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E Anderson

Publications and source records attributed to E Anderson.

At least 127 records · Page 7Linked to original sources
PubMed1994

Effects of 4-hydroxytamoxifen and a novel pure antioestrogen (ICI 182780) on the clonogenic growth of human breast cancer cells in vitro.

We have investigated the effects on breast cancer cell growth of 4-hydroxytamoxifen (4OHT), a conventional antioestrogen with agonist activity, and 7 alpha-[9-(4,4,5,5,5-pentafluoropentylsulphinyl)nonyl]oestra- 1,3,5,(10)- triene-3,17 beta-diol (ICI 182780), a novel, pure antioestrogen, using established human breast cancer cell lines and cancer cells obtained directly from breast cancer patients with malignant pleural effusions who had relapsed on tamoxifen. The effects of the two agents were assessed using the Courtenay-Mills clonogenic assay, which measures the growth of single cancer cells as colonies suspended in soft agar. The standard assay was modified by the use of defined serum- and phenol red-free growth medium. The growth of oestrogen receptor (ER)-positive MCF-7 cells in the assay was oestrogen responsive. Both antioestrogens inhibited the stimulatory effects of 1 nM oestradiol, but ICI 182780 caused significantly greater inhibition than 4OHT at 0.1-1.0 microM concentrations. In the absence of oestradiol, 4OHT but not ICI 182780 caused significant stimulation of colony formation at low (0.01-1.00 nM) concentrations. Neither antioestrogen had any effects on colony formation by the ER-negative Hs578T cell line. Successful colony formation was obtained in primary cultures from six out of eight malignant effusions. Colony formation was significantly stimulated by 0.1 nM oestradiol in four cases and by 10 nM 40HT in two cases. In contrast, ICI 182780 exhibited no intrinsic stimulatory activity and significantly inhibited both oestradiol- and 4OHT-stimulated cell growth. We conclude that the agonist activity of 4OHT and other conventional antioestrogens may cause treatment failure in some patients by stimulating breast cancer cell growth. The new, pure antioestrogen ICI 182780 is a more potent oestrogen antagonist than 4OHT and exhibits no growth-stimulatory activity. This agent may therefore offer therapeutic advantages over conventional antioestrogens in patients with advanced breast cancer and may be effective after conventional agents have failed.

Adult↗
PubMed1994

Hemarthrosis and synovitis associated with hemophilia: clinical use of P-32 chromic phosphate synoviorthesis for treatment.

PURPOSE: To evaluate the clinical usefulness of phosphorus-32 chromic phosphate synoviorthesis in patients with hemophilia, recurrent hemarthrosis, and synovitis. MATERIALS AND METHODS: Forty-four P-32 colloid synoviorthesis procedures were performed in 38 patients with these abnormalities. P-32 colloid was injected intramuscularly in a dose of 1.0 mCi (37.0 MBq) in adult knees and 0.5 mCi (18.5 MBq) in adult elbows. A thin-window Geiger-Müller counter was used to survey treated joints, lymph nodes, and liver in order to detect leakage from the joint. Follow-up extended to a maximum of 4 years after treatment. RESULTS: No evidence of clinically significant leakage was seen. Twenty-two of 28 treatments (78%) with longer than 6 months follow-up were associated with improvement in range of motion and frequency of hemorrhage. Of 15 treatments with longer than 2 years follow-up, 10 (67%) were associated with improvement in range of motion; 12 (80%), with improvement in frequency of hemorrhage; and 12 (80%) with improvement in quality-of-life activities. CONCLUSION: P-32 colloid synoviorthesis is a clinically useful out-patient procedure in patients with hemophilia, recurrent hemarthrosis, and synovitis in whom hemostatic therapy has failed.

Adolescent↗
PubMed1994

Ovulation induction and endometrial steroid receptors.

The endometrial morphology, endometrial steroid receptors and serum steroid hormone concentrations have been studied in 22 infertile women participating in an in-vitro fertilization, gamete intra-Fallopian transfer programme, including nine cases following treatment with gonadotrophin-releasing hormone analogue/human menopausal gonadotrophin/human chorionic gonadotrophin. All patients had normal ovulatory function before treatment and satisfactory response to ovulation induction. Endometrial biopsies were taken in spontaneous and treatment cycles on the fourth day after ovulation had been detected by ultrasound scanning, when endometrial receptors were measured using immunohistochemistry. Histological examination of biopsies in spontaneous cycles showed the majority (20/22) to be 'in-phase', while in two cases luteal phase defect was diagnosed. After ovulation induction, all the biopsies were still morphologically 'in-phase', although a significant reduction had occurred in the nuclear receptor level in both the glands and stroma for both progesterone receptors (gland P = 0.030, stroma P = 0.012 using microscopic analysis; gland P = 0.020, stroma P < 0.001 using a cell analysis system) and oestrogen receptors (gland P = 0.017, stroma P = 0.002 using direct microscopic analysis). This suggests that a reduction in steroid receptors in the endometrium occurs after ovulation induction in the presence of supraphysiological amounts of steroids, which is not associated with detectable morphological changes.

Adult↗
PubMed1993

Expression of activated gelatinase in human invasive breast carcinoma.

The expression of both 92- and 72-kDa gelatinases has been studied in 20 samples of human breast carcinoma by the technique of gelatin zymography. This technique allowed the relative amount of each gelatinase to be determined in small samples of tissue (< 10 mg). More importantly, active and latent forms of the two gelatinases were resolved. Two samples (10-20 mg) were cut from each piece of tumour in order to monitor the variability of gelatinase distribution within that section of tumour. The 72-kDa latent progelatinase was present in 15 of the 20 tumours, with trace amounts in two others. The 62-kDa activated form of this gelatinase was detected in all 15 of the tumours in which the latent form was present. The 92-kDa latent progelatinase was present in 11 of the 20 tumours, with trace amounts in four others. However, the 82-kDa activated form of this gelatinase was only clearly detected in two tumours, although three others showed the presence of trace amounts. The ratio of active to latent forms of the 72-kDa gelatinase ranged from 0.9 to 3.6. There were no marked correlations between gelatinase expression and established staging and prognostic markers. Analysis of three samples of fibroadenoma revealed only very low levels of gelatinase expression. On the basis of these results, activation of the 72-kDa progelatinase appears to be a more common event in invasive breast carcinoma than activation of the 92-kDa progelatinase. However, neither proteinase showed a correlation with metastatic progression, as measured by lymph node involvement.

Biomarkers, Tumor↗
PubMed1993

The participation of growth factors in simulating the quiescent, proliferative, and differentiative stages of rat granulosa cells grown in a serum-free medium.

Ovarian granulosa cells from small antral follicles from immature rats were cultured in a serum-free medium on an extracellular matrix for 10 days with growth factors in an effort to simulate the metabolic states they experience during their differentiation. During in vivo differentiation granulosa cells are initially quiescent, later proliferate and subsequently commence differentiation. With the production of androstenedione by the vascularized theca interna they produce estrogen and when the follicle reaches the preovulatory stage, granulosa cells produce both estrogen and progesterone. Culturing granulosa cells in serum-free medium plus FSH, PDGF, or FSH plus PDGF, the cells remain quiescent. The cells proliferate most consistently (as assessed by DNA quantitation) when cultured in FSH, PDGF, TGF alpha, TGF beta and GH, and undergo the first level of differentiation by producing estrogen (assessed by RIA) when cultured in FSH, PDGF, TGF beta, IGF-I and delta 4-A. Further differentiation is achieved in the presence of FSH, PDGF, TGF alpha, bFGF and delta 4-A when the cells produce both estrogen and progesterone similar to their production in preovulatory follicles. Phase contrast photomicrographs were made to monitor cellular shape changes. Electron microscopic analysis of the quiescent and proliferative cells reveal them to contain the normally occurring organelles. After 8 days in culture, cells producing estrogen, and estrogen and progesterone, contain endoplasmic reticulum of the smooth variety, an organelle which, in cooperation with mitochondria, is known to be involved in the production of steroids such as estrogen and progesterone. Therefore, with the addition of one or more growth factors and androstenedione to FSH-containing serum free medium, the simulated conditions are partially reminiscent of the follicular microenvironment, in which granulosa cells cultured on extracellular matrix can exhibit characteristics of growth and differentiation similar to folliculogenesis.

Androstenedione↗
PubMed1993

Characterization of progesterone biosynthesis in a transformed granulosa cell line.

The study of regulation of steroidogenesis in primary cultures of rat granulosa cells is difficult because the cells do not undergo more than one cell doubling in culture. Furthermore, there is size and steroidogenic heterogeneity in granulosa cells and it is difficult to obtain pure, functionally defined populations. Hence, it is advantageous to develop a homogeneous population of granulosa cells. In this report we describe the characterization of one such cell line (Rao-gcl-29) developed from diethylstilbestrol treated immature rat granulosa cells by transformation with SV40 T antigen. In this cell line cyclic AMP analogs induce high levels of progesterone biosynthesis, though there was no effect on estradiol biosynthesis. Also, FSH and hCG have no effect on progesterone biosynthesis. In the presence of FBS medium (20% fetal bovine serum in DMEM/F-12) and enriched medium (10% fetal bovine serum, 10% horse serum and 2% UltraSer G in DMEM/F-12 medium), 1 mM cAMP analogs induce high levels of progesterone biosynthesis up to 96 h. Ultrastructural features of the cell line resemble those of primary granulosa cells, in addition to forming gap junctions. Cyclic AMP analogs also induced cytochrome P450scc mRNA in this cell line by 48 h, and this effect is apparent by 24 h. Thus, this cell line could be useful in understanding the molecular mechanisms of regulation of cytochrome P450scc gene regulation.

Animals↗
PubMed1993

Serum immunoreactive and bioactive lactogenic hormones in advanced breast cancer patients treated with bromocriptine and octreotide.

6 patients with advanced breast cancer who had failed first and second line endocrine therapies received bromocriptine (1.25-2.5 mg twice daily per os) and octreotide (Sandostatin) via a continuous subcutaneous infusion (200-400 micrograms/24 h) until disease progression. Pre-treatment 24-h profiles of serum lactogenic hormones and their response to standard provocative tests were established and repeated at 2 weeks, and 3 and 6 months (or at tumour progression). Immunoreactive prolactin (ir-PRL), growth hormone (ir-GH) and insulin-like growth factor I (IGF-I) were measured by radioimmunoassay and bioactive lactogenic hormone levels (BLH) were estimated using the Nb2 rat lymphoma cell bioassay. Before treatment all patients showed episodic secretion of ir-PRL, ir-GH and BLH and provocative stimuli resulted in a peak of ir-GH and BLH maximal between 60 and 90 min after injection but no change in ir-PRL. After 2 weeks of treatment, ir-PRL levels were reduced to below the limit of detection in all 6 patients. Peaks of ir-GH and BLH were still apparent, although much reduced. Immunoreactive PRL continued to be profoundly suppressed in 3 of the 4 patients who remained on treatment for 3 to 6 months. Small pulses of ir-GH were still detectable in these patients with which BLH was, again, well correlated. After 2 weeks of treatment, serum IGF-I levels were reduced by 9-54% of the pretreatment values and generally remained suppressed throughout treatment. Clinically, 4 patients did not show disease progression for periods of up to 6 months and side-effects were minimal.

Aged↗
PubMed1993

Effect of tamoxifen on Ki67 labelling index in human breast tumours and its relationship to oestrogen and progesterone receptor status.

This study aimed to investigate the effect of tamoxifen on breast tumour levels of oestrogen and progesterone receptor (ER and PR) and proliferation as defined by the Ki67 antibody. A group of primary breast cancer patients was randomised to receive either tamoxifen (n = 59) or placebo (n = 44) treatment in the interval between clinic and surgery (median 21 days). Frozen sections of breast tumour biopsies obtained before and after treatment were stained immunocytochemically to obtain the percentage of nuclei containing ER and PR, and a Ki67 labelling index (LI). Tamoxifen-treated patients had a median Ki67 LI of 5.6% in the first biopsy falling to 3.0% in the second biopsy (P < 0.001 by Wilcoxon's matched pairs test), whereas placebo-treated patients had a median Ki67 LI of 5.4% in the first biopsy and 5.75% in the second (no significant difference). No significant differences were observed when the median %ER or %PR staining before and after treatment were compared. The Ki67 LI tended to increase with increasing histological grade and was greater in tumours that were ER - ve compared to those that were ER + ve (> 5% nuclei stained), median 7.8% and 4.3% respectively (P = 0.011 by Mann-Whitney U-test). However, the decline in tumour Ki67 LI following anti-oestrogen treatment failed to correlate with ER and PR status or to predict recurrence over a short follow-up period. To our knowledge, this is the first time that tamoxifen treatment has been shown to reduce the Ki67 LI in human breast tumours in vivo. These data indicate that staining with the Ki67 antibody may be useful in monitoring response to anti-oestrogen therapy.

Adult↗
PubMed1993

Microbiological lung surveillance in mechanically ventilated patients, using non-directed bronchial lavage and quantitative culture.

We surveyed bronchial microflora by alternate-day, non-directed bronchial lavage (NBL) in 150 patients requiring mechanical ventilation on an intensive care unit. This simple technique uses a 20 ml non-bronchoscopic lung lavage, then quantitative bacterial culture. NBL bacteriological findings were identical to those obtained by same-day bronchoscopic broncho-alveolar lavage on 16/20 occasions. Using serial NBLs, the bronchial bacterial population was characterized during 65 episodes of pneumonia defined by clinical and retrospective criteria. Mean bacterial colony counts increased significantly during the 2 days preceding the clinical onset of pneumonia, from < or = 10(3) cfu/ml to > or = 10(5) cfu/ml (p < 0.05). In 51 patients showing a clinical response to antibiotic treatment, mean colony counts fell significantly after antibiotic initiation (p < 0.05). By contrast, in 14 patients who showed progressive clinical deterioration or relapse, there was no significant fall in NBL counts, and serial NBLs revealed antibiotic resistance or superinfection. The surveillance data altered clinical management in 42% of patients. Positive NBLs guided the choice of antibiotics, whilst negative NBLs encouraged the withholding of antibiotics, or detection of alternative pathology. We propose routine bacteriological lung surveillance of mechanically ventilated patients using this simple, inexpensive and safe technique.

Anti-Bacterial Agents↗
PubMed1993

Presence of transforming growth factor-alpha messenger ribonucleic acid (mRNA) and absence of epidermal growth factor mRNA in rat ovarian granulosa cells, and the effects of these factors on steroidogenesis in vitro.

Granulosa cell steroidogenesis has been reported to be modulated by transforming growth factor-alpha (TGF alpha) and its biochemical and physiological analog, epidermal growth factor (EGF). In this report, we studied whether TGF alpha or EGF mRNA is produced by granulosa cells, examined the morphological effects of TGF alpha or EGF on granulosa cell cultures, and measured the changes in granulosa cell progesterone production in cells cultured with TGF alpha or EGF. RNA from fresh granulosa cells and from those incubated overnight and for 4, 7, and 10 days with FSH was studied with reverse transcription-polymerase chain reaction for TGF alpha and for EGF. Only TGF alpha mRNA appeared to be present in the granulosa cells. Phase-contrast microscopy revealed that the combination of FSH plus TGF alpha or EGF resulted in cell shape changes and an increase in lipid droplets in the granulosa cells. Electron microscopy revealed that the endoplasmic reticulum increased in the granulosa cells incubated with either EGF or FSH plus EGF. Mitochondria of granulosa cells incubated with growth factors possessed ultrastructural features consistent with those found in preovulatory granulosa cells. Culture of the granulosa cells with FSH plus TGF alpha or with FSH plus EGF resulted in significantly elevated progesterone and 20 alpha-hydroxyprogesterone levels. The highest level of progesterone production was on the eighth day of culture. We conclude that TGF alpha mRNA is produced by granulosa cells and that granulosa cell differentiation, as defined by morphological and biochemical criteria, is significantly stimulated in vitro by the combination of FSH and TGF alpha.

20-alpha-Dihydroprogesterone↗
PubMed1993

Functional and ultrastructural characteristics of two types of rat granulosa cell cultured in the presence of FSH or transforming growth factor alpha (TGF-alpha).

Granulosa cells were isolated from 15-day-old, 25-day-old or PMSG-primed rats and were separated by Percoll gradient (20 to 60%) into five fractions. The cells in fraction 2 were mostly small cells (6.96-9.57 microns) and fractions 3 and 4 had a relatively high population of large cells (10.96-13.05 microns) which were sorted to collect a pure population of large cells. Aliquots of small or large cells were cultured separately in serum-free defined DMEM/F-12 medium containing 50 ng FSH ml-1, or 10 ng transforming growth factor alpha (TGF-alpha) ml-1 for 3 days. In PMSG-primed rats, the large cells produced 3.2-fold more progesterone than did small cells (with FSH/TGF alpha: 255 +/- 35.0 versus 77.32 +/- 14.5 x 10(-6) ng, day 1). Large and small cells from 25-day-old rats produced similar amounts of progesterone (FSH/TGF alpha: 65.68 +/- 9.6 versus 78.25 +/- 12.3 x 10(-6) ng, day 1). In 15-day-old rats, large and small cells produced very low concentrations of progesterone (FSH/TGF alpha: 4.69 +/- 1.2 versus 2.66 +/- 1.0 x 10(-6) ng, day 1). Large cells from PMSG-primed rats had characteristics of steroidogenic cells, i.e. smooth endoplasmic reticulum and well-developed mitochondria with tubular cristae compared with small cells, whereas small and large cells from 25- and 15-day-old rats contained the regularly occurring organelles without the endoplasmic reticulum of the smooth variety and mitochondria with lamellar cristae. This study shows that the heterogeneity of granulosa cells is related to size, metabolic response to FSH, TGF-alpha or to both factors and morphological features, all of which may be associated with the transition from preantral to preovulatory stages of follicle differentiation.

Animals↗
PubMed1993

Identification and localization of bacterial endosymbionts in hydrothermal vent taxa with symbiont-specific polymerase chain reaction amplification and in situ hybridization techniques.

Invertebrates that contain endosymbiotic chemoautotrophic eubacteria are widely distributed in a variety of reducing marine habitats, including deepsea hydrothermal vents. The mechanisms of symbiont transmission in these invertebrates are not understood. To test the hypothesis that symbionts are transmitted via the eggs of hosts, we used group-specific hybridization probes complementary to 16S ribosomal RNAs (rRNAs) to look for symbionts in eggs and ovaries. 16S rRNA sequences were examined for domains unique to the symbionts of three vent animals: Calyptogena magnifica, Bathymodiolus thermophilus, and Riftia pachyptila. Three 16S rRNA-directed oligodeoxynucleotide hybridization probes (CG-1255R, RP-1243R, BT-1255R) specific for these endosymbionts were synthesized and evaluated by dot-blot hybridization. At higher stringencies, all three probes showed a high degree of specificity for their target endosymbionts rRNAs. The probes were also used as polymerase chain reaction (PCR) primers for detection of the symbiont 16S rRNA genes in genomic DNA isolated from host tissues known to contain symbionts. All three symbiont-specific probes were highly sensitive and specific as PCR primers; they successfully amplified 1 pg target DNA. However, all amplifications of extracted egg DNA from the vestimentiferan R. pachyptila with either universal eubacterial (Eub A/B) or the Riftia symbiont-specific (RP-1243R/Eub B) primer sets were unsuccessful. Nonradioactive in situ hybridizations were performed on ovarian tissue from the vestimentiferan Ridgea piscesae using RP-1243R, 3' end-labeled with digoxigenin-11-dUTP (Boehringer Mannheim). The probe was subsequently detected with an alkaline phosphatase-conjugated immunoglobulin G antibody specific for the digoxigenin moeity. The probe bound only to the tissue of R. pisceasae coincident with the known location of symbiont cells and was not detected in any region of the ovary. These data indicate that transovarial symbiont transmission in the vestimentiferans does not take place and that symbiont acquisition is probably a post-spawning event.

Animals↗
PubMed1992

X-ray laser microscopy of rat sperm nuclei.

The development of high brightness and short pulse width (< 200 picoseconds) x-ray lasers now offers biologists the possibility of high-resolution imaging of specimens in an aqueous environment without the blurring effects associated with natural motions and chemical erosion. As a step toward developing the capabilities of this type of x-ray microscopy, a tantalum x-ray laser at 44.83 angstrom wavelength was used together with an x-ray zone plate lens to image both unlabeled and selectively gold-labeled dried rat sperm nuclei. The observed images show approximately 500 angstrom features, illustrate the importance of x-ray microscopy in determining chemical composition, and provide information about the uniformity of sperm chromatin organization and the extent of sperm chromatin hydration.

Animals↗
PubMed1992

Cystogenesis of the ovarian antral follicle of the rat: ultrastructural changes and hormonal profile following the administration of dehydroepiandrosterone.

Immature 27-day-old female Sprague-Dawley rats were administered daily subcutaneous injections of dehydroepiandrosterone (DHEA, 5 mg/100 g BW) to induce the formation of ovarian follicular cysts. Groups of rats were killed on days 0, 10, 15, 20, 25, and 30. Ovaries from each group of rats were processed for light and electron microscopy and for follicular or cystic fluid hormone analysis. Normal antral follicle fluid, PMSG-treated preovulatory follicular fluid, and cystic fluids were analyzed for progesterone (P), estrone (E1), estradiol (E2), testosterone (T), delta 4-androstenedione (delta 4-A), 5 alpha-dihydrotestosterone (DHT), luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin (PRL). DHEA induced anovulation, acyclicity, and the formation of follicular cysts. In certain antral follicles, there was a dramatic increase in the quantities of smooth endoplasmic reticulum (SER) in the granulosa cells and many mitochondria had tubular cristae. Further depletion of granulosa cell number was associated with intense blebbing of the cytoplasm into the follicle antrum. Formation of the ovarian follicular cyst was completed when the entire cyst was lined by a single layer of transformed granulosa cells in contact via adhering, gap, and tight junctions. These cells had little cytoplasm, mitochondria with lamellar cristae, vast basal and apical bands of microfilaments, and an extensive array of smooth-surfaced endocytotic invaginations on the basal plasma membrane. These endocytotic pits may subsequently form smooth-surfaced vesicles and thereby serve as one mechanism for moving fluid from the ovarian interstitium into the cyst. Theca interna cells were rarely observed in the peripheral regions of the cyst. Abundant smooth muscle cells were located beneath the basement membrane of the epithelial cells comprising the cyst wall. These acquired morphological and physiological features may ensure persistence of the ovarian cyst and thus potentiate a chronic pathological condition. In this study it was also shown that progesterone, estrone, and estradiol as well as androgen concentration increased in the follicle after PMSG treatment. With DHEA treatment, the follicular cystic fluid concentrations of these steroids progressively increased to extremely high levels concurrent with the development of the follicular cysts.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Activity analysis of sterile products technicians.

Work sampling techniques were used to determine the amount of time sterile products technicians spent performing predefined activities. Twenty-two predefined activities were divided into three major categories: admixture preparation techniques, total parenteral nutrition preparation techniques, and other activities. The total time spent by all sterile products technicians revealed the greatest amount of time consumed preparing sterile products in minibags (362.2 minutes), whereas drug manufacturers piggyback (DMPB) doses required 65.8 minutes. Preparation of these small volume parenterals took approximately 1.3 minutes per dose, whereas syringes consumed 123.5 minutes, or approximately 1.8 minutes per dose. Preparation of miscellaneous products required 57.7 minutes, or 1.9 minutes per dose. TPN consumed 240.7 minutes in total, or 5.5 minutes per bottle. Other activities included paperwork (154.8 minutes), communication (169.1 minutes), and sorting prepared intravenous solutions by nursing unit and time of administration (102.5 minutes). Work sampling was effective in quantifying activities performed by sterile products technicians.

Boston↗
PubMed1992

1987 to 1991 cost and utilization of Class IV HIV patients.

The 1987 to 1991 direct medical costs and service utilization of Class IV Human Immunodeficiency Virus (HIV) patients cared for at a Group Health Cooperative of Puget Sound (GHC) are described and compared across four time periods: 1987-'88, 1989, 1990, and 1991. Cost and utilization information for an age- and sex-matched control group of GHC enrollees not having Class IV HIV conditions are also compared to those of the Class IV HIV group. Data are presented on pharmacy, inpatient care, outpatient visits by physician specialty, laboratory, radiology, home health/hospice and other costs. The costs of the Class IV HIV population are, on average, 20 times those of the control group. The percent distribution of the control group's costs did not experience much change from 1989 to 1991. Conversely, the Class IV HIV group experienced a shift in costs from the inpatient to outpatient setting from 1987-'88 to 1989. This shift was temporary, as the locus of care shifted back to the inpatient setting over the following 2 years. Anecdotal evidence suggests that antiretroviral treatment may have led to a period in which patients required less intensive settings to manage their illness. Inpatient costs may have increased as the initial benefit of zidovudine treatment began to wane. The Class IV HIV population had greater percent of total expenses in pharmacy, laboratory, radiology, and home health/hospice services, and lower percent of total expenses in outpatient primary and specialty care than the control group.

Adult↗
PubMed1991

Oral contraceptive (OCP) use increases proliferation and decreases oestrogen receptor content of epithelial cells in the normal human breast.

The effect of ingestion of oral contraceptives (OCP) on cell proliferation and oestrogen (ER) and progesterone receptor (PR) expression of the epithelial cells of the normal human breast was compared with findings in controls not taking OCPs. Histologically normal breast tissue was removed during operation for fibroadenoma or reduction mammoplasty in 216 women whose mean age was 28.1 +/- 8.5 years (+/- SD range 14-53 years). During natural cycles the mean proportion of cells expressing ER was 3.94 +/- 3.71 (% mean +/- SD, range 0-20.8, n = 51), while of those expressing PR it was 12.1 +/- 7.1% (range 3.0-36.1, n = 47). There was a significant decline in ER during the menstrual cycle [p = 0.001 by multiple linear regression (MLR)], but there was no significant change in the proportion which expressed PR. The mean proportion of proliferating cells (LI) was 2.50 +/- 2.42 (range 0-11.5, n = 147). There was a significant increase of LI during the cycle (p = less than 0.001, MLR) and a significant inverse relationship between LI and ER (r = -0.29, p less than 0.01). Use of the OCP significantly reduced the number of cells which expressed ER and increased the LI earlier in the cycle. No effect of OCP use on the number of PR+ cells was detectable. We conclude that significant changes in the proportions of ER+ and proliferating cells occur during natural menstrual cycles. These changes are perturbed by ingestion of OCPs, so that there is greater suppression of ER and a longer period of high proliferation during the menstrual cycle. These results may explain the relationship between OCP use and the possible risk of breast cancer.

Adolescent↗