Solitary bronchioloalveolar carcinoma: CT criteria

The computed tomographic (CT) scans of 30 patients with solitary bronchioloalveolar carcinoma were reviewed. Common features at CT included the peripheral or subpleural location of a pulmonary mass (25 cases), pseudocavitation (18 cases), heterogeneous attenuation (17 cases), irregular margins forming a star pattern (22 cases), and pleural tags (21 cases). Using these CT criteria, four independent observers attempted to identify cases of bronchioloalveolar carcinoma from a larger sample of lung cancers and benign lesions by categorizing a series of test cases into four probability categories. Although the bronchioloalveolar carcinomas were correctly ranked in the two highest probability categories 75% of the time (in 45 of 60 cases), there was considerable overlap with other lung lesions, particularly with adenocarcinoma and large cell undifferentiated carcinoma. However, even though the typical features of bronchioloalveolar carcinoma are not invariable or highly specific, they are characteristic enough to suggest the diagnosis.     

Identification of a gene disrupted by a microdeletion in a patient with X-linked retinitis pigmentosa (XLRP)

The gene for the most frequent from of X-linked retinitis pigmentosa (XLRP), RP3, has been assigned by genetic and physical mapping to a segment of less than 1000 kbp, which is flanked by the marker DXS1110 and the ornithine transcarbamylase (OTC) gene. In search of microdeletions, we have screened the DNA of 30 unrelated patients with XLRP by employing a representative set of YAC-derived DNA fragments that were generated by restriction enzyme digestion and PCR amplification. In one of these patients, a 6.4 kbp microdeletion was detected which was not present in the DNA of 444 male controls. A cosmid contig spanning the deletion was constructed and used to isolate cDNAs from retina-specific libraries. Exons corresponding to these expressed sequences as well as other putative exons were identified by sequencing more than 30 kbp of the critical region. So far, no point mutations in these putative exon sequences have been identified.      

Positional cloning of the gene for X-linked retinitis pigmentosa 3: homology with the guanine-nucleotide-exchange factor RCC1

The gene for retinitis pigmentosa 3 (RP3), the most frequent form of X- linked RP (XLRP), has been mapped previously to a chromosome interval of less than 1000 kbp between the DXS1110 marker and the OTC locus at Xp21.1-p11.4. Employing a novel technique, YAC Representation Hybridization (YRH)', we have recently identified a small XLRP associated microdeletion in this interval, as well as several putative exons including the 3' end of a gene that was truncated by the deletion. cDNA library screening and sequencing of a cosmid centromeric to the deletion has now enabled us to identify numerous additional exons and to detect several point mutations in patients with XLRP. The predicted gene product shows homology to RCC1, the guanine-nucleotide- exchange factor (GEF) of the Ras-like GTPase Ran. Our findings suggest that we have cloned the long-sought RP3 gene, and that it may encode the GEF of a retina-specific GTP-binding protein.      

Comprehensive mutational scanning of the p53 coding region by two- dimensional gene scanning

A comprehensive mutational scanning test for the p53 coding region based on multiplex PCR and two-dimensional DNA electrophoresis was designed and evaluated. In a 2-step multiplex PCR, the p53 coding region (exons 2-11) was amplified as a single 8646-bp fragment by long- distance PCR in step one. This fragment served as a template for the subsequent co-amplification of the individual exons in two multiplex groups in step two. The multiplex products were then separated, first on the basis of size in non-denaturant polyacrylamide gels and then on the basis of sequence by denaturing gradient gel electrophoresis (DGGE). Primers for optimal PCR, melting behavior and 2-D gel distribution were designed using a recently developed computer program. The resulting two-dimensional gene scanning (TDGS) test was evaluated by screening, in a blinded fashion, 29 coded DNA samples from Li- Fraumeni syndrome patients with previously identified germline mutations. All mutations were correctly detected. This assay provides an accurate, cost-effective and non-radioactive method for simultaneous mutational scanning of all p53 coding exons.      

Associations between both genetic and environmental biomarkers and lung cancer: evidence of a greater risk of lung cancer in women smokers

This molecular epidemiologic case-control study of lung cancer incorporated three complementary biomarkers: the glutathione S- transferase M1 (GSTM1) null genotype, a potential marker of susceptibility, and polycyclic aromatic hydrocarbon-DNA adducts (PAH- DNA) and sister chromatid exchanges (SCE), both indicators of environmentally induced genetic damage. Associations between biomarkers and lung cancer were investigated, as were possible gene-environment interactions between the GSTM1 null genotype and tobacco smoke exposure. Subjects included 136 primary non-small cell lung cancer surgical patients and 115 controls at the Columbia Presbyterian Medical Center. Questionnaire and Tumor Registry data, pre-treatment blood samples and biomarker measurements on blood were obtained. Overall, GSTM1 null genotype was significantly associated with lung cancer [odds ratio (OR) = 2.04, 95% confidence interval (CI) = 1.13-3.68]. ORs for GSTM1 and lung cancer were significant in females (2.50, 1.09-5.72) and smokers (2.25, 1.11-4.54) and not significant in males (1.4, 0.58-3.38) and non-smokers (0.88, 0.18-4.33). However, ORs for males versus females and smokers versus non-smokers did not differ significantly. The OR for GSTM1 and lung cancer in female smokers was 3.03 (1.09- 8.40), compared with 1.42 (0.53-4.06) in male smokers. In contrast to PAH-DNA adducts in leukocytes, SCE did not differ between cases and controls. Neither biomarker differed significantly between the two GSTM1 genotypes. The combined effect of elevated PAH-DNA adducts and GSTM1 genotype on case-control status (16.19, 1.2-115) appeared multiplicative. Results suggest that the effect of the GSTM1 null genotype is greatest in female smokers, which is consistent with other evidence that indicates that women are at higher risk of lung cancer than males, given equal smoking. Persons with both the GSTM1 deletion and elevated PAH-DNA adducts may represent a sensitive subpopulation with respect to carcinogens in tobacco smoke and other environmental media.      

A Medicare-Associated Spike in U.S. Cancer Rates at Age 65, 2000–2010

Age 65 represents a transition point where most U.S. residents begin Medicare coverage. We examined whether or not delays in medical care near this age extend to cancer diagnosis. We calculated single-year-of-age cancer incidence rates by site and stage for the most common cancer sites (i.e., prostate, female breast, lung, and colorectal) for the 2000–2010 period using data from the SEER 18 registries, and we used Poisson regression to identify a possible age-65 effect. The analysis was repeated on comparable Canadian data. Cancer rates at age 65 were found to be as much as 15% above expected in the U.S. data, with the age-65 effect strongly associated with site- and stage-specific survival. A smaller association was seen in the Canadian data. We found strong evidence that diagnosis of less severe cancers spikes at age 65. Delay of medical care prior to this age has complex policy implications.The 65th birthday is a major life milestone for many Americans. It corresponds to the age when nearly all become eligible for health-care coverage through Medicare, when many begin receiving Social Security benefits, and when many choose to retire. This age boundary has been shown to have profound effects on health and health-care utilization. For example, rates of medical screening, diagnosis, and treatment for conditions that are low urgency, asymptomatic, and reimbursable by Medicare are found at much higher levels among those aged 65 years than those aged 64 years.^1–3 It has been suggested that this phenomenon is driven by the low-cost “Welcome to Medicare” physical examination instituted in 2005, but too few people have taken advantage of this feature for it to explain much of the difference.⁴In contrast, rates of “nondeferrable admissions,” defined as conditions where hospital admission rates through emergency departments do not diminish on weekends, show no change at age 65 years.⁵ For those who are uninsured or underinsured, there are clear financial incentives to postpone nonurgent medical encounters until Medicare is available. The effect is too large, however, to be explained by the behavior of the uninsured and underinsured alone. Even some people who are fully insured postpone treatment until age 65 years, either because of the perception that Medicare is a more generous health-care plan than other insurance plans or because postponing is more convenient.⁵ Recovering from a hip replacement while retired, for example, may be more practical than attempting to do so while employed.None of the existing research on pent-up demand for Medicare has, to our knowledge, specifically considered cancer incidence. We hypothesized that cancer should follow the same pattern as seen for other medical conditions. Specifically, screen-detected, asymptomatic, nonlethal tumors should show an unusually high incidence rate at age 65 years relative to other ages, while advanced-stage, low-survival tumors should show no difference. If correct, this observation should inform the current discussion regarding the extent to which certain cancers are being overdiagnosed and overtreated as a consequence of aggressive screening,⁶ as the Medicare program may be unwittingly bearing an undue share of the cost of such treatment. Conversely, underdiagnosis and undertreatment of those approaching 65 years of age may also be unduly shortening life spans among this group.We measured the elevation in cancer rates at age 65 years above what would be expected based on the otherwise smooth trend between ages 55 and 75 years. We considered prostate, female breast, lung, and colorectal cancers—the four most common cancer sites—which accounted for approximately 54% of all incident cases in the United States during the 2000–2010 period. Each of these cancers is detectable through screening, although at the time of writing only colorectal cancer screening for those aged 50–75 years was unequivocally endorsed by the U.S. Preventive Services Task Force (USPSTF).⁷ Breast cancer screening for women aged 50–74 years is generally recommended, but the guidelines for women older than 40 years of age are currently under review.^8,9 Lung cancer screening is recommended only for current or recent heavy smokers aged 55–80 years,¹⁰ and prostate cancer screening is not recommended at all.¹¹ We further investigated the relationship between the age-65 effect and the severity of the cancer, as measured by five-year survival. Finally, we compared the results from the United States with equivalent results from Canada, where no change in health-care insurance status occurs at age 65, but where 65 is also a popular retirement age.     

A diaphragmatic retroperitoneal cyst

Diaphragmatic lesions are usually congenital bronchogenic cysts. A patient with a known diaphragmatic cyst presented with new onset right upper quadrant pain. Repeat imaging showed enlargement of the cyst, the CA19–9 cancer marker was raised at 312iu/ml (normal: <27iu/ml) and positron emission tomography combined with computed tomography showed focally increased uptake in the cystic wall. In view of symptoms and risk of neoplasia, the lesion was excised. Histology showed a benign epidermoid cyst. Features falsely suggesting neoplasia have been reported previously with benign splenic cysts but not with a benign diaphragmatic epidermoid cyst.     

Is caring the ethical ideal?

This paper will examine the claim that caring is an appropriate ethical ideal for nursing. Initially it will examine nursing's philosophy of care and caring, highlighting some areas of difficulty and dissatisfaction articulated by many of its contemporary theorists Evaluation of the notion of caring as an appropriate ethical ideal for nursing will be balanced against those in opposition, and in this process their critique will be discussed This discussion will focus on areas such as virtue, virtue ethics, moral responsibility, feminine values, mothering and the debate between male and female caring Different forms of caring will be evaluated and balanced against different forms of nursing The paper will then suggest that current views which hold aloft nursing as a bedmate of caring may be detrimental to both the cared-for and the carer, advocating in the process a move toward change