Combined screening for autoantibodies to IA-2 and antibodies to glutamic acid decarboxylase in first degree relatives of patients with IDDM. The DENIS Study Group. Deutsche Nikotinamid Interventions-Studie

To determine the value of antibodies to the intracytoplasmic domain of the tyrosine phosphatase IA-2 (anti-IA-2ic) and glutamic acid decarboxylase (GADA) for identification of subjects at risk for insulin-dependent diabetes mellitus (IDDM) we investigated 1238 first degree relatives of patients with IDDM for the presence of anti-IA-2ic and GADA and compared the results with cytoplasmic islet cell antibodies (ICA). Anti-IA-2ic were observed in 54 (4.4%) first degree relatives, in 51 of 86 (59.3%) ICA positive relatives and in 3 of 4 individuals who developed overt IDDM within a follow-up period of 1 to 28 months. GADA were found in 78 of 1238 (6.3%) first degree relatives. They were detected in 22 of 35 (62.9%) sera with ICA alone and in 1 of 3 subjects with anti-IA-2ic in the absence of ICA. Of the 1238 subjects 37 (3.0%) sera were positive for all three antibodies. Both anti-IA-2ic and GADA were positively correlated with high levels of ICA. Anti-IA-2ic and GADA were detected in 39.1 and 47.8% of subjects with ICA of less than 20 Juvenile Diabetes Foundation units (JDF-U) but in 66.7 and 76.2% of individuals with ICA of 20 JDF-U or more, respectively (p < 0.05). The levels of ICA and GADA in first degree relatives with at least one additional marker were significantly higher than in subjects with ICA alone (p < 0.005) or GADA alone (p < 0.03). The combination of anti-IA-2ic and GADA identified 84.9% of all ICA positive subjects and 93.7% of individuals with high level ICA (> or = 20 IDF-U). All 4 individuals who progressed to IDDM had either IA-2ic or GADA. Our data indicate that primary screening for anti-IA-2ic and GADA provides a powerful approach with which to identify subjects at risk for IDDM in large-scale population studies which may represent the basis for the design of new intervention strategies.     

Epidemiology, clinical aspects, and biology of IDDM patients under age 40 years. Comparison of data from Antwerp with complete ascertainment with data from Belgium with 40% ascertainment. The Belgian Diabetes Registry

OBJECTIVE: To compare the incidence rate of IDDM in the age-groups 0-14 and 15-39 years in Antwerp, Belgium, and to compare demographic, clinical, and biological data from Antwerp IDDM patients with 92% ascertainment with those from a larger Belgian patient group with 40% ascertainment. RESEARCH DESIGN AND METHODS: Incident cases of IDDM were reported by physicians of the Belgian Diabetes Registry and in Antwerp by several other sources. In Antwerp, completeness of ascertainment was calculated by the capture-recapture method. Demographic and clinical data were collected by questionnaire. Blood was sampled for HLA-DQ genotyping and, in new-inset patients, for autoantibodies. RESULTS: In Antwerp, the age- and sex-standardized IDDM incidence rates were similar in both age-groups (0-14 years: 11.8/100,000; 15-39 years: 8.9/100,000). The incidence rate decreased in girls above age 15 years (6.9/100,000; P = 0.003) but not in boys (11.0/100,000). Both in Antwerp and Belgium, IDDM was diagnosed more frequently in the 15-39 years age-group (60% of all cases) than under age 15 years, with a lower prevalence of acute symptoms, ketonuria, high-risk HLA-DQ genotype, and autoantibodies against insulin, islet cells, and IA-2, but with a higher prevalence of GAD65 autoantibodies. CONCLUSIONS: In Antwerp, the incidence rate of IDDM under age 15 years is intermediately high compared with the rates in other European regions. It is similar in the 15-39 years age-group, but with a marked male predominance. Demographic, clinical, and biological data show the same age-dependent heterogeneity as the data collected nationwide, with 40% ascertainment indicating the representativeness of the latter.     

A simple and rapid microSepharose assay for GAD65 and ICA512 autoantibodies in diabetes. Diabetes Incidence Study in Sweden (DISS)

Three scales, the Fake Bad Scale, the Fake Good Scale, and the Fake Bad-Fake Good scales were developed and evaluated with respect to their capacity to detect response manipulation on the Multiple Affect Adjective Check List-Revised. Cutting scores for each scale were cross-validated in two samples consisting of three groups: (1) college students simulating either "fake good" or "fake bad," (2) college students under standard instructions, and (3) psychiatric patients. Cutting scores on the three scales were compared with cutting scores established for the MAACL-R Dysphoria and Positive Affect plus Sensation Seeking. Analysis indicated that these scales were more accurate than the Positive Affect plus Sensation Seeking and the Dysphoria scales in detecting response manipulation.     

The prevalence of cutaneous manifestations in IDDM patients and their association with diabetes risk factors and microvascular complications

A questionnaire was administered to a random sample of family practitioners, internists, cardiologists, and geriatricians to examine the current management of heart failure patients with preserved versus reduced left ventricular systolic function. In patients with preserved systolic function, electrocardiogram at rest, chest x-ray, echocardiography, digitalis, angiotensin-converting enzyme inhibitors, and restriction of dietary sodium and physical activity are used less often, whereas calcium channel blockers and beta blockers are given more often than to patients with reduced systolic function.     

Early development and spreading of autoantibodies to epitopes of IA-2 and their association with progression to type 1 diabetes

Autoimmunity precedes clinical type 1 diabetes, and indicators of maturing autoimmune responses may be useful markers for disease prediction. To study this, epitope maturation of autoantibodies to the related protein tyrosine phosphatase (PTP)-like autoantigens IA-2 and IA-2beta was examined in sequential samples from birth in a cohort of 21 offspring developing multiple islet autoantibodies and a similar cohort of 48 relatives of patients with type 1 diabetes recruited at an older age. Initial reactivity in offspring was heterogeneous against the IA-2 juxtamembrane region (10/21) and PTP domains (13/21), and both specificity and extent of initial IA-2/IA-2beta autoantibodies were associated with HLA class II genotype. Intra-IA-2 epitope spreading and/or intermolecular spreading to IA-2beta epitopes were observed in seven offspring. In contrast, in older relatives, IA-2/IA-2beta Ab reactivity was stable and spreading rare. Development of diabetes in children was associated with the presence of Abs to the IA-2 juxtamembrane region (risk by age 5 yr, 52% vs 0% in those with PTP domain Abs only; p < 0.02), and 5 of 26 relatives who developed diabetes had IA-2 Abs only against the juxtamembrane region. The findings show that autoantibody reactivity to IA-2/IA-2beta is dynamic in the young, show that the juxtamembrane region of IA-2 is an early IA-2 autoantibody target, and suggest that these Abs are a risk factor for development of type 1 diabetes in infancy.     

The use of the Color-Your-Life technique with pediatric cancer patients and their siblings.

Examined the use of the Color-Your-Life (CYL) technique with 18 pediatric cancer patients (CPS), 20 siblings of pediatric patients (SIBS) and 40 controls, all aged 7–13 yrs. Findings show no differences were found between the groups for the percentages of colors. However, there were differences with respect to the way these groups represented negative emotions. SIBS tended to use the color/affect pair red/mad to indicate feelings of depression, while CPS used the absence of color, leaving white space on the paper. The Children's Depression Inventory (A. E. Kazdin, 1990) significantly correlates with the amount of blue (sad) that the Ss drew. However, this was not true for the State-Trait Anxiety Inventory for Children (C. D. Speilberger et al, 1973) and the amount of black (scared/nervous). CPS and SIBS who completed the CYL technique prior to completing the inventories had higher scores on these instruments than the children who completed the written instruments 1st. This finding was the opposite for controls, suggesting that these groups of Ss have different reactions to completing the CYL activity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Linkage and association between a CD4 gene polymorphism and IDDM in Danish IDDM patients. The Danish IDDM Epidemiology and Genetics Group, and The Danish Study Group of Diabetes in Childhood

PURPOSE: Our purpose was to determine the neuroradiologic findings of Marinesco-Sj?gren syndrome on plain skull radiographs, CT, and MR images. METHODS: Eight patients with proved Marinesco-Sj?gren syndrome (age range, 4 to 56 years) had a total of nine CT scans, seven MR imaging studies, and two plain radiographic examinations of the skull. The findings were reviewed retrospectively, with particular attention to the size of the posterior fossa and cerebellum. RESULTS: All patients had hypoplastic cerebellar hemispheres and a hypoplastic vermis in a small posterior fossa. One patient had a midline posterior fossa cyst and another had agenesis of the corpus callosum. CONCLUSION: Hypoplasia of the cerebellar hemispheres and the vermis and a small posterior fossa are the most prominent neuroradiologic findings in Marinesco-Sj?gren syndrome.     

Age and family relationship accentuate the risk of insulin-dependent diabetes mellitus (IDDM) in relatives of patients with IDDM

The international community of diabetologists is rapidly becoming involved in intervention trials aimed at preventing insulin-dependent diabetes in high risk relatives. Whereas age and relationship to a proband with insulin-dependent diabetes mellitus interacting with detected islet cell autoantibodies (ICA) are risk factors, their independent contribution to that risk remains unclear. In a prospective study of 6851 nondiabetic relatives of 2742 probands conducted between 1979-1993, we found age, but not relationship, to be a dramatic risk variable in ICA-positive persons as estimated by the Cox regression model. The 5-yr risk of insulin-dependent diabetes mellitus was 66% for those found to have ICA detectable before age 10 yr, falling progressively to less than 16% for ICA-positive relatives over age 40 yr. In ICA-negative relatives, age and relationship are independent prognostic variables.     

Interplay of four idiotypes and interaction with autoantibodies in lupus patients, their relatives and their spouses

Our aim was to investigate links between systemic lupus erythematosus (SLE)-associated autoantibodies, idiotypes (Id) and genetic predisposition to their development. We studied four public Ids (16/6, WRI 176 beta, RT72 and RT84), identified the Km and Gm phenotypes and sought six selected autoantibodies in 32 SLE patients, 174 of their relatives and 15 spouses. Though anti-double-stranded DNA antibody was uncommon in the relatives (9%), the range of antinuclear reactivities was as broad in the relatives as in the probands. Antibodies to the synthetic peptide U1-RNP-A 35-38 were found in 56% of the patients, 28% of their relatives and 20% of the spouses, whereas antibodies to the Golgi apparatus was present in 7% of the patients, 26% of their relatives and 33% of the spouses. However, most of these family members were unaffected. RT84 Id was positively associated with antibodies to Sm-D peptide 1-20 and to Ro/SSA 60 kD peptide 304-324, but negatively associated with anti-dsDNA activity. The median of age was significantly lower in the RT84 Id-positive than in the RT84 Id-negative individuals. These data suggest that genetic as well as environmental factors are involved in the aetiology of SLE. In addition, RT84-carrying immunoglobulins (Ab2) might be directed to one of many cross-reactive Ids of dsDNA-binding antibodies (Ab1), perhaps down-regulating their production.     

Prediction of insulin-dependent diabetes mellitus in siblings of children with diabetes. A population-based study. The Childhood Diabetes in Finland Study Group

The relationship between parental divorce occurring during adolescence and young adult psychosocial adjustment was examined, as was the role of family process variables in clarifying this relationship. Participants were young Caucasian adults from divorced (n = 119) and married (n = 123) families. Assessments were conducted during adolescence and 6 years later during early adulthood. Young adults from married families reported more secure romantic attachments than those from divorced families; however, differences were not evident in other domains of psychosocial adjustment after demographic variables were controlled. Three family process variables (parent-adolescent relationship, interparental conflict, and maternal depressive symptoms) were examined as potential mediators and moderators of the association between parental divorce and young adult adjustment. No evidence supporting mediation or moderation was found; however, the parent-adolescent and parent-young adult relationships, particularly when the identified parent was the father, emerged as significant predictors of young adult psychosocial adjustment.     

I. Adrenal cortex and steroid 21-hydroxylase autoantibodies in adult patients with organ-specific autoimmune diseases: markers of low progression to clinical Addison's disease

Adrenal cortex antibodies (ACA) were measured by immunofluorescence in 8840 adult patients with organ-specific autoimmune diseases without overt hypoadrenalism. Sixty-seven (0.8%) patients were ACA-positive, with the highest prevalence in those with premature ovarian failure (8.9%). Forty-eight ACA-positive and 20 ACA-negative individuals were enrolled into a prospective study. Antibodies to steroid 21-hydroxylases (21-OH), steroid 17 alpha-hydroxylase (17 alpha-OH) and cytochrome P450 side chain cleavage enzyme (P450scc) were measured by immunoprecipitation assay. Human leucocyte antigens D-related (HLA-DR) genotyping was also carried out and adrenal function assessed by ACTH test. On enrollment, 75% of ACA-positive patients had a normal adrenal function, while 25% revealed a subclinical hypoadrenalism. 21-OH antibodies were positive in 91% of ACA-positive sera. Eleven patients were positive for steroid-cell antibodies by immunofluorescence, and 9 revealed a positivity for antibodies to 17 alpha-OH and/or P450scc. During the prospective study, overt Addison's disease developed in 21% and subclinical hypoadrenalism in 29% of ACA-positive patients, while 50% maintained normal adrenal function. Progression to Addison's disease was more frequent in patients with subclinical hypoadrenalism, high titers of ACA and higher levels of 21-OH antibodies, complement-fixing ACA and HLA-DR3 status. All 20 persistently ACA-negative patients were also negative for antibodies to 21-OH, 17 alpha-OH, and P450scc, and all maintained normal adrenal function during follow-up. In conclusion, the detection of ACA/21-OH antibodies in adults is a marker of low progression toward clinical Addison's disease.     

Marital status and quality in middle-aged women: Associations with levels and trajectories of cardiovascular risk factors.

The current study compared cardiovascular risk profiles and trajectories (i.e., within-person changes) of women who were married or cohabitating and who had high relationship satisfaction with those of women with moderate or low satisfaction and with those of women who were single, divorced, and widowed. Participants were 493 women from the Healthy Women Study, a prospective investigation of health during and after the menopausal transition. Risk factors were measured across more than 5 occasions and 13 years, on average. Data were analyzed using a multilevel modeling technique. Overall, women in relationships with high satisfaction had lower levels of biological, lifestyle, and psychosocial risk factors when compared with the other groups. In some cases, women in satisfying marriages also showed a lower risk trajectory on risk factors relative to other women. Hence, marriage appears to confer health benefits for women, but only when marital satisfaction is high. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Management and outcomes for black patients with acute myocardial infarction in the reperfusion era. National Registry of Myocardial Infarction 2 Investigators

Data from a national registry of myocardial infarction patients from June 1994 to April 1996 were analyzed to compare the presenting characteristics, acute reperfusion strategies, treatment patterns, and clinical outcomes among black and white patients. Blacks presented much later to the hospital after the onset of symptoms (median 145 vs 122 minutes, p <0.001), were more likely to have atypical cardiac symptoms (28% vs 24%, p <0.001), and nondiagnostic electrocardiograms during the initial evaluation period compared with whites (37% vs 31%, p <0.001). Also, blacks were less likely to receive intravenous thrombolytic therapy (adjusted odds ratio [OR] 0.76, 95% confidence intervals [CI] 0.71 to 0.80), coronary arteriography (adjusted OR 0.85, 95% CI 0.77 to 0.95), other elective catheter-based procedures (adjusted OR 0.87, 95% CI 0.78 to 0.96), and coronary artery bypass surgery (adjusted OR 0.66, 95% CI 0.58 to 0.75) than their white counterparts. Despite these differences in treatment, there were no significant differences in hospital mortality between blacks and whites.     

The role of cardiac troponin T and other new biochemical markers in evaluation and risk stratification of patients with acute chest pain syndromes

Electrocochleography (ECochG) was used to evaluate cochlear function in guinea pigs with experimentally induced endolymphatic hydrops (ELH) before and after osmotic dehydration with either glycerol or urea. We surgically induced ELH in the right ears of 9 guinea pigs, while the right ears of 6 guinea pigs received a sham operation. The left ears of the 15 animals constituted the normal group. Eight weeks after surgery, summating potential (SP) and action potential (AP) amplitudes were measured prior to and following the administration of glycerol or urea. The SPs and SP/AP ratios were reduced in all groups, with no significant differences among groups or between dehydrating agents. Some of the hydropic ears, however, did show an increased AP threshold and a recruitment effect. In measurements from 6 additional animals, serum osmolarity increased more with urea than with glycerol. The guinea pig model remains valuable for investigation of ELH, even though it differs in significant respects from ELH in humans.     

Associations of marijuana use and sex-related marijuana expectancies with HIV/STD risk behavior in high-risk adolescents.

Multiple studies suggest an association of marijuana use with increased rates of sexual risk behavior and sexually transmitted diseases (STDs). Most studies have focused on global associations of marijuana use with sexual risk outcomes and few have examined relevant cognitive variables. Adolescents in the juvenile justice system are at elevated risk for HIV/STDs and preliminary evidence suggests that marijuana is a potentially important cofactor for sexual risk behavior in this population. This study evaluated global, situational and event-level associations of marijuana use and sex-related marijuana expectancies with sexual risk outcomes in a large, racially diverse sample of adjudicated youth (n = 656, 66% male, mean age = 16.7 years). Cross-sectional and prospective analyses identified associations of marijuana use and dependence symptoms with sexual risk outcomes, including lower frequency of condom use and higher STD incidence. Stronger sex-related marijuana expectancies predicted greater intentions for and frequency of marijuana use in sexual situations. In event-level analyses that controlled for alcohol, marijuana use predicted a significantly decreased likelihood of condom use; this association was moderated by sex-related marijuana expectancies. Mediation analyses suggested that behavioral intentions partly accounted for the prospective association of expectancies with marijuana use before sex. These results provide further evidence that marijuana use is a potentially important cofactor for HIV/STD transmission in high-risk adolescents and suggest that cognitive factors could be important for characterizing this association. (PsycINFO Database Record (c) 2010 APA, all rights reserved)