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Biomedical subjects

J M Herron

Publications and source records attributed to J M Herron.

At least 19 recordsLinked to original sources
PubMed1998

A systemic bioactivity comparison of double-strength and regular-strength beclomethasone dipropionate MDI formulations.

BACKGROUND: The efficacy and safety of regular-strength beclomethasone dipropionate MDI prescribed within its recommended dosing range of 2 to 5 puffs three to four times daily has been well established in more than 25 years of worldwide use. A more concentrated formulation delivering 84 microg per puff was developed to provide for a more convenient twice-daily dosing regimen. OBJECTIVE: This randomized, single-blinded, positive and placebo-controlled, parallel-group, multiple-dose bioactivity study was conducted to assess the potential of a new beclomethasone dipropionate 84 microg double-strength metered-dose inhaler (Vanceril 84 microg Double Strength Inhalation Aerosol/Key) to cause hypothalamic-pituitary-adrenocortical axis suppression. METHODS: Beclomethasone dipropionate double-strength 84 microg was compared with beclomethasone dipropionate regular-strength 42 microg, orally administered prednisone, and placebo inhaler after 36 consecutive days of administration in adults with moderate asthma. Beclomethasone dipropionate double-strength was administered as 5 puffs BID and beclomethasone dipropionate regular-strength was administered as 10 puffs BID for the same total daily dose of 840 microg of beclomethasone dipropionate. Oral prednisone was administered by mouth at 10 mg once a day. The potential for hypothalamic-pituitary-adrenocortical axis suppression was evaluated by an adrenocorticotropic hormone (ACTH) stimulation test using cosyntropin 250 microg in 500 mL normal saline infused over six hours on the 36th day of treatment. Sixty-four patients completed this study. RESULTS: No clinically significant post-study findings were observed from physical examination, electrocardiogram, or clinical laboratory evaluation for any treatment group. No serious or unexpected adverse events were reported. On the 36th day of treatment, there was a significant (P < .01) difference in the plasma cortisol concentration response to cosyntropin stimulation between the prednisone and placebo treatment groups at the sixth hour of infusion. There was no significant difference in the plasma cortisol concentration response to cosyntropin stimulation between the beclomethasone dipropionate double-strength and beclomethasone dipropionate regular-strength treatment groups and the placebo group. In addition, comparison of the response between the beclomethasone dipropionate double-strength and beclomethasone dipropionate regular-strength groups showed no significant difference. CONCLUSION: Beclomethasone dipropionate, administered either via a double-strength (84 microg/puff) or regular-strength (42 microg/puff) inhaler dosed at 840 microg/day showed no evidence of hypothalamic-pituitary-adrenocortical axis suppression in adults with moderate asthma.

Administration, Inhalation↗
PubMed1997

Proteinase-free myeloperoxidase increases airway epithelial permeability in a whole trachea model.

In cystic fibrosis the bronchiectatic conducting airways have large numbers of neutrophils in their walls and in their luminal contents. The neutrophil's primary granule enzyme activities of elastase and peroxidase are increased in the sputum of these patients. It has been postulated that these enzymes--together or individually--act to damage the airway epithelium. However, only peroxidase activity has consistently correlated with the degree of structural and functional airway disease in these patients with leakage of plasma protein into the airway lumen (Regelmann et al., Pediatr Pulmonol, 1995; 19:1-9). The present study was designed to test whether human neutrophil-derived myeloperoxidase can independently produce bronchial epithelial damage without the presence of proteases, as measured by increased permeability of the airway epithelium. Human peripheral blood neutrophils were purified, their primary granules isolated, and their peroxidase purified using affinity and ion exchange column chromatography. Activity of the proteinase-free peroxidase was measured using a chromogenic substrate. The effect of this peroxidase on the permeability of excised rat tracheas was measured using radioactive and fluorescent-labeled non-ionic molecules of varying molecular weight. Rat tracheas exposed to 15 minute treatments with either 130 U of peroxidase or hydrogen peroxide (10(-5) M) did not show a significant increase in the permeability of the epithelium to [3H]inulin, [14C]sucrose, and fluorescein isothiocyanate dextran 20 compared with control tracheas. However, those tracheas exposed to 130 U peroxidase followed by 10(-5) M hydrogen peroxide showed an increased permeability to each of the three test solutes. We conclude that proteinase-free myeloperoxidase, in the presence of non-toxic concentrations of its substrates, hydrogen peroxide and halide, produced increases in permeability to non-ionic molecules in the rat trachea within 15 minutes.

Animals↗
PubMed1997

Preliminary clinical evaluation of a high-resolution telemammography system.

RATIONALE AND OBJECTIVES: The authors designed, assembled, tested, and clinically evaluated a high-quality, fast, and relatively inexpensive telemammography system. METHODS: The authors designed a telemammography system that uses a high-resolution film digitizer and high data compression (> or = 40:1) to send images over regular telephone lines to a high-resolution laser printer that produces images with the look and feel of the original image and can operate in a hub and spokes mode. The authors then evaluated the system's performance. In a preliminary clinical study, interpretations of the laser-printed system's output of 119 cases were compared with the original interpretations, followed by a review of any clinically significant differences. RESULTS: With the exception of the laser printer, which is a modified off-the-shelf product, all hardware components of the system are commercially available products. The system digitizes (50 microns pixel size), compresses, transmits, receives, decompresses, and prints a 30 MB mammography file in less than 4 minutes. In the clinical study, there were 13 differences (in 13 cases) in the level of concern or recommendations. Seven were found to be clinically insignificant by a third-party review. The remaining six were reviewed by the original interpreter, and three were determined to be significant enough for further action. All were found to result from intra-reader variability rather than differences in visualization of possible abnormalities. CONCLUSIONS: Almost real-time, high-quality telemammography without geographic boundaries is possible with the use of high-level data compression. Telemammography with laser-printed film as the display may make it possible to offer mammographic services in remote locations while using commercially available technology.

Evaluation Studies as Topic↗
PubMed1995

Sputum peroxidase activity correlates with the severity of lung disease in cystic fibrosis.

Patients with cystic fibrosis (CF) of the same age differ significantly in their degree of pulmonary disease. Based on preliminary observations, we postulated that the activity of myeloperoxidase would be significantly increased in patients with greater structural lung damage than in those with less lung damage. Acid extracts of weighed sputum samples were assayed for lactoferrin concentrations by ELISA. Activities of peroxidase, cathespsin G, and elastase (with and without proteinase 3) were determined by kinetic analysis using chromogenic substrates. The patients were divided into quartiles based on their Brasfield chest-radiograph score. Patients in the first quartile (least amount of structural lung abnormality) were compared to those in the fourth quartile. The concentration of lactoferrin, a specific (secondary) granule protein of neutrophils, did not differ between the two patient groups. However, the activities of the neutrophil primary granule proteins, peroxidase, elastase, and elastase plus proteinase 3, were significantly elevated in the group with the most structural lung abnormality. Sputum albumin concentration was used to estimate leakages of plasma proteins into the airways. Peroxidase activity, but not the activity of cathepsin G, of elastase, or of elastase plus proteinase 3, correlated significantly with albumin/g sputum in both quartile groups. To confirm the association of sputum peroxidase activity with differences in lung structure and to test its correlation with lung function, spirometry was performed in a second group of patients during the week prior to the time of sputum sampling. In this second group, increased sputum peroxidase activity was associated with worse Brasfield scores and with decreased percent-predicted forced expiratory volume in 1 sec.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Fosinopril monotherapy: relationship between blood pressure reduction and time of administration.

The time to peak antihypertensive effect and the trough-to-peak ratio were determined in 64 Caucasian patients (19 men, 45 women) with mild to moderate hypertension [supine diastolic blood pressure (DBP) 95 to 115 mmHg]. They received placebo or fosinopril 10, 20, or 40 mg once daily for 4 weeks. The study consisted of a 4-week placebo lead-in, 4 weeks' double-blind treatment, and a 1-week placebo washout period. Vital signs were determined biweekly before dosing, and blood pressures were measured every 1 to 2 h during two 27-h periods at the beginning and end of treatment. After the first and last doses of all three regimens, the peak effect on blood pressure occurred 5 to 7 h after all three dosages. Neither peak nor trough blood pressure changes showed a clear dose-response relationship. Trough to peak ratios for the first dose, corrected for placebo effects, were 79% for fosinopril 10 mg, 48% for fosinopril 20 mg, and 74% for fosinopril 40 mg, and the trough-to-peak ratios for the last dose were 41% for fosinopril 10 mg, 32% for fosinopril 20 mg, and 44% for fosinopril 40 mg. In the 38 responders among the 48 patients receiving fosinopril (supine DBP decrease of at least 5 mmHg at 24 h postdose), trough-to-peak ratios ranged from 50 to 81%, and the range indicates that fosinopril is efficacious when administered once daily. Adverse effects were mild to moderate, and no patient discontinued treatment. Changes in the laboratory test results, electrocardiograms, or the results of physical examinations were unremarkable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Increased monocyte oxidase activity in cystic fibrosis heterozygotes and homozygotes.

Freshly isolated monocytes from cystic fibrosis (CF) heterozygotes and homozygotes had significantly increased oxygen uptake and superoxide formation after surface glycoprotein stimulation than did monocytes from age- and sex-matched controls. Lack of differences among the genotypes in inhibition by simple sugars of the concanavalin A-stimulated superoxide production and lack of differences in concanavalin A-binding surface proteins suggested that different regulation of the oxidase pathway produced the increased oxygen uptake and superoxide formation in CF patients and carriers. This regulatory role is consistent with the predicted structure of the CF gene product. The results support the hypothesis that the mononuclear phagocytes of CF heterozygotes have a significantly increased ability to kill intracellular microbes and may confer a selective advantage to the host.

Adolescent↗
PubMed1989

Sustained-release diltiazem: duration of antihypertensive effect.

The antihypertensive activity of a sustained-release preparation of diltiazem (given each 12 hours) was assessed in 96 patients with supine diastolic blood pressure (BP) between 95 and 110 mm Hg in a multicenter, randomized, double-blind, placebo run-in, parallel-group trial comparing optimally titrated doses of diltiazem and placebo. The aim was to assess the onset of action as well as the extent and variability of BP control of this formulation during the 12-hour interval. Diltiazem was titrated from 120 mg bid to 180 mg bid as necessary to lower BP. At baseline, on the first day of titration, and at the end of 8 weeks, BP was evaluated at 0, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dosing. The onset of action was within 2 hours, and the effect was maintained throughout the 12-hour period. Mean BP for the diltiazem group at baseline was 154/101 mm Hg. At week 8, BP was 148/93 mm Hg at hour "0" (P less than .02 and P = .0001 for systolic and diastolic BP vs. placebo), 139/84 mm Hg at the nadir at hour 5 (P = .0001), and 149/91 mm Hg at the end of the 12-hour period (P less than .02 and P = .0001 for systolic and diastolic BP). Diltiazem was significantly more effective than placebo (P = .0001) with 50% of patients controlled to a diastolic pressure of less than 90 mm Hg at 7 of the 10 evaluation points, including the evaluation point of 12 hours post-dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Metabolic effects of antihypertensive therapy with a calcium antagonist.

The effect of diuretics to increase serum glucose, low-density lipoprotein cholesterol and triglycerides, as well as the adverse changes in triglycerides and high-density lipoprotein cholesterol produced by nonselective beta blockers, have been largely ignored in the treatment of hypertension. However, a number of trials have shown that reductions in serum lipids can alter cardiovascular mortality. Calcium antagonists have become major drugs in the treatment of hypertension, and some data suggest that calcium antagonists may increase serum glucose levels. Significantly less data on lipid effects have been published. Lipid and glucose effects were examined in an 8-week antihypertensive study using a sustained-release preparation of diltiazem titrated from 240 to 360 mg/day in a twice-daily regimen in a randomized, double-blind, placebo-controlled parallel trial in 96 patients. Average supine blood pressure at week 8 was 156/98 mm Hg, standing blood pressure with placebo 152/100 mm Hg, and with diltiazem 147/91 and 144/93 mm Hg. There were no statistically significant changes in serum lipids or glucose in the diltiazem or placebo group or between the groups. Mean values (mg/dl) at baseline and week 8 in the diltiazem group were, respectively, for cholesterol 215 and 218, high-density lipoprotein cholesterol 50 and 51, low-density lipoprotein cholesterol 128 and 133, triglycerides 169 and 175, and glucose 113 and 110. Thus, this large and placebo-controlled study shows that diltiazem is among the antihypertensives with no adverse long-term lipid or glucose effects.

Blood Glucose↗
PubMed1987

Roxithromycin in the therapy of Streptococcus pyogenes throat infections.

Roxithromycin in two dosage regimens was compared with erythromycin in the therapy of 227 patients with throat infectious due to Streptococcus pyogenes. All three groups had the same clinical efficacy but roxithromycin 300 mg daily was less effective than erythromycin 500 mg qds in eradicating S. pyogenes while there were less antibiotic-related side effects with roxithromycin 150 mg bd than with erythromycin.

Adolescent↗
PubMed1983

Nonsurgical management of extradural hematomas in children.

With the advent of computerized tomography (CT), an increasing number of patients with only minimal neurological symptoms and no signs of brain herniation are found to harbor subacute or chronic extradural hematomas (EH's). The authors present the cases of 11 symptomatic but neurologically normal children with medium to large EH's managed by close observation. These EH's were discovered 4 hours to 6 days after injury; three were in the posterior fossa, seven over the frontoparietal convexity, and one in the temporal fossa. These clots were followed by serial CT scans. Nine children recovered without surgery from 4 to 18 days after injury, and all had evidence on CT of spontaneous clot resorption. Of these nine EH's, five clots displayed volume expansion from 5 to 16 days after injury before final resorption occurred. Expansion correlated with persistence or increase in symptoms, whereas resorption correlated with improvement. Two patients showed gradual uncal herniation on Days 6 and 8, respectively, presumably during the "expansile phase" of their clots. Both had emergency craniotomy and recovered without morbidity. It is hypothesized that the resorption dynamics of the subacute or chronic EH are similar to that of the chronic subdural hematoma, with predictable volume changes, and the outcome of each lesion depends on the interplay between the patient's intracranial pressure buffering capacity and the rate of volume change. If subtle signs of brain dysfunction are adopted to signal the failure of conservative treatment and the need for craniotomy, these patients may be safely, and many successfully, managed without surgery. Factors that influence outcome of medical treatment include the size, location, configuration, and the rapidity of accumulation of the clot, the presence of associated intradural lesions, the extracranial decompression of blood through skull diastases, and the age of the patient. These factors, the criteria for patient selection, and the indications for immediate operative intervention are discussed.

Adolescent↗
PubMed1982

Diode array digital radiography: initial clinical experience.

Initial clinical results are described for a new method of digital radiography based on high-detail self-scanning linear diode arrays which overcome many of the limitations of present film or other digital methods. The technique uses a fan-shaped x-ray beam to produce a nearly scatter-free image on a phosphor strip that is fiber-optically coupled to six self-scanning arrays of light-sensitive diodes spaced 0.025 mm, thus providing 6,144 discrete sensors across the field of view. Because these diodes have a greatly expanded dynamic range and operate at very low noise, it becomes possible to visualize small density differences or contrast below 1% both in the light and dark areas of the image. Because of the efficiency of detection and display, radiation doses can be reduced for a given information content. Our preliminary clinical studies have shown to broad application of our method in examining the chest and abdomen and in performing intravenous digital arteriography.

Angiography↗
PubMedDate not supplied

Lack of hypothalamic-pituitary-adrenal axis suppression with once-daily or twice-daily beclomethasone dipropionate aqueous nasal spray administered to patients with allergic rhinitis.

The potential for a newly developed, double-strength (0.084%) beclomethasone dipropionate (BDP) aqueous (AQ) nasal suspension to produce effects associated with exposure to systemic corticosteroids was assessed by the plasma cortisol response to cosyntropin stimulation induced by a 6-hour intravenous infusion of 250 micrograms of cosyntropin in 500 mL of normal saline. Sixty-four patients with allergic rhinitis were enrolled in this study. Patients were randomly assigned to one of the following four treatment groups: (1) BDP AQ Forte (0.084%) nasal spray 336 micrograms once daily; (2) BDP AQ (0.042%) nasal spray 168 micrograms twice daily; (3) placebo nasal spray twice daily; or (4) oral prednisone 10 mg once daily in the morning. After 36 consecutive days of treatment, there was a significant (P < 0.01) difference in the plasma cortisol response to cosyntropin stimulation between the prednisone and placebo groups; however, there were no significant differences between the BDP AQ Forte or the BDP AQ groups compared with the placebo group. Secondary analyses comparing BDP AQ Forte administered as 336 micrograms once daily with BDP AQ administered as 168 micrograms twice daily showed no significant differences in plasma cortisol responses to cosyntropin stimulation. No serious adverse events were reported. Adverse events consisted of headache, pharyngitis, or nasal irritation, with headache being reported most frequently. These adverse events were similarly distributed among active treatment groups and were similar to placebo. No clinically relevant changes were observed in any treatment group in findings on clinical laboratory tests, physical examination, or electrocardiography. Vital signs, obtained daily, were consistent with values observed in healthy individuals. No patient exhibited signs of oral candidiasis. All patients met the plasma cortisol concentration criteria for discharge relative to expected hypothalamic-pituitary-adrenal axis function. In conclusion, there were no significant differences in plasma cortisol responses to cosyntropin stimulation between groups of patients with allergic rhinitis treated with either BDP AQ Forte (0.084%) nasal spray 336 micrograms once daily or BDP AQ (0.042%) nasal spray 168 micrograms twice daily compared with the placebo group. These results indicate that the dosing regimens of BDP AQ nasal suspensions used in this study lack systemic effects and are safe and well tolerated.

Administration, Intranasal↗
PubMedDate not supplied

Safety and tolerability of once-daily mometasone furoate aqueous nasal spray in children.

Sensitive and reproducible assessments of hypothalamic-pituitary-adrenal (HPA) axis function were used to assess the systemic exposure and tolerability of mometasone furoate aqueous nasal spray (MFNS) in 96 children aged 3 to 12 years with allergic rhinitis. In the first phase of the study, older children (aged 6 to 12 years) received MFNS at 50, 100, or 200 micrograms or placebo once daily for 7 days, and plasma cortisol concentrations were measured by radioimmunoassay before and after treatment. Plasma cortisol concentrations were not statistically significantly different from baseline values on day 7 or day 8 (1 day after treatment was stopped). Also, the mean plasma cortisol and 24-hour urinary free-cortisol concentrations of the MFNS-treated and placebo groups were not statistically significantly different. Additionally, mometasone furoate was undetectable in almost all plasma samples collected at 0.5, 1, and 2 hours after dosing on days 1 and 7. Because these findings indicated that MFNS could be safely administered to patients aged 6 to 12 years, a more rigorous assessment was conducted in younger patients (aged 3 to 5 years). The younger patients also received MFNS at 50, 100, or 200 micrograms or placebo once daily, but for a longer duration (14 days). HPA axis function was determined by the response to cosyntropin stimulation on the final day of treatment. The younger patients demonstrated a normal cortisol response to cosyntropin stimulation on day 14; that is, all the patients had an increase in plasma cortisol concentration of at least 7 micrograms/dL to at least 18 micrograms/dL. Mean plasma cortisol concentrations for the MFNS-treated groups were not statistically significantly different from the mean concentration for the placebo group, either before or after cosyntropin stimulation. MFNS was also found to be well tolerated by both the younger and older children, with headache the most frequently reported adverse event in both the placebo- and MFNS-treated groups. No clinically relevant changes in the results of physical examinations, clinical laboratory determinations, or electrocardiography were noted. These results indicate that the intranasal administration of up to 200 micrograms of MFNS once daily for up to 14 days in children aged 3 to 12 years who have allergic rhinitis is well tolerated and does not result in clinically relevant systemic exposure.

Administration, Intranasal↗
PubMedDate not supplied

Simultaneous mass spectrometry and thermoconductivity measurements of end-tidal xenon concentrations: a comparison.

Studies in which the rate of local cerebral blood flow is determined by xenon-enhanced computerized tomography require measurement of end-tidal gas. A mass spectrometer and a thermoconductivity detector were compared in measuring the concentration of xenon in end-tidal gas both in humans and in a clinically simulated ("breathing bag") system. The experiments showed that the two instruments provided virtually identical results up to a rate of 18 breaths/min, at which rate recorded concentrations showed marginal degradation with the thermoconductivity detector. Given the absence of a significant difference in the ability of the mass spectrometer and the thermoconductivity detector to measure end-tidal xenon concentration, the thermoconductivity detector appears to be a satisfactory alternative in studies measuring the rate of local cerebral blood flow by enhanced computerized tomography.

Cerebrovascular Circulation↗
PubMedDate not supplied

The development of a xenon/computed tomography cerebral blood flow quality assurance phantom.

A simple, easy to use, quality assurance and performance test phantom was developed for the xenon/computed tomography (CT) cerebral blood flow method. The phantom combines an inhalation system which allows for the simulation of xenon buildup or washout in the arterial blood as well as a multisection translatable cylinder in which several sections can be scanned during a preselected protocol to simulate the CT enhancement in brain tissue during a study. The phantom and scanning protocol are described and their use is demonstrated. The results compare favorably to the theoretically expected fast, intermediate, and slow "flow" values designed into the phantom.

Cerebrovascular Circulation↗