Microgels and nanogels with catalytic activity.

Molecular imprinting has grown considerably over the last decade with more and more applications being developed. The use of this approach for the generation of enzyme-mimics is here reviewed with a particular focus on the most recent achievements using different polymer formats such as microgels and nanogels, beads, membranes and also silica nanoparticles.

The development of novel organically modified sol-gel media for use with ATR/FTIR sensing.

The ability to prepare and develop novel pre-concentration media by the sol-gel process, and their integration with mid-infrared transparent waveguides has been demonstrated. This research approach resulted in a mid-infrared sensing methodology in which the properties (porosity, functionality, polarity, etc.) of the recognition layer could be tailored by variation of the sol-gel precursors and processing conditions. Cross-linker type and concentration notably influenced p-xylene absorption and diffusion rate. Unreacted silanol groups appeared to be the dominant factor in the hydrophobicity of sol-gel layers. Variation of sol-gel precursors and thermal treatment altered both film cross-link density and polarity, as demonstrated by variation in the rate of analyte diffusion and equilibrium analyte concentration. The use of a novel 1 : 1 PTMOS : DPDMS material as pre-concentration medium in this analytical sensing approach was validated through the determination of p-nitrochlorobenzene in an aqueous environment. The response demonstrated linearity between 0-30 mg L(-1) with a correlation coefficient of 0.989 and a limit of detection of 0.7 mg L(-1). Sensing times for p-nitrochlorobenzene were also reduced from several hours to 24 minutes, without loss of measurement accuracy or sensitivity, by a 10 degrees C increase in the sensing temperature and the use of a predictive Fickian model previously developed by this research group.

A randomized, double-blinded comparison of Thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients.

BACKGROUND: The aim of this study was to compare the efficacy and safety of Thymoglobulin (a rabbit-derived polyclonal antibody) to Atgam (a horse-derived polyclonal antibody) for induction in adult renal transplant recipients. METHODS: Transplant recipients (n=72) were randomized 2:1 in a double-blinded fashion to receive Thymoglobulin (n=48) at 1.5 mg/kg intravenously or Atgam (n=24) at 15 mg/kg intravenously, intraoperatively, then daily for at least 6 days. Recipients were observed for at least 1 year of follow-up. RESULTS: By 1 year after transplantation, 4% of Thymoglobulin-treated patients experienced acute rejection compared with 25% of Atgam-treated patients (P=0.014). The rate of acute rejection was lower with Thymoglobulin than Atgam (relative risk=0.09; P=0.009). Rejection was less severe with Thymoglobulin than Atgam (P=0.02). No recurrent rejection occurred with Thymoglobulin compared with 33% with Atgam (P=NS). Patient survival was not different, but the composite end point of freedom from death, graft loss, or rejection, the "event-free survival," was superior with Thymoglobulin (94%) compared with Atgam (63%; P=0.0005). Fewer adverse events occurred with Thymoglobulin (P=0.013). Leukopenia was more common with Thymoglobulin than Atgam (56% vs. 4%; P<0.0001) during induction. The mean absolute lymphocyte count remained below baseline with Thymoglobulin throughout the study (P<0.007), but with Atgam, significant lymphocyte reductions occurred only at day 7. The incidence of cytomegalovirus disease was less with Thymoglobulin than Atgam at 6 months (10% vs. 33%; P=0.025). CONCLUSIONS: Brief (7-day) induction with Thymoglobulin resulted in less frequent and less severe rejection, a better event-free survival, less cytomegalovirus disease, fewer serious adverse events, but more frequent early leukopenia than induction with Atgam. These results may in fact be explained by a more profound and durable beneficial lymphopenia.

Hyperleptinaemia of end-stage renal disease is corrected by renal transplantation.

BACKGROUND: Previous studies have reported that patients with end-stage renal disease (ESRD) have elevated plasma leptin concentrations, but the cause and significance of the elevations are unknown. We studied leptin concentrations in 29 adults undergoing renal transplantation, to determine if restoration of renal function reduced leptin concentrations in ESRD. METHODS: Leptin concentrations were measured by radioimmunoassay in plasma specimens collected within 1 week before transplant, 6 days post-transplant, and 60 days post-transplant. RESULTS: Mean plasma leptin concentrations were higher in both male and female ESRD patients compared with a control population of similar age and body mass index (BMI), but most of the disparity was due to a minority of patients with grossly elevated concentrations; the majority of ESRD patients had normal or near-normal leptin concentrations after accounting for their adiposity with BMI. Six days after successful renal transplantation, average plasma leptin concentrations decreased to control levels. The grossly elevated pretransplant concentrations in a minority of patients were greatly reduced in relation to BMI, and the reduction persisted to 60 days post-transplant. The decrease in creatinine with transplant did not correlate with the decrease in leptin. CONCLUSIONS: These results demonstrate that restoration of renal function in ESRD patients reduces hyperleptinaemia, which provides further evidence of a cause/effect relationship between impaired renal function and abnormal leptin metabolism.

Protection of encapsulated human islets implanted without immunosuppression in patients with type I or type II diabetes and in nondiabetic control subjects.

Human islets were macroencapsulated in permselective hollow fiber membrane devices and successfully allotransplanted subcutaneously with > 90% viability after 2 weeks in situ. Recipients were patients with type I or type II diabetes and normal control subjects; none was immunosuppressed. Between 150 and 200 islet equivalents were implanted in each of the nine patients. No adverse patient complications were observed. Biocompatibility of devices was excellent. Insulin-positive beta-cells were confirmed in encapsulated islets recovered from the implanted devices in all patient populations including the type I diabetic patients. Glucose-stimulated insulin release could be demonstrated in vitro from recovered islets. These data demonstrate that macroencapsulated human islets can survive at the subcutaneous site and that permselective membranes can be designed to protect against both allogeneic immune responses as well as the autoimmune component of type I diabetes.

Change in metabolic control and functional status after hospitalization. Impact of patient activation intervention in diabetic patients.

OBJECTIVE: To determine whether a short intervention to enhance patient information seeking and decision making during hospitalization results in improved metabolic control and functional status in patients with diabetes mellitus. RESEARCH DESIGN AND METHODS: A randomized clinical trial was conducted in which control patients received a comprehensive 3-day evaluation and educational program, whereas experimental patients received a 45-min patient activation intervention and a 1-h self-administered booster in addition to the program. Metabolic control and functional status were measured at baseline and 4 mo postdischarge. RESULTS: During their discharge discussions, experimental patients asked significantly more questions than control patients (7.4 vs. 3.0, P less than .001) and 4 mo later reported significantly fewer physical limitations in activities of daily living than the control group (P = 0.02). Improvement in metabolic control was statistically significant only for experimental patients (P = 0.02), although their glycosylated hemoglobin levels were not significantly lower than control patients' at follow-up. The intervention did not diminish physician satisfaction with patient interactions, although it may have increased physician frustration with responsibilities that competed with patient care. CONCLUSIONS: These results suggest that the addition of a patient activation intervention to a comprehensive diabetes management program may substantially enhance physical functioning among adults with diabetes mellitus.

Self-care predictors of metabolic control in NIDDM patients.

The objective of this study was to evaluate whether the relationship between self-care behavior and metabolic control is comparable in patients with non-insulin-dependent diabetes mellitus (NIDDM) on insulin and not on insulin. We studied 84 NIDDM patients hospitalized for an elective admission in Washington University's Model Demonstration Unit. At admission, patients reported the frequency of exercise, blood glucose monitoring, and meal skipping for the previous 2 wk. Metabolic control over the previous 8-12 wk was determined from glycosylated hemoglobin assays. In cross-sectional analysis controlling for patient sociodemographic and health characteristics, glycosylated hemoglobin levels were positively related to meal skipping (P = 0.0008) and negatively related to the frequency of blood glucose monitoring (P = 0.0025). Self-care behaviors explained 26% of the variance in glycosylated hemoglobin levels in NIDDM patients. Multivariate modeling demonstrated no significant interaction effects between insulin treatment and self-care on metabolic control. In conclusion, these findings support the clinical significance of self-care activities for metabolic control in NIDDM patients, particularly meal skipping and blood glucose monitoring.

The intensive insulin therapy team.

The use of a team approach to the management of patients using intensive insulin therapy (IIT) has been supported by policy/position statements of both the American Association of Diabetes Educators and the American Diabetes Association. A course designed and taught by a health care team within the Washington University Diabetes Research and Training Center was offered to 18 multidisciplinary health care teams desiring information about initiating IIT programs. Course outcomes demonstrated positive responses to the team approach to team education but raised questions about the actual composition and functioning of the health care "team." While a well-defined team with IIT knowledge and skills is essential for the development of a comprehensive and safe approach to IIT programs, it is not clear who should be offering these programs.

An assessment instrument to measure physicians' knowledge of diabetes management.

A 57-item multiple choice test to assess physicians' knowledge of current approaches to diabetes management was devised by a multidisciplinary team that developed the test's case studies and questions. This test was revised based on critiques by diabetologists and other specialists at the Washington University Medical Center and its Diabetes Research and Training Center. A pilot test of the instrument was conducted with 95 residents from five accredited residency training programs and 17 medical students, and the results demonstrated consistent gaps in the respondents' knowledge in several major categories of diabetes management. The test was validated by administering it to 20 endocrinologists with known diabetes expertise and 16 nonspecialist family practice and internal medicine physicians. Analysis of these results revealed significant differences in test performance between the nonspecialists and experts. This initial body of data was used to refine the instrument further to the 56-item test presently being administered nationwide by the diabetes center to groups of family practice and internal medicine physicians and to residents and medical students.