Resting respiratory tract dendritic cells preferentially stimulate T helper cell type 2 (Th2) responses and require obligatory cytokine signals for induction of Th1 immunity

Consistent with their role in host defense, mature dendritic cells (DCs) from central lymphoid organs preferentially prime for T helper cell type 1 (Th1)-polarized immunity. However, the "default" T helper response at mucosal surfaces demonstrates Th2 polarity, which is reflected in the cytokine profiles of activated T cells from mucosal lymph nodes. This study on rat respiratory tract DCs (RTDCs) provides an explanation for this paradox. We demonstrate that freshly isolated RTDCs are functionally immature as defined in vitro, being surface major histocompatibility complex (MHC) II lo, endocytosishi, and mixed lymphocyte reactionlo, and these cells produce mRNA encoding interleukin (IL)-10. After ovalbumin (OVA)-pulsing and adoptive transfer, freshly isolated RTDCs preferentially stimulated Th2-dependent OVA-specific immunoglobulin (Ig)G1 responses, and antigen-stimulated splenocytes from recipient animals produced IL-4 in vitro. However, preculture with granulocyte/macrophage colony stimulating factor increased their in vivo IgG priming capacity by 2-3 logs, inducing production of both Th1- and Th2-dependent IgG subclasses and high levels of IFN-gamma by antigen-stimulated splenocytes. Associated phenotypic changes included upregulation of surface MHC II and B7 expression and IL-12 p35 mRNA, and downregulation of endocytosis, MHC II processing- associated genes, and IL-10 mRNA expression. Full expression of IL-12 p40 required additional signals, such as tumor necrosis factor alpha or CD40 ligand. These results suggest that the observed Th2 polarity of the resting mucosal immune system may be an inherent property of the resident DC population, and furthermore that mobilization of Th1 immunity relies absolutely on the provision of appropriate microenvironmental costimuli.     

Assessment of the nutritional state of dialysis patients

Obstructive sleep apnea syndrome (OSAS) has been associated with a higher than normal cardiovascular morbidity and mortality. Some OSAS patients lack the sleep-related, nocturnal decrease, or "dip," in blood pressure which is seen in normal individuals. These subjects, called "non-dippers," may be at greater risk for cardiovascular problems. We studied 40 OSAS patients (including 3 women) and 6 control subjects, all identified by polysomnography, for nocturnal blood pressure "dipping." We performed a second nocturnal polysomnogram to determine their apnea and hypopnea indices, (A + H)I, and oxygen saturation levels at the beginning of the study and then initiated 48 hours of ambulatory blood pressure monitoring, with data points collected every 30 minutes. Controls, which included one hypertensive subject, were all dippers. Nineteen OSAS subjects (48% of OSAS individuals) were systolic non-dippers and only 9 of them (22.5%) were diastolic non-dippers. We considered the following clinical variables as potential predictors of non-dipping: age, body mass index, respiratory disturbance index, years of reported loud snoring by bed partners, lowest oxygen saturation during nocturnal sleep, and percentage of sleep time spent with oxygen saturation below 90%. Multiple regression analyses indicated respiratory disturbance index as the only significant variable for systolic (p = 0.04) and diastolic (p = 0.03) blood pressure non-dipping. When we forced the following two nonsignificant variables into the model, they showed a very meager impact: number of years with reported loud snoring (p = 0.4 and p = 0.5, respectively for systolic and diastolic blood pressure non-dipping) and age (p = 0.5 and p = 0.6). The calculated model explained only a low percentage of the variance with an r2 of 0.25 and 0.26 for systolic and diastolic blood pressure non-dipping, respectively. Analysis of hypertension/normotension and dipping/non-dipping failed to show a significant relationship in the studied population. Fifty percent of the normotensive OSAS subjects were non-dippers and 43% of the hypertensive OSAS subjects were also non-dippers. We found a relationship between increasing respiratory disturbance index and increasing average 24-hour systolic blood pressure only when OSAS subjects were non-dippers and hypertensive.     

Long-term T cell memory requires the surface expression of self-peptide/major histocompatibility complex molecules

How memory T cells are maintained in vivo is poorly understood. To address this problem, a male-specific peptide (H-Y) was identified and used to activate female anti-H-Y T cells in vitro. Anti-H-Y T cells survived in vivo for at least 70 days in the absence of antigen. This persistence was not because of the intrinsic ability of memory T cells to survive in vivo. Instead, the survival and function of adoptively transferred memory cells was found to require transporter of antigen protein 1-dependent expression of self-peptide/major histocompatibility complex class I molecules in recipient animals. Therefore, it appears that the level of T cell receptor engagement provided by transporter of antigen protein 1-dependent, self-peptide/major histocompatibility complexes is sufficient to maintain the long-term survival and functional phenotype of memory cells in the absence of persistent antigen. These data suggest that positive selection plays a role not only in T cell development but also in the maintenance of T cell memory.     

Operative videothoracoscopy in the surgical treatment of penetrating firearms wounds of the chest

We prospectively analyzed our experience with operative videothoracoscopy (OVT) performed in a field military hospital in cases of penetrating firearms wounds of the thorax (PFAWT) sustained in Chechnya. From February to April 1996, we treated 206 wounded patients, of whom 37 (18.0%) had sustained chest injuries. PFAWT were present in 23 soldiers, accounting for 62.2% of all chest injuries. Twelve injuries were confined to the thorax, eight patients had associated injuries, and three soldiers had thoracoabdominal injuries. Nineteen patients had pleural drainage performed during medical evacuation. The thoracic injuries were right-sided (17), involved bullets or shell splinters (23); were through and through (16), represented solitary wounds (19), and were associated with internal organ injuries (21). Fifteen patients had indications for OVT when they were delivered from the battle-field 1.5 to 22 hours after injury. All patients manifested signs of hemorrhagic shock and hemodynamic instability. Indications for OVT were ongoing intrapleural bleeding (6), clotted hemothorax (6), or marked air leakage (3) preventing lung inflation with the OP-02 apparatus (field modification). OVT revealed 12 lung wounds, nine of which were multiple wounds, pleural bleeding in 6 patients, clotted hemothorax in 11 patients, and foreign bodies in 5 patients. Two patients underwent thoracotomy, one for suspicion of heart injury and the second because we could not adequately visualize and control bleeding revealed at OVT to be from the intercostal artery in the left costovertebral angle. Eight of 23 patients had no indication for operative videothoracoscopy and were managed with continued pleural aspiration and drug therapy. Wedge resection of the lung using an Endo-GIA-30 stapler was necessary in two patients because of parenchymal destruction and bleeding. Evacuation of clotted blood by fragmentation and aspiration was satisfactory in all cases. Satisfactory manual suturing of selected lung injuries was obtained largely with intracorporeal knot tying. The duration of the procedures ranged from 40 to 90 minutes. No morbidity nor mortality was encountered in patients undergoing OVT. Postoperative pain was minimized by using OVT placement of catheters in the chest wall soft tissue with local administration of 2% Trimecain. Patients were able to stand in 10 to 12 hours and to walk by the end of the first postoperative day. All patients who underwent OVT were evacuated without drains by the third or fourth postoperative day, all tolerating sitting and standing positions. We conclude that early OVT in the military field hospital for continued bleeding, clotted hemothorax, and continued major air leakage has several advantages in military patients with PFAWT: early definition and management of organ injury; identification and control of bleeding in most instances; earlier and more accurate assessment for thoracotomy; vigorous lavage and removal of projectiles such as bone fragments and evacuation of clotted hemothorax; early debridement with suture closure of the thoracic wall canal; and minimal postoperative pain with dramatically reduced suppurative sequelae and bronchopleural fistulae.     

Measurement of myocardial blood flow with oxygen-15 labelled water: comparison of different administration protocols

Positron emission tomography (PET) in conjunction with C15O2 or H215O can be used to measure myocardial blood flow (MBF) and tissue fraction (TF), i.e. the fraction of the tissue mass in the volume of the region of interest. However, with C15O2 inhalation, the tissue fraction in the septum is overestimated. Bolus injection of H215O together with arterial cannulation gives very precise results but is invasive. The purpose of this study was to develop a method which circumvents these problems. A four-parameter model with parameters for MBF, TF and spill-over fractions from both left and right ventricular cavities was developed. This method was compared with a three-parameter model (no right ventricular cavity spill-over) in both septal and non-septal regions of interest for three different administration protocols: bolus injection of H215O, infusion of H215O and inhalation of C15O2. It was found that MBF can be measured with intravenous administration of H215O without the requirement for arterial cannulation. The four-parameter protocol with bolus injection was stable in clinical studies. The four-parameter model proved essential for the septum, where it gave highly significantly better fits than did the three-parameter model (P<0.00003 in each of 15 subjects). Administration of H215O together with this four-parameter model also circumvented the problem of overestimation of TF in the septum seen with C15O2 inhalation. In addition, the radiation dose of H215O protocols is lower than that of C15O2 inhalation. Using a left atrial input curve instead of a left ventricular cavity input curve gave the same mean MBF and TF.     

Secondary prevention of ischemic heart disease after coronary revascularization

This study was aimed to assess the compliance with policies for secondary prevention of coronary heart disease (CHD) one year after coronary artery revascularization with special attention to the management of hyperlipidemia. One year after coronary revascularization during the year 1994, patients were contacted by letter to determine the modification of their risk factors, the treatment patterns for hypercholesterolemia and to have their plasma lipid level and blood pressure measured. Of the 245 consecutive patients contacted (110 after coronary artery bypass grafting, and 135 after percutaneous transluminal coronary angioplasty), 186 (76%) provided the information required for further analysis. Excluding the patients older than 65 years, only 29 out of 97 patients (30%) with a total cholesterol of more than 5.2 mmol/l, and only 20 out of 52 patients (38%) with a total cholesterol of more than 6.2 mmol/l were receiving lipid lowering therapy 1 year after coronary artery revascularization. In contrast, 97% (n = 180) of the entire population studied were taking antiplatelet drugs and/or coumadine. Participation in an in-house rehabilitation program yielded a positive influence on smoking, but not on treatment of hypercholesterolemia. In conclusion, only a small proportion of patients with documented CHD and hypercholesterolemia were being treated for their lipid disorder 1 year after coronary artery revascularization. In contrast, the great majority of patients received antiplatelet and/or coumadine therapy: These results indicate that the compliance with published treatment guidelines for hyperlipidemia in patients with CHD is still highly inadequate, irrespective of the participation in a rehabilitation program.     

Stochastic response surface methods (SRSMs) for uncertainty propagation: application to environmental and biological systems

Indicators of self-efficacy and motivation to change (stage of change) with regard to drinking and to drinking and driving were examined in a sample of Driving Under the Influence (DUI) offenders in a court-mandated intervention program. Self-administered questionnaires that contained pertinent measures were completed by 210 consenting offenders (34 of whom were female) during the intervention program. A factor analysis of efficacy and stages of change items showed distinct factors for the respective constructs; however, drinking and drinking-and-driving items of the same type (e.g., efficacy or stages of change) tended to codefine common factors, and the factor pattern suggested that motivations and efficacy for changing drinking behavior are critical for avoiding the drinking-and-driving sequence. Most participants were classified into the action stage in both drinking and drinking-and-driving domains. In regression analysis, contemplation of action and self-efficacy measures pertaining to drinking and driving predicted prior crashes and arrests; however, after accounting for recent alcohol problems, action items pertaining to drinking and driving were the best predictors of recent drinking-and-driving incidents.