The Diagnostics and Management of Bronchopulmonary Sequestration: An International Survey among Specialized Caregivers.

BACKGROUND: Our objective was to explore the treatment preferences for bronchopulmonary sequestration (BPS) among an international group of specialized caregivers. METHODS: Sixty-three participants from 17 countries completed an online survey concerning the diagnostics, treatment, and follow-up. Recruitment took place among members of the Collaborative Neonatal Network for the first European Congenital Pulmonary Airway Malformation Trial Consortium and through the Association for European Pediatric and Congenital Cardiology working group database. RESULTS: Most of the 63 participants were pediatric surgeons (52%), followed by pediatric pulmonologists (22%), and pediatric cardiologists (19%). The majority (65%) treated more than five cases per year and 52% standardly discussed treatment in a multidisciplinary team. Half of the participants (52%) based the management on the presence of symptoms, versus 32% on the intralobar or extralobar lesion localization. Centers with both surgical and interventional cardiac/radiological facilities (85%) preferred resection to embolization in symptomatic cases (62 vs. 15%). In asymptomatic cases too, resection was preferred over embolization (38 vs. 9%); 32% preferred noninterventional treatment, while 11% varied in preference. These treatment preferences were significantly different between surgeons and nonsurgeons (p < 0.05). Little agreement was observed in the preferred timing of intervention as also for the duration of follow-up. CONCLUSIONS: This survey demonstrates a variation in management strategies of BPS, reflecting different specialist expertise. Most centers treat only a handful of cases per year and follow-up is not standardized. Therefore, management discussion within a multidisciplinary team is recommended. Recording patient data in an international registry for the comparison of management strategies and outcomes could support the development of future guidelines. LEVEL OF EVIDENCE: Level IV.

The value of post-operative chemotherapy after chemoradiotherapy in patients with high-risk locally advanced rectal cancer-results from the RAPIDO trial.

BACKGROUND: Pre-operative chemoradiotherapy (CRT) rather than radiotherapy (RT) has resulted in fewer locoregional recurrences (LRRs), but no decrease in distant metastasis (DM) rate for patients with locally advanced rectal cancer (LARC). In many countries, patients receive post-operative chemotherapy (pCT) to improve oncological outcomes. We investigated the value of pCT after pre-operative CRT in the RAPIDO trial. PATIENTS AND METHODS: Patients were randomised between experimental (short-course RT, chemotherapy and surgery) and standard-of-care treatment (CRT, surgery and pCT depending on hospital policy). In this substudy, we compared curatively resected patients from the standard-of-care group who received pCT (pCT+ group) with those who did not (pCT- group). Subsequently, patients from the pCT+ group who received at least 75% of the prescribed chemotherapy cycles (pCT ≥75% group) were compared with patients who did not receive pCT (pCT-/- group). By propensity score stratification (PSS), we adjusted for the following unbalanced confounders: age, clinical extramural vascular invasion, distance to the anal verge, ypT stage, ypN stage, residual tumour, serious adverse event (SAE) and/or readmission within 6 weeks after surgery and SAE related to pre-operative CRT. Cumulative probability of disease-free survival (DFS), DM, LRR and overall survival (OS) was analysed by Cox regression. RESULTS: In total, 396/452 patients had a curative resection. The number of patients in the pCT+, pCT >75%, pCT- and pCT-/- groups was 184, 112, 154 and 149, respectively. The PSS-adjusted analyses for all endpoints demonstrated hazard ratios between approximately 0.7 and 0.8 (pCT+ versus pCT-), and 0.5 and 0.8 (pCT ≥75% versus pCT-/-). However, all 95% confidence intervals included 1. CONCLUSIONS: These data suggest a benefit of pCT after pre-operative CRT for patients with high-risk LARC, with approximately 20%-25% improvement in DFS and OS and 20%-25% risk reductions in DM and LRR. Compliance with pCT additionally reduces or improves all endpoints by 10%-20%. However, differences are not statistically significant.

Continuous glucose monitoring in acute ischemic stroke patients treated with endovascular therapy: A pilot study to assess feasibility and accuracy.

INTRODUCTION: Hyperglycemia is common in acute ischemic stroke and is associated with larger infarct volume and unfavorable functional outcome, also in patients who undergo reperfusion therapy. Hyperglycemia during reperfusion may be a therapeutic target. However, previous randomized trials on the effect of glucose lowering in the acute phase of ischemic stroke failed to demonstrate effects on clinical outcome. Inaccurate glucose measurements and not focussing on patients who undergo reperfusion therapy are possible explanations. Our aim was to study the feasibility and accuracy of continuous glucose monitoring (CGM) in patients with acute ischemic stroke undergoing endovascular treatment (EVT). METHODS: All consecutive patients with ischemic stroke and large vessel occlusion (LVO) of the anterior circulation who were eligible for endovascular therapy within 24 hours of symptom onset and presenting at the emergency department of Isala Hospital Zwolle, the Netherlands, were enrolled in this study. CGM was performed using a Freestyle Libre Flash 2 device (FSL-CGM, Abbot Diabetes Care, Alameda, California, USA) which was implanted on arrival at the emergency department. Feasibility was defined as the number of patients who could be registered for 24 hours and delay in door-to-groin time because of sensor implantation. Accuracy of CGM versus capillary and venous based plasma glucose values was determined with the Parkes error grid analysis. RESULTS: Twenty-three patients were included of whom 20 completed 24 hours monitoring (87%). One patient did not give permission to use the data; one sensor broke during implantation and one meter was broken after a sensor was shot in so no measurements could be recorded. There was no significant delay in treatment due to implantation of the sensor and no adverse events. One hundred percent of CGM data are in zones A and B of the Parkes error grid analysis so data out of the sensor can be interpreted as accurate. CONCLUSION: In this study, we showed that continuous glucose monitoring in patients with acute ischemic stroke due to large vessel occlusion of the anterior circulation in patients who were treated with endovascular therapy is feasible, safe and accurate.

Health-related quality of life in patients with advanced melanoma treated with ipilimumab: prognostic implications and changes during treatment.

BACKGROUND: We have previously reported that the safety and efficacy of ipilimumab in real-world patients with metastatic melanoma were comparable to clinical trials. Few studies have explored health-related quality of life (HRQL) in real-world populations receiving checkpoint inhibitors. This study reports HRQL in real-world patients receiving ipilimumab and assesses the prognostic value of patient-reported outcome measures. PATIENTS AND METHODS: Ipi4 (NCT02068196) was a prospective, multicentre, interventional phase IV trial. Real-world patients (N = 151) with metastatic melanoma were treated with ipilimumab 3 mg/kg intravenously as labelled. HRQL was assessed by the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire at baseline and after 10-12 weeks. RESULTS: The European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire was completed by 93% (141/151 patients) at baseline, and by 82% at 10-12 weeks. Poor performance status and elevated C-reactive protein (CRP) were associated with worse baseline HRQL. Clinically relevant and statistically significant deteriorations in HRQL from baseline to weeks 10-12 were reported (P <0.05). Baseline physical functioning [hazard ratio (HR) 1.96, P = 0.016], role functioning (HR 2.15, P <0.001), fatigue (HR 1.60, P = 0.030), and appetite loss (HR 1.76, P = 0.012) were associated with poorer overall survival independent of performance status, lactate dehydrogenase (LDH), and CRP. We further developed a prognostic model, combining HRQL outcomes with performance status, LDH, and CRP. This model identified three groups with large and statistically significant differences in survival. CONCLUSIONS: Systemic inflammation is associated with impaired HRQL. During treatment with ipilimumab, HRQL deteriorated significantly. Combining HRQL outcomes with objective risk factors provided additional prognostic information that may aid clinical decision making.

Effect of metformin on outcome after acute ischemic stroke in patients with type 2 diabetes mellitus.

INTRODUCTION: Diabetes mellitus is a well-known risk factor for ischemic stroke and is associated with unfavorable outcome after stroke. Metformin is recommended as first-line treatment in these patients. Pre-stroke metformin use might have neuroprotective properties resulting in reduced stroke severity. However, results of the effects of pre-stroke metformin use on functional outcome are conflicting and has not been previously described in patients with type 2 diabetes mellitus regardless of stroke severity or revascularization treatment. In this study, we aimed to assess the association between metformin use and functional outcome in patients with type 2 diabetes mellitus and acute ischemic stroke. METHODS: We used data from patients with known type 2 diabetes mellitus who were admitted with acute ischemic stroke between 2017 and 2021 in the Isala Hospital Zwolle and Medisch Spectrum Twente (MST) Enschede, the Netherlands. The association between pre-stroke metformin use and favorable functional outcome at 3 months (defined as modified Rankin Scale (mRS) < 3) was expressed as Odds Ratios (ORs) with corresponding confidence intervals (CIs). Adjustments were made for age, sex, hyperglycemia on admission and revascularization treatment by means of multiple logistic regression. RESULTS: Nine hundred thirty seven patients were included of whom 592 patients (63%) used metformin. Six hundred seventy eight (74%) patients were hyperglycemic on admission. Median mRS was 3 (IQR 2-6) and 593 patients (63%) had a favorable outcome. Pre-stroke metformin use was associated with favorable outcome (aOR of 1.94 (95%- CI 1.45-2.59)). CONCLUSION: In this study, we showed that pre-stroke metformin use was associated with favorable outcome after acute ischemic stroke in patients with diabetes mellitus type 2.

Association of hyperglycemia and computed tomographic perfusion deficits in patients who underwent endovascular treatment for acute ischemic stroke caused by a proximal intracranial occlusion: A subgroup analysis of a randomized phase 3 trial (MR CLEAN).

INTRODUCTION: Hyperglycemia is highly prevalent in patients with acute ischemic stroke and is associated with increased risk of symptomatic intracranial hemorrhage, larger infarct size and unfavorable outcome. Furthermore, glucose may modify the effect of endovascular treatment (EVT) in patients with ischemic stroke. Hyperglycemia might lead to accelerated conversion of penumbra into infarct core. However, it remains uncertain whether hyperglycemia on admission is associated with the size of penumbra or infarct core in acute ischemic stroke. In this study, we aimed to assess the association between hyperglycemia and Computed Tomographic Perfusion (CTP) derived parameters in patients who underwent EVT for acute ischemic stroke. METHODS: We used data from the MR CLEAN study (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Hyperglycemia was defined as admission serum glucose of >7.8 mmol/L. Dichotomized and quantiles of glucose levels were related to size of core, penumbra and core penumbra ratio. Hypoperfused area is mean transient time 45% higher than that of the contralateral hemisphere. Core is the area with cerebral blood volume of <2 mL/100 g and penumbra is the area with cerebral blood volume > 2 mL/100 g. Core-penumbra ratio is the ischemic core divided by the total volume of hypoperfused tissue (core plus penumbra) multiplied by 100. Adjustments were made for age, sex, NIHSS on admission, onset-imaging time and diabetes mellitus. RESULTS: Hundred seventy-three patients were included. Median glucose level on admission was 6.5 mmol/L (IQR 5.8-7.5 mmol/L) and thirty-five patients (20%) were hyperglycemic. Median core volume was 33.3 mL (IQR 13.6-62.4 mL), median penumbra volume was 80.2 mL (IQR 36.3-123.5 mL) and median core-penumbra ratio was 28.5% (IQR 18.6-45.8%). Patients with hyperglycemia on admission had larger core volumes and core penumbra ratio than normoglycemic patients with a regression coefficient of 15.1 (95% confidence interval (CI), 1.8 to 28.3) and 11.5 (95% confidence interval (CI), 3.4 to 19.7) respectively. CONCLUSION: Hyperglycemia on admission was associated with larger ischemic core volume and larger core-penumbra ratio in patients with acute ischemic stroke who underwent endovascular treatment.

The mitochondrial DNA constitution shaping T-cell immunity in patients with rectal cancer at high risk of metastatic progression.

PURPOSE: A significant percentage of colorectal cancer patients proceeds to metastatic disease. We hypothesised that mitochondrial DNA (mtDNA) polymorphisms, generated by the high mtDNA mutation rate of energy-demanding clonal immune cell expansions and assessable in peripheral blood, reflect how efficiently systemic immunity impedes metastasis. PATIENTS AND METHODS: We studied 44 rectal cancer patients from a population-based prospective biomarker study, given curative-intent neoadjuvant radiation and radical surgery for high-risk tumour stage and followed for metastatic failure. Blood specimens were sampled at the time of diagnosis and analysed for the full-length mtDNA sequence, composition of immune cell subpopulations and damaged serum mtDNA. RESULTS: Whole blood total mtDNA variant number above the median value for the study cohort, coexisting with an mtDNA non-H haplogroup, was representative for the mtDNA of circulating immune cells and associated with low risk of a metastatic event. Abundant mtDNA variants correlated with proliferating helper T cells and cytotoxic effector T cells in the circulation. Patients without metastatic progression had high relative levels of circulating tumour-targeting effector T cells and, of note, the naïve (LAG-3+) helper T-cell population, with the proportion of LAG-3+ cells inversely correlating with cell-free damaged mtDNA in serum known to cause antagonising inflammation. CONCLUSION: Numerous mtDNA polymorphisms in peripheral blood reflected clonal expansion of circulating helper and cytotoxic T-cell populations in patients without metastatic failure. The statistical associations suggested that patient's constitutional mtDNA manifests the helper T-cell capacity to mount immunity that controls metastatic susceptibility. TRIAL REGISTRATION: ClinicalTrials.gov NCT01816607; registration date: 22 March 2013.

Epidermal growth factor receptor-inhibition (EGFR-I) in the treatment of neuropathic pain.

BACKGROUND: Neurobiological work has demonstrated that expression of mitogen-activated protein kinases (MAPK) is upregulated on neurones and glial cells after nerve damage. Furthermore, the epidermal growth factor receptor (EGFR) has been identified as having a key role in this process and subsequent interruption of this using EGFR-Inhibitors (EGFR-I), may improve neuropathic pain. The aim of this report was to explore if EGFR-I attenuated neuropathic pain in humans. METHODS: A selection of patients with neuropathic pain were treated off-label with one of four EGFR-Is, approved for the treatment of cancer. All patients had chronic and severe neuropathic pain (as defined by diagnostic criteria). Pain intensity, interference with function, and adverse events were prospectively registered. RESULTS: Twenty patients were treated. Eighteen patients experienced clinically significant pain relief after treatment with EGFR-I. Median observed pain reduction for all patients was 8.5 (IQR=5-9.5) points on a 0-10 numeric rating scale. Neuropathic pain spike duration and frequency also improved. Pain relief was most often achieved within 24 h and was more rapid in cases of i.v. than oral administration. All four EGFR-I that were tested were of equal efficacy. The duration of pain relief was consistent with the individual drugs' half-lives. No cases of drug-tolerance were observed. Side-effects were predominantly skin reactions. One grade 3 adverse event was registered. Median follow-up for responders was 7 months (Range 1-37). CONCLUSIONS: EGFR-I improves neuropathic pain and this is in keeping with basic science work. Controlled clinical trials are now eagerly awaited to assess this further.

Randomized trial of the effectiveness of a non-pharmacological multidisciplinary face-to-face treatment program on daily function compared to a telephone-based treatment program in patients with generalized osteoarthritis.

OBJECTIVE: To compare the effectiveness of a non-pharmacological multidisciplinary face-to-face self-management treatment program with a telephone-based program on daily function in patients with generalized osteoarthritis (GOA). DESIGN: A pragmatic single-blind randomized clinical superiority trial involving 147 patients clinically diagnosed with GOA, randomly allocated to either a 6 week non-pharmacological multidisciplinary face-to-face treatment program comprising seven group sessions or a 6 week telephone-based treatment program comprising two group sessions combined with four telephone contacts. Both programs aimed to improve daily function and to enhance self-management to control the disease. The programs critically differed in mode of delivery and intensity. Daily function (primary outcome) and secondary outcomes were assessed at baseline, 6, 26 and 52 weeks. Data were analyzed using linear or logistic multilevel regression models corrected for baseline, sex and group-wise treatment. RESULTS: No differences in effectiveness between both treatment programs were observed on the primary outcome (group difference (95% CI): -0.03 (-0.14, 0.07)) or on secondary outcome measures, except for a larger improvement in pain in the face-to-face treatment group (group difference (95% CI): 1.61 (0.01, 3.21)). Within groups, significant improvements were observed on several domains, especially in the face-to-face group. However, these benefits are relatively small and unlikely to be of clinical importance. CONCLUSIONS: We found no differences in treatment effect between patients with GOA who followed a non-pharmacological multidisciplinary face-to-face self-management program and those who received a telephone-delivered program. Besides, our findings demonstrated limited benefits of a self-management program for individuals with GOA. Dutch Trial Register trial number: NTR2137.

An educational improvement project to track patient encounters: toward a more complete understanding of third-year medical students' experiences.

BACKGROUND: At the University of Missouri School of Medicine (MUSOM), "commitment to improving quality and safety in healthcare" is one of eight key characteristics set as goals for our graduates. As educators, we have modelled our commitment to continuous improvement in the educational experiences through the creation of a method to monitor and analyse patient encounters in the third year of medical school. This educational improvement project allowed course directors to (1) confirm adequate clinical exposure, (2) obtain prompt information on student experiences, (3) adjust individual student rotations to meet requirements and (4) ascertain the range of clinical experiences available to students. DISCUSSION: Data illustrate high levels of use and satisfaction with the educational innovation. We are in our second year using the new Patient Log (PLOG) process and are now considering expanding the use of PLOG into the fourth year of medical school.

Determination of the inflammatory potential of bioaerosols from a duck-fattening unit by using a limulus amebocyte lysate assay and human whole blood cytokine response.

Inhalation of bioaerosols from animal houses can induce acute inflammatory reactions in the respiratory tract. Determination of the concentration of airborne endotoxins is widely used to characterize this risk. In this study, the activity of bioaerosol samples from a duck-fattening unit to induce interleukin-1beta (IL-1beta) in human blood and to react with Limulus Amebocyte Lysate (LAL) was investigated. The activity detected in the whole blood assay correlated well with the endotoxic activity found in the LAL assay (Spearmen's rho = 0.902). However in all samples, the inflammation-inducing potential was overestimated by the LAL assay. It is assumed that this overestimation could be, in part, a result of an overestimation of the inflammatory potential of endotoxins originating from Pseudomonadaceae by the LAL assay. Pseudomonadaceae were regularly isolated from the air of the duck-fattening unit. The results presented here indicate that the whole blood assay can be used besides the LAL assay as an additional method to characterize the inflammation-inducing potential of bioaerosols.

Gonadal regeneration in masculinized female or steroid-treated rainbow trout (Oncorhynchus mykiss).

In salmonids, the development of an indifferent gonad into a testis or an ovary is normally determined chromosomally but can be reversed or changed by the administration of exogenous steroids during specific times in embryonic development. Because the gonads of sexually mature rainbow trout (RBT) are capable of regeneration following surgical removal and since regeneration of some tissue involves dedifferentiation, the objective of this experiment was to determine if the phenotypic sex of RBT gonads could be reversed during the regenerative process. In experiment 1, male RBT were surgically gonadectomized (Gx) or left intact and subsequently treated with estradiol-17beta, a steroid that feminizes male RBT embryos. All Gx males regenerated testicular tissue regardless of treatment. Likewise, the gonads of sham-operated, intact fish treated with exogenous estrogen showed no evidence of sex-reversal. In experiment 2, testes from masculinized females (XX genotype; male phenotype) were surgically removed. In all cases, only testicular tissue was regenerated in the masculinized females. Taken together, these results are consistent with the conclusion that gonads of salmonid fishes are not susceptible to sex-reversing stimuli during the regenerative process and that gonadal regeneration in salmonids is a result of cellular proliferation of the remaining gonadal remnant.

Oligoclonality of Vdelta1 and Vdelta2 cells in human peripheral blood mononuclear cells: TCR selection is not altered by stimulation with gram-negative bacteria.

Despite the enormous potential repertoire of gammadelta T cells, there are several observations which suggest that the expressed gammadelta repertoire in the periphery of normal individuals is often quite restricted. To assess selective expansions among gammadelta T cells from both adult and newborn blood samples, PBMC from 12 normal adults and cord blood from 15 normal newborns were analyzed for TCRDV1 and TCRDV2 junctional diversity by CDR3 size spectratyping and single-strand conformational polymorphism. Although TCRBV usage showed extensive heterogeneity in adults and newborns, both populations often showed CDR3 region restriction for TCRDV1 and TCRDV2. Analysis of the CDR3 spectratype patterns of newborn twins suggested that clonal selection for TCRDV is independent of genetic background. The possible role of Gram-negative bacteria in driving selective responsiveness of gammadelta T cells in PBMCs from adults was examined by in vitro stimulation with Escherichia coli and Pseudomonas aeruginosa. Donors whose TCRDV repertoire was highly clonal in the unstimulated blood cells showed the same predominant clones among the bacteria-stimulated cultures. In individuals whose gammadelta T cells were less restricted, in vitro stimulation did not select for clonality; rather, the TCRDV repertoires were similar before and after bacterial stimulation. Together, these data indicate that gammadelta T cells are often clonally restricted in adults as well as in newborns and suggest that the prominent stimulatory activity of Gram-negative bacteria does not by itself account for the restriction or diversity of the gammadelta T cell repertoire.

Escherichia coli and Pseudomonas aeruginosa induce expansion of V delta 2 cells in adult peripheral blood, but of V delta 1 cells in cord blood.

Human peripheral blood T cells proliferate in response to Escherichia coli and Pseudomonas aeruginosa. We observed that during the first few days after stimulation a large percentage of the responding PBMC were gamma delta T cells. In our study we characterized the early T cell responses of freshly isolated adult and newborn PBMC to soluble preparations of heat-killed E. coli and P. aeruginosa. Specimens from all healthy adults tested showed intense proliferation in response to both bacterial preparations; at 6 days, the responding cells were mainly T cell blasts, of which high percentages (up to 80%) were gamma delta T cells, most expressing V delta 2/V gamma 9. All newborn blood specimens tested also showed T cell proliferative responses, which included a marked expansion of gamma delta T cells, mainly of the V delta 1 subset. Populations of purified V delta 1 and V delta 2 T cells were obtained from adult PBMC following stimulation with E. coli; both subsets proliferated upon rechallenge with the bacterial preparations. Protease treatment of the bacterial preparations did not appreciably affect their ability to induce expansion of gamma delta T cells in either adult or cord blood, indicating that the stimulatory components were not proteins. The response of gamma delta T cells from newborns indicates that prior exposure to bacterial products is not necessary and suggests that gamma delta T cells are important elements in natural immunity to these extracellular organisms.

Evaluation of a parent child drug education program.

The purpose of the study was to evaluate the effectiveness of a parent-child drug education program. One thousand four hundred and forty-seven fourth, fifth, and sixth grade students and 2,036 of their parents participated in the study. Results indicated that the program produced changes in the responses of children and their parents to questions concerning attitudes, use, perceptions of use, and intended use of drugs.

Responses of human T cells to dominant discrete protein antigens of Escherichia coli and Pseudomonas aeruginosa.

Normal human beings have circulating T lymphocytes that proliferate in response to Escherichia coli and Pseudomonas aeruginosa. We performed the present study to characterize the nature of the responding T cells and to determine whether distinct or shared conventional antigens, superantigens or polyclonal activators account for T cell proliferation. Long term antigen-specific T cell lines were generated by repeated stimulation of PBMC from four donors with soluble antigen preparations of E. coli or P. aeruginosa. This resulted in the emergence of distinct T cell populations, which responded to strains of either E. coli or P. aeruginosa, but not to both. Trypsin treatment of the bacterial preparations largely eliminated their ability to stimulate the T cells. The T cell lines were predominantly CD4+ and their proliferation to bacterial antigens was optimal using autologous APC. E. coli T cell lines proliferated not only in response to the E. coli strain with which they were initially selected, but also to four different strains of E. coli, as well as to several related Gram-negative species. P. aeruginosa selected T cells exhibited proliferative responses to six different P. aeruginosa strains, but not to the other Gram-negative species. The finding that repeated stimulation of PBMC with E. coli or P. aeruginosa leads to CD4+ T cells highly reactive with conventional protein antigens specific either for E. coli or P. aeruginosa indicates that these bacteria possess separate dominant protein antigens that drive the proliferation of peripheral blood T cells.

T lymphocyte responses to antigens of gram-negative bacteria in pyelonephritis.

We showed previously that large numbers of T lymphocytes accumulate within a few days in the kidneys of rats with ascending pyelonephritis induced with Escherichia coli or Pseudomonas aeruginosa. CD4+ T cells propagated from the lesions exhibited MHC-restricted proliferative responses to formalin-fixed bacteria of the species used to induce infection. In the present study we investigated further the nature of the antigens responsible for the T cell proliferation and studied the ability of different bacterial strains and species to produce proliferative responses. We found that heat-killed bacteria were more stimulatory than formalin-fixed bacteria, and that soluble supernatants of heat-killed organism were also effective. The stimulatory effects of supernatants were destroyed by trypsin and the responses were MHC-restricted. Twelve different E. coli strains, with or without characteristics of uropathogenicity in humans, were all highly stimulatory to T cells derived from a kidney infected with a single E. coli strain. Strains of Klebsiella pneumoniae, Enterobacter aerogenes, and Serratia marcescens--species of Enterobacteriaceae closely related to E. coli--were also stimulatory, whereas more distantly related bacteria--Proteus, Morganella, and P. aeruginosa--were not. T cells propagated from kidneys infected with P. aeruginosa responded to supernatants of this organism, but not to E. coli supernatants. We conclude that a protein antigen (or antigens) shared by strains of E. coli and related Enterobacteriaceae, but not by other gram-negative bacteria, produce MHC-restricted proliferative responses of CD4+ T cells that infiltrate rat kidneys infected with E. coli.

Effects of a take-home drug prevention program on drug-related communication and beliefs of parents and children.

Five hundred and eleven fourth, fifth, and sixth grade students and their parents from six schools in northwest Arkansas participated in this study. Students were blocked on school and grade level, then assigned randomly by class to either the intervention Keep A Clear Mind (KACM) program or a waiting list control. KACM students received four weekly correspondence lessons designed to be completed at home with a parent. KACM students reported significantly less perceived peer use of alcohol, tobacco, and marijuana, as well as significantly less peer pressure susceptibility to experiment with cigarettes. Mothers in the KACM program reported significantly more recent and frequent communication with their children about refusing drugs, and significantly greater discussions with their children regarding how to resist peer pressure to use alcohol, tobacco, and marijuana. Intervention program fathers reported significantly more communication with their children concerning how to resist peer pressure to drink alcohol and use tobacco, and significantly greater motivation to help their children avoid drug use. No significant differences were found between groups on student intentions to use drugs. These data suggest a print medium that emphasizes parent-child activities holds promise for accessing families and enhancing drug prevention communication.