Clinical significance of a cytologic diagnosis of atypical glandular cells of undetermined significance.

OBJECTIVE: To assess the clinical significance of a cytologic diagnosis of atypical glandular cells of undetermined significance (AGUS) and determine the most appropriate evaluation of these patients. STUDY DESIGN: Between 1993 and 1995, 44,217 Papanicolaou smears were evaluated at Allegheny University Hospitals, Medical College of Pennsylvania Campus. There were 108 (0.24%) cases of AGUS smears during that time. No clinical information was available for 14 patients, and 19 were lost to follow-up. The charts of the remaining 75 cases were retrospectively reviewed. RESULTS: Tissue specimens were available for 62 of the 75 patients. There were 26 (42%) with no significant histopathologic findings, 13 (21%) with polyps, 5 (8%) cases of endometrial hyperplasia, 2 (3%) with endometrial adenocarcinoma, 12 (19%) with cervical intraepithelial neoplasia (CIN), 1 (2%) with adenosquamous carcinoma of the cervix, 2 (3%) with cervical adenocarcinoma in situ and 1 (2%) case of metastatic breast cancer. The total number of patients with significant histopathology other than polyps was 23 (37%). The median age of the patients was 49 years. There were more cases of endometrial hyperplasia and endometrial cancer (19%) in women 49 years or older than in younger women; only one (3%) case of endometrial hyperplasia was detected in the younger age group (P = .057). Patients who underwent more-aggressive evaluation (colposcopy and biopsies plus endometrial sampling, cone biopsy or hysterectomy) had greater numbers of abnormal histopathologic findings (55%) than patients who underwent endometrial sampling only (21%) or those who underwent colposcopy and biopsy only (33%). This difference approaches statistical significance (P = .057). A significant proportion of patients with a history of CIN and a cytologic diagnosis of AGUS were found to have CIN (47%), while 8% of those with no history of CIN were found to have CIN (P = .002). Fifty percent of patients with a history of cancer (all had breast cancer) and AGUS had abnormal histopathology. Patients with a subclassification of AGUS "favor neoplasia" had a greater proportion of significant histopathology (72%) as compared to AGUS "unspecified" (26%) and AGUS "favor reactive" (20%) (P = .003). CONCLUSION: A significant proportion of women with a cytologic diagnosis of AGUS have abnormal histopathology. Heightened awareness should be raised in patients with AGUS and a history of CIN or cancer and in those with the AGUS subclassification "favor neoplasia."

[Hypotensive effects of safflower yellow in spontaneously hypertensive rats and influence on plasma renin activity and angiotensin II level].

Safflower yellow (SY) is a mixture of chalconoid compounds extracted from Carthamus tinctorius L. Ig SY 1-2 g.kg-1.d-1 lowered the blood pressure of spontaneously hypertensive rats (SHR), for about 1.86-3.86 kPa. Five weeks after administration of SY, the plasma renin activity and angiotensin II level diminished in the SHR experimental groups. These suggest that the decrease of blood pressure is mediated by the renin-angiotensin system.

[The in vitro effects of purified protein derivative (PPD) on the lymphocytes and phagocytes from patients with active pulmonary tuberculosis and healthy tuberculin reactors].

In a previous report, we found no difference in surface markers of lymphocytes and phagocytes between patients with active pulmonary tuberculosis and healthy tuberculin reactors. In this communication, 45 cases of active pulmonary tuberculosis and 21 cases of healthy tuberculin reactors were studied with regard to the changes of surface markers of lymphocytes and the expression of Fc and complement receptors on phagocytes after in vitro incubation with PPD. After PPD stimulation, the monocytes with Fc and complement receptors tended to increase in tuberculin-positive but not in tuberculin-negative patients or healthy tuberculin reactors, and the active T lymphocytes were markedly increased in normal individuals but not in patients. Thus, the failure of lymphocytes from patients to respond to in vitro PPD activation with increased active T lymphocytes may account for the establishment of tuberculous infection after exposure to mycobacteria and the inability of the monocytes from tuberculin-negative patients to be activated by PPD in vitro correlates with negative skin test in vivo.

Further study on the role of active T lymphocytes in human immunity to tuberculous infection.

Lymphocytes from healthy tuberculin reactors, but not those from patients with active pulmonary tuberculosis and positive tuberculin skin test, were able to respond drastically to the in vitro purified protein derivative (PPD) stimulation with a marked increase in active T lymphocytes. Furthermore, the active T lymphocytes, but not late T lymphocytes, from normals were able to secrete a soluble factor (lymphokine)which was capable of activating in vitro the active T lymphocytes of the patients.

Different responses of monocytes and active T lymphocytes to in vitro challenge of purified protein derivative (PPD) in patients with active tuberculosis and healthy tuberculin reactors.

In order to ascertain the roles of phagocytes and T lymphocytes in the defense of tuberculous infection, 21 cases of healthy tuberculin reactors and 45 cases of active tuberculosis were studied with regard to the expression of Fc and complement receptors on phagocytes and changes of surface markers of lymphocytes after in vitro incubation with purified protein derivative (PPD). After PPD stimulation, the monocytes with Fc and complement receptors tended to increase in tuberculin-positive but not in tuberculin-negative patients in patients. Thus the failure of the monocytes to be activated by PPD in vitro correlates with negative skin test in vivo and the inability of the lymphocytes from patients to respond to in vitro PPD activation with increased active T lymphocytes may account for the establishment of tuberculous infection after exposure to virulent tubercle bacilli.

[Influence of aminophylline on immune function of mice].

The effects of aminophylline (Ami) on immune systems in normal NIH mice were studied. Ami ig 25, 50 and 100 mg/(kg.d) x 8-10 d increased hemolytic ability of plaque forming cells and antibody concentration while it decreased the delayed type hypersensitivity (DTH) reaction and peripheral white blood cells phagocytosing function. Ami 1, 5, 10 micrograms/ml also promoted lymphocyte transformation of [methyl-3H] TdR incorporation induced by PHA in vitro.

[Humoral and cell-mediated immunities in patients with pulmonary tuberculosis (author's transl)].

Humoral and cell-mediated immunities were studied in 38 patients with pulmonary tuberculosis proved by sputum smears and/or cultures and chest X-rays. Nineteen healthy adults were included as control. The results showed that while the mean numbers of total white blood cell count, polymorphonuclear leukocytes, monocytes, B-lymphocytes and serum IgG concentration were significantly increased in patients, there was no difference in the mean numbers of lymphocytes, total T-lymphocytes, active T-lymphocytes, polymorphonuclear leukocytes and monocyteswith Fc and complementreceptor and serum IgA and IgM concentrations between these two groups. These data indicate that the patients with pulmonary tuberculosis are able to respond to infections with Mycobacterium tuberculosis, but subtle functional derangement of lymphocytes of patients still can not be ruled out.

Prenatal detection of fetal anomalies in pregnancies complicated by insulin-dependent diabetes mellitus.

OBJECTIVES: We evaluated the clinical utility of a comprehensive program of prenatal diagnostic testing for congenital anomalies in pregnancies complicated by insulin-dependent diabetes mellitus. STUDY DESIGN: Data were retrospectively analyzed from 289 diabetic women and their newborns from August 1987 to July 1993. Our protocol included initial hemoglobin A1 and maternal serum alpha-fetoprotein determinations and comprehensive fetal ultrasonography inclusive of a standard four-chamber view of the heart and detailed multiimage fetal echocardiography. RESULTS: Anomalies were identified in 29 of 289 (10%) fetuses and neonates: 12 cardiac only, 14 noncardiac, and 3 combined. In 21 of the 29 (72%) neonates the anomalies were detected prenatally. Twelve of 15 (80%) cardiac and 10 of 17 (59%) noncardiac lesions were identified prenatally. Cardiac lesions, especially of the cardiac septum and great vessels, accounted for 50% of all fetal defects. Malformations of the neuroaxis, skeleton, and genitourinary system were also detected. There were six neonatal deaths and four therapeutic pregnancy terminations associated with congenital anomalies. Although the hemoglobin A1 level was statistically significantly increased in 22 mothers of anomalous fetuses (p = 0.017), the actual difference between affected and nonaffected pregnancies was not clinically meaningful and much overlap occurred. Although 96% of women with a normal hemoglobin A1 level were delivered of normal infants, only 14% of those with an elevated value had a malformed fetus. Similarly, although 89% of gravid women with a normal maternal serum alpha-fetoprotein level were delivered of nonaffected fetuses, only 7.3% of patients with an elevated value had a malformed fetus. For the detection of cardiac defects, the sensitivity of the four-chamber view compared with detailed multiimage fetal echocardiography was 33% and 92%, respectively. CONCLUSIONS: This study demonstrates the utility of a comprehensive program to detect fetal anomalies in pregnancies complicated by diabetes mellitus.