Prolonged tamoxifen exposure selects a breast cancer cell clone that is stable in vitro and in vivo

The effects of long-term tamoxifen exposure on cell growth and cell cycle kinetics were compared between oestrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. In the MCF-7 cell line, prolonged tamoxifen exposure (0.5 mumol/l for > 100 days) blocked cells in G0-G1 of the cell cycle, and slowed the doubling time of cells from 30 to 59 h. These effects corresponded to an increase in the cellular accumulation of tamoxifen over time [mean area under concentration curve (AUC) = 77.92 mumoles/10(6)/cells/day]. In contrast, in the MDA-MB-231 cell line, long-term tamoxifen exposure had no obvious effect on the doubling time, and reduced cellular tamoxifen accumulation (mean AUC = 50.50 mumoles/10(6)/cells/day) compared to the MCF-7 cells. Flow cytometric analysis of MDA-MB-231 cells demonstrated that a new tetraploid clone emerged following 56 days of tamoxifen exposure. Inoculation of the MDA-MB-231 tetraploid clone and MDA-MB-231 wildtype cells into the opposite flanks of athymic nude mice resulted in the rapid growth of tetraploid tumours. The tetraploid tumours maintained their ploidy following tamoxifen treatment for nine consecutive serial transplantations. Histological examination of the fifth transplant generation xenografts revealed that the tetraploid tumour had a 25-30 times greater mass, area of haemorrhage and necrosis, a slightly higher mitotic index and was more anaplastic than the control neoplasm. The control wildtype MDA-MB-231 tumours maintained a stable ploidy following tamoxifen treatment until the eighth and ninth transplantation, when a tetraploid population appeared, suggesting that tamoxifen treatment may select for this clone in vivo. These studies suggest that prolonged tamoxifen exposure may select for new, stable, fast growing cell clones in vitro as well as in vivo.     

Normal-incidence InAs self-assembled quantum-dot infrared photodetectors with a high detectivity

An InAs/AlGaAs quantum-dot infrared photodetector based on bound-to-bound intraband transitions in undoped InAs quantum dots is reported. AlGaAs blocking layers were employed to achieve low dark current. The photoresponse peaked at 6.2 /spl mu/m. At 77 K and -0.7 V bias, the responsivity was 14 mA/W and the detectivity, D*, was 10/sup 10/ cm/spl middot/Hz/sup 1/2//W.     

Adherence to pharmacologic management of hypertension

Adherence to pharmacologic therapy of hypertension is low (in the range of 50-70%) and has important implications both for blood pressure control and cardiovascular complications. Based on a review of the literature using the levels of evidence grading technique, determinants of adherence to the pharmacologic therapy of hypertension have been assessed. Additionally, interventions to improve compliance were evaluated. Patient-centred, health care provider-centred and drug-specific factors have all been shown to affect adherence rates. We conclude that the extent of adherence to pharmacologic therapy is modifiable. Measurable improvements in adherence can be obtained from simplified medication regimens and a combination of behaviour strategies, including the tailoring of pill-taking to patients' daily habits and rituals, the advocacy of self-monitoring of pills and blood pressure, and the institution of reward systems.     

Transmission electron microscopic analysis of kidney glomeruli obtained by fine-needle aspiration

Aspiration biopsy of tumors and transplanted organs is a popular atraumatic method for diagnosis and also for the management of patients. Apart from the cytological analyses, it is clear that large aggregates of cells are obtained and these may be examined by electron microscopy. A study was carried out with dogs to assess the yield of intact glomeruli and tubules, resulting from a standard fine-needle aspiration procedure. Employing a 20-gauge needle, yields of approximately ten intact glomeruli were obtained with a tissue processing protocol that utilized filtration through a nylon mesh and backwashing, to resuspend the trapped aggregates. Processing for electron microscopy was carried out in microcentrifuge tubes. The ultrastructural preservation was excellent and the extension of these studies to investigations of not only renal transplantation, but also for diagnosis in human renal diseases of a broad spectrum, is suggested.     

Microstructural engineering applied to the controlled cooling of steel wire rod: Part I. Experimental design and heat transfer

The goal of this study was to develop a mathematical model which incorporates heat flow, phase transformation kinetics, and property-structure-composition relationships to predict the mechanical properties of steel rod being control cooled under industrial conditions. Thus, the principles of microstructural engineering have been brought to bear on this interdisciplinary problem by combining computer modeling with laboratory measurements of heat flow, austenite decomposition kinetics, microstructure and mechanical properties, and industrial trials to determine heat transfer and obtain rod samples under known conditions. Owing to the length and diversity of the study, it is reported in three parts,_[8191]the first of which is concerned with the heat flow measurements. A relatively simple and reliable technique, involving a preheated steel rod instrumented with a thermocouple secured at its centerline, has been devised to determine the cooling rate in different regions of the moving bed of rod loops on an operating Stelmor line. The measured thermal response of the rod has been analyzed by two transient conduction models (lumped and distributed parameter, respectively) to yield overall heat-transfer coefficients for radiation and convection. The adequacy of the technique has been checked by cooling instrumented rods under well-defined, air crossflow conditions in the laboratory and comparing measured heat-transfer coefficients to values predicted from well-established equations. The industrial thermal measurements have permitted the characterization of a coefficient to account for radiative interaction among adjacent rod loops near the edge and at the center of the bed. Formerly Graduate Student, The University of British Columbia.     

Paget's disease of the breast in a man without underlying breast carcinoma

A case of histologically confirmed Paget's disease of the breast in a 72 year old man, without underlying breast carcinoma, is reported. This report raises questions about the pathogenesis of this condition and suggests that Paget's disease is an independent, intraepidermal carcinoma rather than a direct extension of intraductal carcinoma of the breast to the nipple and areola.     

Ethnic differences in the length of the menstrual cycle during the postmenarcheal period

In 1989, 125 African-American and 123 European-American girls aged 12-14 years were enrolled in a 2-year study in which they maintained a menstrual calendar, recording the date and amount of menstrual bleeding. Weight, exercise, and stress during the previous week were recorded at the start of each menstrual cycle. Although only minor ethnic differences were observed in expected cycle length (29.3 vs. 28.8 days for European-American and African-American girls, respectively), more prominent differences were observed in the between-subjects standard deviation of cycle length (2.9 vs. 2.2 days, respectively) and in the odds of having a cycle longer than 45 days (odds ratio=1.86, 95% confidence interval 1.17-2.97) for European-American compared with African-American girls. Low weight for height and high levels of exercise increased the probability of having a cycle longer than 45 days and decreased expected cycle length of 13- to 45-day cycles. Additional investigation of potential ethnic differences in menstrual cycle characteristics is warranted.     

Successful pregnancies in the presence of spinal muscular atrophy: two case reports

We report two cases of successful pregnancy in women with chronic, infantile onset, or type II spinal muscular atrophy, both of whom delivered healthy, unaffected babies. The patients required concurrent management by a physiatrist, pulmonologist, and perinatologist throughout the pregnancy. Complications included recurrent urinary tract infections, dyspnea and worsening of pulmonary function, wheelchair seating and positioning problems, and musculoskeletal and low back pain. These problems resolved postpartum. One woman had vaginal delivery, the other had caesarean section, both of which were well-tolerated. Because of severe musculoskeletal deformity, pelvic assessment is necessary to determine the mode of delivery. The uterus has normal contractility and effective labor patterns can be established. Spinal/epidural anesthesia may be contraindicated because of spine deformity. The pregnancies had no deleterious effect on the progression of the disease in our patients, both of whom reported a positive experience with great personal fulfillment.     

Improved method for harvesting human Schwann cells from mature peripheral nerve and expansion in vitro

The pharmacological profile of a novel dual inhibitor, tepoxalin and of its carboxylic acid metabolite on cyclooxygenase and lipoxygenase pathways was evaluated by in vitro incubation with synovial tissue. Tissue specimens obtained at surgery in rheumatoid arthritis (RA, n = 10) or osteoarthritis (OA, n = 11) patients were incubated. Tepoxalin (10(-7), 10(-6), 10(-5) M) decreased eicosanoid release calculated in % of tyrode control for OA: LTC4 to 71-33%, 6-keto-PGF1a to 37-20%, PGE2 to 29-6%. For RA: LTC4 to 56-22%, 6-keto-PGF1a to 43-22%, PGE2 to 57-32%. Similarly, its metabolite (10(-7), 10(-5)M) decreased release in OA: LTC4 to 99 and 60%, PGE2 to 42 and 20%, 6-keto-PGF1a to 54 and 25%. In RA:LTC4 to 81 and 45%, PGE2 to 61 and 30%, 6-keto-PGF1a to 46 and 18%. Significance (P < 0.05) was achieved for all but 1 group (LTC4 metabolite at 10(-7)M vs tyrode). In summary a marked and dose dependent decrease of LT and PG release was obtained when incubating the dual inhibitor tepoxalin and its active carboxylic acid metabolite with synovial tissue at doses expected to be reached in the joint during therapy.