Pre-transplant predictors of one yr weight gain after kidney transplantation.

Clinically useful predictors of weight gain could be used to reduce the epidemic of post-kidney transplant obesity and resulting co-morbidities. The purpose of this study was to identify predictors of weight gain at 12 months following kidney transplant in a cohort of 96 recipients. Demographic, clinical, and environmental data were obtained at transplant and 12 months. Descriptive, correlational, and Bayesian network analysis were used to identify predictors. For the 52 (55.9%) recipients who gained weight, the average amount gained was 9.18 ± 6.59 kg. From the 15 baseline factors that met inclusion criteria, Bayesian network modeling identified four baseline predictors for weight gain: younger age, higher carbohydrate consumption, higher trunk fat percentage, and higher perception of mental health quality of life. Three are modifiable through either pre- or immediate post-transplant clinical intervention programs.

Parents' attachment histories and children's externalizing and internalizing behaviors: exploring family systems models of linkage.

Twenty-seven mothers and 27 fathers were given the Adult Attachment Interview (M. Main & R. Goldwyn, in press) when their children were 3.5 years old. Continuous ratings of narrative coherence, probable experience quality (parents perceived as loving), and state of mind (current anger at parents) were entered as latent variables in partial least squares structural equation models that included observational measures of marital quality and parenting style. Models that include fathers' attachment histories predicted more variance in kindergarten teachers' descriptions of children's externalizing behavior, whereas models that include mothers' attachment histories predicted more variance in children's internalizing behavior. Marital data added predictive power to the equations. Discussion is focused on the importance of integrating attachment and family systems approaches, and of parents' gender and marital quality, in understanding specific links between parents' attachment histories and their young children's externalizing and internalizing behaviors.

Conversion to sirolimus in solid organ transplantation: a single-center experience.

BACKGROUND: Calcineurin inhibitors are associated with adverse events, including nephrotoxicity and diabetes that might reduce the benefits of long-term graft survival. We report our experience in converting kidney (K), kidney-pancreas (KP), pancreas (P), and (L) recipients from a calcineurin inhibitor/mycophenolate mofetil (MMF)/prednisone dose-induced nephrotoxicity (K = 9, KP = 5, P = 1, L = 5), hemolytic uremic syndrome (HUS) (K = 7, KP = 5), chronic allograft nephropathy (K = 12, L = 1), and glucose intolerance (K = 9, KP = 6, P = 2, L = 2). METHODS: The conversion protocol consisted of an abrupt discontinuation of the calcineurin inhibitor with sirolimus (8-12 mg, PO loading dose) initiated 24-72 hours after stopping the calcineurin inhibitor. Sirolimus was titrated to target trough levels of 12-16 ng/mL. Daclizumab 2 mg/kg IV was given to all KP and P recipients on days 0 and 14 postconversion. RESULTS: Resolution of HUS occurred in 12 of 12 patients (100%) with a drop in serum creatinine from 3.3 +/- 1.5 to 1.8 +/- 0.9 mg/dL (P =.04). Sirolimus conversion due to nephrotoxicity, HUS, and chronic allograft nephropathy improved serum creatinine from 2.9 +/- 1.4 to 2.2 +/- 0.9 mg/dL (P =.01). Eleven of 19 patients (58%) resolved glucose intolerance. Two patients suffered rejection due to noncompliance. Increases in cholesterol (208 +/- 70 to 243 +/- 77 mg/dL, P <.05) and triglycerides (232 +/- 145 to 265 +/- 148 mg/dL, P = NS), and minimal reduction in platelet values (243 +/- 85 to 237 +/- 85, P = NS) occurred. CONCLUSIONS: These data suggest that a calcineurin inhibitor-free immunosuppressive regimen with sirolimus, mycophenolate mofetil, and steroids preserves graft function in patients with clinical indications warranting calcineurin inhibitor discontinuation.

Heart rate variability, mortality, and exercise in patients with end-stage renal disease.

CONTEXT: Cardiac autonomic function has been associated with mortality in patients with end-stage renal disease. It is unknown whether end-stage renal disease patients who have succumbed to sudden cardiac death can be better identified by a newer test of heart rate variability that uses spectral analysis, rather than laboratory evoked measures. OBJECTIVE: This series of studies sought to characterize cardiac autonomic function in patients awaiting kidney transplantation, identify factors associated with heart rate variability, identify tests which distinguish patients at-risk for death, and compare evoked measures with 24-hour heart rate variability measures. PATIENTS: Data were collected on 184 nondiabetics, 60 type 1 diabetics, and 34 type 2 diabetics with end-stage renal disease, all of whom had been referred for kidney transplantation. MAIN OUTCOME MEASURES: The 278 patients and 67 healthy control subjects underwent evoked tests (changes in heart rate with deep breathing and Valsalva maneuver) and 24-hour heart rate variability Holter monitoring (time and frequency domains). Five patients had sudden cardiac deaths during the study. RESULTS: Data showed that end-stage renal disease patients, particularly diabetics, had compromised autonomic function. The standard deviation of all R-to-R intervals for the electrocardiogram recording (< 50 minutes in 60% of the deceased patients), a 24-hour heart rate variability time domain measure, holds the promise of identifying patients at increased risk for death. Exercise was identified as a factor associated with better autonomic function. Examining relationships between 24-hour heart rate variability and characteristics of patients who succumb to death could make quantification of the mortality risk for individual pretransplant end-stage renal disease patients possible, much as it has in other populations. The data from this study may also make it possible to design interventions, such as exercise, aimed at reducing mortality risk.

Posttransplant improvement in heart rate variability correlates with improved quality of life.

A prospective evaluation of 37 kidney and 20 kidney-pancreas transplant recipients was conducted to assess the relationship between pre- to posttransplant changes in heart rate variability (HRV) and quality of life (QoL). Assessments of 24-hour interbeat variability (pNN50 and rMSSD, SDNN, SDANN) and power spectral analysis of total, low (sympathetic), and high (parasympathetic) frequency components of HRV were performed. The Sickness Impact Profile was used to assess three dimensions of QoL (physical, psychosocial, and total functioning) prior to and at 6 months following transplantation. Changes in vagally mediated time domain measures of HRV were related to changes in physical and total functioning. Stronger correlations occurred between biobehavioral measures in kidney-pancreas recipients, with the strongest relationships occurring between changes in HRV frequency domain measures and changes in physical functioning. Findings indicate that changes in HRV and QoL are related, suggesting that interventions that enhance transplant recipients' HRV may also enhance their QoL.

Adult attachment and adult child-older parent relationships.

Adult attachment status, concurrent and early relationships with parents, and depressive symptoms were assessed in 53 adults. Individuals with consistent reports of relationships--positive or negative--were most coherent in their narratives. Depressive symptoms were associated with negativity in both recalled and current relationships with parents, but were not correlated with coherence of narratives. Clinical implications of the findings are discussed.

Transitions to parenthood: his, hers, and theirs.

PIP: This study explores marital processes that may underlie the apparent decline in satisfaction with marriage in partners becoming parents for the 1st time. The study assessed 47 couples expecting a 1st child and 15 couples not yet decided about having a child at pretest, post 1 (6 months post partum of 9 months after pretest) and post 2 (18 months postpartum or 21 months after pretest). Questionnaires examined: 1) psychological sense of self; 2) partners' role arrangements and communication; 3) parenting ideology; 4) perceptions of the family of origin; and 5) social support and life stress, including parents' work patterns. Parenthood seems to bring more change, and more negative change, in each of the 5 domains of family life that were investigated for comparable couples not having a 1st child experience over a similar period of time. Quantitative data support this conclusion in 4 of the 5 domains (individuals sense of self, marital, parent-child, and outside the family). Interview data suggest that new parents' relationships with their families of origin also undergo change at this time. Although shifts within domains often showed patterns similar to change in overall satisfaction with the marriage, the connection between the 2 was not linear and direct, especially for women. Men and women in transition to parenthood become increasingly different from one another; the results suggest that increased gender differentiation accompanying the transition to parenthood is a factor in accounting for marital satisfaction decline.^ieng

Sirolimus: mammalian target of rapamycin inhibitor to prevent kidney rejection.

Current immunosuppressive therapies are effective but can be associated with significant adverse reactions. Sirolimus works differently from the immunosuppressants currently available, and except for increased lipid levels, the adverse reaction profile of sirolimus does not appear to overlap to any great extent with that associated with cyclosporine or tacrolimus. While additional research is needed, the initial clinical data in kidney recipients suggest that sirolimus, in combination with cyclosporine or tacrolimus, might have the potential to reduce the frequency of rejection episodes, permit reductions in cyclosporine or tacrolimus dosage, and permit steroid withdrawal (Kelly, 1999).

Assessing the risk of impaired glucose metabolism in overweight adolescents in a clinical setting.

OBJECTIVE: The study aims were to examine the relationship between adiposity and surrogate indices of pancreatic beta-cell function and insulin sensitivity obtained from an oral glucose tolerance test (OGTT) in overweight adolescents and determine which factors best predict impaired glucose metabolism (IGM). METHODS: In a sample of adolescents (n=209) severity of overweight was determined by relative body mass index (RBMI). Insulin sensitivity (QUICKI, CISI) and beta-cell function (Fasting insulin: FI; Insulinogenic Index: deltaI30/deltaG30). RESULTS: IGM was present in 26.8% (n=56), of which five had type 2 diabetes (T2DM). IGM prevalence was similar among RBMI strata. Once RBMI reached 150%, pronounced deterioration in CISI occurred (approximately 55%) (P<0.0001) while less dramatic reductions were seen in QUICKI (P<0.05), with fasting blood glucose (FBG) and beta-cell indices remaining stable. Compared to those with normal glucose tolerance, the IGM group exhibited higher beta-cell activity (FI, P<0.0001; deltaI30/deltaG30, P=0.004) with reduced insulin sensitivity (CISI, P<0.0001; QUICKI, P<0.0002). CISI was the single predictor of IGM (P<0.0001). Low insulin sensitivity increased adolescents' chance for IGM (CISI: OR=6.49, 95%CI=2.63, 16.05, P<0.0001; QUICKI: OR=3.16, 95%CI=1.61, 6.05, P=0.0006) as did beta-cell deterioration (deltaI30/delta G30: OR=3.18, 95%CI=1.33, 7.59, P=0.0069). Normal FBG occurred in 37.5% of youth with IGM. CONCLUSION: The prevalence of IGM escalates in overweight adolescents, even at lower levels of overweight, and is associated with pronounced deterioration of insulin sensitivity. Current screening recommendations for FBG underestimate the prevalence of IGM in overweight adolescents thus limiting the opportunity for earlier intervention to prevent progression to diabetes.

Beyond meta-analysis: a plea for a family systems view of attachment.

De Wolff and van Ijzendoorn's (1997) meta-analysis of parental antecedents of infant attachment focuses almost entirely on maternal behavior. I argue here that although the meta-analysis method makes an important contribution to summarizing research studies, it limits the conceptual understanding of attachment to simple causal models, and ignores family systems models that could illuminate our understanding of the development of secure and insecure attachment in children.

Structural and functional perspectives on classification and seriation in psychotic and normal children.

This study describes a strategy for examining cognitive functioning in psychotic and normal children without the usual confounding effects of marked differences in cognitive structure that occur when children of the same age are compared. Participants were 14 psychotic children, 12 males and 2 females, mean age 9-2, matched with normal children at preoperational and concrete operational stage levels on a set of Piagetian classification tasks. The mean age of the normal children was 6-4, replicating the usually found developmental delay in psychotic samples. Participants were then compared on both structural level and functional abilities on a set of tasks involving seriation of sticks; the higher-level children were also administered a seriation drawing task. Analysis of children's processes of seriating and seriation drawings indicated that over and above the structural retardation, psychotic children at all levels showed functional deficits, especially in the use of anticipatory imagery. The implications for general developmental theory are that progress in structural development is not sufficient for imaginal development, and that structural development of logical concepts is relatively independent of the development of imagery. It was suggested that "thought disorder" may not be a disordered structure of thinking or a retardation in psychotic populations but rather a mismatch between higher-level logical structures and lower-level functions.

Modeling of a medical transcription system.

This article describes a methodology for modeling a medical transcription system by means of the discrete system computer simulation language, GPSS. Used on a personal computer, GPSS allows the medical record supervisor to explore numerous modes of operation and alternative transcription system configurations. Design and operating improvements that can be achieved by studying the performance of the model are also discussed.

Assessing young children's views of their academic, social, and emotional lives: an evaluation of the self-perception scales of the Berkeley Puppet Interview.

In a prospective, longitudinal study we examined the psychometric properties of the self-perception scales of the Berkeley Puppet Interview (BPI). A total sample of 97 young children were assessed with the BPI at 3 time points: preschool, kindergarten, and first grade. The BPI assesses young children's self-perceptions of their school adjustment in 6 domains: academic competence, achievement motivation, social competence, peer acceptance, depression-anxiety, and aggression-hostility. Results showed that 4 1/2- to 7 1/2-year-olds possess a multidimensional self-concept that can be reliably measured and that the BPI is sensitive to normative changes and individual differences in young boys' and girls' views of themselves. Support for the method's validity was derived from consistent and meaningful patterns of convergence between children's self-perceptions and ratings by adult informants--mothers, fathers, and teachers--as well as standardized test scores. In fact, in this study, the concordance between young children's self-reports and parallel ratings by teachers or mothers were consistently as strong as if not stronger than the concordance between mothers' and teachers' ratings.

Race affects insulin and GLP-1 secretion and response to a long-acting somatostatin analogue in obese adults.

OBJECTIVE: This study investigated (1) the effect of octreotide-LAR (Sandostatin-LAR Depot; Novartis) on the enteroinsular axis in a biracial cohort of severely obese adults, (2) whether octreotide suppression of insulin secretion occurs by both a direct beta-cell effect and through mediating a glucagon-like peptide 1 (GLP-1) response, and (3) whether differences in GLP-1 concentrations could explain racial differences in insulin concentrations. DESIGN: Prospective, open-label trial using a pre-post test design. SETTING: Single university, clinical research center. SUBJECTS: In all, 42 healthy, severely obese Caucasian and African-American (AA) adults (93% female, 64% Caucasian, age=37.8+/-1.2 y, weight=123+/-4.2 kg, BMI=44.5+/-1 kg/m(2)), recruited through physician referral and newspaper ads, participated in the study. INTERVENTIONS: Indices of beta-cell activity, insulin and GLP-1 response before and during a 75-gm oral glucose tolerance test were determined before and after 24 weeks of octreotide-LAR. RESULTS: AA exhibited higher beta-cell activity, and insulin and GLP-1 concentrations than Caucasians. Octreotide-LAR suppressed the insulin and GLP-1 levels in both groups.

Suppression of insulin secretion is associated with weight loss and altered macronutrient intake and preference in a subset of obese adults.

PURPOSE: Hyperinsulinemia is a common feature of many obesity syndromes. We investigated whether suppression of insulin secretion, without dietary or exercise intervention, could promote weight loss and alter food intake and preference in obese adults. METHODS: Suppression of insulin secretion was achieved using octreotide-LAR 40 mg IM q28d for 24 weeks in 44 severely obese adults (89% female, 39% minority). Oral glucose tolerance testing was performed before and after treatment, indices of beta-cell activity (CIRgp), insulin sensitivity (CISI), and clearance (CP/I AUC) were computed, and leptin levels, 3-day food records and carbohydrate-craving measurements were obtained. DEXA evaluations were performed pre- and post-therapy in an evaluable subgroup. RESULTS: For the entire cohort, significant insulin suppression was achieved with simultaneous improvements in insulin sensitivity, weight loss, and body mass index (BMI). Leptin, fat mass, total caloric intake, and carbohydrate craving significantly decreased. When grouped by BMI response, high responders (HR; DeltaBMI<-3 kg/m(2)) and low responders (LR; DeltaBMI between -3 and -0.5) exhibited higher suppression of CIRgp and IAUC than nonresponders (NR; DeltaBMI-0.5). CISI improved and significant declines in leptin and fat mass occurred only in HR and LR. Conversely, both leptin and fat mass increased in NR. Carbohydrate intake was markedly suppressed in HR only, while carbohydrate-craving scores decreased in HR and LR. For the entire cohort, DeltaBMI correlated with DeltaCISI, Deltafat mass, and Deltaleptin. DeltaFat mass also correlated with DeltaIAUC and DeltaCISI. CONCLUSIONS: In a subcohort of obese adults, suppression of insulin secretion was associated with loss of body weight and fat mass and with concomitant modulation of caloric intake and macronutrient preference.

Racial differences in glucagon-like peptide-1 (GLP-1) concentrations and insulin dynamics during oral glucose tolerance test in obese subjects.

Obese African-American (AA) subjects have higher resting and stimulated insulin concentrations than obese Caucasians (C), which could not be explained by the severity of obesity or the degree of insulin sensitivity. We investigated whether differences in glucagon-like peptide-1 (GLP-1), the most potent incretin that regulates insulin secretion, might explain racial differences in insulin response. Accordingly, we measured fasting and stimulated glucose, insulin, and GLP-1 levels during a 3-h oral glucose tolerance test (OGTT) in 26 obese C (age 38+/-2 y, body mass index 44+/-1 kg/m(2)) and 16 obese AA (age 36+/-2 y, BMI 46+/-2 kg/m(2)) subjects. Corrected insulin response (CIR(30)), a measure of beta-cell activity, whole body insulin sensitivity index (WBISI), and area under the curve (AUC) for insulin, GLP-1, and C-peptide/insulin ratio were computed from the OGTT. Glucose levels, fasting and during the OGTT, were similar between racial groups; 32% of the C and 31% of the AA subjects had impaired glucose tolerance. With a similar WBISI, AAs had significantly higher CIR(30) (2.3+/-0.4 vs 1.01+/-0.1), insulin response (IAUC: 23 974+/-4828 vs 14 478+/-1463), and lower insulin clearance (0.07+/-0.01 vs 0.11+/-0.01) than C (all, P<0.01). Obese AAs also had higher fasting GLP-1 (6.7+/-2.5 vs 4.5+/-1.1) and GLP-1AUC (1174.7+/-412 vs 822.4+/-191) than C (both, P<0.02). Our results indicate that obese AAs had higher concentrations of GLP-1 both at fasting and during the OGTT than obese C. The increased GLP-1 concentration could explain the greater insulin concentration and the increased prevalence of hyperinsulinemia-associated disorders including obesity and type 2 diabetes in AAs.