Presence of rhinovirus in the respiratory tract of adolescents and young adults with asthma without symptoms of infection.

BACKGROUND: Viral respiratory infections have been associated with up to 80% of wheezing episodes and asthma exacerbations. However, studies on the role of these viruses in asthmatic patients in the interval between exacerbations are sparse. This study aimed to determine the presence of respiratory viruses, without symptoms of infection, in the airways of young asthmatics as compared to healthy controls. MATERIAL AND METHODS: Patients 10-35 years of age with stable asthma and a group of healthy controls were analyzed regarding the presence of RNA from common respiratory viruses in nasopharyngeal aspirates by PCR. Self-reported asthma control and quality of life, fraction of exhaled nitric oxide (FeNO), spirometry, and bronchial responsiveness to methacholine were recorded. Blood samples were collected to assess IgE sensitisation and eosinophil cationic protein (ECP) levels. RESULTS: In 354 patients with asthma and 108 healthy controls, human rhinovirus (HRV) was the only virus detected (4.5% of asthmatics vs. 0.9% of controls; p = 0.08). HRV(+) asthma patients had a higher degree of aeroallergen IgE sensitisation (median 37.7 vs. 10.4 kUA/L, p = 0.04), and a tendency for higher levels of serum ECP (median 17.2 vs. 12.6 µg/L, p = 0.07), as compared to their HRV(-) counterparts. CONCLUSIONS: Absence of symptoms of respiratory tract infection notwithstanding, HRV seems to be more prevalent in the airways of adolescents and young adults with asthma and a high degree of aeroallergen IgE sensitisation than in controls. The presence of HRV seems also to be related to systemic eosinophilic inflammation despite ongoing treatment with inhaled corticosteroids.

The department of Veterans Affairs oral health services and eligibility.

The Department of Veterans Affairs (VA) operates one of the largest health care systems in the nation; more than 2.5 million veterans receive care annually. Among the special foci of care within VA is the Dental Service. The Department of Veterans Affairs Dental Service is the largest dental care system in the nation and the largest hospital-based dental care system in the world, receiving more than 1.2 million visits annually. The authors describe the VA dental care system and the larger health care system in which it is embedded. How the system is organized, who is eligible for services, who uses care, and what types of services are used are detailed. Compared with medical care, eligibility for VA dental care is more complex and differs for inpatients and outpatients. Outpatients account for 65% of patient visits and 76% of treatment provided in VA dental clinics. The two largest groups of users are inpatients with compelling medical needs (17%) and outpatients who are totally disabled (24%). A wide variety of services is provided, ranging from diagnostic and preventive care to insertion of crowns, bridges, and removable prostheses. Changes in the nation's health care system mandate introspection by all health agencies. The goal of the VA Dental Service is to become veterans' first choice for dental care. Information needed by VA to best respond to the needs of veterans include the following: (1) reasons for why eligible veterans do not use VA dental care; (2) veterans' oral health needs; (3) definition of optimum care and whether it varies as a person moves from functional independence to dependence; (4) whether VA is providing the most cost-efficient care possible and is best utilizing allied health professions; and (5) whether this care is best provided in a hospital setting. Modifications of data gathering systems are required as a first step to providing the needed information.

Relations of body fat and fat distribution to the serum lipid, apolipoprotein and insulin concentrations of Samoan men and women.

OBJECTIVE: To examine relations between obesity and serum concentrations of lipoprotein cholesterol, apolipoproteins, triglycerides and insulin in American and Western Samoans. Associations are also described between these CHD risk factors and abdominal adiposity, and the potential mediating role of insulin in these relationships is examined. DESIGN: Cross-sectional, using a sub-sample from an observational epidemiological study of cardiovascular disease risk factors among Samoans. MEASUREMENT: Obesity is estimated by the body mass index (BMI), and fat distribution by the abdomen-hip circumference ratio (AHR). All biochemical parameters were measured in the fasted stated. SUBJECTS: The sub-sample is 178 men and 147 women who were free from hypertension, diabetes and heart disease. RESULTS: In multivariate linear regression analyses in men the BMI was positively associated with levels of total cholesterol, the total-HDL cholesterol ratio, apolipoprotein B, and the log of triglyceride and insulin concentrations, and negatively associated with HDL and HDL2 cholesterol. The quadratic term for BMI was also found to be significantly predictive of all metabolic parameters in men, except for the log of serum insulin concentrations. Among the women, in contrast, BMI levels were significantly associated only with concentrations of HDL2 cholesterol, triglyceride and insulin. In men, the associations between the AHR and the metabolic parameters were similar to those described for the BMI, but showed no indication of non-linearity. Addition of the log of insulin to these models had little effect on the relations between the AHR and the lipid parameters, with the exceptions of total cholesterol and triglycerides. As with BMI, the AHR was much les predictive of metabolic parameters in women than in men, with a significant relation existing only with the log of insulin concentrations. CONCLUSIONS: These cross sectional data indicate that overall and abdominal adiposity are important correlates of serum lipid parameters among Samoan men, though the associations with BMI are attenuated at higher levels. Neither anthropometric indicator has much relation with these CHD risk factors among the women, perhaps due to extremely high levels of obesity in this group.

Body fat distribution and sleep apnea severity in women.

The contribution of body fat distribution to sleep-disordered breathing in women has not been examined in detail (to our knowledge). Fifty women under 65 years of age were diagnosed as having obstructive sleep apnea (OSA) by all-night polysomnography in a 6-month period. Twenty-five women underwent body fat measurements of skin folds and circumferences. The 12 premenopausal and 13 postmenopausal women did not differ in regard to apnea hypopnea index (AHI), SaO2 nadir, body mass index (BMI), or anthropometric measurements. The AHI for these 25 patients was related to the severity of obesity assessed by triceps and subscapular skin folds, the sum of the skin folds, waist circumference, and BMI. The SaO2 nadir correlated with triceps and subscapular skin folds, the sum of the skin folds, and neck skin fold. Clinical features of this same group of 25 women were then compared with those of 45 men with OSA previously described by our laboratory. The women, despite similar age, had less severe OSA than the men (AHI of 34.4 +/- 5.4 vs 51.1 +/- 4.9, p < 0.05). Despite similar BMIs and waist circumference, the men had evidence of a greater degree of upper body obesity with a larger subscapular skin fold thickness, waist-hip ratio, and neck circumference. In addition, for a given degree of upper-body obesity, men had more severe sleep apnea. These findings may explain, at least in part, the greater severity of OSA in the men.

Prevalence of hypertension, dyslipidemia, and dyslipidemic hypertension.

BACKGROUND: It has been proposed that dyslipidemic hypertension is part of a distinct metabolic syndrome related to insulin resistance. This paper describes the prevalence and cross-sectional relations of dyslipidemic hypertension in a population-based sample of men and women. METHODS: In two southeastern New England communities, 11,199 randomly selected participants were evaluated as part of a cross-sectional surveillance program of coronary heart disease risk factors between 1981 and 1990. RESULTS: The frequency of dyslipidemia was 38% and of hypertension was 26.5%; the conjoint frequency (dyslipidemic hypertension) was 15.0%, which is 1.49 times the expected value if the two diseases were independent P < .05). Using a discrete multivariate model, dyslipidemia and hypertension were associated with sex, obesity, and diabetes mellitus. The excess association of dyslipidemic hypertension, compared with individual effects of dyslipidemia and hypertension, was not related to these factors. CONCLUSIONS: This study suggests that dyslipidemic hypertension is common but may not be a unique entity associated with a distinct metabolic syndrome.

Inhibitors of 11 beta-hydroxysteroid dehydrogenase and 5 beta-steroid reductase in urine from patients with congestive heart failure.

Recently, the current authors reported the presence in normotensive male and female urines of reproducibly measurable levels of naturally occurring substances in partially purified extracts of urine with inhibitory activity like glycyrrhetic acid (GA) towards both 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) and steroid 5 beta-reductase (5 beta-SR) in vitro. Since these substances mimic two known inhibitory activities of GA, they have been named 'Glycyrrhetic Acid-Like Factors', abbreviated as 'GALFs' or, more specifically 11 beta-GALF for substance(s) active against 11 beta-OHSD, and 5 beta-GALF for those inhibitory to 5 beta-SR. Administration of glycyrrhetic acid in man leads to cortisol-dependent mineralocorticoid hypertension, owing to impaired inactivation of cortisol by 11 beta-OHSD, and may be associated with increased sensitivity to mineralocorticoids owing to impaired 5 beta-SR. In this preliminary report, the results are described of a study on the presence of GALF factors in urines collected from patients with congestive heart failure (CHF) and mild essential hypertension. The results show that in such patients there are increased amounts of both 11 beta- and 5 beta- GALFs compared to normotensive. The possible physiological significance of these results is discussed.

Adiposity and cardiovascular risk factors in men with obstructive sleep apnea.

STUDY OBJECTIVE: To assess anthropometric characteristics of patients with obstructive sleep apnea (OSA) and their relationship to cardiovascular risk factors (dyslipidemia, hypertension, glucose intolerance) and severity of breathing abnormalities during sleep. DESIGN: Case series. SETTING: Referral-based sleep disorder center serving Rhode Island and Southeastern Massachusetts. PATIENTS: Forty-five men, 26 to 65 years old, with OSA diagnosed by clinical and polysomnographic criteria. RESULTS: By national health survey criteria, 51 percent of patients were in the upper fifth percentile for weight, whereas 91 to 98 percent were in the upper fifth percentile for skinfold thicknesses (triceps, subscapular, triceps plus subscapular). Severe upper body obesity, as defined by a waist-hip ratio (WHR) greater than or equal to 1.00, was present in 51 percent of the patients. The WHR, however, did not correlate significantly with the severity of respiratory disturbances during sleep. The patients had higher prevalences of hypertension and impaired glucose tolerance than expected, but normal prevalences of hypercholesterolemia, low high-density lipoprotein cholesterol, and overt diabetes mellitus. Skinfold thicknesses correlated more closely with the severity of OSA than did body mass index (BMI) or neck circumference. CONCLUSION: Men with OSA have a marked excess of body fat that is not always reflected in measurements of body weight or BMI. Also, upper body obesity, hypertension, and impaired glucose tolerance occur more frequently than expected in this population. Severe adiposity may not only promote development of the respiratory abnormalities of OSA, but also may contribute directly to the increased cardiovascular risk associated with OSA.

Daytime hypertension in obstructive sleep apnea. Prevalence and contributing risk factors.

We examined the prevalence of daytime hypertension in a modern sample of patients with obstructive sleep apnea (OSA) and assessed the relative risk factors contributing to the development of hypertension in this disorder. Daytime hypertension was present in 92 (45 percent) of 206 male and female patients with OSA. Stepwise logistic regression revealed that only age and body mass index (BMI) were predictors of hypertension in this population. A subsample of 152 male patients with OSA was then compared to 904 men identified from a geographically and ethnically similar general population. When one controlled for age and BMI, the prevalence of hypertension in the two groups was the same except for those aged 25 to 44 years who were markedly obese (BMI greater than 31 kg/m2). In this group, 47 percent of the patients with OSA were hypertensive vs 26 percent of control subjects (p less than 0.05). Our data suggest that the high prevalence of hypertension in OSA is primarily related to age and the excess obesity seen in these patients. In morbidly obese young patients with OSA, factors directly related to OSA may also be contributing to the development of hypertension. With increasing age, other competitive risks may obscure any independent effect that OSA may exert.

Causes and consequences of blood pressure alterations in obstructive sleep apnea.

The obstructive sleep apnea (OSA) syndrome has been considered to be a cause of both transient blood pressure elevations during sleep and sustained hypertension during the awake state. The purpose of this review was to examine critically the existing literature regarding (1) the blood pressure alterations associated with OSA, (2) causal mechanisms relating specific blood pressure alterations to OSA, and (3) potential consequences of the systemic circulatory abnormalities associated with OSA. Particular attention was directed at studies that assessed the prevalence of OSA in patients with hypertension and that examined the effects on blood pressure of treatment of OSA. We conclude that patients with OSA have abnormal sleep blood pressure patterns, manifested most frequently by apnea-associated blood pressure elevations. Confounding factors such as obesity and antihypertensive drug therapy, and conflicting evidence regarding changes in daytime blood pressure after therapy for OSA, make it premature to conclude that OSA and daytime hypertension are directly associated. Circumstantial evidence suggests that the blood pressure alterations that occur during sleep could contribute to the high cardiovascular morbidity in patients with OSA. Further research into the relationship between OSA and hypertension should improve the future care of patients with these conditions and enhance our understanding of cardiopulmonary pathophysiology.

Severe hyponatremia: an association with lisinopril?

A 63-year-old white woman with a history of hypertension and chronic obstructive pulmonary disease presented to the emergency room with worsening shortness of breath, anorexia, coughing, increased thirst, and leg edema of two weeks' duration. Medications included lisinopril 10 mg/d, which had been started six weeks earlier, sustained-release theophylline 300 mg q12h, and an albuterol inhaler. The lisinopril was discontinued on admission. Serum sodium concentration was 109 mmol/L; the osmolality of the blood and of the urine were 253 mOsmol and 438 mOsmol, respectively, with a specific gravity of 1.025 and a urine sodium of 17 mmol/L. The hyponatremia initially was considered to be the syndrome of inappropriate antidiuretic hormone secretion in response to the patient's suspected pneumonia. Due to worsening blood pressure, lisinopril was restarted and the serum sodium concentration dropped from 134 to 126 mmol/L. Evaluation of the patient's hyponatremia included assessment of thyroid, adrenal, hepatic, and cardiac function that were within normal limits. The patient was discharged on the following medications: sustained-release theophylline 300 mg tid, prednisone 10 mg/d, albuterol inhaler 2 puffs q6h, and sustained-release verapamil 240 mg/d for blood pressure control. Her serum sodium concentration has remained between 135 and 140 mmol/L during hospitalizations for exacerbations of chronic obstructive pulmonary disease and for pneumonias 10 and 12 months after discharge.

Effects of n-3 fatty acids in essential hypertension.

We examined the effects on blood pressure, plasma lipoproteins, and platelet function when marine oil supplements (rich in n-3 fatty acids) or vegetable oil supplements (rich in n-6 fatty acids) were added to the usual diets of patients with mild essential hypertension. In a randomized, double-blind, parallel-group study, patients received 50 g of either marine oil (n = 8) or vegetable oil (n = 8) daily for 6 weeks following a baseline observation period. Diastolic blood pressure declined during treatment with fish oil (mean +/- SEM, 96 +/- 2 v 89 +/- 2 mm Hg, P = .02), but did not change with vegetable oil (92 +/- 1 v 94 +/- 1 mm Hg). Systolic blood pressure did not change significantly during either treatment. Serum triglycerides declined (by approximately 30%) in patients receiving only marine oil, but total cholesterol, LDL-, HDL-, HDL2-, and HDL3-cholesterol-subfractions and apolipoproteins A-I and B were unchanged in both treatment groups. Bleeding time increased by 33% during treatment with marine oil but did not change with vegetable oil supplements. Marine oil did not alter in vitro platelet aggregation thresholds. The lack of a significant correlation between blood pressure changes and platelet membrane fluidity, plasma renin activity, aldosterone, norepinephrine, or epinephrine suggests that these variables did not mediate the antihypertensive effect of the marine oil. We conclude that large doses of marine oil reduce diastolic blood pressure, lower triglycerides, and increase bleeding time in patients with mild hypertension.

Hormone and catecholamine responses accompanying the antinatriuresis of glucose ingestion.

The purpose of this study was to determine the importance of various neurohormonal systems in mediating the sodium retention associated with glucose ingestion. Eight normotensive men were randomized to receive, after an overnight fast, glucose (1 mg/kg po) in water, and water alone, during two studies seven to ten days apart. Sodium excretion declined 38 +/- 5% from baseline one to two hours after glucose ingestion (P less than .005), but did not change significantly on the control day. Urinary norepinephrine and dopamine did not change during glucose or control studies. Peak serum insulin levels after glucose correlated inversely with the decline in sodium excretion (r = .67, P less than .10). Plasma renin activity (PRA) increased after glucose ingestion (P less than .01), but changes in PRA did not correlate with changes in sodium excretion. We conclude that the antinatriuresis following glucose ingestion does not result from alterations in noradrenergic-dopaminergic activity or changes in the renin-angiotensin-aldosterone axis. Insulin may modulate renal sodium metabolism directly, or through a yet unknown mechanism.

Derivation of urinary dopamine from plasma dopa.

1. We estimated the extent to which circulating dopa (3,4-dihydroxyphenylalanine) is the source of urinary dopamine (DA; 3,4-dihydroxyphenethylamine). Tritiated dopa ([3H]dopa) was infused for 90 min into the left renal artery of seven anaesthetized foxhounds, and levels of labelled and unlabelled dopa and DA were measured in the ureteral urine and in the femoral arterial and left renal venous plasma. 2. Only a small percentage of [3H]dopa delivered to the kidneys was excreted as [3H]DA (0.59% from the left kidney, 0.68% from the right); however, the arterial concentration of endogenous dopa (1220 pg/ml) and the renal plasma flows (144 and 141 ml/min by p-aminohippurate clearances) were such that all of the urinary excretion of endogenous DA (about 1 ng/min from each kidney) could be accounted for by uptake and decarboxylation of circulating endogenous dopa. 3. Plasma dopa is the main source of urinary DA.

Antihypertensive therapy with ketanserin: metabolic and hemodynamic effects.

Ketanserin, a serotonin-2-receptor antagonist, was administered to 12 subjects with mild to moderate hypertension in a randomized, double-blind, placebo-controlled crossover trial. After 6 weeks of ketanserin (40 mg every 12 h), blood pressures measured 12 h after dosing were not significantly different from those obtained during the placebo period. However, 2 h after ketanserin administration, supine systolic and diastolic blood pressures declined 11 +/- 10 mm Hg (p less than 0.01) and 6 +/- 5 mm Hg (p less than 0.005) from predose values, whereas placebo caused no change in either systolic or diastolic blood pressure. At the time of peak antihypertensive activity, plasma renin activity, aldosterone, growth hormone, and prolactin levels were unchanged. Prolactin levels decreased slightly (4.1 +/- 3.0 vs. 3.7 +/- 2.9 ng/ml, p less than 0.05) during ketanserin therapy when measured 12 h after dosing. Other pituitary hormones, serum testosterone, plasma catecholamines, and plasma lipids showed no changes. Heart rate was also unchanged. Stroke volume, measured 2 h after dosing, increased (70 +/- 22 vs. 85 +/- 31 ml, p less than 0.05) with ketanserin therapy, but cardiac output did not change significantly. Ketanserin has a moderate antihypertensive effect and neutral metabolic-hormonal profile when used as monotherapy for the treatment of hypertension. However, further studies are needed to define the frequency of dosing that will provide 24-h antihypertensive activity.

Metabolic and hemodynamic effects of antihypertensive treatment with ketanserin.

Ketanserin, a serotonin-2-receptor antagonist, was administered to 12 subjects with mild to moderate hypertension in a randomized, double-blind, placebo-controlled crossover trial. After 6 weeks of ketanserin (40 mg every 12 hours), blood pressures measured 12 hours after dosing were not significantly different from those obtained after placebo. However, 2 hours after ketanserin administration, supine systolic and diastolic blood pressures declined 11 +/- 10 mm Hg (P less than 0.01) and 6 +/- 5 mm Hg (P less than 0.005) from predose values, whereas placebo caused no change in either systolic or diastolic blood pressure. Except for a slight decline in serum prolactin levels 12 hours after dosing with ketanserin, no changes were observed in pituitary hormone levels, serum testosterone, plasma catecholamines, plasma renin activity, aldosterone, or lipoproteins. Stroke volume, measured 2 hours after dosing, increased with ketanserin therapy, but cardiac output, systemic resistance, and heart rate were unchanged. Ketanserin has a moderate antihypertensive effect and neutral metabolic-hormonal profile when used as monotherapy for the treatment of hypertension. However, further studies are needed to define the frequency of dosing that will provide 24 hours of antihypertensive activity.