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Biomedical subjects

J D Arnold

Publications and source records attributed to J D Arnold.

At least 37 records · Page 2Linked to original sources
PubMed1991

Postnatal changes in proximal and distal tubular sodium reabsorption in healthy very-low-birth-weight infants.

We studied 7 healthy very-low-birth-weight male infants with a mean birth weight of 1,195 g and a gestational age of 29.0 weeks, from birth to 6 weeks. The filtered Na load increased fivefold but urine Na excretion decreased from 3.4 to 0.1% of the filtered Na load. The efficiency of Na reabsorption increased 8% in the proximal tubule compared with 66% in the distal tubule. Because greater than 90% of Na reabsorption always occurred proximally, the smaller percentage increase in efficiency of the proximal tubule contributed as much as the larger percentage increase in efficiency of the distal tubule to the postnatal improvement in renal Na conservation.

Absorption↗
PubMed1990

Pharmacokinetic and pharmacodynamic comparison of an osmotic release oral metoprolol tablet and the metoprolol conventional tablet.

Four double-blind, Latin-square studies were conducted to compare the pharmacokinetics and pharmacodynamic bioavailability of metoprolol OROS (oral osmotic) and the conventional tablet (CT) of metoprolol. Metoprolol OROS (7/95 mg or 14/190 mg) was administered once daily in doses equivalent to 100 mg of metoprolol CT given once, twice, thrice, and four times a day. In all four studies, lower peak plasma concentrations and longer times to peak were observed after metoprolol OROS than after metoprolol CT, indicating a controlled-release profile for metoprolol OROS. beta-Adrenergic blockade, as measured by reductions in exercise heart rate, was lower after metoprolol OROS than after metoprolol CT, but metoprolol OROS provided a smoother and more sustained beta-blockade. All four doses of metoprolol OROS at steady state produced relative pharmacodynamic bioavailability that ranged from 87% to 104% of that produced by equivalent doses of metoprolol CT.

Administration, Oral↗
PubMed1990

Comparative assessment of enprofylline and theophylline for chronic obstructive airways disease in the elderly.

Enprofylline, a recently developed xanthine derivative, is a more potent bronchodilator than theophylline. This study compares the efficacy and safety of enprofylline with theophylline for chronic obstructive airways disease (COAD) in elderly subjects. The study was of a randomized double-blind parallel design and commenced with a 1-week reference period when oral bronchodilators were withdrawn. Patients were then treated with either enprofylline or theophylline 150 mg bd for 2 weeks (period 1) followed by 300 mg bd for a further 3 weeks (period 2). Patients recorded peak expiratory flow rate (PEFR) and adverse experiences, if any, in a diary, daily. Of 111 patients recruited for the study, 85 entered active treatment (theophylline, n = 44; enprofylline, n = 41). Mean age was 72 years and mean bronchodilator reversibility was 22%. Enprofylline increased mean morning PEFR by 11% (period 1) and 19% (period 2) whereas theophylline increased PEFR by 13% and 19%, respectively. From the enprofylline group 29% were withdrawn from the study due mainly to headache and nausea/vomiting and from the theophylline group 7% were withdrawn due mainly to nausea/vomiting. Mean plasma concentrations of enprofylline were 2.0 mg l-1 and 3.4 mg l-1, and with theophylline 5.4 mg l-1 and 10.0 mg l-1 at the end of periods 1 and 2, respectively. Enprofylline and theophylline produced similar improvements in lung functions and symptoms of chronic obstructive airways disease, but enprofylline was less well tolerated than theophylline.

Aged↗
PubMed1990

Early neonatal hyperkalaemia in the extremely premature newborn infant.

The incidence of hyperkalaemia in 43 consecutive infants born at less than 28 weeks gestation and cared for in our neonatal intensive care unit was documented. Plasma K levels were related to indices of renal function as well as to the degree of illness in the infants. The mean gestational age was 26.0 weeks (range 24-27 weeks) and the mean birthweight was 815 g (range 395-1170 g). Twenty-six of the infants (60%) had at least one plasma K greater than 5.5 mmol/L and 13 (30%) had a maximum plasma K greater than 7 mmol/L. The mean postnatal age at which the plasma K exceeded 7 mmol/L was 25 h (range 10-39 h). Five infants with plasma K greater than 7 mmol/L developed cardiac arrhythmias and four died of this complication. Only one infant had a large intraventricular haemorrhage. Only two of 16 infants with an initial plasma K less than 5 mmol/L had a maximum plasma K greater than 7 mmol/L, compared with eight of 10 with an initial plasma K greater than 6 mmol/L (P less than 0.005). Plasma K also correlated directly with plasma urea (P less than 0.001) and plasma creatinine (P less than 0.025), and inversely with urine volume (P less than 0.05). Plasma K did not correlate with K intake, arterial pH, presence of asphyxia, severity of respiratory illness, gestation or birthweight. The rapidity with which the plasma K concentration reached potentially hazardous levels in some infants makes it imperative to measure plasma K within 6 h of birth and to continue to monitor levels at least every 6 h for the first 48 h in all infants born at less than 28 weeks gestation.

Arrhythmias, Cardiac↗
PubMed1989

Etodolac, a new nonsteroidal anti-inflammatory drug: gastrointestinal microbleeding and endoscopic studies.

A review of the literature is presented on the gastrointestinal effects of etodolac, a new nonsteroidal anti-inflammatory drug (NSAID), as evaluated in both microbleeding and endoscopic studies. In four microbleeding studies, gastrointestinal blood loss in healthy subjects was estimated by a 51Cr-erythrocyte labeling method before drug treatment, after 7 days of treatment with NSAIDs including etodolac, and 1 week after the last day of treatment. In these 7-day studies, the gastrointestinal blood loss seen with etodolac (600 to 1200 mg/day) was similar to that seen with placebo and significantly (p less than 0.05) less than that seen with aspirin (2600 mg/day), naproxen (750 mg/day), ibuprofen (2400 mg/day), or indomethacin (200 mg/day). Naproxen, ibuprofen, and indomethacin caused mean daily blood losses in excess of 1 ml/day over baseline values. The increase with aspirin was 4 to 5 ml/day. In contrast, the greatest mean daily increase in blood loss with etodolac therapy was 0.2 ml. In a 4-week study of etodolac (600 and 1000 mg/day) and piroxicam (20 mg/day) given to patients with osteoarthritis or rheumatoid arthritis, blood loss seen with etodolac was comparable to that seen with placebo and significantly less than that seen with piroxicam. Gastrointestinal irritation was also assessed by endoscopy after 1 week of NSAID or placebo treatment. Endoscopy scores after etodolac treatment (up to 1200 mg/day) were similar to scores at baseline and after placebo and were significantly lower than scores following treatment with aspirin (3900 mg/day), indomethacin (200 mg/day), ibuprofen (2400 mg/day), or naproxen (100 mg/day). The effects of etodolac (600 or 1000 mg/day) and diclofenac (150 mg/day) were not different from each other or from baseline. These data indicate that etodolac, in these studies, did not cause clinically significant gastrointestinal microbleeding or visible gastric injury. By the criteria used in these studies, etodolac is less irritating to the gastrointestinal tract than aspirin, indomethacin, ibuprofen, naproxen, or piroxicam, and compares favorably with diclofenac.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

Distribution of plasma vitamin E levels in supplemented very low birthweight infants.

The distribution of plasma Vitamin E (VE) was determined in 25 very low birthweight (VLBW) infants who were supplemented with 100 mg/kg per day of alpha-tocopherol acetate, given intragastrically. Their mean birthweight was 917 g and mean gestational age was 28 weeks. Mean plasma VE levels after 1 and 6 weeks' supplementation were 2.7 mg/dL (s.e.m. = 1.0) and 6.4 mg/dL (s.e.m. = 1.4), respectively (the difference was not significant). There was wide variability in plasma VE levels in these infants despite being on an identical dose of tocopherol. Plasma VE was less than 0.5 mg/dL in 12% of samples, 0.5-3.0 mg/dL in 32%, 3.1-5.0 mg/dL in 18%, and 5.1-20 mg/dL in 38%. Fifteen of the 25 infants had at least one level in the range which has been associated with an increased incidence of septicaemia and necrotizing enterocolitis (greater than 5.0 mg/dL). These data suggest that if a policy of VE supplementation for VLBW infants is chosen, monitoring of plasma VE levels appears necessary so that the dosage can be adjusted in order to maintain plasma VE within the optimal range. This study's dosage regimen of supplementing infants with 100 mg/kg per day of VE was associated with a high incidence of elevated plasma VE levels and it is concluded that it is not advisable to use such large doses of VE in the premature newborn.

Female↗
PubMed1989

The influence of in-utero transfer on perinatal mortality in a tertiary care centre.

From March 1, 1986 through February 28, 1989 inclusive there was a total of 8,319 births with a birth-weight of 500 g or more at Royal North Shore Hospital (RNS). Three hundred and sixty one births (4.3%) resulted from in-utero transfer of high risk pregnancies (IUT); the remainder were booked at RNS. There were 141 perinatal deaths of which 55 (39%) occurred in infants transferred in-utero. For the whole population delivered at RNS the perinatal mortality rate was 17.0/1,000 births (10.8/1,000 for booked patients versus 152.4/1,000 for IUT births), the stillbirth rate was 7.1/1,000 births (5.4/1,000 for booked patients versus 44.3/1,000 for IUT births) and the neonatal mortality rate was 9.9/1,000 livebirths (5.4/1,000 for booked patients versus 113.0/1,000 for IUT livebirths). These data show that crude perinatal mortality statistics from individual hospitals do not necessarily reflect their standard of care. Although the infants transferred in-utero comprised only 4.3% of the total population they constituted more than one third of the perinatal deaths at RNS. Their very high group specific mortality rates are related to their degree of prematurity and associated maternal and neonatal conditions.

Female↗
PubMed1988

Effect of cetamolol on epinephrine-induced hypokalemia.

The effect of cetamolol (an investigational cardioselective beta blocker with intrinsic sympathomimetic activity) on the hypokalemic response to epinephrine infusions in normal subjects was evaluated and compared with placebo and two other beta-adrenergic blocking drugs. After two daily doses of cetamolol 15 mg, atenolol (a cardioselective beta blocker) 50 mg; a long-acting propranolol preparation (a nonselective beta blocker) 80 mg; or placebo, 12 men (mean age, 26.7 years) were infused with epinephrine. The resulting average plasma epinephrine level was 1123 pg/mL, whereas average baseline serum potassium levels for the four treatment groups ranged from 3.94 to 4.07 mEq/L. Epinephrine-induced hypokalemia occurred in the placebo group (maximum potassium decrease of 1.00 mEq/L) and in the atenolol group (maximum potassium decrease of 0.59 mEq/L); potassium levels did not decrease but rose slightly in subjects receiving cetamolol or propranolol. Subjects treated with placebo or atenolol also demonstrated statistically significant prolongation of the QTc interval (0.039 seconds with placebo; 0.023 seconds with atenolol) and frequently developed T-wave flattening and U-wave appearance. After pretreatment with cetamolol or propranolol, however, the QTc interval was unaffected, T-wave abnormalities did not occur, and U waves appeared only rarely. The results of this study indicate that cetamolol blocks epinephrine-induced hypokalemia and associated electrocardiographic changes.

Acetamides↗
PubMed1988

Single-dose and multiple-dose pharmacokinetics of etintidine in healthy volunteers.

The present study was designed to determine the single- and multiple-dose pharmacokinetic profiles of the H2 receptor antagonist etintidine in healthy volunteers. Etintidine was rapidly absorbed and eliminated after the oral administration of 300 mg base equivalent of etintidine HCl in a capsule formulation to 11 healthy subjects. Comparison of the pharmacokinetics after a single dose and during steady state showed no significant differences (p greater than 0.05) in the mean values of Cmax, tmax, oral clearance, elimination rate constant, and renal clearance, indicating no significant accumulation of etintidine and no apparent time-dependent changes in the pharmacokinetics of etintidine during multiple dose administration.

Absorption↗
PubMed1988

Postnatal age at time of death in infants born at 24-32 weeks' gestation.

Medical records of all 483 infants live-born at 24-32 weeks' gestation in our hospital during the years 1982-86 were reviewed in order to determine postnatal age at time of death for those who died in the first year after birth. Twenty-seven died from immaturity without receiving intensive care and 11 died from lethal congenital malformations. Eighty (18%) of the remaining 445 who received intensive care died: 31% on day 1, 45% on days 2-7, 12% on days 8-28 and 11% on days 29-365. The neonatal mortality rate for those receiving intensive care was 160/1000, and the postneonatal mortality rate was 20/1000. Delayed mortality was most common in infants of 26-27 weeks' gestation, with 20% (five) of their deaths occurring after 28 days. In each gestational age range, the majority of hospital admission days were occupied by survivors (24-25 weeks = 62%; 26-27 weeks = 91%; 28-29 weeks = 91%; 30-32 weeks = 99%) rather than non-survivors. Whilst postneonatal mortality is a significant concern, these data suggest that if infants born at less than 33 weeks' gestation are offered intensive care and survive the early neonatal period, the long-term outcome is more likely to be survival rather than delayed death. Furthermore, the majority of hospital admission days invested in such infants involves those who will be discharged home rather than those who will not.

Gestational Age↗
PubMed1988

Increased incidence of respiratory distress syndrome in infants following pregnancies complicated by hypertension.

We assessed the relationship between maternal hypertension during pregnancy and the incidence of respiratory distress syndrome (RDS) in 263 infants born at 32 weeks' gestation or less. Two-hundred and twenty-three mothers were normotensive and 40 were hypertensive. RDS occurred significantly more commonly in infants of hypertensive mothers than in controls (60% vs 33%; p = 0.001). The association between maternal hypertension and an increased rate of RDS remained after adjustment for differences between groups with respect to gestational age, mode of delivery, administration of antenatal steroids and other complications of pregnancy, except for delivery in the absence of labour. The increased rate of RDS related to the severity of hypertension but did not relate to the duration of hypertension or to maternal treatment with beta-blockers. In those infants who developed RDS there was no significant difference in the severity of the illness between the hypertensive group and the controls.

Adult↗
PubMed1987

Bioavailability and pharmacokinetics of a new sustained-release potassium chloride tablet.

The bioavailability of a new sustained-release potassium chloride (KCl) tablet, designed for once-a-day dosing, was compared to a KCl elixir using urinary excretion data. The study utilized 25 male volunteers dosed in a crossover design in a dietary/activity-controlled environment. The regimens consisted of a total of 80 mEq of potassium in three equally divided doses of elixir every 6 hr and a single 80-mEq dose using four 20-mEq sustained-release (SR) tablets. The mean time to maximum rate of potassium urinary excretion was 2.2 hr for the first elixir dose and 5.5 hr after the SR tablet (P less than 0.01), thereby supporting the prolonged-release properties of this formulation. After correction for baseline urinary potassium excretion, the mean total 24-hr urinary potassium excretion was 42.18 mEq for the elixir and 40.41 mEq for the SR tablet. The results indicate that the absorption pattern from the SR tablet is equal to three doses of KCl elixir dosed 6 hr apart.

Adult↗
PubMed1987

Kinetics of potassium excretion following oral supplements: evidence of induced natriuresis.

Twenty-four healthy normal volunteers were given 40 mEq of three oral formulations of K+ as potassium chloride in a three-way Latin square design. Pharmacokinetic characteristics of potassium disposition were determined using urinary excretion data. Potassium was absorbed almost instantaneously from the 10% (w/v) solution, while a slow first-order absorption could explain the slow release of potassium from Slow-K and the new slow-release tablet. A biphasic elimination of potassium observed during the first 24 hr of urinary excretion suggested the body's adaptive process of changes in rates of elimination of potassium to maintain homeostasis. There was no significant difference (P = 0.25) in total recoveries of potassium in urine during 48 hr of urinary collection among the three formulations (mean +/- SE: solution, 35 +/- 7.1 mEq; Slow-K, 38.1 +/- 7.8 mEq; and new formulations, 33.5 +/- 6.8 mEq). An increased excretion of sodium was observed and correlated with increased potassium excretion following oral potassium administration which could not be explained by changes in urine flow rate. The clinical significance of such an increase in natriuresis is yet to be determined.

Administration, Oral↗
PubMed1987

Adrenocortical responsiveness in neonates weaned from the ventilator with dexamethasone.

Adrenocortical responsiveness was assessed in eight very low birthweight neonates who had bronchopulmonary dysplasia and had been weaned from mechanical ventilation using dexamethasone. Three of the eight infants did not respond to ACTH stimulation during the first week after cessation of dexamethasone, but all three responded normally when retested at least 1 month later. The present authors have thus demonstrated that some infants have at least temporary adrenocortical unresponsiveness after prolonged courses of glucocorticoid therapy, and suggest that adrenocortical function should be assessed in all infants who are weaned from mechanical ventilation using dexamethasone.

Adrenal Cortex↗
PubMed1985

Oros controlled-release formulations of metoprolol: an approach to the development of a system for once daily administration.

A combined biopharmaceutical and haemodynamic approach to the development of a metoprolol Oros controlled-release delivery system for once daily administration is reported. Two studies, each involving 18 healthy volunteers, were performed in which twice daily administration of 100 mg conventional metoprolol tartrate tablets was compared with once daily administration of Oros systems containing 190 mg metoprolol fumarate but with different drug release rates. Plasma drug concentrations and beta-adrenoceptor blocking effects were measured over 24 h on days 1 and 5 of each treatment, and pre-dose in the interval between the main study days. The results of the first study with a 19 mg/h Oros system indicated that this rate was too rapid to provide the required response under steady-state dosing conditions. Theoretical calculations based on a one-compartment pharmacokinetic model and input functions for hypothetical Oros systems were then performed to define the optimal release rate for a once daily preparation. The results of the second study confirmed that a 14 mg/h system possessed the required characteristics in that it maintained more uniform beta-adrenoceptor blockade throughout 24 h, and produced pre-dosing plasma concentrations and haemodynamic effects which were identical to those for the conventional tablet twice daily regimen.

Adolescent↗