RESUMEN
In an experimental study (October 2010 Mannheim Germany) with 99 Caucasian volunteers, the skin colour (L*, a*, b*) and the reflectance spectra of human skin were compared to the Fitzpatrick's sun-reactive skin photo types (SPT). For this purpose, the skin colour and the reflectance spectra of human skin were determined using non-invasive method with a newly developed fibre optic detection device. The device, based on reflectance spectroscopy, was designed and optimized using a commercial optical analysis Software. By means of the measured spectra of scattered light, the colour values and the absorption spectra of the skin were calculated. Neither any of the L*, a*, b* colour values nor any of the parameters of the absorbance spectra can be used alone to assess the skin type properly. Therefore, an ordinal logistic regression analysis was performed, using the statistical computing software r, to correlate the skin types with the measured optical parameters. It turned out that the detection device combined with the extended statistical analysis gives a better estimate of skin type in respect of the measured optical parameters than a procedure with only L*, a*, b* colour values. Even with the extended methodology, the procedure gives only a rough estimation of the skin type.
Asunto(s)
Tecnología de Fibra Óptica , Piel/anatomía & histología , Adulto , Femenino , Humanos , Masculino , Población Blanca , Adulto JovenRESUMEN
During the 15th International Histocompatibility and Immunogenetics Workshop (IHIWS), 14 human leukocyte antigen (HLA) laboratories participated in the Analysis of HLA Population Data (AHPD) project where 18 new population samples were analyzed statistically and compared with data available from previous workshops. To that aim, an original methodology was developed and used (i) to estimate frequencies by taking into account ambiguous genotypic data, (ii) to test for Hardy-Weinberg equilibrium (HWE) by using a nested likelihood ratio test involving a parameter accounting for HWE deviations, (iii) to test for selective neutrality by using a resampling algorithm, and (iv) to provide explicit graphical representations including allele frequencies and basic statistics for each series of data. A total of 66 data series (1-7 loci per population) were analyzed with this standard approach. Frequency estimates were compliant with HWE in all but one population of mixed stem cell donors. Neutrality testing confirmed the observation of heterozygote excess at all HLA loci, although a significant deviation was established in only a few cases. Population comparisons showed that HLA genetic patterns were mostly shaped by geographic and/or linguistic differentiations in Africa and Europe, but not in America where both genetic drift in isolated populations and gene flow in admixed populations led to a more complex genetic structure. Overall, a fruitful collaboration between HLA typing laboratories and population geneticists allowed finding useful solutions to the problem of estimating gene frequencies and testing basic population diversity statistics on highly complex HLA data (high numbers of alleles and ambiguities), with promising applications in either anthropological, epidemiological, or transplantation studies.
Asunto(s)
Genética de Población/métodos , Antígenos HLA/genética , Inmunogenética , Grupos de Población/genética , Programas Informáticos , Frecuencia de los Genes , HumanosRESUMEN
Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease caused by defective lymphocyte apoptosis and is characterized by non-malignant lymphoproliferation, hepatosplenomegaly, autoimmune manifestations and increased risk of both Hodgkin's and non-Hodgkin's lymphoma. Most forms of the disease are due to germ line mutations of the FAS gene and manifest during the first years of life with fluctuating lymphadenopathies, hemolysis, immune thrombocytopenia. During the second decade of life disease manifestations improve spontaneously but autoimmune problems still occur and there is an increased risk of lymphoproliferative malignancy. We describe a typical case of ALPS in a now 44 year old man, followed since the age of 2 for disease manifestations that were unclear at the beginning.
Asunto(s)
Síndrome Linfoproliferativo Autoinmune/diagnóstico , Adolescente , Adulto , Síndrome Linfoproliferativo Autoinmune/clasificación , Síndrome Linfoproliferativo Autoinmune/genética , Diagnóstico Diferencial , Mutación de Línea Germinal , Humanos , MasculinoRESUMEN
Covered oesophageal stents are often used to treat dysphagia in patients with inoperable oesophageal cancer. Stent migration is a well-known but usually benign complication. We report the case of a patient whose esophageal stent migrated into the distal ileum with perforation hereof. A laparoscopic stent extraction and intestinal repair was necessary to treat the perforation.
Asunto(s)
Trastornos de Deglución , Neoplasias Esofágicas , Estenosis Esofágica , Migración de Cuerpo Extraño , Perforación Intestinal , Migración de Cuerpo Extraño/complicaciones , Migración de Cuerpo Extraño/diagnóstico por imagen , Humanos , Perforación Intestinal/diagnóstico por imagen , Perforación Intestinal/etiología , Perforación Intestinal/cirugía , Stents/efectos adversosRESUMEN
An Antiphospholipid syndrome (APS) was diagnosed in a patient who had massive pulmonary embolisation from a right atrial thrombus. The (APS) is an autoimmune disease defined by the presence in the serum of at least one type of autoantibody known as antiphospholipid antibody (aPL) and the occurrence of at least one clinical feature from a list of potential disease manifestations, the most common of which are venous or arterial thrombosis, recurrent fetal loss and thrombocytopenia. The prevalence of APS in a series of patients from internal medicine is 2 percent. The mean age at diagnosis is 42 years. The pathogenesis of APS associated with clinical manifestations seems to result from a variety of effects of aPL on coagulation pathways,but the exact mechanism of action of aPL on these pathways is not completely understood. The APS can be primary or secondary to a disease. Thrombosis is the most frequent clinical manifestation of APS. It involves many organs, resulting on multiorgan failure: this is the catastrophic APS. The treatment is the same whether the APS is primary or secondary. It is mainly symptomatic and consists in the prevention of thrombosis at short and long-term by using aspirin and/or anticoagulants. Immunomodulating treatment can be offered but its efficiency at long-term is unproven. The mortality varies according to the etiology and the clinical manifestations. The mortality rate is 50 percent in catastrophic APS, despite treatment.
Asunto(s)
Síndrome Antifosfolípido/diagnóstico , Adulto , Edad de Inicio , Anticuerpos Antifosfolípidos/sangre , Anticoagulantes/uso terapéutico , Síndrome Antifosfolípido/tratamiento farmacológico , Aspirina/uso terapéutico , Coagulación Sanguínea , Humanos , Trombosis/etiología , Trombosis/prevención & controlAsunto(s)
Enucleación del Ojo , Melanoma/patología , Neoplasias Gástricas/secundario , Neoplasias de la Úvea/patología , Adulto , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Comunicación Interdisciplinaria , Laparoscopía , Melanoma/diagnóstico , Melanoma/cirugía , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirugía , Factores de Tiempo , Resultado del Tratamiento , Neoplasias de la Úvea/diagnóstico , Neoplasias de la Úvea/cirugíaRESUMEN
We performed a phase I-II trial of escalating doses of cisplatin (CDDP: 50-100 mg/m2 per course) plus carboplatin (CBDCA: 300-400 mg/m2 per course) as a potential way in which to maximize platinum doses without causing excessive toxic effects in patients with advanced ovarian cancer. Thirty-three patients with nonoptimally debulked disease of FIGO (International Federation of Gynecology and Obstetrics) stages IIc-IV [median age: 60 yr; median WHO (World Health Organization) performance status: 2; no prior chemotherapy] received a median of six courses of therapy. CBDCA was infused on day 1 and CDDP on day 2 with an aggressive 48-hour hydration regimen. Myelosuppression was dose-limiting: at the highest dose levels, WHO grade 4 neutropenia and thrombocytopenia led to dose reduction and/or treatment delay in 45% of the patients. Nonhematologic toxic effects included acute nausea and vomiting (97% of the patients), mild alopecia (45%), ototoxic effects (39%), neurotoxic effects (21%), and renal toxic effects (serum creatinine greater than 1.5 mg/dL: 12.5%). The pathologic complete response rate was 22%. We conclude that CBDCA and CDDP can be given safely in combination at reasonably high doses (CBDCA at 300 mg/m2 per course and CDDP at 100 mg/m2 per course) over a 6-month period, provided a close hematologic follow-up is conducted. Randomized clinical trials are needed to define whether this regimen is any better than standard combination chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/administración & dosificación , Compuestos Organoplatinos/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Médula Ósea/efectos de los fármacos , Carboplatino , Cisplatino/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Compuestos Organoplatinos/efectos adversosRESUMEN
PURPOSE: We compared prospectively the antitumor efficacy of two combination chemotherapy regimens with two different dose levels of epirubicin as first-line treatment for advanced breast cancer. PATIENTS AND METHODS: One hundred forty-one fully assessable patients were randomized to receive either our intensified schedule (group A, n = 71) of epirubicin 50 mg/m2 on days 1 and 8 (every 3 weeks), or a non-intensified program (group B, n = 70) in which epirubicin was only administered on day 1. Both groups also received fluorouracil (5 FU) and cyclophosphamide 500 mg/m2 on day 1 of each course. RESULTS: A statistically significant difference in response rate was observed (69% in group A v 41% in group B, P < .001) for both locally advanced (LA) and recurrent metastatic (RM) disease. Response duration (22 v 14 months, P < .01) and time to progression (TTP; 19 v 8 months, P < .02) were also significantly improved. Overall survival was similar in both groups. However, univariate and/or multivariate analyses showed a meaningful relationship between type of treatment allocated, dose-intensity (DI) of epirubicin, and response rate, as well as between TTP and survival. Ultimately, TTP and survival were also influenced by further treatment modalities, namely, hormonotherapy and chemotherapy. CONCLUSION: This study validates prospectively the concept of a dose-response relationship for an anthracycline-based chemotherapy in previously untreated advanced breast cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Epirrubicina/administración & dosificación , Análisis Actuarial , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Ciclofosfamida/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Fluorouracilo/administración & dosificación , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: A phase II randomized trial was conducted in patients with advanced non-small-cell lung cancer (NSCLC) to determine if the combination of moderate-dose cisplatin and carboplatin was active (primary end point) and could avoid the long-term limiting (renal, auditive, neurologic) toxicity of high-dose cisplatin, which prevents prolonged administration (secondary end point). PATIENTS AND METHODS: One hundred twenty-one patients, registered between April 1990 and September 1991, were randomized to receive high-dose cisplatin (120 mg/m2 intravenously [IV] on day 1) or a combination of moderate-dose carboplatin (200 mg/m2 IV on day 1 and moderate-dose cisplatin (30 mg/m2 IV on days 2 and 3). One hundred nine patients were eligible: 56 in the cisplatin arm and 53 in the combined arm; 52 and 47, respectively, were assessable for response. All had stage IV disease (or stage IIIB with pleural effusion) and none had received prior chemotherapy. RESULTS: There was a 23% objective response rate to cisplatin (23% of the eligible patients) and a 22% response rate to cisplatin plus carboplatin (21% of the eligible patients). The overall survival rate was not significantly different between the two study arms, but responders in the combined arm survived significantly longer than those in the high-dose cisplatin arm (respective median survival durations, 66 and 30 weeks). Although there was no difference between the arms for alopecia, emesis, and leukopenia, the combined arm was significantly associated with more thrombocytopenia (although rarely severe) and, more importantly, with less renal (19% v 36%), auditive (4% v 16%), and neurologic (0% v 16%) toxicity of any grade. CONCLUSION: The regimen combining moderate-dose cisplatin and carboplatin was active against advanced NSCLC and significantly less toxic than high-dose cisplatin.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Análisis Actuarial , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: A randomized trial was conducted in patients with small-cell lung cancer (SCLC) to determine if survival can be improved by a weekly chemotherapy regimen combining various drugs. PATIENTS AND METHODS: Two hundred twenty-three patients were randomized to receive either six courses of a multiple-drug combination (MDC) regimen (Adriamycin [ADR; doxorubicin; Farmitalia Carlo Erba, Milan, Italy] 25 mg/m2 intravenously [i.v.] on day 1; etoposide [VP16] 120 mg/m2 i.v. on day 1; cyclophosphamide [CPA] 500 mg/m2 i.v. on day 1; cisplatin 60 mg/m2 i.v. on day 8; vindesine [VDS] 3 mg/m2 i.v. on day 8; vincristine [VCR] 2 mg i.v. on day 15; methotrexate [MTX] 100 mg/m2 i.v. on day 15), or a standard chemotherapy (SC) regimen (ADR 50 mg/m2 i.v. on day 1; CPA 1 g/m2 i.v. on day 1; VP16 80 mg/m2 i.v. on days 1 to 3). RESULTS: In 98 MDC-treated and 101 SC-treated assessable patients, we observed 69% and 62% objective responses rates, respectively. There was no significant difference in survival, with median durations and 2-year overall survival rates of 49 and 43 weeks and 8.5% and 7.9%, respectively. There was a significant increase in response rate in favor of MDC patients with limited disease (84% v 62%). Toxicity was tolerable, although SC was more hematotoxic, with 76% (v 59%) experiencing leukopenia and 17% (v 7%) experiencing thrombocytopenia (grades III and IV). If the cumulative doses received were nearly equal to the scheduled cumulative doses in both arms, the total relative dose-intensity (RDI) was significantly higher in the SC arm. The difference was due to increased treatment delays in the MDC arm. CONCLUSION: Weekly MDC failed to improve survival rates in patients with SCLC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Esquema de Medicación , Análisis Factorial , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: To compare a full-dose epirubicin-cyclophosphamide (HEC) regimen with classical cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy and with a moderate-dose epirubicin-cyclophosphamide regimen (EC) in the adjuvant therapy of node-positive breast cancer. PATIENTS AND METHODS: Node-positive breast cancer patients who were aged 70 years or younger were randomly allocated to one of the following treatments: CMF for six cycles (oral cyclophosphamide); EC for eight cycles (epirubicin 60 mg/m(2), cyclophosphamide 500 mg/m(2); day 1 every 3 weeks); and HEC for eight cycles (epirubicin 100 mg/m(2), cyclophosphamide 830 mg/m(2); day 1 every 3 weeks). RESULTS: Two hundred fifty-five, 267, and 255 eligible patients were treated with CMF, EC, and HEC, respectively. Patient characteristics were well balanced among the three arms. One and three cases of congestive heart failure were reported in the EC and HEC arms, respectively. Three cases of acute myeloid leukemia were reported in the HEC arm. After 4 years of median follow-up, no statistically significant differences were observed between HEC and CMF (event-free survival [EFS]: hazards ratio [HR] = 0.96, 95% confidence interval [CI], 0.70 to 1.31, P =.80; distant-EFS: HR = 0.97, 95% CI, 0.70 to 1.34, P =.87; overall survival [OS]: HR = 0.97, 95% CI, 0.65 to 1.44, P =.87). HEC is more effective than EC (EFS: HR = 0.73, 95% CI, 0.54 to 0.99, P =.04; distant-EFS: HR = 0.75, 95% CI, 0.55 to 1.02, P =.06; OS HR = 0.69, 95% CI, 0.47 to 1.00, P =.05). CONCLUSION: This three-arm study does not show an advantage in favor of an adequately dosed epirubicin-based regimen over classical CMF in the adjuvant therapy of node-positive pre- and postmenopausal women with breast cancer. Moreover, this study confirms that there is a dose-response curve for epirubicin in breast cancer adjuvant therapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bélgica/epidemiología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Quimioterapia Adyuvante/métodos , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Metotrexato/administración & dosificación , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estadísticas no Paramétricas , Tasa de SupervivenciaRESUMEN
In order to identify specific DNA sequences useful as 'genetic landmarks' in the construction of a complete map of the human mdr1 (multidrug-resistance) gene, we investigated the introns in the central region. In intron 14, we identified a long stretch of a homopyrimidine.homopurine sequence most probably adopting an unconventional DNA conformation, followed by a cluster of three Alu repeated sequences in an inverted orientation. Here, we describe the structure, formation and nucleotide sequence of these DNA elements.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Resistencia a Múltiples Medicamentos/genética , Intrones/genética , Secuencias Repetitivas de Ácidos Nucleicos/genética , Secuencia de Bases , Clonación Molecular , ADN/química , Humanos , Datos de Secuencia Molecular , Conformación de Ácido Nucleico , Análisis de Secuencia de ADN/métodos , Homología de Secuencia de Ácido NucleicoRESUMEN
OBJECTIVES: To determine the motor cortex degeneration in patients with amyotrophic lateral sclerosis (ALS) using proton magnetic resonance spectroscopy, and to prove that proton magnetic resonance spectroscopy is suited to monitor the course of disease with follow-up examinations. MATERIALS AND METHODS: We studied 33 patients with ALS whose conditions were diagnosed according to the El Escorial World Federation of Neurology criteria. Nine patients with ALS were followed up for up to 2 years. The control group included 20 healthy volunteers and 4 patients with multifocal motor neuropathy. Proton magnetic resonance spectroscopy determined levels of the brain metabolites N-acetylaspartate (NAA), choline, inositol-containing compounds, glutamate/glutamine, and phosphocreatine. RESULTS: Patients with ALS showed a significant reduction in the NAA-choline (P <.001) and NAA-phosphocreatine (P <.005) metabolite ratios and significantly elevated choline-phosphocreatine (P <.005) ratios compared with controls. Inositol-phosphocreatine ratios were also elevated in case patients, but the increase was less pronounced (P <.05). No differences in glutamate/glutamine-phosphocreatine ratios were detected between case patients and controls. An analysis of subgroups demonstrated less significant differences in NAA-choline metabolite ratios (P<.05), even in patients with pure lower motor neuron syndrome (suspected ALS). No changes in metabolite T1 and T2 relaxation times were observed. Patients with multifocal motor neuropathy showed normal metabolic ratios. Progressive alterations in affected metabolite ratios could be documented in the follow-up examinations. CONCLUSIONS: Spectroscopic changes in the motor cortices of patients with ALS correspond with a reduction in levels of NAA and an elevation in levels of choline and inositol compounds. Since NAA is exclusively expressed in neurons, the observed decrease of NAA reflects neuronal loss or dysfunction. Inositol and choline are associated with plasma membrane metabolism, so the release of these compounds may be related to membrane disorders.
Asunto(s)
Esclerosis Amiotrófica Lateral/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Corteza Motora/metabolismo , Adulto , Anciano , Esclerosis Amiotrófica Lateral/patología , Análisis de Varianza , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , ProtonesRESUMEN
For 15 years, an overflowing literature has been published about MDR-1 gene expression in tumor cell lines and in cancerous tissues at various stages of disease and treatment (chemotherapy-naive, during treatment and at relapse). However, the clinical significance of this particular feature, if it seemed obvious in the 1980s as a factor responsible for the development of chemoresistance, is currently reconsidered. MDR-1 gene expression seems to be, at least in some instances, a hallmark of tumor cell aggressiveness and of chemoresistance rather than its cause, the mechanisms of which are probably far more complex. The failure of MDR reversal trials might result from the misunderstood or overvalued role of MDR expression in cancer cells rather than from a lack of control of pharmacological parameters. This review summarizes recent data and hypothesis about the expression of P-170 and its clinical significance in some important human tumor types, suggesting that it should rather be considered in the future as an adverse prognostic factor.
RESUMEN
The cause of ALS is not known but there are four main hypotheses about its etiology. First, an excess of extracellular glutamate in the CNS of patients with ALS resulting from a defect in glutamate reuptake may have excitotoxic effects on motor neurons. Clinical trials suggest the antiglutamate agent riluzole improves survival of patients with the disease. Second, ALS may be an autoimmune disease, but immunologically-based treatments have been unsuccessful. The third hypothesis is that ALS results from a lack of neurotrophic growth factors. Preliminary results from clinical trials indicate recombinant human insulin-like growth factor I offers therapeutic promise. Finally, familial ALS is sometimes linked to a gene encoding a Cu/Zn-binding superoxide dismutase; the mutations in ALS are thought to result in gain of function of dismutase activity. The involvement of superoxide dismutase in sporadic ALS is unclear.
Asunto(s)
Esclerosis Amiotrófica Lateral/etiología , HumanosRESUMEN
We studied two families with five affected members suffering from ptosis and slowly progressive limb-girdle muscle weakness. All patients had abnormal decremental response on low-frequency nerve stimulation, but there were no repetitive responses to single stimuli. The patients improved on anti-acetylcholinesterase drugs. Intercostal muscle was obtained for special studies from one patient of each family. In vitro microelectrode studies were done in Patient 1. Miniature end-plate potentials were of low amplitude, and the quantal content of the evoked end-plate potentials was normal. Light microscopy revealed a marked type 1 fiber predominance. Acetylcholinesterase reactivity was dispersed over increased length of individual fibers in Patient 2. On morphometry of the end-plate ultrastructure, the number of secondary synaptic clefts per neuromuscular junction and the expansion of the postsynaptic area were markedly reduced. In Patient 1, but not in Patient 2, the envelopment of the nerve terminal by Schwann cell was increased. Acetylcholine-receptor (AChR) density was reduced as judged by the reduced immunoreactivity to antibodies against different receptor subunits. Immunohistochemical analysis of proteins known to be involved in orchestrating the end-plate structure showed deficiency of the AChR-associated protein utrophin. These patients appear to have a defect in the development or maintenance of the postsynaptic clefts; whether this defect results from or causes a reduced expression of utrophin or AChR is unclear.
Asunto(s)
Proteínas del Citoesqueleto/deficiencia , Proteínas de la Membrana/deficiencia , Placa Motora/química , Miastenia Gravis/congénito , Miastenia Gravis/genética , Receptores Colinérgicos/deficiencia , Adulto , Animales , Proteínas del Citoesqueleto/análisis , Proteínas del Citoesqueleto/genética , Femenino , Humanos , Masculino , Proteínas de la Membrana/análisis , Proteínas de la Membrana/genética , Ratones , Ratones Noqueados , Microscopía Electrónica , Placa Motora/ultraestructura , Miastenia Gravis/patología , Linaje , Receptores Colinérgicos/análisis , Receptores Colinérgicos/genética , Vesículas Sinápticas/ultraestructura , UtrofinaRESUMEN
The efficacy of ondansetron was compared with metoclopramide in the prophylaxis of nausea and vomiting induced by cyclophosphamide greater than or equal to 500 mg/m2 in combination with doxorubicin greater than or equal to 40 mg/m2 or epirubicin greater than or equal to 40 mg/m2. complete anti-emetic protection in the 24 h following chemotherapy was achieved in 26 of 40 (65%) patients treated with ondansetron compared with 17 of 42 (41%) patients treated with metoclopramide. Severe nausea was present in 3% of patients in the ondansetron group and 31% in the metoclopramide group. A worst day analysis of control of emesis and nausea on days 2 and 3 following chemotherapy also demonstrated ondansetron to be more effective than metoclopramide. Both treatments were well tolerated. Ondansetron is more effective as an anti-emetic than metoclopramide in this type of cytostatic therapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Imidazoles/uso terapéutico , Metoclopramida/uso terapéutico , Náusea/prevención & control , Vómitos/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Ondansetrón , Ensayos Clínicos Controlados Aleatorios como Asunto , Antagonistas de la Serotonina , Vómitos/inducido químicamenteRESUMEN
Anthracyclines and taxanes are the most potent cytotoxic agents available for treating breast cancer. With combined therapy (either epirubicin or doxorubicin with paclitaxel [Taxol; Bristol-Myers Squibb Company, Princeton, NJ]), response rates of 70% to 90% have been reported. To achieve a maximal dose intensity per week, we decided to combine epirubicin 100 mg/m2 with escalating doses of paclitaxel, at successive dose levels of 135, 150, 165, and 180 mg/m2 in a 2-week schedule, with administration of subcutaneous granulocyte colony-stimulating factor 5 microg/kg from days 2 through 10. To date, 16 patients have been included, with six patients treated at level 1 (100/135 mg/m2 epirubicin/paclitaxel), four at level 2 (100/150 mg/m2), four at level 3 (100/165 mg/m2), and two at level 4 (100/180 mg/m2). The median age of all subjects is 55 years (range, 41 to 65 years). Five patients had received chemotherapy in the adjuvant setting. Of 79 treatment courses, 78 are evaluable for toxicity. The mean number of courses per patient is six (range, two to six courses). At dose level 1, one episode of febrile neutropenia with grade 4 thrombocytopenia occurred. No grade 4 extrahematologic adverse event has been noted so far. At dose level 2, we achieved a dose intensity per week of epirubicin 50 mg/m2 and paclitaxel 75 mg/m2, as expected. At dose level 3, the dose intensity per week was 47.5 mg/m2 and 78.8 mg/m2, respectively (expected 50 and 82.5 mg/m2). The current response rate, evaluated in 14 of 16 patients, is four complete remissions and eight partial remissions, for an overall response rate of 85%. Two patients had stable disease. Granulocyte colony-stimulating factor following epirubicin/paclitaxel on a 2-week schedule permits a very high dose intensity per week for both drugs and produces a high response rate in patients with advanced or metastatic breast cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Adulto , Anciano , Supervivencia sin Enfermedad , Epirrubicina/administración & dosificación , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Paclitaxel/administración & dosificaciónRESUMEN
The purpose of this study was to determine the activity of a 4-drug combination chemotherapy: cisplatin, mitomycin C, vindesine and 5-fluorouracil (5-FU) in patients with advanced non-small cell lung cancer (NSCLC). Chemotherapy consisted of the administration of cisplatin (30 mg/m2 d 1-4), mitomycin C (10 mg/m2 d 1), vindesine (3 mg/m2 d 1) and 5-FU (1 g/m2 d 1-4 by continuous intravenous infusion). In patients older than 70 years, and in those who received prior irradiation or chemotherapy, cisplatin and 5-FU were omitted on day 4. Courses were repeated every 4 weeks and evaluation of response was performed after the first 2 courses. In case of response, treatment was continued until best response or untolerable toxicity. Among 182 eligible patients, 75% had received no prior therapy; 41% had locoregional disease and 59% metastatic disease; 41% lost more than 5% of their pretherapy body weight. A 34% objective response rate was observed in the 164 evaluable patients (31% in all the eligible patients) including 4 complete and 52 partial responses. Patients with locoregional disease had a significantly better response rate than those with metastases (44% vs 27%). The overall median survival was 26 weeks. Significant hematological toxicity was documented but the most serious adverse event was the occurrence of 18 (10%) cardiac or sudden deaths. These toxic deaths were significantly associated with a 5% loss of body weight prior to therapy. The addition of 5-FU to combination of cisplatin, mitomycin C and vindesine does not improve antitumoral effect but results in very significant cardiac toxicity.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Cisplatino/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Mitomicinas/administración & dosificación , Pronóstico , Análisis de Supervivencia , Vindesina/administración & dosificaciónRESUMEN
We review a certain number of medical applications of a new non-euclidean geometry: the fractal geometry described by Mandelbrot. Examples come from anatomy, cytology, general physiology and physiopathology. Furthermore, real clinical applications are shown, in particular, in cardiology, neurology, ophtalmology, radiology and other imaging techniques. An easy reading mathematical approach is added. Some of the fractal images will certainly capture your attention and spur your interest for further applications of this new concept.