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Biomedical subjects

M A Hanson

Publications and source records attributed to M A Hanson.

At least 73 records · Page 4Linked to original sources
PubMed1998

Fetal endocrine responses to prolonged reduced uterine blood flow are altered following bilateral sectioning of the carotid sinus and vagus nerves.

The present study examines the effect of carotid sinus/vagosympathetic denervation on fetal endocrine responses to prolonged reduced uterine blood flow (RUBF). Fetal sheep had vascular catheters inserted following bilateral sectioning of the carotid sinus and vagus nerves (denervated, n = 7) or sham denervation (intact, n = 7). Uterine blood flow was mechanically restricted at 126.1 +/- 0.7 days (mean +/- S.E.M.) for 24 h, decreasing arterial oxygen saturation by 47.3 +/- 2.6% (P < 0.01). Fetal plasma samples were obtained at -1, 3, 6, 12 and 24 h for subsequent analyses of arginine vasopressin (AVP), angiotensin II and catecholamines. The AVP response to prolonged RUBF was markedly attenuated in denervated fetuses (15.6 +/- 3.6 to 34.9 +/- 6.0 pg/ml) when compared with intact (10.0 +/- 1.4 to 127.3 +/- 28.4 pg/ml). In contrast, intact fetuses demonstrated no change in plasma angiotensin II concentrations with RUBF whereas denervated fetuses demonstrated a marked increase from 47.5 +/- 18.9 to 128.7 +/- 34.2 pg/ml. The norepinephrine and epinephrine responses to prolonged RUBF were attenuated in denervated fetuses (950.1 +/- 308.9 and 155.8 +/- 58.5 to 1268.3 +/- 474.6 and 290.6 +/- 160.2 pg/ml respectively) when compared with intact (1558.3 +/- 384.4 and 547.3 +/- 304.7 pg/ml to 3289.2 +/- 1219.8 and 896.8 +/- 467.8 pg/ml respectively). These results support a role for the peripheral chemoreceptors in mediating fetal endocrine responses to prolonged RUBF, which may in part lead to the altered cardiovascular responses observed in denervated fetuses under these conditions.

Angiotensin II↗
PubMed1998

Short-term urinary flow impairment deregulates PAX2 and PCNA expression and cell survival in fetal sheep kidneys.

Renal malformations account for most children with chronic renal failure and are often associated with urinary tract anatomical obstruction. We examined cellular and molecular events after experimental urinary flow impairment in fetal sheep. Ovine gestation lasts 144 to 150 days with the metanephros appearing at 27 to 30 days. We generated complete unilateral ureteric anatomical obstruction at 90 days when a few layers of glomeruli had formed. After 10 days, we recorded ureteric and pelvic dilatation with renal parenchymal weight greater than contralateral organs or those from unoperated fetuses. The nephrogenic cortex was replaced by disorganized cells separated by edema and prominent vascular spaces. Cortical histology was dominated by cysts associated with malformed glomerular tufts. Cystic epithelia expressed PAX2, a growth-stimulating transcription factor down-regulated during normal maturation, and proliferating cell nuclear antigen, a surrogate marker of cycling cells. Detection of apoptosis using propidium iodide and in situ end labeling showed a significant increase of the point prevalence of death in the obstructed cortex. Hence, PAX2 and proliferating cell nuclear antigen expression as well as death were deregulated, as we previously reported in human kidney malformations. Medullary collecting ducts and loops of Henle were also disrupted, correlating with impaired urinary dilution and sodium reabsorption. Therefore, complex aberrations of morphogenesis, gene expression, cell turnover, and urine composition occur relatively early after experimental impairment of fetal urinary flow.

Animals↗
PubMed1997

Carotid blood flow changes with behavioral states in the late gestation llama fetus in utero.

This study tested the hypothesis that in the llama fetus changes in cerebral blood flow are closely associated with changes in cerebral oxidative metabolism such as occur during transitions between electrocortical states. For the first time reported in any species, instantaneous changes in common carotid blood flow, employed as a continuous index of cerebrovascular perfusion, were related to instantaneous changes in electrocortical activity. Three late gestation fetal llamas were surgically prepared under general anesthesia with vascular catheters, a tracheal and amniotic catheter, and with electrodes implanted to monitor the fetal electrocorticogram (ECoG). In addition, Transonic flow probes were placed around a common carotid artery and a femoral artery. At least 4 days after surgery fetal arterial blood, amniotic and tracheal pressures, carotid and femoral blood flows and the fetal ECoG were recorded continuously. Our results suggest a close association between increases in common carotid blood flow and low voltage ECoG in the llama fetus. Close coupling between instantaneous changes in carotid blood flow and electrocortical states together with the lack of an increase in brain blood flow without increased cerebral oxygen extraction during hypoxemia in the llama fetus supports a fall in cerebral oxidative metabolism in this species during hypoxemic episodes.

Animals↗
PubMed1997

Development of carotid chemoreceptor dynamic and steady-state sensitivity to CO2 in the newborn lamb.

1. The maturation of carotid chemoreceptor steady-state and dynamic responses to CO2 in newborn lambs was measured. In total, sixteen fibres (13 lambs) were studied at 3-4 days, nineteen fibres (13 lambs) at 5-9 days and twenty-one fibres (17 lambs) at 10-24 days after birth. 2. Steady-state CO2 sensitivity was measured over a range of arterial CO2 pressures (Pa,CO2) at four levels of arterial O2 pressure (Pa,O2): hyperoxia (Hyp), 115-150 mmHg; normoxia (Nx), 90-105 mmHg; moderate hypoxia (ModHx), 40-60 mmHg; and severe hypoxia (SvHx), 20-35 mmHg. 3. Steady-state CO2 sensitivity was present at all ages, and a significant effect of age (P < 0.001) and Pa,O2 (P < 0.025) (ANOVA) was observed. Older lambs were unable to sustain an increase in chemoreceptor discharge during SvHx as CO2 was increased. 4. Dynamic CO2 sensitivity was measured by producing alternations in end-tidal CO2 levels (etCO2) (alternation amplitude, 1.23 +/- 0.07% (mean +/- S.E.M.); etCO2, 7.56 +/- 0.15%) over 2-8 s at two Pa,O2 levels only: 80-100 (Nx) and 40-60 mmHg (ModHx). Peak and trough values of the oscillation in chemoreceptor discharge were plotted against maximum and minimum etCO2 for the control and CO2-loaded breaths. Dynamic CO2 sensitivity was calculated as the slope between these points. 5. Dynamic CO2 sensitivity was greater than steady-state sensitivity in Nx (P < 0.05) and ModHx (P < 0.01, Student's paired t test). Unlike steady-state CO2 sensitivity, there was no significant effect of age or Pa,O2 on dynamic sensitivity (P > 0.39 and P > 0.68, respectively, ANOVA). 6. Our results show that the neonatal lamb possesses a carotid body steady-state CO2 sensitivity within a few days of birth, an age when hypoxia sensitivity is low. This CO2 sensitivity increases with age, perhaps due to the increasing interaction between CO2 and O2. Dynamic sensitivity of the carotid body to CO2 is mature at birth and does not increase with age, as predicted if the response of the carotid body to rapid changes in CO2 is independent of the sensitivity to the partial pressure of O2 (PO2).

Aging↗
PubMed1997

Residency training in Massachusetts: a new approach to state-university collaboration.

Traditional state-university collaborations, known as public-academic liaisons (PALs), have resulted in improved quality of service and enhanced residency training. Recent national trends for treating persons with serious mental illness, including moving services from institutional settings to community-based care and emphasizing the use of rehabilitative approaches as well as changes in the health care delivery system itself, have led to preliminary rethinking of some discrete aspects of more traditional approaches. Rather than discrete changes, Massachusetts has responded to these emerging trends with a new and comprehensive initiative that emphasizes one set of statewide standards in these emerging content areas for all residency training programs. Consistent with new practices in health care delivery, this new initiative was fielded through a process of competitive bidding rather than through traditional allocation of service positions. The development, implementation, and initial outcomes of this new approach are presented and implications for mental health administrators are discussed.

Community Mental Health Services↗
PubMed1997

Umbilical flow distribution to the liver and the ductus venosus: an in vitro investigation of the fluid dynamic mechanisms in the fetal sheep.

OBJECTIVES: The study aimed to determine whether an inherent difference in vascular resistance between the liver and the ductus venosus influences the distribution of umbilical blood to the two sections of the circulation. STUDY DESIGN: Flow was measured in vitro in six fetal sheep liver preparations, perfused at varying pressures with saline solution or with blood of hematocrit 25% to 26% or 41% to 42%, with an occluded or open ductus venosus, at a temperature of 19 degrees C to 21 degrees C with likely absence of local control mechanisms. RESULTS: There was a linear relationship between pressure and flow through the liver, except at very low pressures when the linearity was broken. A closing pressure of 1 to 4 mm Hg was noted, lowest with saline solution and highest with hematocrit 42%. An open ductus venosus reduced overall resistance and brought down the closing pressure to <1 mm Hg. This also occurred during perfusion with high hematocrit. Thus at low pressures a proportionally greater fraction of umbilical flow was directed through the ductus venosus. CONCLUSIONS: The different physical properties of the portal vasculature and of the ductus venosus, pressure and viscosity, have a substantial impact on distribution of umbilical flow to the two parts of the circulation. Reduced umbilical venous pressure and increased hematocrit favor an increased fraction of flow through the ductus venosus.

Animals↗
PubMed1997

Red nucleus inhibits breathing during hypoxia in neonates.

Conscious, anaesthetized and decerebrate young mammals respond to acute hypoxia with an initial increase in breathing followed by a fall to, or to below, pre-hypoxic levels--the biphasic ventilatory response. The ventilatory rise is due to sustained hypoxic stimulation of the peripheral chemoreceptors. We present evidence from brain stem and peripheral chemoreflex studies supporting the concept that, in addition to the peripheral chemoreceptors, hypoxia also activates brain stem pathways that inhibit ventilation. A key part of the inhibitory pathway is an area within the red nucleus. Destruction of this area in young decerebrate rabbits abolishes the ventilatory fall during hypoxia, yet has no effect on respiratory control during normoxia and does not affect arterial blood pressure changes in hypoxia. In support of this hypothesis, we report that there are neurones within the red nucleus that increase their discharge in hypoxia. The role of higher brain stem/hypothalamic function in central respiratory control during hypoxia in the fetus and neonate are considered.

Animals↗
PubMed1997

Do we now understand the control of the fetal circulation?

Physiological research has now given us a reasonably complete picture of fetal cardiovascular control in late gestation, especially with respect to the responses to acute hypoxaemia. Reflex, endocrine and auto/paracrine mechanisms all play a part. This review questions how complete our knowledge is when we address the clinically important issues of the influence of gestational age, sustained hypoxia and the effects of nutrition in altering the programming of cardiovascular development.

Animals↗
PubMed1997

Pulse oximetry--physiological considerations.

Fetal well-being depends on the level of oxygenation in vital organs such as the heart and brain. In this review, we discuss the physiological parameters which underlie the use of pulse oximetry to evaluate fetal conditions intrapartum. Whilst the measurement of haemoglobin oxygen saturation (SaO2) depends on partial pressure of oxygen (PO2), the relation is alinear, is relatively insensitive to changes in PO2 at the upper physiological range, and it is affected by the Bohr shift. Oxygen content of the blood cannot be determined without measurement of haemoglobin (Hb) content and this can change quite quickly. In hypoxia for example, oxygen delivery to an organ, e.g. the brain, cannot be assessed without simultaneous measurement of blood flow, which again changes with fetal condition. Lastly, it is not possible to gauge fetal tissue unless some measure of, for example, cytochrome aa3 oxidation is used: tissue oxidation in relation to oxygen delivery can change due to local vascular readjustments and changes in metabolism. We conclude that use of SaO2 to assess fetal well-being is fraught with difficulties, and that much more research is needed before its routine clinical use can be considered.

Female↗
PubMed1997

Hospital downsizing and patients' assaults on staff.

Although the downsizing and closing of state mental hospitals is occurring with increasing frequency nationwide, there appears to be only one case study of the clinical impacts of downsizing state hospitals. In this study, Snyder reported a four-fold increase in frequency of assaults on staff as the hospital census decreased. The present paper is a second case study of state hospital downsizing and closing in which the frequency of assaults on staff decreased by 63%. Possible explanations for the two differing outcomes are considered, and some general guidelines for the downsizing and closing of state hospitals are proposed.

Adolescent↗
PubMed1997

The effect of carotid sinus denervation on fetal heart rate variation in normoxia, hypoxia and post-hypoxia in fetal sheep.

OBJECTIVE: To investigate whether carotid sinus nerve reflexes are linked to the increase in heart rate variation in acute (one hour) hypoxia in late gestation fetal sheep DESIGN: Comparison of short term variation between intact and carotid sinus denervated fetuses in normoxia, hypoxia and post-hypoxia. SUBJECTS: Sixteen chronically catheterised pregnant sheep in late gestation. RESULTS: There was no significant difference in short term variation between intact and denervated fetuses in normoxia. In intact fetuses short term variation increased significantly in hypoxia. In denervated fetuses it tended to increase in hypoxia, but this was not statistically significant. During the post-hypoxia period, short term variation increased significantly in denervated fetuses, although at this time it was decreasing in intact fetuses. When the decrease in pH was small intact fetuses showed a significantly greater increase in short term variation than denervated fetuses in hypoxia. In contrast, short term variation increased similarly in both groups when the pH decrease was greater (> 0.03 in early hypoxia and > 0.05 in late hypoxia). CONCLUSIONS: Carotid sinus nerve reflexes have an important influence on heart rate variation in hypoxia and post-hypoxia. It appears that other mechanisms (e.g. a rise in circulating catecholamines) are linked to an increase in heart rate variation when mild acidemia occurs in hypoxia.

Animals↗
PubMed1997

The role of carotid chemoreceptors in the effects of hypoxia on renal blood flow in the late gestation sheep fetus.

Previous studies of the effect of hypoxia on fetal renal haemodynamics have demonstrated a fall, a rise or no change in renal blood flow (RBF). The underlying mechanisms are not understood but involve a balance between neural vasoconstrictor and opposing vasodilator mechanisms. Since carotid chemoreflex mechanisms contribute to vasoconstriction in other fetal vascular beds and in the adult renal vasculature, we examined their effects on RBF during 1 h of acute hypoxia in late gestation fetal sheep (n = 12). Renal blood flow was measured continuously and urine collected at 15 min intervals. Seven fetuses underwent bilateral section of the carotid sinus nerves (CSD fetuses). During hypoxia CSD fetuses showed a transient initial rise in RBF (P < 0.05) and then a subsequent fall (P < 0.05) to levels comparable with that recorded in intact fetuses. There was no change in urine output in either intact or CSD fetuses during hypoxia. Thus the initial fall in RBF during hypoxia is a carotid chemoreflex but other mechanisms, e.g. vasoconstrictor hormones, contribute to the sustained response.

Animals↗
PubMed1997

Personnel selection.

This chapter reviews literature from approximately mid-1993 through early 1996 in the areas of performance and criteria, validity, statistical and equal opportunity issues, selection for work groups, person-organization fit, applicant reactions to selection procedures, and research on predictors, including ability, personality, assessment centers, interviews, and biodata. The review revolves around three themes: (a) attention toward criteria and models of performance, (b) interest in personality measures as predictors of job performance, and (c) work on the person-organization fit selection model. In our judgment, these themes merge when it is recognized that development of performance models that differentiate criterion constructs reveal highly interpretable relationships between the predictor domain (i.e. ability, personality, and job knowledge) and the criterion domain (i.e. technical proficiency, extra-technical proficiency constructs such as prosocial organizational behavior, and overall job performance). These and related developments are advancing the science of personnel selection and should enhance selection practices in the future.

Journal Article↗
PubMed1997

The effect of hypercapnia and hypercapnia associated with central cooling on breathing in unanesthetized fetal lambs.

In utero breathing activity is present periodically, but it must become continuous at birth. We investigated the effect of hypercapnia and of hypercapnia combined with central cooling on fetal breathing in seven chronically instrumented fetal lambs of 131-134-d gestation, using an extracorporeal membrane oxygenation (ECMO) system to control fetal blood gases and fetal temperature. During fetal hypercapnia (from a partial pressure of arterial CO2 (Paco2) 6.18 +/- 0.11 kPa to Paco2 7.39 +/- 0.15 kPa) frequency, amplitude, and incidence of fetal breathing movements during low voltage electrocortical activity (LV ECoG) increased significantly compared with isocapnic control on ECMO, but breathing remained absent during high voltage electrocortical activity (HV ECoG). During hypercapnia accompanied by central cooling (Paco2 7.90 +/- 0.13 kPa, temperature decreased by 2.1 degrees C) there were similar changes in fetal breathing movements during LV ECoG, but in four out of seven fetuses fetal breathing movements continued throughout HV ECoG. Hypercapnia accompanied by central cooling can thus override the inhibitory effects of HV ECoG on fetal breathing movements. This may be due to changes in sensitivity to CO2 produced by an increase in afferent input to the CNS.

Animals↗
PubMed1997

Initiation and maintenance of continuous breathing at birth.

Changes in arterial PCO2 (PaCO2) and body temperature normally occurring at the moment of birth may play a role in the initiation and maintenance of continuous breathing. To clarify these mechanisms, five chronically instrumented fetal lambs were connected to an extracorporeal membrane oxygenation (ECMO) system. ECMO was initiated in utero at a flow rate sufficient to support the fetus totally, the umbilical cord was occluded, and the fetuses were delivered into a warm isotonic saline bath. Breathing activity was present periodically before connection to the ECMO system and on ECMO during fetal normocapnia and normoxia. Near delivery there were no breathing movements, because all ewes were in labor. After delivering the fetuses into the warm saline bath, breathing movements remained episodic, being absent during high voltage electrocortical activity, whereas fetal PaCO2 remained constant. However, after 36-192 min, breathing activity became present continuously in all animals, at a time when fetal central temperature decreased. Once initiated, continuous breathing could be stopped by reducing the PaCO2. We conclude that maintenance of fetal PaCO2 and a slow decrease in central temperature after cord occlusion delays the establishment of continuous breathing, and that the level of PaCO2 is important in the maintenance of breathing activity during early postnatal life.

Animals↗
PubMed1996

The role of nitric oxide synthesis in cardiovascular responses to acute hypoxia in the late gestation sheep fetus.

1. In fetal sheep (123-129 days gestation) we investigated the effect of acute isocapnic hypoxia (Pa,O2, 12 +/- 0.6 mmHg) on the fetal heart rate (FHR), mean systemic arterial blood pressure (MAP), carotid blood flow (CBF), femoral blood flow (FBF), carotid vascular resistance (CVR) and femoral vascular resistance (FVR) with the infusion of either the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) or saline vehicle. 2. During normoxia, CBF was lower (P < 0.05) and MAP, FVR and CVR were higher with L-NAME than with vehicle infusion (P < 0.01, P < 0.05 and P < 0.01, respectively). FHR fell 15 min after the onset of L-NAME infusion (P < 0.05). During hypoxia in both groups, FHR showed an initial rapid fall (P < 0.05) and subsequent return to prehypoxic levels, and there was a fall in FBF (P < 0.01). MAP increased during hypoxia with vehicle (P < 0.05) but not L-NAME infusion: thus MAP was similar during hypoxia in the two groups. The rebound tachycardia seen during recovery in the vehicle group (P < 0.01) was not evident in the L-NAME group. The rise in CBF and fall in CVR during hypoxia with vehicle (P < 0.01 and P < 0.05, respectively) was absent with L-NAME infusion. FVR rose during hypoxia in both groups (P < 0.05). 3. Thus NOS inhibition alters basal systemic vascular tone in the late gestation fetus. The rise in CBF and fall in CVR during hypoxia is absent with NOS inhibition.

Animals↗
PubMed1996

Red nucleus lesions abolish the biphasic respiratory response to isocapnic hypoxia in decerebrate young rabbits.

1. The respiratory response to isocapnic hypoxia (inspired O2 fraction (FI,O1), 0.1-0.12) was measured in twelve vagotomized, paralysed, artificially ventilated young rabbits (aged 26.6 +/- 0.4 days), following pre-collicular decerebration. Phrenic nerve efferent activity was used as an index of central respiratory output (RO). In hypoxia RO increased after 1-2 min (phase 1) but decreased over the subsequent 3-4 min to, or below, the pre-hypoxic control level (phase 2). 2. We used electrical stimulation to target areas in the mesencephalon which inhibit RO. Profiles of the response to stimulation were determined in a grid of electrode penetrations made mediolaterally and rostrocaudally at the level of the superior colliculi, in normoxia. Histology confirmed that stimulation in the red nucleus (RN) inhibited RO profoundly. 3. Electrolytic lesions were made bilaterally in RN inhibitory sites or in adjacent areas. The respiratory response to isocapnic hypoxia was measured again post-lesioning. 4. In six rabbits with bilateral lesions in the RN, phase 2 of the respiratory response was abolished and RO remained elevated throughout the hypoxic exposure. However, in six rabbits with unilateral lesions in the RN, or with bilateral lesions placed in areas outside the RN that did not inhibit RO on electrical stimulation, the respiratory response remained biphasic. 5. In both groups of animals, blood pressure increased during 1-3 min of hypoxia before decreasing to pre-hypoxic levels. This cardiovascular response remained biphasic irrespective of whether animals showed a biphasic respiratory response or a sustained increase in RO after lesioning. 6. We conclude that structures within the RN are crucial to the mechanism producing a fall in RO during isocapnic hypoxaemia in the neonate.

Animals↗