A new model of embolic stroke produced by photochemical injury to the carotid artery in the rat

We report a new model of embolic stroke in the rat, based on endothelial disruption and platelet aggregation in the carotid artery, which leads to distal embolization and focal brain infarction. The common carotid artery was irradiated for 6.5 minutes with the focused beam of an argon laser operated at a wavelength of 514.5 nm with a peak power of 2 W and an average power of 400 mw. Ipsilateral cerebral infarcts, ranging in size from 0.1 to 1.7 mm, were produced by platelet emboli in 12 of 13 rats. A total of 44 infarcts were observed in the 12 rats: 29 in the cortex, 6 in the hippocampus, 5 in the thalamus, and 4 in the basal ganglia. Scanning electron microscopy identified platelet aggregates in the carotid artery and in a deep cortical arteriole 50 minutes after the photochemical lesion. Twenty-four hours after the experiment, scanning electron microscopy of the carotid artery revealed damaged endothelium but few remaining adherent platelets. More intense laser irradiation in 8 rats, leading to carotid occlusion, produced an infarct in only 1. This new model can be used to study the acute and chronic pathological changes in the brain associated with platelet embolism.     

Polymorphisms in DNA repair genes as risk factors for spina bifida and orofacial clefts

Repairing DNA damage is critical during embryogenesis because development involves sensitive periods of cell proliferation, and abnormal cell growth or death can result in malformations. Knockout mouse experiments have demonstrated that disruption of DNA repair genes results in embryolethality and structural defects. Studies using mid-organogenesis rat embryos showed that DNA repair genes were variably expressed. It is hypothesized that polymorphisms that alter the functionality of DNA repair enzymes may modify the risk of malformations. We conducted a case-control analysis to investigate the relationship between DNA repair gene polymorphisms and the risk of spina bifida and oral clefts. Newborn screening blood spot DNA was obtained for 250 cases (125 spina bifida, 125 oral clefts) identified by the California Birth Defects Monitoring Program, and 350 non-malformation controls identified from birth records. Six single nucleotide polymorphisms of five DNA repair genes representing three distinct repair pathways were interrogated including: XRCC1 (Arg399Gln), APE1 (Asp148Glu), XRCC3 (Thr241Met), hOGG1(Ser326Cys), XPD (Asp312Asn, Lys751Gln). Elevated or decreased odds ratios (OR, adjusted for race/ethnicity) for spina bifida were found for genotypes containing at least one copy of the variant allele for XPD [751Gln, OR = 1.62; 95% confidence interval (CI) = 1.05-2.50] and APE 148 (OR = 0.58; CI = 0.37-0.90). A decreased risk of oral clefts was found for XRCC3 (OR = 0.62; CI = 0.39-0.99) and hOGG1 (326 Cys/Cys, OR = 0.22; CI = 0.06-0.78). This study suggested that polymorphisms of DNA repair genes, representing different major repair pathways, may affect risk of two major birth defects. Future, larger studies, examining additional repair genes, birth defects, and interaction with exposures are recommended.     

The partnership between breast cancer advocates and scientists

The National Breast Cancer Coalition (NBCC) is a grassroots organization that represents breast cancer advocates and is committed to eradicating breast cancer. NBCC defines a breast cancer advocate as someone who has been personally affected by the disease (e.g., a breast cancer survivor, family member, or friend), represents a constituency, and is motivated to join the fight against the disease. One of the organization's goals is to ensure that breast cancer advocates have a seat at the table when decisions are made about breast cancer research and policy. To accomplish this goal, NBCC educates advocates so that they can participate in and make meaningful contributions to legislative, scientific, and regulatory decision-making bodies. In addition to creating educational opportunities for advocates, NBCC has spearheaded several initiatives designed to directly increase the quality and quantity of breast cancer research. NBCC has also played a major role in making funding available to breast cancer researchers. Two of NBCC's most notable programs include Project LEAD, an intensive science-training course for breast cancer advocates, and the Environmental Initiative, a collection of activities designed to improve research into the relationship between breast cancer and the environment. Breast cancer advocates trained by NBCC have partnered with the scientific community and individual scientists to improve the peer review, design, and implementation of breast cancer research.     

The fallacy of the lacune hypothesis

We review the definition, pathogenesis, natural history, and prognosis and describe the first experimental model of lacunes. Defined pathologically or radiologically, lacunes are small cerebral infarcts which become cystic and are caused by occlusion of small arteries. The clinical definition of lacune is confused. The word "lacune" means a small stroke. While the immediate mortality rate from a small stroke is low, many patients are unable to return to work and the long-term prognosis is guarded. Photochemical damage to the carotid artery of rats produces microemboli to the brain, resulting in cavitary lesions resembling lacunes in humans. The "lacune hypothesis" is a fallacy because small cerebral infarcts are not caused solely by a combination of hypertension and small vessel disease, and the various "lacunar syndromes" are simply small strokes which should be investigated as such.     

Lactation and breast cancer risk.

BACKGROUND: Data from the Carolina Breast Cancer Study, a population-based, case-control study of breast cancer in African-American and white women residents of North Carolina, were evaluated to determine whether specific aspects of lactation are associated with a reduction in the risk of breast cancer. METHODS: Analyses included 751 parous cases and 742 parous controls frequency-matched on age and race. Information on lactation, reproductive history, lifestyle characteristics and family history were obtained through a personal interview. RESULTS: When women who breastfed were compared to those who never breastfed, odds ratios and 95% confidence intervals of 0.8 (0.5-1.1) and 0.7 (0.5-0.9) were found for women 20-49 years and 50-74 years, respectively. Similar inverse associations were observed for each of three categories of lifetime duration (1-3, 4-12, 13+ months). The inverse associations persisted and did not vary when number of children breastfed, ages at first and last lactation and lactational amenorrhoea were examined. CONCLUSIONS: Our findings suggest that any lactation, regardless of duration or timing, is associated with a slight reduction in the risk of breast cancer among younger and older parous women.     

Liver resection for colorectal cancer: liver metastases in the aged

The purpose of this study was to determine the morbidity and mortality in elderly patients undergoing liver resections for metastatic colon cancer and compare them with those of a control group of younger patients. The charts of all patients undergoing liver resection for colon cancer were retrospectively reviewed. Patients less than 70 years of age (Group A) were compared with patients 70 years of age or older (Group B). Between 1971 and 1995, 167 liver resections were performed for metastatic colorectal cancer. Of these, 41 patients were in Group A and 126 patients were in Group B. The mean age of Group A was 74.5 years, and that of Group B was 57 years. American Society of Anesthesiologists (ASA) classification was similar for both groups (Groups A and B were 75.6% and 81.1% ASA class II, respectively). Anatomic resections were performed in 49 per cent and wedge resections in 51 per cent of patients in Group A, and 68 and 32 per cent in Group B, respectively. Estimated blood loss was slightly less for Group A (1575 vs 1973 cm3), as was operative time (4.0 vs 4.7 hours). In-hospital mortality rate was 7.3 per cent for Group A and 2.4 per cent for Group B. The major morbidity rates were 29 and 17.5 per cent, respectively. Intensive care unit care was necessary in 73 per cent (mean length of stay 3.9 days) for Group A and 62.6 per cent (mean length of stay 2.0 days) for Group B. The average length of hospitalization was 13.1 days for Group A and 16.6 days for Group B. The recurrence rates were similar for the two groups [56% (Group A) vs 66% (Group B)], but mean survival was longer for younger patients (22.9 vs 33.5 months). We conclude that liver resection for colorectal cancer liver metastases in properly selected patients older than 70 years of age can be performed with acceptable morbidity and mortality rates. The long-term survival for older patients is less than that for younger patients, but is still a significant length of time. Therefore, we conclude that age alone is not a contraindication to liver resection for colorectal cancer metastases in patients older than 70.     

Identification of a basal-like subtype of breast ductal carcinoma in situ

Microarray profiling of invasive breast carcinomas has identified subtypes including luminal A, luminal B, HER2-overexpressing, and basal-like. The poor-prognosis, basal-like tumors have been immunohistochemically characterized as estrogen receptor (ER)-negative, HER2/neu-negative, and cytokeratin 5/6-positive and/or epidermal growth factor receptor (EGFR)-positive. The aim of this study was to determine the prevalence of basal-like ductal carcinoma in situ in a population-based series of cases using immunohistochemical surrogates. A total of 245 pure ductal carcinoma in situ cases from a population-based, case-control study were evaluated for histologic characteristics and immunostained for ER, HER2/neu, EGFR, cytokeratin 5/6, p53, and Ki-67. The subtypes were defined as: luminal A (ER+, HER2-), luminal B (ER+, HER2+), HER2 positive (ER-, HER2+), and basal-like (ER-, HER2-, EGFR+, and/or cytokeratin 5/6+). The prevalence of breast cancer subtypes was basal-like (n = 19 [8%]); luminal A, n = 149 (61%); luminal B, n = 23 (9%); and HER2+/ER-, n = 38 (16%). Sixteen tumors (6%) were unclassified (negative for all 4 defining markers). The basal-like subtype was associated with unfavorable prognostic variables including high-grade nuclei (P < .0001), p53 overexpression (P < .0001), and elevated Ki-67 index (P < .0001). These studies demonstrate the presence of a basal-like in situ carcinoma, a potential precursor lesion to invasive basal-like carcinoma.     

Minimally Invasive Technique Leads to Decreased Morbidity and Mortality in Small Bowel Resections Compared to an Open Technique: An ACS-NSQIP Identified Target for Improvement

Background

We hypothesize that currently minimally invasive techniques are underutilized, leading to unnecessary morbidity and mortality. The objective of the study was to compare morbidity and mortality rates in patients receiving a minimally invasive (MIS) small bowel resection to patients receiving an open (OP) small bowel resection.

Methods

Patients in the National Surgical Quality Improvement Program (NSQIP) database who underwent a small bowel resection between 2007 and 2011 were enrolled in the study and grouped whether they received a MIS procedure (n?=?1,780) or an OP procedure (n?=?17,701). The primary endpoint of the study was to evaluate the difference in morbidity (excluding mortality) and mortality in patients undergoing a minimally invasive procedure compared to an open procedure.

Results

The MIS technique is utilized in 9.0 % of patients undergoing a small bowel resection. Significantly lower mortality rate (2.9 vs. 8.2 %; p?<?0.001) and mean morbidity rate (1.7 vs. 4.3 %; p?<?0.001) were demonstrated in the MIS group. Significantly lower mean major morbidity rate (1.4 vs. 3.9 %; p?<?0.001) and mean minor morbidity rate (2.6 vs. 5.5 %; p?<?0.001) were demonstrated in the MIS group.

Conclusion

The MIS technique in small bowel resections appears to be underutilized, with only 9.0 % of patients in need of a small bowel resection undergo the minimally invasive approach. Wider utilization of the MIS technique could lead to significantly decreased morbidity and mortality.     

Higher clinical performance during a surgical clerkship is independently associated with matriculation of medical students into general surgery

Background

The purpose of our study was to determine the predictive impact of individual academic measures for the matriculation of senior medical students into a general surgery residency.

Methods

Academic records were evaluated for third-year medical students (n = 781) at a single institution between 2004 and 2011. Cohorts were defined by student matriculation into either a general surgery residency program (n = 58) or a non–general surgery residency program (n = 723). Multivariate logistic regression was performed to evaluate independently significant academic measures.

Results

Clinical evaluation raw scores were predictive of general surgery matriculation (P = .014). In addition, multivariate modeling showed lower United States Medical Licensing Examination Step 1 scores to be independently associated with matriculation into general surgery (P = .007).

Conclusions

Superior clinical aptitude is independently associated with general surgical matriculation. This is in contrast to the negative correlation United States Medical Licensing Examination Step 1 scores have on general surgery matriculation. Recognizing this, surgical clerkship directors can offer opportunities for continued surgical education to students showing high clinical aptitude, increasing their likelihood of surgical matriculation.