RESUMO
OBJECTIVE: To delineate the genetic, neurodevelopmental and epileptic spectrum associated with GRIN2A alterations with emphasis on epilepsy treatment. METHODS: Retrospective study of 19 patients (7 females; age: 1-38 years; mean 10.1 years) with epilepsy and GRIN2A alteration. Genetic variants were classified according to the guidelines and recommendations of the American College of Medical Genetics (ACMG). Clinical findings including epilepsy classification, treatment, EEG findings, early childhood development and neurodevelopmental outcome were collected with an electronic questionnaire. RESULTS: 7 out of 19 patients fulfilled the ACMG-criteria of carrying "pathogenic" or "likely pathogenic variants", in twelve patients the alterations were classified as variants of unknown significance. The spectrum of pathogenic/likely pathogenic mutations was as follows: nonsense n = 3, missense n = 2, duplications/deletions n = 1 and splice site n = 1. First seizures occurred at a mean age of 2.4 years with heterogeneous seizure types. Patients were treated with a mean of 5.6 AED. 4/5 patients with VPA had an improved seizure frequency (n = 3 with a truncation: n = 1 missense). 3/5 patients with STM reported an improvement of seizures (n = 2 truncation, n = 1 splicing). 3/5 CLB patients showed an improvement (n = 2: truncation; n = 1 splicing). Steroids were reported to have a positive effect on seizure frequency in 3/5 patients (n = 1 each truncation, splicing or deletion). CONCLUSIONS: Our data indicate that children with epilepsy due to pathogenic GRIN2A mutations present with different clinical phenotypes and a spectrum of seizure types in the context of a pharmacoresistant epilepsy providing information for clinicians treating children with this form of genetically determined epileptic syndrome.
Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/genética , Receptores de N-Metil-D-Aspartato/genética , Adolescente , Adulto , Criança , Pré-Escolar , Resistência a Medicamentos/genética , Feminino , Humanos , Lactente , Masculino , Mutação , Fenótipo , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Glucose transporter type 1 deficiency syndrome is a genetically determined, treatable, neurologic disorder that is caused by an insufficient transport of glucose into the brain. It is caused by a mutation in the SCL2A1 gene, which is so far the only known to be associated with this condition. Glucose transporter type 1 deficiency syndrome consists of a wide clinical spectrum that usually presents with cognitive impairment, epilepsy, paroxysmal exercise-induced dyskinesia, acquired microcephaly, hemolytic anemia, gait disturbance, and dyspraxia in different combinations. However, there are other clinical manifestations that we consider equally peculiar but that have so far been poorly described in literature. In this review, supported by a video contribution, we will accurately describe this type of clinical manifestation such as oculogyric crises, weakness, paroxysmal kinesigenic and nonkinesigenic dyskinesia in order to provide an additional instrument for a correct, rapid diagnosis.
Assuntos
Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Erros Inatos do Metabolismo dos Carboidratos/fisiopatologia , Proteínas de Transporte de Monossacarídeos/deficiência , Adolescente , Erros Inatos do Metabolismo dos Carboidratos/genética , Criança , Pré-Escolar , Diagnóstico Diferencial , Progressão da Doença , Feminino , Transportador de Glucose Tipo 1/genética , Humanos , Lactente , Masculino , Proteínas de Transporte de Monossacarídeos/genética , Mutação , Fenótipo , Estudos Retrospectivos , Gravação em Vídeo , Adulto JovemRESUMO
AIMS: Numerous studies have demonstrated the utility of extremely low frequencies (ELF) electromagnetic fields in the treatment of pain. Moreover, the effects of these fields seems to depend on their respective codes (frequency, intensity, waveform). In our study we want to assess the effects of the TAMMEF (Therapeutic Application of a Musically Modulated Electromagnetic Field) system, whose field is piloted by a musical signal and its parameters (frequency, intensity, waveform) are modified in time, randomly varying within the respective ranges, so that all possible codes can occur during a single application. PATIENTS AND METHODS: Sixty subjects, affected by shoulder periarthritis were enrolled in the study and randomly divided into three groups of 20 patients each: A exposed to TAMMEF, B exposed to ELF, C exposed to a simulated field. All subjects underwent a cycle of 15 daily sessions of 30 minutes each and a clinical examination upon enrollment, after 7 days of therapy, at the end of the cycle and at a follow-up 30 days later. RESULTS: All the patients of groups A and B completed the therapy without the appearance of side effects: they presented a significant improvement of the subjective pain and the functional limitation, which remained stable at the follow-up examination. In group C, there was no improvement of the pain symptoms or articular functionality. CONCLUSIONS: This study suggests that the TAMMEF system is efficacious in the control of pain symptoms and in the reduction of functional limitation in patients with shoulder periarthritis. Moreover, the effects of the TAMMEF system cover those produced by the ELF field.
Assuntos
Terapia por Estimulação Elétrica/métodos , Campos Eletromagnéticos , Periartrite/terapia , Modalidades de Fisioterapia/instrumentação , Articulação do Ombro , Dor de Ombro/terapia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Música , Medição da Dor , Periartrite/fisiopatologia , Recuperação de Função Fisiológica , Articulação do Ombro/fisiopatologia , Dor de Ombro/fisiopatologia , Resultado do TratamentoRESUMO
UNLABELLED: The aim this study was to assess the efficacy of cisplatin-epirubicin-vinorelbine, as primary chemotherapy, in reducing the tumour burden in T2-3 N0-2 breast carcinomas. Breast conservative surgery (BCS) rate, clinical and pathological complete response (pCR), toxicity and 5-year disease-free survival (DFS) and overall survival (OS) were evaluated. PATIENTS AND METHODS: Eighty-eight women with tumours > or =2.5 cm were treated with cisplatin (P) 50 mg/m2, epirubicin (E) 100 mg/m2 and vinorelbine (V) 25 mg/m2, every 3 weeks. RESULTS: Fifty-six out of the 88 patients (63.6%) underwent BCS, notably including 12/23 patients with initial tumours >5 cm. The overall clinical response was 72.8% (cCR=11.4%), pCR 20.5% and pTO+pNO 17%. No cardiac toxicity was observed. Grade 3/4 adverse events were leukopenia (9.4%), neutropenia (7.9%), nausea and vomiting (7.3%). After a median follow-up of 5 years, 24 patients (27.3%) had developed local or distant metastases. The mean DFS and OS were 51.7 (SE 2.38) and 57.02 (SE 1.98) months, respectively, and were significantly higher in pCR patients in comparison to the others (63.05 vs. 48.76, p<0.01 and 64.59 vs. 55.04, p<0.05, respectively). CONCLUSION: The PEV regimen was highly effective in reducing the tumour burden, especially for large tumours. The rate of pCR was similar to that obtained by other, including taxane-based regimens, and was well-tolerated. The study demonstrated the feasibility of such a regimen even in small centres, and being of low cost this combination could be of value in the application of primary therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Cisplatino/administração & dosagem , Terapia Combinada , Intervalo Livre de Doença , Epirubicina/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , VinorelbinaRESUMO
OBJECTIVE: Single-agent epirubicin was tested as primary chemotherapy treatment in patients with early breast cancer >3 cm. METHODS: 100 women with locally advanced breast cancer >3 cm were treated with three cycles of single-agent epirubicin at a dose of 120 mg/m2. All patients showing tumor shrinkage to less than 3 cm were considered candidates for conservative surgery (quadrantectomy); in the remaining patients modified radical mastectomy was carried out. Postsurgical treatment consisted of CMF chemotherapy except for postmenopausal node-positive, estrogen-positive patients who were assigned to hormonal treatment with tamoxifen and postmenopausal node-negative, estrogen-positive ones who did not receive any treatment. RESULTS: Quadrantectomy was carried out in 71 patients. At the median follow-up time of 69 months, the relapse rate was 29.6% among patients who underwent quadrantectomy (21 out of 71) and 58.6% among patients who underwent modified radical mastectomy (17 out of 29). CONCLUSIONS: Single-agent chemotherapy with anthracyclines could appear to be an effective treatment in inducing a tumor downstaging in patients with early breast cancer >3 cm. This treatment can be administered outside clinical trials in patients who desire to preserve their body integrity. Further prospective, randomized trials are needed in order to validate and better define the role of epirubicin in the neoadjuvant strategy of breast cancer patients.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma/tratamento farmacológico , Epirubicina/uso terapêutico , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma/patologia , Carcinoma/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Itália , Metástase Linfática , Mastectomia Radical Modificada , Mastectomia Segmentar , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVE: Numerous studies have demonstrated the utility of extremely low frequencies (ELF) electromagnetic fields in clinical practice. Moreover, the effects of these fields seems to depend on their respective codes (frequency, intensity, waveform). In our study we want to value the effects of the TAMMEF (Therapeutic Application of a Musically Modulated Electromagnetic Field) system, which field is piloted by a musical signal. METHODS: Ninety subjects, affected by primary osteoarthritis of the knee, were enrolled in the study and randomly divided into three groups of 30 patients each: A exposed to TAMMEF, B exposed to ELF, C exposed to a simulated field. All subjects underwent a cycle of 15 daily sessions of 30 minutes each and a clinical examination upon enrolment, after 7 days of therapy, at the end of the cycle and at a follow-up 30 days later: RESULTS: All the patients of groups A and B completed the therapy without the appearance of side effects: they presented a significant improvement of the subjective pain and the functional limitation, which remained stable at the follow-up examination. In group C, there was no improvement of the pain symptoms or articular functionality. CONCLUSIONS: This study suggests that the TAMMEF system is efficacious in the control of pain symptoms and in the reduction of functional limitation in patients with knee osteoarthritis. Moreover, the effects of the TAMMEF system cover those produced by the ELF field.
Assuntos
Artralgia/terapia , Campos Eletromagnéticos , Musicoterapia/métodos , Osteoartrite do Joelho/terapia , Idoso , Artralgia/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Recuperação de Função Fisiológica/efeitos da radiação , Resultado do TratamentoRESUMO
Pain is a highly distressing symptom for patients with advanced cancer. WHO analgesic ladder is widely accepted as a guideline for its treatment. Our aim was to describe pain prevalence among patients diagnosed with advanced non-small-cell lung cancer (NSCLC), impact of pain on quality of life (QoL) and adequacy of pain management. Data of 1021 Italian patients enrolled in three randomised trials of chemotherapy for NSCLC were pooled. QoL was assessed by EORTC QLQ-C30 and LC-13. Analgesic consumption during the 3 weeks following QoL assessment was recorded. Adequacy of pain management was evaluated by the Pain Management Index (PMI). Some pain was reported by 74% of patients (42% mild, 24% moderate and 7% severe); 50% stated pain was affecting daily activities (30% a little, 16% quite a bit, 3% very much). Bone metastases strongly affected presence of pain. Mean global QoL linearly decreased from 64.9 to 36.4 from patients without pain to those with severe pain (P<0.001). According to PMI, 616 out of 752 patients reporting pain (82%) received inadequate analgesic treatment. Bone metastases were associated with improved adequacy and worst pain with reduced adequacy at multivariate analysis. In conclusion, pain is common in patients with advanced NSCLC, significantly affects QoL, and is frequently undertreated. We recommend that: (i). pain self-assessment should be part of oncological clinical practice; (ii). pain control should be a primary goal in clinical practice and in clinical trials; (iii). physicians should receive more training in pain management; (iv). analgesic treatment deserves greater attention in protocols of anticancer treatment.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/complicações , Neoplasias Pulmonares/complicações , Manejo da Dor , Dor/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/complicações , Neoplasias Ósseas/secundário , Carcinoma Pulmonar de Células não Pequenas/secundário , Feminino , Humanos , Itália , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Medição da Dor , Prevalência , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de DoençaRESUMO
Gemcitabine is considered the gold standard treatment for unresectable pancreatic adenocarcinoma. Intra-arterial drug administration had shown some interesting results in small phase II studies. In this study, patients were randomly assigned to receive gemcitabine at a dose of 1,000 mg/m2 over 30 minutes intravenously weekly for 7 weeks, followed by 1 week of rest, then weekly for 3 weeks every 4 weeks or FLEC: 5-fluoruracil 1,000 mg/m2, leucovorin 100 mg/m2, epirubicin 60 mg/m2, carboplatin 300 mg/m2 infused bolus intra-arterially into celiac axis at a 3-week interval 3 times or 5-fluorouracil 400 mg/m2 plus folinic acid 20 mg/m2 for 5 days every 4 weeks for 6 cycles. The primary endpoint was overall survival, while time to treatment failure, response rate, clinical benefit response were secondary endpoints. Sixty-seven patients were randomly allocated gemcitabine and 71 were allocated FLEC intra-arterially. Patients treated with FLEC lived for significantly longer than patients on gemcitabine (p=0.036). Survival at 1 year increased from 21% in the gemcitabine group to 35% in the FLEC group. Median survival was 7.9 months in the FLEC group and 5.8 months in the gemcitabine group. Median time to treatment failure was longer with FLEC (5.3 vs 4.2 months for FLEC vs gemcitabine respectively; p=0.013). Clinical benefit was similar in both groups (17.9% for gemcitabine and 26.7% for FLEC; p=NS). CT-scan partial response was similar in both groups (5.9% for gemcitabine and 14% for FLEC; p=NS). Toxicity profiles were different. Compared with gemcitabine, the FLEC regimen given intra-arterially improved survival in patients with unresectable pancreatic adenocarcinoma.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carboplatina/administração & dosagem , Desoxicitidina/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intra-Arteriais , Infusões Intravenosas , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Análise de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
The present study describes supportive care (SC) in patients with advanced non-small-cell lung cancer (NSCLC), evaluating whether it is affected by concomitant chemotherapy, patient's performance status (PS) and age. Data of patients enrolled in three randomised trials of first-line chemotherapy, conducted between 1996 and 2001, were pooled. The analysis was limited to the first three cycles of treatment. Supportive care data were available for 1185 out of 1312 (90%) enrolled patients. Gastrointestinal drugs (45.7%), corticosteroids (33.4%) and analgesics (23.8%) were the most frequently observed categories. The mean number of drugs per patient was 2.43; 538 patients (45.4%) assumed three or more supportive drugs. Vinorelbine does not produce substantial variations in the SC pattern, while cisplatin-based treatment requires an overall higher number of supportive drugs, with higher use of antiemetics (41 vs 27%) and antianaemics (10 vs 4%). Patients with worse PS are more exposed to corticosteroids (42 vs 30%). Elderly patients require drugs against concomitant diseases significantly more than adults (20 vs 7%) and are less frequently exposed to antiemetics (12 vs 27%). In conclusion, polypharmacotherapy is a relevant issue in patients with advanced NSCLC. Chemotherapy does not remarkably affect the pattern of SC, except for some drugs against side effects. Elderly patients assume more drugs for concomitant diseases and receive less antiemetics than adults.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Vimblastina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Antieméticos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/secundário , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Vimblastina/administração & dosagem , Vinorelbina , GencitabinaRESUMO
Gemcitabine is considered the golden standard treatment for unresectable pancreatic adenocarcinoma. Intra-arte-rial drug administration had shown a deep rationale with some interesting results. In a multicenter phase III trial, we compared gemcitabine given weekly with a combination of 5-fluoruracil, leucovorin, epirubicin, carboplatin (FLEC) administered intra-arteriously as first-line therapy in unresectable pancreatic adenocarcinoma. Patients were randomly assigned to receive gemcitabine at a dose of 1,000 mg/m2 over 30 minutes intravenously weekly for 7 weeks, followed by 1 week of rest, then weekly for 3 weeks every 4 weeks or 5-fluoruracil 1,000 mg/m2, leucovorin 100 mg/m2, epirubicin 60 mg/m2, carboplatin 300 mg/m2 infused bolus intra-arteriously at three-weekly interval for 3 times. The primary end point was overall survival, while time to treatment failure, response rate, clinical benefit response were secondary endpoints. Sixty-seven patients were randomly allocated gemcitabine and 71 were allocated FLEC intra-arterially. Patients treated with FLEC lived for significantly longer than patients on gemcitabine (p=.036). Survival at 1 year was increased from 21% in the gemcitabine group to 35% in the FLEC group. Median survival was 7.9 months in the FLEC group and 5.8 months in the gemcitabine group. Median time to treatment failure was longer with FLEC (5.3 vs 4.2 months for FLEC vs gemcitabine respectively; p=.013). Clinical benefit was similar in both groups (17.9% for gemcitabine and 26.7% for FLEC; p=NS). CT-scan partial response was similar in both group (5.9% for gemcitabine and 14% for FLEC; p=NS). Toxicity profiles were different. Compared with gemcitabine, FLEC regimen given intra-arteriously, improved survival in patient with unresectable pancreatic adenocarcinoma.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/mortalidade , Adulto , Idoso , Carboplatina/administração & dosagem , Desoxicitidina/administração & dosagem , Intervalo Livre de Doença , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intra-Arteriais , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Análise de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
Our aim was to study the activity and toxicity of the gemcitabine plus vinorelbine (Gem Vin) combination and to identify the optimal dose. Previously untreated patients aged < 70 years, with stage IV or IIIb (not candidates for radiotherapy) non-small cell lung cancer were eligible. Studied dose-levels of Gem Vin, administered on days 1 and 8 every 3 weeks, were (mg m(-2)): level I = 1000/25; level II = 1200/25; level III = 1000/30; level IV = 1200/30. A feasibility study was performed at each dose-level, followed by a single-stage phase II study. Dose-level IV was unfeasible because of grade 4 neutropenia. Overall, out of 126 patients enrolled in phase II studies, there were one complete and 32 partial responses (response rate 26%: 95% CI 18-34%). Response rates were 27.9%, 21.4% and 29.3% at levels I, II and III, respectively. The treatment was well tolerated. Toxicity was less frequent and severe at level I. Overall median survival was 33 weeks (95% CI 28-40). Descriptive quality of life analysis showed that patients with a worse baseline global health status score tended to drop out of the study earlier than those with a better score. Gem Vin is feasible at different doses. It is sufficiently active and well tolerated. A phase III study to compare the effect on quality of life of Gem Vin (level I) vs cisplatin-based chemotherapy is ongoing.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Qualidade de Vida , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina , GencitabinaRESUMO
AIMS: As melatonin has been found to play a role in the mechanisms of cardiovascular regulation, we designed the present study to evaluate whether the evening ingestion of the pineal hormone might interfere with the antihypertensive therapy in hypertensive patients well-controlled by nifedipine monotherapy. METHODS: Forty-seven mild to moderate essential hypertensive outpatients taking nifedipine GITS 30 or 60 mg monotherapy at 08.30 h for at least 3 months, were given placebo or melatonin 5 mg at 22.30 h for 4 weeks according to a double-blind cross-over study. At the end of each treatment period patients underwent a 24 h noninvasive ambulatory blood pressure monitoring (ABPM) during usual working days; sleeping period was scheduled to last from 23.00 to 07.00 h. RESULTS: The evening administration of melatonin induced an increase of blood pressure and heart rate throughout the 24 h period (DeltaSBP = + 6.5 mmHg, P < 0.001; DeltaDBP = + 4.9 mmHg, P < 0.01; DeltaHR = + 3.9 beats min-1, P < 0.01). The DBP as well as the HR increase were particularly evident during the morning and the afternoon hours. CONCLUSIONS: We hypothesize that competition between melatonin and nifedipine, is able to impair the antihypertensive efficacy of the calcium channel blocker. This suggests caution in uncontrolled use of melatonin in hypertensive patients. As the pineal hormone might interfere with calcium channel blocker therapy, it cannot be considered simply a dietary supplement.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Melatonina/farmacologia , Nifedipino/uso terapêutico , Adulto , Idoso , Estudos Cross-Over , Método Duplo-Cego , Interações Medicamentosas , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: We have recently suggested that bolus 5-fluorouracil (5-FU) may work via a RNA directed mechanism while continuous infusion 5-FU may kill cells via a thymidylate synthase related pathway. It may thus be possible to selectively modulate each schedule biochemically. We have compared an alternating regimen of bolus and continuous infusion 5-FU, selectively modulated for the schedule of administration, with modulated bolus 5-FU in advanced colorectal cancer patients. PATIENTS AND METHODS: Two hundred fourteen patients from nineteen Italian centers were randomized to the control arm consisting of biweekly cycles of MTX, 200 mg/m2 on day 1, followed by bolus 5-FU 600 mg/m2 on day 2 and 6-S-leucovorin rescue, or to the experimental arm consisting of two biweekly cycles of the same regimen as in the control arm alternated to three weeks of continuous infusion 5-FU (200 mg/m2 day) + weekly bolus 6-S-leucovorin, 20 mg/m2. RESULTS: Nine CR and twenty-seven PR were obtained on one hundred eleven evaluable patients treated in experimental arm (RR = 32%, 95% confidence interval (95% CI): 24%-42%), while two CR and eleven PR were observed among one hundred three evaluable patients in control arm (RR = 13%, 95% CI: 7%-21%). WHO grade 3-4 toxicity occurred in 13% of cycles of experimental arm and in 8% of cycles in control arm. The PFS was significantly longer in experimental arm (6.2 vs. 4.3 months, odds ratio 0.66, P = 0.003), while the overall survival was similar in both arms (14.8 months in experimental arm vs. 14.1 months in control arm); quality of life was similar as well. Eighty percent of patients receiving second-line chemotherapy in control arm were treated with continuous infusion 5-FU. CONCLUSIONS: Alternating, schedule-specific biochemical modulation of FU is more active than MTX --> 5-FU as first-line treatment of advanced colorectal cancer. However, the overall survival was similar suggesting that alternating bolus and infusional 5-FU upfront may be as effective as giving them in sequence as first- and second-line treatment.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/administração & dosagem , Adulto , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Conjuntivite/induzido quimicamente , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Fluoruracila/efeitos adversos , Gastroenteropatias/induzido quimicamente , Humanos , Infusões Intravenosas , Injeções Intravenosas , Leucovorina/administração & dosagem , Tábuas de Vida , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Cooperação do Paciente , Qualidade de Vida , Terapia de Salvação , Análise de Sobrevida , Resultado do TratamentoRESUMO
In a randomized clinical trial, gemcitabine (GEM) was more effective than 5-fluorouracil (5-FU) in advanced pancreatic cancer patients. GEM and 5-FU have different mechanisms of action and their combination, from a theoretical point of view, could result in a higher activity. To test activity and feasibility of such a combination, a multi-institutional phase II study was initiated in November 1996 by the Italian Group for the study of Digestive Tract Cancer (GISCAD). Primary objectives of this study were to determine the activity in terms of response rate and clinical benefit, while the secondary objective was toxicity. According to the optimal two-stage phase II design, 54 patients were enrolled. Schedule was: GEM 1000 mg m(-2) intravenous (i.v.), and 5-FU 600 mg m(-2) bolus i.v. weekly for 3 weeks out of every 4. All the 54 patients were symptomatic (pain, weight loss, dyspepsia). A clinical benefit was obtained in 28 patients (51%) (95% confidence interval (CI) 38-64%). Two patients achieved a partial response and 34 a stable disease. Median survival for all the patients was 7 months. Side-effects were mild: no gastrointestinal or haematological grade 3-4 toxicity (WHO) were recorded. We observed only six episodes of grade 2 (WHO) leukopenia and seven episodes of thrombocytopenia. Although the non-randomized design of this study suggests caution in the interpretation of these data, in consideration of the low incidence of toxicity and the favourable results obtained in terms of clinical benefit, it may be worthwhile to test more active schedules of 5-FU (continuous infusion) in combination with gemcitabine.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , GencitabinaRESUMO
The influence of acute sleep deprivation during the first part of the night on 24-h blood pressure monitoring (ABPM) was studied in 36 never-treated mild to moderate hypertensive patients. According to a crossover design, they were randomized to have either sleep deprivation or a full night's sleep 1 week apart, during which they were monitored with ABPM. Urine samples for analysis of nocturnal urinary excretion of norepinephrine were collected. During the sleep-deprivation day, both mean 24-h blood pressure and mean 24-h heart rate were higher in comparison with those recorded during the routine workday, the difference being more pronounced during the nighttime (P < .01). Urinary excretion of norepinephrine showed a significant increase at night during sleep deprivation (P < .05). Blood pressure and heart rate significantly increased in the morning after a sleep-insufficient night (P < .05). These data suggest that lack of sleep in hypertensive patients may increase sympathetic nervous activity during the night and the following morning, leading to increased blood pressure and heart rate. This situation might represent an increased risk for both target organ damage and acute cardiovascular diseases.
Assuntos
Pressão Sanguínea/fisiologia , Hipertensão/fisiopatologia , Privação do Sono/fisiologia , Adulto , Idoso , Monitorização Ambulatorial da Pressão Arterial , Ritmo Circadiano , Creatinina/urina , Estudos Cross-Over , Feminino , Seguimentos , Frequência Cardíaca , Humanos , Hipertensão/etiologia , Hipertensão/urina , Masculino , Pessoa de Meia-Idade , Norepinefrina/urina , Prognóstico , Fatores de Risco , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/fisiopatologiaRESUMO
A 17-year-old female followed for atypical eating disorder characterized by restriction was noted to worsen medically during winter months in each of 2 consecutive years. A trial of bright light therapy was initiated during the second admission. Within days of light treatment, the patient showed signs of clinical improvement in mood and eating. Within 1 month of light treatment, the patient's depression ratings decreased from a Beck Depression Inventory (BDI) score of 37 (severe) to 17 (mild/moderate). In addition, her eating improved moderately as revealed both by a slight decrease in Eating Attitudes Test (EAT) score (78 to 64) and by significant improvements in dietary intake and medical status. The present report suggests that light therapy may be a useful adjunct in the clinical management of eating-disordered youth who present with seasonal patterns of exacerbation. Controlled studies of light treatment in younger eating disorder populations are warranted.
Assuntos
Anorexia Nervosa/complicações , Fototerapia , Transtorno Afetivo Sazonal/complicações , Transtorno Afetivo Sazonal/terapia , Adolescente , Anorexia Nervosa/psicologia , Feminino , Humanos , Transtorno Afetivo Sazonal/diagnóstico , Índice de Gravidade de DoençaRESUMO
AIM: To explore the feasibility and activity of a combined regimen of high-dose epirubicin and cisplatin as an alternative to current treatments for non-small cell lung cancer (NSCLC). METHOD: Forty-four patients with stage IIIb or IV NSCLC, median Karnofsky index 90, were enrolled. Epirubicin (60 mg/m2) was administered on days 1 and 2 and cisplatin (100 mg/m2) on day 1. Treatment was repeated every 21 days for a maximum of six cycles. A hematopoietic growth factor (G-CSF) was used only for patients reaching codified nadir count values. RESULTS: A total of 130 cycles were administered with a mean of 2.9 cycles per patient. Of 41 assessable patients one showed a complete response and 15 had partial responses (overall response rate, 39%). Grade 3 or 4 leukopenia and grade 3 hemoglobin toxicity were seen in 40% and 14%, respectively, of the administered cycles. The most common nonhematologic toxic events were nausea and vomiting, mucositis, anorexia, and asthenia. CONCLUSIONS: This epirubicin-cisplatin regimen seemed effective and was generally well tolerated, and therefore suitable for use in an outpatient setting.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Esquema de Medicação , Epirubicina/administração & dosagem , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Resultado do TratamentoRESUMO
OBJECTIVE: To determine whether the evening intake of 5 mg melatonin affects 24 h arterial blood pressure and heart-rate profiles. METHODS: Twenty-one young normotensive subjects were administered placebo or melatonin for 4 weeks, according to a cross-over double-blind design, and were subjected to ambulatory blood pressure monitoring on the first and last days of each treatment period. RESULTS: The chronic melatonin intake caused a decrease in systolic blood pressure throughout the 24 h period (109.1+/- 7.2 versus 113.6 +/- 8.15 mmHg, P < 0.05), a decrease in diastolic blood pressure (by 6.4 mmHg, P < 0.05) limited to the second half of the night, a slight lowering of the heart rate during the diurnal hours (78.6 +/- 7.6 versus 81.5 +/- 10.1 beats/min, P < 0.05) and an acceleration of a similar degree during the second half of the night. The slight hypotensive action and the diurnal heart-rate lowering may be explained theoretically in terms of various complex and synergistic mechanisms that so far have been verified only in experimental studies on animals. The etiology of the nocturnal heart-rate acceleration remains unknoiwn. Further controlled studies are needed in order to better understand the cardiovascular effects of melatonin and to evaluate possible pharmacologic interactions. CONCLUSION:
RESUMO
BACKGROUND: Although leucovorin (LV) + 5-fluorouracil (5-FU) is considered the treatment of choice for advanced colorectal cancer in most countries, the optimal schedule of this combination has not yet been established. Low-dose LV appears to be as active as high-dose LV in the daily-times-five regimen, but no randomized study of the levorotatory stereoisomer (6S-LV) given at two different dose levels has been published. PATIENTS AND METHODS: Between November 1991 and June 1994, 422 patients (all with measurable disease previously untreated with chemotherapy) were randomized to 6S-LV (100 mg/sqm/i.v.) + 5-FU (370 mg sqm/15 min i.v. infusion), both administered for 5 days every 28 days (arm A), or to 6S-LV (10 mg/sqm/i.v./5-FU (doses as above), also given for 5 days every 28 days (arm B). The primary endpoint of the study was the comparison of response rates (WHO criteria): the secondary endpoint was the assessment of survival and tolerability. No evaluation of the quality of life or the symptomatic effect of treatment was planned. RESULTS: The response rate was 9.3% in arm A (95% CI: 5.4-13.1), with 2 CR and 18 PR, and 10.7% in arm B (95% CI: 6.5-14.9), with 3 CR + 19 PR, without any significant difference (P = 0.78). The median time to progression was eight months in both groups and overall survival was 11 months, with no difference between treatments. Toxicity mainly consisted of gastrointestinal side effects (mucositis and diarrhoea), which were rarely severe (grade 3-4: 5%-10% of patients) and similar in the two groups. CONCLUSIONS: In this large-scale multicentre trial, the low and high doses of 6S-LV appeared to be equivalent in terms of the biochemical modulation of 5-FU in advanced colorectal cancer although, for several reasons (including the timing and the strict criteria of response evaluation, the high number of patients with unfavourable prognostic factors, the multi-institutional nature of the study, the dose and modality of 5-FU administration), the response rate was lower than that reported in some of the other published studies. Given the considerable difference in economic cost between the two dosages, the use of high-dose 6S-LV in the daily-times-five regimen is not recommended in clinical practice.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND AND METHODS: Familial occurrence of immunoglobulin-related (AL) amyloidosis has occasionally been reported. In this work we describe the concomitance of systemic amyloidosis and monoclonal gammopathy (one case of Waldenström's macroglobulinemia and two cases without multiple myeloma or related diseases) in three Italian siblings, two males and one female. RESULTS AND CONCLUSIONS: All of them showed a common pattern of polyneuropathy to different degrees; two presented a sicca syndrome and one also suffered from nephropathy. Two of them showed the same HLA typing with the same light chain type (k), but had different presenting symptoms. Polyneuropathy and a history of peptic disease in two cases was suggestive of type III familial amyloidotic polyneuropathy (FAP) occurring in the setting of a familial monoclonal component. However, immunohistochemical studies on different tissue specimens using anti-apolipoprotein A1 and anti-transthyretin antibodies were negative. Further screening of DNA samples for transthyretin (TTR) gene mutations was also negative. Clinical and laboratory investigations ruled out reactive or senile amyloidosis and immunohistochemical studies with anti-light chain antibodies on amyloidotic tissue specimens were positive. As a consequence, this family represents a new case of familial AL-amyloidosis.