RESUMEN
A prospective study was carried out to determine the prevalence of autonomic dysfunction in patients with lymphoma, and to assess the effect on this of chemotherapy. Twenty consecutive patients presenting with Hodgkin's disease, high-grade non-Hodgkin's lymphoma, or low-grade non-Hodgkin's lymphoma were studied. All had advanced disease, requiring combination chemotherapy which included the use of vinca alkaloids. Clinical assessment and standard cardiovascular autonomic function tests were carried out prior to and following completion of chemotherapy. Although no patients had clinical evidence of autonomic neuropathy at presentation, 16 (80%) had abnormal cardiovascular autonomic function tests. There was no correlation with the presence or absence of mediastinal disease. There was significant improvement in autonomic scores with treatment despite the use of drugs of known neurological toxicity. Some patients showed residual abnormalities of autonomic function despite disease resolution. We suggest that subclinical autonomic dysfunction is common in patients with lymphoma, and probably represents a paraneoplastic syndrome--the pathogenesis and prevalence of which deserve further study. This phenomenon may predispose patients with lymphoma to develop gastrointestinal and genitourinary dysfunction, or postural hypotension, and should be considered during the evaluation of the neurotoxicity of chemotherapy regimens.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/etiología , Linfoma/complicaciones , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Corazón/inervación , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Linfoma no Hodgkin/complicaciones , Linfoma no Hodgkin/tratamiento farmacológico , Síndromes Paraneoplásicos/etiología , Estudios ProspectivosRESUMEN
In diabetic subjects, polyol pathway activity might inhibit neutrophil function and cause nerve damage. The effects of ponalrestat, an aldose reductase inhibitor, were assessed on neutrophil intracellular killing of Escherichia coli and on autonomic function in diabetic subjects in a randomized double-blind, placebo-controlled, crossover trial. We studied 31 diabetic subjects with autonomic dysfunction and 21 age- and sex-matched control subjects. During two 12-wk treatment periods, the diabetic subjects took either 600 mg of ponalrestat or matching placebo once daily. Neutrophil killing of E. coli was measured by a microbiological assay technique. Kmax by neutrophils from the diabetic subjects was lower than in the control group (Kmax of diabetic subjects 54.5 +/- 26.4 vs. control subjects 67.3 +/- 16.3, P = 0.045). Ponalrestat significantly increased bacterial killing in the diabetic subjects (Kmax of ponalrestat 75.1 +/- 16.5 vs. placebo 58.2 +/- 20.8, P = 0.003) so that there was no longer any significant difference in Kmax between the control subjects and the diabetic subjects on active treatment. Ponalrestat had no significant effect on a range of standard cardiovascular autonomic nerve function tests. We conclude that neutrophil killing of E. coli is impaired in diabetic subjects with autonomic dysfunction. This is restored to normal by ponalrestat.
Asunto(s)
Aldehído Reductasa/antagonistas & inhibidores , Sistema Nervioso Autónomo/efectos de los fármacos , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Neuropatías Diabéticas/sangre , Neuropatías Diabéticas/tratamiento farmacológico , Escherichia coli , Neutrófilos/fisiología , Fagocitosis/efectos de los fármacos , Ftalazinas/uso terapéutico , Análisis de Varianza , Sistema Nervioso Autónomo/fisiopatología , Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Neuropatías Diabéticas/fisiopatología , Método Doble Ciego , Escherichia coli/aislamiento & purificación , Femenino , Radicales Libres/sangre , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Neutrófilos/efectos de los fármacos , Sueño , Maniobra de Valsalva , VigiliaRESUMEN
OBJECTIVE: To determine whether changes in hand skin blood flow in diabetic men could be demonstrated with liquid crystal contact thermography and to assess the relative effects of autonomic neuropathy and microangiopathy on these changes. RESEARCH DESIGN AND METHODS: Thirty-four diabetic and 12 age-matched nondiabetic men comprised the study. The diabetic men were categorized according to standard cardiovascular autonomic function tests and the presence or absence of background or proliferative retinopathy and/or proteinuria. Bilateral hand thermograms were measured at rest and after immersion of the right hand in ice-cold water. RESULTS: Diabetic men with definite or severe autonomic neuropathy (n = 13) had a high frequency of anisothermal baseline thermograms (77 vs. 25% in nondiabetic subjects, P less than 0.05). After ice-cold water immersion, right-hand recovery was abnormally slow (514 +/- 157 arbitrary U, area under the curve) compared with nondiabetic men (685 +/- 135 arbitrary U, P less than 0.01). Diabetic men with proliferative retinopathy (n = 8) all had definite or severe autonomic neuropathy and showed the same abnormalities. Diabetic men with nor or early autonomic changes showed normal thermographic patterns. CONCLUSIONS: These results are consistent with increased palmar arteriovenous shunt blood flow or capillary closure in the hands of diabetic patients with definite or severe autonomic neuropathy. They indicate that thermoregulatory reflex changes in hand skin blood flow are controlled by the autonomic nervous system. It is possible, however, that diabetic microangiopathy, associated with the presence of proliferative retinopathy, also independently affects hand skin blood flow.