Primary Care Ethics is Just Medical Ethics: A Philosophical Argument for the Feasibility of Transitioning Acute Care Ethics to the Primary Care Setting.

Whether practiced by ethics committees or clinical ethicists, medical ethics enjoys a solid foundation in acute care hospitals. However, medical ethics fails to have a strong presence in the primary care setting. Recently, some ethicists have argued that the reason for this disparity between ethics in the acute and primary care setting is that primary care ethics is distinct from acute care ethics: the failure to translate ethics to the primary care setting stems from the incorrect belief that acute care ethics can be applied to the primary care setting. In this paper, I argue that primary care ethics and acute care ethics are species of the same ethical genus, and that the ethical differences are not ones of kind but of circumstance. I do this by appealing to the role obligations that underlie acute care and primary care clinicians' medical ethical obligations and the shared institutions that ground those obligations.

Activity-Based Probes for Glycosidases: Profiling and Other Applications.

Glycosidases mediate the fragmentation of glycoconjugates in the body, including the vital recycling of endogenous molecules. Several inherited diseases in man concern deficiencies in lysosomal glycosidases degrading glycosphingolipids. Prominent is Gaucher disease caused by an impaired lysosomal ß-glucosidase (glucocerebrosidase, GBA) and resulting in pathological lysosomal storage of glucosylceramide (glucocerebroside) in tissue macrophages. GBA is a retaining glucosidase with a characteristic glycosyl-enzyme intermediate formed during catalysis. Using the natural suicide inhibitor cyclophellitol as a lead, we developed mechanism-based irreversible inhibitors of GBA equipped with a fluorescent reporter. These reagents covalently link to the catalytic nucleophile residue of GBA and permit specific and sensitive visualization of active enzyme molecules. The amphiphilic activity-based probes (ABPs) allow in situ detection of active GBA in cells and organisms. Furthermore, they may be used to biochemically confirm the diagnosis of Gaucher disease and they might assist in screening for small compounds interacting with the catalytic pocket. While the focus of this chapter is ABPs for ß-glucosidases and Gaucher disease, the described concept has meanwhile been extended to other retaining glycosidases and related disease conditions as well.

Low-dose computed tomography (LDCT) in workers previously exposed to asbestos: detection of parenchymal lung disease.

OBJECTIVES: To evaluate the lungs of asymptomatic asbestos-exposed workers who were screened for lung cancer and mesothelioma using low-dose computed tomography (LDCT) for parenchymal abnormalities. METHODS: Three hundred fifteen baseline LDCT studies of the chest of participants with at least 20 years' exposure to asbestos or presence of pleural plaques before enrollment on chest radiographs were analyzed. RESULTS: Three hundred fifteen subjects were studied. The mean age was 61.7 years, and the mean exposure to asbestos was 26.9 years. One hundred seventy-five (56%) participants had absence of parenchymal findings with a mean age of 58.7 years, mean exposure of 24.6 years, and a mean smoking pack years of 19. One hundred forty subjects (44%) had parenchymal findings (138 men and 2 women) with a mean age of 65.3 years, mean exposure of 29.73 years, and a mean smoking pack years of 21.5 years. Participants who had parenchymal manifestations were more likely to be older and have longer exposure to asbestos compared to participants who had no relevant parenchymal findings. There was no statistical difference in the mean smoking pack years between the groups with and without parenchymal findings. CONCLUSIONS: Low-dose CT could demonstrate parenchymal lung manifestations in this higher-risk asymptomatic group with prior exposure to asbestos in the setting of screening for lung cancer and mesothelioma. Individuals with longer exposure to asbestos and of higher age have more pulmonary abnormalities. The age and the latency of exposure play an important role given that the asbestos-related parenchymal abnormalities on LDCT were more prevalent in the elderly participants and with longer periods of exposure.

Lung cancer screening using low-dose computed tomography in at-risk individuals: the Toronto experience.

OBJECTIVE: The Department of Medical Imaging at the University Health Network in Toronto is performing a lung cancer screening study, utilizing low-dose computed tomography (LDCT) as the modality. Baseline and annual repeat results are reported on the first 3352 participants, enrolled between June 2003 and May 2007. METHODS: Enrollment was limited to those aged 50 years or older, with a smoking history of at least 10 pack-years, no previous cancer and general good health. A helical low-dose CT (LDCT) of the chest was performed using 120kVp, 40-60mA, images were reconstructed with 1-1.25mm overlapping slices. The primary objectives were the detection of parenchymal nodules and diagnosis of early stage lung cancer. Baseline LDCTs were termed positive if at least one indeterminate non-calcified nodule 5mm or larger in size, or non-solid nodule 8mm or larger in size was identified. Follow up periods for individuals with a positive baseline LDCT were determined by nodule characteristics. RESULTS: The median age at baseline was 60 years (range 50-83), with a median of 30 pack-years of cigarette smoking (range 10-189). Baseline CT evaluations were positive in 600 (18%) participants. To date, 2686 (80%) of the participants have returned for at least one annual repeat screening LDCT. Biopsies have been recommended for 82 participants since the study began, and 64 have been diagnosed with screen-detected cancer (62 lung, two plasmacytoma of the rib). A total of 65 lung cancers have been diagnosed (62 screen-detected, 3 interim), 57 are NSCLC (82% with known stage are stage I or II) and the rate of surgical resection was 80%. Sensitivity and specificity of the protocol in successfully diagnosing early stage lung cancers were 87.7% and 99.3%, respectively. CONCLUSIONS: Data indicate that LDCT can identify small lung cancers in an at-risk population. The diagnostic algorithm results in few false-positive invasive procedures. Most cancers are detected at an early stage, where the cancer is resectable with a greater potential for cure. Long-term follow up of lung cancer cases will be carried out to determine survival.

Does intensive follow-up alter outcome in patients with advanced lung cancer?

BACKGROUND: Despite aggressive multimodality treatment, 5-year survival of stage III non-small cell lung cancer (NSCLC) remains <30%. To detect relapse, progression, or development of a second primary cancer early, many clinicians perform follow-up scans. To assess the impact of routine scanning, we compared clinical trial patients who had study-mandated scans with those treated off-study who had less intensive radiologic follow-up. METHODS: The hospital cancer registry and trials databases were searched for patients with locally advanced NSCLC who had undergone multimodality treatment with curative intent. Baseline demographics were collected as well as frequency and results of clinical and radiologic follow-up. RESULTS: Forty trial patients and 35 nontrial control patients were identified. Trial patients underwent significantly more imaging, particularly in the first 2 years (2.9 versus 2.0 body scans per year, p = 0.0016; 1.1 versus 0.4 brain scans per year, p < 0.001) but did not have more frequent follow-up visits. Forty-five cancers were detected (41 relapses, four metachronous primary tumors) in 44 (59%) patients. Of these, 28 (64%) sought medical attention that led to detection before a scheduled appointment or procedure. There was no significant difference in time to relapse or second primary in trial and nontrial patients (p = 0.80). Twenty-three patients had localized relapse, but only 15 could be treated with curative intent. Despite the trial group demonstrating a higher number of asymptomatic cancers and being offered potentially curative therapy more frequently, there was no significant difference in survival between trial and nontrial patients. CONCLUSION: In patients with locally advanced NSCLC, frequent cross-sectional imaging does not alter survival after combined modality therapy.

Forensic aspects of behavioral pediatrics.

This article provided many situations in which the pediatrician may cross paths (if not swords) with members of the legal profession. It is extremely rare for the doctor to avoid some aspect of the law for an entire career. The article has provided common examples of the pediatrician's possibilities for involvement in the legal system and suggestions for making the experience less anxiety-provoking, and, instead, gratifying. Our American legal system, imperfect though it is, is probably the best and fairest in the world; attorneys and judges should not be considered the enemy. They may look to pediatricians for guidance in difficult cases in which children must be protected. By comprehensively reviewing all documents provided, preparing well, and, most importantly, remaining scrupulously honest throughout the process, a pediatrician has the opportunity to serve the system well, assist children and their families, and even, perhaps, make the system a bit better.

Trioxolanes: A new generation of compounds with wide-ranging activities.

Direct biological activity of a 1,2,4-trioxolane derivative was assessed in vitro using bacteria and fungi causing common infections. The product was found to be uniformly active against all organisms tested. In addition, it is active against certain tumour cells and protozoa and is also an immunomodulator. These observations are discussed in the light of the product's potential use in the clinical management of conditions in which its use is indicated.