Tailored written invitations for second round breast cancer screening: a randomised controlled trial

OBJECTIVES: Firstly, to determine if attendance for second round mammography screening in those sent a tailored letter (that is, making reference to their screening history) is increased compared with those sent a standard letter; secondly, to investigate the acceptability of tailored letters. SETTING: North West Glasgow Breast Screening Centre. METHODS: A randomised controlled trial. RESULTS: Overall attendance was unrelated to whether the women were sent a tailored or standard letter; 60% of those sent the standard letter attended (922/1531) compared with 62% of those sent the tailored letter (956/1552) (chi 2 = 0.61, P = 0.4) (difference 2%; 95% confidence interval -2% to 5%). There were no significant differences in percentage attendance within each of the study subgroups: women who attended previously and received an all clear result, women who attended previously and received a false positive result, women who were invited previously and failed to attend, and women who were previously too young to be invited for screening. However, there was a statistically significant difference in percentage attendance between these four groups, independent of letter type (chi 2 = 510, P < 0.00001). Although women found the letters acceptable and understandable, they did not seem to pay close attention to the content. CONCLUSIONS: Tailoring invitation letters does not have a significant effect on uptake rates for breast screening and does not justify the additional workload required.     

Prevention of T cell anergy by signaling through the gamma c chain of the IL-2 receptor

When stimulated through their antigen receptor without requisite costimulation, T cells enter a state of antigen-specific unresponsiveness termed anergy. In this study, signaling through the common gamma chain of the interleukin-2 (IL-2), IL-4, and IL-7 receptors in the presence of antigen was found to be sufficient to prevent the induction of anergy. After culture with IL-2, IL-4, or IL-7, Jak3 kinase was tyrosine-phosphorylated, which correlated with the prevention of anergy. Therefore, a signal through the common gamma chain may regulate the decision of T cells to either clonally expand or enter a state of anergy.     

Shedding of the soluble IL-6 receptor is triggered by Ca2+ mobilization, while basal release is predominantly the product of differential mRNA splicing in THP-1 cells

The soluble IL-6 receptor (sIL-6R) is generated through either proteolytic shedding of the cognate receptor (PC-sIL-6R), or released as the product of differential mRNA splicing (DS-sIL-6R). Using monocytic THP-1 cells, we demonstrate that both mechanisms are independently regulated, and that each process contributes to sIL-6R production. Shedding of the IL-6R was activated by the Ca2+ ionophore, ionomycin, and inhibited by the TNF-alpha protease inhibitor (TAPI). In contrast, basal sIL-6R release was unaffected by Ca2+ depletion and largely insensitive to TAPI. Moreover, although IL-6R shedding was inactivated by serum starvation, non-stimulated production remained intact. Basal sIL-6R production via differential mRNA splicing was shown through the inhibitory action of brefeldin A and an enzyme-linked immunosorbent assay specific for DS-sIL-6R. Release of this isoform was unaffected by ionomycin or TAPI, indicating that Ca2+ mobilization activates PC-sIL-6R generation, but not DS-sIL-6R. The divergent control of these sIL-6R isoforms indicates that they may independently influence the inflammatory response.     

Proximal locking screw repositioning in reconstruction femoral nails

Chard (Beta vulgaris L. var. cicla) is one of the plants used as hypoglycaemic agent by diabetics in Turkey and it has been reported to reduce blood glucose. The purpose of this study was to investigate the effect of feeding chard on diabetes induced impairments in rat skins. Uncontrolled induced diabetes caused significant increases in nonenzymatic glycosylation of skin proteins, lipid peroxidation and blood glucose. Administration of chard extract inhibited these effects except the increase in lipid peroxidation. SDS-polyacrylamide gel electrophoresis revealed no significant differences in any protein bands between any of the groups. The data indicate that the use of chard may be effective in preventing or at least retarding the development of some diabetic complications.     

Loss of cytotoxic T lymphocyte function in Chediak-Higashi syndrome arises from a secretory defect that prevents lytic granule exocytosis

CTLs from patients with Chediak-Higashi syndrome (CHS) are unable to destroy target cells recognized via the TCR. To determine the mechanism responsible for the loss of cytotoxicity, CD8+ CTL clones have been derived from a patient with CHS. Individual CTL clones show poor killing that can be increased in longer assays. However, in the presence of cycloheximide, the small amount of killing observed is abolished, indicating killing arises from newly synthesized proteins, rather than from proteins stored in granules. In this study, we show that the CHS CTL clones express normal levels of the lytic proteins granzyme A, granzyme B, and perforin, which are processed properly during biosynthesis and targeted correctly to giant lytic granules. Despite the difference in size, CHS and normal lytic granules are similar, in that both contain the lysosomal enzyme cathepsin D and the lytic protein granzyme A, and lack the mannose-6-phosphate receptor (MPR). However, unlike normal CTL clones, the CHS CTL clones are unable to secrete their giant granules in which the lytic proteins are stored. After cross-linking the TCR, CHS CTL clones fail to secrete granzyme A, as assayed by both enzyme release and confocal microscopy. We suggest that the defect in CHS lies in a protein that is involved in membrane fusion and is essential for the secretion of lysosomal compartments in certain hemopoietic cells.     

Isolated agenesis of the mastoid antrum

The first isolated case of agenesis of the mastoid antrum, previously only described in association with the congenital syndromes trisomy 13 and mandibulofacial dysostosis, is reported. The loss of this important surgical landmark may result in disorientation and iatrogenic trauma. The surgeon must be aware of its existence, and where it is suspected the middle fossa dura should be exposed and followed posteriorly until the lateral sinus is encountered.     

Developmental regulation of the brain polyamine-stress-response

A transient increase in brain polyamine metabolism, termed the polyamine-stress-response is a common response to stressful stimuli. Previous studies have implicated an over-reactive polyamine response as a component of the maladaptive brain response to stressful events, and as a novel molecular mechanism involved in the pathophysiology of affective disorders. Ample evidence indicates that stressful experiences during early life can alter normal developmental processes and may result in pathophysiological and behavioral changes in the adult. Additionally, an important characteristic of affective disorders is their age dependency, a phenomenon that may be correlated with a maladaptive regulation of the hypothalamic-pituitary-adrenocortical (HPA) neuroendocrine system. In the present study we measured the activities of the enzymes ornithine decarboxylase and S-adenosylmethionine decarboxylase as markers of polyamine synthesis and found that unlike adults, immature rats do not show the characteristic brain polyamine-stress-response. Instead of the characteristic increase observed in adults, ornithine decarboxylase activity in immature animals was reduced or remained unchanged (for up to 16 days of age) after a dexamethasone injection or restraint stress application. The ontogenesis of this ornithine decarboxylase response was brain region-specific, indicating its dependence on the stage of neuronal maturation. Animals treated with dexamethasone at 7 days of age, showed increased behavioral reactivity in the open-field test as adults and an attenuated increase in ornithine decarboxylase activity after a re-challenge with dexamethasone at age 60 days. The results indicate that: (1) the brain polyamine-stress-response is developmentally regulated and its ontogenesis is brain region-specific, indicating dependence on the stage of neuronal maturation; (2) the switch to a mature polyamine-stress-response pattern coincides with the cessation of the stress hyporesponsive period in the HPA system: (3) activation of the polyamine-stress-response, as in the mature brain, appears to be a constructive reaction, while its down-regulation, as in the developing brain, may be implicated in neuronal cell death; (4) an attenuated dexamethasone-induced increase in ornithine decarboxylase activity implicates an altered polyamine-stress-response in the maladaptive response of the brain to stressful events.     

Dose uniformity of ferromagnetic seed implants in tissue with discrete vasculature: a numerical study on the impact of seed characteristics and implantation techniques

There is evidence of a two-way interaction between gastric acid secretion and H. pylori-associated gastritis. Gastric acid secretion influences the density of H. pylori colonisation, its distribution within the stomach and the severity of the mucosal inflammatory response to the infection. In addition, H. pylori gastritis alters gastric acid secretion. In subjects with a predominant antral gastritis, it increases acid secretion predisposing to duodenal ulcer, whereas in others with predominant body gastritis, acid secretion is impaired and the subjects have an increased risk of gastric cancer. The two-way interaction between acid secretion and H. pylori gastritis is observed when H. pylori-positive subjects are treated with proton pump inhibitor agents. The inhibition of acid secretion induces a body gastritis and this inflammation of the body mucosa inhibits acid secretion thus augmenting the anti-secretory effect of the drug. In this article, we discuss the interaction between gastric acid secretion and H. pylori gastritis and its importance in determining disease outcome.     

Lack of significant effect of coffee and caffeine on fluoride metabolism in rats

It has been reported that rat plasma fluoride (F) concentrations are higher by up to 100% when F is administered ig in coffee or a caffeine solution compared with when it is administered in water. It was hypothesized that the consumption of caffeinated beverages has contributed to the prevalence of dental fluorosis. The present studies were done to determine the physiological mechanisms for these effects. For approximately 2 h after F was administered in coffee, plasma F concentrations were higher than when administered in water, decaffeinated coffee, or a caffeine solution (3 mg/kg), but the intergroup differences were small and generally not statistically significant. The 4-hour plasma AUC values did not differ with statistical significance. There were no differences among the groups in the renal or extrarenal (skeletal) clearances of F, which suggested that the higher plasma F concentrations in the coffee groups may have been due to a slight and transient increase in absorption rate. The possibility that caffeine per se might elevate endogenous plasma F and calcium concentrations was excluded after caffeine (25 mg/kg) ig without F was given. In addition, the renal excretion, clearance, and fractional renal clearance of calcium did not differ among the groups. The results indicated that decaffeinated coffee and caffeine had no effect on F metabolism, whereas caffeinated coffee appeared to increase the initial absorption rate but not the 4-hour bio-availability.(ABSTRACT TRUNCATED AT 250 WORDS)