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Biomedical subjects

L H Hamilton

Publications and source records attributed to L H Hamilton.

At least 19 recordsLinked to original sources

Multicenter, double-blind, multiple-dose, parallel-groups efficacy and safety trial of azelastine, chlorpheniramine, and placebo in the treatment of spring allergic rhinitis.

Azelastine, a novel antiallergic medication, was compared with chlorpheniramine maleate and placebo for efficacy and safety in the treatment of spring allergic rhinitis in a multicenter, double-blind, multiple-dose, parallel-groups study. One hundred fifty-five subjects participated. Subjects ranged in age from 18 to 60 years of age and had at least a 2-year history of spring allergic rhinitis, confirmed by positive skin test to spring aeroallergens. Medications were given four times daily; the azelastine groups received 0.5, 1.0, or 2.0 mg in the morning and evening with placebo in the early and late afternoon; the chlorpheniramine group received 4.0 mg four times daily. Daily subject symptom cards were completed during a screening period to assess pretreatment symptoms and during a 4-week treatment period while subjects received study medications. Individual symptoms, total symptoms, and major symptoms were compared to determine efficacy of medication. Elicited, volunteered, and observed adverse experiences were recorded for each subject and compared among groups. Vital signs, body weights, serum chemistry values, complete blood cell counts, urine studies, and electrocardiograms were obtained for each subject and compared among groups. Symptoms relief in the group receiving the highest concentration of azelastine (2.0 mg twice daily) was statistically greater than in the placebo group during all weeks of the study. Lower doses of azelastine were statistically more effective than placebo only during portions of the first 3 weeks of the study. In contrast, although the chlorpheniramine group did have fewer symptoms than the placebo group during the study, the difference never reached statistical significance during any week of the study. There were no serious side effects in any of the treatment groups. Drowsiness and altered taste perception were increased significantly over placebo only in the high-dose azelastine group. Azelastine appears to be a safe, efficacious medication for seasonal allergic rhinitis.

Adolescent

The role of selectivity in the pathogenesis of eating problems in ballet dancers.

Forty-nine dancers from four national ballet companies in America (N = 32) and the People's Republic of China (N = 17) were surveyed (mean age, 24.6 +/- 4.18) from highly and moderately selective dance companies. The less selected American dancers reported significantly more eating problems (46% vs 11%; P less than 0.05), anorectic behaviors (2.77 vs 1.11; P less than 0.05), and familial obesity (42% vs 5%; P less than 0.05) than the Americans chosen from a company school. Differences were not found on these variables between the highly selected American and Chinese dancers. All of the groups reported a delay in menarche and weighed approximately 14% below their ideal weight for height. These data suggest that dancers who have survived a stringent process of early selection may be more naturally suited to the thin body image demanded by ballet and so less at risk for the development of eating problems. In addition, delayed menarche is typical of the majority of national dancers and probably is reflective of genetic and environmental factors.

Adolescent

The relation of eating problems and amenorrhea in ballet dancers.

Exercise-induced amenorrhea has received considerable attention in the medical literature. The combination of exercise and low body weight is thought to exert synergistic effects in the pathogenesis of amenorrhea, while the role of dieting and eating problems, another possible causative mechanism, has not been examined. A sample of 55 adult dancers in national and regional classical ballet companies was studied; their mean age was 24.7 yr. Fifty-six percent of the dancers had delayed menarche (age 14 or later) and 19% of the sample were currently amenorrheic (5 months or longer). One-third of the dancers reported having had an eating problem (self-reported anorexia nervosa or bulimia). Amenorrhea and reported eating problems were significantly related: 50% of amenorrheics reported anorexia nervosa while 13% of the normals did. In addition, prolonged amenorrhea was significantly related to dieting (as measured by EAT-26 scales, a measure of dieting behavior). As expected, leanness and absolute weight also were related to prolonged amenorrhea. Amenorrhea in this sample of adult dancers was not related to current activity level or age at which training began. Thus, eating problems may be one factor in the pathogenesis of prolonged amenorrhea in certain athletic groups.

Adult

Scoliosis and fractures in young ballet dancers. Relation to delayed menarche and secondary amenorrhea.

In a survey of 75 dancers (mean age, 24.3 years) in four professional ballet companies, we found that the prevalence of scoliosis was 24 percent and that it rose with increases in age at menarche. Fifteen of 18 dancers (83 percent) with scoliosis had had a delayed menarche (14 years or older), as compared with 31 of 57 dancers (54 percent) without scoliosis (P less than 0.04). The dancers with scoliosis had a slightly higher prevalence of secondary amenorrhea (44 percent vs. 31 percent), the mean (+/- SD) duration of their amenorrhea was longer (11.4 +/- 18.3 vs. 4.1 +/- 7.4 months; P less than 0.05), and they scored higher on a questionnaire that assessed anorectic behavior. The incidence of fractures was 61 percent (46 of 75 dancers), and it rose with increasing age at menarche. Sixty-nine percent of the fractures that were described were stress fractures (mostly in the metatarsals), and their occurrence had an even stronger correlation with increased age at menarche. The incidence of secondary amenorrhea was twice as high among the dancers with stress fractures (P less than 0.01), and its duration was longer (P less than 0.05). In 7 of 10 dancers in whom endocrine studies were performed, the amenorrheic intervals were marked by prolonged hypoestrogenism. These data suggest that a delay in menarche and prolonged intervals of amenorrhea that reflect prolonged hypoestrogenism may predispose ballet dancers to scoliosis and stress fractures.

Adolescent

The nonexpansile, equilibrated concentration of perfluoropropane gas in the eye.

Bubbles of 100% perfluoropropane (0.4 ml) were injected into the vitreous cavities of 31 New Zealand White rabbits. Gas bubbles were aspirated from eyes at six and 12 hours and at one, two, three, four, five, seven, nine, and 14 days, and were analyzed by gas chromatography. The nonexpansile concentration of perfluoropropane (found at maximum expansion of the gas bubble at four days) was approximately 12%. The gas bubble concentration equilibrated at seven days with a perfluoropropane concentration of approximately 10% with little change through 14 days. Using a similar protocol, we injected 0.56-ml bubbles of 100% perfluoropropane into the vitreous cavities of three owl monkeys. When sampled on day 4 for analysis by gas chromatography, results were comparable to the rabbit data. A 12% concentration of perfluoropropane should approximate the ideal composition of a gas mixture for a total fluid-gas exchange. This would achieve complete retinal tamponade without later compromise of intraocular pressure by further expansion.

Animals

Pediatric endotracheal tube designed for high-frequency ventilation.

Using pediatric endotracheal tubes (ETs) designed for high-frequency jet ventilation (HFJV), we demonstrated that when the fraction of the ventilatory cycle spent in inflation (Ti) was 0.3 or greater, entrainment of air flow was unaffected by frequencies up to at least 900 cycle/min. Flow through the jet opening was related to drive pressure (PD) at the ventilator, and to the diameter of the external connector to the jet tube in the ET. Maximal entrainment was completed within a 2.5-cm section downstream from the jet opening in these small ETs. When the jet opening was closer than 2.5 cm to the tip, output from the ET was compromised. Pressure measured in the lumen of the ET was most negative at the axial location of the jet opening. Its amplitude at that point reflected a balance between jet-flow velocity (a reflection of PD) and back-pressure (or airway pressure). ET lumen diameter had little effect on entrainment or on total flow through the ET. PD, Ti, and frequency can be regulated to optimize the output for an ET.

Humans

Evaluation of a rapid breath hydrogen analyzer for clinical studies of carbohydrate absorption.

A second-generation gas chromatograph for the analysis of H2 in expired air has been developed. It incorporates a solid-state detector with high sensitivity for H2 and has a small, internal pump which supplies air as the carrier gas, thus eliminating the need for a large tank of compressed gas for the carrier. A reference gas of known H2 concentration is, of course, still required. The entire system weighs 6.0 kg and is completely portable, requiring only 120 V electric current for use. The instrument has a mean intersample interval of less than 2 min, with H2 concentration registered on a digital display. The output has a track-hold feature which permits the output, in parts per million H2, to be retained by the meter so the reading can be verified. The chromatogram can also be recorded on a conventional analog strip-chart recorder. The sensitivity and precision are superior to those of a thermal conductivity H2 gas chromatograph. Moreover, the rapid response time encourages frequent calibration checks with the reference gas. This analyzer offers significant advantages over previous H2-measuring systems for breath-analysis tests used both for diagnostic clinical practice and for field studies of nutritional assessment.

Breath Tests

Measurement of ventilation using digitally filtered transthoracic impedance.

A seven-stage low-pass digital filter was used to remove the cardiac artifact and motion interference from a respiratory transthoracic impedance signal in human subjects. After removal of these artifacts, the mean difference from a conventional gasometer technique fell from 5% to 1.6%. When the impedance technique was used to measure ventilation during air breathing, the addition of a breathing valve with a mouthpiece and noseclip induced the following changes in ventilatory parameters: 7% drop in frequency, 24% increase in tidal volume, 49% increase in inspiratory time, 56% increase in expiratory time, 10% decrease in inspiratory flow rate, and 4% decrease in ratio of respiratory time to total breath duration. These alterations were not significant at elevated inspired CO2 levels. The digitally filtered transthoracic impedance technique provides an accurate technique for measuring ventilatory parameters without the perturbations induced by using a conventional breathing valve technique even when cardiac and motion artifacts were prominent.

Adult

Time course of lung volume changes during prolonged treadmill exercise.

It has been known since the 1920s that runners completing marathon races have reduced forced vital capacity (FVC) values. To investigate the time course of these lung volume alterations, we measured FVC and residual volume (RV) in 11 runners before, after, and at 30-min intervals during a 2.5-h treadmill run at just under their marathon pace (70% VO2max). Mean distance run was 21.5 +/- 1.5 (SD) miles in the 2.5-h period. During the first 60 min, both RV and total lung capacity (TLC) decreased by 110 ml, however, this change was not significant (P greater than 0.05). A high correlation (r = 0.93) was observed between delta RV and delta TLC during the first 5 min, while FVC remained unchanged. From 60-90 min, all lung volumes remained constant. From 90-150 min, lung volumes changed in a direction similar to that observed after a marathon, i.e., FVC decreased significantly (5.51 to 5.37 liter between 90 and 150 min, P less than 0.05), TLC remained unchanged (7.41 vs 7.42 liter, P greater than 0.05), and RV showed a nonsignificant increase from 1.90 to 2.05 liter (P greater than 0.05). The data are consistent with multiple mechanisms playing a role in pulmonary function changes during prolonged exercise. The smaller mean decrease in FVC observed in this study, as compared to that found during a marathon, suggested that the marathon imposes a greater demand on the lungs than did treadmill exercise of the duration and relative intensity used in this study.

Adult

Regulation of PaCO2 and ventilation in humans inspiring low levels of CO2.

This study was designed to determine whether 1) arterial PCO2 (PaCO2) increases when inspired PCO2 (PICO2) is increased from less than 0.4 Torr (eupnea) to 7 or 14 Torr, and 2) ventilatory sensitivity to CO2 (delta VE/ delta PaCO2) is greater at low levels of PICO2 (7-21 Torr) than it is at higher levels (28-42 Torr). Human subjects were studied while seated in an environmental chamber that permitted alteration of PICO2 by changing the chamber PCO2. In study 1, arterial blood was sampled over the final 5 min of a eupneic period and again 10-15 min later when PICO2 was 7 or 14 Torr. With this protocol, PACO2 was increased above eupnea by 0.7 (P less than 0.02) and 0.9 Torr (P less than 0.01) when PICO2 was 7 and 14 Torr, respectively. In study 2, arterial blood was sampled every 5 min during two 1-h periods of eupnea that were separated by 3 h during which PICO2 was increased by 7 Torr each 0.5 h. With this protocol there was no consistent difference in PACO2 between eupneic periods and periods when PICO2 was 7-14 Torr. There was a progressively increased hypercapnia as PICO2 was increased from 7 to 42 Torr. The delta VE/ delta PaCO2 was less than half for data obtained at low relative to high PICO2. The two studies demonstrated that measurement error and physiologic variation necessitate using a "powerful" experimental design (study 1) to detect small increases in PaCO2. On the basis of these results, we have concluded that there is no apparent reason to postulate a sensory mechanism other than the carotid and intracranial chemoreceptors to account for the hyperpnea during CO2 inhalation. Specifically, isocapnic hyperpnea probably does not occur.

Adult

Ventilatory response to inspired CO2 in normal and carotid body-denervated ponies.

The purpose of these studies was to gain insight into mechanisms regulating pulmonary ventilation (VE), arterial CO2 partial pressure (PaCO2), and arterial pH (pHa) in ponies when inspired CO2 partial pressure (PICO2) is above normal. Ponies were studied four times daily each weekday for 2 wk in an environmental chamber. Each study consisted of a 15-min control period (PICO2 = 0.7 Torr) followed by a 15- to 30-min experimental period during which PICO2 in the chamber was 0.7, 7, 14, 21, 28, or 42 Torr (PIO2 = 147 Torr throughout). Between 11 and 15 min of each period, four 3-ml samples of arterial blood were drawn, each over 45 s. In 12 normal ponies, elevation of PICO2 to 7 Torr caused PaCO2 to increase approximately 0.4 Torr (P less than 0.01) and pHa to decrease approximately 0.003 (P less than 0.02) relative to control. The hypercapnia and acidosis increased progressively as PICO2 was increased in 7- to 14-Torr increments to 42 Torr (P less than 0.02). Accordingly, the hyperpnea in these ponies during CO2 inhalation could have been mediated by carotid and intracranial chemoreceptors. One month after carotid body denervation (CBD) in nine ponies, PaCO2 during control conditions was 6 Torr above normal, but during CO2 inhalation, PaCO2 changed less from control than during CO2 inhalation before CBD (P less than 0.01). The delta VE/ delta PaCO2 near eupneic PaCO2 appeared to be above normal 1 mo after CBD (P less than 0.01). The mechanism of this increase was not discernible from our data. Finally, our data indicated that the magnitude of the hypercapnia and acidosis during CO2 inhalation was inversely related to PaCO2 and breathing frequency during control conditions.

Acid-Base Equilibrium

Effect of elevated PICO2 on metabolic rate in humans and ponies.

The primary purpose of this study was to determine the effect of acute (20-30 min) elevations of inspired CO2 partial pressure (PICO2) on whole-body O2 consumption (VO2). In human subjects, VO2 increased approximately 15 ml.min-1.m-2 with each 7-Torr increment in PICO2 from 0.4 to 28 Torr (P less than 0.05), but VO2 did not change significantly when PICO2 was increased from 28 to 35 and 42 Torr (P greater than 0.05). In ponies, VO2 did not change when PICO2 was increased from 0.7 to 7 Torr (P greater than 0.05), but it increased about 6 ml.min-1.m-2 with each 7-Torr increment in PICO2 from 7 to 28 Torr, and it increased 18 ml.min-1.m-2 when PICO2 was increased from 28 to 42 Torr (P less than 0.05). At low PICO2 the delta VO2/ delta VE was 25 and 7 ml/l for humans and ponies, respectively, where VE is pulmonary ventilation. These values exceeded the expected O2 cost of breathing; hence, some factor, such as shivering or nonshivering thermogenesis, contributed to the elevated VO2. At high PICO2, VE increased without a proportional increase in VO2; thus the delta VO2/ delta VE decreased to about 2.5 ml/l in ponies and to near 0.0 in humans. Accordingly, at high PICO2 some VO2-suppressing factor partially counteracted those factors stimulating VO2. The maximum decrease from control pHa was 0.061 and 0.038 in humans and ponies, respectively. It is questionable whether this mild acidosis was sufficient to suppress VO2. In both species, pulmonary excretion of metabolic CO2 and the respiratory exchange ratio were below control during CO2 inhalation (P less than 0.01), which suggested an increased tissue storage of CO2.

Adult

A study of sustained action pseudoephedrine in allergic rhinitis.

A single capsule of sustained release pseudoephedrine (SUDAFED S.A., Burroughs Wellcome Co.) was shown by objective and subjective measurements to be superior to placebo in relieving nasal congestion associated with allergic rhinitis. The drug had no discernible effect on (1) the degree of wetness perceived in the mouth or nose, (2) a complex of symptoms which included sneezing, coughing, sniffing, swallowing, itching of eyes and nose or (3) number of nose blows. The study was marked by an absence of serious adverse reactions.

Adult

A computer program for calculating respiratory anatomic dead space.

The Fowler technique for estimating anatomic dead space (VD -- the volume of the airway conducting system) on the basis of CO2 changes in the expired air of a single breath was adapted to computer analysis. The areas above and below the sigmoid CO2 curve in the region of transition from inspired to alveolar concentration were simultaneously integrated (forward and backward) on a time base until the sum of the two integrated values equalled the total area representing the transition. The point on the CO2 curve was defined as the CO2 midpoint. Expiratory flow was then integrated with time from its beginning to the CO2 midpoint, and the resultant volume represented VD for that breath. The computer program was able to compensate for differences in response time between the gas monitor and the flow measuring device and was able to integrate the areas rapidly. The program provided a rapid calculation of VD, which compared well with values calculated by tedious, manual methods.

Carbon Dioxide

Effect of xylometazoline nasal spray on nasal conductance in subjects with coryza.

The ability of xylometazoline topical spray to reduce nasal congestion was evaluated in 44 normal subjects with coryza due to upper respiratory infection. Rating scales were completed for the subjective response and nasal airway resistance (expressed as nasal conductance, Gn) measured for the objective response over six hours. In 30 subjects, post treatment Gn was compared to the measurement after their colds had subsided. The increase in Gn following xylometazoline was rapid and profound, remaining significantly elevated for the six hour period, and it was greater than the asymptomatic value from 10 minutes to nearly five hours. Other symptoms were not markedly affected by the medication. Subjective scores indicated continued relief after treatment, but the small negative correlation suggested that rating scales were not reliable indices of nasal congestion. No differences were observed in the responses when cigarette smokers were compared with nonsmokers.

Administration, Intranasal