Microbial infections,immunomodulation, and drugs of abuse

The use of recreational drugs of abuse has generated serious health concerns. There is a long-recognized relationship between addictive drugs and increased levels of infections. Studies of the mechanisms of actions of these drugs became more urgent with the advent of AIDS and its correlation with abused substances. The nature and mechanisms of immunomodulation by marijuana, opiates, cocaine, nicotine, and alcohol are described in this review. Recent studies of the effects of opiates or marijuana on the immune system have demonstrated that they are receptor mediated, occurring both directly via specific receptors on immune cells and indirectly through similar receptors on cells of the nervous system. Findings are also discussed that demonstrate that cocaine and nicotine have similar immunomodulatory effects, which are also apparently receptor mediated. Finally, the nature and mechanisms of immunomodulation by alcohol are described. Although no specific alcohol receptors have been identified, it is widely recognized that alcohol enhances susceptibility to opportunistic microbes. The review covers recent studies of the effects of these drugs on immunity and on increased susceptibility to infectious diseases, including AIDS.     

Sister chromatid exchanges in patients with retinoblastoma

Spontaneous and mitomycin C(MMC)-induced sisyer chromatid exchanges were studied in 11 patients with retinoblastoma and 7 normal controls. Spontaneous rates were similar in patients and in controls. The MMC-induced rate was found to be significantly higher in bilaterally affected patients than in controls. It is suggested that this increase may be due to a DNA repair deficiency. However, it is not possible to clarify wether this abnormality is associated with the retinoblastoma gene or with another factor acting on the degree of expressivity of the disease in gene carriers.     

Attentional characteristics of infants and toddlers with Williams syndrome during triadic interactions

Two studies were conducted to consider the looking behavior of infants and toddlers with Williams syndrome (WS).In Study 1,the looking behavior of a 10-month-old girl with WS during play sessions with her mother and with a stranger was compared to that of 2 groups of infants who were developing normally (ND),1 matched for chronological age and the other for developmental age. The infant with WS spent more than twice as much time looking at her mother as the infants in either contrast group did. She also spent twice as much time looking at the stranger.In addition, during 78%of this time, her gaze at the stranger was coded as extremely intense. Looks of this intensity were virtually never made by the ND infants. In Study 2,the looking behavior of 31 individuals with WS ages 8 to 43 months during a genetics evaluation was compared to that of 319 control children in the same age range (242 with developmental delay due to causes other than WS).Twenty-three of the 25 participants with WS aged 33 months or younger demonstrated extended and intense looking at the geneticist. In contrast, none of the control participants looked extensively or intently at the geneticist. Findings are discussed in the context of previous research on arousal and focused attention during normal development and on temperament and personality of older children and adults with WS. It is argued that the unusual looking patterns evidenced by infants and toddlers with WS presage the unusual temperament and personality of older individuals with WS, and the possibility of a genetic basis for these behaviors is addressed.     

Health surveillance project among single homeless men in Bristol

The establishment of a health surveillance system for the single homeless is described. Health checks were performed in two Salvation Army hostels by a district nurse supported by general practitioners and other workers from one health centre. High levels of morbidity were discovered and the residents were largely treated by the primary health care team. Those residents who were referred to other agencies were shown to have a high attendance rate. An open access clinic was later set up by the district nurse in one of the hostels. This was well received by residents and staff and reduced the call out rate for the general practitioners.

In some parts of the UK, special medical centres for the single homeless have been established on the premiss that it is unrealistic to expect general practitioners to provide an adequate service. However, this study describes an effective service based on primary care which is acceptable to homeless people while being relatively cheap and easy to administer. We recommend the development of a peripatetic service as outlined in this study, offering health care at hostels, day centres and other places where the homeless are to be found.

     

A critical function for type I interferons in cancer immunoediting

'Cancer immunoediting' is a process wherein the immune system protects hosts against tumor development and facilitates outgrowth of tumors with reduced immunogenicity. Although interferon-gamma (IFN-gamma) is known to be involved in this process, the involvement of type I interferons (IFN-alpha/beta) has not been elucidated. We now show that, like IFN-gamma, endogenously produced IFN-alpha/beta was required for the prevention of the growth of primary carcinogen-induced and transplantable tumors. Although tumor cells are important IFN-gamma targets, they are not functionally relevant sites of the actions of the type I interferons. Instead, host hematopoietic cells are critical IFN-alpha/beta targets during development of protective antitumor responses. Therefore, type I interferons are important components of the cancer immunoediting process and function in a way that does not completely overlap the functions of IFN-gamma.     

Cluster-Randomized Controlled Trial of An Athletic Trainer-Directed Spit (Smokeless) Tobacco Intervention for Collegiate Baseball Athletes: Results After 1 Year

Context: Athletes in the United States are at high risk for using spit (smokeless) tobacco (ST) and incurring its associated adverse health effects.Objective: To examine whether an athletic trainer-directed ST intervention could decrease initiation and promote cessation of ST use among male collegiate baseball athletes.Design: Stratified, cluster-randomized controlled trial.Setting: Fifty-two California colleges.Patients or Other Participant(s): A total of 883 subjects in 27 intervention colleges and 702 subjects in 25 control colleges participated, as did 48 certified athletic trainers.Intervention(s): For college athletic trainers and associated dental professionals, a 3-hour video conference, and for collegiate athletes, an oral cancer screening with feedback and brief counseling during the preseason health screenings, athletic trainer support for cessation, and a peer-led educational baseball team meeting.Main Outcome Measure(s): The subjects' ST use over 1 year was assessed by self-report. At the end of the study, the certified athletic trainers were mailed a survey assessing their tobacco use and perceptions and behavior related to tobacco control in the athletic environment. We used multivariable logistic regression models for clustered responses (generalized estimating equations) to test the difference between groups in ST-use initiation and cessation and to identify significant overall predictors of noninitiation and cessation of ST use.Results: Of the 1585 athletes recruited, 1248 (78.7%) were followed up at 12 months. In addition, 48 of the 52 athletic trainers (92%) responded to the 1-year follow-up survey. The ST-use initiation (incidence) was 5.1% in intervention colleges and 8.4% in control colleges (generalized estimating equation odds ratio = 0.58, 95% confidence interval = 0.35-0.99). Predictors of ST noninitiation were low lifetime tobacco and monthly alcohol use (odds ratio = 1.98, 95% confidence interval = 1.40- 2.82) and athletic trainers' report that the baseball coach supported ST-use prevention activities (odds ratio = 1.43, 95% confidence interval = 1.11-1.83). Although at 1 year, cessation of ST use was relatively high in both groups (36%), we noted no significant difference between the groups (odd ratio = 0.94, 95% confidence interval = 0.70-1.27).Conclusions: The intervention was significantly effective in preventing incident ST use but did not significantly increase cessation beyond that seen in the control group. The latter finding is inconsistent with previous studies and may be explained by spillover of the intervention to control colleges, other anti-tobacco activity in control colleges, and/or the small sample of dependent ST users enrolled in the study.     

Cortical auditory processing and communication in children with autism: electrophysiological/behavioral relations.

The purpose of the present study was to investigate the relations between late auditory evoked potentials (AEPs) recorded at temporal sites (the N1c wave or Tb) and verbal and non-verbal abilities in children with autism. The study was performed in 26 mentally retarded children with autism (AUT) aged 4-8 years (mean age +/- S.E.M. = 71 +/- 2 months; mean verbal and non-verbal developmental quotient +/- S.E.M. = 36 +/- 4 and 48 +/- 3). The stimuli used were 750 Hz tone bursts of 200 ms duration delivered binaurally at different intensity levels (50, 60, 70, 80 dB SPL) with 3-5 s interstimulus intervals. Temporal AEPs were first compared to those of a group of 16 normal children (NOR) in the same age range (mean age +/- S.E.M. = 69 +/- 3 months). We then focused on the AUT group and considered relations between temporal AEPs and the severity of disorders of verbal and non-verbal communication assessed using a behavior rating scale. AEPs recorded on left and right temporal sites were of smaller amplitude in the AUT group than in the NOR group. Increasing intensity-related amplitude was observed on both sides in NOR and only on the right side in AUT. The lack of intensity effect on the left side resulted in a particular pattern of asymmetry at the highest level of intensity (80 dB SPL) with greater N1c amplitude on the right than on the left side (the reverse was found in the NOR group). Electro-clinical correlations indicated that the greater the amplitude of the right temporal N1c responses, the higher the verbal and non-verbal communication abilities. This suggests a developmental reorganization of left-right hemisphere functions in autism, with preferential activation of the right hemisphere for functions usually allocated to the left hemisphere, particularly those involving the secondary auditory areas situated on the lateral surface of the superior temporal gyrus where the N1c/Tb wave is generated.     

Differences in airway remodeling between subjects with severe and moderate asthma

BACKGROUND: Airway remodeling in asthma comprises a range of structural changes. Several studies have suggested an association between these changes and disease severity. The relationship between the extent of remodeling and lung function is not well defined. OBJECTIVE: We sought to contrast the structural changes in the airways of well-defined groups of subjects with severe and moderate asthma and to correlate the extent of remodeling with disease severity. METHODS: Endobronchial biopsy specimens were obtained from 15 subjects with severe and 13 subjects with moderate asthma. Epithelial integrity, cell-layer areas, subepithelial fibrosis, and the distance between epithelial and airway smooth muscle (ASM) layers were measured by means of image analysis. Collagen was identified by using Van Giesen stain, and ASM was defined by using smooth muscle alpha-actin immunostaining. Specific immunostains were performed for the evaluation of RANTES, IL-8, and eotaxin expression as markers of ASM phenotype. RESULTS: ASM area was greater in subjects with severe (0.24+/- 0.03 mm(2)) than in subjects with moderate (0.05+/- 0.01 mm(2)) asthma (P<.001). The distance between the epithelial and ASM layers was less in the severe group (0.12+/- 0.01 mm) than in the moderate group (0.24+/- 0.02, P<.001). A trend toward greater subepithelial fibrosis in subjects with severe asthma did not reach statistical significance. IL-8 and eotaxin expression, but not RANTES expression, were increased in the ASM of subjects with severe asthma compared with in subjects with moderate asthma. CONCLUSION: Smooth muscle alteration is the key structural change that distinguishes severe from moderate asthma, and phenotypic change in ASM might contribute to the difficulty in obtaining adequate control in some subjects with severe asthma.     

Evaluation of a microsphere-based flow cytometric assay for diagnosis of celiac disease

The multiplexed particle-based flow cytometric technology proposes a new approach for the diagnosis of autoimmune diseases combining the advantages of conventional methods with the ability to quantitatively determine multiple autoantibodies in the same sample, simultaneously and rapidly. Recently, a commercial kit (FIDIS Celiac, Biomedical Diagnostics, Mane la Vallé, France) was introduced for the simultaneous detection of IgA anti-tissue transglutaminase (anti-tTG), IgG, and IgA anti-gliadin antibodies (AGA). This study was undertaken to evaluate and compare the FIDIS Celiac kit with standardized commercial ELISAs (QUANTA Lite, INOVA Diagnostics Inc., San Diego, CA). A disease group consisted of 21 samples from untreated patients with biopsy confirmed celiac disease (CD), and two control groups of historical sera (207 from regular blood donors and 181 from chronically infected hepatitis patients) were studied. All control sera were negative for IgA anti-endomysial antibodies (EmA) and had an IgA concentration above the lower normal limit. Concerning the reproducibility, intra- and inter-assay coefficients of variation (CVs) ranging between 2% and 12%, and between 3% and 21%, respectively, were observed. Regarding the diagnostic quality, each assay was compared to the disease diagnosis using the McNemar test and the kappa (K) parameter, while ROC analysis was applied. Generally, the performance of FIDIS assay was proved almost equally adequate to that of ELISA in the detection of IgA anti-tTG antibodies, IgA and IgG AGA. However, the performance of FIDIS assay was found surmounting that of ELISA among hepatitis patients, possibly due to the avoidance of debris and unbound cross contaminants and, hence, the "noise" of such materials in samples under analysis. Taking our results together with the simplicity and the high throughput of FIDIS assay, its overall performance in the diagnosis of CD seems better than that of ELISA.