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Performance profiles of the functional independence measure.

The functional independence measure (FIM) is used to determine the degree of disability that patients experience and the progress that they make through programs of medical rehabilitation. Rasch analysis is a statistical technique for constructing interval measures from ordinal data that was applied to derive FIM measures. The major factors that are taken into account to produce FIM measures are the relative difficulty in performance of FIM items and the ability of the persons tested. Our analyses showed the relative difficulties that patients experienced in performing items in the FIM. There were two dominant patterns of difficulty, one for motor FIM items and the other for cognitive FIM items. The patterns were consistent across impairment groups, although not identical. Of the motor items, eating and grooming were easiest whereas stair climbing, tub/shower transfers and locomotion were most difficult. Of the cognitive items, expression and comprehension were easiest and problem solving was the most difficult. The patterns of difficulty in performing FIM items are illustrated by analysis of the following impairment groups: for motor items, orthopedic conditions, stroke with left hemiparesis and spinal cord dysfunction; for cognitive items, orthopedic conditions, brain dysfunction, stroke with right hemiparesis and spinal cord dysfunction. By understanding patterns of difficulty in performing FIM items according to types of impairment and levels of function, clinicians may more precisely design treatment programs, use services and predict outcomes of medical rehabilitation.

Activities of Daily Living↗

Improved cardiovascular risk profile and renal function in renal transplant patients after randomized conversion from cyclosporine to tacrolimus.

Cyclosporine is considered to contribute to the high cardiovascular morbidity and mortality in patients after renal transplantation. Tacrolimus may be more favorable in this respect, but controlled data are scarce. In this prospective randomized study in 124 stable renal transplant patients, the effects of conversion from cyclosporine to tacrolimus on cardiovascular risk factors and renal function were investigated. Follow-up was 6 mo. Statistical analysis was performed by ANOVA for repeated measurements. The serum creatinine level decreased from 137 +/- 30 micromol/L to 131 +/- 29 micromol/L (P < 0.01). Three months after conversion from cyclosporine to tacrolimus, mean BP significantly decreased from 104 +/- 13 to 99 +/- 12 mmHg (P < 0.001). Serum LDL cholesterol decreased from 3.48 +/- 0.80 to 3.11 +/- 0.74 mmol/L (P < 0.001,) and serum apolipoprotein B decreased from 1018 +/- 189 to 935 +/- 174 mg/L (P < 0.001). Serum triglycerides decreased from 2.11 +/- 1.12 to 1.72 +/- 0.94 mmol/L (P < 0.001). In addition, both rate and extent of LDL oxidation were reduced. The fibrinogen level decreased from 3638 +/- 857 to 3417 +/- 751 mg/L (P < 0.05). Plasma homocysteine concentration did not change. Three months after conversion, plasma fasting glucose level temporarily increased from 5.4 +/- 1.3 mmol/L to 5.8 +/- 1.9 mmol/L (P < 0.05). Conversion to tacrolimus resulted in a significant reduction of the Framingham risk score. In conclusion, conversion from cyclosporine to tacrolimus in stable renal transplant patients has a beneficial effect on renal function, BP, serum concentration and atherogenic properties of serum lipids, and fibrinogen.

Adult↗

Blood lipid peroxides in TIA: relation to platelet function and metabolic profile.

Patients with transient ischemic attacks (TIA) were previously shown to have high plasma values of thiobarbituric acid-reactive substances (TBA-RS). To study whether these changes could be related to platelet activability, TBA-RS was investigated in 24 TIA patients before and 24 h after 1 g aspirin, an inhibitor of platelet cyclooxygenase pathway. Baseline TBA-RS values were significantly higher in TIA than in controls. Conversely, TIA patients had TBA-RS values after aspirin similar to controls, suggesting that the increase of plasma TBA-RS was not attributable to platelet hyperfunction. The evaluation of metabolic profile showed that patients with highest TBA-RS had hypercholesterolemia, hypertriglyceridemia, and/or diabetes mellitus. This study suggests that the increase of plasma TBA-RS in TIA could be an epiphenomenon of altered metabolic pathway.

Administration, Oral↗

Limited role for SREBP-1c in defective glucose-induced insulin secretion from Zucker diabetic fatty rat islets: a functional and gene profiling analysis.

Accumulation of intracellular lipid may contribute to defective insulin secretion in type 2 diabetes. Although Zucker diabetic fatty (ZDF; fa/fa) rat islets are fat-laden and overexpress the lipogenic master gene, sterol regulatory element binding protein 1c (SREBP-1c), the contribution of SREBP-1c to the secretory defects observed in this model remains unclear. Here we compare the gene expression profile of lean control (fa/+) and ZDF rat islets in the absence or presence of dominant-negative SREBP-1c (SREBP-1c DN). ZDF islets displayed elevated basal insulin secretion at 3 mmol/l glucose but a severely depressed response to 17 mmol/l glucose. While SREBP-1c DN reduced basal insulin secretion from ZDF islets, glucose-stimulated insulin secretion was not improved. Of 57 genes differentially regulated in ZDF islets and implicated in glucose metabolism, vesicle trafficking, ion fluxes, and/or exocytosis, 21 were upregulated and 5 were suppressed by SREBP-1c DN. Genes underrepresented in ZDF islets were either unaffected (Glut-2, Kir6.2, Rab3), stimulated (voltage-dependent Ca(2+) channel subunit alpha1D, CPT2, SUR2, rab9, syt13), or inhibited (syntaxin 7, secretogranin-2) by SREBP-1c inhibition. Correspondingly, SREBP-1c DN largely corrected decreases in the expression of the transcription factors Pdx-1 and MafA but did not affect the abnormalities in Pax6, Arx, hepatic nuclear factor-1alpha (HNF1alpha), HNF3beta/Forkhead box-a2 (Foxa2), inducible cyclic AMP early repressor (ICER), or transcription factor 7-like 2 (TCF7L2) expression observed in ZDF islets. We conclude that upregulation of SREBP-1c and mild increases in triglyceride content do not explain defective glucose-stimulated insulin secretion from ZDF rats. However, overexpression of SREBP-1c may contribute to enhanced basal insulin secretion in this model.

Animals↗

Proteomic Profiling of Pulmonary Function and Cardiovascular Disease Risk in the Atherosclerosis Risk in Communities Study.

BACKGROUND: Pulmonary function is linked to cardiovascular disease risk; however, the underlying mechanisms remain unclear. We aimed to identify protein biomarkers associated with pulmonary function and examine their impact on incident chronic obstructive pulmonary disease, coronary heart disease, heart failure, and all-cause mortality. METHODS: Data from White and Black Americans in the Atherosclerosis Risk in Communities study (visit 2: N=11&#x2009;354, mean age=57 years; visit 5: N=3517, mean age=75 years), a prospective cohort, were analyzed. Linear regression assessed associations between protein levels and pulmonary function measures, including forced expiratory volume in 1 second and forced vital capacity. The impact of the identified proteins on incident chronic obstructive pulmonary disease, coronary heart disease, heart failure, and mortality was estimated using logistic regression and Cox proportional hazards models. Pathway enrichment and Mendelian randomization explored underlying biological functions and causal effects. RESULTS: Of 4766 proteins analyzed, 364 were cross-sectionally associated with forced expiratory volume in 1 second (and forced vital capacity (false discovery rate<0.05). Ninety-four and 270 proteins had concordant positive and negative effects, respectively. Five pathways related to pulmonary and cardiac function were enriched. Of the 364 proteins, 112 were linked to all 4 outcomes, where 86 were associated with increased risk (odds ratio/hazard ratio [OR/HR], 1.05-1.42) and 26 with reduced risk (OR/HR, 0.69-0.96). Six proteins (STAT3 [signal transducer and activator of transcription 3], MIC-1 [growth differentiation factor 15], apoA-II [apolipoprotein A-II], TPST1 [protein-tyrosine sulfotransferase 1], integrin a1b1 [integrin alpha-I: beta-1 complex], and BLC [C-X-C motif chemokine 13]) showed potential inverse causal effects on with forced expiratory volume in 1 second and forced vital capacity, and integrin a1b1 demonstrated consistent inverse associations with chronic obstructive pulmonary disease, coronary heart disease, and heart failure risks. CONCLUSIONS: Proteins associated with pulmonary function may influence CVD risk. Six proteins, including integrin a1b1, represent promising targets for future interventions.

Aged↗

Molecular profile and partial functional analysis of novel endothelial cell-derived growth factors that regulate hematopoiesis.

Recent progress has been made in the identification of the osteoblastic cellular niche for hematopoietic stem cells (HSCs) within the bone marrow (BM). Attempts to identify the soluble factors that regulate HSC self-renewal have been less successful. We have demonstrated that primary human brain endothelial cells (HUBECs) support the ex vivo amplification of primitive human BM and cord blood cells capable of repopulating non-obese diabetic/severe combined immunodeficient repopulating (SCID) mice (SCID repopulating cells [SRCs]). In this study, we sought to characterize the soluble hematopoietic activity produced by HUBECs and to identify the growth factors secreted by HUBECs that contribute to this HSC-supportive effect. Extended noncontact HUBEC cultures supported an eight-fold increase in SRCs when combined with thrombopoietin, stem cell factor, and Flt-3 ligand compared with input CD34(+) cells or cytokines alone. Gene expression analysis of HUBEC biological replicates identified 65 differentially expressed, nonredundant transcripts without annotated hematopoietic activity. Gene ontology studies of the HUBEC transcriptome revealed a high concentration of genes encoding extracellular proteins with cell-cell signaling function. Functional analyses demonstrated that adrenomedullin, a vasodilatory hormone, synergized with stem cell factor and Flt-3 ligand to induce the proliferation of primitive human CD34(+)CD38(-)lin(-) cells and promoted the expansion of CD34(+) progenitors in culture. These data demonstrate the potential of primary HUBECs as a reservoir for the discovery of novel secreted proteins that regulate human hematopoiesis.

Adrenomedullin↗

Kallikrein gene delivery improves serum glucose and lipid profiles and cardiac function in streptozotocin-induced diabetic rats.

We investigated the role of the kallikrein-kinin system in cardiac function and glucose utilization in the streptozotocin (STZ)-induced diabetic rat model using a gene transfer approach. Adenovirus harboring the human tissue kallikrein gene was administered to rats by intravenous injection at 1 week after STZ treatment. Human kallikrein transgene expression was detected in the serum and urine of STZ-induced diabetic rats after gene transfer. Kallikrein gene delivery significantly reduced blood glucose levels and cardiac glycogen accumulation in STZ-induced diabetic rats. Kallikrein gene transfer also significantly attenuated elevated plasma triglyceride and cholesterol levels, food and water intake, and loss of body weight gain, epididymal fat pad, and gastrocnemius muscle weight in STZ-induced diabetic rats. However, these effects were blocked by icatibant, a kinin B2 receptor antagonist. Cardiac function was significantly improved after kallikrein gene transfer as evidenced by increased cardiac output and +/-delta P/delta t (maximum speed of contraction/relaxation), along with elevated cardiac sarco(endo)plasmic reticulum (Ca2+ + Mg2+)-ATPase (SERCA)-2a, phosphorylated phospholamban, NOx and cAMP levels, and GLUT4 translocation into plasma membranes of cardiac and skeletal muscle. Kallikrein gene delivery also increased Akt and glycogen synthase kinase (GSK)-3beta phosphorylation, resulting in decreased GSK-3beta activity in the heart. These results indicate that kallikrein through kinin formation protects against diabetic cardiomyopathy by improving cardiac function and promoting glucose utilization and lipid metabolism.

Adenoviridae↗

Effect of a chicken-based diet on renal function and lipid profile in patients with type 2 diabetes: a randomized crossover trial.

OBJECTIVE: To assess the effect of replacing red meat with chicken in the usual diet and the effect of a low-protein diet on glomerular filtration rate (GFR), urinary albumin excretion rate (UAER), and lipid levels in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A randomized, crossover, controlled trial was conducted with 28 patients with type 2 diabetes (seven women; mean age 58.1 years): 15 patients were normoalbuminuric (UAER <20 microg/min), and 13 patients were microalbuminuric (UAER 20-200 microg/min). A chicken-based diet (red meat replaced with chicken) and a low-protein diet were compared with the patients' usual diet. Patients followed each diet for 4 weeks with a 4-week washout period between. GFR ((51)Cr-EDTA single-injection technique), 24-h UAER (immunoturbidimetry), apolipoprotein B, total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were measured after each diet. RESULTS: Normoalbuminuric and microalbuminuric patients with diabetes were analyzed separately. In normoalbuminuric patients, GFR after the chicken (101.3 +/- 22.9 ml x min(-1) x 1.73 m(-2)) and low-protein diets (93.8 +/- 20.5 ml x min(-1) x m(-2)) was lower than after the usual diet (113.4 +/- 31.4 ml x min(-1) x 1.73 m(-2); P < 0.05). In microalbuminuric patients, apolipoprotein B levels were lower after the chicken (113.5 +/- 36.0 mg/dl) and low-protein diets (103.5 +/- 40.1 mg/dl) than after the usual diet (134.3 +/- 30.7 mg/dl; P < 0.05). Only the chicken diet reduced UAER (median 34.3 microg/min) compared with the low-protein (median 52.3 microg/min) and usual (median 63.8 microg/min) diets (P < 0.05). Glycemic control and blood pressure did not change after the diets. CONCLUSIONS: A normoproteic diet with chicken as the only source of meat may represent an alternative strategy for treatment of patients with type 2 diabetes and microalbuminuria.

Adult↗

Language and conversational abilities in Williams syndrome: how good is good?

Grammatical performance of individuals with Williams syndrome (WS) has been reported as being unimpaired, despite their comparatively low IQ and poor general cognitive ability. Specific language impairment (SLI) is often seen as the converse of WS, showing poor linguistic ability relative to level of cognitive functioning. Detailed profiles of language functioning in four children with WS and four with SLI are presented which show a much less clear-cut picture than is often portrayed and suggest that children with WS may be less linguistically able than is commonly reported. A comparison of results on standardised tests with performance in real conversations shows that not only the children with SLI but also those with WS have significant linguistic difficulties. This has clear implications for their management by speech and language therapists.

Child↗

Effect of temperature-season on bovine adrenal cortical function, blood cell profile, and milk production.

Data collected monthly for one calendar year from Holstein cows lactating under Louisiana ambient climatic conditions comprised a total of 264 cow-months. The year was divided into seasons of cool, intermediate, and hot temperatures. The hot season elicited depressions in circulating corticoids and percent hematocrit. Leukocytosis was a response to increasing ambient temperature primarily accounted for by an increase in circulating neutrophils. Progression from intermediate to hot season gave evidence of eosinophila, and in addition, a relative eosinopenia may have been induced by increased adrenal cortex activity. Milk production was depressed during the hot temperature-season and showed no significant relationship with corticoids of plasma. Rectal temperatures and respiration rates were indicative of heat stress in the hot temperature-season and gave significant negative correlations with circulating corticoid concentration.

Adrenal Cortex↗

Blood pressure and cardiac autonomic function in relation to risk factors and treatment perspectives in Type 1 diabetes.

The cumulative incidence of diabetic nephropathy in Type 1 diabetes mellitus is in the order of 25 30%. The recognition that elevated blood pressure (BP) is a major factor in the progression of these patients to end-stage renal failure has led to the widespread use of antihypertensive therapy in order to preserve glomerular filtration rate and ultimately to reduce mortality. The routine measurement of microalbuminuria allows early identification of the subgroup of patients at increased risk of developing clinical nephropathy. Microalbuminuric Type 1 diabetic patients show a number of characteristic pathological abnormalities. In addition to elevated BP and abnormal circadian rhythm, there are also associated abnormalities of vagal function, lipid profile and endothelial function, as well as an increased prevalence of retinopathy. The first section of this two-part review focusses on the early changes associated with renal involvement in Type 1 diabetes. It addresses the associations between urinary albumin excretion, glycaemic control, smoking, BP, circadian BP variation, QT interval abnormalities and autonomic function in three groups of patients; those with normoalbuminuria, those progressing towards microalbuminuria and those with established low-grade microalbuminuria.

Albuminuria↗