[Clinical and radiological features of cerebral venous thrombosis in a children cohort]. / Características clínicas y radiológicas de una cohorte de niños con trombosis venosa intracraneal.

INTRODUCTION: Cerebral venous thrombosis (CVT) is an uncommon and poorly studied condition in the pediatric population. OBJECTIVES: To describe and compare the clinical and radiological features of non-neonatal children with CVT according to age and to analyze their association with functional impairment or mortality at hospital discharge. METHODOLOGY: An observational cohort study of chil dren older than 30 days with a first CVT diagnosed with imaging/venography by magnetic resonance (IMR/VMR). We measure functionality with the modified Rankin scale defining marked impairment with 3 to 5 points. We used U-Mann-Whitney test to compare ages averages between groups with and without the different studied variables (significance < 0.05). We used logistic regression analyses to estimate the risk of adverse outcome for each variable expressed in Odds Ratios (ORs) and 95% confidence intervals (CI). RESULTS: Among 21 patients recruited, 42.8% were girls, median age 6.27 years (Interquartile range: 0.74-10). The average age was lower in children with diagnostic delay > 48 hours (p = 0.041), score < 12 in the Glasgow coma scale (p = 0.013), seizures (p = 0.041), sinus rectus thrombosis (p = 0.011), and intracranial hemorrhage (p = 0.049); while it was significantly higher in children with intracranial hypertension syndrome (p = 0.008). The presence of some chro nic systemic condition (OR = 11.2; CI = 1.04-120.4), deep CVT (OR = 14; CI = 1.3-150.8), and brain ischemia (OR = 15.8; CI = 1.4-174.2) was associated with marked functional impairment or mor tality at discharge. CONCLUSIONS: Clinical and radiological features of CVT are age-related. Chronic illnesses, deep venous system involvement, and brain ischemia predict adverse short-term outcomes.

Alterations in the antioxidant defense system in prepubertal children with a history of extrauterine growth restriction.

PURPOSE: The role of oxidative stress is well known in the pathogenesis of acquired malnutrition. Intrauterine growth restriction has been associated with an imbalance in oxidative stress/antioxidant system. Therefore, early postnatal environment and, consequently, extrauterine growth restriction might be associated with alterations in the antioxidant defense system, even in the prepubertal stage. METHODS: This is a descriptive, analytical, and observational case-control study. The study included two groups; 38 Caucasian prepubertal children born prematurely and with a history of extrauterine growth restriction as the case group, and 123 gender- and age-matched controls. Plasma exogenous antioxidant (retinol, ß-carotene, and α-tocopherol) concentrations were measured by HPLC; antioxidant enzyme activities of catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase were determined in lysed erythrocytes by spectrophotometric techniques. RESULTS: Catalase and glutathione peroxidase concentrations were significantly lower in extrauterine growth restriction children than in controls (P < 0.001). Lower plasma retinol concentrations were found in the case group (P = 0.029), while concentrations of ß-carotene and α-tocopherol were higher (P < 0.001) in extrauterine growth restriction prepubertal children as compared with controls. After correction by gestational age, birth weight, and length, statistically significant differences were also found, except for retinol. CONCLUSIONS: Prepubertal children with a history of extrauterine growth restriction present alterations in their antioxidant defense system. Knowing these alterations may be important in establishing pharmacological and nutritional treatments as this situation might be associated with higher metabolic disorders in adulthood.

[Health service needs of migrant women from a basic health area: A qualitative study]. / Necesidades sentidas de salud en mujeres migrantes de una zona básica de salud: estudio cualitativo.

OBJECTIVES: To know the needs and lack of information on health issues of Maghrebi women. SUBJECTS, MATERIAL AND METHOD: Design: Qualitative study technique nominal group (TGN). SUBJECTS: 14 North African women from Association for Solidarity and Rapprochement of Cultures (ASAC) from the rural clinic of La Aljorra who knew and understood Spanish, older age, and lived in the town for more than 3 years. Material and method TGN asks: «What daily health issues for you and your family worry you the most and do you need answers?¼ Individual reflection and list that were discussed among them, joining the group consensus. Subsequently, they were prioritized individually and a definitive list of their prioritized health needs was made. RESULTS: Thirty-six percent of the ASAC associates attended. At first, 17 topics were written on health needs for which they wanted a response. The final topics chosen and grouped by them were 6: 1) Contraceptive methods; 2) Relationship problems; 3) Thyroid; 4) How to cure the sciatic nerve?; 5) Anemia and 6) Stress. 70% related to the area of sexuality. CONCLUSIONS: 1) Qualitative research is an adequate consensus method to obtain information on little-known topics and directly from the person involved; 2) The Moroccan migrant woman considers information about sexuality and couple relationships very important; 3) Another pathology unknown to them and emerging in the area is thyroid; 4) Stress and its repercussions; 5) Sciatica and its consequences are also important when being agricultural workers.

[Radiosurgery as adjuvant treatment of a recurrent adult medulloblastoma. Ultra-early response]. / Radiocirugía como tratamiento complementario del meduloblastoma recidivadodel adulto: respuesta ultratemprana.

The role of radiosurgery after multimodality treatment of recurrent desmoplastic adult medulloblastoma is analyzed. The ultra-early clinical and pathological response of this tumor to adjunctive radiosurgery is stressed.

[Bone marrow stem cell transplantation in amyotrophic lateral sclerosis: technical aspects and preliminary results from a clinical trial]. / Terapia celular para la esclerosis lateral amiotrófica: aspectos técnicos y resultados preliminares del estudio CMN/ELA.

Patients with amyotrophic lateral sclerosis (ALS) experience progressive and irreversible paralysis as a result of the continued loss of motor neurons, which leads to death in less than five years. To date, there is no treatment that can change the progression of this disease. Bone marrow stem cells have shown neural regenerative and neural repairing properties. Specifically, our group showed in a murine model of the disease that these cells, when injected in the spinal cord, can rescue motor neurons through the secretion of GDNF. Based on these results, we designed a phase I/II clinical trial for the purpose of demonstrating the viability of the intraspinal injection of autologous bone marrow mononuclear cells in patients with bulbar onset ALS, with an evolution between 6 and 36 months, with a forced vital capacity (FVC) 50% and T90 29%. This article describes the technique for extracting 60 mL of bone marrow used for the intervention, processing it by density gradient, and the neurosurgical technique used for implanting it. After 6 months of follow-up, the few adverse events reported in the first seven patients included seem to show that the procedure is safe and viable. Most of these patients, including two with a rapid deterioration, have stabilized the progression of their FVC and the neurologic scales measured. The data obtained so for seem to justify the design of new trials more oriented toward the efficacy of the procedure.

[Usefulness of hyperbaric oxygen in the treatment of radionecrosis and symptomatic brain edema after LINAC radiosurgery]. / Eficacia del oxígeno hiperbárico en el tratamiento de la radionecrosis y el edemacerebral sintomáticos tras radiocirugía con acelerador lineal.

Radionecrosis with brain edema is a complication of radiosurgery. Three female patients harbouring a frontal pole, petrous and parasagital parietoocipital meningiomas respectively who had been treated with LINAC radiosurgery are presented. Those patients developed, between two and eight months later, a severe symptomatic radionecrosis with a huge brain edema resistant to the usual steroid therapy. Only after 40 sessions of hyperbaric oxygen, a good remission of the lesions was obtained. There are few cases reported in the literature with such a good outcome. Consequentely, this therapy must be taken into account to treat this type of radiosurgical complication before considering surgery.

Cavernomas in children with brain tumors: a late complication of radiotherapy.

BACKGROUND: Delayed complications of radiation therapy comprise cerebral atrophy, radionecrosis and induction of tumors. Recent reports indicate the possibility of the "de-novo" formation of intracranial cavernomas in patients submitted to radiation therapy to the brain. OBJECTIVES: To report three children, two with medulloblastomas and one with a pineal germinoma, treated with radiotherapy that developed intracerebral cavernous hemangiomas some years after treatment. With this work, we aim to draw attention to this occurrence in the neurosurgical community. RESULTS: The patients were two girls and one boy with ages comprised between 2.5 and 7 years (mean 5.2 years). The average interval from irradiation to the appearance of cavernoma was of 5.3 years (range 5-6 years). The lesions were found during the routine neuroimaging studies performed for the follow-up of their primary neoplasms. No patient showed signs or symptoms related to the cavernomas. However, the three children will need both clinical and neuroimaging surveillance to monitor the evolution of these incidentally discovered lesions. CONCLUSIONS: Intracranial cavernomas can occur years after cerebral radiation therapy. In spite of previous reports that show a high incidence of bleeding lesions, cavernomas may be found incidentally during the neuroimaging surveillance studies that are performed to children with brain tumors previously treated with radiotherapy. In these cases, a conservative attitude seems to be advisable, reserving surgery only for those lesions that grow or bleed.

[Brain abscess. Evaluation of prognostic factors: does the use of antibiotic prescribing protocols improve outcome?]. / Abscesos cerebrales: análisis de factores pronóstico e influencia del tratamiento antibiótico protocolizado en su evolución.

BACKGROUND: the aim of this study was to evaluate prognostic factors in brain abscess (AB) and influence of management with antibiotic prescribing protocols (APP). PATIENTS AND METHODS: observational study of a cohort of non-paediatric patients with BA admitted at a 944-bed hospital (1976-2005). Data collection from clinical records has been done according to a standard protocol. We analysed epidemiological, clinical, radiological, microbiological and laboratory data associated with mortality. From 1976 to 1983 (Period I), antibiotic treatment was not done according to any internal APP; from 1983 (Period II), antibiotic management was done according to a APP designed by infectious diseases specialists and neurosurgeons. Predictors of mortality were identified by univariate analysis. The influence of the use of APP in outcome was assessed. RESULTS: 104 patients with BA were included (mean age 45 years; range 12-86); presumed primary pathogenic mechanism of BA was identified in 89%; microbiologic diagnosis was made in 76%. Overall mortality was 16.3%. Factors statistically associated with higher mortality were: age > 40 years, ultimately fatal underlying disease, acute severe clinical condition at the onset of BA, altered mental status and inadequate empirical treatment; 33 patients were treated in Period I and 71 in Period II; no statistically significant differences were found between epidemiological, clinical, radiological or microbiological characteristics of the groups except for mean age (> 40 years in 36% and 62% respectively in Period I and II). Rates of resolution of BA were 60 vs. 77.4% (p < 0.05); relapses 21 vs. 7% (p < 0.05) and mortality 18 vs. 15.4% (p > 0.05), in Period I and II respectively. CONCLUSIONS: main prognostic factors associated with mortality in patients with BA are age, rapidly fatal underlying disease, acute severe clinical condition at the onset of BA, altered mental status and inadequate empirical treatment. Empiric treatment according to APP was associated with greater resolution and lower relapse rates.

[Biofeedback and electrostimulation in the treatment of non monosymptomatic enuresis]. / Biofeedback y electroestimulación como tratamiento de la enuresis no monosintomática.

AIM: To show our experience with biofeedback and electrostimulation techniques in the treatment of non monosymptomatic enuresis. METHODS: We reviewed biofeedback and electrostimulation techniques in the treatment of complicated enuresis carried out in our institution between 1995 and 2000. We report 99 patients (65 girls and 34 boys) with ages ranging from 5 to 14 years old. A complete urodinamy study divided the patients into 5 groups: detrusor-sphincter dysfunction (DSD) (47 patients), detrusor overactivity (DO) (25 patients), urge syndrome (US) (15 patients), sphincter hypertony (SH) (10 patients) and "retentionist" bladder (RB) (2 patients). Success was defined as less than three wet nights in a month. Biofeedback and electrostimulation program was designed in 10 sessions per week (20 minutes each session) with SIGMAX-Biomedical software. Tibial electrostimulation with SANS-UroSurge equipment was indicated when biofeedback and electrostimulation techniques failed (12 sessions per week, 30 minutes each session). RESULTS. The success rate has been 78.9% in DSD group, 80% in DO group, 85% in US group, 75% in SH group, 100% in RB group. CONCLUSIONS: Effectiveness of biofeedback and electrostimulation techniques in the treatment of non monosymptomatic enuresis has been reported and seems to be permanent in time.

Humanization in healthcare arises from the need for a holistic approach to illness. / Implantación de un proyecto de humanización en una Unidad de Cuidados Intensivos.

Suffering is not only exclusive to patients or their relatives, but also to the health professionals, who feel to be at the center of the depersonalization process. Over-technification and the fact that the disease process is sometimes the only focal point of our activities, together with the ever-increasing influence of institutional power seen in recent times, all cause the health professional to be the first in demanding a change in health institution dynamics. Following initial reflection from one of the most technified medical specialties (Intensive Care Medicine), classically isolated from the rest of the Hospital and from the community, we implemented a project aimed at securing integration and empathy in our approach to patients and their relatives in the Intensive Care Unit (ICU) of Infanta Margarita Hospital. The project was designed to incorporate tools for working on the most important elements of a humanization plan, i.e., the patients, their relatives, the health professionals and the community, attempting to disclose the work done in the ICU over a period of 12 months. This project is referred to as the Project ICU Infanta Margarita: 1 year: 12 months for 12 commitments.

"Benign" shaken baby syndrome. Case report.

The authors report an infant with clinical and neuroimaging findings of shaken baby syndrome. The pitfalls encountered in the assessment on the cause of the bilateral frontal and interhemispheric subdural hematomas in this child are also briefly discussed. We have called this condition "benign" shaken baby syndrome and emphasize that not always acute subdural hematomas are of non-accidental nature.

[Postoperative delirium in patient neurosurgical: evaluation by means of the Abbreviated Mental Test]. / Delirio postoperatorio en pacientes neuroquirúrgicos: evaluación mediante el Test Mental Abreviado.

OBJECTIVES: To assess the incidence and characteristics of postoperative changes in the higher cerebral functions after elective intracranial surgery under general anesthesia. PATIENTS AND METHODS: This is a prospective study of 60 patients, aged 18-81 years, submitted to neurosurgical operations, allocated into two groups of 30 patients each: intracranial surgery group, patients submitted to craniotomy, and extracranial surgery group or control group, patients submitted to spinal procedures. All patients were given the Abbreviated Mental Test (AMT) on the day before to the operation, and then 2 and 24 hours after the end of the procedure. All individuals were managed with the same anesthetic technique. RESULTS: No differences in regard to demographics, duration of the operation, ASA physical state, and habits were found between the two groups. No differences in the pre-surgical and post-surgical AMT mean score were encountered between patients submitted to intracranial 9.87 +/- 0.35 or to spinal surgeries 9.80 +/- 0.41. Similarly, there were no significant differences between the two groups in the results of the AMT performed at 2 and 24 hours after the end of the surgeries. Only two subjects undergoing spinal procedures had a score of < or = 8 in the AMT performed 2-hours after the operation, while none showed a decrease in the 24-hour test score. CONCLUSIONS: Patients submitted to intracranial surgery did not show any changes in cognitive or attention functions during the first postoperative 24 hours as assessed by the AMT.

Evaluación de la calidad de vida en Esclerosis Múltiple a través del MSQOL-54 y su relación con la salud de la persona / Assessment of Quality of Life in Multiple Sclerosis through the MSQOL-54 and its relation to the health of the caregiver

Objetivo: El objetivo del presente estudio fue evaluar la Calidad de Vida Relacionada con la salud (CVRS) en personas con Esclerosis Múltiple (EM) mediante el cuestionario MSQOL-54 y analizar su relación con la salud de las personas cuidadoras principales a través del cuestionario GHQ-12 y un cuestionario de salud física autopercibida. Metodología: Se evaluó a 115 personas con diagnóstico de EM y a 79 personas cuidadoras principales. Resultados: Los resultados obtenidos señalan la significativa afectación de la CVRS de las personas con EM y su relación con la salud de las personas cuidadoras principales. Se encontraron relaciones significativas entre la salud física y mental de la persona con EM y un mayor número de enfermedades, peor salud mental y menor autopercepción de salud en la persona cuidadora. Conclusiones: Los resultados obtenidos señalan la significativa afectación de la CVRS de las personas con EM y su relación directa con la salud de las personas cuidadoras principales. (AU)

[Syndromes of overdrainage of ventricular shunting in childhood hydrocephalus]. / Síndromes de hiperdrenaje de las válvulas en hidrocefalia infantil.

Overdrainage in ventricular shunting constitutes a difficult to prevent and to treat complication. The authors reviewed a retrospective series of 512 children submitted to a ventricular shunting procedure aimed at analysing factors influencing this type of complication. The causes for the hydrocephalus were congenital (n=172), post-myelomeningocele (n=123), posthemorrhagic (n=103), tumoral (n=64), postmeningitis (n=40) and posttraumatic (n=10). Eighty-eight children (17.8%) evolved with a complication related to the excessive function of the valve. The authors investigated the relationship between hydrocephalus' etiology and type of overdrainage syndromes. The most frequent complication was ventricular catheter block (n=50), followed by symptomatic slit ventricle syndrome (SVS) (n=19), subdural hematoma (n=10) and trapped fourth ventricle (n=9). There were no statistical differences regarding complications for each etiologic subset of hydrocephalus. SVS occurred in 19 children (3.71%), a low rate according to the current literature. Posthemorrhagic and postinfectious hydrocephalus grouped together showed a higher rate of SVS (p=0.005), a feature that we attributed to the cerebral destruction caused by these two conditions. Treatment of SVS was complex and required diverse procedures, applied in an escalated way, which included five decompressive craniectomies. The authors suggest avoiding, as much as possible, the use of ventricular shunts, and recommend the alternative use of new technology valves and neuroendoscopic procedures.

Rantes production during development of cardiac allograft vasculopathy.

BACKGROUND: RANTES (regulated on activation, normal T cell expressed and secreted) production has been shown to correlate with mononuclear cell recruitment and precede intimal thickening in cardiac allograft vasculopathy (CAV). However, the cells that produce RANTES in CAV are undefined. Therefore, in an MHC II-mismatched murine model of CAV, we sought to (1) define the cellular sources of RANTES and (2) determine the role of CD4+ lymphocytes in RANTES production during CAV development. METHODS: B6.CH-2bm12 strain donor hearts were transplanted heterotopically into wild-type (WT) or CD4 knockout (CD4KO) C57BL/6 mice (MHC II mismatch). No immunosuppression was used. Recipients were sacrificed at 7, 14, and 24 days. Intragraft RANTES gene expression and protein levels were determined with ribonuclease protection assay and ELISA, respectively. At days 7 and 24, RANTES production by graft-infiltrating cells was defined with intracellular RANTES staining and multicolor FACS analysis. Intimal thickening was quantitated morphometrically. In murine hearts and in six explanted human hearts with advanced CAV, RANTES was also localized immunohistochemically. RESULTS: NK, NKT, and gammadelta+ cells, in addition to CD4+, CD8+ lymphocytes, and CD11b+ macrophages, produced RANTES in early and late stages of CAV. RANTES-producing NK, NKT, and gammadelta+ cells tripled in number during CAV development; by day 24, NK and gammadelta+ cells each outnumbered CD4+ lymphocytes and CD11b+ macrophages. The presence of CD4+ lymphocytes was required for sustained RANTES production in allografts, which correlated with mononuclear cell recruitment and preceded intimal thickening. In murine and explanted human hearts with advanced CAV, RANTES immunolocalized with graft-infiltrating mononuclear cells and vessel wall cells. CONCLUSIONS: We present evidence that other cell types in addition to CD4+, CD8+ T lymphocytes, and CD11b+ macrophages contribute significantly to RANTES production in CAV. In this MHC II-mismatched murine model of CAV, sustained RANTES production requires CD4+ lymphocytes, correlates with mononuclear cell recruitment, and precedes intimal thickening. In experimental and human CAV, vessel wall cells may also produce RANTES. Interventions aimed at inhibiting RANTES production in CAV may need to target several types of cells, and neutralization of RANTES bioactivity may reduce mononuclear cell recruitment and CAV development.

Early and late chemokine production correlates with cellular recruitment in cardiac allograft vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy (CAV) remains the leading cause of late mortality in heart transplant recipients. Activated T lymphocytes and macrophages infiltrate the donor heart before vascular intimal thickening develops, but the specific mediators of mononuclear cell recruitment leading to CAV are unknown. Therefore, we sought to define the relationship between chemokine gene expression and production, T lymphocyte and macrophage recruitment, and intimal thickening in a murine model of CAV. METHODS: B10.A or B10.BR strain hearts were transplanted heterotopically into B10.BR mice. Recipients were killed at 1, 4, 7, 14, and 30 days. Donor hearts were assayed for chemokine gene expression with ribonuclease protection and for protein with ELISA. Intragraft cellular infiltration was defined immunohistochemically. Intimal thickening was quantitated morphometrically. RESULTS: Early and late patterns of intragraft chemokine expression associated with distinct cellular infiltration were identified. First, transient MIP-2 and MCP-1/JE production in isografts and allografts correlated with neutrophil and macrophage infiltration. MCP-1/JE production and macrophage infiltration was greater in allografts than isografts. Second, allografts demonstrated sustained lymphotactin, RANTES, and IP-10 expression, beginning at day 4, correlating with persistent macrophage and T lymphocyte infiltration. Intimal thickening became evident at 14 days. Isografts did not display the late pattern of sustained chemokine gene expression, cellular infiltration, or intimal thickening. CONCLUSIONS: Transient, early MIP-2, and MCP-1/JE production in isografts and allografts correlated with neutrophil and macrophage recruitment, and is likely related to ischemia-reperfusion. In allografts, the delayed induction of chemokines specific for macrophages and T lymphocytes correlated with mononuclear cell infiltration and preceded intimal thickening. This study thus demonstrates a dual pattern of chemokine induction correlating with intragraft mononuclear cell recruitment, associated with ischemia-reperfusion and CAV development. Chemokine-directed interventions may interfere with leukocyte trafficking and inhibit CAV development.

CD8+ lymphocytes augment chronic rejection in a MHC class II mismatched model.

UNLABELLED: Chronic rejection, or cardiac allograft vasculopathy (CAV), remains the leading cause of late death in heart transplant recipients. The precise role and contributions of T lymphocyte subsets to CAV development remains unknown. METHODS: Donor hearts from B6.C-H2bm12 mice were transplanted into T lymphocyte subset knockout recipients and T lymphocyte-reconstituted nude recipients. No immunosuppression was used. Intimal proliferation was measured morphometrically. In vitro studies were performed to analyze the donor-specific activation status of recipient CD8+ lymphocytes by examining cellular proliferation, interleukin-2 secretion, and interleukin-2Ralpha expression. Intracellular cytokine staining assay was performed to determine both the profile and source of intragraft cytokines. RESULTS: Hearts transplanted into wild-type recipients developed severe CAV by 24 days. Intimal lesions were absent in the hearts that were transplanted into nude and CD4-/- knockout mice (containing CD8+ lymphocytes). In contrast, the donor hearts in CD8-/- knockout recipients (containing CD4+ lymphocytes) developed CAV, but significantly less than in wildtype. Adoptive transfer of T lymphocyte subset populations into nude recipients confirmed that CAV was absolutely contingent on CD4+ lymphocytes, and that CD8+ lymphocytes played an additive role in intimal lesion progression in the presence of CD4+ lymphocytes. Although CD8+ lymphocytes alone did not cause CAV in vivo, we demonstrated that MHC class II disparate alloantigens activated CD8+ lymphocytes both in vivo and in vitro. Finally, both CD4+ and CD8+ lymphocytes contributed to the intragraft IL-2 and IFN-gamma production. CONCLUSIONS: In this MHC class II mismatched murine model, CAV is a T lymphocyte dependent event, and absolutely contingent on the presence of CD4+ lymphocytes. Furthermore, CD8+ lymphocytes (1) are activated by MHC class II disparate antigens and (2) play a significant role in the progression of lesion development. Finally, both CD4+ and CD8+ lymphocytes contribute to CAV development via secretion of IFN-gamma, a known mediator of CAV in this model.

Differential expression of RANTES chemokine, TGF-beta, and leukocyte phenotype in acute cellular rejection and quilty B lesions.

BACKGROUND: Because of the complexity of the trabeculated endocardial surface and tangential histologic sectioning, the differentiation of acute cellular rejection (ACR) from Quilty B lesions (QB) in endomyocardial biopsies (EMBs) is problematic. We hypothesized that the phenotype chemokine RANTES (regulated upon activation, normal T cell expressed and secreted) expression of infiltrating cells and the pattern of expression of transforming growth factor-beta (TGF-beta) may distinguish ACR from QB. In previous studies, the number of RANTES-positive cells and the expression of TGF-beta correlated with the severity of rejection. METHODS: We used immunohistochemical techniques to stain sections of human EMBs with only QB (n = 14) or with only ACR (International Society for Heart and Lung Transplantation Grades 1A and 1B, n = 7; Grades 3A and 3B, n = 7) for B (CD20) and T-lymphocytes (CD3), macrophages (CD68), RANTES, and TGF-beta expression. We graded the percentage of positive cells from 0 to 4 (1 = 1% to 25%; 2 = 26% to 50%; 3 = 51% to 75%, and 4 = 76% to 100%). RESULTS: When ACR was compared with QB, we found no difference in the proportion of myocardial B cells (0.9 +/- 0.3 vs 1.1 +/- 0.3, p = 0.17); however, we found a lesser proportion of T cells (1.8 +/- 0.5 vs. 2.8 +/- 0.9, p <0.01) but more macrophages (2.9 +/- 0.5 vs. 1.1 +/- 0.6, p < 0.0001) in ACR than in QB. We also found more RANTES-positive leukocytes in ACR vs. QB (2.8 +/- 1.3 vs. 1.9 +/- 0.9, p = 0.03). In QB, many endocardial vessels stained for TGF-beta (2.9 +/- 1.6). Myocardial vessels and injured myocytes in both ACR and QB expressed TGF-beta. CONCLUSIONS: In ACR, although T-lymphocytes are numerous, more than 50% of infiltrating cells are macrophages and more than 50% express RANTES. In QB lesions, more than 50% of infiltrating cells are T-lymphocytes and less that 50% of leukocytes will express RANTES. B cells are present in both ACR and QB, but on average comprise only 25% of the cells present. Thus, a relatively simple immunohistochemical analysis of endomyocardial biopsies may be useful in distinguishing ACR from QB.

7-Nitroindazole prevents dopamine depletion caused by low concentrations of MPP+ in rat striatal slices.

A significant loss of dopamine was found in rat striatal slices incubated with 1-methyl-4-phenylpyridinium ion (MPP+) at a concentration of 2 microM or higher. The addition of 7-nitroindazole, a specific inhibitor of neuronal nitric oxide synthase (nNOS), prevented this effect on dopamine when the concentration of MPP+ was between 2-5 microM, but not at higher concentrations. This protection was reproduced with other less specific NOS-inhibitors, such as nitro-arginine and nitro-arginine methylester. 7-nitroindazole did not protect against the dopamine depletion caused by the non-specific mitochondrial chain blocker rotenone. Neither MPP- nor rotenone significantly increased the nitrite concentration in striatal slices, measured as an index of nitric oxide production. The basal production of nitric oxide may be enough to trigger the dopamine depletion at very low concentrations of MPP+, probably acting synergistically with cytosolic calcium increase. Higher concentrations of MPP+ are toxic by themselves without the mediation of nitric oxide. The inhibition of nNOS may protect against dopamine loss at early stages of a neurodegenerative process, and it could then be considered in the treatment or prevention of neurodegenerative human processes such as Parkinson's disease.

Caspase inhibition protects nigral neurons against 6-OHDA-induced retrograde degeneration.

6-Hydroxydopamine (6-OHDA) administered intrastriatally to adult rats in a single injection causes neurodegeneration of the nigrostriatal pathway and loss of > 50% of dopamine neurons in substantia nigra pars compacta 30 days after administration. The death of nigral neurons occurs, at least partially, by a caspase-mediated mechanism. The nigral loss of dopaminergic neurons could be prevented by stereotaxical administration of zVAD.fmk, a caspase inhibitor, into the substantia nigra, indicating that 6-OHDA-induced nigrostriatal degeneration involves caspase activation. These results suggest that caspases are probably involved in neurodegenerative chronic processes such as Parkinson's disease and might be considered as possible targets in the treatment of such neurological disorders.