Airway hyperresponsiveness, inflammation, and subepithelial collagen deposition in recently diagnosed versus long-standing mild asthma. Influence of inhaled corticosteroids.

This study aimed at documenting airway inflammation and subepithelial collagen deposition in patients using only inhaled beta(2)-agonists with either recently diagnosed asthma (RDA: /= 13 yr, n = 16) and at the influence of an intense inhaled corticosteroid (ICS) treatment on these parameters, in relation to changes in airway responsiveness. Patients had a methacholine inhalation test and a bronchoscopy with bronchial biopsies before and after an 8-wk treatment with inhaled fluticasone propionate (FP), 1,000 microgram/day. Baseline FEV(1) (mean +/- SEM) was normal and similar in both groups (RDA: 98.1 +/- 2.7, LSA: 94.5 +/- 4.6%). Geometric mean methacholine PC(20) was lower in LSA than in RDA (0.44 versus 3.37 mg/ml) at baseline and improved similarly by 1.85 and 1.86 double concentrations with FP treatment. PC(20) normalized (>/= 16 mg/ml) in five patients with RDA and two patients with LSA. Baseline mean bronchial cell counts (per mm(2) connective tissue surface) for CD3(+), CD4(+), CD8(+), CD25(+), EG1(+), CD45ro(+), and AA1(+) cells were similar in both groups. With FP, EG1(+) (p < 0.001), EG2(+) (p = 0.018), and AA1(+) counts (p = 0.009) decreased significantly in both groups while CD45ro(+) (p = 0.02) counts decreased only in LSA. Baseline type 1 and type 3 collagen deposition underneath the basement membrane was similar in RDA and LSA and did not change significantly after FP. This study shows that recent compared to long-standing mild asthma is associated with a similar degree of airway inflammation and subepithelial fibrosis, and a similar improvement in airway hyperresponsiveness after 8 wk on high-dose ICS. It also indicates that once asthma becomes symptomatic, airway responsiveness cannot normalize in most subjects over such a time period, even with a high dose of ICS.

Plasminogen activator inhibitor 1 messenger RNA expression and molecular evidence for del(7)(q22) in uterine leiomyomas.

We analyzed the expression of plasminogen activator inhibitor 1 (PAI-1) in 16 leiomyomas and adjacent myometrium of women who underwent a hysterectomy while in the proliferative (n = 8) and secretory phases (n = 8) of the menstrual cycle. We localized the PAI-1 and its mRNA expression in smooth muscle and vessel endothelial cells of uterine tissues using immunocytochemistry and in situ hybridization. The expression of PAI-1 mRNA was higher in 11 (68.75%) of 16 leiomyomas compared with the adjacent myometrium (leiomyoma/myometrium ratio, 1.4-3.0; mean, 2.045). The leiomyoma:myometrium ratio of PAI-1 mRNA expression did not change during the proliferative (Phase I) and secretory (Phase II) phases of the menstrual cycle. In the remaining five samples, the leiomyoma:myometrium ratio of PAI-1 mRNA expression was close to 1 (0.8-1.2; mean, 0.92). Because the locus of the PAI-1 gene is on chromosome 7q22, we screened for loss of heterozygosity (LOH) in these samples using the PAI-1 marker and D7S471, an anonymous marker 12 cM telomeric to PAI-1. Four of five samples with low leiomyoma:myometrium ratio had LOH for the PAI-1 and/or D7S471 markers. The fifth sample demonstrated a noninformative analysis for these markers but had LOH for the D7S515, D7S666, and D7S518 markers, all centromeric to PAI-1. Because del(7)(q22), associated with a relatively low PAI-1 mRNA expression, can deregulate matrix proteinases and growth factors' activity in leiomyomas, it is conceivable that del(7)(q22) results in heterogeneous leiomyoma biology.

Sonographic appearance of primary small bowel carcinoid tumor.

BACKGROUND: To assess the value of sonography in the diagnostic work-up of small bowel carcinoid tumors and characterize their sonographic appearance. METHODS: We retrospectively reviewed the sonographic findings (size, shape, echogenicity, contour, location, wall thickening, serosal transgression, vascularity) of all cases of carcinoid tumors investigated between January 1988 and January 1993. Six tumors, in five patients with histologic proof, were analyzed and, when possible, correlation with pathological or surgical results was made. RESULTS: In four out of five cases, the tumor was not suspected clinically prior to sonography; in one case, a small synchronous lesion was only found at surgery. Its sonographic appearance was a hypoechoic, homogenous, predominantly intraluminal mass with smooth intraluminal contour and attached to the wall by a broad base with interruption of the submucosa and thickening of the muscularis propria in all cases. There were signs of serosal transgression in four cases, puckering and retraction in two cases, hypervascularity in two cases, and mesenteric involvement in three cases. All lesions were located in the ileum and the mean diameter was 22 x 17 mm. CONCLUSION: Ultrasonography was useful in the detection of primary carcinoid tumors of small bowel. Their sonographic characteristics were described and some of them were highly suggestive of the diagnosis.

A randomized, double-blind, placebo-controlled study on the effect of conjugated estrogens on skin thickness.

OBJECTIVE: Our purpose was to assess the potential benefit of therapy with conjugated estrogens therapy on skin thickness in postmenopausal women. STUDY DESIGN: Sixty postmenopausal women were randomly allocated to receive conjugated estrogens or placebo treatment for 12 months. Neither participants nor investigators were aware of the group allocation. Skin thickness was measured by ultrasonography at baseline and after 6 to 12 months of treatment. Histologic changes were evaluated by skin biopsy at baseline and after 12 months' treatment. Quality of life and adverse events were recorded at each visit and at the end of treatment. RESULTS: Treatment with conjugated estrogens for 12 months significantly increases, at the level of the right great trochanter, the thickness of the skin (p < 0.01), as assessed by ultrasonography, and of the dermis (p < 0.05), as assessed by skin biopsy. No statistically significant difference was observed in the control population. Quality of life was reported to be improved (p < 0.05) in women treated with estrogen compared with those in the placebo group. CONCLUSION: The results may help postmenopausal women to better appraise the benefits of estrogen replacement therapy, and they provide further evidence of the potential of conjugated estrogens in preventing skin aging.

Body weight and prognostic indicators in breast cancer. Modifying effect of estrogen receptors.

The relations of body weight, height, and Quetelet index to axillary node involvement at diagnosis, estrogen receptor status, and histologic features of the primary tumor were examined in 656 patients with a newly diagnosed infiltrating breast carcinoma first treated in Québec City from July 1982 to December 1984. Node involvement increased with body weight and Quetelet index. This association was more regular and much stronger among patients with estrogen receptor-positive tumors than among those with estrogen receptor-negative breast cancers. Among patients with estrogen receptor-positive tumors, the percentage with involved nodes at diagnosis increased regularly from 32.9% among lean patients (Quetelet index less than 21 kg/m2) to 65.6% among obese women (Quetelet index greater than 27 kg/m2). This trend was seen even after adjustment for age and tumor size. In contrast, among patients with estrogen receptor-negative breast cancers, the association of weight and Quetelet index with node involvement were weak and irregular. The modifying effect of estrogen receptor status on the relation of obesity to node involvement was apparent in pre- and post-menopausal women. Body weight and Quetelet index were not related to estrogen receptor status or to any of the measured histologic features of breast tumors including nuclear grade, histologic grade, tubule formation, mitotic activity, and size of nucleus of cancer cells. These findings suggest that the observed deleterious effect of obesity on breast cancer prognosis is unlikely to be an artifact of delayed diagnosis in overweight patients. It may be due to hormonal changes associated with increases in body weight.

Dietary fat in relation to prognostic indicators in breast cancer.

The relation of diet, especially fat intake, to recognized prognostic indicators for breast cancer was investigated in 666 women with a newly diagnosed infiltrating breast carcinoma. Diet during the year preceding diagnosis was assessed by interview using a food frequency questionnaire covering the intake of 114 food items. Prognostic indicators included axillary node involvement at diagnosis, estrogen receptor status, and selected histologic features of the primary tumor such as nuclear grade, histologic grade, tubule formation, mitotic activity, and nuclear size of tumor cells. After adjustment for total energy intake, age, body weight, and tumor size at diagnosis, an increase in saturated fat intake was related to an increased frequency of node involvement at diagnosis among postmenopausal patients. In contrast, an elevation in polyunsaturated fat intake was related to a reduction of the percentage of patients with positive nodes at diagnosis. This relation was observed among both premenopausal and postmenopausal patients. Dietary fat was not related to the estrogen receptor status of tumors. No association was found between dietary habits and histologic features of the primary tumor. These data suggest that dietary fat may have an effect on the growth or spread of breast cancer during the preclinical phase of the disease and that this effect may vary according to the type of fat considered.