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We present data on the use of filter-paper blood collection for measurement of glycosylated whole-blood proteins (gWB) (hemoglobin and plasma proteins). A capillary blood sample, obtained by fingerprick, is spotted directly onto filter paper (Schleicher & Schuell 903). The blood spot is washed briefly with alcohol (ethanol or isopropanol) to remove free glucose and dried before shipment to the laboratory. In the laboratory, the blood is eluted from the paper and analyzed for gWB by a colorimetric method. The gWB is primarily a measure of glycosylated hemoglobin (gHb) with a small contribution from glycosylated plasma protein. Concentrations of gWB and gHb are highly correlated (r = 0.91). The filter-paper method offers advantages over currently available methods for quantifying gHb and may be particularly useful in screening for diabetes and for assessing glycemic control in patients from remote areas.

Significant progress has been made in the investigation of placebo effects. Recent research shows that they are genuine psychobiological events attributable to the overall therapeutic context. Placebo effects can appear in experimental trials as well as in clinical settings. There is some initial evidence that patients may be more prone to these effects, compared to healthy people, and it has also been shown that placebo effects may last up to several years after treatment. On the psychological level, expectancy via instructions and expectancy via classical conditioning have been identified as the two primary mechanisms. Both seem to be important in boosting subjective reliefs across different diseases, even if most of our knowledge about the neurobiology of the phenomenon ‘‘placebo effect’’ comes from the field of pain and analgesia. On the neurobiological level, recent research has identified multiple placebo mechanisms, although more research is needed. This topical issue will bring together three different aspects: (a) an analysis of the most relevant psychological strategies to induce bodily placebo-related changes; (b) best evidence of neurobiologically significant placebo effects; and (c) implications of placebo research for clinical practice. By integrating these three perspectives, it will offer a broad survey of this topic for both scientists and clinicians. Issues addressed may include evidence for psychological strategies for harnessing significant placebo-induced effects, for example, brain-endogenous release of opioids, and how such benefits can be obtained in patients suffering from, for example, chronic pain. Thus, we solicit papers for this topical issue of the Zeitschrift f r Psychologie that examine these three aspects of placebo research. In addition to suggestions for full original or review articles, shorter research notes and opinion papers are also welcome. We invite researchers of various areas of psychology and medicine to submit their abstracts on potential papers electronically to either of the guest editors: Regine Klinger (rklinger@uni-hamburg.de) Luana Colloca (luana.colloca@nih.gov) How to submit: Interested authors should submit a letter of intent including: (1) a working title for the manuscript, (2) names, affiliations, and contact information for all authors, and (3) an abstract of no more than 500 words detailing the content of the proposed manuscript. There is a two-stage submissions process. Initially, interested authors are requested to submit only abstracts of their proposed papers. Authors of the selected abstracts will then be invited to submit full papers. All papers will undergo blind peer review.

21-Hydroxylase (21-OH) deficiency is characterized by an excess of androgen in both sexes and premature skeletal maturation resulting in short adult stature and male infertility. To achieve optimal height in children and fertility in adults, the replacement treatment of 21-OH deficiency with glucocorticoids should be regulated in order to adequately reduce the excess of androgens while minimizing the dose of glucocorticoids required. Neonatal screening for 21-OH deficiency is based on the measurement of the 17 alpha-hydroxyprogesterone (17-OHP) level from blood spotted on filter paper. The aim of this study was to examine whether repeated daily blood sampling on filter paper can assist in improving the monitoring of, and compliance to, 21-OH deficiency treatment.During a 5-year period (1989-1994) we instructed 8 patients with 21-OH deficiency (2 males with salt losing, 2 males and 1 female simple virilizing, and 1 male and 2 females with nonclassical 21-OH deficiency) aged 1.3-36 years to sample blood on filter papers 1-4 times a day and send the papers to our neonatal screening laboratory by mail. On 62 occasions we measured both serum and filter paper 17-OHP levels in order to assess the degree of correlation between the two methods.Comparison between the filter paper and serum 17-OHP levels showed a correlation coefficient of r = 0.87. The filter paper levels were almost always higher than the serum levels. The serum 17-OHP levels were1 ng/ml whenever the filter paper levels were3 ng/ml. On long-term follow-up of 17-OHP filter paper levels we observed major diurnal and day-to-day fluctuations which might not have been noticed on routine follow-up clinic visits.Filter paper follow-up of 17-OHP levels can assist in optimizing the replacement treatment in patients with 21-OH deficiency while reinforcing compliance and decreasing the need for frequent clinic visits and hospitalizations. By adjusting the glucocorticoid type, dose, and time of administration to each patient we should be able to achieve optimal growth without bone age acceleration in children, to avoid overtreatment, and to improve fertility in adults.

SummaryUsing the paper chromatographic technic significant changes in the protein patterns have been demonstrated in patients with multiple sclerosis. We are unable to state at present the relationship of these changes to the activity of the disease, but our evidence would seem to indicate that they may occur concomitantly with, or immediately following the onset of exacerbation. Furthermore the changes in protein patterns revert to normal during remissions.

In spite of many attempts to modify the filtrate reaction of Brdicka's cancer test, none of them gave better results than the original one. We already reported that in patients with acute leukemia the first maximum of Brdicka's filtrate wave was often higher than the second maximum. Such phenomenon presumably depends on the high contents of polysaccharides in molecules of these blood mucoproteins. In this paper further efforts were made to clarify the factors influencing on the shape of the protein double wave, and to find out the polarographic characteristics and clinical significance of electrophoretically separated mucoprotein with special reference to the wave form. Among many experimental conditions, the temperature in polarographic cells was found to be most sensitive factor to affect the protein wave shape, so that all experiments were carried out at the constant temperature (20°C±0.05). Serum mucoprotein was evidently separated into two fractions, M1 fraction an M2 fraction, by paper electroyhoresis in McIlvaine's buffer of pH 4, 4. These two fractions showed polarographically different shape each other. The M1 fraction, the most rapidly anodic moving one, showed left side elevation in shape; in other words, the first maximum was higher than the second maximum. On the contraly, M2 fraction showed right side elevation in shape; the second maximum was higher than the first maximum. Furthermore, it was very interesting from clinical point of view that the characteristic shape of M1 fraction was to some extent variable depending on diseases. From the clinical observation on 259 cases including 119 cases of cancer and 11 cases of leukemia, it was revealed that in neoplastic patients the wave shape of M1 fraction showed clearcut difference from those in normal; Δh (distance from the second maximum to the first maximum) of M1 fraction in neoplastic patients was larger than that in normal. Thus, the cancer detection rate has markedly elevated as compared with the original filtrate test, namely from 77% to 90%o in our study.

Filter paper electrophoretic analyses of serum were carried out in a series of eighteen proved cases of multiple myeloma, twenty-three normal controls and 130 patients with non-myelomatous diseases, and compared with the results of classical Tiselius electrophoresis and chemical fractionation. Abnormal electrophoretic patterns were found in all of the cases of multiple myeloma studied, and tall narrow spikes representing abnormal proteins with varying mobilities in the globulin range were demonstrated in 78 per cent. The latter were considered diagnostic of myelomatosis since similar patterns have not been described in any other disease and since none were observed in any of the present controls. In six of the eighteen cases the diagnosis was first established on the basis of these electrophoretic patterns and subsequently confirmed by bone marrow biopsy. In eight others they were merely confirmatory in previously diagnosed cases. Of special interest were the diagnostic patterns found in four patients in whom myelomatosis was not suspected. There were significant quantitative differences between the results obtained by filter paper and classical electrophoresis, and the results of both differed from those of chemical fractionation. However, the diagnostic peaks of myelomatosis were equally well demonstrated by both electrophoretic methods. It is concluded (1) that the electrophoretic patterns of serum obtained by both the filter paper and Tiselius methods exhibit highly characteristic peaks in a high proportion of individuals with multiple myeloma, (2) that such patterns are of great diagnostic value and (3) that the filter paper method offers the advantages of simplicity, low cost and speed, without any loss in sensitivity or specificity, which make it especially valuable for screening large numbers of specimens in patients suspected of having myelomatosis.

Micelle-associated epoetin is still a possible explanation for the upsurge of pure red blood cell aplasia associated with subcutaneous use of epoetin alpha in patients with chronic renal failure.

Research studies on the side effects of commonly prescribed drugs constituted the three most read papers published by the BMJ in 2005, according to an internal audit that assessed their use by readers. Studies that showed increased risk of myocardial infarction in patients taking cyclo-oxygenase-2 (COX 2) inhibitors and that explored the link between selective serotonin reuptake inhibitors and suicide came top. For the audit Sara Schroter, the BMJ 's senior researcher, analysed research papers using three measures: the number of citations a paper received, the number of times it was accessed on the web, and the number of rapid responses it generated. The top scoring paper was a case-control study that showed greater risk of myocardial infarction in patients taking the COX 2 inhibitor rofecoxib (Vioxx) and in patients taking diclofenac …

18536 Background: Electronic diaries have been developed and facilitate collection of quality of life data. However there is concern that their use may alter the properties of the validated quality of life questionnaires which have traditionally been collated using a paper and pencil methodology. This study aimed to compare the results of e-diary and paper and pencil collection of FACT-L and EQ-5D quality of life data, and to ascertain patient preferences for the different modes of collection. Methods: Fifty patients with previously treated locally advanced or metastatic NSCLC were randomised in a 1:1 ratio to either complete a paper version of the questionnaires (FACT-L and EQ-5D) followed by the e-diary (Palm Tungsten W;CRF inc. Helsinki), or e-diary followed by paper questionnaire. Patient preference, ease of use and time for completion were recorded on a separate paper questionnaire. Results: The majority (88%) of the FACT-L and all (100%) of the EQ-5D individual question responses were within ± 1 point by the two methods, although for FACT-L 29% of patients had a total score greater than ± 6 points different by the two methods. There was no significant difference in FACT-L group mean total score for the two methods. The mean completion time was shorter for the paper and pencil than the e-diary (p < 0.0001). However, most patients stated that they preferred the e-diary to paper and pencil (60% vs. 12%). Conclusions: This study suggests that the mode of administration of the FACT-L and EQ-5D had a relatively small effect on the group mean responses given to the questionnaires. However data at the individual patient level looks quite variable between mode of administration. The group results obtained using the e-diary should therefore be comparable to the originally validated paper method, with the advantages of improved patient acceptability and ease of reliable interfacing with trial databases. However care need to be taken in interpreting data at the individual level. No significant financial relationships to disclose.

candidategeneandthetheorythatsympatheticoveractivityisan underestimated contributor to ESRD.Although considerable further evidence would need to fol-low to verify the putative causal chain, ideally early develop-ments would be that others would reproduce the findings inlarger populations, and longitudinal studies in patient groupsor animal models would demonstrate that sympathetic over-activity (and lower catestatin) precedes progressive decline torenal failure. Eventually, then, the value of these CHGA hap-lotypes and catestatin as markers and perhaps the benefits ofmedication that is capable of limiting the distorted sympa-thetic outflow, perhaps limiting certain adrenergic effects,might then be worth assessment in those who are at high riskfor ESRD.DISCLOSURES

The absorption of tear fluid into the Schirmer-I-filter paper was evaluated by serial measurements in 5 normal volunteers and in 32 patients with Sjogren's syndrome. The length of wetting was correlated to the weight of tear fluid absorbed in the paper strips. A linear relationship was demonstrated. We conclude that the Schirmer-I-test implies reproducible and fairly precise estimation of the tear flow even in cases of small lengths of wetting. The test is reliable, simple and useful for the diagnosis and follow-up of dry eyes, especially in patients with Sjogrens syndrome.

Aims: Major general surgical operations, especially for malignancy, are associated with a high risk of venous thrombo-embolic (VTE) complications, of which about 40 per cent occur after discharge. In this systematic review we examine the value of extended thrombo-prophylaxis. Methods: Three randomized, controlled trials, which studied 1 week versus 4 weeks of thromboprophylaxis (TP) with low molecular weight heparin (LMWH), were included in the analysis. We used RevMan (Version 4.1.1, Oxford & England 2000) to perform the meta-analysis using fixed odds ratio (OR) to compare groups. All patients undergoing venography were considered and only objectively confirmed VTE events were included in the efficacy analysis. All patients randomized to prolonged prophylaxis and who received a dose of study drug were considered in the safety analysis. Results: A total of 683 patients were randomized to receive LMWH for 1 week (333 patients) or 4 weeks (350 patients). Total VTE events occurred in 16 (4.8 per cent) patients in the extended group and 40 (11.4 per cent) in the control group (OR = 0.39, 95 per cent CI 0.21–0.71; P = 0.002). The risk of bleeding was 3.5 per cent in both groups (OR 0.99, 95 per cent CI 0.47–2.06; P = 1). Conclusions: Extended TP results in significant reduction of the risk of developing VTE in patients undergoing major general surgical operations without any increase in the risk of bleeding.

Management of diverticular disease has significantly improved in the last decade. Antibiotic treatment is used for symptom relief and prevention of complications. In Italy, the non-absorbable antibiotic rifaximin is one of the most frequently used drugs, and it is perceived as the reference drug to treat symptomatic diverticular disease. Its non-systemic absorption and high faecal concentrations have oriented rifaximin use to the gastrointestinal tract, where rifaximin exerts eubiotic effects representing an additional value to its antibiotic activity. This position paper was commissioned by the Italian Society of Gastroenterology governing board for a panel of experts (RC, GB, BA) to highlight the indications for treatment of diverticular disease. There is a lack of rationale for drug use for the primary prevention of diverticulitis in patients with diverticulosis; thus, rifaximin use should be avoided. The cyclic use of rifaximin, in association with high-fibre intake, is safe and useful for the treatment of symptomatic uncomplicated diverticular disease, even if the cost-efficacy of long-term treatment remains to be determined. The use of rifaximin in the prevention of diverticulitis recurrence is promising, but the low therapeutic advantage needs to be verified. No evidence is available on the efficacy of rifaximin treatment on acute uncomplicated diverticulitis.

THE following technique for the separation of phenols, phenolic acids and their derivatives by one-dimensional paper partition chromatography has been developed as part of a two-dimensional method (to be published shortly) for the investigation of serum and urinary phenols in patients suffering from acute uraemia.

Parathyroid hormone (PTH) determination is of greatest importance for patients suffering from parathyroid gland disorders and for the follow-up of bone turnover in patients suffering from chronic kidney disease (CKD). Two generations of PTH assays are simultaneously present on the market for PTH quantification. As these assays are not yet standardized, this results in a significant level of confusion in the care of CKD patients. One key objective of the IFCC Committee for Bone Metabolism is to improve this situation. In this position paper, we will highlight the current state of PTH testing and propose a pathway to ultimately overcome issues resulting from PTH assay variability.