Patterns of antibiotic use in hospital-acquired infections.

BACKGROUND: Monitoring the use of antimicrobials in hospitalized patients is critical owing to the risk of resistance selection. This study aimed to describe the patterns of antimicrobial prescription for the most frequent healthcare-associated infections (HAIs) in France, relating drugs and microbiological data. METHODS: We used data from the 2017 point-prevalence survey of HAI and antimicrobial use in France, a large nationally representative sample survey of inpatients. We sought unambiguous correspondence between individual indications of antibiotic regimen and HAI sites to determine which molecules were directed towards which pathogen, considering its resistance profile. RESULTS: Among 75,698 adult patients from 401 hospitals, 5.1% had an active HAI and 4.3% were being treated for an HAI. The two most frequent antibiotic indications were lower respiratory tract (LRTI, 27.7%) and urinary tract infections (UTI, 18.4%). For LRTI, the most prescribed antibiotic was amoxicillin-clavulanic acid (27.6%) and most frequently isolated pathogens (each accounting for around 17% of isolates) were Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. Meticillin-resistant S. aureus LRTI was more likely to be treated with linezolid. For UTI, ofloxacin, ceftriaxone, amoxicillin/co-amoxiclav were most-prescribed (∼13% each) and E. coli predominantly isolated (52.0%). Extended-spectrum beta-lactamase-producing E. coli UTI were more likely treated by fosfomycin, pivmecillinam or ertapenem. CONCLUSIONS: This study provides a baseline of antimicrobial use in relation to microbiological information in patients with the most common HAIs. These results can serve to direct future efforts in antimicrobial stewardship. Our work could be extended to a broader population, notably in Europe where similar surveys have been conducted.

Systematic review and meta-analysis of the evidence for oral nutritional intervention on nutritional and clinical outcomes during chemo(radio)therapy: current evidence and guidance for design of future trials.

Background: Driven by reduced nutritional intakes and metabolic alterations, malnutrition in cancer patients adversely affects quality of life, treatment tolerance and survival. We examined evidence for oral nutritional interventions during chemo(radio)therapy. Design: We carried out a systematic review of randomized controlled trials (RCT) with either dietary counseling (DC), high-energy oral nutritional supplements (ONS) aiming at improving intakes or ONS enriched with protein and n-3 polyunsaturated fatty acids (PUFA) additionally aiming for modulation of cancer-related metabolic alterations. Meta-analyses were carried out on body weight (BW) response to nutritional interventions, with subgroup analyses for DC and/or high-energy ONS or high-protein n-3 PUFA-enriched ONS. Results: Eleven studies were identified. Meta-analysis showed overall benefit of interventions on BW during chemo(radio)therapy (+1.31 kg, 95% CI 0.24-2.38, P = 0.02, heterogeneity Q = 21.1, P = 0.007). Subgroup analysis showed no effect of DC and/or high-energy ONS (+0.80 kg, 95% CI -1.14 to 2.74, P = 0.32; Q = 10.5, P = 0.03), possibly due to limited compliance and intakes falling short of intake goals. A significant effect was observed for high-protein n-3 PUFA-enriched intervention compared with isocaloric controls (+1.89 kg, 95% CI 0.51-3.27, P = 0.02; Q = 3.1 P = 0.37). High-protein, n-3 PUFA-enriched ONS studies showed attenuation of lean body mass loss (N = 2 studies) and improvement of some quality of life domains (N = 3 studies). Overall, studies were limited in number, heterogeneous, and inadequately powered to show effects on treatment toxicity or survival. Conclusion: This systematic review suggests an overall positive effect of nutritional interventions during chemo(radio)therapy on BW. Subgroup analyses showed effects were driven by high-protein n-3 PUFA-enriched ONS, suggesting the benefit of targeting metabolic alterations. DC and/or high-energy ONS were less effective, likely due to cumulative caloric deficits despite interventions. We highlight the need and provide recommendations for well-designed RCT to determine the effect of nutritional interventions on clinical outcomes, with specific focus on reaching nutritional goals and providing the right nutrients, as part of an integral supportive care approach.

Outbreak of CTX-M-15-producing Enterobacter cloacae associated with therapeutic beds and syphons in an intensive care unit.

An outbreak of extended-spectrum ß-lactamase-producing Enterobacter cloacae (ESBL-ECL) occurred in our intensive care unit (ICU) and involved 18 patients (8 infected and 10 colonized). The mean age of patients was 69 years, and all infected patients had underlying medical conditions. Within hours' recognition of the spread of ESBL-ECL, the infection control team requested for staff education, reinforcement of infection control measures, and environmental screening. New transmissions were observed in the institution after weeks of enhanced infection control measures. Microbial swabbing revealed bacterial contamination of some mattresses and syphons with epidemiologic links between environmental, screening, and clinical isolates. This outbreak resulted in the temporary closure of the ICU for complete biocleaning.

Probable nosocomial transmission of listeriosis in neonates.

Listeria monocytogenes was isolated in two neonates born consecutively in the same hospital in France. The isolates had indistinguishable pulsed-field electrophoresis profiles. Retrospective epidemiological investigations found no evidence of a food-borne or environmental source. Infection control protocols and decontamination processes were in accordance with standard recommendations. The timing of onset of these infections within the same maternity unit, and the similarity of pulsed-field gel electrophoresis profiles suggests cross-infection of L. monocytogenes between the two neonates.

Comparative effects of well-balanced diets enriched in α-linolenic or linoleic acids on LC-PUFA metabolism in rat tissues.

The intake of the essential fatty acid precursor α-linolenic acid (ALA) contributes to ensure adequate n-3 long-chain polyunsaturated fatty acid (LC-PUFA) bioavailability. Conversely, linoleic acid (LA) intake may compromise tissue n-3 PUFA status as its conversion to n-6 LC-PUFA shares a common enzymatic pathway with the n-3 family. This study aimed to measure dietary ALA and LA contribution to LC-PUFA biosynthesis and tissue composition. Rats were fed with control or experimental diets moderately enriched in ALA or LA for 8 weeks. Liver Δ6- and Δ5-desaturases were analyzed and FA composition was determined in tissues (red blood cells, liver, brain and heart). Hepatic Δ6-desaturase activity was activated with both diets, and Δ5-desaturase activity only with the ALA diet. The ALA diet led to higher n-3 LC-PUFA composition, including DHA in brain and heart. The LA diet reduced n-3 content in blood, liver and heart, without impacting n-6 LC-PUFA composition. At levels relevant with human nutrition, increasing dietary ALA and reducing LA intake were both beneficial in increasing n-3 LC-PUFA bioavailability in tissues.

Fatty Acid Desaturase 3 (Fads3) is a singular member of the Fads cluster.

Since its identification in 2000, no function has been attributed to the Fatty Acid Desaturase 3 (Fads3) gene. This gene is located within the Fads cluster, which also contains Fads1 and Fads2, coding respectively for the Δ5- and Δ6- desaturases. Based on the sequence homology between these three genes, Fads3 may be a new fatty acid desaturase. It is thus essential to understand its involvement in Polyunsaturated Fatty Acid (PUFA) biosynthesis in order to improve our knowledge on lipid metabolism. Gene expression studies provided evidences on the specificity of Fads3 compared to Fads1 and Fads2, concerning the tissue distribution, alternative splicing and regulation. These works also identified possible physiological functions in which Fads3 could be involved. Thus, the Fads3 gene was transcripted in many tissues, and displayed a weak expression in the liver compared to other organs such as the lung or spleen. Fads3 was also showed to be a target gene for NK-κB, MYCN or p63 transcription factors and could consequently be involved in cell survival mechanisms. Polymorphism analysis underlined the possible implication of Fads3 in lipid homeostasis, particularly by modulating cholesterol and triglyceride plasma levels. In terms of proteins, FADS3 has been recently described in rodents. One of the identified isoforms may display the classical structure of a fatty acid desaturase but no enzymatic activity has been observed yet. Therefore, it is essential to consider the desaturase diversity in terms of catalysis and substrates to elucidate the FADS3 function.

Nosocomial infections and hospital mortality: a multicentre epidemiology study.

The aim of this study was to evaluate the number of deaths associated with nosocomial infections (NI) and the contribution of these NI to death. A multicentre descriptive study was conducted in 16 tertiary-care hospitals (14 222 beds) in Northern France. Medical records of consecutive patients who died at least 48 h after admission were reviewed for cause of death, NI and disease severity, before admission and before NI onset. The contribution of NI to death was assessed by agreement between two physicians according to a three-category scale of probability. Among the 1945 patients who died during the study, 26.6% had an NI. According to the agreed diagnosis, NI contributed to the deaths of 284 (14.6%) patients(certainly for 6.6% and possibly for 8%), thereby ranking NI as the fourth most frequent cause of death. Considering the deaths that had not been anticipated independently of NI two weeks before they occurred, NI definitely contributed to 2.8% of them. Lower respiratory tract, bloodstream and surgical wound infections were responsible for 39, 20 and 14%, respectively,of all NI in these patients. The impact of NI on in-hospital mortality seems to be lower than had previously been estimated in France based on US data from the 1970s and 1980s. To improve healthcare quality, further studies are needed to elucidate the processes that may contribute to fatal severe NI.

Surgical resection and chemotherapy improve survival rate for patients with hepatoblastoma.

BACKGROUND: The authors reviewed retrospectively their experience in 30 children with hepatoblastoma (HB). Despite an increased trend in the incidence of HB during the last 2 decades, an encouraging cure rate has been achieved with complete resection of the tumor and chemotherapy before or after surgery with cisplatin plus doxorubicin (Adriamycin) or cisplatin plus vincristine plus 5-Fluorouracil. RESULTS: There were 10 female and 20 male patients. For the period from 1963 to 1980 there were 8 patients, and for the period from 1981 to 1998 there were 22 patients. Their mean age at surgery was 16 months (range, 3.5 months to 5.5 years). Tumors were localized to the right lobe in 10 (42%), to the left lobe in 7 (29%), and in both lobes in 7 (29%) of the resected patients. Tumors were greater than 10 cm in size in 16 (67%) of these patients. Twenty-four patients (80%), underwent liver resection before or after chemotherapy. One patient (3%) with an unresectable tumor received chemotherapy and a liver transplant. In 5 patients (17%) the hepatic involvement was too extensive for resection. The types of resection performed were right lobectomy in 7, left lobectomy in 6, right trisegmentectomy in 8, left trisegmentectomy in 2, and middle hepatectomy in 1. The overall survival rate for 35 years of the study was 60% (18 of 30). With the association of surgery and chemotherapy (1981 through 1998) survival rate is 82% (14 of 17). Overall median follow-up in our study is 8 years (range, 2.5 to 24 years). CONCLUSIONS: There has been a dramatic improvement in the results of treatment of hepatoblastoma. Formerly, only 25% to 30% of patients were cured, whereas today, with combination of chemotherapy and surgery, 75% to 80% may be cured.

Abdominal injuries associated with thoraco-lumbar fractures after motor vehicle collision.

PURPOSE: The goal of the current study was to evaluate the risk of intraabdominal injury in children who sustained spinal fractures in a motor vehicle collision (MVC). METHODS: Between 1980 and 1999, 48 patients, 24 girls and 24 boys, with a mean age of 12.8 years (range, 4 to 17) were reviewed. Twenty-nine were rear seat passengers, 12 front seat, and 7 unknown. Fifty-eight percent wore a seat belt. Thirty fractures involved the lumbar spine, 12 the thoracic, and 6 combined. Computed tomography (CT) scan, abdominal ultrasound, and peritoneal lavage were used to screen for abdominal injuries. RESULTS: Twenty-two of 48 patients had an intraabdominal injury. Eighteen (38%) required an early (<24 hours; n = 12) or delayed (n = 6) therapeutic laparotomy. Fourteen patients were rear seat passengers, 15 wore a seat belt, and 13 had an abdominal wall ecchymoses (AWE). They were 17 lumbar fractures (13 Chance) and one thoracic. The most common findings at laparotomy were hollow viscus injury (n = 12), mesenteric tear (n = 9), and solid organ injury (n = 8). Seventy-two percent of patients presenting with a lumbar fracture and AWE needed a therapeutic laparotomy. The overall survival rate was 98% with only 1 death. The mean hospital stay was 22.4 days. In this study, 38% of patients presenting with a spinal fracture required laparotomy, 68% of whom had simultaneous lumbar fracture and AWE. CONCLUSION: In light of these results, the authors propose that laparoscopy or laparotomy should be strongly considered in patients sustaining lumbar fracture and AWE after MVC. J Pediatr Surg 36:760-762.

Inducible nitric oxide synthase attenuates chronic colitis in human histocompatibility antigen HLA-B27/human beta2 microglobulin transgenic rats.

Rats transgenic for HLA-B27/human beta2-microglobulin develop a spontaneous multisystem inflammatory disorder that closely mimics human spondyloarthropathies. Prominent features of this disorder are gut inflammation that predominates in the colon, and arthritis. Several mediators such as IFN-gamma, IL-1beta, TNF-alpha, and inducible nitric oxide synthase (iNOS) have been found increased in the inflamed colonic mucosa. In the colon of HLA-B27 transgenic rats, iNOS is predominantly expressed by epithelial cells, and iNOS transcripts are detected in the hip cartilage of those rats, but not in nontransgenic littermates. The role of iNOS in this disorder was evaluated by administering the corticosteroid dexamethasone, or the NOS inhibitor L-N6-(1-iminoethyl)lysine (L-NIL) to HLA-B27 transgenic rats with established disease. Treatment with dexamethasone attenuated some aspects of gut inflammation, although it had no effect on iNOS expression. In contrast, treatment with L-NIL effectively inhibited iNOS activity, and resulted in an increase in colitis. Cytokine transcripts in the colon were modified by these treatments: IFN-gamma and IL-1beta were decreased after dexamethasone treatment, whereas administration of L-NIL resulted in decreased IFN-gamma, and TNF-alpha. A trend towards increased IL-1b expression was observed which could have contributed to the L-NIL pro-inflammatory effect. These results suggest that iNOS exerts a protective effect on colitis, in the inflammatory disorder of HLA-B27 transgenic rats.

Portal venous decompression with H-type mesocaval shunt using autologous vein graft: a North American experience.

BACKGROUND/PURPOSE: Portal hypertension in children often is caused by prehepatic venous obstruction or intrahepatic fibrosis without cirrhosis. This situation is uniquely amenable to shunting; this report details the experience of 3 North American centers with an H-type mesocaval shunt using autologous vein, which has been widely used in European centers. METHODS: Retrospective chart review was conducted of records from 1980 through 1999 at 3 North American institutions. Charts were reviewed for etiology of portal hypertension, diagnostic workup, preoperative management, operative results and complications, postoperative shunt patency, patient well-being, and eventual need for liver transplantation. RESULTS: Twenty patients were identified with prehepatic causes of venous obstruction undergoing shunt therapy. Eleven had portal venous thrombosis or cavernous transformation. Of these, 3 had umbilical catheters placed in the neonatal period. Five children had American-Indian cirrhosis, 1 had congenital hepatic fibrosis, and 3 had hepatic fibrosis associated with polycystic kidney disease. Patients presented at a median age of 3.7 years and underwent follow-up for an average of 4.3 years after surgery. These patients had an average of 3.6 bleeding episodes, (with 3.9 attempts at sclerotherapy) and received 3 units of blood preoperatively. Average age at operation was 8 years, average weight was 30 kg, and perioperative blood requirement was 200 mL. In general, patients did well postoperatively; 2 patients required reoperation for lymphatic leaks, and there was 1 death caused by a leaking G-tube, unrelated to shunt functioning. Two patients had transient encephalopathy postoperatively, and 1 patient had severe pancreatitis. All shunts remain patent, with good function and no further bleeding. CONCLUSIONS: These results are encouraging, and we would suggest that the H-type mesocaval shunt utilizing autologous vein be considered for wider use in pediatric patients with prehepatic cause of portal hypertension. An algorithm for the work-up of pediatric patients with variceal bleeding is presented, with the recommendation that shunt surgery be considered early in patients with a prehepatic or fibrotic causes of portal hypertension.

Nitric oxide in rheumatology.

Nitric oxide (NO) is attracting considerable interest because it mediates many functions. This gas is ubiquitously produced in the body by three enzymes, called NO synthases. Two NO synthases are constitutively expressed, one in the nervous system and the other in the blood vessels, where it regulates tissue perfusion. The third NO synthase can be induced by several stimuli (bacterial endotoxins, cytokines), most notably in inflammatory cells and chondrocytes. The effects of NO produced by the inducible NO synthase range from T-cell response modulation to formation of free radicals responsible fortissue damage and cartilage matrix degradation. Administration of NO synthase inhibitors in animal models of arthritis yields ambiguous effects, often with prevention of arthritis, but sometimes with worsening of established arthritis. The data available to date do not support the use of such inhibitors in the treatment of human arthritis.

[Blunt injuries of the pancreas in children]. / Traumatismes fermés du pancréas chez l'enfant.

STUDY AIM: Conservative management is mainly proposed for pancreatic trauma without ductal injuries. The aim of this retrospective study was to assess our experience with traumatic pancreatic injuries and to compare patients with medical or surgical treatment. PATIENTS AND METHOD: From January 1989 to December 1998, 21 children, 13 boys and 8 girls with a mean age of 8 years (range: 1 to 17 years) were treated for pancreatic injuries. Main mechanisms of injuries were bicycle's falls (n = 7), passengers in motor vehicle collision (n = 6), and other road collisions (n = 5). Diagnosis of pancreatic trauma in 17 patients was made through ultrasonography and/or CT scan. In 4 patients, the diagnosis was made intraoperatively. Associated injuries were splenic (n = 6), hepatic (n = 5) and duodenal (n = 5). Thirteen patients had only medical treatment and 8 patients required laparotomy. The two groups were comparable according to the rate of high grade pancreatic lesions. RESULTS: Two complications, a pancreatic fistula and a pseudocyst, occurred in the operative group and improved spontaneously. One death due to a head trauma, one acute pancreatitis and seven pancreatic pseudocysts (six required percutaneous drainage), occurred after medical treatment. The mean hospital stay, shorter after medical treatment, was not significantly different between the two groups (26 days vs 32 days). During the follow-up, no late complications have been observed. CONCLUSION: Traumatic pancreatic injuries are rarely lethal but are often associated with other intra-abdominal injuries. Conservative treatment is advocated for grade 1 to 4 isolated pancreatic injuries. This conservative approach may be associated with the development of post-traumatic pancreatic pseudocysts which are easily cured by percutaneous drainage.

Animal models of the spondyloarthropathies.

Several lines of rats transgenic for human leukocyte antigen (HLA)-B27 spontaneously develop a multisystemic inflammatory disease resembling human spondyloarthropathies. This disease is mediated by cells of the immune system and is dependent on the presence of a normal bacterial flora. Both antigen-presenting cells expressing high levels of HLA-B27 and T cells appear to be of importance in the pathogenesis of this model. HLA-B27 transgenic/b2- microglobulin deficient mice also develop arthritis, under the influence of the bacterial flora. In both types of model, CD8+ T cells appear to be unnecessary, arguing against the "arthritogenic peptide" hypothesis.

Caspase-8 specificity probed at subsite S(4): crystal structure of the caspase-8-Z-DEVD-cho complex.

Caspase-8 is an initiator enzyme in the Fas-mediated pathway of which the downstream executioner caspase-3 is a physiological target. Caspases are cysteine proteases that are specific for substrates with an aspartic acid residue at the P(1) position and have an optimal recognition motif that incorporates four amino acid residues N-terminal to the cleavage site. Caspase-8 has been classified as a group III caspase member because it shows a preference for a small hydrophobic residue at the P(4) substrate position. We report the X-ray crystallographic structure of caspase-8 in complex with benzyloxycarbonyl-Asp-Glu-Val-Asp-aldehyde (Z-DEVD), a specific group II caspase inhibitor. The structure shows that the inhibitor interacts favourably with the enzyme in subsite S(4). Kinetic data reveal that Z-DEVD (K(i) 2 nM) is an almost equally potent inhibitor of caspase-8 as the specific group III inhibitor Boc-IETD-aldehyde (K(i) 1 nM). In view of this finding, the original classification of caspases into three specificity groups needs to be modified, at least for caspase-8, which tolerates small hydrophobic residues as well as the acidic residue Asp in subsite S(4). We propose that the subsite S(3) must be considered as an important specificity-determining factor.

Repair of the huge umbilical hernia in black children.

Surgical repair of large umbilical hernias may present a challenging surgical problem. The currently described surgical techniques often yield disappointing results. The authors describe a new technique that allows for the repair of the fascial defect and the creation, with the use of a square cutaneous flap, of a neoumbilicus with sufficient depth and a good cosmetic appearance.

Past and future of biliary atresia.

BACKGROUND: With the advent of liver transplantation the outcome of children with biliary atresia (BA) has improved. Is Kasai hepatic portoenterostomy (KHPE) still a valuable option for the treatment of these patients? METHODS: From 1974 to 1998, 77 patients with biliary atresia have been treated at our institution: 50 girls and 27 boys. RESULTS: Seventy-four patients had a KHPE, and 3 patients had no KHPE because of delay in diagnosis. A total of 65 of 74 patients (88%) had undergone KHPE type I, 4 patients (5.4%) KHPE type II, 3 patients (4%) had a Suruga modification, and 2 patients (2.6%) had a portocholecystostomy. Among the 74 patients, 11 were lost to follow-up and their cases were considered failures. Seventeen of our patients are alive at long-term follow-up after KHPE. Among the 77 patients, 33 (43%) had an orthotopic liver transplantation (OLT). Successful KHPE patients underwent transplant at a mean age of 9 years, and KHPE failed at a mean age of 11 months. A total of 25 of 77 (32%) of patients are alive thanks to OLT. In the cohort, the overall survival rate for the KHPE plus OLT is 42 of 77 (55%). Mortality and morbidity rates were more frequent among the younger patients who had early OLT after KHPE failure. In our series, overall survival rate was improved when the patient had a successful KHPE (P < .001). CONCLUSIONS: Kasai hepatic portoenterostomy (KHPE) continues to be a valuable procedure in the treatment of infants with biliary atresia (BA). Successful KHPE permits transplantation at an age at which mortality and morbidity are decreased leading to a better outcome.

The three-dimensional structure of caspase-8: an initiator enzyme in apoptosis.

BACKGROUND: In the initial stages of Fas-mediated apoptosis the cysteine protease caspase-8 is recruited to the cell receptor as a zymogen (procaspase-8) and is incorporated into the death-signalling complex. Procaspase-8 is subsequently activated leading to a cascade of proteolytic events, one of them being the activation of caspase-3, and ultimately resulting in cell destruction. Variations in the substrate specificity of different caspases have been reported. RESULTS: We report here the crystal structure of a complex of the activated human caspase-8 (proteolytic domain) with the irreversible peptidic inhibitor Z-Glu-Val-Asp-dichloromethylketone at 2.8 A resolution. This is the first structure of a representative of the long prodomain initiator caspases and of the group III substrate specificity class. The overall protein architecture resembles the caspase-1 and caspase-3 folds, but shows distinct structural differences in regions forming the active site. In particular, differences observed in subsites S(3), S(4) and the loops involved in inhibitor interactions explain the preference of caspase-8 for substrates with the sequence (Leu/Val)-Glu-X-Asp. CONCLUSIONS: The structural differences could be correlated with the observed substrate specificities of caspase-1, caspase-3 and caspase-8, as determined from kinetic experiments. This information will help us to understand the role of the various caspases in the propagation of the apoptotic signal. The information gained from this investigation should be useful for the design of specific inhibitors.

Pleuropulmonary blastoma: a rare pathology with an even rarer presentation.

BACKGROUND: Pleuropulmonary blastoma is among the rarest tumors of childhood. Three types have been described: cystic, solid, and mixed. To date, bilateral disease has not been documented. METHODS AND RESULTS: A 5-week-old girl presented with a history of fever. Chest x-ray showed bilateral diffuse cystic lesions. Bowel obstruction developed that required laparotomy. Multiple small bowel polyps were resected. The patient was readmitted 4 months later with deteriorating respiratory status. She underwent sequential thoracotomies for resection of multiple bullae under high-frequency oscillatory ventilation. Small bowel polypectomies were again required because of obstruction. Lung lesions were compatible with pulmonary blastoma but could not be correlated with intestinal polyposis. Bilateral cystic renal lesions were seen on ultrasound scan. Her disease progressed, despite chemotherapy, with the appearance of metastatic iris lesions. She again underwent laparotomies for multiple recurrent generalized small bowel polyps that were causing obstruction. Expanding renal cysts affected kidney function, and she died at 14 months of age. CONCLUSIONS: The rare association between pleuropulmonary blastoma and Wilms' tumor or nephroblastomatosis is known but rarely reported. Lacking pathological evidence, we can only speculate that this was the case. We have been unable to demonstrate any histological association between the renopulmonary and digestive lesions. Despite many unanswered questions, we are likely dealing with a "syndrome" of sorts with a dire outcome, despite aggressive treatments.

Cytotoxic T-cell-mediated response against Yersinia pseudotuberculosis in HLA-B27 transgenic rat.

Yersinia-induced reactive arthritis is highly associated with HLA-B27, the role of which in defense against the triggering bacteria remains unclear. The aim of this study was to examine the capacity of rats transgenic for HLA-B27 to mount a cytotoxic T-lymphocyte (CTL) response against Y. pseudotuberculosis and to determine the influence of the HLA-B27 transgene on this response. Rats transgenic for HLA-B*2705 and human beta(2)-microglobulin of the 21-4L line, which do not spontaneously develop disease, and nontransgenic syngeneic Lewis (LEW) rats were infected with Y. pseudotuberculosis. Lymph node cells were restimulated in vitro, and the presence of for Y. pseudotuberculosis-specific CTLs against infected targets was determined. Infection of 21-4L rats triggered a CD8(+) T cell-mediated cytotoxic response specific for Y. pseudotuberculosis. Analysis of this response demonstrated restriction by an endogenous major histocompatibility complex molecule. However, no restriction by HLA-B27 was detected. In addition, kinetics studies revealed a weaker anti-Yersinia CTL response in 21-4L rats than in nontransgenic LEW rats, and the level of cytotoxicity against 21-4L lymphoblast targets sensitized with Y. pseudotuberculosis was lower than that against nontransgenic LEW targets. We conclude that HLA-B27 transgenic rats mount a CTL response against Y. pseudotuberculosis that is not restricted by HLA-B27. Yet, HLA-B27 exerts a negative effect on the level of this response, which could contribute to impaired defense against Yersinia.