RESUMEN
We report a case of consciousness disorder following the fourth course of chemotherapy with cisplatin (CDDP) and 5- fluorouracil (5-FU) in a patient with esophageal cancer. A 74-year-old man was admitted to our hospital to receive chemotherapy for esophageal cancer. Six days after chemotherapy, the patient showed impaired consciousness and his serum sodium concentration was found to be 125 mEq/L, but no edema or dehydration was noted. This hyponatremic state was diagnosed as CDDP-induced syndrome of inappropriate secretion of antidiuretic hormone (SIADH) on the basis of serum and urine hypo-osmolality. Accordingly, fluid intake was restricted and sodium supplements were administered, resulting in an appropriate increase in the serum sodium concentration to 132 mEq/L in 4 days.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trastornos de la Conciencia/etiología , Neoplasias Esofágicas/tratamiento farmacológico , Síndrome de Secreción Inadecuada de ADH/inducido químicamente , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Trastornos de la Conciencia/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Síndrome de Secreción Inadecuada de ADH/diagnóstico , Síndrome de Secreción Inadecuada de ADH/tratamiento farmacológico , Masculino , Sodio/uso terapéuticoRESUMEN
BACKGROUND: Thyrotropin-releasing hormone (TRH) is now used as a therapeutic agent for various neurological disorders. Animal study has shown that TRH was attributable to increased cerebral blood flow (CBF). AIMS: There have been occasional reports that TRH therapy was effective for improving symptoms of persistent disturbance of consciousness after acute encephalitis or encephalopathy during childhood. To determine whether TRH has an effect on increasing CBF to patients who have consciousness disturbance caused by acute encephalitis or encephalopathy, and to determine the optimal method of administration. METHODS: Sixteen patients aged 0.7-10.9 years (mean age, 3.2+/-3.1 years) who presented with persistent disturbance of consciousness resulting from acute encephalitis or encephalopathy and were treated with TRH. Regional CBF (rCBF) was measured by single photon emission computed tomography before and after TRH therapy. The alteration rates of rCBF were compared between the divided two groups concerning the dose levels, dosing periods, and treatment lags. RESULTS: The alteration rates of rCBF of the high dose group were higher than those of the low dose group. Differences in the dosing periods and treatment lags did not cause any significant difference of the alteration rates of rCBF. CONCLUSION: The study showed that higher alteration rates of the CBF were observed in the higher dosing group, and TRH have the potency of increasing CBF. TRH therapy would have the potential for effective treatment of persistent consciousness disturbance caused by childhood acute encephalitis or encephalopathy.
Asunto(s)
Daño Encefálico Crónico/tratamiento farmacológico , Daño Encefálico Crónico/fisiopatología , Circulación Cerebrovascular/efectos de los fármacos , Encefalitis/tratamiento farmacológico , Encefalitis/fisiopatología , Hormona Liberadora de Tirotropina/uso terapéutico , Autorradiografía , Encéfalo/diagnóstico por imagen , Daño Encefálico Crónico/diagnóstico por imagen , Niño , Preescolar , Trastornos de la Conciencia/diagnóstico por imagen , Trastornos de la Conciencia/tratamiento farmacológico , Trastornos de la Conciencia/fisiopatología , Diagnóstico por Imagen , Relación Dosis-Respuesta a Droga , Encefalitis/diagnóstico por imagen , Femenino , Humanos , Lactante , Yofetamina , Masculino , Radiofármacos , Hormona Liberadora de Tirotropina/administración & dosificación , Hormona Liberadora de Tirotropina/efectos adversos , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
A boy suffering from epileptic seizures experienced five episodes of a twilight state. His twilight states continued for at least two weeks, and were characterized by behavioral disorders and severe autonomic symptoms. Sometimes functional ileus was present. The electroencephalographic finding in the first episode was 6-per-second phantom spike and wave complex (PSW). For treatment, a combination of carbamazepine and sodium valproate was useful in preventing the reappearance of the episode of the twilight state and in suppressing PSW. From the clinical and electroencephalographic findings and therapeutic response to antiepileptics, the episodes were considered to have originated in localized epileptic discharges in the hippocampal, amygdaloidal and hypothalamic regions.
Asunto(s)
Sistema Nervioso Autónomo/fisiopatología , Trastornos del Conocimiento/fisiopatología , Trastornos de la Conciencia/fisiopatología , Electroencefalografía , Epilepsia Tónico-Clónica/fisiopatología , Amígdala del Cerebelo/fisiopatología , Sistema Nervioso Autónomo/efectos de los fármacos , Carbamazepina/uso terapéutico , Niño , Trastornos de la Conciencia/tratamiento farmacológico , Quimioterapia Combinada , Epilepsia Tónico-Clónica/tratamiento farmacológico , Potenciales Evocados/efectos de los fármacos , Hipocampo/fisiopatología , Humanos , Hipotálamo/fisiopatología , Obstrucción Intestinal/fisiopatología , Masculino , Ácido Valproico/uso terapéuticoRESUMEN
Phase I evaluation of spiromustine was performed using an every-3-week schedule and a weekly X 3 schedule. Neurotoxicity was the dose-limiting toxicity presenting as alterations in cortical integrative functions (orientation, language, coordination), leading to a decrease in the level of consciousness. Traditional criteria for grading neurotoxicity poorly characterized these toxicities. The maximum tolerated dose was 6 mg/m2 every 3 weeks and 3 mg/m2 weekly X 3. Concurrent murine studies confirmed spiromustine as a schedule independent drug with toxicity correlating with peak plasma levels. Physostigmine had little effect on decreasing neurotoxicity in the murine model. The solvating agent used was not responsible for the neurotoxicity. Injection of spiromustine on a split-dose schedule decreased the acute neurological toxicity in mice and allowed a larger total dosage to be delivered (compared to single bolus dosage). Based on these results a split-dose schedule is suggested for future clinical trials.