Long-term effects of cognitive rehabilitation on brain, functional outcome and cognition in Parkinson's disease.

BACKGROUND AND PURPOSE: Cognitive rehabilitation has demonstrated efficacy in producing short-term cognitive and brain changes in patients with Parkinson's disease (PD). To date, no study has assessed the long-term effects of cognitive rehabilitation using neuroimaging techniques in PD. The aim was to assess the longitudinal effects of a 3-month cognitive rehabilitation programme evaluating the cognitive, behavioural and neuroimaging changes after 18 months. METHODS: Fifteen patients with PD underwent a cognitive, behavioural and neuroimaging assessment at pre-treatment (T0 ), post-treatment (T1 ) and after 18 months (T2 ). This study examined the long-term effects (from T0 to T2 ) and the maintenance of the changes (from T1 to T2 ). T1-weighted, diffusion-weighted, functional magnetic resonance imaging during both a resting-state and a memory paradigm were acquired. Voxel-based morphometry and tract-based spatial statistics were used for grey and white matter analyses. A region-of-interest-to-region-of-interest approach was used for resting-state functional connectivity (FC) and a model-based approach was used for brain activation during the memory paradigm. RESULTS: Patients with PD showed increased cognitive performance, decreased functional disability, increased brain FC and activation at T2 compared with T0 (P < 0.05, FDR). Moreover, patients showed maintenance of the improvements in cognition and functionality, and maintenance of the increased brain FC and activation at T2 compared with T1 . However, significant grey matter reduction and alterations of white matter integrity were found at T2 (P < 0.05, FWE). CONCLUSIONS: Findings suggest that the improved cognitive performance and increased brain FC and activation after cognitive rehabilitation were significantly maintained after 18 months in patients with PD, despite the structural brain changes, consistent with a progression of neurodegenerative processes.

Brief report: the adolescent Child-to-Parent Aggression Questionnaire: an examination of aggressions against parents in Spanish adolescents.

The objective of this study was to develop a questionnaire to assess child-to-parent aggression in adolescents and to document the extent of the problem. The questionnaire developed in this study, the Child-to-Parent Aggression Questionnaire (CPAQ), includes forms of physical and psychological aggression directed at both the mother and the father. It also includes open questions about the reasons for the aggressive acts. The CPAQ was completed by a sample of 2719 adolescents (age range: 13-18 years old, 51.4% girls). Confirmatory factor analysis supported a four-factor correlated structure (physical aggression against mother, physical aggression against father, psychological aggression against mother, and psychological aggression against father). Psychological and physical aggression against the mother was more frequent than against the father. However, there were no differences with regard to severe forms of aggression. Girls scored significantly higher on all indicators of psychological aggression, including severe psychological aggression. Nevertheless, except for the prevalence of physical aggression against mothers, which was higher in females, there were no significant differences in physical aggression against parents. Finally, the reasons provided by the adolescents for the aggression included both instrumental (e.g., to obtain permission to get home late and to access their computers) and reactive reasons (e.g., anger and self-defense). These findings highlight the complexity of child-to-parent aggression in adolescence.

[Magnetic resonance imaging in long-term assessment after surgery for aortic coarctation]. / Valoración a largo plazo con resonancia magnética en pacientes corregidos de coartación de aorta.

OBJECTIVES: Spin echo or gradient echo magnetic resonance imaging provides enough information to plan patient management and can be completed with the use of three-dimensional magnetic resonance angiography to evaluate the need for reintervention, assess follow-up, or discharge the patient. PATIENTS AND METHODS: From 1990-2003, we evaluated 101 patients after initial corrective surgery for aortic coarctation at the age of 3.1 +/- 3 years, with subsequent postoperative assessment at 1 year and again 12.4 +/- 4.2 years later. No mortality was registered during the follow-up. Corrective surgery was performed in 32 patients (31.6 %) before the first month of life. All the patients were evaluated with spin-echo and echo gradient and 34 were evaluated with magnetic resonance angiography. The patients were classified into two groups: group A consisted of 68 patients (11 < 1 month old) with no complications. End-to-end anastomosis was performed in 55, the Alvarez technique in five, the Waldhausen technique in six, and conduit in two. Group B consisted of 33 patients complicated with early aortic recoarctation (21 corrected before the age of 1 month). End-to-end anastomosis was performed in 29, the Alvarez technique in two, and grafting in two. During the follow-up, 43 reinterventions were performed. Isthmus diameter/descending aorta diameter at the diaphragmatic level and repaired site diameter/descending aorta diameter at the diaphragmatic level were measured. RESULTS: Group A: the isthmus diameter/descending aorta diameter at the diaphragmatic level index was 0.92 +/- 0.08 and the repaired site diameter/ descending aorta diameter at diaphragmatic level index was 0.90 +/- 0.05. Twenty-three patients were assessed by means of three-dimensional magnetic resonance angiography, which revealed two late stenosis (one in a 10-year-old patient with an end-to-end anastomosis performed previously, and another in an 18-year-old patient with a proximal and distal obstructed conduit). Group B: the isthmus diameter/descending aorta diameter index was 0.84 +/- 0.1 and the repaired site diameter/ descending aorta diameter index was 0.82 +/- 0.11. Eleven patients were assessed by means of three-dimensional magnetic resonance angiography, which revealed five stenosis indexes (0.53-0.73) surgically corrected before the age of 2 months, four with an initial technique based on end-to-end anastomosis and one with a graft. CONCLUSIONS: Our results support the influence of young age, the use of end-to-end anastomosis and grafts in recoarctation and their late influence on recurrent recoarctation. The patients in group A were discharged in childhood or adulthood after periodic follow-up every 5 years with magnetic resonance angiography for 18 years with results within the normal range, while patients in group B required longer follow-up.

Alternating combination VCMP/VBAP chemotherapy versus melphalan/prednisone in the treatment of multiple myeloma: a randomized multicentric study of 487 patients.

PURPOSE: To determine whether combination chemotherapy with alternating cycles of vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) and vincristine, carmustine (BCNU), Adriamycin (doxorubicin; Farmitalia, Carlo-Erba Laboratories, Spain), and prednisone (VBAP) is better than the standard melphalan-prednisone (MP) regimen in multiple myeloma (MM). PATIENTS AND METHODS: From January 1985 to December 1989, 28 institutions of the Spanish Cooperative Group for Hematological Malignancies Treatment, Spanish Society of Hematology (PETHEMA) entered 487 eligible patients with symptomatic MM into the study. Patients were randomized to receive either MP or alternating courses of VCMP and VBAP. Logistic regression and the Cox proportional hazards models were used to assess the association between patients' characteristics and response rate and survival, respectively. RESULTS: Among 449 patients who were assessable for response, the overall response rate to MP was 51.8% (31.5% objective response plus 20.3% partial response) as compared with 62.7% (45.2% objective response plus 17.5% partial response) to VCMP/VBAP (P = .025). Also, a significantly higher proportion of objective responses was observed with combination chemotherapy (45.2% v 31.5%; P = .004). The factors associated with an unfavorable response rate in the overall series were low platelet count, treatment with MP, high creatinine level and immunoglobulin, (IgG) monoclonal (M)-component. No significant differences were found when survival rates of both groups of patients were compared. However, patients with IgA myeloma treated with VCMP/VBAP survived significantly longer than those who received MP (median, 20.2 v 38.4 months; P < .005). CONCLUSION: These results indicate that combination chemotherapy improves response rate in MM. However, this does not result in a significantly different survival rate, except for patients with IgA myeloma, who survive significantly longer with combination chemotherapy.

Splenectomy for poor graft function after allogeneic bone marrow transplantation in patients with chronic myeloid leukemia.

We report four patients with chronic myeloid leukemia (CML) that showed poor graft function after a non-T-depleted bone marrow transplantation (BMT) from an HLA-compatible sibling donor and who were successfully treated with splenectomy. Conditioning was done with cyclophosphamide (CY) and total body irradiation (TBI) without additional splenic irradiation. Three patients had enlarged spleens before BMT. The nucleated cell dose infused ranged from 2.3-3.2 x 10(8)/kg. Bone marrow (BM) examination prior to splenectomy showed BM aplasia (three cases) or hypocellularity (one case). At splenectomy no patient had evidence of cytomegalovirus (CMV) infection or severe acute GVHD; and three patients had moderately enlarged spleens. All patients were transfusion dependent. Complete hematological recovery was obtained in all patients. BM cellularity was normal 1 month after splenectomy. Complete chimerism of donor origin was documented. The four patients are alive (+16 to +58 months after BMT). Thus, in patients with CML, a poor graft function may be successfully corrected by splenectomy.

Acquired von Willebrand's syndrome associated with hydatid disease of the spleen--disappearance after splenectomy.

A new case of acquired von Willebrand's syndrome (vWS) is described in a 31-year-old woman with a hydatid splenomegaly and with a history of repeated abortions at an advanced stage of pregnancy, a positive serology for syphilis and a mildly elevated titre of antinuclear antibodies, with no family history of bleeding. There is an inhibitory effect on factor VIII: C (antihaemophilic factor) as well as on factor VIIIR: Ag (related antigen) and on factor VIIIR: RCo (ristocetin cofactor), and it is precipitated by rabbit anti-IgG antiserum. This inhibitory effect was demonstrated using the patient's plasma heated to 56 degrees C for one hour so as to dissociate circulating immunocomplexes. All the abnormalities of haemostasis, as well as the positive serology for syphilis, disappeared after splenectomy, and the ANA titre reverted to normal. The clinical and biological peculiarities of the case are discussed, and are interpreted in the light of the findings recorded in patients showing "lupus" anticoagulant.

Disappearance of lupus anticoagulant after allogeneic bone marrow transplantation.

Lupus anticoagulant antibodies have never been reported to disappear after either allogeneic or autologous bone marrow transplantation in humans. We report the first case of disappearance of lupus anticoagulant antibodies in a patient without systemic lupus erythematosus or clinical evidence of other autoimmune disorders, who received an allogeneic bone marrow transplant as treatment for chronic myeloid leukemia. Although marrow transplantation is not a recognized therapy for antiphospholipid syndrome, our observation should be considered another example of the capability of intensive chemo-radiotherapy followed by stem cell transplantation to ablate a pathologic marrow clone resulting in an autoimmune disorder and improve, or even cure, some severe autoimmune diseases.

Allogeneic BMT in a patient with CML and prior disseminated infection by mycobacterium avium complex.

A patient with chronic myeloid leukemia (CML) who developed a disseminated infection by mycobacterium avium complex (MAC) was successfully treated with rifampin, ethambutol, isoniazid, cycloserin and ciprofloxacin. Diagnosis was proven by histologic examination of hepatic biopsy and culture of the liver biopsy material. Two years later the patient underwent allogeneic bone marrow transplantation (BMT) from an HLA-matched sibling donor. Antimycobacterial prophylaxis to MAC with ethambutol, cycloserin and ciprofloxacin was given throughout the immediate post-transplant period. On day +25 post-BMT secondary prophylaxis was changed to ciprofloxacin and clarithromycin due to hepatic toxicity. Treatment was maintained until day 100 without side effects. There was no evidence of recurrent mycobacteriosis. Eight months after BMT the patient is well, with a good performance status and chronic graft-versus-host disease (GVHD) limited to the oral mucosa. Thus, MAC infection prior to transplant need not be a contraindication to successful BMT.

Pneumococcal pericarditis with cardiac tamponade in a patient with chronic graft-versus-host disease.

We report a case of pneumococcal pericarditis in a 13-year-old boy following allogeneic BMT from an HLA-identical unrelated donor. The post-transplant course was complicated by chronic GVHD which led to reinstitution of immunosuppressive therapy. Eight months after BMT the patient developed pericarditis with cardiac tamponade, and Streptococcus pneumoniae was isolated in the pericardiocentesis fluid. This is the first reported case of pneumococcal pericarditis after BMT. Although pericardial effusions after allogeneic BMT are often sterile and related to conditioning therapy or associated with chronic GVHD, rapid microbiological investigation and empirical treatment with antibiotics are necessary. Prophylaxis for pneumococcal infection in patients with chronic GVHD is recommended.

Autologous peripheral blood stem cell transplantation in a patient with previous invasive middle ear mucormycosis.

A 52-year-old male diagnosed with acute myeloid leukemia (AML) developed an invasive middle-ear mucormycosis during the neutropenic period after consolidation chemotherapy which resolved successfully with surgery and antifungal therapy. The patient underwent autologous peripheral blood stem cell transplantation (APBSCT) in first complete remission with antifungal prophylaxis with liposomal amphotericin B (AmB). There was no clinical, radiological or microbiological data of mycotic reactivation. This is the first reported stem cell transplantation (SCT) in a patient with prior invasive mucormycosis.

Invasive pulmonary aspergillosis prior to BMT in acute leukemia patients does not predict a poor outcome.

Eight patients with acute leukemia (AL) and invasive pulmonary aspergillosis (IPA) developing during previous antileukemic therapy underwent BMT (autologous in 6 cases and allogeneic 2). IPA was treated prior to BMT with full doses of amphotericin B, associated with surgical resection in three cases. One patient was treated with amphotericin B and itraconazole. Prior to BMT, seven patients had minimal residual pulmonary lesions. All patients received amphotericin B (0.5 mg/kg/day) during the aplastic period prior to engraftment. One patient died of Gram-negative septic shock before engraftment. Seven patients achieved complete hematological engraftment without any evidence of IPA reactivation. Amphotericin B was well tolerated with only minimal transient renal dysfunction in three patients. Later pulmonary complications related to IPA were observed in only one patient who developed a self-limited episode of hemoptysis. One patient died of CMV pneumonitis and two of leukemia relapse. Four patients survive disease-free and without complications related to IPA. We conclude that the reactivation of correctly treated IPA can be successfully prevented in BMT patients by use of prophylactic amphotericin B. With this approach, prior IPA is not a contraindication to BMT.

Translocation (10;11)(p13;p15) in an infant acute myeloid leukemia with MLL gene rearrangement.

Molecular rearrangements of the MLL gene at the 11q23 region have been identified in most cases of infant leukemia, regardless of the phenotype. We present a case of acute myeloid leukemia which coexpressed myeloid and lymphoid markers in a 12-month-old girl. Karyotype analysis revealed the presence of a thus far unreported translocation t(10;11)(p13;p15). Although no 11q23 abnormalities were cytogenetically detectable, an MLL gene molecular rearrangement was found.

Treatment of acute leukemia in children: recent advances and future challenges.

Recently advances have been made in the treatment of acute leukemia in children, it is now possible to cure more than 70% of children with acute lymphoblastic leukemia. With the introduction of more intensive chemotherapy regimens in patients at higher risk of relapse and the identification of cases that could be less intensely treated to diminish long-term toxicity, it could be possible to improve these excellent results. In contrast, pediatric acute myeloid leukaemia seems to be a more heterogeneous disease and its response to conventional chemotherapy is not as uniform. Introduction of new and more efficacious therapies is necessary to improve the poor outcome, especially among patients with high-risk features.

[Right aortic arch with a retroesophageal segment: a nuclear magnetic resonance study]. / Arco derecho con aorta retroesofágica: estudio con resonancia magnética nuclear.

The first two cases of retroesophageal right aortic arch studied by magnetic resonance imaging are reported. Both previously underwent angiography. The importance of MRI (magnetic resonance imaging) in the diagnostic procedure is discussed and its practice as alternative to angiography is suggested.

[Evaluation of pulmonary arteries using nuclear magnetic resonance in patients with pulmonary atresia]. / Evaluación de las ramas pulmonares con resonancia magnética nuclear en pacientes con atresia pulmonar.

OBJECTIVES: Patients with pulmonary atresia and a ventricular septal defect have one outlet vessel; the aorta. The pulmonary arteries may be present or absent, and there is a collateral shunt. Magnetic resonance imaging is used to study this. MATERIAL AND METHODS: We evaluated 10 patients with pulmonary atresia with ventricular septal defect. Five were males and the others were females, ages ranged between 1 day and 25 years, three patients were newborns. We used common planes, but mainly: axial-transverse and coronal, normal and right or left oblique projections. RESULTS: The size of the ventricular septal defect was 1.75 +/- 0.67 cm (0.5-3.2). The pulmonary trunk was absent in 7 patients, it was atretic in 2 and it was present in one. Confluent pulmonary branches were seen in 6 patients (right 0.58 +/- 0.12, left 0.53 +/- 0.19), not confluent in 2 (with only one branch in each case) and absent in the other two. There was collateral shunt flowing from the descending aorta in 7 patients, from the ascending aorta in two and from the aortic in the final case. The ascending aorta was dilated in all cases (diameter 3.04 +/- 1.39), afterwards the relation between the ascending aorta and the descending aorta was 1.87 +/- 0.25. The aortic arch was right sided in 5 patients. CONCLUSIONS: Magnetic resonance imaging is an alternative diagnostic method to angiocardiography. It gives complete information about the size, the position and the connection of the pulmonary arteries. It is also useful to evaluate the aortopulmonary to bronchial shunt.

[An imaging and color echo-Doppler study of interventricular defects]. / Estudio de los defectos interventriculares por imagen y ECO-Doppler color.

OBJECTIVE: Evaluation of ventricular septal defect with two-dimensional echocardiography and color flow Doppler. PATIENTS AND METHODS: We had studied by this method 180 patients; 97 males and 83 (mean age 1.5 +/- 1 years) diagnosed of a VSD. Cases with a complex cardiopathy were excluded from the study. The VSD was classified according to its location and relation to the tricuspid anulus and semilunar valves in perimembranous VSD, muscular VSD and subarterial double committed defect. The colour Doppler identified one or two areas of low through the ventricular septum with a zona of proximal acceleration throughout systole. Every group can be evaluated in different views but they all have a selective echocardiographic view except for muscular trabecular VSD. RESULTS: Seventy-six patients had perimembranous VSD (30 inlet, 26 trabecular and 20 infundibular-outlet), 102 had muscular VSD (3 inlet, 97 trabecular and 2 infundibular-outlet) and 2 had a subarterial double committed defect. A ventricular septal aneurysm was associated in 20 patients with muscular or perimembranous defects. Six patients, 2 of the perimembranous trabecular VSD, 2 muscular-trabecular VSD and 2 subarterial were initially misclassified. In this last 2 cases the turbulence created in the pulmonary valve was wrongly interpreted as pulmonary valvular stenosis; subcostal view for both tracts is necessary to avoid such mistake. In conclusion, color Doppler flow mapping is very useful to differentiate the various types as VSD and aids identification of multiples ventricular septal defects.

[Chronic eosinophilic pneumonia in a patient treated with allogenic bone marrow transplantation]. / Neumonía eosinófila crónica en un paciente tratado con trasplante de médula ósea alogénico.

A 39 year old patient diagnosed of severe aplastic anemia and treated with allogenic bone marrow transplantation and who presented chronic eosinophilic pneumonia eight months after the transplant is presented. The patient had no previous history of asthma or atopy. Conditioning was performed with cyclophosphamide and total body irradiation. Prophylaxis of the graft versus host disease was carried out with cyclosporin and short course of methotrexate. At day 30 mild graft versus host disease appeared which spontaneously resolved. A progressive increase in the number of eosinophils was observed from day +40 reaching 1.05 x 10(9)/l at day +180 coinciding with suspension of the cyclosporine. The patient remained asymptomatic with no evidence of chronic graft versus host disease. At 8 months following allogenic transplantation the patient developed three episodes of fever, cough, moderate dyspnea and pulmonary infiltrates. Respiratory tests showed a restrictive pattern. Bronchoalveolar lavage contained 20% of eosinophils. Upon lung biopsy alveolar infiltration by eosinophils, lymphocytes and mononuclear cells was observed. Diagnosis of chronic eosinophilic pneumonia was made with initiation of steroid treatment. A drastic response was observed. The patient remained asymptomatic without recurrence and without evidence of chronic graft versus host disease. This picture may have been caused by the donor eosinophils given that retrospective evaluation demonstrated a persistent moderate eosinophilia in the donor.

[Bone marrow autotransplantation in patients with acute myeloblastic leukemia in primary remission]. / Autotrasplante de medula ósea en pacientes con leucemia mieloblástica aguda en primera remisión.

Fifteen bone marrow autotransplants (BMAT) in patients with acute myeloblastic leukemia (AML) were performed after the first remission. The mean age was 37 years (range 12 to 60 years). According to the morphological classification FAB, 8 patients had monocytic leukemia (M4, M5) and 7 myeloid leukemia (M1, M2, M3). The mean interval elapsed between the date of complete remission and the BMAT was 3.9 months (range 1 to 5-9 months). In 8 patients this interval was longer than 6 months and in 7 cases it was shorter than 6 months. After achievement of the complete remission all patients underwent certain cycles of intensification before the BMAT. Eight patients received only a cycle whereas 7 patients received more than one cycle (between 2 and 4). The conditioning protocol consisted of cyclophosphamide (CP) (60 mg/kg x 2) and total body radiotherapy (TBR) (10 Gy) in 9 patients; CP and busulfan in five; and CP, cytarabine at high doses and melphalan in one case. Marrow extraction was performed after completion of chemotherapy of intensification. In 5 cases the bone marrow was depleted of leukemic cells by previous in vitro treatment with ASTA-Z. There are at present 8 alive patients. The survival free of illness was 51.8%. Seven patients died: 3 cases because relapse of the leukemia, 3 due to attachment failure of the transplantation, and one patient suffered a viral myocarditis. The survival free of illness was significantly longer in those patients transplanted after 6 months of the complete remission.

[Comparison of chemotherapy CHOP vs. CHOP/VIA in the treatment of aggressive non-Hodgkin's lymphoma: a randomized multicenter study of 132 patients. The PETHEMA group. Program for Study and Therapeutics of malignant hemopathies. Spanish Association of Hematology and Hemotherapy]. / Comparación de la quimioterapia CHOP frente a CHOP/VIA para el tratamiento de los linfomas no hodgkinianos agresivos: estudio multicéntrico aleatorizado en 132 pacientes. Grupo PETHEMA. Programa para el Estudio y la Terapéutica de las Hemopatías Malignas. Asociación Española de Hematología y Hemoterapia.

BACKGROUND: To compare standard chemotherapy CHOP (cyclophosphamide, adriamycin, vincristine and prednisone) with the regimen CHOP/VIA (VP-16, iphosphamide and cytarabine) in terms of response to therapy, response duration, survival and toxicity in patients with aggressive lymphoma. PATIENTS AND METHODS: 132 patients (84 males and 48 females; median age, 55 years) were included from 12 Spanish Institutions, diagnosed of non-Hodgkin's lymphoma of intermediate or high grade, in stages II-IV and previously untreated. Patients were randomized to receive CHOP or CHOP/VIA. RESULTS: After excluding 14 not assessable cases, 62 patients (52.5%) received CHOP, and 56 (47.5%) CHOP/VIA. No significant differences were found on main prognostic factors between such groups. Response was assessable in 114 cases (CHOP: 61; CHOP/VIA: 53) 39 patients (64%) receiving CHOP achieved complete response (CR), and 2 (3%) partial response (PR), whereas in the CHOP/VIA group CR and PR rates were 63% (34/53), and 7% (4/53), respectively. 14 patients (36%) treated with CHOP and 12 (35%) treated with CHOP/VIA eventually relapsed, with an actuarial risk of relapse at 36 months of 43% and 40%, respectively. Median survival was 37 months. No differences were found between both therapeutic groups, with an overall survival at 36 months from diagnosis of 53.5% (CI 95%: 40-67) for CHOP and 48% (CI 95%: 34-62) for CHOP/VIA. Finally, toxicity was not different for both arms. CONCLUSION: In the present study in patients with aggressive NHL chemotherapy regimens CHOP and CHOP/VIA showed similar results in terms of response, response duration, survival and toxicity.