[Update on the zoonotic potential of Chlamydia]. / Update zum Zoonosepotential von Chlamydien.

INTRODUCTION: Knowledge of the obligate intracellular bacteria from the Chlamydiaceae family has increased significantly in recent years. Not only new chlamydia species, such as Chlamydia avium or C. buteonis in birds have been described, but also known chlamydia in new host species, such as C. psittaci in horses. This review article provides an up-to-date overview of the zoonotic potential of C. psittaci, C. abortus, C. caviae and C. felis and summarizes current findings on other chlamydia species in different animal species; supplemented by information on optimal sampling and pathogen detection.

INTRODUCTION: Les connaissances sur les bactéries intracellulaires obligatoires de la famille des Chlamydiaceae ont considérablement augmenté ces dernières années. Non seulement de nouvelles espèces de Chlamydies, telles que Chlamydia avium ou C. buteonis chez les oiseaux, ont été décrites, mais également des Chlamydies déjà connues ont été mises en évidence chez de nouvelles espèces hôtes, telles que C. psittaci chez les chevaux. Cet article de synthèse fournit une vue d'ensemble actualisée du potentiel zoonotique de C. psittaci, C. abortus, C. caviae et C. felis et résume les connaissances actuelles sur d'autres espèces de Chlamydies chez différentes espèces animales ; il est complété par des informations sur l'échantillonnage optimal et la détection des agents pathogènes.

Calidad de vida tras una intervención comunitaria sociomotriz en mayores con riesgo social. Ensayo clínico / Quality of life after a social-physical activity community intervention in elderly people with social risk. Clinical trial

Objetivo Valorar la efectividad de un programa sociomotriz en la mejora de la calidad de vida relacionada con la salud de pacientes mayores de 65años con riesgo social. Material y métodos Ensayo clínico aleatorizado. Ámbito: comunitario; atención primaria y centro educativo público. Sujetos: mayores de 65años con riesgo social que acudieron al centro de salud durante el período de estudio y cumplieron los criterios de inclusión, n=102. Intervenciones: los sujetos se aleatorizaron en dos grupos; el grupo de intervención realizó dos sesiones semanales de una hora de ejercicio físico durante 4meses, sesiones mensuales sobre hábitos saludables y tres jornadas de actividades sociales; el grupo control recibió los consejos habituales. Se evaluó la calidad de vida mediante el cuestionario SF-36, previamente y al finalizar el programa. Resultados Completaron el estudio 80 sujetos (edad media 71,5±5 años; 91,3% mujeres). Basalmente no existieron diferencias significativas entre grupos y sus componentes sumarios estandarizados físico y mental del SF-36 estuvieron por debajo de los valores de referencia poblacionales (p<0,01). Tras el programa, el grupo de intervención mejoró significativamente respecto al grupo control en las 8 escalas del SF-36 y en los componentes sumarios, con un incremento mayor de 4puntos (p<0,01) en el componente físico y de 10 puntos en el mental (p<0,01). Conclusiones El programa comunitario de intervención sociomotriz mejora la calidad de vida relacionada con la salud de los mayores con riesgo social (AU)

Objective To assess the effectiveness of a social-physical activity program to improve the health-related quality of life of patients over 65years old with social risk. Material and methods Randomized clinical trial. Setting: Community; primary care and public schools. Subjects: patients over 65years old with social risk, who went to the health center during the study period and met the inclusion criteria, n=102. Interventions: Subjects were randomized into two groups. The intervention group conducted two weekly sessions of 1hour of physical exercise, for 4months; monthly sessions on healthy habits and three days of social activities. The control group received the usual advice. Quality of life was assessed using the SF-36 questionnaire; previously and at the end of the program. Results The study was completed by 80 subjects (mean age 71.5±5 years; 91.3% women). Baseline, there were no significant differences between groups, and their standardized physical and mental summary components of the SF-36 were below the population reference values (P<.01). After the program, the intervention group improved significantly, compared to the control group, in the 8 scales of the SF-36 and in the summary components, with a greater increase of 4points (P<.01) in the physical component, and 10 points in the mental component (p<0.01). Conclusion The community program of social-physical activity intervention improves the health-related quality of life in older people at social risk (AU)

[Quality of life after a social-physical activity community intervention in elderly people with social risk. Clinical trial]. / Calidad de vida tras una intervención comunitaria sociomotriz en mayores con riesgo social. Ensayo clínico.

OBJECTIVE: To assess the effectiveness of a social-physical activity program to improve the health-related quality of life of patients over 65years old with social risk. MATERIAL AND METHODS: Randomized clinical trial. SETTING: Community; primary care and public schools. SUBJECTS: patients over 65years old with social risk, who went to the health center during the study period and met the inclusion criteria, n=102. INTERVENTIONS: Subjects were randomized into two groups. The intervention group conducted two weekly sessions of 1hour of physical exercise, for 4months; monthly sessions on healthy habits and three days of social activities. The control group received the usual advice. Quality of life was assessed using the SF-36 questionnaire; previously and at the end of the program. RESULTS: The study was completed by 80 subjects (mean age 71.5±5 years; 91.3% women). Baseline, there were no significant differences between groups, and their standardized physical and mental summary components of the SF-36 were below the population reference values (P<.01). After the program, the intervention group improved significantly, compared to the control group, in the 8 scales of the SF-36 and in the summary components, with a greater increase of 4points (P<.01) in the physical component, and 10 points in the mental component (p<0.01). CONCLUSIONS: The community program of social-physical activity intervention improves the health-related quality of life in older people at social risk.

[Functional physical condition after a multi-component community intervention of active aging: Pragmatic clinical trial]. / Condición física funcional tras una intervención comunitaria multicomponente de envejecimiento activo. Ensayo clínico pragmático.

OBJECTIVE: The objective is to assess the effectiveness of a multicomponent program of active aging in the improvement of the functional physical condition of patients older than 65years old with social risk. MATERIAL AND METHODS: Pragmatic clinical trial non-blinded. SETTING: Community activity; primary care and public education center. PARTICIPANTS: Patients older than 65years and diagnosed with social risk. The patients who attended at the health center and fulfilled the inclusion criteria were selected consecutively (n=102). INTERVENTIONS: The patients were randomized into the intervention group or to the control group. The intervention included two weekly sessions of 1h of exercise during 4months, monthly health education sessions, and three days of social activities. The control group received the regular tips. The physical conditions were evaluated before and at the end the study. RESULTS: Eighty of the patients completed the study. Their middle age was 71.5±5 years old, and 91.3% of them were women. There was no significant differences between both groups. After the intervention, all the test for physical qualities improved in the intervention group; in the 6-minutes walk test the patients improved their mark in a 98% from the baseline marks, with an average increase of 65±35m. Flexibility improved in the 60% of the patients (95%CI: 50-70); strength increased an 84% (95%CI: 76-92), and dynamic balance increased a 79% (95%CI: 70-88). In control group improve some test marks but it had no statistical significance. CONCLUSIONS: The socio-motor intervention program coordinated between health services and educational centers improves the functional physical condition of the elderly with social risk.

Parental Self-Efficacy in New Mothers Predicts Infant Growth Trajectories.

The purpose of this study was to examine whether parental self-efficacy (PSE) is associated with change in infant weight-for-length z score (WLZ) from age 3 to 12 months. Data were drawn from the Infant Care, Feeding, and Risk of Obesity study, conducted with low-income, African American mother-infant dyads (n = 127). PSE was measured at infant age of 3 months. Infant anthropometrics were measured at infant age of 3 and 12 months, WLZ change between these time points was calculated, and infants stratified into WLZ change categories (expected, excessive, or slow). To analyze the data, ANCOVA, multiple regression, and post hoc techniques were used. Controlling for infant birthweight, PSE at 3 months was associated with infant WLZ change (η2 = 0.05, p = .04). Mothers of infants who exhibited excessive growth had higher PSE than mothers of infants who exhibited slow growth (Tukey-adjusted p = .03). This finding suggests that infants of mothers with high PSE may have increased obesity risk, but more research is needed.

Self-efficacy, infant feeding practices, and infant weight gain: An integrative review.

It has been suggested that self-efficacy specific to parenting or feeding may influence the decisions parents make regarding infant feeding; however, a review of this topic has not been conducted. The purpose of this integrative review is to synthesize the literature regarding the potential role of self-efficacy in infant feeding practices or infant weight gain. A total of 40 articles were used to guide this review, which were classified into three categories examining an association with self-efficacy (1) breastfeeding; (2) infant feeding practices such as parental feeding style and dietary quality; and (3) infant weight gain. Evidence regarding breastfeeding self-efficacy (BFSE) and breastfeeding is extensive; mothers with a higher sense of BFSE more often initiate breastfeeding and breastfeed for longer durations. The evidence regarding self-efficacy and the association with infant feeding practices other than breastfeeding is sparse. However, several studies report that mothers who have a higher sense of self-efficacy are more likely to follow infant feeding practices which align with recommendations. The authors have speculated an association between self-efficacy and infant weight gain; yet, to date, no study has found a significant association. More research is needed on the topic, particularly in diverse populations and with fathers and mothers.

Application in Europe of a urine-based rapid diagnostic test for confirmation of Schistosoma mansoni infection in migrants from endemic areas.

In February 2015, a male patient from Eritrea with persistent abdominal pain and rectal bleeding was diagnosed with Schistosoma mansoni infection upon examination of a rectal biopsy. In May 2015, repeated stool microscopy identified S. mansoni infection in another Eritrean patient with abdominal pain and considerable eosinophilia (34%). Use of point-of-care circulating cathodic antigen (POC-CCA) tests on urine confirmed S. mansoni infection in both patients. Wider application of non-invasive POC-CCA urine tests will improve schistosomiasis diagnosis and clinical management in migrants.

Severity of rhinovirus infection in hospitalized adults is unrelated to genotype.

OBJECTIVES: To determine whether rhinovirus (RV) species is associated with more severe clinical illness in adults. METHODS: Seventy-two RV-positive viral respiratory samples from adult patients were sequenced and analyzed phylogenetically after reverse transcriptase polymerase chain reaction of the region spanning the VP4 gene and 5' terminus of the VP2 gene. The clinical features and severity of illness associated with the different RV species were compared. RESULTS: Phylogenetic analysis identified three distinct clusters as RV-A (54%), B (11%), or C (35%) species. In an unadjusted model, patients with RV-B infection were significantly more likely to have the composite outcome variable of death or intensive care unit admission (P=.03), but this effect diminished when controlling for patient sex. A logistic model of the relationship between RV species and adverse outcomes produced nonsignificant odds ratios when controlling for patient sex. CONCLUSIONS: Infection with RV-A or RV-B was associated with greater severity of illness in our adult population; however, the association disappeared after controlling for confounders.

Gastrointestinal pathogens detected by multiplex nucleic acid amplification testing in stools of pediatric patients and patients returning from the tropics.

BACKGROUND: Gastrointestinal infections are caused by a broad spectrum of pathogens. Conventional diagnostic procedures are resource and time consuming due to single pathogen testing, often in different laboratories. METHOD: We analyzed 312 consecutive stool samples from pediatric patients (n = 127) with gastroenteritis or from adult travelers returning from the tropics with suspected parasite infestation (n = 185) using commercial multiplex nucleic acid amplification testing (NAT) (xTAG gastrointestinal pathogen panel, Luminex) covering 15 diarrhea-causing pathogens. The results of the positive samples and a representative number of negative samples were compared to standard methods, including NAT, direct antigen detection (DAD), bacterial culture and microscopy. RESULTS: Of the 185 samples from adult travelers, 21 (11 %) were multiplexNAT-positive, with enterotoxigenic Escherichia coli (4 %) being the predominant pathogen. Microscopic examination revealed Blastocystis hominis in 23 % not covered by the panel. MultiplexNAT scored positive in 66 pediatric samples (52 %), with rotavirus (27 %) being the most prevalent. All adenovirus-, rotavirus-, Clostridium difficile- and Cryptosporidium-positive samples were confirmed in external laboratories, but only 40 % of norovirus- and 29 % of Giardia-positive samples. Analysis of frozen specimens by bacterial culture showed the highest discrepancies with the multiplexNAT. CONCLUSION: Our study demonstrates broad detection of relevant gastroenteritis pathogens by multiplexNAT with a short turnaround time. This is important for diagnosis, infection control and empiric management of gastroenteritis patients, but may be selectively complemented by bacterial culture and resistance testing.

Strongyloides stercoralis larvae excretion patterns before and after treatment.

The variability of larval excretion impedes the parasitological diagnosis of Strongyloides stercoralis in infected individuals. We assessed the number of larvae excreted per gram (LPG) stool in 219 samples from 38 infected individuals over 7 consecutive days before and in 470 samples from 44 persons for 21 consecutive days after ivermectin treatment (200 µg kg-1 BW). The diagnostic sensitivity of a single stool sample was about 75% for individuals with low-intensity infections (⩽1 LPG) and increased to 95% for those with high-intensity infections (⩾10 LPG). Doubling the number of samples examined per person increased sensitivity to more than 95%, even for low-intensity infections. There was no indication of a cyclic excretion of larvae. After treatment, all individuals stopped excreting larvae within 3 days. Larvae were not detected during any of the following 18 days (total 388 Baermann and 388 Koga Agar tests). Two stool samples, collected on consecutive days, are recommended in settings where low or heterogeneous infection intensities are likely. In this way, taking into account the possible biological variability in excretion, the efficacy of ivermectin treatment can be assessed as soon as 4 days after treatment.

Comparison of the Kato-Katz method and ether-concentration technique for the diagnosis of soil-transmitted helminth infections in the framework of a randomised controlled trial.

Soil-transmitted helminth infections are a major public health problem. An accurate diagnosis is important in order to identify individuals and communities in need of intervention, and for monitoring drug efficacy and potential emergence of resistance. We compared the accuracy of the Kato-Katz method and ether-concentration technique for the diagnosis of soil-transmitted helminth infections within a randomised controlled trial. Quadruplicate Kato-Katz thick smears (duplicate Kato-Katz from two stool samples each) were examined before (baseline) and 3 weeks after treatment (follow-up). Additionally, at baseline and follow-up, the first stool sample was subjected to an ether-concentration method. We determined the prevalence, sensitivity, negative predictive value, diagnostic agreement and cure rates for single and duplicate Kato-Katz thick smears from the first stool sample, quadruplicate Kato-Katz thick smears produced from two stool samples and single ether-concentration as compared to our 'gold' standard (i.e. quadruplicate Kato-Katz plus ether-concentration). Quadruplicate Kato-Katz revealed a higher sensitivity than single ether-concentration for Trichuris trichiura at baseline (94.3 % vs. 88.5 %, p = 0.002) and follow-up (93.8 % vs. 83.5 %, p < 0.001). In contrary, at follow-up, ether-concentration showed a higher sensitivity than quadruplicate Kato-Katz for Ascaris lumbricoides diagnosis (86.7 % vs. 46.7 %, p = 0.012). The ether-concentration method showed similar or slightly higher sensitivity than the Kato-Katz technique based on a single stool sample for all soil-transmitted helminth infections. The estimated cure rates were heavily dependent on the diagnostic technique and sampling effort. In conclusion, data on the prevalence of soil-transmitted helminth infections and the efficacy of anthelminthics are greatly influenced by the diagnostic method and sampling effort. The ether-concentration technique is a valuable alternative to the Kato-Katz method for helminth diagnosis.

[Case-cohort surveys]. / Les enquêtes cas-cohorte.

In this paper, we present the main tools for conception, implementation and analysis of case-cohort surveys. In particular, we describe the classical weighted estimators, the weighted approach recently suggested by Breslow et al. and the multiple imputation approach, an alternative to weighted analysis of case-cohort data. Variance estimators are also described. We show how to obtain the subcohort size. Finally, we mention the functions and procedures available in R, SAS and Stata software and we illustrate their implementation using simulated subcohorts from the PRIME cohort.

Severity of human rhinovirus infection in immunocompromised adults is similar to that of 2009 H1N1 influenza.

This retrospective chart review of patients at a tertiary referral center compares characteristics and clinical features of patients diagnosed with human rhinovirus (HRV) infection to those of patients with 2009 H1N1 influenza A (pH1N1) during the pandemic respiratory season of 2009 to 2010. Hospital admission rates, intensive care unit (ICU) admissions, and mortality were not statistically different between the HRV and pH1N1 groups; however, more patients in the HRV group were considered immunocompromised.

Organ donation in Switzerland: a survey on marginal or extended criteria donors (ECD) from 1998 to 2009.

BACKGROUND: The widening gap between the numbers of patients on the waiting list for organ transplantation and the insufficient numbers of organ donors results in the use of "critical" donors, so-called marginal donors or extended criteria donors. Data concerning the evaluation of extended criteria donors (ECD) in Switzerland are sparse. METHODS: All organ donors in Switzerland between 1.1.1998 and 30.6.2009 have been evaluated for special criteria. ECD were defined on the basis of at least one of seven criteria: six DOPKI criteria (ECD-DOPKI) and/or age ≥60 yr (ECD-Age). Once included in the study, special features, short time follow-up (first 7 days after transplantation) and the cold ischaemia time of all the transplanted organs were evaluated. RESULTS: During the period 1.1.1998 to 30.6.2009, a total of 408 organ donors were classified as ECD, reflecting 39% of all organ donors in this time period. Despite the fact that all organ donors in this study fulfilled at least one inclusion criterion, the number of recipients with satisfactory primary organ function was always higher than the respective number with a negative primary outcome within the first seven days after transplantation. A longer cold ischaemia time was associated with organs showing insufficient primary organ function compared to organs with satisfactory primary function. A relevant causal relationship cannot be investigated on the basis of our limited data. In addition, a longer observation period would be necessary to draw a more precise conclusion. CONCLUSIONS: ECD as defined by DOPKI and/or age represent a high proportion of all organ donors in Switzerland but show a remarkably good outcome.

[How can serology contribute to the diagnosis of parasitic diseases?]. / Comment la sérologie peut-elle aider à l'établissement du diagnostic des parasites?

From a technical standpoint the most widely used tests for serology include the ELISA (enzyme linked immunosorbent assay), the IFA (indirect fluorescence assay), and the immunoblot. ELISA tests are widely used as screening assays since they harbor a high sensitivity. The main pitfall of serologies is the frequency of cross-reactions, especially between the different helminths. This is why positive results should be confirmed by a second test method with a higher specificity. Results need also to be put in the perspective of the patient history, clinical signs and laboratory findings. Serological tests are most appropriate when the parasite cannot be documented by direct examination (by eye or under the microscope) and during the pre-patent period. Serologies for parasites are also useful when an unexplained eosinophilia is present.

Single application of low-dose mycophenolate mofetil-OX7-immunoliposomes ameliorates experimental mesangial proliferative glomerulonephritis.

IgA nephropathy, one of the most frequent forms of glomerulonephritis, characterized by mesangial hypercellularity and glomerular extracellular matrix (ECM) expansion, often leads to end-stage renal disease over a prolonged period. We investigated whether antiproliferative treatment in a single low dose specifically targeted to the glomerular mesangium by immunoliposomes (ILs) results in an amelioration of mesangial proliferative glomerulonephritis in rats (anti-Thy1.1 nephritis). Mycophenolate mofetil (MMF) containing ILs was generated that targets the Thy1.1 antigen (OX-7) in rat mesangial cells. Treatment benefit of a single intravenous dose of these ILs given 2 days after disease induction was investigated by stereology, immunohistochemistry, and functional analyses (creatinine, albuminuria) until day +9 and was compared among untreated and free MMF-treated rats using six male Wistar rats per group. MMF-loaded OX7-IL prevented creatinine increase and albuminuria. Stereological analyses of MMF OX7-IL-treated animals yielded 30% reduction of mesangial cells on day +9 and a 40% reduction of glomerular ECM volume on day +5, compared with all of the other nephritic animals. Furthermore, at days +5 and +9 we observed decreased ECM content and decreased glomerular volume (day +5) in the MMF-OX7-IL-treated group compared with the nephritic group treated with free MMF. In conclusion, MMF-OX7-IL-based directed drug delivery represents a novel approach for treating mesangial cell-mediated forms of glomerulonephritis.

Meta-analyses qualify metzincins and related genes as acute rejection markers in renal transplant patients.

Definition of acute renal allograft rejection (AR) markers remains clinically relevant. Features of T-cell-mediated AR are tubulointerstitial and vascular inflammation associated with excessive extracellular matrix (ECM) remodeling, regulated by metzincins, including matrix metalloproteases (MMP). Our study focused on expression of metzincins (METS), and metzincins and related genes (MARGS) in renal allograft biopsies using four independent microarray data sets. Our own cases included normal histology (N, n = 20), borderline changes (BL, n = 4), AR (n = 10) and AR + IF/TA (n = 7). MARGS enriched in all data sets were further examined on mRNA and/or protein level in additional patients. METS and MARGS differentiated AR from BL, AR + IF/TA and N in a principal component analysis. Their expression changes correlated to Banff t- and i-scores. Two AR classifiers, based on METS (including MMP7, TIMP1), or on MARGS were established in our own and validated in the three additional data sets. Thirteen MARGS were significantly enriched in AR patients of all data sets comprising MMP7, -9, TIMP1, -2, thrombospondin2 (THBS2) and fibrillin1. RT-PCR using microdissected glomeruli/tubuli confirmed MMP7, -9 and THBS2 microarray results; immunohistochemistry showed augmentation of MMP2, -9 and TIMP1 in AR. TIMP1 and THBS2 were enriched in AR patient serum. Therefore, differentially expressed METS and MARGS especially TIMP1, MMP7/-9 represent potential molecular AR markers.

Microscopic diagnosis of sodium acetate-acetic acid-formalin-fixed stool samples for helminths and intestinal protozoa: a comparison among European reference laboratories.

The present study aimed to compare the diagnostic performance of different European reference laboratories in diagnosing helminths and intestinal protozoa, using an ether-concentration method applied to sodium acetate-acetic acid-formalin (SAF)-preserved faecal samples. In total, 102 stool specimens were analysed during a cross-sectional parasitological survey in urban farming communities in Côte d'Ivoire. Five SAF-preserved faecal samples were prepared from each specimen and forwarded to the participating reference laboratories, processed and examined under a microscope adhering to a standard operating procedure (SOP). Schistosoma mansoni (cumulative prevalence: 51.0%) and hookworm (cumulative prevalence: 39.2%) were the predominant helminths. There was excellent agreement (kappa > 0.8; p < 0.001) among the reference laboratories for the diagnosis of S. mansoni, hookworm, Trichuris trichiura and Ascaris lumbricoides. Moderate agreement (kappa = 0.54) was found for Hymenolepis nana, and lesser agreement was observed for other, less prevalent helminths. The predominant intestinal protozoa were Entamoeba coli (median prevalence: 67.6%), Blastocystis hominis (median prevalence: 55.9%) and Entamoeba histolytica/Entamoeba dispar (median prevalence: 47.1%). Substantial agreement among reference laboratories was found for E. coli (kappa = 0.69), but only fair or moderate agreement was found for other Entamoeba species, Giardia intestinalis and Chilomastix mesnili. There was only poor agreement for B. hominis, Isospora belli and Trichomonas intestinalis. In conclusion, although common helminths were reliably diagnosed by European reference laboratories, there was only moderate agreement between centres for pathogenic intestinal protozoa. Continued external quality assessment and the establishment of a formal network of reference laboratories is necessary to further enhance both accuracy and uniformity in parasite diagnosis.

Experimental heart transplantation: effect of cyclosporine on expression and activity of metzincins.

Metzincins, such as matrix metalloproteases (MMP), and extracellular matrix (ECM) proteins are differentially regulated in inflammation. We hypothesised that metzincins are also dysregulated in experimental acute cardiac allograft rejection. We investigated the Dark Agouti-to-Lewis (DA-to-Lew) rat model of acute cardiac allograft rejection. Cyclosporine (CsA) (7.5 mg/kg/d) was given from transplantation to sacrifice (day +5). At that time, mRNA levels were analysed by Affymetrix genechip and quantitative reverse transcription polymerase chain reaction (qRTPCR). MMP protein and activities were analysed by immunohistology, fluorometry, zymography and Western blots. In untreated rejected DA allografts, mRNA levels of MMP-2/-7/-9/-/12-/14, a disintegrin and metalloprotease (ADAM)-17, tissue inhibitor of metalloprotease (TIMP)-1/-3 were increased, whereas MMP-11/-16/-24 and TIMP-2/-4 were lowered compared to native DA hearts. With respect to these untreated allografts, CsA lowered mRNA levels of MMP-7, TIMP-1/-3 (TIMP-2/-4 remained relatively low) and ADAM17, but augmented mRNA levels of MMP-11/-16/-23 and of many ECM genes. Immunohistology showed increased staining of MMP-2 in acute rejection (AR). Overall MMP activity was augmented in both transplanted groups, but CsA reduced MMP-9 activity and MMP-14 production. Taken together, MMP and TIMP were upregulated during acute AR. CsA ameliorated histology of rejection but showed potential pro-fibrotic effects. Thus, MMP and TIMP may play a role in acute cardiac allograft rejection, and beneficial modification of the MMP-ECM balance requires interventions beyond CsA.