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Biomedical subjects

M A Hanson

Publications and source records attributed to M A Hanson.

At least 145 records · Page 8Linked to original sources

Respiration of conscious kittens in acute hypoxia and effect of almitrine bismesylate.

Respiration was measured noninvasively in conscious kittens at an ambient temperature of 28-32 degrees C. Inspired O2 fraction (FIO2) was reduced abruptly from 0.21 to 0.12, 0.10, or 0.08 for 5 min on the day of birth and then on days 4, 7, 14, and 28. The ventilatory response to hypoxia was biphasic, as reported previously in anesthetized kittens, with minute ventilation (VE) increasing in the first minute and then falling towards control over the next 4 min. The fall in VE was due to a consistent fall in tidal volume, the changes in frequency during the second phase being more variable. The size of the first phase of the response increased up to 14 days, but the time at which the peak increase in VE occurred was not correlated with age. The degree of the secondary fall in VE was similar at each age and at each FIO2 studied. The degree of the biphasic response was significantly reduced after administration of almitrine (2 mg/kg ip) on days 1 and 4, but almitrine did not affect the response in older kittens.

Acute Disease↗

The response to hypoxia of arterial chemoreceptors in fetal sheep and new-born lambs.

Carotid chemoreceptor activity was detected in each of fourteen halothane or pentobarbitone anaesthetized exteriorized fetal lambs of 90-143 days gestational age. Activity was about 5 Hz at a Pa,O2 of 25 mmHg and it increased as Pa,O2 was reduced, either by compressing the umbilical cord or by reducing the (FIO2) oxygen fraction of the gas used to ventilate the ewe. Activity increased briskly when 1-2 ml CO2-saturated saline was injected retrogradely into the lingual artery, but not when saline of pH 7.4 or fetal arterial blood was injected. In two fetuses near-term chemoreceptor activity was recorded continuously whilst the umbilical cord was ligated and ventilation with air started. Activity increased 200-500% as Pa,O2 fell, but then fell to below control as Pa,O2 rose. We suggest that these changes in activity reflect those occurring naturally at birth. No spontaneous chemoreceptor activity could be detected on the day of birth in twelve pentobarbitone anaesthetized lambs delivered vaginally or by Caesarean section at 135-146 days. Single baroreceptor activity could however be recorded in these lambs, and chemoreceptor activity could be elicited by hypercapnia. Spontaneous chemoreceptor activity was detected in six of seven lambs more than 2 days old. In eight conscious lambs the steady-state respiratory response to isocapnic hypoxia was variable on the day of birth. In six of these lambs the response was significantly greater by the third day. We conclude that the arterial chemoreceptors are active and responsive in the fetus, but quiescent in the lamb on the day of birth when Pa,O2 has risen. The hypoxic sensitivity of the chemoreceptors is reset from the fetal to the adult range over the next few days.

Action Potentials↗

Breathing pattern of kittens during hypoxia.

In 19 pentobarbital sodium-anesthetized kittens aged 5-34 days, inspired O2 was reduced from 21 to 6-12%. Respiratory frequency (f) and tidal volume (VT) increased within 30 s. Over 5 min f fell to about 60% below control; VT usually fell but remained above control. Arterial pressure fell in 80% of trials, sometimes before f fell. Arterial CO2 was below control, but raising inspired CO2 to keep expired CO2 at control did not prevent the fall in f and VT. The relation between VT and esophageal pressure or diaphragm electromyogram (EMG) did not change consistently, nor was the ratio of high to low frequencies in the diaphragm EMG altered. Carotid chemoreceptor discharge increased within 15 s, and at 5 min it was much above control. We conclude that the change in the breathing pattern in hypoxia is probably due to the activation of a central mechanism.

Abdominal Muscles↗

A cellular factor involved in the formation of a DNA-synthesizing complex from DNA polymerase I in Escherichia coli.

A factor ('E') has been identified which stabilizes an endogenous DNA-synthesizing complex involving DNA polymerase I. The complex is separated from free DNA polymerase by polyacrylamide gel electrophoresis. The factor will reform the complex after it has been dissociated and will convert a preparation of DNA polymerase I to complex. The factor and the DNA-synthesizing complex both appear to be localized at the cell membrane.

DNA Polymerase I↗

The effect on breathing of abruptly reducing the discharge of central chemoreceptors.

Tris, a powerful CO2 buffer, was injected through one vertebral artery directly at the central chemoreceptive region in bilaterally vagotomized pentobarbitone anaesthetized cats. This was intended to reduce central chemoreceptor drive abruptly. Injections in inspiration shortened that inspiration and prolonged the following expiration. Injections given early in expiration often prolonged that expiration and also the following inspiration, but most injections given in an expiration shortened that expiration and also shortened the following inspiration. Tidal volume (VT) was invariably reduced. A plot of VT against delay from an injection to the termination of inspiration shows that VT falls with a half time of about one second. The changes in the pattern of breathing were similar to those after abrupt removal of carotid body chemoreceptor discharge (Nye et al., 1981) though the latency to the first response of air flow was about 100 msec longer. These observations support the idea that peripheral and central chemoreceptors have similar connections with the respiratory centre.

Animals↗

The effects on respiration in the cat of the sudden excitation of cerebral vascular nociceptors by carbon dioxide.

1. Injection of CO2-saturated saline in a distal direction into either a vertebral artery or an internal maxillary artery in pentobarbitone-anaesthetized cats produced abrupt changes in respiration. Vertebral-artery injections produced a transient inhibition of respiration, followed by a stimulation of it. Internal-maxillary-artery injections produced only the inhibition. 2. Injections during inspiration usually shortened that inspiration, reduced its volume and prolonged the following expiration. In the first 30% of an expiration they prolonged that expiration, but given in the next 50% they shortened it. In the last 20% of expiration internal-maxillary-artery injections again slightly prolonged the expiration. 3. Phenyl diguanide injected into either a vertebral or an internal maxillary artery also produced abrupt effects on respiration. 4. The effects of CO2-saturated saline were abolished by intravenous acetazolamide, suggesting that nociceptors may be affected by a change in local pH. 5. The effects may arise from the excitation of vascular nociceptors, and our observations may suggest a way of studying in animals the receptors responsible for headache.

Acetazolamide↗

The effect on breathing of abruptly stopping carotid body discharge.

In bilaterally vagotomized, decerebrate or pentobarbitone anaesthetized cats, intense carotid body discharge (FET O2 ca. 0.075) was abruptly removed by injections centrally of 100% O2-equilibrated Ringer into both external carotid arteries. In an inspiration the injections usually shortened that inspiration, reduced its volume and prolonged the immediately following expiration. Early in expiration they prolonged that expiration, but later in expiration they shortened it. The inspiratory results can be reconciled with von Euler's model of the inspiratory off-switch if the off-switch acts early because a reduction in chemoreceptor input lowers its threshold more rapidly than it reduces the input to it. The threshold falls to half of its final value in about one second. The respiratory centres respond to decreases in carotid body activity nearly as quickly as to increases, and expiration can be altered independently of the preceding inspiration. We present a simple model of the control of expiratory duration.

Animals↗

Studies on the localization of pulmonary carbonic anhydrase in the cat.

1. We considered whether some of the carbonic anhydrase of the lung is on the surface of the pulmonary capillaries so that it acts directly on plasma as it traverses the pulmonary capillaries to accelerate CO2/pH equilibration. 2. Experiments were performed on spontaneously breathing cats or saline-perfused cat lungs. 3. In intact cats, Tris buffer injected suddenly into the right atrium transiently lowered end-tidal CO2, FET, CO2. The rate of CO2 uptake came within an order of magnitude of taxing the calculated diffusing capacity of the lungs. The fall in FET, CO2 was much reduced by giving the carbonic anhydrase inhibitors benzolamide or acetazolamide intravenously, or even by adding benzolamide to the injected Tris. The fall in FET, CO2 could be increased by adding carbonic anhydrase to the injected Tris. 4. In saline-perfused lungs ventilated with 5% CO2 in O2, Tris or alkalinized albumin solution injected into the pulmonary artery transiently lowered FET, CO2 and the effect was reduced by the addition of benzolamide or acetazolamide to the injectate. Injecting Tris bubbled with 15% CO2 caused a rise in FET, CO2, also reduced by benzolamide. 5. We conclude that pulmonary carbonic anhydrase is readily accessible to large or small molecular wight buffers in the capillaries and to inhibitors, and we suggest that it is located on the luminal surface of the capillary endothelium.

Acetazolamide↗

The location of carbonic anhydrase in relation to the blood-brain barrier at the medullary chemoreceptors of the cat.

1. The role of carbonic anhydrase near the medullary chemoreceptors has been investigated in the cat. Vertebral artery injections have been used to cause abrupt changes in respiration as a result of changes in the activity of medullary chemoreceptors. 2. Injections of 100% CO2-saline were used to stimulate respiration and of Tris or alkalinized albumin solution to cause a reduction in respiration. 3. The injections gave rapid effects. We studied the effect on these of benzolamide (1-4 mg/kg i.v.) a carbonic anhydrase inhibitor which does not easily cross the blood-brain barrier and acetazolamide (50 mg/kg i.v.) an inhibitor which crosses the barrier more easily. 4. The effects of Tris were much reduced after benzolamide. Even addition of benzolamide to the injected Tris or albumin was sufficient to reduce their effects. 5. The effects of CO2-saline were reduced only after acetazolamide i.v. Whereas addition of carbonic anhydrase to injected Tris potentiated the effects on respiration, after acetazolamide this potentiation was much less marked. 6. It is concluded that carbonic anhydrase acts in the region of the medullary chemoreceptors at two sites: (a) outside the blood-brain barrier, probably at the luminal surface of the capillary endothelium, where it may act on plasma buffers, and (b) inside the barrier, in association with the chemoreceptors, where it may accelerate CO2/pH equilibration.

Animals↗

Selective hearing screening for young children.

A "selective" hearing screening program was instituted in an early education project. Three-year-old children were deemed "at risk" for mild-to-moderate hearing loss if they met one of the risk criteria established by the Joint Committee on Infant Hearing Screening, if they had recurrent ear infections, or if there was parent or staff concern about the child's hearing. Based on these criteria, 31 per cent of the 228 children in the project were eligible for full audiologic evaluation at a speech and hearing center. The parents of 45 children took advantage of this special evaluation. Twenty-nine per cent of these selected children had some hearing loss documented. The highest yields of abnormal hearing were for children "at risk" because of recurrent ear infections (42%), and parent for educational staff concern (71%).

Child↗

The Pediatric Examination of Educational Readiness: validation of an extended observation procedure.

The Pediatric Examination of Educational Readiness (PEER) is a standardized observation system for use by health care professionals. It combines a prekindergarten physical examination with a neurodevelopmental and behavioral assessment. The PEER was field tested on 386 children, of whom 22% revealed a "definite concern" in one area of development or behavior, 8% in two, and 14% in three or more areas. (A concern was a finding that required direct intervention, continuing surveillance or further evaluation.) Children with multiple areas of concern were found to have lower teacher rating scores at the end of kindergarten than those with isolated or no concerns. An observation procedure, such as the PEER, can be a productive part of the pediatric assessment of children entering kindergarten.

Child↗

Carbon dioxide sensitivity of aortic chemoreceptors in the cat.

Steady state CO2 sensitivity in the aortic chemoreceptors was variable. For 70.3% of the steady state response lines to increasing CO2 the slope was not significantly different from zero. For 24.3%, it was significantly positive and for 5.4% significantly negative. In contrast, in 86.7% of cases the oscillating response to alternate breaths of high and low CO2 suggested a transient response line which was significantly steeper than the steady state line. Removing CO2 from a high CO2 content inspirate for one breath caused a distinct drop in discharge on 83.3% of occasions. The significance of such transient CO2 sensitivity in the absence of clear steady state sensitivity is discussed.

Animals↗