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Biomedical subjects

G H Parsons

Publications and source records attributed to G H Parsons.

33 records · Page 2Linked to original sources

Intracranial pressure during epileptic seizures.

A comatose 31-year-old male with presumed viral encephalitis and frequent partial motor seizures was paralyzed with pancuronium in an attempt to reduce recurrent elevation of intracranial pressure (ICP) associated with each seizure. ICP was continuously monitored with a Richmond Bolt and 5 electrographic seizures originating in the left frontal area were recorded. Each ictal episode was associated with stable blood pressure and an increase of ICP. The average seizure duration was 78 +/- 17 sec (mean +/- S.D.) and the average maximum increase of ICP above baseline during the seizures was 6.5 +/- 0.6 mm Hg with average peak ICP of 16.0 +/- 0.86 mm Hg. A simple mathematical model predicts the rate of increase of ICP, the peak ICP, the phase difference between maximum spike frequency and maximum ICP, and the rate at which ICP returns to pre-ictal values after termination of the seizure. The predicted values of ICP closely approximate the experimentally derived data. Therefore, the time course of the ICP appears to be determined by the frequency of the fundamental units of abnormal synchronized activity (the epileptogenic spike) and the CSF pressure-volume dynamics existing at the time of the seizure. An average increment of ICP per spike can be calculated for each seizure. The model also predicts that patients may develop high ICPs due to prolonged seizures. Prolonged unrecognized seizures may occur in patients who are therapeutically paralyzed as demonstrated by the case described here.

Adult↗

The value of serial serum angiotensin converting enzyme determinations in hospitalized patients with lung disease.

Abnormal serum angiotensin converting enzyme (ACE) activity has been reported in various human lung disorders and in laboratory animals with acute lung injuries. To test the value of serum ACE activity as an indicator of lung damage and its assistance in diagnosis or prognosis, 328 serum samples were obtained from 108 hospitalized patients with lung disease and 26 normal subjects. When patients were clinically grouped by disease entity, only the sarcoidosis group showed elevated mean serum ACE. Significantly increased serum ACE was found in 17 patients with various lung diseases (15% of hospitalized patients) 12 of whom also had concomitant liver disease. It is hypothesized that the liver may play a role in the normal metabolism of ACE being released by lung endothelial injury. Significantly low levels were seen in many acute and chronic lung injuries; specifically the groups with chronic obstructive lung disease, lung cancer, acute pneumonia, aspiration pneumonitis, gram-negative sepsis, acute myocardial infarction, and congestive heart failure. Serial measures of ACE in 71 patients with lung injuries showed that significantly decreasing levels over successive days were associated with a very high mortality. A single ACE measurement did not predict the presence or extent of lung injury, or aid in diagnosis or prognosis, but serial levels are of value prognostically.

Adult↗

Elimination of "hook-effect" in two-site immunoradiometric assays by kinetic rate analysis.

Two-site or sandwich immunoradiometric assays (IRMAs) offer theoretical advantages over competitive immunoassay systems for sensitivity, precision, and rapid incubation. The practical realization of these advantages has been limited by the phenomenon of the "high-dose hook effect," such that high concentrations of an analyte give similar responses to those of much lower concentrations. We have developed a kinetic rate monitoring IRMA system for use with the Kineti-Count 48TM, an automated kinetic radioassay analyzer, which eliminates "hook-effect" interference, thereby permitting optimal assay design for increasing sensitivity and reducing incubation time. Practical illustration of these concepts is demonstrated by a 10-min, automated, quantitative assay we developed for human choriogonadotropin. The assay can detect as little as 1.2 int. units/L and kinetically screens for the hook effect. Kinetic rate analysis of the two-site IRMA and potentially of nonisotopic counterparts permits improvements in the speed and reliability of these immunoassays.

Autoanalysis↗

Use of a solid-state multihead gamma counter in a second-generation system for solid-phase immunoassay.

Simultaneous advances in detector technology and solid-phase separation systems, as well as the availability of powerful desktop computers, have made possible the development of "second-generation" solid-phase immunoassays. These retain the advantages of classical solid phase while significantly accelerating reaction kinetics. Hapten assays--such as for digoxin, thyroxin, and triiodothyronine uptake--in batches of 48 are processed in about 20 min from reagent introduction until hard-copy printout, with minimal operator involvement. The system also functions as a 48-detector gamma counter, capable of counting and reducing data for any 125I-based RIA that can be run in a 12 X 75 mm test tube. System control, data management, and computer screen displays of kinetic data are provided by an unmodified Hewlett Packard HP-87XM computer. User-friendly disc-based software facilitates the creation and storage of counting and data reduction protocols for as many as 30 RIAs from various manufacturers as well as up to 30 of our own assays.

Computers↗

Effect of sodium nitroprusside on hypoxic pulmonary vasoconstriction in the dog.

The objective of the study was to determine the direct actions of sodium nitroprusside (SNP) on the pulmonary vasculature actively constricted by hypoxic ventilation in the closed-chest dog. In 21 supine anesthetized (pentobarbital sodium, 25 mg/kg) dogs the left lower lobe was catheterized with a 20 F wedged-flow catheter. With constant flow to this lung lobe, lobar pulmonary artery pressure (PAP), left ventricular end-diastolic pressure (LVEDP), and lobar pulmonary vascular resistance (PVR) were studied during room air and 10% O2 mechanical ventilation. With lobar flow and LVEDP constant, observed changes of lobar PAP and PVR represent direct effects on vascular tone unaffected by passive factors. Ventilation with 10% O2 resulted in a significant increase in lobar PAP [12.2 +/- 1.6 to 17.2 +/- 1.2 (SE) Torr] and PVR [42.2 +/- 13.3 to 61.2 +/- 15.0 (SE) Torr X 1(-1) X min]. Then during continued hypoxia in 12 animals, femoral vein infusion of SNP at doses of 1, 2, and 5 microgram X kg-1 X min-1 resulted in significant decreases in lobar PAP to 14.8 +/- 1.5, 14.8 +/- 1.5, and 13.4 +/- 1.6 Torr, respectively, and in PVR to 56.7 +/- 14.1, 54.0 +/- 13.9, and 47.8 %/- 13.2 Torr X 1(-1) X min, respectively. In six animals the sequence of drug infusion was then reversed with similar results. It is concluded that the actively constricted pulmonary vascular bed is directly dilated by SNP infusion.

Animals↗

Mechanisms of pulsus paradoxus in upper airway obstruction.

Pulsus paradoxus, a greater than 10 Torr systolic pressure fluctuation during the respiratory cycle, is seen in upper airway obstruction. To test the hypotheses 1) that blood is pooled in the pulmonary circulation with reduced return to the left heart during inspiration and 2) that inspiration increases left ventricular afterload, the following was done. Esophageal pressure (Pes), pericardial pressure (Pp), left atrial transmural pressure (Platm), and left ventricular transmural pressure at end-isovolumic systole (Plvtm) were recorded during partially obstructed inspirations in spontaneously breathing dogs anesthetized with pentobarbital (25 mg/kg). Changes in Pes and Pp were nearly identical (r = 0.9883) confirming that changes in Pes adequately reflect changes in Pp. During inspiration Platm and Plvtm increased 0.5 and 0.4 Torr, respectively, per Torr decrease in Pes suggesting that increased blood return to left atrium and increased left ventricular afterload occur. Similar changes were observed during near constant thoracic volume (total airway block) and cardiac reflex blockade (atropine 0.05 mg/kg and propranolol 0.5 mg/kg). Thus mechanical factors including left ventricular afterload appear of major importance in producing pulsus paradoxus in upper airway obstruction.

Airway Obstruction↗

Hemoptysis.

Hemoptysis is an alarming symptom that should not be dismissed lightly. A thorough evaluation will lead to the correct diagnosis in 80 to 90 percent of cases. Surgery is occasionally necessary where life-threatening hemorrhage is present but, more commonly, appropriate therapy can only be determined when the etiology is discovered, thus mandating a careful, thorough diagnostic search.

Adult↗

Coronary-bronchial blood flow and airway dimensions in exercise-induced syndromes.

1. We have an incomplete understanding of integrative cardiopulmonary control during exercise and particularly during the postexercise period, when symptoms and signs of myocardial ischaemia and exercise-induced asthma not present during exercise may appear. 2. The hypothesis is advanced that baroreflex de-resetting during exercise recovery is normally associated with (i) a dominant sympathetic vasoconstrictor effect in the coronary circulation, which, when associated with obstructive coronary disease, may initiate a potentially positive-feedback cardiocardiac sympathetic reflex (variable myocardial ischaemia with symptoms and signs); and (ii) a dominant parasympathetic bronchoconstrictor effect in the presence of bronchovascular dilatation, which, when associated with raised mediator release in the bronchial wall, reinforces the tendency for airway obstruction (variable dyspnoea results). 3. There is a need for new techniques to examine hypotheses concerning autonomic control, during and after exercise, of the coronary and bronchial circulations and the dimensions of airways. Accordingly, a new ultrasonic instrument has been designed named an 'Airways Internal Diameter Assessment (AIDA) Sonomicrometer'. It combines pulsed Doppler flowmetry with transit-time sonomicrometry of airway circumference and single-crystal sonomicrometry of airway wall thickness. Initial evaluation suggests it is relatively easy to apply during thoracotomy in recovery animals. The component devices are linear and will measure target variables with excellent accuracy. 4. In anaesthetized sheep, intubated with controlled ventilation, intravenous isoproterenol causes large increases in bronchial blood flow, a fall in arterial pressure and a reduction in airway circumference. This may reflect the dominant action of reflex vagal activity over direct beta-adrenoceptor inhibition of bronchial smooth muscle, the reflex source being baroreflex secondary to the fall in arterial pressure. These findings provide insight into the integrative mechanisms underlying the paradoxical negative effects sometimes observed when beta-adrenoceptor agonists are used in asthma.

Animals↗

Canine nonresponders to alveolar hypoxic vasoconstriction and quantitative restoration of the response by aspirin I-3.

Hypoxic pulmonary vasoconstriction is characterized by considerable variability in rate of response (pulmonary vascular resistance [PVR] as a function of time under hypoxia). To further define this response, forty-five closed chest dogs were anaesthetized (pentobarbitone sodium), intubated, and mechanically ventilated. Constant left lower lobar pulmonary artery flow was maintained through a balloon tipped 14F catheter via an extracorporeal pump at a rate to achieve lobar pulmonary artery pressure (Plobar) equal to main pulmonary artery pressure (PPA) and thereafter held constant. Left ventricular end diastolic pressure (PLVED) was measured by left ventricular catheter and lobar pulmonary artery flow rate (Q) by flow meter. Lobar PVR (mmHg/min per 1) was calculated every 15 min. Ventilation with 10% oxygen (O2) separated two groups based on the increase in PVR over time: twenty-two rapid hypoxic responders [HR] (slope= delta PVR/delta min greater than 0.3) and twenty-three slow or nonresponders [NR] (slope less than 0.1). The twenty-three NR were divided into two groups. Ten NR dogs (NR control) had no change in mean PVR (23.9, s.d. = 8.2, to 24.1, s.d. = 9.6) over a mean of 78 min and were used as controls. Thirteen NR dogs (NR ASA) had no change in mean PVR (32.9, s.d. = 9.5, to 32.3, s.d. = 9.8) over 75 min and were given aspirin (ASA), 10-15 mg/kg intra-arterially. The NR ASA group mean PVR then increased from 32.3 (s.d. = 9.8) to 59.1 (s.d. = 23.9, 82.9% increase, P less than 0.01) over a mean of 54 min. The mean PVR for the twenty-two HR rose from 39.8 (s.d. = 34.0) to 64.5 (s.d. = 36.6, 62.1% increase, P less than 0.01) over a mean of 72 min. The slopes of rate of response for HR (0.66) and for NR ASA (0.88) were not significantly different. The absolute values of PVR reached after plateau for HR and for NR ASA (after ASA) were also not different. Aspirin restored the NR capability to develop pulmonary vasoconstriction in response to alveolar hypoxia. The rate of response and the absolute level of response reached were also restored by aspirin.

Animals↗