Deliberating about Bioethics

In some sense, bioethics was built on conflicts. Abortion, physician-assisted suicide, patients’ demand for autonomy all are staple and contentious issues. And the controversies continue to proliferate. What forum best serves such debates? A look at political theories of democracy can help answer that question. The most promising for bioethics debates are theories that ask citizens and officials to justify any demands for collective action by giving reasons that can be accepted by those who are bound by the action. This conception has come to be known as deliberative democracy.     

Safety pharmacology of the respiratory system: Techniques and study design

The known effects of drugs from a variety of pharmacologic/therapeutic classes on the respiratory system and worldwide regulatory requirements support the need for conducting respiratory evaluations in safety pharmacology. The objective of these studies is to evaluate the potential for drugs to cause secondary pharmacologic or toxicologic effects that influence respiratory function. Changes in respiratory function can result either from alterations in the pumping apparatus that controls the pattern of pulmonary ventilation or from changes in the mechanical properties of the lung that determine the transpulmonary pressures (work) required for lung inflation and deflation. Defects in the pumping apparatus are classified as hypo- or hyperventilation syndromes and are evaluated by examining ventilatory parameters in a conscious animal model. The ventilatory parameters include respiratory rate, tidal volume, minute volume, peak (or mean) inspiratory flow, peak (or mean) expiratory flow, and fractional inspiratory time. Defects in mechanical properties of the lung are classified as obstructive or restrictive disorders and can be evaluated in animal models by performing flow-volume and pressure-volume maneuvers, respectively. The parameters used to detect airway obstruction include peak expiratory flow, forced expiratory flow at 25 and 75% of forced vital capacity, and a timed forced expiratory volume, while the parameters used to detect lung restriction include total lung capacity, inspiratory capacity, functional residual capacity, and compliance. Measurement of dynamic lung resistance and compliance, obtained continuously during tidal breathing, is an alternative method for evaluating obstructive and restrictive disorders, respectively, and is used when the response to drug treatment is expected to be immediate (within minutes post-dose). The species used in the safety pharmacology studies conducted in our laboratory are the same as those used in toxicology studies since pharmacokinetic and toxicologic/pathologic data are available in these species. These data can be used to help select test measurement intervals and doses and to aid in the interpretation of functional change. The techniques and procedures for measuring respiratory function parameters are well established in guinea pigs, rats, and dogs.     

Desmoplastic malignant melanoma presenting with orbital involvement

Desmoplastic malignant melanoma (DMM) is a rare variant of spindle cell melanoma. We report a case of DMM of the forehead secondarily involving the orbit. The diagnosis was based on light microscopic features, including prominent peripheral cell nest formation and spindle cell fascicles in densely collagenous stroma. Immunohistochemical studies showed strong uniform staining for S100 antigen throughout the tumour. It was negative for HMB 45, smooth muscle actin, desmin, cytokeratins and Type IV collagen. Electron microscopy showed neither melanosomes nor myelin figures. The clinical and histological characteristics of desmoplastic malignant melanoma, and its differential diagnosis of malignant schwannoma, are discussed. DMM has a poor prognosis, since it tends to invade deeply, recur locally and metastasise readily.     

Diagnostic accuracy of progressive supranuclear palsy in the Society for Progressive Supranuclear Palsy brain bank.

Diagnostic accuracy has been addressed previously for Parkinson's disease in a brain bank collection, but accuracy of progressive supranuclear palsy (PSP) has not been addressed in a similar setting. Clinical and genetic features of pathologically confirmed cases of PSP were compared with misdiagnosed cases to determine ways to improve diagnostic accuracy. Medical records were reviewed for 180 cases sent to the Society of Progressive Supranuclear Palsy Brain Bank that had standardized neuropathologic evaluations as well as determination of apolipoprotein E and tau genotypes. Of the 180 cases studied, 137 had PSP and 43 had other pathologic diagnoses. Corticobasal degeneration (CBD), multiple system atrophy (MSA), and diffuse Lewy body disease (DLBD) accounted for 70% of the misdiagnosed cases. History of tremor, psychosis, dementia, and asymmetric findings were more frequent in misdiagnosed cases. The frequency of H1 tau haplotype (93 vs. 80%) and H1H1 genotype (86 vs. 66%) were significantly greater and APOE epsilon4 carrier state was significantly less (17 vs. 41 %) in PSP compared with misdiagnosed cases. Pathologic evaluation of clinically diagnosed PSP remains important for definitive diagnosis, and CBD, MSA, and DLBD are the disorders most likely to be misdiagnosed as PSP. Tremor, psychosis, early dementia, asymmetric findings, absence of H1 haplotype, and presence of APOE epsilon4 should raise questions about a diagnosis of PSP.     

Stenting of the left carotid artery to relieve anginal symptoms.

Stenting of the carotid artery is usually performed either to prevent an acute neurologic event or to treat episodes of recurrent transient ischemic attacks. Occasionally, it may be performed for other indications. We describe the case of a patient with prior coronary artery bypass grafting using a left internal mammary arterial graft, in addition to left carotid artery to left subclavian artery bypass for symptomatic left subclavian stenosis, who subsequently underwent left common carotid artery stenting to relieve anginal symptoms.     

Radiographic changes induced after cervical facet radiofrequency denervation

BACKGROUND CONTEXT: Paraspinal infections after zygapophyseal (facet) radiofrequency denervation (RFD) are a serious but rare complication of this procedure. We are aware of only one case report of an epidural abscess after facet joint injection. PURPOSE: To report post-procedure inflammatory changes after cervical facet RFD. STUDY DESIGN: Case report. PATIENT SAMPLE: A 35-year-old Caucasian female. METHODS: Retrospective case review. RESULTS: The patient underwent cervical RFD and was admitted to the hospital 7 days after her procedure with severe neck pain. Magnetic resonance imaging (MRI) with contrast revealed what appeared to be evidence of a paraspinal muscle abscess although blood tests were negative. She was treated with antibiotic therapy, yet she never developed systemic signs of infection. A follow-up MRI without contrast revealed no evidence of infection, and she was discharged home on hospital day 6. At her first follow-up visit, she was still experiencing scalp pain and paraspinal muscle spasm. During subsequent follow-up visits, she has continued to improve clinically without experiencing signs of infection. Another follow-up MRI 6 weeks after her discharge home revealed persistent minimal left paraspinal enhancement at C2-3, possibly representing post-procedure granulation tissue with no evidence of abscess. CONCLUSIONS: Post-procedural MRI findings after radiofrequency lesioning can resemble radiographic findings associated with a paraspinal abscess. Patients with radiographic findings consistent with abscess should only be treated if clinical signs or symptoms of systemic infection are present.