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Biomedical subjects

R B Mellins

Publications and source records attributed to R B Mellins.

At least 19 recordsLinked to original sources

Educational programs for children with asthma.

During the last decade, research on the behavioral aspects of childhood asthma has focussed on three goals: (1) learning how families manage asthma at home and use health care services; (2) identifying specific problems they encounter in managing asthma, and (3) developing and evaluating educational programs to teach families to overcome these problems and to manage asthma effectively in the home environment. This paper will describe the research findings on the problems families face in managing asthma, review the available and evaluated health education programs that have been developed to solve them and suggest strategies for physicians and other health care providers to incorporate health education into routine office care for asthma.

Adaptation, Psychological

Communication within low income families and the management of asthma.

This study examines the effects of communication between low income urban parents and children about a chronic disease on the extent to which parent and child effectively manage the illness. Four asthma communication factors were identified by principal component analysis. We found that mothers whose preferred language was Spanish, and families who were not receiving public assistance, communicated more frequently about asthma in general. Spanish speaking mothers and their children communicated more about potential home treatments for asthma, and the more adults in the household the less there was communication about the need for emergency services for asthma. Mothers who preferred to speak Spanish had higher levels of management of the most recent asthma attack. Those whose children communicated with them about asthma in general were higher level managers. Children who influenced their parents' decisions about school attendance, and those whose mothers were more highly educated, had higher levels of asthma attack management. More educated mothers, ones whose children were younger at the time of the onset of asthma, and one who received public assistance, were more involved "in general" in their child's asthma care.

Adult

Inhibition of converting enzyme activity by acute hypoxia in dogs.

We studied the effect of a change in oxygen tension on converting enzyme activity in anesthetized, paralyzed, catheterized dogs ventilated with room air, 100% O2, and hypoxic gas mixtures. Bradykinin was continuously infused into the femoral vein and simultaneous samples drawn from the pulmonary artery and left atrium; bradykinin was extracted into ethanol and measured by radioimmunoassay. Clearance of bradykinin by lung converting enzyme decreased from 96% at PaO2 levels above 95 Torr to 0% below 26 Torr. Inhibition of enzyme activity was rapid in onset (less than 2 min), closely correlated with PaO2 (r = 0.92, P less than 0.001), and reversible within 2 min after return to room air breathing. Converting enzyme activity of the systemic vascular bed was also inhibited by hypoxia; kininase I activity was unaffected by oxygen tension. Although arterial bradykinin concentrations in the range of 0.5 ng/ml produced hypotension in normoxic animals, elevations to 30 ng/ml had no hypotensive effect in hypoxic dogs. During acute hypoxia, venous bradykinin will pass through the lung unmetabolized, and local levels of angiotensin II and bradykinin will vary in vascular beds with different oxygen tensions, providing a finely-graded mechanism for blood flow regulation.

Animals

Maturation of ventilation and ventilatory pattern in normal sleeping infants.

Noninvasive studies of ventilation and ventilatory pattern were performed serially in 15 normal infants in the first 4 mo of life during REM and quiet sleep with the barometric method. We measured tidal volume (VT), total respiratory cycle time (Ttot), inspiratory time (Ti), expiratory time (TE), mean inspiratory flow (VT/TI), and respiratory "duty cycle" (TI/Ttot). Vt, Ttot, TI, TE, VT/TI, and VT/Ttot but not TI/Ttot increased with age. In all age groups, Ttot, TI, and TE but not VT/TI were greater in quiet than in REM sleep. In the first 2 mo of life, VT was greater in quiet than in REM sleep; in the older infants, VT/Ttot was smaller in quiet than in REM sleep. TI/Ttot was not dependent on sleep state. Thus, because VT/Ttot = VT/TI X TI/Ttot, the increase in VT/Ttot with age results from an increase in mean inspiratory flow rather than from changes in respiratory "duty cycle". Further, the "on-switching" as well as the "off-switching" of inspiratory activity depends on sleep state.

Aging

Increased circulating bradykinin during hypothermia and cardiopulmonary bypass in children.

To determine whether cold could activate the kallikrein-kinin system in vivo as it does in vitro, the circulating systemic concentrations of bradykinin were serially measured in 10 cyildren with congenital diseases of the heart undergoing corrective cardiac surgery. Bradykinin was measured by radioimmunoassay in blood samples obtained before, during and after profound hypothermia (to 18 degrees C) and cardiopulmonary bypass. The circulating concentrations of bradykinin increased significantly as body temperature decreased during surface cooling. The increase in circulating bradykinin was associated with a decrease in the circulating level of bradykininogen, the precursor of bradykinin. With the onset of cardiopulmonary bypass and hence, removal of the lung and pulmonary converting enzyme from the circulation, there was a further rise in the already elevated concentrations of bradykinin. This is the first in vivo demonstration that hypothermia leads to an increase in the circulating concentrations of bradykinin.

Blood Pressure

Inhibition of angiotensin converting enzyme activity in cultured endothelial cells by hypoxia.

Endothelial cells in tissue culture degrade bradykinin and convert angiotensin I to angiotensin II. These are both functions of a single dipeptidyl hydrolase, angiotensin converting enzyme. Monolayer cultures were prepared from human, rabbit, pig, and calf vessels. Angiotensin converting enzyme activity was assessed by adding either bradykinin or angiotensin I to the cells in culture flasks, and measuring residual peptide over time by radioimmunoassay. Peptide degradation was inhibited by the specific converting enzyme inhibitor, SQ 20881. The flasks were equilibrated with varying hypoxic gas mixtures: hypoxia rapidly (less than 2 min) decreased enzyme activity and room air restored it as rapidly. The extent to which activity was reduced was a direct function of PO2 (r = 0.93, P less than 0.001), and there was no enzyme activity below a PO2 of 30 mm Hg. Four preparations were studied with respect to decrease in enzyme activity by hypoxia: (a) intact cells in monolayer, (b) sonicated cells, (c) sonicated cells from which converting enzyme was partially dissolved by a detergent, and (d) purified converting enzyme. Hypoxia had progressively less of an inhibiting effect on the enzyme activity of the preparations as the degree of cell integrity decreased. Hypoxia inhibits angiotensin converting enzyme activity in cultured endothelial cells, but the effect of hypoxia is not on the enzyme per se, but appears to be a unique characteristic of the endothelial cell.

Animals

The QT interval in aborted sudden infant death syndrome infants.

The QT interval was measured in 12 normal and 7 aborted sudden infant death syndrome (SIDS) infants in rapid eye movement (REM) and quiet sleep at monthly intervals through the age of 4 months. An accuracy of better than 2 msec was assured by high resolution of the digitized signal and calibration of each QT measurement with an accurately generated time code. In contrast to current speculations, the QT index was significantly smaller in the infants with aborted SIDS than in the normal infants in both REM and quiet sleep (P less than 0.05). In addition, as in normal infants, the QTc was smaller in REM than in quiet sleep (P less than 0.01). Although these results offer no support for the hypothesis that SIDS results from prolongation of the QT interval, they suggest that aborted SIDS infants have a functional abnormality in the autonomic nervous system.

Autonomic Nervous System

Effect of sleep state on the QT interval in normal infants.

Twenty QT intervals selected at random from the middle periods of rapid eye movement (REM) and quiet sleep were measured in 12 normal infants studied at 2 weeks and 1, 2, 3, and 4 months of life. A digitizing system, consisting of a precision rotational potentiometer mounted on a pair of calipers and an A/D converter, was used for measurements. An accuracy of +/- 2 msec was achieved by high resolution of the digitized signal and calibration of each QT measurement with an accurately generated time code. Sleep staging was done visually using an electroencephalogram (EEG), an electrooculogram (EOG), a submental electromyogram (EMG), and behavioral criteria. Our results show that the QT index (QTc = QT/square rootRR) was significantly greater during quiet sleep (mean = 0.439) than during REM sleep (mean = 0.433) (P less than 0.01) and that this difference existed at all ages studied.

Electrocardiography

Congenital failure of automatic control of ventilation, gastrointestinal motility and heart rate.

A new congenital syndrome characterized by the simultaneous failure of control of ventilation (Ondine's curse) and intestinal motility (Hirschsprung's disease) is reported in three infants, all of whom died in the first few months of life; two were siblings. Detailed studies in one also revealed markedly decreased esophageal motility and abnormal control of heart rate. In one infant, minute ventilation was lower in quiet than in REM sleep and lower in both states of sleep than in wakefulness. Although the mean inspiratory flow was decreased in quiet sleep, the hypoventilation resulted primarily from a decrease in respiratory frequency. Intravenous doxapram increased ventilation but did not reverse respiratory failure. Aminophyllin, progesterone, physostigmine and chlorpromazine did not change ventilation significantly; imipramine resulted in a significant decrease. Both long and short-term variability of the heart rate were markedly decreased when compared with the normal infant. Although neuropathologic studies postmorten did not reveal an anatomic defect, we postulate that a developmental abnormality in serotonergic neurons is responsible for this new syndrome.

Doxapram

Effect of hyperinflation and atelectasis on fluid accumulation in the puppy lung.

The effects of hyperinflation and of atelectasis on accumulation of fluid in the lung was studied in 12 anesthetized spontaneously breathing puppies. Vascular pressures were raised and the plasma colloid osmotic pressure was reduced by the infusion of 0.9% saline thus promoting the formation of pulmonary edema. A tracheostomy was performed and the left lower lobe catheterized in all puppies. In five puppies hyperinflation of the left lower lobe was achieved by applying a continuous positive airway pressure (CPAP) of 10 Torr. In seven other puppies the left lobe was made atelectatic by occluding its bronchus after ventilating the lungs with 100% oxygen. The right lung was ventilated to ambient pressure in all puppies. The extravascular lung water content was determined by the difference in wet and dry lung weights corrected for residual blood. We found that hyperinflation produced by CPAP enhanced and atelectasis opposed fluid accumulation in the puppy lung.

Animals

Gestational changes in pulmonary converting enzyme activity in the fetal rabbit.

Changes in angiotensin-converting enzyme were measured in the lungs of fetal rabbits isolated and perfused in situ at varying ages from 22 days gestation to 7 days of age under controlled conditions of flow, pH, and temperature. Enzyme activity was assessed by infusing bradykinin or angiotensin I in Krebs-Henseleit solution and measuring residual peptide in the effluent by radioimmunoassay. The levels of substrate studied were below those required for enzyme saturation. Lungs of 22 day gestation fetuses removed only one-third of either peptide. The activity at term and in neonatal life resulted in more than 80% peptide removal. The time of the greatest rise in the percent substrate cleared occurs earlier than the time of the greatest increase in lung and body weight. The lower percentage of substrate cleared in early gestation appears to result in part from a limited surface area for enzyme activity in the primitive fetal pulmonary microvascular bed, since morphological studies with fluorescein-tagged anticonverting enzyme antibody demonstrated the presence of enzyme in the lung as early as 17 days of gestation. Electron micrographs of the pulmonary endothelial cell surface reveal that the degree of surface infolding and hence surface area increases with gestation. The higher percentage of substrate cleared in later gestation closely parallels the structural and ultrastructural development of the vascular bed. The presence of converting enzyme in the placenta by the second third of gestation and the large size of the placenta suggest that this organ may be a major locus of converting enzyme activity in the fetus.

Angiotensin I

Agenesis of the left lung and total anomalous pulmonary venous connection. Hemodynamic studies before and after complete surgical correction.

A female infant with unilateral pulmonary agenesis developed congestive heart failure dominated by symptoms of obstructive disease of the airways at 3 1/2 months of age. Cardiac catheterization revealed total anomalous pulmonary venous connection to the right atrium. Despite a massive left-to-right shunt with one pulmonary artery receiving the entire right ventricular output since birth, the patient's resting pulmonary vascular resistance was normal. Open heart surgery to repair the cardiac lesion was performed when the infant was four months of age. Subsequent studies revealed an excellent anatomic and functional repair, with normal pulmonary arterial pressures. One year following surgery, the child is asymptomatic and has normal growth and development.

Blood Pressure