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Biomedical subjects

J B Harris

Publications and source records attributed to J B Harris.

At least 91 records · Page 5Linked to original sources
PubMed1988

Oral bioavailability of slow-release theophylline from unencapsulated beads in preschool children with chronic asthma.

The relative bioavailability of two slow-release theophylline formulations using bead-filled capsules. Slo-bid and Theo-Dur Sprinkle, was examined in randomized crossover multiple-dose trials using collected saliva. Two groups of seven preschool-age asthmatic children received one of these and Slo-Phyllin Gyrocaps as a reference. Dose-normalized areas under the saliva concentration-time curves were significantly less than the reference for Theo-Dur Sprinkle (p = .02) but not for Slo-bid with the relative bioavailability determinations of 66 +/- 8% (mean +/- SEM) and 109 +/- 5% for Theo-Dur Sprinkle and Slo-bid, respectively. The less complete absorption of Theo-Dur Sprinkle during clinical use in preschool-age children is consistent with the malabsorptive effects of food previously reported for the former but not the latter formulation.

Administration, Oral↗
PubMed1987

Use of bronchial provocation with histamine to compare the pharmacodynamics of inhaled albuterol and metaproterenol in patients with asthma.

Because measurement of effects on airway responsiveness may have advantages over the study of bronchodilatation for the evaluation of the effects of inhaled beta 2-agents, we developed a method using airway responsiveness for the independent quantitation of the relative potencies and rates of decline in effect of these drugs. This methodology was applied to the evaluation and comparison of inhaled metaproterenol and albuterol. The effects of two different doses of each drug (one and two inhalations of albuterol and two and four inhalations of metaproterenol from commercially available metered-dose inhalers) were compared with a double-blind, randomized, placebo-controlled, crossover study of 13 subjects. The effects of metaproterenol and albuterol declined at rates that were not significantly different. However, based on the effects on activity ratio at 30 minutes, each puff of metaproterenol was an estimated 0.37 times as potent as each puff of albuterol (95% confidence limits, 0.22 to 0.52). In recommended two puff doses, measurable effects of albuterol persisted longer than effects of metaproterenol. However, this appears to be because of a greater initial effectiveness of two puffs of albuterol rather than differences in the rates at which the effects of the two drugs declined with time. Airway responsiveness thus appears to be a useful tool for evaluating inhaled beta 2-agonists and designing beta 2-agonist dosing regimens.

Adolescent↗
PubMed1987

Relationship between rate and extent of absorption of oral theophylline from Uniphyl brand of slow-release theophylline and resulting serum concentrations during multiple dosing.

The relationship between a standardized assessment of rate and extent of absorption of slow-release theophylline and serum concentrations during multiple dosing was examined in eight healthy adult volunteers. Each subject received single doses of a reference theophylline solution in addition to single and multiple doses of Uniphyl, a "once-a-day" theophylline formulation, administered after an overnight fast and after a large breakfast. Extent of absorption was similar during single and multiple dosing but was significantly greater when dose was taken after breakfast; 68 +/- 7% (mean +/- SEM) and 61 +/- 4% of administered doses were absorbed during single and multiple dosing, respectively, when breakfast was withheld, whereas 83 +/- 4% and 86 +/- 4% of administered doses were absorbed when single and multiple doses, respectively, followed breakfast. Observed mean serum concentrations during multiple dosing approximated values predicted from the single-dose study; mean peak serum concentrations averaged more than twice the tough for both predicted and observed values after both fasting and postprandial administration. These data demonstrate incomplete absorption of theophylline from Uniphyl with greater extent of absorption when Uniphyl is taken after food. The study also provides further documentation that characterization of rate and extent of absorption from single doses permit prediction of the mean serum concentration-time profile during multiple dosing at defined rates of theophylline elimination. This provides the potential to anticipate fluctuations in serum concentrations at clinically relevant elimination rates that deviate from the mean of samples typically used for study.

Administration, Oral↗
PubMed1987

Early intervention with short courses of prednisone to prevent progression of asthma in ambulatory patients incompletely responsive to bronchodilators.

The effect of high orally administered doses of prednisone for 1 week early in the course of an acute exacerbation of asthma incompletely responsive to bronchodilators was examined in 41 patients randomly assigned to receive either prednisone or an identical appearing placebo. All 22 of the patients who received prednisone improved during the week of treatment, although one had a subsequent exacerbation 5 days after discontinuing the study medication. Of the 19 who received placebo, eight required rescue intervention (P = less than 0.004) in association with continued symptoms, increased frequency of metered-dose inhaler use, and decreased pulmonary function; the other 11 improved at about the same rate as those who received prednisone. Although the mean initial FEV1 was suggestively lower among those who did not improve and required intervention, there was considerable overlap with those who improved spontaneously, and no reliable distinguishing characteristics were found at entry into the study that could serve as predictors of those who would or would not improve spontaneously. There were no clinically important adverse effects from the prednisone. Because continued symptoms of asthma often result in emergency care or hospitalization, these data support early intervention with orally administered prednisone for acute exacerbations that do not respond fully to bronchodilators, at least in those patients with a prior history of a protracted course or emergency care.

Adolescent↗
PubMed1987

Acetylcholine synthesis at the rat neuromuscular junction.

Acetylcholine (ACh) synthesis in homogenates of rat soleus muscles had two components. One component, specifically inhibited by bromoacetylcholine (BrACh), had a Km for choline of 0.26 mM; the other, resistant to BrACh, had a Km for choline of 45 mM. The component with a low Km was absent from denervated muscle, and was identical in kinetic terms to ACh synthesising activity in homogenates of sciatic nerve. It is therefore considered choline acetyltransferase (ChAT)-specific. The use of BrACh as a specific inhibitor of ChAT activity allowed the calculation of ACh synthesis at individual motor end-plates in the soleus muscle of the rat: 2.1 X 10(-3) nmol h-1. Since the number of muscle fibres and the number of motor units are known for this muscle, ACh synthesis per motor unit could be calculated: 0.15 nmol h-1. It is concluded that BrACh can be used as a specific inhibitor of ChAT activity in homogenates of skeletal muscle and that its use will obviate the necessity of dividing biopsied muscle or small rodent muscles into neural and aneural segments.

Acetylcholine↗
PubMed1987

Acute viral laryngotracheitis complicated by herpes simplex virus infection.

We report the development of HSV-1 laryngotracheitis during the resolution phase of typical viral laryngotracheobronchitis (LTB) in an infant. This case represents an uncommon complication of viral LTB which has previously been described only at autopsy and suggests that prolonged use of systemic corticosteroids may lead to secondary infections, such as HSV-1. Therefore, we recommend that corticosteroid therapy for LTB be limited to 48 degrees in duration. This case also demonstrates that when an atypical clinical course is being followed by a patient who has LTB, then early diagnostic intervention is indicated. If HSV-1 is identified, anti-viral chemotherapy should be initiated and artificial airway management may be necessary. Tracheal intubation may be used, but, if extensive subglottic ulceration occurs, the subglottis should be bypassed in order that the chance of subglottic stenosis be minimized. In this case, early identification by bronchoscopy and viral cultures resulted in a successful combined medical-surgical management and total resolution with no sequelae.

Bronchitis↗
PubMed1986

Spontaneous electrical activity in muscles of dystrophic (dy/dy) mice.

Spontaneous electrical activity of tibialis anterior (TA) muscles was recorded using extracellular electrodes in dystrophic and phenotypically normal mice. Abnormal levels of spontaneous activity were recorded in the muscles of adult dystrophic mice. The activity was reduced by more than 75% after sciatic nerve section in anaesthetised dystrophic mice suggesting that most of the activity was neurally mediated. No abnormal activity was seen in the biceps brachii muscles of adult dystrophic mice. No abnormal spontaneous activity was seen in young (2-3-week-old) dystrophic mice. As degeneration of muscle fibres begins at about 7 days of age in dystrophic hindlimb muscles, the onset of the abnormal spontaneous EMG activity could not be considered causally related to muscle fibre degeneration.

Age Factors↗
PubMed1986

Neuromuscular transmission in the murine mutants "motor end-plate disease" and "jolting".

Mice with the inherited disorder "motor end-plate disease" suffered from a progressive neuromuscular weakness and muscular wasting. The weakness resulted from a failure of evoked transmitter release from the motor nerve terminals. The failure in transmission was all-or-nothing in nature. The numbers of muscle fibres in skeletal muscle and myelinated axons in several major nerve trunks were no different from normal. The loss in muscle bulk was caused by the neuromuscular defect and not from a loss of motor units or muscle fibres. The inherited murine disorder "jolting" was allelic with "motor end-plate disease". Affected "jolting" mice suffered no detectable morphological abnormality in skeletal muscle or peripheral nerve. The physiological properties of skeletal muscle and the characteristics of neuromuscular transmission were indistinguishable from normal.

Action Potentials↗
PubMed1986

Cerebellar structure and function in the murine mutant "jolting".

The morphology of the cerebellar cortex of the murine mutant "jolting" and its phenotypically normal littermate was studied. The general organisation of the cerebellum of normal mice was similar in all respects to that described for other vertebrate species. In "jolting" mice aged 4 months or more there was a marked loss of Purkinje cells and spheroids were present on Purkinje cell axons. An ultrastructural examination showed that the spheroids contained randomly orientated neurofilaments, degenerating mitochondria and autophagic vacuoles. The abnormalities in the cerebellum appeared confined to the Purkinje cells. Extracellular recordings were made of the electrical activity of the cerebellar cortex of anaesthetised mice. In the cerebellar cortex of "jolting" animals, Purkinje cells generated little spontaneous activity, but complex discharges resulting from climbing fibre inputs were indistinguishable from normal. The abnormal electrical activity of Purkinje cells in "jolting" mice could be seen in animals as young as 3 weeks. It was concluded that the "jolting" mouse suffers from a cerebellar ataxia.

Action Potentials↗
PubMed1986

Muscle necrosis caused by the sub-units of crotoxin.

The effects of the basic (CB) and acidic (CA) subunits of crotoxin on rat skeletal muscle in vivo have been studied. CB caused muscle necrosis, with damage limited to an outer rim of muscle fibres in rat soleus. The inflammatory response was relatively small. CA was apparently inactive, but the effect of CB was potentiated if injected in combination with CA. Not only were more muscle fibres damaged, but the damage was more diffuse. There was no relationship between the number of muscle fibres damaged and the extent of the oedema (measured as increase in wet weight.

Animals↗
PubMed1985

The effects of Anemonia sulcata toxin II on vertebrate skeletal muscle.

Some effects of the sea anemone toxin, ATX-II, on vertebrate skeletal muscle have been described. At a concentration of 1 X 10(-7)-1 X 10(-6)M, ATX-II caused a sodium-dependent depolarization of the muscle fibres of the rat soleus and extensor digitorum longus, of the mouse soleus and extensor digitorum longus and of the chicken posterior latissimus dorsi. The muscle fibres of the frog sartorius were insensitive to the toxin. Action potentials generated by direct stimulation were prolonged by ATX-II, but the degree of prolongation was variable. Chicken posterior latissimus dorsi muscle fibres were most sensitive in this regard, and mouse extensor digitorum longus were least sensitive. Both denervated and immature muscle fibres were more sensitive to ATX-II than mature innervated muscle fibres. The sensitivity to ATX-II declined rapidly as muscle fibres matured. In some muscles, the prolongation of the action potential was enhanced by repetitive stimulation, but not by the passive depolarization or hyperpolarization of the muscle fibres. The actions of ATX-II could be reversed by washing in all but the innervated soleus of the mature rat.

Action Potentials↗
PubMed1985

Reversal of paralysis in nerve-muscle preparations isolated from animals with hereditary motor endplate disease.

Motor endplate disease (med) in the mouse is an hereditary disorder of the skeletal neuromuscular system. Affected animals suffer a 'functional denervation' of skeletal muscle (Duchen & Stefani, 1971). Muscle fibres do not respond to indirect excitation, but motor nerve terminals release transmitter spontaneously. Spontaneous transmitter release can be enhanced by raising [K+]o or by exposing muscles to red-back spider venom and functional transmission following indirect stimulation may be restored by 4-aminopyridine.

4-Aminopyridine↗
PubMed1985

Effect of intrauterine antibiotic lavage after cesarean birth on postoperative morbidity.

Intrauterine lavage using broad-spectrum antibiotics after cesarean section has been reported to reduce maternal morbidity, but many such patients are not at high risk for postoperative infection. This study tested intrauterine antibiotic lavage in patients at risk for infectious morbidity. The patients were randomly assigned to one of three groups based on the last digit of the hospital admission number. Group I received no lavage, group II received lavage with 800 ml of saline plus 2 gm of cefamandole nafate in the intrauterine incision, bladder flap and peritoneal cavity, and group III received a similar lavage using 800 ml of saline alone. There was a significant decrease in maternal hyperpyrexia (simple morbidity) as well as serious infection in both lavage groups as compared to the control group (p less than 0.01 and 0.05, respectively). Also, there was significantly reduced morbidity when the antibiotic lavage was compared to the saline technique (p less than 0.001). The use of intrauterine lavage with saline, with or without antibiotics, appears helpful in reducing postoperative morbidity in patients at high risk for infectious morbidity after cesarean section.

Anti-Bacterial Agents↗
PubMed1984

Effects of sea-anemone toxin (ATX-II) on the frequency of miniature endplate potentials at rat neuromuscular junctions.

Soleus and extensor digitorum longus muscles were isolated from rats. The muscles were exposed to ATX-II, a toxin isolated from extracts of the sea-anemone Anemonia sulcata . The toxin caused a dose-dependent increase in the frequency of miniature endplate potentials in both types of muscle. The increase in frequency could be reversed by the application of tetrodotoxin (TTX), and could be prevented by prior exposure of the muscles to TTX. It is concluded that ATX-II causes a sodium-dependent depolarization of the nerve-terminal membrane.

Action Potentials↗
PubMed1983

Preliminary observations of satellite cells in undamaged fibres of the rat soleus muscle assaulted by a snake-venom toxin.

Satellite cells were studied in the undamaged part of the rat soleus muscle rendered partially necrotic by a subcutaneous injection of notexin, the myotoxic toxin purified from the venom of the Australian snake Notechis scutatus scutatus. Nuclei of satellite cells were twice as numerous as in the controls, with a decreasing gradient in the number of satellite cells with distance from the necrotic area. The cells were in an activated state with an increased cytoplasmic volume and prominent organelles. Occasionally, mitosis of some satellite cells was observed. Between the satellite cell and the muscle fibre, an unusually wide space was frequently seen, within which a "new" basal lamina was often visible. It is suggested that the role of the satellite cells of undamaged muscle fibres in the regeneration of necrotic muscle is worthy of more detailed investigation.

Animals↗