Structural effects on the pH-dependent fluorescence of naphthalenic derivatives and consequences for sensing/switching.

Naphthalenic compounds are a rich resource for designers of fluorescent sensing/switching/logic systems. The degree of internal charge transfer (ICT) character in the fluorophore excited states can vary from negligible to substantial. Naphthalene-1,8;4,5-diimides (11­13), 1,8-naphthalimides (16) and 4-chloro-1,8-naphthalimides (15) are of the former type. The latter type is represented by the 4-alkylamino-1,8-naphthalimides (1). Whether ICT-based or not, these serve as the fluorophore in 'fluorophore-spacerreceptor'switching systems where PET holds sway until the receptor is bound to H+. On the other hand, 4-dialkylamino-1,8-naphthalimides (3­4) show modest H+-induced fluorescence switching unless the 4-dialkylamino group is a part of a small ring (5). Electrostatic destabilization of a non-emissive twisted internal charge transfer (ICT) excited state is the origin of this behaviour. An evolution to the nonemissive twisted ICT excited state is responsible for the weak emission of the model compound 6 (and related structures 7 and 8) across the pH range. Twisted ICT excited states are also implicated in the switch 9 and its model compound 10, which are based on the 6-dialkylamino-3H-benzimidazo[2,1-a]-benz[d,e]isoquinolin-3-one fluorophore.

Quality error rates in point-of-care testing.

BACKGROUND: Although a theoretical consideration suggests that point-of-care testing (POCT) might be uniquely vulnerable to error, little information is available on the quality error rate associated with POCT. Such information would help inform risk/benefit analyses when one considers the introduction of POCT. METHODS: This study included 1 nonacute and 2 acute hospital sites. The 2 acute sites each had a 24-h central laboratory service. POCT was used for a range of tests, including blood gas/electrolytes, urine pregnancy testing, hemoglobin A(1c) (Hb A(1c)), blood glucose, blood ketones, screening for drugs of abuse, and urine dipstick testing. An established Quality Query reporting system was in place to log and investigate all quality errors associated with POCT. We reviewed reports logged over a 14-month period. RESULTS: Over the reporting period, 225 Quality Query reports were logged against a total of 407 704 POCT tests. Almost two-thirds of reports were logged by clinical users, and the remainder by laboratory staff. The quality error rate ranged from 0% for blood ketone testing to 0.65% for Hb A(1c) testing. Two-thirds of quality errors occurred in the analytical phase of the testing process. These errors were all assessed as having no or minimal adverse impact on patient outcomes; however, the potential adverse impact was graded higher. CONCLUSIONS: The quality error rate for POCT is variable and may be considerably higher than that reported previously for central laboratory testing.

The development of a system for the reporting, classification and grading of quality failures in the clinical biochemistry laboratory.

BACKGROUND: There is no agreed system for the reporting, classification and grading of the severity of quality failures in the clinical biochemistry laboratory. METHODS: A 'Quality Query' reporting system was set up to log all quality failures identified by staff and service users. Quality failures were classified into three major groups of the preanalytical, analytical and postanalytical phases with appropriate subcategories in each group. The severity of each quality failure was graded using a five-point scoring system incorporating both actual ('A') and potential ('P') score elements. The 'A' score measured the actual adverse impact of the quality failure on patient care, while the 'P' score measured the 'worst case' potential outcome that might have resulted. The system was assessed over a 19-month period. RESULTS: Three hundred and ninety-seven Quality Query reports were completed (0.085% of all requests). Breakdown by cause: pre-analytical phase--88.9%, analytical phase--9.6%, post-analytical phase--1.5%. The quality failure severity 'A' scores were skewed towards a low adverse impact on patient care: 72.7% allocated an 'A' score of 1 (least severe grade). The 'P' scores were skewed towards a high potential impact on patient care: 65.9% allocated a 'P' score of 5 (most severe grade). CONCLUSIONS: The Quality Query reporting system proved easy to integrate into routine laboratory practice. Although the great majority of quality failures had minimal adverse impact on patient care, the potential for adverse outcomes was much higher. This system generates important information on laboratory performance and helps inform risk management priorities.

Abnormalities of serum apo A1 containing lipoprotein particles in patients with primary biliary cirrhosis.

Patients with primary biliary cirrhosis (PBC) do not appear to have an increased risk of cardiovascular disease despite elevations in serum cholesterol. Recent evidence has pointed to LpA1 (an apo A1 containing particle which contains apo A1 but not apo A2) in protecting against atherosclerosis. The aim of this study was to investigate apo Al containing particles in the serum of patients with PBC. Lipids and apolipoproteins were measured in 31 patients with PBC (30 females) and 27 control subjects (26 females). Patients were divided into 3 groups: group 1 with bilirubin < 18 micromol/l (n = 17); group 2 with bilirubin > 18 micromol/l (n = 11); and group 3 with end stage liver disease (ESLD, n = 3). As expected group 1 and 2 patients had higher total cholesterol, HDL cholesterol and phospholipids than control subjects. Apo B and apo A1 concentrations were similar to control subjects. However, LpA1 was greatly increased: 0.96 g/l (0.60-1.50), median (range) in group 1 and 1.09 g/l (0.75-1.33) in group 2 versus 0.62 g/l (0.45-0.93) for controls both P < 0.005 and the percentage of total apo A1 in the LpA1 fraction was increased: 54.8% (37.9-63.4) in group 1 and 55.7% (47.8-73.7) in group 2 versus 36.8% (25.1-49.1) for controls, both P < 0.005. Apo A2 concentration was reduced in group 1 0.38 g/l (0.30-0.51) and group 2 0.31 g/l (0.14-0.58) versus controls 0.43 g/l (0.36-0.57), P < 0.05 and P < 0.005 respectively. Patients with ESLD had reduced HDL cholesterol, apo A1, LpA1 and apo A2 compared to controls. These results suggest that PBC is associated with an altered distribution of apo A1 favouring an increased concentration of the protective LpA-I particles. Increased LpA1 concentration may be one of the factors contributing to the paradoxically low incidence of atherosclerosis in PBC patients.

Determination of a diabetes control and complications trial-aligned HbA(1c) reference range in pregnancy.

A diabetes control and complications trial (DCCT)-aligned 95% inter-fractile reference range for glycated haemoglobin in non-diabetic pregnancy was determined as 4.1-5.9% (n=493; two-sided 90% confidence intervals around the lower and upper limits are 4.0-4.2% and 5.8-6.0%, respectively).

Determination of thiamine by high-performance liquid chromatography.

High-performance liquid chromatographic methods for the determination of thiamine (vitamin B1) in foodstuffs or biological tissues and fluids are outlined and discussed. The methods are often similar and interchangeable, sample extraction and clean up procedures being the major difference. Most of the methods use either ultraviolet or fluorescence detection. Fluorescence detection requires either precolumn or postcolumn oxidation of thiamine to thiochrome. A number of methods are recommended and problems with standardization are emphasized.

Determination of the total protein and triglyceride content of human breast milk on the Synchron CX7 Delta analyser.

BACKGROUND: Premature babies have improved clinical outcomes when fed breast milk with a relatively high protein content. Since there was no convenient way of measuring the macronutrition of breast milk we used our routine laboratory pyrogallol red dye binding method for cerebrospinal fluid microprotein (MTP) and our routine method for serum triglyceride to determine the total protein and triglyceride content of human breast milk. METHODS: The total protein contents of whole and defatted breast milk samples, randomly collected from 115 nursing mothers, analysed using a pyrogallol red dye binding assay on a Synchron CX7 Delta analyser were compared with the total protein contents determined by dry combustion analysis. Triglyceride concentrations, determined on the Synchron CX7 Delta analyser were compared with their respective creamatocrits. RESULTS: Passing and Bablok regression analysis (95% confidence interval) gave the following regression equations: y = 5.98(5.48 to 6.56)x-1.32(-2.02 to -0.73) where y is whole milk MTP (g/L) and x is dry combustion analysis (g/100 g); y = 7.09 (6.54 to 7.78)x-2.44 (-3.46 to -1.67) where y is volume-corrected defatted milk MTP (g/L) and x is dry combustion analysis (g/100 g); y = 7.52 (6.86 to 8.24)x+0.90(-2.42 to 3.37) where y is whole milk triglyceride (mmol/L) and x is creamatocrit (%). CONCLUSION: The Synchron CX7 Delta total protein and triglyceride assays provide practical, rapid and reliable methods for the determination of the macronutrition in human milk.

Clinical outcome indicators, disease prevalence and test request variability in primary care.

AIM: To describe differences in biochemistry test request rates (adjusted for practice size) between general practices and to investigate whether differences in HbA(1c) and thyroid function test request rates are related either to the practice prevalence of hypothyroidism and diabetes or to Quality and Outcome Framework (QOF) scores. METHODS: Information on test request rates, prevalence of diabetes and hypothyroidism, and QOF data over a one-year period were obtained from 58 practices covering a population of 284,609 patients. Spearman's rank correlation tests were used to investigate relationships between adjusted test request rates. RESULTS: There was wide variability in adjusted test request rates (lowest for HbA(1c) and highest for immunoglobulins). The ranking of practices for different tests was highly correlated. There was no relationship between adjusted test request rates for HbA(1c) and thyroid function and the reported prevalence of diabetes and hypothyroidism, respectively, nor was there any relationship with QOF scores in diabetes and hypothyroidism. CONCLUSIONS: There is wide variability in test request rates in general practice that do not appear to be related to disease prevalence or crude clinical outcome measures.

High-performance liquid chromatographic determination of thiamine diphosphate in erythrocytes using internal standard methodology.

A high-performance liquid chromatography method for the determination of thiamine diphosphate (vitamin B1) in erythrocytes is presented. The method is robust, accurate and reproducible and due to the use of acetylaneurine as an internal standard, offers advantages over previous methods.

Stability of cefepime in peritoneal dialysis solution.

OBJECTIVE: To determine the stability of cefepime in peritoneal dialysis solution. DESIGN: Cefepime HCl was added to premade bags of Delflex peritoneal dialysis solution with 1.5% dextrose to produce a cefepime concentration of approximately 100 microg/mL. Peritoneal dialysis solution bags were stored at 4, 25, and 37 degrees C to simulate refrigeration, room temperature, and body temperature, respectively. Samples were drawn at scheduled times up to 336, 168, and 48 hours, respectively, after the addition of cefepime HCl. Cefepime concentrations were measured by HPLC. SETTING: This study was performed at a university-affiliated tertiary care hospital. OUTCOME MEASURE: If the mean concentration of the samples at a given time and condition was >90% of the initial concentration, cefepime was considered stable at that time and condition. RESULTS: The mean HPLC results for samples drawn at each time and condition were all >90%. CONCLUSIONS: Cefepime is stable in peritoneal dialysis solution with dextrose 1.5% for 14 days refrigerated, seven days at room temperature, and 48 hours at 37 degrees C.