Plasma IL-6 levels correlate with clinical and ultrasound measures of arthritis in patients with systemic lupus erythematosus.

OBJECTIVE: The objective of this paper is to elucidate the role of specific cytokines in lupus (SLE) arthritis. METHODS: Fifty SLE and 40 RA patients had an ultrasound (US) scan of their hand as per standardized protocols. US scores were expressed per joint and as a total 'US activity' score, (sum of power Doppler (PD) and grey-scale synovial hypertrophy scores in all joints) and a total erosion score. SLE disease activity was assessed (BILAG and SELENA-SLEDAI). Plasma levels of IL-6, TNF-alpha and BLyS were measured using sandwich ELISA kits (Quantikine kits, R & D). RESULTS: On the basis of the US results SLE patients were divided into three groups: erosive arthritis (n = 20), non-erosive arthritis (n = 18) and those with a normal US scan (n = 12). Across the SLE groups plasma IL-6 levels correlated with CRP (p < 0.001), hand deformity scores (p = 0.005), BILAG musculoskeletal score (p = 0.009), wrist PD score (p = 0.01), the presence of tenosynovitis (p = 0.008) and total US activity score (p < 0.001) (which remained constant when corrected for total BILAG score). Neither TNF-alpha nor BLyS levels correlated with US or clinical measures of lupus arthritis; however, TNF-alpha correlated with total BILAG score (p < 0.001). CONCLUSION: This is the first study to examine levels of specific cytokines in a cohort of SLE patients stratified in terms of joint disease by US, where the most significant finding is that IL-6 levels correlated both with clinical and US measures of arthritis disease activity.

Effects of reduced dietary protein and supplemental rumen-protected essential amino acids on the nitrogen efficiency of dairy cows.

When fed to meet the metabolizable protein requirements of the National Research Council, dairy cows consume an excess of N, resulting in approximately 75% of dietary N being lost to the environment as urine and feces. Reductions in environmental N release could be attained through an improvement in N efficiency. The objective of this study was to determine if the predicted reduction in milk yield associated with feeding a low-protein diet to lactating dairy cows could be avoided by dietary supplementation with 1 or more ruminally protected (RP) AA. Fourteen multiparous and 10 primiparous Holstein cows, and 24 multiparous Holstein × Jersey crossbred cows were used in a Youden square design consisting of 8 treatments and 3 periods. The 8 dietary treatments were (1) a standard diet containing 17% crude protein [CP; positive control (PC)], (2) a 15% CP diet [negative control (NC)], (3) NC plus RP Met (+M), (4) NC plus RP Lys (+K), (5) NC plus RP Leu (+L), (6) NC plus RP Met and Lys (+MK), (7) NC plus RP Met and Leu (+ML), and (8) NC plus RP Met, Lys, and Leu (+MKL). Dry matter intake was not affected by treatment. Crude protein intake was lower for NC and RP AA treatments compared with the PC treatment. No detrimental effect was detected of the low-CP diet alone or in combination with AA supplementation on milk and fat yield. However, milk protein yield decreased for NC and +MKL diets, and lactose yield decreased for the +MKL compared with the PC diet. Milk urea N concentrations were lower for all diets, suggesting that greater N efficiency was achieved by feeding the low-protein diet. Minimal effects of treatments on arterial plasma essential AA concentrations were detected, with only Ile and Val being significantly lower in the NC than in the PC diet. Phosphorylation ratios of signaling proteins known to regulate mRNA translation were not affected by treatments. This study highlights the limitations of requirement models aggregated at the protein level and the use of fixed postabsorptive efficiency to calculate milk protein requirements. Milk protein synthesis regulation by signaling pathways in vivo is still poorly understood.

Changes in fine structure during silk protein production in the ampullate gland of the spider Araneus sericatus.

The ampullate silk gland of the spider, Araneus sericatus, produces the silk fiber for the scaffolding of the web. The fine structure of the various parts of the gland is described. The distal portion of the duct consist of a tube of epithelial cells which appear to secrete a substance which forms the tunica intima of the duct wall. At the proximal end of the duct there is a region of secretory cells. The epithelium of the sac portion contains five morphologically distinct types of granules. The bulk of the synthesis of silk occurs in the tail of the gland, and in this region only a single type of secretory droplet is seen in the epithelium. Protein synthesis can be stimulated by the injection of 1 mg/kg acetylcholine into the body fluids. 10 min after injection, much of the protein stored in the cytoplasm of the epithelial cells has been secreted into the lumen. 20 min after stimulation, the ergastoplasmic sacs form large whorls in the cytoplasm. Protein, similar in electron-opacity to protein found in the lumen, begins to form in that portion of the cytoplasm which is enclosed by the whorls. The limiting membrane of these droplets is formed by ergastoplasmic membranes which lose their ribosomes. No Golgi material has been found in these cells. Protein appears to be manufactured in the cytoplasm of the tail cells in a form which is ready for secretion.

Synthetic myosin filaments.

A stable preparation of myosin filaments was formed in a medium at pH 8.0. The filament length varied from 0.2 to 0.5 micron. Most of the material sedimented at 21S, but there was a minor peak (due to monomer) at 6.8S. The filaments did not taper and had large bulbous irregularities at the ends.

Colour Doppler ultrasound of the ocular circulation in patients with systemic lupus erythematosus identifies altered microcirculatory haemodynamics.

We assessed whether quantitative analysis of Doppler flow velocity waveforms is able to identify subclinical microvascular abnormalities in SLE and whether eigenvector analysis can detect changes not detectable using the resistive index (RI). Fifty-four SLE patients with no conventional cardiovascular risk factors, major organ involvement or retinopathy were compared to 32 controls. Flow velocity waveforms were obtained from the ophthalmic artery (OA), central retinal artery (CRA) and common carotid artery (CA). The waveforms were analysed using eigenvector decomposition and compared between groups at each arterial site. The RI was also determined. The RI was comparable between groups. In the OA and CRA, there were significant differences in the lower frequency sinusoidal components (P < 0.05 for each component). No differences were apparent in the CA between groups. Eigenvector analysis of Doppler flow waveforms, recorded in proximity of the terminal vascular bed, identified altered ocular microvascular haemodynamics in SLE. Altered waveform structure could not be identified by changes in RI, the traditional measure of downstream vascular resistance. This analytical approach to waveform analysis is more sensitive in detecting preclinical microvascular abnormalities in SLE. It may hold potential as a useful tool for assessing disease activity, response to treatment, and predicting future vascular complications.

A randomised interventional trial of omega-3-polyunsaturated fatty acids on endothelial function and disease activity in systemic lupus erythematosus.

OBJECTIVE: To determine the clinical effect of dietary supplementation with low-dose omega-3-polyunsaturated fatty acids on disease activity and endothelial function in patients with systemic lupus erythematosus. METHODS: A 24-week randomised double-blind placebo-controlled parallel trial of the effect of 3 g of omega-3-polyunsaturated fatty acids on 60 patients with systemic lupus erythematosus was performed. Serial measurements of disease activity using the revised Systemic Lupus Activity Measure (SLAM-R) and British Isles Lupus Assessment Group index of disease activity for systemic lupus erythematosus (BILAG), endothelial function using flow-mediated dilation (FMD) of the brachial artery, oxidative stress using platelet 8-isoprostanes and analysis of platelet membrane fatty acids were taken at baseline, 12 and 24 weeks. RESULTS: In the fish oil group there was a significant improvement at 24 weeks in SLAM-R (from 9.4 (SD 3.0) to 6.3 (2.5), p<0.001); in BILAG (from 13.6 (6.0) to 6.7 (3.8), p<0.001); in FMD (from 3.0% (-0.5 to 8.2) to 8.9% (1.3 to 16.9), p<0.001) and in platelet 8-isoprostanes (from 177 pg/mg protein (23-387) to 90 pg/mg protein (32-182), p = 0.007). CONCLUSIONS: Low-dose dietary supplementation with omega-3 fish oils in systemic lupus erythematosus not only has a therapeutic effect on disease activity but also improves endothelial function and reduces oxidative stress and may therefore confer cardiovascular benefits.

Enhancement of undergraduate rheumatology teaching through the use of musculoskeletal ultrasound.

OBJECTIVES: Musculoskeletal ultrasound (MSUS) is increasingly being used by rheumatologists in routine clinical practice to aid with diagnosis and therapy monitoring in the rheumatic conditions. Undergraduate teaching in anatomy is often regarded as problematic and various approaches are in use in UK medical schools. To our knowledge no study to date describes the use of MSUS to facilitate understanding of pathology in the musculoskeletal system at undergraduate level. Accordingly, we wished to explore the usefulness of a short practical ultrasound course for medical undergraduates in learning basic and pathological features of the musculoskeletal system. METHODS: As part of the third-year undergraduate medical musculoskeletal attachment at Queens University Belfast, a 12-week student-selected component (SSC) entitled 'Diagnostic Musculoskeletal Ultrasound in Rheumatology' was offered. The course was a combination of lectures, hand-outs, practical demonstration and supervised hands-on scanning with three methods of summative assessment employed (MCQ paper, practical examination and general attitude). RESULTS: The course involved approximately 30 h work for the two tutors. Seven students completed the course with an overall mean score of 85.3% attained in the assessment. The feedback on the course from the students was extremely positive. CONCLUSION: Musculoskeletal ultrasound could be utilized to enhance the delivery of undergraduate teaching in rheumatology.

Effect of ethanol/trisodium citrate lock on the mechanical properties of carbothane hemodialysis catheters.

AIMS: The objective of this study was to investigate the effect of three locking solutions on the mechanical properties of carbothane hemodialysis catheters. METHODS: Catheters were exposed in vitro to one of three locking solutions (heparin 5000 U/ml; 4% trisodium citrate (TSC) or 30% ethanol/4% TSC). Each solution was locked in six catheters and bathed at 37 degrees C for 9 weeks. Changes in the mechanical properties namely, force at break, elongation at break and elastic modulus of the catheters were determined by tensile testing. RESULTS: The ethanol/TSC lock has an effect on the properties of carbothane hemodialysis catheters. The force at break was significantly lower in the ethanol/TSC group compared to the heparin and TSC groups (113.26 N, 191.97 N and 229.72 N, respectively, p < 0.01). Similarly, elongation at break was lower in the ethanol/TSC group, compared to the heparin and TSC groups (stretched 21.97, 38.29, and 42.42 times original length respectively, p < 0.01). The elastic modulus was not significantly different. CONCLUSIONS: The effect of the ethanol/TSC lock on the catheters is unlikely to prohibit clinical use. After 9 weeks of exposure to the solution, the catheter segments could still be stretched to 22 times their length and withstand 11.5 kg (113 N) of force. Clinically produced forces during dialysis are many times smaller than the force required to break the catheters examined in this study. Therefore, the ethanol/TSC lock shows promise as a new catheter locking solution for the treatment of catheter-related infections. Further clinical studies are required.

Lysolecithin acyltransferase and alveolar phosphatidylcholine palmitate in experimental acute alveolar injury in the dog lung.

Lysolecithin acyltransferase (EC 2.3.1.23) activities in lung homogenates and in subcellular fractions, and fatty acid composition of phosphatidylcholine (PC) in lung lavage were studied in dogs with acute alveolar injury induced by N-nitroso-N-methylurethane. The specific activity in the microsomal fraction was 10 and 3 times higher than those of homogenate and mitochondrial fractions, respectively. Both the lysolecithin acyltransferase activities and the proportions of palmitate in alveolar lavage PC increased during the early phase of injury (days 2-4), and decreased during peak injury (days 6-8). Such correlation was not found during the recovery period (day 15). During recovery, specific and total activities of the enzyme were nearly 2- and 3-fold, respectively, those of controls. Nevertheless, the palmitate proportions in PC were normal, indicating that the increased enzyme activity in vitro was not reflected in increased PC palmitate during recovery. This finding indicates that the enzyme activity per cell was normal during recovery and suggests that the increase in specific and total activities is due to massive regeneration of type II cells and that the enzyme is localized mainly in these cells. The decrease in the proportion of palmitate in lavage PC during peak injury may lead to abnormality of surfactant function.

Photoreceptor spike responses in the hardshell clam, Mercenaria mercenaria.

Spikes were recorded from single axons in the siphonal nerve of the hardshell clam Mercenaria mercenaria which respond to dimming of light. No axons were found to respond to the onset, or increase, of illumination. In a dark-adapted state there is little or no ongoing spike activity. The responsive area of a single axon is a circle of approximately 85 microm diameter on the inner siphon wall. The number of spikes elicited at the off of constant-duration flashes grows as approximately the 0.4 power of flash intensity. For constant intensity and constant light-time fraction, the off-response increases with increasing duration at least up to 500 s duration. For long durations, the response grows as the logarithm of stimulus duration. Subthreshold light can suppress the off-response from preceding illumination. In a light-adapted state, the off-response is greater and its latency shorter than in the dark-adapted state. The fine structure of groups of cell processes thought to comprise the photoreceptor in Mercenaria is described. On the basis of morphological and physiological findings it is suggested that phototransduction occurs in the fine distal processes of the axons from which we have recorded. Axonal processes were found to contain well organized pentalaminar whorls which may be the site of photo-pigment concentration. The action spectrum obtained from the integrated responses of nerve bundles appears to be that of a single Dartnall pigment having maximal absorption at about 510 nm.

Distinctive effects of G-CSF, GM-CSF and TNFalpha on neutrophil apoptosis in systemic lupus erythematosus.

OBJECTIVE: To investigate the influence of culture with G-CSF GM-CSF and TNFalpha on neutrophil apoptosis, comparing neutrophils from SLE patients with rheumatoid arthritis (RA) patients and healthy control subjects. METHODS: Neutrophils were isolated from SLE (n= 10), RA (n= 10) and healthy control subjects (n= 10), and cultured with two different concentrations of G-CSF, GM-CSF and TNFalpha. Proportion of apoptotic neutrophils at T=0, T=2hrs and T=24hrs was measured using FITC-labelled annexinV and flow cytometry. RESULTS: Significantly more neutrophils were apoptotic at T=0 in the SLE subjects than in the other groups (median, range--Control 3.5% (0.3-7.9) SLE 9.5% (2.9-29.1) RA 3.0% (0.4-23.0) p<0.05). Following culture for 24 hours with 1ng/ml G-CSF the proportion of apoptotic neutrophils from SLE subjects was significantly increased (median, range = 51.6% (27.0-84.0) without G-CSF v 66.8% (31.8-89.2) with G-CSF p<0.05). This was not observed with RA or control subjects, in whom the trend was towards inhibition of apoptosis. Similar trends were seen with GM-CSF There was significant induction of apoptosis in SLE neutrophils after 2 hr culture with 1ng/ml TNFalpha (median, range = 2.3% (0.1-8.0) without TNFalpha v 5.2% (1.0-22.4) with TNFalpha). No significant change was seen in the other groups. There was an inverse correlation between total neutrophil count and the degree of induction of apoptosis by G-CSF and GM-CSF, determined at a range of time-points and cytokine concentrations CONCLUSIONS: Neutrophils from SLE patients display resistance to the apoptosis-inhibiting effects of G-CSF and possibly GM-CSF, and appear more susceptible to the apoptosis-inducing action of TNFalpha, the greatest resistance being observed in the more neutropenic patients.

Age-related changes in non-receptor dependent generation of reactive oxygen species from phagocytes of healthy adults.

Several authors have shown that neutrophil generation of reactive oxygen species (ROS) declines with advancing age. Similar changes have also been suggested in monocytes. In both cases alterations in second messenger activity have been implicated as the most likely explanation for these observations. The aim of this study was to investigate the effect of age on phagocyte ROS generation, stimulated by the direct activation of protein kinase C (PKC). Venous blood was drawn from normal healthy subjects, cells were separated on a double density gradient into mononuclear and polymorphonuclear (pmn) cells. Phorbol myristate acetate (PMA) was employed as a cell stimulus. Superoxide generation was measured by cytochrome c reduction and myeloperoxidase (MPO) products by measurement of peak luminol chemiluminescence (CL). Fifty-eight subjects, 25 males and 33 females, were studied, median age 49 years (range 26-88 years). Polymorphonuclear cell superoxide generation was significantly higher in males and there was a trend towards higher pmn MPO product generation in males. Using Spearman's ranked correlation coefficient, monocyte superoxide generation was negatively correlated with age (r = -0.473, P < 0.001). No changes in the generation of MPO products was found. There were also trends towards a negative correlation of pmn cytochrome c reduction and peak luminol CL with age in males but not females. Since PMA directly activates protein kinase C, reduced monocyte superoxide generation with increasing age appears to be related to alterations in the ROS generating system downstream of the cell receptor. Impaired monocyte superoxide generation may have implications for non-specific defence against certain infections and early tumour growth in the elderly. Factors underlying these changes in monocyte function therefore require further study.

Differential effects of mepacrine, chloroquine and hydroxychloroquine on superoxide anion generation, phospholipid methylation and arachidonic acid release by human blood monocytes.

The 4-aminoquinolines chloroquine (CQ) and hydroxychloroquine (HCQ), and previously the 9-aminoacridine mepacrine (quinacrine) (MP), have been widely used in the treatment of inflammatory disorders such as rheumatoid arthritis and systemic lupus erythematosus. Their effects are believed to be mediated through phagocytic cells but the precise biochemical basis remains uncertain. We have investigated the effects of these drugs on monocyte superoxide anion (SO) generation elicited by 5 different stimuli-opsonised zymosan (STZ), FMLP, A23187, TPA and fluoride--and sought correlations with effects on two processes which have been linked with monocyte activation, namely arachidonate (AA) release and transmethylation of phosphatidyl ethanolamine (PE) to phosphatidylcholine (PC). In all experiments conditions were adjusted to achieve leucocyte concentrations of drug comparable to those found during in vivo therapy. Neither CQ nor HCQ had any marked effect on SO release induced by TPA, A23187 or fluoride ion, excluding a significant effect on protein kinase C (PKC), calmodulin-dependent kinase(s) or the membrane-bound, superoxide generating NADP(H) oxidase. In contrast MP inhibited the response to TPA and A23187. Each drug also had different effects on surface receptor-dependent responses; thus HCQ inhibited FMLP- but not STZ-induced SO release, whereas CQ and MP inhibited the response to both stimuli. Each drug also displayed different effects on AA release and phospholipid (PL)-methylation; MP and HCQ, but not CQ, inhibited STZ-stimulated AA release while MP and CQ but not HCQ inhibited basal rates of PL-methylation in mononuclear cells (MNC). However, only MP inhibited PL-methylation in an enriched monocyte population. We conclude that despite their close structural similarity, MP, CQ and HCQ each have different metabolic effects and their actions cannot simply be attributed to inhibition of lysosomal functions. Other possible mechanisms of action are discussed. The selective effects of each drug also provide further evidence for multiple pathways of monocyte activation.

Class II major histocompatibility complex antigen expression on unstimulated and gamma-interferon stimulated monocytes from patients with multiple sclerosis, rheumatoid arthritis and normal controls.

HLA-DR, HLA-DQ, and HLA-DP antigen expression was assessed by immunofluorescent flow cytometry on monocytes from 19 patients with active multiple sclerosis (MS), 19 with inactive MS, 7 patients with early active rheumatoid arthritis (RA), and 19 normal controls. Percentage positivity and median channel fluorescence (MCF) were determined after separation of the monocytes (TO) and following 48 h culture with (T48 + IFN) and without (T48) recombinant gamma interferon (rIFN-gamma). The percentage positivity of the cells was normal at TO for all groups of patients for each of the HLA types but statistically significantly increased above normal, on monocytes from patients with inactive MS, after culture with rIFN-gamma. At TO, the MCF values for HLA-DQ, and HLA-DP were statistically significantly increased above normal on monocytes from patients with active MS indicating some pre-programming of the cells in vivo. After culture, when the carry-over from baseline TO values was eliminated, the increment in MCF for HLA-DR, on monocytes from patients with inactive MS, was statistically significantly lower than normal in the non-gamma-IFN cultures but was normal in the presence of rIFN-gamma. Conversely, the increment in MCF for HLA-DP on monocytes from patients with active MS was significantly lower than normal after culture with rIFN-gamma. Therefore, the stimulation required to increase antigen density on cells already expressing antigen may be different to that required to stimulate de novo expression on negative cells. Both systems appear to be abnormal in MS, possibly reflecting differences in disease activity, while only one system appears abnormal in RA.

Alveolar epithelial injury causing respiratory distress in dogs: physiologic and electron-microscopic correlations.

Structural and mechanical changes were correlated in 29 dogs with acute alveolar injury induced by the subcutaneous administration of N-nitroso-N-methylurethane (NNNMU). The injury was characterized by necrosis and repair of alveolar epithelium while the vascular endothelium remained essentially intact. Compliance of the lung (CL) decreased and elastic recoil increased as epithelial necrosis occurred. During recovery, improved elastic recoil coincided with epithelial regeneration, although CL remained abnormal. The late phase was characterized histologically by widespread closure of clusters of alveoli alternating with dilated small air spaces. The process resulted in distortion of lung architecture and resembled interstitial fibrosis. Reduced lung volume and decreased distensibility of dilated small air spaces may have accounted for the persistently abnormal CL. Because of the specific site of anatomic involvement, the predictable evolution of deranged lung mechanics, and the similarity to human lung injury (adult respiratory distress syndrome), the lung injured by administration of N-nitroso-N-methylurethane is a suitable model to study pathophysiology and types of therapy in a controlled setting.

Bilateral upper lobe Pneumocystis carinii pneumonia in a patient receiving inhaled pentamidine prophylaxis.

A 46-year-old man with AIDS, receiving inhaled pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis, developed bilateral upper lobe infiltrates. Bronchoalveolar lavage confirmed the diagnosis of PCP. Therapy with intravenous trimethoprim-sulfamethoxazole (TMP-SMX) was begun, with gradual resolution of these infiltrates noted. An explanation for the development of upper lobe PCP, despite aerosol chemoprophylaxis, is presented and emphasizes the importance of aerosol particle size (and therefore of nebulizer type) on the distribution of inhaled pentamidine.

Monocyte esterase deficiency in malignant neoplasia.

A survey of the incidence of monocyte esterase deficiency in 4000 inpatients (including 808 with malignant neoplastic disease) and 474 normal controls was performed using an automated esterase method. A highly significant excess of patients with malignant disease and the deficiency was evident when compared with normal controls or all other patients. Within the group of patients with malignant disease the demonstrable excess occurred in B chronic lymphocytic leukaemia, non-Hodgkin's and Hodgkin's lymphoma, and carcinoma of the gastrointestinal tract. There was also a significant excess of patients with the deficiency attending the renal unit, both among patients who had had renal transplants and those who had not. A familial incidence of monocyte esterase deficiency was found in 19 (35%) of first degree relatives of those patients in whom family studies were done. It is suggested that the reason for the increased prevalence of the anomaly in these disorders might be that the diminution of esterase activity has a role in their development.

Interleukin-10 receptor expression in systemic lupus erythematosus and rheumatoid arthritis.

OBJECTIVE: We aimed to determine the expression of the interleukin-10 receptor (IL10R) on circulating leukocytes in SLE and rheumatoid arthritis, and correlate this with plasma IL-10 levels and disease activity. METHODS: Peripheral blood was sampled from 20 SLE patients, 14 rheumatoid arthritis patients, and 14 healthy controls. IL-10R expression was determined by immunofluorescence labelling and flow cytometric analysis. Plasma IL-10 levels were measured by ELISA. RESULTS: IL-10R was highly expressed on monocytes, and to a lesser degree on neutrophils in all 3 patient groups. Only a small percentage of lymphocytes expressed IL-10R in all three groups. There was no significant difference in IL-10R expression on the surface of monocytes, neutrophils or lymphocytes in any of the 3 groups. IL-10R expression did not correlate with plasma IL-10 levels or disease activity. CONCLUSION: This study has shown no difference in surface IL-10R expression between SLE, rheumatoid arthritis and normal subjects. Deficient or excessive circulating leukocyte surface IL-10R expression therefore does not seem to play a role in the pathogenesis of SLE or rheumatoid arthritis. Functional IL-10R studies would be of interest.

Neutrophils from systemic lupus erythematosus patients demonstrate increased nuclear DNA damage.

OBJECTIVE: (i) To determine the levels of nuclear DNA damage in freshly isolated and cultured neutrophils from SLE patients (SLE), rheumatoid arthritis patients (RA) and healthy individuals and relate these to the percentage of apoptotic neutrophils. (ii) To assess rates of repair of neutrophil oxidative DNA damage. METHODS: The comet assay was used to quantify nuclear DNA damage in neutrophils from SLE patients (n = 20), control subjects (n = 15) and RA patients (n = 15). Levels of DNA damage were related to apoptosis as assessed by annexin V binding and morphology. Rates of repair of neutrophil oxidative DNA damage was measured by incorporating formamidopyrimidine-DNA glycosylase (FPG) into the comet assay. RESULTS: Nuclear DNA damage in freshly isolated and cultured (20 h) neutrophils was significantly greater in SLE patients (median = 12.5%, 27.3%; respectively) compared with RA patients (median = 9.4%, p = 0.002; 19.3%, p = 0.002; respectively) and control subjects (median = 8.2%, p = 0.003; 18.7%, p = 0.01, respectively). Significantly higher levels of circulating apoptotic neutrophils were demonstrated in SLE patients compared to RA and control subjects. Similar findings were observed following 20 h cultured neutrophil preparations. However, no significant direct correlation between neutrophil apoptosis and DNA damage was observed. Neutrophils from 3 of 5 SLE patients demonstrated an impaired ability to repair oxidatively modified DNA. CONCLUSION: Neutrophils from SLE patients display increased DNA damage and, additionally, may demonstrate defective repair of oxidative DNA damage. These features, in addition to increased rates of neutrophil apoptosis, may act as contributing factors to autoantigen excess and immune activation.

Ethanol/trisodium citrate for hemodialysis catheter lock.

AIMS: The objective of this study was to confirm the compatibility of ethanol and 4% trisodium citrate (TSC) for potential use as a catheter locking solution. METHODS: Increasing concentrations of ethanol were combined with 4% TSC in glass test tubes and stored at 37 degrees C over 72 hours. Each tube was visually inspected to determine the highest compatible concentration. To confirm visual compatibility, HPLC analysis was used to compare the concentration of TSC in control solutions (n = 6) to solutions containing both TSC and the highest concentration of ethanol that was visually compatible (n = 6). Compatibility in carbothane hemodialysis catheters was then confirmed in vitro. RESULTS: Results of the compatibility tests indicated that 30% ethanol was the maximum concentration visually compatible with 4% TSC. Ethanol concentrations of 35% or above form a crystalline precipitate in the glass test tubes within 72 hours. HPLC analysis showed no difference in the concentration of TSC in the control solutions compared to the TSC/ethanol solutions when incubated in glass test tubes. A slight, but statistically significant increase in the TSC concentration (1.27%; p < 0.0001) was observed when the ethanol/TSC solution was incubated in carbothane hemodialysis catheters. This slight increase may be due to ethanol absorption into the catheter polymer. Further studies are underway to determine if an ethanol/TSC lock affects the mechanical properties of these carbothane hemodialysis catheters. CONCLUSIONS: We conclude that 30% ethanol is compatible with 4% trisodium citrate in carbothane hemodialysis catheters in vitro. Until the lock's affect on carbothane hemodialysis catheters is known, it cannot yet be recommended for clinical use.