RESUMEN
This retrospective study was carried out at eight Neonatal Intensive Care Units (NICU) Centers worldwide on 33 newborns presenting at birth with pleural, pericardial, or abdominal chylous effusions. Diagnosis of chylous effusion is based on findings of fluid with a milk-like appearance, a concentration of triglycerides in pleural effusion >1.1 mmol/l, and a total cell count >1,000 cells/ml with a predominance of >80% lymphocytes. Thirty-three newborns met the inclusion criteria and were studied. Six subjects who presented at birth with fetal effusion were treated by in-utero pleuro-amniotic shunt. Five of these patients are alive at follow-up. At birth, pleural drainage was performed in 29/33 patients and abdominal drainage was carried out in 3/33. Total parenteral nutrition (TPN) was given to 32/33 patients; 19/23 patients were fed a medium-chain triglycerides (MCT). No adverse effects were observed. Eight patients were treated with Octreotide at dosages ranging from 1 to 7 mcg/kg/hour for 8 to 35 days. All patients showed decreased chylous production. Two patients were treated by pleurodesis. Twenty-two babies are alive after at least 6 months follow-up, 9/33 are deceased, and 2 were lost to follow-up. Clinical conditions of survivors are basically good except for lung involvement [chronic lung disease (CLD) or lung lymphangiectasia] and lymphedema. All patients were using a MCT diet at follow-up with good control of chylous effusion. Visceral chylous effusions of the fetus and neonate are rare disorders, and there currently is only partial agreement on decision-making strategies. We suggest the need for an international prospective trial in an effort to establish the efficacy and effectiveness of diagnostic and therapeutic options described in this article.
Asunto(s)
Quilotórax/congénito , Ascitis Quilosa/congénito , Quilotórax/diagnóstico , Quilotórax/terapia , Ascitis Quilosa/diagnóstico , Ascitis Quilosa/terapia , Femenino , Humanos , Recién Nacido , Masculino , Octreótido/uso terapéutico , Estudios Retrospectivos , Triglicéridos/administración & dosificaciónRESUMEN
Traumatic brain injury causes progressive tissue atrophy and consequent neurological dysfunction, resulting from neuronal cell death in both animal models and patients. Fas (CD95) and Fas ligand (FasL/CD95L) are important mediators of apoptosis. However, little is known about the relationship between Fas and FasL and neuronal cell death in mice lacking the genes for inflammatory cytokines. In the present study, double tumor necrosis factor/lymphotoxin-alpha knockout (-/-) and interleukin-6-/- mice were subjected to closed head injury (CHI) and sacrificed at 24 hours or 7 days post-injury. Consecutive brain sections were evaluated for Fas and FasL expression, in situ DNA fragmentation (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling; TUNEL), morphologic characteristics of apoptotic cell death and leukocyte infiltration. A peak incidence of TUNEL positive cells was found in the injured cortex at 24 hours which remained slightly elevated at 7 days and coincided with maximum Fas expression. FasL was only moderately increased at 24 hours and showed maximum expression at 7 days. A few TUNEL positive cells were also found in the ipsilateral hippocampus at 24 hours. Apoptotic, TUNEL positive cells mostly co-localized with neurons and Fas and FasL immunoreactivity. The amount of accumulated polymorphonuclear leukocytes and CD11b positive cells was maximal in the injured hemispheres at 24 hours. We show strong evidence that Fas and FasL might be involved in neuronal apoptosis after CHI. Furthermore, Fas and FasL upregulation seems to be independent of neuroinflammation since no differences were found between cytokine-/- and wild-type mice.
Asunto(s)
Lesiones Encefálicas/metabolismo , Encéfalo/metabolismo , Proteína Ligando Fas/metabolismo , Heridas no Penetrantes/metabolismo , Receptor fas/metabolismo , Animales , Apoptosis , Encéfalo/patología , Lesiones Encefálicas/patología , Antígeno CD11b/metabolismo , Modelos Animales de Enfermedad , Técnica del Anticuerpo Fluorescente Indirecta , Técnicas para Inmunoenzimas , Etiquetado Corte-Fin in Situ , Interleucina-6/deficiencia , Interleucina-6/genética , Linfotoxina-alfa/deficiencia , Linfotoxina-alfa/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neuronas/metabolismo , Neuronas/patología , Neutrófilos/patología , Organismos Libres de Patógenos Específicos , Factor de Necrosis Tumoral alfa/deficiencia , Factor de Necrosis Tumoral alfa/genética , Regulación hacia Arriba , Heridas no Penetrantes/patologíaRESUMEN
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in young people in industrialized countries. Although various anti-inflammatory and antiapoptotic modalities have shown neuroprotective effects in experimental models of TBI, to date, no specific pharmacological agent aimed at blocking the progression of secondary brain damage has been approved for clinical use. Erythropoietin (Epo) belongs to the cytokine superfamily and has traditionally been viewed as a hematopoiesis-regulating hormone. The newly discovered neuroprotective properties of Epo lead us to investigate its effect in TBI in a mouse model of closed head injury. Recombinant human erythropoietin (rhEpo) was injected at 1 and 24 h after TBI, and the effect on recovery of motor and cognitive functions, tissue inflammation, axonal degeneration, and apoptosis was evaluated up to 14 days. Motor deficits were lower, cognitive function was restored faster, and less apoptotic neurons and caspase-3 expression were found in rhEpo-treated as compared with vehicle-treated animals (P<0.05). Axons at the trauma area in rhEpo-treated mice were relatively well preserved compared with controls (shown by their density; P<0.01). Immunohistochemical analysis revealed a reduced activation of glial cells by staining for GFAP and complement receptor type 3 (CD11b/CD18) in the injured hemisphere of Epo- vs. vehicle-treated animals. We propose that further studies on Epo in TBI should be conducted in order to consider it as a novel therapy for TBI.
Asunto(s)
Apoptosis , Eritropoyetina/farmacología , Eritropoyetina/fisiología , Traumatismos Cerrados de la Cabeza/patología , Neuronas/patología , Animales , Antiinflamatorios/farmacología , Axones/metabolismo , Encéfalo/patología , Antígeno CD11b/biosíntesis , Antígenos CD18/biosíntesis , Caspasa 3 , Caspasas/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Eritropoyetina/química , Eritropoyetina/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Hematopoyesis , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Inflamación , Masculino , Ratones , Neuronas/metabolismo , Ratas , Proteínas Recombinantes/química , Factores de TiempoRESUMEN
Increases in peripheral type benzodiazepine receptors (PTBR) have been utilized for the detection of neuroinflammation and neurotoxicity in the brain. We have investigated the relationship between PTBR and NMDA receptor binding density in mice with closed head injury (CHI) using quantitative autoradiography. CHI was induced by a weight drop in nine mice, four of which received a single injection of the rat sarcoma (Ras) inhibitor famesyl thiosalicylate (FTS) 1 h after the insult. Sham controls received anesthesia but no contusion. The neurological status of the mice was evaluated at 1 h, and hence up to 7 days using a neurological severity score (NSS). Animals were killed 7 days after CHI and consecutive brain sections were incubated with [3H]PK11195, a PTBR antagonist, or [3H]MK801, an n-methyl-d-aspartate receptor (NMDAR) use-dependent antagonist. CHI produced large (two- to threefold), widespread increases in PK11195 binding in the traumatized hemisphere and a significant decrease (20%-40%) in NMDAR binding limited to regions at close proximity to the lesion. Histologically, these regions were characterized by glial proliferation and neuronal loss. Significant increases in PTBR binding, but no concomitant decrease in NMDAR, were identified in several regions remote from the lesion, including the contralateral ventrolateral striatum and the ipsilateral ventral thalamus. Drug treatment significantly improved the neurological deficits but had only a marginal effect on PTBR. These results support a complex role for glial activation and PTBR increases in the context of CHI.
Asunto(s)
Traumatismos Cerrados de la Cabeza/fisiopatología , Receptores de GABA-A/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animales , Antioxidantes/farmacología , Autorradiografía , Benzoatos/farmacología , Encéfalo/patología , Maleato de Dizocilpina/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Farnesol/análogos & derivados , Farnesol/farmacología , Ácido Glutámico/fisiología , Traumatismos Cerrados de la Cabeza/metabolismo , Traumatismos Cerrados de la Cabeza/patología , Interpretación de Imagen Asistida por Computador , Isoquinolinas/farmacología , Ratones , Neuroglía/metabolismo , Receptores de GABA-A/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Compuestos de Sulfhidrilo , TimerosalRESUMEN
The expression of the chemokines macrophage inflammatory protein (MIP)-2 and MIP-1alpha and of their receptors CXCR2 and CCR5 was assessed in wild type (WT) and TNF/lymphotoxin-alpha knockout (TNF/LT-alpha-/-) mice subjected to closed head injury (CHI). At 4 h after trauma intracerebral MIP-2 and MIP-1alpha levels were increased in both groups with MIP-2 concentrations being significantly higher in WT than in TNF/LT-alpha-/- animals (p < 0.05). Thereafter, MIP-2 production declined rapidly, whereas MIP-1alpha remained elevated for 7 days. Expression of CXCR2 was confined to astrocytes and increased dramatically within 24 h in both mouse types. Contrarily, CCR5 expression remained constitutively low and was mainly localized to microglia. These results show that after CHI, chemokines and their receptors are regulated differentially and with independent kinetics.
Asunto(s)
Corteza Cerebral/metabolismo , Quimiocinas/metabolismo , Encefalitis/metabolismo , Traumatismos Cerrados de la Cabeza/metabolismo , Receptores de Quimiocina/metabolismo , Animales , Astrocitos/metabolismo , Corteza Cerebral/fisiopatología , Quimiocina CCL3 , Quimiocina CCL4 , Quimiocina CXCL2 , Encefalitis/fisiopatología , Regulación de la Expresión Génica/fisiología , Traumatismos Cerrados de la Cabeza/fisiopatología , Linfotoxina-alfa/genética , Linfotoxina-alfa/metabolismo , Proteínas Inflamatorias de Macrófagos/metabolismo , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microglía/metabolismo , Monocinas/metabolismo , Receptores CCR5/metabolismo , Receptores de Interleucina-8B/metabolismo , Factor de Necrosis Tumoral alfa/deficiencia , Factor de Necrosis Tumoral alfa/genética , Regulación hacia Arriba/genéticaRESUMEN
Scald injuries caused by hot liquids are not a frequently reported cause of pediatric respiratory and alimentary tract burns. Aspiration of molten wax with subsequent pharyngeal or laryngeal burns has not been described at all, to the best of our knowledge. A case of an adolescent who presented with airway burns and atelectasis subsequent to aspiration of molten wax is herein described and discussed.
Asunto(s)
Bronquios/lesiones , Quemaduras/complicaciones , Laringe/lesiones , Faringe/lesiones , Atelectasia Pulmonar/etiología , Quemaduras/diagnóstico , Quemaduras/patología , Niño , Humanos , Inhalación , Masculino , Lengua/lesiones , CerasRESUMEN
Aortopulmonary (AP) window is an uncommon cardiac anomaly which is frequently associated with other cardiac anomalies. Concomitant repair of all intra- and extracardiac anomalies is usually recommended. Between October 1993 and July 1994, 4 patients aged 37 days, 4 weeks, 3.5 and 1.5 years, respectively, underwent repair of AP window and associated malformations. The associated anomalies consisted of interrupted aortic arch (IAA), and atrial and ventricular septal defects in the 1st patient, patent ductus arteriosus in the 2nd, inlet ventricular septal defect in the 3rd and congenital narrowing of the right pulmonary artery and a patent foramen ovale in the 4th. Extreme metabolic acidosis after repair of IAA in the 1st, dictated ligation of the AP window before repair of the intracardiac anomalies at 2 months of age. In the 2nd and 3rd, repair of the window and associated anomalies was performed in a single stage. In the 4th, left pulmonary artery banding preceded complete repair. All patients are doing well at 18, 13, 12 and 11 months, respectively, of follow-up after their last operation. Surgical management of AP window may have to be staged according to the physiological influence of the associated anomalies in each patient, to minimize the cumulative risk of complete repair.
Asunto(s)
Anomalías Múltiples/cirugía , Defecto del Tabique Aortopulmonar/cirugía , Cardiopatías Congénitas/cirugía , Acidosis , Procedimientos Quirúrgicos Cardíacos/métodos , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Complicaciones PosoperatoriasRESUMEN
BACKGROUND: We examined whether or not continuous arteriovenous hemofiltration (CAVH), in the absence of renal failure, would improve either hemodynamic abnormalities or survival in a canine model of septic shock. STUDY DESIGN: Escherichia coli 0111, as an intraperitoneal clot, was surgically implanted into 21 one- to two-year-old purpose-bred beagles. The dogs were randomized to no CAVH (control group, n = 7), sham CAVH (extracorporeal circulation without hemofiltration, n = 7), or true CAVH (hemofiltration with removal of 600 mL/hour of ultrafiltrate, n = 7). Hemofiltration began one hour after clot implantation and continued for six hours. All dogs received antibiotics and had serial hemodynamic and laboratory evaluations. RESULTS: During the first seven hours of the study, all dogs displayed a progressive, significant decrease in mean arterial pressure, cardiac index, left ventricular ejection fraction, and serum pH (all p < 0.05). Two of seven dogs in the control group, one of seven dogs in the sham CAVH group, and one of seven dogs in the true CAVH group survived seven days after clot implantation. True CAVH, which included fluid replacement with lactated Ringer's solution, significantly increased serum lactate and decreased serum bicarbonate levels after six hours (both p < 0.05). However, pH did not differ between the three treatment groups (p > 0.20). Continuous arteriovenous hemofiltration therapy had no significant effect on cardiovascular abnormalities or survival. CONCLUSIONS: The results of this study suggest that CAVH would be unlikely to provide benefit to patients with gram-negative septic shock, in the absence of renal failure.
Asunto(s)
Infecciones por Escherichia coli/terapia , Hemofiltración , Choque Séptico/terapia , Animales , Bicarbonatos/sangre , Presión Sanguínea/fisiología , Gasto Cardíaco/fisiología , Modelos Animales de Enfermedad , Perros , Infecciones por Escherichia coli/sangre , Infecciones por Escherichia coli/fisiopatología , Circulación Extracorporea , Fluidoterapia , Concentración de Iones de Hidrógeno , Soluciones Isotónicas/uso terapéutico , Lactatos/sangre , Estudios Prospectivos , Presión Esfenoidal Pulmonar/fisiología , Lactato de Ringer , Choque Séptico/sangre , Choque Séptico/fisiopatología , Volumen Sistólico/fisiología , Tasa de Supervivencia , Trombosis/microbiología , Función Ventricular Izquierda/fisiologíaRESUMEN
Monoclonal antibodies (MAbs) specific for O polysaccharide or core oligosaccharide/lipid A of Escherichia coli O111:B4 lipopolysaccharide (LPS) were compared in canine septic shock. Animals received O-specific, core-specific, or control murine IgG2a MAbs (or saline) before intraperitoneal implantation of an E. coli O111:B4-infected clot. Animals were further randomized to ceftriaxone or saline. O-specific MAb significantly reduced bacteremia and endotoxemia but not serum tumor necrosis factor. Core-specific MAb significantly increased mean arterial pressure from day 4 to 28 (P = .02). In dogs not receiving ceftriaxone, survival was enhanced by O-specific MAb (4/5) compared with core-specific MAb (0/5) and control (1/8) (P = .03). Survival rates were similar (P = .22) but survival was prolonged in antibiotic-treated animals also receiving O-specific MAb (P = .02 vs. core-specific MAb and controls) or core-specific MAb (P = .08 vs. controls). These data support the complex role of LPS in sepsis and the discrete functional effects of MAbs specific for different elements of LPS.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Endotoxinas/inmunología , Escherichia coli/inmunología , Lipopolisacáridos/inmunología , Choque Séptico/inmunología , Animales , Bacteriemia/inmunología , Temperatura Corporal , Peso Corporal , Ceftriaxona/uso terapéutico , Modelos Animales de Enfermedad , Perros , Escherichia coli/aislamiento & purificación , Hemodinámica , Antígenos O , Polisacáridos Bacterianos/inmunología , Choque Séptico/sangre , Choque Séptico/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/análisisRESUMEN
We investigated whether the third component of complement (C3) is involved in the pathophysiology of endotoxic shock, and if it is involved, whether it plays a protective role or whether it mediates shock and multiple organ failure. In a prospective, controlled investigation, six Brittany spaniels that were homozygous for a genetically determined deficiency of C3 (C3 deficient, < 0.003% of normal serum C3 levels) and six heterozygous littermates (controls, approximately 50% of mean normal serum C3 level) were given 2 mg/kg of reconstituted Escherichia coli 026:B6 acetone powder as a source of endotoxin, intravenously. All animals were given similar fluid and prophylactic antibiotic therapy, and had serial hemodynamic variables obtained. After E. coli endotoxin infusion, C3-deficient animals had higher peak levels of endotoxin and less of a rise in temperature than controls (P < 0.05). During the first 4 h after E. coli endotoxin infusion, C3-deficient animals had significantly greater decreases in mean central venous pressure and mean pulmonary artery pressure than controls (P < 0.02). During the first 48 h after E. coli endotoxin infusion, C3-deficient animals had significantly greater decreases in mean arterial pH, left ventricular ejection fraction, and mean pulmonary capillary wedge pressure, and greater increases in mean arterial lactate, arterial-alveolar O2 gradient, and transaminases (aspartate aminotransferase and alanine aminotransferase) than controls, (all P < 0.05). After E. coli endotoxin infusion, C3-deficient animals compared to controls had significantly less of a decrease in mean C5 levels (P < 0.01), but similar (P = NS) increases in circulating tumor necrosis factor levels, bronchoalveolar lavage neutrophils, and protein, and similar (P = NS) decreases in blood leukocytes and platelets. Two of six C3-deficient animals and two of six controls died. In summary, after intravenous infusion of E. coli endotoxin, canines with C3 deficiency have decreased endotoxin clearance and worse E. coli endotoxin-induced shock and organ damage. Thus, the third component of the complement system plays a beneficial role in the host defense against E. coli endotoxic shock.
Asunto(s)
Complemento C3/inmunología , Endotoxinas/inmunología , Escherichia coli/inmunología , Insuficiencia Multiorgánica/inmunología , Choque Séptico/inmunología , Análisis de Varianza , Animales , Líquido del Lavado Bronquioalveolar , Complemento C3/deficiencia , Perros , Femenino , Corazón/fisiopatología , Hemodinámica , Concentración de Iones de Hidrógeno , Riñón/fisiopatología , Hígado/fisiopatología , Pulmón/fisiopatología , Masculino , Insuficiencia Multiorgánica/sangre , Estudios Prospectivos , Choque Séptico/sangre , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The occurrence of hypoxia during endotracheal tube suctioning and its prevention was examined in 25 hemodynamically stable and non-cyanosed pediatric patients. In each patient 4 suction and treatment protocols were studied: 1. pre- and post-suction arterial blood gases (ABG) with no treatment (control). 2. ABG with pre-suction oxygenation. 3. ABG with presuction hyperinflation. 4. ABG with postsuction hyperinflation. With no presuction treatment the PO2 and saturation fell significantly after suctioning from control level of 116.6 +/- 9.4 mmHg to 93 +/- 9.3 mmHg post-suction and 97.2 +/- 0.4% to 92.8 +/- 1.4% (p less than 0.001) respectively. In 6 patients with low but adequate pre-suction PO2, hypoxic levels (PO2 less than 60 mmHg) were found post-suction. The significant fall in PO2 was completely prevented by pre-suction oxygenation. Post-suction hyperinflation induced a rapid return of the PO2 to control levels. These results suggest that severe hypoxia might occur during endotracheal suctioning and can be prevented by pre-oxygenation. We recommend 1 min oxygenation with FiO2 1.0 prior to suctioning procedures and intermittent hyperinflation with 100% oxygen during repeated endotracheal suction passes to prevent hypoxia, especially in children in respiratory failure who already have low or borderline pre-suction PO2.
Asunto(s)
Análisis de los Gases de la Sangre , Hipoxia/sangre , Intubación Intratraqueal , Succión/efectos adversos , Niño , Preescolar , Protocolos Clínicos , Femenino , Humanos , Hipoxia/etiología , Hipoxia/terapia , Lactante , Recién Nacido , Insuflación , Unidades de Cuidado Intensivo Pediátrico , Masculino , Terapia por Inhalación de Oxígeno , Estudios Prospectivos , Respiración ArtificialRESUMEN
Most causes of superior vena cava (SVC) obstruction are extracardiac. In rare instances, an intracardiac process may obstruct the venous return from the SVC. This is illustrated by a report of a patient with a congenital coronary artery fistula to the right atrium obstructing the SVC return. We propose a classification and clinical approach to the differential diagnosis of SVC obstruction.
Asunto(s)
Anomalías de los Vasos Coronarios/complicaciones , Síndrome de la Vena Cava Superior/etiología , Preescolar , Femenino , Fístula/complicaciones , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias del Mediastino/complicacionesRESUMEN
A four year old girl with infective endocarditis had unexplained facial swelling. Cross sectional echocardiography showed that a large right coronary artery fistula to the right atrium was obstructing the distal superior vena cava. The diagnosis was confirmed by cardiac catheterisation and at operation. The child was symptom free one year after operation.
Asunto(s)
Anomalías de los Vasos Coronarios/complicaciones , Fístula/complicaciones , Atrios Cardíacos , Vena Cava Superior , Preescolar , Constricción Patológica/etiología , Femenino , HumanosRESUMEN
In a prospective study, we determined whether routine immediate tracheal aspiration at birth is necessary in meconium-stained but otherwise normal infants delivered vaginally and having a 1-minute Apgar score greater than 8. A total of 572 newborn infants who met these criteria were randomly allocated to one of two groups. All infants underwent oropharyngeal suctioning with a DeLee catheter while the head was still on the perineum. In group I (n = 308) suctioning of the trachea under direct vision was performed instantly at birth; in group II (n = 264) this procedure was not done. There was no mortality among infants in the study, but morbidity, mainly pulmonary and laryngeal disorders, occurred in six of 308 group I infants and in none of the group II infants (P less than 0.025). Immediate tracheal suction is not a harmless intervention, and should be considered superfluous in a vigorous term neonate born with meconium-stained amniotic fluid.
Asunto(s)
Intubación Intratraqueal/efectos adversos , Síndrome de Aspiración de Meconio/terapia , Trastornos Respiratorios/etiología , Puntaje de Apgar , Humanos , Recién Nacido , Estudios Prospectivos , Distribución Aleatoria , Ruidos Respiratorios/etiología , SucciónRESUMEN
This prospective study was performed to determine the frequency of unexplained unconjugated hyperbilirubinemia associated with bacterial infection during the first week of life. Of 5805 infants delivered between September 1984 and December 1986, 93 jaundiced newborns without evidence of septicemia fulfilled the following criteria to be enrolled in the study: weight greater than 2500 g, gestational age greater than 38 weeks, age less than 7 days, and unexplained unconjugated bilirubin greater than 170 mumol/L (greater than 10 mg/dL) during the first 48 hours of life and/or greater than 255 mumol/L (greater than 15 mg/dL) thereafter. Evaluation for septicemia included blood and urine cultures, and white cell and thrombocyte counts. The study disclosed three (3.2%) infants who developed septicemia before any clinical suspicion had been aroused. It is concluded that bacterial infections should be considered a possible cause of neonatal unconjugated hyperbilirubinemia during the first week of life, regardless of the clinical condition of the infant.
Asunto(s)
Ictericia Neonatal/etiología , Sepsis/complicaciones , Femenino , Humanos , Recién Nacido , Masculino , Estudios Prospectivos , Sepsis/diagnósticoRESUMEN
Myelin basic protein (MBP) was serially measured in 177 CSF samples of 33 patients with leptomeningeal metastases and in 34 cancer controls. The mean level in cancer controls (free of neural involvement) was 5.7 +/- 0.33 ng/ml (normal less than 5 ng/ml) with abnormal elevation of MBP detected in 17%. The activity of the leptomeningeal disease was classified as either acute-progressive, stable or in remission on the basis of clinical and CSF cytological findings. CSF MBP levels were analysed in each stage. Abnormal elevation of MBP was detected in 74% of the 68 samples obtained in the acute-progressive stage (mean +/- SEM: 18.25 +/- 1.4 ng/ml, P less than 0.0001), in 24% of the 79 samples in the stable phase (mean: 7.99 +/- 0.8 ng/ml, NS) and in 20% of the 30 samples in remission (mean 5.7 +/- 0.3 ng/ml, NS). Similar changes in levels of CSF MBP were also observed in longitudinal studies of patients responding to treatment or relapsing to the acute stage. Eight patients developed treatment induced necrotizing leukoencephalopathy with typical CT-scan findings; elevated levels of CSF MBP were detected in 7 of them (mean: 21 +/- 3 ng/ml) when measured within 2 weeks of diagnosis but not when measured 2 months earlier. Our study suggests that in leptomeningeal metastases, CSF MBP levels are indicators of the disease activity, particularly if longitudinal determinations are used.