Usefulness of prophylactic antibiotics in preventing infection after internal fixation of closed hand fractures.

Prophylactic antibiotics (PA) have been shown to be ineffective in reducing the incidence of surgical site infection (SSI) in clean wounds associated with elective surgery of the hand. Routine administration of PA for internal fixation of hand fractures is a subject that has been scarcely studied. We hypothesized that PA do not reduce SSI incidence in fixation of closed hand fractures. We did a retrospective comparative study in patients who underwent open or closed reduction and internal fixation of a hand and carpus fracture. Patient demographics, past medical history, fracture characteristics and the type of internal fixation used were extracted from our electronic archives. Follow-up period lasted for 1 year, during which any form of clinically evident SSI, such as pus formation, wound dehiscence and positive bacterial culture was documented. A total of 107 patients met the inclusion criteria, 63 in the control group and 44 in the test group. The overall infection rate was 6.5%. All infections (3 in the control group and 4 in the test group) were pin-tract infections that resolved completely after pin extraction. Our study did not find significant differences between groups (P = 0.442). No specific fracture pattern was associated with increased total infection rate (p = 0.898). In this study, we found no support for routine administration of PA prior to internal fixation of closed fractures of the hand and carpus. PA should still be administered in selected patients, such as those with decreased immunity or open fractures. Further large-scale research is needed to establish proper guidelines, to reduce the adverse effects of antibiotic treatment.

Internal fixation of metacarpal fractures using wide awake local anesthesia and no tourniquet.

We sought to report on the use of wide-awake local anesthesia and no tourniquet (WALANT) for internal fixation of metacarpal fractures. We retrospectively examined 10 patients with metacarpal fractures that required either closed reduction and internal fixation (CRIF) or open reduction and internal fixation (ORIF). WALANT was administered 20minutes before the surgery outside the operating room. Once the area was numb, an open or closed reduction was made followed by internal fixation of the fracture using plating, intramedullary screws or Kirshner wires (K-wires). We used intraoperative X-ray to confirm anatomic reduction and correct internal fixation. After proper reduction and fixation, the active range of motion (AROM) was assessed while the patient was awake. Patients were discharged the next day after evaluating their neurovascular status and establishing pain control. Follow-up evaluations were carried out at 2, 6 and 12 weeks postoperatively. All individuals underwent uneventful operations. No significant pain or bleeding was recorded during the operation. Nine out of ten patients regained full AROM at the 12-week follow-up visit in the outpatient clinic. One patient still had slight reduction of range of motion (ROM) of the 5th metacarpophalangeal joint. No neurovascular damage or surgical site morbidity was recorded. CRIF and ORIF of simple metacarpal fractures can be executed successfully using WALANT with good functional results without increased morbidity compared to monitored anesthesia care.

Vitamin D: an instrumental factor in the anti-phospholipid syndrome by inhibition of tissue factor expression.

BACKGROUND AND AIMS: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by thrombosis, obstetric complications and the presence of anti-phospholipid antibodies such as anti-ß2GPI-Abs. These antibodies may set off the coagulation cascade via several mechanisms, including the induction of tissue factor (TF) expression. Vitamin D has recently emerged as an immunomodulator that might exert an anti-thrombotic effect. Therefore, we studied serum vitamin D levels in a cohort of APS patients, as well as the effect of vitamin D in an in vitro model of APS-mediated thrombosis. METHODS: Serum vitamin D levels were measured in 179 European APS patients and 141 healthy controls using the LIAISON chemiluminescent immunoassay, and the levels were evaluated in conjunction with a wide spectrum of clinical manifestations. In an vitro model, anti-ß2GPI antibodies were purified from four patients with APS to evaluate the expression of TF in activated starved human umbilical vein endothelial cells. The effect of vitamin D (1,25-dihydroxyvitamin D, 10 nm) on anti-ß2GPI-Abs mediated TF expression was analysed by immunoblot. RESULTS: Vitamin D deficiency (serum level ≤15 ng/ml) was documented in 49.5% of our APS patients versus 30% of controls (p<0.001) and was significantly correlated with thrombosis (58% vs 42%; p<0.05), neurological and ophthalmic manifestations, pulmonary hypertension, livedo reticularis and skin ulcerations. In vitro vitamin D inhibited the expression of TF induced by anti-ß2GPI-antibodies. CONCLUSIONS: Vitamin D deficiency is common among APS patients and is associated with clinically defined thrombotic events. Vitamin D inhibits anti-ß2GPI-mediated TF expression in vitro. Thus, vitamin D deficiency might be associated with decreased inhibition of TF expression and increased coagulation in APS. Evaluation of vitamin D status and vitamin D supplementation in APS patients should be considered.

Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin D?

BACKGROUND: Low serum vitamin D concentrations have been reported in several autoimmune disorders. OBJECTIVE: To assess whether low serum vitamin D concentrations are related to disease activity of patients with systemic lupus erythematosus (SLE). METHODS: 378 patients from several European and Israeli cohorts were pooled and their disease activity was measured by two different methods: 278 patients had SLE disease activity-2000 (SLEDAI-2K) scores and 100 patients had European Consensus Lupus Activity Measurement (ECLAM) scores. In order to combine the two systems the scores were converted into standardised values (z-scores), enabling univariate summary statistics for the two variables (SLEDAI-2K and ECLAM). The commercial kit, LIAISON 25-OH vitamin D assay (310900-Diasorin) was used to measure serum concentration of 25-OH vitamin D in 378 patients with SLE. RESULTS: A significant negative correlation was demonstrated between the serum concentration of vitamin D and the standardised values (z-scores) of disease activity scores as measured by the SLEDAI-2K and ECLAM scales (Pearson's correlation coefficient r=-0.12, p=0.018). CONCLUSIONS: In a cohort of patients with SLE originating from Israel and Europe vitamin D serum concentrations were found to be inversely related to disease activity.

Vaccines as a trigger for myopathies.

Vaccines are considered to be among the greatest medical discoveries, credited with the virtual eradication of some diseases and the consequent improved survival and quality of life of the at-risk population. With that, vaccines are among the environmental factors implicated as triggers for the development of inflammatory myopathies. The sporadic reports on vaccine-induced inflammatory myopathies include cases of hepatitis B virus, bacillus Calmette-Guérin, tetanus, influenza, smallpox, polio, diphtheria, diphtheria-pertussis-tetanus, combination of diphtheria with scarlet fever and diphtheria-pertussis-tetanus with polio vaccines. However, a significant increase in the incidence of dermatomyositis or polymyositis after any massive vaccination campaign has not been reported in the literature. In study patients with inflammatory myopathies, no recent immunization was recorded in any of the patients. Moreover, after the 1976 mass flu vaccination, no increase in the incidence of inflammatory myopathies was observed. Although rare, macrophagic myofasciitis has been reported following vaccination and is attributed to the aluminium hydroxide used as an adjuvant in some vaccines. Prospective multicenter studies are needed to identify potential environmental factors, including vaccines, as potential triggers for inflammatory myopathies.

The diagnostic utility of anti-cyclic citrullinated peptide antibodies, matrix metalloproteinase-3, rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein in patients with erosive and non-erosive rheumatoid arthritis.

OBJECTIVE: To compare the diagnostic utility of laboratory variables, including matrix metalloproteinase-3 (MMP-3), anticyclic citrullinated peptide (CCP) antibodies, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) in patients with erosive and non-erosive rheumatoid arthritis (RA). METHODS: We assembled a training set, consisting of 60 patients with RA, all fulfilling the revised criteria of the American College of Rheumatology. A commercial enzyme linked immunosorbent assay (ELISA) was used both to test for anti-CCP antibodies (second generation ELISA kit) and MMP; RF were detected by latex-enhanced immunonephelometric assay. CRP was measured by latex turbidimetric immunoassay. RESULTS: The levels of anti-CCP antibody titers and ESR were significantly higher in patients with erosive disease than those in non-erosive RA patients (p < 0.001 and 0.0341) respectively. Moreover, a higher frequency of elevated titers of anti-CCP antibodies was found in RA patients with erosions compared to patients with non-erosive RA (78.3% vs. 43.2% respectively). The ROC curves of anti-CCP passed closer to the upper left corner than those other markers and area under the curve (AUC) of anti-CCP was significantly larger than AUC of other markers (0.755 for anti-CCP, 0.660 for ESR, 0.611 for CRP, 0.577 for RF, and 0.484 for MMP-3 female). A positive predictive value was higher for anti-CCP antibodies in comparison to other markers. We did not find significant statistical correlation between anti-CCP antibody titers and inflammatory markers such as ESR or CRP. However, we confirmed the correlation of elevated titers of anti-CCP antibodies and RF in both groups of patients whereas the degree of correlation was more significant in non-erosive patients. CONCLUSION: The results of our study suggest that the presence of elevated anti-CCP antibody titers have better diagnostic performance than MMP-3, RF, CRP and ESR in patients with erosive RA.

Perceived efficacy among patients of various methods of complementary alternative medicine for rheumatologic diseases.

OBJECTIVE: The purpose of this cross-sectional survey was to obtain and analyze data on self-perceived efficacy of different types of complementary alternative medicine (CAM) by patients with various rheumatologic conditions. METHODS: Patients followed in rheumatology outpatient clinics were screened for the use of CAM. Patients reporting the use of CAM were asked to participate in face-to-face structured interviews, specifying the various CAM types they used, and grading their subjective impression of efficacy of each CAM type on a scale of 1-10. RESULTS: 350 consecutive patients were screened and 148 reported using CAM. In general, homeopathy and acupuncture were the most commonly used CAM types (44% and 41% of the CAM users, respectively). The mean number of different CAM methods used by a CAM user was 1.9 +/- 1.1. Patients with fibromyalgia used significantly more CAM methods (2.7 +/- 1.4, p = 0.005). On patients' self-perceived efficacy scale of 1-10, the mean score of the whole group was 5.3 +/- 3.2. Acupuncture and homeopathy achieved significantly higher self-perceived efficacy scores in CAM users with spondylo-arthropathies and osteoarthritis, respectively, when compared to some of the other disease groups. Satisfaction was lowest among CAM users with rheumatoid arthritis, vasculitis and connective tissue diseases. CONCLUSION: In general, CAM users were less than moderately satisfied with self-perceived-efficacy of CAM therapies. However efficacy of specific CAM methods differed significantly among patients in different disease groups.

Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene.

BACKGROUND: There is an association between C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and methotrexate related toxicity. OBJECTIVE: To examine the relations between the recently described A1298C polymorphism of the MTHFR gene, plasma homocysteine, methotrexate toxicity, and disease activity in patients with rheumatoid arthritis. DESIGN: A cross sectional study on 93 methotrexate treated patients with rheumatoid arthritis, comprising a clinical interview and physical examination to determine disease activity and methotrexate related adverse reactions. Genotype analysis of the MTHFR gene was carried out and fasting plasma homocysteine and serum folate concentrations were measured. The data were analysed using univariate analysis. Allele and genotype distributions were compared with those of a healthy control group. RESULTS: The frequency of the 1298CC genotype (24.7%) in the rheumatoid study group was greater than expected in the general population (12.8%, p<0.001). This genotype was associated with a significantly low rate of methotrexate related side effects. The odds ratio for side effects in patients with wild type 1298AA genotype v 1298CC genotype was 5.24 (95% confidence interval, 1.38 to 20). No correlation of disease activity variables or plasma homocysteine with MTHFR A1298C and C677T polymorphisms was observed. CONCLUSIONS: 1298CC polymorphism was more common in methotrexate treated rheumatoid patients than expected in the population, and was associated with a reduction in methotrexate related adverse effects. The A1298C polymorphism of the MTHFR gene may indicate a need to adjust the dose of methotrexate given to patients with rheumatoid arthritis.

Guillain-Barré syndrome following hepatitis B vaccination.

A 52-year-old woman developed Guillain-Barré syndrome 10 weeks after immunization with recombinant hepatitis B vaccine. Common infectious causes of GBS were ruled out. The temporal relationship between GBS and hepatitis B virus (HBV) vaccination was suggestive of a vaccine-induced cause. The possible mechanisms of this very, rare complication are discussed.

10th International Congress on Antiphospholipid Antibodies--summary.

The 10th International Congress on Antiphospholipid Antibodies (Sicily, Italy, September 29-October 3, 2002) (Fig. 1) provided enlightening aspects on the recent developments in antiphospholipid syndrome (APS) and antiphospholipid antibodies in more than 150 lectures and posters. Researchers from all aspects of medicine attended the meeting, implicating the systemic characteristics of APS. The important breakthroughs are summarized.

Familial mediterranean fever - a review and update.

Familial Mediterranean fever (FMF) is an autosomal recessive disease, which primarily affects populations surrounding the Mediterranean basin. The disease occurs predominantly in Turks, Armenians, Arabs, and Sephardic Jews. FMF is characterized by recurrent attacks of fever and peritonitis, pleuritis, arthritis or erysipelas-like erythema. Amyloidosis causing renal failure is one of the most severe complications of the disease. In 1997, the gene associated with FMF (MEFV) was isolated. It encodes a protein consisting of 781 amino acids and is expressed mainly in leukocytes. It was named "pyrin" indicating its relation to fever or "marenostrin" (our sea), referring to the Mediterranean focus of the disease. The exact pathogenesis of FMF is not known. Since the MEFV gene encodes a protein that resembles cytokines, which can down-regulate inflammation, it was suggested that pyrin may also have a similar effect. Thus, in FMF patients lacking this protein (or its activity) due to hereditary defects, there is no suppression or inhibition of the inflammatory process, thereby leading to a full-blown attack. Current studies suggest a limited phenotype-genotype correlation. It seems that other genetic and environmental modifiers influence the expression of FMF. Colchicine has been the drug of choice for FMF. It controls the FMF attacks and prevents the development of amyloidosis. Nevertheless, about 5-10% are non-responders and new therapies and approaches for these cases are currently under investigation. The prognosis of FMF patients is favorable, provided they are treated continuously with colchicine. Under this treatment most of the patients are free of acute inflammatory attacks and they will not develop amyloidosis.

Anisotropy in judging the absolute direction of motion.

The angular dependence of precision measurements is well established as the oblique effect in motion perception. Recently, it has been shown that the visual system also exhibits anisotropic behaviour with respect to accuracy of the absolute direction of motion of random dot fields. This study aimed to investigate whether this angular dependent, directional bias is a general phenomenon of motion perception. Our results demonstrate, for single translating tilted lines viewed foveally, an extraordinary illusion with perceptual deviations of up to 35 degrees from veridical. Not only is the magnitude of these deviations substantially larger than that for random dots, but the general pattern of the illusion is also different from that found for dot fields. Significant differences in the bias, as a function of line tilt and line length, suggest that the illusion does not result from fixed inaccuracies of the visual system in the computation of direction of motion. Potential sources for these large biases are motion integration mechanisms. These were also found to be anisotropic. The anisotropic nature and the surprisingly large magnitude of the effect make it a necessary consideration in analyses of motion experiments and in modelling studies.

Computing feature motion without feature detectors: a model for terminator motion without end-stopped cells.

Pointlike object features such as line-endings, have a privileged position in the computation of the veridical direction of object motion. Experiments confirm that the human visual system relies heavily on such features if they are present. It has been proposed that units such as end-stopped cells might be necessary for the computation of feature motion instead of the simple cells used in plaid motion models. Conventional plaid motion models have not been applied to feature motion. We present here a model, based on ordinary simple cells, using two parallel pathways (Fourier and non-Fourier) for the computation of the direction of two dimensional motion. Although similar in structure to popular models of plaid motion, our model includes a novel scheme for contrast normalisation and incorporates spatial pooling at the level of MT cells. The model predictions are consistent with psychophysical results for plaids. Furthermore, it computes directions within 5 degrees of the physical motion of line-endings. It is shown that the non-Fourier signal is necessary for the computation of veridical motion.

Factors limiting peripheral pattern discrimination.

Previous reports indicate that some foveally discriminable compound gratings are indiscriminable in peripheral vision, even when they are scaled by the ratio of peripheral to foveal grating acuity. To determine the stimulus properties that limit peripheral discrimination, we used Gaussian derivatives of various orders. These patterns are spatially localized and have intrinsic even or odd symmetry. Our results show that certain odd symmetric patterns are discriminable in the periphery, while others are not. Furthermore, certain even symmetric patterns are not peripherally discriminable. These data are consistent with three limitations on peripheral pattern discrimination: (1) Patterns that produce different maximum neural responses will be peripherally discriminable. (2) Positional uncertainty and undersampling degrade discrimination of high spatial frequency patterns in the periphery. (3) Patterns generating substantial neural activity within a constrained region are processed as textures in peripheral vision so that pattern details within that region are no longer available for discrimination. A neural model incorporating inhibition of simple cells by complex cells implements a transition between contour analysis and texture analysis in peripheral vision and explains the experimental data.

Maturation of the pattern-reversal VEP in human infants: a theoretical framework.

Visual evoked potentials to pattern reversal (PR-VEPs) are used to assess the integrity and maturation of the visual pathways in infants and young children. To establish normal ranges and to facilitate interpolation, we consider the maturation rate of PR-VEPs using published normative data. Curves based on the logistic function (a sigmoid model) are introduced and compared with three other models: (1) the power law function; (2) the sum of two decaying exponentials; and (3) a two-stage linear model. Although methods vary somewhat, remarkable consistency among laboratories is found for the maturation of the major positivity (P1) of PR-VEP. The P1 occurs at approximately 260 ms in neonates and is quite variable. It matures rapidly before 12-14 weeks of age and becomes much less variable. The logistic model provides a parsimonious description of P1 maturation with most rapid maturation at around 6 weeks of age for large patterns and around 9 weeks for small patterns. As inter-laboratory agreement is generally good, the normal ranges based on this model could be used in centres, which do not have their own normative databases for infant VEPs.

Contrast discrimination, non-uniform patterns and change blindness.

Change blindness--our inability to detect large changes in natural scenes when saccades, blinks and other transients interrupt visual input--seems to contradict psychophysical evidence for our exquisite sensitivity to contrast changes. Can the type of effects described as 'change blindness' be observed with simple, multi-element stimuli, amenable to psychophysical analysis? Such stimuli, composed of five mixed contrast elements, elicited a striking increase in contrast increment thresholds compared to those for an isolated element. Cue presentation prior to the stimulus substantially reduced thresholds, as for change blindness with natural scenes. On one hand, explanations for change blindness based on abstract and sketchy representations in short-term visual memory seem inappropriate for this low-level image property of contrast where there is ample evidence for exquisite performance on memory tasks. On the other hand, the highly increased thresholds for mixed contrast elements, and the decreased thresholds when a cue is present, argue against any simple early attentional or sensory explanation for change blindness. Thus, psychophysical results for very simple patterns cannot straightforwardly predict results even for the slightly more complicated patterns studied here.

Severe migratory polyarthritis following in vivo CAMPATH-1G.

CAMPATH-1G is an IgG2b rat antihuman (CDw52) monoclonal antibody (MoAb) which is currently being used for T cell depletion in the setting of allogeneic bone marrow transplantation (BMT). In addition it elicits substantial lymphoid depletion, an effect which is being explored for remission induction in patients with lymphoid malignancies and for treating patients with various autoimmune disorders, in particular rheumatoid arthritis. Recently, in vivo CAMPATH-1G has been introduced to achieve increased immunosuppression in the pretransplant conditioning, for prevention of graft rejection following T cell depleted BMT. Here we describe a patient with T cell lymphoblastic lymphoma who received in vivo CAMPATH-1G as part of the pretransplant conditioning regimen and who, 6 days after the first dose, developed severe migratory polyarthritis. This is the first report of severe migratory polyarthritis as a very unusual complication following CAMPATH-1G MoAb administration.

Successful treatment of pure red cell aplasia in systemic lupus erythematosus with erythropoietin.

We describe a 32-year-old woman who developed severe anemia due to pure red cell aplasia in the course of systemic lupus erythematosus (SLE). After failure of therapy with high doses of glucocorticoids and immunoglobulins, and despite high levels of endogenous erythropoietin, she was treated with human recombinant erythropoietin with dramatic and sustained improvement. Based on this case and on the literature review of erythropoietin therapy in pure red cell aplasia, we suggest that erythropoietin should be used in SLE associated pure red cell aplasia before cytotoxic therapy.

Long-term trends in blood lead levels among children in Chicago: relationship to air lead levels.

OBJECTIVES: To evaluate trends in blood lead levels among children in Chicago from 1968 through 1988, and to determine the impact of the changes in the Centers for Disease Control and Prevention (CDC) blood lead level of concern. METHODS: We reviewed a systematic sample of blood lead screening records of the Chicago Department of Health Laboratory for high-risk children aged 6 months to 5 years. Median blood lead levels for each quarter of the years 1974 through 1988 were determined and regressed against mean air lead levels recorded at air-monitoring stations in Chicago during the same period. RESULTS: Median blood lead levels declined from 30 micrograms/dL in 1968 to 12 micrograms/dL in 1988, and were strongly associated with declining average air lead levels (r = .8, P < .001) from 1974 through 1988. A regression model using log-transformed data predicted a decline of 0.56 microgram/dL in the median blood lead level with each 0.1 microgram/m3 decline in the mean air lead level when the air lead level was near 1.0 microgram/m3; the predicted slope was steeper at lower air lead levels. Despite the nearly 20-fold reduction in air lead levels, the median blood lead level of 12 micrograms/dL in 1988 indicates substantial continuing lead exposure. The CDC blood lead level of concern was lowered twice from 1968 to 1988, but due to the decline in blood lead levels, fewer than 30% of the children were above the level of concern throughout most of the study. CONCLUSION: Although substantial lead exposure persists in Chicago, reductions in airborne lead emissions seem to have contributed to a long-term decline in the median blood lead level of high-risk Chicago children.