation triggered by the smoking-related pressor response. The baroreflex is impaired by smoking, however, indicating that partial inability to reflexly counteract the effect of sympathetic activation is also responsible for the pressor response.

Adult↗
PubMed1994

Physical training and baroreceptor control of sympathetic nerve activity in humans.

In nine sedentary subjects (16.5 +/- 0.4 years, mean +/- SEM) we measured blood pressure (Finapres device), heart rate (electrocardiogram), and postganglionic muscle sympathetic nerve activity (microneurography from the peroneal nerve) at rest and during intravenous infusion of phenylephrine and nitroprusside. These measurements were performed before and after 10 weeks of endurance training (2 h/d, 5 d/wk) that increased maximum oxygen consumption from 34.8 +/- 2.1 to 40.4 +/- 1.8 mL/kg per minute (P < .02). Basal mean blood pressure and muscle sympathetic nerve activity were lower after than before endurance training (86.5 +/- 2.6 versus 97.5 +/- 1.8 mm Hg, P < .05, and 14.0 +/- 1.8 versus 21.2 +/- 2.3 bursts per minute, P < .02), and the changes in these variables were closely related (r = .95, P < .01). Similar mean blood pressure increases induced by phenylephrine caused greater reductions in heart rate and muscle sympathetic nerve activity after than before endurance training (-8.6 +/- 0.8 versus -6.1 +/- 1.1 beats per minute, P = NS, and -78.0 +/- 4.6% versus -53.6 +/- 4.8%, P < .05). Likewise, similar mean blood pressure reductions induced by nitroprusside caused greater increases in heart rate and muscle sympathetic nerve activity after than before endurance training (18.6 +/- 3.0 versus 12.4 +/- 2.4 beats per minute, P < .05, and 128.1 +/- 26% versus 63.2 +/- 11%, P < .02). No alteration in hemodynamics, oxygen consumption, muscle sympathetic nerve activity, and baroreceptor reflex sensitivity occurred in four other age-matched sedentary subjects studied before and after a 10-week observation period without endurance training.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Diurnal blood pressure variation and dietary salt in spontaneously hypertensive rats.

We have previously reported that high dietary salt exposure significantly increases daytime mean arterial pressure in spontaneously hypertensive rats (SHR) but not in normotensive Wistar-Kyoto (WKY) controls. In the present study, we used a telemetry monitoring system to evaluate the effects of high dietary salt exposure on diurnal variation of mean arterial pressure and heart rate in SHR and WKY rats. After implantation of a radio frequency transducer, SHR and WKY rats were maintained on either high (8%) or basal (1%) salt diets. Hemodynamic values were then analyzed for diurnal variation with the use of a nonlinear data-fitting program. After 2 weeks of dietary exposure, high salt-fed SHR had significantly greater 24-hour mean arterial pressure (156 +/- 3 mmHg) than SHR receiving basal (135 +/- 2 mmHg) and WKY rats receiving high (100 +/- 2 mmHg) or basal (100 +/- 1 mmHg) salt diets. Rhythm analysis indicated significant increases in both daytime and nighttime mean arterial pressure during high salt exposure in SHR. In WKY rats, high salt exposure increased nighttime but not daytime mean arterial pressure, with no net effect on 24-hour mean arterial pressure. High dietary salt exposure significantly decreased heart rate in both SHR and WKY rats, and it did not significantly alter the pattern of diurnal blood pressure or heart rate variation. These results indicate that WKY rats manifest an acute sensitivity to salt ingestion but have compensatory mechanisms sufficient to prevent sustained increases in mean arterial pressure; such mechanisms are lacking in SHR.

Animals↗
PubMed1994

Muscle sympathetic nervous system activity in black and Caucasian hypertensive subjects.

OBJECTIVE: To compare muscle sympathetic nerve activity (MSNA) in age- and weight-matched African-Americans and American Caucasians with primary hypertension. DESIGN: Using microneurography, we compared MSNA at rest and in response to cold-pressor testing and handgrip exercise in 13 hypertensive African-Americans and 12 hypertensive American Caucasians. METHODS: All subjects were withdrawn from antihypertensive medications for at least 2 weeks before the study. MSNA was recorded from the left peroneal nerve. RESULTS: Resting MSNA was similar in the Blacks and the Caucasians. Increases in muscle efferent activity, mean arterial pressure and heart rate in response to the cold pressure and handgrip exercise were not significantly different in Black and in Caucasian subjects. CONCLUSION: MSNA, either at rest or in response to certain laboratory stressors, is not different in Black and in Caucasian hypertensive subjects with similar resting blood pressures.

Age Factors↗
PubMed1993

Excitatory sympathetic reflex in NaCl-sensitive spontaneously hypertensive rats.

We have previously demonstrated blunted reflex responses of lumbar sympathetic nerve activity during volume expansion in NaCl-sensitive spontaneously hypertensive rats maintained on basal (1% NaCl) diets compared with NaCl-resistant spontaneously hypertensive rats, Wistar-Kyoto rats, and Sprague-Dawley rats. The current study tested the hypothesis that chronic ingestion of a high (8%) NaCl diet further blunts cardiopulmonary reflex function in the NaCl-sensitive spontaneously hypertensive rat. After 3 weeks of a 1% or 8% NaCl diet, male rats of all four strains were instrumented with femoral arterial and venous cannulas and lumbar nerve recording electrodes at 10 weeks of age. Two days later, conscious rats were infused with whole blood to expand blood volume. NaCl-sensitive spontaneously hypertensive rats maintained on a 1% NaCl diet had blunted responses of nerve activity to acute volume expansion compared with control strains. NaCl-sensitive spontaneously hypertensive rats maintained on an 8% NaCl diet had increases in nerve activity responses to volume expansion. In a second experiment, the volume expansion protocol was repeated in anesthetized NaCl-sensitive spontaneously hypertensive rats that had been subjected to sinoaortic denervation after 3 weeks of a 1% or 8% NaCl diet. After sinoaortic denervation, an increase in nerve activity was again observed during volume expansion in animals fed the 8% NaCl diet. In animals fed the 1% NaCl diet, changes in nerve activity were variable. The excitatory response was significantly reduced after bilateral vagotomy. These studies suggest that blood pressure regulation in NaCl-sensitive spontaneously hypertensive rats is a complex interaction of excitatory and inhibitory sympathetic reflex systems that is altered by high dietary NaCl exposure.

Animals↗
PubMed1993

Normotensive blacks have heightened sympathetic response to cold pressor test.

The purpose of this study was to compare sympathetic nerve activity responses to the cold pressor test in black and white normotensive subjects. We recorded muscle sympathetic nerve activity (microneurography of the peroneal nerve), arterial blood pressure, and heart rate in 9 normotensive American blacks (24 +/- 2 years, mean +/- SEM) and 10 normotensive American whites (28 +/- 2 years) at rest and during hand immersion in ice water (cold pressor test). Body weight was not different in the two groups (72.4 +/- 3.7 versus 74.1 +/- 3.8 kg, black versus white subjects). During supine rest, mean arterial pressure (92 +/- 2 versus 93 +/- 3 mm Hg, black versus white), heart rate (66 +/- 4 versus 62 +/- 3 beats per minute, black versus white), and muscle sympathetic nerve burst frequency (12 +/- 2 versus 17 +/- 3 bursts per minute, black versus white) were not different in the two groups. During the cold pressor test, mean arterial pressure, heart rate, and muscle sympathetic nerve activity increased from supine rest in both groups. The magnitudes of increases in mean arterial pressure and total minute muscle sympathetic nerve activity were significantly greater in blacks than whites (33.5 +/- 3 versus 22.4 +/- 3 mm Hg and 416 +/- 24% versus 243 +/- 31% of control, respectively, black versus white, P < .05). The increases in heart rate were most significantly different for the two groups. These data suggest that the enhanced pressor response to cold stress observed in normotensive blacks is attributable to greater increases in peripheral sympathetic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Hypertension in blacks: socioeconomic stress and sympathetic nervous system activity.

Primary hypertension is almost twice as prevalent among American blacks as among whites. Causes of this increased prevalence of hypertension remain elusive. Elevation of sympathetic nervous system activity, in part secondary to increased levels of socioeconomic stress, is hypothesized as playing a role. Increased sympathetic nervous system activity may increase peripheral vascular resistance directly or through increased vascular reactivity. Microneurography allows direct measurement of peripheral sympathetic nervous system activity. Application of this technique will allow comparison of sympathetic nervous system activity in black and white subjects and provide additional insight into the role of the sympathetic nervous system in the development of hypertension in blacks.

Black or African American↗