Repeated stimulation of CD4 effector T cells can limit their protective function

Chronic infections often result in CD8 T-cell deletion or functional nonresponsiveness. However, to date no definitive studies have attempted to determine the impact of repeated T cell receptor stimulation on CD4 effector T cell generation. We have determined that when antigen presentation is limited to 2 d, optimum in vitro CD4 effector generation is achieved. Alternatively, repeated stimulation results in decreased CD4 effector expansion, decreased cytokine production, and altered migration. Similarly, functionally impaired effectors develop in vivo when antigen-pulsed antigen-presenting cells are replenished every 24 h during a primary immune response. CD4 effectors that are generated with repeated stimulation provide no protection during influenza infection, and have an impaired ability to provide cognate help to B cells. These results suggest that duration of antigen presentation dictates CD4 effector function, and repeated T cell receptor stimulation in vitro and in vivo that exceeds an optimal threshold results in effectors with impaired function.     

Comparison of opioid agonists in maintaining responding and in suppressing morphine withdrawal in rhesus monkeys

Sixteen opioid agonists were studied for their capacity both to maintain responding previously reinforced by codeine and to suppress the withdrawal syndrome induced by morphine deprivation in rhesus monkeys. All compounds, which included examples from each of the major chemical families of opioids, maintained responding at rates above those maintained by saline. There were differences among the compounds in the maximal response rates maintained, and large differences in their potencies in maintaining responding. In morphine-dependent monkeys, the abstinence signs that developed 14 h after the last morphine dose were suppressed completely by all of the compounds except codeine. There was a strong positive correlation (r=0.92) between the potency of a compound in maintaining drug-reinforced responding and the potency of the compound in suppressing the morphine withdrawal syndrome.     

Efficacy of cognitive-behavioral intervention for juvenile primary fibromyalgia syndrome

OBJECTIVE: There are currently no controlled studies of behavioral interventions for juvenile primary fibromyalgia syndrome (JPFM). In this small-sample randomized study, we tested the efficacy of a behavioral intervention, i.e., coping skills training (CST), for the treatment of adolescents with JPFM. Outcomes tested in this study were functional disability, pain intensity, pain-coping efficacy, and depressive symptoms. METHODS: Thirty patients with JPFM were randomly assigned to 8 weeks of either CST or self-monitoring. Adolescents in the CST condition received training in active pain-coping techniques, while those in the self-monitoring condition monitored daily pain intensity and sleep quality with no instructions about behavior change. After posttreatment assessment, subjects were crossed over into the opposite treatment arm for 8 weeks (so that all adolescents eventually received both CST and self-monitoring) and were reassessed at Week 16. RESULTS: At Week 8, adolescents in both conditions showed significant decrease in depressive symptoms and functional disability. Those who received CST showed significantly greater ability to cope with pain than those in the self-monitoring condition and a trend toward decreased pain intensity. At Week 16, adolescents had significantly lower levels of disability and depressive symptoms compared to baseline, but those who received self-monitoring followed by CST seemed to receive the most benefit. CONCLUSION: CST can lead to improved functioning among JPFM patients. Although some of the improvement may be due to increased monitoring and attention, CST provides the specific benefit of improving adolescents' ability to cope with pain.     

Neither neutrophils nor reactive oxygen species contribute to tissue damage during Pneumocystis pneumonia in mice

Neutrophils are implicated in the damage of lung tissue in many disease states, including infectious diseases and environmental insults. These effects may be due to oxidative or nonoxidative functions of the neutrophil or both. We examined the role of neutrophils in pulmonary damage during infection with the opportunistic fungal pathogen Pneumocystis sp. in four mouse models of neutrophil dysfunction. These were (i) a knockout of the gp91(phox) component of NADPH oxidase, in which reactive oxygen species (ROS) production is greatly reduced; (ii) a double knockout of gp91(phox) and inducible nitric oxide synthase, in which ROS and nitric oxide production is greatly decreased; (iii) a knockout of the chemokine receptor CXCR2, in which accumulation of intra-alveolar neutrophils is severely diminished; and (iv) antibody depletion of circulating neutrophils in wild-type mice with the monoclonal antibody RB6. Surprisingly, in each case, indicators of pulmonary damage (respiratory rates, arterial oxygen partial pressures, and intra-alveolar albumin concentrations) were the same in knockout mice and comparable wild-type mice. Therefore, whereas neutrophils are a valid correlative marker of lung damage during Pneumocystis infection, neither neutrophils nor ROS appear to be the causative agent of tissue damage. We also show that there is no difference in Pneumocystis burdens between wild-type and knockout mice, which supports the idea that neutrophils do not have a major role in the clearance of this organism.     

Three Hundred Sixty Degree Feedback: program implementation in a local health department.

Three Hundred Sixty Degree Feedback systems, while popular in business, have been less commonly implemented in local public health agencies. At the same time, they are effective methods of improving employee morale, work performance, organizational culture, and attainment of desired organizational outcomes. These systems can be purchased "off-the-shelf," or custom applications can be developed for a better fit with unique organizational needs. We describe the City of Milwaukee Health Department's successful experience customizing and implementing a 360-degree feedback system in the context of its ongoing total quality improvement efforts.     

Management of infected aortic prosthetic grafts

The management of infected prosthetic grafts is one of the most challenging problems facing vascular surgeons. High mortality and morbidity rates with traditional treatment have led many surgeons to consider different and novel strategies. Diagnosis is usually straightforward, but occasionally is unclear even after extensive clinical and radiologic investigations. Although routine total graft excision for all infected aortic grafts is still favored by some vascular surgeons, most favor only partial graft excision if only the distal limb of the graft is involved. Placement of in situ autologous vein or cryopreserved grafts have gained popularity, and investigations are continuing regarding the use of in situ antibiotic and silver-coated prosthetic grafts. In this article the authors review the incidence and etiology of aortic graft infections, methods to prevent these complications, the diagnosis of infected aortic grafts, and lastly the management of these complicated cases, including total graft excision and partial and complete graft preservation.     

Uterine contraction frequency before and after successful tocolytic therapy for preterm uterine contractions

OBJECTIVE: To examine the association between prelabor uterine contraction frequency (UCF) and the success of tocolytic therapy for preterm labor (PTL). STUDY DESIGN: Eleven centers conducted a prospective, observational study of UCF recorded between 22(0/7) and 36(6/7) weeks' gestational age or until delivery > or = 2 times/d on > or = 2 d/wk in women with singleton pregnancies with and without risk factors for preterm birth. Uterine contraction data obtained from patients diagnosed with PTL allowed comparison of mean UCF both before and after an acute episode of PTL treated with either intravenous, subcutaneous or oral tocolysis. The signed rank test was used to analyze differences in UCF before and after tocolytic therapy and between women who were or were not successfully treated with a labor-inhibiting agent. RESULTS: Of 454 enrolled women, 128 were diagnosed with PTL, and 74 were successfully treated with a labor-inhibiting agent. The mean UCF preceding PTL was not different between those women successfully treated and those who delivered as a consequence of the PTL episode. There was no difference (P = .653) in mean UCF between the week before PTL (UCF 0.60 +/- 0.8, median 0.30) and the first week of monitoring after successful tocolysis (UCF 0.82 +/- 1.4, median 0.27). CONCLUSION: The mean UCF immediately preceding PTL does not predict tocolytic success or failure.