A multi-perspective service evaluation exploring tuberculosis contact screening attendance among adults at a North London hospital.

BACKGROUND: Non-attendance at TB contact screening clinics has been highlighted as a common phenomenon across a number of sites during recruitment to the PREDICT TB Study. This has obvious implications for the safety of patients, their communities and for NHS resources. The objective of this study was to explore why adults who have been in contact with TB do, and do not, attend their screening appointment, thereby allowing identification of interventions to reduce non-attendance. METHODS: A multi-method approach was taken using 15 questionnaires with adults who attended for screening, 15 telephone questionnaires with adults who did not attend and in-depth interviews with 8 TB nurses. Interviews were coded to trace emerging descriptive themes, then refined through an iterative process of interpretation and recoding. RESULTS: Findings from the questionnaires and interviews were categorized into three principle themes following analysis: awareness, hospital factors and leadership. These themes deconstruct the complex phenomena of patients' lack of attendance at this TB contact screening service. CONCLUSION: Recommendations related to issues of leadership, outreach services, flexibility of clinic timing and awareness amongst both the local community and GPs were made.

cAMP-mediated signaling normalizes glucose-stimulated insulin secretion in uncoupling protein-2 overexpressing beta-cells.

We investigated whether an increase in cAMP could normalize glucose-stimulated insulin secretion (GSIS) in uncoupling protein-2 (UCP2) overexpressing (ucp2-OE) beta-cells. Indices of beta-cell (beta-TC-6f7 cells and rodent islets) function were measured after induction of ucp2, in the presence or absence of cAMP-stimulating agents, analogs, or inhibitors. Islets of ob/ob mice had improved glucose-responsiveness in the presence of forskolin. Rat islets overexpressing ucp2 had significantly lower GSIS than controls. Acutely, the protein kinase A (PKA) and epac pathway stimulant forskolin normalized insulin secretion in ucp2-OE rat islets and beta-TC-6f7 beta-cells, an effect blocked by specific PKA inhibitors but not mimicked by epac agonists. However, there was no effect of ucp2-OE on cAMP concentrations or PKA activity. In ucp2-OE islets, forskolin inhibited ATP-dependent potassium (K(ATP)) channel currents and (86)Rb(+) efflux, indicative of K(ATP) block. Likewise, forskolin application increased intracellular Ca(2+), which could account for its stimulatory effects on insulin secretion. Chronic exposure to forskolin increased ucp2 mRNA and exaggerated basal secretion but not GSIS. In mice deficient in UCP2, there was no augmentation of either cAMP content or cAMP-dependent insulin secretion. Thus, elevating cellular cAMP can reverse the deficiency in GSIS invoked by ucp2-OE, at least partly through PKA-mediated effects on the K(ATP) channel.

Physiological increases in uncoupling protein 3 augment fatty acid oxidation and decrease reactive oxygen species production without uncoupling respiration in muscle cells.

Decreased uncoupling protein (UCP)3 is associated with insulin resistance in muscle of pre-diabetic and diabetic individuals, but the function of UCP3 remains unclear. Our goal was to elucidate mechanisms underlying the negative correlation between UCP3 and insulin resistance in muscle. We determined effects of physiologic UCP3 overexpression on glucose and fatty acid oxidation and on mitochondrial uncoupling and reactive oxygen species (ROS) production in L6 muscle cells. An adenoviral construct caused a 2.2- to 2.5-fold increase in UCP3 protein. Palmitate oxidation was increased in muscle cells incubated under normoglycemic or hyperglycemic conditions, whereas adenoviral green fluorescent protein infection or chronic low doses of the uncoupler dinitrophenol had no effect. Increased UCP3 did not affect glucose oxidation, whereas dinitrophenol and insulin treatments caused increases. Basal oxygen consumption, assessed in situ using self-referencing microelectrodes, was not significantly affected, whereas dinitrophenol caused increases. Mitochondrial membrane potential was decreased by dinitrophenol but was not affected by increased UCP3 expression. Finally, mitochondrial ROS production decreased significantly with increased UCP3 expression. Results are consistent with UCP3 functioning to facilitate fatty acid oxidation and minimize ROS production. As impaired fatty acid metabolism and ROS handling are important precursors in muscular insulin resistance, UCP3 is an important therapeutic target in type 2 diabetes.

Evaluation of eight decision rules for low-level radioactivity counting.

In low-level radioactivity measurements, it is often important to decide whether a measurement differs from background. A traditional formula for decision level (DL) is given in numerous sources, including the recent ANSI/HPS N13.30-1996, Performance Criteria for Radiobioassay and the Multi-Agency Radiation Survey and Site Investigation Manual (MARSSIM). This formula, which we dub the N13.30 rule, does not adequately account for the discrete nature of the Poisson distribution for paired blank (equal count times for background and sample) measurements, especially at low numbers of counts. We calculate the actual false positive rates that occur using the N13.30 DL formula as a function of a priori false positive rate a and background Poisson mean mu = rhot, where rho is the underlying Poisson rate and t is the counting time. False positive rates exceed a by significant amounts for alpha < or = 0.2 and mu < 100 counts, peaking at 25% at mu approximately equal to 0.71, nearly independent of alpha. Monte Carlo simulations verified calculations. Currie's derivation of the N13.30 DL was based on knowing a good estimate of the mean and standard deviation of background, a case that does not hold for paired blanks and low background rates. We propose one new decision rule (simply add 1 to the number of background counts), and we present six additional decision rules from various sources. We evaluate the actual false positive rate for all eight decision rules as a function of a priori false positive rate and background mean. All of the seven alternative rules perform better than the N13.30 rule. Each has advantages and drawbacks. Given these results, we believe that many regulations, national standards, guidance documents, and texts should be corrected or modified to use a better decision rule.

Improving health physics measurements by performance testing.

Testing standards have been written to establish minimum performance requirements for personnel dosimeters, radiation survey instruments and bioassay laboratory measurements. These standards were subjected to experimental evaluation and to a consensus review to ensure that the requirements were practical. Programs have been established, using the personnel dosimeter standards, to improve and control the performance of dosimeter processors. Similar implementation of performance testing of instruments will improve reliability of field measurements. Initiation of a program based on the bioassay standard will improve the accuracy, precision, and detectability levels for measuring radioactivity in occupationally exposed workers. Evaluating the performance of health-physics measurement tools will improve the accuracy and precision of measurement and add to our knowledge of personnel exposures. Performance testing will become a more widely recognized tool for maintaining high-quality programs, and the concept will be applied to other measurements as well.

The growth and metastasis of four commonly used tumour lines implanted into eight different sites: evidence for site and tumour effects.

The growth and metastasis of four commonly used experimental tumour lines have been compared after the implantation of cells into a lobe of the liver, the spleen, the left kidney, the peritoneal cavity, the thorax, the right thigh muscle, subcutaneously into the dorsolumbar region and intravenously into the tail vein or the right femoral vein. This was done to assess the importance of site in affecting metastatic distribution, and to determine whether any general conclusions could be drawn as to the role of this factor. Tumours grew at variable rates in different sites, but this did not affect the extent or distribution of metastasis. Each line gave a characteristic pattern that could be considerably modified by site. For example, in the spleen, metastasis was always extensively to the liver; in the kidney, and to some extent in the muscle, metastasis was similar to that obtained for intravenously injected cells; in the peritoneal cavity or thorax, metastasis was usually lower than from other sites; and in the liver, the metastasis to other lobes of the liver and to the lungs was modified. Many of these findings could be explained by both specific and non-specific factors operating at each site. It is suggested that interactions at the primary site of tumour growth may be very important in affecting metastasis, and that in the future more attention should be given to this factor in order to make progress in understanding tumour spread.

Studies on glomerular basement membrane in experimental diabetes using lectin histochemistry in Wistar rats.

This study was designed to establish whether specific early changes in carbohydrate content of proteins in the glomerulus of the diabetic rat could be detected. Lectin staining of kidney sections from streptozotocin-induced diabetic rats were compared with similar sections from healthy and diabetic rats that were treated with insulin. Animal groups were killed 1 month, 3 months and 6 months after induction of diabetes. There were no differences in the staining of the glomerular basement membrane between control, insulin-treated and diabetic rats for the lectins concanavalin A, lotus tetragonolobus, soybean and kidney bean, with and without trypsinisation. Staining of the glomerular basement membrane with wheat germ agglutinin after trypsinisation was significantly increased in the diabetic group when compared to both healthy and insulin-treated groups (p less than 0.01). It was concluded that, in experimental diabetes mellitus in the rat, there is an accumulation of substances in the glomerular basement membrane and mesangium with an affinity for wheat germ agglutinin, most probably N-acetyl glucosamine, and this is partially prevented by insulin treatment.