Fate and function of anti-CD3/CD28-activated T cells following adoptive transfer: IL-2 promotes development of anti-tumor memory T cells in vivo.

BACKGROUND: Adoptive immunotherapy with T cells activated through CD3 alone requires exogenous IL-2 for T-cell function and survival after transfer, but the in vivo cytokine requirement of T cells activated through CD3 and CD28 is unknown. We hypothesized that CD3/CD28-activated T cells, unlike those activated through CD3 alone, might develop into long-lived memory T cells, either with or without systemic IL-2. METHODS: We used MHC class I-restricted TCR transgenic T cells from the OT-1 mouse, specific for the surrogate tumor Ag ovalbumin (OVA), to assess the trafficking kinetics, antigenic responsiveness and anti-tumor efficacy of dual-activated T cells in vivo as a function of IL-2 administration. At days 7, 14, and 28 after transfer, lymph node cells and splenocytes were examined for donor cell persistence and antigenic responsiveness by FACS and ELISA, respectively. RESULTS: In IL-2-treated mice, donor CD8+ T cells persisted and developed a memory phenotype, based on CD44 and Ly6c expression at day 28, while mice given no IL-2 had fewer donor cells at all time points. OVA-specific release of IFN-gamma was higher from lymphocytes of IL-2-treated mice compared with no-IL-2 mice (P<0.02 at all time points). In mice challenged with an OVA-bearing subline of the AML leukemia model C1498, IL-2 did not confer added protection from tumor challenge at 1 or 2 weeks after adoptive transfer, but gave improved survival at 4 weeks post-transfer. DISCUSSION: We conclude that exogenous IL-2 is not required for anti-tumor activity of CD3/CD28-activated CD8+ cells early after adoptive transfer, but promotes T-cell persistence that confers disease protection at more remote times.

Health conditions in the tribal villages of South Bihar: an epidemiologic survey.

In order to understand and establish an effective approach toward sustainable rural health development in the tribal region of South Bihar, an extensive socio-medical survey on over 90% of the houses of four tribal villages was undertaken. Using both a family-based questionnaire and screening physical examinations, the vital statistics, disease prevalence rates, immunization rates, and use of maternal health services in this neglected and previously unstudied area were determined. Local health-related behaviours and attitudes as well as nutritional status and family dietary intake were also focused upon. The results indicate that disease prevalence and mortality rates are significantly higher than expected and that existing services are less effective than previously thought. More importantly, the survey offers evidence that the fundamental obstacle toward improved community health remains a vast lack of health awareness and education in the villages; specifically in the areas of nutrition, immunization, diarrhoea prevention and treatment, maternity care, and family planning. Surveys of this kind provide vital information to health professionals working in underserved areas in India and should be an integral part of any such developmental undertaking.

Perceptual asymmetries in schizophrenia: subtype differences in left hemisphere dominance for dichotic fused words.

OBJECTIVE: Dichotic listening techniques have been used to study hemispheric dominance for language in schizophrenia. The authors' goal was to compare subjects with paranoid and undifferentiated subtypes of schizophrenia. METHOD: The Fused Rhymed Words Test was used to compare perceptual asymmetries in 16 patients with paranoid schizophrenia, 28 patients with undifferentiated schizophrenia, and 29 healthy comparison subjects. RESULTS: Patients with paranoid schizophrenia had the largest left hemisphere advantage and patients with undifferentiated schizophrenia had the smallest. The asymmetry of healthy subjects was intermediate. Hemisphere advantage varied as a function of gender only in the patients with undifferentiated schizophrenia. CONCLUSIONS: The findings support the hypotheses that undifferentiated schizophrenia is associated with underactivation of left hemisphere resources for verbal processing and that paranoid schizophrenia is characterized by preserved left hemisphere processing.

Impact of changes in transportation and commuting behaviors during the 1996 Summer Olympic Games in Atlanta on air quality and childhood asthma.

CONTEXT: Vehicle exhaust is a major source of ozone and other air pollutants. Although high ground-level ozone pollution is associated with transient increases in asthma morbidity, the impact of citywide transportation changes on air quality and childhood asthma has not been studied. The alternative transportation strategy implemented during the 1996 Summer Olympic Games in Atlanta, Ga, provided such an opportunity. OBJECTIVE: To describe traffic changes in Atlanta, Ga, during the 1996 Summer Olympic Games and concomitant changes in air quality and childhood asthma events. DESIGN: Ecological study comparing the 17 days of the Olympic Games (July 19-August 4, 1996) to a baseline period consisting of the 4 weeks before and 4 weeks after the Olympic Games. SETTING AND SUBJECTS: Children aged 1 to 16 years who resided in the 5 central counties of metropolitan Atlanta and whose data were captured in 1 of 4 databases. MAIN OUTCOME MEASURES: Citywide acute care visits and hospitalizations for asthma (asthma events) and nonasthma events, concentrations of major air pollutants, meteorological variables, and traffic counts. RESULTS: During the Olympic Games, the number of asthma acute care events decreased 41.6% (4.23 vs 2.47 daily events) in the Georgia Medicaid claims file, 44.1% (1.36 vs 0.76 daily events) in a health maintenance organization database, 11.1% (4.77 vs 4.24 daily events) in 2 pediatric emergency departments, and 19.1% (2.04 vs 1.65 daily hospitalizations) in the Georgia Hospital Discharge Database. The number of nonasthma acute care events in the 4 databases changed -3.1%, +1.3%, -2.1%, and +1.0%, respectively. In multivariate regression analysis, only the reduction in asthma events recorded in the Medicaid database was significant (relative risk, 0.48; 95% confidence interval, 0.44-0.86). Peak daily ozone concentrations decreased 27.9%, from 81.3 ppb during the baseline period to 58.6 ppb during the Olympic Games (P<.001). Peak weekday morning traffic counts dropped 22.5% (P<.001). Traffic counts were significantly correlated with that day's peak ozone concentration (average r = 0.36 for all 4 roads examined). Meteorological conditions during the Olympic Games did not differ substantially from the baseline period. CONCLUSIONS: Efforts to reduce downtown traffic congestion in Atlanta during the Olympic Games resulted in decreased traffic density, especially during the critical morning period. This was associated with a prolonged reduction in ozone pollution and significantly lower rates of childhood asthma events. These data provide support for efforts to reduce air pollution and improve health via reductions in motor vehicle traffic.

Factors influencing a communitywide campaign to administer hepatitis A vaccine to men who have sex with men.

OBJECTIVES: A hepatitis A outbreak among men who have sex with men (MSM) led to a publicly funded vaccination campaign. We evaluated the MSM community's response. METHODS: A cohort of MSM from 5 community sites was surveyed. RESULTS: Thirty-four (19%) of 178 potential vaccine candidates received the vaccine during the campaign. We found a linear relation between the number of exposures to campaign information and the likelihood of vaccination (P < .001). Vaccination was independently associated with awareness of the outbreak and the vaccine, having had sexual relations with men for 12 years or longer, having recently consulted a physician, and routinely reading a local gay newspaper. CONCLUSIONS: The difficult task of vaccinating MSM can be aided by repetitive promotional messages, especially via the gay media.

Escherichia coli O157:H7 outbreak associated with an improperly chlorinated swimming pool.

A cluster of gastrointestinal illnesses, including one case of hemolytic-uremic syndrome and one culture-confirmed Escherichia coli O157:H7 infection, followed a trailer park pool party. We interviewed a cohort of party attendees and park residents. A primary case was defined as the first gastrointestinal illness within a household between 5 July and 20 July in which the titer of IgG antibody to E. coli O157 (if determined) was elevated. Of 51 party attendees and trailer park residents, 18 developed a gastrointestinal illness, including 10 who met the definition of a primary case. Swimming in the pool significantly increased the risk of primary illness (relative risk = 6.3; 95% confidence interval = 1.8-18.9). No other exposure was significantly associated with primary illness, after pool exposure was controlled for. The implicated pool had little to no chlorine added during the period of 4-10 July. This outbreak provides new evidence of the importance of proper pool maintenance in controlling the spread of E. coli O157:H7.

The use of thermography in sympathetically maintained pain.

This paper reviews the symptomatology, pathophysiology, and treatment of reflex sympathetic dystrophy and sympathetically maintained pain. It is the author's experience that there exists a group of patients who present with chronic, unexplained pain following trauma, but lack the physical findings and positive investigative tests to confirm the diagnosis of reflex sympathetic dystrophy. For these patients, thermography serves as a useful and sensitive test to diagnosis sympathetically maintained pain. This paper presents six case reports in which thermography was used to diagnosis sympathetic dysfunction as the cause of chronic pain.

Abdominal aortic aneurysmectomy without preoperative angiography. A prospective study.

In an attempt to analyze whether routine angiography is necessary prior to elective abdominal aortic aneurysmectomy (AAA), a prospective study was designed in which this examination was obtained only for specific indications. These included significant hypertension, renal dysfunction, symptoms of visceral ischemia, suprarenal extension of the aneurysm or a coexisting thoracic aneurysm, and diminished or absent femoral pulses. A consecutive series of 124 abdominal aortic aneurysms is reported, in which 110 procedures were performed electively. Preoperative angiograms were obtained in only ten patients (9.1%) and in nine of these an alteration in the usual operative strategy resulted. In the remaining 100 patients undergoing elective AAA without preoperative aortography, acceptable morbidity and mortality rates were obtained despite the intraoperative discovery of iliac aneurysms in 25 patients (23%) and accessory renal arteries in three patients (2.7%). In the absence of specific indications for angiography, the mainstay of the preoperative evaluation for abdominal aortic aneurysms should be computed tomography (CT). The preoperative workup can be done entirely on an outpatient basis.

Limb salvage in elderly patients. Is aggressive surgical therapy warranted?

With the continued increase in life expectancy in the United States, the number of elderly patients presenting with limb-threatening atherosclerotic occlusive disease will also rise. The risk of arterial reconstructive surgery has been considered prohibitive in many of these individuals. During a six-year period, 50 patients aged 80 years or greater underwent a total of 64 surgical procedures for limb-threatening ischemia: 17 men (34%) and 33 women (66%). Ages ranged from 80 to 97 with a mean of 84 years. The procedural mortality rate was 3.1%. Cumulative life table survival rates for these patients were at 1 year, 92%; at 2 years, 76%; and at 3 years, 76%. The cumulative life table limb salvage rates were 92%, 88%, and 83% at the same intervals. Of the patients who died during the follow-up periods, 79% still had their previously-threatened limb intact. The results in these patients, as well as those from other series, support an aggressive policy of arterial reconstruction for elderly patients with limb-threatening ischemia. Age, per se, is not a contraindication to revascularization.

Matas, Antyllus, and endoaneurysmorrhaphy.

Much can be learned about the history of vascular surgery by tracing the treatment of aneurysms. Rudolph Matas played a major role in the development of the current therapy for these lesions. In the centennial of the signal case that set him on the road to surgical immortality, the details and setting of this operation are reviewed.

Psychological factors associated with pediatric asthma death: a review.

The preceding review of the literature on pediatric asthma death encompasses a broad range of emotional and psychological variables, some of which may ultimately prove to be meaningfully related to asthma death in childhood. However, the essential question of the role of psychological factors in pediatric asthma death remains unanswered. This area of investigation is still in its earliest stages, having relied heavily to date on retrospection, anecdotal recordings, and theoretical speculation. Additionally, conceptualization of the problem has been impeded not only by the remaining medical mysteries of asthma, but by considerable overlap among the psychological constructs considered, and a lack of clarity and confirming evidence about the physiological and/or behavioral mechanisms which would mediate the influence of proposed psychological factors on the course of the disease. As has been common in the history of psychosomatic research, there has been a tendency to search for a unitary underlying psychological factor that would account for asthma death (e.g., anxiety, psychopathology, a symbiotic mother-child relationship, or nebulizer overuse). However, a perusal of the literature casts doubt on the likelihood that a single psychological factor will provide the answers. Rather, serious problems in pediatric asthma management and fatal outcome appear more likely to be the end result of disruptions in the complex interactions and delicate balance among physiological, pharmacological, environmental, and interpersonal factors. The interpersonal milieu itself may represent potentially complicated and dangerous elements as it consists of medical staff, patient, and family members, each with his or her own limitations of intellect, judgment, and capacity to cope with emotional stress and the stress engendered by a chronic, sometimes frustrating, and potentially lethal disease. Nevertheless, the literature offers a variety of features which thus far have been found to characterize at least some cases of pediatric asthma death. There is fairly consistent agreement demographically that children under 5 yr of age and between the ages of 10 and 14 yr are at increased risk, as are nonwhite children. Sex-related differences are less clear. While a standard medical profile of the pediatric asthma patient at high risk for a fatal outcome does not yet exist, a number of "increased risk" indicators have been suggested, including for example, a history of particularly severe asthma, rapid onset attacks, and medical complications.(ABSTRACT TRUNCATED AT 400 WORDS)