Two cases of toxoplasmic encephalitis in patients with acute T-cell leukaemia and lymphoma

Two cases of opportunistic cerebral infections in HIV-negative cancer patients due to chemotherapy induced immunosuppression are reported. A 61-year-old patient with low grade lymphoma (immunocytoma as referred to the Kiel classification) developed stereotactical biopsy proven toxoplasmic encephalitis 6 months after initiation of fludarabine treatment. The lymphoma had been diagnosed 8 years earlier and had been treated with several different regimens. In the second case, a 55-year-old patient developed neurological symptoms while in complete remission from acute T-cell leukaemia. The patient had been treated with a multidrug chemotherapy regimen including radiotherapy of the brain and intrathecal chemotherapy. When toxoplasmic encephalitis was bioptically diagnosed the patient was on maintenance chemotherapy with methotrexate and mercaptopurine for 12 months. The patients' characteristics and outcome are reported and the potential pathogenesis is discussed.     

Risk factors for colonoscopic perforation: A population-based study of 80118 cases

AIM: To assess the incidence and risk factors associated with colonic perforation due to colonoscopy. METHODS: This was a retrospective cross-sectional study. Patients were retrospectively eligible for inclusion if they were 18 years and older and had an inpatient or outpatient colonoscopy procedure code in any facility within the Geisinger Health System during the period from January 1, 2002 to August 25, 2010. Data are presented as median and inter-quartile range, for continuous variables, and as frequency and percentage for categorical variables. Baseline comparisons across those with and without a perforation were made using the two-sample t -test and Pearson’s χ2 test, as appropriate.RESULTS: A total of 50 perforations were diagnosed out of 80118 colonoscopies, which corresponded to an incidence of 0.06% (95%CI: 0.05-0.08) or a rate of 6.2 per 10000 colonoscopies. All possible risk factors associated with colonic perforation with a P -value < 0.1 were checked for inclusion in a multivariable logbinomial regression model predicting 7-d colonic perforation. The final model resulted in the following risk factors which were significantly associated with risk of colonic perforation: age, gender, body mass index, albumin level, intensive care unit (ICU) patients, inpatient setting, and abdominal pain and Crohn’s disease as indications for colonoscopy. CONCLUSION: The cumulative 7 d incidence of colonic perforation in this cohort was 0.06%. Advanced age and female gender were significantly more likely to have perforation. Increasing albumin and BMI resulted in decreased risk of colonic perforation. Having a colonoscopy indication of abdominal pain or Crohn’s disease resulted in a higher risk of colonic perforation. Colonoscopies performed in inpatients and particularly the ICU setting had substantially greater odds of perforation. Biopsy and polypectomy did not increase the risk of perforation and only three perforations occurred with screening colonoscopy.     

Adiponectin promotes the migration of circulating angiogenic cells through p38-mediated induction of the CXCR4 receptor

Aims

Adiponectin (adipo) and exercise training (ET) contribute to the maintenance of a normal vascular tone by influencing vascular NO bioavailability and concentration and function of circulating angiogenic cells (CAC). The molecular mechanisms are only partially understood. Aim of the present study was to elucidate the effects of adipo on CAC migration and the underlying signaling pathways. Furthermore, the impact of ET on adiponectin-mediated CAC migration was investigated.

Methods and results

CACs were isolated from peripheral blood and exposed to different adipo concentrations. Adipo (5 μg/ml) enhanced the ability of CACs to migrate following an SDF-1 gradient by 345%. This was associated with a significant increase in CXCR4 expression on the surface of CACs as compared to control (10.1 ± 1.5 vs. 33.2 ± 4.5% CXCR4 positive cells, p < 0.05). Adiponectin-induced CAC migration and CXCR4-upregulation were mediated through adipo-receptor 1 (AdipoR1) and blocked by an inhibitor of PI3-kinase, p38MAP kinase and NFκb. Adipo-stimulated migration of CACs, CXCR4 expression and p38MAPK-activation is impaired in patients with coronary artery disease (CAD). ET over 4 weeks partially corrects adiponectin-stimulated CAC migration and CXCR4 expression in patients with CAD (n = 10). No change was observed in the control group (n = 10).

Conclusion

Adipo improves the migratory capacity of CACs in response to SDF1, partially through an upregulation of CXCR4. This is mediated through a pathway that involves binding of adipo to the AdipoR1 and subsequent PI3kinase/p38MAPK/ NFκb activation. In addition ET corrects the adiponectin responsiveness of CACs, and thereby might promote endogenous repair of damaged endothelium.     

Longevity for free? Increased reproduction with limited trade-offs in Drosophila melanogaster selected for increased life span

Selection for increased life span in Drosophila melanogaster has been shown to correlate with decreased early fecundity and increased fecundity later in life. This phenomenon has been ascribed to the existence of trade-offs in which limited resources can be invested in either somatic maintenance or reproduction. In our longevity selection lines, we did not find such a trade-off. Rather, we find that females have similar or higher fecundity throughout life compared to non-selected controls. To determine whether increased longevity affects responses in other traits, we looked at several stress resistance traits (chill coma recovery, heat knockdown, desiccation and starvation), geotactic behaviour, egg-to-adult viability, body size, developmental time as well as metabolic rate. Longevity selected flies were more starvation resistant. However, in females longevity and fecundity were not negatively correlated with the other traits assayed. Males from longevity selected lines were slower at recovering from a chill induced coma and resting metabolic rate increased with age, but did not correlate with life span.     

Laboratory selection for increased longevity in Drosophila melanogaster reduces field performance

Drosophila melanogaster is frequently used in ageing studies to elucidate which mechanisms determine the onset and progress of senescence. Lines selected for increased longevity have often been shown to perform as well as or superior to control lines in life history, stress resistance and behavioural traits when tested in the laboratory. Functional senescence in longevity selected lines has also been shown to occur at a slower rate. However, it is known that performance in a controlled laboratory setting is not necessarily representative of performance in nature. In this study the effect of ageing, environmental temperature and longevity selection on performance in the field was tested. Flies from longevity selected and control lines of different ages (2, 5, 10 and 15 days) were released in an environment free of natural food sources. Control flies were tested at low, intermediate and high temperatures, while longevity selected flies were tested at the intermediate temperature only. The ability of flies to locate and reach a food source was tested. Flies of intermediate age were generally better at locating resources than both younger and older flies, where hot and cold environments accelerate the senescent decline in performance. Control lines were better able to locate a resource compared to longevity selected lines of the same age, suggesting that longevity comes at a cost in early life field fitness, supporting the antagonistic pleiotropy theory of ageing.     

Neuropsychological Functioning of Opiate-Dependent Patients: A Nonrandomized Comparison of Patients Preferring either Buprenorphine or Methadone Maintenance Treatment

Objectives: In the present study, we investigated whether buprenorphine as a partial μ -opioid receptor agonist is associated with less cognitive impairment than methadone. Methods: Neuropsychological functioning of opioid-dependent patients, previously assigned to methadone (MMP, n = 30) or buprenorphine (BMP, n = 26) maintenance treatment according to their own preference, was compared and dose effects were investigated. Results: MMP and BMP performed equally well on all measures of neuropsychological functioning including the trail making test, the continuous performance test, and a vigilance task. However, patients receiving a higher dose of methadone were impaired in a vigilance task. Conclusions: In a free-choice administration of methadone or buprenorphine, there seems to be no difference in cognitive functioning. Possible explanations are discussed.     

Recording of Pacing Stimulus Artifacts by Endovascular Defibrillation Lead Systems: Comparison of True and Integrated Bipolar Circuits

Background: The occurrence ICD undersensing of ventricular fibrillation due to the presence of a pacing stimulus artifact (PSA) is in part related to the amplitude of the artifact recorded on the ICD rate sensing circuit. There is little comparative data regarding PSA amplitude recorded by commercial ICD rate-sensing circuits.Purpose: To compare PSA amplitude recorded by commercial endovascular defibrillation leads utilizing integrated or true bipolar sensing circuits.Methods: Nineteen large (60–120 kg) pigs were utilized. Two different commercial endovascular defibrillation leads were evaluated, each with its distal tip located at the right ventricular apex: (1) Medtronic Transvene; and (2) CPI Endotak. Three different rate-sensing circuits were evaluated: (1) Transvene true bipolar (tip-ring); (2) Transvene integrated bipolar (tip-coil); and (3) Endotak integrated bipolar (tip-coil). Using a separate pacing lead located at the left ventricular apex (n = 19 animals) or right ventricular outflow tract (n = 10 animals), pacing was performed at a pulse width of 0.5 milliseconds at outputs of 1.5, 5 and 10 volts. PSA amplitude was recorded at each output by each circuit.Results: During pacing from the left ventricular apex, at each pacing output voltage the PSA amplitude recorded by the true bipolar circuit (0.6 ± 0.1 mV at 1.5 volts, 2.0 ± 0.5 mV at 5 volts, 3.7 ± 0.8 mV at 10 volts) was significantly smaller than recorded by the Transvene integrated circuit (1.4 ± 0.3 mV at 1.5 volts, 3.8 ± 0.7 mV at 5 volts, 4.1 ± 0.8 mV at 10 volts) or the Endotak integrated circuit (1.8 ± 0.4 mV at 1.5 volts, 4.2 ± 1.0 mV at 5 volts, 6.3 ± 1.8 mV at 10 volts). During pacing from the right ventricular outflow tract, at each pacing output voltage the PSA amplitude recorded by the true bipolar circuit (0.7 ± 0.1 mV at 1.5 volts, 1.7 ± 0.4 mV at 5 volts, 4.0 ± 0.7 mV at 10 volts) was significantly smaller than recorded by the Transvene integrated circuit (1.1 ± 0.4 mV at 1.5 volts, 3.9 ± 1.2 mV at 5 volts, 7.5 ± 1.8 mV at 10 volts) or the Endotak integrated circuit (1.6 ± 0.7 mV at 1.5 volts, 4.3 ± 1.7 mV at 5 volts, 7.5 ± 2.6 mV at 10 volts). For both pacing sites, the PSA amplitude recorded by the two integrated circuits was not significantly different.Conclusions: For a given pacing output voltage, PSA amplitude recorded by commercial endovascular rate sensing/defibrillation leads is greater when the sensing circuit is integrated than when it is true bipolar. These data may be helpful in planning ICD implantation in patients with previously implanted permanent pacemakers.     

Flavopiridol Induces Apoptosis in Chronic Lymphocytic Leukemia Cells Via Activation of Caspase-3 Without Evidence of bcl-2 Modulation or Dependence on Functional p53

Flavopiridol has been reported to induce apoptosis in lymphoid celllines via downregulation of bcl-2. The in vitro activity offlavopiridol against human chronic lymphocytic leukemia (CLL) cells andpotential mechanisms of action for inducing cytotoxicity were studied.The in vitro viability of mononuclear cells from CLL patients (n = 11) was reduced by 50% at 4 hours, 24 hours, and 4 days at aflavopiridol concentration of 1.15 µmol/L (95% confidence interval[CI] ±0.31), 0.18 µmol/L (95% CI±0.04), and 0.16 µmol/L (95% CI ±0.04), respectively. Loss ofviability in human CLL cells correlated with early induction ofapoptosis. Exposure of CLL cells to 0.18 µmol/L of flavopiridolresulted in both decreased expression of p53 protein and cleavage ofthe caspase-3 zymogen 32-kD protein with the appearance of its 20-kD subunit. Contrasting observations of others in tumor cell lines, flavopiridol cytotoxicity in CLL cells did not correlate with changesin bcl-2 protein expression alterations. We evaluated flavopiridol'sdependence on intact p53 by exposing splenocytes from wild-type(p53^+/+) and p53 null (p53^/) micethat demonstrated no preferential cytotoxicity as compared with amarked differential with F-ara-a and radiation. Incubation of CLL cellswith antiapoptotic cytokine interleukin-4 (IL-4) did not alter theLC₅₀ of flavopiridol, as compared with a marked elevationnoted with F-ara-a in the majority of patients tested. These datademonstrate that flavopiridol has significant in vitro activity againsthuman CLL cells through activation of caspase-3, which appears to occurindependently of bcl-2 modulation, the presence of IL-4, or p53 status.Such findings strongly support the early introduction of flavopiridolinto clinical trials for patients with B-CLL.     

Early intensive care unit intervention for trauma care: what alters the outcome?

This review focuses on early management of multiple trauma patients with traumatic brain injury. Early usage of multislice computed tomography can substantially shorten the time spent on diagnostic workup in the emergency room and, therefore, speeds the initiation of lifesaving interventions for the control of hemorrhage. The important role of hemostatic angiographic embolization and its timing, in addition to surgical control of bleeding in patients suffering from pelvic fracture or organ lesions, is emphasized. The ongoing controversy regarding the strategy of fluid resuscitation is discussed. The concept of permissive hypotension seems to be promising but is absolutely contraindicated in patients with traumatic brain injury. Coagulation management should be guided by coagulation monitoring, including thromboelastography. A novel approach to reduce major bleeding is the application of recombinant factor VIIa. Strong effort should be directed toward the management of traumatic brain injury and the maintenance of cerebral perfusion pressure. The optimization of treatment of patients with multiple trauma, including brain injury, is a multidisciplinary task.     

Preparation of FFP as a by-product of plateletpheresis

BACKGROUND: To reduce the production costs of single-donor platelets (SDPs), a study was conducted to investigate whether plasma collected as a by-product of plateletpheresis satisfies the quality requirements for FFP without impairing the quality of the SDP component. STUDY DESIGN AND METHODS: Ninety-two donors with platelet (PLT) counts <270 x 10(9) per L underwent plateletpheresis using an automated cell separator (Spectra Apheresis System with the Leukoreduction System [LRS], Gambro BCT, Lakewood, CO). The machine was programmed to collect 3 x 10(11) PLTs in 250 mL of plasma with an additional unit of 350 mL of plasma or 3 x 10(11) PLTs in 250 mL of plasma without additional plasma in 10 procedures. FV and FVIII and residual RBCs, WBCs, and PLTs in the plasma were measured for quality control. RESULTS: FV was 0.87 +/- 0.18 IU per mL, and FVIII was 1.32 +/- 0.48 IU per mL in the plasma components (n = 41). The recovery was 94.1 +/- 5.5 percent for FV and 102.2 +/- 9.5 percent for FVIII when compared with the donors' predonation values. Residual cells were 0.002 +/- 0.009 x 10(9) RBCs per L (n = 30), 12 +/- 6 x 10(9) PLTs per L (n = 30), and 0.32 +/- 0.37 x 10(6) WBCs per L (n = 92). CONCLUSIONS: Using the automated cell separator and special software, it is possible to collect plasma as a by-product of plateletpheresis that meets the properties requested for FFP without impairing the quality of the SDP components. The content of clotting factors is within the requested range for FFP. Residual cell counts are within all European and U.S. specifications for FFP, and the WBC content even satisfies the criteria for WBC-reduced blood components. The collection of FFP as a by-product does not cause any additional costs and thus helps to reduce the costs in preparing blood components.