Phonological similarity in the serial recall task hinders item recall, not just order.

The phonological similarity effect in short-term memory (STM) is the finding that serial recall of lists of similar sounding items is poorer than that of dissimilar sounding items. This is traditionally argued to be due to a detrimental effect on memory for the order of the words in the list and not on memory for the words themselves. Models that propose forgetting from STM is due to interference must invoke an additional compensatory process where the shared element of the words acts as a cue to recall, in order to account for the lack of an effect on memory for the words. However, the possibility of a detrimental effect of phonological similarity on item memory when these compensatory processes are not available has not been investigated. Two experiments (n = 60 and n = 57) in which similarity is operationalized in a way that precludes usage of compensatory processes are reported. The results clearly demonstrate that item recall is poorer for similar lists than dissimilar lists when similarity is defined in this way.

Reflex testing to define action limits for community-based requests.

BACKGROUND: Critical values are required to be phoned 24/7. Other abnormal results fall short of the thresholds used to define critical values and may only be required to be phoned during the day. Community-based requestors prefer not to be contacted unless a result is critical and contacting them requires substantial staff resource. It is common practice to add tests to requests to expedite diagnosis or clarify the significance of a particular result using algorithms. METHODS: We devised algorithms for reflex addition of tests which allowed the differentiation of significantly abnormal results as either critical values or those that only require day phoning. RESULTS: Algorithms identified 158 out of 309 tests as being critical (51%) over nine months. Reflex addition of serum bicarbonate identified 4% of serum glucose (24.9-37.9 mmol/L) as critical. Use of estimated glomerular filtration rate by reflex addition of serum creatinine identified 68% of serum lithium (1.49-1.99 mmol/L) as critical. Addition of serum potassium, calcium and magnesium identified 21% of serum digoxin (>2.49 nmol/L) as critical and addition of serum potassium and calcium to all samples with serum magnesium (<0.31 mmol/L) identified hypocalcaemia in all cases. The addition of serum creatinine and potassium as markers for rhabdomyolysis-induced acute renal failure did not help in the differentiation of serum creatine kinase>4999 µ/L. CONCLUSIONS: Use of reflex tests helped inform a phoning system based on the division of results into critical values and non-emergency abnormal values. This avoids disturbing requestors unnecessarily and conserves staff time at night.

Changes in bone mineral parameters, vitamin D metabolites, and PTH measurements with varying chronic kidney disease stages.

Vitamin D deficiency is associated with an increased risk of many diseases (skeletal and nonskeletal). Emerging data also associate high concentrations of serum parathyroid hormone (PTH) with morbidity and increased mortality in patients both with and without known chronic kidney disease (CKD). Understanding the relationship between vitamin D and PTH and the determinants of PTH is therefore important. We performed a cross-sectional study of 203 patients with varying stages of CKD randomly recruited from the Renal Unit database at our institution. Detailed case review was performed, and samples of fasting blood were taken for biochemical analyses. We measured standard biochemistry, 25-hydroxyvitamin D (25-OHD), 1,25-OHD, and three PTH measurements [1-84 PTH, total PTH, and derived N-terminal truncated, 7-84 PTH (cPTH)]. Vitamin D deficiency was high, with 86% of patients having 25-OHD levels below 30 ng/ml. Estimated glomerular filtration rate (eGFR) was not associated with 25-OHD levels, whereas 1,25-OHD was lower in those with CKD stage 5 versus stage 4, who were not treated with vitamin D metabolites (18 vs. 65 pg/ml, respectively; P < 0.05). All three PTH measurements increased with worsening eGFR, with this finding being more pronounced in those patients who were not treated with vitamin D metabolites. The slope of the regression line of cPTH on eGFR tended to be steeper, -0.90, compared to -0.81 for total PTH and -0.80 for 1-84 PTH (P = 0.06). The ratio of total PTH to cPTH did decrease significantly through the range of CKD stages (P = 0.03). The determinants of PTH were similar for all three PTH measurements, with eGFR having a strong inverse relationship, with weaker relationships for 25-OHD and ionized calcium on multivariate analyses. We confirm that there is a complex relationship between 25-OHD, eGFR, and PTH. Total PTH, 1-84 PTH, and cPTH increase with increasing CKD stages, with a relatively greater increase in cPTH, although the clinical significance of this finding remains uncertain. The three PTH measurements had similar correlations with the biochemical and clinical variables studied, suggesting that either total PTH or 1-84 PTH can be used in clinical practice when evaluating vitamin D and PTH status.

Phaeochromocytoma: diagnostic challenges for biochemical screening and diagnosis.

The aim of this article is to provide knowledge of the origin of catecholamines and metabolites so that there can be an informed approach to the methods for biochemical screening for a possible phaeochromocytoma; The article includes a review of catecholamine and metadrenaline metabolism, with methods used in biochemical screening. In the adrenal medulla and a phaeochromocytoma, catecholamines continuously leak from chromaffin granules into the cytoplasm and are converted to metadrenalines. For a phaeochromocytoma to become biochemically detectable, metnoradrenaline secretion needs to rise fourfold, whereas noradrenaline secretion needs to rise 15-fold. The prevalence of a sporadic phaeochromocytoma is low; therefore false-positive results exceed true-positive results. Assay sensitivity is high because it is important not to miss a possible phaeochromocytoma. The use of urine or plasma fractionated metadrenalines as the first-line test has been recommended due to improved sensitivity. A negative result excludes a phaeochromocytoma. Only after a sporadic phaeochromocytoma has been diagnosed biochemically is it cost effective to request imaging. Sensitivities and specificities of the assays differ according to pre-test probabilities of the presence of a phaeochromocytoma, with hereditary and incidentalomas having a higher pre-test probability than sporadic phaeochromocytoma. In conclusion, in screening for a possible phaeochromocytoma, biochemical investigations should be completed first to exclude or establish the diagnosis. The preferred biochemical screening test is fractionated metadrenalines, including methoxytyramine so as not to miss dopamine-secreting tumours.

Differential diagnosis of chylothorax in a patient on parenteral nutrition: a case report.

Parenteral nutrition (PN) is widely used when enteral feeding is contraindicated or not possible in patients who are malnourished or at risk of malnutrition, but it is not without complications. We describe the rare complication of PN-related chylothorax that can lead to extensive investigations if not picked up early with clinical suspicion and simple biochemical tests.

Nitric oxide bioavailability and its potential relevance to the variation in susceptibility to the renal and vascular complications in patients with type 2 diabetes.

OBJECTIVE: We compared the renal and systemic vascular (renovascular) response to a reduction of bioavailable nitric oxide (NO) in type 2 diabetic patients without nephropathy and of African and Caucasian heritage. RESEARCH DESIGN AND METHODS: Under euglycemic conditions, renal blood flow was determined by a constant infusion of paraminohippurate and changes in blood pressure and renal vascular resistance estimated before and after an infusion of L-Ng-monomethyl-L-arginine. RESULTS: In the African-heritage group, there was a significant fall in renal blood flow (Delta-46.0 ml/min per 1.73 m(2); P < 0.05) and rise in systolic blood pressure (Delta 10.0 mmHg [95% CI 2.3-17.9]; P = 0.017), which correlated with an increase in renal vascular resistance (r(2) = 0.77; P = 0.004). CONCLUSIONS: The renal vasoconstrictive response associated with NO synthase inhibition in this study may be of relevance to the observed vulnerability to renal injury in patients of African heritage.

Risk factors for fractures and falls in older women with type 2 diabetes mellitus.

Type 2 diabetes mellitus (DM) is associated with an increased risk of hip fractures despite patients with this condition having normal to high bone mineral density (BMD). Therefore, nonskeletal risk factors may be important in the etiology of fractures in these patients. The aim of this cross-sectional retrospective study was to determine risk factors for falling and fracture in older women with type 2 DM. We randomly recruited 150 women from a community-based diabetes register. They underwent detailed clinical assessment, and BMD was measured by dual-energy X-ray absorptiometry (DXA) and heel quantitative ultrasound (QUS). Mean age was 74 years, mean duration of DM 11 years, mean body mass index 30 kg/m2, and mean HbA1c 7.6%. Mean BMD Z scores were significantly higher than the manufacturer's reference range for all skeletal sites. Previously, 53/150 (35%) of the women had reported a low trauma fracture. The fracture group did not differ significantly from the nonfracture group by age, diabetes-related risk factors or DXA BMD Z scores. However, QUS variables were lower in the fracture group (P = 0.04). A history of one or more falls in the previous 12 months was reported by 61/89 (41%) women. Fallers had a higher vibration perception threshold vs. nonfallers (mean 21.1 vs. 17.6 volts, respectively; P = 0.05). There were no other differences in diabetes or fall-related risk factors. These data suggest that reduced vibration perception (a measure of peripheral neuropathy) is an important risk factor for falling and that QUS, as opposed to DXA, may be a more useful method for fracture risk prediction in older women with type 2 DM. These findings need to be confirmed prospectively.

A practical method of measuring glomerular filtration rate by iohexol clearance using dried capillary blood spots.

BACKGROUND: Exogenous tracer-based methods of measuring glomerular filtration rate (GFR) are difficult to perform, whilst creatinine-based estimation formulae are inaccurate. METHODS: We assessed a new technique of measuring iohexol clearance using timed dried capillary blood spots. A reference GFR was measured in 81 subjects (GFR 15-124 ml/min/1.73 m(2)) by iohexol clearance using three venous samples (2, 3 and 4 h after an intravenous bolus). GFR was estimated by six test methods; iohexol clearance using (i) 3 blood spots (2, 3, 4 h); (ii) 2 blood spots (2, 4 h) and (iii) 1 blood spot (4 h); (iv) the Modification of Diet in Renal Disease (MDRD) formula; (v) the Cockcroft-Gault formula, and (vi) a formula estimating GFR from serum cystatin C concentration. For each test method the bias and precision were calculated as the mean and standard deviation (SD) of the 'GFR differences' (test method GFR - reference GFR). RESULTS: The limits of agreement (bias +/-1.96 x SD; in ml/min/1.73 m(2)) were: (i) 1.1 +/- 15.1 for 3-spot iohexol clearance; (ii) 0.6 +/- 14.9 for 2-spot iohexol clearance; (iii) 4.5 +/- 21.2 for 1-spot iohexol clearance; (iv) -15.7 +/- 33.3 for the MDRD formula; (v) -9.6 +/- 32.9 for the Cockcroft-Gault formula, and (vi) -12.1 +/- 31.7 for the Cystatin C formula. The accuracy of all six test methods was similar among individuals with GFR <60 ml/min/ 1.73 m(2); however, in individuals with GFR > or =60 ml/min/ 1.73 m(2), the MDRD, Cockcroft-Gault and Cystatin C formulae were all imprecise and systematically underestimated GFR. CONCLUSIONS: Blood spot iohexol clearance provides a potentially practical method of estimating GFR accurately in large-scale epidemiological studies especially among individuals without established chronic kidney disease.

GFR estimation using cystatin C is not independent of body composition.

BACKGROUND: Cystatin C (CysC) is an endogenous marker of glomerular filtration rate (GFR) that is claimed to be unaffected by body composition. In this study, we tested this speculation. METHODS: In 77 patients with chronic kidney disease (mean age, 65.1 +/- 11.9 [SD] years; mean indexed GFR, 45.7 +/- 28.6 mL/min/1.73 m(2) [0.76 +/- 0.48 mL/s]), we evaluated kidney function (GFR) by means of inulin clearance. CysC level was determined by using a particle-enhanced turbidimetric immunoassay. Total lean (LM) and fat masses were measured by means of dual-energy x-ray absorptiometry. Multiple regression was used to analyze relationships between absolute GFR, LM, fat mass, demographic and anthropometric variables (age, sex, height, and weight), and CysC levels. Then prediction equations were built that included only CysC level or CysC level and LM. Their performance to predict absolute GFR was evaluated in a subset of patients with extreme body composition (LM or fat mass > +/-1 SD of the entire sample). RESULTS: Only absolute GFR and LM significantly explained variance in CysC levels, and an equation including LM explained more variance in absolute GFR than an equation including CysC level alone. Consequently, the equation including LM performed better than the equation with only CysC level, especially in patients with extreme body composition, showing reduced bias and improved limits of agreement and accuracy (71.4% versus 51.4% of patients' predicted GFR did not deviate by >30% of GFR). CONCLUSION: LM is a previously unrecognized, but important, factor affecting CysC level, and GFR estimation improves when including LM. CysC level is not independent of body composition, as previously assumed, and hence accounting for body composition improves CysC-based GFR estimation.

Bioelectrical impedance can be used to predict muscle mass and hence improve estimation of glomerular filtration rate in non-diabetic patients with chronic kidney disease.

BACKGROUND: In this article (the second of two companion studies), we report whether bioelectrical impedance analysis (BIA) can be used to predict muscle mass in patients with chronic kidney disease (CKD), and whether using this predicted muscle mass can improve the estimation of glomerular filtration rate (GFR). METHODS: Seventy five non-diabetic patients with CKD (mean age +/- SD, 65.1 +/- 12.0 years; mean GFR 45.9 +/- 28.8 ml/min/1.73 m2) underwent body composition analysis by dual energy X-ray absorptiometry to provide a criterion marker of skeletal muscle mass (appendicular lean mass, ALM). Validity of a published BIA equation to predict ALM was evaluated and a new BIA equation was generated (ALM(BIA)) and cross-validated by the leave-one-out procedure. Renal inulin clearance provided a criterion measure of GFR (GFR(inu)). The performance of the equation including ALM(BIA) to estimate GFR(inu) was compared with demographic variables as used in the modification of diet in renal disease (MDRD) equation, by determining bias, limits of agreement and accuracy. RESULTS: The previously published BIA equation to predict ALM was not valid in these patients with CKD. In contrast, our new ALM(BIA) equation cross-validated successfully. Compared with the MDRD demographic variables, using ALM(BIA) to predict GFR(inu) improved estimation performance, showing reduced bias (4.3 vs 15.6 ml/min) and improved limits of agreement (41.1 vs 59.2 ml/min) and accuracy (69.7 vs 39.4% of patients' predicted GFR did not deviate by more than 30% of GFR(inu)). CONCLUSIONS: ALM(BIA) provides a clinically obtainable and valid method to predict muscle mass in patients with CKD, and using ALM(BIA) improves the estimation of GFR(inu). Researchers developing future GFR estimation equations should consider including ALM(BIA).

The relationship between estimated glomerular filtration rate, demographic and anthropometric variables is mediated by muscle mass in non-diabetic patients with chronic kidney disease.

BACKGROUND: In this study (the first of two related papers), we report whether the relationship between the demographic and anthropometric variables (DA, i.e. age, gender, height and weight) employed in current creatinin (Cr)-based glomerular filtration rate (GFR) estimation equations and actual GFR is mediated by muscle mass. METHODS: We studied 77 patients (mean age +/- SD, 65.1 +/- 11.9 years) with chronic kidney disease (mean GFR 45.7 +/- 28.6 ml/min/1.73 m2). Actual GFR was measured by the renal clearance of inulin (GFR(inu)). Appendicular lean mass (ALM) and its index (ALMI) by dual energy X-ray absorptiometry provided markers of muscle mass. Multiple regression analyses identified variables explaining variance in (i) GFR, (ii) ALM and (iii) Cr. RESULTS: (i) The DA variables used in the abbreviated modification of diet in renal disease (MDRD) equation accounted for only 59.6% (P < 0.001) of the variance in GFR(inu), whilst adding ALMI explained an additional 10.4% variance (P < 0.001). If ALMI was entered first, the relationship between DA variables and GFR(inu) was reduced (for weight) or completely abolished (for age, gender and height). (ii) After inputting all the commonly used DA variables, 17.2% of the variance in ALM was unexplained. (iii) All the DA variables explained only 60.6% (P < 0.001) of the variance in Cr, whilst adding ALM explained an additional 4.2% variance (P < 0.005). CONCLUSIONS: Muscle mass explained more variance in GFR(inu) than MDRD DA variables and mediated the relationship between GFR(inu) and DA variables. Furthermore, DA variables failed to account for individual differences in muscle mass or Cr. Consequently, there is a need to validate simpler, clinically obtainable measures of muscle mass and determine whether these measures will improve GFR estimation.

Urinary and plasma organic acids and amino acids in chronic fatigue syndrome.

Previous work by others have suggested the occurrence of one or more chemical or metabolic 'markers' for ME/CFS including specific amino acids and organic acids and a number of unidentified compounds (CFSUM1, CFSUM2). We have shown elsewhere that CFSUM1 is partially derivatised pyroglutamic acid and CFSUM2 partially derivatised serine and have suggested and demonstrated that the analytical methods used were unsuitable to identify or to accurately quantify urinary metabolites. We have now made a detailed analysis of plasma and urinary amino acids and of urinary organic acids from patients with ME/CFS and from three control groups. Fasting blood plasma and timed urine samples were obtained from 31 patients with CFS, 31 age and sex-matched healthy controls, 15 patients with depression and 22 patients with rheumatoid arthritis. Plasma and urinary amino acids and urinary organic acids were determined using established and validated methods and data compared by statistical analysis. None of the previously reported abnormalities in urinary amino acids or of organic acids could be confirmed. Results however provide some evidence in patients with ME/CFS for underlying inflammatory disease and for reduced intramuscular collagen with a lowered threshold for muscle micro-injury. These factors in combination may provide a basis for the fatigue and muscle pain that are the major symptoms in these patients.

Effect of short-term supplementation of potassium chloride and potassium citrate on blood pressure in hypertensives.

Randomized trials have shown that increasing potassium intake lowers blood pressure. However, most previous trials used potassium chloride, whereas potassium in fruits and vegetables is not a chloride salt. It is unclear whether a nonchloride salt of potassium has a greater or lesser effect on blood pressure compared with potassium chloride. We performed a randomized crossover trial comparing potassium chloride with potassium citrate (96 mmol/d, each for 1 week) in 14 hypertensive individuals. At baseline, blood pressure was 151+/-16/93+/-7 mm Hg with a 24-hour urinary potassium of 81+/-24 mmol. During the randomized crossover part of the study, blood pressure was 140+/-12/88+/-7 mm Hg with potassium chloride (24-hour urinary potassium: 164+/-36 mmol) and 138+/-12/88+/-6 mm Hg with potassium citrate (24-hour urinary potassium: 160+/-33 mmol). These blood pressures were significantly lower compared with that at baseline; however, there was no significant difference in blood pressure between potassium chloride and potassium citrate, mean difference (95% confidence interval): 1.6 (-2.3 to 5.6) mm Hg for systolic and 0.6 (-2.4 to 3.7) mm Hg for diastolic. Our results, in conjunction with the evidence from many previous trials that potassium chloride has a significant blood pressure-lowering effect, suggest that potassium citrate has a similar effect on blood pressure as potassium chloride. These results support other evidence for an increase in potassium intake and indicate that potassium does not need to be given in the form of chloride to lower blood pressure. Increasing the consumption of foods high in potassium is likely to have the same effect on blood pressure as potassium chloride.

Anaphylactic reaction to intravenous sinistrin (Inutest).

Inulin clearance is the 'gold standard' for the determination of glomerular filtration rate. This is the first report of anaphylaxis following intravenous administration of inulin.