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Biomedical subjects

J L Larson

Publications and source records attributed to J L Larson.

67 records · Page 4Linked to original sources

Caring for individuals using home ventilators: an appraisal by family caregivers.

This article describes a study of the effects of caregiving on family members who assumed primary responsibility for managing the care of ventilator-assisted individuals in the home. Thirteen caregivers were interviewed and five variables associated with their role were assessed: caregiving tasks, burden of caregiving, impact of caregiving, mastery of the caregiving role, and satisfaction with caregiving. Data were collected using the Caregiving Appraisal Scale (CAS), a list of caregiving tasks, and a semistructured interview. Caregivers assumed multiple responsibilities for individuals who were completely ventilator-dependent (n = 5), partially ventilator-dependent (n = 3), or nocturnally ventilated (n = 5). Caregivers reported feeling moderate levels of both the burden and the negative impact of caregiving but a positive sense of mastery and satisfaction. They described problems with home healthcare nurses, insurance coverage, and equipment suppliers. Lack of preparation, in terms of education provided by healthcare professionals, limited their ability to manage these problems quickly and effectively. Caregivers suggested that healthcare providers expand discharge planning to include provision of problem-solving strategies.

Adult↗

The use of recombinant DNA techniques to study tylosin biosynthesis and resistance in Streptomyces fradiae.

A substantial amount of information on the biosynthesis of tylosin has been obtained over the past ten years. Physiological studies and experiments with tylosin-blocked (tyl) mutants have suggested the probable pathway by which tylactone is converted to tylosin. The development of recombinant DNA methodology for streptomycetes in general, and for Streptomyces fradiae in particular, has allowed us to apply gene cloning techniques in further studies of tylosin biosynthesis in S. fradiae. The macrocin O-methyltransferase (MOMT), which catalyzes the last step in tylosin biosynthesis, was purified, and the sequence of the 35 amino acids at its amino-terminus was determined. A synthetic 44 base oligonucleotide probe was constructed on the basis of the amino acid sequence. The probe was used to identify sequences containing the MOMT structural gene in bacteriophage and cosmid libraries of S. fradiae DNA. Complementation of tyl mutants with the cloned DNA sequences identified nine tyl biosynthetic genes (tylC, D, E, F, H, J, K, L, and M) in a 42 kb stretch of DNA. Genes complementing four mutant classes, tylA, B, G, and I were not found. A tylosin-resistance gene, tlrB, was located just left of the tyl gene cluster. Tylosin-sensitive mutants of S. fradiae, which were isolated from regenerated protoplasts and which have pleiotropic deficiencies in tylosin biosynthesis, contained deletions which included at least some of the identified tyl loci and one or both of two tylosin-resistance genes, tlrB and tlrC. Possible schemes for the functional organization of the tyl region of the S. fradiae genome are discussed.

DNA, Bacterial↗

Respiratory muscle strength in older adults.

Gender-related effects and two measures of muscularity, handgrip strength and fat-free mass (FFM), were examined to determine their relationship to respiratory muscle strength. Subjects were 101 healthy older adults. In 75 subjects, the magnitude of learning effect was examined over four weekly sessions. Maximal inspiratory pressure (PImax) was lower with increasing age in women, and maximal expiratory pressure (PEmax) was lower with increasing age in both genders. The PEmax correlated with handgrip strength and FFM in men only. Performance of PImax plateaued by the third visit in both men and women. Performance of PEmax plateaued by the third measure in women and was unchanged across four measurements for men.

Aged↗

Incremental threshold loading in patients with chronic obstructive pulmonary disease.

The purpose of this research was to study the reproducibility of incremental threshold loading, a test of inspiratory muscle endurance, in patients with mild to severe chronic obstructive pulmonary disease. Twenty-seven patients completed four weekly visits. A significant difference was noted between the first visit and subsequent visits for the maximum absolute load that patients could tolerate, but no difference was noted in the load relative to inspiratory strength. Breathing pattern did not change significantly among visits to account for the differences in absolute load. Patients had a tendency to use rapid shallow breathing at the end of the test, suggesting that they approached the limits of their endurance and thus nearly fatigued their inspiratory muscles.

Aged↗

Reliability and validity of the 12-minute distance walk in patients with chronic obstructive pulmonary disease.

Validity and test-retest liability of the 12-minute distance (12MD) walk, a measure of functional status, were examined in patients with chronic obstructive pulmonary disease. Four tests were administered at weekly intervals. Performance increased (p < .01) over the first three tests. Test-retest reliability was r34 = .98 (df = 46) for tests 3 and 4. The 12MD walk correlated with the Sickness Impact Profile, Physical Dimension (r = -.45); forced expiratory volume in 1 second % predicted ( r = .40); maximal inspiratory pressure (PImax) (r = .52); and exercise-related breathlessness (r = -.49). Exercise-related breathlessness and PImax accounted for 42% of the variance. The validity and reliability of the 12MD walk were supported.

Aged↗

Test-retest reliability of symptom-limited cycle ergometer tests in patients with chronic obstructive pulmonary disease.

BACKGROUND: Symptom-limited exercise tests are widely used to evaluate the effects of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD), but the reliability of these tests is not well established in COPD patients. OBJECTIVES: We compared test-retest reliability of two repeated symptom-limited exercise tests between COPD patients and healthy elderly subjects and between male and female patients. METHOD: Fifty-six COPD patients (40 men, 16 women) and 16 healthy subjects (6 men, 10 women) performed two symptom-limited exercise tests approximately 2 weeks apart. Measures of oxygen uptake (VO2), minute ventilation (VE), heart rate, and ratings of breathlessness and leg fatigue were obtained at peak exercise at each symptom-limited exercise test. RESULTS: Repeated measures of peak exercise responses were stable for patients and healthy subjects and for male and female patients. Although mean percent error (absolute difference/mean) for peak exercise responses was low, some individuals' values exceeded 10%. There was no difference in the percent error between COPD patients and healthy subjects or between men and women with COPD. Test-retest reliability was lower for breathlessness ratings than for other peak exercise responses for all groups. CONCLUSIONS: Repeated symptom-limited exercise tests are reliable in COPD patients and healthy subjects. However, some individuals are less reliable, and these patients may require more than one exercise test to establish reliable performance.

Aged↗

High-intensity inspiratory muscle training in patients with chronic obstructive pulmonary disease and severely reduced function.

PURPOSE: This study examined the effects of inspiratory muscle training (IMT) with high-intensity inspiratory pressure loads on respiratory muscle performance and exertional dyspnea. METHODS: This was a randomized single-blind clinical trial. Twenty-seven patients with chronic obstructive pulmonary disease (18 men, 9 women) with severe to very severe airflow obstruction and severely limited functional performance were assigned randomly to an IMT group (n = 12) or an educational control group (n = 15). The IMT group trained with a threshold loaded device for 30 minutes a day for 16 weeks using interval training techniques. Training was initiated with inspiratory pressure loads equal to 30% of maximal inspiratory pressure (Plmax) and increased as tolerated to 60% of Plmax. Dependent variables were measured before and after 4 months of IMT: inspiratory muscle strength (Plmax), respiratory muscle endurance (discontinuous incremental threshold loading test [DC-ITL]), dyspnea (Chronic Respiratory Disease Questionnaire [CRQ]), and the Borg Category-Ratio Scale ratings of perceived breathing difficulty (RPBD) at equal loads during the DC-ITL. RESULTS: In the IMT group, Plmax increased from 64 +/- 15 to 75 +/- 17 cm H2O (P < .05), performance on the DC-ITL test increased from a maximal load of 37 +/- 12 to 53 +/- 13 cm H2O (P < .05), RPBD decreased from 5.5 +/- 2.5 to 3.8 +/- 2.6 for equal loads on the DC-ITL (P < .05) and the CRQ Dyspnea Scale improved from 18.1 +/- 5.1 to 22.4 +/- 5.2 (P < .05). CONCLUSIONS: Inspiratory muscle training at high-intensity loads significantly improved inspiratory muscle strength, respiratory muscle endurance, and respiratory symptoms during daily activities and respiratory exertion.

Aged↗

Gastrointestinal effects of modified guar gum and soy polysaccharide as part of an enteral formula diet.

Dietary fiber supplementation may improve gastrointestinal tolerance and decrease diarrhea in patients receiving enteral formula diets. To compare the effects of two dietary fibers on bowel function parameters and short-chain fatty acid excretion we fed 11 healthy men three defined enteral formula diets in random order for 18 days each. The test diets consisted of a fiber-free formula and daily intakes of maltodextrin (0 g of fiber), 15 g of total dietary fiber as an enzymatically modified guar gum, and 15 g of total dietary fiber as soy polysaccharide. Data were also collected while subjects consumed self-selected diets for 5 days. Mean transit time was longer and fecal moisture content was lower on 0 g of fiber and modified guar than on the self-selected and soy diets. Furthermore, mean transit time was slightly longer and fecal nitrogen excretion greater on modified guar compared with 0 g of fiber. Daily fecal output and frequency of defecation were greater, fecal pH was lower, and fecal butyrate concentrations were higher on the self-selected diet compared with the enteral formula diets. However, there was no difference in these parameters among the three liquid diets. Thus, despite significant differences in mean transit time, few differences in other parameters of bowel function were observed when healthy subjects consumed enteral formula diets containing 0 g of fiber and 15 g of total dietary fiber as modified guar and soy.

Adult↗

Chronic effects of the novel glucocorticosteroid RPR 106541 administered to beagle dogs by inhalation.

The preclinical safety of RPR 106541, a novel 17-thiosteroid, was evaluated in young adult and mature dogs by inhalation exposure for 26 weeks and 52 weeks, respectively. A dry powder formulation of RPR 106541 in lactose was administered to young adult dogs (approximately 6 months of age at initiation) at doses of 0 (air and placebo controls), 10, 100, or 1,000 microg/kg/d for 26 weeks. A solution-based aerosol formulation was administered to mature dogs (approximately 10 months at initiation) from a pressurized metered dose inhaler at 0 (air and placebo controls), 10, 50, and 150 microg/kg/d for 52 weeks. Clinical evidence of glucocorticosteroid-induced immunosuppression was observed by weeks 20-26 following relatively high dose exposures (100 microg/kg/d and 1,000 microg/kg/d) in young dogs receiving the dry powder formulation for 26 weeks. Classic glucocorticosteroid effects were observed, including adrenocortical atrophy, reduced bone mass with retention of epiphyseal growth plates in long bones, prominence of stromal adipose tissue in bone marrow, and atrophy of lymphoid tissues. Inhalation administration of RPR 106541 to sexually mature dogs facilitated more definitive characterization of endocrine affects of RPR 106541 as compared with administration in younger, sexually immature animals. Significant effects in female reproductive organs included absence of corpora lutea in association with atresia of vesicular follicles within the ovaries, endometrial hyperplasia, and lobular development of mammary tissue. Discordant development of mammary tissue, accumulation of secretory material within hyperplastic endometrial glands, and hypertrophy of uterine lining epithelium in absence of ovulation were consistent with a secondary progestin effect by a potent glucocorticosteroid.

Administration, Inhalation↗

Toxicologic and carcinogenic effects of the type IV phosphodiesterase inhibitor RP 73401 on the nasal olfactory tissue in rats.

RP 73401, a type IV phosphodiesterase inhibitor, caused toxic effects in the nasal olfactory region of Sprague-Dawley rats when administered by either oral or inhalation exposure. A single oral administration of RP 73401 (at a dose of > or = 50 mg/kg) or 5-day inhalation exposure (1 hr/day) at a dose of approximately 1.0 mg/kg per day caused degeneration and sloughing of the olfactory surface epithelium. Degeneration and loss of Bowman's glands were noted in the underlying lamina propria and submucosa. Electron microscopy of these lesions demonstrated that sustentacular cells and the epithelial cells lining Bowman's glands were the primary target cells in the olfactory mucosa. The earliest ultrastructural changes detected in these cells were dilatation and vesiculation of the endoplasmic reticulum, suggesting that metabolic activation is important for the toxic effects. In repeated-dose studies, 13 wk of oral dosing at 2.0 or 6.0 mg/kg per day resulted in subtle disorganization of the olfactory epithelium, whereas basal cell hyperplasia in the olfactory epithelium was identified in a 6-month inhalation study at a dose of 1.0 mg/kg per day. A 2-yr inhalation carcinogenicity study resulted in tumors of the nasal olfactory region in rats treated at 0.5 and 1.0 mg/kg per day. Most tumors were classified as olfactory neuroblastomas, and immunohistochemistry on selected tumors was consistent with their being of neuroectodermal origin. Of the species studied (rat, mouse, and dog), the olfactory toxicity of RP 73401 was confined to the rat, and the toxicity was likely related to metabolic activation by olfactory epithelial cells rather than the phosphodiesterase activity of the compound.

Administration, Inhalation↗

Inspiratory muscle training in patients with chronic obstructive pulmonary disease.

The effects of 6 months of muscle training with an inspiratory pressure load equal to 30% of the maximal inspiratory pressure (PImax) was compared with sham training with a light inspiratory pressure load. In this double-blind randomly assigned study, 67 patients with chronic obstructive pulmonary disease were followed for 6 months. Both groups demonstrated improvements in performance of PImax, respiratory muscle endurance time for breathing against an inspiratory pressure load equal to 66% of PImax, 12-minute distance walk, and dyspnea. The treatment group did not demonstrate significant effects beyond those observed in the control group. Improvements in performance were related to improved coordination of the inspiratory muscles and desensitization to dyspnea.

Activities of Daily Living↗