Key signalling nodes in mammary gland development and cancer. Mitogen-activated protein kinase signalling in experimental models of breast cancer progression and in mammary gland development

Seven classes of mitogen-activated protein kinase (MAPK) intracellular signalling cascades exist, four of which are implicated in breast disease and function in mammary epithelial cells. These are the extracellular regulated kinase (ERK)1/2 pathway, the ERK5 pathway, the p38 pathway and the c-Jun N-terminal kinase (JNK) pathway. In some forms of human breast cancer and in many experimental models of breast cancer progression, signalling through the ERK1/2 pathway, in particular, has been implicated as being important. We review the influence of ERK1/2 activity on the organised three-dimensional association of mammary epithelial cells, and in models of breast cancer cell invasion. We assess the importance of epidermal growth factor receptor family signalling through ERK1/2 in models of breast cancer progression and the influence of ERK1/2 on its substrate, the oestrogen receptor, in this context. In parallel, we consider the importance of these MAPK-centred signalling cascades during the cycle of mammary gland development. Although less extensively studied, we highlight the instances of signalling through the p38, JNK and ERK5 pathways involved in breast cancer progression and mammary gland development.     

Sensitivity to feared stimuli in obsessive-compulsives: A dichotic listening analysis

The experiment reported here was designed to test whether fear-relevant stimuli are preceived more readily than neutral ones, and whether vigilance for the former is due to fear or to familiarity. Eleven obsessive-compulsives were administered a dichotic listening task before and after treatment by exposure and response prevention. Behavioral (button press) and physiological (skin conductance response) measures revealed that fear-relevant words were detected more than neutral words before but not after treatment. Additionally, the magnitude of the skin conductance response was greater to fearrelevant than to neutral targets before but not after treatment. These findings suggest that sensitivity to fear-relevant stimuli is due to fear and not familiarity.     

Ultrasonographic evaluation of the cervix: transperineal versus endovaginal imaging.

OBJECTIVE: This study compares transperineal and endovaginal ultrasonography of the gravid cervix to evaluate image quality and assess for a systematic difference in cervical lengths measured by the 2 techniques. METHODS: Transperineal and endovaginal ultrasonography of the cervix was performed on 64 pregnant women. Two physicians reviewed the images and rated the relative diagnostic value of the techniques for assessing the cervix and for evaluating for placenta previa. Cervical length was measured prospectively in both techniques. Data were analyzed to determine if there is a systematic difference in length using the 2 approaches and if length differences are dependent on gestational age. RESULTS: There was a strong reviewer preference for endovaginal ultrasonographic images over transperineal images for both assessing the cervix (P< .001) and evaluating for placenta previa (P< .001). Despite this, transperineal and endovaginal ultrasonographic images were frequently rated as similar in diagnostic quality by both reviewers for depicting the cervix (35.9% of patients) and evaluating for placenta previa (57.8% of patients). The mean length of the cervix was slightly shorter at transperineal ultrasonography (28.4 mm) than at endovaginal ultrasonography (30.1 mm). When cervical lengths were subdivided by gestational age, however, a significant length discrepancy was found only in the 14- to 20-week gestational age range. In this age range, mean cervical length at transperineal ultrasonography (28.6 mm) averaged 5.5 mm less than at endovaginal ultrasonography (34.1 mm). CONCLUSIONS: Both transperineal and endovaginal ultrasonography can provide satisfactory images of the cervix, but endovaginal images are frequently superior to transperineal images. Endovaginal ultrasonography should be considered the optimal method for imaging the cervix in most situations. Transabdominal or transperineal ultrasonography can also be used, but if the cervix is not adequately depicted from these perspectives, endovaginal ultrasonography is indicated. Transperineal measurements of cervical length can be significantly shorter than endovaginal measurements, particularly before 20 weeks; therefore, short cervical lengths documented at transperineal ultrasonography before 20 weeks should be confirmed by endovaginal ultrasonography.     

Male infertility. 3. Endocrine causes

Endocrine causes of male infertility range from easily manageable disorders such as hypothyroidism to complex problems such as pituitary tumors. Proper management requires a thorough understanding of the hypothalamic-pituitary-testicular axis. Hormonal evaluation is performed only when the patient's history and results of physical examination indicate an endocrine problem. With proper identification and treatment, most of these problems can be successfully managed.     

Inequalities in access to diabetes care: evidence from a historical cohort study

OBJECTIVE: To establish which factors predict attendance at a hospital diabetes clinic and for diabetes review in general practice. DESIGN: A historical cohort study of individuals with diabetes identified from general practice records. Information on service contacts and other clinical, social, and demographic variables was collected from general practice records and postal questionnaires. SETTING: Seven Leicestershire general practices. SUBJECTS: Individuals registered with study practices who had a diagnosis of diabetes made before 1990. MAIN OUTCOME MEASUREMENTS: Attendance at a hospital diabetes clinic or for a documented diabetes review in general practice at least once between 1990 and 1995. RESULTS: 124 (20%) had at least one recorded diabetes review in general practice and 332 (54%) attended a hospital diabetes clinic at least once. The main predictors of attending a hospital clinic were younger age, longer duration of diabetes, and treatment with insulin. Access to a car (OR 1.34, 95% CI 1.06 to 1.71), home ownership (OR 1.48, 95% CI 1.14 to 1.58) and a non-manual occupation (OR 1.56, 95% CI 1.09 to 2.24) were all associated with an increased likelihood of attending, although living in a less deprived area was not. The main predictors of attending for review in general practice were older age, less co-morbidity, and being white. Living in a more deprived area was related to a reduced chance of review in general practice (OR 0.81, 95% CI 0.76 to 0.86) while individual socioeconomic indicators were not. CONCLUSIONS: Whilst an indicator of area deprivation predicts reduced likelihood of review in general practice, individual indicators predict reduced likelihood of attending outpatients. This suggests a need for different approaches to tackling inequalities in access to care in primary and secondary care settings.     

Sterilization and disinfection in general practice within university health services.

A postal questionnaire on 'sterilization and disinfection' was sent to all 144 nurse members of the British Association of Health Services in Higher Education (BAHSHE). Forty-nine (34%) completed valid questionnaires were returned. Despite the majority of practices performing minor surgical procedures such as cervical cytology (N= 40, 82%), ear syringing (N= 44, 90%) and wound dressing (N= 49, 100%), only 11 (22%) had access to a sterile supply department (SSD), and the definitions of sterilization and disinfection were only identified by 23 (52%) and 14 (32%) of the respondents, respectively. Forty-one (84%) respondents had a benchtop sterilizer (30 had a benchtop sterilizer, 11 a vacuum sterilizer and two had both), although there was considerable confusion on their appropriate use and maintenance. Just over half had written procedures for sterilizer use, no practice changed the sterilizer water on a daily basis as recommended by the Medical Devices Agency (MDA), few kept a sterilizer logbook and even fewer had read the MDA Device Bulletin on benchtop sterilizers. The majority of respondents voiced an interest in attending a workshop on sterilization and disinfection. We conclude that despite the location of the general practices within an academic environment, the concept of infection control is clearly not understood by university health service staff. As the implications of a failure to implement proper infection control procedures are potentially serious, the need for adequate education and training of staff is of critical importance.     

Motion artifact suppression technique (MAST) for MR imaging

A technique has been developed that significantly improves the image resolution and reduces motion artifacts in conventional two-dimensional Fourier transform and three-dimensional Fourier transform magnetic resonance imaging sequences. Modifications on the gradient waveforms completely refocus the transverse magnetization at the echo time, regardless of the motion occurring between the time of the 90 degrees radiofrequency excitation and the echo time (within-view). This accomplishes suppression of motion artifacts and regains the signal from flowing blood and CSF. Images of the head, abdomen, chest, and spine are reproduced which show the increase in signal and anatomical detail that would otherwise be degraded and lost in artifact noise. This technique has reduced the practical difficulty of obtaining clinically diagnostic T2-weighted abdominal images. It also has allowed diagnostic quality T1- and T2-weighted images to be obtained with one acquisition per view, thus reducing the total scan time.