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The properties of soft matter nanoparticles like exosomes are interesting for drug delivery and diagnostics applications. However, the simultaneous characterization of multiple properties, e.g., size and zeta potential, can only be done serially and is highly sensitive to the purification prior to characterization. Here we show how a salt gradient established in a nanofluidic channel induces opposing transport of particles and liquid that trap the particles. Particles are thus accumulated in the trap. We show how optical microscopy images of the particle positions in the salinity gradient provide a measurement of the size and surface charge. We demonstrate the method on a sample of exosomes and on individual particles. Finally, we show how biomolecular reactions at the surface of the nanoparticle can be detected from the optical microscopy analysis of the particles’ trapping position.

Abstract Background Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus reported to be associated with prostate cancer (PC) and chronic fatigue syndrome (CFS). While the association of XMRV with CFS and PC has recently been discredited, no studies have been performed in Australian patients to investigate the association between PC and XMRV or related murine leukemia virus (MLV) in matched PC and normal tissue. Methods Genomic DNA (gDNA) was purified from matched normal and cancer formalin-fixed paraffin-embedded (FFPE) prostate tissue from 35 Australian PC patients with Gleason scores ranging from 7 – 10. The presence of the ribonuclease L (RNase L) polymorphism R462Q was determined by allele specific PCR. Samples were screened for XMRV and related murine leukemia virus (MLV) variants by qPCR. Contaminating mouse DNA was detected using qPCR targeting mouse intracisternal A particle long terminal repeat DNA. Results gDNA was successfully purified from 94% (66/70) of normal and cancer FFPE prostate tissues. RNase L typing revealed 8% were homozygous (QQ), 60% were heterozygous (RQ) and 32% were wild-type (RR) for the RNase L mutation. None of the 66 samples tested were positive for XMRV or related MLV sequences using broad MLV or XMRV specific primers with detection sensitivities of 1 viral copy of MLV/XMRV and XMRV DNA, respectively. Conclusions Using highly sensitive qPCR we found no evidence of XMRV or related gammaretroviruses in prostate tissues from 35 Australian PC patients. Our findings are consistent with other studies demonstrating that XMRV is a laboratory contaminant that has no role in the aetiology of PC.

Abstract Background Transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative diseases caused by novel infectious agents referred to as prions. Prions appear to be composed primarily, if not exclusively, of a misfolded isoform of the cellular prion protein. TSE infectivity is remarkably stable and can resist many aggressive decontamination procedures, increasing human, livestock and wildlife exposure to TSEs. Findings We tested the hypothesis that UV-ozone treatment reduces levels of the pathogenic prion protein and inactivates the infectious agent. We found that UV-ozone treatment decreased the carbon and prion protein content in infected brain homogenate to levels undetectable by dry-ashing carbon analysis or immunoblotting, respectively. After 8 weeks of ashing, UV-ozone treatment reduced the infectious titer of treated material by a factor of at least 105. A small amount of infectivity, however, persisted despite UV-ozone treatment. When bound to either montmorillonite clay or quartz surfaces, PrPTSE was still susceptible to degradation by UV-ozone. Conclusion Our findings strongly suggest that UV-ozone treatment can degrade pathogenic prion protein and inactivate prions, even when the agent is associated with surfaces. Using larger UV-ozone doses or combining UV-ozone treatment with other decontaminant methods may allow the sterilization of TSE-contaminated materials.

In the domain of organic mixed ionic-electronic conductors (OMIECs), simultaneous transport and coupling of ionic and electronic charges are crucial for the function of electrochemical devices in organic electronics. Understanding conduction mechanisms and chemical reactions in operational devices is pivotal for performance enhancement and is necessary for the informed and systematic development of more promising materials. Surface-enhanced Raman spectroscopy (SERS) is a potent tool for monitoring electrochemical evolution and dynamic doping in operational devices, offering enhanced sensitivity to subtle spectral changes. We demonstrate the utility of SERS for in situ tracking of doping in OMIECs in an organic light-emitting electrochemical cell (LEC) containing a conjugated polymer (poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene]; MEH-PPV), a molecular anion (lithium triflate), and an electrolyte network (poly(ethylene oxide); PEO). SERS enhancement is achieved via an interleaved layer of gold particles formed by spontaneous breakup of a deposited thin gold film. The results successfully highlight the ability of SERS to unveil time-resolved MEH-PPV doping and polaron formation, elucidating the effects of triflate ion transfer in the operating device and validating the electrochemical doping model in LECs.

Introduction: The regenerative and immunomodulatory properties of multipotent mesenchymal stromal cells (MSCs) make them an intriguing asset for therapeutic applications. An off-the-shelf approach, using pre-expanded cryopreserved allogenic MSCs, bypasses many practical difficulties of cellular therapy. Reconstitution of a MSC product away from cytotoxic cryoprotectants towards a preferred administration solution might be favorable for several indications. Variations in MSC handling accompanied by a non-standardized use of reconstitution solutions complicate a general clinical standardization of MSC cellular therapies. In this study, we aimed to identify a simple and clinically compatible approach for thawing, reconstitution, and post-thaw storage of cryopreserved MSCs., Methods: Human adipose tissue-derived MSCs were expanded in human platelet lysate (hPL) supplemented culture medium and cryopreserved using a dimethyl sulfoxide (DMSO)-based cryoprotectant. Isotonic solutions (saline, Ringer's acetate and phosphate buffered saline (PBS)) with or without 2% human serum albumin (HSA) were used as thawing, reconstitution, and storage solutions. MSCs were reconstituted to 5 × 10 6 MSCs/mL for evaluating MSC stability. Total MSC numbers and viability were determined using 7-aminoactinomycin D (7-AAD) and flow cytometry., Results: For thawing cryopreserved MSCs the presence of protein was proven to be essential. Up to 50% of MSCs were lost when protein-free thawing solutions were used. Reconstitution and post-thaw storage of MSCs in culture medium and widely used PBS demonstrated poor MSC stability (>40% cell loss) and viability (<80%) after 1 h of storage at room temperature. Reconstitution in simple isotonic saline appeared to be a good alternative for post-thaw storage, ensuring >90% viability with no observed cell loss for at least 4 h. Reconstitution of MSCs to low concentrations was identified as critical. Diluting MSCs to <10 5 /mL in protein-free vehicles resulted in instant cell loss (>40% cell loss) and lower viability (<80%). Addition of clinical grade HSA could prevent cell loss during thawing and dilution., Conclusion: This study identified a clinically compatible method for MSC thawing and reconstitution that ensures high MSC yield, viability, and stability. The strength of the method lies within the simplicity of implementation which offers an accessible way to streamline MSC therapies across different laboratories and clinical trials, improving standardization in this field., Competing Interests: All the authors declare no conflict of interest., (© 2023 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Object: Improve shimming capabilities of ultra-high field systems, with addition of an accessible low-complexity B 0 shim array for head MRI at 7 T., Materials and Methods: An eight channel B 0 shim coil array was designed as a tradeoff between shimming improvement and construction complexity, to provide an easy to use shim array that can be employed with the standard 7 T head coil. The array was interfaced using an open-source eight-channel shim amplifier rack. Improvements in field homogeneity for whole-brain and slice-based shimming were compared to standard second-order shimming, and to more complex higher order dynamic shimming and shim arrays with 32 and 48 channels., Results: The eight-channel shim array provided 12% improvement in whole brain static shimming and provided 33% improvement when using slice-based shimming. With this, the eight-channel array performed similar to third-order dynamic shimming (without the need for higher order eddy current compensation). More complex shim arrays with 32 and 48 channels performed better, but require a dedicated RF coil., Discussion: The designed eight-channel shim array provides a low-complexity and low-cost approach for improving B 0 field shimming on an ultra-high field system. In both static and dynamic shimming, it provides improved B 0 homogeneity over standard shimming., (© 2022. The Author(s).)

Objectives:  The objective of this study was to concurrently acquire an inductive k-space trajectory measure and corresponding imaging data by an MR scanner., Materials and Methods:  1D gradient measures were obtained by digital integration, regularized using measured gradient coil currents and recorded individually by the scanner concurrently with raw MR data. Gradient measures were frequency modulated into an RF signal receivable by the scanner, yielding a k-space trajectory measure from the cumulative phase of the acquired data. Generation of the gradient measure and frequency modulation was performed by previously developed custom, versatile circuitry., Results:  For a normal echo planar imaging (EPI) sequence, the acquired k-space trajectory measure yielded slightly improved image quality compared to that obtained from using the scanner's estimated eddy current-compensated k-space trajectory. For a spiral trajectory, the regularized inductive k-space trajectory measure lead to a 76% decrease in the root-mean-square error of the reconstructed image., Discussion:  While the proof-of-concept experiments show potential for further improvement, the feasibility of inductively measuring k-space trajectories and increasing the precision through regularization was demonstrated. The approach may offer an inexpensive method to acquire k-space trajectories concurrently with scanning.

Objective: In microstrip transmission line (MTL) transmit/receive (transceive) arrays used for ultrahigh field MRI, the array length is often constrained by the required resonant frequency, limiting the image coverage. The purpose of this study is to increase the imaging coverage and also improve its parallel imaging capability by utilizing a double-row design., Methods: A 16-channel double-row MTL transceive array was designed, constructed, and tested for human head imaging at 7 T. Array elements between two rows were decoupled by using the induced current elimination or magnetic wall decoupling technique. In vivo human head images were acquired, and g-factor results were calculated to evaluate the performance of this double-row array., Results: Testing results showed that all coil elements were well decoupled with a better than -18 dB transmission coefficient between any two elements. The double-row array improves the imaging quality of the lower portion of the human head, and has low g-factors even at high acceleration rates., Conclusion: Compared with a regular single-row MTL array, the double-row array demonstrated a larger imaging coverage along the z-direction with improved parallel imaging capability., Significance: The proposed technique is particularly suitable for the design of large-sized transceive arrays with large channel counts, which ultimately benefits the imaging performance in human MRI.

Aerosol nucleation has been studied experimentally in purified, atmospheric air, containing trace amounts of water vapor, ozone, and sulfur dioxide. The results are compared with model calculations. It is found that an increase in ionization by a factor of 10 increases the production rate of stable clusters by a factor of approximately 3, probably due to ion-induced nucleation.

To assess the cancer risk of monoclonal gammopathy of undetermined significance (MGUS) we identified 1229 cases of MGUS in the period 1978 to 1993. Data on cancer occurrence in the MGUS cohort were obtained from the Danish Cancer Registry. The expected numbers of cancer cases were calculated from age-, sex-, county-, and period-specific cancer incidence rates. In the MGUS cohort 64 new cancers with a known association with M-components were diagnosed versus 5.0 expected giving a standardized incidence ratio (SIR) of 12.9 (95% confidence interval, 9.9-16.5). The relative risks of developing multiple myeloma (SIR 34.3), Waldenström's macroglobulinemia (SIR 63.8), and non-Hodgkin's lymphoma (SIR 5.9) were significantly increased and independent of time passed from detection of the M-component. The relative risk of chronic lymphocytic leukemia was not significantly increased, SIR 2.7 (0.5-7. 7). Among cancer sites without known association with M-components 141 cases were observed versus 94.6 expected giving a SIR of 1.5 (1. 3-1.8). This enhanced risk was seen for several non-hematological cancer sites but for most cancer sites the risk was dependent on time passed from detection of the M-component, indicating a bias rather than a causal role of MGUS., (Copyright 2000 Wiley-Liss, Inc.)

The ILV1 gene of Saccharomyces cerevisiae encodes the anabolic threonine deaminase, which catalyzes the first committed step in isoleucine biosynthesis. Strains devoid of a functional Ilv1p have a requirement for isoleucine. Threonine can also be deaminated by a second serine/threonine deaminase encoded by the CHA1 gene. CHA1 is regulated by transcriptional induction by serine and threonine, and enables yeast to utilize the hydroxyamino acids as sole nitrogen source. Phenotypic suppression of ilv1 can occur by inducer-mediated transcriptional activation of the CHA1 gene. To identify mutations in putative trnas-acting factors regulating CHA1 expression, we have isolated and characterized three extragenic suppressors of ilv1. A dominant mutation, SIL4 (suppressor of ilv1), is allelic to HOM3. It increases the size of the threonine pool, by 15- to 20-fold, which is sufficient to induce CHA1 transcription, thereby creating a metabolic bypass of ilv1. A second dominant mutation, SIL3, and a recessive mutation, sil2, both suppress ilv1 by causing inducer-independent, constitutive transcription of CHA1. Importantly, sil2 and SIL3 increase the expression of a CHA1p-lacZ translational gene fusion, demonstrating that they exert their action through the CHA1 promoter. Genetic analysis showed that both SIL3 and sil2 are alleles of CHA4, a positive regulator of CHA1, i.e., they convert Cha4p to a constitutive activator.

Migration of neutrophils in patients with paroxysmal nocturnal haemoglobinuria (PNH) was studied using two different complement-free in vitro model systems, subagarose and transendothelial migration. In the subagarose migration assay the mean migration distance of PNH neutrophils was slightly, but significantly, reduced to 1236 microns (range 753-1586, n = 6) compared to a normal mean of 1476 microns (range 1076-1768, n = 6, P = 0.016). By immunocytochemical staining for the urokinase type plasminogen activator receptor (uPAR) which is a glycosyl-phosphatidyl-inositol (GPI) anchored protein expressed by normal, but not by PNH-affected, neutrophils, it was shown that the uPAR-positive subpopulation of normal neutrophils predominated among the faster migrating cells (60-80% normal cells at the front of migration) while uPAR-negative (i.e. PNH-affected neutrophils) were more numerous close to the application well (5-30% normal cells). When migration of neutrophils was tested across a monolayer of human umbilical vein endothelial cells (HUVEC) cultured on polycarbonate filters, there was a 3-4-fold impairment of the migration of the PNH-affected neutrophils both in the absence of stimulation and after stimulation with fMLP (P < 0.001 in both cases). After IL-1 stimulation of the endothelium the impairment was even more pronounced (8-fold difference, P < 0.001). When the endothelial cells were grown on collagen-coated filters the impairment of the migration of PNH neutrophils was less pronounced, but still significant after stimulation with fMLP and IL-1 (2-fold, P < 0.05 in both cases). These results demonstrate that there is a complement-independent impairment of migration of neutrophils from patients with PNH which may be related to their failure to express GPI-linked proteins involved in cell migration and/or adhesion such as the uPA receptor and the CD66b antigen.

We report the outcome of 95 patients older than 60 years with de novo acute non-lymphocytic leukaemia (ANLL), treated in two institutions during a 10 year period. Thirty-two patients, mean age 78 years, did not receive any chemotherapy, and their median survival was 38 days. Five patients in good clinical condition, aged 60-63 years, were treated conventionally with an anthracycline and cytarabine, and three patients obtained a complete remission (CR) lasting 73, 417, and 1050 days. Fifty-eight patients were treated with low-dose cytarabine (LDC) for remission-induction and maintenance. Eighteen patients obtained CR, yielding a remission rate of 31%. The median duration of remission was 380 days and median survival of the same group was 498 days. LDC is valuable in the treatment of ANLL in the elderly. Controlled studies are warranted to define the indications for LDC versus conventional therapy in the large grey zone of elderly patients.

In order to examine the short- and long term effects of basal/bolus insulin therapy on the metabolic regulation assessed by glycosylated haemoglobin (HbA1c) the first 201 patients in the diabetes out-patient clinic of the Section of Endocrinology, Department of Medicine, Aalborg Hospital, assigned for this treatment were prospectively studied. In all 201 patients a significant decrease in mean HbA1c value was observed after 21 months on multiple injection therapy (8.5% vs 8.1%; p < 0.001). The higher the HbA1c value on conventional therapy, the greater was the observed decrease in HbA1c following six months on basal/bolus therapy (r = 0.57, p < 0.001). According to an anonymous questionnaire completed by the first 140 patients six months after the start of multiple injection therapy, 97% of the patients preferred to continue with basal/bolus therapy with NovoPen, and 87% felt that they had achieved a better general condition and that the basal/bolus regime made their daily life easier. It is concluded that basal/bolus therapy with NovoPen may combine the attainment of improved metabolic control assessed by a decrease in mean HbA1c in many poorly regulated patients and the subjective experience of an improved quality of life.

The effect of a daily supplement with 4 g of n-3 polyunsaturated fatty acids (PUFA) for 9 months to 24 healthy volunteers on neutrophil and monocyte chemotaxis was studied using the under-agarose technique. Autologous serum and n-formyl-methionyl-leucyl-phenylalanine were used as chemoattractants. The effect after 9 months of supplementation with n-3 PUFA was also compared to results after short-term supplementation with n-3 PUFA for 6 weeks. Monocyte chemotaxis was reduced after 9 months of supplementation with n-3 PUFA to the same extent as after 6 weeks supplement. Neutrophil-directed migration towards chemoattractants was reduced after 9 months on fish oil, and this decrease was significantly greater than the decrease obtained after 6 weeks of supplementation. The spontaneous migration of neutrophils was significantly attenuated after 9 months compared to baseline and to 6 weeks. These findings lend support to a role for n-3 PUFA in the management of chronic inflammatory and atherosclerotic vascular diseases.

Granulocytes isolated from whole blood of 10 volunteers with Hypaque/Ficoll or Percoll gradient centrifugation showed a significant inhibition of their chemotactic response when incubated with diatrizoate. The influence of 4 different i.v. injected radiographic contrast media (CM) on granulocyte chemotaxis was evaluated using the under agarose assay. Each CM was injected in 10 consecutive outpatients referred for urography. Cells and serum were obtained before and 20 min after the injection of CM. Autologous serum was used as chemoattractive agent, and the cell suspensions from both samples were tested against serum drawn both before and after the injection of CM. No significant changes in granulocyte chemotaxis or the chemotactic potential of serum were seen. Furthermore, there was no change in the chemotactic response towards homologous serum or N-fmlp after injection of diatrizoate or iohexol. In conclusion, the investigation did not unveil any change in granulocyte chemotaxis 20 min after the injection of CM in the 40 subjects studied.

Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFAs) has been shown to inhibit neutrophil and monocyte chemotaxis in healthy subjects and, with respect to neutrophils, also in various patient groups. We studied the effect of dietary supplementation with n-3 PUFAs on monocyte and neutrophil chemotaxis in patients with hyperlipidemia. Chemotaxis was investigated with the under-agarose assay, using autologous serum and N-formyl-methionyl-leucyl-phenylalanine as chemoattractants. The patients were examined before and after 6 weeks of supplementation with 6 g n-3 PUFAs daily. Monocyte chemotaxis was reduced after n-3 PUFA supplementation in type IIa patients but was unaffected in patients with type IV hyperlipidemia. Furthermore, monocyte chemotaxis was increased in untreated type IIa patients compared with normocholesterolemic controls. We also studied the dose-response effects of n-3 PUFAs on monocyte and neutrophil chemotaxis in healthy men given 1.3, 4, and 9 g n-3 PUFAs daily for 6-week periods. Monocyte and neutrophil chemotaxis was reduced after n-3 PUFA supplements in a dose-dependent fashion, with the majority of the effect observed after the low dose. These results lend support to the notion of an antiatherosclerotic effect of n-3 PUFAs and may provide an explanation for the hitherto-unexplained effect of low doses of n-3 PUFAs in coronary heart disease.

One of the important functions of granulocytes is the ability to respond to a chemoattractive signal by migration. The influence of radiographic contrast media (CM) on the chemoattractive properties of serum was investigated by under agarose technique for chemotaxis. No chemotactic response was seen when serum was incubated with different concentrations of CM after heat inactivation. The CM did not generate the heat stable complement split product C5a-desarg which would have resulted in a chemotactic response. Without heat inactivation all complement available in the serum was activated by the agarose in the chemotaxis assay. Low concentrations of iohexol and iodixanol brought about an increased chemotactic response relative to a reference with saline instead of CM. This may be due to activation of heat labile chemoattractants from other sources than the complement cascade. At high concentrations of all five investigated CM, a decreased number of granulocytes migrated over a shorter distance when compared with the reference, and this may be due to interactions between the CM and chemoattractants or their precursors.

We have studied the effect of dietary supplementation with 4 g of n-3 polyunsaturated fatty acids (n-3 PUFA) daily for 6 wk on plasma lipids, haemostasis and monocyte chemotaxis in 10 patients with untreated hypertension. Total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides did not change, but the ratio of total to HDL-cholesterol was significantly reduced after the fish oil supplement. Platelet function was unaltered by intake of n-3. Plasma fibrinogen and fibronectin decreased after supplementation with n-3 PUFA, while the effects on fibrinolysis were equivocal. Monocyte chemotaxis was reduced by the supplement. These data lend support to a role for an increased intake of n-3 PUFA in the management of patients with hypertension.

A case of acute thrombocytopenic haemorrhage caused by infectious mononucleosis is presented. The differential diagnostic deliberations and the treatment are discussed.

In a study of the variation of fertility in boars of the Duroc breed from Danish AI stations, chromosome investigation has been conducted on 11 boars with high and 11 with low fertility, respectively, out of a total of 98 boars having normal semen quality according to AI standards. All 22 boars had the normal chromosome number. C-band polymorphism at chromosome 16 and 17 was more frequent in the low fertility boars compared with high fertile ones (P less than 0.01), and on average a C-band polymorphic boar sired 0.99 piglet less per litter than a non-polymorphic. More investigations are warranted before application of the results can be brought into practical swine breeding.

For the assessment of ileal bile acid conservation the retention of orally administered 75Se-23-selena-25-homotaurocholic acid (SeHCAT), a gamma-ray-emitting radioisotope-labelled synthetic bile acid, was measured by an uncollimated abdominal gamma camera in 89 patients with various gastrointestinal disorders and in 20 persons without gastrointestinal complaints. A significant differences in retention was observed between patients with and without previously detected ileal disease. However, it was not possible by use of the test to differentiate between the various types of diarrhoea. Hence the test is not recommended in the routine investigation of patients with diarrhoea.

We have investigated chemotaxis of polymorphonuclear granulocytes (PMN) from 7 well characterized RA patients with intense disease activity, before and after steroid treatment. Increased spontaneous and directed granulocyte migration was observed in 6 out of 7 patients before steroid treatment. In 5 patients these parameters were reduced after treatment. In contrast to this, decreased chemotaxis of polymorphonuclear granulocytes (PMN) from patients with Rheumatoid Arthritis (RA), have been reported earlier. This has been suggested as a partial explanation of the increased morbidity of these patients. Plasma levels of Complement C3d were initially increased in all patients and were slightly reduced following treatment. PMN migration in highly active RA cases is increased and responds markedly to steroid treatment, in contrast to the complement activation. The mainly unaffected, increased levels of plasma C3d might, in part, explain the early recurrence of symptoms often seen when steroid medication is withdrawn. Our results contrast with earlier findings and need to be confirmed in further studies.

The ultrastructure of spirochetes obtained from rectal biopsies of patients with intestinal spirochetosis was studied by means of negative staining and ultrathin sectioning. The cells were sigmoidal with tapered ends, 2 to 6 microns long, with a wavelength of 2 microns. Four flagella were inserted at each end of the cells. The maximal cell width was about 0.2 microns. The spirochetes were cultured on tryptose soy blood agar plates. They were anaerobic and grew, although very slowly, at 37 to 38.5 degrees C in an atmosphere of 5% CO2-95% H2. Two types of colonies could be distinguished. The growth characteristics and the morphology of the isolated spirochetes differ from those of previously isolated spirochetal strains. Consequently, it is proposed that the present strains constitute a new genus, Brachyspira, of the family Treponemataceae. The type species is Brachyspira aalborgi, the type strain of which is 513A (NCTC 11492).

The ability of serum to attract normal neutrophil granulocytes was investigated in 11 uremic patients before and after hemodialysis using a modified assay system for granulocyte migration under agarose. The chemotactic responses towards serum from the uremic patients were significantly decreased (p less than 0.01) prior to hemodialysis compared to control serum from a healthy individual. Hemodialysis acutely normalized the depressed chemotactic responses. It is concluded that hemodialysis improves the ability of uremic serum to attract neutrophils, and it is suggested that this improvement might be due to removal of granulocyte inhibitory factors from the sera.

The plasma fibronectin concentration (PF) was measured in 48 patients with chronic inflammatory bowel disease (CIBD) and in 48 age- and sex-matched healthy controls, using electroimmunoassay and a functional (gelatin-binding) assay. Whereas no difference in immunochemically measured PF was found between the two groups, patients with CIBD had significantly lower gelatin-binding PF than healthy controls (p less than 0.001). Immunochemically measured PF increased, whereas functionally measured PF tended to decrease with increasing disease activity.

In order to elucidate the kinetics of haemodialysis-induced activation of complement, leucopenia and release of granulocyte-elastase, 10 patients (three females and seven males; mean age 47.8 years) were extensively studied during a 4 h haemodialysis treatment and for the following 24 h, and further compared with a healthy control group. Prior to dialysis patients had normal leucocyte count, plasma elastase bound to alpha 1-proteinase inhibitor (E-alpha 1P1) and total haemolytic complement, whereas plasma C3d was higher and plasma C5a lower than in controls. Haemodialysis induced initial leucopenia and subsequent rebound phenomenon lasting 24 h post treatment. These alterations were due to almost selective changes in neutrophile count as monocyte and lymphocyte counts, apart from decrease in the first 30 min, were unchanged. Total haemolytic complement decreased initially during dialysis and rose at the end. Generation of C5a within the dialyser was evident by demonstration of high levels of this anaphylatoxin in dialyser effluent plasma; maximal values observed coincided with the nadir of leukopenia. Plasma C3d and E-alpha 1P1 both progressively rose during dialysis. After termination of extracorporeal circulation the disappearance rates (T/2) were approximately 6 h and 2.5 h respectively. Haemodialysis thus induces changes in the complement and leucocyte system resembling an acute inflammation, which out-lasts the treatment period.

We describe a newly developed method for fast determination of neutrophil chemotaxis and orientation in concentration gradients of chemotactic factors. The system implements video-based real-time scanning and image analysis of neutrophil migration under agarose, using an interactive easy-to-use computer program. Two methods for determining cell orientation are presented. No statistically significant difference between the methods was found. The analysis program distinguishes between chemokinetic and chemotactic behaviour of the cells (P less than 0.01).

We compared serum concentrations of cathodic trypsin-like immunoreactivity, pancreatic lipase, and pancreatic isoamylase as diagnostic tests of chronic pancreatitis (and of pancreatic steatorrhea in the 41 patients with steatorrhea) in 105 patients (57 men, 48 women) consecutively investigated because of clinical suspicion of chronic pancreatitis. Chronic pancreatitis (36 patients), pancreatic steatorrhea (24 patients), and other diseases were diagnosed without knowledge of the serum levels of the three enzymes. When evaluated by means of receiver operating characteristic curves, no differences were found in diagnostic performance of the enzymes with regard to chronic pancreatitis or pancreatic steatorrhea. The sensitivity and specificity for recognition of chronic pancreatitis ranged from 0.306 to 0.444 and from 0.942 to 0.986 when the discrimination values were chosen to give highest efficiencies. The similar ranges for pancreatic steatorrhea were 0.500-0.708 and 0.882-0.941. In conclusion, none of the three enzymes had any advantage over the others as diagnostic tests of chronic pancreatitis or of pancreatic steatorrhea. Only positive test results have clinical importance because of the low sensitivities of the three enzymes.

Plasma lipids and haemostasis were investigated in 17 patients with hyperlipidaemia before and after 6 weeks supplementation with 6 g n-3 fatty acids. Nine of the patients had type IIa and 8 had type IV hyperlipidaemia. No effect on plasma cholesterol, LDL- or HDL-cholesterol were seen, but plasma triglycerides decreased after n-3 supplementation. Apolipoprotein B increased and apolipoprotein A1 decreased after the oil supplement. The bleeding time was prolonged, but platelet aggregation was unaltered by n-3 fatty acids. Protein C activity increased in type IIa and decreased in type IV after the supplement. Fibrinolysis was markedly depressed while von Willebrand factor antigen was reduced after intake of n-3 fatty acids.