Biomedical subjects

M A Hanson

Publications and source records attributed to M A Hanson.

At least 55 records · Page 3Linked to original sources

PubMed1999

Mechanisms of noradrenaline-induced vasorelaxation in isolated femoral arteries of the neonatal rat.

Isolated arteries from the femoral circulation of Wistar rats mounted on a small vessel myograph demonstrated age related tension development to noradrenaline (NA, 1 x 10(-8) - 5 x 10(-5) M) day 20 greater than day 10 (P<0.005); day 100 greater than day 20 (P<0.001) and depolarizing potassium (125 mM) buffer day 20 greater than day 10 (P<0.001). NA evoked dilatation in femoral arteries from neonatal rats (10 days) when added to unstimulated vessels or to those preconstricted with the thromboxane mimetic, U46619. Relaxation to NA was inhibited by L-NAME (0.1 mM) (P<0.001), endothelial removal (P<0.001) and the alpha2-adrenoceptor antagonist, yohimbine (0.1 microM) (P<0.001). Alpha1- or beta-adrenoceptor antagonism was without effect. Relaxation was evoked in femoral arteries of the 10-day-old rats by the alpha2-adrenoceptor agonist UK14304 (1 x 10(-8) - 5 x 10(-5) M). This relaxation was also abolished by L-NAME (0.1 mM) (P<0.001) or endothelial removal (P<0.001). Alpha2-adrenoceptor-mediated vasorelaxation was the predominant response to NA stimulation in femoral arteries of the neonatal rat. These responses were endothelium-dependent and were NO-mediated.

Animals↗

PubMed1999

Validation of diameter measurements by ultrasound: intraobserver and interobserver variations assessed in vitro and in fetal sheep.

OBJECTIVES: Blood flow evaluation in the fetus is hampered by inaccuracy in the measurement of vessel diameter. The impact of biological variation on reproducibility studies is unknown. The present study evaluated diameter measurements carried out with modern ultrasound equipment by assessing inter- and intraobserver variations. DESIGN: Repeated measurements analyzed by a general factorial model of analysis of variance. METHODS: Three observers measured repeatedly (six or more times for each tube and session) silicone tube implants (0.6, 2.2 and 6 mm), applying ultrasound imaging in eight fetal sheep, and the same silicone tubes in vitro. Analysis of variance was carried out on 199 observations made in vitro and 537 in vivo. RESULTS: The upper 95% confidence limit for the intra- and interobserver variations was higher for measurements made in vivo than in vitro. It was highest for the largest diameter and varied between 0.10 and 0.38 mm. When the diameter was determined as an average of repeated measurements, the error was reduced: six measurements in vivo had upper 95% confidence limits for intraobserver variation of 0.04 and 0.09 mm for diameters of 0.6 and 6 mm, respectively. CONCLUSIONS: The results show that ultrasound diameter measurements have a high reproducibility even for vessels of small dimensions when repeated measurements are taken with high-frequency ultrasound under favorable conditions. The low variation described in the present investigation of silicone tubes, compared to previous studies, suggests that diameter changes of living vessels represent a separate source of measurement variation.

Animals↗

PubMed1999

Temporal changes in fetal cardiovascular, behavioural, metabolic and endocrine responses to maternally administered dexamethasone in the late gestation fetal sheep.

OBJECTIVE: To determine the primary (0-12 h) and secondary (12-24 h) effects of dexamethasone on fetal heart rate, short term heart rate variation, blood pressure, breathing movements and electrocortical activity, blood gas exchange, metabolism and adrenocortical function in the late gestation sheep fetus. DESIGN: Comparison of the effects of a single maternally administered intramuscular injection of dexamethasone (12 mg) with those of saline vehicle from 1 h before injection to 24 h post-injection. Fetal cardiovascular and behavioural parameters were recorded continuously. Fetal and maternal blood samples were taken at regular intervals for blood gas, glucose and lactate, cortisol and adrenocorticotrophin measurements. SAMPLE: Sixteen chronically instrumented singleton fetal sheep at 127-133 days of gestation (term is about 147 days). RESULTS: During the primary phase short term heart rate variation fell (P < 0.001), and this was associated with a transient fall in the incidence of fetal breathing movements, a fall in fetal heart rate and a rise in fetal blood pressure. By 12 h there was a significant increase in short term heart rate variation (P < 0.001) and a rise in fetal heart rate, but blood pressure and fetal breathing movements had returned to normal. Dexamethasone significantly reduced fetal PaO2 throughout most of the experimental period, particularly 1 h post-injection (P < 0.005). Fetal and maternal plasma cortisol and adrenocorticotrophin concentrations fell significantly from 1 h post-injection. CONCLUSIONS: The effects of dexamethasone on fetal heart rate variation are more complex than previously described with both a fall and an increase observed depending on the time at which heart rate variation was measured after injection. Dexamethasone also caused a significant fall in fetal PaO2, and although this was not to hypoxic levels in normoxic fetuses it does raise questions about the potential impact of dexamethasone on chronically hypoxic fetuses.

Adrenocorticotropic Hormone↗

PubMed1999

Altered fetal cardiovascular responses to prolonged hypoxia after sinoaortic denervation.

This study examines the role of the peripheral chemoreceptors in mediating fetal cardiovascular responses to prolonged hypoxia secondary to reduced uterine blood flow (RUBF). Fetal sheep were chronically instrumented for continuous heart rate (FHR), blood pressure (FBP), and carotid blood flow (CBF) measurements after bilateral sectioning of the carotid sinus and vagus nerves (denervated, n = 7) or sham denervation (intact, n = 7). Four days postoperatively, uterine blood flow was mechanically restricted, reducing fetal arterial oxygen saturation by 47.3% (P < 0.01). An initial bradycardia was observed in intact (184.0 +/- 10.7 to 160.5 +/- 10.7 beats/min, not significant) but not denervated fetuses, followed by a tachycardia (180.0 +/- 2.2 to 193.7 +/- 2.7 beats/min, P < 0.05). FHR increased in denervated fetuses (175.5 +/- 8.7 to 203. 0 +/- 17.9 beats/min, P < 0.05). FBP increased transiently in intact fetuses from 45.1 +/- 1.0 to 55.4 +/- 3.0 mmHg at 2 h (P < 0.01), whereas denervated fetuses demonstrated a decrease in FBP from 47.1 +/- 4.2 to 37.2 +/- 3.7 mmHg (not significant). CBF increased (P < 0. 05) in both intact and denervated fetuses from 39.3 +/- 2.8 and 29.7 +/- 3.8 ml. min-1. kg-1 to 47.7 +/- 0.4 and 39.1 +/- 0.3 ml. min-1. kg-1, respectively, whereas carotid vascular resistance decreased only in denervated fetuses (1.7 +/- 0.1 to 1.1 +/- 0.02 mmHg. ml-1. min. kg-1, P < 0.05). We conclude that the peripheral chemoreceptors play an important role in mediating fetal cardiovascular responses to prolonged RUBF.

Animals↗

PubMed1999

Effect of maternal nutrient restriction in early gestation on development of the hypothalamic-pituitary-adrenal axis in fetal sheep at 0.8-0.9 of gestation.

The fetal hypothalamic-pituitary-adrenal (HPA) axis has numerous key roles in development. Epidemiological data have linked adverse prenatal nutrition with altered organ development and increased incidence of disease in adult life. We studied HPA axis development in resting and stimulated states in late gestation fetal sheep, following 15% reduction in maternal nutritional intake over the first 70 days of gestation (dGA). Fetuses from control (C) and nutrient-restricted (R) ewes were chronically catheterised and response profiles for ACTH and cortisol were determined at 113-116 and 125-127 dGA after administration of corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP). At 126-128 dGA cortisol profiles were also determined following ACTH administration. Basal ACTH and cortisol concentrations were not different between C and R fetuses. In R fetuses, ACTH response to CRH+AVP was significantly smaller at 113-116 dGA (P<0.01), and cortisol responses were smaller at both 113-116 dGA (P<0.01) and 125-127 dGA (P<0.0001). Cortisol response to ACTH was also smaller in R fetuses (P<0.001). We conclude that, in late gestation fetal sheep, pituitary and adrenal responsiveness is reduced following modest maternal nutrient restriction in early gestation.

Adrenocorticotropic Hormone↗

PubMed1999

Pharmacoeconomics of schizophrenia in the 21st century.

During the next century-if not before-a variety of issues associated with mental health care in the United States need to be addressed and resolved nationwide, including securing full parity for patients with psychiatric disorders, improving the overall medical health of psychiatric patients, establishing the effectiveness as well as the efficacy of new drugs and educating health care providers about new drugs and new uses for older drugs, and using all costs to evaluate new therapeutic strategies or medications. The following discussion covers some of the major findings from studies conducted in the Commonwealth of Massachusetts, touches on some of the areas mentioned above, and is intended to serve as a springboard for exchanges among professionals in the health care community who care for psychiatric patients.

Antipsychotic Agents↗

PubMed1999

Development of a draft British standard: the assessment of heat strain for workers wearing personal protective equipment.

Existing methods for estimating heat stress, enshrined in British/International Standards (the Wet Bulb Globe Temperature (WBGT) index [BS EN 27243] and the Required Sweat Rate equation [BS EN 12515; ISO 7933 modified]), assume that the clothing worn by the individual is water vapour permeable; the WBGT index also assumes that the clothing is relatively light. Because most forms of personal protective equipment (PPE) either have a higher insulative value than that assumed or are water vapour impermeable, the Standards cannot be accurately applied to workers wearing PPE. There was, therefore, a need to develop a British Standard which would allow interpretation of these existing Standards for workers wearing PPE. Relevant information was obtained through reviewing the literature and consulting experts. Two questionnaire surveys of potential users of the Standards were conducted, and physiological data collected both experimentally and in work situations were considered. The information collected was used to develop the draft British Standard. It provides information and data on: The general effect of PPE on heat balance of the body (the ability of the body to maintain its 'core' temperature within an acceptable range). The effect of specific forms of PPE on metabolic heat production rate. The thermal insulation and evaporative resistance of types of PPE. The effect of the closure of the garments to the body on heat transfer. The effect of the PPE on the proportion of the body covered. The effect of an air supply (for example, Breathing Apparatus [BA]) to the wearer. Guidance is given on conducting an analysis of the work situation, taking account of the impact of PPE. Detailed methods of interpreting both BS EN 27243 and BS EN 12515 for workers wearing PPE are given, taking account of the factors listed above. Three worked examples using BS EN 27243 and BS EN 12515 are given in the Annex of the draft Standard.

Body Temperature Regulation↗

PubMed1998

The effect of repeated acute hypoxaemia on fetal cardiovascular development in the sheep.

1. Hypoxaemia during intrauterine life may be important in the development of cardiovascular diseases in later life. Thus it was the aim of this study to investigate the effect of repeated acute hypoxia on the cardiovascular development and growth of the fetus. 2. Fourteen fetal sheep (105-109 days gestational age) were instrumented with amniotic and vascular catheters, an electrocardiogram (ECG) electrode and a flow probe around the femoral artery. Seven animals were given repeated acute isocapnic hypoxaemia (Pa,O2 reduced to ca. 13 mmHg) for 1 h every day for 14 days and they were compared to seven animals which remained normoxic throughout with respect to fetal mean arterial blood pressure (MAP), fetal heart rate (FHR), and fetal baro- and chemoreflexes. 3. No differences were found between the two groups of fetuses in FHR, MAP, baro- or chemoreflexes, femoral blood flow, femoral vascular resistance or fetal growth. 4. Repeated acute hypoxaemia of a moderate degree over a period of 2 weeks in late gestation does not affect cardiovascular development or growth in the fetal sheep.

Animals↗

PubMed1998

The role of endothelin-A receptors in cardiovascular responses to acute hypoxaemia in the late gestation sheep fetus.

1. In unanaesthetized chronically instumented fetal sheep (118-121 days gestation) we investigated the effect of acute isocapnic hypoxaemia (arterial Po2, 12.5 +/- 0.6 mmHg) on heart rate (FHR), mean systemic arterial blood pressure (MABP), carotid and femoral blood flows (CBF and FBF, respectively), and carotid and femoral vascular resistances (CVR and FVR, respectively) with the infusion of either the endothelin-A (ETA) receptor antagonist FR139317, or saline vehicle. 2. During normoxaemia FHR (P < 0.05) and CBF (P < 0. 01) were greater, and CVR (P < 0.01) was lower with FR139317 than with vehicle infusion. CVR remained lower with FR139317 than with vehicle infusion during hypoxaemia (P < 0.01) and recovery (P < 0. 05). During hypoxaemia the rapid initial bradycardia, the increase in MABP and FVR and the decrease in FBF were similar with vehicle and FR139317 infusion. In both groups plasma endothelin-1 concentration ([ET-1]) was unaltered by hypoxaemia. The increase in CBF during hypoxaemia with vehicle (P < 0.01) was absent with FR139317 infusion. 3. Thus in the late gestation ovine fetus endogenous ET-1 modulates basal FHR, CBF and CVR via ETA receptors. Modulation of CBF and CVR persists during hypoxaemia but ETA receptors do not appear to contribute to the decrease in femoral blood flow measured during acute hypoxaemia.

Animals↗

PubMed1998

Angiotensin II and cardiovascular chemoreflex responses to acute hypoxia in late gestation fetal sheep.

1. In six intact and nine carotid sinus denervated (CSD) fetal sheep (125-128 days gestation) we measured heart rate (FHR), mean systemic arterial blood pressure (MAP), femoral and carotid blood flows (FBF and CBF), and femoral and carotid vascular resistances (FVR and CVR). Three experiments were conducted on successive days: normoxia followed by acute isocapnic hypoxia (Pa,O2 to ca 12 mmHg) with infusion of vehicle (HV experiment), the same protocol but with infusion of the angiotensin converting enzyme (ACE) inhibitor, captopril (HC experiment), and normoxia alone with captopril infusion (NC experiment). Plasma angiotensin II concentration ([AII]) was measured in these fetuses, and in a separate group of fetuses (n = 5) that were infused with the nitric oxide (NO) synthesis inhibitor N G-nitro-L-arginine methyl ester (L-NAME) or saline vehicle. 2. During normoxia, cardiovascular parameters and plasma [AII] were unaltered by captopril infusion, apart from a fall in MAP (NC experiment only, P < 0.05) and FHR (HC experiment only, P < 0.05) in intact and CSD fetuses, respectively. No differences were observed between intact and CSD groups. 3. At the onset of hypoxia the rapid initial fall in FHR and rise in FVR was attenuated in CSD fetuses. In all fetuses FHR returned towards prehypoxic levels as hypoxia continued. In contrast, during hypoxia with vehicle infusion (HV experiment) plasma [AII] rose to a similar level in intact and CSD fetuses. 4. In both intact and CSD fetuses, the rise in [AII] during hypoxia was blocked by captopril or L-NAME infusion. In CSD, but not intact, fetuses infused with captopril the rise in MAP was absent, and the fall in FBF and rise in FVR did not reach significance during hypoxia. 5. Thus, during normoxia CSD alone, or combined with ACE inhibition, does not consistently alter basal cardiovascular control in the late gestation fetus. The rise in [AII] during hypoxia is not mediated by carotid reflexes but may involve NO-dependent mechanisms. In intact fetuses, AII does not appear to be pivotal in cardiovascular control during hypoxia. It is only when carotid reflex mechanisms are removed that a role for AII in the regulation of MAP and peripheral blood flow during hypoxia becomes apparent. These findings lend weight to the idea of multiple mechanisms of fetal cardiovascular control during hypoxia.

Angiotensin II↗

PubMed1998

Initial evaluation and treatment of infertility in a primary-care setting.

Infertility is a condition that primary-care physicians frequently encounter. The infertility work-up necessitates an understanding of the physiology and anatomy of the female and male partners. A systematic work-up can be initiated by a primary-care physician. Infertility problems are stressful for the couple, and initial assessment by their own physician may help them work through the process as well as prepare them if they need to seek the care of a reproductive endocrinologist for further assessment or for assisted reproductive techniques. Infertility services are expensive and are rarely completely covered by many health insurance plans; therefore, a cost-effective evaluation is important. In the managed-care environment, a primary-care physician can begin the investigation and decide which patients require more advanced assessment and treatment. Helping a couple through the stages of an infertility investigation is a professionally rewarding experience.

Decision Trees↗

PubMed1998

Blood velocity profile in the ductus venosus inlet expressed by the mean/maximum velocity ratio.

Mean blood velocity (Vmean) is needed for calculating blood flow and possibly the pressure gradient across the ductus venosus. Interference from low velocities from neighbouring vessels makes the direct Doppler measurement of Vmean unreliable. Therefore, it is suggested that Vmean can be derived more reliably from the maximum velocity (Vmax) once the velocity profile, expressed as the ratio Vmean/Vmax, is known. To determine this ratio, ultrasound was performed in 10 fetal sheep during acute experiments under general anaesthesia to ensure good recording control and optimal insonation. Based on 33 Doppler measurements at the ductus venosus inlet, the ratio Vmean/Vmax was determined to be 0.69 (SD +/- 0.07) regardless of Vmax, pulsatility index, vessel diameter, or angle of insonation. These results confirm the previous prediction based on a computational model that the velocity profile is partially blunted. The equation Vmean = 0.7Vmax is recommended for determining Vmean in the ductus venosus.

Anesthesia, General↗

PubMed1998

Role of chemoreceptors in effects of chronic hypoxia.

Effects of chronic hypoxia on chemoreceptors and chemoreflexes in the fetus and neonate are reviewed. The effects are discussed in relation to those in the adult, in which there is an apparent paradox between the increase in chemoreflex gain during acclimatisation to the hypoxia of altitude vs the 'blunting' reported during chronic hypoxia. The possible location and importance of "chemoreceptors" in the brainstem is discussed. In the neonate, chronic hypoxia blunts the ventilatory response to acute hypoxia, an effect largely due to blunting of chemoreceptor sensitivity. Whether this is mediated via a reduction or delay in the normal process of postnatal resetting of hypoxia sensitivity is not known. In addition, there is evidence that the effects on neonatal chemoreceptors are reversible on return to normoxia. Such differences from the adult suggest that special processes, affected by chronic hypoxia, operate in the neonate. In the fetus there is no direct information on the effect of chronic hypoxia on chemoreceptor responses, but it appears that chemoreflexes are augmented, as may occur in the adult during acclimatisation to hypoxia. Recent evidence suggests that arterial chemoreceptors play an important role in fetal cardiovascular and endocrine responses to prolonged hypoxaemia. This will be a productive avenue for future research.

Acclimatization↗

PubMed1998

Public-academic liaison research centers in an era of managed care.

Public-Academic Liaison research centers (PALs) have traditionally provided benefits to both state mental health authorities (SMHAs) and academic institutions. The advent of managed care, austere state fiscal budgets, and a restructured national research development capacity suggests the need for new administrative approaches to PAL research efforts to maintain these benefits in this era of rapidly changing health care. This brief report outlines one such approach by the Massachusetts SMHA in its efforts to establish two PAL research centers: one for clinical neuroscience, and one for behavioral and forensic science. Preliminary two-year outcomes are presented, and the implications of the model are discussed.

Education, Medical↗

PubMed1998

Replicated declines in assault rates after implementation of the Assaulted Staff Action Program.

A program to address the psychological sequelae of patients' assaults on psychiatric health care staff--the Assaulted Staff Action Program (ASAP)--was previously shown to be associated with a notable decline in the assault rate at the state hospital where it was implemented. This study examined whether these findings would be replicated when ASAP was introduced at three additional state hospitals. Assault rates during the three months before implementation were compared with rates in the first four quarters after implementation. Each facility reported a similar significant decline in rates during the first quarter after implementation and no additional declines in the next three quarters.

Adult↗

PubMed1998

Elevation of metabolic rate by pyrogen administration does not affect the gain of respiratory peripheral chemoreflexes in unanesthetized kittens.

We previously reported that reducing environmental temperature from 30 to 25 degrees C increases the gain of respiratory chemoreflexes. To investigate the role of increased metabolism in mediating the effect on the gain of the respiratory chemoreflex, we compared the respiratory responses, at ca. 26 degrees C to breath-by-breath alternations of inspired gas between air and 14% oxygen (hypoxia run) or air and 5% CO2 (CO2 run) with that to alteration of air between two inspired lines (control run) before and after the injection of a pyrogen (IL-1beta 400 ng/kg i.p.) in eight kittens at 27-35 d of postnatal age. The respiratory chemoreflex was quantified from the alternations in inspiratory and expiratory variables produced during test runs in terms of the direction and the amplitude of the alternation for each variable and compared with the results of control runs at the same temperature. Pyrogen administration produced a rise in rectal temperature and in oxygen consumption. However, there was no difference in the chemoreflex response to hypoxia or CO2 runs, in terms of either the pattern or of the amplitude of alternation, before and after the injection of the pyrogen. We conclude that the increase in the gain of chemoreflex observed during cooling in a previous study is not due to an increase in metabolism. Some change in input from thermoreceptors may bias the gain of chemoreflexes.

Animals↗

PubMed1998

The cerebral hemodynamic response to asphyxia and hypoxia in the near-term fetal sheep as measured by near infrared spectroscopy.

This study examined the hypothesis that the cerebrovascular response to asphyxia of the late gestation sheep fetus is characterized by an increase in cerebrovascular resistance and a fall in cerebral blood flow (CBF) rather than the fall in resistance and increase in CBF which occurs in acute hypoxemia. In eight unanesthetized late gestation fetal sheep (123- to 125-d gestation) we evaluated continuous changes in carotid blood flow (CaBF) as an index of global CBF and total cerebral Hb concentrations as an index of global cerebral blood volume (CBV) using ultrasound flow probes and near infrared spectroscopy respectively. Asphyxia was induced by rapid and complete occlusion of the umbilical cord for 10 min. We also examined the fetal response to 1 h of acute 9% isocapnic hypoxia for comparison purposes. During hypoxia we observed a sustained increase in CaBF (p < 0.05) and CBV (p < 0.01) and a fall in carotid vascular resistance (p < 0.05). During asphyxia there was no significant rise in CBV, a fall in CaBF (p < 0.05), and a rise in carotid vascular resistance (p < 0.01). CaBF fell at a time when mean arterial pressure was elevated (p < 0.01). These data strongly suggest that fetal CBF does not increase and may even fall during severe asphyxia of rapid onset. Furthermore, our near infrared spectroscopy data show that the relative changes in total cerebral Hb concentrations may reflect the type and severity of the insult to which the fetus is exposed.

Animals↗

PubMed1998

Chemoreflex contribution to adrenocortical function during acute hypoxemia in the llama fetus at 0.6 to 0.7 of gestation.

This study tested the hypothesis that the fetal llama, a species adapted to the chronic hypoxia of life at high altitude, demonstrates a potent carotid chemoreflex influence on adrenocortical responses during acute hypoxemia. Plasma ACTH and cortisol concentrations, and mesencephalic and adrenal blood flows were measured during a 1-h period of acute hypoxemia in six intact and four carotid sinus-denervated llama fetuses at 0.6-0.7 of gestation. Fetal PaO2 was reduced from approximately 23 to about 14 mm Hg in both intact and carotid-denervated groups during acute hypoxemia. During hypoxemia, fetal plasma ACTH, adrenal blood flow, and, therefore, delivery of ACTH to the adrenals increased to similar extents in both intact and carotid-denervated fetal llamas. Despite this, the increase in plasma cortisol in hypoxemia in intact fetuses was absent in carotid-denervated fetuses. In addition, the increase in delivery of cortisol to the mesencephalon calculated in intact fetuses during hypoxemia did not occur in the carotid-denervated group. These data suggest that the integrity of the carotid chemoreceptors is indispensable to cortisol release during acute hypoxemia in the llama fetus, even at 0.6-0.7 of gestation.

Adrenal Cortex↗