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IL-13 and IFN-gamma secretion by activated T cells in HIV-1 infection associated with viral suppression and a lack of disease progression.

The immunopathology of HIV-1 infection includes immune defects in T cell cytokine secretion, resulting in decreased Ag-specific responses. In this report, IL-13 and IFN-gamma were analyzed in progressive HIV-1 disease. Both cytokines exert positive effects on Ag presentation and inhibit HIV-1 infection of macrophages. Anti-CD3/anti-CD28-activated PBMC from HIV-1-infected individuals (n = 74) compared with uninfected subjects (n = 30) secreted significantly less IL-13 (median, 0.64 ng/ml vs 2.07 ng/ml; p < 0. 001) and IFN-gamma (median, 40.96 ng/ml vs 129.5 ng/ml; p < 0.005). Decreased IL-13 and IFN-gamma secretion in HIV infection was present in sorted CD4+ and CD8+ T cell subsets, and additional analysis determined concurrent deficiency at the protein and transcriptional level. Longitudinal analysis showed that cytokine secretion levels correlated positively with CD4 count and negatively with plasma HIV-1 viral load. Patients changing to suppressive antiretroviral therapy during the study showed increases in IL-13 and IFN-gamma secretion. Overall, results show a decline in IL-13 and IFN-gamma secretion in progressive HIV-1 infection and suggest a role for both cytokines as part of T cell adaptive responses associated with a lack of disease progression.

CD4-Positive T-Lymphocytes↗

Mental development in infants with cleft lip and/or palate.

OBJECTIVE: Investigated mental development in infants and toddlers with cleft lip and/or palate (CLP). DESIGN: This was a retrospective analysis of developmental scores on qualified children between 4 and 36 months of age. Cross-sectional analysis included children in four age groups (6, 12, 18, and 24 months); longitudinal analysis included children at mean age 9.1 (range = 4 to 15) months at Time 1 and 24 months (range = 16 to 36) at Time 2. PARTICIPANTS: Cross-sectional analysis included 180 children (59% male participants) in four diagnostic groups (cleft lip only [CL], cleft lip and palate [CLP], cleft palate only [CP], and Pierre Robin). The longitudinal sample included 85 children (64% male children) in the same diagnostic groups. MAIN OUTCOME MEASURES: Mental Scale (MDI) of the Bayley Scales of Infant Development. RESULTS: Mean MDIs were in the average range but decreased significantly between youngest and oldest groups in both cross-sectional (F(3,179) = 4.9, p<.01) and longitudinal samples (F(1,84) = 6.87, p<.01). There was a significant difference among cleft types (F(3,179) = 3.5, p<.025). Infants with CL obtained the highest scores, and infants with Pierre Robin Sequence obtained the lowest. Perceptual-motor development in the first year of life was predictive of developmental status at age 2. CONCLUSIONS: The number of children with CLP who may be at risk for developmental problems during the second year of life is greater than would be expected. Children at greatest risk may demonstrate early delays in acquisition of perceptual-motor skills during the first year of life.

Analysis of Variance↗

Gender differences in language of AD patients: a longitudinal study.

We examined gender differences in probable Alzheimer's disease (AD) patients on language measures at four data collections (entry, 6, 12, and 18 months) and a normal elderly (NE) comparison group at entry and 18 months. Comparison of gender differences in language abilities of 60 (29 men, 31 women) early (Clinical Dementia Ratings I and II) AD subjects at entry revealed significant effects for gender on the Boston Naming Test (BNT) and Peabody Picture Vocabulary Test-Revised (PPVT-R) but not on the Word Fluency Test, shortened Token Test, or modified Reporter's Test. The 37 subjects (18 men, 19 women) who completed less than four data collection sessions compared with the 23 subjects (11 men, 12 women) who completed all four sessions differed on education and Reporter's Test scores. Longitudinal analysis of measures showed that gender differences persisted for the BNT and PPVT-R and that time differences were found on all measures. Gender differences remained after correcting for age, education, duration of illness, and mental status. We found no differences for the NE comparison group for gender or time. All AD subject trends were downward, suggesting that (1) language is affected over time in AD, (2) both men and women decline at similar rates, and (3) language abilities of women are more severely impaired at all time points.

Aged↗

Height velocity in Argentinean girls with Turner's syndrome.

Height velocities from birth to maturity derived from 1,049 height increments measured over intervals 0.85-1.15 years were studied from a sample of 187 patients with Turner's syndrome (TS) diagnosed on the basis of karyotype. Length of follow up in each girl varied from 1.0 to 11.0 years. Cross-sectional analysis showed a relatively stable growth velocity during pubertal ages. However, longitudinal analysis of individual growth curves showed the existence of a small growth spurt in 37 out of 47 girls with available data during pubertal years. Mean peak height velocity (PHV) of this spurt was 5.7 cm/year, SD 1.34; mean age at PHV was 12.66 years, SD 1.70. Selected percentiles were calculated using the least mean squares (LMS) method. Results show that a small growth spurt in girls with TS may be more frequent than previously thought.

Adolescent↗

Marriage and alcohol use: a longitudinal study of "maturing out".

Earlier findings have suggested that marriage may provide protection from a variety of physical and psychological problems. In particular, numerous studies have demonstrated a consistent relationship between marital status and alcohol use. To examine this relationship more carefully, we performed a longitudinal analysis of data collected on the Youth Cohort of the National Longitudinal Survey of Labor Market Experience. Four marital transition groups were constructed based upon marital status across a 3-year period: stably single, married year 3, married year 2 and stably married. Results of repeated-measures MANCOVAS performed on alcohol-use patterns across time as a function of marital-transition group supported the notion that individuals begin moderating their alcohol consumption prior to their actual transition to married status with the trend continuing into the first year of marriage. The data further suggested that this decline in alcohol use stabilizes shortly thereafter, apparently within 1 year after marriage.

Adolescent↗

Functional data analysis with application to periodically stimulated foetal heart rate data. I: functional regression.

Functional regression is used to model longitudinal data where the number of measurements on the functional covariate is much greater than the number of subjects in the study. Thus, functional regression can be thought of as singular longitudinal analysis. We have modified existing functional regression techniques to the case of a functional covariate with a repeated stimulus. We applied this modified functional regression to periodically stimulated foetal heart rates. The heart rate tracings were used as a predictor of the child's psychomotor development at approximately 18 months of age. In the past, this type of data has been analysed using the partially subjective concept of habituation. By using the entire heart rate tracings through functional regression, we have the advantage that habituation does not need to be defined and all available information is used to predict later child development.

Adult↗

[Indices allowing early detection of chronic pulmonary emphysema].

To establish criteria allowing early detection of pathologically significant alterations in pulmonary emphysema caused by smoking, pulmonary-function tests and high-resolution computed tomography were done in 104 subjects categorized into three groups: nonsmoking healthy adults, smokers with a normal FEV1%, and smokers with a low FEV1% (cross-sectional analysis). Fifty-six of the 104 patients underwent pulmonary-function testing and high-resdution computed fomography once per year for 3 years (longitudinal analysis). Cross-sectional and longitudinal analyses showed that abnormalities in functional residual capacity, in single-breath diffusing capacity for carbon monoxide, and in the average tomographic density of sections in the lower lung fields obtained after a deep inspiration could be used to predict whether the disease would reach an advanced stage, even if the patients had no significant symptoms at the time of testing. Relative areas of low-attenuation regions, which were alleged to directly reflect the size of emphysematous areas, appear not to be useful for early detection of pathological emphysema.

Chronic Disease↗

Characteristics of assaultive psychiatric patients: fifteen-year analysis of the Assaulted Staff Action Program (ASAP).

This study reports on a fifteen-year longitudinal analysis of the characteristics of assaultive patients in one public-sector mental health care system. The data were gathered within the context of the Assaulted Staff Action Program (ASAP), a crisis intervention service for staff victims. The fifteen-year findings were consistent with previous worldwide research on assaultive patients and included both older male patients with schizophrenia and younger personality-disordered patients as high-risk assailants. Both groups had appreciable histories of violence toward others, personal victimization, and substance use disorders. The role of these three clinical variables in association with subsequent assaults, the role of trauma in female assailants, and the consistency of the fundamental characteristics of assaultive patients during several service system initiatives were examined. Implications for research and intervention are discussed.

Adult↗

Establishing the constructs of childhood behavioral disturbances in a Chinese population: a questionnaire study.

The behavioral problems of Chinese children were examined in a questionnaire study of a representative sample of 3,069 seven-year-old Chinese schoolboys in Hong Kong using Rutter's questionnaires for completion by parents and teachers. Separate robust dimensions of hyperactivity, antisocial, and neurotic behaviors were evident. The correlations among different dimensions were similar to those reported in the West. Short-term longitudinal analysis suggested that these dimensions were stable over time and that antisocial behaviors might develop in hyperactive children. The finding highlights the necessity of differentiating the hyperactive domain from the antisocial one. A significant source effect was found in all three dimensions. Chinese schoolboys had nearly two times the level of questionnaire-rated hyperactivity compared with school boys in the West; but it is premature to conclude that hyperactivity is more common in Chinese schoolboys in Hong Kong. Cross-cultural differences in adults' expectations and tolerance remain a plausible explanation.

Caregivers↗

What proportion of couples undergoing unrestricted in vitro fertilization treatments can expect to bear a child?

A 200-patient cohort has been established so that longitudinal analysis can determine the likelihood of an individual in vitro fertilization (IVF) entrant achieving a viable uterine pregnancy or a live baby. After a minimum of 39 months of access to repeated treatment cycles, 24% have achieved at least one viable pregnancy by undergoing an average of 2.48 treatment cycles per cohort member. Life-table analysis shows that most of these pregnancies have occurred in the first year after entering the program. Many members have undergone only one or two treatment cycles. In the future, greater emphasis will need to be placed on factors which encourage couples to undergo additional cycles of treatment. This, as much as technical advances, may increase outcome figures.

Actuarial Analysis↗

[Sudden infant death syndrome in Hamburg. An epidemiologic analysis of 62 cases].

During a two years period (1978/79) all 62 victims of sudden and unexplained death in Hamburg have been analysed retrospectively. For statistical analysis a control group of 297 healthy life births was used. The overall incidence of SIDS amounted to 2.4 per 1,000 life births. In the VLBW children the figure raised up to 9.1%. SGA children were highly overrepresented. Amongst Turkish mothers there were only two cases (3.2%) significantly less than with other groups. (9.1% of all life births in 1979 were Turkish). An ethnological factor can be discussed. In the lowest social class more SIDS cases were encountered. The analysis of the circumstances around death confirmed previous results. A consecutive and longitudinal analysis of SIDS cases seems mandatory for evaluating the effect of preventive methods.

Age Factors↗

Fall of cholesterol with time on dialysis: impact on atherogenicity.

The majority of patients treated for chronic renal failure die from cardiovascular complications. Lipid abnormalities in this group are thought to contribute to this high mortality. The authors have shown that hemodialysis patients with longer months on dialysis tend to have lower total cholesterol (TC) levels. This study extends data to examine lipid disturbances in 53 continuous ambulatory peritoneal dialysis (CAPD) and 126 hemodialysis patients using multivariate analysis. Longitudinal values after 9-10 months were measured in 16 CAPD patients and 52 hemodialysis patients. Analysis of covariance for all patients demonstrated an inverse correlation of TC (p = 0.003), high-density lipoprotein (HDL) cholesterol (p = 0.01), and apolipoprotein A-I levels (p less than 0.02) with months on dialysis. In addition, the TC level was higher in women (p less than 0.001) and CAPD patients (p less than 0.001), and correlated with age (p = 0.02) and albumin (p less than 0.001). HDL cholesterol was higher in blacks (p less than 0.001) but was not affected by gender, dialysis modality, age, or albumin. Diabetic status, serum parathyroid hormone, and blood pressure were not significant variables for TC or HDL-C. The atherogenic risk indicators, TC/HDL cholesterol (p less than 0.001) and apolipoprotein B (p less than 0.02) were higher in whites than in blacks. Longitudinal study revealed lower TC levels in individual hemodialysis patients (p less than 10(-6) by paired t-test), the fall being greater for patients with fewer total months on dialysis (p less than 0.04, by analysis of covariance). CAPD patients had no change in TC by paired t-test.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins↗

Profile comparisons of physical growth for monozygotic and dizygotic twin pairs.

Three different methods of analysing similarity of physical growth curves within MZ and DZ twin pairs are compared. The concordance of the curves for each pair can be measured by either a multiple regression coefficient (R2) or the square root of the sum of squared differences between corresponding deviation points (D). The latter seems to be a more appropriate measure of profile contour similarity, mainly because the distance between curves is allowed for. An intra-class correlation based on a longitudinal analysis of variance seems to be a useful measure of average profile similarity for comparing groups of individuals. The distributions of the D measures, calculated for all MZ and DZ twin pairs, show MZ pairs to have significantly smaller D-values for both height and weight, on average, than DZ pairs. The intra-class correlations also show a higher concordance in developmental profile for MZ in comparison to DZ.

Adolescent↗

Developmental typology of trajectories to nighttime bladder control: epidemiologic application of longitudinal latent class analysis.

The authors aimed to characterize developmental trajectories to nighttime continence by applying two latent class models-longitudinal latent class analysis (LLCA) and latent class growth analysis (LCGA)-to data on nighttime bed-wetting from a population-based birth cohort, the Medical Research Council 1946 National Survey of Health and Development cohort. Data on a binary outcome (wetting in the past month vs. not wetting) were available for children at six ages (4, 6, 8, 9, 11, and 15 years) assessed in 1950, 1952, 1954, 1955, 1957, and 1961. For 3,272 children with complete data (62.5% of the cohort), results of sequential model comparisons (T classes vs. T + 1 classes) and chi-square goodness-of-fit tests were evaluated using parametric bootstrapping. At least four trajectory classes (LLCA and LCGA) were identified. Associations between class membership and the prevalence of related measures were examined using a confirmatory latent class analysis approach. Inclusion of 1,483 children with partially incomplete data (n = 4,755; 90.9% of the cohort) enabled the authors to refine trajectories further: normal development (prevalence = 84.0%); delayed acquisition of bladder control ("transient" (8.7%) and "persistent" (1.8%)), capturing primary enuresis; chronic bed-wetting (2.6%), or experiencing night wetting until age 15 years; and a final trajectory (relapse = 2.9%) capturing secondary or onset enuresis. This empirically based, typologic approach to analysis of extensive longitudinal data in a general population sample provides an alternative perspective to that offered by traditional diagnostic criteria.

Adolescent↗

Prospective serial analysis of interleukin-2 and soluble interleukin-2 receptor in relapsing-remitting multiple sclerosis.

We performed a longitudinal analysis of serum interleukin-2 (IL-2) and soluble IL-2 (sIL-2R) concentrations in 60 patients with relapsing-remitting (R-R) multiple sclerosis (MS) as well as in 33 age- and sex-matched normal controls. Overall, we found that serum IL-2 levels remained low (less than 10 U/ml) and did not change appreciably over time; however, marked fluctuations in sIL-2R levels were observed in both the patient and control groups. Using patients as their own controls, we calculated an interrelapse (disease stable) mean sIL-2R concentration as a baseline for comparison with relapse values; sIL-2R levels greater than the 90th percentile of the Student's t distribution of stable values were defined as "peaks." There were a total of 27 sIL-2R peaks, eight (30%) of which correlated with clinical relapses but were potentially predictive of only 18% (8/45) of all the recorded clinical relapses. There was no difference in disease severity (Expanded Disability Status Scale) score between peak-correlated and noncorrelated relapses. Our data suggest that despite reports of elevated levels of IL-2 and sIL-2R in MS, neither may be a useful marker for predicting clinical disease activity in R-R MS.

Adolescent↗

Does lymphatic absorption change with the duration of peritoneal dialysis?

BACKGROUND: Ultrafiltration failure is an important complication of long-term peritoneal dialysis (PD). A high effective lymphatic absorption rate (ELAR) can contribute to impaired ultrafiltration. It is unknown whether the ELAR increases with time on PD. OBJECTIVE: The relationship between the ELAR and duration of PD was analyzed, as well as the correlation between the ELAR and other transport parameters. We also studied the relation between the ELAR and cancer antigen 125 (CA125) a marker for mesothelial cell mass. SETTING: Peritoneal dialysis unit in the Academic Medical Center, Amsterdam. DESIGN: Cross-sectional and longitudinal studies of standard peritoneal permeability analyses (SPAs; 4-hour dwells, dextran 70 as a volume marker) with glucose 3.86% in 130 PD patients. METHODS: SPAs were analyzed in 130 stable PD patients (77 males). Median duration of PD was 25 months (range 1-214) in a cross-sectional study. The last SPA from each patient was analyzed. The longitudinal analysis included 24 patients (12 males) from whom at least 3 SPAs were available with a minimum interval of 8 months. Dextran 70, 1 g/L, was administered intraperitoneally at the initiation of the test. Lymphatic absorption was calculated from the disappearance rate of dextran 70 during the 4-hour dwell. Therefore, the ELAR included both transmesothelial and subdiaphragmatic uptake of dextran 70. RESULTS: Median ELAR was 1.43 mL/minute (range 0.17- 6.59 mL/minute). No relationship was found between the ELAR and duration of PD in the cross-sectional analysis, nor was there a trend in time for 20 of the 24 patients studied longitudinally. In 4 patients, a negative trend was found. None of these had ultrafiltration failure and all 4 patients had a different cause for end-stage renal failure. The ELAR was correlated with parameters of peritoneal solute transport, but not with CA125 when investigated in a cross-sectional analysis. Only after 48 months of PD treatment was a significant relationship between the ELAR and CA125 seen (r = 0.46, p < 0.05). CONCLUSIONS: No time trend is present for the effective peritoneal lymphatic absorption rate, and it is not associated with patient or technique survival. Although increased lymphatic absorption is one of the causes of ultrafiltration failure, it is unlikely to contribute to the development of ultrafiltration failure in long-term PD patients with well-maintained transcapillary ultrafiltration.

Adolescent↗

Polymorphisms in the androgen receptor and type II 5 alpha-reductase genes and prostate cancer prognosis.

BACKGROUND: Cytosine-adenine-guanine repeat length of the androgen receptor gene and the A49T and V89L polymorphisms of the 5 alpha-reductase (SRD5A2) gene have been associated with prostate cancer. METHODS: We investigated the relationship of the three genetic polymorphisms to tumor grade among 211 men who had undergone radical prostatectomy. Subjects had prostate cancer <3 cm(3) with a percentage of cancer represented by Gleason grade 4 or 5 (% Gleason grade 4/5) of either > or = 20% or < or = 5%. We also examined the association between those genetic markers and prostate specific antigen (PSA) failure among 112 subjects with > or = 20% Gleason grade 4/5. RESULTS: In cross-sectional analysis, none of the polymorphisms was a significant predictor of % Gleason grade 4/5. In longitudinal analysis, the LL genotype at the V89L site was associated with statistically significant four- to sixfold increase in PSA failure risk after adjustment for clinicopathologic variables. CONCLUSIONS: We observed poorer prognosis among men with the LL genotype at codon 89 of the SRD5A2 gene. Lack of consistency between studies must be resolved before clinical utility of this marker is established.

Biomarkers, Tumor↗

Limiting dilution analysis of antigen stimulated IL-4 and IFN-gamma production in human mononuclear cell populations.

Limiting dilution analysis (LDA) of fresh human mononuclear cell populations has previously been used to estimate the frequency of specific B cells, CTL, proliferative T cells, or cells capable of IL-2 production in various clinical situations. Such approaches evaluate the intensity of the response but provide little information concerning the balance between Th1- vs. Th2-like patterns of cytokine gene expression. Here, we describe development of an LDA method to obtain quantitative estimates of the frequency of antigen-specific IFN-gamma or IL-4 producing cells in human peripheral blood. The approach utilizes 3-4 day antigen-mediated restimulation of mononuclear cell populations freshly derived from grass pollen sensitive allergic rhinitis subjects. IFN-gamma and IL-4 production in culture supernatants are determined by ELISA and CT.h4S bioassay. Cytokine production elicited in this assay is CD4 dependent and antigen specific. As such, it provides a useful non-invasive approach for rapid evaluation of low frequency, antigen-induced cytokine production in the circulating repertoire. This method can readily be extended to analysis of other cytokines in other immunologic disorders or in infectious disease states, allowing longitudinal analysis of individuals and facilitating efforts to establish clear correlations between in vivo patterns of cytokine gene expression and disease exacerbation and remission.

Adolescent↗