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Biomedical subjects

A R Clark

Publications and source records attributed to A R Clark.

At least 73 records · Page 4Linked to original sources
PubMed1997

The economic impact of psoriasis increases with psoriasis severity.

BACKGROUND: Psoriasis treatments are known to be costly, but little is known about the financial impact of psoriasis and the way in which it relates to the severity of the disease. OBJECTIVE: This study was performed to obtain an estimate of the treatment costs faced by patients with psoriasis. METHODS: A total of 578 anonymous mail surveys were distributed to patients with psoriasis; 318 surveys were returned (55%). Psoriasis severity was assessed with the previously validated Self-Administered Psoriasis Area Severity Index (SAPASI). RESULTS: The total and out-of-pocket expenses to care for psoriasis were correlated with psoriasis severity (r = 0.26, p = 0.0001). There were no sex (p = 0.9) or racial (p = 0.4) differences in total expenditures. Severity was correlated with how bothersome to the patient was the cost of treatment (r = 0.30, p = 0.0001), the time required for treatment (r = 0.38, p = 0.0001), and the time lost from work (r = 0.23, p = 0.0001). Lower quality of life at work and in money matters also correlated with severity of psoriasis. Higher family income was associated with less time spent caring for psoriasis and less interference with work around the home. CONCLUSION: As expected, the expenses caring for psoriasis are greater for patients with more severe disease. These costs and other financial implications are associated with lower quality of life for patients with more severe psoriasis.

Absenteeism↗
PubMed1997

Commercial tanning bed treatment is an effective psoriasis treatment: results from an uncontrolled clinical trial.

Phototherapy is highly effective in the therapy of psoriasis, but patient access to phototherapeutic facilities is not universal. Commercial tanning facilities are universal, but their efficacy in psoriasis treatment is unestablished. Our purpose was to conduct a study to assess the effect of a commercial tanning unit outfitted with nonprescription lamps on psoriasis. We conducted a 6-wk open study of 20 adult patients with stable psoriasis vulgaris. Clinical response was defined as a decrease in the Psoriasis Area Severity Index (PASI) or the Self-Administered PASI (SAPASI) by > or = 10%. There were 16 men and 4 women who participated with a mean (+/-SD) age of 43.0 +/- 14.8 y. Initial and final health-related quality of life information collected included the following instruments: the Brief Symptom Inventory (BSI), the Psoriasis-Related Stressor Scale (PRSS), and the Psoriasis Disability Scale (PDS). Side effects of tanning therapy were closely monitored. Fifteen subjects completed the entire 6-wk trial, and exit data on all subjects were used for analysis. The mean number of tanning sessions was 19 +/- 7.6 with a median of 19 and range of 3 to 29. Analysis of all 20 enrolled subjects found that 16 (80%) showed clinical response as measured by PASI, whereas 17 (85%) showed SAPASI response. Initial and final PASI scores decreased (p = 0.0001) from 7.96 +/- 1.77 to 5.04 +/- 2.5, and SAPASI scores also decreased (p = 0.02) from 11.8 +/- 4.4 to 7.9 +/- 7.7. When controlled for age and sex, a dose-response relationship was demonstrated with the PASI and SAPASI (p < 0.02). Decreases in the mean BSI and PRSS scales were demonstrated (p < 0.02), confirming the clinical significance of the reductions in disease severity scores. Episodes of mild burning occurred in 7 of 20 (35%) participants. Three subjects reported itching after one or two tanning sessions. This study showed that a tested commercial nonprescription tanning unit improved both psoriasis severity and health-related quality of life. Commercial tanning bed treatments may be a useful approach in patients unable to obtain office-based ultraviolet treatments.

Adult↗
PubMed1997

A new method for bronchial-provocation testing in asthmatic subjects using a dry powder of mannitol.

We developed a bronchial provocation test (BPT) with a dry powder preparation of mannitol. The mannitol was inhaled from gelatin capsules containing 5, 10, 20, or 40 mg to a cumulative dose of 635 mg, and was delivered via an inhalator, Halermatic, or Dinkihaler device. We studied the airway sensitivity to inhaled mannitol, the repeatability of the response, and the recovery after challenge in 43 asthmatic subjects 18 to 39 yr of age who had a 20% decrease in FEV1 in response to inhaling a 4.5% NaCl. We compared this with the airway response to methacholine in 25 subjects. The geometric mean (GM) for the dose of dry mannitol required to reduce the FEV1 by 15% of the baseline value (PD15) was 64 mg, with a 95% confidence interval (CI) of 45 to 91. Subjects responsive to mannitol had a PD20 to metacholine of < 7.8 mumol, with a GM of 0.7 mumol (CI: 0.4 to 1.2). For the first of two challenges to mannitol the PD15 was 59 mg (CI: 36 to 97) and for the second the PD15 was 58 mg (CI: 35 to 94) p = 0.91 (n = 23). Spontaneous recovery to within 5% of baseline occurred within 60 min and within 10 min after 0.5 mg terbutaline sulfate was inhaled. Arterial oxygen saturation (SaO2) remained at 93% or above during mannitol challenge. Subjects tolerated the inhalation of the mannitol well. A dry powder preparation of mannitol may be suitable to develop for bronchial provocation testing.

Administration, Inhalation↗
PubMed1997

The effect of inhaling a dry powder of sodium chloride on the airways of asthmatic subjects.

Wet aerosols of 4.5% sodium chloride (NaCl) are often used to assess the bronchial responsiveness associated with asthma. We questioned whether dry NaCl could be used as an alternative. Dry powder NaCl was inhaled from capsules containing either 5, 10, 20 or 40 mg to a cumulative dose of 635 mg. The powder was delivered via an Inhalator or Halermatic. The airway sensitivity to the dry and wet NaCl was compared in 24 patients with asthma aged 19-39 yrs. All subjects responded to both preparations and the geometric mean (95% confidence intervals) for the provocative dose of NaCl causing forced expiratory volume in one second (FEV1) to fall 20% from baseline (PD[20,NaCl]) for dry NaCl was 103 mg (68-157) versus 172 mg (102-292), p<0.03 for the wet NaCl. The response to dry NaCl was reproducible and on repeat challenge the PD20 was 108 mg (75-153). The mean maximum fall in FEV1 was approximately 25% on each of the two test days. Spontaneous recovery occurred within 60 min after challenge with dry NaCl and within 5 min after bronchodilator. There were no serious side-effects requiring medical attention, however some patients coughed on inhalation of the 40 mg dose and three gagged. Arterial oxygen saturation remained within normal limits. We conclude that a suitably prepared dry powder of sodium chloride could potentially replace wet sodium chloride to assess bronchial responsiveness in patients with asthma, but further studies are required to establish the long-term stability of the dry powder preparation.

Administration, Inhalation↗
PubMed1996

MDIs: physics of aerosol formation.

The aerosol clouds produced by metered dose inhalers are very dynamic and dramatic changes in both droplet size and velocity take place within the first few centimeters of the spray plume. It is the interaction of this dynamic cloud with the geometry of the mouth and oropharynx that controls the extent of oral deposition and hence the ability of the MDI to deliver a respiratory therapeutic to the lung. Oral deposition is controlled by inertial mechanisms and in order to develop meaningful in-vitro test methods consideration must be given to both the velocity and droplet size distribution of the cloud. The correct design of the inlet ports used to convey MDI clouds in aerosol sizing instruments is therefore crucial to the development of successful in-vitro methodologies. The use of large sampling chambers or the characterization of residual aerosol droplets is unlikely to produce meaning product comparisons or satisfactory product control data.

Administration, Inhalation↗
PubMed1996

The pulmonary deposition of two aerosol preparations of nedocromil sodium delivered by MDI assessed by single photon emission computed tomography.

The pulmonary deposition and pharmacokinetics of fine and coarse radioactive aerosols of nedocromil sodium, of mass median aerodynamic diameters 16 microns and 24 microns respectively, delivered by metered dose inhaler (MDI) have been investigated. The corresponding geometric standard deviations of the particle size distributions were 5.32 and 3.93. Pulmonary deposition was assessed by both planar radionuclide scintigraphy and multi-modality three dimensional imaging using single photon emission computed tomography (SPECT) and x-ray computed tomography (CT). The three dimensional data were analysed by transformation to a hemispherical shape based on the fractional radial distance of each point in the lung from the centre to the corresponding extrapolated point on the periphery. This enabled parameters on the variation of both concentration of deposition and total amount deposited with penetration distance to be calculated. For both planar and SPECT data the central to peripheral concentration ratio (C/P ratio) was calculated. The three dimensional C/P ratio showed a median value (3.21) which was significantly higher than for the planar imaging (2.03) (p < 0.001). The parameter used to express the variation of total amount deposited was the median dose position. This showed that for both aerosols 50% of the dose was deposited at sites with a percentage central to peripheral distance of greater than 68%. There was a trend for total percentage of the fine aerosol in the lungs to be higher than for the coarse and for its deposition to be more peripheral. In addition the mean concentrations in blood were measured to be greater for the fine aerosol. However these differences were relatively small and none were individually statistically significant. The technique of combined SPECT and CT imaging was shown to be valuable in obtaining more accurate information on pulmonary distribution of inhaled aerosol deposition. The merits, limitations and potential applications of the technique are discussed.

Administration, Inhalation↗
PubMed1996

Disease severity measures in a population of psoriasis patients: the symptoms of psoriasis correlate with self-administered psoriasis area severity index scores.

Because of the difficulty and expense of objectively measuring psoriasis severity, very little information exists on the severity of psoriasis in populations. We determined severity in a psoriasis patient population using the validated self-administered psoriasis area and severity index (SAPASI). This population consisted of 578 university dermatology clinic psoriasis patients, and data were analyzed from 317 (55%) questionnaire respondents. The majority of our sample was women (57%), and non-Caucasians represented a larger portion (8 %) in our sample compared with some previous studies. In our population, the reported frequencies of skin and joint symptoms were as follows: pruritus (95 %), skin burning (81 %), joint pain (69%), arthritis (51%), and psoriatic arthritis (20%). The SAPASI was significantly associated with severity of pruritus, burning, joint pain, and psoriatic arthritis. There was a significant negative correlation between the number of treatments employed and the SAPASI. This study provides results of a detailed measurement of the severity of psoriasis in a psoriasis patient population and relates this severity to population characteristics.

Adolescent↗
PubMed1996

The self-administered psoriasis area and severity index is valid and reliable.

The self-administered psoriasis area and severity index (SAPASI) is a structured instrument for measuring the severity of psoriasis. This study examines the validity, reliability, and responsiveness of the SAPASI. Trained personnel performed a psoriasis area and severity index (PASI) assessment on the same day a SAPASI was obtained from 80 subjects. The validity of the SAPASI was demonstrated using the PASI as the standard (r2 = 0.59, p = 0.0001). Significant correlations were found between SAPASI and PASI for body surface area (r = 0.62-0.75), erythema (r = 0.39), induration (r = 0.24) and scale (r = 0.38). Test-retest reliability was assessed in 19 subjects with repeated evaluations within 2 d. Correlations between the first and second SAPASI scores (r = 0.82) were highly significant (p = 0.0001). Inter-rater reliability of SAPASI body surface area measurements among five raters was very high (intraclass correlation coefficient R = 0.953). The SAPASI was responsive to changes in severity over time as demonstrated by correlation with changes in PASI scores (r = 0.63, p = 0.0002). We conclude that this structured patient self-report instrument facilitates quantitative assessment of psoriasis.

Evaluation Studies as Topic↗
PubMed1996

Alternative therapies commonly used within a population of patients with psoriasis.

Alternative therapies are known to be employed by dermatology patients. This study investigates the use of alternative medical treatments for psoriasis and the sociodemographic variables, conventional medical treatment, and psoriasis disease severity. Our study population consisted of 578 university dermatology clinic patients with psoriasis and data was analyzed from 317 (55 percent) questionnaire respondents. The majority of our sample were women (57 percent) and nonwhites represented 8 percent of our sample. Psoriasis severity was measured using the validated Self-Administered Psoriasis Area and Severity Index. Alternative medicine was used by 62 percent of respondents. Excluding sunlight and nonprescription tanning equipment, 51 percent used one or more of the remaining alternative therapeutic modalities. The psoriasis severity was worse in those who had tried herbal remedies, vitamin therapy, and dietary manipulation. With the exception of vitamin therapy, we observed no association between the intensity of conventional medical treatment and alternative treatment. The present or prior use of herbal remedies was correlated with the use of vitamin therapy and sunbathing, and dietary interventions were significantly correlated with vitamin therapy. Of the 113 (36 percent) who had used nonprescription tanning equipment for their psoriasis, 68 percent believed this modality was effective. We found that alternative medical therapies were widely utilized by subjects participating in this study. Clinicians need to continue to be aware of nonallopathic remedies employed by their patients to discover useful information about future therapies and to monitor for adverse effects.

Adolescent↗
PubMed1995

A silencer and an adjacent positive element interact to modulate the activity of the human insulin promoter.

A negative regulatory element (NRE) is located between positions -279 and -261 relative to the transcription start site of the human insulin gene. The NRE contains at least three distinct overlapping binding sites for several nuclear proteins. These proteins may be distinguished by their interaction with mutant variants of the NRE. Mutagenesis of two of these protein-binding sites within an insulin gene fragment containing sequences from position -361 to position +112 attenuated the negative activity of the NRE, confirming the importance of these sites in the function of the NRE. When placed in isolation upstream of the herpes-simplex-virus thymidine-kinase promoter, the NRE exhibited stimulatory activity in non-beta (BHK) and beta (HIT) cells. The positive activity within the NRE was mapped to a sequence that resembled the binding site for the ubiquitous factor Oct-1. These results indicated that the negative activity of the NRE was dependent on its interaction with other regulatory sites within the insulin gene. Thus, the NRE exhibited negative activity in transfected HIT cells when placed upstream of an insulin gene fragment (positions -261 to +112). However, its activity was modulated in a positive manner by inclusion of additional sequences from position -279 to -341. This region contains the CT3 box that binds the homeodomain protein IUF1 (insulin upstream factor 1). The NRE resembled a silencer, being at least partly independent of precise location and orientation, and being able to operate upon a variety of promoters. The role of the NRE is unclear, although it may be involved in restricting expression of the insulin gene to cells of the islets of Langerhans.

Animals↗
PubMed1995

Identification and characterization of a functional retinoic acid/thyroid hormone-response element upstream of the human insulin gene enhancer.

A deletion analysis of the human insulin gene extending to 2 kb upstream of the transcription start site provided evidence of regulatory sequences located upstream of the insulin-linked polymorphic region (ILPR). Within this ILPR-distal region is a sequence (Ink, for insulin kilobase upstream) which contains three potential nuclear hormone-receptor half-sites, closely matching the consensus sequence AGGTCA. These sequences are arranged as a palindromic element with zero spacing over-lapping a direct repeat with 2 bp spacing. The Ink sequence was used in electrophoretic mobility-shift assays within nuclear extracts from COS-7 cells overexpressing the vitamin D, thyroid hormone or retinoic acid receptors, or from an insulin-expressing hamster cell line, HIT-T15. These studies suggest that the insulin-expressing cell line contains thyroid hormone and retinoic acid receptors at least, and that these receptors are able to recognize the Ink sequence. Three copies of the Ink sequence were placed upstream of the thymidine kinase promoter and firefly luciferase reporter gene. In COS-7 cells expressing the appropriate nuclear hormone receptor, this construct was responsive to both thyroid hormone (18-fold) and all-trans-retinoic acid (31-fold). In HIT-T15 cells the same construct responded to all-trans-retinoic acid, but not to thyroid hormone. Within the context of a 2 kb insulin gene fragment, the Ink sequence was shown to be activated by retinoic acid and by the retinoic acid receptor, but acted as a negative element in the presence of both retinoic acid and the retinoic acid receptor. Mutagenesis studies demonstrated that the palindromic sequence was important for the retinoic acid response, and for binding of complexes containing retinoic acid receptor. In human islets of Langerhans, retinoic acid was shown to stimulate insulin mRNA levels. These results demonstrate that a functional nuclear hormone-receptor-response element is located upstream of the human ILPR. As retinoic acid and thyroid hormone are frequently involved in developmental regulatory processes, it is possible that this element may be important in the process of islet cell differentiation.

Animals↗
PubMed1995

Comparison of three jet nebulizer aerosol delivery systems used to administer recombinant human DNase I to patients with cystic fibrosis. The Pulmozyme rhDNase Study Group.

STUDY OBJECTIVE: To compare the degree of improvement in pulmonary function achieved with recombinant human DNase I (rhDNase) administered by three different aerosol delivery systems: DeVilbiss Pulmo-Aide compressor with the Marquest Acorn II nebulizer, the Hudson T Up-draft nebulizer, and the Pari LC Jet Plus nebulizer with the Pari Inhalier Boy compressor. These produce similar aerosols in vitro in terms of size distribution and activity of delivered rhDNase. STUDY DESIGN: Multicenter, randomized, open-label, parallel-group comparison of changes from baseline in pulmonary function variables in each test group. Patients were treated with rhDNase (2.5 mg bid) for 15 days, administered with three different aerosol delivery systems. SETTING: Outpatient clinics at 26 sites in the United States. PATIENTS: 397 patients > 5 years of age with cystic fibrosis and baseline forced vital capacity (FVC) values between 40 and 70% of predicted values. RESULTS: All three nebulizers gave comparable improvements in pulmonary function. FEV1 increased by an average of 13.2 to 14.1%, FVC by 10.9 to 11.8% and forced midexpiratory flow (FEF25-75) by 16.5 to 17.1%. No unusual or unexpected adverse events were reported other than those that would be expected in patients with cystic fibrosis. CONCLUSIONS: Recombinant human DNase I produced a similar magnitude of improvement in the pulmonary function of patients with cystic fibrosis when the drug was administered using three different types of nebulizer systems with similar in vitro delivery and safety characteristics.

Adult↗
PubMed1994

Nutrient regulation of insulin gene expression.

The beta cell of the islets of Langerhans contributes along with other factors to glucose homeostasis by sensing changes in the plasma glucose concentrations and adjusting the rate of insulin production and release. Over short periods of time, insulin production is controlled principally through translation of pre-existing mRNA. Over longer periods, insulin mRNA levels are modulated through effects on the rate of transcription of the insulin gene, and also through changes in the rate of decay of insulin mRNA. These long-term effects may be important in allowing the beta cell to adapt to changes in diet or periods of fasting. Several mechanisms involved in the control of the rate of translation of insulin mRNA have been described. Effects of glucose metabolism on the turnover of insulin mRNA have yet to be characterized in detail. At the level of transcription, cis-acting DNA elements and trans-acting factors involved in the transient response of the insulin gene to changes in intracellular cAMP levels, or to signals generated as a result of glucose metabolism, have been identified.

Animals↗
PubMed1993

The helix-loop-helix transcription factor USF (upstream stimulating factor) binds to a regulatory sequence of the human insulin gene enhancer.

Two important sequence elements, designated insulin enhancer binding site 1 (IEB1) or NIR and IEB2 or FAR, are involved in regulating expression of the rat insulin I gene. These elements bind a helix-loop-helix transcription factor, insulin enhancer factor 1 (IEF1). The IEB1 site is highly conserved among insulin genes but the IEB2 site is not conserved. To investigate the factors binding at the equivalent IEB1 and IEB2 sites in the human insulin gene enhancer, electrophoretic mobility shift assays were performed using a variety of cell extracts and probes specific for the homologous IEB1 and IEB2 sites. The results indicate that a factor with similar tissue distribution and binding characteristics to those of IEF1 binds to the IEB1 site in the human insulin gene, but that a separate factor, identified as the adenovirus major late transcription factor [MLTF, or upstream stimulating factor (USF)] binds to the IEB2 site.

Base Sequence↗