RESUMEN
OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy data, and adverse effects of olanzapine as a treatment for schizophrenia and to determine the advantages and disadvantages of this atypical antipsychotic agent compared with currently marketed agents. DATA SOURCES: A MEDLINE computer literature search was conducted to retrieve all English-language studies and review articles involving olanzapine published as of October 1, 1996. The manufacturer of the drug, Eli Lilly and Company, provided the clinical investigator's brochure and abstracts of unpublished Phase III clinical trials. STUDY SELECTION: Animal studies evaluating the pharmacology of olanzapine were evaluated, as were all open-label and double-blind studies involving the evaluation of olanzapine for the treatment of patients with schizophrenia. DATA EXTRACTION: All available clinical studies were reviewed and the interpretation of data for each study was influenced by the size of the study sample, the nature of the inclusion and exclusion criteria, and the data analysis techniques used. DATA SYNTHESIS: Olanzapine is a thienobenzodiazepine analog with an in vitro receptor affinity profile similar to that of clozapine. Olanzapine exhibits linear kinetics over the dosage range studied and is extensively metabolized in humans. Clinical evaluations to date have shown olanzapine to be at least as efficacious as typical antipsychotic agents in the treatment of the acute phase of schizophrenia. The drug was well tolerated, with significantly fewer extrapyramidal adverse effects than haloperidol. Current data suggest that olanzapine may be more effective than haloperidol for the treatment of negative symptoms; moreover, preliminary data suggest that fewer relapses occur over the course of treatment in patients treated with olanzapine compared with those taking haloperidol. CONCLUSIONS: The exact place of olanzapine in the therapy of psychotic patients remains unclear, as more data are needed to evaluate the long-term efficacy of this agent, its impact on negative symptoms, and its potential use in patients resistant to the standard agents. Despite limitations in the current database, olanzapine is a promising treatment option for patients with schizophrenia.
Asunto(s)
Antipsicóticos/uso terapéutico , Pirenzepina/análogos & derivados , Esquizofrenia/tratamiento farmacológico , Anciano , Animales , Antipsicóticos/farmacocinética , Antipsicóticos/farmacología , Benzodiazepinas , Niño , Ensayos Clínicos como Asunto , Humanos , Olanzapina , Pirenzepina/farmacocinética , Pirenzepina/farmacología , Pirenzepina/uso terapéuticoRESUMEN
Olanzapine is a potential new "atypical" antipsychotic agent. This double-blind, acute phase study compared two doses of olanzapine [1 mg/day (Olz1.0); 10 mg/day (Olz10.0)] with placebo in the treatment of 152 patients who met the DSM-III-R criteria for schizophrenia and had a Brief Psychiatric Rating Scale (BPRS)-total score (items scored 0-6) > or = 24. In overall symptomatology improvement [BPRS-total score and Positive and Negative Syndrome Scale (PANSS)-total score], Olz10.0 was statistically significantly superior to placebo. In positive symptom improvement (PANSS-positive score, BPRS-positive score), Olz10.0 was statistically significantly superior to placebo. In negative symptom improvement (PANSS-negative score), Olz10.0 was statistically superior to placebo. Olz 1.0 was clinically comparable to placebo in all efficacy comparisons. The only adverse event to show an overall statistically significant incidence difference was anorexia (reported for 10% of placebo-treated and 0% of Olz10.0-treated patients). The Olz10.0-treated patients improved over baseline with respect to parkinsonian and akathisia symptoms, and these changes were comparable with those observed with placebo. There were no dystonias associated with Olz10.0 treatment. At endpoint, the incidence of patients with elevated prolactin values did not differ statistically significantly between placebo-treated and Olz10.0-treated patients. Olanzapine appears to be not only safe and effective, but a promising atypical antipsychotic candidate.
Asunto(s)
Antipsicóticos/uso terapéutico , Pirenzepina/análogos & derivados , Esquizofrenia/tratamiento farmacológico , Adulto , Benzodiazepinas , Método Doble Ciego , Femenino , Humanos , Masculino , Olanzapina , Pirenzepina/administración & dosificación , Pirenzepina/uso terapéuticoRESUMEN
Olanzapine is a potential new "atypical" antipsychotic agent. The double-blind acute phase of this study compared three dosage ranges of olanzapine (5 +/- 2.5 mg/day [Olz-L], 10 +/- 2.5 mg/day [Olz-M], 15 +/- 2.5 mg/day [Olz-H]) to a dosage range of haloperidol (15 +/- 5 mg/day [Hal]) and to placebo in the treatment of 335 patients who met the DSM-III-R criteria for schizophrenia. In overall symptomatology improvement (Brief Psychiatric Rating Scale [BPRS]-total), Olz-M, Olz-H, and Hal were significantly superior to placebo. In positive symptom improvement (BPRS-positive), Olz-M, Olz-H, and Hal were comparable and significantly superior to placebo. In negative symptom improvement (Scale for the Assessment of Negative Symptoms [SANS]-composite), Olz-L and Olz-H were significantly superior to placebo and Olz-H was also significantly superior to Hal. The most common treatment-emergent adverse events included somnolence, agitation, asthenia, and nervousness. No acute dystonia was observed with olanzapine. Treatment-emergent parkinsonism occurred with Olz-H at approximately one-third the rate of Hal, and akathisia occurred with Olz-H at approximately one-half the rate of Hal. Prolactin elevations associated with olanzapine were not significantly greater than those observed with placebo and were also significantly less than those seen with haloperidol.
Asunto(s)
Antipsicóticos/uso terapéutico , Haloperidol/uso terapéutico , Pirenzepina/análogos & derivados , Esquizofrenia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Acatisia Inducida por Medicamentos/epidemiología , Antipsicóticos/administración & dosificación , Antipsicóticos/efectos adversos , Benzodiazepinas , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Discinesia Inducida por Medicamentos/epidemiología , Femenino , Haloperidol/administración & dosificación , Haloperidol/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Olanzapina , Pirenzepina/administración & dosificación , Pirenzepina/efectos adversos , Pirenzepina/uso terapéutico , Escalas de Valoración PsiquiátricaRESUMEN
Fluoxetine is an efficacious, nonsedative antidepressant, but its selective efficacy on symptoms of insomnia has not been thoroughly explored. In this analysis, the effects of fluoxetine versus placebo on symptoms of insomnia were evaluated in three clinical subgroups: patients with baseline sleep disturbance, melancholia, or reduced rapid eye movement (REM) latency. Eighty-nine outpatients with major depression completed 2 nights of polysomnography (PSG) and were randomized to fluoxetine or placebo. Within each subgroup of patients, fluoxetine was statistically significantly more effective than placebo in improving non-sleep Hamilton Rating Scale for Depression (HAM-D) items (HAM-D-17 total minus scores from Items 4, 5, and 6). Numerical improvement in HAM-D sleep total (sum of HAM-D Items 4, 5, and 6) was also seen for fluoxetine versus placebo. Fluoxetine did not exacerbate sleep disturbance either at Week 1 or at endpoint. These findings suggest that fluoxetine is an effective antidepressant in patients with baseline sleep disturbance, melancholia, and reduced REM latency.
Asunto(s)
Fluoxetina/uso terapéutico , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Adolescente , Adulto , Depresión/tratamiento farmacológico , Trastorno Depresivo/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Efecto Placebo , Escalas de Valoración Psiquiátrica , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Sueño REM/efectos de los fármacos , Resultado del TratamientoRESUMEN
[11C]Dapoxetine.HCl, S-(+)-N,N-dimethyl-a-[2-(naphthalenyloxy)ethyl] benzenemethanamine hydrochloride, a potent serotonin re-uptake inhibitor was prepared from its mono-methyl precursor, S-(+)-N-methyl-a-[2-(naphthalenyloxy)ethyl]benzene methanamine hydrochloride. Biodistribution was determined in rats at 5, 30 and 60 min after injection and preliminary PET studies were performed in a Rhesus monkey. 11CH3I was bubbled into a solution of S-(+)-N-methyl-alpha-[2-(naphthalenyloxy)ethyl]benzene methanamine hydrochloride (3.0 mg in DMSO) and the mixture was heated at 110 degrees C for 8 min. [11C]Dapoxetine.HCl was purified by HPLC on a C18 cartridge eluted with MeOH:phosphate buffer, pH 7,2 (75:25) with a 10% yield (end of synthesis). The time required for the synthesis was 40 min, from the end of bombardment. Radiochemical purity of the final product was > 99% and specific activity was routinely > 400 mCi/mumol [EOS]. In the biodistribution studies the highest concentration (%ID/g +/- SEM) of dapoxetine.HCl was detected in lung: 4.56 +/- 0.27 (5 min), 1.28 +/- 0.18 (30 min) and 0.67 +/- 0.04 (60 min). Brain accumulation was 0.76 +/- 0.02 (5 min), 0.46 +/- 0.04 (30 min) and 0.27 +/- 0.01 (60 min). Preliminary PET studies demonstrated significant displaceable binding in the cerebral cortex and subcortical grey matter. These results demonstrate that [11C]dapoxetine.HCl can be prepared in high purity and may be useful for the in vivo evaluation of serotonin re-uptake mechanisms.
Asunto(s)
Antidepresivos/síntesis química , Antidepresivos/farmacocinética , Bencilaminas/síntesis química , Bencilaminas/farmacocinética , Radioisótopos de Carbono/química , Naftalenos/síntesis química , Naftalenos/farmacocinética , Inhibidores Selectivos de la Recaptación de Serotonina/síntesis química , Inhibidores Selectivos de la Recaptación de Serotonina/farmacocinética , Animales , Femenino , Marcaje Isotópico , Macaca mulatta , Masculino , Ratas , Ratas Sprague-Dawley , Distribución Tisular , Tomografía Computarizada de EmisiónRESUMEN
Sulofenur (LY186641), a diarylsulfonylurea, was evaluated clinically utilizing either a daily x 21 schedule or a daily x 5 (with 2 days off) for 3 weeks schedule. Eighteen patients with refractory solid tumors received 47 evaluable courses of sulofenur given p.o. daily x 21 every 28 days at five dose levels while 14 received 29 courses of sulofenur given daily x 5 for 3 weeks every 28 days at three dose levels. Toxicities included anemia, methemoglobinemia and hemolysis. One patient experienced a fatal subendocardial infarction on the daily x 21 schedule. One partial response was observed in a patient with a sertoli cell tumor on the daily x 5 for 3 weeks schedule. Daily x 5 for 3 weeks is the schedule recommended for phase II trials.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Compuestos de Sulfonilurea/uso terapéutico , Administración Oral , Anemia/inducido químicamente , Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Cromatografía Líquida de Alta Presión , Esquema de Medicación , Femenino , Hemólisis/efectos de los fármacos , Humanos , Masculino , Metahemoglobinemia/inducido químicamente , Persona de Mediana Edad , Compuestos de Sulfonilurea/efectos adversos , Compuestos de Sulfonilurea/farmacocinéticaAsunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Esquema de Medicación , Femenino , Fiebre/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , GemcitabinaRESUMEN
A novel deoxycytidine analog, gemcitabine (2',2'-difluorodeoxycytidine [dFdC]), has been studied in a phase I clinical and pharmacology trial. Doses ranging from 10 to 1,000 mg/m2 were administered over 30 minutes weekly times 3 weeks every 4 weeks. The maximum-tolerated dose (MTD) was 790 mg/m2. The dose-limiting toxicity was myelosuppression, with thrombocytopenia and anemia quantitatively more important than granulocytopenia. Nonhematologic toxicity was minimal. Two responses in patients with adenocarcinomas of the colon and lung were documented. The maximum dFdC plasma concentration, reached after 15 minutes of infusion, was proportional to the total dose administered. Elimination, due mainly to deamination, was rapid (terminal half-life [t1/2], 8.0 minutes) and dose independent. The deamination product 2',2'-difluorodeoxyuridine (dFdU) was eliminated with biphasic kinetics characterized by a long terminal phase (t1/2, 14 hours); it was the sole metabolite detected in urine. The concentration of dFdC 5'-triphosphate in circulating mononuclear cells increased in proportion to the dFdC dose at infusions between 35 and 250 mg/m2. No further increment in dFdC 5'-triphosphate (dFdCTP) was observed at higher doses, which resulted in plasma dFdC concentrations greater than 20 mumol/L (350 to 1,000 mg/m2), suggesting saturation of dFdC 5'-phosphate accumulation. The recommended dose for phase II clinical trials in solid tumors is 790 mg/m2/wk.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Desoxicitidina/análogos & derivados , Neoplasias/tratamiento farmacológico , Adulto , Anciano , Antimetabolitos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/farmacocinética , Desoxicitidina/efectos adversos , Desoxicitidina/farmacocinética , Desoxicitidina/uso terapéutico , Evaluación de Medicamentos , Semivida , Humanos , Tasa de Depuración Metabólica , Persona de Mediana Edad , GemcitabinaRESUMEN
Vinzolidine (VZL) is a semisynthetic vinca alkaloid with broad antitumor activity in animal models of malignancy but had unpredictable toxic effects when given orally to humans. To minimize the toxic effects due to potential erratic gastrointestinal absorption, this drug was restudied in man as an intravenous preparation given as a rapid injection every two weeks. The maximum tolerated dose (MTD) on this schedule was 9.0 mg/m2 with unpredictable leukopenia (usually occurring 5-14 days post treatment but appearing erratically), constipation, paralytic ileus, and inappropriate ADH syndrome as major toxicities. Nonhematologic toxicities were dose-limiting. Repetitive dosing at two week intervals was associated with leukopenia at D 14-15 in some but not all patients treated above 5.0 mg/m2 precluding further treatment on schedule. In contrast, the oral MTD of this agent in our prior studies was 45 mg/m2 with no evidence of delayed leukopenia. Intrapatient variability of toxicity was small; interpatient variability of toxicity was substantial and did not correlate with prior therapy. Because of the presence of delayed hematologic toxicity on repetitive dosing schedules, intravenous VZL should be given on a dosing schedule longer than 14 days. No antitumor activity was seen in this study.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Alcaloides de la Vinca/uso terapéutico , Adulto , Anciano , Antineoplásicos Fitogénicos/administración & dosificación , Esquema de Medicación , Evaluación de Medicamentos , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Alcaloides de la Vinca/administración & dosificaciónRESUMEN
The metabolism and disposition of LY186641, a diarylsulfonylurea with antineoplastic activity identified in preclinical tests, was determined in 21 patients who received 23 courses of orally administered drug. A linear correlation was found between the dose of drug administered and LY186641 peak plasma concentrations and LY186641 area under the curve measurements. Clearance (135 +/- 36 ml/h/m2), terminal half-life (31 +/- 11 h), and volume of distribution (10.2 +/- 2.8 liters) were independent of drug dose. No LY186641 was excreted in urine. Hydroxy and keto metabolites of LY186641 were identified in plasma and urine samples. Urinary excretion of these metabolites during the initial 48 h following drug administration accounted for 20% of LY186641 disposition. Plasma half-life of the hydroxy and keto metabolites was longer than that of parent drug (3.3 and 3.1 days, respectively). Plasma concentrations of parent drug correlated with the presence of methemoglobinemia, the dose-limiting toxicity found with LY186641.
Asunto(s)
Neoplasias/metabolismo , Compuestos de Sulfonilurea/farmacocinética , Administración Oral , Semivida , Humanos , Metahemoglobinemia/inducido químicamente , Compuestos de Sulfonilurea/administración & dosificación , Compuestos de Sulfonilurea/efectos adversos , Compuestos de Sulfonilurea/sangre , Factores de TiempoRESUMEN
The semi-synthetic vinca alkaloid vinzolidine was administered to advanced cancer patients as an intravenous bolus on a three day schedule every 21 days. Forty-two patients were treated in this phase I trial. Five partial remissions (breast--1, melanoma--2, renal cancer--2) were seen in 30 evaluable patients. The dose limiting toxicities were myelosuppression and neuropathy. Erratic myelosuppression from course to course within the same patient as seen in previous trials with oral vinzolidine, was not observed with the intravenous formulation. The measured pharmacokinetic parameters conformed best to a 2-compartment model with a mean terminal half-life of 23 hours. The anti-tumor activity observed during this phase I trial and acceptable toxicity provide the basis for initiating phase II studies in selected forms of cancer.
Asunto(s)
Antineoplásicos/uso terapéutico , Alcaloides de la Vinca/uso terapéutico , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Antineoplásicos/toxicidad , Evaluación de Medicamentos , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Alcaloides de la Vinca/administración & dosificación , Alcaloides de la Vinca/farmacocinética , Alcaloides de la Vinca/toxicidadRESUMEN
LY186641 (diarylsulfonylurea, [DSU]) is a novel anticancer agent because of its unique diarylsulfonylurea chemical structure, broad-spectrum antisolid-tumor activity in preclinical models, presumed novel mechanism of action and preclinical toxicities of methemoglobinemia (Met Hgb) and decreased red blood cell (RBC) survival. In this study, the in vitro drug sensitivity of human tumors as well as clinical pharmacology and toxicology of DSU in patients with cancer were examined. DSU was administered orally, daily for 7 days with a 3-week treatment cycle. Dose-limiting toxicities were Met Hgb and RBC hemolysis. The maximum-tolerated dose was found to be 1,200 mg/m2/d for 7 days. In pharmacokinetic studies, DSU was found to have a prolonged serum half-life (approximately 30 hours) and a large area under the plasma disappearance curve (8,883.3 micrograms.hr/mL at 1,200 mg/m2/d). A partial remission was observed in one patient with refractory ovarian cancer. In conclusion, DSU can be safely administered to cancer patients and does display antitumor activity. Potential means of obviating the toxicities of this compound are discussed.
Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias/tratamiento farmacológico , Compuestos de Sulfonilurea/administración & dosificación , Adulto , Anciano , Antineoplásicos/farmacocinética , Relación Dosis-Respuesta a Droga , Evaluación de Medicamentos , Humanos , Persona de Mediana Edad , Compuestos de Sulfonilurea/farmacocinética , Ensayo de Tumor de Célula MadreRESUMEN
Between February 1987 and July 1988, 45 patients with advanced refractory cancer were treated with LY186641, a diarylsulfonylurea that has shown a broad spectrum of activity in preclinical testing. Patients received a weekly p.o. dose of LY186641 for 6 consecutive weeks; responding and stable patients continued weekly therapy until progression occurred. Using a standard phase I study design, the first three patients received LY186641 at 30 mg/m2 week; the dose was escalated in subsequent patients until dose-limiting toxicity occurred. Methemoglobinemia was the major toxicity observed and was dose related. Methemoglobin levels peaked approximately 24 h after LY186641 was administered and fell to low levels after 48 h. Six patients developed fatigue, cyanosis, and dyspnea associated with serum methemoglobinemia levels of greater than 20%; four of these patients were subsequently removed from the study. Hemolytic anemia was also observed but was clinically significant in only 10 patients. Other side effects were mild and infrequent. The maximum tolerated dose of LY186641, when given at this schedule, was 2550 mg/m2/week. No objective tumor responses were observed.
Asunto(s)
Antineoplásicos/efectos adversos , Neoplasias/tratamiento farmacológico , Compuestos de Sulfonilurea/efectos adversos , Evaluación de Medicamentos , Femenino , Humanos , Masculino , Metahemoglobinemia/inducido químicamente , Persona de Mediana Edad , Compuestos de Sulfonilurea/farmacocinética , Compuestos de Sulfonilurea/uso terapéutico , Factores de TiempoRESUMEN
Two indium-111 labeled anti-melanoma murine monoclonal antibodies (MAb), 96.5 and ZME-018, each recognizing separate antigens on melanoma cells, were administered intravenously to 17 patients with melanoma in a sequential fashion to determine whether: 1) additional tumor sites could be imaged with the combination compared to a single Mab; 2) the first MAb influenced the biodistribution and tumor localization of the second; and 3) significantly toxicity occurred with the combination. Patients were randomized to receive either 96.5, followed by ZME-018, ZME-018 followed by 96.5, or each MAb followed by itself (controls). Infusions of the second MAb occurred 10 days after the first infusion. Gamma camera images were obtained 72 hours after each antibody infusion. There were 139 known metastatic sites of which 72 lesions were localized by either MAb for an overall sensitivity of 52%. The detection rate was higher when lesions only greater than 1.5 cm were considered. Imaging results were independent of MAb administration sequence. When ZME-018 was given as the first infusion, when ZME-018 was given as a second infusion (p = NS). However, mean sensitivities using 96.5 as the first or second infusion were 48% and 66% respectively (p = NS). There was not a significant number of sites detected by MAb 2 that were missed by MAb 1. Human anti-murine antibody (HAMA) response occurred in seven of eight patients studied; two patients who experienced toxicity had levels of HAMA greater than 2000 ng/ml. We conclude that the use of these two murine anti-melanoma monoclonal antibodies given in sequential fashion did not significantly change the imaging sensitivity from that seen with each individual antibody. Moreover, with the exception of one patient, mean plasma half-life of the MAb did not change significantly, suggesting that overall clearance mechanisms were not saturated by the consecutive doses of monoclonal antibody or significantly altered by the presence of HAMA.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Radioisótopos de Indio/administración & dosificación , Melanoma/secundario , Adulto , Ensayos Clínicos como Asunto , Femenino , Humanos , Masculino , Melanoma/diagnóstico por imagen , Persona de Mediana Edad , Cintigrafía , Distribución AleatoriaRESUMEN
A rare case of extensive dermal uptake of Tc-99m MDP associated with renal failure is reported. The mechanism of Tc-99m MDP uptake in such examples of metastatic calcification is not proved, but may relate to adsorption onto hydroxyapatite crystals. This phenomenon is useful in demonstrating distribution of nonvisceral metastatic calcification.
Asunto(s)
Calcinosis/diagnóstico por imagen , Enfermedades de la Piel/diagnóstico por imagen , Medronato de Tecnecio Tc 99m , Adulto , Calcinosis/etiología , Femenino , Humanos , Fallo Renal Crónico/complicaciones , Hígado/diagnóstico por imagen , Cirrosis Hepática/congénito , Enfermedades Renales Poliquísticas/complicaciones , Cintigrafía , Piel/diagnóstico por imagen , Enfermedades de la Piel/etiologíaRESUMEN
The clinical utility of a computer-generated dynamic cine display (rotating display) of the unprocessed projection images of the liver and spleen obtained with rotating gamma-camera tomography was prospectively compared with that of the standard multi-view static scintigram display. Two hundred cases were independently and blindly analyzed by three observers. Each study was coded from 1-5, indicating the certainty of normality or abnormality present. When abnormality was noted, the study was assessed for the presence of metastatic disease, inhomogeneous uptake, hepatosplenomegaly, and colloid distribution shift. ROC analysis was then performed on the initial coding for certainty of abnormality, and the causes for discrepancies were evaluated from the assessment of the type of abnormality present. No significant interdisplay differences could be demonstrated. In the small percentage of cases where interdisplay disagreement occurred, this was usually accompanied by marked interobserver variation and was most commonly due to differing assessment of organ size. It is concluded that the static and rotating display formats can be used interchangeably in the evaluation of technetium-99m-labeled sulfur colloid liver studies.
Asunto(s)
Hepatopatías/diagnóstico por imagen , Enfermedades del Bazo/diagnóstico por imagen , Tomografía Computarizada de Emisión/métodos , Presentación de Datos , HumanosRESUMEN
A prospective comparison of conventional scintigrams and single-photon emission computed tomography (SPECT) studies of the liver and spleen was carried out. Care was taken to insure high-quality, artifact-free studies. Two hundred patients were imaged by both methods. A definitive diagnosis of normal was established in 86 cases, abnormal in 107 cases, and seven cases were indeterminate. All studies were read by two observers and graded as to degree and type of abnormality seen. ROC curves were constructed and errors of interpretation studied to identify problems. One observer showed no difference in performance between the two methods. The other showed a small improvement with SPECT. Image artifacts apparently contributed to errors of interpretation in 24 of 54 cases using SPECT. SPECT appears comparable with conventional scintigraphy and may improve specificity. Improvements are needed in SPECT imaging equipment and image display capability to realize fully the potential of SPECT.
Asunto(s)
Hepatopatías/diagnóstico por imagen , Enfermedades del Bazo/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Humanos , CintigrafíaRESUMEN
Eight middle mediastinal pheochromocytomas were located by means of 131I- meta- iodobenzylguanidine scintigraphy. The exact anatomic location of the lesions was confirmed by means of dynamic computed tomographic scanning following bolus injection of contrast medium. In all but one case the lesion had not been detected prior to scintigraphy despite extensive investigations including arteriography, venography with sampling, computed tomography with infusion of contrast medium, and in some cases surgical exploration of the abdomen and chest. Accurate anatomic location of the lesion permitted resection of five lesions from the cardiac atria and one from the aortopulmonary window. A sixth case in which an atrial pheochromocytoma was found by coronary angiography was not cured by resection of the primary tumor, and 131I- meta- iodobenzylguanidine scintigraphy revealed extensive metastases. Thus 131I- meta- iodobenzylguanidine scintigraphy has been of considerable value in the location of pheochromocytomas of the middle mediastinum, which may be a more frequent site than previously recognized.
Asunto(s)
Neoplasias Cardíacas/diagnóstico por imagen , Feocromocitoma/diagnóstico por imagen , 3-Yodobencilguanidina , Adolescente , Adulto , Anciano , Femenino , Neoplasias Cardíacas/cirugía , Humanos , Radioisótopos de Yodo , Yodobencenos , Masculino , Persona de Mediana Edad , Feocromocitoma/cirugía , Cintigrafía , Tomografía Computarizada por Rayos XRESUMEN
We have evaluated thirty patients with malignant metastatic phaeochromocytoma with regard to clinical features, indices of catecholamine secretion, histology of lesions and a number of imaging procedures including scintigraphy with the recently developed sympathetic tissue-seeking radiopharmaceutical 131I-metaiodobenzylguanidine (131I-MIBG). The primary tumour was extra-adrenal in 13 cases. The commonest site of metastases was the axial skeleton (20 cases), followed by liver (four cases), lymph nodes (four cases), peritoneum (two cases) and lung (three cases). The malignancies were indolent, the mean time following the initial diagnosis was 9.18 years (range 0 to 33 years) and the mean duration of known metastases 3.71 years (range 0 to 18 years). There was a wide range of abnormalities in plasma and urinary catecholamines which did not correlate with the extent of tumour spread, histological pattern (mitotic index, Zellballen pattern, capsular or vascular invasion pleomorphism or necrosis) or 131I-MIBG uptake by tumour deposits. 131I-MIBG scintigraphy was found to be a useful technique for determining the extent of metastatic disease in most cases (26 of 30) and in some patients (16 of 30) was more sensitive than other radiological procedures. No false positive scans were encountered.