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Biomedical subjects

R J Martin

Publications and source records attributed to R J Martin.

At least 253 records · Page 14Linked to original sources
PubMed1992

Tracheal smooth muscle responses to substance P and neurokinin A in the piglet.

The tachykinins substance P (SP) and neurokinin A (NKA) have been shown to induce airway smooth muscle contraction in mature animals, and the enzyme neutral endopeptidase (NEP) modulates this effect. We evaluated maturation of SP- and NKA-induced tracheal smooth muscle contraction and modulation of their effects by NEP in anesthetized, paralyzed, and artificially ventilated piglets less than 4 days, 2-3 wk, and 10 wk of age. Tracheal smooth muscle tension was measured in vivo from an open tracheal segment by use of a force transducer. Intravenous SP caused a dose-dependent increase in tracheal tension in all three age groups; however, the response in less than 4-day-old piglets was significantly weaker than in 2- to 3- and 10-wk-old piglets. NKA caused a dose-dependent increase in tracheal tension only in 2- to 3- and 10-wk-old piglets. The response of tracheal tension to NKA was weaker than the response to SP in all age groups. Atropine (2 mg/kg) significantly diminished the responses of tracheal tension to SP and NKA, indicating a cholinergic contribution to these responses at all ages. Intravenous thiorphan, a known NEP inhibitor, potentiated the effects of SP only in 2- to 3- and 10-wk-old piglets and did not affect the response of tracheal tension to NKA at any age. Biochemical analyses demonstrated a significant increase in tracheal NEP activity in comparably aged piglets over the first 10 wk of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Biochemical and cytochemical studies of preadipocyte differentiation in serum-free culture of porcine stromal-vascular cells: interaction of dexamethasone and growth hormone.

Stromal-vascular cells from adipose tissue of pigs 5-7 days of age were grown in serum for 2-3 days and switched to serum-free (insulin, transferrin and selenium) conditions +/- test hormones for 6-7 days. The interaction of dexamethasone (DEX) and human growth hormone (hGH) was evaluated since glucocorticoids augment and hGH antagonizes the effect of insulin. Low levels (1-10 nM) of DEX with insulin doubled (p less than 0.05) specific activity of glycerol phosphate dehydrogenase (GPDH) and doubled (p less than 0.05) the number of detectable fat cells relative to insulin alone. DEX with insulin enhanced the morphological differentiation of preadipocytes and markedly increased fat cell cluster numbers in the presence of hGH. Furthermore, 1-10 nM of DEX partially blocked (p greater than 0.05) the inhibitory effect of 10 nM hGH on GPDH activity, but 1-100 nM DEX had no effect (p greater than 0.05) on the ability of hGH to compromise lipid deposition. DEX alone (no insulin or hGH) induced the appearance of esterase-reactive but lipid-free cells. Cells with these characteristics were increased in number by DEX in the presence of hGH but were nearly absent in the presence of insulin and DEX. Therefore, transient exposure to GH in vivo may have no permanent effect on adipose tissue development in the continued presence of glucocorticoids.

Adipose Tissue↗
PubMed1992

Overnight theophylline concentrations and effects on sleep and lung function in chronic obstructive pulmonary disease.

Circadian alterations in lung function occur in respiratory disorders, with the nadir during the sleep-related hours. Higher therapeutic serum theophylline concentrations (STC) during the night have been shown to improve lung function in reversible airway disease. To determine what effect higher nocturnal STC would have in patients with chronic obstructive pulmonary disease (COPD) on overnight lung function, oxygen saturation, and sleep quality, two different theophylline products were used to give higher or lower STC during the night. We found that with a higher STC (15.0 +/- 1.0 versus 11.0 +/- 1.0 micrograms/ml, p = 0.005) at 7:00 A.M., the overnight changes in FEV1 (+7.4 +/- 5.7% versus -18.9 +/- 7.9%, respectively) and FVC (+1.8 +/- 7.5% versus -17.2 +/- 3.9%, respectively) were significantly better. However, there was no apparent effect on oxygen saturation (mean sleep values for higher STC were 85.3 +/- 1.2%, and for lower STC they were 86.5 +/- 0.8%). The higher STC did not adversely affect sleep latency, sleep efficiency, or sleep staging. We conclude that a higher therapeutic STC during sleep will improve lung function without altering oxygen saturation in patients with COPD. In this group of patients, the higher STC did not interfere with sleep characteristics.

Administration, Oral↗
PubMed1992

Spectrum of corticosteroid sensitivity in nocturnal asthma.

The nocturnal worsening of asthma is a common problem, and the contribution of inflammation to its pathogenesis remains unclear. We investigated the responses of 11 asthmatic subjects to overnight intravenous infusion of hydrocortisone. Prior to the study, all the subjects demonstrated clinically stable daytime asthma but persistent nocturnal worsening of spirometry. As a group, their overnight decrement in FEV1 improved from 46 +/- 4% at baseline to 12 +/- 3% (p less than 0.001) after steroid infusion. Nine of the 11 subjects demonstrated individual improvement in their overnight decrements in FEV1 of greater than 40%. The mean improvement between baseline and steroid infusion nights was 67 +/- 11%. A spectrum of response was evident, and only four of the subjects reached the normal circadian variability in overnight FEV1 measurements of less than 8%. We conclude that the nocturnal worsening of asthma often has a significant corticosteroid-sensitive component that may be both dose- and time-dependent.

Asthma↗
PubMed1992

Risk factors for the degradation of lung elastic fibers in the ventilated neonate. Implications for impaired lung development in bronchopulmonary dysplasia.

In order to evaluate the risk for proteolytic destruction of lung parenchymal elastic fibers in ventilated premature infants, the concentrations of elastase were determined in tracheal aspirates of 65 infants from whom we obtained a total of 327 sequential samples. Elastase was detected at least once in 39 of the 65 infants studied. Eleven of these infants were ventilated with greater than 60% oxygen for greater than 5 days. In 19 infants, the presence of elastase was associated with positive bacterial and/or viral cultures and/or elevated ratios (greater than 0.22) of immature neutrophils to total neutrophils. Elastase was not detected in the lung secretions of 26 infants ventilated with greater than 60% oxygen for less than 3 days, suggesting minimal risk for elastic fiber destruction in the intubated infant who neither has pneumonia nor requires prolonged hyperoxic ventilation. The risk for elastic fiber destruction was further evaluated by analyzing sequential urine and tracheal aspirate samples for the presence of an elastolytic degradation product of elastin (desmosine). The biochemical data indicated a potential risk for proteolytic destruction of elastic fibers in association with infection and/or prolonged hyperoxic exposure. In addition, autopsy specimens obtained from three of the infants revealed structurally abnormal lung parenchymal elastic fibers. Because elastic fibers are believed to provide the structural support for alveolar septal development, proteolytic degradation of these fibers may be a significant factor in the impaired lung development that occurs in infants with bronchopulmonary dysplasia.

Bronchopulmonary Dysplasia↗
PubMed1992

Timing of prednisone and alterations of airways inflammation in nocturnal asthma.

Asthmatic subjects prone to nocturnal worsening demonstrate overnight recruitment of inflammatory cells into the airways. The influence of dose timing on the ability of corticosteroids to block circadian recruitment of inflammatory cells into asthmatic airways and attenuate the nocturnal worsening of asthma is unclear. In a double-blind, placebo-controlled, crossover design, we evaluated the response of seven asthmatic subjects with respect to overnight spirometry, blood eosinophil counts, and bronchoalveolar lavage cytology to a single variably timed 50 mg oral dose of prednisone given at 0800, 1500, or 2000 h. Compared to placebo, a single prednisone dose at 1500 h resulted in a reduction in the overnight percentage fall in FEV1 (-28.2 +/- 7.3 versus -10.4 +/- 4.5%, p = 0.04) and improvement in the 0400 h FEV1 (2.53 +/- 0.38 versus 3.43 +/- 0.38 L, p = 0.03). In contrast, neither a 0800 nor 2000 h prednisone dose compared to placebo resulted in overnight spirometric improvement. Also following the 1500 h prednisone dose, blood eosinophil counts were significantly reduced at both 2000 and 0400 h. Lastly, the 1500 h dosing resulted in a pan-cellular reduction in bronchoalveolar lavage cytology (p < or = to 0.05 for all cell lines compared to placebo), but neither alternative dose schedule significantly reduced any cell line. Our data support the relevance of timing of prednisone dose in altering the inflammatory milieu and spirometric decline associated with nocturnal worsening of asthma.

Adult↗
PubMed1992

Alae nasi activation in preterm infants during oral feeding.

Preterm infants may demonstrate impaired ventilation during oral feeding with resultant hypoxemia and hypercarbia. This study was designed to determine whether infants activate a representative upper airway muscle, the ala nasi, in response to these ventilatory changes. Ten preterm infants (postconceptional age at study 35 +/- 4 wk, weight 2.2 +/- 0.1 kg) were studied during a control period, continuous feeding, subsequent intermittent feeding, and a period of nonnutritive sucking. Nasal airflow was measured with a pneumotachometer to quantify minute ventilation. The alae nasi electromyogram (EMGAN) was recorded with surface electrodes, and sucking pressure was detected by a catheter in the feeding nipple. End-tidal CO2 and O2 saturation were also recorded during each period. The percentage of breaths associated with EMGAN activity increased from 41 +/- 13% during the control period to 95 +/- 5% and 93 +/- 7% during continuous and intermittent sucking, respectively (p < 0.05). Eighty-seven +/- 5% of EMGAN activity occurred during inspiration. During continuous and intermittent sucking, the amplitude of EMGAN activity also increased (6.8 +/- 5.2 and 6.7 +/- 4.0 arbitrary units/breath, respectively) compared with the control period (2.4 +/- 2.8 units/breath, p < 0.05). In association with the increase in EMGAN activity, O2 saturation fell from 98 +/- 1% in the control period to 95 +/- 1% during both continuous and intermittent feeding (p < 0.05), and minute ventilation fell from 274 +/- 80 mL/min/kg during the control period to 190 +/- 81 and 208 +/- 57 mL/min/kg during continuous and intermittent feeding, respectively (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Dioxide↗
PubMed1992

Voltage-activated currents in somatic muscle of the nematode parasite Ascaris suum.

1. Voltage-activated currents in cell bodies of the somatic muscle cells of Ascaris suum were studied using a two-microelectrode voltage-clamp technique. Cells recorded from had resting membrane potentials around -35 mV and had input conductances in the range 1-10 microS. 2. In cells bathed in artificial perienteric fluid, depolarizing steps from a holding potential of -35 mV elicited outward currents at a threshold of -15 mV. These currents had inwardly directed inflections on the rising phase, suggesting the presence of more than one current. Hyperpolarizing steps did not activate current. 3. Tetraethylammonium (TEA+, 69 mmol l-1) blocked the outward currents and allowed a voltage-dependent inactivating Ca2+ current to be observed. The peak current-voltage relationship was U-shaped with a threshold around -15 mV and peak at +5 mV. The reversal potential of the Ca2+ current was estimated by extrapolation to be +45 mV. 4. The permeability of the voltage-activated outward currents was studied by examining reversal potentials of tail currents. The reversal potentials were linearly dependent on the logarithm of the extracellular potassium concentration if extracellular [K+] was greater than 10 mmol l-1. The Na+/K+ permeability ratio of the currents was 0.04. 5. Inactivation, seen as a decline following the peak of the K+ current, was produced by maintained depolarization. The recovery from inactivation was complex and could be described by the sum of two exponentials with time constants of 0.67 s and 20.1 s. Steady-state inactivation of the K+ currents was observed at a range of holding potentials. Only a proportion (34%) of the total K+ current was inactivated by holding potentials more positive than -20 mV. 6. Extracellular application of 5 mmol l-1 4-aminopyridine (4-AP) selectively abolished an early fast component of the K+ current (the peak). The 4-AP-sensitive current decayed quickly with a time constant of around 10 ms; a Boltzmann fit to its activation curve had a half-maximal activation voltage of +14 mV and a 'slope' of 10.5 mV. The 4-AP-resistant current decayed with a time constant of around 1 s; a Boltzmann fit to its activation curve had a half-maximal activation voltage of +29 mV and a 'slope' of 12 mV. 7. Depolarization activates a Ca2+ current and two K+ currents: the K+ currents were separated into lower-threshold, fast-inactivating (Ia-like) and higher-threshold, slowly inactivating (Ik-like) currents.

Aminopyridines↗
PubMed1992

Norepinephrine inhibits rat pre-adipocyte proliferation.

Hormonal and neural status are major determinants for cellular growth. The purpose of this study was to assess the influence of the adrenergic hormones on pre-adipocyte growth in primary cell culture. Stromal-vascular cells were obtained from the inguinal pad of young rats and grown in culture for two weeks. Cells were exposed to norepinephrine (NE) during the proliferative phase of growth, labelled by [3H]-thymidine incorporation and then placed on a differentiation promoting medium. Adipocytes and stromal cells were separated using a density gradient, and [3H]-thymidine content was determined for both cell types. NE reduced [3H]-thymidine uptake indicating a reduction in pre-adipocyte proliferation. NE-induced inhibition of pre-adipocyte growth was blocked by the presence of propranolol, whereas phenoxybenzamine had no effect, thereby suggesting that NE-inhibition is through beta-adrenoceptors. Pre-adipocytes were treated with NE for varying lengths of time to investigate whether cells were desensitized to chronic beta-adrenergic stimulation. In addition, adenosine deaminase (ADA) was also applied to eliminate adenosine which may accumulate during NE stimulation. Neither the duration of NE exposure nor ADA treatment affected adrenergic control of adipocyte growth. These studies indicate that NE reduces pre-adipocyte proliferation and therefore may be an important negative regulatory component of adipocyte growth.

Adenosine Deaminase↗
PubMed1992

Pharmacokinetics of low-dose methotrexate in adult asthmatics.

Several reports have been published on the disposition of methotrexate (MTX) when given in low dosages, but none in asthmatic patients. To address this matter, pharmacokinetic studies were performed in nine patients with severe, steroid-requiring asthma (ages 18-76 yrs) after the sixth weekly intramuscular dose of MTX. Theophylline pharmacokinetic studies were also performed at baseline prior to the start of MTX treatment and at the time of the MTX studies. Total systemic clearance of MTX, given as mean (SD), was 122.6 (25.1) ml/minute, volume of distribution at steady state 0.49 (0.2) L/kg, half-life 3.1 (0.3) hours, mean residence time 5.0 (0.6) hours, and renal clearance 89.1 (36.3) ml/minute. These values are similar to those previously reported for other patient populations receiving low-dose MTX. Eight of these patients were evaluated for changes in theophylline pharmacokinetics. Theophylline clearance at week 6 decreased an average of 19% from baseline and correlated inversely with total MTX clearance. Percentage change in theophylline clearance from baseline was inversely correlated with MTX nonrenal clearance, but was not statistically significant. This finding may indicate competition for clearance pathways between MTX and theophylline.

Adolescent↗
PubMed1992

Apnea of prematurity.

Apnea is a common, treatable disorder of respiration in premature infants, which usually resolves over time. The definition and classification of apnea are discussed, as well as its epidemiology and natural history. The pathophysiology of apnea is considered in detail, including the chemosensory and reflex input that modulates respiration and the involvement of upper airway control in the etiology of obstructive apnea. Finally, diagnosis and therapy are reviewed, and the relationship of apnea of prematurity to the underlying disorder in sudden infant death syndrome is considered.

Apnea↗
PubMed1992

Assessment of functional ability in Alzheimer disease: a review and a preliminary report on the Cleveland Scale for Activities of Daily Living.

Assessment of activities of daily living (ADL) in Alzheimer disease (AD) is critical in establishing the diagnosis, monitoring disease progression, evaluating the efficacy of treatment interventions, and determining the need for health and social services. The proper method to measure ADL depends on the purposes to which the scale is to be put. Existing ADL scales differ as to the type of behaviors assessed, the nature of the observations made, and the manner in which the observations are quantified. These scales were not specifically designed to evaluate changes in the nature and extent of the broad spectrum of functional difficulties seen in individuals with AD. We describe the Cleveland Scale for Activities of Daily Living (CSADL), an informant-based instrument designed to expand upon the capacity of existing physical and instrumental ADL scales by assessing both premorbid and current component acts (e.g., initiation versus implementation) of daily living functions.

Activities of Daily Living↗
PubMed1992

Oxygen desaturation complicates feeding in infants with bronchopulmonary dysplasia after discharge.

Recurrent episodes of hypoxemia may affect the growth, cardiac function, neurologic outcome, and survival of infants with bronchopulmonary dysplasia (BPD). As oral feeding might stress these infants by compromising pulmonary function even after hospital discharge, we measured oxygen saturation (SaO2) via pulse oximetry before, during the initial 10 minutes of, and immediately after oral feeding in 11 patients with BPD, 12 very low birth weight infants, and 23 healthy full-term infants. All infants with BPD had been previously discharged from the hospital after weaning from supplemental oxygen. Studies were done at a mean postconceptional age of 43 weeks while the infants were fed at home by one of their parents. Levels of SaO2 for the three groups were comparable before and during feeds. After feeding, the infants with BPD had significantly lower mean levels of SaO2 (84 +/- 8% [SD] vs 93 +/- 4% and 93 +/- 3%, respectively; P less than .01). They also spent more time after feeding with an SaO2 less than 90% (64 +/- 34% of time vs 27 +/- 33% for the very low birth weight and 22 +/- 20% for the term group; P less than .01) and greater time with an SaO2 less than 80% (37 +/- 28% vs 4 +/- 10% and 4 +/- 8%, respectively; P less than .01). Desaturation in infants with BPD was related to larger volume and faster oral intake during feeding. Thus, the data indicate that desaturation after feeding remains a recurrent problem for survivors of BPD after discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Weight↗
PubMed1992

Nocturnal asthma.

The nocturnal worsening of asthma is a common problem that can have significant related morbidity and mortality. There are many circadian biologic rhythms that contribute to the increased nocturnal bronchial reactivity and decrement in lung function. Therapy directed at the nocturnal aspect of this asthma process can produce marked improvement in symptoms and lung function.

Adrenal Cortex Hormones↗
PubMed1991

Lack of benefit of methotrexate in severe, steroid-dependent asthma. A double-blind, placebo-controlled study.

OBJECTIVE: To determine the effect of low-dose methotrexate in asthmatic patients on steroid use, asthma symptom scores, pulmonary function, airway reactivity, blood cellular components, and immunoglobulin E levels. DESIGN: A randomized, double-blind, parallel, placebo-controlled, 13-week clinical trial with follow-up of patients in an open trial of methotrexate at the conclusion of the double-blind study. SETTING: An asthma care outpatient clinic. PATIENTS: From February 1988 to March 1990, 19 patients with severe, steroid-dependent asthma were enrolled in the study. Two of these patients were excluded from analysis. INTERVENTIONS: Patients were administered methotrexate or placebo intramuscularly, to assure complete absorption, once weekly during the 13-week study. RESULTS: Patients on methotrexate and placebo both significantly decreased their steroid dose by 39.6% (95% CI, 25.1% to 54.1%, P = 0.001) and 40.2% (CI, 17.9% to 67.4%, P = 0.003), respectively. Pulmonary function did not differ significantly between the methotrexate and placebo groups. In addition, airway reactivity and symptom scores were unchanged on methotrexate or placebo. No significant toxicities were seen during the course of the 13-week blinded study, but one patient on methotrexate and prednisone in the follow-up period developed Pneumocystis carinii pneumonia and died. Despite continuing methotrexate for up to 1 year, and increasing methotrexate to 30 mg weekly, no significant benefit of methotrexate on asthma control could be shown. CONCLUSION: Our study does not support the use of methotrexate in the treatment of severe asthma.

Adrenal Cortex Hormones↗
PubMed1991

Effect of glucoprivation on glutamate decarboxylase activity in the ventromedial nucleus.

Activity of the GABA-synthesizing enzyme, glutamate decarboxylase (GAD), was measured in brain areas involved in glucoregulation 60 min after a glucoprivie challenge. The rate of GAD activity in the ventromedial nucleus of the hypothalamus (VMN) increased in a dose-dependent manner in response to intraperitoneal injection of 2-deoxy-D-glucose (2-DG). The increase in VMN GAD activity was significantly correlated with an increase in food intake (r2 = .77, p less than 0.01). The increase in VMN GAD activity was not due to the higher food intake since rats receiving 2-DG and denied access to food also had elevated rates of VMN GAD activity. VMN GAD activity was increased 28% and 32% after intracerebroventricular injection of 2-DG or 5-thioglucose, respectively. The rates of GAD activity in the lateral hypothalamus and area postrema were not affected by either peripherally or centrally administered 2-DG. The increase in VMN GAD activity after glucoprivation may be involved in the regulation of blood glucose by influencing food intake.

Animals↗