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Biomedical subjects

K R Rajagopal

Publications and source records attributed to K R Rajagopal.

At least 37 records · Page 2Linked to original sources
PubMed1989

Thyroid hormone resistance in a large kindred: physiologic, biochemical, pharmacologic, and neuropsychologic studies.

PURPOSE: Thyroid hormone resistance affects the pituitary gland and a variety of other tissues. We studied a large kindred with this disorder and measured a number of clinical markers of tissue metabolism to determine if these markers were useful in elucidating the sites and degree of resistance. PATIENTS: A kindred of 89 persons in four generations was identified; 44 had thyroid function tests, and 14 (five to 67 years old) were found to have thyroid hormone resistance. RESULTS: The inheritance pattern was autosomal dominant, with no common HLA haplotype. Physiologic measurements in five affected members showed marked heterogeneity. Four patients had normal baseline cardiac contractility, but only two experienced a shortening of their QKd interval into the hyperthyroid range with triiodothyronine (T3) therapy. Intrathyroidal 127I content was increased in two patients and was normal in two. Bone mineral content was normal in two men, but two women had marked osteopenia. The propositus, hypothyroid after inappropriate 131I therapy, had a hypothyroid ventilatory response to hypercapnea. This response became low normal during T3 (100 micrograms/day) administration but not during long-term thyroxine (T4) (300 micrograms/day) administration. Three other patients had values within normal limits and one had a hyperthyroid ventilatory response. Peripheral biochemical markers of thyroid hormone action were measured in 13 affected and 19 unaffected family members. Sex hormone-binding globulin was increased in zero of 13 affected patients (versus 19 of 20 hyperthyroid, chi 2:p less than 0.001); ferritin was elevated in two of 13 patients (versus 11 of 20 hyperthyroid, p less than 0.02); angiotensin converting enzyme activity was increased in one of 13 patients (versus 12 of 20 hyperthyroid, p less than 0.025). The eldest patient had marked cardiac sensitivity despite normal biochemical markers. We attempted to suppress the integrated thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) using T3 (72 and 100 percent suppression in two patients), dopamine (40 percent suppression in one), 3,5,3'-triiodothyroacetic acid (TRIAC) (94 percent suppression in one), and verapamil (10 percent and 40 percent suppression in two). Neuropsychologic function was studied in 14 individuals (11 affected, three unaffected). Although mild impairments were detected, they were not specific for thyroid hormone resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1989

Determinants of maximum exercise capacity in patients with chronic airflow obstruction.

Patients with chronic airflow obstruction (CAO) often develop impairment of respiratory muscle function. We hypothesized that inspiratory muscle strength, as assessed by resting, peak inspiratory pressure (PIP) may be an important determinant of maximum exercise capacity in patients with CAO. Twenty ambulatory male patients (mean age, 56 +/- 3 years [+/- SE]) with CAO (FEV1, 1.72 +/- 0.21 L) comprised the studied population. Oxygen consumption at incremental cycle ergometry to tolerance (VO2max, 1.80 +/- 0.20 L/min) served as the dependent variable for regression vs measures of resting pulmonary function. Significant correlations with VO2max included power output in watts (r = 0.951), VEmax (r = 0.858), Dsb (r = 0.841), PIP (r = 0.816), age (r = -0.809), FEV1 (r = 0.763), and FVC (r = 0.663). The FEV1, Dsb, and PIP each entered into a multiple linear regression relationship describing VO2max. Also, when paired with VEmax as independent variables in multiple regression, PIP and Dsb each improved description of VO2max over VEmax alone (p less than 0.05), whereas FEV1 and FVC did not (p greater than 0.05). We conclude that factors other than ventilatory capacity also have a quantitative effect on VO2max and that PIP constitutes a determinant of maximum exercise capacity in patients with CAO.

Exercise Test↗
PubMed1988

Respiratory control in presenile dementia.

To evaluate the role of the cerebral cortex in the response to externally added inspiratory flow-resistive load, we studied 7 patients manifesting clinical presenile dementia of the Alzheimer's type. All subjects exhibited diffuse cerebral cortical atrophy on computerized tomography of the brain. The mean age of the group was 45.6 yr. The rebreathing technique was used to assess minute ventilation (VE) and occlusion pressure (P100) responses to progressive hypercapnia. Rebreathing runs were performed before and during the addition of an inspiratory flow-resistive load of 18 cm H2O.L-1.s. The respiratory control data of these patients were compared with data obtained by similar techniques in a matched normal volunteer control group. In the patient group, with the addition of load, the VE/PCO2 response slope decreased (p less than 0.005), whereas the P100/PCO2 response slope did not significantly change. In the control group, P100/PCO2 response slope increased with load to maintain ventilation. These results suggest that in presenile dementia, during added inspiratory load, the drop in VE is associated with an inadequate increase in respiratory neuromuscular output. This lack of load compensation in patients with presenile dementia suggests a role for the cerebral cortex in the response to externally added load.

Adult↗
PubMed1988

Neuropsychologic symptoms in obstructive sleep apnea improve after treatment with nasal continuous positive airway pressure.

To describe the affective changes associated with sleep restoration we assessed psychologic symptoms using the Profile of Mood States questionnaire before and two months after treatment with nasal continuous positive airway pressure (NCPAP) in seven men with obstructive sleep apnea (OSA). The results were compared with those of a control group of patients with OSA who did not receive NCPAP. Two of six mood factors, depression and fatigue, improved significantly following treatment with NCPAP. Total Mood Disturbance (TMD) score was used to assess global mood differences. The mean TMD score for the patients before treatment was 1.7 and during treatment decreased to -7.6 (p less than 0.05). This mean decrease of 9.3 in the TMD score implies generalized improvement in mood. These findings support the opinion that sleep fragmentation and abnormalities of respiration during sleep are at least partially responsible for affective changes seen in sleep apnea. These psychologic disturbances improve after treatment with NCPAP.

Affect↗
PubMed1988

The effect of participation in a regular exercise program upon aerobic capacity during pregnancy.

This study examined the questions of whether pregnancy decreases physical fitness, as measured by maximal oxygen consumption, between the second and third trimesters, and whether maintaining a regular exercise program during the second half of pregnancy affects fitness. At the beginning of their second trimester, pregnant women were randomly assigned to either a nonexercising control group or an exercising group. They completed a maximal progressive exercise test on a cycle ergometer at 20 and 30 weeks, during which pulmonary parameters of aerobic capacity were measured. The exercising group demonstrated greater improvement in aerobic capacity than did the control group, manifested by increases in tidal volume and oxygen consumption and a stable ventilatory equivalent for oxygen. Pregnancy did not reduce maximal oxygen consumption between the second and third trimesters of pregnancy.

Adult↗
PubMed1987

Orthodeoxia: a new finding in interstitial fibrosis.

Orthodeoxia--arterial desaturation accentuated by the upright position and improved by recumbency--has been described earlier with true pulmonary vascular shunts and intracardiac shunts. This phenomenon has been described in some parenchymal lung diseases, but has not been reported with interstitial fibrosis. We describe 2 patients with predominantly basal interstitial fibrosis, disabling dyspnea, and severe hypoxemia who demonstrated this positional oxygenation change. Large or surgically correctable arteriovenous malformations (AVM), or intracardiac shunts, were not demonstrated in either patient. This finding has important implications for oxygen prescription and the explanation of positional dyspnea.

Aged↗
PubMed1987

Pulmonary function in sickle cell trait.

Pulmonary function abnormalities, which have been reported to occur in persons with sickle cell trait (hemoglobin AS), could intensify the hypoxic stimulus for the systemic formation of sickle cells at high altitude. We sought to determine whether pulmonary function abnormalities occur as a result of exposure to high altitudes in persons with hemoglobin AS. In a prospective study, 13 men with hemoglobin AS ("cases") and 13 controls (hemoglobin AA) matched by age, sex, and race were exposed to five to seven altitude simulations (ranging from 1524 to 7620 m [5000 to 25,000 ft]) in a hypobaric chamber. Measurements of diffusing capacity for carbon monoxide (DLco), forced vital capacity, forced expiratory volume in one second, and forced midexpiratory flow were obtained before and after each exposure. Data before exposures did not differ statistically between cases and controls. Altitude had no systematic effect on DLco or spirometric values in cases compared with values in controls (p greater than 0.05). Individual declines in forced vital capacity or DLco of more than 10% occurred with similar frequency in both groups. Measurements made after the series of exposures showed no change from those made before. We conclude that short serial exposures to hypoxia at high altitudes does not acutely or cumulatively alter DLco or spirometric values in healthy, nonexercising persons with sickle cell trait.

Adult↗
PubMed1987

Obstructive sleep apnea in adults with tonsillar hypertrophy.

Tonsillar enlargement is a more common cause of obstructive sleep apnea (OSA) in the pediatric population than it is in adults. The small number of reported cases suggests that tonsillectomy for adult patients with this association may be as a successful as it is known to be for children. We compared polysomnographic findings and/or symptomatology both before and after tonsillectomy in six patients aged 22 to 52 years, who had adenotonsillar hypertrophy and OSA. Tonsillectomy provided lasting relief of OSA in four patients. We review the literature for available polygraphic data from similar patients before and after tonsillectomy. Our combined experience indicates that many adults with OSA can clearly benefit from removal of hypertrophied tonsils. Such success may, for some adults, be transient or may not occur. This should be considered during initial patient counseling and when planning postoperative follow-up.

Adenoids↗
PubMed1986

Overnight nasal CPAP improves hypersomnolence in sleep apnea.

Eleven adult men with sleep apnea underwent nocturnal polysomnography on two successive nights. The first study, done without NCPAP, served as the control. The second (treatment) was done with the application of 7.5 to 15 cm H2O nasal continuous positive airway pressure (NCPAP). A subjective sleepiness index (SSI) was noted upon awakening from each night of polygraphic recording. During the control night, the mean frequency of apnea episodes/sleep hr was 35.95 +/- 4.5 SE, and the mean duration was 28.68 +/- 2.7 sec. Mean frequency of disorder of breathing (DOB) episodes/sleep hr was 19.25 +/- 6.2 and mean duration of DOB episodes was 23.1 +/- 2.8 sec. During the treatment night, all obstructive apnea episodes were abolished. During the control night, the mean decrease in arterial oxygen saturation during obstructive apnea episodes was 11.2 +/- 1.9 percent and the mean lowest saturation was 67.6 +/- 4.0 percent. NCPAP eliminated arterial oxygen desaturation. While 44.5 +/- 5.7 percent of total sleep time was spent in either apnea or disordered breathing during the control night, NCPAP decreased this to 0.73 +/- 0.3 percent. In addition to the improvement in respiration during sleep, SSI decreased from a mean of 3.73 +/- 0.49 after the control night to 1.64 +/- 0.24 after treatment, reflecting an improvement in daytime hypersomnolence. We conclude that nasal CPAP is effective in eliminating obstructive apnea episodes, and results in a marked decrease in daytime hypersomnolence after one treatment night.

Adult↗
PubMed1986

Effects of medroxyprogesterone acetate in obstructive sleep apnea.

We studied the effects of medroxyprogesterone acetate, a respiratory stimulant, on the incidence and duration of episodes of apnea and disordered breathing in 13 nonhypercapnic men with obstructive sleep apnea. Nocturnal polysomnography was done before and after four weeks of treatment with medroxyprogesterone acetate (60 mg/day) and one week after cessation of treatment. There were no significant (p less than 0.05) differences in the mean frequency of apneic episodes per hour of sleep before (31.3 +/- 5.7 [+/- SE]), during (26.8 +/- 6.6), or after (23.6 +/- 7.0) treatment, or in the mean number of disordered breathing episodes per hour of sleep before (19.4 +/- 5.6), during (21.4 +/- 5.8), or after (23.1 +/- 6.3) the period of treatment. Medroxyprogesterone did not alter significantly the total time of apnea or the total time for disordered breathing, expressed as percentages of total sleep time. Arterial oxygen desaturation during apnea and disordered breathing did not change with treatment. Medroxyprogesterone increased the minute ventilation and occlusion pressure responses to hypercapnia measured in the awake state; however, the results of this study demonstrate that medroxyprogesterone does not improve the breathing disorders during sleep in the nonhypercapnic patient with obstructive sleep apnea.

Adult↗
PubMed1985

Prediction of ventilation at maximal exercise in chronic air-flow obstruction.

In chronic air-flow obstruction (CAO), inspiratory mechanics constitute a potential mechanism of compensation for limitation of expiratory air flow. We sought to determine whether assessment of inspiratory function could improve our ability to predict ventilation at maximal exercise (Ve max) in patients with CAO. Resting inspiratory and expiratory pulmonary function studies from 20 patients with ventilatory limitation of exercise due to CAO provided data for development of a new regression model for Ve max. Maximal exercise was quantitated from breath-by-breath analysis of exercise responses at cycle ergometry with work increments of 25 watts each min to tolerance. Multiple regression analysis by 3 methods gave identical results. A 2-variable formula containing peak inspiratory flow rate (PIFR) and the forced expiratory volume in one second (FEV1) correlated strongly with Ve max (r = 0.967) in the formula Ve max (L/min) = 21.34 FEV1 (L) + 6.28 PIFR (L/s) +3.94 (95% Cl = +/- 18 L/min). This model was significantly different from published models containing FEV1 alone (p = 0.0002) and was not improved by additional variables. Similar formulas derived for emphysematous and bronchitic clinical types of CAO did not exhibit significantly different slope and intercept coefficients. Both PIFR and FEV1 correlated strongly with tidal volume at maximal exercise. The PIFR also correlated well with resting peak inspiratory airway pressure (r = 0.775). We conclude that consideration of PIFR in addition to FEV1 can improve our clinical ability to predict Ve max in patients with CAO.

Adult↗
PubMed1985

Pulmonary involvement in mixed connective tissue disease.

To determine the frequency of pulmonary function abnormalities in mixed connective tissue disease (MCTD), we studied 16 consecutive patients. Spirometry, total lung capacity (TLC), diffusing capacity (Dco), static lung compliance (Cst), and tests of respiratory muscle function (peak inspiratory pressure [PIP] and the maximum change in transdiaphragmatic pressure [delta PDI] during a diaphragmatic Müeller maneuver) were obtained. Airway resistance (RAW) and frequency dependence of compliance were also measured. Static lung compliance was less than 0.2 L/cm H2O in four of nine patients. The PIP was less than 75 cm H2O in only one patient and delta PDI was greater than 45 cm H2O in all ten patients evaluated. Frequency dependence of compliance was abnormal in seven of ten patients, whereas RAW was increased in only three of eight patients. The TLC and DCO were less than 80 percent of the predicted values in ten of 16 and 14 of 16 patients respectively. There was no correlation between the level of extractable nuclear antigen and pulmonary function abnormalities. The study did not identify significant abnormalities in respiratory muscle function.

Adult↗
PubMed1984

Control of breathing in obstructive sleep apnea.

We studied the responses of ventilation and occlusion pressure (P100) to hypercapnia, with and without the application of an inspiratory flow-resistive load (12 cm H2O/L/sec), in eight control subjects and in eight subjects with obstructive sleep apnea who did not retain carbon dioxide while awake. The hypercapnic response was assessed by a modification of the Read rebreathing technique. For a given endtidal carbon dioxide, ventilation in control subjects was the same with or without load, and P100 was increased with loading. In contrast, the subjects with sleep apnea decreased their ventilation during loading and did not increase their P100 in response to loading. Relationships between ventilation and P100 were similar in the two groups both with and without load. We conclude that patients with occlusive sleep apnea do not exhibit the normal increase in neural drive to compensate for inspiratory flow-resistive loading.

Adult↗
PubMed1984

Obstructive sleep apnea in hypothyroidism.

To determine the incidence and frequency of sleep apnea in persons with hypothyroidism, 11 consecutive patients with newly diagnosed disease were studied before and during thyroid hormone replacement therapy. Nine patients had episodes of apnea, with the number of episodes per hour of sleep ranging from 17 to 176 (mean, 71.8). Six of the nine patients were obese and had 99.5 episodes per hour compared with 16.3 episodes per hour in the 3 nonobese patients (p less than 0.02). After 3 to 12 months of thyroxine replacement therapy, mean apnea frequency decreased from 71.8 +/- 18.0 (SE) to 12.7 +/- 6.1 episodes per hour, without reduction in body weight. There were fewer changes in sleep stage per hour during treatment (22.1 +/- 4.9) than pretreatment (57.6 +/- 14.5). Carbon dioxide response tests done under non-loaded and flow-resistive loaded conditions before and during thyroxine replacement therapy showed increases in the loaded respiratory effort and ventilation during thyroxine treatment. Sleep apnea episodes are common in persons with untreated hypothyroidism, even with normal lung function. Thyroxine replacement therapy decreases apnea frequency, even without change in body weight.

Adult↗
PubMed1983

An analysis of respiratory drive components during flow-resistive respiratory loading.

Inspiratory flow-resistive loading normally causes an additional respiratory drive that limits the resistance-induced decrease in minute ventilation (load compensation). Occlusion pressures (P100) were measured during CO2 rebreathing with and without added inspiratory loads in normal persons and persons with obstructive sleep apnea (OSA). At each point obtained during loaded breathing, the additional drive due to resistive loading was determined by subtracting CO2-dependent drive (estimated from the nonloaded run) from total drive. In normal subjects, the additional drive correlated with each of four different estimates of load magnitude. In OSA subjects, there was no significant increase in drive due to loading and ventilation decreased markedly during loading. The relationships among ventilation rate, load, and drive, with and without load compensation, were analyzed using a 4-quadrant feedback control diagram. The diagram enables the prediction of ventilation rate for any end-tidal CO2 in the loaded and nonloaded cases, and the flow decrement that will occur as a result of added inspiratory resistance.

Airway Resistance↗