High incidence of meningeal leukemia in lymphoid blast crisis of chronic myelogenous leukemia

Fifteen patients with lymphoid blast crisis of chronic myelogenous leukemia (LyBC-CML) and five patients with acute lymphoblastic leukemia converting to Philadelphia-positive (Ph+) chronic myeloid leukemia (ALL Ph + CML) were followed. Seven of 15 (46.7%) LyBC-CML patients developed meningeal leukemia within a median period of 6 months (range 2–11 months), while there was no medullary relapse. Five of these responded well to triple intrathecal therapy. In the ALL Ph + CML patients, in spite of central nervous system (CNS) prophylaxis with IT MTX and 18 Gy cranial radiation, two of five patients (40%) experienced meningeal leukemia, one isolated and the other with medullary relapse. The data confirm that LyBC-CML patients experience a high incidence of meningeal leukemia. The role of CNS prophylaxis is not very clear, but its use may delay development and reduce morbidity due to CNS disease.     

Continuous real time endotracheal tube cuff pressure waveform

Endotracheal tube cuff pressure monitoring is one of the standard degrees of care afforded to anesthetized patients in the operative theater. Traditional pressure transducer when used to monitor cuff pressure provides real time continuous sine wave pressure waveform which has not been described in literature so far. This unique waveform needs to be further processed and evaluated to check its utility in airway pressure monitoring.     

Base excision DNA repair levels in mitochondrial lysates of Alzheimer's disease

Alzheimer's disease (AD) is a senile dementia with increased incidence in older subjects (age >65 years). One of the earliest markers of AD is oxidative DNA damage. Recently, it has been reported that preclinical AD patient brains show elevated levels of oxidative damage in both nuclear and mitochondrial nucleic acids. Moreover, different oxidative lesions in mitochondrial DNA are between 5- and 10-fold higher than in nuclear DNA in both control and AD postmortem brains. We previously showed that there is a significant loss of base excision repair (BER) components in whole tissue extracts of AD and mild cognitive impairment subjects relative to matched control subjects. However, comprehensive analysis of specific steps in BER levels in mitochondrial extracts of AD patient brains is not available. In this study, we mainly investigated various components of BER in mitochondrial extracts of AD and matched control postmortem brain samples. We found that the 5-hydroxyuracil incision and ligase activities are significantly lower in AD brains, whereas the uracil incision, abasic site cleavage, and deoxyribonucleotide triphosphate incorporation activities are normal in these samples.     

Anti-HBs Titers Following Pentavalent Immunization (DTwP-HBV-Hib) in Term Normal Weight <Emphasis Type="Italic">vs</Emphasis> Low Birthweight Infants

Objective

To compare anti-HBs titers between term low birth weight (1800-2499 g) infants and normal birthweight infants, 6 weeks after last dose of primary immunization with pentavalent vaccine, and to study adverse events following immunization (AEFI) with pentavalent vaccine.

Design

Cohort study.

Setting

Tertiary-care hospital predominantly catering to urban poor population of East Delhi.

Participants

265 low birthweight (1800-2499 g) and 265 normal birthweight (2500-4000 g) infants. Monovalent Hepatitis B vaccine was administered within 24 hours of birth followed by three primary doses of pentavalent vaccine at 6, 10 and 14 weeks. Anti-HBs titers were estimated after 6 weeks of third dose of pentavalent vaccine. Adverse events following immunization (AEFI) month were observed for a month after each dose of pentavalent vaccine.

Main outcome measures

Anti HBs antibody titers after 6 weeks of primary immunization, and AEFI.

Result

443 (83.5%) infants (225 low birthweight and 218 normal birthweight infants) completed the follow-up. Seroprotection against hepatitis B virus was achieved in both groups after pentavalent vaccine administration. Anti HBs GMTs in low birthweight infants (194.8 mIU/mL) and normal birthweight infants (204.2 mIU/mL) were comparable (P = 0.17). No serious adverse events were observed in either group.

Conclusion

Three primary doses of pentavalent vaccine administered along with zero dose of Hepatitis B vaccine at birth provide good seroprotection. The vaccine appears to be safe in both low birth weight and normal birthweight infants born at term.

     

Identification of heat shock protein 90 inhibitors to sensitize drug resistant side population tumor cells using a cell based assay platform

Current cancer therapeutics are identified based on initial tumor regression screens that mostly kill differentiated tumor cells, sparing the rare cancer stem cells (CSCs). Being rare and difficult to characterize, it remains a challenge to identify compounds active against them. Side population (SP) cells identified in multiple cancer cell line panels expressing mitochondrial Cytochrome C-EGFP were evaluated for identifying possible drug candidates utilizing high-throughput imaging. We identified heat shock protein 90 inhibitors as potential agents to sensitize SP cells to anticancer drugs. Hsp90 inhibitors induced down regulation of Akt leading to proteasomal degradation of survivin and consequent mitochondrial apoptosis. A successful screening platform for identifying compounds targeting drug resistant side population cells was developed.     

Desmoplastic small round cell tumor: extra abdominal and abdominal presentations and the results of treatment

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare malignant neoplasm of adolescent males. Current multimodality treatment prolongs life and rarely achieves cure. AIM: To review the presenting features, histopathology and outcome of 18 patients with DSRCT treated at a single institution. SETTING AND DESIGN: This is a retrospective observational study of patients with DSRCT who presented at the Tata Memorial Hospital between January 1994 to January 2005. MATERIALS AND METHODS: Eighteen patients of DSRCT seen during this period were evaluated for their clinical presentation, response to chemotherapy and other multimodality treatment and overall survival. The cohort of 18 patients included 11 males (61%) and 7 females (39%) with a mean age of 16 years (Range 1(1/2)--30 years). Majority (83%) presented with abdomino-pelvic disease. The others, involving chest wall and extremities. There were 6 patients (33%) with metastatic disease at presentation. RESULTS: The treatment primarily included a multimodality approach using a combination of multiagent chemotherapy with adjuvant surgery and radiotherapy as applicable. A response rate of 39% (CR-1, PR-6), with chemotherapy was observed. The overall response rate after multimodality treatment was 39% (CR-5, PR-2). The overall survival was poor except in patients who had complete excision of the tumor. Conclusion:0 Abdomino-pelvic site was the commonest presentation, the disease can occur at other non-serosal surfaces also. Despite aggressive treatment the outcome was poor. However, complete surgical excision seems to provide a better survival.     

Immune-mediated thrombocytopenia following dactinomycin therapy in a child with alveolar rhabdomyosarcoma: the unresolved issues

The authors report a case of severe dactinomycin-induced thrombocytopenia in a child with alveolar rhabdomyosarcoma. The phenomenon is consistent with an immune process leading to the formation of platelet-specific antibodies. This study shows that this can be induced even with the first dose of actinomycin, and its persistence is unpredictably prolonged and does not correlate linearly in an inverted fashion with the platelet count. It will be important to identify the subsets of patients who can develop this phenomenon by molecular techniques and to define the exact mechanism in vitro leading to formation of these antibodies. This would facilitate profiling the therapy, preventing the need for multiple platelet transfusions with their obvious hazards.     

The pattern of expression of Mn and Cu-Zn superoxide dismutase varies among squamous cell cancers of the lung,larynx, and oral cavity

BACKGROUND: Despite the importance of reactive oxygen species (ROS) in the development of smoking-related cancers, little is known about the pattern of expression of ROS scavengers in these cancers. METHODS: In this present study, we examined the expression of manganese superoxide dismutase (Mn-SOD) and copper/zinc superoxide dismutase (Cu-Zn-SOD), which are essential enzymes that eliminate ROS, in squamous cell cancers (SCCs) of the lung (n = 12), larynx (n = 13), and oral cavity (n = 20). RESULTS: SCCs of larynx and oral cavity showed significantly enhanced immuhistochemical expression of Mn-SOD compared with the matched uninvolved epithelium. The higher expression of Mn-SOD was shown to be late and early events in the process of SCC development in the larynx and the oral cavity, respectively. The expression of Mn-SOD in SCCs of the lung was significantly lower compared with luminal cells of the uninvolved epithelium but not compared with basal cells or an average expression of SOD in basal and luminal cells. The expression of both Mn-SOD and cytoplasmic or nuclear Cu-Zn-SOD in bronchial epithelium adjacent to invasive cancer was significantly lower compared with its expression in the uninvolved bronchial epithelium away from cancer. This resulted in a significant difference in SOD expression between cancer and uninvolved bronchial epithelium away from cancer but not between cancer and uninvolved epithelium adjacent to cancer. CONCLUSIONS: There are significant differences in the expression of Mn-SOD and Cu-Zn-SOD among SCCs of the lung, larynx, and oral cavity. The results also suggest that variations in distance between cancer and uninvolved tissues evaluated could contribute to conflicting results of SOD expression.