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Objective: To determine the opinions of selected physicians in our community about use of warfarin for patients with nonrheumatic atrial fibrillation, and to determine the relation of the physicians' opinions to their practices.Design: Survey of physicians, using eight hypothetical clinical vignettes to characterize physicians' opinions about use of warfarin in patients with nonrheumatic atrial fibrillation, according to patient age, risk of bleeding, and risk of stroke.Setting: Two teaching hospitals and five community-based practices.Participants: Eighty physicians who cared for 189 consecutive patients with nonrheumatic atrial fibrillation.Measurements and Main Results: The survey response rate was 73%. Nearly all responding physicians (90%) recommended warfarin for at least one vignette. However, physicians recommended warfarin less often for vignettes depicting 85-year-old patients than for matched vignettes depicting 65-year-old patients (odds ratio [OR] 0.03; 95% confidence interval [CI] 0.01, 0.08), and less often for cases with specified risk factors for bleeding than for matched cases without the risk factors (OR 0.01; 95% CI 0.004, 0.03); warfarin was recommended more often for cases with a recent stroke than for matched cases without this history (OR 8.2; 95% CI 3.6, 18). In practice, warfarin was prescribed more often (p < or = .05) by physicians reporting good personal experience and by those who had favorable opinions about its use. However, even physicians with good experience and favorable opinions did not prescribe warfarin to half of their patents for whom warfarin was independently judged appropriate.Conclusions: Physicians' opinions frequently opposed warfarin for older patients with nonrheumatic atrial fibrillation, and for those with bleeding risk factors. Physicians' opinions, as well as other barriers to warfarin therapy, most likely contribute to its infrequent prescription. [ABSTRACT FROM AUTHOR]

Objective: To determine how often warfarin was prescribed to patients with nonrheumatic atrial fibrillation in our community in 1992 when randomized trials had demonstrated that warfarin could prevent stroke with little increase in the rate of hemorrhage, and to determine whether warfarin was prescribed less frequently to older patients-the patients at highest risk of stroke but of most concern to physicians in terms of the safety of warfarin.Design: Cross-sectional study. Appropriateness of warfarin was classified for each patient based on the independent judgments of three physicians applying relevant evidence and guidelines.Setting: Two teaching hospitals and five community-based practices.Patients: Consecutive patients with nonrheumatic atrial fibrillation (n = 189).Measurements and Main Results: Warfarin was prescribed to 44 (23%) of the 189 patients. Warfarin was judged appropriate in 98 patients (52%), of whom 36 (37%) were prescribed warfarin. Warfarin was prescribed to 11 (14%) of 76 patients aged 75 years or older with hypertension, diabetes mellitus, or past stroke, the group at highest risk of stroke. In a multivariable logistic regression model controlling for appropriateness of warfarin and other patient characteristics, patients aged 75 years or older were less likely than younger patients to be treated with warfarin (odds ratio 0.25; 95% confidence interval 0.10, 0.65).Conclusions: Warfarin was prescribed infrequently to these patients with nonrheumatic atrial fibrillation, especially the older patients and even the patients for whom warfarin was judged appropriate. These findings indicate a substantial opportunity to prevent stroke. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the accuracy and clinical utility of the Outpatient Bleeding Risk Index for estimating the probability of major bleeding in outpatients treated with warfarin. The index was previously derived in a retrospective cohort of 556 patients from a different hospital (derivation cohort).Subjects and Methods: We enrolled 264 outpatients starting warfarin (validation cohort) to validate the index prospectively. All patients were identified upon hospital discharge, and physician estimates of the probability of major bleeding were obtained before discharge in the validation cohort.Results: Major bleeding occurred in 87 of 820 outpatients (6.5%/yr). The index included four independent risk factors for major bleeding: age 65 years or greater; history of gastrointestinal bleeding; history of stroke; and one or more of four specific comorbid conditions. In the validation cohort, the index predicted major bleeding: the cumulative incidence at 48 months was 3% in 80 low-risk patients, 12% in 166 intermediate-risk patients, and 53% in 18 high-risk patients (c index, 0.78). The index performed better than physicians, who estimated the probability of major bleeding no better than expected by chance. Of the 18 episodes of major bleeding that occurred in high-risk patients, 17 were potentially preventable.Conclusions: The Outpatient Bleeding Risk Index prospectively classified patients according to risk of major bleeding and performed better than physicians. Major bleeding may be preventable in many high-risk patients by avoidance of over-anticoagulation and nonsteroidal anti-inflammatory agents. [ABSTRACT FROM AUTHOR]

Introduction: Enhanced recovery after surgery (ERAS) for peri-hilar cholangiocarcinoma (pCCA) has not been described in the literature. This study examined patients undergoing pCCA resection within a standard post hepatectomy ERAS pathway to define achievable targets suitable for these patients., Methods: Patients undergoing pCCA resection at University Hospital Aintree (January 2009-October 2017) were identified. Achievement of key ERAS outcomes was assessed. Patients were stratified on incidence of major complications and pre-operative cardiopulmonary exercise testing. Chi Square and Mann Whitney analyses were undertaken as appropriate. Achievable ERAS targets were derived from patients who did not develop a major complication., Results: 46 patients underwent resection with enhanced recovery. Median age 65 (24 male: 22 female). Key ERAS outcomes in patients who did not experience major complications are described as medians (interquartile range): length of stay 8 days (6-13), duration critical care 2 days (2-4), inotropes 6 h (0-24), epidural 3 days (3-4), early mobilization day 1 (1-2), full mobilization day 3 (3-4), urinary catheter removal day 4 (3-5), NGT removal day 1 (1-2) and restoration oral nutrition day 2 (2-4). Patients deemed high risk pre-operatively or those who developed major complications post-operatively required significantly longer critical care (p = 0.008 and p = 0.002 respectively). Other ERAS targets remained achievable in similar timeframes., Conclusions: ERAS for pCCA is achievable. Applicable ERAS standards are defined which take into account minor complications. High risk patients and those with major complications can be appropriately managed in an ERAS pathway, though there is increased need for critical care support., (Copyright © 2019. Published by Elsevier Ltd.)

The Myc family proteins are key regulators of animal growth and development. dMyc, the only Drosophila member of the Myc gene family, is orthologous to the mammalian c-Myc oncoprotein. Extensive studies have revealed much about both upstream regulators and downstream target genes in the sphere of Myc regulation. Here, we review some of the critical discoveries made using the Drosophila model, in particular those studies that have explored the essential role of the Myc family in growth and cell cycle progression and identified many of the upstream signals and downstream targets common to both c-Myc and dMyc.

Dronc is a caspase recruitment domain-containing Drosophila caspase that is expressed in a temporally and spatially restricted fashion during development. Dronc is the only fly caspase known to be regulated by the hormone ecdysone. Here we show that ectopic expression of dronc in the developing fly eye leads to increased cell death and an ablated eye phenotype that can be suppressed by halving the dosage of the genes in the H99 complex (reaper, hid, and grim) and enhanced by mutations in diap1. In contrast to previous reports, we show that the dronc eye ablation phenotype can be suppressed by coexpression of the baculoviral caspase inhibitor p35. Dronc also interacts, both genetically and biochemically, with the CED-4/Apaf-1 fly homolog, Dark. Furthermore, extracts made from Dark homozygous mutant flies have reduced ability to process Dronc, showing that Dark is required for Dronc processing. Finally, using the RNA interference technique, we show that loss of Dronc function in early Drosophila embryos results in a dramatic decrease in cell death, indicating that Dronc is important for programmed cell death during embryogenesis. These results suggest that Dronc is a key caspase mediating programmed cell death in Drosophila.

Background: Older persons frequently experience a decline in function following an acute medical illness and hospitalization., Objective: To test the hypothesis that a multicomponent intervention, called Acute Care for Elders (ACE), will improve functional outcomes and the process of care in hospitalized older patients., Design: Randomized controlled trial., Setting: Community teaching hospital., Patients: A total of 1,531 community-dwelling patients, aged 70 or older, admitted for an acute medical illness between November 1994 and May 1997., Intervention: ACE includes a specially designed environment (with, for example, carpeting and uncluttered hallways); patient-centered care, including nursing care plans for prevention of disability and rehabilitation; planning for patient discharge to home; and review of medical care to prevent iatrogenic illness., Measurements: The main outcome was change in the number of independent activities of daily living (ADL) from 2 weeks before admission (baseline) to discharge. Secondary outcomes included resource use, implementation of orders to promote function, and patient and provider satisfaction., Results: Self-reported measures of function did not differ at discharge between the intervention and usual care groups by intention-to-treat analysis. The composite outcome of ADL decline from baseline or nursing home placement was less frequent in the intervention group at discharge (34% vs 40%; P = .027) and during the year following hospitalization (P = .022). There were no significant group differences in hospital length of stay and costs, home healthcare visits, or readmissions. Nursing care plans to promote independent function were more often implemented in the intervention group (79% vs 50%; P = .001), physical therapy consults were obtained more frequently (42% vs 36%; P = .027), and restraints were applied to fewer patients (2% vs 6%; P = .001). Satisfaction with care was higher for the intervention group than the usual care group among patients, caregivers, physicians, and nurses (P < .05)., Conclusions: ACE in a community hospital improved the process of care and patient and provider satisfaction without increasing hospital length of stay or costs. A lower frequency of the composite outcome ADL decline or nursing home placement may indicate potentially beneficial effects on patient outcomes.

Homeobox genes of the Msx and Mox families are coexpressed in the vertebrate embryo in regions of epithelial-mesenchymal interactions. Here we show that a member of each family is expressed in extra-embryonic structures where epithelial and mesenchymal cell layers contact. In situ hybridization studies on first trimester human placental sections reveal that MSX2 and MOX2 are expressed predominantly in the cytotrophoblast cell layer. In term placenta, MSX2 and MOX2 are expressed in the syncytiotrophoblast. This is the first study to describe the expression of MOX2 in human tissues and to show that members of the Msx and Mox families of homeobox genes are expressed where epithelial and mesenchymal cell layers contact in the human placenta. A combinatorial code of homeobox genes that includes members of the Msx, Mox and Dlx families has been predicted to regulate epithelial-mesenchymal cell interactions in the vertebrate embryo. We have shown that MSX2, MOX2, DLX4 and the HB24 homeobox gene are expressed in the epithelial and mesenchymal cell types that form the placenta. We predict that this combination of homeobox genes is involved in regulating epithelial-mesenchymal cell interactions in extraembryonic tissues.

Bcl-2 family of proteins are key regulators of apoptosis. Both proapoptotic and antiapoptotic members of this family are found in mammalian cells, but no such proteins have been described in insects. Here, we report the identification and characterization of Debcl, the first Bcl-2 homologue in Drosophila melanogaster. Structurally, Debcl is similar to Bax-like proapoptotic Bcl-2 family members. Ectopic expression of Debcl in cultured cells and in transgenic flies causes apoptosis, which is inhibited by coexpression of the baculovirus caspase inhibitor P35, indicating that Debcl is a proapoptotic protein that functions in a caspase-dependent manner. debcl expression correlates with developmental cell death in specific Drosophila tissues. We also show that debcl genetically interacts with diap1 and dark, and that debcl-mediated apoptosis is not affected by gene dosage of rpr, hid, and grim. Biochemically, Debcl can interact with several mammalian and viral prosurvival Bcl-2 family members, but not with the proapoptotic members, suggesting that it may regulate apoptosis by antagonizing prosurvival Bcl-2 proteins. RNA interference studies indicate that Debcl is required for developmental apoptosis in Drosophila embryos. These results suggest that the main components of the mammalian apoptosis machinery are conserved in insects.

Caspases play an essential role in the execution of programmed cell death in metazoans. Although 14 caspases are known in mammals, only a few have been described in other organisms. Here we describe the identification and characterization of a Drosophila caspase, DRONC, that contains an amino terminal caspase recruitment domain. Ectopic expression of DRONC in cultured cells resulted in apoptosis, which was inhibited by the caspase inhibitors p35 and MIHA. DRONC exhibited a substrate specificity similar to mammalian caspase-2. DRONC is ubiquitously expressed in Drosophila embryos during early stages of development. In late third instar larvae, dronc mRNA is dramatically up-regulated in salivary glands and midgut before histolysis of these tissues. Exposure of salivary glands and midgut isolated from second instar larvae to ecdysone resulted in a massive increase in dronc mRNA levels. These results suggest that DRONC is an effector of steroid-mediated apoptosis during insect metamorphosis.

Objective: To learn how often patients receive skin cancer preventive services in dermatologists' offices., Design: Survey of dermatology patients and dermatologists., Setting: Dermatology practices of full-and part-time faculty at a midwestern medical school., Participants: Patients were randomly selected from clinical sessions of 11 dermatologists. Of 200 patients enrolled, 162 (81%) responded to the survey. Ten (91%) of the dermatologists responded, and 4 additional dermatologists from the faculty were also surveyed., Main Outcome Measures: Patients' and dermatologists' reports of the provision of skin cancer prevention counseling and screening for skin cancer., Results: Most patients (93%) had been informed about the risks of sun exposure, but for only 27% was a dermatologist the main source of information. Although 76% of patients had seen a dermatologist at least twice in the last 5 years, only 34% reported that they had ever received a total-body screening examination for skin cancer. Most patients (55%) would like to learn more about skin cancer prevention, and responded that they would learn best from a brochure (43%) or from a dermatologist (42%). All dermatologists believed that some skin cancer preventive services should be provided to each patient, but they varied widely in the proportion of their white adult patients to whom they provided such services. For example, with respect to counseling about sunscreens, the same number of dermatologists (4 [29%]) responded that they counsel 25% or less of their patients, and more than 75% of their patients., Conclusion: There is wide variation in how often skin cancer preventive services are provided in dermatologists' offices.

The adult human endometrium rapidly cycles through stages of cell proliferation, differentiation and degeneration. Inappropriate endometrial cell differentiation is a contributing factor in diseases such as endometrial carcinoma and endometriosis. We have identified two homeobox genes that may play a role in the control of endometrial cell differentiation and development. In-situ mRNA hybridization experiments were used to show differential expression of DLX4 at different phases of the endometrial cycle. Higher levels of DLX4 expression were observed in proliferative phase endometrial epithelium compared with secretory phase endometrial epithelium. The HB24 homeobox gene was shown to be expressed in both the proliferative and secretory phase endometrial epithelium. We predict that DLX4 and HB24 will be required for the transcriptional control of genes important for endometrial cell differentiation. Furthermore, we propose that DLX4 and HB24 are part of a conserved combinatorial code of homeobox genes that are required for controlling epithelial-mesenchymal cell interactions in the endometrium.

Homeobox genes of the Distal-less (Dlx) family are expressed in the vertebrate embryo in regions where epithelial cell layers contact adjacent mesenchymal cells. This study shows that the human Dlx family member, DLX4, is expressed in the placenta, primarily in regions where epithelial and mesenchymal cell layers contact. In situ hybridization studies at first trimester human placental sections revealed that DLX4 was expressed predominantly in the cytotrophoblast stem cell layer. In term placenta, DLX4 was expressed in the syncytiotrophoblast. Northern analysis revealed two DLX4 transcripts in first trimester placenta of 2.8 and 3.0 kb. Elevated levels of DLX4 mRNA were detected in a choriocarcinoma derived cell line when compared with a cytotrophoblast cell line and normal placenta. This is the first study to show that a member of the Dlx family of homeobox genes is expressed in regions of epithelial and mesenchymal cell layer contact in the human. Accumulated evidence from several studies suggest that a combinatorial code of homeobox genes is required to regulate epithelial-mesenchymal cell interactions in the vertebrate embryo. It is predicted that a similar combination of homeobox genes, that includes DLX4, is involved in regulating epithelial-mesenchymal cell interactions in extraembryonic tissues. DLX4 may also have a role in the regulation of the genes important for trophoblast invasion since the level of expression in trophoblast cell lines reflects invasive potential.

Background & Aims: Survival of patients with end-stage liver disease is variable and difficult to predict. A two-phase prospective cohort study was conducted at five teaching hospitals to develop and evaluate a model for prediction of death., Methods: Five hundred thirty-eight hospitalized patients with a history of chronic liver disease and two or more signs of decompensation were studied., Results: The cumulative incidence of death was 30% at 30 days and 50% at 6 months. In 295 patients in phase I, time till death was independently associated (P < 0.01) with five factors measured on study day 3: renal insufficiency, cognitive dysfunction, ventilatory insufficiency, age > or = 65 years, and prothrombin time > or = 16 seconds. These risk factors stratified 243 patients in phase II into three groups with cumulative incidences of death at 30 days of 12%, 40%, and 74%, respectively. Integration of the prognostic model with physicians' predictions led to improved estimates of the probability of death. Although performance of liver transplantation after study entry was independently associated with enhanced survival, the intensity of other acute therapies was not., Conclusions: Five risk factors were associated with the risk of death in patients with end-stage liver disease and provided a quantitative basis to complement physicians' prognostic estimates.

Context: Major teaching hospitals are perceived as being more expensive than other hospitals and, thus, unattractive to managed care. However, little empirical data exist about their relative quality and efficiency. The current study compared severity-adjusted mortality and length of stay (LOS) in teaching and nonteaching hospitals., Design: Retrospective cohort study., Setting: Thirty hospitals in northeast Ohio., Patients: A total of 89851 consecutive eligible patients discharged in 1991 through 1993 with myocardial infarction, congestive heart failure, obstructive airway disease, gastrointestinal hemorrhage, pneumonia, or stroke., Main Outcome Measures: In-hospital mortality and LOS of patients in major teaching (n=5), minor teaching (n=6), and nonteaching (n=19) hospitals were adjusted for admission severity of illness using multivariable models based on demographic and clinical data abstracted from patients' medical records., Results: The adjusted odds of death was 19% lower (95% confidence interval [CI], 2%-34%; P=.03) for patients in major teaching hospitals compared with non-teaching hospitals but was similar (95% CI, 7% lower to 28% higher; P=.28) for patients in minor teaching hospitals. The findings were generally consistent in analyses stratified according to diagnosis, age, race, predicted risk of death, and other covariates. In addition, risk-adjusted LOS was 9% lower (95% CI, 8%-10%; P<.001) among patients in major teaching hospitals relative to nonteaching hospitals but was similar (95% CI, 2% lower to 11% higher; P=.17) in minor teaching hospitals. Major teaching hospitals also cared for higher proportions of nonwhite and poorly insured patients., Conclusions: Risk-adjusted mortality and LOS were lower for patients in major teaching hospitals than for patients in minor teaching and nonteaching hospitals. If generalizable to other regions, the results provide evidence that hospital performance, as assessed by 2 commonly used indicators, may be higher in major teaching hospitals. These findings are noteworthy at a time when the viability of many major teaching hospitals is threatened by powerful health care market forces and by potential changes in federal financing of graduate medical education.

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.

Skindex is a quality-of-life instrument for skin diseases. To determine its convergent validity and its advantage relative to a generic measure, we compared responses of 132 dermatology patients to Skindex and the Medical Outcomes Study 36-item Short-Form Survey (SF-36). We hypothesized that (i) correlations between similar scales would be strong but not redundant (r = 0.5-0.6), and (ii) Skindex scores would correlate more highly with responses about skin disease-related aspects of health, and SF-36 scores would correlate more highly with responses concerning general health. As measured by the SF-36, patients reported general health status similar to the normal population, and SF-36 scores did not correlate with dermatologists' judgments about the severity of skin disease. Correlations between the same scales of the two instruments were as hypothesized (range of r, 0.44-0.56), and patients with low, medium, or high responses to Skindex differed similarly in SF-36 scores. On the other hand, some patients who reported on the SF-36 that they were free of physical symptoms (37% of patients) or social effects (54%) on Skindex, reported such effects from their skin disease. Also, responses about skin-related health aspects correlated more highly with Skindex than SF-36 (for skin condition, mean r = 0.42 vs 0.28; for disfigurement, 0.38 vs 0.24). Conversely, responses concerning general health correlated more highly with SF-36 than Skindex (for self-reported health status, mean r = 0.28 vs 0.16; for co-morbidity, 0.48 vs 0.37). This study further supports the validity of Skindex and also suggests that both generic and disease-specific health status measures can contribute to the assessment of patients with skin diseases.

Objective: To determine the opinions of selected physicians in our community about use of warfarin for patients with nonrheumatic atrial fibrillation, and to determine the relation of the physicians' opinions to their practices., Design: Survey of physicians, using eight hypothetical clinical vignettes to characterize physicians' opinions about use of warfarin in patients with nonrheumatic atrial fibrillation, according to patient age, risk of bleeding, and risk of stroke., Setting: Two teaching hospitals and five community-based practices., Participants: Eighty physicians who cared for 189 consecutive patients with nonrheumatic atrial fibrillation., Measurements and Main Results: The survey response rate was 73%. Nearly all responding physicians (90%) recommended warfarin for at least one vignette. However, physicians recommended warfarin less often for vignettes depicting 85-year-old patients than for matched vignettes depicting 65-year-old patients (odds ratio [OR] 0.03; 95% confidence interval [CI] 0.01, 0.08), and less often for cases with specified risk factors for bleeding than for matched cases without the risk factors (OR 0.01; 95% CI 0.004, 0.03); warfarin was recommended more often for cases with a recent stroke than for matched cases without this history (OR 8.2; 95% CI 3.6, 18). In practice, warfarin was prescribed more often (p < or = .05) by physicians reporting good personal experience and by those who had favorable opinions about its use. However, even physicians with good experience and favorable opinions did not prescribe warfarin to half of their patents for whom warfarin was independently judged appropriate., Conclusions: Physicians' opinions frequently opposed warfarin for older patients with nonrheumatic atrial fibrillation, and for those with bleeding risk factors. Physicians' opinions, as well as other barriers to warfarin therapy, most likely contribute to its infrequent prescription.

Objective: To determine how often warfarin was prescribed to patients with nonrheumatic atrial fibrillation in our community in 1992 when randomized trials had demonstrated that warfarin could prevent stroke with little increase in the rate of hemorrhage, and to determine whether warfarin was prescribed less frequently to older patients-the patients at highest risk of stroke but of most concern to physicians in terms of the safety of warfarin., Design: Cross-sectional study. Appropriateness of warfarin was classified for each patient based on the independent judgments of three physicians applying relevant evidence and guidelines., Setting: Two teaching hospitals and five community-based practices., Patients: Consecutive patients with nonrheumatic atrial fibrillation (n = 189)., Measurements and Main Results: Warfarin was prescribed to 44 (23%) of the 189 patients. Warfarin was judged appropriate in 98 patients (52%), of whom 36 (37%) were prescribed warfarin. Warfarin was prescribed to 11 (14%) of 76 patients aged 75 years or older with hypertension, diabetes mellitus, or past stroke, the group at highest risk of stroke. In a multivariable logistic regression model controlling for appropriateness of warfarin and other patient characteristics, patients aged 75 years or older were less likely than younger patients to be treated with warfarin (odds ratio 0.25; 95% confidence interval 0.10, 0.65)., Conclusions: Warfarin was prescribed infrequently to these patients with nonrheumatic atrial fibrillation, especially the older patients and even the patients for whom warfarin was judged appropriate. These findings indicate a substantial opportunity to prevent stroke.

To measure the effects of skin disease on patients' quality of life, we developed a 61-item self-administered survey instrument called Skindex. Skindex has eight scales, each of which addresses a construct, or an abstract component, in a comprehensive conceptual framework: cognitive effects, social effects, depression, fear, embarrassment, anger, physical discomfort, and physical limitations. Item responses are standardized from 0 (no effect) to 100 (maximal effect); a scale score is the average of responses to items addressing a construct. In 201 patients seen by dermatologists, mean scale scores (+/-SD) ranged from 14 (+/-17) for physical limitations to 31 (+/-22) for physical discomfort. Scale scores were reproducible after 72 h (r = 0.68-0.90) and were internally consistent (Cronbach's alpha = 0.76-0.86). Construct validity was assessed in two ways: (i) in a comparison of patients with inflammatory dermatoses and patients with isolated lesions, patients with inflammatory dermatoses had higher scale scores, and (ii) in an exploratory factor analysis, 78% of the common variance was explained by seven factors that correlated with the scale scores of Skindex. Most of the a priori scale scores changed in the expected direction in patients who reported that their skin conditions had improved or worsened after 6 mo. Finally, physicians' judgments of disease severity did not consistently correlate with Skindex scores. These preliminary data suggest that Skindex reliably and responsively measures the effects of skin disease on patients' quality of life and may supplement clinical judgments of disease severity.

Prolonged or repeated exposure to beta-agonist medications may result in a desensitization of the agonist-mediated response. Under certain conditions, such agonist-induced desensitization may limit the efficacy of administered beta-adrenergic agonists to elicit bronchodilation. Accordingly, the present study was designed to study the mechanism of acute beta-adrenergic desensitization in maturing rabbit tracheal smooth muscle (TSM). Isometric tension was measured in tracheal ring segments isolated from newborn and mature rabbits and half-maximally contracted with Methacholine (Meth) or KCl. TSM segments were serially relaxed with repetitive single doses of isoproterenol (ISO: 0.1, 1.0, 10, or 100 microM) or prostaglandin E2 (PGE2: 0.1 or 10 microM). Serial administration of ISO-elicited dose-dependent desensitization of relaxation in mature and newborn TSM, contracted with either Meth or KCl. In contrast, the relaxant response to PGE2 was retained in the ISO-desensitized tissue. Repeated administration of PGE2 elicited no desensitization of PGE2 responsiveness, but did induce some dose-dependent desensitization of the ISO response in mature TSM. Compared to mature tissues, newborn TSM developed subtotal desensitization to 100 microM ISO and no ISO desensitization in response to PGE2. Thus, these findings demonstrate that (1) beta-adrenoceptor responsiveness undergoes dose-dependent homologous and, to a lesser extent, heterologous desensitization in rabbit TSM; and (2) both beta-adrenergic desensitization mechanisms increase with postnatal maturation.

To determine whether glucocorticoids and beta-adrenoceptor agonists act independently to inhibit airway smooth muscle (ASM) proliferation, the present study investigated the effects of methylprednisolone (MP) and isoproterenol (ISO) alone and in combination on leukotriene D4-induced ASM proliferation. MP and ISO had no effect on unstimulated ASM cell growth. In contrast, MP and ISO demonstrated dose-dependent inhibition of LTD4-induced proliferation, and the inhibitory effect was additive for combinations of MP and ISO. The competitive cAMP receptor antagonist, Rp-cAMPS, ablated the ISO-induced inhibition but had no affect on the inhibitory response to MP. In cells exposed to both ISO and MP, Rp-cAMPS attenuated the growth inhibition to levels achieved by MP alone. Accordingly, these findings demonstrate that glucocorticoids and beta-adrenergic agonists inhibit LTD4-induced ASM proliferation, and that their inhibitory effects are mediated by different signaling pathways.

This study evaluated whether behaviors often taught as part of social skills training are judged favorably by others. Community judges evaluated the performances of people in various situations requiring one of three social skills: following instructions, accepting criticism, and negotiating to resolve conflicts. These skills were displayed in videotaped scenes by actors with and without mental retardation who acted out roles that had different types of authority relationships, and when different components or clusters of behavior (nonverbal, specific verbal, or general verbal behaviors) were performed well or poorly. The highest ratings by judges were of videotaped scenes that depicted correct use of all behaviors, regardless of which skill was being examined, whether or not the actor had mental retardation, or what the relationship was between the two actors. The lowest ratings were of videotaped scenes that depicted poor performance of all behaviors, and intermediate ratings were obtained when only some of the behaviors were performed poorly. These results, as well as the verbal responses of judges to questions, indicated that the different behaviors commonly used in teaching the skills of following instructions, accepting criticism, and negotiating are relevant to judgment of social performance, and are likely to be reinforced and maintained by social contingencies.

The percent body fat (PBF) and 15 anthropometric measurements were measured in 221 obese white females randomly assigned to validation and cross-validation groups. Two new anthropometric equations for the prediction of the percent of body fat were generated by multiple regression. Equation 1 includes the residual lung volume (RV) as a factor and had a correlation coefficient (r) of 0.85 and a standard error of the estimate (SEE) of 3.9%. Equation 2 does not include the RV and has an r of 0.82 and an SEE of 4.3%. Both equations were more precise than two previous widely used equations. In a subgroup of 37 subjects who underwent weight loss, equation 1 gave a more precise estimate of the change in PBF. We conclude that the new equations permit a better prediction of the PBF in obese white females.

Therapeutically efficacious doses of 131I-antibody result in a loss in circulating white blood cells; the granulocyte population is suppressed by 80-85% and the agranulocytes by 60-65% following 2 mCi of 131I-antibody in hamsters. The administration of 100,000 units of human recombinant interleukin 1 24 h prior to radioantibody can prevent the loss in WBC from 1 mCi of radioantibody and reduce the loss from 2 mCi of antibody. Recombinant murine granulocyte-macrophage colony-stimulating factor is also a potent stimulator of myelopoiesis and may also be useful as a method of reducing radioantibody-induced myelosuppression. The tumor uptake of radioantibody in animals treated with recombinant interleukin 1 is reduced by 30% 1 day after injection of radioantibody but returns to levels seen in animals not treated with the cytokine at 96 and 168 h. Therapeutic efficacy is not compromised by doses of interleukin 1 used to prevent myelosuppression. Therefore, the use of cytokines will permit the use of higher doses of radioantibody for greater tumor therapy with less myelotoxicity than in the absence of cytokine treatments.