Publications

One of the most abundant protein products of human secretory endometrium is glycodelin, a glycoprotein previously referred to as PP14. Although the precise function of this protein is unknown, its unique glycosylation pattern is believed to affect immunomodulatory activity during human embryonic implantation and inhibition of sperm-egg binding after ovulation. Having confirmed the expression of glycodelin in secretory endometrial glands, we used purified endometrial epithelial cell cultures to demonstrate the hormonal regulation of glycodelin synthesis and secretion. The findings were corroborated by transiently transfecting glycodelin gene promoter-reporter constructs into human epithelioid HeLa and Ishikawa cells. Our results indicate that glycodelin protein production by endometrial epithelial cells is directly up-regulated 4- to 9-fold by progestins and antiprogestins in vitro. Transcriptional regulation of the glycodelin gene promoter expressed in HeLa cells is progesterone receptor-dependent. As observed in the primary endometrial cells, progestins and antiprogestins both act as agonists on the in vitro expression of this endometrial gene. Our findings provide insight into the regulation of this abundant endometrial protein and raise interesting questions about the physical nature of the interaction of agonist- and antagonist-bound progesterone receptors with the glycodelin gene promoter.

OBJECTIVES

Accurate measurement of asthma severity is critical for research evaluating asthma health outcomes. There are, however, no widely accepted asthma severity measures. A severity-of-asthma score, which is based on self-reported information, was previously developed and validated in subjects recruited from pulmonary and allergy subspecialty practices. The purpose of this study was to validate the severity-of-asthma score in subjects treated by family practice physicians and to compare asthma severity in subjects treated by family practitioners (n = 150) with those seen by allergists (n = 217) and pulmonologists (n = 384).

METHODS

The study was an ongoing panel study of adults with asthma. Subjects were a random sample of board-certified family practice, allergy, and pulmonary physicians. Each physician registered patients with asthma aged 18 to 50 years. Of 869 subjects registered, 751 (86%) completed structured telephone interviews. The family practice panel was recruited approximately 3 years after the subspecialty panel.

RESULTS

In the family practice subjects, the severity-of-asthma score demonstrated internal consistency (Cronbach's alpha 0.76) and concurrent validity, correlating strongly with asthma-specific quality of life, SF-36 General Health and Physical Functioning scales, and subject-perceived asthma severity. After controlling for demographic characteristics, a 5-point score increment was associated with increased emergency department visits, urgent physician visits, and restricted activity days. The mean severity score was highest in the pulmonary group (11.8 +/- 6.3), followed by the allergy (10.3 +/- 5.3) and family practice (9.3 +/- 5.5) groups.

CONCLUSIONS

The severity-of-asthma score was a valid measure in generalist-treated subjects. Asthma severity varied significantly by physician specialty.

OBJECTIVES

This study sought to determine the prevalence, characteristics, relation to clinical features and evolution of aortic root disease and valve disease associated with ankylosing spondylitis (AKS).

BACKGROUND

Aortic root disease and valve disease are common in patients with AKS, but their clinical and prognostic implications have not been well defined.

METHODS

Forty-four outpatients with AKS and 30 age- and gender-matched healthy volunteers underwent initial transesophageal echocardiography and rheumatologic evaluations. Twenty-five patients underwent clinical and echocardiographic follow-up 39+/-10 months later.

RESULTS

Aortic root disease and valve disease were common in patients (82%) as compared with controls (27%; p < 0.001). Aortic root thickening, increased stiffness and dilatation were seen in 61%, 61% and 25% of patients, respectively. Valve thickening (41% for the aortic and 34% for the mitral valve) manifested predominantly (74%) as nodularities of the aortic cusps and basal thickening of the anterior mitral leaflet, forming the characteristic subaortic bump. Valve regurgitation was seen in almost half of patients, and 40% had moderate lesions. Except for the duration of AKS, aortic root disease and valve disease were unrelated to the activity, severity or therapy of AKS. During follow-up of 25 patients, in up to 24% new aortic root or valve abnormalities developed, in 12% existing valve regurgitation worsened significantly and in 20% abnormalities resolved. Twenty percent of patients developed heart failure, underwent valve replacement, had a stroke or died, as compared with 3% of control subjects.

CONCLUSIONS

Aortic root disease and valve disease are common in patients with AKS, are unrelated to clinical features of AKS, can resolve or progress over time and are associated with clinically important cardiovascular morbidity.

BACKGROUND

Major depression is associated with increased mortality, but it is not known whether patients who report depressive symptoms have greater mortality.

SUBJECTS AND METHODS

We performed a prospective cohort study of 7518 white women 67 years of age or older who were recruited from population-based listings in Baltimore, Md, Minneapolis, Minn, Portland, Ore, and the Monongahela Valley, Pa. Participants completed the Geriatric Depression Scale (short form) and were considered depressed if they reported 6 or more of 15 possible symptoms of depression. Women were followed up for an average of 6 years. If a participant died, we obtained a copy of the official death certificate and hospital records, if available, and used International Classification of Diseases, Ninth Revision, codes to classify death attributable to cardiovascular, cancer, or noncancer, noncardiovascular cause.

RESULTS

Mortality during 7-year follow-up varied from 7% in women with no depressive symptoms to 17% in those with 3 to 5 symptoms to 24% in those with 6 or more symptoms of depression (P<.001). Of 473 women (6.3%) with 6 or more depressive symptoms at baseline, 24% died (111 deaths in 2610 woman-years of follow-up) compared with 11% of women who reported 5 or fewer symptoms of depression (760 deaths in 41 460 woman-years of follow-up) (P<.001). Women with 6 or more depressive symptoms had a 2-fold increased risk of death (age-adjusted hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.75-2.61; P<.001) compared with those who had 5 or fewer depressive symptoms. This association remained strong after adjusting for potential confounding variables, including history of myocardial infarction, stroke, diabetes mellitus, hypertension, chronic obstructive pulmonary disease, smoking, perceived health, and cognitive function (HR, 1.47; 95% CI, 1.14-1.88; P=.003). Depressive symptoms were associated with an increased adjusted risk of death from cardiovascular diseases (HR, 1.8; 95% CI, 1.2-2.5; P= .003), and non-cancer, noncardiovascular diseases (HR, 1.8; 95% CI, 1.2-2.7; P = .01), but were not associated with deaths from cancer (HR, 1.0; 95% CI, 0.6-1.7; P=.93).

CONCLUSIONS

Depressive symptoms are a significant risk factor for cardiovascular and noncancer, noncardiovascular mortality but not cancer mortality in older women. Whether depressive symptoms are a marker for, or a cause of, life-threatening conditions remains to be determined.