Keratoacanthomas frequently show chromosomal aberrations as assessed by comparative genomic hybridization

Keratoacanthomas are commonly occurring benign skin lesions localized to sun-exposed areas. They typically develop rapidly and may show cellular atypia and infiltration like cutaneous squamous cell carcinomas, but they finally regress spontaneously. This benign lesion shows a high degree of genetic instability as assessed by comparative genomic hybridization, with 35.7% (25 of 70) of the analyzed lesions harboring chromosomal aberrations. The same frequency of genetic imbalance was found in lesions from immunosuppressed organ transplant recipients (36.4%, 20 of 55) and in patients with keratoacanthomas without immunosuppression (33.3%, five of 15), indicating a common pathway in both situations. Recurrent aberrations, given as a fraction of lesions with aberrations, were gains on 8q (20.0%), 1p and 9q (each 16.0%), and deletions on 3p (20.0%), 9p (20.0%), 19p (20.0%), and 19q (16.0%). Many of the most frequently appearing aberrations in keratoacanthomas were not detected in any of the 10 squamous cell carcinomas analyzed, whereas some aberrations were shared by both types of lesions. Aberrations were found in early and late stages of keratoacanthoma development, indicating a role for genetic instability in the progression as well as involution of keratoacanthomas. There were no significant correlations between cytologic atypia and genetic imbalance, or between degree of infiltration and genetic aberrations, although there was a trend for keratoacanthomas with severe atypia to have aberrations. Thus malignant phenotypic development does not appear to be driven by the detected genetic aberrations. More detailed studies of chromosomal areas with recurrent aberrations are needed for the localization of putative genes that determine the biologic behavior of keratoacanthomas, and that may distinguish them from squamous cell carcinomas.     

Cerebral Doppler and misrepresentation of flow changes

To determine whether cerebral blood flow velocity (CBFV) measurements were representative of cerebral blood flow (CBF) changes in pathological flow situations five newborn piglets were investigated. They underwent measurements of CBF by electromagnetic flowmetry on a modified common carotid artery where extracerebral branches were tied off simultaneously with Doppler recording either from the same precerebral or an intracerebral artery. The two methods agreed well within moderate carbon dioxide and blood pressure changes. During severe hypotension and hypertension Doppler overestimated CBF by 25-100%. During transfusion of infected or incompatible blood the two methods differed in opposite directions with Doppler reading from 30-200% of CBF. Transfusion of chilled blood caused CBFV to overestimate 15% and heated blood caused 20% underestimation. These results could be explained by diameter changes in response to variation in myogenic tone or vasoactive substances. CBFV measurements could be seriously misleading in severe clinical derangements where neonatal brain damage might occur.     

Early detection of breast cancer based on gene-expression patterns in peripheral blood cells

Introduction

Existing methods to detect breast cancer in asymptomatic patients have limitations, and there is a need to develop more accurate and convenient methods. In this study, we investigated whether early detection of breast cancer is possible by analyzing gene-expression patterns in peripheral blood cells.

Methods

Using macroarrays and nearest-shrunken-centroid method, we analyzed the expression pattern of 1,368 genes in peripheral blood cells of 24 women with breast cancer and 32 women with no signs of this disease. The results were validated using a standard leave-one-out cross-validation approach.

Results

We identified a set of 37 genes that correctly predicted the diagnostic class in at least 82% of the samples. The majority of these genes had a decreased expression in samples from breast cancer patients, and predominantly encoded proteins implicated in ribosome production and translation control. In contrast, the expression of some defense-related genes was increased in samples from breast cancer patients.

Conclusion

The results show that a blood-based gene-expression test can be developed to detect breast cancer early in asymptomatic patients. Additional studies with a large sample size, from women both with and without the disease, are warranted to confirm or refute this finding.     

Quality of cardiopulmonary resuscitation during out-of-hospital cardiac arrest

Context  Cardiopulmonary resuscitation (CPR) guidelines recommend target values for compressions, ventilations, and CPR-free intervals allowed for rhythm analysis and defibrillation. There is little information on adherence to these guidelines during advanced cardiac life support in the field. Objective  To measure the quality of out-of-hospital CPR performed by ambulance personnel, as measured by adherence to CPR guidelines. Design and Setting  Case series of 176 adult patients with out-of-hospital cardiac arrest treated by paramedics and nurse anesthetists in Stockholm, Sweden, London, England, and Akershus, Norway, between March 2002 and October 2003. The defibrillators recorded chest compressions via a sternal pad fitted with an accelerometer and ventilations by changes in thoracic impedance between the defibrillator pads, in addition to standard event and electrocardiographic recordings. Main Outcome Measure  Adherence to international guidelines for CPR. Results  Chest compressions were not given 48% (95% CI, 45%-51%) of the time without spontaneous circulation; this percentage was 38% (95% CI, 36%-41%) when subtracting the time necessary for electrocardiographic analysis and defibrillation. Combining these data with a mean compression rate of 121/min (95% CI, 118-124/min) when compressions were given resulted in a mean compression rate of 64/min (95% CI, 61-67/min). Mean compression depth was 34 mm (95% CI, 33-35 mm), 28% (95% CI, 24%-32%) of the compressions had a depth of 38 mm to 51 mm (guidelines recommendation), and the compression part of the duty cycle was 42% (95% CI, 41%-42%). A mean of 11 (95% CI, 11-12) ventilations were given per minute. Sixty-one patients (35%) had return of spontaneous circulation, and 5 of 6 patients discharged alive from the hospital had normal neurological outcomes. Conclusions  In this study of CPR during out-of-hospital cardiac arrest, chest compressions were not delivered half of the time, and most compressions were too shallow. Electrocardiographic analysis and defibrillation accounted for only small parts of intervals without chest compressions.      

Poststroke epilepsy: occurrence and predictors--a long-term prospective controlled study (Akershus Stroke Study)

PURPOSE: The aims of the study were to assess the occurrence of poststroke epilepsy (PSE) in patients with ischemic strokes, to identify predictors, and to investigate whether treatment in a stroke unit (SU) influenced the long-term outcomes of epilepsy. METHODS: Patients with PSE, defined as those having two ore more unprovoked epileptic seizures > or = 1 week after an ischemic stroke, were identified from a cohort of 484 patients with ischemic strokes. The patients were prospectively assessed 7-8 years after stroke or until death. Different variables were studied to look for possible predictors. RESULTS: From 484 patients with ischemic strokes, PSE developed in 12 (2.5%) and 15 (3.1%) patients during the first year and 7-8 years after stroke, respectively. Eight (53%) of these patients were treated in a stroke unit (SU), and seven (47%) were treated in a general medical ward (GMW). The mean age of those who developed PSE and those who did not was 74.3 years and 76.3 years, respectively. In a multivariate analysis, a Scandinavian Stroke Scale (SSS) score < 30 on admission was a significant predictor for developing PSE [odds ratio (OR), 4.9; p = 0.004). CONCLUSIONS: The prevalence of PSE, 7 to 8 years after an ischemic stroke, was 3.1%. SSS scores < 30 on admission were a significant predictor for PSE. Neither treatment in SU versus GMW, cortical location, nor age at onset of stroke seemed to influence the risk of developing PSE.