Brain-heart crosstalk: the many faces of stress-related cardiomyopathy syndromes in anaesthesia and intensive care.

Neurogenic stress cardiomyopathy (NSC) is a well-known syndrome complicating the early phase after an acute brain injury, potentially affecting outcomes. This article is a review of recent data on the putative role of localization and lateralization of brain lesions in NSC, cardiac innervation abnormalities, and new polymorphisms and other genetic causes of the sympathetic nervous system over-activity. Concerns regarding the management of stress-related cardiomyopathy syndromes during the perioperative period are also discussed. Future clinical research should explore whether specific factors explain different patient susceptibilities to the disease and should be directed towards early identification and stratification of patients at risk, so that such patients can be more carefully monitored and appropriately managed in critical care and during the perioperative period.

Prospective study of high-dose chemotherapy and autologous peripheral stem cell transplantation in adult patients with advanced desmoplastic small round-cell tumour.

A total of 10 desmoplastic small round-cell tumour patients were treated by high-dose chemotherapy with stem cell support. After high-dose chemotherapy, no complete response conversion was obtained and EWS-WT1 fusion transcript detection was positive in the peripheral blood during follow-up in all patients. High-dose chemotherapy did not seem to change the results in desmoplastic small round-cell tumour.

Reduced intensity conditioning regimen followed by glycosylated G-CSF mobilized PBSCT in patients with solid tumors and malignant lymphomas.

The aim of this pilot study was to exploit the graft-versus-tumor potential of allogeneic transplants while improving safety of the procedure. Twelve patients with advanced hematological malignancies and solid tumors underwent a low intensity conditioning regimen (fludarabine and cyclophosphamide) followed by an allogeneic peripheral blood stem cell transplantation. The median time to achieve an absolute neutrophil count of more than 0.5 x 10(9)/l and an untransfused platelet count of more than 20 x 10(9)/l was 15 and 14 days, respectively. The main extra-hematological toxicities were mucositis and infections. Acute graft-versus-host (GVHD) disease was experienced by 62% of evaluable patients (grade II/B or III/C 80%) responsive to steroids. Extensive chronic GVHD was observed in 62% of patients. Non-relapse transplant-related mortality by day +30 was observed in three patients (25%). Eight out of 12 patients were full donor chimeric by day +100. One patient showed a mixed chimerism at day +37 when he died from progressive disease. One patient was in complete remission (CR) before allogeneic transplantation, and after transplantation four patients achieved CR and four experienced progressive disease. Our study confirms that a low intensity conditioning regimen for allogeneic stem cell transplantation is feasible and effective in heavily pretreated patients.

Mobilizing potential of ifosfamide/vinorelbine-based chemotherapy in pretreated malignant lymphoma.

The mobilizing potential and therapeutic activity of ifosfamide/vinorelbine-containing regimens with G-CSF support were explored in patients with pretreated malignant lymphomas. Ten patients with non-Hodgkin's lymphoma (NHL) received ifosfamide and vinorelbine, and 17 with Hodgkin's disease (HD) received ifosfamide, vinorelbine and gemcitabine (IGEV regimen), as induction chemotherapy before high-dose chemotherapy (HDT) with peripheral blood stem cell (PBSC) support. Most of the patients had been heavily pretreated with various chemotherapy regimens +/- radiotherapy. The target yield was > or =3 x 10(6) CD34+ cells/kg of body weight in order to support the subsequent myeloablative chemotherapy. The optimal PBSC harvest occurred on days 11 and 12, with no difference in CD34+ cell mobilization kinetics between the ifos- famide/vinorelbine and IGEV regimens. The median number of CD34+ cells/kg body weight collected was 10.9 x 10(6) (range 1.76-61.1 x 10(6)). The median total CD34+ cell/microl, CFU-GM and white blood cells (WBC) for all individual collections was 81.5/microl, 10 x 10(4)/kg, and 17 900/microl, respectively. The target yield of CD34+ cells was reached in 24 of 27 patients. Hematological side-effects were acceptable and no treatment-related hospitalizations or toxic deaths occurred. Fifteen patients have so far received high-dose therapy and PBSC reinfusion with rapid engraftment. These results confirm that ifosfamide and vinorelbine-based chemotherapy regimen with G-CSF support can be successfully and safely used to mobilize PBSCs.

Allogeneic peripheral blood stem cell transplantation with reduced intensity conditioning in primary refractory prolymphocytic leukemia: graft-versus-leukemia effect without graft-versus-host disease.

A patient with progressive prolymphocytic leukemia (PLL) received an allogeneic stem cell transplant using a reduced intensity conditioning regimen to avoid prohibitive toxicities. Early in the post-transplant period, a high donor-derived CD8+ count was observed. One year from transplantation, the patient was in complete remission, fully donor chimeric and with a normal performance status, suggesting that this approach may represent a useful treatment option in patients with refractory PLL.

Diffuse large-cell lymphoma of the testis.

PURPOSE: To evaluate clinical outcome of patients with testicular diffuse large-cell lymphoma treated with conventional-dose systemic chemotherapy. PATIENTS AND METHODS: This study is a retrospective analysis of adult patients with testicular diffuse large-cell lymphoma who were treated with a doxorubicin-based chemotherapy regimen at our institution, the Istituto Nazionale Tumori of Milan. Twenty-nine assessable patients, with a median age of 61 years, were identified. Sixteen patients had limited stage (Ann Arbor stage I/II) disease, whereas 13 patients had a testicular mass and distant organ involvement (Ann Arbor stage IV). Patients were retrospectively classified according to the International Prognostic Index. RESULTS: After a median follow-up of 82 months, 22 patients presented disease progression and 22 patients had died. Actuarial median time to treatment failure and overall survival were 44 and 41 months for patients with limited stage and 9 and 16 months for patients with advanced stage, respectively. Eight patients failed initial treatment, and 14 patients relapsed from clinical remission after a median disease-free time of 17 months (range, 6 to 98 months). Median survival time after progression of lymphoma was 5 months (range, 0 to 22 months). In nine (41%) of the 22 failing patients, the initial site of relapse was either the CNS or the contralateral testis; the remaining patients experienced relapse in multiple extranodal sites. CONCLUSION: Poor prognosis of patients with diffuse large-cell lymphoma calls for more effective treatment strategies, such as high-dose chemotherapy programs for younger patients or specifically designed chemotherapy regimens for patients not suitable for high-dose treatment, with the purpose to provide control of both systemic disease and disease of the CNS and contralateral testis. The potential benefit of contralateral testicular irradiation has to be taken into account in the treatment planning.

Factors associated with progression to AIDS and mortality in a cohort of HIV-infected patients with hemophilia followed up since seroconversion.

Progression to AIDS and death were evaluated in 112 patients, 84 with hemophilia A and 28 with hemophilia B. Seroconversion period and age at seroconversion were similar in both groups. 36/112 patients died: 21/84 with hemophilia A (25%) and 15/28 (54%) with hemophilia B. Mean survival time was 11.7 years. The 10-year cumulative survival was 75.8%. It was lower in hemophilia B (56.2%) compared to hemophilia A patients (82.4%; p = 0.002). 37 patients (33%) developed full-blown AIDS: 26 with hemophilia A (31%) and 11 with hemophilia B (39%). Mean AIDS-free survival time was 11.4 years. The 10-year cumulative AIDS-free survival was 71.2%. It was 74.8% in hemophilia A and 60.3% in hemophilia B patients. CD4 counts lower than 200/cmm occurred in 62 patients (56%): 45 with hemophilia A (54%) and 17 with hemophilia B (63%). The mean time to CD4 counts lower than 200 was 9.4 years. Mean survival time in older seroconverters (35 year old or more) was shorter than in younger (9.5 vs. 11.7 years, p < 0.05). Mean CD4 cell counts at seroconversion were similar in hemophilia A and B patients and in different age classes at seroconversion. CD4 cell counts at seroconversion affected the survival: 90% seroconverters with CD4 cell counts of 800/cmm or more were alive at 10 years vs. 60% of seroconverters with CD4 cell counts lower than 800 (p < 0.05).

Anti-alpha interferon immunization: safety and immunogenicity in asymptomatic HIV positive patients at high risk of disease progression.

A randomized, placebo-controlled trial was designed to evaluate safety and immunogenicity of an anti-cytokine vaccine in high risk HIV-positive patients. This strategy was aimed to modulate the impaired cytokine regulation in AIDS. Twelve asymptomatic patients on antiretroviral therapy for at least 1 year and with CD4 cell counts between 100-300/mm3 were randomized to receive adjuvanted formol-inactivated interferon alpha-2a (IFN alpha) and continue the current antiretroviral treatment, whatever it was, or to receive the adjuvant alone and the current antiretroviral treatment. All patients received 4 i.m. injections monthly, followed by booster injections every 3 months. Clinical status, immunology and virology were monitored. Immune response to vaccination was evaluated in term of antibody detection (ELISA) and serum anti-IFN alpha neutralizing capacity. Only local discomfort and transient fever were reported. All vaccines except one showed increased levels of anti-IFN alpha Abs and developed serum IFN alpha neutralizing capacity. Viral load did not increase in vaccinees while it remained unchanged or even increased in placebo-treated patients. None of them showed HIV-related symptoms and all had their CD4 cell counts stabilized over 18 months, whereas 2 placebo-treated patients developed full-blow AIDS. In conclusion, anti-IFN alpha vaccine was safe and immunogenic. Stable clinical and immunological status over 18 months was observed in vaccinees coupled to increased serum IFN alpha neutralizing capacity.

[Influence of various gastrointestinal disorders and dysproteinemia on the determination of blood digitalis by means of radioimmunoassay]. / Influenze di alcune turbe dell'apparato gastro - enterico e della disprotidemia sulla determinazione della digitalemia mediante dosaggio radio-immunologico.

Radioimmunologically determined digoxin and beta methyl digoxin values were the same in cardiopaths with and without clinical and instrumental changes referable to chronic cirrhosis or hepatitis. Lower values, however, were noted when gastroenteric disturbances were present. This was especially true of beta methyl digoxin in subjects with hyperkinetic-hyperchlorhydric syndromes due to depressed gastric pH, with a consequent inhibition of beta methyl digoxin absorption, presumably caused by lability of the molecule as a result of methylation of the terminal digitoxose group.