An analysis of Korsakoff patients recall following varying types of distractor activity.

Ten alcoholic Korsakoff patients and ten alcoholic control subjects were given several short-term memory, distractor type tasks in which consonant trigrams (verbal) and random shapes (nonverbal) were employed as the to-be-retained materials. The Korsakoff patients demonstrated a severe verbal memory deficit when the retention interval was filled with verbal distractor activity, but their retention of the same verbal material was intact when a nonverbal distractor task was used. In contrast, the Korsakoff patients' retention of nonverbal material was impaired regardless of the nature of the distractor activity. In fact, their retention of nonverbal material was impaired even when an unfilled retention interval was used.     

Phase-II trial with vindesine for regression induction in patients with leukemias and hematosarcomas

Summary Vindesine (VDS) has been submitted to a phase-II trial, the results of which were assessed in terms of regression induction. VDS was given weekly IV in doses of 2 mg/m² on two consecutive days to 59 patients, 55 of whom were evaluable. A high proportion of complete (36%) and over 50% partial regressions were obtained in acute lymphoid leukemias (ALL) (overall response 63%) whatever the perceptible phase, in blastic crisis of chronic myeloid leukemia (55%), and some responses were recorded in lymphosarcoma (40%). No effect has so far been seen in acute myeloid leukemia or in Hodgkin's disease. Malignant neoplasms of the immunoblastic type seem to be particularly sensitive to VDS. Continuous 48 h IV infusion can induce a remission where an IV push administration of the same dose has failed. One remarkable characteristic of VDS is the apparent absence of cross-resistance with VCR: in acute leukemic forms, 55% of patients who failed to obtain remission induction after three weekly injections of VCR (used in combination chemotherapy) achieved a complete or partial remission with VDS. The toxicity was mainly neurologic (paralytic ileus, constipation, paresthesias, loss of reflexes) and hematologic (leukopenia and thrombopenia), and was not more significant than with the other agents: four patients died of infection or hemorrhage.     

Safety and efficacy of two different doses of capecitabine in the treatment of advanced breast cancer in older women.

PURPOSE: To evaluate the safety and efficacy of capecitabine in older women with advanced breast cancer. PATIENTS AND METHODS: Seventy-three eligible patients (median age, 73 years; range, 65 to 89 years) were enrolled. The first 30 patients received oral capecitabine 1,250 mg/m(2) twice daily on days 1 to 14 every 21 days. Due to the occurrence of two toxic deaths, capecitabine 1,000 mg/m(2) twice daily was given to the subsequent 43 patients. RESULTS: All patients were assessable for safety and efficacy. A total of 351 treatment cycles were administered (median, six per patient; range, one to eight cycles). Dose reductions due to toxicities were required in 30% of patients in the standard-dose group, but capecitabine was given without a dose reduction to 95% of patients in the low-dose group. Capecitabine demonstrated a favorable safety profile. The overall incidence of grade 3/4 toxicities was low: the most common events reported in /= 24 weeks. In the low-dose group, the response rate was 34.9% (95% CI, 21% to 50.9%). An additional 15 patients had prolonged stabilization. The median time to disease progression was 4 months in either group. CONCLUSION: This study shows that capecitabine is safe and effective in the elderly breast cancer patient. Based on the overall results, the capecitabine dose of 1,000 mg/m(2) twice daily merits consideration as "standard" for older patients who do not have severely impaired renal function.     

Pneumomediastinum and abdominal pain: which correlation?

The case of a female patient with abdominal pain, fever and dyspnea appeared abruptly, is reported. Two days previously the patient underwent endoscopic colic polypectomy. Preliminary abdominal and chest X-ray showed colic and tenual air-fluid levels, a modest amount of pneumomediastinum and soft tissue emphysema of the neck. The cause of the latter finding was referable to five sites of origin: the lung parenchyma, mediastinal airways, the esophagus, the neck and the abdominal cavity. For symptom worsening thoracoabdominal CT was performed. It confirmed the pneumomediastinum and soft tissue emphysema of the neck and presence of intra and retroperitoneal free air as for perforation. Colonoscopy is a routine procedure in the diagnosis and therapy of colonopathies, but colic iatrogenic perforation is a dangerous complication not to be underestimated.     

Is the gefitinib plus trastuzumab combination feasible in breast cancer patients?

We have previously demonstrated that combined treatment of breastcancer cells that co-express epidermal growth factor receptor(EGFR) and ErbB-2 with the EGFR tyrosine kinase inhibitor (TKI)gefitinib plus trastuzumab results in a synergistic antitumoreffect [1]. Similar findings have been obtained by independentresearch groups [2]. Following these results,     

The role of ultrasound of sentinel nodes in the pre- and post-operative evaluation of stage I melanoma patients

We have investigated the role of high-resolution ultrasound (US) in the analysis of sentinel node(s) in melanoma patients in pre-operative staging and follow-up. One hundred and six lymph node basins in 88 melanoma patients undergoing sentinel node biopsy (SNB) were examined: 25 (23.6%) were US positive for metastases and 81 (76.4%) were negative. Subsequent histological analysis of the 81 negative lymph nodes confirmed the absence of metastases in 80 cases (98.8%), whereas, in the 25 US-positive lymph nodes, metastases were found in 16 cases (64%). The follow-up of all patients submitted to SNB in our unit included a US investigation of operated and contralateral nodal basins every 4 months for the first 3 years and then every 6 months. Of a total of 300 patients, four (1.6%) were found to have locoregional nodal disease during follow-up. In three of these four patients, US was crucial in indicating the presence of nodal metastases, which would have gone undetected on physical examination. The result of this study (negative predictive value of 98.7%) introduces the possibility of selecting patients who may avoid an SNB procedure based on the results of pre-operative US examination.     

In vitro inhibition of promyelocytic leukemia/retinoic acid receptor-alpha (PML/RARalpha) expression and leukemogenic activity by DNA/LNA chimeric antisense oligos

Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by the chromosomal translocation t(15:17) that leads to the expression of promyelocytic leukemia/retinoic acid receptor-alpha (PML/ RARalpha) oncofusion protein. The block of differentiation at the promyelocytic stage of the blasts and their increased survival induced by PML/RARalpha are the principal biological features of the disease. Therapies based on pharmacological doses of retinoic acid (RA, 10(-6) M) are able to restore APL cell differentiation in most cases, but not to achieve complete hematological remission because retinoic acid resistance occurs in many patients. In order to elaborate alternative therapeutic approaches, we focused our attention on the use of antisense oligonucleotides as gene-specific drug directed to PML/RARalpha mRNA target. We used antisense molecules containing multiple locked nucleic acid (LNA) modifications. The LNAs are nucleotide analogues that are able to form duplexes with complementary DNA or RNA sequences with highly increased thermal stability and are resistant to 3'-exonuclease degradation in vitro. The DNA/LNA chimeric molecules were designed on the fusion sequence of PML and RARalpha genes to specifically target the oncofusion protein. Cell-free and in vitro experiments using U937-PR9-inducible cell line showed that DNA/LNA oligonucleotides were able to interfere with PML/RARalpha expression more efficiently than the corresponding unmodified DNA oligo. Moreover, the treatment of U937-PR9 cells with these chimeric antisense molecules was able to abrogate the block of differentiation induced by PML/RARalpha oncoprotein. These data suggest a possible application of oligonucleotides containing LNA in an antisense therapeutic strategy for APL.