Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects

CONTEXT: Thyroid disease and the metabolic syndrome are both associated with cardiovascular disease. OBJECTIVE: The aim of this study was to explore the hypothesis that thyroid function, in euthyroid subjects, is associated with components of the metabolic syndrome, including serum lipid concentrations and insulin resistance. METHODS: A total of 2703 adult inhabitants of a middle-sized city in The Netherlands participated in this cross-sectional study. Subjects who were not euthyroid were excluded, as were subjects taking thyroid medication, medication for diabetes, and subjects for whom medication data were not available (n = 1122). Homeostasis model assessment for insulin resistance (HOMA-IR) (mU*mmol/liter2) was calculated as fasting insulin (mU/liter) times fasting glucose (mmol/liter) divided by 22.5. The metabolic syndrome was defined according to National Cholesterol Education Program's Adult Treatment Panel III criteria. RESULTS: After adjustment for age and sex, free T4 (FT4) was significantly associated with total cholesterol [standardized beta (beta) = -0.059; P = 0.014], low-density lipoprotein cholesterol (beta = -0.068; P = 0.004), high-density lipoprotein cholesterol (beta = 0.100; P < 0.001), and triglycerides (beta = -0.102; P < 0.001). Both FT4 and TSH were significantly associated with HOMA-IR (beta = -0.133; P < 0.001 and beta = 0.055; P = 0.024, respectively). Median HOMA-IR increased from 1.42 in the highest tertile of FT4 to 1.66 in the lowest tertile of FT4. FT4 was significantly related to four of five components of the metabolic syndrome (abdominal obesity, triglycerides, high-density lipoprotein cholesterol, and blood pressure), independent of insulin resistance. CONCLUSIONS: We have demonstrated an association between FT4 levels within the normal reference range and lipids, in accordance with the earlier observed association between (sub)clinical hypothyroidism and hyperlipidemia. Moreover, low normal FT4 levels were significantly associated with increased insulin resistance. These findings are consistent with an increased cardiovascular risk in subjects with low normal thyroid function.     

Detrusor glycogen reflects the functional history of bladders with partial outlet obstruction

OBJECTIVE: To assess the relationship between glycogen content in bladder detrusor tissue and historical bladder function in a guinea-pig model of partial bladder outlet obstruction (PBOO). MATERIALS AND METHODS: In male immature guinea pigs PBOO was created with a silver ring around the proximal urethra; a control group had a sham operation for comparison. Longitudinal individual urodynamic data were obtained weekly, so that guinea pigs were killed at different levels of bladder dysfunction. Bladder sections were stained with periodic acid-Schiff (PAS) to assess overall morphology and glycogen granule density, scored from 0 (no glycogen) to 3. Glycogen scores were related to both the end-stage and historical extremes of bladder function values. RESULTS: Glycogen granules were seen only in the detrusor; as their number increased their location expanded from only close to the serosa (glycogen score 1), through the detrusor (score 2) up to the urothelium (score 3). A glycogen score of 0 correlated with normal values for all urodynamic variables. Compared with a glycogen score of 0 a score of 1 correlated with significant (P < 0.05) changes in end-stage compliance (decrease) and contractility (increase) and significantly higher historical values for contractility, pressure and number of unstable contractions (NUC). In the group with a glycogen score of 2 there were significant changes in both the end-stage values and historical extremes for compliance, pressure, contractility and NUC (all P < 0.05). In the group with a glycogen score of 3 all these changes were even more dramatic, except for the end-stage contractility, for which the increase was not significant. From glycogen score 0 to score 3 all changes increased in magnitude. CONCLUSION: A high glycogen content reflects a history of abnormal urodynamic function. This finding exemplifies the added value of structural analysis to urodynamic studies. Further studies are needed to relate bladder structure to the potential for functional recovery.     

Favorable results of the surgical treatment of intra-articular crush fractures of the distal femur]

Severely comminuted intra-articular femoral fractures are usually associated with major soft-tissue damage as a part of serious multiple injuries. Surgical treatment should aim at exact anatomical restoration of the articular surface. Internal fixation should be stable so that functional after-treatment is possible, a condition of achieving an optimal result. In a period of over 7 years, 24 patients with 26 intra-articular comminuted fractures were operated on. Twenty patients had multiple injuries (ISS > 18), 11 fractures were complicated. Postoperatively, impaired wound healing occurred in three elderly patients; in two of these amputation was necessary. Considering the severity of the injury, the long-term results were good: ten of the 16 patients examined with 18 fractures recovered completely, in the other cases the functional result wa adequate to good. Surgical treatment of comminuted intra-articular fractures of the distal femur is to be adapted to the individual case; depending on the fracture type and the associated damage a selection is to be made from various implants and techniques. With consistent, individually adapted application of the current AO techniques good results can be obtained.     

Effects of dietary fiber and insulin treatment on serum levels of lipids and lipoprotein (a) in patients with type II diabetes mellitus]

OBJECTIVE. As lipoprotein(a) is an independent risk factor for the development of coronary heart disease we determined the effect on serum lipid and lipoprotein(a) levels of dietary fibre and of treatment with insulin in patients with diabetes mellitus type II. METHODS. Twelve type II diabetic patients (mean age 62 (SD 10) yrs, body mass index 25.8 (SD 3.5) kg/m2), all treated with oral antidiabetic agents, were studied in a randomised cross-over trial, in which they used breads meals prepared with guar gum (a mean of 11.2 g guar per day) for 3 months in comparison with normal high-fibre bread. Fifteen other patients (age 70 (8), BMI 27.4 (5.6) kg/m2) poorly controlled on oral hypoglycaemic agents, were treated with insulin. RESULTS. The guar treatment of the 12 patients resulted in lower total cholesterol (5.24 vs 5.7 mmol/l, p less than 0.1) and LDL cholesterol (3.77 vs 4.33 mmol/l, p less than 0.001) in comparison with normal high-fibre bread. Lipoprotein(a) levels were not different (76 vs 82 mg/l). Insulin therapy in the 15 other patients decreased HbA1c levels after 6 months from 11.0 to 7.7% (p less than 0.001), total cholesterol from 6.8 to 6.1 mmol/l (p less than 0.05), and LDL cholesterol from 4.4 to 4.1 mmol/l (p less than 0.05). Lp(a) decreased only slightly in 11/15 patients, from 491 to 441 mg/l (p = 0.07). CONCLUSION. Neither the use of the dietary fibre guar nor improved metabolic control with insulin therapy lowered elevated lipoprotein(a) levels in type II diabetic patients.     

Detection of fetal red cells in fetomaternal hemorrhage using a fetal hemoglobin monoclonal antibody by flow cytometry

BACKGROUND: The laboratory determination of the level of fetal cells in maternal circulation remains an important support in the obstetrical management of women with suspected uterine trauma and in the proper dose administration of anti-D for prevention of Rh hemolytic disease of the newborn. Limitations in the sensitivity and precision of the widely used manual Kleihauer-Betke test have prompted an increased utilization of flow cytometric methods for fetal cell detection in maternal blood samples. STUDY DESIGN AND METHODS: Murine monoclonal antibodies directed against fetal hemoglobin (HbF) were developed, conjugated to fluorescein isothiocyanate, and used in a multiparametric flow cytometric assay developed for the quantitation of fetal red cells. A rapid intracellular staining method using brief glutaraldehyde fixation and Triton X-100 permeabilization prior to monoclonal antibody incubation was developed, along with optimization of the flow cytometric analysis protocol for the analysis of 50,000 cells. The performance of the assay was assessed for linearity and precision and correlated with the Kleihauer-Betke acid elution method. RESULTS: The anti-HbF flow cytometric method showed good correlation with the Kleihauer-Betke method (r2 = 0.86) and superior precision with a CV < 15 percent for blood samples with > 0.1 percent fetal cells. Analysis of 150 blood samples from nonpregnant adults, including individuals with elevated HbF due to hemoglobinopathies and hereditary persistence of HbF, gave a mean value of 0.02 percent fetal cells, and all results were less than 0.1 percent. CONCLUSIONS: The anti-HbF flow cytometric method for detection of fetal cells offers a simple, reliable, and more precise alternative to the Kleihauer-Betke manual technique for the assessment of fetomaternal hemorrhage. The method has additional potential applications for the study of HbF levels or frequency of adult red cells with low levels of HbF (F cells) in individuals with hemoglobinopathies.     

Purification of Hageman factor (factor XII) on columns of popcorn- agarose

Purification of Hageman factor (HF, factor XII) from human plasma is a tedious procedure and the product is not always in the precursor form. Hojima has described a protein derived from corn kernels that inhibits the enzymatic properties of HF. This inhibitor binds to the precursor form of HF. Rapid purification of HF was achieved by using as the major purification step adsorption of this clotting factor to popcorn inhibitor bound to agarose. The product had a specific activity of 50.0 to 67.1 coagulant units of HF per milligram protein, and the yield was 33% to 40% of the HF content of the starting plasma. The purified protein displayed a single band upon unreduced or reduced sodium dodecyl sulfate polyacrylamide gel electrophoresis and less than 0.1% was in an activated form, as measured in coagulant assays. The technique described is more rapid and reliable than methods described earlier.     

An audit of consent refusals in clinical research at a tertiary care center in India

Background and Rationale:

Ensuring research participants’ autonomy is one of the core ethical obligations of researchers. This fundamental principle confers on every participant the right to refuse to take part in clinical research, and the measure of the number of consent refusals could be an important metric to evaluate the quality of the informed consent process. This audit examined consent refusals among Indian participants in clinical studies done at our center.

Materials and Methods:

The number of consent refusals and their reasons in 10 studies done at our center over a 5-year period were assessed. The studies were classified by the authors according to the type of participant (healthy vs patients), type of sponsor (investigator-initiated vs pharmaceutical industry), type of study (observational vs interventional), level of risk [based on the Indian Council of Medical Research (ICMR) “Ethical Guidelines for Biomedical Research on Human Participants”], available knowledge of the intervention being studied, and each patient''s disease condition.

Results:

The overall consent refusal rate was 21%. This rate was higher among patient participants [23.8% vs. healthy people (14.9%); P = 0.002], in interventional studies [33.6% vs observational studies (7.5%); P < 0.0001], in pharmaceutical industry-sponsored studies [34.7% vs investigator-initiated studies (7.2%); P < 0.0001], and in studies with greater risk (P < 0.0001). The most common reasons for consent refusals were multiple blood collections (28%), inability to comply with the study protocol (20%), and the risks involved (20%).

Conclusion:

Our audit suggests the adequacy and reasonable quality of the informed consent process using consent refusals as a metric.KEY WORDS: Autonomy, consent, India, reason, refusal, risk