Low-cost air quality portable sensors and their potential use in respiratory health.

Air pollution is an environmental risk for the general population and for patients with various diseases, particularly respiratory diseases. Little data are available on personal exposure, but the recent emergence of low-cost air quality sensors (LCSs) should enable a better understanding of the health impacts of air pollution at the individual level. However, the reliability and accuracy of most sensors in the market have not been established, and a thorough understanding of their strengths and limitations is needed. We therefore conducted a review to address the following questions: 1) What is an LCS and what is the extent of its possible application? 2) Is the data obtained a reliable indicator of exposure? 3) What are the advantages and disadvantages of LCSs? 4) Could LCSs be useful in investigating the impact of air pollution on respiratory health? Further studies are needed to promote the use of LCS in research settings and among respiratory patients. This will allow us to monitor exposure levels, provide alerts and study the respiratory effects of individual-level air pollution.

Results from the second WHO external quality assessment for the molecular detection of respiratory syncytial virus, 2019-2020.

Background: External quality assessments (EQAs) for the molecular detection of human respiratory syncytial virus (RSV) are necessary to ensure the standardisation of reliable results. The Phase II, 2019-2020 World Health Organization (WHO) RSV EQA included 28 laboratories in 26 countries. The EQA panel evaluated performance in the molecular detection and subtyping of RSV-A and RSV-B. This manuscript describes the preparation, distribution, and analysis of the 2019-2020 WHO RSV EQA. Methods: Panel isolates underwent whole genome sequencing and in silico primer matching. The final panel included nine contemporary, one historical virus and two negative controls. The EQA panel was manufactured and distributed by the UK National External Quality Assessment Service (UK NEQAS). National laboratories used WHO reference assays developed by the United States Centers for Disease Control and Prevention, an RSV subtyping assay developed by the Victorian Infectious Diseases Reference Laboratory (Australia), or other in-house or commercial assays already in use at their laboratories. Results: An in silico analysis of isolates showed a good match to assay primer/probes. The panel was distributed to 28 laboratories. Isolates were correctly identified in 98% of samples for detection and 99.6% for subtyping. Conclusions: The WHO RSV EQA 2019-2020 showed that laboratories performed at high standards. Updating the composition of RSV molecular EQAs with contemporary strains to ensure representation of circulating strains, and ensuring primer matching with EQA panel viruses, is advantageous in assessing diagnostic competencies of laboratories. Ongoing EQAs are recommended because of continued evolution of mismatches between current circulating strains and existing primer sets.

Surgical treatments of atraumatic avascular necrosis of the shoulder.

Humeral head atraumatic avascular necrosis is a rare diagnosis. It concerns young patients with a high functional demand. The treatments are mostly surgical. The radiographic classification of Cruess assesses the severity of the humeral head avascular necrosis and guides surgical indications. This chapter reports a review of the literature based on meta-analyses and clinical series. Surgical treatments may be conservative or prosthetic. Conservative treatments include core decompression, bone grafting and arthroscopic debridement. Prosthetic replacements are performed by resurfacing, hemiarthroplasty or total arthroplasty. For low-grade asvascular necrosis, core decompression may be functionally effective and doesn't impair later surgical procedures. For high grades, prosthetic replacements achieve good functional outcomes. Hemiarthroplasty should be preferred if the glenoid cartilage is intact, with low rates of wear complications and better long-term outcome than shoulder arthroplasty.

[How to improve patient's access to Respiratory Rehabilitation?] / Comment améliorer l'accès des patients à la réadaptation respiratoire ?

Despite effectiveness and clear international guidelines, respiratory rehabilitation remains underutilized: less than 15% of suitable patients in France and worldwide receive this treatment. The factors of this lack of referral and uptake have been studied and are not limited to a problem of quantitative adequacy of supply and demand. The lack of knowledge of health professionals, patients, payers, heterogeneous programs which does not necessary correspond to the needs of the patient (modalities, geography, duration), the lack of trained and available professionals, the profile of patients and prescribers and the quality of the programs are identified as potentially hindering the completion of a rehabilitation program. It is essential to analyze these barriers and to find solutions to the greatest number of respiratory patients can benefit optimal healthcare and integrate into a coherent care planning.

The epidemiological signature of influenza B virus and its B/Victoria and B/Yamagata lineages in the 21st century.

We describe the epidemiological characteristics, pattern of circulation, and geographical distribution of influenza B viruses and its lineages using data from the Global Influenza B Study. We included over 1.8 million influenza cases occurred in thirty-one countries during 2000-2018. We calculated the proportion of cases caused by influenza B and its lineages; determined the timing of influenza A and B epidemics; compared the age distribution of B/Victoria and B/Yamagata cases; and evaluated the frequency of lineage-level mismatch for the trivalent vaccine. The median proportion of influenza cases caused by influenza B virus was 23.4%, with a tendency (borderline statistical significance, p = 0.060) to be higher in tropical vs. temperate countries. Influenza B was the dominant virus type in about one every seven seasons. In temperate countries, influenza B epidemics occurred on average three weeks later than influenza A epidemics; no consistent pattern emerged in the tropics. The two B lineages caused a comparable proportion of influenza B cases globally, however the B/Yamagata was more frequent in temperate countries, and the B/Victoria in the tropics (p = 0.048). B/Yamagata patients were significantly older than B/Victoria patients in almost all countries. A lineage-level vaccine mismatch was observed in over 40% of seasons in temperate countries and in 30% of seasons in the tropics. The type B virus caused a substantial proportion of influenza infections globally in the 21st century, and its two virus lineages differed in terms of age and geographical distribution of patients. These findings will help inform health policy decisions aiming to reduce disease burden associated with seasonal influenza.

DETECTION OF NON-INFLUENZA VIRUSES IN ACUTE RESPIRATORY INFECTIONS IN CHILDREN UNDER FIVE-YEAR-OLD IN COTE D'IVOIRE (JANUARY - DECEMBER 2013).

BACKGROUND: Influenza sentinel surveillance in Cote d'Ivoire showed that 70% of Acute Respiratory Infections (ARI) cases remained without etiology. This work aims to describe the epidemiological, clinical, and virological pattern of ARI that tested negative for influenza virus, in children under five years old. MATERIALS AND METHODS: one thousand and fifty nine samples of patients presenting influenza Like Illness (ILI) or Severe Acute Respiratory Infections (SARI) symptoms were tested for other respiratory viruses using multiplex RT-PCR assays targeting 10 respiratory viruses. RESULTS: The following pathogens were detected as follows, hRV 31,92% (98/307), hRSV 24.4% (75/329), PIV 20.5% (63/307), HCoV 229E 12,05% (37/307), hMPV 6.2% (19/307), HCoVOC43 1.0% (3/307) and EnV 1.0% (3/307). Among the 1,059 specimens analyzed, 917 (86.6%) were ILI samples and 142 (23.4%) were SARI samples. The proportion of children infected with at least one virus was 29.8% (273/917) in ILI cases and 23.9% (34/142) in SARI cases. The most prevalent viruses, responsible for ILI cases were hRV with 35.89% (98/273) and hRSV in SARI cases with 41.2% (14/34) of cases. Among the 1,059 patients, only 22 (2.1%) children presented risk factors related to the severity of influenza virus infection. CONCLUSION: This study showed that respiratory viruses play an important role in the etiology of ARI in children. For a better understanding of the epidemiology of ARI and improved case management, it would be interesting in this context to expand the surveillance of influenza to other respiratory viruses.

Epidemiology of rubella infection and genotyping of rubella virus in Cote d'Ivoire, 2012-2016.

Rubella is a contagious disease caused by the rubella virus (RuV) that can lead to serious birth defects when women are infected in early pregnancy. This study aimed to describe the epidemiology and genetic diversity of rubella viruses in Cote d'Ivoire (CIV). Blood or oral fluid samples collected from suspected measles cases were first tested for the presence of measles specific IgM antibodies by enzyme-linked immunosorbent assay (ELISA). All measles IgM negative or indeterminate samples were tested for rubella IgM antibody using ELISA. Rubella-IgM-positive samples were tested by real-time reverse transcription polymerase chain reaction (RT-PCR) for the presence of rubella virus RNA. Real-time RT-PCR-positive RNA samples were used as template to amplify the 739 nt region used for rubella genotyping. PCR-positive samples were sequenced and phylogenetic analysis performed. Between 2012 and 2016, 4121 serums and 126 oral fluids were collected through the measles surveillance system. Of these, 3823 and 108 respectively were measles IgM negative or indeterminate. Subsequent testing for rubella found that 690 of 3823 (18%) serum samples and 25 of 108 (23%) oral fluid samples were rubella IgM-positive. The 739 nt segment of the E1 glycoprotein gene was amplified and sequenced for two serums and seven oral fluids samples. Phylogenetic analysis showed that the rubella viruses from CIV belonged to genotypes 1G (eight samples) and 2B (one sample). Rubella virus genotype 2B was found in CIV for the first time. These data contribute to baseline information on rubella virus strains found in CIV before the introduction of rubella vaccine.

Distribution of influenza virus types by age using case-based global surveillance data from twenty-nine countries, 1999-2014.

BACKGROUND: Influenza disease burden varies by age and this has important public health implications. We compared the proportional distribution of different influenza virus types within age strata using surveillance data from twenty-nine countries during 1999-2014 (N=358,796 influenza cases). METHODS: For each virus, we calculated a Relative Illness Ratio (defined as the ratio of the percentage of cases in an age group to the percentage of the country population in the same age group) for young children (0-4 years), older children (5-17 years), young adults (18-39 years), older adults (40-64 years), and the elderly (65+ years). We used random-effects meta-analysis models to obtain summary relative illness ratios (sRIRs), and conducted meta-regression and sub-group analyses to explore causes of between-estimates heterogeneity. RESULTS: The influenza virus with highest sRIR was A(H1N1) for young children, B for older children, A(H1N1)pdm2009 for adults, and (A(H3N2) for the elderly. As expected, considering the diverse nature of the national surveillance datasets included in our analysis, between-estimates heterogeneity was high (I2>90%) for most sRIRs. The variations of countries' geographic, demographic and economic characteristics and the proportion of outpatients among reported influenza cases explained only part of the heterogeneity, suggesting that multiple factors were at play. CONCLUSIONS: These results highlight the importance of presenting burden of disease estimates by age group and virus (sub)type.

A new approach for endoscopic neurolysis of the suprascapular nerve at the spinoglenoid notch: A preliminary cadaver study.

The suprascapular nerve (SSN) can become compressed at its 2 scapular attachments: the suprascapular and the spinoglenoid notch. The objective of this study was to describe a new arthroscopic approach for SSN neurolysis at the spinoglenoid notch. Ten cadaver shoulders were used. Two were dissected to simulate the "classical" arthroscopic approach and to help in the creation of a new "direct medial retrospinal" approach. Eight other shoulders were used to validate this new approach, with control of the whole juxta-glenoid course of the SSN as criterion of success. The retrospinal posterior approach allowed the entire juxta-glenoid segment of the SSN to be explored in 6 cases out of 8. One exploration was incomplete, another not feasible. SSN neurolysis at the spinoglenoid notch was feasible in cadavers on a retrospinal approach.

Temporal Patterns of Influenza A and B in Tropical and Temperate Countries: What Are the Lessons for Influenza Vaccination?

INTRODUCTION: Determining the optimal time to vaccinate is important for influenza vaccination programmes. Here, we assessed the temporal characteristics of influenza epidemics in the Northern and Southern hemispheres and in the tropics, and discuss their implications for vaccination programmes. METHODS: This was a retrospective analysis of surveillance data between 2000 and 2014 from the Global Influenza B Study database. The seasonal peak of influenza was defined as the week with the most reported cases (overall, A, and B) in the season. The duration of seasonal activity was assessed using the maximum proportion of influenza cases during three consecutive months and the minimum number of months with ≥80% of cases in the season. We also assessed whether co-circulation of A and B virus types affected the duration of influenza epidemics. RESULTS: 212 influenza seasons and 571,907 cases were included from 30 countries. In tropical countries, the seasonal influenza activity lasted longer and the peaks of influenza A and B coincided less frequently than in temperate countries. Temporal characteristics of influenza epidemics were heterogeneous in the tropics, with distinct seasonal epidemics observed only in some countries. Seasons with co-circulation of influenza A and B were longer than influenza A seasons, especially in the tropics. DISCUSSION: Our findings show that influenza seasonality is less well defined in the tropics than in temperate regions. This has important implications for vaccination programmes in these countries. High-quality influenza surveillance systems are needed in the tropics to enable decisions about when to vaccinate.

Are ligament-tensioning devices interchangeable? A study of femoral rotation.

BACKGROUND: During total knee arthroplasty (TKA), femoral rotation can be adjusted either in relation to bony landmarks or by tensioning the ligaments with the knee in 90° of flexion. The primary objective of this study was to compare femoral rotations achieved using various ligament-tensioning devices. The secondary objective was to compare these femoral rotations to that indicated by the transepicondylar axis (TEA). MATERIAL AND METHODS: We performed 13 posterior-stabilised TKA procedures using HiFit (Ceraver(®)) on cadaver knees. Before performing the posterior condyle cut, we used an original method to measure the femoral rotation induced by five different ligament-tensioning devices (2 with a ratchet mechanism, 1 with screws, 1 force-sensing device, and 1 with spacer blocks) and the central tibio-femoral distance (CTFD). RESULTS: Both ratchet tensioners provided significantly greater mean external rotation values (P=0.002), of 4.94° and 4.46°, respectively, compared to the force-sensing and spacer tensioners. Significant differences were found across devices for CTFD, with a mean difference of about 2mm between the ratchet and screw tensioners versus the force-sensing and spacer tensioners. The mean differences in rotations obtained using the tensioners versus the TEA were close to 0° but with standard deviations greater than 4°. CONCLUSION: Femoral rotation was dependent on the distraction force applied to the joint. Tensioners that did not measure the distraction force were associated with greater distraction force and external rotation values. The TEA criterion did not reliably indicate good ligament balance. LEVEL OF EVIDENCE: Experimental study.

Epidemiological and virological characteristics of influenza B: results of the Global Influenza B Study.

INTRODUCTION: Literature on influenza focuses on influenza A, despite influenza B having a large public health impact. The Global Influenza B Study aims to collect information on global epidemiology and burden of disease of influenza B since 2000. METHODS: Twenty-six countries in the Southern (n = 5) and Northern (n = 7) hemispheres and intertropical belt (n = 14) provided virological and epidemiological data. We calculated the proportion of influenza cases due to type B and Victoria and Yamagata lineages in each country and season; tested the correlation between proportion of influenza B and maximum weekly influenza-like illness (ILI) rate during the same season; determined the frequency of vaccine mismatches; and described the age distribution of cases by virus type. RESULTS: The database included 935 673 influenza cases (2000-2013). Overall median proportion of influenza B was 22·6%, with no statistically significant differences across seasons. During seasons where influenza B was dominant or co-circulated (>20% of total detections), Victoria and Yamagata lineages predominated during 64% and 36% of seasons, respectively, and a vaccine mismatch was observed in ≈25% of seasons. Proportion of influenza B was inversely correlated with maximum ILI rate in the same season in the Northern and (with borderline significance) Southern hemispheres. Patients infected with influenza B were usually younger (5-17 years) than patients infected with influenza A. CONCLUSION: Influenza B is a common disease with some epidemiological differences from influenza A. This should be considered when optimizing control/prevention strategies in different regions and reducing the global burden of disease due to influenza.

Assessment of Exposure to Perchloroethylene and its Clinical Repercussions for 50 Dry-Cleaning Employees.

The purpose of this article is the assessment of occupational exposure to perchloroethylene (PCE) and its clinical repercussions for dry-cleaning employees. The authors measured atmospheric levels of PCE and blood levels in a population of 50 exposed employees then conducted a study of clinical symptomatology in exposed and non-exposed subjects linked with this solvent. Fifty employees and 95 controls were studied. The median value of atmospheric PCE was 7 ppm (0.22-33), and the median blood level of PCE was 73.6 µg/l (11.8-144). These levels were correlated statistically to the action of sludge scraping and to the existence of automatic scrapers (p < 0.01). Eight percent of PCE blood levels were higher than the biological levels recently set in France. The exposed population did not show excessive signs of drowsiness nor of pre-narcotic syndrome or other symptoms studied. Dry-cleaning employees were exposed to PCE at atmospheric levels lower than the French and American chronic recommended exposure levels but some results were higher than recommended values. For PCE blood levels for the general working population, results were respectively lower than French and American national recommended levels in 92% and 94% cases. Risk should be considered, however, carefully in women of childbearing age, as 64% exceeded the recommended blood levels for pregnant women. This exposure did not generate any studied neurobehavioral symptomatology.

Pandemic Influenza A(H1N1) in Cote d'Ivoire: health-care providers' knowledge of influenza and attitudes towards vaccination.

INTRODUCTION: During the 2009 influenza A(H1N1) pandemic (pH1N1), different methods were promoted to reduce the spread of influenza, including respiratory etiquette and vaccination. To identify knowledge gaps about influenza and to plan the vaccination campaign against the pandemic in Côte d'Ivoire, a survey was conducted among health-care providers (HCPs) to assess their knowledge about influenza and their willingness to be vaccinated. METHODOLOGY: A cross-sectional survey was performed in the city of Abidjan on 16-18 February 2010, in the three university teaching hospitals, a randomly selected general hospital, and two randomly selected private clinics. In face-to-face interviews, 383 health-care professionals were asked questions about their knowledge of influenza, means of influenza prevention, and their willingness to be vaccinated. Data analysis, both univariate and multivariate, was performed using SPSS. RESULTS: Willingness to be vaccinated against pH1N1 was 80% (n = 284), and 83% of the HCPs would recommend the vaccine to others. The respiratory mode of transmission of influenza was known by 85% (n = 295) of the participants and 50% (n = 174) believed that seasonal influenza virus and pH1N1 virus were different. In a multivariate model, the factors significantly associated with willingness to receive pH1N1vaccine were fear of pH1N1 disease (OR = 2.1; IC = 1.02-4.35), having only a high school education (OR = 8.28; IC = 2.04-33.60), and feeling at risk to contract pH1N1 (OR = 11.43; IC = 4.77-27.38). CONCLUSION: The willingness to be vaccinated against influenza A (H1N1) by health professionals is real.

Sentinel surveillance for influenza and other respiratory viruses in Côte d'Ivoire, 2003-2010.

BACKGROUND: Many countries in Africa have lacked sentinel surveillance systems for influenza and are under-represented in data used for global vaccine strain selection. OBJECTIVES: We describe 8 years of sentinel surveillance data and the contribution of influenza and other viruses to medically attended influenza-like illness (ILI) in Côte d'Ivoire. METHODS: Sentinel surveillance was established in 2003. Nasopharyngeal (NP) specimens and epidemiologic data are collected from persons of all ages presenting with ILI at sentinel sites. Respiratory specimens have been tested for influenza using various viral and molecular diagnostic methods. A subset of 470 specimens collected from children aged 0-5 years were tested for multiple respiratory viruses using RT-PCR. RESULTS: From 2003 to 2010, 5074 NP specimens were collected from patients with ILI. Overall, 969/5074 (19%) of these specimens tested positive for influenza. Seasonal influenza A(H1N1) viruses predominated during 5 years and influenza A(H3N2) viruses predominated during 3 years. Influenza B viruses cocirculated with influenza A viruses during each year from 2004 to 2010. Seasonal peaks in influenza circulation were observed during the months of May, June, and October, with the largest peak corresponding with the primary rainfall season. Of 470 specimens collected from children under aged 5 who were tested for multiple respiratory viruses, a viral respiratory pathogen was detected in 401/470 (85%) of specimens. Commonly detected viruses were RSV (113 of 470 specimens, 24%), rhinoviruses (85/470, 18%), influenza (77/470, 16%), and parainfluenza (75/470, 16%). CONCLUSION: In Côte d'Ivoire, there is a significant annual contribution of influenza and other respiratory viruses to medically attended ILI.

[Niemann-Pick disease type B identified following an episode of bronchopneumonia]. / Maladie de Niemann-Pick de type B révélée par une atteinte bronchopulmonaire.

Niemann Pick disease type B (NPD type B) is a rare autosomal recessive lipid storage disorder, characterized by a partial deficiency of sphingomyelinase. We report the case of an adult male patient affected by NPD type B and diagnosed at 39-years-of age. Pulmonary CT scan revealed a cranio-caudal gradient with nodular centrilobular ground glass opacities and thickening of the interlobular septa. Pathological examination of the bronchoalveolar lavage showed foamy alveolar macrophages and vacuolated bronchial epithelial cells on bronchial biopsy. Diagnostic confirmation was achieved by a decrease in cell lysosomal enzyme activity and by the presence of the homozygous DeltaR608 mutation in the acid sphingomyelinase gene (SMPD1).

Comparative disposition and metabolism of paraherquamide in sheep, gerbils, and dogs.

The disposition and metabolism of paraherquamide (PHQ), a potent and broad-spectrum anthelminthic, were examined in sheep, dogs, and gerbils. The metabolism of PHQ in these species was extensive and marked by significant species differences both in vitro and in vivo. In sheep and gerbils, PHQ metabolism occurs mainly at the pyrrolidine moiety, generating several metabolites that, for the most part, retained nematodicidal activity in vitro. In dogs, the dioxepene group was also extensively metabolized, ultimately resulting in formation of a catechol and loss of pharmacological activity. After oral administration of [3H]PHQ to intact sheep, gerbils, and dogs, the majority of the administered radioactivity was recovered in feces. Intact PHQ accounted for 0% (dogs) to approximately 30% (sheep and gerbils) of drug-related material in feces. A detailed investigation of the composition of the intestinal content of sheep indicated that a significant amount of the dose was still present in the rumen 24 h after dose and that PHQ underwent significant dehydration in the cecum. The oral pharmacokinetic parameters of PHQ in sheep and dogs suggest that its absorption is rapid in both species but that its apparent elimination rate is significantly higher in the dog (t(1/2) approximately 1.5 h) than it is in sheep (t(1/2) approximately 8.5 h). The short elimination half-life and the absence of PHQ or other active components in the dog gastrointestinal tract provide a potential explanation of the lack of efficacy of PHQ in this species.

Reduction of 13-deoxydoxorubicin and daunorubicinol anthraquinones by human carbonyl reductase.

Carbonyl reductase (CR) catalyzes the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of several carbonyls. Anthracyclines used to treat cancer are reduced by CR at the C13 carbonyl and the resulting metabolites are implicated in the cardiotoxicity associated with anthracycline therapy. CR also is believed to have a role in detoxifying quinones, raising the question whether CR catalyzes reduction of anthracycline quinones. Steady-state kinetic studies were done with several anthraquinone-containing compounds, including 13-deoxydoxorubicin and daunorubicinol, which lack the C13 carbonyl, thus unmasking the anthraquinone for study. k(cat) and k(cat)/K(m) values for 13-deoxydoxorubicin and daunorubicinol were nearly identical, indicating that that the efficiency of quinone reduction was unaffected by the differences at the C13 position. k(cat) and k(cat)/K(m) values were much smaller for the analogs than for the parent compounds, suggesting that the C13 carbonyl is preferred as a substrate over the quinone. CR also reduced structurally related quinone molecules with less favorable catalytic efficiency. Modeling studies with doxorubicin and carbonyl reductase revealed that methionine 234 sterically hinder the rings adjacent to the quinone, thus accounting for the lower catalytic efficiency. Reduction of the anthraquinones may further define the role of CR in anthracycline metabolism and may influence anthracycline cytotoxic and cardiotoxic mechanisms.

Doxorubicin cardiac dysfunction: effects on calcium regulatory proteins, sarcoplasmic reticulum, and triiodothyronine.

Utilizing a model of chronic doxorubicin cardiomyopathy, this study examines the relationship between changes in expression and function of calcium handling proteins and contractile dysfunction. A possible mechanism to account for this relationship is suggested. New Zealand white rabbits were injected with either doxorubicin (1 mg/kg, twice weekly for 8 wk) or 0.9% NaCl. Gene transcript, protein levels, and the function of several proteins from the left ventricle were assessed. Protein levels of sarcoplasmic reticulum (SR) Ca2+ transporting ATPase (SERCA2a and b), Ca2+ release channel (RYR2), calsequestrin, Na/Ca exchanger, mRNA levels of RYR2, and [3H]-ryanodine binding (B(max)) to RYR2 were significantly decreased in doxorubicin-treated rabbits; protein levels of phospholamban, dihydropyridine receptor alpha2 subunit, and SR Ca2+ loading rates were not decreased. However, only protein levels of SERCA2 and RYR2, mRNA levels of RYR2, and Bmax of RYR2 significantly regressed with left-ventricular fractional shortening. Analysis of contractile function of atrial preparations isolated from doxorubicin-treated rabbits revealed that doxorubicin diminished contractility (dF/dt) of rest-potentiated contractions consistent with SR dysfunction. Serum concentrations of free triiodothyronine (T3) decreased in doxorubicin-treated rabbits. Our results suggest that chronic doxorubicin administration in the rabbit causes a SR-dependent contractile dysfunction that may result, in part, from decreased T3.

Anthracycline cardiotoxicity in transgenic mice overexpressing SR Ca2+-ATPase.

Chronic anthracycline administration results in a time- and dose-dependent cardiomyopathy. The Ca-ATPase of the sarcoplasmic reticulum, SERCA2, has been implicated as a principal target for anthracycline-induced cardiotoxicity. This hypothesis predicts that improved SERCA2 function would provide protection from cardiotoxic effects of anthracycline administration. Doxorubicin was administered (1.7 mg/kg three times weekly; cumulative dose of 20 mg/kg) to 10 transgenic mice that overexpressed SERCA2 and to 10 isogenic littermates. Survival was monitored for 60 days and histologic comparisons were made of cardiac tissue. Survival in the transgenic mice was worse (1/10 60-day survivors) compared to isogenic control mice (7/10 60-day survivors). There was a greater degree of histologic damage exhibited in hearts from transgenic mice compared to isogenic controls when all available hearts were examined. These data do not support a role of SERCA2 in ameliorating anthracycline cardiotoxicity.