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Biomedical subjects

M A Hanson

Publications and source records attributed to M A Hanson.

At least 91 records · Page 5Linked to original sources

Violence and the lax milieu?: preliminary data.

Recently, Rosenbaum noted a rise in the number of patient assaults on staff. He attributed this increase to a lax milieu of impaired structures, boundaries, and leadership. This case study reports on a sharp decline in violence on three lax units in one state mental hospital, when new management fielded initiatives to strengthen the structures and boundaries on these three units. The implications of the findings are discussed.

Hospital Administration↗

Effect of ambient temperature on respiratory chemoreflex in unanaesthetized kittens.

We compared the respiratory responses to breath-by-breath alternations of air and 14% oxygen (hypoxia run), air and 5% CO2 (CO2 run) or air from two gas lines (control run) at ambient temperatures of 25-26 degrees C and 30-31 degrees C in nine kittens at 3-7, 11-18 and 30-39 days post-natal age. Chemoreflex responses were measured from alternations in inspiratory and expiratory variables during test runs and compared with those of control runs. At 25-26 degrees C, no significant respiratory alternations were present in hypoxia runs at days 3-7, while alternations were significant at older ages. In CO2 runs alternation was significant at each age group. At 30-31 degrees C, no significant respiratory alternation was present in either hypoxia or CO2 runs for any age group. Thus respiratory chemoreflexes decrease at a warmer environmental temperature in kittens. This may explain how elevated environmental temperature predisposes neonates to respiratory failure.

Animals↗

Development of respiratory chemoreflexes to hypoxia and CO2 in unanaesthetized kittens.

To investigate differences in the postnatal development of the respiratory peripheral chemoreflex response to hypoxia and to CO2, we measured the responses to switching inspired gas on an alternate breath basis between two air lines (control runs), air and 14% oxygen (hypoxia runs) and air and 5% CO2 (CO2 runs) in nine kittens studied sequentially during quiet sleep between 3-7, 11-18, 24-31 and 35-39 days of postnatal age. The response was quantified in terms of the breath-by-breath alternations in respiratory volumes, durations and flows. There was little response to control runs at any age. The hypoxia response was not different from control at days 3-7 but became significantly different at older ages. In contrast, the CO2 response was different from control in each age group. The pattern of response was different between hypoxia runs and CO2 runs until 35-39 days, when the patterns became similar. The results show that chemoreflex responses to CO2 are present even at an age when hypoxia sensitivity is low.

Animals↗

Evolution of anthocyanin biosynthesis in maize kernels: the role of regulatory and enzymatic loci.

Understanding which genes contribute to evolutionary change and the nature of the alterations in them are fundamental challenges in evolution. We analyzed regulatory and enzymatic genes in the maize anthocyanin pathway as related to the evolution of anthocyanin-pigmented kernels in maize from colorless kernels of its progenitor, teosinte. Genetic tests indicate that teosinte possesses functional alleles at all enzymatic loci. At two regulatory loci, most teosintes possess alleles that encode functional proteins, but ones that are not expressed during kernel development and not capable of activating anthocyanin biosynthesis there. We investigated nucleotide polymorphism at one of the regulatory loci, cl. Several observations suggest that cl has not evolved in a strictly neutral manner, including an exceptionally low level of polymorphism and a biased representation of haplotypes in maize. Curiously, sequence data show that most of our teosinte samples possess a promoter element necessary for the activation of the anthocyanin pathway during kernel development, although genetic tests indicate that teosinte cl alleles are not active during kernel development. Our analyses suggest that the evolution of the purple kernels resulted from changes in cis regulatory elements at regulatory loci and not changes in either regulatory protein function nor the enzymatic loci.

Alleles↗

The effect of halothane on phrenic and chemoreceptor responses to hypoxia in anesthetized kittens.

We examined the effect of halothane on phrenic never and carotid sinus discharge during hypoxia in anesthetized kittens. In 12 animals, phrenic amplitude was measured during normoxia, during isocapnic hypoxia, and after a return to normoxia, both with and without halothane. Without halothane, all animals had an increase in phrenic amplitude during hypoxia. With halothane, half the animals showed an increase in phrenic amplitude followed by a decline. In a second group of animals, recordings were obtained from single or a few fiber strands of carotid sinus nerve. Without halothane, an increase in chemoreceptor discharge frequency during hypoxia was seen. With 1.0% halothane, frequency was decreased during normoxia and did not increase during hypoxia. Thus, halothane's effect on the ventilatory response to hypoxia, as measured by phrenic discharge, is at least partially explained by an effect on peripheral chemoreceptors.

Action Potentials↗

Unilateral cooling in the region of locus coeruleus blocks the fall in respiratory output during hypoxia in anaesthetized neonatal sheep.

In nineteen alpha-chloralose-anaesthetized 3- to 8-day-old lambs, the effect of cooling focally in the region of the locus coeruleus on respiratory output, as measured from phrenic nerve activity, was examined during normoxia and isocapnic hypoxia, and during infusion of adenosine or saline. Eleven lambs showed a 'biphasic' respiratory response to hypoxia, with an initial increase in phrenic nerve activity (phase 1) being followed by a decline to prehypoxic levels (phase 2). Cooling to 26-34 degrees C unilaterally in the locus coeruleus reversed the fall in respiratory output. When the probe temperature was returned to body temperature (39 degrees C) respiratory output fell again to phase 2 levels. Cooling had no effect during normoxia. In these lambs, adenosine infusion (0.3 mg kg-1 min-1 intra-arterially) during normoxia also decreased respiratory output. During adenosine infusion, cooling again increased respiratory output. Saline infusion did not affect respiratory output during normoxia with or without cooling. The other lambs did not show a biphasic respiratory response, i.e. increased respiratory output was maintained during isocapnic hypoxia. In these lambs adenosine had no effect on respiratory output. Cooling/rewarming the probe did not affect respiratory output during normoxia or hypoxia, or during adenosine or saline infusion. These results show that focal cooling in the dorsal pons at the locus coeruleus removes the inhibition of respiratory output seen in the neonatal biphasic respiratory response to hypoxia, but does not affect breathing in normoxia. This suggests that an important component of the biphasic respiratory response is mediated by the activation of neurones inhibitory to respiratory output, and involves either axons of passage or cell bodies lying in the locus coeruleus. Furthermore, the inhibitory effects of adenosine on breathing in the neonate appear to be mediated via this site.

Animals↗

Chemoreflex and endocrine components of cardiovascular responses to acute hypoxemia in the llama fetus.

We tested the hypothesis that the llama fetus has a blunted cardiovascular chemoreflex response to hypoxemia by investigating the effects of acute hypoxemia on perfusion pressure, heart rate, and the distribution of the combined ventricular output in 10 chronically instrumented fetal llamas at 0.6-0.7 gestation. Four llama fetuses had the carotid sinus nerves sectioned. In the intact fetuses, there was a marked bradycardia, an increase in perfusion pressure, and a pronounced peripheral vasoconstriction during hypoxemia. These cardiovascular responses during hypoxemia in intact fetuses were accompanied by a pronounced increase in plasma vasopressin, but not in plasma angiotensin II concentrations. Carotid denervation prevented the bradycardia at the onset of hypoxemia, but it did not affect the intense vasoconstriction during hypoxemia. Plasma vasopressin and angiotensin II levels were not measured in carotid-denervated fetuses. Our results do not support the hypothesis that the carotid chemoreflex during hypoxemia is blunted in the llama fetus. However, they emphasize that other mechanisms, such as increased vasopressin concentrations, operate to produce an intense vasoconstriction in hypoxemia. This intense vasoconstriction in the llama fetus during hypoxemia may reflect the influence of chronic exposure to the hypoxia of high altitude on the magnitude and gain of fetal cardiovascular responses to a superimposed acute episode of hypoxemia.

Acid-Base Equilibrium↗

Effects of hypoxia on urinary organic acid and hypoxanthine excretion in fetal sheep.

Severe birth asphyxia leads to a transient organic aciduria and increased hypoxanthine excretion. To investigate its origin and timing, we analyzed urine from 12 late gestation fetal sheep in utero subjected to moderately severe isocapnic hypoxia for 1 h. In six fetuses the carotid sinus nerves were cut to determine whether reflex peripheral vasoconstriction contributed to the changes in excretion. After a control period of 1 h, maternal inspired oxygen was reduced for 1 h so that fetal arterial oxygen tension fell significantly from 2.86 +/- 0.12 kPa (mean +/- SEM) to 1.55 +/- 0.04 kPa. The ewes were returned to normoxia, and monitoring was continued for 1 h. Fetal heart rate, arterial blood pressure, and femoral arterial blood flow (intact fetuses only) were recorded, and arterial pH, blood gases, and lactate were measured. Urine collected via a bladder catheter was analyzed for organic acids and hypoxanthine with gas chromatography-mass spectrometry. In intact fetuses, hypoxia increased excretion of hypoxanthine and several organic acids, notably lactic acid and intermediates of valine catabolism. Changes were apparent by 15 min, significant by 45 min, and maximal after reoxygenation. In denervated fetuses, there were small, significant, increases in organic acids and hypoxanthine by 45 min of hypoxia, but there was no surge in excretion posthypoxia. Hypoxia caused a large, significant, fall in femoral arterial blood flow in intact fetuses. We conclude that the extent of the reflex peripheral vasoconstriction, particularly in skeletal muscle, determines the amount of organic acid and hypoxanthine excretion and may explain similar biochemical disturbances after birth asphyxia. Urinary lactic acid measurement has a potential value for grading birth asphyxia.

Animals↗

The effects of anaemia on heart, placenta and body weight, and blood pressure in fetal and neonatal rats.

1. Reports that maternal anaemia in pregnancy is associated with a greater placental: birth weight ratio, which predisposes towards high postnatal blood pressure in the human, led us to examine the effects of maternal anaemia during pregnancy on placental size, fetal and neonatal growth, and blood pressure development in the rat. 2. Nutritional anaemia was induced in female rats prior to mating and maintained throughout pregnancy and up until weaning of the pups. Fetuses were studied at 20 days of gestation (E20). Pups were studied on postnatal days 20 (P20) and 40 (P40), having been weaned onto normal rat chow at 21 days. 3. In the anaemic group placental: fetal body weight ratios were lower compared with controls. Body weights at all ages were lower in the anaemic group than in controls, despite a greater rate of growth in the anaemic group between P20 and P40. 4. At P20 heart weights of the anaemic group were almost twice that of controls, suggesting an alteration in their cardiovascular development. However, paradoxically, the systolic blood pressure of the anaemic group was lower than that of controls. 5. By P40 the systolic blood pressure of the anaemic group (136 +/- 3 mmHg) had increased and was greater than that in control pups (126 +/- 3 mmHg). 6. In conclusion, we have shown that there is a pronounced postnatal rise in systolic blood pressure associated with maternal anaemia during pregnancy, which is not related to a greater placental: birth weight ratio. Before weaning, anaemic pups have a lower systolic blood pressure than controls and there is an important association between the rate of postnatal growth and blood pressure.

Anemia↗

Alpha 1- and alpha 2-adrenoreceptor actions of phentolamine and prazosin on breathing movements in fetal sheep in utero.

1. We studied the effects of systemic administration of the alpha 1- and alpha 2-adrenoreceptor antagonist phentolamine and the selective alpha 1-adrenoreceptor antagonist prazosin on fetal breathing movements (FBM) and electrocortical activity (ECoG) in fetal sheep. In one group of fetuses (group I; n = 7) the effects of phentolamine were measured during normoxia and hypoxia. In the second group of fetuses (group II; n = 8) the effects of either phentolamine, or combined phentolamine and prazosin, or prazosin alone, were measured during normoxia. 2. In group I fetuses, the incidence of FBM increased after phentolamine treatment. An increase in the incidence and mean episode duration of low-voltage ECoG (LV-ECoG) was also measured after phentolamine treatment. These effects of phentolamine persisted during hypoxia. 3. In group II fetuses a pronounced decrease in the incidence of FBM occurred after administration of prazosin following either phentolamine or saline pretreatment. These effects of prazosin on FBM were independent of an effect on ECoG activity. 4. We conclude that catecholamines have a stimulatory role on FBM mediated via an alpha 1-adrenoreceptor mechanism. Phentolamine leads to an increase in FBM by preferentially antagonizing presynaptic alpha 2-adrenoreceptors over postsynaptic alpha 1-adrenoreceptors. This influence of phentolamine on FBM may be secondary to its effect on ECoG. Promotion of LV-ECoG by catecholamines is mediated via an alpha 1-independent mechanism.

Adrenergic alpha-1 Receptor Antagonists↗

Modulation by "central" PCO2 of the response to carotid body stimulation in man.

We describe a method to assess the effects of PCO2, around and below eucapnia, on the neuromuscular ventilatory response to a standard peripheral chemoreceptor stimulus. Subjects were "passively" hyperventilated (without respiratory muscle activity), at a constant level of ventilation. Stimuli (3-7 breaths N2) were delivered over a range of steady-state PETCO2 (25-43 mmHg). Stimuli during hypocapnia were coupled with a transient increase in FICO2 so that the stimulus to the peripheral chemoreceptors was always "hypoxia at eucapnia". Responses to the stimuli (quantified from the reduction in peak inflation pressure and the magnitude of the evoked diaphragm electromyographic activity) decreased in a graded manner as steady-state PETCO2 fell, disappearing at 7.5 mmHg below eucapnia. Carotid body chemoreceptor recordings from two anaesthetised cats, indicated that the peak firing rate during such stimuli was independent of steady-state PETCO2. The results suggest that the central sensitivity to a peripheral chemoreceptor input may be modulated by changes in steady-state PCO2 around eucapnia and during mild hypocapnia.

Adult↗

Patients' threats. Expanded definition of assault.

Most studies of patient assaults against staff operationally define violence as episodes of unwanted physical or sexual contact. This study empirically assessed a broader range of patient violence by including verbal and nonverbal threats in addition to sexual and physical assaults. Preliminary data from a statewide survey suggested that patient threats were frequent events. Data from a team of staff assaulted by patients in one hospital suggested that some verbal threats produced as much psychological distress for staff victims as did some physical assaults. These findings suggest the need to consider including threats in future studies of patient assaults.

Aggression↗

Blood pressure and cardiovascular reflex development in fetal sheep. Relation to hypoxaemia, weight, and blood glucose.

We measured mean arterial blood pressure (MAP), fetal heart rate (FHR), the baroreflex, weight, blood gases, blood glucose and lactate in chronically instrumented fetal sheep for 14 days from Day 105 to Day 109 gestation, with or without daily administration of 1 h of acute isocapnic hypoxaemia (arterial O2 partial pressure, PaO2, 11-13 mm Hg; 1 mm Hg = 133 Pa). Fetuses subjected to hypoxia showed no significant differences in MAP or FHR v. control fetuses. However, examination of all fetuses together revealed that there were two distinct groups: those showing a rise in MAP over the 14 days ('pressure up' group, PU), and those in which blood pressure did not increase or showed only a slight decrease ('pressure down' group, PD). PU fetuses were proportionately larger than PD fetuses. In contrast to PU fetuses, PD fetuses had lower blood glucose concentration, arterial O2 saturation (SaO2), PaO2, total haemoglobin, haematocrit and oxygen content, and higher lactate concentration, pH and PaCO2. PU fetuses showed a shift of the baroreflex MAP/R-R interval curve to the right, however, the PD group showed a shift upwards from Day 1 to Day 14. The PD group responded to hypoxia with a greater increase in MAP than the PU group. Thus, repeated acute moderate isocapnic hypoxia does not affect development of MAP or FHR in late gestation fetal sheep. However, MAP follows different trajectories in individual fetuses, related to fetal size and the availability of oxygen and/or glucose. Cardiovascular chemoreflexes and baroreflexes are also different, depending on the MAP trajectory. These data indicate an important association between growth and blood pressure development, and also show that differences in growth are associated with changes in cardiovascular control.

Animals↗

Circulatory responses to acute asphyxia in intact and chemodenervated fetal sheep near term.

The study concerned the role of the carotid sinus nerves in the effects of acute asphyxia on the fetal circulation. Fetal sheep (n = 12) were instrumented at approximately 130 days' gestation for placement of fetal vascular catheters and an occluder around the maternal descending aorta below the renal arteries. In 7 fetuses the carotid sinus nerves were cut. On the third post-operative day, asphyxia was produced by occluding the maternal aorta for 2 min and fetal blood flows were determined by the radio-labelled microsphere technique. In control, there were no differences between intact and denervated fetuses in blood gases, cardiovascular variables or blood flows, with the exception of lower blood flows to the cerebrum, caudate nucleus, kidney, skeletal muscle and scalp in the denervated group (P < 0.01). Fetal heart rate, cardiac output, stroke volume and the rate-pressure product were similar in asphyxia, with the exception that mean arterial pressure was lower in denervated fetuses after 2 min of asphyxia. Noradrenaline and adrenaline concentrations peaked at 2 min, then declined, the increase being smaller (P < 0.01) in denervated fetuses. Regional blood flows were similar in the two groups. Vascular resistance was lower in the placenta and abdominal aorta at 2 min in denervated fetuses. There were few differences in organ blood flows between intact and denervated fetuses, and the differences in flow in normoxia for the kidney, skeletal muscle and scalp (but not cerebrum, caudate nucleus and hippocampus) disappeared in asphyxia. This study confirms that section of the carotid sinus nerves has little effect on arterial blood pressure and fetal heart rate in normoxia but produces small differences in the responses to acute severe asphyxia, e.g. in arterial blood pressure and catecholamines, giving evidence for the operation of chemoreflexes. The lower blood flow to cerebrum, caudate nucleus, kidney, skeletal muscle and scalp in denervated fetuses in normoxia suggests a tonic vasodilatation, part of the drive for which comes from carotid chemo- or baroreceptors.

Animals↗

Carotid sinus nerve section and the increase in plasma cortisol during acute hypoxia in fetal sheep.

1. We studied the effects of acute isocapnic hypoxia on plasma concentrations of adrenocorticotrophic hormone (ACTH) and cortisol in sixteen sheep fetuses at 118-125 days of gestation (term is 147 days). Eight fetuses had their carotid sinus nerves cut (denervation); the remaining eight had these nerves left intact. 2. There were no differences in the plasma concentrations of ACTH or cortisol between intact and denervated fetuses during normoxia. 3. Whilst plasma cortisol increased in early (after 15 min) and late (after 45 min) hypoxia in intact fetuses, the rise in cortisol in denervated fetuses was delayed, increasing significantly only by late hypoxia. 4. In contrast, plasma ACTH concentrations were increased in early and late hypoxia in both intact and denervated fetuses. The rise was smaller in denervated fetuses, but was not significantly different from that in intact fetuses. 5. Our results indicate that, in the sheep fetus, carotid sinus nerve section delays the rise in plasma cortisol in response to acute hypoxia without affecting the ACTH response. Further work is needed to establish the mechanism underlying this effect of denervation.

Acute Disease↗

Effect of carotid denervation on plasma vasopressin levels during acute hypoxia in the late-gestation sheep fetus.

1. We measured plasma concentrations of arginine vasopressin (AVP), arterial, venous and amniotic pressures, and carotid and femoral blood flows in fifteen chronically instrumented fetal sheep at 119-125 days of gestation. In eight of the fetuses the carotid sinus nerves were cut (denervated fetuses); the other seven remained intact and served as controls (intact fetuses). 2. In the intact fetuses during hypoxia there was an increase in plasma [AVP] and in perfusion (arterial-venous) pressure, a transient bradycardia, and an increase in carotid and a decrease in femoral blood flow. Whilst femoral vascular resistance (perfusion pressure/femoral blood flow) increased, there were no changes in carotid vascular resistance during hypoxia. 3. In the denervated fetuses no significant bradycardia, fall in femoral blood flow or increase in femoral vascular resistance was present soon after the onset of hypoxia but plasma AVP increased to similar concentrations to those observed in intact fetuses during hypoxia. 4. We conclude that carotid denervation does not affect plasma [AVP] during hypoxia in fetal sheep. This suggests that (1) AVP release during hypoxia is not mediated by a carotid chemoreflex and (2) AVP does not play an important role in these initial fetal cardiovascular responses. Furthermore, we previously reported that intact fetuses survive acute hypoxia better than denervated fetuses following phentolamine treatment, and we believe this to be due to the action of a non-alpha-adrenergic vasoconstrictor released in part via a carotid chemoreflex. The present results suggest that this vasoconstrictor is not AVP.

Acute Disease↗