RESUMEN

BACKGROUND: The index case of Mycobacterium chimaera infection in a patient following open cardiac surgery in the state of Queensland, Australia prompted a centralized coordinated response to mitigate the risk. AIM: To describe the public health response to M. chimaera contamination of heater-cooler units (HCUs) and patient infection. METHODS: A public health sector strategy was developed with national and international consultation to respond to the threat of HCUs contaminated with M. chimaera. Data linkage of non-tuberculous mycobacterium notifications and selected procedures was undertaken where potential use of HCUs was identified through hospitalization records. Water sampling and testing protocols were standardized. Public disclosure and patient notification were undertaken. FINDINGS: A single case of disseminated M. chimaera infection in a patient has been diagnosed to date in Queensland, Australia. Ten of 12 (83%) LivaNova Stockert 3T HCUs from five hospitals tested positive for M. chimaera. In total, 5650 patients were notified by post of their potential risk of exposure. Use of the telehealth call centre was modest. M. chimaera was also found in extracorporeal membrane oxygenation heater units produced by two other device manufacturers, four of which tested positive prior to commissioning for use. CONCLUSIONS: Rapid international collaboration optimized the Queensland Health response to potential M. chimaera exposure during cardiac surgery. State-wide collaboration ensured a transparent, consistent approach to contacting patients and informing the public of the potential risk. A framework for ongoing risk management, clinical awareness and laboratory diagnosis was established. No further cases of M. chimaera infection have been identified in Queensland.

Asunto(s)

RESUMEN

BACKGROUND: Healthcare-associated Staphylococcus aureus bacteraemia (HA-SAB) results in morbidity, mortality, and increased healthcare costs, and these infections are frequently regarded as preventable. AIM: To implement a multi-modal prevention programme for improved processes regarding peripheral intravenous cannula (PIVC) insertion and maintenance, in order to reduce PIVC-associated HA-SAB events in a large Australian health service. METHODS: Baseline clinical practice was evaluated for a 12-month pre-intervention period. Measures to reduce HA-SAB risk were introduced between January and September 2013: staff education, improved documentation (including phlebitis scoring), and availability of standardized equipment. Post-intervention auditing was performed during the 27 months following intervention. Baseline and post-intervention HA-SAB and PIVC-associated infection rates were compared. Interrupted time-series and Bayesian change-point analyses were applied to determine the impact of interventions and timing of change. FINDINGS: Significantly improved documentation regarding PIVC insertion and management was observed in the post-intervention period, with fewer PIVCs left in situ for ≥4 days (2.6 vs 6.9%, P<0.05). During the baseline period a total of 68 HA-SAB events occurred [1.01/10,000 occupied bed-days (OBDs)] and 24 were PIVC-associated (35% of total, rate 0.39 per 10,000 OBDs). In the post-intervention period, a total of 83 HA-SAB events occurred (0.99 per 10,000 OBDs) and 12 were PIVC-associated (14.4% of total, rate 0.14 per 10,000 OBDs). PIVC-associated SAB rates were 63% lower in the post-intervention period compared to baseline (P=0.018) with a change point observed following full bundle implementation in October 2013. CONCLUSION: A successful multi-modal hospital-wide campaign was introduced to reduce PIVC-associated SAB rates. Evaluation of cost-effectiveness and sustainability is required.

Asunto(s)

RESUMEN

We studied the performance of the LMA Supreme against a cuffed tracheal tube, our standard method of airway control during percutaneous tracheostomy, in 50 consecutive patients from three general critical care units. The primary outcome measure was adequacy of ventilation calculated as the difference in arterial carbon dioxide tension before and after tracheostomy. On an intention-to-treat analysis, there was no difference in the increase in arterial carbon dioxide tension between groups, with a median (IQR [range]) for the LMA Supreme of 0.9 (0.3-1.6 [0-2.8]) kPa, and for the tracheal tube of 0.8 (0.4-1.2 [0-2.5]) kPa, p = 0.82. Eight patients out of 25 (32%) crossed over from the LMA Supreme group to the tracheal tube group before commencement of tracheostomy due to airway or ventilation problems, compared with none out of 25 in the tracheal tube group, p = 0.01, and tracheostomy was postponed in two patients in the LMA Supreme group due to poor oxygenation. There were more clinically important complications in the LMA Supreme group compared with the tracheal tube group.

Asunto(s)

RESUMEN

We evaluated the population structure and temporal dynamics of the dominant community members within sewage influent from two wastewater treatment plants (WWTPs) in Milwaukee, WI. We generated > 1.1 M bacterial pyrotag sequences from the V6 hypervariable region of 16S rRNA genes from 38 influent samples and two samples taken upstream in the sanitary sewer system. Only a small fraction of pyrotags from influent samples (∼ 15%) matched sequences from human faecal samples. The faecal components of the sewage samples included enriched pyrotag populations from Lactococcus and Enterobacteriaceae relative to their fractional representation in human faecal samples. In contrast to the large number of distinct pyrotags that represent faecal bacteria such as Lachnospiraceae and Bacteroides, only one or two unique V6 sequences represented Acinetobacter, Aeromonas and Trichococcus, which collectively account for nearly 35% of the total sewage community. Two dominant Acinetobacter V6 pyrotags (designated Acineto tag 1 and Acineto tag 2) fluctuated inversely with a seasonal pattern over a 3-year period, suggesting two distinct Acinetobacter populations respond differently to ecological forcings in the system. A single nucleotide change in the V6 pyrotags accounted for the difference in these populations and corresponded to two phylogenetically distinct clades based on full-length sequences. Analysis of wavelet functions, derived from a mathematical model of temporal fluctuations, demonstrated that other abundant sewer associated populations including Trichococcus and Aeromonas had temporal patterns similar to either Acineto tag 1 or Acineto tag 2. Populations with related temporal fluctuations were found to significantly correlate with the same WWTP variables (5-day BOD, flow, ammonia, total phosphorous and suspended solids). These findings illustrate that small differences in V6 sequences can represent phylogenetically and ecologically distinct taxa. This work provides insight into microbial community composition and dynamics within the defined environment of urban sewer infrastructure.

Asunto(s)

RESUMEN

We examined the association between water exposures and acute diarrhoeal illness (ADI) in children under non-outbreak conditions in a major US metropolitan area. We used a nested case-control study of children seen in an urban/suburban emergency department. Cases were those seen for a complaint of diarrhoea, while controls were age-matched children with a non-gastrointestinal complaint. Parents of subjects completed a validated water-use survey. Stratum-specific adjusted odds ratios (aOR) were calculated for the three main water effects: water source [surface vs. ground (well)], drinking-water type (tap vs. bottled), and use of water filters. Of 2472 subjects, 45% drank mostly or only bottled water. Well-water use was associated with increased odds of ADI compared to surface water [aOR 1·38, 95% confidence interval (CI) 1·01-1·87]. Use of bottled water did not affect the odds of ADI in well-water users, but increased the odds of ADI for surface-water users (aOR 1·27, 95% CI 1·02-1·57). We conclude that well-water use and bottled-water use are associated with increased odds of ADI in children.

Asunto(s)

RESUMEN

The release of untreated sewage introduces non-indigenous microbial populations of uncertain composition into surface waters. We used massively parallel 454 pyrosequencing of hypervariable regions in rRNA genes to profile microbial communities from eight untreated sewage influent samples of two wastewater treatment plants (WWTPs) in metropolitan Milwaukee. The sewage profiles included a discernible human faecal signature made up of several taxonomic groups including multiple Bifidobacteriaceae, Coriobacteriaceae, Bacteroidaceae, Lachnospiraceae and Ruminococcaceae genera. The faecal signature made up a small fraction of the taxa present in sewage but the relative abundance of these sequence tags mirrored the population structures of human faecal samples. These genera were much more prevalent in the sewage influent than standard indicators species. High-abundance sequences from taxonomic groups within the Beta- and Gammaproteobacteria dominated the sewage samples but occurred at very low levels in faecal and surface water samples, suggesting that these organisms proliferate within the sewer system. Samples from Jones Island (JI--servicing residential plus a combined sewer system) and South Shore (SS--servicing a residential area) WWTPs had very consistent community profiles, with greater similarity between WWTPs on a given collection day than the same plant collected on different days. Rainfall increased influent flows at SS and JI WWTPs, and this corresponded to greater diversity in the community at both plants. Overall, the sewer system appears to be a defined environment with both infiltration of rainwater and stormwater inputs modulating community composition. Microbial sewage communities represent a combination of inputs from human faecal microbes and enrichment of specific microbes from the environment to form a unique population structure.

Asunto(s)

RESUMEN

AIMS: The purpose of the work was to evaluate the mCP method to correctly identify and enumerate Clostridium perfringens that are present in surface waters impacted by a mixture of faecal pollution sources. METHODS: Clostridium perfringens were enumerated and isolated from sewage influent, surface water and suspended sediments using the mCP method. Molecular characterization of isolates was performed using species-specific PCR, along with full-length sequencing of the 16S rRNA gene for a subset of isolates. RESULTS: The environmental isolates were presumptively identified as C. perfringens based on utilization of sucrose, inability to ferment cellobiose and a positive action for acid phosphatase activity. All isolates (n = 126) were classified as C. perfringens based on positive results with species-specific PCR with a subset confirmed as C. perfringens based on the 16S rRNA gene identity. CONCLUSIONS: The molecular results indicated all of the presumptive positive isolates were C. perfringens regardless of the source, e.g. sewage influent or environmental water samples. Sequencing revealed that C. perfringens obtained from sewage and the aquatic environment were nearly identical (c. 99.5% similarity). SIGNIFICANCE AND IMPACT OF THE STUDY: From this study we conclude that the mCP method is a robust approach to enumerate and isolate C. perfringens from aquatic environments that receive diverse sources of faecal pollution.

Asunto(s)

RESUMEN

AIMS: The Escherichia coli burden at a Great Lakes urban beach was evaluated during the summer months to determine if sand served as a reservoir for E. coli, and if there was evidence of cell replication in situ. Field and laboratory studies investigated the effects of moisture, temperature and UV on E. coli densities in the sand. METHODS AND RESULTS: Sand samples (n = 481) were collected across three distinct transects of the beach, the top, a middle streamline, and the berm, over 15 sample days. The highest levels were found in the middle streamline, which was affected by stormwater discharge from nearby outfalls and roosting gulls; daily geometric mean levels of these seven sites ranged from 6700 to 40,900 CFU per 100 g of sand. Escherichia coli levels were greatest in samples with moisture levels between 15% and 19%, and were significantly higher than 0-4 and 20-24% ranges (P < 0.05). Pre- and post-rain samples at the beach demonstrated an increase in E. coli levels nearly 100-fold within 30 min, suggesting sand washout as a major mechanism for loading of E. coli into the beach waters. Rep PCR analysis of 160 isolates obtained from eight sites demonstrated that 21% of the isolates fell into one of the six clonal patterns, suggesting that bacteria may be able to replicate and possibly colonize beach sand. Sand field plots inoculated with E. coli cells containing pGFPuv that expresses GFP (green fluorescent protein) as a marker showed an initial two- to 100-fold increase at 24 h, depending on the temperature condition. The sand appeared to provide considerable protection from UV exposure as no significant difference was seen in cell densities within the first 2-4 cm of sand between exposed and unexposed plots (P < 0.05). CONCLUSIONS: Beach sand may act as a reservoir for E. coli. Replication of cells appears to be one possible contributing factor to the persistently high levels, as indicated by both field studies and laboratory studies, and warrants further investigation. Moisture content of sand may also be a determinant of cell persistence in the sand environment. SIGNIFICANCE AND IMPACT OF THE STUDY: Escherichia coli is used as an indicator organism for faecal pollution at most Great Lakes coastal beaches; therefore, a better understanding of how E. coli might survive, or possibly replicate, in the environment would improve interpretation of beach monitoring results.

Asunto(s)

RESUMEN

BACKGROUND: Many different embryo selection criteria have been used in assisted reproductive technologies (ART), but there are no published prospective studies to ascertain their usefulness in predicting implantation. METHODS: In a prospective trial, 20 early scoring parameters previously reported to influence clinical outcome were collected, but embryos were selected for transfer by current laboratory protocols; day 1 pronuclear (PN) (Z) score combined with day 3 or 5 morphology. Data points for each oocyte/embryo were scored independently and tracked individually. Data were analysed retrospectively for parameters most likely to result in a positive pregnancy test, fetal heartbeat (FHB) and delivery. RESULTS: Results indicated that day 1 PN morphology and nucleolar precursor body (NPB) ratio, day 2 cell number, blastomere symmetry and nucleation and the ability to cleave from day 2 to day 3 were the six most significant factors in fetal development. This outcome was then applied prospectively over 8 months. The implantation rate (IR) and clinical pregnancy rate (CPR) increased in each age group, and the number of embryos used decreased. CONCLUSION: In conclusion, early parameters that include PN morphology, number and ratio of NPBs per nucleus and the day 2 morphology of cleaving embryos are stronger positive predictors of implantation than day 3 morphology or the ability to achieve the blastocyst stage of development. Parameters that were most consistently correlated with no delivery were lack of PN symmetry, day 2 multinucleation and uneven cell size. Day 3 and day 5 parameters were not significant compared with the combination of early parameters.

Asunto(s)

RESUMEN

Biological filters combining microbial activity and rapid sand filtration are used in drinking water treatment plants for enhanced biodegradable organic matters (BOM) removal. Biofilms formed on filter media comprised of bacteria enclosed in a polymeric matrix are responsible for the adsorption of BOM and attachment of planktonic microorganisms. This study investigated the removal of Escherichia coli cells injected into laboratory-scale biofilters and the role of biofilm in retaining the injected E. coli. Green fluorescent protein was used as a specific marker to detect and quantify E. coli in the biofilms. About 35% of the total injected E. coli cells were observed in the filter effluents, when initial cell concentrations were measured at 7.4 x 10(6) CFU/mL and 1.6 x 10(7) CFU/mL in two separate experiments. The results from real-time PCR and plate count analysis indicated that 95% of the E. coli retained inside the filters were either non-viable or could not be recovered by colony counting techniques. Injected cells were unevenly distributed inside the filter with more than 70% located at the top 1/5 of the filter. Images obtained from an epifluorescent microscope showed that E. coli cells were embedded inside the biofilm matrix and presented mainly as microcolonies intertwined with other microorganisms, which was consistent with findings from standard plate count methods and qPCR.

Asunto(s)

RESUMEN

Some Trypanosoma brucei lines infect humans whereas others do not because the parasites are lysed by human serum. We have developed a robust, quantitative in vitro assay based on differential uptake of fluorescent dyes by live and dead trypanosomes to quantify the extent and kinetics of killing by human serum. This method has been used to discriminate between 3 classes of human serum resistance; sensitive, resistant and intermediate. TREU 927/4, the parasite used for the T. brucei genome project, is intermediate. The phenotype is expressed in both bloodstream and metacyclic forms, is stably expressed during chronic infections and on cyclical transmission through tsetse flies. Trypanosomes of intermediate phenotype are distinguished from sensitive populations of cells by the slower rate of lysis and by the potential to become fully resistant to killing by human serum as a result of selection or long-term serial passaging in mice, and to pass on full resistance phenotype to its progeny in a genetic cross. The sra gene has been shown previously to determine human serum resistance in T. brucei but screening for the presence and expression of this gene indicated that it is not responsible for the human serum resistance phenotype in the trypanosome lines that we have examined, indicating that an alternative mechanism for HSR exists in these stocks. Examination of the inheritance of the phenotype in F1 hybrids for both bloodstream and metacyclic stages from 2 genetic crosses demonstrated that the phenotype is co-inherited in both life-cycle stages in a manner consistent with being a Mendelian trait, determined by only one or a few genes.

Asunto(s)

RESUMEN

Anaemia is a common finding in critically ill patients. There are often multiple causes. Obvious causes include surgical bleeding and gastrointestinal haemorrhage but many patients have no overt bleeding episodes. Phlebotomy can be a significant source of blood loss. In addition, critically ill patients have impaired erythropoiesis as a consequence of blunted erythropoietin production and direct inhibitory effects of inflammatory cytokines. The ability of a patient to tolerate anaemia depends on their clinical condition and the presence of any significant co-morbidity; maintenance of circulating volume is of paramount importance. There is no universal transfusion trigger. Current guidelines for critically ill and perioperative patients advise that at Hb values <70 g/L red blood cell transfusion is strongly indicated and at Hb values >100 g/L transfusion is unjustified. For patients with Hb values in the range 70 to 100 g/L the transfusion trigger should be based on clinical indicators. Most stable critically ill patients can probably be managed with a Hb concentration between 70 and 90 g/L. Uncertainties exist concerning the most appropriate Hb concentration for patients with significant cardio-respiratory disease.

Asunto(s)

RESUMEN

We conducted a comprehensive regional spatial assessment of bacterial water quality in order to determine the points of entry of fecal pollution into a swimming beach area on Lake Michigan that historically has had numerous water quality advisories for elevated levels of Escherichia coli (E. coli). Intensive, consecutive-day water samples were collected during dry and rainy conditions across multiple shoreline and offshore sites, and E. coli levels were enumerated from these samples. For both dry and rainy days, shoreline sites demonstrated significantly higher E. coli levels than offshore regions. We found that offshore (10-150m from shore) E. coli levels did not exceed 235CFU/100ml in more than 5% of the samples collected for 19 surveys (n=209). In contrast, samples taken at the beach area exceeded 235CFU/100ml in 66% of the samples collected for 43 shoreline surveys (n=675). Locally high E. coli levels coincided with bird presence and stormwater at the swimming beach located within the marina, and were unrelated to E. coli levels in connecting harbor waters. We conclude that beach water quality may be impacted by local, persistent contamination, which may confound routine beach monitoring and prevent the detection of regional pollution from other sources.

Asunto(s)

Asunto(s)

RESUMEN

OBJECTIVE: To compare the M-COVX and the Deltatrac II metabolic monitors under clinical conditions. DESIGN: Prospective clinical comparison. SETTING: A general Intensive Care Unit of a university hospital. PATIENTS: Twenty mechanically ventilated critically ill patients. INTERVENTIONS: The monitors were compared at FiO(2) 0.3, 0.5, and 0.7 in each patient where possible. MEASUREMENTS AND RESULTS: Pulmonary gas exchange measurements were recorded using the two monitors sequentially (Deltatrac(before), M-COVX, Deltatrac(after)). Each measurement consisted of five consecutive 1-min readings of VO(2) and VCO(2). We compared the Deltatrac(before) with the Deltatrac(after) and the mean of the Deltatrac with the M-COVX. There was no clinically significant bias between the two monitors for VO(2) or VCO(2) but the limits of agreement (LOA) were wide (bias +/-95% LOA: VCO(2) -13 +/- 30 ml/min, -8 +/- 36 ml/min, 7 +/- 50 ml/min; VO(2) -7 +/- 50 ml/min, -5 +/- 56 ml/min, 6 +/- 64 ml/min, at FiO(2) 0.3, 0.5, and 0.7, respectively). The Deltatrac before and after measurements displayed good agreement for VCO(2) but poorer agreement for VO(2) (bias +/- 95% LOA: VCO(2) 0 +/- 18 ml/min, -6 +/- 16 ml/min, -1 +/- 12 ml/min; VO(2) 2 +/- 12 ml/min, 3 +/- 38 ml/min, 10 +/- 42 ml/min, at FiO(2) 0.3, 0.5, and 0.7, respectively). Using within-patient standard deviation as a measure of reproducibility suggested that for VO(2) the M-COVX performed better than the Deltatrac at high FiO(2), and for VCO(2) Deltatrac was better at lower FiO(2). CONCLUSIONS: The M-COVX is a suitable integrated device for measuring metabolic gas exchange in ventilated patients.

Asunto(s)

RESUMEN

This study compared the rates of proliferation and apoptosis of cells within nodules of Dupuytren's disease and nodules from patients that had been injected preoperatively with steroid (Depo-Medrone). It also compared the effects of steroids in apoptosis in cultured Dupuytren's cells and control fibroblasts from palmar fascia and fascia lata. Steroids reduced the rate of fibroblast proliferation and increased the rate of apoptosis of both fibroblasts and inflammatory cells in Dupuytren's tissue. Steroids also produced apoptosis of cultured Dupuytren's cells but not of palmar fascia and fascia lata cells.

Asunto(s)

RESUMEN

Bacterial strains were isolated from beach water samples using the original Environmental Protection Agency method for Escherichia coli enumeration and analyzed by pulsed-field gel electrophoresis (PFGE). Identical PFGE patterns were found for numerous isolates from 4 of the 9 days sampled, suggesting environmental replication. 16S rRNA gene sequencing, API 20E biochemical testing, and the absence of beta-glucuronidase activity revealed that these clonal isolates were Klebsiella, Citrobacter, and Enterobacter spp. In contrast, 82% of the nonclonal isolates from water samples were confirmed to be E. coli, and 16% were identified as other fecal coliforms. These nonclonal isolates produced a diverse range of PFGE patterns similar to those of isolates obtained directly from untreated sewage and gull droppings. beta-Glucuronidase activity was critical in distinguishing E. coli from other fecal coliforms, particularly for the clonal isolates. These findings demonstrate that E. coli is a better indicator of fecal pollution than fecal coliforms, which may replicate in the environment and falsely elevate indicator organism levels.

Asunto(s)

RESUMEN

BACKGROUND: Latex allergy affects health care workers as a high-risk cohort. Hev b 5 is a major latex allergen reacting with serum IgE from 92% of latex-allergic health care workers. Because CD4(+) T-cell recognition is central to the specific immune response to allergens, identification of dominant T-cell epitopes is important for the development of specific immunotherapy for latex allergy. OBJECTIVE: Our purpose was to map T-cell epitopes of Hev b 5 in health care workers. METHODS: Six latex-allergic health care workers (grade 3 to 4 enzyme allergosorbent test score) were studied. Peripheral blood latex specific 3-week T-cell lines were generated and screened for proliferative response to overlapping 20-mer peptides of Hev b 5. Supernatants collected at 48 hours were analyzed by ELISA for IL-5 and IFN-gamma. RESULTS: Dot immunoblotting with use of recombinant Hev b 5/maltose-binding protein indicated serum-specific IgE in 5 of 6 patients. T-cell reactivity to one or more Hev b 5 peptides was identified in these 5 donors, but not in the sixth. Hev b 5 (46-65) induced T-cell proliferation in all 5 donors. Hev b 5 (109-128) stimulated T cells from 3 of these patients. Proliferative responses were accompanied by substantial IL-5 secretion and minimal IFN-gamma, indicating a T(H)2-predominant cytokine profile. CONCLUSIONS: Five of 6 latex-allergic patients demonstrated T-cell responsiveness to Hev b 5 consistent with a major T-cell reactive latex allergen. Two T-cell immunodominant regions of Hev b 5 were identified, and reactivity to these sites was associated with strong IL-5 but minimal IFN-gamma production.

Asunto(s)

RESUMEN

STUDY OBJECTIVES: To determine whether the lungs of patients with fulminant hepatic failure release lactate, and if so, whether this release relates to systemic lactate concentration or acid base status. Another objective was to examine the accuracy of lactate flux calculations in critically ill patients. DESIGN: Prospective observational study. SETTING: The ICU of a major teaching hospital. PATIENTS: Twelve patients with fulminant hepatic failure; 30 other critically ill patients in whom a pulmonary artery catheter was in place. INTERVENTIONS: None. MEASUREMENT AND RESULTS: The precision of whole-blood lactate measurements was assessed in 30 patients with critical illnesses of variable etiology who had a wide range of arterial lactate concentrations. The reliability of lactate measurements decreased with increasing lactate concentration. In each patient with liver failure, pulmonary lactate flux was calculated on three occasions using the Fick principle. Arterial blood lactate concentration was consistently higher than venous concentrations, indicating lactate release by the lungs (mean difference, 0.15 mmol/L; 95% confidence interval, 0.09 to 0.21; p<0.001). Mean pulmonary lactate production for the 12 patients was 83 mmol/h (range, 22 to 210 mmol/h). No patient had significant acute lung injury. Correlations were found among the arterial lactate concentration and both the arteriovenous (AV) lactate difference (p<0.025) and pulmonary lactate production (p<0.05), but not with acid-base status or cardiac output. The reliability of individual AV lactate difference calculations and pulmonary lactate flux calculations was poor. CONCLUSION: The lungs release lactate in patients with fulminant hepatic failure at a rate proportional to the degree of systemic hyperlactatemia. However, the measurement errors associated with pulmonary lactate flux calculations using the Fick principle are large, so individual measurements should be interpreted with caution.

Asunto(s)

RESUMEN

Dupuytren's disease is a chronic inflammatory process which produces contractures of the fingers. The nodules present in Dupuytren's tissue contain inflammatory cells, mainly lymphocytes and macrophages. These express a common integrin known as VLA4. The corresponding binding ligands to VLA4 are vascular cell adhesion molecule-1 (VCAM-1) present on the endothelial cells and the CS1 sequence of the fibronectin present in the extracellular matrix. Transforming growth factor-beta (TGF-beta) is a peptide hormone which has a crucial role in the process of fibrosis. We studied tissue from 20 patients with Dupuytren's disease, four samples of normal palmar fascia from patients undergoing carpal tunnel decompression and tissue from ten patients who had received perinodular injections of depomedrone into the palm five days before operation. The distribution of VLA4, VCAM-1, CS1 fibronectin and TGF-beta was shown by immunohistochemistry using an alkaline phosphorylase method for light microscopy. In untreated Dupuytren's tissue CS1 fibronectin stained positively around the endothelial cells of blood vessels and also around the surrounding myofibroblasts, principally at the periphery of many of the active areas of the Dupuytren's nodule. VCAM-1 stained very positively for the endothelial cells of blood vessels surrounding and penetrating the areas of high nodular activity. VCAM-1 was more rarely expressed outside the blood vessels. VLA4 was expressed by inflammatory cells principally in and around the blood vessels expressing VCAM-1 and CS1 but also on some cells spreading into the nodule. TGF-beta stained positively around the inflammatory cells principally at the perivascular periphery of nodules. These cells often showed VLA4 expression and co-localised with areas of strong production of CS1 fibronectin. Normal palmar fascia contained only scanty amounts of CS1 fibronectin, almost no VCAM-1 and only an occasional cell staining positively for VLA4 or TGF-beta. In the steroid-treated group, VCAM-1 expression was downregulated in the endothelium of perinodular blood vessels and only occasional inflammatory cell expression remained. Expression of CS1 fibronectin was also much reduced but still occurred in the blood vessels and around the myofibroblast stroma. VLA4-expressing cells were also reduced in numbers. A similar but reduced distribution of production of TGF-beta was also noted. Our findings show that adherence of inflammatory cells to the endothelial wall and the extravasation into the periphery of the nodule may be affected by steroids, which reduce expression of VCAM-1 in vivo. This indicates that therapeutic intervention to prevent the recommencement of the chronic inflammatory process and subsequent fibrosis necessitating further surgery may be possible.

Asunto(s)