RESUMEN
The association of Dilantin (hydantoin) therapy and lymphadenopathy in the form of "pseudolymphoma" or malignant lymphoma has been reported primarily in the clinical literature in single case reports or small series, most of which contain very few pathologic details. We studied a series of 25 lymph node lesions collected at the Armed Forces Institute of Pathology from 1965 to 1991 that were suspected to be related to intake of the antiseizure medication Dilantin. Each case had been coded by the Environmental and Toxicology Department according to the so-called "operational degrees of certainty," which gives the possibility that a pathologic change is the result of a drug. Of the 25 cases, six were coded as probable, 17 as possible, and two as coincidental. The male:female ratio was 11:14, and patient ages ranged from 24 to 81 years (median, 53 years). Documented lymphadenopathy developed 1 week to 30 years (median, 5 years) after the start of Dilantin. The histologic features were reviewed in 25 of 25 cases, and the immunophenotypic data was available in 18 of 25. Fifteen of 25 cases showed a benign histology, which we primarily classified according to the presence or absence of immunoblastic hyperplasia. Seven cases were non-Hodgkin's lymphoma, and three were Hodgkin's disease. In two of five cases for which sequential biopsies were available for review, there was progression from paracortical hyperplasia to malignant lymphoma. Our report describes the clinicopathologic features of 25 cases of Dilantin-associated lymphadenopathy and confirms the heterogeneity and nonspecificity of these histologic patterns.
Asunto(s)
Enfermedades Linfáticas/inducido químicamente , Enfermedades Linfáticas/patología , Fenitoína/efectos adversos , Adulto , Anciano , Femenino , Humanos , Hiperplasia/inducido químicamente , Inmunofenotipificación , Linfoma/inducido químicamente , Linfoma/patología , Masculino , Persona de Mediana EdadRESUMEN
The possibility that service in Vietnam has had an adverse effect on Vietnam veterans and is the cause of some of their current illnesses has been a controversial issue in the post-Vietnam period. Addressing this problem, a pathology study has been carried out at the Armed Forces Institute of Pathology (AFIP). Pathologic diagnoses found in Vietnam veterans have been compared with a control group of contemporary veterans without Vietnam service. This has revealed no statistically significant or unexplained differences in their demographic, anatomic, or morphologic findings. The essential similarity of their disease profiles to date fails to suggest the presence of any unique environmental factor that might have acted on the Vietnam group.
Asunto(s)
Personal Militar , Morbilidad , Ácido 2,4,5-Triclorofenoxiacético/efectos adversos , Ácido 2,4-Diclorofenoxiacético/efectos adversos , Adulto , Anciano , Agente Naranja , Defoliantes Químicos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/inducido químicamente , Neoplasias/epidemiología , Neoplasias/patología , Dibenzodioxinas Policloradas/efectos adversos , Distribución Aleatoria , Estados Unidos , VietnamRESUMEN
The clinical and pathological findings in 22 women with a distinctive hemorrhagic cellular (HC) leiomyoma of the uterus are described. Characterized by a dense cellularity accompanied by hemorrhage and edema, 17 occurred in women taking oral contraceptives, three occurred in pregnant women, and one was found in a woman 3 days postpartum. One woman, not pregnant or taking steroids, was using hydrochlorothiazide. Recognition of this special form of leiomyoma associated with the use of reproductive steroids is needed to avoid confusing it with leiomyosarcoma. The major differences with leiomyosarcoma are that HC leiomyomas are generally small, often multiple, and have discrete areas of hemorrhage and tearing artifact, but little or no atypia. Also, their mitotic activity is confined to a narrow zone adjacent to the hemorrhage.
PIP: A series of hemorrhagic cellular leiomyomas of the uterus, associated with oral contraceptives (17) or pregnancy (4) is described. Another woman was taking hydrochlorothiazide only. Clinical features included, most often, abnormal uterine bleeding in 18, followed by rapid enlargement to the size of a 12-14-week gestation in 9, pain in 8, and rupture of the leiomyoma in 2 women. The duration of symptoms ranged from a few hours in 7 to 16 months in 1 woman. 13 had used combined, and 1 sequential pills, ranging from 1 month to over 5 years. The size of the leiomyomas ranged from 0.7 to 11 cm, with a mean of 4.2. 6 were hemorrhagic and cystic. Microscopically they consisted of circumscribed, densely cellular proliferations of oval and spindle- shaped smooth-muscle cells with central hemorrhage and edema. 3 to 4 mitotic figures appeared per 10 high power fields in the most active areas. These leiomyomas differ from those seen in pregnancy in their cellularity, patchy hemorrhage, and edema. They differ from leiosarcomas in their smaller cells, less atypia, fewer abnormal mitotic figures, small size, multiple arrangement, multiple discrete areas of hemorrhage and discrete periphery. It is probably the progestin in the combined oral contraceptive that causes development of leiomyoma.
Asunto(s)
Anticonceptivos Orales/administración & dosificación , Leiomioma/patología , Complicaciones Neoplásicas del Embarazo/patología , Neoplasias Uterinas/patología , Adulto , Anticonceptivos Orales/efectos adversos , Diagnóstico Diferencial , Femenino , Humanos , Leiomioma/diagnóstico , Leiomioma/cirugía , Leiomiosarcoma/diagnóstico , Leiomiosarcoma/patología , Persona de Mediana Edad , Embarazo , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/cirugíaRESUMEN
Hepatic histopathology and clinical-pathologic correlations were studied in 77 patients who met clinical criteria for halothane hepatotoxicity. They were divided into groups based on the type of surgery (minor or major) and outcome (nonfatal, biopsy group or fatal, autopsy group). The two nonfatal groups (minor surgery and major surgery) and the two fatal groups (minor surgery and major surgery) were comparable with regard to age, time of onset from exposure, peak aminotransferase values and peak bilirubin determinations. A spectrum of histologic patterns was identified in these patients. It ranged from panlobular and multifocal spotty necrosis resembling viral hepatitis through submassive confluent zonal necrosis to massive necrosis. Progression of severity of injury from spotty to massive necrosis was more closely related to multiple exposures to halothane (and especially repeated exposure within less than three months), than to the extensiveness of the associated surgical procedures.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Halotano/efectos adversos , Adulto , Anciano , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Autopsia , Biopsia , Femenino , Humanos , Hepatopatías/enzimología , Hepatopatías/patología , Regeneración Hepática , Masculino , Persona de Mediana Edad , Necrosis , Factores de TiempoRESUMEN
Pathologic studies of women with fatal cerebrovascular disease who have received oral contraceptives are infrequently found in the literature. Three cases of this type are reported here. The pathologic findings included an intrinsic vascular lesion in the form of intimal hyperplasia with and without associated thrombosis, found in arteries supplying the brain. Similar vascular lesions have been reported previously in other sites of the vascular system in association with exogenous or endogenous steroids. They have also been found in other species under the influence of steroids. This hyperplasia of vessel intima may be found in association with other clinicopathologic entities, but stigmata of other diseases were not found in these three patients.
Asunto(s)
Trastornos Cerebrovasculares/patología , Anticonceptivos Orales/efectos adversos , Adulto , Encéfalo/patología , Trastornos Cerebrovasculares/inducido químicamente , Anticonceptivos Hormonales Orales/efectos adversos , Femenino , Humanos , Hiperplasia/patología , Embarazo , Trombosis/patologíaRESUMEN
Although consideral information is available concerning the structural and biochemical changes in the skeletal muscles of patients with malignant hyperthermia, little is known of the cardiac changes in this disease. However, ventricular fibrillation and cardiac arrest are frequent in these patients. In 3 patients with malignant hyperthermia, contraction bands and foci of myofiberlysis were found in the heart at necropsy. Ultrastructurally, areas of myofiber overstretching adjacent to contraction bands and foci of extensive myofiberlysis were associated with disruptions of the sarcolemma. Similar ultrastructural findings have been reported in the skeletal muscles of these patients and are thought responsible for the hyperkalemia which is a constant feature of malignant hyperthermia. Our findings suggest that the ventricular arrhythmias, frequent in this disease, are the result of direct damage to cardiac muscle rather then secondary to elevated plasma levels of potassium.
Asunto(s)
Hipertermia Maligna/patología , Miocardio/patología , Adulto , Calcio/metabolismo , Femenino , Paro Cardíaco/etiología , Humanos , Masculino , Hipertermia Maligna/complicaciones , Contracción Miocárdica , Miocardio/metabolismo , Potasio/metabolismo , Sarcolema/ultraestructura , Fibrilación Ventricular/etiologíaRESUMEN
The morphologic findings in 102 validated cases of adverse drug reactions classified in the "causative" and "probable" category are reported. All of them are well documented cases of drug associated reactions. The patterns of tissue reactions in these cases are divided into the following categories: inflammation, degeneration and infiltration, hypoplasia and aplasia, hyperplasia, necrosis, circulatory disturbances and vascular abnormalities, and teratogenesis. Degeneration and infiltration constitute the most common tissue reaction pattern present in these cases. The liver is the organ most frequently affected. Anti-infective drugs were associated with the highest number of adverse drug reactions, followed by antineoplastic drugs.
Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Adolescente , Médula Ósea/efectos de los fármacos , Células de la Médula Ósea , Edema Encefálico/inducido químicamente , Niño , Preescolar , Hígado Graso/inducido químicamente , Femenino , Hemorragia Gastrointestinal/inducido químicamente , Hiperplasia Gingival/inducido químicamente , Humanos , Hiperplasia , Lactante , Recién Nacido , Infarto/inducido químicamente , Inflamación/inducido químicamente , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Pulmón/efectos de los fármacos , Masculino , Miocardio/patología , Necrosis , Atrofia Óptica/inducido químicamente , Edema Pulmonar/inducido químicamente , Retina/efectos de los fármacos , Piel/efectos de los fármacos , Trombosis/inducido químicamente , Glándula Tiroides/efectos de los fármacosRESUMEN
A study of 827 cases of adverse drug reactions (ADRs) in which autopsies were done was carried out to determine the relative frequency of drugs that caused adverse reactions, their sites of action, and the variety of pathologic processes induced by them. Because a variety of nondrug factors played critical roles in generating many of the ADRs, these 827 cases were divided into seven groups. Only one of these groups (25% of the total) met the criteria of ADRs in the usual definitional sense and were also lethal. The validity of the diagnoses of both the ADRs and the basic diseases being treated was strengthened by the addition of morphologic findings to the data base and by the use of an analytic algorithm that was specifically developed for and directed to the evaluation of ADRs.
Asunto(s)
Quimioterapia/mortalidad , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Errores de Medicación , Medicina , Métodos , Persona de Mediana Edad , Preparaciones Farmacéuticas/administración & dosificación , Especialización , Estados UnidosRESUMEN
The evaluation of adverse drug reactions (ADR's) in clinical patients is usually a complex and multifactorial problem. A methodology for this evaluation has been derived from the experience with over 3,000 cases. Illustrative cases are presented to demonstrate in detail a variety of means of linking a drug with an ADR. Emphasis is placed on the frequent diagnostic utility of accurate time-related information, in addition to the use of historical, clinical-laboratory and morphologic findings.