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Biomedical subjects

R L Williams

Publications and source records attributed to R L Williams.

At least 289 records · Page 16Linked to original sources
PubMed1983

Disturbances of the sleep-waking cycle in patients with vascular brain stem lesions.

Continuous polygraphic recordings of six patients with vascular brain stem lesions were evaluated to investigate the relationship between 1) the localization or extent of the lesions and the alteration of the sleep-waking cycle, and 2) the evolution of the clinical condition and the sleep-waking cycle. Absent REM sleep and severely disorganized NREM sleep were associated with extensive pontine lesions involving the pontine tegmentum. In "locked-in" syndrome, the neural mechanisms responsible for both REM and NREM sleep continued to function, but the sleep-waking cycle was disturbed and marked by sleep-onset REM periods. Lesions in the lower brain stem resulted in absent slow-wave sleep and sleep-onset REM, suggesting that vascular lesions may involve the neural mechanisms responsible for slow-wave sleep. In general, the acute stage of illness was marked by increased awakenings and time spent awake, absent REM sleep, and little or no slow-wave sleep. These results indicate that continuous polygraphic recordings can reveal severe abnormalities due to vascular lesions of the brain stem whereas the waking EEG can only detect mild abnormalities. Improvement in the organization of the sleep-waking cycle in successive polygraphic examinations is likely to be followed by an improvement of the clinical condition. Continuous polygraphic recording is thus a valuable prognostic indicator for vascular brain stem lesions.

Aged↗
PubMed1983

Controlling the rise in cesarean section rates by the dissemination of information from vital records.

The recent rapid increase in cesarean childbirth is a source of growing public health concern. We suggest that one method of ameliorating the rise would be to disseminate hospital-specific cesarean section rates. To make such rates comparable between hospitals, it is necessary to adjust for variations in maternal and newborn factors associated with cesarean section. We therefore applied an indirect standardization technique to three years of California vital records data. The results show sizable variations in cesarean section rates among individual hospitals and by hospital type, both before and after standardization. For such a method to be effective, complete and accurate information from birth certificates is an obvious prerequisite.

Birth Weight↗
PubMed1983

Differential effects of oral reading to improve comprehension with severe learning disabled and educable mentally handicapped students.

The purpose of this study was to evaluate the effectiveness of oral reading as a teaching technique for improving reading comprehension of 11 Educable Mentally Handicapped or Severe Learning Disabled adolescents. Students were tested on their ability to answer comprehension questions from a short factual article. Comprehension improved following the oral reading for students with a reading grade equivalent of less than 5.5 (measured from the Wide Range Achievement Test) but not for those students having a grade equivalent of greater than 5.5. This association was statistically significant (p = less than .01). Oral reading appeared to improve comprehension among the poorer readers but not for readers with moderately high ability.

Adolescent↗
PubMed1983

Sleep disorders in the elderly.

Sleep disorders are difficult to distinguish from changes in sleep typically occurring after age 60. Sleep laboratory evaluation is needed to differentiate normal sleep alterations from the similar but more severe symptoms of depression or organic brain syndrome, and to detect sleep apnea, the most common sleep disorder found in geriatric patients. This disorder may be fatal, especially if a hypnotic drug is prescribed. Since biologic rhythms are easily disturbed in the elderly, education about sleep habits may be the most helpful therapy.

Adult↗
PubMed1983

Disposition of caffeine and its metabolites in man.

The disposition of caffeine and its metabolites was studied in six healthy subjects by use of sensitive and specific assays. The primary degradation of caffeine in man was found to be N-demethylation and/or ring oxidation to theophylline, paraxanthine, theobromine and 1,3,7-trimethyluric acid. These compounds were further degraded to dimethylated uric acids, monomethylxanthines and monomethyluric acids. About 3 and 6% of the drug was converted to theophylline and theobromine, respectively. The elimination of paraxanthine after its formation did not follow linear kinetics. A large urine recovery of 1-methylxanthine after caffeine administration in comparison with the amount recovered after administration of theophylline suggests an inhibitory effect on the degradation of this metabolite by either caffeine itself or another metabolite of caffeine. Caffeine and its primary metabolites, dimethylxanthines, were extensively reabsorbed in the renal tubule. Their renal clearances were highly urine flow-dependent and their urinary excretion varied with urine output during the study. About 70% of the dose was recovered in the urine. Postulated degradation pathways of caffeine are discussed.

Adult↗
PubMed1982

Identifying the sources of the recent decline in perinatal mortality rates in California.

The perinatal mortality rate in California decreased rapidly in the 1970s; neonatal mortality fell about twice as fast as fetal mortality. Decreases in birth-weight-specific mortality accounted for 81 per cent of the decline in the perinatal rate, with only 19 per cent due to improvements in birth weight. No improvement was observed in the birth-weight distribution for blacks. The decrease in mortality rates was significantly faster for cesarean deliveries than for vaginal births. By 1977, all birth-weight-specific fetal mortality rates for cesarean sections were equal to those for vaginal deliveries or lower. For infants weighing less than 2000 g, perinatal mortality rates were also significantly lower for infants born by cesarean section than for infants delivered vaginally. These results suggest that much of the recent decrease in perinatal mortality rates can be attributed to the advent of neonatal intensive care and the increased rate of cesarean section.

Black or African American↗
PubMed1982

Disposition of zomepirac sodium in man.

Five healthy male human subjects were administered 200 mg oral solution doses of zomepirac-14C sodium. Plasma and urine samples were analyzed for zomepirac, hydroxyzomepirac, and zomepirac glucuronide. Zomepirac was the major circulating compound, with zomepirac glucuronide and hydroxyzomepirac accounting for the remainder of the radioactivity. Elimination half-lives for zomepirac, zomepirac glucuronide, and hydroxyzomepirac were 7.6, 8.2, and 7.8 hours, respectively. The dose was completely recovered in the urine (95 per cent in 72 hours). Zomepirac glucuronide constituted up to 90 per cent of the urinary radioactivity, with zomepirac and hydroxyzomepirac about 5 per cent each. The urinary zomepirac was probably present as a result of hydrolysis of zomepirac glucuronide. The plasma clearance of zomepirac was 189 +/- 23 ml/min. The metabolites were cleared by the kidney at rates of 343 +/- 88 ml/min (zomepirac glucuronide) and 339 +/- 88 ml/min (hydroxyzomepirac). Thus, metabolic clearance appears to be the sole mode of zomepirac elimination. The metabolites are then rapidly cleared by the kidneys.

Adult↗
PubMed1982

Hydrochlorothiazide pharmacokinetics and pharmacologic effect: the influence of indomethacin.

It is known that nonsteroidal antiinflammatory drugs such as indomethacin can attenuate the pharmacologic effect of loop diuretics such as furosemide and ethacrynic acid and that indomethacin may also reduce the pharmacologic response to chlorothiazide. To examine further this potential drug-drug interaction, we administered 50- an 100-mg single oral doses of hydrochlorothiazide with and without indomethacin to 10 healthy, normal subjects. We observed no significant influence of indomethacin to 10 healthy, normal subjects. We observed no significant influence of indomethacin either on the pharmacokinetics of hydrochlorothiazide or the pharmacologic response to this diuretic. The adsorption and disposition of hydrochlorothiazide demonstrate that this drug is rapidly absorbed and produces a diuretic and natriuretic response that peaks at approximately 2 hours after dosing and is essentially terminated 12 hours after dosing. There appeared to be no greater pharmacologic response to the 100-mg than to the 50-mg hydrochlorothiazide dose in the ten subjects in this study.

Adult↗
PubMed1982

Comparison of effects of cyanide and acetylcholine on renal hemodynamics and sodium excretion.

The present study compared the effects of acetylcholine to cyanide under the same experimental conditions of renal clearance in anesthetized dogs. Since cyanide is one of the few drugs for which the mechanism of action is known (cytotoxic hypoxia), some insight may be gained into the renal effects of acetylcholine since both produce direct natriuresis and diuresis. Infusion of 0.2 microgram/kg/min of acetylcholine and 12.0 microgram/kg/min of sodium cyanide into the left renal artery resulted in similar effects, i.e., increased fractional excretion of sodium, potassium, calcium, and magnesium. These effects were immediate and ipsilateral. Both agents increased the renal plasma flow to the same extent. In addition, regression plots of the relation between changes in sodium excretion and changes in renal plasma flow were similar for both agents. The pattern of similar renal functional changes suggested that acetylcholine is not a mere renal vasodilator but that its action is also medicated through alterations on direct transport of ions.

Acetylcholine↗
PubMed1982

Relative bioavailability of chlorthalidone in humans: adverse influence of polyethylene glycol.

The bioavailability of two commercial preparations of chlorthalidone was studied in healthy male subjects. Reference solutions/suspensions for the two products were chlorthalidone dissolved in a solution of water-polyethylene glycol and a solution/suspension of chlorthalidone. Bioavailability of the chlorthalidone in water-polyethylene glycol solution was significantly reduced in comparison to one of the commercial preparations, and trends in the data suggested that it was less well absorbed than either the chlorthalidone in water solution/suspension or the other commercial preparation of chlorthalidone. These data, together with previous reports indicating that polyethylene glycol may retard the absorption of some drugs in vitro, suggest that this compound should not be used to aid dissolution of drug in a reference standard for bioavailability investigations.

Adult↗
PubMed1982

Pharmacokinetics of triamterene and its metabolite in man.

The pharmacokinetic profiles of triamterene and hydroxytriamterene sulfuric acid ester, the major metabolite of triamterene, were studied in six normal male volunteers using a newly developed specific HPLC analytical method. Following a 100 mg oral dose of triamterene, the plasma concentration time course of the sulfate conjugate parallels that of triamterene in all subjects, but concentrations of the metabolite were more than 10 times higher than unchanged triamterene concentrations at identical sampling times. Interestingly, the renal clearance of the sulfate conjugate was less than that of triamterene. These characteristic features of triamterene disposition were fitted to a compartment model incorporating a first-pass metabolic process. Unbound fractions of triamterene and metabolite in plasma were 0.39 and 0.10 (mean of 6 subjects), respectively. The low unbound fraction of the metabolite in plasma most probably accounts for the low renal clearance of the sulfate conjugate as compared with triamterene.

Adult↗