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Biomedical subjects

J Kowal

Publications and source records attributed to J Kowal.

At least 19 recordsLinked to original sources

QT interval dispersion as a new marker of restenosis after percutaneous transluminal coronary angioplasty of isolated single-vessel coronary artery stenosis.

BACKGROUND: There are no reliable non-invasive markers of restenosis after percutaneous transluminal coronary angioplasty (PTCA). The aim of our study was to measure changes in QT interval dispersion after PTCA and to determine whether restenosis subsequently affects QT interval dispersion. METHODS AND RESULTS: Fifty-six consecutive patients - 41 men and 15 women (mean age: 56.2 +/-8.3 years) - with isolated stenosis of the left anterior descending artery who underwent successful PTCA were studied. A symptom-limited treadmill exercise test was performed within 7 days after PTCA and then again before repeated angiography. Repeated coronary angiography revealed restenosis in 15 patients (26.8%) and no signs of significant stenosis in 41 patients (73.2%). QT interval dispersion in the group of patients with restenosis measured before exercise increased from baseline 34 +/- 7 to 49 +/- 15 ms after 6 months (p < 0.01) and QT interval dispersion measured immediately after exercise increased from baseline 38 +/- 4 to 68 +/- 21 ms after 6 months (p < 0.001). In contrast, patients without restenosis showed no significant changes in QT interval dispersion measured before (baseline: 34 +/- 9 ms; after 6 months 33 +/- 12 ms; p = NS) and immediately after exercise (baseline: 34 +/- 12 ms; after 6 months: 33 +/- 10; p = NS). When QT interval dispersion > or =60 ms (measured 6 months after PTCA procedure) was considered as a potential marker of restenosis, this indicator had very high sensitivity and specificity when measured immediately after exercise (80 and 95% respectively). CONCLUSIONS: QT interval dispersion significantly increases in the group of patients with documented restenosis and may be a simple, non-invasive marker of restenosis. However, further studies are needed to confirm this observation.

Angioplasty, Balloon, Coronary↗

A randomized controlled psycho-education intervention trial: Improving psychological readiness for successful HIV medication adherence and reducing depression before initiating HAART.

The purpose of this study was to evaluate a novel psycho-educational intervention intended to increase patients' medication preparedness and treatment adherence skills before initiating highly active antiretroviral therapy (HAART). Sixty-three HIV-positive patients not currently on antiretroviral therapy participated in a randomized controlled trial of a standardized, four-session psycho-educational intervention (Supportive Therapy for Adherence to Antiretroviral Treatment; STAART). Session topics included learning techniques to increase medication adherence and learning effective strategies to cope with stress and depression. Patients completed psychological questionnaires assessing psychological readiness to initiate HAART and depressed mood. They completed both measures at study baseline and at four-weeks post-baseline. After controlling for baseline medication readiness scores, intervention patients (n = 30) reported significantly higher mean medication readiness following the STAART intervention (four-weeks post-baseline) (27.3+/-6.9) compared to controls (n = 33; 24.6+/-9.9; p < 0.05). Among depressed patients (n = 27), those receiving the intervention (n = 15) reported significantly lower mean depression scores at four-weeks post-baseline (22.5+/-12.9) compared to controls (n = 12; 27+/-9.9; p < 0.05). The STAART intervention enhanced HIV treatment readiness by better preparing patients prior to initiating HAART. It was also beneficial for reducing depressive symptoms in depressed, HIV-positive patients.

Adaptation, Psychological↗

Kinetic analysis and subambient temperature on-line on-column derivatization of an active aldehyde.

The chromatographic analysis of aldehydes under typical reversed-phase conditions may be a challenging task due to an equilibrium process leading to the formation of a gem diol species regardless of acidic or basic conditions. Initially, a reversed-phase HPLC gradient elution was developed to determine the amount of a n acetylenic aldehyde in a reaction mixture. Significant fronting was observed under acidic and basic conditions even at -5 degrees C. In order to circumvent this problem, a reversed-phase HPLC gradient method on a C18 column at subambient temperature was developed using diethylamine as a mobile phase additive for on-line on-column derivatization of the aldehyde moiety. The on-line on-column reaction rate for the derivatization of the aldehyde with diethylamine was determined as a function of column temperature. An Arrhenius plot was constructed and the activation energy was calculated. The chromatographic behavior of the derivatized acetylenic aldehyde and products formed in-situ in the chromatographic system were studied at various temperatures ranging from -10 to 60 degrees C. It was found that the reaction products could be controlled by adjusting the column temperature. Different reaction pathways were identified as a function of temperature. The products and the reaction pathways were characterized by NMR, LC-MS and UV spectra.

Aldehydes↗

Safety of MR scanning in patients with nonferromagnetic aneurysm clips.

The purpose of this study was to report our surveillance of patients with nonferromagnetic aneurysm clips (NFAC) who have undergone magnetic resonance imaging (MRI). Forty-six patients with NFAC underwent MRI over a 7-year period. Medical records were studied for evidence of subjective or objective clinical findings as a result of the MRI scan. In two patients with subjective complaints, computed tomograms (CT) were reviewed and patient interviews conducted. No significant neurologic signs or longterm symptoms were experienced. Two patients did not complete their MRI scans due to transient unilateral head pain in one and head "pressure" in another. CT scans in these patients demonstrated no evidence for hemorrhage or visible change in clip position. We documented no objective adverse outcome of patients undergoing MRI with NFAC, confirming that MRI can be performed safely in patients with nonferromagnetic aneurysm clips. The cause of subjective complaints in two of our patients is unknown.

Adult↗

Testing relationships from the hierarchical model of intrinsic and extrinsic motivation using flow as a motivational consequence.

The purpose of this study was to test a motivational model based on Vallerand's (1997) Hierarchical Model of Intrinsic and Extrinsic Motivation. This model incorporates situational and contextual motivational variables, and was tested using a time-lagged design. Master's level swimmers (N = 104) completed a questionnaire on two separate occasions. At Time 1, situational social factors (perceptions of success and perceptions of the motivational climate), situational motivational mediators (perceptions of autonomy, competence, and relatedness), situational motivation, and flow were assessed immediately following a swim practice. Contextual measures of these same variables were assessed at Time 2, 1 week later, with the exception of flow. Results of a path analysis supported numerous links in the hypothesized model. Findings are discussed in light of research and theory on motivation and flow.

Adolescent↗

Prolonged hypoxic stress increases adrenal cholesterol reserve in rats without causing adrenal hypertrophy.

1. It is known that, in rats, hypoxia stimulates adrenal steroidogenesis, but our understanding of the hypoxic effect on the glandular parameters remains incomplete. 2. Adrenals were collected and analysed from rats that had been exposed to hypoxic conditions for 3 weeks. 3. The results reveal increased adrenal concentrations of corticosterone, free cholesterol and total cholesterol without a change in glandular weight and protein concentration. The increased total cholesterol is primarily associated with enriched cholesteryl adrenate (CE22: 4), cholesteryl arachidonate (CE20: 4) and cholesteryl oleate (CE18: 1).

Adrenal Cortex↗

Effects of prolonged ACTH-stimulation on adrenocortical accumulation of lipofuscin granules in aged rats.

Subcellular deposition of lipofuscin granules is a marker of aging. Human and rodent adrenal cortices accumulate lipofuscin granules with age, but the mechanism that leads to the accumulation is not known. The ultrastructural appearance of lipofuscin granules resembles that of secondary lysosomes. Since adrenocortical subcellular events are predominantly influenced by ACTH action, we therefore studied the effect of prolonged ACTH-stimulation on adrenocortical accumulation of secondary lysosome-like granules, designated herein as lipofuscin granules. Using aged Fischer 344 male rats as a model, we found that a 7 day ACTH stimulation exerts a reducing effect on adrenocortical lipofuscin accumulation. Thus, adrenocortical accumulation of lipofuscin granules with age in vivo may not be an irreversible process.

Adrenal Cortex↗

Effects of prolonged ACTH-stimulation on adrenocortical cholesterol reserve and apolipoprotein E concentration in young and aged Fischer 344 male rats.

Changes in the morphology of rat adrenal cortex with age include increased accumulations of lipid droplets and lipofuscin granules. Because glandular concentrations of cholesteryl esters (CE) and apolipoprotein (apo) E are also increased in parallel, the utilization or metabolism of lipid-droplet stored CE for steroidogenesis might be altered in aging cells. To explore this possibility, adrenocortical cholesterol storage and utilization were studied in 3-6 months-old (mo) (Y) rats and 20-23 mo (O) Fischer 344 male rats. Both groups received either adrenocorticotropin (ACTH1-39, Acthar gel) or gelatin alone daily for seven consecutive days. We found that: (a) the CE concentration in O rats, but not Y animals, was diminished by ACTH. The depleted CE in stimulated-O rats was replenished within five days post stimulation. Failure to deplete CE in stimulated-Y rats was not associated with an insufficient dose of the hormone, since stimulation of Y animals with higher doses of ACTH actually increased the CE concentration. In contrast, adrenocortical free cholesterol concentration remained constant during stimulation regardless of age. (b) The depleted CE in stimulated-O rats was principally comprised of cholesteryl adrenate, cholesteryl arachidonate and cholesteryl cervonate. The accumulated CE in stimulated-Y animals was primarily comprised of cholesteryl adrenate, cholesteryl arachidonate and cholesteryl oleate. (c) Whereas in stimulated-Y rats adrenal apoE concentration declined, the concentration in stimulated O animals was well maintained. (d) In vitro, adrenal homogenate or cytosolic fraction from stimulated-O rats displayed a higher capacity to hydrolyze exogenous CE than its Y counterpart. However, cholesterol esterification with external fatty acid substrates in adrenal homogenate or microsomal fraction was comparable in the two age-groups. Our findings revealed altered adrenocortical cholesterol reserve in O rats to cope with prolonged ACTH-stimulation. Changes in apoE levels and CE hydrolysis activity may be factors associated with this alteration. Depletion and accumulation of adrenocortical CE are reflected in parallel changes in cholesteryl adrenate and cholesteryl arachidonate, suggesting physiologic importance of these polyunsaturated fatty acids during sustained steroidogenesis.

Adrenal Cortex↗

Clinical epidemiology of endocrine disorders in the elderly.

Many epidemiologic studies have examined age-related processes in humans. Some of the difficulties with these studies are noted. Endocrinologic changes of aging often are compensated for by feedback mechanisms and do not cause dysfunction. Common aging changes are reviewed.

Aged↗

Do acute care for elders units increase hospital costs? A cost analysis using the hospital perspective.

OBJECTIVE: To compare the hospital costs of caring for medical patients on a special unit designed to help older people maintain or achieve independence in self-care activities with the costs of usual care. DESIGN: A randomized controlled study. PARTICIPANTS: A total of 650 medical patients (mean age 80 years, 67% women, 41% nonwhite) assigned randomly to either the intervention unit (n = 326) or usual care (n = 324). MEASURES: The hospital's resource-based cost of caring for patients was determined from the hospital's cost-accounting system. The cost of the intervention program was estimated and included in the intervention patients' total hospital cost. RESULTS: The development and maintenance costs of the intervention added $38.43 per bed day to the intervention patients' hospital costs. As a result, the cost per day to the hospital was slightly higher in the intervention patients than in the control patients ($876 vs $847, P = .076). However, the average length of stay was shorter for intervention patients (7.5 vs 8.4 days, P = .449). As a result, the hospital's total cost to care for intervention patients was not greater than caring for usual-care patients ($6608 in intervention patients vs $7240 in control patients, P = .926). Sensitivity analysis demonstrated that the cost of the intervention program would need to be 220% greater than estimated before intervention patients would be more expensive then control patients. There were no examined subgroups of patients in whom care on the intervention unit was significantly more expensive than care on the usual-care unit. Ninety-day nursing home use was lower in intervention than control patients (24.1% vs 32.3%, P = .034). Ninety-day readmission rates (36.7% vs 41.1%, P = .283) and caregiver strain scores (3.3 vs. 2.7, P = .280) were similar. CONCLUSION: Caring for patients on an intervention ward designed to improve functional outcomes in older patients was not more expensive to the hospital than caring for patients on a usual-care ward even though the intervention ward required a commitment of hospital resources.

Activities of Daily Living↗

A phase I trial of a new recombinant human beta-interferon (BG9015) for the treatment of patients with recurrent gliomas.

Primary brain tumors represent an important cause of cancer-related morbidity and mortality in the United States. Despite advances in neurosurgery and radiotherapy, the median survival of patients with malignant gliomas remains less than 1 year. A contributing factor to the poor prognoses of these patients is the diffuse, infiltrative nature of these tumors, which limits the effectiveness of focal therapies (i.e., surgery and radiation). Unfortunately, standard chemotherapy has been of limited benefit in the treatment of malignant gliomas, underlying the necessity for new drugs with novel mechanisms of action. On the basis of promising in vitro and clinical data demonstrating significant antiglioma activity of purified IFN-beta and a synthetic IFN-beta (Betaseron), we conducted a Phase I trial of a new, nonmutated, glycosylated recombinant human IFN-beta (BG9015) in patients with recurrent, high-grade astrocytomas. In this trial, we demonstrate that the maximally tolerated dose of BG9015 is 6 million units/m2 delivered by intramuscular injection three times per week. Dose-limiting neurotoxicity was seen in both patients treated at 8 million units/m2. Additionally, we demonstrate that high BG9015 serum levels are associated with a fall in natural killer cell number, radiographic response, and prolonged survival. We conclude that BG9015 has activity in patients with malignant gliomas, although the therapeutic index may be narrow. Future studies will be needed to confirm the observation that natural killer cell number and activity as well as BG9015 serum levels are important markers of antitumor activity.

Adult↗

Characterization and identification of an adrenal age-related nonpolar fluorescent substance.

The adrenal cortexes of humans and rodents accumulate lipofuscin with age, but the chemical nature of the substance that produces lipofuscin fluorescence in the gland is not known. Analysis of rat adrenal nonpolar lipids revealed a fluorescence profile with increased intensity in the lipids extracted from older animals (23-24 months > 6 months > 6 weeks). The peak occurred at a wavelength of 470 +/- 5 nm(n = 26) when excited at 340 nm. After sucrose density gradient centrifugation, the fluorescent substance was primarily concentrated in subcellular lipid droplets rather than supernatant or particulate. Prolonged stimulation of rats with ACTH for 7 consecutive days caused 14-51% decreases in the fluorescence levels, with a tendency of return to control levels poststimulation regardless of age. In contrast, the nonpolar lipids of mouse adrenal tumor (Y1) cells, which contain no lipofuscin, did not display this fluorescence in the presence or absence of ACTH. The chromatographic characteristics of the substance in a silica gel-60 column resembled those of authentic retinyl palmitate and cholesteryl oleate. Analysis of the substance by HPLC demonstrated at least three prominent peaks, designated XI-3 in order. X1 and X2 were minor peaks; X3 was the major peak. Whereas none of the peaks comigrated with cholesteryl esters, X1 comigrated with authentic retinyl palmitate. Determination of the fatty acid component of the major fluorescent substance X3 by gas-liquid chromatography disclosed stearic acid. Retinyl stearate was, therefore, synthesized. The fluorescent profiles, HPLC retention time and mass spectrometric fragmentation of purified X3 substance were all identical to those of the synthetic compound. In contrast, the rat liver principally accumulated retinyl palmitate with age. Thus, we conclude that 1) the major nonpolar fluorescent substance accumulated in the rat adrenal with age is retinyl stearate, which may be a fluorophore of adrenal lipofuscin; 2) ACTH action may be related to this accumulation; and 3) the type of retinyl ester accumulated in aged animals is organ specific.

Adrenal Cortex↗

Apolipoprotein E is increased in aged rat kidney.

There is growing evidence to indicate that apolipoprotein (apo) E may be associated with age-related disorders and altered longevity in humans. Using rats as a model, we measured apoE in plasma, brain, heart, kidney, liver and spleen in aged (24-25 mo) and younger rats (6-8 mo). The results disclosed that: (a) the plasma concentrations of immunoreactive apoE in aged rats were higher than those in young animals by 70% (P < 0.01); (b) there was no age-related difference of apoE in the brain, heart, liver or spleen; (c) in contrast, the concentrations of apoE in the kidney of aged rats were markedly higher than those of young animals by 490% (P < 0.01). Our data suggest that, in the rat, age-related change in the organ concentrations of apoE is heterogeneous, and the selective increase in the kidney may have physiologic importance which merits further study.

Aging↗

A randomized trial of care in a hospital medical unit especially designed to improve the functional outcomes of acutely ill older patients.

BACKGROUND: Older persons who re hospitalized for acute illnesses often lose their independence and are discharged to institutions for long-term care. METHODS: We studied 651 patients 70 years of age or older who were admitted for general medical care at a teaching hospital; these patients were randomly assigned to receive usual care or to be cared for in a special unit designed to help older persons maintain or achieve independence in self-care activities. The key elements of this program were a specially prepared environment (with, for example, uncluttered hallways, large clocks and calendars, and handrails); patient-centered care emphasizing independence, including specific protocols for prevention of disability and for rehabilitation; discharge planning with the goal of returning the patient to his or her home; and intensive review of medical care to minimize the adverse effects of procedures and medications. The main outcome we measured ws the change from admission to discharge in the number of five basic activities of daily living (bathing, getting dressed, using the toilet, moving from a bed to a chair, and eating) that the patient could perform independently. RESULTS: Twenty-four patients in each group died in the hospital. At the time of discharge, 65 (21 percent) of the 303 surviving patients in the intervention group were classified as much better in terms of their ability to perform basic activities of daily living, 39 (13 percent) as better, 151 (50 percent) as unchanged, 22 (7 percent) as worse, and 26 (9 percent) as much worse. In the usual care group, 40 (13 percent) of the 300 surviving patients were classified as much better, 33 (11 percent) as better, 163 (54 percent) as unchanged, 39 (13 percent) as worse, and 25 (8 percent) as much worse (P = 0.009). The difference between the groups remained significant (P = 0.04) in a multivariable model in which we controlled for potentially confounding base-line characteristics of the patients. Lengths of stay and hospital charges were similar in the two groups. Fewer patients assigned to the intervention group were discharged to long-term care institutions (43 patients [14 percent], as compared with 67 patients [22 percent] in the usual-care group; P = 0.01). Among the 493 patients discharged to private homes, similar proportions (about 10 percent) in the two groups were admitted to long-term care institutions during the three months after discharge. CONCLUSIONS: Specific changes in the provision of acute hospital care can improve the ability of a heterogeneous group of acutely ill older patients to perform basic activities of daily living at the time of discharge from the hospital and can reduce the frequency of discharge to institutions for long-term care.

Activities of Daily Living↗

Aging in rats is associated with an increase in adrenal apolipoprotein E.

Extrahepatic tissues including the adrenal cortex are capable of synthesizing apolipoprotein E (apoE). Locally synthesized apoE is believed to affect cellular uptake, transport and redistribution of cholesterol within that organ. We and another laboratory have previously reported that the adrenal cortex of aged rats has an elevated cholesteryl ester content. The aim of this work was to investigate whether this elevation is accompanied by increased adrenal apoE levels in aged rats. A Western blotting technique with polyclonal goat anti-human-apoE antiserum was employed as a probe for studies. The results showed that: (a) anti-human-apoE antiserum not only detected apoE in human plasma and adrenal homogenate, but also cross-reacted with a protein (or proteins) resembling apoE in rat plasma and adrenal homogenate (or supernatant) with a molecular weight of 34,000-36,000; (b) rat adrenal apoE concentration (per unit weight of protein) increased with age; (c) the increase did not result from blood trapped in the gland, because after organ perfusion the adrenal of aged rats persistently exhibited 58% more apoE than that of young animals. In conclusion, rat adrenal apoE concentration appears to increase with age. Whether this increase mechanistically causes the accumulation of cholesteryl esters in the aged rat adrenal remains to be investigated.

Adrenal Cortex↗