Hormone-induced refractoriness to mammary carcinogenesis in Wistar- Furth rats

One of the most consistent results in the epidemiology of human breast cancer is the inverse relationship of risk and early full-term parity. The goal of this study was to investigate the molecular mechanisms through which early full-term pregnancy protects the breast from cancer development. We used Wistar-Furth (WF) rats as our experimental system and mimicked pregnancy using estrogen and progesterone (E/P). Sexually mature female rats were treated with steroid hormones for 21 days and after 28 days of gland involution, the rats were administered MNU. Rats that received a high dose of 20 microg E and 20 mg P exhibited an 82% reduction in the incidence of mammary adenocarcinomas as compared to the rats receiving only blank pellets. Decreasing doses of E/P were partially protective suggesting that complete differentiation of the gland was not required for refractoriness. We measured the RNA expression levels of several target genes involved in the regulation of mammary cell proliferation and/or differentiation including estrogen receptor (ER) and progesterone receptor (PR), cyclins D1 and D2, the cell cycle inhibitors p16, p21 and p27, and the tumor suppressor p53. At the time of MNU treatment we found no significant differences in the expression of these genes, with the possible exception of p21, indicating that hormone treatment did not result in constitutive changes in expression levels. The numbers of apoptotic cells were low and comparable in the hormone exposed and age-matched virgin gland (AMV) at the time of carcinogen challenge and remained low for 8 days after MNU treatment. The number of BrdU-labeled cells at the time of carcinogen challenge were also low in both the AMV (1.8%) and hormone exposed (0.8%) animals. In contrast, cell proliferation in the AMV (5.7%) was significantly different from both the parous involuted (1.2%) and the E/P-treated involuted (1.5%) animals 8 days after MNU treatment. We interpret these data to indicate that hormone treatment results in mammary epithelial cells that have persistent alterations in intracellular pathways governing proliferation responses to carcinogens.      

Platelet function in autoimmune (idiopathic) thrombocytopenic purpura

Platelets play an essential role in the formation of haemostatic plugs. The quantitative defect of platelets in autoimmune (idiopathic) thrombocytopenic purpura (ITP) can result in bleeding complications, but most ITP patients have platelets with normal or enhanced function. Platelets in ITP are large, young, so-called "stress" platelets with increased platelet-associated autoimmune antibody (immunoglobulin G). Young stress platelets are more functional platelets, and their presence may account for bleeding times in ITP patients that are shorter than would be predicted on the basis of the patients' (low) platelet counts. Some ITP patients have significant mucocutaneous bleeding with platelet counts >50 × 10⁹ l⁻¹; this may be due to qualitative platelet dysfunction (e.g. brought about by inhibitory antiplatelet autoantibodies).     

Correlates of prone infant sleeping position by period of birth

Intervention to avoid the prone sleeping position during infancy has occurred in various countries after evidence that it increases the risk of sudden infant death syndrome (SIDS). This study examined cohort data to determine if correlates of the prone position differed by period of birth, before intervention (1 May 1988 to 30 April 1991) compared with after intervention (1 May 1991 to 30 April 1992). The usual prone sleeping position was more closely associated with the following factors after intervention: teenage motherhood, low maternal education, paternal unemployment, unmarried motherhood, non-specialist antenatal care, not reading books to prepare for a baby, poor smoking hygiene, and bottle feeding. For example, the association of usual prone position with being unmarried shown by the odds ratio (95% confidence interval) was 0.54 (0.47 to 0.63) in the period before intervention and 1.92 (1.18 to 3.15) in the period after intervention. The alteration in correlates of the prone position reported here provide an example to support the theoretical concept that well known 'modifiable' risk factors for disease tend to be associated with each other in both populations and individuals. This phenomenon was not evident in the population before intervention, that is, before the prone sleeping position became a well known SIDS risk factor.     

Cerebral blood flow velocity in term newborns following intrapartum fetal asphyxia

Twenty-six term newborns with intrapartum fetal asphyxia, determined biochemically (umbilical artery base deficit < 12mmol/1), were compared with 59 normal newborns to determine the effect of intrapartum fetal asphyxia on newborn blood pressure and cerebral blood flow velocity following delivery. Cerebral blood flow velocity observations with concurrent measures of blood pressure and heart rate were obtained during the 24 h after delivery and after 24 h. After delivery, diastolic blood pressure in the newborns of the asphyxia group was significantly greater than that of the newborns of the normal group and this difference persisted after 24 h. Cerebral blood flow velocity in the newborns of the asphyxia group was of the same order as that of the newborns of the normal group during the 24 h after delivery. However, there was a significant increase in both peak systolic and end-diastolic blood flow velocity after 24 h. The duration of metabolic acidosis may be a factor in the occurrence of this delayed cerebral blood flow velocity response. Observations of cerebral blood flow velocity should be continued for more than 24 h following delivery to determine the effect of intrapartum fetal asphyxia.     

Partial thickness supraspinatus tears: Diagnosis by magnetic resonance arthrography

Two patients, with clinical symptoms of advanced impingement syndrome, presented for radiologic evaluation. The magnetic resonance (MR) images of each patient were interpreted as representing a full thickness tear of the supraspinatus tendon. Magnetic resonance arthrography was performed on both patients to further determine the extent of the tear. Using this technique, both patients were diagnosed correctly as having partial thickness tears; one on the articular surface and the other on the bursal surface of the tendon. This information is useful in surgical planning and in patient outeome.