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The Zurich Study. XVIII. Obsessive-compulsive disorders and syndromes in the general population.

The cross-sectional and longitudinal association between obsessive-compulsive syndrome (OCS) and other psychiatric problems and the course over 11 years was examined in a Swiss cohort of young adults. As the prevalence of obsessive-compulsive disorders, defined according to the DSM-III was very low (n = 5), we applied a lower diagnostic threshold based on obsessive-compulsive symptoms and social impairment, to define an OCS. The weighted lifetime prevalence rate for OCS at age 30 years was 5.5%. The mean age of onset was 17.1 +/- 4.9 years for males, and 19.1 +/- 5.1 year for females. OCS was associated with all subtypes of depressive disorders as well as with social phobia and agoraphobia. Although the longitudinal analysis showed no stability at the diagnostical level, there was some stability on the symptom level. Perhaps subjects with OCS learned in time to cope and to live with their symptoms without suffering.

Adaptation, Psychological↗

The importance of triglycerides: results from the Prospective Cardiovascular Münster (PROCAM) Study.

In the PROCAM study hypertriglyceridaemia was much more common among men (18.6%) than women (4.2%). Prevalence increased with age in women, but remained nearly constant at about 20% in men aged 35 years or more. In a multiple regression analysis a strong negative correlation between triglycerides and HDL cholesterol was found. A positive relationship was observed with cholesterol, blood glucose, factor VIIc, and PAI-1 in both sexes. Only in men, triglycerides are positively correlated with Apo A-I, body mass index, cigarette smoking, and alcohol consumption. Postmenopausal women showed higher triglyceride levels than premenopausal women. No independent relationships were observed to age, blood pressure, Lp(a), Apo A-II, Apo B, AT-III, protein C, fibrinogen, and oral contraceptives. A longitudinal analysis of data from 4474 male PROCAM participants aged 40-64 years with a follow-up of 4 years did not identify triglycerides as an independent risk factor, but the data suggest hypertriglyceridaemia is an additional risk factor for CHD, when excessive triglycerides coincide with a high ratio of plasma cholesterol to HDL-cholesterol and with low HDL-cholesterol values.

Adolescent↗

Distinct patterns of T cell receptor distribution of peripheral blood CD8+ cells during different stages of chronic infection with hepatitis B virus.

We compared the Vbeta TCR repertoires of CD8+ peripheral blood lymphocytes between 21 patients with chronic hepatitis B (CHB) and 9 healthy individuals, using RT-PCR analysis. Several differences were seen between CHB patients and controls, including a marked increase in the expression of two to five Vbeta families in the CHB patients. There was no evidence for a superantigen effect, although an increase in Vbeta7 was seen in 64% of patients. A significant under-expression of Vbeta families were also detected, particularly in patients with active liver disease in which under-expression of Vbeta14 and Vbeta15 was associated with acute exacerbations of liver disease. We also did a longitudinal analysis of the TCR repertoire in two patients over a period of 6 months, from the initiation of a disease flare to its resolution. One patient continued to experience spontaneous flares following the completion of this study, while the other patient underwent spontaneous remission with long-term (> 12 months) loss of HBeAg following resolution of the flare. The TCR repertoires of both patients were altered during the flare, and there was a higher degree of TCR variability in the patient who went into remission.

Adult↗

Characterization and geographic location of sources of radioactivity lost downhole in the course of oil and gas exploration and production activities in Texas, 1956 to 2001.

Case reports describing sources of radioactivity lost downhole in Texas from 1956 to 2001 were obtained from the Texas Department of Health Bureau of Radiation Control and entered into a computerized database. The events of the 45-y period of analysis were characterized, examining aspects such as source type, amount of activity, location of loss, depth, and date of occurrence. Results of the study found that 316 downhole source incidents were reported to the agency during this period of time, representing a total of 426 distinct sources of radioactivity lost downhole within the boundaries of the State of Texas. The sources lost were predominantly AmBe, accounting for 74 TBq of radioactivity at the time of loss, and Cs, accounting for 16.3 TBq of radioactivity. A longitudinal analysis of the data showed the average loss per active oil and gas rig in Texas (known as "rig count") at approximately 24 losses per 1,000 rigs. Specific geographic information was largely missing from many of the records, which prevented the geolocation of wells described to contain lost radioactive sources. As a result, most wells could only be located to the county level, and no comprehensive geographical information system (GIS) map could be accurately created from the data. However, when available, source location information was standardized to permit the characterization of the sources reported as lost. This effort produced the first dedicated compendium of lost downhole sources for the State of Texas and provides an important source of information for regulatory agencies. The ability to provide prompt information about the fate and location of sources of radioactivity is important to regulatory officials, given the recent concerns about radiation source inventory control in the post 9/11 world as it relates to the possible creation of radiological dispersal devices.

Fuel Oils↗

Retrospective, longitudinal, and cross sectional study of visual acuity impairment in choroideraemia.

BACKGROUND/AIMS: Few studies have reported on the change in visual acuity (VA) in patients with choroideraemia. In order to determine the degree and rate of VA impairment associated with this disease, the central VA was analysed in a large group of patients with choroideraemia. METHODS: The authors completed a retrospective, cross sectional review of 115 patients with choroideraemia from three tertiary care centres. A longitudinal analysis was performed on 45 of these patients who met the inclusion criteria of at least three visits over a minimum period of 4.5 years. Multiple linear regression analysis was used to explore the 5 year rate of VA change while controlling for initial VA and initial age. Multiple logistic regression was also used to investigate VA impairment. RESULTS: In the cross sectional group (n = 115), 84% (87/103) of patients under the age of 60 had a VA of 20/40 or better while 33% (4/12) of patients 60 years of age or older had a VA of 20/200 or worse at their most recent visit. The majority of the patients (93%) in the longitudinal subgroup of 45 patients had a VA of 20/30 or better at their initial visit. The mean 5 year rate of VA change was 0.09 logMAR equivalent (approximately one line on the Lighthouse chart). CONCLUSION: In this cohort of patients with choroideraemia, there was typically a slow rate of VA loss and the prognosis for central VA retention was, as a group, favourable until the seventh decade.

Adolescent↗

Serologic evidence of human metapneumovirus circulation in Uruguay.

First identified in 2001, the human metapneumovirus (hMPV), is a respiratory tract pathogen that affects young children, elderly, and immunocompromised patients. The present work represents the first serologic study carried out in Uruguay. It was performed with the purpose of obtaining serological evidence of hMPV circulation in Uruguay and to contribute to the few serologic reports described until now. Sixty nine serum samples collected between 1998 and 2001 by vein puncture from patients without respiratory symptoms or underlying pathology aged 6 days to 60 years were examined using an indirect immunofluorescence assay (IFA). The global seropositivity rate of the samples was 80% (55/69). Rates of 60% (15/25) and 91% (40/44) were observed for the pediatric and adult cohorts, respectively. Results obtained from a longitudinal analysis of 6 children aged 6 days to 18 months are discussed. These results are a clear evidence of hMPV circulation in Uruguay, at least since 1998, and reinforce the previous data on worldwide circulation of this virus.

Adolescent↗

Sexual dimorphism in body composition changes during the pubertal period: as shown by French-Canadian children.

Size and velocity growth curves of stature to represent skeletal growth, lean arm circumference to represent muscle growth, and the sum of three skinfolds to represent fat tissue changes, are presented for a longitudinal study of Montreal school-age chidren. Both a chronological age scale, and one relative to the individual ages of peak growth velocity in stature, are used. Intercorrelations between the various components are tabulated for age groups based on the two scales. The three skinfolds are also analyzed separately. The results show that such simple anthropometric measures can be usefully taken to represent the growth of different body components. Longitudinal analysis reveals that, whereas the relationship of muscular to statural growth in boys is purely maturational, it is not so for girls, and that the different skinfolds show complex sexual differences in growth during the pubertal period.

Adipose Tissue↗

A longitudinal cephalometric study on unilateral cleft lip and palate subjects.

The facial growth of nine male and 9 female subjects with surgically repaired unilateral cleft lips and palates was compared to that of 20 male and 15 female non-cleft individuals. Different cephalometric landmarks were identified on the cranial base and maxillary complex, and eleven different parameters were measured. Univariate longitudinal growth profile and mean vector analyses as well as multivariate and cross-sectional comparisons were performed between male, female, and combined normal and cleft groups. Linear data comparisons indicated statistically significant differences in the growth profile and mean vector analyses of several of the parameters describing the relationship (SNA and SNAns) and dimensions (Ans-Ptm and A-Ptm) of the maxillary complex. Incremental data comparisons on the same parameters (SNA, SNAns, Ans-Ptm and A-Ptm) indicated statistically significant differences in the mean vector longitudinal analysis and the univariate cross-sectional analysis. Most of these significant differences were concentrated in the older age comparisons (7 to 8, 8 to 9, and 9 to 10 years). Where significant differences existed, the normal sample increments were usually greater than the cleft sample increments.

Cephalometry↗

Effects of preterm extrauterine visual experience on the development of the human visual system: a flash VEP study.

To compare the functional maturation of the human visual system between intra- and extrauterine course flash visual evoked potentials (VEPs) in preterm infants (gestational age 24 to 36 weeks). Previously established normal values, with special reference to the two components of the N1 wave, were employed (Tsuneishi 1995). A cross-sectional analysis of 124 infants at 36 weeks postmenstrual age (PMA), showed that there are no differences in the absolute values of VEP peak latencies depending on the postnatal age (PNA). Conversely, the N1 wave form changes with increasing PNA from a wave in which the early peak (N1a) has a higher amplitude than the late peak (N1b) into the reverse situation with a higher amplitude of the N1b as compared to N1a. This observation may correlate with the maturation of the neuronal networks in the visual cortex. In a longitudinal analysis of 50 infants followed for more than 5 sessions of weekly recordings, we found that the individual rapid decrease in the N1a latency, which may reflect the initiation of myelination in the optic radiation, most frequently occurs at around 37 weeks PMA, regardless of PNA. Preterm extrauterine visual experience has little effect on the myelination process in the visual pathway, but has a marked effect on the developmental changes in VEP wave form which reflect the developmental changes of the neuronal networks in the visual cortex.

Cross-Sectional Studies↗

Renal outcomes in pediatric liver transplantation.

The outcomes of 294 orthotopic liver transplants performed in 221 children at The University of Chicago Children's Hospital between October 1984 and October 1992 have been retrospectively reviewed. Medical information for 281 transplant in 210 children was sufficient for inclusion in this analysis. The mean age at transplant was 4.1 +/- 5.0 yr. Forty-four percent of the children were male, and 16% of the transplants were living-related. Four children received combined liver-kidney transplants. Seventy-six percent of the children are currently alive. The incidence of acute renal failure occurring following transplantation and requiring dialysis was 6.2% with a mortality rate of 85%. Early postoperative hypertension was seen in 65% of the children and persistent hypertension of greater than 12 months duration was seen in 28%. Sixteen percent of children developed metabolic acidosis requiring sustained sodium bicarbonate supplementation. Aggregate and longitudinal analysis of serial calculated glomerular filtration rates revealed abnormal renal function in approximately one third of children at any given time period following transplantation. The renal dysfunction was unrelated to age at transplant, type of transplant, gender, previous transplants, rejection episodes, courses of nephrotoxic drugs, presence of hypertension, or cyclosporin dose. This review supports prior studies which document abnormal renal function following orthotopic liver transplantation in a significant proportion of children.

Acidosis↗

The effect of air pollution on inner-city children with asthma.

The effect of daily ambient air pollution was examined within a cohort of 846 asthmatic children residing in eight urban areas of the USA, using data from the National Cooperative Inner-City Asthma Study. Daily air pollution concentrations were extracted from the Aerometric Information Retrieval System database from the Environment Protection Agency in the USA. Mixed linear models and generalized estimating equation models were used to evaluate the effects of several air pollutants (ozone, sulphur dioxide (SO2), nitrogen dioxide (NO2) and particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10) on peak expiratory flow rate (PEFR) and symptoms in 846 children with a history of asthma (ages 4-9 yrs). None of the pollutants were associated with evening PEFR or symptom reports. Only ozone was associated with declines in morning % PEFR (0.59% decline (95% confidence interval (CI) 0.13-1.05%) per interquartile range (IQR) increase in 5-day average ozone). In single pollutant models, each pollutant was associated with an increased incidence of morning symptoms: (odds ratio (OR)=1.16 (95% CI 1.02-1.30) per IQR increase in 4-day average ozone, OR=1.32 (95% CI 1.03-1.70) per IQR increase in 2-day average SO2, OR=1.48 (95% CI 1.02-2.16) per IQR increase in 6-day average NO2 and OR=1.26 (95% CI 1.0-1.59) per IQR increase in 2-day average PM10. This longitudinal analysis supports previous time-series findings that at levels below current USA air-quality standards, summer-air pollution is significantly related to symptoms and decreased pulmonary function among children with asthma.

Air Pollutants↗

Rate of functional decline in Huntington's disease. Huntington Study Group.

OBJECTIVE: To determine the rate of functional decline in a large cohort of patients with Huntington's disease (HD) followed at 43 sites by the Huntington Study Group (HSG). METHODS: The annual rate of functional decline was measured using the Total Functional Capacity Scale (TFC) and the Independence Scale (IS) in 960 patients with definite HD followed prospectively for a mean of 18.3 months. All patients were rated with the Unified Huntington's Disease Rating Scale (UHDRS). Sample size calculations for hypothetical clinical trials were calculated. RESULTS: A factor analysis of the UHDRS at baseline yielded 15 factors accounting for 77% of the variance. The TFC score declined at a rate of 0.72 units/year (standard error [SE] 0.04) and the IS score declined at a rate of 4.52 units/year (SE 0.23). Lower TFC score at baseline, indicating more severe impairment, was associated with less rapid annual decline in TFC score, perhaps reflecting the floor effect of the scale. The annual rate of decline for 575 patients with baseline TFC scores of 7 to 13 was 0.97 (SE 0.06), was 0.38 (SE 0.08) for 270 patients with baseline TFC scores of 3 to 6, and was 0.06 (SE 0.1) for 101 patients with TFC scores of 0 to 2. In multivariate analysis (n = 960), longer disease duration and better cognitive status at baseline were associated with a less rapid rate of decline in TFC score, whereas depressive symptomatology was the only factor associated with more rapid decline on the IS score. Age at onset of HD, sex, weight, and education did not affect decline on either score. CONCLUSIONS: The comparable rates of decline on the TFC and the IS scores with other published studies suggest that these estimates of functional decline are representative of HD patients who are evaluated at HSG research sites. In longitudinal analysis, longer disease duration and better neuropsychological performance at baseline were associated with a less rapid rate of decline in TFC score, whereas depressive symptomatology at baseline was associated with a more rapid decline in the IS score. These rates of functional decline and the covariates that modify them should be considered in estimating statistical power and designing future therapeutic trials involving HD patients with early or moderately severe disease.

Activities of Daily Living↗

[Prognostic value of early normalization of CA 125 during chemotherapy in stages III and IV ovarian tumors].

The value of early CA 125 assays and analysis of its diminution kinetics during chemotherapy have been the subject of numerous studies. In contrast, routine utilization of CA 125 assays in clinical practice remains controversial or at best difficult to apply because the definitions and prognostic values associated with CA 125 assays vary greatly from one study to the next. This study was designed to determine whether serial CA 125 assays during induction chemotherapy for ovarian carcinoma, using simple evaluation criteria directly applicable in routine clinical practice such as early normalization (level < 35 UI/ml) are predictive of response to treatment or improved survival. This retrospective longitudinal analysis concerned a historical population of 140 patients with ovarian carcinoma stages III and IV treated at the Antoine-Lacassagne Cancer Center between 1978 and 1993. All the patients were treated by chemotherapy based on platinum salts every 21 days. Serum CA 125 assays were performed both before and after surgery and during each chemotherapy cycle. Eighty-four patients had a pre-operative CA 125 assay. No difference is observed in survival as a function of their preoperative CA 125 concentration (p = 0.4). Sixty-seven patients had a CA 125 assay the 6th week after initiation of chemotherapy, 62 the 9th week and 47 the 18th week. Normalization of CA 125 the 6th week (p = 0.0001), the 9th week (p = 0.0008) and the 18th week (p = 0.03) after the initiation of the chemotherapy cycle are correlated with survival. The median survival in our study is 42 months if the CA 125 is below 35 UI/ml the 6th week versus 13 months if the level of CA 125 remains more than 35 UI/ml. In all, 66 of the 105 FIGO stage III patients underwent second-look surgery. Normalization of CA 125 levels is correlated with the absence of any gross residual tumor at the second-look procedure, the 6th week of chemotherapy (p = 0.0019), the 9th week of chemotherapy (p = 0.0003) and the 18th week of chemotherapy (p = 0.0015). This correlation is not confirmed when the presence of histologic residual tumor in biopsy specimens obtained during second-look surgery is taken into consideration. Overall, 88% of patients whose CA 125 levels failed to normalize during evaluation at the second cycle of chemotherapy have residual tumor at second-look surgery. Outside of clinical trials, repeated early CA 125 assays to determine the chemosensitivity and the prognosis of patients with ovarian carcinoma are of little interest compared to a single CA 125 assay at the 6th week after initiation of chemotherapy. This approach seems to be a good compromise between the information sought and its practical use. However the interest of early modification of chemotherapy regimen after 2 cycles, if the level of CA 125 remains more than 35 UI/ml, will have to be showed.

Adenocarcinoma↗

Apolipoprotein E epsilon 4 affects new learning in cognitively normal individuals at risk for Alzheimer's disease.

The Apolipoprotein E (APOE) epsilon 4 allele is an important risk factor for Alzheimer's disease (AD). Given the interest in early identification of at-risk individuals, we examined memory decline as a function of APOE status and age in cognitively intact participants aged 48-77 years old (yo). Participants were grouped by age (<60 versus > or =60) and APOE (epsilon4+/-). Longitudinal analysis of several components of memory over a 2-year interval showed a significant Age-by-APOE interaction reflecting a decline in new learning for the > or =60 epsilon4+ group only. Among epsilon4+, 76% of the > or =60 participants showed a decline versus 32% of the <60, but the amount of decline in new learning over the 2-year interval within the > or =60 group was not further influenced by age. That is, the size of the 2-year change was the same for 60 and 70 year old participants. This suggests that longitudinal study of new learning is a sensitive measure for detecting early cognitive changes in at-risk individuals that precede the symptomatic onset of mild cognitive impairment and AD.

Aged↗

Antigenic stimulation specifically reactivates the replication of archived simian immunodeficiency virus genomes in chronically infected macaques.

Human immunodeficiency virus/simian immunodeficiency virus (SIV) diversification is a direct consequence of viral replication and occurs principally in secondary lymphoid organs where CD4(+) T cells are activated and proliferate. However, the evolution of viral quasispecies may also be driven by various nonexclusive mechanisms, including adaptation to specific immune responses and modification of viral fitness. Analysis of viral quasispecies in SIV-infected macaques subjected to repeated antigenic stimulations allowed us to demonstrate transient expansions of SIV populations that were highly dependent upon activation of antigen-specific T cells. T-cell clones expanded in response to a particular antigen were infected by a specific viral population and persisted for prolonged periods. Upon a second stimulation by encounter with the same antigen, these specific genomes were at the origin of a new burst of replication, leading to rapid but transient replacement of the viral quasispecies in blood. Finally, longitudinal analysis of SIV sequence variation during and between antigenic stimulations revealed that viral evolution is mostly constrained to periods of strong immunological activity.

Amino Acid Sequence↗

Early correction of cell cycle perturbations predicts the immunological response to therapy in HIV-infected patients.

OBJECTIVE: To determine whether changes in the indices of HIV-associated cell cycle dysregulation (i.e., increased expression of cyclin B1 and abnormal nucleolar structure) may predict the level of immunological reconstitution in HIV-infected patients treated with highly active antiretroviral therapy (HAART). METHODS: Cross-sectional and longitudinal analysis of viral load, CD4 T cell counts, cyclin B1 expression, and AgNOR number and area of distribution in 30 HIV-infected patients who were studied before and up to 6 months after initiation of HAART. RESULTS: In HIV-infected individuals, the level of cell cycle dysregulation correlated with the type of response to HAART. While low levels of dysregulation were present in patients with complete (both virological and immunological) response to HAART, high levels were present in HAART-treated patients with limited CD4 T cell increases despite persistent viral suppression (immunological non-responders). Importantly, the level of correction of cell cycle dysregulation after 60 days of therapy predicted the level of immune reconstitution after 6 months. CONCLUSION: These observations suggest that correction of cell cycle dysregulation predicts a good immunological response to HAART and that sequential analysis of cell cycle dysregulation might help to identify patients that could benefit from alternative, immune-based interventions in addition to standard HAART.

Antiretroviral Therapy, Highly Active↗

Evaluation of the presence of 2-LTR HIV-1 unintegrated DNA as a simple molecular predictor of disease progression.

In a preliminary cross-sectional analysis of 109 human immunodeficiency virus type 1 (HIV-1)-infected subjects the presence of 2-long terminal repeat (LTR) unintegrated circular HIV-1 DNA in peripheral blood mononuclear cells (PBMC) was found to be associated with both symptomatic infection (P = 0.0037) and low CD4 counts (P = 0.0004). To investigate the prognostic significance of the presence of 2-LTR HIV-1 DNA, a subset of 23 2-LTR-negative and 25 2-LTR-positive asymptomatic individuals were followed up for 12-24 months. The two groups did not differ in terms of baseline CD4 counts, zidovudine (ZDV) therapy, and duration of HIV-1 infection. Longitudinal analysis of CD4 values did not indicate a significantly different CD4 outcome between the two groups. However, when only ZDV-treated subjects were considered, a significant (P = 0.042) decrease in CD4 counts was found at month 24 with respect to baseline in 2-LTR-positive (n = 12) but not in 2-LTR-negative (n = 11) patients. Moreover, when > 40% CD4 loss from baseline and/or development of CDC stage B or C symptoms were considered as indicators of disease progression, there was a significantly higher number of events in the whole 2-LTR-positive group than in the whole 2-LTR-negative group (P = 0.0197 at month 12, P = 0.0299 at month 18, P = 0.0373 at month 24). Thus, the presence of 2-LTR HIV-1 DNA in PBMC merits further investigation as a simple, qualitative, molecular predictor of disease progression and decreased response to antiretroviral therapy.

Cross-Sectional Studies↗

Alcohol and drug use in a Scottish cohort: 10 years on.

This paper reports the findings from a survey which elicited detailed information on patterns of alcohol use amongst a cohort of young adults. It is the fourth wave of data collection in a longitudinal study which began in 1979 on a study group of 1036 15-16 year olds attending schools in the Lothian region of Scotland. The longitudinal analysis presented here suggests that for this cohort, patterns of alcohol use at age 15-16 bear little relation to those at age 24-25 years. These findings are discussed, and compared in detail with the more limited alcohol data from the larger-scale National Child Development Study.

Adolescent↗