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OBJECTIVE: In the Netherlands, patients with ovarian cancer are offered genetic testing. Pre-test preparation may help counseling patients. The aim of this study was to determine if use of a web-based intervention, leads to more effective genetic counseling of ovarian cancer patients. METHODS: Between 2016 and 2018, 127 ovarian cancer patients referred for genetic counseling in our hospital participated in this trial. 104 Patients were analyzed. All patients filled out questionnaires pre- and post-counseling. The intervention group also completed a questionnaire after visiting an online tool. Length of consultation, patients' satisfaction, knowledge, anxiety, depression and distress were compared before and after counselling. RESULTS: The intervention group had the same level of knowledge compared to the counseling group, but at an earlier point in time. They were satisfied with the intervention (86%) and better prepared for counseling (66%). The intervention did not lead to shorter consultations. No differences in levels of anxiety, depression, distress and satisfaction were observed. CONCLUSION: Although consultation length was unaffected, the improvements in knowledge after online education and patients satisfaction indicates that this tool can be an effective addition to genetic counseling. PRACTICE IMPLICATIONS: Use of an educational tool may lead to a more effective, personalized way of genetic counselling and enables shared decision making.
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Asesoramiento Genético , Intervención basada en la Internet , Neoplasias Ováricas , Asesoramiento Genético/psicología , Neoplasias Ováricas/genética , Neoplasias Ováricas/psicología , Humanos , Femenino , Países Bajos , Satisfacción del Paciente , Conocimientos, Actitudes y Práctica en Salud , Ansiedad , Adulto , Persona de Mediana EdadRESUMEN
The new Dutch guidelines on hereditary and familial ovarian carcinoma recommend genetic testing of all patients with epithelial ovarian cancer (EOC). With this study, we aimed to obtain insight into (1) the acceptance and timing of the offer of genetic counseling in women with EOC, (2) reasons for accepting or declining genetic counseling, and (3) psychological differences between women who did and did not have genetic counseling. A multicenter questionnaire survey was performed in patients with EOC in four Dutch oncology centers. The questionnaire addressed whether, how, and when genetic counseling was offered, women's arguments to accept or decline genetic counseling, and included the Cancer Worry Scale (CWS) and the Hospital Anxiety and Depression Scale (HADS). A total of 67 women completed the questionnaire, of which 43 had genetic counseling. Despite a wide variability in the timing of the offer of genetic counseling, 89% of the women were satisfied with the timing. No significant differences were found between the CWS and HADS scores for the timing of the offer of genetic counseling and whether or not women had genetic counseling. Taking the small sample size into account, the results tentatively suggest that genetic counseling may have limited impact on the psychosocial wellbeing of women with EOC. Therefore, we assume that implementation of the new guidelines offering genetic counseling to all patients with EOC will not cause considerable additional burden to these patients.
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BACKGROUND: Patients with hereditary diffuse gastric cancer and a CDH1 mutation have a 60-80 per cent lifetime risk of developing diffuse gastric cancer. Total prophylactic gastrectomy eliminates this risk, but is associated with considerable morbidity. The effectiveness (removal of all gastric mucosa) and outcomes of this procedure were evaluated retrospectively. METHODS: All consecutive individuals undergoing a prophylactic gastrectomy for a CDH1 mutation or gastric signet ring cell foci at the authors' institute between 2005 and 2017 were included. RESULTS: In 25 of 26 patients, intraoperative frozen-section examination (proximal resection margin) was used to verify complete removal of gastric mucosa. All definitive resection margins were free of gastric mucosa, but only after the proximal margin had been reresected in nine patients. In the first year after surgery, five of the 26 patients underwent a relaparotomy for adhesiolysis (2 patients) or jejunostomy-related complications (3 patients). Six patients were readmitted to the hospital within 1 year for nutritional and/or psychosocial support (4 patients) or surgical reintervention (2 patients). Mean weight loss after 1 year was 15 (95 per cent c.i. 12 to 18) per cent. For the 25 patients with a follow-up at 1 year or more, functional complaints were reported more frequently at 1 year than at 3 months after the operation: bile reflux (15 versus 11 patients respectively) and dumping (11 versus 7 patients). The majority of patients who worked or studied before surgery (15 of 19) had returned fully to these activities within 1 year. CONCLUSION: The considerable morbidity and functional consequences of gastrectomy should be considered when counselling individuals with an inherited predisposition to diffuse gastric cancer. Intraoperative frozen-section examination is recommended to remove all risk-bearing gastric mucosa.
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Antígenos CD/genética , Cadherinas/genética , Gastrectomía/métodos , Síndromes Neoplásicos Hereditarios/prevención & control , Procedimientos Quirúrgicos Profilácticos/métodos , Neoplasias Gástricas/prevención & control , Adulto , Femenino , Estudios de Seguimiento , Gastrectomía/efectos adversos , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Mutación , Síndromes Neoplásicos Hereditarios/cirugía , Procedimientos Quirúrgicos Profilácticos/efectos adversos , Estudios Retrospectivos , Estómago/patología , Estómago/cirugía , Neoplasias Gástricas/cirugía , Resultado del TratamientoRESUMEN
Gastrointestinal stromal tumors (GISTs) occur mostly sporadically. GISTs associated with a familial syndrome are very rare and are mostly wild type for KIT and platelet-derived growth factor alpha (PDGFRA). To date 35 kindreds and 8 individuals have been described with GISTs associated with germline KIT mutations. This is the third family described with a germline p.Trp557Arg mutation in exon 11 of the KIT gene. The effect of imatinib in patients harboring a germline KIT mutation has been rarely described. Moreover, in some studies imatinib treatment was withheld considering the lack of evidence for efficacy of this treatment in GIST patients harboring a germline KIT mutation. This paper describes a 52-year old patient with a de novo germline p.Trp557Arg mutation with multiple GISTs throughout the gastrointestinal tract and cutaneous hyperpigmentation. Imatinib treatment showed long-term regression of the GISTs and evident pathological response was seen after resection. Remarkably, the hyperpigmentation of the skin also diminished during imatinib treatment. Genetic screening of the family revealed the same mutation in two daughters, both with similar cutaneous hyperpigmentation. One daughter, aged 23, was diagnosed with multiple small intestine GISTs, which were resected. She was treated with adjuvant imatinib which prompted rapid regression of the cutaneous hyperpigmentation. Imatinib treatment in GIST patients harboring a germline KIT mutation shows favorable and long-term responses in both the tumor and the phenotypical hyperpigmentation.
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Antineoplásicos/uso terapéutico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Hiperpigmentación/tratamiento farmacológico , Mesilato de Imatinib/uso terapéutico , Síndromes Neoplásicos Hereditarios/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-kit/genética , Adulto , Edad de Inicio , Antineoplásicos/farmacología , Exones/genética , Femenino , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/patología , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Mutación de Línea Germinal , Humanos , Hiperpigmentación/genética , Mesilato de Imatinib/farmacología , Síndromes Neoplásicos Hereditarios/diagnóstico , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/patología , Proteínas Proto-Oncogénicas c-kit/antagonistas & inhibidores , Recto/diagnóstico por imagen , Recto/patología , Piel/efectos de los fármacos , Piel/patología , Estómago/diagnóstico por imagen , Estómago/patología , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
Only a minority of individuals who undergo cancer genetic counseling experience heightened levels of psychological distress, but many more experience a range of cancer genetic-specific psychosocial problems. The aim of this study was to estimate the prevalence of such psychosocial problems, and to identify possible demographic and clinical variables associated significantly with them. Consenting individuals scheduled to undergo cancer genetic counseling completed the Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire, the Hospital Anxiety and Depression Scale (HADS) and the Distress Thermometer (DT) prior to or immediately following their counseling session. More than half of the 137 participants reported problems on three or more domains of the PAHC, most often in the domains 'living with cancer' (84%), 'family issues' (46%), 'hereditary predisposition' (45%), and 'child-related issues' (42%). Correlations between the PAHC, the HADS and the DT were low. Previous contact with a psychosocial worker, and having a personal history of cancer were associated significantly with HADS scores, but explained little variance (9%). No background variables were associated significantly with the DT. Previous contact with a psychosocial worker, and having children were significantly associated with several PAHC domains, again explaining only a small percentage of the variance (2-14%). The majority of counselees experience specific cancer genetic counseling-related psychosocial problems. Only a few background variables are associated significantly with distress or psychosocial problems. Thus we recommend using the PAHC or a similar problem-oriented questionnaire routinely in cancer genetic counseling to identify individuals with such problems.
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Ansiedad/diagnóstico , Depresión/diagnóstico , Asesoramiento Genético/psicología , Predisposición Genética a la Enfermedad/psicología , Síndromes Neoplásicos Hereditarios/psicología , Estrés Psicológico/diagnóstico , Adolescente , Adulto , Anciano , Ansiedad/epidemiología , Ansiedad/psicología , Depresión/epidemiología , Depresión/psicología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Síndromes Neoplásicos Hereditarios/genética , Países Bajos/epidemiología , Prevalencia , Estrés Psicológico/epidemiología , Estrés Psicológico/psicología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Approximately 70% of counselees undergoing cancer genetic counseling and testing (CGCT) experience some degree of CGCT-related psychosocial problems. We evaluated the efficacy of an intervention designed to increase detection and management of problems 4 weeks after completion of CGCT. In this randomized, controlled trial, 118 participants completed a CGCT-related problem questionnaire prior to an - audiotaped - telephone session with their counselor 1 month after DNA-test disclosure. For those randomized to the intervention group (n = 63), a summary of the questionnaire results was provided to the counselor prior to the telephone session. Primary outcomes were discussion of the problems, counselors' awareness of problems, and problem management. Secondary outcomes included self-reported distress, cancer worries, CGCT-related problems, and satisfaction. Counselors who received a summary of the questionnaire were more aware of counselees' problems in only one psychosocial domain (practical issues). No significant differences in the number of problems discussed, in problem management, or on any of the secondary outcomes were observed. The prevalence of problems was generally low. The telephone session, combined with feedback on psychosocial problems, has minimal impact. The low prevalence of psychosocial problems 1 month post-CGCT recommends against its use as a routine extension of the CGCT procedure.
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Asesoramiento Genético/psicología , Neoplasias/genética , Neoplasias/psicología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/epidemiología , Países Bajos/epidemiología , Evaluación de Resultado en la Atención de Salud , Aceptación de la Atención de Salud , Satisfacción del Paciente , Prevalencia , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
Birt-Hogg-Dubé (BHD) syndrome is a cancer disorder caused by a pathogenic FLCN mutation characterized by fibrofolliculomas, lung cysts, pneumothorax, benign renal cyst, and renal cell carcinoma (RCC). In this case we describe a patient with bilateral renal tumour and a positive familial history for pneumothorax and renal cancer. Based on this clinical presentation, the patient was suspected for BHD syndrome, which was confirmed after molecular testing. We discuss the importance of recognizing this autosomal dominant cancer disorder when a patient is presented at the urologist with a positive family history of chromophobe renal cell cancer or a positive familial history for renal cell cancer and pneumothorax.
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BACKGROUND: BRCAness is defined as shared tumour characteristics between sporadic and BRCA-mutated cancers. However, how to exactly measure BRCAness and its frequency in breast cancer is not known. Assays to establish BRCAness would be extremely valuable for the clinical management of these tumours. We assessed BRCAness characteristics frequencies in a large cohort of triple-negative breast cancers (TNBCs). METHODS: As a measure of BRCAness, we determined a specific BRCA1-like pattern by array Comparative Genomic Hybridisation (aCGH), and BRCA1 promoter methylation in 377 TNBCs, obtained from 3 different patient cohorts. Clinicopathological data were available for all tumours, BRCA1-germline mutation status and chemotherapy response data were available for a subset. RESULTS: Of the tumours, 66-69% had a BRCA1-like aCGH profile and 27-37% showed BRCA1 promoter methylation. BRCA1-germline mutations and BRCA1 promoter methylation were mutually exclusive events (P=1 × 10(-5)). BRCAness was associated with younger age and grade 3 tumours. Chemotherapy response was significantly higher in BRCA1-mutated tumours, but not in tumours with BRCAness (63% (12 out of 19) vs 35% (18 out of 52) pathological complete remission rate, respectively). CONCLUSION: The majority of the TNBCs show BRCAness, and those tumours share clinicopathological characteristics with BRCA1-mutated tumours. A better characterisation of TNBC and the presence of BRCAness could have consequences for both hereditary breast cancer screening and the treatment of these tumours.
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Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Genes BRCA1 , Heterocigoto , Adolescente , Adulto , Anciano , Neoplasias de la Mama/metabolismo , Análisis Mutacional de ADN , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Adulto JovenRESUMEN
Antibody-dependent cellular cytotoxicity (ADCC) is one of the possible mechanisms of action of the chimeric CD20 monoclonal antibody IDEC-C2B8 (rituximab). As granulocyte-colony stimulating factor (G-CSF) greatly enhances the cytotoxicity of neutrophils in ADCC, the efficacy of rituximab might be enhanced by the addition of G-CSF. In a phase I/II clinical trial, we investigated the safety and efficacy of the combination of rituximab and G-CSF (5 microg/kg/day, administered for 3 days, starting 2 days before each infusion) in 26 relapsed low-grade lymphoma patients. Adverse events occurred in 25/26 patients and mainly consisted of (grade I/II) fever (29%) and allergic reactions (19%). In phases I and II (375 mg/m(2) rituximab+G-CSF), 19 patients were evaluable for efficacy. The response rate was 42% (8/19; 95% CI 20-67%), with 16% (3/19) complete remissions and 26% (5/19) partial remissions. The median duration of response was 18 months, the median time to progression was 24 months. We conclude that the combination of rituximab and G-CSF is well tolerated. Although the overall response rate seems comparable to that reported for rituximab monotherapy, remission duration in this pilot phase II study is remarkably long. Randomized comparison with rituximab monotherapy should substantiate this promising finding.
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Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Linfoma de Células B/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales/toxicidad , Anticuerpos Monoclonales de Origen Murino , Relación Dosis-Respuesta a Droga , Factor Estimulante de Colonias de Granulocitos/toxicidad , Humanos , Lactoferrina/sangre , Elastasa de Leucocito/sangre , Persona de Mediana Edad , Activación Neutrófila/efectos de los fármacos , Recurrencia , Inducción de Remisión , RituximabRESUMEN
The apoptotic pathway activated by chimeric anti-CD20 monoclonal antibodies (rituximab, IDEC.C2B8) was analyzed using the Burkitt lymphoma cell line Ramos. Crosslinking of CD20 (CD20XL) induced apoptosis in Ramos cells, which involved loss of mitochondrial membrane potential (Deltapsi(m)), the release of cytochrome-c (cyt-c), and activation of caspases-9 and -3. Nevertheless, several lines of evidence showed that the apoptotic outcome did not depend on these events. First, under circumstances where Ramos cells display resistance to either CD95- or B cell receptor (BCR)-induced apoptosis, CD20XL-induced apoptosis was not affected, pointing to a distinct pathway. Second, the broad-spectrum caspase inhibitor zVAD-fmk prevented processing of caspase-9, -3 and PARP as well as DNA fragmentation, but did not block apoptosis as measured by annexin V staining, cell size and membrane integrity. Lastly, Bcl-2 overexpression blocked cyt-c release and the decrease in Deltapsi(m), and completely prevented CD95- or BCR-mediated apoptosis; however, it did not affect CD20XL-induced cell death. We conclude that although CD20XL can initiate the mitochondrial apoptosis pathway, CD20-induced apoptosis does not necessarily require active caspases and cannot be blocked by Bcl-2. Since most chemotherapeutic drugs require the activation of caspases to exert their cytotoxicity, these findings provide an important rationale for the use of CD20 mAbs in chemoresistant malignancies.
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Anticuerpos Monoclonales/farmacología , Antígenos CD20/inmunología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Linfocitos B/efectos de los fármacos , Caspasas/metabolismo , Mitocondrias/efectos de los fármacos , Clorometilcetonas de Aminoácidos/farmacología , Anticuerpos Monoclonales de Origen Murino , Linfocitos B/patología , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patología , Inhibidores de Caspasas , Inhibidores de Cisteína Proteinasa/farmacología , Grupo Citocromo c/metabolismo , Activación Enzimática , Humanos , Immunoblotting , Etiquetado Corte-Fin in Situ , Potenciales de la Membrana , Mitocondrias/enzimología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Rituximab , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/metabolismo , Células Tumorales Cultivadas/patologíaRESUMEN
UNLABELLED: At the end of September 2001 the Inspectorate for Health Protection and Veterinary Public Health and the National Poisons Control Centre (NPCC) were informed about adverse health effects after consumption of a herbal tea. During consultations it was suggested that Japanese star anise (Illicium anisatum L.), which is known to contain a neurotoxin, may have been inadvertently mixed into the herbal tea. In view of the severity of the adverse health effects and the clear association with consumption of a specific herbal tea, the supplier was urgently advised to withdraw the suspected herbal tea from the market. A total of 63 persons reported symptoms of general malaise, nausea and vomiting 2-4 hours following consumption of the herbal tea. Twenty-two persons required hospitalisation, of whom 16 due to generalised tonic-clonic seizures. Medical investigations revealed no underlying pathology and after supportive treatment, the patients were discharged in good health. Morphologic and organoleptic investigations of the suspected herbal tea indicated that this possibly contained Japanese star anise. NMR analysis of the herbal tea confirmed the presence of the neurotoxin anisatin, a non-competitive GABA-antagonist which can cause hyperactivity of the central nervous system and tonic-clonic seizures. CONCLUSION: Ingestion of a herbal tea containing anisatin caused the reported serious adverse health effects. Close cooperation between clinicians, the Inspectorate for Health Protection and Veterinary Public Health and the NPCC played a vital role in preventing further harm to public health.
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Bebidas/envenenamiento , Brotes de Enfermedades , Epilepsia/epidemiología , Epilepsia/etiología , Illicium/envenenamiento , Adulto , Femenino , Contaminación de Alimentos , Antagonistas del GABA/envenenamiento , Humanos , Lactonas/envenenamiento , Países Bajos/epidemiología , Neurotoxinas/envenenamiento , Sesquiterpenos/envenenamiento , Compuestos de Espiro/envenenamientoRESUMEN
Rituximab, a chimeric CD20 monoclonal antibody (mAb), is widely used in the treatment of patients with low-grade non-Hodgkin's lymphoma. Possible anti-tumour mechanisms involve complement-mediated lysis and/or antibody-dependent cellular cytotoxicity (ADCC). Because G-CSF greatly enhances the cytotoxicity of neutrophils (PMN) in ADCC, the clinical efficacy of rituximab might be enhanced by the addition of G-CSF. Therefore, we investigated the neutrophil-mediated CD20-dependent cellular cytotoxicity in B cell lines. In contrast to previous studies by others, we found that G-CSF-primed PMN are capable of functioning as effector cells in CD20-dependent cellular cytotoxicity. However, HLA class II mAbs were far more effective. The differences between HLA class II- and CD20-mediated PMN-ADCC were not due to: (1) the use of chimeric (hIgG1) mAbs vs mIgG2a mAbs; (2) HLA class II-induced apoptosis as an 'ADCC-sensitising' mechanism; (3) CD20-induced inhibition of ADCC; (4) inferior membrane mobility of CD20. Analysis of Fcgammareceptor (FcgammaR) involvement showed that although CD20-induced ADCC was mediated mainly via FcgammaRI, for optimal lysis FcgammaRI and FcgammaRII were both required. In contrast, in HLA class II-dependent ADCC both FcgammaRI and II were capable of independently inducing maximum lysis. The mechanism underlying these differences in FcgammaR-binding and activation remains to be elucidated.
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Citotoxicidad Celular Dependiente de Anticuerpos/inmunología , Antígenos CD20/inmunología , Factor Estimulante de Colonias de Granulocitos/farmacología , Neutrófilos/inmunología , Anticuerpos Biespecíficos/inmunología , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales de Origen Murino , Apoptosis/efectos de los fármacos , Linfocitos B/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Humanos , Fragmentos Fc de Inmunoglobulinas/inmunología , Monocitos/inmunología , Activación Neutrófila/efectos de los fármacos , Rituximab , Células Tumorales Cultivadas/citología , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/inmunologíaRESUMEN
Treatment with rituximab, a chimaeric anti-CD20 monoclonal antibody, can be associated with moderate to severe first-dose side-effects, notably in patients with high numbers of circulating tumour cells. The aim of this study was to elucidate the mechanism of these side-effects. At multiple early time points during the first infusion of rituximab, complement activation products (C3b/c and C4b/c) and cytokines [tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and IL-8] were measured in five relapsed low-grade non-Hodgkin's lymphoma (NHL) patients. Infusion of rituximab induced rapid complement activation, preceding the release of TNF-alpha, IL-6 and IL-8. Although the study group was small, the level of complement activation appeared to be correlated both with the number of circulating B cells prior to the infusion (r = 0.85; P = 0.07) and with the severity of the side-effects. We conclude that complement plays a pivotal role in the pathogenesis of side-effects of rituximab treatment. As complement activation can not be prevented by corticosteroids, it might be relevant to study the possible role of complement inhibitors during the first administration of rituximab.
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Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/efectos adversos , Activación de Complemento , Citocinas/sangre , Linfoma no Hodgkin/inmunología , Adulto , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales de Origen Murino , Antineoplásicos/uso terapéutico , Complemento C3b/análisis , Complemento C3c/análisis , Complemento C4/análisis , Complemento C4b/análisis , Femenino , Humanos , Interleucina-6/sangre , Interleucina-8/sangre , Recuento de Linfocitos , Linfoma no Hodgkin/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos , Rituximab , Estimulación Química , Factor de Necrosis Tumoral alfa/análisisRESUMEN
1. Hypokalaemic periodic paralysis is characterized by attacks of muscle weakness. Glucose, insulin and an abnormal regulation of ATP-sensitive potassium channels may be involved in these attacks. We studied the effect of hyperglycaemia and of the potassium channel opener pinacidil on insulin release and muscle strength in patients with hypokalaemic periodic paralysis. 2. Insulin release was assessed on two occasions in four patients with hypokalaemic periodic paralysis and in eight matched control subjects, with and without treatment with 25 mg pinacidil orally, during a hyperglycaemic glucose clamp at a blood glucose level of 10 mmol/l, in a placebo-controlled, double-blind study. Muscle strength was measured in the hypokalaemic periodic paralysis patients before and during hyperglycaemia using a handheld dynamometer. 3. During the clamp, the mean glucose concentration (10-180 min) in control subjects was 9.9 +/- 0.07 and 10.0 +/- 0.03 mmol/l with and without pinacidil respectively, and in patients with hypokalaemic periodic paralysis was 10.0 +/- 0.04 and 10.1 +/- 0.06 mmol/l respectively (not significantly different). In both groups, the areas under the insulin curve from 0 to 10 min (first-phase insulin release) and from 30 to 180 min (second phase) were not different on the pinacidil study day compared with on the placebo day. The areas under the insulin curve of the first and second phases also did not differ between control subjects and patients with hypokalaemic periodic paralysis (with or without pinacidil). The M/I ratio, a measure of insulin sensitivity, was not different in the two groups. On the placebo day, baseline muscle strength in patients with hypokalaemic periodic paralysis was 165 +/- 16 N for the hip abductors and 168 +/- 19 N for the knee flexors. During the period of hyperglycaemia on the placebo day, muscle strength did not decrease in either muscle group. On the pinacidil study day, an increase in muscle strength was found only in the two hypokalaemic periodic paralysis patients with the lowest mean muscle strength (< 150 N) on the placebo day. The two hypokalaemic periodic paralysis patients with a mean muscle strength on the placebo day > 150 N showed no increase in muscle strength with pinacidil. 4. Insulin secretion and sensitivity were normal in patients with hypokalaemic periodic paralysis. Hyperglycaemia during hyperglycaemic clamping did not provoke paralytic attacks and did not result in a decrease in muscle strength. The potassium channel opener pinacidil had no effect on insulin secretion in hypokalaemic periodic paralysis patients or in normal subjects. Pinacidil may enhance muscle strength in those hypokalaemic periodic paralysis patients who suffer partial paralytic attacks.