New instrument for automatic recording of clot lysis.

An experimental instrument that determines and records automatically the end-point of clot lysis is described. The instrument is unique in that it measures the end product of lysis directly and quantitatively, unlike currently available indirect methods that rely on the optical or mechanical changes indicative of lysis. Data showing that the instrument is capable of yielding reliable, reproducible results in a variety of experimental conditions are presented.     

Agreement between interview information and physician records on history of menopausal estrogen use

A case-control study of the association between replacement estrogen use and breast cancer risk was conducted between 1975 and 1980 on Oahu, Hawaii. Data from this study were used to compare menopausal estrogen histories obtained through a personal interview with information from the subject's physician(s) or clinical records. The sample included 344 breast cancer cases, 344 hospital controls, and 344 neighborhood controls. Study participants included Japanese and white women aged 45-74 years who were residents of Oahu. Interviewers asked participants whether they had ever used replacement or menopausal estrogens for 1 month or longer. The month and year of initial use and the duration of use for each preparation were recorded for the users. Questions were also asked about a number of other medications. Information on estrogen use from the users and nonusers was then verified by the physician(s) or clinic(s) named by the study subject. The results showed moderate to substantial agreement between users and physicians on ever/never use of estrogens (kappa = 0.74), duration of estrogen use (intraclass correlation coefficient (rI) = 0.54), and age at initial use of estrogens (rI = 0.57). There was no differential misclassification by the case-control status of the subject. Agreement tended to be better for Japanese subjects, younger subjects, nonsmokers, and those of higher socioeconomic status, as measured by two indicators, college education and home ownership. Agreement was also negatively influenced by the duration of estrogen use and length of recall. These results suggest that women can recall estrogen use with a high degree of accuracy and support the use of a personal interview for obtaining information on replacement estrogens in case-control studies.     

Adverse dermatologic reaction to transdermal nitroglycerin

The incidence of adverse effects from transdermal nitroglycerin systems is reported to be very low. A cutaneous reaction from Transderm-Nitro is described. The patient in this case was a 63-year-old male with a history of chronic obstructive lung disease, adult onset diabetes mellitus, peptic ulcer disease, congestive heart failure, and angina pectoris. Seven weeks after having used a Transderm-Nitro-5 patch daily, the patient was found to have two macular erythematous areas on his chest that corresponded to the exact sites of the nitroglycerin patch. Follow-up with the same patient, using a placebo Transderm-Nitro, elicited a reaction similar in appearance. The exact causative agent is unknown, but it is believed to be from the transdermal delivery system and not the nitroglycerin.     

Testing the importance of p27 degradation by the SCFskp2 pathway in murine models of lung and colon cancer

Decreased expression of the CDK inhibitor p27kip1 in human tumors directly correlates with increased resistance to chemotherapies, increased rates of metastasis, and an overall increased rate of patient mortality. It is thought that decreased p27 expression in tumors is caused by increased proteasomal turnover, in particular activation of the pathway governed by the SCFskp2 E3 ubiquitin protein ligase. We have directly tested the importance of the SCFskp-mediated degradation of p27 in tumorigenesis by analyzing the tumor susceptibility of mice that express a form of p27 that cannot be ubiquitinated and degraded by this pathway (p27T187A). In mouse models of both lung and colon cancer down-regulation of p27 promotes tumorigenesis. However, we found that preventing p27 degradation by the SCFskp2 pathway had no impact on tumor incidence or overall survival in either tumor model. Our study unveiled a previously unrecognized role for the control of p27 mRNA abundance in the development of non-small cell lung cancers. In the colon cancer model, the frequency of intestinal adenomas was similarly unaffected by the p27T187A mutation, but, unexpectedly, we found that it inhibited progression of intestinal adenomas to carcinomas. These studies may guide the choice of clinical settings in which pharmacologic inhibitors of the Skp2 pathway might be of therapeutic value.     

Chronic thromboembolic pulmonary hypertension (CTEPH): updated Recommendations of the Cologne Consensus Conference 2011

In the 2009 European Guidelines on the diagnosis and treatment of pulmonary hypertension (PH), one section covers aspects of pathophysiology, diagnosis and treatment of chronic thromboembolic pulmonary hypertension (CTEPH). The practical implementation of the guidelines for this disease is of crucial importance, because CTEPH is a subset of PH which can potentially be cured by pulmonary endarterectomy (PEA). Nowadays, CTEPH is commonly underdiagnosed and not properly managed. Any patient with unexplained PH should be evaluated for the presence of CTEPH, and a ventilation/perfusion (V/Q) lung scan is recommended as screening method of choice. If the V/Q scan or CT angiography reveals signs of CTEPH, the patient should be referred to a specialized center with expertise in the medical and surgical management of this disease. Every case has to be reviewed by an experienced PEA surgeon for the assessment of operability. In this updated recommendation, important contents of the European guidelines were commented, and more recent information regarding diagnosis and treatment was added.