Cell-cycle characteristics - alterable determinants of remission duration in a study of 179 standard risk newly diagnosed patients with acute myeloid-leukemia

Prognostic factors were related to remission duration among 179 standard risk newly diagnosed acute myeloid leukemia (AML) patients who received identical induction and consolidation therapies. Following a bromodeoxyuridine infusion, labeling indices of bone marrow aspirate/biopsy, durations of S-phase and cell cycle (Tc) were determined. Patients with slowly cycling myeloblasts had longer remissions (Log rank p=0.03) than those with rapidly cycling myeloblasts. Multivariate analysis demonstrated that both WBC and Tc contributed to remission duration (p=0.01 and 0.005 respectively). Patients with slowly proliferating leukemias have longer remissions probably due to slower regrowth of leukemia between chemotherapy courses.     

Prognosis of penetrating trauma in elderly patients: a comparison with younger patients

BACKGROUND: It has previously been shown that elderly patients have a worse prognosis than their younger counterparts after sustaining blunt trauma. This is due in part to a higher incidence of comorbid conditions as well as less physiologic reserve in an elderly population sustaining largely blunt trauma. We compared the outcome after penetrating trauma in elderly patients to matched "younger" patients to determine whether they had a similarly poor prognosis. METHODS: Elderly patients (> or = 65 years) were identified from our trauma registry. Sex, mechanism of injury, and Abbreviated Injury Score/Injury Severity Score were determined from the registry. Patients presenting with traumatic arrest were excluded. The registry was then searched for patients aged 15 to 40 years with the same sex, mechanism of injury, and Abbreviated Injury Score in each region. A chart review was then performed to determine additional details of their hospital stay. The two groups were then compared using Student's t test and Fisher's exact chi2 test, as appropriate. RESULTS: Eighty-five elderly patients (OLD group) were admitted with penetrating trauma between 1983 and 1998. They were compared with 85 matched young patients (YOUNG group). Each group included 66 male and 19 female patients. In each group, gunshot wounds occurred in 45.9%, stab wounds in 52.9%, and shotgun wounds in 1.2% of patients. The average Injury Severity Score in each group was 5.5 +/- 5.6 (range, 1-29) and the regional Abbreviated Injury Scores were likewise equal in both groups. The OLD patients had an average hospital stay of 6.9 +/- 9.1 days compared with 4.3 +/- 5.7 days in the YOUNG patients (p < 0.05). Twenty-seven OLD patients spent 7.3 +/- 9.2 days in the intensive care unit compared with 19 YOUNG patients who stayed 3.4 +/- 3.2 days (p < .05). A total of 91 comorbidities were identified in 58 OLD patients compared with 18 in 15 YOUNG patients (p < .0001). Eighty-six invasive procedures were performed in the OLD group compared with 96 in the YOUNG group (p = not significant). Nineteen OLD patients (22.3%) and 15 YOUNG patients (17.6%) suffered one or more complications, including death (p = not significant). A total of 91% of surviving OLD patients were discharged to home compared with 100% of surviving YOUNG patients (p < .01). CONCLUSION: Elderly patients who sustain penetrating trauma have more comorbidities than their younger counterparts. This may account for their longer hospital stay and lesser ability to be discharged home. These patients do not have an increased complication rate and should continue to be managed aggressively.     

Impact of critical care reconfiguration and track-and-trigger outreach team intervention on outcomes of haematology patients requiring intensive care admission

Patients with haematological disorders have previously been considered to have poor outcomes following admission to intensive care units. Although a number of haematology centres from outside the UK have now demonstrated improved outcomes, the continuing perception of poor outcomes in this patient group continues to adversely affect their chances of being admitted to some intensive care units (ICUs). Over the past 10 years, there have been many advances within the disciplines of both haematology and intensive care medicine. This study was done to assess outcomes and the impact of an early warning scoring system (EWS) and early involvement of ICU outreach teams. One hundred five haematology patients (haematopoietic stem cell transplant (HSCT) or non-HSCT) had 114 admissions to ICU between April 2006 and August 2008 which coincided with hospital-wide implementation of EWS. The survival to ICU discharge was 56 (53%). Thirty-three (33%) patients were alive at 6 months giving a 1-year survival of 31%. Of the 39 HSCT patients, nine were post-autologous and 30 post-allogeneic transplant. The survival to ICU discharge was 22 (56%) with 14 (36%) patients alive at 6 months. One year survival was 36%. Prior to the introduction of EWS and critical care outreach team (2004), survival to ICU discharge was 44% which has increased to 53% (2006–2008). This is despite an increase in mechanical ventilation in 2006–2008 (50%) as compared to 2004 (32%).The improvement in ICU survivorship was even more prominent in HSCT patients (37% in 2004 versus 56% in 2006–2008). There was a trend towards decreasing Acute Physiology and Chronic Health Evaluation scores with time, suggesting appropriate patients being identified earlier and having timely escalation of their treatment.     

Cocaine-mediated Alteration in Tight Junction Protein Expression and Modulation of CCL2/CCR2 Axis Across the Blood-Brain Barrier: Implications for HIV-Dementia

One of the hallmark features underlying the pathogenesis of HIV encephalitis is the disruption of blood–brain barrier (BBB). Cocaine, often abused by HIV-infected patients, has been suggested to worsen the HIV-associated dementia (HAD) via unknown mechanisms. The objective of the present study was to explore the effects of cocaine on BBB permeability using human brain microvascular endothelial cells (HBMECs). Additionally, because the chemokine CCL2 and its receptor CCR2 play a crucial role in the recruitment of inflammatory cells into the central nervous system in HAD brains, we tested for the effect of cocaine in modulating the CCL2/CCR2 axis. Our findings suggest that exposure of HBMECs to cocaine correlated with the breakdown of ZO-1 tight junction protein and reorganization of the cytoskeleton resulting in stress fiber formation. Furthermore, cocaine also modulated upregulation of the CCL2/CCR2 axis in monocytes. These findings conform to the multifaceted effects of cocaine leading to accelerated progression of HIV-1 neuropathogenesis.