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Biomedical subjects

R L Holland

Publications and source records attributed to R L Holland.

At least 19 recordsLinked to original sources
PubMed1994

Single dose human pharmacology of umespirone.

We have compared the cognitive, EEG, and neuroendocrine effects of single doses of umespirone (20 mg and 80 mg) with those of buspirone (30 mg) and placebo in double-blind, cross-over studies in 44 healthy men. The pattern and time-course of the cognitive effects with umespirone and buspirone were dissimilar. Peak effects of buspirone were seen shortly after dosing and then receded, whilst the effects of umespirone persisted for up to 23 h. Although both drugs objectively impaired attention, buspirone reduced subjective alertness, calmness, and contentedness, whilst umespirone increased subjective alertness and contentedness and showed potential to improve secondary verbal memory. The EEG effects of umespirone were different from those seen with buspirone; they included a decrease of power in the alpha 1 band and the beta bands in the frontocentral area and an increase in the delta and theta bands in the occipitotemporal area. Umespirone had a later onset of action than buspirone but its effects lasted longer. Similar transient increases in serum prolactin and growth hormone concentrations were seen with buspirone and 80 mg umespirone; umespirone 20 mg had no effect. Plasma concentrations of ACTH and adrenaline and serum concentrations of cortisol were unaffected by either dose of umespirone. There was some evidence that buspirone increased ACTH and cortisol concentrations in some cases, and that umespirone increased noradrenaline concentrations. The frequency of adverse events was higher with buspirone than with 80 mg of umespirone. At the lower dose of umespirone, the frequency was similar to that with placebo.

Adult↗
PubMed1992

Fluvoxamine does not interact with alcohol or potentiate alcohol-related impairment of cognitive function.

OBJECTIVE: To assess whether fluvoxamine alters the pharmacokinetics of alcohol or potentiates alcohol-related impairment of cognitive function. METHODS: The study design required partially "blinded" balanced crossover studies, each involving 12 healthy male volunteers who each received a 40 gm dose of intravenous or oral alcohol after single and multiple doses of 50 mg fluvoxamine. Main outcome measures for pharmacokinetics were venous blood alcohol and plasma fluvoxamine. Main outcome measures for pharmacodynamics were word recall, simple and choice reaction time, number vigilance, memory scanning, and word recognition. RESULTS: The pharmacokinetics of intravenous alcohol were not affected by concomitant administration of fluvoxamine. Compared with placebo-alcohol, alcohol slightly increased the rate of fluvoxamine absorption, but the area under the plasma concentration-time curve from 0 to 12 hours at steady state was unchanged. As expected, alcohol significantly impaired cognitive function in volunteers. However, fluvoxamine did not potentiate the effects of alcohol and in some instances appeared to reverse the effects or reduce their duration. Fluvoxamine was well tolerated: only mild adverse effects were reported, and none of those required intervention. CONCLUSION: Fluvoxamine does not interact significantly with alcohol or potentiate alcohol-related impairment of cognitive function.

Administration, Oral↗
PubMed1990

A multi-centre open study in general practice to evaluate the efficacy and acceptability of zopiclone 7.5 mg nocte in patients requiring the prescription of an hypnotic.

This was an open study of the efficacy and acceptability of zopiclone 7.5 mg nocte as a somnifacient. The study population comprised 108 insomniac patients (70 female, 38 male) aged 22-74 years who received zopiclone 7.5 mg for 7 consecutive nights. Based on subjective sleep assessments, zopiclone reduced the patients' difficulty in falling asleep, increased the number of hours slept and decreased the number of nocturnal awakenings (p less than 0.001). The majority of patients reported sleeping well or very well. The quality of sleep improved (p less than 0.0001), and the incidence of waking earlier than desired decreased (p less than 0.001), with respect to baseline, after receiving zopiclone. Physicians rated efficacy as good or very good in the majority of patients. Zopiclone was efficacious both in patients who had not previously received hypnotic therapy (n = 37) and in patients who transferred directly to zopiclone from a benzodiazepine hypnotic (n = 26). Whilst receiving zopiclone, patients reported feeling better in the morning than they did prior to treatment (p less than 0.004); 78% expressing satisfaction with zopiclone as an hypnotic. Physicians reported zopiclone treatment to be without side-effects in the majority of patients. In conclusion, zopiclone appears to be an effective and well-tolerated hypnotic that may play a role in the treatment of insomnia in the general population.

Adult↗
PubMed1990

A comparative study of zopiclone and triazolam in patients with insomnia.

Zopiclone, a cyclopyrrolone derivative, was compared with triazolam in a double-blind, randomized, parallel group study in general practice patients suffering from insomnia. Both drugs were found to be effective compared to baseline assessment in that they increased the number of hours of sleep, reduced the number of nocturnal wakenings and reduced the latency of falling asleep. In addition, both drugs improved patients' condition following awakening, with zopiclone showing slight superiority. In both treatment groups, there was a transient period of poor sleep after withdrawal of the drug, and one patient in each group withdrew from the study for this reason. There were no serious adverse reactions during the trial.

Adult↗
PubMed1990

The effect of zopiclone 7.5 mg on the sleep, mood and performance of shift workers.

Shift workers often complain of an inability to sleep well between successive periods of work. The purpose of the study was to assess the influence of zopiclone, hypnotic with minimal residual effects, on work-time performance and mood. In this double-blind, cross-over study, 12 healthy male volunteers, aged between 18 and 35 years, from the Royal Air Force, working 12 h shifts in radar installations, were given zopiclone 7.5 mg at bed time or placebo for 2 shift cycles in a randomized order. Zopiclone significantly improved night time sleep, with a trend towards improvement of day-time sleep. There was no effect on psychomotor performance (assessed by critical flicker fusion threshold, choice reaction time and digit symbol substitution test) nor on mood (assessed by visual analogue scales). It can be concluded that zopiclone is a safe hypnotic which can be used by shift workers without impairing work time performance.

Adolescent↗
PubMed1989

Management of the second stage of labor: a review (Part I).

The second stage of labor is defined as that time from the completion of dilitation of the cervix to the delivery of the infant. Considerable controversy exists in the current obstetric and midwifery literature concerning the appropriate management of this stage of labor. With increased use of regional anesthesia, electronic fetal monitoring and the shift in favor of active management of labor, the second stage is often accompanied by forceful bearing-down efforts, repeated Valsalva maneuvers and an increase in the use of forceps, vacuum extraction and episiotomies. Probably the single strongest point resulting in active intervention in the second stage of labor is the rigid use of the Friedman Curve. This approach tends to insist upon a predetermined time interval and promotes early intervention. The opinions on both sides of this controversy are the topic of this review.

Female↗
PubMed1989

Management of the second stage of labor: a review (Part II). Maternal positioning as it relates to the management of the second stage of labor is reviewed.

In the previous article, the rigid use of the Friedman Curve, breathing techniques, and other management options for the second stage of labor were examined. This article concentrates on the affect of maternal positioning, on the length of the second stage of labor, and summarizes the contents of that former article and this one.

Female↗
PubMed1987

Indomethacin: effects on cold-induced pain and the nervous system in healthy volunteers.

The sensitivity of the cold-induced pain (CP) model to the non-steroidal anti-inflammatory drug (NSAID) indomethacin was studied in healthy volunteers. Effects on the central nervous system were also sought. Subjects received single oral doses of indomethacin 50 and 100 mg, dipipanone 8 mg and placebo, according to a double-blind, randomised, balanced, cross-over design with an interval of 7 days between occasions. A test battery was performed before each treatment and then at 45, 105 and 165 min post treatment. Pain scores were unaltered by indomethacin at either dose, but the drug certainly affected the CNS, increasing respiratory drive and changing self-assessed mood. It is concluded that the CP model is insensitive to indomethacin, even in doses which have clear-cut CNS effects. The respiratory stimulant action of indomethacin may deserve further study.

Adult↗
PubMed1987

Effects of triprolidine and dipipanone in the cold induced pain test, and the central nervous system of healthy volunteers.

1 Twelve healthy volunteers took part in a study of the interaction between the antihistamine triprolidine and the opioid dipipanone in the cold induced pain (CP) test and tests of sedation. They received placebo, triprolidine 2.5 mg, dipipanone 8 mg or the combination of the two active treatments according to a double-blind, randomised, balanced, crossover design. 2 Antihistamine activity was demonstrated by triprolidine reducing the size of wheals and flares produced by intradermal histamine 1.6 micrograms. However, triprolidine produced no analgesia in the CP test, nor did it enhance the analgesia produced by dipipanone alone. 3 Neither treatment alone produced statistically significant sedation, assessed by visual analogue scales (VAS), side effect check list, body sway and reaction times. However, the combination did cause significant sedation. 4 Dipipanone reduced pupil size, depressed respiration, and decreased salivation. Triprolidine had no effects on pupil size and respiration, but reduced salivation slightly. It was concluded that histaminergic (H1) mechanisms are unlikely to be involved in pain produced by cold.

Adult↗
PubMed1987

Dipipanone and nifedipine in cold induced pain; analgesia not due to skin warming.

The mechanism of the pain relief produced by opiates in normal volunteers in the cold induced pain test has been investigated. In a double-blind placebo controlled study, hand skin temperature during a 3 min immersion in water at 1 degree C was not affected by either the opioid dipipanone 8 mg or the vasodilator nifedipine 10 and 20 mg. During this immersion, dipipanone produced significant pain relief. Nifedipine reduced pre-immersion blood pressures and raised heart rates, however, it did not significantly alter pain scores. It is concluded that vasodilatation and local warming do not play a role in the relief of pain by opiates in the cold immersion test.

Adult↗
PubMed1987

Effects of carbon dioxide on mental performance.

Although elevated levels of inspired CO2 have been recorded in work situations, little is known about effects of concentrations greater than 6% on mental performance. We have measured the effects of inhaling 0, 4.5, 5.5, 6.5, or 7.5% CO2 for 20 min on normal young adults unhabituated to CO2. Performance of reasoning tasks, such as AB logic problems, was significantly slowed at the higher levels of CO2, with a threshold at end-tidal PCO2 close to 51 Torr. Accuracy of reasoning and short-term memory were not significantly affected. More prolonged studies with inhalation of 6.5% CO2 showed that after the first 10 min ventilation tended to increase, end-tidal PCO2 to fall, and slowing of reasoning to recover, but substantial decrement in performance continued for 80 min, by which time performance virtually stabilized. On return to air breathing, preexposure performance was resumed within 10 min. Also caused by 6.5% CO2 was a significant rise in subjectively assessed irritability and discomfort, with no significant change in alertness or in either registration or recall of long-term memory.

Adult↗
PubMed1986

External cephalic version: a clinical experience.

Eighty-five normal women underwent external cephalic version (ECV) for breech presentation in the late 3rd trimester. The protocol included real time ultrasonic scanning and pre- and post-procedure electronic fetal monitoring. Subcutaneous terbutaline sulfate (0.25 mg.) was administered to (43/85 or 50.5%) of ECV candidates and rendered the procedure easier for patient and operator. A single operator, head-over-heels technique assisted by supine Trendelenberg's position was used. Rh negative women were routinely administered 300 mcg of immune globulin. Successful ECV (53/85, 62.5%) was related to maternal parity, but not to gestational age nor eventual delivery weight. In this series only engagement of the breech was reliable in predicting ECV failure. Fifty of 51 (98.1%) successfully verted women delivered a cephalic presentation infant at term. Cesarean section was performed in 5/51 of these patients (9.8%) for routine obstetrical indications. In one case, compound presentation at term resulting in dystocia and eventual cesarean section was believed related to prior successful version. In contrast, 15/30 (50%) of the ECV failure patients went on to operative delivery despite a liberal institutional policy toward term vaginal breech trials. In addition, the only serious fetal complication in this series, meconium aspiration, occurred in a vaginally delivered breech infant. It is unlikely that late 3rd trimester ECV will impact on out overall rate of cesarean delivery. In North America prematurity is the greatest risk factor in malpresentation and our policy increasingly is to permit attempts at term breech vaginal delivery. Nonetheless, ECV deserves serious consideration. When successful, ECV avoids the costs and/or risks of either cesarean section or vaginal trial of breech.(ABSTRACT TRUNCATED AT 250 WORDS)

Breech Presentation↗
PubMed1985

Effects of raised body temperature on reasoning, memory, and mood.

Volunteers' body core temperatures were raised to 38.80-39.05 degrees C within a few minutes by immersion in water at 41 degrees C. Tests were then made with the subjects insulated and cooling slowly. Control immersions were made in water at 37 degrees C when core temperatures remained at 36.60-37.40 degrees C. Neither memory registration nor recall of memories registered an hour earlier, nor immediate ability to recall digit spans forward or backward was affected by the increase in core temperature. The increase in temperature did not have any significant effect on accuracy of performance of verbal logic problems or of two-digit subtractions. However, the increase in core temperature was associated with a significant increase in the speed of performance of the tests, by 11 and 10%, respectively. The warm immersions also induced a significant decrease in alertness and an increase in irritability as assessed subjectively by the volunteers; control immersions had no such effects.

Adult↗
PubMed1981

An assessment of the spread of the signal for terminal sprouting within and between muscles.

Certain muscles of the mouse and rat have been studied in order to assess how far a signal from denervated muscle can spread to elicit terminal sprouting from intact endplates. Denervation of the muscles surrounding the rat foot 4th lumbrical muscle caused no terminal sprouting in the 4th lumbrical itself. In the hemidenervated mouse gluteus maximus terminal sprouting was restricted to the central region of the muscle where innervated and denervated fibres intermingle. There was no enhancement of such sprouting if the underlying and closely apposed gluteus medius was simultaneously denervated. Hemidenervation of the mouse diaphragm and interscutularis, where intact endplates lie near to denervated muscle fibres, produced no terminal sprouting. Hemidenervation of the mouse platysma, where intact endplates often lie adjacent to denervated muscle fibres, similarly produced no significant response. However, all muscles were capable of producing extensive terminal sprouting in response to paralysis induced by botulinum toxin. The stimulus for terminal sprouting produced by an inactive muscle fibre must therefore be effective only on the fibre's own terminal or immediately adjacent terminals.

Animals↗
PubMed1981

Restoration of focal multiple innervation in rat muscles by transmission block during a critical stage of development.

1. The soleus, extensor digitorum longus and peroneus tertius muscles of the hind leg were paralysed by botulinum toxin injection in neonatal rats varying in age from 8 to 31 days. The soleus muscle was similarly paralysed in adult rats.2. Muscles were excised after different periods of block, neuromuscular transmission was assessed in vitro, and the nerve terminal size and amount of terminal sprouting and multiple innervation determined histologically using silver (Ag) and zinc iodide-osmium (ZIO) tetroxide stains.3. Recovery from the block induced by botulinum toxin was more rapid in immature multiply-innervated muscles than in muscles of older rats in which all multiple innervation had been eliminated.4. Terminals in muscles blocked during the first month after birth grew rapidly in size and developed a characteristic granulose morphology in the first few days following the block. This change did not occur in fully adult rat solei.5. Sprouts growing from the terminals were infrequent in muscles paralysed before day 16. Terminal sprouts were more frequent in muscles paralysed between 16 and 31 days of age, but were very infrequent in adult solei.6. In confirmation of Thompson, Kuffler & Jansen (1979) paralysis begun at 10 days was followed initially by a continued fall in multiple innervation detected electrophysiologically. After 2 days the percentage of muscle fibres with more than one input rose. The extra inputs did not come from terminal sprouts. They innervated the single synaptic site on each muscle fibre as they do during normal synaptogenesis.7. The amount of multiple innervation regained 5-10 days after the start of paralysis became progressively less the later paralysis started and was approximately equal to the level existing at the time the block was begun. Thus paralysis starting on or after day 16 (when all excess inputs have normally withdrawn) caused no return of multiple innervation.8. The return of multiple inputs and the swelling of the nerve terminals are presumably responses of the motoneurone to growth stimuli from inactive muscle. It is not clear whether the return of multiple innervation in the 10-15 day old rats is due to reactivation of inputs still in close contact with the end-plate before withdrawal or to regrowth of partly retracted nerve branches.9. A parallel is drawn between the limited period when inactivity can reinstate multiple innervation, and the critical period in the developing visual cortex.

Aging↗