Rash y anemia aplásica inducidos por fenitoína: caso clínico / Phenytoin-induced rash and aplastic anemia: case report

Rash is a common side effect associated with antiepileptic drugs. The rate of a phenytoin rash is 5.9 percent and increases to 25 percent in those with another antiepileptic drug rash. Aplastic anemia is an adquired hematopoietic stem-cell disorder characterized by pancytopenia of the peripheral blood and hypocellular bone marrow. The use of phenytoin is associated with a 3.5 fold increased risk of aplastic anemia. We report a case of a 70-year-old woman who developed two severe adverse reactions simultaneously with phenytoin: a maculopapular pruritic rash with involvement of mucous and an aplastic anemia. Both conditions normalized after phenytoin withdrawal.

El rash es un efecto secundario común asociado al uso de fármacos antiepilépticos. La frecuencia de rash con fenitoína se ha estimado en un 5,9 por ciento y asciende a un 25 por ciento en pacientes que han presentado rash con otro fármaco antiepiléptico. La anemia aplásica es una anomalía adquirida de las células madre hematopoyéticas caracterizada por pancitopenia de la sangre periférica y médula ósea hipocelular. Los pacientes tratados con fenitoína presentan un riesgo 3,5 veces mayor de desarrollar anemia aplásica. Presentamos el caso de una mujer de 70 años que desarrolló dos reacciones adversas severas y simultáneas a la fenitoína: un exantema maculopapular pruriginoso con compromiso de mucosas y una anemia aplásica. Ambas condiciones se resolvieron completamente con la suspensión del fármaco.

Atrofia cerebelosa por el virus JC en un paciente con SIDA / Cerebellar atrophy by the JC virus in a patient with AIDS

The progressive multifocal leukoencephalopathy (PML) is a demyelinating CNS disease, characterized by lysis of injected oligodendrocytes by JC virus (JCV). Immunodeficiency is a predisposing factor for acquiring the disease and at least 5 percent of AIDS patients may develop PML. Among patients infected with HIV has also been described the lysis of the granullar cells of the cerebellum and cerebellar atrophy, attributed to a variant of the JCV. We present 37 years old HIV infected men, with postural dizziness, followed by gait disturbances, and a cerebellar syndrome, scanned speech, hyperreflexia, pendular reflexes, Babinski sign and mild cognitive impairment were present. Brain MRI showed hyperintense areas of the white matter in the cerebral hemispheres, thalamus and brainstem, associated with incipient atrophy of the cerebellum. The CSF was normal except for the PCR positive for the JCV. The patient received antiretroviral therapy. A second MRI, eight months later, showed a slightly increase in lesions of the cerebral hemispheres, and the left cerebellar hemisphere, but had developed a marked cerebellar atrophy. After two years, the patient remained with a serious cerebellar syndrome. That in association with the slow course of the disease and the particular cerebellar lesions, are suggestive of a mixed JCV infection of both, the typical and mutant type, in this patient. This is the first case of cerebellar atrophy by the JCV reported in the Chilean literature.

La leucoencefalopatía multifocal progresiva es un proceso desmielinizante del SNC, que se caracteriza por la lisis de los oligodendrocitos infectados por el virus JC. La inmunodeficiencia es un factor predisponente para adquirir la enfermedad y al menos el 5 por ciento de los pacientes con SIDA pueden desarrollar una LMP. Entre pacientes infectados con VIH también se ha descrito una lisis de las células granulosas del cerebelo y atrofia cerebelosa, atribuida a una variante del virus JC. Se presenta un hombre de 37 años portador de VIH, que consulta por vértigos posturales, seguidos de alteraciones de la marcha y un síndrome cerebeloso, palabra escandida, hiperreflexia, reflejos pendulares, Babinski y un leve deterioro cognitivo. La RM cerebral mostró áreas de hiperintensidad en T2 de la substancia blanca en los hemisferios cerebrales, en los tálamos y en estructuras bulbo-protuberanciales, asociadas a una atrofia incipiente del cerebelo. El LCR era normal, salvo la PCR positiva para el VJC. El paciente estaba con terapia antiretroviral que se mantuvo. Una segunda RM, ocho meses después, mostró leve aumento de las lesiones de los hemisferios cerebrales, de la protuberancia y del hemisferio cerebeloso izquierdo, pero se había incrementado la atrofia de la corteza cerebelosa. Después de dos años, el paciente ha mantenido el síndrome cerebeloso, que unido a la detención clínica de la enfermedad y a la atrofia del cerebelo, sugieren que este paciente pudiera tener una doble infección por VJC tanto de la variedad típica como de la mutante. Este sería el primer caso de atrofia cerebelosa por el VJC pesquisado en Chile.

[Fusion of SPECT with computed tomography or magnetic resonance for the interpretation of abnormal tracer uptake]. / Utilidad clínica de la fusión SPECT/CT con marcadores externos en patología oncológica.

BACKGROUND: Interpretation of abnormal foci with high tracer uptake may require morphological correlation. Fusion of functional images obtained by single photon emission computed tomography (SPECT) and anatomical images obtained by computed tomography (CT) or magnetic resonance (RM) allows an integrated comprehension of complementary information. AIM: To demonstrate that SPECT/CT fusion with external markers is useful in clinical practice to clarify the location and pathological meaning of questionable foci. MATERIAL AND METHODS: Thirty four pairs of images from separate equipments (31 SPECT/CT and 3 SPECT/RM) pertaining to 29 patients, were fused. Fifty one foci of abnormal tracer uptake of uncertain pathological meaning were analyzed. These were classified before and after the fusion as probably malignant or probably benign. RESULTS: Seventy percent of patients had a differentiated thyroid carcinoma. The fusion localized 100% of foci. Nine percent had a normal and 26% an abnormal anatomy. Before fusion 82% of foci were classified as potentially malignant. This figure changed to 59% after the fusion (p <0.01). Therefore the suspicion of malignancy was presumptively confirmed in 72% of foci and fusion results would have reached a 27% of incremental diagnostic value in 14 cases that changed of category (11 with differentiated thyroid carcinoma, one with colorectal cancer, one with a nasal Ewing sarcoma and one with a brain tumor). CONCLUSIONS: The fusion of SPECT and CT is useful in selected patients, specially those with differentiated thyroid carcinoma. The fusion of SPECT and RM is also feasible.

Utilidad clínica de la fusión SPECT/CT con marcadores externos en patología oncológica / Fusion of SPECT with computed tomography or magnetic resonance for the interpretation of abnormal tracer uptake

Background: Interpretation of abnormal foci with high tracer uptake may require morphological correlation. Fusion of functional images obtained by single photon emission computed tomography (SPECT) and anatomical images obtained by computed tomography (CT) or magnetic resonance (RM) allows an integrated comprehension of complementary information. Aim To demonstrate that SPECT/CT fusion with external markers is useful in clinical practice to clarify the location and pathological meaning of questionable foci. Material and methods: Thirty four pairs of images from separate equipments (31 SPECT/CT and 3 SPECT/RM) pertaining to 29 patients, were fused. Fifty one foci of abnormal tracer uptake of uncertain pathological meaning were analyzed. These were classified before and after the fusion as probably malignant or probably benign. Results: Seventy percent of patients had a differentiated thyroid carcinoma. The fusion localized 100 percent of foci. Nine percent had a normal and 26 percent an abnormal anatomy. Before fusion 82 percent of foci were classified as potentially malignant. This figure changed to 59 percent after the fusion (p <0.01). Therefore the suspicion of malignancy was presumptively confirmed in 72 percent of foci and fusion results would have reached a 27 percent of incremental diagnostic value in 14 cases that changed of category (11 with differentiated thyroid carcinoma, one with colorectal cancer, one with a nasalEwingsarcoma and one with a brain tumor). Conclusions: The fusion of SPECT and CT is useful in selected patients, specially those with differentiated thyroid carcinoma. The fusion of SPECT and RM is also feasible.

Diagnóstico de Muerte / The diagnosis of death

This paper undertakes an analysis of the scientific criteria used in the diagnosis of death and underscores the importance of intellectual rigor in the definition of medical concepts, particularly regarding such a critical issue as the diagnosis of death. Under the cardiorespiratory criterion, death is defined as ½the irreversible cessation of the functioning of an organism as a whole¼ and the tests used to confirm this criterion (negative life-signs) are sensitive and specific. In this case, cadaverous phenomena appear immediately following the diagnosis of death. On the other hand, doubts have arisen concerning the theoretical and the inner consistency of the criterion of brain death, since it does not satisfy the definition of ½the irreversible cessation of the functioning of an organism as a whole¼, nor the requirement of ½total and irreversible cessation of all functions of the entire brain, including the brain stem¼. There is evidence to the effect that the tests used to confirm this criterion are not specific enough. It is clear that brain death marks the beginning of a process that eventually ends in death, though death does not occur at that moment. From an ethical point of view, the conflict arises between the need to provide an unequivocal diagnosis of death and the possibility of saving a life through organ transplantation. The sensitive issue of brain death calls for a more thorough and in-depth discussion among physicians and the community at large (Rev Méd Chile 2004; 132: 95-107).

The alien hand syndrome: classification of forms reported and discussion of a new condition.

The term "alien hand" refers to a variety of clinical conditions whose common characteristic is the uncontrolled behavior or the feeling of strangeness of one extremity, most commonly the left hand. A common classification distinguishes between the posterior or sensory form of the alien hand, and the anterior or motor form of this condition. However, there are inconsistencies, such as the phenomenon of diagonistic dyspraxia, which is largely a motor syndrome despite being more frequently associated with posterior callosal lesions. We discuss critically the existing nomenclature and we also describe a case recently reported by us which does not fit any previously reported condition, termed agonistic dyspraxia. We propose that the cases of alien hand described in the literature can be classified into at least five broad categories: (i) diagonistic dyspraxia and related syndromes, (ii) alien hand, (iii) way-ward hand and related syndromes, (iv) supernumerary hands and (v) agonistic dyspraxia.

[Ethical problems in the biomedical research projects, presented to the Ethical Committee of the Medical School at the Pontificia Universidad Católica of Chile]. / Problemas éticos en los proyectos de investigación biomédica, presentados al Comité de Etica de la Escuela de Medicina de la Pontificia Universidad Católica de Chile.

BACKGROUND: The higher methodological complexity of either diagnostic or therapeutic procedures has raised concern about the ethical principles that should underlie the conduct of biomedical research involving humans. AIM: To evaluate ethical problems of research proposals submitted to an ethics committee. MATERIAL AND METHODS: All research proposals involving humans, submitted within a two years period to the ethics committee of the School of Medicine of the Catholic University, were retrospectively reviewed. "Ethical problem" was defined as any explicit disagreement with the ethical principles and guidelines for the protection of human subjects involved in biomedical research, according to the Helsinki declaration. RESULTS: In 20 of 44 reviewed projects, an ethical problem was identified. The most common problems were the absence or inadequacy of the informed consent, the justification of the use of placebo and problems related to the methodological aspects of the research, particularly the lack of an adequate control group when the potential benefits of a new drug were evaluated. CONCLUSIONS: According to the Nüremberg code, the Helsinki declaration and the International Principle of Ethics in Biomedical Research, we analyse ethical problems and suggest judgement elements for them.

[Ethical features related to clinical decisions in neonatology. Preliminary study]. / Aspectos éticos relacionados con las decisiones clínicas en neonatología. Estudio preliminar.

BACKGROUND: Personnel working in neonatal intensive care units frequently face difficult ethical problems related to the initiation, maintenance or withdrawal of life support therapies. AIM: To assess the importance of ethical issues in the clinical decision making of health care providers in neonatal intensive care units. MATERIAL AND METHODS: A questionnaire based on five clinical vignettes that assessed judgments about quality of life, impact of parent's opinions and decision making in emergency situations and with different degrees of certainty, was designed. Eleven neonatologists and 20 nurses and midwives specialized in neonatology anonymously answered this questionnaire. RESULTS: There was a great inter individual variability in therapeutic approaches in cases with a bad vital and neurological prognosis. In cases of medical emergencies with uncertain diagnoses, bad vital prognosis but neurological indemnity, most professionals coincided in delivering all possible therapeutic options. Parent's opinions had a great impact in medical decisions, except when there was neurological indemnity. CONCLUSIONS: The specific responsibilities of the different agents in medical decision making must be delimited. Parents do not have absolute rights over their offspring and physicians must reject useless therapies.

[Ethical and clinical decisions in a terminally ill cancer patient with metastatic cancer. The problem of euthanasia]. / Decisiones etico-clínicas en el caso de un paciente terminal con cáncer metastásico. El problema de la eutanasia.

The easiness of medical technology to prolong life in patients with severe cognitive or biological deterioration, the existence of cultural tendencies that underscore the importance of patient's self determination and economical considerations have posed the problem of euthanasia among patients, their families, society and medical teams. A propos of an exemplary patient, the ethical principles that allow the distinction between passive euthanasia and withdrawal of life support measures are analyzed. The analysis of active euthanasia, leads to the conclusion that it is not compatible with the ethical principles that classically have inspired medical actions.

Orden de no resucitar / Do not resuscitate orders

Con el propósito de ilustrar y comentar los principios involucrados en la decisión de formular y la aplicación de órdenes de no reanimar, se describe el caso de una paciente de 14 meses de edad, nacida prematuramente de padres consanguíneos, con encefalopatías hipóxica isquémica, daño cerebral severo, parálisis cerebral, grave desnutrición, retraso del crecimiento, neumonia de aspiración reiterada, neumonia en evolución e insuficiencia respiratoria. Presentada al comité de ética de un hospital pediátrico de Santiago metropolitano, éste recomendó no emplear respirador mecánico y no reanimar, conductas que fueron respetadas en la paciente, que falleció dos días después. Los fundamentos de esta decisión se encuentran en los principios de beneficiencia, proporcionalidad del tratamiento para los resultados esperados, justicia y autonomía de esta decisión, que debe distinguirse de la eutanasia pasiva, en la que se omiten acciones con la intención de acelerar la muerte del paciente, por la diferente intencionalidad con que se aplica

Decisiones ético-clínicas en el caso de un paciente terminal con cáncer metastásico: el problema de la eutanasia / Ethical and clinical decisions in a terminal patient with metastasic cancer: the euthanasia problem

The easiness of medical technology to prolong life in patients with severe cognitive or biological deterioration, the existence of cultural tendencies that underscore the importance of patient's self determination and economical considerations have posed the problem of euthanasia among patients, their families, society and medical teams. A propos of an exemplary patient, the ethical principles that allow the distinction between passive euthanasia and with drawal of life support measures ane analysed. The analysis of active euthanasia, leads to the conclusion that it is not comptible with the ethical principles that classically have inspired medical actions

[Clinical and legal aspects of brain death criteria: evaluation of the degree of knowledge of neurologists and neurosurgeons]. / Aspectos clínicos y legales de los criterios de muerte cerebral: evaluación de su grado de conocimiento por neurólogos y neurocirujanos.

The level of knowledge of clinical and legal aspects of brain death criteria was tested in 25 neurologists and 15 neurosurgeons. The answers were wrong or the questionnaire had not been responded in 36.9% of the cases. The highest percentage of mistakes concerned the apnea test and what Chilean law said regarding brain death. No differences were found between neurologists and neurosurgeons. Physicians with less than 10 years were better informed than those with more than 10 years of medical practice (p < 0.005). Although brain death as a criterion of death is accepted by Chilean law in order to donate organs for transplantation, a considerable percentage of physicians (30%) rejected this concept. The significant lack of knowledge found in this study may suggest that brain death diagnosis is being inadequately performed in many cases. This fact raises important medical, ethical and legal considerations.

[Lymphomatoid granulomatosis: a clinical case]. / Granulomatosis linfomatoidea: caso clínico.

A 49 year old woman with a fluctuating painful ophthalmoplegia and a history of polyarthralgia is reported. On examination, additional findings included a maxillary subcutaneous infiltration, sphenoidal sinusitis and pulmonary nodes. Lung and sinus biopsy demonstrated findings compatible with lymphomatoid granulomatosis. The patient was treated with prednisone and cyclophosphamide, with good response of neurological and dermatological findings.

Inhibition in carotid body chemoreceptors mediated by D-2 dopaminoceptors: antagonism by benzamides.

Inhibition of chemosensory nerve impulses in the cat is evoked by dopamine (DA) applied to carotid body chemoreceptors. Pharmacological characterization of the dopaminoceptors involved in this action was determined through their blockade with benzamides, selective antagonists of D-2 receptors. Both metoclopramide and sulpiride were effective blockers of DA-induced chemosensory inhibition. Furthermore, both drugs induced an immediate increase in the frequency of carotid nerve chemosensory impulses, suggesting the presence of previous tonic inhibition of chemoreceptor discharges by endogenous DA released from glomus cells.

Cardiovascular responses to hypoxia in the spontaneously breathing cat: reflexes originating from carotid and aortic bodies.

The heart rate (fH) and systemic arterial pressure (Pa) responses to transient anoxemic and cytotoxic hypoxia were studied in 18 pentobarbitone-anesthetized, spontaneously breathing cats, by applying N2 tests and i.v. injections of NaCN. Hyperventilation was accompanied by short-latency increases in Pa and fH; they persisted after bilateral vagotomy, sparing the aortic nerves. Acute section of carotid or aortic nerves in different sequences reduced both fH and Pa responses, the contribution of both pairs of nerves being similar. The recording of carotid chemosensory discharges showed transient stimulus-dependent increases in their frequency, to which the ensuing fH and Pa rises were correlated. After sectioning the four buffer nerves, hypoxia provoked long-lasting hypotension and bradycardia. Tachycardia was also observed in response to hypoxia in 4 out of 6 chloralose-anesthetized spontaneously breathing cats, the other two presenting bradycardia. The direction of these cyanide-induced changes in fH was not modified by bilateral vagotomy. It is concluded that tachycardia and hypertension in response to hypoxia are not vagally-mediated consequences of hyperventilation.