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Biomedical subjects

A Maloney

Publications and source records attributed to A Maloney.

13 recordsLinked to original sources
PubMed2001

The therapeutic ratio of R-albuterol is comparable with that of RS-albuterol in asthmatic patients.

BACKGROUND: It has been suggested that R-albuterol produces bronchodilation that is comparable with that of racemic albuterol (RS-albuterol) on a 4:1 dose-for-dose basis but systemic side effects on a 2:1 basis, implying better therapeutic ratio for R-albuterol. OBJECTIVE: We sought to carefully compare the bronchodilating and systemic effects of R- and RS-albuterol by using a crossover study design. METHODS: Twenty asthmatic patients (15.1%-28.7% FEV(1) reversibility) were given R-albuterol (6.25-1600 microg), S-albuterol (6.25-1600 microg), RS-albuterol (12.5-3200 microg), or placebo in a crossover, double-blind, placebo-controlled fashion. Cumulative doses were given with a Mefar dosimeter, and FEV(1), heart rate, and plasma K(+) levels were measured 20 minutes after each dose. RESULTS: Both R- and RS-albuterol produced dose-related improvement in FEV(1) and, at higher doses, increased heart rate and decreased plasma K(+) levels. Neither placebo nor S-albuterol had any significant effect. Individual estimates of the potency ratio for R-albuterol/RS-albuterol were calculated and summarized across all subjects. The geometric mean potency ratio for effects on FEV(1) was 1.9 (95% CI, 1.3-2.8), on HR of 1.9 (95% CI, 1.3-2.9), and on K(+) level of 1.7 (95% CI, 1.3-2.1). CONCLUSION: All pharmacologic effects of RS-albuterol reside with the R-enantiomer, and S-albuterol is clinically inactive. The R-albuterol/RS-albuterol potency ratios for local (FEV(1)) and systemic effects (heart rate and K(+)) are similar, suggesting a comparable therapeutic ratio for R-albuterol and RS-albuterol in asthmatic subjects.

Adult↗
PubMed2000

Gene expression profiling of human colon cancer cells following inhibition of signal transduction by 17-allylamino-17-demethoxygeldanamycin, an inhibitor of the hsp90 molecular chaperone.

A number of molecular therapeutic agents, derived from exploiting our knowledge of the oncogenic pathways that are frequently deregulated in cancer, are now entering clinical trials. One of these is the novel agent 17-allylamino-17-demethoxygeldanamycin that acts to inhibit the hsp90 molecular chaperone. Treatment of four human colon cancer cell lines with iso-effective concentrations of this agent resulted in depletion of c-raf-1 and akt and inhibition of signal transduction. We have used gene expression array analysis to identify genes responsive to treatment with this drug. The expression of hsp90 client protein genes was not affected, but hsc hsp70, hsp90beta, keratin 8, keratin 18 and caveolin-1 were deregulated following treatment. These observations were consistent with inhibition of signal transduction and suggested a possible mechanism of resistance or recovery from 17-allylamino-17-demethoxygeldanamycin treatment. The results shed light on the molecular mode of action of the hsp90 inhibitors, and suggest possible molecular markers of drug action for use in hypothesis testing clinical trials. Oncogene (2000) 19, 4125 - 4133

Antibiotics, Antineoplastic↗
PubMed1999

Determinants of physical functioning in coronary patients: response to cardiac rehabilitation.

BACKGROUND: Coronary heart disease is a major cause of disability. There has been little study of the effect of cardiac rehabilitation on measures of self-reported physical functioning. METHODS: Physical functioning was measured using the Medical Outcomes Study-Short-Form Questionnaire. Determinants of physical function were analyzed in 303 patients with coronary heart disease. Response of physical function to a 3-month exercise rehabilitation program was then determined. RESULTS: At baseline, women had lower physical function scores than men, despite similar age and diagnostic distribution. Older patients had lower physical function than younger patients. Aerobic exercise capacity, leg and arm strength, and comorbidity and depression scores were all significant predictors of baseline physical function (r range, 0.46 to -0.22). Physical function score increased significantly after exercise conditioning, with a mean (+/- SD) overall score increase from 66 +/- 23 to 80 +/- 20 on a scale of 0 to 100. The best baseline determinant of a favorable physical function improvement after rehabilitation was a low baseline physical function score. The best training-related correlate of improved physical function score was a decrease in mental depression score. CONCLUSIONS: Self-reported physical function in coronary patients is related to age, sex, fitness, and mood state. Physical functioning improves after cardiac rehabilitation in all age, sex, and diagnostic groups, but particularly in patients with low baseline values. These data support the concept that cardiac rehabilitation effectively prevents and treats cardiac disability.

Adult↗
PubMed1999

Effects of altering cycling technique on gluteus medius syndrome.

OBJECTIVE: We discuss how altering the cycling technique of a cyclist receiving periodic chiropractic care helped in the management of gluteus medius syndrome. CLINICAL FEATURES: A 24-year-old male amateur cyclist had numbness and tingling localized to a small region on the superior portion of the right buttock. The area involved demonstrated paresthesia to light touch sensory evaluation. The cyclist had received chiropractic adjustments 2 days before the onset of the symptoms. One week earlier, the patient began riding a new bicycle with different gearing than his previous one. Manual-resisted muscle testing created soreness in the lumbosacral area and buttocks. Trigger points were identified in the right gluteus medius. Standing lumbar spine flexion was 70 degrees, limited by tight hamstrings. INTERVENTION AND OUTCOME: Because the patient was already receiving periodic chiropractic care, no passive therapy was used. Patient education regarding the difference in gear selection in bicycles of a higher quality was provided. He was instructed to train in lower gears than he had previously used and to maintain a cadence of 70 to 90 revolutions of the pedals per minute. After 2 days, the paresthesia on the right buttock resolved. The trigger points were only mildly tender with minimal residual soreness of the involved muscles. CONCLUSION: Management of gluteus medius syndrome by altering the cadence and gear development for a bicyclist is discussed. Either frank or cumulative injury to the gluteus medius muscle is the typical etiologic factor for this syndrome. Repetitive strain of the patient's gluteus medius muscle as a result of poor cycling technique appeared to be the cause here. Knowledge of bicycle fitting, training techniques, and bicycle mechanics appeared necessary to resolve the problem.

Adult↗
PubMed1997

Motor vehicle rollover and static stability: an exposure study.

OBJECTIVES: This study examined vehicle rollovers in terms of site-specific exposure and speeds of vehicles of varying stability. METHODS: Fifty-one rollover sites in two states were visited at the same time of day and day of week as the rollover. A sample of vehicles moving in the same direction as the rollover were observed, and vehicle-specific data were obtained from identification numbers. RESULTS: Low stability, exacerbated by the addition of passengers, increased the risk of rollover. Speed was not correlated with stability and is not a confounder. CONCLUSIONS: Rollovers could be substantially reduced if motor vehicles were manufactured with a static stability of 1.2 or greater.

Accidents, Traffic↗
PubMed1995

Primary gastric lymphoma in clinical practice 1973-1992.

This study assessed the presentation, treatment, and prognosis of primary gastric lymphoma in general hospital practice and its relation to infection with Helicobacter pylori. The number of patients that would on the current recommendations have been suitable for H pylori eradication therapy was also examined. All lymphomas were graded according to a standard classification of gut lymphoma into high and low grade disease. Forty five patients (mean age 65 years) were identified. The overall five year survival was 40% with a trend in favour of an improved prognosis for low grade and stage I disease. H pylori was present in 80%. Only one of 18 patients with a low grade mucosa associated lymphoid tissue tumour had mucosal disease alone, which responded to omeprazole and amoxycillin. All other patients had bulk disease. These patients were treated by surgery, chemotherapy or radiotherapy or a combination of these treatments. In district hospital practice, most cases of primary gastric lymphoma have bulk disease at presentation. Even in patients with low grade gastric lymphoma on histological examination, many on the current evidence would not be suitable for anti-H pylori therapy alone.

Aged↗
PubMed1993

On the frequency and reproducibility of orthostatic blood pressure changes in healthy community-dwelling elderly during 60-degree head-up tilt.

The postural effects of 20 minutes of 60-degree head-up tilt on systolic, diastolic, and mean arterial blood pressures (BPs), heart rate, and rhythm were studied in 70 healthy, community-dwelling volunteer subjects of both sexes, divided into three age groups. Group A consisted of 30 subjects, with a mean age of 76 years (range 65 to 95 years); group B had 19 subjects, with a mean age of 54 years (range 45 to 64 years); and group C had 21 subjects, with a mean age of 33 years (range 24 to 44 years). To qualify, subjects had to have a systolic BP of 150 mm Hg or less and a diastolic BP of < 90 mm Hg, be taking no prescribed medications, have had no previous syncopal episodes, and have absence of any significant medical illness. Nine of 30 (30%) subjects in group A, 1 of 19 (5%) subjects in group B, and 2 of 21 (9.5%) subjects in group C exhibited asymptomatic postural drops in systolic blood pressure > 20 mm Hg (p < 0.05). The mean time for the systolic blood pressure drops in group A was 9.2 minutes. Results were reproducible upon retesting after 1 week.

Adult↗
PubMed1992

The efficacy of nasal septal surgery.

Nasal septal deformity is a frequent clinical entity, and septoplasty comprises one of the most common procedures performed by otolaryngologists today. Its efficacy seems intuitive, however the literature reveals relatively few papers confirming its utility. In this study, all patients undergoing septal reconstruction (excluding septorhinoplasty) at three major teaching hospitals in Vancouver during the years 1988 to 1990 were reviewed retrospectively in a two-pronged study. Information was collected concerning symptoms, physical findings and surgical technique. In the second phase, patients were contacted by telephone in a blinded fashion. Data was collected concerning patient satisfaction regarding various parameters including initial and ultimate symptom resolution, acceptance of nasal packing and postoperative complications. The following conclusions may be drawn: 1) Septoplasty was successful in relieving nasal obstruction in 70.5% of patients. 2) Turbinate surgery including outfracturing appears to significantly improve the outcome of surgery. 3) Rhinitis, including allergy, congestion, postnasal drip and rhinorrhea did not significantly affect success in relieving nasal obstruction. 4) Nasal packing did not significantly affect the outcome, but was the most frequently complained of aspect of the surgery. Therefore, we do not feel nasal packing is necessary.

Adolescent↗
PubMed1991

Solution stability of the monoclonal antibody-vinca alkaloid conjugate, KS1/4-DAVLB.

A 3-month solution stability study at 5 degrees C of the monoclonal antibody-vinca alkaloid conjugate KS1/4-DAVLB indicated that phosphate-buffered saline solutions at pH 4.5-5.5 had little tendency to lose vinca by hydrolysis, improved vinca stability, showed acceptable physical stability, and formed minimal amounts of soluble aggregates compared to solutions at pH 6.5-7.4. Hydrolysis and aggregation with concomitant loss of stability were accelerated at 30 degrees C throughout the pH range investigated. As determined by ELISA, the binding properties of KS1/4-DAVLB to tumor antigens were not affected by pH or temperature. A formulation suitable for initial clinical trials in cancer patients is described.

Antibodies, Monoclonal↗
PubMed1984

Age-dependent alterations in the physicochemical properties of rat liver microsomes.

Aging results in a significant decline in liver drug metabolism which is largely attributable to changes in the microsomal mixed function oxidase system. For example, the mixed function oxidase system in the livers of senescent rats is characterized by: (1) a reduced cytochrome P-450 content; (2) a decline in the specific activity of NADPH-cytochrome c (P-450) reductase; and (3) a slower rate of ethylmorphine N-demethylation in comparison to young adult animals. Since several factors intrinsic to the microsomes may influence the efficacy of the mixed function oxidase system, e.g. the phospholipid and cholesterol contents, the saturation index of the fatty acids and the fluidity of the membranes, we conducted a physicochemical analysis of liver microsomes isolated from young adult (3-4 months), mature (12-16 months) and senescent (25-27 months) male Fischer rats. Although the microsomal cholesterol content did not change appreciably between maturity and senescence, there was a marked decline in the total phospholipid content. This resulted in a significant increase in the cholesterol/phospholipid ratio, 0.49 to 0.65 between 16 and 27 months of age. The age-related changes in the total phospholipid content were largely reflected in each of the major fractions, i.e. phosphatidylcholine, phosphatidylinositol and phosphatidylethanolamine + phosphatidylserine. Small increases in the relative percentages of highly unsaturated fatty acid species were offset by similar decreases in the more frequent and more saturated species as a function of increased age. As a result, the net change in the fatty acid saturation index was probably minimal. However, the increase in the cholesterol/phospholipid ratio most likely contributes to the significant decline in the order parameter of microsomes isolated from old rats which, in turn, may impair the functional capacity of the hepatic mixed function oxidase system.

Aging↗