Bioethics for clinicians: 5. Substitute decision-making.

Substitute decision-making is a means of making health care decisions on behalf of people who are incapable of making these decisions for themselves. It is based on the ethical principle of respect for autonomy. Substitute decision-making poses two main questions: Who-should make the decision for the incapable person, and, How should the decision be made? Because the applicable statutory and common law varies across Canada, clinicians should become familiar with the legal requirements of their own province or territory.     

The patterns of cell death and of macrophages in the developing forebrain of the tree shrew Tupaia belangeri

The patterns of cell death and of macrophages were investigated in the forebrain and eyes of the tree shrew Tupaia belangeri during five phases of optic cup formation. Seventeen embryos were studied. Three- dimensional reconstructions were made from one embryo of each phase. In phase 1 (V-shaped optic evagination) a midline band of cell death passes through the closing anterior neuroporus. From phases 2 (optic vesicle) to 5 (far-advanced invagination) the midline band of cell death extends in the dorsal wall of the forebrain to its rostral pole and, further, into its ventral wall. At the approximate future position of the optic chiasm this ventral pycnotic area, predicted but so far unidentified by others, is connected to a previously described second band of cell death passing through the optic anlagen. Recently, evidence has been presented that chicken embryos develop holoprosencephaly and cyclopia when ventral forebrain structures are lost secondary to experimentally induced apoptosis. Our findings in Tupaia suggest that, in cases of spontaneous malformations of this kind, such an atypical pycnotic area in the ventral telencephalon might result from the defective regulation of cell death processes during optic cup formation. In the forebrain and eyes of Tupaia, the occurrence of bands of cell death precedes the appearance of the earliest intraepithelial macrophages. From phase 3 (onset of invagination) onwards almost all of them are concentrated along the band of cell death.     

CD15 (LeuM1) immunoreactivity: Prognostic factor for sporadic and hereditary medullary thyroid cancer?

Patients treated for sporadic and hereditary medullary thyroid carcinoma (MTC) have varying rates of persistent disease, recurrence, and survival. The aim of this study was to correlate the immunoreactivity of the monoclonal antibody CD15 (LeuM1) to initial clinical findings and the outcome of treatment. The primary tumors of 75 patients with sporadic MTC, 7 with hereditary disease, and 3 members of MEN 2A families were studied. Of these subjects 74 (87%) showed no or little immunoreactivity (<15% positive cells; score 0) in most tumors. The remaining 13% had surgery for tumors with more than 15% cells with positive staining (score I). There was no correlation between LeuM1 immunoreactivity and sex, age, and type of MTC. There was, however, a significant correlation with the pTNM classification and UICC staging. The prognosis for patients with score 0 was significantly better than score 1 patients. CD15 immunoreactivity appears to be a predictive factor in sporadic and hereditary MTC. Lymph node dissection seems to be more successful in patients with score 0 tumors than in those with score 1 tumors. The question of reoperation in patients with recurrence of disease (especially with biochemical recurrence or persistence) should be discussed on the basis of CD15 immunoreactivity.

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Resumen Los pacientes tratados para carcinoma medular, esporádico y hereditario, de la glándula tiroides (CMT) exhiben grandes variaciones en las tasas de enfermedad persistente, recidiva y sobrevida. El propósito del presente estudio fue establecer la correlación entre la inmunorreactividad del anticuerpo CD15 (LeuM1) y los hallazgos clínicos iniciales, así como con el resultado final del tratamiento.Se estudiaron los tumores primarios de 75 pacientes con CMT esporádico, de siete con enfermedad hereditaria y de 3 miembros de familias con síndrome NEM2A.Setenta y cuatro pacientes (87%) exhibieron ninguna o muy baja inmunorreactividad (menos de 15% de células positivas; puntaje 0) en la mayoría de los tumores. El 13% restante fue sometido a cirugía por tumores con más de 15% de las células con coloración positiva (puntaje 1). No se evidenció correlación entre la inmunorreactividad LeuM1 y el sexo, edad o tipo del CMT. Sin embargo, sí apareció una correlación significativa con la clasificiación pTNM y la estadificación de la UICC. El pronóstico de los pacientes con puntaje 0 resultó significativamento mejor que el de los pacientes con puntaje 1.La inmunorreactividad CD15 parece ser un factor de predicción de pronóstico en el CMT esporádico y familiar. La disección ganglionar parece ser más exitosa en pacientes con tumores de puntaje 0 que en los que portan tumores con puntaje 1.El interrogante en cuanto a reoperación en pacientes con recidiva de la enfermedad (especialmente cuando hay recidiva o persistencia bioquímica) debe ser considerada con base en la inmunorreactividad CD15.

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Résumé Les taux de maladie persistante, de récidive et de survie chez des patients traités pour cancer médullaire sporadique et héréditaire de la thyroïde (CMT) sont très variables. Le but de cette étude a été de corréler l'immunoréactivité des anticorps monoclonaux CD15 (LeuM1) à des données cliniques initiales et l'évolution finale du traitement des CMT. On a étudié 75 patients ayant un CMT primitif, sept ayant une maladie héréditaire, et trois membres d'une famille MEN 2A. Soixante quatre patients (87%) avaient peu ou pas d'immunoréactivité (moins de 15% de cellules positive: score = 0). Les 13% restants ont eu une chirurgie pour les tumeurs ayant un pourcentage > 15 (score = 1). Il n'y avait aucune corrélation entre l'immunoréactivité LeuM1 et le sexe, l'âge et le type de CMT. Il y avait, en revanche, une corrélation significative entre la classification pTMN et le stage UICC. Le pronostic des patients ayant un score = 0 était significativement meilleur que celui des patients ayant un score = 1. L'immunoréactivité CD15 apparaît comme étant un facteur pronostique des CMT. Le curage lymphatique

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Members and institutions are listed in Table 1.     

Intra-operative support via augmented reality techniques in endoscopic surgery.

Computer assisted operation planning systems are gaining increasing recognition in the field of surgery. These systems offer new possibilities for preparing an intervention, with the goal of reducing the amount of expensive operating-room time required for the intervention. The safest and most effective surgical approach should always be selected, but it is often difficult to transfer the output of the planning system to the intra-operative situation so that the planning results can be considered during the actual intervention. At the Fraunhofer Institute for Computer Graphics (IGD) in Darmstadt and the Centre for Advanced Media Technology (CAMTech) in Singapore methods are being developed to bridge the gap between the external planning session and the intra-operative case: Augmented Reality (AR) techniques are used to overlay preoperative scanned image data, as well as results of the planning session, on the operation field.     

Lessons to be learned from a complicated case of rhino-cerebral mucormycosis in a renal allograft recipient

Fungal infections still represent a serious complication after organ transplantation. Early diagnosis and aggressive treatment are crucial. Because of the many diagnostic problems involved, we present a case of mucormycosis--primarily affecting the paranasal sinuses with later intracranial extension--in a highly immunized recipient of a third renal transplant. Although fungal infection was suspected from various imaging techniques, only the detection of typical fungal hyphae in the infected tissue was diagnostic. Neither the blood tests and cerebrospinal fluid examinations performed nor cultures from maxillary sinus fluid were of any diagnostic help. Surgical debridement from a transnasal as well as an intracranial approach and systemic amphotericin B together with the discontinuation of immunosuppression after removal of the rejected graft were able to save the patient. This case stresses the importance of early diagnosis that can only be made from tissue biopsies and allows appropriate timely treatment.     

Role of Tyrosine Kinase in Desflurane-induced Preconditioning

Background: Short administration of volatile anesthetics preconditions myocardium and protects the heart against the consequences of subsequent ischemia. Activation of tyrosine kinase is implicated in ischemic preconditioning. The authors investigated whether desflurane-induced preconditioning depends on activation of tyrosine kinase.

Methods: Sixty-four rabbits were instrumented for measurement of left ventricular pressure, cardiac output, and myocardial infarct size (IS). All rabbits were subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. Rabbits underwent a treatment period consisting of either no intervention for 35 min (control group, n = 12) or 15 min of 1 minimum alveolar concentration desflurane inhalation followed by a 10-min washout period (desflurane group, n = 12). Four additional groups received the tyrosine kinase inhibitor genistein (5 mg/kg) or lavendustin A (1.3 mg/kg) at the beginning of the treatment period with (desflurane-genistein group, n = 11; desflurane-lavendustin A group, n = 12) or without desflurane inhalation (genistein group, n = 9; lavendustin A group, n = 8).

Results: Hemodynamic values were similar in all groups during baseline (left ventricular pressure, 87 +/- 14 mmHg [mean +/- SD]; cardiac output, 198 +/- 47 ml/min), during coronary artery occlusion (left ventricular pressure, 78 +/- 12 mmHg; cardiac output, 173 +/- 39 ml/min), and after 2 h of reperfusion (left ventricular pressure, 59 +/- 17; cardiac output, 154 +/- 43 ml/min). IS in the control group was 55 +/- 10% of the area at risk. The tyrosine inhibitors had no effect on IS (genistein group, 56 +/- 13%; lavendustin A group, 49 +/- 13%; each P = 1.0 vs. control group). Desflurane preconditioning reduced IS to 40 +/- 15% (P = 0.04 vs. control group). Tyrosine kinase inhibitor administration had no effect on IS reduction (desflurane-genistein group, 44 +/- 13%; desflurane-lavendustin A group, 44 +/- 16%; each P = 1.0 vs. desflurane group).     

Aktuelle und effektive bildgebende Diagnostik von Sprunggelenk und Fuß

Projection radiographic techniques have been used in a standardized manner for decades for the diagnosis of conditions of the foot and ankle; the indications for them and the pattern of findings useful in the initial diagnosis and monitoring of the course are generally known to clinical radiology staff. Computed tomography has been introduced as an extension of the basic procedures performed for diagnosis in the ankle and the hindfoot. In the case of complex fractures, however, specialist experience is essential. CT is an easily accessible investigative procedure and is meanwhile economical and very powerful. Magnetic resonance imaging supplements the range of investigations in special cases when there are particular problems. Microfractures, findings indicative of inflammation and/or dystrophy and, in particular questions concerning the musculoligamentous support system are the situations in which such investigations are needed. Ultrasound has an additive value vis-à-vis magnetic resonance imaging and is an easily accessible and highly effective examination procedure both for the primary diagnosis and for serial monitoring. Financial constraints in the healthcare sector are increasingly limiting purely medical indications. Regardless of this development, the retention of projection radiography, computer tomography, and magnetic resonance imaging must be demanded for the initial diagnosis in the care of foot and ankle injuries. The earliest possible implementation of all these techniques for the initial diagnosis is the first step towards effective treatment. Cafrefully chosen and, if appropriate, complementary strategies are needed for monitoring of the course and for assessment.     

Facial Nerve Neuroma: Surgical Concept and Functional Results

This study reviewed the management and outcomes of 11 facial nerve neuromas treated in our institution during the past two decades with particular emphasis on surgical concepts and functional outcomes. All patients underwent complete surgical resection of their tumor. Eight patients (73%) were followed on an outpatient basis. A retrospective chart review for pre- and postoperative clinical and radiological data was performed. All facial neuromas were multi-segment tumors. All segments of the facial nerve were represented, but 54% involved the geniculate ganglion and 45% involved the labyrinthine or tympanic portions of the nerve, or both. Depending on the extent of sensorineural hearing loss, surgical removal was performed through the middle cranial fossa or translabyrinthine approach. To obtain adequate nerve reconstruction, we combined intra- and extracranial approaches (e.g., the transmastoidal and transtemporal routes). Regardless of the type of nerve reconstruction, the best recovery achieved was moderate facial weakness (House-Brackmann Grade III) in 75% of the patients, even in a patient who was Grade IV preoperatively. The choice of treatment for facial neuromas and surgical approach depends on the extent of tumor, grade of facial palsy, and hearing function. When facial palsy is present, complete resection is clearly indicated. In patients without facial dysfunction, a conservative strategy consisting of clinical and radiological observation should be considered as a treatment option.     

A method to remove artifacts in attenuation-corrected myocardial perfusion SPECT Introduced by misalignment between emission scan and CT-derived attenuation maps.

Nonuniform soft-tissue attenuation affects the diagnostic accuracy of SPECT in myocardial perfusion imaging. The attenuation map required for attenuation correction can be acquired using x-ray tomography (CT). Frequent findings in attenuation-corrected images are defects in the apical and anterior myocardial wall. We assume that these are artifacts produced by misalignment of SPECT images and the attenuation map. METHODS: One hundred forty patients underwent myocardial perfusion imaging with 99mTc-methoxyisobutylisonitrile. Twenty-seven of 140 showed pronounced defects in the apical or anterior wall only after CT-based attenuation correction. SPECT and corresponding CT slices were examined for misalignment in the ventrodorsal direction (y-direction) visually and by threshold-based delineation of the body surface. Mismatched studies were realigned and image reconstruction and analysis were redone. The effect of the correction was assessed visually and by semiquantitative analysis based on a 20-segment model using 4D-MSPECT. RESULTS: In 15 of 27 patients, the improved coregistration led to smaller and less-pronounced defects in the regions mentioned. In 6 of 27 patients, former defects were judged as normal. No improvement was seen in only 4 patients. In these 4 subjects, the mismatch in the y-direction was <1 pixel (7 mm), and visual inspection suggested a coincident mismatch in the craniocaudal direction. In 2 cases, coregistration was not possible because the body outline extended beyond the CT field of view. Semiquantitative analysis revealed a significant increase of the relative uptake in the apex; in the apical segments of the anterior, septal, and inferior wall; and in the mid-anterior and mid-anteroseptal segment. Basal segments of the anterolateral, lateral, and inferolateral wall and the middle inferolateral segment showed a significant decrease of relative uptake. CONCLUSION: Misalignment in the y-direction between SPECT and the attenuation map can lead to artifacts in the apical, septal, and anterior wall, which will appear as defects. It also can cause overcorrection in the basal inferior and lateral segments. There is evidence that mismatches along the other directions may have a similar effect. The coregistration of SPECT and the attenuation map needs to be verified for every patient, even when using integrated dual-modality imaging devices.