Polyadenylic acid sequences in the virion RNA of poliovirus and Eastern Equine Encephalitis virus.

Poliovirus virion RNA contains a single covalently bound sequence of polyadenylic acid which is approximately 49 nucleotides long. A single, slightly longer polyadenylic acid sequence is contained in Eastern Equine Encephalitis virus RNA. Since these viruses are otherwise dissimilar these sequences may play a common role in viral replication, possibly in translation of the viral RNA.

The AsTex: clinimetric properties of a new tool for evaluating hand sensation following stroke.

OBJECTIVES: To investigate the clinimetric properties and clinical utility of the AsTex((R)), a new clinical tool for evaluation of hand sensation following stroke. DESIGN: The AsTex((R)) was administered on two occasions separated by a week to appraise test-retest reliability, and by three assessors on single occasion to establish inter-rater reliability. Pilot normative values were collected in an age-stratified sample. Clinical utility was evaluated based on ease of administration, ceiling and floor effects, and responsiveness to sensory recovery. PARTICIPANTS: Test-retest (n = 31) and inter-rater (n = 31) reliability and normative values (n = 95) for the AsTex((R)) were established in neurologically normal participants aged 18-85 years. Test-retest reliability was investigated in 22 individuals a mean of 46 months (range 12-125) post stroke and clinical utility was evaluated in an additional 24 subacute stroke participants a mean of 29.4 days (range 12-41) post stroke. MAIN MEASURE: The AsTex((R)). RESULTS: The AsTex((R)) demonstrated excellent test-retest (intraclass correlation coefficient (ICC) = 0.98, 95% confidence interval (95% CI) = 0.97-0.99) and inter-rater reliability (ICC = 0.81, 95% CI = 0.73-0.87) in neurologically normal participants. Test-retest reliability of the AsTex((R)) in individuals following stroke was excellent (ICC = 0.86, 95% CI = 0.68-0.94). The AsTex((R)) was simple to administer, demonstrated small standard error of measurement (0.14 mm), minimal floor and ceiling effects (12.5% and 8.3%) and excellent responsiveness (standardized response mean = 0.57) in subacute stroke participants. CONCLUSION: The AsTex((R)) is a reliable, clinically useful and responsive tool for evaluating hand sensation following stroke.

Cigarette smoking and sleep disturbance.

BACKGROUND: Individuals with sleep complaints often exhibit unhealthy lifestyles, including obesity, excessive alcohol use, lack of physical exercise, and cigarette smoking. We sought to explore the relationship between cigarette smoking, poor sleep habits, and sleep complaints. Several lines of evidence suggest a relationship between cigarette smoking and sleep disturbance, including the effects of nicotine and nicotine withdrawal on sleep, a tendency for nonsmokers to be more alert in the morning, an association between cigarette smoking and snoring, and a tendency for individuals who engage in one unhealthy behavior also to engage in others. METHOD: A total of 484 individuals aged 14 to 84 years completed a comprehensive sleep and health questionnaire. There were 99 high school students from grades 9 through 12 (45 boys and 54 girls, of whom 38 [38%] were smokers), who completed an in-class survey. In addition, 385 adults aged 20 to 84 years (122 men and 263 women, of whom 77 [20%] were smokers) from a random sample of 1000 completed a mail survey. The effects of age and smoking status on sleep, health, and daytime function were assessed by multivariate analysis of variance. RESULTS: Cigarette smokers were significantly more likely than nonsmokers to report problems going to sleep, problems staying asleep, daytime sleepiness, minor accidents, depression, and high daily caffeine intake. CONCLUSION: Individuals with sleep complaints should be queried about tobacco use. Those who are smokers should be advised that there is a relationship between cigarette smoking and sleep disturbance.

Early onset chromosome 14-linked distal myopathy (Laing).

A dominantly inherited form of distal myopathy with onset in early childhood was first reported in a 4-generation Australian family in 1995. In the present report we provide further information on the clinical phenotype and natural history of this myopathy, and on the electromyogram and magnetic resonance imaging findings in affected individuals. The pattern of muscle involvement was similar to that in the 'tibial' forms of distal myopathy such as the Finnish (Udd) and Markesbery-Griggs types, with additional involvement of the finger extensors and of some more proximal limb and neck muscles. However, the age of onset was earlier than in these other myopathies and rimmed vacuoles were not found in biopsies from two affected individuals. Evidence of possible anticipation was found in one branch of the family. The gene locus for this myopathy had been mapped to 14q11.2-q13. The linkage region has been refined to a 24 cM region between D14S283 and D14S49 and mutations have been excluded in the PABP2 gene for oculopharyngeal muscular dystrophy which lies within this region.

Sleep-disordered breathing in healthy aged persons: two- and three-year follow-up.

We report the results of a study of the effects of sleep-disordered breathing in a cohort of healthy elderly subjects followed longitudinally for 3 years. In a comprehensive evaluation of daytime functioning, including medical history and physical examination, pulmonary function testing and neuropsychiatric testing, we found very little difference in the neuropsychiatric or medical sequelae between those subjects with moderate [apnea+hypopnea index (AHI) > or = 5] and low (AHI < 5) levels of sleep-disordered breathing at baseline. Although there were no differences in the electrocardiogram, pulse rate or cardiac history data, a mild association was found between indices of sleep-disordered breathing and pulmonary function. We conclude that moderate levels of sleep-disordered breathing in an otherwise asymptomatic healthy geriatric patient should probably not be considered pathologic in the short term.

Self report on sleep symptoms in older adults: correlates of daytime sleepiness and health.

Sleep problems in the healthy elderly were studied in 628 community-dwelling older adults. Self-report of daytime sleepiness in this group was evaluated. Self-reported snoring was significantly associated with reports of daytime sleepiness (p < 0.001), and reported health showed significant associations with age group (p < 0.001), reports of breathing problems (p < 0.001), and reports of excessive daytime sleepiness (p < 0.01). The data strongly support the impact of sleep-related factors on self-perceptions of health in community dwelling older adults. Even as a subjective self-report measure, snoring readily predicts self-reported problems with daytime sleepiness.

Sleep-disordered breathing in healthy aged persons: one-year follow-up of daytime sequelae.

We studied the waking medical, sleep, and psychological status of 28 healthy older persons who had undergone nocturnal polysomnography and daytime assessment approximately 1-year earlier. In a previous report based on this sample, we found that sleep-disordered breathing (SDB) indices were not related to concurrent measurements of daytime functioning. However, in the present study, we observed relationships between the original SDB indices and several measures of cardiopulmonary functioning obtained 1 year later. At follow-up, subjects with originally high levels of SDB had significantly higher systolic blood pressure and poorer pulmonary function test results, were more likely to report irregular heartbeats in the previous year, and had experienced more disruptive snoring than the remaining subjects. When combined with other recent data, these results raise the possibility that SDB exerts an insidious pathological influence on the health and daytime functioning of otherwise healthy older persons.

Systemic cardiovascular and metabolic effects associated with the inhalation of an increased dose of albuterol. Influence of mouth rinsing and gargling.

We designed this investigation to assess the occurrence of systemic beta adrenergic side effects associated with the inhalation of an increased dose of the beta2 receptor agonist albuterol. Since therapeutic aerosols delivered by metered dose inhaler (MDI) are preferentially deposited in the mouth and pharynx, we wished to determine whether mouth rinsing and gargling with water might reduce the magnitude of such side effects by partially removing oral and pharyngeal drug residues. Serum glucose, insulin and potassium concentrations, forced expiratory volume in one second (FEV1), heart rate (HR), and blood pressure (BP) were measured as parameters of beta-adrenergic stimulation. Each of eight nonmedicated mild asthmatic patients was studied on two separate days after an overnight fast. Measurements were obtained twice before and then repeatedly at various times up to three hours after inhalation of ten albuterol doses (total dose approximately 1 mg) delivered by MDI. On either day the patient did, or did not, rinse the mouth and gargle after drug inhalation. Aerosol-administered albuterol significantly increased HR, FEV1, systolic BP and serum concentrations of glucose and insulin and lowered diastolic BP as early as five min after inhalation, indicating early systemic drug absorption. Peak changes in all measured parameters were observed within 30 min after treatment. Mouth rinsing and gargling removed 24 +/- 11 percent of the total albuterol dose delivered, but did not lower the magnitude or shift the time course of these side effects or bronchodilation. Our data suggest that cardiovascular and metabolic side effects are associated with the inhalation of an increased dose of albuterol and that mouth rinsing and gargling are not effective in reducing the magnitude of these systemic effects.

The effect of sleep loss on breathing in chronic obstructive pulmonary disease.

We have previously shown that one night of sleep deprivation results in significant deterioration of spirometric performance and ventilatory responsiveness to inhaled carbon dioxide in normal people. Since even a small decrease in pulmonary function may be clinically important in patients with chronic limitation of airflow, we undertook the present study to assess the effects of sleep loss on breathing in patients with chronic obstructive pulmonary disease (COPD). Criteria for inclusion in this study were a ratio of the forced expiratory volume in one second over the forced vital capacity (FEV1/FVC) of less than 60 percent, no hospital admission for pulmonary disease within two weeks of testing, stable (less than 30 percent variation) in tests of pulmonary function on two occasions within three months of testing, and no history of asthma. We studied 15 men (mean age, 57 +/- 3 years) on two consecutive mornings. Patients were studied with and without sleep deprivation in a randomized fashion. Patients were hospitalized for the study so that sleep deprivation, medications, smoking, and diet could be monitored and enforced. We found small but statistically significant falls in FEV1 (1.06 +/- 0.11 to 1.00 +/- 0.09 L; p less than 0.05) and in FVC (2.56 +/- 0.20 to 2.43 +/- 0.17 L; p less than 0.05) following sleep deprivation. Changes of similar magnitude which were not statistically significant occurred in maximal voluntary ventilation (MVV) and response to carbon dioxide. The arterial oxygen (PaO2) and carbon dioxide (PaCO2) tensions were not affected. Maximal expiratory pressure at the mouth increased slightly, but there was a fall in maximal inspiratory pressure (MIP) at the mouth. We conclude that sleep loss is associated with small but significant falls in FEV1 and FVC, as well as changes of similar magnitude in MVV, minute ventilation, and MIP in patients with severe COPD. Although the sleep loss which frequently accompanies exacerbations of COPD may be a slight additional stress of pulmonary reserve, a single night's loss of sleep in the patient with stable chronic airflow obstruction does not have major clinical consequences.

The effects of hypoxemia on cardiac output. A dose-response curve.

To establish a dose-response curve for the effects of isocapnic hypoxemia on cardiac output (CO), we studied 20 healthy men, aged 20 to 34 years, using a tight-fitting face mask and an isocapnic partial rebreathing system (a modified anesthesia machine). We blended oxygen and hypoxic gas to achieve arterial oxygen saturations (SaO2) of 80, 85, and 90 percent; subjects also breathed 100 percent oxygen and room air (RA). Target SaO2 and end-tidal carbon dioxide were continuously monitored using an ear oximeter and CO2 gas analyzer. Subjects experienced the five SaO2 measurements in random order. CO was measured noninvasively at approximately two-minute intervals, using continuous-wave Doppler echocardiography. Mean cardiac output increased with increasing hypoxemia from 6.84 L/min at FIo2 1.0 to 8.44 L/min at SaO2 80 percent (p less than 0.0005); the increase was entirely due to increased heart rate. We concluded that cardiac output increases significantly in a dose-response manner in response to acute isocapnic hypoxemia in normal persons.

Effect of sleep position on sleep apnea and parafunctional activity.

Parafunctional activity (toothgrinding, toothclenching and bruxism) is a common problem which may lead to masticatory muscle and temporomandibular joint pain, and may result from sleep arousal or disturbances. Sleep apnea is another common sleep disorder which results in disrupted sleep architecture and frequent arousals. Because sleep apnea leads to sleep arousals, and because sleep arousals are thought to result in increased parafunctional activity, we undertook the present study to determine the relationship between sleep apnea and parafunctional activity. We were also interested in assessing the effects of sleep posture on sleep disordered breathing and parafunctional activity. We prospectively studied 24 patients who were referred to the clinical sleep apnea laboratory for study. They underwent standard nocturnal polysomnographic examination; in addition, masticatory activity was measured with a masseter electromyogram. Patients slept in the supine and lateral decubitus positions. Nocturnal clenching was slightly higher in patients with sleep apnea than those without (12.2 vs 7.6 clenches/hr, p = 0.18), and there was a correlation between the clench index (CI) and apnea plus hypopnea index (A + HI) by linear regression (r = 0.49, p less than 0.05). There were significant falls in both the A + HI (64.4 +/- 28.8 vs 36.5 +/- 36.7, p = 0.02) and CI (12.5 +/- 12.1 vs 7.0 +/- 8.6, p = 0.04) in the lateral decubitus vs supine sleeping positions. We conclude that there is an association between obstructive sleep apnea and parafunctional activity, that sleep position affects the incidence of both sleep disordered breathing and parafunctional activity, and that analysis of apneas and hypopneas in both supine and lateral decubitus sleeping positions may be helpful.

Sleep-disordered breathing in healthy, aged persons. Fifth and final year follow-up.

The frequency of sleep-disordered breathing (SDB) events increases dramatically with age, although the clinical significance of this phenomenon is uncertain. We report herein on data from the fifth follow-up observation of a cohort of healthy elderly which we selected, evaluated, and followed up in an effort to address this issue. Baseline observations on this group of 95 normal older persons medically screened for good health included standard nocturnal polysomnograms and daytime assessment of medical, sleep/wake, and psychological variables. At fifth-year follow-up, 42 subjects returned for assessment. Comparison of returning vs nonreturning subjects indicated no significant differences in baseline characteristics between these groups. Division of returning subjects into moderate (apnea-hypopnea index [AHI] > or = 5) vs low (AHI < 5) SDB at baseline resulted in 10 subjects in the moderate group and 32 subjects in the low group. The two groups were comparable with regard to sex, weight, and education, although the moderate SDB group was significantly older (70.4 years) than the low SDB group (64.8 years). Follow-up medical, sleep/wake, and psychological data were contrasted for the two groups using a mixed design multivariate analysis of variance (repeated measures factor-time-6 observations; between-subjects factor SDB level, 2 groups). There were no statistically significant effects of SDB or interactions of SDB and time across this 5-year follow-up. These results confirm observations from the third-year follow-up. We conclude that observation of a moderate level of SDB in an otherwise healthy older person is apparently not a significant risk across a 5-year follow-up period and therefore does not seem to warrant investigation beyond a thorough medical history and physical examination to rule out other disorders.

What is hypopnea, anyway?

Quantitation of apneas and hypopneas is routinely included in studies of epidemiology, diagnosis, and treatment of sleep-disordered breathing (SDB). The definition of apnea appears clear-cut in the sleep literature. In contrast, the literature contains remarkable variety in both recording techniques and definitions of hypopnea. The purpose of this study was to characterize the variety in the definitions and techniques used to identify hypopnea in clinical sleep laboratories. One hundred surveys were mailed to 100 accredited sleep laboratories. Each laboratory was asked to provide its criteria and equipment used to define hypopnea. Forty-five surveys (45 percent) were returned. No two laboratories used the same definition and measures of hypopnea. We conclude that there is no consensus about either recording techniques or definitions of hypopnea. Thus, epidemiologic studies and reports of interventions on SDB that do not include precise definitions of hypopnea must be interpreted with caution.

Efficacy of 1.4 percent sodium citrate in maintaining arterial catheter patency in patients in a medical ICU.

PURPOSE: The primary purpose of this study was to compare the efficacy of 1.4 percent sodium citrate with heparin, 4 U/ml, for maintaining radial artery catheter patency in patients in the medical ICU. PATIENTS AND METHODS: Patients in the medical ICU (n = 40) were randomized to either a 1.4 percent sodium citrate or heparin 4 U/ml arterial line flush solution in a double-blind, parallel fashion. The flush solutions were continuously infused at approximately 3 ml/h over a maximum of 96 h. Catheter survival rates were compared using Kaplan-Meier survival curves. The frequency of catheter malfunctions and corrective manipulations were recorded and compared. Coagulation status (APTT, PT) and ionized calcium values were monitored to evaluate the systemic effects of sodium citrate. RESULTS: Ninety-four percent of catheters flushed with sodium citrate were functional at 48 h compared with 88 percent for heparin (p > 0.05). At 96 h, 80 percent vs 88 percent of the catheters were functional in the citrate and heparin groups, respectively (p > 0.05). Frequency of catheter malfunctions did not differ between the two groups. No systemic effects of sodium citrate were observed. CONCLUSION: Arterial catheter flush solutions containing sodium citrate (1.4 percent) are an effective and safe alternative to heparin in patients requiring peripheral arterial catheterization.

Sleep-disordered breathing in the healthy elderly. Clinically significant?

We evaluated sleep/wake, medical, and psychological parameters in a cohort of healthy men and women between 50 and 80 years of age. Consistent with previous investigations of sleep-disordered breathing (SDB) in older persons, nocturnal breathing disturbances were quite common in our normal-aged subjects, with more than 15 percent experiencing five or more SDB events per hour of sleep. However, when SDB indices were correlated with comprehensive measures of daytime functioning, the number of statistically significant relationships was at or below expectations from chance alone. Additionally, comparison of high-SDB subjects (AHI greater than or equal to 5) with low-SDB subjects (AHI less than 5) failed to reveal reliable differences on measures of daytime functioning. We conclude that SDB occurring in otherwise healthy older persons is not a cause for immediate concern, although longitudinal studies may yet demonstrate significant long-term sequelae of SDB in this population.

Treatment of obstructive sleep apnea. A preliminary report comparing nasal CPAP to nasal oxygen in patients with mild OSA.

Nasal CPAP is presently accepted as first-line therapy for obstructive sleep apnea, but a significant minority of patients do not tolerate nasal CPAP. The purpose of this study was to compare the benefits of nasal CPAP, nasal oxygen (O2), and placebo (air) using patients as their own controls. We studied eight men, aged 33 to 72 (mean 57 years), who had mild obstructive sleep apnea. To be eligible for study, patients had to have an apnea plus hypopnea index greater than or equal to 5, plus one or more of the following: blood pressure greater than 150/95 mm Hg, multiple sleep latency test mean score less than or equal to 10 minutes, or significant nocturnal cardiac ectopy. After a baseline study, patients received a month each of nocturnal O2 at 4 LPM and air at 4 LPM, presented in random order. The third month of treatment consisted of nasal CPAP (range 2.5 to 12.5 cm H2O). Patients underwent evaluation at baseline and after each month of treatment. It was concluded that oxygen was more effective in improving oxygenation and hypopneas than is nasal CPAP. However, oxygen did not reduce apneas or improve daytime hypersomnolence as well as nasal CPAP in patients with mild OSA. Oxygen might be considered as an alternate form of treatment for patients who are not hypersomnolent, or as an adjunct to nasal CPAP.

The acute effects of the enkephalin analogue BW 942C in humans.

BW 942C hydrochloride is an enkephalin analogue that has exhibited a wide separation between antidiarrheal dosages and dosages inducing adverse effects in animals. This has likewise been the case in humans when administered orally. In this study, the safety and tolerance of single 0.5-mg doses of intravenous BW 942C compared with placebo were assessed in humans. Four healthy male volunteers received BW 942C, and two received placebo. The effects of BW 942C on serum growth hormone (GH), luteinizing hormone (LH), prolactin (PR), and follicle-stimulating hormone (FSH) were assessed in three of these volunteers. No significant changes were apparent in vital signs, in clinical chemistry, hematologic and urine studies following BW 942C administration. BW 942C did not appear to alter mood as assessed by two psychologic mood scales. Prolactin levels tended to increase in volunteers receiving BW 942C two hours postinfusion. Luteinizing hormone concentrations decreased slightly at two and six hours. No trends in FSH or GH could be identified. Pulmonary function testing did not reveal any significant changes in oximetry, spirometry, or plethysmography in any of the subjects. A marked decrease in CO2 responsiveness in two subjects may indicate that BW 942C has mild ventilatory depressant effects. Untoward effects experienced in volunteers receiving BW 942C included heaviness in the limbs, nasal stuffiness, mouth dryness, facial flushing, skin rash, and prickling sensations. These effects bear a striking similarity to those experienced after parenteral administration of other enkephalin analogues. Intravenous administration of BW 942C up to 0.5 mg appears safe from a laboratory, physiologic, and clinical perspective with unusual untoward effects that may preclude rational use of the drug by the parenteral route.

Idiopathic inflammatory myopathies: optimum immunosuppressive treatment.

The idiopathic inflammatory myopathies include polymyositis and dermatomyositis, which tend to be responsive to drug therapy, and inclusion body myositis, which is often unresponsive or only partially responsive to drugs. Corticosteroids are considered the first line treatment of these disorders, and as well as being anti-inflammatory are immunosuppressive when used at dosages above prednisolone 20 mg/day or equivalent. In those patients who are refractory to corticosteroids, or are prone to develop complications from corticosteroids, second line drugs such as methotrexate, azathioprine or intravenous immunoglobulin should be introduced. These therapies tend to be slow acting, but response often occurs in 4 to 6 weeks and allows the dosage of corticosteroid to be reduced more rapidly. In those occasional patients with inflammatory myopathies that are refractory to corticosteroids and second line agents, one should consider adding in a third line agent such as cyclosporin, chlorambucil or cyclophosphamide. Although most clinicians would use these immunosuppressive drugs singly in combination with corticosteroids, multiple drug therapy should be considered in severe refractory cases.

Influence of the cardioprotective agent dexrazoxane on doxorubicin pharmacokinetics in the dog.

The influence of dexrazoxane on doxorubicin pharmacokinetics was investigated in four dogs using the two treatment sequences of saline/doxorubicin or dexrazoxane/doxorubicin. Intravenous doses of 1.5 mg/kg doxorubicin and 30 mg/kg (the 20-fold multiple) dexrazoxane were given separately, with doxorubicin being injected within 1 min of the dexrazoxane dose. Both doxorubicin and its 13-dihydro metabolite doxorubicinol were quantified in plasma and urine using a validated high-performance liquid chromatographic (HPLC) fluorescence assay. The doxorubicin plasma concentration versus time data were adequately fit by a three-compartment model. The mean half-lives calculated for the fast and slow distributive and terminal elimination phases in the saline/doxorubicin group were 3.0 +/- 0.5 and 32.2 +/- 12.8 min and 30.0 +/- 4.0 h, respectively. The model-predicted plasma concentrations were virtually identical for the saline and dexrazoxane treatment groups. Analysis of variance of the area under the plasma concentration-time curve (AUCo-infinity), terminal elimination rate (lambda z), systemic clearance (CLs), and renal clearance (CLr) for the parent drug showed no statistically significant difference (P greater than 0.05) between the two treatments. Furthermore, the doxorubicinol plasma AUCo-t value and the doxorubicinol-to-doxorubicin AUCo-t ratio showed no significant difference, demonstrating that dexrazoxane had no effect on the metabolic capacity for formation of the 13-dihydro metabolite. The total urinary excretion measured as parent drug plus doxorubicinol and the metabolite-to-parent ratio in urine were also unaffected by the presence of dexrazoxane. The myelosuppressive effects of doxorubicin as determined by WBC monitoring revealed no apparent difference between the two treatments. In conclusion, these results show that drug exposure was similar for the two treatment arms. No kinetic interaction with dexrazoxane suggests that its coadministration is unlikely to modify the safety and/or efficacy of doxorubicin.