[A sudden onset of groin pain]. / Plotselinge pijn in de lies.

We describe an 11-year-old boy with sudden onset of right groin pain which occurred during soccer. He was diagnosed with an avulsion fracture of the lesser trochanter, a hyperextension and rotation trauma due to traction on the iliopsoas tendon. The treatment was conservative and full function returned.

An atypical presentation of a mesenteric Meckel's diverticulum in a 7-year-old warmblood mare: case report.

BACKGROUND: Meckel's diverticula are a rare cause of small intestinal strangulation, diagnosed at laparotomy or necropsy. This congenital anomaly of the gastrointestinal tract originates from a remnant of the vitelline duct. In reported equine cases, they present as a full-thickness diverticulum on the antimesenteric border of the distal jejunum or proximal ileum. CASE PRESENTATION: On laparotomy a Meckel's diverticulum positioned at the mesenteric side was found to be the cause of small intestinal strangulation. This position is very uncommon and to the best knowledge of the authors there is no unambiguous description of another case. CONCLUSIONS: Meckel's diverticula should be on the list of differential diagnoses in cases of small intestinal strangulation. As in humans, equine Meckel's diverticula can have the standard antimesenteric as well as a more exceptional mesenteric location. This case adds to the series of anecdotal reports of anomalies with regard to Meckel's diverticula in the horse.

Immunosuppressive therapy in patients with IgA nephropathy.

BACKGROUND: There is limited evidence to support cytotoxic therapy in patients with IgA nephropathy and renal insufficiency. We studied the effect of cytotoxic therapy in patients with IgA nephropathy and renal insufficiency, and evaluated possible predictors of response. METHODS: Retrospective analysis of patients with IgA nephropathy who received immunosuppressive therapy. The primary outcome measure was progression of renal disease, defined as an increase in serum creatinine levels of ≥ 50% or development of end-stage renal disease. RESULTS: From 1996 to 2008, 19 patients with biopsy-proven IgA nephropathy were treated with cytotoxic agents and prednisone because of renal insufficiency and÷ or severe proteinuria. Characteristics of patients at the start of therapy: age 42±11 years, serum creatinine 208 (96-490) µmol÷l, estimated glomerular filtration rate (eGFR) 33 (12-65) ml÷min÷1.73 m2, and protein- creatinine ratio 3.8 (0.6-18.2) g÷10 mmol. Follow-up after initiation of therapy was 35 (7-133) months. Ten patients had progressive renal disease, whereas eGFR was stable in nine. Serum creatinine levels and proteinuria at the start of treatment were not significantly different between responders and non- responders. Proteinuria response at six months after start of therapy proved a good predictor: proteinuria decreased by ≥ 50% and÷or reached levels below 1 g÷day in 8÷9 responders. In contrast, proteinuria decreased by more than 50% and reached levels < 1 g÷day in only 3÷10 non-responders (p < 0.01). CONCLUSION: Prolonged immunosuppressive therapy with cytotoxic agents and prednisone may benefit a subgroup of patients with progressive IgA nephropathy. A reduction of proteinuria ≥ 50% to levels below 1 g÷day within six months predicts a favourable long-term response.

The natural course of chronic exertional compartment syndrome of the lower leg.

PURPOSE: The aim of this study was to investigate the natural course of chronic exertional compartment syndrome (CECS) in the lower leg. METHODS: Twelve military men [mean age 30 (SD 4)] diagnosed with CECS after intracompartmental pressure (ICP) measurements immediately post-exercise in 21 legs, who did not undergo a fasciotomy, were reviewed and participated in a repeat pressure measurement after a mean time of 50 months (SD 15). RESULTS: Sixteen of 21 legs still showed an ICP of 35 mm Hg or more (the cut-off point) at the second visit. All twelve patients still had typical complaints. Mean ICP at index measurement was 58 (SD 15) mm Hg. At the second visit, it was 51 (SD 15) mm Hg. Six patients chose to undergo a subcutaneous fasciotomy, and these six patients all benefited in the short term. CONCLUSION: The natural course of CECS seems to be persistent symptoms over time. LEVEL OF EVIDENCE: Case series with no comparative group, Level IV.

State observers and Kalman filtering for high performance vibration isolation systems.

There is a strong scientific case for the study of gravitational waves at or below the lower end of current detection bands. To take advantage of this scientific benefit, future generations of ground based gravitational wave detectors will need to expand the limit of their detection bands towards lower frequencies. Seismic motion presents a major challenge at these frequencies and vibration isolation systems will play a crucial role in achieving the desired low-frequency sensitivity. A compact vibration isolation system designed to isolate in-vacuum optical benches for Advanced Virgo will be introduced and measurements on this system are used to present its performance. All high performance isolation systems employ an active feedback control system to reduce the residual motion of their suspended payloads. The development of novel control schemes is needed to improve the performance beyond what is currently feasible. Here, we present a multi-channel feedback approach that is novel to the field. It utilizes a linear quadratic regulator in combination with a Kalman state observer and is shown to provide effective suppression of residual motion of the suspended payload. The application of state observer based feedback control for vibration isolation will be demonstrated with measurement results from the Advanced Virgo optical bench suspension system.

The pathology and pathogenesis of experimental severe acute respiratory syndrome and influenza in animal models.

Respiratory viruses that emerge in the human population may cause high morbidity and mortality, as well as concern about pandemic spread. Examples are severe acute respiratory syndrome coronavirus (SARS-CoV) and novel variants of influenza A virus, such as H5N1 and pandemic H1N1. Different animal models are used to develop therapeutic and preventive measures against such viruses, but it is not clear which are most suitable. Therefore, this review compares animal models of SARS and influenza, with an emphasis on non-human primates, ferrets and cats. Firstly, the pathology and pathogenesis of SARS and influenza are compared. Both diseases are similar in that they affect mainly the respiratory tract and cause inflammation and necrosis centred on the pulmonary alveoli and bronchioles. Important differences are the presence of multinucleated giant cells and intra-alveolar fibrosis in SARS and more fulminant necrotizing and haemorrhagic pneumonia in H5N1 influenza. Secondly, the pathology and pathogenesis of SARS and influenza in man and experimental animals are compared. Host species, host age, route of inoculation, location of sampling and timing of sampling are important to design an animal model that most closely mimics human disease. The design of appropriate animal models requires an accurate pathological description of human cases, as well as a good understanding of the effect of experimental variables on disease outcome.

A clinical decision model identifies patients at risk for delayed diagnosed injuries after high-energy trauma.

OBJECTIVE: Tertiary trauma survey is widely implemented in trauma care to identify all injuries in trauma patients. However, various studies consistently show that some trauma patients have missed injuries. In this study, we developed a clinical decision model to identify patients who are at risk for delayed diagnosed injuries. METHODS: During a period of 18 months, we collected the medical records of all the adult patients who presented after a high-energy trauma at the emergency department of a Dutch trauma centre. The type of trauma, patient characteristics, the radiology studies performed, Glasgow Coma Scale, Revised Trauma Score, and Injury Severity Score (ISS) were registered. We thoroughly screened all medical records for delayed diagnosed injuries. Stepwise logistic regression analysis was used to identify the variables associated with the outcome delayed diagnosed injuries and to develop a clinical prediction model. RESULTS: We included 475 patients. Thirteen (2.7%) patients with delayed diagnosed injuries were identified. Stepwise logistic regression analysis revealed several models with the ISS, ICU admittance, and CT-head as predictive variables. The model we proposed with the ISS could identify patients who are at a risk for delayed diagnosed injuries with a sensitivity of 92.3% and a specificity of 86.4%. CONCLUSION: Our newly developed clinical decision model can identify patients who are at a risk for delayed diagnosed injuries and who should undergo an intensified search for potential unidentified injuries.

Modification of the ferret model for pneumonia from seasonal human influenza A virus infection.

The primary complication of seasonal influenza in humans is viral pneumonia. A conventional animal model--intranasal inoculation of ferrets with 10(6) median tissue culture infectious dose of virus--results in disease that is neither consistent nor comparable with severe viral pneumonia in humans. Therefore, the authors modified the experimental procedures by increasing the median tissue culture infectious dose to 10(9) and by inoculating via the intratracheal route, testing these procedures with H1N1 strains (A/Bilthoven/3075/1978 and A/Netherlands/26/2007) and H3N2 strains (A/Bilthoven/16190/1968 and A/Netherlands/177/2008) of seasonal influenza virus. The ferrets of all groups (n = 3 per virus strain) had clinical signs, increased body temperature, virus excretion from day 1, loss of body weight, and increased relative lung weight at 4 days postinoculation. All ferrets had severe pulmonary consolidation, and histologic examination revealed moderate to severe necrotizing bronchointerstitial pneumonia with severe edema, necrosis of alveolar epithelium, inflammatory infiltrates in alveolar septa and lumina, epithelial regeneration, and perivascular and peribronchiolar inflammatory infiltrates. The lesions were associated with the presence of influenza virus antigen in respiratory epithelium by immunohistochemistry. Although all 4 virus strains caused pulmonary lesions of comparable severity, virus isolation in the lungs, trachea, nasal concha, and tonsils showed higher mean virus titers in the H1/07 and H3/68 groups than in the H1/78 and H3/08 groups. In conclusion, the above H1N1 and H3N2 strains cause severe pneumonia in ferrets by use of the modified experimental procedures and provide a good model for pneumonia caused by seasonal influenza A virus infection in humans.

Fatal interstitial lung disease associated with high erlotinib and metabolite levels. A case report and a review of the literature.

INTRODUCTION: Erlotinib is an agent in the class of oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Although this class of agents is considered to be relatively safe, the most serious, but rare, adverse reaction is drug-associated interstitial lung disease (ILD). This potentially fatal adverse reaction has been often described with gefitinib, but has been less well described for erlotinib. We here describe a case report of fatal interstitial lung disease in a Caucasian man associated with erlotinib and high erlotinib and metabolite plasma levels and discuss it in the context of all documented cases of erlotinib associated ILD. METHODS: Our case was described and for the literature review a Pubmed and Google Scholar search was conducted for cases of erlotinib associated ILD. The retrieved publications were screened for relevant literature. RESULTS: Besides our case, a total of 19 cases of erlotinib-associated ILD were found. Eleven out 19 cases had a fatal outcome and in only one case erlotinib plasma concentrations were measured and found to be high. CONCLUSION: Erlotinib-associated ILD is a rare, serious and often fatal adverse reaction. Most likely, the cause for erlotinib-associated ILD is multifactorial and high drug levels may be present in patients without serious adverse reactions. However, considering the pharmacology of EGFR inhibitors, high drug and metabolite levels may play a role and future studies are warranted to identify risk factors and to investigate the role of elevated levels of erlotinib and its metabolites in the development of pulmonary toxicity.

[Waveboard-related injuries. Greater protection is advised]. / Letsels bij 'waveboarden'. Aanbeveling om meer bescherming te dragen.

OBJECTIVE: Waveboarding, a type of skateboarding, is a new craze among children. The aim of this study is to describe how many children visit the emergency department as a consequence of waveboarding and the types of injury they have. DESIGN: Retrospective, descriptive. METHOD: All records of children aged 5 to 15 years who had visited the emergency department of the Medical Center Alkmaar in the period March to May 2010 were examined. If a case of waveboard-related injury was found then the type of injury was noted. For all of the injuries a phone call was made to try to find out if protective gear had been worn. RESULTS: A total of 1418 records from 2010 were investigated. In 132 cases, a waveboard-related injury was found. Contusion was found in 31% of cases and a fracture in 64% of cases. The 2 most frequently occurring sites of injury were the forearm and wrist (53%) and the elbow (14%). In 3% of the waveboard-related injuries the child concerned had worn any protective gear. CONCLUSION: Children who visited the emergency department due to waveboard-related injuries mainly had injuries to the wrists, forearm and elbow. Only 3% of the children wore protective gear when waveboarding. As effective protection against accident-related injuries exists for skaters, the wearing of protective gear during waveboarding can be expected to lead to a reduced number of injuries.

Comparative pathology of select agent influenza a virus infections.

Influenza A virus infections may spread rapidly in human populations and cause variable mortality. Two of these influenza viruses have been designated as select agents: 1918 H1N1 virus and highly pathogenic avian influenza (HPAI) virus. Knowledge of the pathology of these virus infections in humans, other naturally infected species, and experimental animals is important to understand the pathogenesis of influenza, to design appropriate models for evaluation of medical countermeasures, and to make correct diagnoses. The most important complication of influenza in humans is viral pneumonia, which often occurs with or is followed by bacterial pneumonia. Viremia and extrarespiratory disease are uncommon. HPAI viruses, including HPAI H5N1 virus, cause severe systemic disease in galliform species as well as in anseriform species and bird species of other orders. HPAI H5N1 virus infection also causes severe disease in humans and several species of carnivores. Experimental animals are used to model different aspects of influenza in humans, including uncomplicated influenza, pneumonia, and virus transmission. The most commonly used experimental animal species are laboratory mouse, domestic ferret, and cynomolgus macaque. Experimental influenza virus infections are performed in various other species, including domestic pig, guinea pig, and domestic cat. Each of these species has advantages and disadvantages that need to be assessed before choosing the most appropriate model to reach a particular goal. Such animal models may be applied for the development of more effective antiviral drugs and vaccines to protect humans from the threat of these virus infections.

Pandemic 2009 H1N1 influenza virus causes diffuse alveolar damage in cynomolgus macaques.

The pathogenesis of lower respiratory tract disease from the pandemic 2009 H1N1 (H1N1v) influenza A virus is poorly understood. Therefore, either H1N1v virus or a seasonal human H1N1 influenza A virus was inoculated into cynomolgus macaques as a nonhuman primate model of influenza pneumonia, and virological, pathological, and microarray analyses were performed. Macaques in the H1N1v group had virus-associated diffuse alveolar damage involving both type I and type II alveolar epithelial cells and affecting an average of 16% of the lung area. In comparison, macaques in the seasonal H1N1 group had milder pulmonary lesions. H1N1v virus tended to be reisolated from more locations in the respiratory tract and at higher titers than seasonal H1N1 virus. In contrast, differential expression of messenger RNA transcripts between H1N1v and seasonal H1N1 groups did not show significant differences. The most upregulated genes in H1N1v lung samples with lesions belonged to the innate immune response and proinflammatory pathways and correlated with histopathological results. Our results demonstrate that the H1N1v virus infects alveolar epithelial cells and causes diffuse alveolar damage in a nonhuman primate model. Its higher pathogenicity compared with a seasonal H1N1 virus may be explained in part by higher replication in the lower respiratory tract.

A single immunization with CoVaccine HT-adjuvanted H5N1 influenza virus vaccine induces protective cellular and humoral immune responses in ferrets.

Highly pathogenic avian influenza A viruses of the H5N1 subtype continue to circulate in poultry, and zoonotic transmissions are reported frequently. Since a pandemic caused by these highly pathogenic viruses is still feared, there is interest in the development of influenza A/H5N1 virus vaccines that can protect humans against infection, preferably after a single vaccination with a low dose of antigen. Here we describe the induction of humoral and cellular immune responses in ferrets after vaccination with a cell culture-derived whole inactivated influenza A virus vaccine in combination with the novel adjuvant CoVaccine HT. The addition of CoVaccine HT to the influenza A virus vaccine increased antibody responses to homologous and heterologous influenza A/H5N1 viruses and increased virus-specific cell-mediated immune responses. Ferrets vaccinated once with a whole-virus equivalent of 3.8 microg hemagglutinin (HA) and CoVaccine HT were protected against homologous challenge infection with influenza virus A/VN/1194/04. Furthermore, ferrets vaccinated once with the same vaccine/adjuvant combination were partially protected against infection with a heterologous virus derived from clade 2.1 of H5N1 influenza viruses. Thus, the use of the novel adjuvant CoVaccine HT with cell culture-derived inactivated influenza A/H5N1 virus antigen is a promising and dose-sparing vaccine approach warranting further clinical evaluation.

Preclinical evaluation of a modified vaccinia virus Ankara (MVA)-based vaccine against influenza A/H5N1 viruses.

Highly pathogenic avian influenza viruses of the H5N1 subtype are responsible for an increasing number of infections in humans since 2003. More than 60% of the infections is lethal and new infections are reported frequently. In the light of the pandemic threat caused by these events the rapid availability of safe and effective vaccines is desirable. Modified vaccinia virus Ankara (MVA) expressing the HA gene of an influenza A/H5N1 virus is a promising candidate vaccine that induced protective immunity against infection with homologous and heterologous influenza A/H5N1 viruses in mice. We also evaluated the recombinant MVA vector expressing the HA of influenza A/H5N1 virus A/Vietnam/1194/04 (MVA-HA-VN/04) in non-human primates. Cynomolgus macaques were immunized twice and then challenged with influenza virus A/Vietnam/1194/04 (clade 1) or A/Indonesia/5/05 (clade 2.1) to assess the level of protective immunity. Immunization with MVA-HA-VN/04 induced (cross-reactive) antibodies and prevented virus replication in the upper and lower respiratory tract and the development of severe necrotizing bronchointerstitial pneumonia. Therefore MVA-HA-VN/04 is a promising vaccine candidate for the induction of protective immunity against highly pathogenic avian influenza A/H5N1 viruses.

Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/H5N1 virus.

The transmission of highly pathogenic avian influenza (HPAI) A viruses of the H5N1 subtype from poultry to man and the high case fatality rate fuels the fear for a pandemic outbreak caused by these viruses. However, prior infections with seasonal influenza A/H1N1 and A/H3N2 viruses induce heterosubtypic immunity that could afford a certain degree of protection against infection with the HPAI A/H5N1 viruses, which are distantly related to the human influenza A viruses. To assess the protective efficacy of such heterosubtypic immunity mice were infected with human influenza virus A/Hong Kong/2/68 (H3N2) 4 weeks prior to a lethal infection with HPAI virus A/Indonesia/5/05 (H5N1). Prior infection with influenza virus A/Hong Kong/2/68 reduced clinical signs, body weight loss, mortality and virus replication in the lungs as compared to naive mice infected with HPAI virus A/Indonesia/5/05. Priming by infection with respiratory syncytial virus, a non-related virus did not have a beneficial effect on the outcome of A/H5N1 infections, indicating that adaptive immune responses were responsible for the protective effect. In mice primed by infection with influenza A/H3N2 virus cytotoxic T lymphocytes (CTL) specific for NP(366-374) epitope ASNENMDAM and PA(224-232) SCLENFRAYV were observed. A small proportion of these CTL was cross-reactive with the peptide variant derived from the influenza A/H5N1 virus (ASNENMEVM and SSLENFRAYV respectively) and upon challenge infection with the influenza A/H5N1 virus cross-reactive CTL were selectively expanded. These CTL, in addition to those directed to conserved epitopes, shared by the influenza A/H3N2 and A/H5N1 viruses, most likely contributed to accelerated clearance of the influenza A/H5N1 virus infection. Although also other arms of the adaptive immune response may contribute to heterosubtypic immunity, the induction of virus-specific CTL may be an attractive target for development of broad protective vaccines. Furthermore the existence of pre-existing heterosubtypic immunity may dampen the impact a future influenza pandemic may have.

Pathology and virus distribution in chickens naturally infected with highly pathogenic avian influenza A virus (H7N7) During the 2003 outbreak in The Netherlands.

The largest recorded outbreak of highly pathogenic avian influenza virus of the subtype H7N7 occurred in The Netherlands in 2003. We describe the immunohistochemical and histopathologic findings of 3 chickens naturally infected during this outbreak. Influenza virus antigen occurred in endothelial cells and mononuclear cells of all tissues examined and occurred in parenchymal cells of heart, lung, kidney, pancreas, and trachea, often associated with multifocal inflammation and necrosis. These findings are consistent with the acute stage of highly pathogenic avian influenza from other subtypes. In the severely edematous wattle skin, most endothelial cells contained virus antigen, while in all other tissues virus antigen was only detected in a few endothelial cells. Virus histochemistry showed that this H7N7 virus attached to more endothelial cells in wattle skin than in other vascular beds. This might explain, at least partly, the tropism of the virus and the associated severity of lesions in this tissue.

Urinary excretion of low-molecular-weight proteins as prognostic markers in IgA nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is characterised by high variability in clinical course and outcome. Accurate prediction of prognosis is needed to optimise treatment. Urinary alpha1-microglobulin and beta2-microglobulin are markers of tubulointerstitial injury and predict the risk of end-stage renal disease (ESRD) in idiopathic membranous nephropathy. We questioned the relevance of these markers in IgAN. METHODS: We included patients with biopsy proven IgAN, who were evaluated for proteinuria in our centre between 1995 and 2007. Data were analysed using univariate and multivariate Cox regression for the outcome variables ESRD and progression (rise in serum creatinine of >50% or start of immunosuppressive therapy). RESULTS: Seventy patients (71% men) were selected. Median age was 39 years, median serum creatinine 140 micromol/l, and median proteinuria 2.4 g/day. Median urinary alpha1-microglobulin excretion was 23.5 microg/min (range 3.5-275.3) and median urinary beta2-microglobulin excretion was 0.4 microg/min (range 0.1-62.1). Both alpha1m and beta2m correlated significantly with serum creatinine (r = 0.65, p<0.01 and r = 0.62, p<0.01) and total proteinuria (r = 0.35, p<0.01 and r = 0.28, p<0.05). During follow-up (median 75 months) 25 patients (36%) developed ESRD , and 46 patients (66%) showed progression. 19 patients (27%) were treated with immunosuppressive agents. In univariate analysis urinary alpha1- and beta2-microglobulin predicted ESRD and progression. In multivariate analysis only serum creatinine and urinary protein were independent predictors of both outcomes. CONCLUSION: Urinary excretion of low molecular weight proteins did not offer an advantage over total proteinuria and serum creatinine in predicting prognosis in patients with IgAN.

Recombinant modified vaccinia virus Ankara expressing the hemagglutinin gene confers protection against homologous and heterologous H5N1 influenza virus infections in macaques.

BACKGROUND: Highly pathogenic avian influenza viruses of the H5N1 subtype have been responsible for an increasing number of infections in humans since 2003. More than 60% of infected individuals die, and new infections are reported frequently. In light of the pandemic threat caused by these events, the rapid availability of safe and effective vaccines is desirable. Modified vaccinia virus Ankara (MVA) expressing the hemagglutinin (HA) gene of H5N1 viruses is a promising candidate vaccine that induced protective immunity against infection with homologous and heterologous H5N1 influenza virus in mice. METHODS: In the present study, we evaluated a recombinant MVA vector expressing the HA gene of H5N1 influenza virus A/Vietnam/1194/04 (MVA-HA-VN/04) in nonhuman primates. Cynomolgus macaques were immunized twice and then were challenged with influenza virus A/Vietnam/1194/04 (clade 1) or A/Indonesia/5/05 (clade 2.1) to assess the level of protective immunity. RESULTS: Immunization with MVA-HA-VN/04 induced (cross-reactive) antibodies and prevented virus replication in the upper and lower respiratory tract and the development of severe necrotizing bronchointerstitial pneumonia. CONCLUSION: Therefore, MVA-HA-VN/04 is a promising vaccine candidate for the induction of protective immunity against highly pathogenic H5N1 avian influenza viruses in humans.

Pathology of experimental SARS coronavirus infection in cats and ferrets.

The pathology of severe acute respiratory syndrome-coronavirus (SARS-CoV) infection in cats and ferrets is poorly described, and the distribution of angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV, in the respiratory tracts of these species is unknown. We observed SARS-CoV antigen expression and lesions in the respiratory tracts of 4 cats and 4 ferrets at 4 days postinoculation and ACE2 expression in the respiratory tracts of 3 cats and 3 ferrets without infection. All infected cats and ferrets had diffuse alveolar damage associated with SARS-CoV antigen expression. A novel SARS-CoV-associated lesion was tracheo-bronchoadenitis in cats. SARS-CoV antigen expression occurred mainly in type I and II pneumocytes and serous cells of tracheo-bronchial submucosal glands of cats and in type II pneumocytes of ferrets. ACE2 expression occurred mainly in type I and II pneumocytes, tracheo-bronchial goblet cells, serous epithelial cells of tracheo-bronchial submucosal glands in cats, and type II pneumocytes and serous epithelial cells of tracheo-bronchial submucosal glands in ferrets. In conclusion, the pathology of SARS-CoV infection in cats and ferrets resembles that in humans except that syncytia and hyaline membranes were not observed. The identification of tracheo-bronchoadenitis in cats has potential implications for SARS pathogenesis and SARS-CoV excretion. Finally, these results show the importance of ACE2 expression for SARS-CoV infection in vivo: whereas ACE2 expression in type I and II pneumocytes in cats corresponded to SARS-CoV antigen expression in both cell types, expression of both ACE2 and SARS-CoV antigen in ferrets was limited mainly to type II pneumocytes.