RESUMO
A phase I clinical trial was conducted to evaluate the toxicology and biological activity of a new liposome-incorporated lipophilic disaccharide tripeptide, ImmTher. Twelve patients with advanced nonhematological malignant disease received 13 courses of therapy at dose levels of 200-1,200 micrograms/m2. A course of therapy consisted of once-weekly administration of the drug for 2-12 weeks. The major clinical toxicities observed were chills and hypotension. No renal, hepatic, cardiac, or hematological toxicity was observed. A small decrease in pulmonary diffusion capacity was observed. Biological activity was demonstrated by changes in plasma cytokine levels, changes in in vitro monocyte cytotoxicity, and by a decrease in tumor size. Improvement was observed in three of three patients with metastatic disease to the liver. Response in these three patients correlated with an increase in their tumor necrosis factor and neopterin levels compared with nonresponders. These preliminary indications of biological and clinical activity of a liposome-incorporated lipophilic disaccharide tripeptide in patients with advanced metastatic hepatic disease suggest a potential new therapeutic approach to this common problem.
Assuntos
Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Lipossomos , Neoplasias/tratamento farmacológico , Fosfatidilcolinas/uso terapêutico , Fosfatidilgliceróis/uso terapêutico , Acetilmuramil-Alanil-Isoglutamina/administração & dosagem , Acetilmuramil-Alanil-Isoglutamina/efeitos adversos , Acetilmuramil-Alanil-Isoglutamina/uso terapêutico , Idoso , Biopterinas/análogos & derivados , Biopterinas/metabolismo , Citotoxicidade Imunológica , Avaliação de Medicamentos , Citometria de Fluxo , Humanos , Interleucina-1/metabolismo , Células Matadoras Naturais/imunologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Neopterina , Fosfatidilcolinas/administração & dosagem , Fosfatidilcolinas/efeitos adversos , Fosfatidilgliceróis/administração & dosagem , Fosfatidilgliceróis/efeitos adversos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
A prospective study of the relationship between exacerbations and season in 336 patients with clinically definite multiple sclerosis showed a significant monthly variation as well as a seasonal pattern of exacerbations. The data obtained are compared with earlier studies that have used varying methodologies. The results continue to support the hypothesis that undefined environmental factors influence the course of multiple sclerosis.
Assuntos
Esclerose Múltipla/fisiopatologia , Estações do Ano , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , North Dakota , Estudos Prospectivos , Estatística como AssuntoRESUMO
Two hundred fifty-four patients with definite multiple sclerosis were followed up prospectively for 1 to 5 years (mean, 2.6 years). None of the patients received immunosuppressive medication. Yearly exacerbation rates and each patient's adherence to initial disease type were determined. Disease type was defined at entry and prospectively each subsequent year as stable, relapsing remitting stable, relapsing remitting progressive, or chronic progressive. Exacerbation rates determined prospectively did not decline significantly during 3 years of follow-up, even if patients were stratified by disease duration. Adherence to the initially assigned disease type was highly variable. When followed up for 2 years, 30% of patients with chronic progressive disease had conditions become stable, 32% of patients with stable disease had conditions become chronic progressive, 20% of patients with relapsing remitting disease had conditions become stable, and 20% of patients with relapsing remitting disease had conditions become chronic progressive. Patients with stable or relapsing remitting stable disease switched to one of the progressive categories as frequently (44%) as patients with progressive disease stabilized (46%). Progression of disease measured by changes in Kurtzke Expanded Disability Status Scores did not differ between the different disease types. The results challenge dogma regarding the natural history of exacerbation rates and the assumption that we can reliably assign patients to a specific disease type. The findings have important implications for understanding the natural history of multiple sclerosis and designing clinical trials.
Assuntos
Esclerose Múltipla/epidemiologia , Ensaios Clínicos como Assunto , Estudos de Coortes , Avaliação da Deficiência , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Projetos de Pesquisa , Fatores de TempoRESUMO
Patients with chronic progressive multiple sclerosis often perform more poorly on cognitive tasks than do patients with the relapsing-remitting form of this disease. Whether these differences reflect an independent influence of disease type on cognitive performance is uncertain. We used multiple regression techniques to determine how well performance on a number of tasks done poorly by groups of patients with multiple sclerosis could be predicted by disease type and its confounds: age, disease duration, and disability status as well as other demographic variables. Disease types were assigned longitudinally, based on serial neurological examinations at 6-month intervals over a minimum of 2 years. None of the demographic or clinical variables predicted cognitive performance with more than minimal accuracy. These findings fail to provide support for the assertion that disease type is an important independent determinant of cognitive impairment in multiple sclerosis.
Assuntos
Transtornos Cognitivos/diagnóstico , Pessoas com Deficiência/psicologia , Esclerose Múltipla/psicologia , Adulto , Doença Crônica , Demografia , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Testes Neuropsicológicos , Valor Preditivo dos Testes , Análise de RegressãoRESUMO
The performance of 38 patients with chronic progressive multiple sclerosis was compared with that of 26 age- and education-matched controls on a battery of tests of information-processing speed, verbal fluency, naming, egocentric perception, and anterograde and remote memory. Although there were marked differences in the extent and severity of cognitive disturbance among individual patients, as a group they were impaired compared with controls on all measures. Deficits were most striking on the Symbol-Digit Modalities Test and the verbal fluency measures, tests that require rapid information processing. More than 75% of the patients scored below the tenth percentile for controls on the Symbol-Digit Modalities Test, while 61% scored below the tenth percentile on verbal fluency. Memory disturbances were also common. More than 45% of the patients scored below the tenth percentile. The proportion of impaired patients was quite similar for anterograde and remote memory tests and for recall and recognition procedures. The pattern of memory disturbance and slowed information processing resembled deficits generally observed in subcortical dementias, such as Huntington's disease, but in addition, the patients with multiple sclerosis showed naming difficulties that are usually associated with cortical dementias, such as Alzheimer's disease.
Assuntos
Amnésia/complicações , Esclerose Múltipla/complicações , Adulto , Feminino , Humanos , Idioma , Masculino , Memória , Pessoa de Meia-Idade , Esclerose Múltipla/psicologia , Testes PsicológicosRESUMO
Twenty-seven patients with chronic progressive multiple sclerosis were treated with high-dose intravenous cyclophosphamide induction on either an impatient or outpatient basis. Following induction, patients were randomized to alternate-month outpatient "maintenance" or "no maintenance" therapy. These groups, as well as 24 nonrandomized control patients, were compared with each other after 12, 18, and 24 months of follow-up. All groups were similar in age, sex, duration of disease, and degree of disability before treatment. Fifty-nine percent of all cyclophosphamide-treated patients were stable at 12 months compared with 17% of all patients in the nonrandomized control group at 12 months. A statistically significant difference persisted at 18 and 24 months. A trend favoring maintenance therapy when compared with no maintenance therapy was evident at 12, 18, and 24 months, but was not statistically significant. Inpatient vs outpatient induction therapy failed to influence treatment outcome. Toxic side effects of nausea and vomiting presented a serious obstacle to maintenance therapy as administered in this protocol.
Assuntos
Ciclofosfamida/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Administração Oral , Hormônio Adrenocorticotrópico/administração & dosagem , Adulto , Idoso , Ensaios Clínicos como Assunto , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Hospitalização , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Prednisona/administração & dosagem , Distribuição Aleatória , Projetos de Pesquisa , Fatores de TempoRESUMO
We randomized 59 patients with relapsing-remitting multiple sclerosis to receive azathioprine (AZA) 3.0 mg/kg daily or placebo in a double-masked therapeutic trial. Analysis of data for predetermined primary outcome measures demonstrated a significant difference favoring AZA for observed mean exacerbation rate after 2 years of therapy and time to deterioration in both Ambulation Index and Kurtzke Expanded Disability Status Scale score. This study confirms a modest therapeutic benefit for azathioprine previously reported by other investigators.
Assuntos
Azatioprina/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Adolescente , Adulto , Idoso , Azatioprina/efeitos adversos , Avaliação da Deficiência , Humanos , Pessoa de Meia-Idade , Esclerose Múltipla/mortalidade , Esclerose Múltipla/fisiopatologia , Recidiva , Análise de SobrevidaRESUMO
Following biopsy of a hilar mass, a heart scan performed with 99mTc-pertechnetate showed intense uptake in the mass. The degree of radionuclide concentration suggested that the mass was glandular tissue, most likely an adenoma or adenocarcinoma. Biopsy revealed a mucinsecreting adenocarcinoma. Review of the literature showed examples of active glandular concentration of pertechnetate in the thyroid, gastric mucosa, breast, lacrimal glands, and colon. This case provides an example of reasoning by which the scan interpretation came closer to the actual tissue diagnosis than is usually possible.
Assuntos
Adenocarcinoma/diagnóstico , Neoplasias Pulmonares/diagnóstico , Cintilografia , Tecnécio , Feminino , Cardiopatias/diagnóstico , Humanos , Pessoa de Meia-IdadeRESUMO
The objective of this study was to identify factors related to eating disorders in young adolescent girls. Three hundred eighty-five girls who were attending a career conference at a midwestern university completed the Eating Disorder Instrument (EDI) along with a biographical data sheet. The EDI is designed for the assessment of psychological and behavior traits common in eating disorders. While 81% of the young subjects were assessed to be within the range for ideal weight or were underweight, 78% preferred to weigh less. Only 14% were satisfied with their current weight. Findings for each of the subscales used revealed significant differences among the girls based on intact versus broken family; subjects' actual and preferred weight; whether the family ate meals together; average grades; age and grade in school; fathers' occupation; future career plans; place of residence; and feelings toward their mothers.
Assuntos
Anorexia Nervosa/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Hiperfagia/diagnóstico , Adolescente , Anorexia Nervosa/psicologia , Imagem Corporal , Peso Corporal , Criança , Dieta Redutora/psicologia , Feminino , Humanos , Hiperfagia/psicologia , Testes PsicológicosRESUMO
A study consisting of three components is reported. During Phase One an extensive literature search led to a compiled set of norms for reflexive and voluntary prehensile development. Phase Two included the clinical use and revision of the resultant Erhardt Developmental Prehension Assessment (EDPA). Phase Three involved the testing of the EDPA for interrater reliability, which resulted in highly significant intraclass correlations. Single test item correlations were also analyzed to identify items needing clarification or alteration in preparation for final revision of the instrument. A sample application in the clinical field is illustrated by segments of an EDPA used to develop an Individualized Educational Plan, required by Federal Law 94-142 (Education of All Handicapped Children).
Assuntos
Deficiências do Desenvolvimento/diagnóstico , Pessoas com Deficiência , Mãos/fisiopatologia , Pré-Escolar , Deficiências do Desenvolvimento/terapia , Educação Inclusiva , Feminino , Humanos , Lactente , Masculino , Terapia OcupacionalAssuntos
Ansiedade/psicologia , Depressão/psicologia , Hostilidade , População Rural , Adulto , Feminino , HumanosAssuntos
Identidade de Gênero , Identificação Psicológica , Pais/psicologia , Adolescente , Feminino , Humanos , Masculino , Percepção SocialRESUMO
The need for standardized operational definitions, as well as a more sensitive, easily applied, and reproducible upper extremity functional assessment for following patients in multiple sclerosis clinical trials is evident. Experience with the use of two upper extremity functional assessment instruments--the nine-hole peg test (9HPT) and the box-and-block test (BBT)--is described. The patients, who were followed for six months, experienced subjective change in functional status but failed to show significant change on the pyramidal, cerebellar, or visual functional scores of the Kurtzke Expanded Disability Status Scale (EDSS). The prevalence of upper extremity dysfunction in multiple sclerosis, as measured by the 9HPT and the BBT, is higher than previously appreciated. The 9HPT and BBT are more sensitive in detecting upper extremity functional status change than the EDSS and should prove helpful in following patients in clinical trials.