Mixed lymphocyte reactivity and cell-mediated lympholysis to trinitrophenyl-modified autologous lymphocytes in C57BL/10 congenic and B10.A recombinant mouse strains

Cell-mediated lympholysis (CML) to trinitrophenyl (TNP)-modified autologous splenic lymphocytes has been recently reported in the mouse (1). Both the sensitization and effector phases of this phenomenon were shown to be T-cell mediated. Effector cell specificity studies indicated that modification of the target cells is a necessary but insufficient requirement for cytolysis, and suggested that altered cell surface components controlled by genes mapping in the mouse major histocompatibility H-2 complex (MHC) are important in the specificity of the cytotoxic reaction (1). In allogeneic models the generation of cytotoxic effector cells has been shown to be preceded or accompanied by immunogen- induced proliferation of responding lymphocytes, i.e. a mixed lymphocyte reaction (MLR) (2-5), although the generation of effectors may not necessarily always be the consequence of extensive cell proliferation (5). If the induction of cytotoxic effector lymphocytes by modified syngeneic spleen cells is characteristic of sensitization with cellular alloantigens, one would expect to find that sensitization with TNP-modified autologous cells would also induce thymidine incorporation by the responding cells in the culture. The present report demonstrates that both stimulation of thymidine incorporation and generation of cytotoxic effector cells are part of the in vitro response to TNP-modified autologous lymphocytes. However, the MLR to TNP- modified autologous cells consistently appeared to be less pronounced when compared with an allogeneic MLR, whereas the cytotoxic activity of the effector cells generated by sensitization against TNP-modified autologous cells was frequently as high as that detected against H-2 alloantigens. These two components of reactivity to “modified self” are verified in several C57BL/10 congenic and B10.A recombinant mouse strains.     

Large-volume leukapheresis in pediatric patients: processing more blood diminishes the apparent magnitude of intra-apheresis recruitment

Background: Recruitment of progenitors during a large-volume collection, as defined by increasing relative and absolute numbers of progenitors (colony-forming units-granulocyte-macrophage [CFU-GM] of CD34+ cells), has been reported previously. Study Design and Methods: To ascertain whether intra-apheresis recruitment occurs in pediatric patients who have undergone mobilization with chemotherapy and granulocyte-colony-stimulating factor (G-CSF), each hour's portion of a 4-hour leukapheresis was collected into separate bags, and assessed by complete blood count, CFU-GM, and CD34+ cell assays. Seven pediatric patients (median age, 7; range, 2–19) were studied in connection with 2 to 4 collections each, for a total of 21 collections (with hourly samples). The collections lasted for 4 hours, at an inlet rate of 1 to 3 mL per kg per minute, for daily processing totals of 5 to 12 blood volumes. (One blood volume [mL] is estimated by the patient's weight in kg × 70 mL/kg.) Smaller (younger) patients had inlet rates exceeding 2 mL per kg per minute, and larger (older) patients had rates of 1 to 1.5 mL per kg per minute. CFU-GM and CD34+ cell counts obtained each hour of the collection and divided by the first hour's value were compared by nonparametric repeated-measures ANOVA. Results: Second-, third- and fourth-hour CD34+ progenitor cell counts were arithmetically higher than first-hour counts, but the trend did not reach significance (p = 0.1561). Second-hour counts were higher than first-hour counts in the overall analysis (mean ± standard error [SE], 1.00 and 1.39 ± 0.1, respectively; p = 0.0525) and in children older than 5 years (1.00 vs. 1.70 ± 0.30, respectively; p = 0.0259), but not in children younger than 5 years (p = 0.8125). CFU-GM counts did not differ among the 4 hours of collection (p = 0.1717) or between the first and second hour (p = 0.9587). Conclusion: In larger (older) patients, from whom fewer blood volumes were collected, there is a trend toward intra-apheresis recruitment, although less than reported previously. In the smaller (younger) patients, from whom more blood volumes were collected, no trend was observed. Lack of (or submaximal) prior mobilization in previously reported studies may have facilitated intracollection recruitment. Alternatively, the larger number of blood volumes collected from the smaller (younger) patients may have masked intra-apheresis recruitment. The study documents the feasibility of large-volume, 4-hour leukapheresis in pediatric patients.     

Elevated static compliance of the total respiratory system: Early predictor of weaning unsuccess in severe COPD patients mechanically ventilated

Objective To assess in a group of COPD patients mechanically ventilated for an episode of acute respiratory failure the respiratory mechanics with a simple and non invasive method at the bedside in order to evaluate if these parameters may be predictive of weaning failure or success.Design A prospective study.Setting Intensive care and intermediate intensive care units.Patients 23 COPD patients ventilated for acute respiratory failure and studied within 24 hours from intubation.Methods Using end-expiratory and end-inspiratory airway occlusion technique, we measured PEEPi, static compliance of the respiratory system (Crs, st) maximum respiratory resistance (Rrsmax) and minimum respiratory resistance (Rrsmin).Measurements and results The weaned group (A) and the not weaned group (B) were not different regarding to static PEEPi (group A 8.5±4.0 vs group B 8.9±2.6 cmH₂O), to Rrsmax (22.4±5.3 versus 22.2±9.0 cmH₂O/l/s) and to Rrsmin (17.6±5.5 versus 17.9±8.0 cmH₂O/l/s), while a significant difference (p<0.001) has been found in Cst, rs (62.7±17.5 versus 111.6±18.0 ml/cm H₂O). The threshold value of 88.5 ml/cmH₂O was identified by discriminant analysis and provided the best separation between the two groups, with a sensitivity of 0.85 and a specificity of 0.87.Conclusion Cst, rs measured non invasively in the first 24 h from intubation, provided a good separation between the patients who were successfully weaned and those who failed.     

Changes in the practice of non-invasive ventilation in treating COPD patients over 8 years

OBJECTIVE: We reviewed data of 208 episodes of acute respiratory failure due to chronic obstructive pulmonary disease treated by non-invasive ventilation (NIV) in our Respiratory Intensive Care Unit (RICU) from its opening in 1992 to 1999. MATERIAL AND METHODS: We assessed whether the rate of NIV success, the severity of the disease, and the associated costs changed in this period during which the staff and the equipment did not change. RESULTS: The failure rate was constant over the years (17.2% on average). The severity of the episodes of ARF, defined by pH and APACHE II at admission, worsened during the years. The statistical change point test allowed us to identify 1997 as the year of a significant change in the severity of admission pH and therefore to identify two different periods: 1992-1996 (mean pH = 7.25+/-0.07) and 1997-1999 (7.20+/-0.08; P<0.001). In this latter period the risk of failure for a patient with a pH <7.25 was threefold lower than in 1992-1996. In 1997-1999 an increasing number of episodes of ARF with a pH >7.28 were treated in the Medical Ward (20% vs 60%). This allowed a significant reduction of daily cost per patient treated with NIV (558+/-8 Euros vs 470+/-14 Euros, respectively; P<0.01). CONCLUSIONS: We conclude that, over time, experience with NIV may progressively allow more severely ill patients to be treated without changing the rate of success. The daily cost of NIV per patient can be reduced by treating less severely ill patients outside the RICU.     

Severity of neuropsychiatric symptoms and dopamine transporter levels in dementia with Lewy bodies: A 123I‐FP‐CIT SPECT study

Neuropsychiatric symptoms are frequent in dementia with Lewy bodies (DLB). Dopamine transporter (DAT) imaging with ¹²³I‐labeled ligand N‐δ‐(fluoropropyl)‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)tropene (¹²³I‐FP‐CIT), which reliably measures midbrain dopaminergic dysfunction, has provided important evidence on the neurobiological substrate of some of these symptoms including apathy and depression. However, little is known on DAT levels and other distressing symptoms such as delusions and hallucinations. Therefore, ¹²³I‐FP‐CIT imaging was performed in 18 well‐characterized patients with DLB, and striatal DAT levels were correlated with the frequency/severity ratings of several neuropsychiatric symptoms. A wide range of neuropsychiatric symptoms could be observed in the sample. Significant correlations were observed between decreased striatal DAT levels and visual hallucinations. Although there were no correlations between striatal DAT levels and other neuropsychiatric symptoms, when considering the putamen and the caudate nucleus separately, delusions, depression, and apathy were inversely correlated to decreased caudate DAT levels. Theseresults provide intriguing evidence on the involvement of the mesocortical dopaminergic pathways in neuropsychiatric symptoms in DLB. © 2009 Movement Disorder Society     

Systemic administration of doxorubicin impairs aversively motivated memory in rats

There is growing clinical evidence of cognitive impairment in cancer patients treated with chemotherapy, especially in women treated with drug combinations for breast cancer. Clinical studies have a difficult task of defining which drugs individually are responsible for the cognitive changes and published papers evaluating single agents in experimental models are scanty. In the present study we have investigated the effect of single escalating doses of doxorubicin (DOX) on memory for inhibitory avoidance conditioning (IA) in rats. The doses used were comparable to those applied in the clinic. When given systemically before training, higher doses of DOX impaired IA memory retention measured 24 h and 7 days, but not 3 h after training. DOX did not affect IA retention when given either before or after training in a multiple-trial IA training protocol. Control experiments showed that DOX produced a decrease in exploratory behavior assessed by the number of rearings performed during exploration of an open field. The results indicate that a single systemic administration of DOX might impair long-term aversive learning.     

Acute pulmonary embolism: comparison and integration of perfusion lung scintigraphy with multislice spiral CT

PURPOSE: This study compared and integrated the data from perfusion lung scintigraphy and multislice computed tomography (CT) for the emergency diagnosis of acute pulmonary embolism in nuclear medicine and radiology departments operating around the clock. MATERIALS AND METHODS: One hundred and seven patients with a clinical and laboratory suspicion of acute pulmonary embolism who had already undergone chest radiography were divided into four groups according to the time interval between onset of clinical suspicion and performance of the two diagnostic examinations (0-24 h, 24-48 h, 0-48 h, 2-7 days). Cohen's test for the analysis of statistical concordance was used. RESULTS: Perfusion lung scintigraphy and multislice CT were positive in 29/107 (27.1%) and negative in 78/107 (72.89%). Positive concordance (PC) was found in 22 cases and negative concordance (NC) in 71 cases: 0-24 h: PC in 12, NC in 32 cases; 24-48 h: PC in 3, NC in 15 cases; 0-48 h: PC in 15, NC in 47 cases; 2-7 days: PC in 7, NC in 24 cases. CONCLUSIONS: Perfusion lung scintigraphy and multislice CT demonstrated elevated concordance if performed within 7 days of the onset of suspicion of acute pulmonary embolism. Concordance was higher if the examinations were completed within 24-48 h. In suspected acute pulmonary embolism, it is mandatory to reach a correct diagnosis within few hours--48 at the most.