Lymphocyte responses after cytomegalovirus infection in bone marrow transplant recipients--a one-year follow-up

A group of 46 bone marrow transplant (BMT) recipients were studied by lymphocyte stimulation with cytomegalovirus (CMV) antigen before, and repeatedly in the first year after, BMT. Of these, 25 patients developed CMV infection and 68% of these got a positive lymphocyte response to CMV. The recipients with an early response (up to 3 months) to CMV antigen after the CMV infection were less prone to develop chronic graft-versus-host disease (GVHD) than those who responded later or not at all (P = 0.002). After the CMV infection, the increased lymphocyte CMV reactivity remained in recipients without chronic GVHD, but recipients with chronic GVHD usually lost their reactivity. The results suggest that it may be possible to predict patients who are not going to develop chronic GVHD by studying lymphocyte responses to CMV infections.     

Successful mobilization of Ph-negative blood stem cells with intensive chemotherapy + G-CSF in patients with chronic myelogenous leukemia in first chronic phase

The aim of the study was to investigate the feasibility of mobilizing Philadelphia chromosome negative (Ph-) blood stem cells (BSC) with intensive chemotherapy and lenograstim (G-CSF) in patients with CML in first chronic phase (CP1). During 1994-1999 12 centers included 37 patients <56 years. All patients received 6 months' IFN, stopping at median 36 (1-290) days prior to the mobilization chemotherapy. All received one cycle of daunorubicin 50 mg/m2 and 1 hour infusion on days 1-3, and cytarabine (ara-C) 200 mg/m2 24 hours' i.v. infusion on days 1-7 (DA) followed by G-CSF 526 microg s.c. once daily from day 8 after the start of chemotherapy. Leukaphereses were initiated when the number of CD 34+ cells was >5/microl blood. Patients mobilizing poorly could receive a 4-day cycle of chemotherapy with mitoxantrone 12 mg/m2/day and 1 hour i.v infusion, etoposide 100 mg/m2/day and 1 hour i.v. infusion and ara-C 1 g/m2/twice a day with 2 hours' i.v infusion (MEA) or a second DA, followed by G-CSF 526 microg s.c once daily from day 8 after the start of chemotherapy. Twenty-seven patients received one cycle of chemotherapy and G-CSF, whereas 10 were mobilized twice. Twenty-three patients (62%) were successfully (MNC >3.5 x 10(8)/kg, CFU-GM >1.0 x 10(4)/kg, CD34+ cells >2.0 x 10(6)/kg and no Ph+ cells in the apheresis product) [n = 16] or partially successfully (as defined above but 1-34% Ph+ cells in the apheresis product) [n = 7] mobilized. There was no mortality during the mobilization procedure. Twenty-one/23 patients subsequently underwent auto-SCT. The time with PMN <0.5 x 10(9)/l was 10 (range 7-49) and with platelets <20 x 10(9)/l was also 10 (2-173) days. There was no transplant related mortality. The estimated 5-year overall survival after auto-SCT was 68% (95% CI 47 - 90%), with a median follow-up time of 5.2 years.We conclude that in a significant proportion of patients with CML in CP 1, intensive chemotherapy combined with G-CSF mobilizes Ph- BSC sufficient for use in auto-SCT.     

Effects of maternal intravenous nicotine administration on locomotor behavior in pre-weanling rats

Maternal tobacco use is associated with adverse developmental outcomes in offspring, including hyperactivity. Animal studies attempting to model this phenomenon have primarily used continuous s.c. nicotine infusion as the method of nicotine administration, which does not model the intermittent bolus delivery of nicotine associated with smoking in humans. The purpose of the present experiment was to examine the locomotor activity of pre-weanling offspring of pregnant rats exposed to an i.v. nicotine dosing protocol that approximates the pattern of nicotine exposure in moderate to heavy smokers. Pregnant rats were administered an i.v. bolus of 0.03 mg/kg nicotine (N=13) or saline (N=10) every 14 min for 16 h/day, resulting in a total daily dose of 2 mg/kg (base), from gestational day 4 to delivery. Pups from each litter were tested for spontaneous locomotor activity on postnatal days (PND) 19-21 and nicotine-induced locomotor activity on PND 22. Mean birth weight was significantly lower in nicotine-exposed pups compared to controls, but body weights were equivalent between groups by the time of behavioral testing. Mean total distance traveled, vertical counts, and stereotypy counts were lower on PND 19 in nicotine-exposed pups compared to controls, but only the difference in mean stereotypy counts was statistically significant. Within-session analysis revealed that both distance traveled and stereotypy were significantly decreased in nicotine-exposed pups in the first 5 min of the session on PND 19. Total time spent in the center of the field was also lower in nicotine-exposed pups. Nicotine-induced increases in activity on PND 22 did not differ according to gestational exposure. These findings demonstrate that prenatal nicotine exposure in a model that mimics the pattern of nicotine exposure from cigarette smoking in humans results in offspring that exhibit low birth weight and hypoactivity in a novel environment.     

Comparison of genotoxic and inflammatory effects of particles generated by wood combustion, a road simulator and collected from street and subway

The health effects of exposure to airborne particles are of increasing concern in society. In order to protect public health, a clarification of the toxic properties of particles from different sources is of importance. The aim of this study was to investigate and compare the genotoxicity and the ability to induce inflammatory mediators of nine different particle types from wood and pellets combustion, from tire-road wear and collected from an urban street and a subway station. The comet assay was used to assess genotoxicity after exposure of the human lung cell line A549. Inflammatory effects were measured as induction of IL-6, IL-8 and TNF-alpha after exposure of human macrophages. We found that all particles tested caused DNA damage and those from the subway caused more damage than the other particles (p<0.001) likely due to redox-active iron. In contrast, particles collected from an urban street were most potent to induce inflammatory cytokines. Particles from tire-road wear collected using a road simulator were genotoxic and able to induce cytokines. Finally, more effective combustion of wood led to less emission of particles, but those emitted did not show less toxicity in this study.     

Effect of phenytoin on interleukin-1β production in human gingival fibroblasts challenged to tumor necrosis factor αin vitro

Effects and interaction of tumor necrosis factor α (TNFα) and the antiepileptic drug phenytoin (PHT) on interleukin-1β (IL-1β) production as well as on prostaglandin E₂ (PGE₂) formation were studied in gingival fibroblasts in vitro. TNFα, in contrast to PHT, dose-dependently stimulated the production of cell-associated IL-1β. The stimulatory effect of TNFα on IL-1β production was accompanied by enhanced PGE₂ formation. When PHT and TNFα were added simultaneously, the drug potentiated the stimulatory effect of TNFα on both IL-Iβ production and PGE₂ formation. The major PHT metabolite, p-HPPH, did not affect IL-1β production, either alone or in combination with TNFα. The production of IL-1β induced by TNFα and the combination of TNFα and PHT was further enhanced in the presence of the prostaglandin endoperoxide (PGH) synthase inhibitors, indomethacin and flurbiprofen. The PHT-mediated enhancement of TNFα-induced IL-1β production and PGE₂ formation in gingival fibroblasts may be an important link in the pathogenesis of gingival overgrowth induced by PHT.     

Cost-utility estimation of surgical treatment of pancreatic carcinoma aimed at cure

Background  

Little is reported on costs for radical tumor resections of pancreatic carcinoma in relationship to adjusted quality of life survival postoperatively. Therefore, the aim of the present study was to estimate the cost utility of surgical treatment aimed at cure.     

Systolic blood pressure increases in patients with atrial fibrillation regaining sinus rhythm after electrical cardioversion

Direct current (DC) cardioversion is used to convert persistent atrial fibrillation (AF) to sinus rhythm (SR), but there is limited knowledge about how blood pressure (BP) is affected by conversion to SR. We sought to evaluate how BP changed in AF patients who converted to SR, compared to patients still in AF. In this retrospective registry analysis, we included a total of 487 patients, treated with DC cardioversion for persistent AF. We obtained data regarding medical history, medication, BP, and electrocardiogram the day before and 7 days after cardioversion. Systolic BP increased by 9 (±16) mm Hg (P < 0.01) and diastolic BP decreased by 3 (±9) mm Hg (P < 0.01) after conversion to SR. In the group of patients with restored SR, there was a 40% increase in the proportion of patients with a hypertensive BP level (≥140/90 mm Hg) after DC cardioversion compared to before. Patients still in AF had no significant change in BP. Systolic BP increases and diastolic BP slightly decreases when persistent AF is converted to SR. The underlying mechanisms explaining these findings are not known, but may involve either hemodynamic changes that occur when SR is restored, an underestimation of systolic BP in AF, or a combination of both. Our findings suggest that an increased attention to BP levels after a successful cardioversion is warranted.