Mammary intraepithelial neoplasia outgrowths (MINO): MINO and human ductal carcinoma <Emphasis Type="Italic">in situ</Emphasis>

Germ-line mutations in the BRCA1 tumour suppressor gene contribute to familial breast tumour formation, but there is no evidence for direct mutation of the BRCA1 gene in the sporadic form of the disease. In contrast, decreased expression of the BRCA1 gene has been shown to be common in sporadic tumours, and the magnitude of the decrease correlates with disease progression. BRCA1 expression is also tightly regulated during normal breast development. Determining how these developmental regulators of BRCA1 expression are co-opted during breast tumourigenesis could lead to a better understanding of sporadic breast cancer aetiology and the generation of novel therapeutic strategies aimed at preventing sporadic breast tumour progression.     

Influence of caloric restriction on the development of atherosclerosis in nonhuman primates: progress to date

Caloric restriction (CR) has been observed to retard aging processes and extend the maximum life span in rodents. In an effort to evaluate the effect of this nutritional intervention on physiologic variables in higher species, several nonhuman primate trials are ongoing. In particular, a study evaluating the independent effect of CR on the extent of atherosclerosis was initiated in 1993 in 32 adult cynomolgus monkeys. Therefore, the trial was designed to achieve identical cholesterol intake after animals were randomized to a control group or a calorie-restricted group (30% reduction from baseline caloric intake). The animals were routinely evaluated for glycated proteins, plasma insulin and glucose levels, insulin sensitivity, and specific measures for abdominal fat distribution by CT scans over a 4-year interval. The results from 4 years of intervention demonstrate that CR improves cardiovascular risk factors (such as visceral fat accumulation) and improves insulin sensitivity. In contrast to other primate studies with normolipidemic animals, CR had no independent effects on plasma lipid levels and composition in the presence of equivalent amounts of dietary cholesterol intake. Preliminary analysis of atherosclerotic lesion extent in the abdominal aorta has failed to demonstrate differences between control animals and CR animals. Follow- up studies are being conducted to determine the effect of CR on atherosclerosis extent in coronary and carotid arteries.      

Extracellular ATP-dependent suppression of proliferation and induction of differentiation of human HL-60 leukemia cells by distinct mechanisms

Extracellular ATP suppressed the growth of HL-60 leukemia cells and induced their differentiation as revealed by N-formyl-methionyl-leucyl-phenylalanine-induced beta-glucuronidase release. ATP degraded to ADP, AMP, and adenosine, and the effect of ATP on cell growth was mimicked by these metabolites added to the cultures. The stable analog alpha,beta-methylene ATP, however, had only a weak inhibitory effect on cell growth. Adenine nucleotide-induced growth suppression was reversed by uridine, suggesting the involvement of intracellular pyrimidine starvation secondary to adenosine accumulation. Consistent with this, ATP induced intracellular starvation of pyrimidine nucleotides, and this effect was also prevented by pretreatment of cells with uridine. The order of effectiveness of ATP-induced differentiation of HL-60 cells, unlike that for growth suppression, was ATP > ADP > AMP, and adenosine had no effect. Furthermore, uridine had no effect and the stable analog, alpha,beta-methylene ATP also induced HL-60 cell differentiation, suggesting that differentiation was due to ATP per se. We tested the hypothesis that ATP-induced differentiation arises from activation of adenylyl cyclase by the novel P2Y(11) receptor using the cell-permeable inhibitor of protein kinase A, Rp-CPT-cAMPS (8-(4-chlorophenylthio)adenosine-3',5'-cyclic monophosphorothioate, Rp isomer). Rp-CPT-cAMPS (1-100 microM) prevented ATP-induced differentiation of HL-60 cells as assessed by fMLP-induced beta-glucuronidase release. However, Rp-CPT-cAMPS did not prevent ATP-induced growth suppression. Taken together, the data indicate that extracellular ATP suppresses HL-60 growth and induces their differentiation by distinct mechanisms. Growth suppression arises from adenosine generation and consequent pyrimidine starvation. Differentiation arises, at least in part, from a distinct mechanism involving the activation of cell surface P2 receptors coupled to cAMP generation and activation of protein kinase A.     

Percutaneous drainage access: a simplified coaxial technique

We describe an access technique that we have used in 150 nephrostomy and biliary drainage procedures and for access to some abscesses and viscera. The system provides safe coaxial access with a 22-gauge removable hub needle, which then acts as a guide wire and is replaced by an 18-gauge cannula. A major advantage is that only one guide wire is used (0.038-inch) for the entire drainage procedure. No significant complications have occurred to date with this method.     

Pulsatile masses surrounding vascular prostheses: real-time US color flow imaging

A prospective evaluation of color flow mapping and real-time ultrasound was performed to determine if pseudoaneurysms could be distinguished from other causes of masses surrounding vascular grafts of the lower extremities. Twelve palpable pulsatile masses were imaged. Diagnoses were confirmed at angiography (n = 11), computed tomography (n = 7), aspiration biopsy (n = 5), and operative intervention (n = 6). A swirling pattern of blood flow was seen in six of seven cases of pseudoaneurysm. Lack of flow signals was noted in four of the five collections representing hematoma (n = 2) or infection (n = 2). The seventh case was later shown to be an infected, thrombosed pseudoaneurysm. The single false-positive diagnosis was made early in the series when the flow signals detected were due to transmitted arterial pulsations. The authors conclude that color Doppler flow imaging is useful in the differential diagnosis of pulsatile masses associated with prosthetic grafts. Prosthetic graft pseudoaneurysms have a specific appearance of swirling blood flow arising from a wide neck and are distinguishable from traumatic or iatrogenic pseudoaneurysms of the native vascular tree.     

On the development of the European S3 guidelines on the systemic treatment of psoriasis vulgaris: structure and challenges

Background The development of evidence based guidelines is a demanding and time consuming process. Therefore it is important to share the knowledge and discuss the structure of these guidelines in detail. Objectives To present a method report on the development process of the European evidence based guidelines on the systemic treatment of psoriasis vulgaris with the aim to offer guidance to other guidelines groups with lesser experience and to critically appraise the methodology of the guidelines development process. Methods The guidelines are based on the previously evaluated literature from three European national evidence based guidelines and an additional systematic search and evaluation of new literature. Further steps included a structured consensus conference and a DELPHI procedure to develop the recommendations, as well as several internal and external reviews. All steps were coordinated by the Division of evidence based medicine in cooperation with a group of methodologists. Results A total of 114 studies were included, serving as base for the efficacy chapters of the intervention. The recommendations, based on the efficacy and the level of evidence of the included studies were discussed and finally consented by the guidelines group. After subsequent reviews the guidelines were presented to the European Dermatology Forum, European Academy of Dermatology and Venereology and Union Européenne des Médicins Spécialistes for approval and published in October 2009. Conclusion The development of European evidence based guidelines requires a coordinated structure which can be achieved by the integration of an experienced group of methodologists. Nevertheless further improvements are imaginable and might be considered for an update or other European evidence based guidelines.     

Psoriasis and diabetes: a population-based cross-sectional study

Background Previous reports have shown an association between psoriasis and the metabolic syndrome, but there are only a few studies on the association between psoriasis and diabetes. Objectives To study the association between psoriasis and diabetes. Methods A cross‐sectional study was performed utilizing the database of Clalit Health Services (CHS). Patients who were diagnosed with psoriasis were compared with CHS enrolees without psoriasis regarding the prevalence of diabetes. Patients with diabetes were identified using the CHS chronic diseases registry. Chi‐squared tests were used to compare categorical parameters. Logistic regression models were used for multivariate analyses. Results The study included 16 851 patients with psoriasis and 74 987 subjects without psoriasis (control patients). The proportion of diabetes was significantly higher in patients above 35 years (P < 0.05). The age‐adjusted proportion of diabetes was significantly higher in psoriasis patients as compared to the control group [odds ratio (OR), 1.38, P < 0.05] and was similar in men and women (OR, 1.32, 1.45, respectively). A multivariate logistic regression model showed that psoriasis was significantly associated with diabetes, independently of age and gender (OR, 1.58, P < 0.001). Conclusions Our study supports previous reports of an association between psoriasis and diabetes. Dermatologists taking care of patients with psoriasis should be aware of this association and advise the patients to reduce additional risk factors such as smoking, hypertension or dyslipidemia.     

Problem drinking in emergency department patients: the scope for early intervention

OBJECTIVE: To determine the prevalence of previously undiagnosed problem drinking and thereby to assess the suitability of the emergency department for early intervention. DESIGN: Three hundred and fifty ambulatory care patients were assessed by means of a structured interview schedule, physical examination and blood tests. Alcohol intake and presence of alcohol-related problems were recorded, along with history of past advice on drinking and self-perception of an alcohol problem. SETTING: The ambulatory care section of the emergency department of Royal Prince Alfred Hospital, Sydney. PATIENTS: Three hundred and fifty subjects, aged between 18 and 55 years, were sequentially selected over an 18-month period. RESULTS: Forty-one per cent of subjects (95% confidence interval, 36%-46%), 50% of men and 26% of women, were classified as problem drinkers on the basis of hazardous or harmful levels of alcohol consumption, frequent drinking to intoxication, evidence of dependence, or experience of alcohol-related problems. Of these, 63% had not previously received advice on drinking from a health professional and only 28% perceived they had a problem. Of particular note was that 24% of men and 4% of women were drinking 12 or more drinks (120 g of alcohol or more) in a single session on a weekly or more frequent basis. CONCLUSIONS: Many of the problem drinkers attending the emergency department have not previously received advice about their drinking from a health professional. The emergency department therefore offers considerable potential as a site for early detection and intervention in patients with hazardous and harmful alcohol use and related disorders.