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Biomedical subjects

C F George

Publications and source records attributed to C F George.

At least 37 records · Page 2Linked to original sources
PubMed1996

Standards for polysomnography in Canada. The Standards Committees of the Canadian Sleep Society and the Canadian Thoracic Society.

OBJECTIVE: To develop standards for polysomnography in Canada in order to assist in the uniform provision of diagnostic and therapeutic services related to sleep disorders. OPTIONS: Uniform testing versus no current Canadian standards. OUTCOMES: Uniform delivery of health care; reduction in number of repeat studies and their attendant costs. EVIDENCE: Availability of diagnostic laboratories and services, and survey responses (written and oral) from directors of sleep laboratories; the American Thoracic Society statement on indications and standards for cardiopulmonary sleep studies was used as a template. VALUES: Acceptable standards of practice were based on consensus opinion of the standards committees of the Canadian Sleep Society and the Canadian Thoracic Society. The committees comprised specialists in neurology, psychiatry, psychology, respirology and polysomnographic technology; family practitioners and otolaryngologists were also consulted. BENEFITS, HARMS, COSTS: Improved level of care and reduction in duplicate or unnecessary testing; establishment, with available resources, of diagnostic sleep laboratories by appropriately qualified physicians in areas where polysomnography is unavailable. RECOMMENDATIONS: Health care practitioners involved in the diagnosis and treatment of sleep disorders should possess a minimum amount of training (both clinical and research) in sleep disorders medicine. The variables recorded and findings entered in a patient's report must be relevant to the sleep disorder under investigation. The recording equipment must provide reliable, accurate and reproducible data and lend itself to appropriate calibration and quality-control procedures. Facilities for sleep studies must meet patient care safety standards, with provisions for emergency or resuscitative measures when necessary; all personnel must be trained in basic cardiopulmonary resuscitation. VALIDATION: No previous standards concerning polysomnography in Canada exist. The recommended standards were reviewed by all members of the Canadian Sleep Society and a revised document was approved by the Standards Committee of the Canadian Sleep Society and by the Standards and Executive committees of the Canadian Thoracic Society. SPONSORS: These standards are endorsed by the Canadian Sleep Society and the Canadian Thoracic Society. The cost of preparing this statement was borne by the individual members of the standards committees; no external funding was provided.

Calibration↗
PubMed1996

IgH (mu-switch and gamma-1) region restriction fragment length polymorphism in human narcolepsy.

Predisposition to narcolepsy involves genetic factors both in humans and in a canine model of the disorder. In humans, narcolepsy is strongly associated with HLA DR15 and DQB1*0602. In Dobermans and Labradors, narcolepsy is transmitted as a single autosomal recessive gene with full penetrance (canarc-1). Canine narcolepsy is not linked with DLA, the canine equivalent of HLA, but co-segregates with a DNA segment with high homology with the mu immunoglobulin heavy-chain (IgH) switch-like region (S mu). To determine if the IgH locus is involved in genetic predisposition to human narcolepsy, restriction fragment length polymorphisms specific for the IgM and IgG cluster within this locus were studied in sporadic cases of the disease, as well as in five families with two or more affected individuals. Comparisons were made between control populations and both familial and sporadic cases and for patients with and without HLA-DR15 and DQB1*0602. RFLP analysis at the S mu and gamma-1 loci, which cover over 200 kb of 14q32.3, indicates that there is no evidence for any association between the IgH region and human narcolepsy.

Aged↗
PubMed1996

Central and peripheral respiratory electrophysiological studies in myotonic dystrophy.

Acute and chronic respiratory failure is a common and potentially life-threatening feature in patients with myotonic dystrophy (MD). The causes may be varied, and can involve both the central and peripheral nervous system. To evaluate the incidence of respiratory muscle involvement and the function of the central motor inspiratory pathway to phrenic motor neurons we performed magnetic stimulation of the cortex and cervical spinal cord, phrenic nerve conduction studies and needle EMG of diaphragm and intercostal muscles in 25 patients with MD. The results were compared with those from 35 healthy subjects. In addition, pulmonary function tests, blood gas analyses and static mouth pressures were evaluated. Abnormalities in response to magnetic stimulation, including a reduced compound muscle action potential (CMAP) from the diaphragm and increased excitability threshold, indicated impaired central inspiratory drive in 20% of cases. Phrenic nerve conduction showed a reduced diaphragmatic CMAP amplitude in 20%, and a delayed negative peak onset latency in 4% of cases. Abnormalities in diaphragm and intercostal muscle needle EMG were found in 76% of cases, these were mainly myotonic discharges (68%) and a decrease in the number of active motor units (36%). Patients with abnormal respiratory electrophysiological parameters had a significantly lower functional vital capacity (FVC; P = 0.005). The duration of the disease correlated negatively with diaphragmatic CMAP amplitude to phrenic nerve, but not magnetic, stimulation. Our results demonstrate that the involvement of the central inspiratory pathway is common in MD patients. Central and peripheral electrophysiological studies of the diaphragm should be considered in the diagnosis and management of patients with MD and dyspnoea.

Adult↗
PubMed1996

Pharmacokinetics.

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Administration, Oral↗
PubMed1996

Comparison of simulated driving performance in narcolepsy and sleep apnea patients.

Many patients with obstructive sleep apnea (OSA) or narcolepsy have difficulty driving and increased automobile accidents. Previously we have shown that OSA patients perform poorly on a laboratory-based divided-attention driving test (DADT). Patients with narcolepsy may be as sleepy as OSA patients, so we compared performance on the DADT of OSA patients with that of narcolepsy patients. Twenty-one male OSA patients [age 49.3 +/- 12.7 (SD) years; apnea-hypopnea index (AHI) 73 +/- 29] 21 age- and sex-matched controls, and 16 narcoleptics (12 males, four females; age 39.6 +/- 15.2 years) underwent polysomnography followed by daytime sleep latency testing (MSLT). Following a practice session, all subjects were given the DADT for 20 minute prior to each daytime nap of the MSLT. Narcolepsy patients were younger than OSA or controls and more sleepy than OSA patients. Tracking error was much worse in patients than controls (228 +/- 145 cm for OSA vs. 196 +/- 146 for narcolepsy vs. 71 +/- 31 for controls; p < 0.001), although half of either patient group performed as well as controls. There was only a weak relationship between MSLT and tracking in either patient group. We conclude that impairment in laboratory driving performance skills is seen in both groups of sleepy patients but the degree of impairment is difficult to predict from sleepiness alone.

Accidents, Traffic↗
PubMed1996

Simulated driving performance in patients with obstructive sleep apnea.

To assist in determining ability to drive in patients with obstructive sleep apnea (OSA), we developed a divided attention driving test (DADT) based on the work of Moskowitz and Burns (6). We first examined its ability to detect impaired performance by testing normal subjects both sober and impaired by alcohol (mean blood alcohol level, 95 +/- 25 mg/dl). Subsequently, 21 male patients with OSA (age 49.3 +/- 12.7 [SD] yr; apnea hypopnea index [AHI] 73 +/- 29) and 21 age- and sex-matched control subjects underwent polysomnography followed by daytime sleep latency testing (MSLT). Before each day-time nap, subjects were given the DADT for 20 min. Patients who performed much worse than control subjects in all measures, with the largest difference noted in tracking error (OSA, 228 +/- 145 cm versus control 71 +/- 31 cm, p < 1 x 10(-9)). Half of the patients were worse than any control subject, with some showing performance worse than control subjects impaired by alcohol. However, MSLT and AHI explained less than 25% of the variance in tracking error, making individual prediction problematic. We concluded that in laboratory driving performance skills are markedly impaired in over half our group with sleep apnea. Further testing and comparing on-road performance should aid in predicting ability to drive.

Adult↗
PubMed1996

Sleep-disordered breathing in amyotrophic lateral sclerosis.

OBJECTIVE: The purpose of this study was to assess sleep and breathing in patients with amyotrophic lateral sclerosis (ALS) with bulbar muscle involvement. DESIGN: Prospective, controlled study of sleep and breathing measured during polysomnography. SETTING: University teaching hospital and referral center. PATIENTS: Patients with definite ALS and healthy age-matched control subjects. INTERVENTIONS: Eighteen ALS patients and 10 age-matched control subjects underwent one night of polysomnography. Thirteen patients with ALS were studied for a second night. RESULTS: The ALS patients had more arousals per hour (p = 0.008), more stage 1 sleep (p = 0.01), and a shorter total sleep time (TST) (279 +/- 69 vs 331.4 +/- 55.9 min, mean +/- SD, p = 0.04) than the control subjects. The ALS patients had mild sleep-disordered breathing with a greater apnea/hypopnea index (AHI) than the control subjects (p = 0.005). On the second night of polysomnography, there was an increase in TST (p = 0.003) and rapid eye movement (REM) sleep (p = 0.009), an improvement in sleep efficiency (p = 0.02), and less stage 1 sleep (p = 0.04). Eight ALS patients had sleep-disordered breathing consisting of periods of hypoventilation, predominantly during REM sleep. CONCLUSIONS: Sleep-disordered breathing occurs in patients with ALS and is similar to patients without ALS with respiratory muscle weakness. No obstructive sleep apnea was observed. One potential reason for its absence might be the inability of patients with respiratory muscle weakness to generate an inspiratory pressure greater than the upper airway closing pressure. This hypothesis should be addressed in future studies.

Aged↗
PubMed1996

Medicine taking in Southampton: a second look.

1. A 1 in 200 sample of the Southampton electorate were sent a postal questionnaire in January 1993. Of the 756 adults surveyed, 400 (52.9%) returned completed questionnaires. One hundred and eighty-eight (47.0%) of the respondents had been prescribed a medicine within the previous month. 2. Compared with a survey 9 years earlier, medicine taking had increased amongst men (44.1% vs 33.7% NS) and drugs acting on the respiratory system were in more widespread use (19 vs 7 patients P < 0.05). 3. Patterns of storage of medicines were almost identical to those found in 1984. However, methods of disposal were significantly different with 34% of the respondents stating that they would return left-over medicines to the Doctor or Pharmacist compared with 17% in the previous study (P < 0.01). 4. Of those taking medicines 120 (63.8%) had received a manufacturers' information leaflet. Medicines used to treat disorders of the respiratory and cardiovascular systems were most likely to be accompanied by such a leaflet (74% and 70% respectively). 5. Those who received a leaflet were almost all satisfied by it. However, patient awareness of potential side effects remained poor with only 30% being aware of any which their medicine might cause. 6. Despite improvements in attitudes towards medicine taking over time patients awareness of potential adverse effects remains limited. Further research is necessary in order to determine how best to educate patients on this topic.

Adolescent↗
PubMed1995

Factors affecting the absolute bioavailability of nifedipine.

1. Nifedipine was administered to eight volunteers (seven Caucasian, one East Asian of Chinese origin) as a single 10 mg capsule orally and as 2.5 mg intravenously. The pharmacokinetics were determined under fasting conditions and following 200 ml double strength grapefruit juice taken orally both 2 h before and at the time of dosing. 2. In a separate study, the pharmacokinetics of nifedipine were defined in eight South Asian volunteers (with both parents originating from the Indian subcontinent) following 10 mg nifedipine orally and 2.5 mg intravenously. 3. The administration of grapefruit juice did not alter the pharmacokinetics of intravenous nifedipine, but resulted in a significantly increased area under the plasma concentration-time curve (AUC) (191 +/- 59 c.f. 301 +/- 95 ng ml-1 h, P < 0.05) and bioavailability (0.63 +/- 0.18 c.f. 0.86 +/- 0.15, P < 0.05) following oral nifedipine. The elimination half-life was unchanged by administration of grapefruit juice and there was no evidence of decreased formation of the nitropyridine first-pass metabolite. 4. The AUC of nifedipine after intravenous administration was significantly higher in South Asian subjects than in Caucasians (146 +/- 39 c.f. 74 +/- 18 ng ml-1 h, P < 0.002). This was due to a lower systemic clearance in the South Asians which was 50% of that in the Caucasians. The half-life was markedly prolonged in South Asians (4.1 +/- 1.9 c.f. 1.7 +/- 0.5 h, P < 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

The teratogenic metabolites of vitamin A in women following supplements and liver.

Ten healthy female volunteers were given 5 doses of retinol as the palmitate; 50 and 150 mg retinol as an oral supplement, 50 and 150 mg as fried calf liver (50 and 150 g) and 3, 9 or 30 mg by intra-muscular injection. Plasma concentrations of retinyl palmitate were higher after 50 mg retinol given as an oral supplement compared with 50 mg as liver; there was no significant difference between the 150 mg doses. Plasma concentrations of retinol showed only small increases. The peak plasma concentrations (Cmax) of all-transretinoic acid, the principal teratogenic metabolite of retinol, and the area under the concentration-time curve (AUC) were up to 20-times higher after supplements compared to the same dose as liver. Plasma concentrations of all-trans-4-oxo-retinoic acid, 13-cis-retinoic acid and 13-cis-4-oxo-retinoic acid showed smaller differences between supplements and liver. Intra-muscular administration of 30 mg retinol gave retinyl palmitate concentrations similar to those found after the oral doses but did not increase circulating concentrations of the acid metabolites. Based on the formation of all-trans-retinoic acid, liver and supplements are not of equivalent teratogenic potential. Advice to pregnant women on the consumption of liver based on the reported teratogenicity of vitamin A supplements should be reconsidered.

Administration, Oral↗
PubMed1994

The clinical effects and cost-avoidance of a change in perioperative bronchodilator use.

The clinical effects and financial impact of a change in prescribing habits from routine to occasional use of perioperative bronchodilators, following the presentation of drug information, were assessed retrospectively by comparing the outcomes of patients admitted for major thoracic surgery. Eighteen of 24 (75%) patients in Period A (prior to change) received salbutamol bronchodilator therapy versus 10 of 17 (59%) in Period B (following the change) (p = .448). Of the patients who did receive salbutamol aerosols, the mean dose in grams per patient was greater in Period A than in Period B (6.85 +/- 5.96 vs. 2.64 +/- 4.44 respectively p < 0.05). Two patients from Period A and one from Period B were receiving digoxin prior to admission. In the remaining patients, 5 of 22 (23%) in Period A and 1 of 16 (6%) in Period B developed atrial fibrillation requiring digoxin (p = .36). The proportion of patients with obstructive airways disease (OAD) who developed an arrhythmia was not different between the two groups. However, in those patients without OAD an arrhythmia was reported in 9 of 16 patients (56%) receiving salbutamol, versus only 1 of 11 (9%) of those not receiving it (p = 0.032). The number of days patients were hospitalized during Period A and Period B were 10.2 +/- 4.97 and 9.4 +/- 3.68 respectively (p = 0.85). A potential average cost-avoidance of $68.46 per patient could be realized with this new practice. We conclude that a change in prescribing habits had no adverse clinical outcome and resulted in a considerable cost-avoidance.

Aerosols↗
PubMed1993

The influence of dose and ethnic origins on the pharmacokinetics of nifedipine.

The pharmacokinetics of nifedipine capsules was investigated in healthy young Caucasian and South Asian subjects. Both the area under the plasma concentration-time curve (AUC) and terminal half-life of nifedipine were significantly higher in South Asians compared with Caucasian subjects after single oral doses of 10 and 20 mg. The AUC and half-life values of the nitropyridine metabolite were also higher in South Asians than in Caucasian subjects. The serum protein binding of nifedipine was similar in the two groups. The pharmacokinetics were essentially linear in both Caucasian subjects (0 to 30 mg; n = 27) and South Asians (0 to 20 mg; n = 16). There was no indication of a separate subgroup of Caucasian subjects with high AUC values equivalent to the poor metabolizers reported previously. Pharmacodynamic modeling for South Asians gave estimates comparable to those previously reported in Caucasian subjects. Patients of South Asian origin may require lower doses of nifedipine.

Adult↗
PubMed1993

Effects of zolpidem and triazolam on sleep and respiration in mild to moderate chronic obstructive pulmonary disease.

Sleep problems and nocturnal arterial oxygen desaturation are common in patients with chronic obstructive pulmonary disease (COPD). Hence, the safety and efficacy of new hypnotic agents must be ascertained in this group of patients. We performed a double-blind, randomized, single-dose, placebo and active drug controlled, crossover study in 24 patients with insomnia (subjective sleep latency > 30 minutes and sleep duration 4-6 hours) and mild to moderate COPD (mean FEV1 61 +/- 12(SD)% predicted) in order to establish the effects of zolpidem 5 mg and 10 mg on sleep and respiration and to compare these effects with triazolam 0.25 mg. Arterial oxygen saturation for the entire night, by hour and stage, and the apnea-hypopnea index for the entire night were not significantly different with placebo and the various drug conditions. Total sleep time and sleep efficiency were increased over placebo by all three drug conditions. Triazolam was more effective than zolpidem 5 mg but not zolpidem 10 mg, and there was no significant difference between zolpidem 5 mg and zolpidem 10 mg. Zolpidem 10 mg and triazolam both reduced the number of awakenings (> 15 seconds duration) per hour of sleep. Although there was a trend for triazolam to be more efficacious than zolpidem 10 mg, no statistically significant difference was found for any objective or subjective sleep variable. Likewise, zolpidem 10 mg tended to be more efficacious than zolpidem 5 mg, but the difference was only significant in terms of perceived sleep quality and ease of falling asleep.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗