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Biomedical subjects

L C Johnson

Publications and source records attributed to L C Johnson.

At least 19 recordsLinked to original sources
PubMed1994

Evaluation of the potent anti-hepatitis B virus agent (-) cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine in a novel in vivo model.

A murine model was developed to investigate the in vivo activity of anti-hepatitis B virus (HBV) agents. Mice with subcutaneous tumors of HBV-producing 2.2.15 cells showed reductions in levels of HBV in serum and in intracellular levels of HBV when the mice were orally dosed with (-) cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (FTC). No effects on tumor size or alpha-fetoprotein levels were observed. FTC can selectively inhibit HBV replication at nontoxic doses.

Animals↗
PubMed1991

Cardiovascular responses and electroencephalogram disturbances to intermittent noises: effects of nocturnal heat and daytime exposure.

During sleep, in thermoneutral conditions, the noise of a passing vehicle induces a biphasic cardiac response, a transient peripheral vasoconstriction and sleep disturbances. The present study was performed to determine whether or not the physiological responses were modified in a hot environment or after daytime exposure to both heat and noise. Eight young men were exposed to a nocturnal thermoneutral (20 degrees C) or hot (35 degrees C) environment disturbed by traffic noise. During the night, the peak intensities were of 71 dB(A) for trucks, 67 dB(A) for motorbikes and 64 dB(A) for cars. The background noise level (pink noise) was set at 30 dB(A). The noises were randomly distributed at a rate of 9.h-1. Nights were equally preceded by daytime exposure to combined heat and noise or to no disturbance. During the day, the noises as well as the background noise levels were increased by 15 dB(A) and the rate was 48.h-1. Electroencephalogram (EEG) measures of sleep, electrocardiograms and finger pulse amplitudes were continuously recorded. Regardless of the day condition, when compared with undisturbed nights, the nocturnal increase in the level of heart rate induced by heat exposure disappeared when noise was added. Percentages, delays, magnitudes and costs of cardiac and vascular responses as well as EEG events such as transient activation phases (TAP) due to noise were not affected by nocturnal thermal load or by the preceding daytime exposure to disturbances.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Relative and combined effects of heat and noise exposure on sleep in humans.

In a counter-balanced design, the effects of daytime and/or nighttime exposure to heat and/or traffic noise on night sleep were studied in eight healthy young men. During the day, the subjects were exposed to baseline condition (ambient temperature = 20 degrees C; no noise) or to both heat (35 degrees C) and noise. The duration of the daytime exposure was 8 h ending 5 h before sleep onset. The following nights, the subjects slept either in undisturbed (20 degrees C; no noise) or in noise, heat, or noise plus heat-disturbed environments. During the day, the various types of traffic noise were distributed at a rate of 48/h with peak intensities ranging between 79 and 86 dB(A). The background noise level was at 45 dB(A). At night, the peak intensities were reduced by 15 dB(A), the rate was diminished to 9/h, and the background noise was at 30 dB(A). Electrophysiological measures of sleep and esophageal and mean skin temperatures were continuously recorded. The results showed that both objective and subjective measures of sleep were more disturbed by heat than by noise. The thermal load had a larger impact on sleep quality than on sleep architecture. In the nocturnal hot condition, total sleep time decreased while duration of wakefulness, number of sleep stage changes, stage 1 episodes, number of awakenings, and transitions toward waking increased. An increase in the frequency of transient activation phases was also found in slow-wave sleep and in stage 2. In the nocturnal noise condition, only total number of sleep stage changes, changes to waking, and number of stage 1 episodes increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Subjective and objective measures of sleepiness: effect of benzodiazepine and caffeine on their relationship.

As part of a larger project on the effects of benzodiazepine and caffeine on daytime sleepiness, performance and mood, this study examined the relationship among the Multiple Sleep Latency Test, lapses during a tapping task, a Visual Analog Scale, and the Stanford Sleepiness scale. Subjects were 80 male, adult nonsmokers aged 20.3 +/- 2.7 years. The Multiple Sleep Latency Test, Stanford Sleepiness Scale, and the Visual Analog Scale were obtained at two-hour intervals beginning at 0700 h and ending at 1700 h. The tapping task (lapses) was administered each day at 0600 h, 1000 h, and 1400 h. A lapse was a 3-s or greater pause between taps. Correlations between the Multiple Sleep Latency Test and subjective (Visual Analog Scale and the Stanford Sleepiness Scale) measures were significant at 0600 h, but became nonsignificant as the day progressed. Correlations between lapses and the two subjective measures were generally nonsignificant. The two objective measures were significantly correlated in the total group but not in all treatment groups. The subjective measures were significantly correlated in the total sample and in each treatment group. This study reaffirms the importance of time of day when measuring sleepiness, and suggests that subjective and objective measures may measure different aspects of sleepiness.

Adult↗
PubMed1990

Benzodiazepines and caffeine: effect on daytime sleepiness, performance, and mood.

In a double-blind parallel group design, 80 young adult males were divided into eight treatment groups. Subjects received 15 or 30 mg flurazepam, 0.25 or 0.50 mg triazolam, or placebo at bedtime, and 250 mg caffeine or placebo in the morning for 2 treatment days. Two objective (Multiple Sleep Latency Test and lapses) and two subjective (Stanford Sleepiness Scale and Visual Analog Scale) measures of sleepiness, five performance tests, and two mood measures (Profile of Mood Scale and Visual Analog Mood Scale) were administered repeatedly on both days. Significant treatment effects were found for sleepiness but not for performance or mood. Early morning caffeine significantly antagonized next day hypnotic-induced drowsiness and enhanced alertness in the subjects who received bed-time placebo. Flurazepam, 30 mg, subjects were more sleepy than all other groups. Although not significantly different, the flurazepam, 30 mg, group demonstrated a trend toward poorer performance and a more negative mood than all other groups. Caffeine most improved performance of this group. In all groups, sleepiness was greatest and performance and mood poorest in early morning trials and caffeine was most effective at this time.

Adult↗
PubMed1990

Comparison of DuP 996, with physostigmine, THA and 3,4-DAP on hypoxia-induced amnesia in rats.

DuP 996, 3,3-bis(4-pyrindinylmethyl)-1-phenylindolin-2-one, physostigmine (PH), tetrahydroaminoacridine (THA) and 3,4-diaminopyridine (3,4-DAP) were compared for their ability to protect against hypoxia-induced performance deficits in a passive avoidance (PA) task. The ability to retain PA response was found to decrease as the oxygen concentration decreased with the largest retention deficit occurring at 6.5% oxygen. DuP 996 (0.01-0.1 mg/kg SC), 3,4-DAP (0.1-10.0 mg/kg SC), THA (0.3-5.0 mg/kg SC) and PH (0.001-0.1 mg/kg SC) administered one minute after PA training produced dose-dependent increases in retention latencies following exposure to 6.5% oxygen. In comparing each compound for side effects, DuP 996 induced tremor and mortality at 10 and 40 mg/kg SC, respectively, and PH at 0.3 and 0.8 mg/kg SC, respectively. With PH the 0.3 mg/kg SC dose also produced hypersalivation and a decrease in lift strength. THA produced tremor and mortality at 6.0 and 40 mg/kg SC, respectively, and 3,4-DAP at 50 and 200 mg/kg SC, respectively. 3,4-DAP also produced chromodacryorrhea and hypersalivation at 50 mg/kg SC. Dividing the dose necessary to produce mortality by the highest effective dose active in the hypoxia test yielded a safety ratio for DuP 996 of 400, for 3,4-DAP 20, for PH 8, and for THA 8, showing a greater safety margin for DuP 996 than the other cholinergic agents. These results suggest that DuP 996 may be of use in the treatment of diseases associated with cognitive impairment and may have a greater safety margin than other cholinergic agents.

4-Aminopyridine↗
PubMed1990

Daytime sleepiness, performance, mood, nocturnal sleep: the effect of benzodiazepine and caffeine on their relationship.

The present study was part of a larger 3-day, 2-night double-blind parallel group design in which 80 young adult men were divided into eight treatment groups to examine the effects of benzodiazepines and caffeine on nocturnal sleep and daytime sleepiness, performance, and mood. The present study was done to examine further the relationship among daytime sleepiness, performance, mood, and nocturnal sleep and to determine if and how these relationships were affected by the nighttime use of benzodiazepine and the ingestion of caffeine in the morning. Subjects received 15 or 30 mg of flurazepam, 0.25 or 0.50 mg of triazolam, or placebo at bedtime and 250 mg of caffeine or placebo in the morning for two treatment days. Two objective (Multiple Sleep Latency Test and lapses) and two subjective (Stanford Sleepiness Scale and Visual Analog Scale) measures of sleepiness, five performance tests, and two mood measures (Profile of Mood Scale and Visual Analog Scale) were administered repeatedly on both days. Electroencephalogram sleep was recorded on both nights. Objective sleep measures of daytime sleepiness were not significantly related to either performance or mood, but subjects with greater daytime sleepiness had significantly longer and more efficient nocturnal sleep. Neither benzodiazepine or caffeine influenced these relationships. In contrast, higher estimates of subjective sleepiness were significantly associated with poorer mood and tended to be related to poorer performance. Caffeine significantly reduced these relationships. Nocturnal sleep measures were not related to subjective estimates of daytime sleepiness.

Adolescent↗
PubMed1990

Sleep, performance, and plasma levels in chronic insomniacs during 14-day use of flurazepam and midazolam: methodology.

Methods are described for a five-center study of flurazepam and midazolam, in which 107 patients with histories of benzodiazepine use for chronic insomnia were enrolled. Data were available for 99 of these patients. Staff and patient manuals and a behavior-based computer system were specially designed to measure and delineate clearly the study procedures and parameters. Patients were carefully followed and supported during a 20-day washout period and underwent extensive training on psychomotor performance tasks. They received placebo for 2 nights and were then randomly assigned to one of four study treatments--flurazepam 15 or 30 mg, midazolam 15 mg, or placebo--for 14 consecutive nights. All-night sleep electroencephalographic recordings were obtained on study nights--1 and 0 (placebo) and 1, 2, 7, 13, and 14 (treatment nights). Results of four computer-generated psychomotor performance tasks and three cognitive tasks, plus subjective evaluations of sleep, performance, and mood, were recorded in the morning after each night spent in the sleep laboratory. Blood and urine samples were analyzed for drug concentrations in plasma and for compliance with the protocol. A pilot study, using a high (nonclinical) dose of flurazepam (45 mg), preceded the multi-center study and was designed to evaluate tests in healthy volunteers and to familiarize staff with equipment and tests.

Adult↗
PubMed1990

Sleep, performance, and plasma levels in chronic insomniacs during 14-day use of flurazepam and midazolam: an introduction.

A review of the published literature reveals many unanswered questions regarding the effects of sedative-hypnotics on sleep, performance, and mood. The relationship between plasma half-life and hypnotic efficacy is also not clear. A randomized, double-blind, parallel-groups, multicenter study was designed to examine sleep, performance, and mood in patients with insomnia. A large, heterogeneous sample of patients with a history of benzodiazepine use for chronic insomnia was chosen to reflect the adult population for which sedative-hypnotics are often prescribed and to ensure statistical reliability. Although the major focus of the current study was on the effects of two benzodiazepine hypnotics on performance, this study also provided information on the following important issues: (1) effect of dose level; (2) short-versus long-term administration; and (3) significance of plasma half-life as it relates to hypnotic efficacy.

Chronic Disease↗
PubMed1989

Physiotherapy after coronary artery surgery: are breathing exercises necessary?

One hundred and ten men undergoing coronary artery bypass grafting took part in a prospective randomised study comparing three physiotherapy protocols. All patients were taught self supported huffing and coughing by a physiotherapist and encouraged to move about. This comprised the sole treatment for the 37 control patients (group 3). Additional physiotherapy included breathing exercises for the 35 patients in group 1 and use of an incentive spirometer for the 38 patients in group 2. Functional residual capacity (FRC) was measured daily at the bedside until the fifth postoperative day and arterial blood gas tensions were measured on the second and fourth postoperative days. After surgery patients developed a severe restrictive ventilatory defect and profound arterial hypoxaemia. There were no differences between the three groups. Mean FRC on day 2 was 1.90 litres (61% of the preoperative value), increasing to 2.32 1 by day 5 (76% of the preoperative value). The mean arterial oxygen tension was 7.37 kPa on day 2 and 8.58 kPa on day 4. Four patients in group 1, two in group 2, and five in group 3 developed a chest infection. It is concluded that the addition of breathing exercises or incentive spirometry to a regimen of early mobilisation and huffing and coughing confers no extra benefit after uncomplicated coronary artery bypass grafting.

Breathing Exercises↗
PubMed1989

Rebound insomnia: a critical review.

Rebound insomnia, a worsening of sleep compared with pretreatment levels, has been reported upon discontinuation of short half-life benzodiazepine hypnotics. This paper reviews the existing sleep laboratory studies for the presence or absence of rebound insomnia following treatment with triazolam, temazepam, and flurazepam in insomniac patients or poor sleepers and, when possible, in normals. The results indicate that rebound insomnia is a distinct possibility after discontinuation of triazolam in both insomniacs and normal controls. Compared with baseline, disturbed sleep was reported in insomniacs or poor sleepers for the first 1 or 2 nights of withdrawal in seven of nine polygraphically recorded sleep studies following triazolam 0.5 mg and in one of two studies following triazolam 0.25 mg. In one study conducted in normal volunteers, rebound insomnia was observed following triazolam 0.5 mg but not triazolam 0.25 mg. In another study, which used subjective reports of sleep rather than polygraphic recordings, rebound insomnia was significantly attenuated after triazolam 0.5 mg by tapering the dose over 4 nights. The risk of rebound insomnia after temazepam 15 or 30 mg was low. In keeping with its long elimination half-life, flurazepam (30 mg) continued to exert beneficial effects for the first 2-3 withdrawal nights, but the possibility of a mild rebound insomnia cannot be dismissed during the intermediate withdrawal period (nights 4-10) following prolonged, consecutive, nightly administration (more than 30 nights). The benzodiazepine hypnotics are generally preferred over other types (barbiturates or nonbenzodiazepine, nonbarbiturate), but there are advantages and disadvantages related to half-life of the benzodiazepines. The risk of rebound insomnia is greater with the short half-life as compared with the long half-life benzodiazepines.

Anti-Anxiety Agents↗
PubMed1987

Dose level effects of triazolam on sleep and response to a smoke detector alarm.

Thirty-six young adult, male subjects with sleep-onset insomnia were equally divided into placebo, 0.25 mg, and 0.5 mg triazolam groups to examine the effects of the hypnotic, with particular attention to dose level on efficacy, sleep stages, and awakening to a smoke detector alarm. On nights 1 and 4 of a five-consecutive-night protocol, a standard home smoke detector alarm was sounded during stage 2, 5 min after sleep onset, in slow wave sleep (SWS), and at the time of the early morning awakening. The alarm registered 78 dB SPL at the pillow. EEG arousal latency and reaction time to a button press were studied. Failure to awaken to three 1-min alarm presentations was scored as "no response." Both dose levels produced similar reductions in sleep latency, decreases in SWS, increases in stage 2, and increases in sleep efficiency. Both dose levels showed similar sedative effects to the smoke alarm. Fifty percent of triazolam subjects failed to awaken on night 1 during SWS, and EEG arousal and response latencies were significantly slowed. Some drug tolerance or sensitization to the alarm was seen by night 4. By morning, all subjects were easily awakened on both nights. The 0.25 mg dose is clearly an effective dose level for both sleep efficacy and sedative effects to outside noise, which in some instances could pose potential problems.

Adult↗
PubMed1987

Measuring problems in estimating the exposure to passive smoking using the excretion of cotinine.

Quality control studies on cotinine measurements following low level environmental tobacco smoke (ETS) exposure are rare. The exposure to ETS was controlled and systematically changed in a series of experiments in a climatic chamber. Healthy nonsmoking volunteers were exposed to ETS simultaneously. The duration and level of exposure varied using high (8, 17 and 25 ppm CO), and low (2 and 5 ppm CO) exposure levels. The variation between radioimmunoassay (RIA) and gas chromatography (GC) was high as was the variation between the results of RIA laboratories. There was also a high within-laboratory-variation. A 1:10 dilution seems to be preferable over a 1:3 dilution. Freezing the urine samples immediately after collection led to the detection of higher cotinine values than freezing the samples 24 h after collection. Highly reliable data for cotinine were obtained when the urine samples were kept frozen immediately after collection and fractionated sampling over 48-72 h was used. Our data show that estimating low-level ETS exposure by measuring urinary cotinine is highly susceptible to uncontrolled variation and errors. Sufficiently reliable estimates of low-level ETS exposure can be made only when fractionated sampling over 48-72 h is used and when the urine samples are kept frozen just after collection.

Chromatography, Gas↗
PubMed1986

Influence of PaO2 on cerebral macro- and microcirculation as observed by light reflection: time course of changes.

A silicon intensified target camera was used to study cerebral cortical vessels of the cat through a skull window implant, and red cell content changes were measured by light reflectance. Red cell content changes were observed in cerebral arterioles, capillaries, and venules when the PaO2 was decreased by lowering the PiO2. The time course of change in the diameter of the arterioles and venules was measured by selecting a cross section of the vessel plus some surrounding tissue. From the averaged cross-sectional reflectance signal, the change in vessel diameter was followed as a function of time following the PiO2 change. All vessels of greater than 10 microns were observed in focus. Substantial areas where no vessels could be discriminated would contain only capillaries, and changes in light reflectance from such areas would indicate changes in capillary red cell content. The time course of these changes following a step decrease in PiO2 was recorded. Results show that the sequence of red cell content increase in cerebral microcirculation during hypoxia is capillary before venule and arteriole. The times of initial red cell content increase are 37.9 +/- 7 s, 59.7 +/- 7.9 s, and 60.8 +/- 9.1 s, respectively. These results suggest an increase in the capillary bed red cell content as the initial response to hypoxia, but venules and arterioles change only on longer exposure to hypoxia. The sequence of the increase in red cell content suggests the capillaries rather than the arterioles are the vessels which respond to the oxygen autoregulation signal.

Animals↗